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Recent progress in the construction of nanozyme-based biosensors and their applications to food safety assay
Journal Pre-proof Recent progress on the construction of nanozymes-based biosensors and their applications to food safety assay Xianlong Zhang, Di Wu, Xuxia Zhou, Yanxin Yu, Jichao Liu, Na Hu, Honglun Wang, Guoliang Li, Yongning Wu PII:
S0165-9936(19)30347-4
DOI:
https://doi.org/10.1016/j.trac.2019.115668
Reference:
TRAC 115668
To appear in:
Trends in Analytical Chemistry
Received Date: 5 June 2019 Revised Date:
12 September 2019
Accepted Date: 13 September 2019
Please cite this article as: X. Zhang, D. Wu, X. Zhou, Y. Yu, J. Liu, N. Hu, H. Wang, G. Li, Y. Wu, Recent progress on the construction of nanozymes-based biosensors and their applications to food safety assay, Trends in Analytical Chemistry, https://doi.org/10.1016/j.trac.2019.115668. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier B.V. All rights reserved.
1
Recent progress on the construction of nanozymes-based biosensors
2
and their applications to food safety assay
3 4
Xianlong Zhanga, Di Wuf, Xuxia Zhoue, Yanxin Yua, Jichao Liua, Na Huc, Honglun Wangc,
5
Guoliang Li ad* and Yongning Wub
6
a
7
Xi’an 710021, China
8
b
9
Risk Assessment, Beijing 100050, China
School of Food and Biological Engineering, Shaanxi University of Science and Technology,
NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety
10
c
11
Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences，
12
Xining 810001, China
13
d
14
273165, China
15
e
16
310014, China
17
Key Laboratory of Tibetan Medicine Research＆Qinghai Provincial Key Laboratory of Tibetan
Key Laboratory of Life-Organic Analysis of Shandong Province, Qufu Normal University, Qufu
Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou
f
Yangtze Delta Region Institute of Tsinghua University, Zhejiang 314006, China
18
AUTHOR INFORMATION
19
E-mail: [email protected] (Guoliang Li)
20 21 22 1
23
Abstract
24
Food safety as a huge world public health threat has attracted more and more attentions. The
25
effective detection methods are of great importance for guarding food safety. However, the
26
development of reliable and efficient detection methods has been a challenging task due to the
27
complexity of food matrices and trace level of food contaminants. Recently, the emerging
28
nanomaterials with mimetic enzyme activity, namely nanozymes, have been employed for novel
29
biosensor development, which has greatly accelerated the advancement of food safety assay. In
30
this review, we summarize the mechanism and advances on nanozymes-based biosensors
31
including colorimetric biosensors, fluorescence biosensors, chemiluminescent biosensors,
32
electrochemical biosensors, SERS-based biosensors, and other biosensors. Impressively, the
33
applications of nanozymes-based biosensors in food safety screening have also been
34
comprehensively summarized (including mycotoxins, antibiotics, pesticides, pathogens,
35
intentional adulteration, metal ions, and others). In the end, future opportunities and challenges in
36
this promising field are tentatively proposed.
37
Keywords: Colorimetric biosensor
38
Electrochemical biosensor
Fluorescence biosensor
Chemiluminescent biosensor
SERS-based biosensor
Food safety assay
39 40 41 42 43 44 45 46 47 48 2
49
Contents
50
1 Introduction .................................................................................................................................... 6
51
2 Nanozymes-based biosensors ........................................................................................................ 7
52
2.1 Colorimetric biosensors ...................................................................................................... 8
53
2.2 Fluorescence biosensors .................................................................................................... 10
54
2.3 Chemiluminescent biosensors ........................................................................................... 11
55
2.4 Electrochemical biosensors ............................................................................................... 12
56
2.5 SERS-based biosensors ..................................................................................................... 13
57
2.6 Other biosensors ................................................................................................................ 15
58
3 Applications of nanozymes-based biosensors to food safety assay.............................................. 16
59
3.1 Mycotoxins........................................................................................................................ 16
60
3.2 Antibiotics ......................................................................................................................... 18
61
3.3 Pesticides........................................................................................................................... 19
62
3.4 Pathogens .......................................................................................................................... 22
63
3.5 Intentional adulteration ..................................................................................................... 24
64
3.6 Metal ions.......................................................................................................................... 26
65
3.6 Other food contaminants ................................................................................................... 29
66
4 Conclusion and prospective ......................................................................................................... 31
67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 3
84
Abbreviations AAs As(III) AChE APTES AuNZ-PAD ABTS BChE CD CC CN– CLB CL CAP Cu-MOF CuO/3DNPC CoOxH-GO CS-MoSe2 NS ddH2O E ES ECL E. coli O157:H7 ELISA Fe3O4 NPs@ZIF-8 f-MWCNTs GOx GNRs GC-MS H His H 2Q HP1 HRP His@AuNCs HPLC HPLC-MS Kana LPS LOD LFA LFIA L. monocytogenes Lum-AgNPs LAMP MNP MB
amino acids Arsenic (III) acetylcholinesterase 3-aminopropyl triethoxysilane Au nanozyme-based paper chip 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt butyrylcholinesterase carbon dot catechol cyanide clenbuterol chemiluminescent chloramphenicol Cu-based metal-organic framework CuO NPs-modified 3D N-doped porous carbon cobalt hydroxide/oxide-modified graphene oxide chitosan-functionalized molybdenum (IV) selenide nanosheets double distilled H2O glutamic acid Enterobacter sakazakii electrochemiluminescence Escherichia coli O157:H7 enzyme-linked immunosorbent assay Fe3O4 nanoparticles@ZIF-8 functionalized multiwalled carbon nanotubes glucose oxidase Gold nanorods gas chromatography-mass spectrometer histamine histidine hydroquinone hairpin probes 1 horseradish peroxidase histidine-capped gold nanoclusters high performance liquid chromatography liquid chromatography-mass spectrometer kanamycin lipopolysaccharide limit of detection lateral flow assay lateral flow immunoassay Listeria monocytogenes luminol(Lum)-functionalized Ag nanoparticles loop-mediated isothermal amplification magnetic nanoparticle methylene blue 4
MPNP MB-SpinChip MIP MPA MNV NWs NoV NCs NPVMo N.BstNBI OPD OPs OTA PCR POD PMA Pd@AuNR PBNPs PbApt RAC RC RRS RGO SERS SPR S. Enteritidis TMB VBB Van WHO ZEN ZrO2 4-NTP 4-ATP
magnetic polymeric nanoparticle multiplexed bar-chart SpinChip molecularly imprinted polymer 3-mercaptopropionic acid murine norovirus nanowires norovirus nanoclusters (NH4)5PV8Mo4O40 nicking endonuclease o-phenylenediamine organophosphorus pesticides ochratoxin A polymerase chain reactions peroxidase propidium monoazide palladium-gold nanorod Prussian blue nanoparticles Pb2+ aptamer ractopamine resorcinol resonance Rayleigh scattering reduced graphene oxide Surface enhanced Raman scattering surface plasmon resonance Salmonella Enteritidis 3,3’,5,5’-tetramethylbenzidine Victoria blue B vancomycin World Health Organization zearalenone zirconium dioxide 4-nitrothiophenol 4-aminothiophenol
5
85
1 Introduction
86
Food safety as a critical topic of international concern has received worldwide attentions. The
87
hazardous substances in food can cause a huge threat to human health and lead to huge economic
88
losses in food industry around the world. In recent years, food production has made a rapid growth
89
via the Green Revolution with the globalization process. Meanwhile, the potential possibility of
90
food contamination has obviously increased due to the inadvertent entry of trace toxicants [1].
91
Thus, the food safety still remains a great global challenge to human health and development of
92
food industry. To protect the human from the health hazards and risks caused by the food
93
contaminants (the currently common categories of food contaminants leading to the food
94
poisoning mainly include mycotoxins, pathogens, heavy metals, pesticides, metal ions, antibiotics,
95
and so on.), some organizations like World Health Organization (WHO) have developed
96
regulations and legislations for food safety. Furthermore, in last decades, the detection of food
97
contaminants has attracted extensive attentions, because it can be used to identify whether the
98
food is safe [2-4]. So far, a large number of conventional methods have been well established for
99
the detection of food contaminants, such as high-performance liquid chromatography (HPLC),
100
liquid chromatography-mass spectrometer (HPLC-MS), gas chromatography-mass spectrometer
101
(GC-MS), polymerase chain reactions (PCR), and so on. Though these methods show high
102
sensitivity, accuracy, and reliability for food contaminant detection, they are complicated,
103
laborious, and time consuming, particularly depending on the expensive instruments with
104
well-trained personnel. Thus, they are difficult to meet the needs of the fast and on-site screening
105
of massive samples and apply in some situations like in some developing countries and poor areas
106
without detection instruments and specialists [5, 6]. In addition, owing to the complexity of food
107
matrix and the trace level of food contaminants, it is of importance to develop some novel, rapid,
108
and sensitive strategies for the food safety detection. In the last decade, plenty of biosensors have
109
been successfully established as exciting alternatives or as complementary detection tools of
110
traditional methods for rapid and sensitive detection of food contaminants [7].
111
Nanotechnology as an emerging technology has been widely applied in multiple fields, such
112
as transitioning theoretical aspects, medicine, agriculture sector, environment, and so on[8-12].
113
Recently, nanomaterials with enzyme-like catalytic activity, namely nanozyme, have been used to 6
114
develop novel biosensors and improve the sensitivity of biosensors. Nanozymes usually serve as
115
the labels for multi-category signal amplification (e.g. colorimetry, fluorescence, electrochemical,
116
and so on) in the field of analytical chemistry [13-15]. Nanozymes comprise multiple materials
117
(including gold, silver, platinum, molybdenum sulfide, zeolites, and so on) and show the
118
advantages of low cost, simple preparation methods, robust catalytic activity, smooth surface
119
modification, and high stability, which can serve as exciting alternatives to overcome the
120
drawbacks of biological enzymes (such as poor operational stability and low catalytic activity in
121
harsh conditions, the high cost for preparation, isolation, and purification) [16-18]. The great
122
advances have been achieved in the field of the nanozymes in recent years, and some literatures
123
have systematically and comprehensively summarized the progress of nanozymes [16, 19-24].
124
Based on the merits of nanozymes, a great many nanozymes-based biosensors has been
125
successfully developed and widely applied in multiple fields, including biomedical science[25],
126
environmental monitoring[14], agriculture[26], and so on[9, 27-31]. Excitingly, nanozymes as a
127
new initiate also has started providing the opportunities to response some challenges from food
128
safety. Nanozymes for the construction of biosensors has accelerated the development of
129
analytical science for inexpensive, convenient, efficient, rapid and sensitive detection of food
130
contaminants [23]. Compared to conventional methods, nanozymes-based biosensors exhibit some
131
excellent merits such as higher selectivity and sensitivity, more specific target recognition, shorter
132
detection time, and better signal readout [2].
133
To date, the nanozymes-based biosensors for food safety assay are rarely summarized. In this
134
review, we firstly comprehensively summarize the advances of nanozymes-based biosensors,
135
including colorimetric biosensors, fluorescence biosensors, chemiluminescent biosensors,
136
electrochemical biosensors, surface enhanced Raman scattering (SERS)-based biosensors, and
137
other biosensors. Then, attentions are concentrated on the applications of the nanozymes-based
138
biosensors to the determination of food contaminants (including mycotoxins, antibiotics,
139
pesticides, pathogens, intentional adulteration, metal ions, and other food contaminants).
140
2 Nanozymes-based biosensors
141
Recently, nanozyme as an excellent alternative to biological enzyme has been used for signal 7
142
production and amplification in an enzyme-like catalytic manner, which has been applied to
143
construct novel biosensors [25, 32]. To date, a great many nanozymes-based biosensors has been
144
successfully developed based on different modes of nanozymes catalytic mediated signal
145
amplification (e.g. colorimetric sensing, fluorescent sensing, chemiluminescent sensing,
146
electrochemical sensing, and SERS sensing). Herein, we comprehensively summarize the
147
construction of emerging nanozymes-based biosensors, including colorimetric biosensors,
148
fluorescence biosensors, chemiluminescent biosensors, electrochemical biosensors, SERS-based
149
biosensors, and other biosensors.
150
2.1 Colorimetric biosensors
151
Colorimetric biosensors have attracted wide attentions owing to their easy readout and fast
152
visual detection through the naked eyes or low-cost and portable equipment, which can be used to
153
detect the analytes based on the color variation. One of main types of the colorimetric biosensors
154
mainly
155
3,3’,5,5’-tetramethylbenzidine (TMB), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
156
diammonium salt (ABTS), and o-phenylenediamine (OPD) to produce colorimetric output signals
157
[6, 33-37]. However, biological enzymes usually suffer from inherent defects of instabilities and
158
poor sensitivities in disgusting environmental conditions, which greatly hinder the development
159
and applications of colorimetric biosensors. Fortunately, the nanozyme with robust catalytic
160
activity and high stability, as an alternative of biological enzyme, can be used for the construction
161
of colorimetric biosensors to improve the detection selectivity, sensitivity, and stability [13, 38,
162
39]. We selected several typical studies for the mechanism introduction of nanozyme based
163
colorimetric biosensors. For example, Zheng et al. successfully synthesized a new and stable MOF
164
(namely MOF-808) with an excellent peroxidase-like activity under alkaline, neutral, and acidic
165
conditions, which as the catalyst could effectively catalyze the oxidation of TMB to generate a
166
significant color change in the presence of H2O2. On this basis, a novel, facile, and sensitive
167
colorimetric biosensor was constructed [40]. Chen et al. prepared new PtNPs/Cu-TCPP(Fe) hybrid
168
nanosheets by growing the uniform and ultrasmall PtNPs on the novel template ultrathin
169
Cu-TCPP(Fe) nanosheets (the thickness was less than 10 nm) for construction of colorimetric
focuses
on
that
enzymes
catalyze
8
the
chromogenic
substrates
such
as
170
biosensor. Compared to the Cu-TCPP (Fe) nanosheets and PtNPs, the PtNPs/Cu-TCPP(Fe) hybrid
171
nanosheets showed an enhanced peroxidase-like catalytic activity due to the physical mixture
172
between the PtNPs and the PtNPs/Cu-TCPP(Fe) hybrid nanosheets with a good synergistic
173
effect[41]. Using various phosphates to modulate the peroxidase-like activity of the prepared 2D
174
M-TCPP (Fe) nanozymes (M=Cu, Co, or Zn), Qin et al. developed a novel colorimetric biosensor
175
for simultaneously discriminating multiple phosphates [28]. Recently, there are some
176
nanozymes-based biosensors developed for the detection of food contaminants. For example,
177
Cheng et al. successfully prepared a Fe-metal organic framework (MOF) nanoparticle with
178
peroxidase-like activity (named nanozyme). The prepared nanozyme as a signal generation
179
material could be used to catalyze the oxidation of colorimetric substrate (TMB) to produce a blue
180
color. On this basis, a novel nanozyme enhanced colorimetric immunoassay sensor was
181
successfully developed for the detection of Salmonella Enteritidis (S. Enteritidis) in milk samples
182
[36]. In addition, based on the nanozymes with tunable activity, some new colorimetric biosensors
183
have been successfully developed for food safety assay. For example, Sun et al. developed a rapid
184
and sensitive aptamer based colorimetric biosensors for the detection of zearalenone (ZEN) on the
185
basis of the inhibition of AuNPs with the peroxidase-like activity by the ZEN aptamer [42]. In
186
contrast, Wang’s group for the first time developed a novel colorimetric biosensor (Fig.1a) for the
187
determination of mercury (II) (Hg2+) via the activating effect of Hg2+ on the catalytic activities of
188
the chitosan-functionalized molybdenum (IV) selenide nanosheets (CS-MoSe2 NS) nanozyme [43].
189
Recently, based on the degradable γ-MnOOH nanozyme and the domino reaction of
190
acetylcholinesterase (AChE), their group constructed a new colorimetric biosensor (Fig.1b) for
191
sensitive determination of organophosphorus pesticides (OPs). In this biosensor, the γ-MnOOH
192
nanowires (NWs) served as degradable nanozyme and TMB served as a colorimetric substrate,
193
respectively, to achieve a fast and sensitive detection of OPs and monitoring of AChE activity [44].
194
Nanozymes-based colorimetric biosensors have showed some advantages of simplicity,
195
high-speed, portability, and practicality. However, their detection accuracy and sensitivity are
196
easily influenced by the potential interference produced from the sample background color [6, 23].
9
197
2.2 Fluorescence biosensors
198
Fluorescence biosensors are constructed mainly based on the target analytes mediated
199
fluorescence enhancement (“turn-on”) or fluorescence quenching (“turn-off”) [45-51]. Excitingly,
200
the rise of nanozymes has provided a great opportunity for development of fluorescence
201
biosensors. Over the past few years, based on excellent performances of nanozymes for the
202
generation and amplification of fluorescence signals, the nanozymes-based fluorescence
203
biosensors also have attracted widespread research interests, and have been successfully
204
developed for multiple fields, such as biomedical[25], medicine[52], pathogenic microorganisms
205
assay[53], and environmental monitoring[54]. For example, Lin et al. synthesized a MIL-53(Fe)
206
nanozyme with the functions of enzyme-like catalytic activity. The as-prepared MIL-53(Fe)
207
nanozyme was able to catalyze the oxidation of its organic linker terephthalic acid (TA) to produce
208
a fluorescent product (TAOH) by the H2O2 generated from the hydrolysis of glucose with the
209
existence of GOx. On this basis, a label-free fluorescence biosensor was established [55]. In
210
another study, using the bottom-up synthesis method, an amino-functionalized MOF
211
(NH2-Cu-MOF) with peroxidase-like activity was prepared for the construction of fluorescence
212
biosensor [47]. Recently, some nanozymes-based fluorescence biosensors have been developed for
213
food safety assay. On the basis of the novel Fe3O4 nanoparticles@ZIF-8 composites
214
(Fe3O4NPs@ZIF-8) with peroxidase-like catalytic activity, Bagheri et al. constructed a new
215
fluorescence biosensor (Fig.2) for the detection of OPs. The Fe3O4 NPs@ZIF-8 was synthesized
216
by encapsulating magnetic Fe3O4 NPs into ZIF-8, and the catalytic activity of obtained composites
217
was evaluated through the oxidation of substrates [56]. Based on molecular imprinting technique,
218
Bagheri’s group successfully prepared a novel molecularly imprinted polymer (MIP)-capped Ag
219
nanoparticle/Zn-based MOF nanocomposite (AgNPs@ZnMOF) (MIP-capped AgNPs@ZnMOF
220
composite) with an excellent peroxidase mimetic activity for the selective determination of patulin.
221
In this study, the AgNPs fixed on the surface of MOF remarkably improved the catalytic activity
222
of AgNPs due to high surface area of MOF. However, the catalytic activity of AgNPs@ZnMOF
223
composite could be strangely reduced by patulin, which may be ascribed to the electron capturing
224
features of patulin. To achieve a selective interaction between AgNPs@ZnMOF composite and
225
patulin molecules, the MIP layer was innovatively capped on the surface of the prepared 10
226
AgNPs@ZnMOF through the co-polymerization reaction between tetraethyl orthosilicate (TEOS)
227
and monomers 3-aminopropyl triethoxysilane (APTES) in which the patulin was used as a
228
template agent. By the combination between novel AgNPs@ZnMOF nanocomposite with
229
outstanding peroxidase-like activity and the MIP with selective identifying feature, a sensitive
230
fluorescence biosensor was successfully developed for the selective detection of patulin [57]. In
231
addition, Lien et al. successfully prepared a well-dispersed and amorphous cobalt
232
hydroxide/oxide-modified graphene oxide (CoOxH-GO) with excellent peroxidase-mimicking
233
catalytic activity through a simple one-step synthesis strategy. Based on the reaction between Co2+
234
and GO at room temperature, CoOxH was produced and deposited in situ on the surface of GO.
235
The as-prepared CoOxH-GO could be applied to the fluorescent detection of cyanide (CN–) ions,
236
glucose, and H2O2 [54]. Nanozymes-based fluorescence biosensors exhibited the merits of good
237
selectivity, outstanding sensitivity, operational simplicity, portability, and real-time detection [58].
238
However, these nanozymes-based fluorescence biosensors still need to improve their sensitivity,
239
stability, and accuracy by eliminating the potential interferences from food matrix.
240
2.3 Chemiluminescent biosensors
241
Chemiluminescent biosensor as one of promising analytical tools has been numerously
242
constructed based on the emission of light generated from the chemical reactions, which has been
243
employed for the detection of various targets owing to its distinguished merits of simple operation,
244
rapidity, simple equipment with no monochromator, low LOD, and wide linear range [59, 60]. The
245
emergence of nanozymes also provides a promising strategy for development of nanozymes-based
246
chemiluminescent biosensors. For instance, AuNPs, AgNPs, and MIL-type MOFs with
247
peroxidase-like catalytic activity have been widely employed as biomimetic components for
248
construction of chemiluminescence biosensor by catalyzing the reaction of H2O2-luminol system
249
to generate fluorescent signal [61, 62]. Recently, Luo et al. developed new MOFs based solid
250
catalysts (Hemin@HKUST-1) through encapsulating the Hemin into HKUST-1. The prepared
251
Hemin@HKUST-1 showed an excellent enzyme-like catalytic activity to catalyze the reaction of
252
H2O2-Luminol system for establishing a selective and sensitive chemiluminescence biosensor [63].
253
It has been reported that some noble metal nanoparticles (NPs) such as AuNPs and AgNPs with 11
254
peroxidase-like catalytic activity have been applied in construction of chemiluminescence
255
biosensor [61, 62]. In addition, some MIL-type MOFs with intrinsic peroxidase-like catalytic
256
activity such as MIL-53, MIL-100, MIL-101 also have been used for catalyzing the reaction of
257
H2O2-Luminol system for construction of the nanozymes-based chemiluminescence biosensors
258
[64-66]. Recently, some nanozymes-based chemiluminescent biosensors have been developed for
259
food safety assay [62]. Based on the luminol(Lum)-functionalized Ag nanoparticles (Lum-AgNPs)
260
and the H2O2 chemiluminescent (CL) system(Lum-AgNP-H2O2 CL system), He et al. constructed
261
a new, facile, simple, and sensitive NPs-based CL sensor for the determination of carbamate
262
pesticides and OPs[61]. Recently, their group for the first time synthesized iron-based MOGs
263
nanosheet hybrids with the immobilization of AuNPs (AuNPs/MOGs (Fe) hybrids) through a
264
facile in situ grown method under ambient conditions. The as-obtained AuNPs/MOGs (Fe)
265
hybrids showed an excellent peroxidase-like activity, which endowed them with the outstanding
266
property in the field of chemiluminescence (CL) with the existence of H2O2. The remarkably
267
enhanced CL via the prepared AuNPs/MOGs (Fe) hybrids was due to the modification of AuNPs
268
on MOGs (Fe) nanosheets, which could speed up the production of O2•−, OH•, and 1O2 for
269
synergistically accelerating the CL reaction. On this basis, a new sensitive CL biosensor was
270
successfully constructed using the AuNPs/MOGs (Fe) hybrids for detection of OPs [62].
271
2.4 Electrochemical biosensors
272
Electrochemical biosensors are mainly based on the change of output-electrical signals
273
produced from the chemical reactions between the target analytes and electrode-immobilized
274
recognition elements. The generation of electrical signals is related to the concentrations of target
275
analytes, which can achieve the qualitative detections and quantitative assays of target molecules
276
[67-69]. So far, due to their simple operation, low cost, remarkable stability, and sensitive
277
response, electrochemical biosensors have been extensively applied in multiple fields, such as
278
pharmacy, environmental monitoring, chemical treat detection, and clinical diagnosis [69, 70]. To
279
further improve the analytical sensitivity of the electrochemical biosensors, the electrodes need be
280
modified by the catalysts with more uniform dispersion and electrocatalytic sites [71]. In recent
281
years, some nanozymes (including AuNPs, AgNPs, PtNPs, Au@PtNPs, AuPd@AuNPs, Cu-MOF, 12
282
and so on) with outstanding catalytic activity have been used as a new catalyst for catalyzing the
283
electrochemistry signal amplification and constructing novel electrochemical biosensors [72-78].
284
Recently, there are some nanozymes-based electrochemical biosensors developed for food safety
285
assay [79-81]. For example, on the basis of the target-induced replacement of aptamer and the
286
peroxidase-like activity of AuNPs, Wang et al. developed an ultrasensitive and enzyme-free
287
electrochemical biosensor for the determination of kanamycin (Kana) residue. The proposed
288
biosensor with an extremely high sensitivity was employed for the determination of Kana in honey
289
samples [82]. It was worth noting Khairy et al. developed a novel, simple, and sensitive
290
nanozyme-based electrochemical biosensor based on nickel oxide nanoplatelets (NPs) modified
291
screen-printed electrodes. The proposed electrochemical biosensor exhibited the excellent
292
electrochemical performances (including good stability, high selectivity and sensitivity) for the
293
determination of OPs (Parathion) in vegetable, water, and human urine samples [70]. Recently,
294
based on Cu-based MOF (Cu-MOF) modified by AuNPs, Chen et al. developed a new
295
electrochemical biosensor (Fig.3) for the sensitive determination of nitrite. The Cu-MOF
296
decorated by the AuNPs with the excellent catalytic activity and high conductivity (Cu-MOF/Au)
297
showed synergetic catalytic activity for the oxidation of nitrite owing to the large porosity and
298
surface area of Cu-MOF that could stop AuNPs from aggregation and enhance the adsorption of
299
nitrite [71]. Nanozymes-based electrochemical biosensors show the linear resolution over wide
300
ranges, and can be widely applied to the semi-quantitative and qualitative preliminary screening
301
[58, 83]. However, all of these biosensors often require the outstanding electroactivity of analytes,
302
and the dedicated equipment with high precision, accurate functional programs, and professional
303
operators. In addition, due to the electrode fouling and the requirement of charging, the
304
electrochemical biosensors suffer from the poor stability and repeatability [84].
305
2.5 SERS-based biosensors
306
SERS as an emerging and powerful analytical technology has attracted wide attention, which
307
has been rapidly developed for the construction of biosensors owing to the outstanding merits of
308
ultrahigh sensitivity, in situ noninvasive detection, and fingerprint information [85-87]. Recently,
309
some SERS-based biosensors have been successfully established for a sensitive determination of 13
310
target molecules by utilizing the nanozymes to improve the SERS activities [88-91]. For example,
311
utilizing in situ fabrication of the (AgNPs) onto the surface of the MIL-101 (Fe) with the
312
peroxidase-like activity, a new, efficient, and outstanding SERS substrate was developed by
313
Jiang’s group. The combination of the obtained SERS substrate with the numerous Raman hot
314
spots between MIL-101 (Fe) and the high-density AgNPs lead to an outstanding SERS substrate
315
for the construction of SERS-based biosensor [92]. Similarly, the nanozyme with peroxidase-like
316
catalytic activity was prepared through in situ growing the AuNPs into thermally stable and highly
317
porous MIL-101. The prepared AuNPs@MIL-101 nanozymes as the peroxidase mimics were not
318
only able to catalyze the oxidation of Raman-inactive reporter leucomalachite green to produce an
319
active malachite green (MG) in the presence of H2O2, but also serve as the SERS substrates for the
320
enhancement of the Raman signal of the generated MG[93]. In another study, by tuning the
321
amount of Pt, the bifunctional nanozymes (Au@Pt NPs) with simultaneous enzyme-like and
322
plasmonic activities were successfully prepared [94]. By using a three-step strategy (including the
323
solvothermal synthesis, Au seed-induced growth, and low-temperature cycling self-assembly), Ma
324
et al. fabricated a new SERS-active magnetic MOF-based nanozyme (Fe3O4@Au@MIL-100 (Fe))
325
with an excellent peroxidase-like activity as a SERS substrate [88]. In addition, the nanozymes for
326
the construction of SERS-based biosensor has been applied in the field of food safety assay. It was
327
worth noting that Ouyang et al. synthesized AuNP nanozyme to catalyze the nanoreaction between
328
HAuCl4 and H2O2 for the production of AuNPs, which showed the strong SERS effect, strong
329
surface plasmon resonance (SPR) absorption, and resonance Rayleigh scattering (RRS) effect with
330
the existence of Victoria blue B (VBB) molecular probes. Interestingly enough, Pb2+ aptamer
331
(PbApt) could inhibit the catalytic activity of AuNP nanozyme by its adsorption on the surface of
332
AuNP nanozyme, leading to the decrease of SERS, SPR absorption, and RRS effect owing to the
333
decrease of redox products of GNP nanoplasmonic effect. With the addition of the Pb2+, the PbApt
334
would be specifically combined with Pb2+ to generate a stable G-quadruplex and the free AuNP
335
nanozymes, which resulted in the restoration of AuNP nanozyme catalysis and the linear increase
336
of the SPR absorbance, SERS, and RRS intensity with the increase of Pb2+ concentration [95].
337
Based on the catalysis of carbon dot (CD), Li et al. developed a new quantitative analysis strategy
338
with simplicity, good selectivity, and high sensitivity using Au nanosol SERS for the trace
339
detection of Na+ [96]. Recently, our group innovatively prepared a new AuNPs doped COFs 14
340
nanozyme with excellent mimic nitroreductase activity and robust stability, which could catalyze
341
the substrate 4-nitrothiophenol (4-NTP) to generate 4-aminothiophenol (4-ATP) with the existence
342
of NaBH4. By the combination between SERS technology and enzyme-linked immunosorbent
343
assay (ELISA), a sensitive SERS-based biosensor (Fig.4a) was successfully developed for the
344
assay of allergenic proteins [97]. In a very recent study, by utilizing Au-Ag Janus NPs with
345
amplified and stable SERS activity, Zheng et al. constructed a novel ratiometric surface-enhanced
346
Raman scattering aptasensor (Fig.4b) for the detection of ochratoxin A [98]. Although these
347
emerging nanozymes-based SERS biosensors possess the merits of ultrahigh sensitivity, in situ
348
noninvasive detection, and fingerprint information, they still suffer from the interference from
349
complex samples [85]. Therefore, nanozymes-based SERS biosensors still need to be further
350
developed to improve their stability and accuracy.
351
2.6 Other biosensors
352
In addition to the above biosensors, there are some other biosensors reported for food safety
353
assay [99]. For example, based on the nanozyme strip, loop-mediated isothermal amplification
354
(LAMP), and propidium monoazide (PMA), Zhang et al. developed a novel, rapid, ultrasensitive,
355
and continual cascade nanozyme biosensor for the determination of viable Enterobacter sakazakii
356
(ES). In this biosensor, BIO- and FITC-modified primers during the LAMP process were
357
employed for determining the ompA gene of ES. And the combination between LAMP and the
358
PMA treatment was used to distinguish the viable ES from the dead. The Fe3O4 magnetic NPs
359
(MNP) served as the nanozyme probes, and a MNP-based immunochromatographic strip
360
(nanozyme strip) could be was further applied for the signal amplification to achieve a simple
361
visual detection and accurate quantification through a strip reader. Moreover, the products
362
generated by LAMP could be sandwiched between the anti-BIO and the anti-FITC, and the
363
accumulation of Fe3O4 MNPs could achieve a rapid, sensitive, and visual determination of ES. The
364
developed biosensor exhibited the advantages of simplicity, high speed, and high sensitivity due to
365
the use of the LAMP assay and PMA. Furthermore, Fe3O4 MNPs as the nanozyme probes
366
replacing colloidal Au for the introduction of enzyme modification into lateral flow biosensor also
367
improved the sensitivity of biosensor. The proposed biosensor was able to detect bacteria at 10 15
368
cfu/mL within 1 h under the optimal condition, and was applied to quantitative detection of the
369
viable ES in infant powder with a simple sample pretreatment. In addition, the biosensor with low
370
cost, rapidity, high efficiency, and portability possessed high potential for detection of other viable
371
microorganisms through replacement of the primers [99].
372
3 Applications of nanozymes-based biosensors to food safety assay
373
To date, there are plenty of nanozymes-based biosensors successfully developed for food
374
safety assay. Herein, we mainly concentrate the attentions on the applications of the
375
nanozymes-based biosensors to the detection of food contaminants (including mycotoxins,
376
antibiotics, pesticides, pathogens, intentional adulteration, metal ions, and other food
377
contaminants). Some reported applications of nanozymes-based biosensors in the detection of
378
food contaminants were illustrated in Table 1.
379
3.1 Mycotoxins
380
The mycotoxin emerges as one of most common food contaminants due to the wide growth
381
of funguses. However, the mycotoxins are hard to be completely eliminated in the general food
382
preparation processes, and the mycotoxins with a low concentration can also lead to some serious
383
diseases, such as liver disease, kidney disease, cancer, and even death owing to their significant
384
virulence. Therefore, the detection of mycotoxins has become extremely important for protecting
385
the human from the health hazards and risks [100, 101]. Due to their high selectivity and
386
sensitivity, specific target recognition, and shorter detection time, nanozymes-based biosensors
387
have been developed for detection of mycotoxins. For instance, Khataee and co-workers
388
developed a new, selective, and sensitive fluorescence biosensor for the selective determination of
389
patulin (Fig.5a) based on the combination between the new AgNPs@ZnMOF nanocomposites
390
with an excellent peroxidase-like activity and the MIP with selective identifying feature. In this
391
fluorescence biosensor, the prepared MIP-capped AgNPs@ZnMOF could be used to catalyze the
392
reaction between the H2O2 and terephthalic acid to produce a strong florescent product. With the
393
addition of patulin, the fluorescence intensity could be decreased proportional to the concentration
394
of patulin. The established fluorescence biosensor could be used to detect patulin with a 16
395
concentration range of 0.1-10 µmol/L and a low LOD of 0.06 µmol/L[57]. To sensitively and
396
precisely detect the zearalenone (ZEN), Abnous et al. developed a novel colorimetric aptasensor
397
for the detection of ZEN by using the catalytic reaction of AuNPs, 4-nitrophenol (pNP) as the
398
colorimetric substrate, exonuclease III (Exo III)-assisted recycling amplification, and
399
nontarget-induced aptamer walker. Interestingly, without the existence of ZEN, the Apt was
400
capable of walking on the surface of AuNPs with the assist of Exo III and binding to their
401
multiplex complementary strands, resulting in the sample color changing from yellow to colorless.
402
In the presence of ZEN, the Apt and its complementary strand could exist as the single-stranded
403
DNAs (ssDNA) on the AuNP surface, leading to the decrease of AuNP catalytic activity and the
404
less amounts of pNP contacting with AuNPs due to the steric hindrance from the Apt/ZEN
405
complexes. And the color of the pNP remained yellow in this case. The developed biosensor could
406
be used for the detection of ZEN with a wide linear range of 20-80000 ng/L, and with a low LOD
407
of 10 ng/L[102]. Recently, on the basis of aptamer-regulated oxidase activity, Huang et al.
408
successfully developed a new and simple “turn-on” colorimetric biosensor for the determination of
409
biomolecular (Fig.5b). Compared to metal oxide-based oxidase nanozymes, the prepared
410
MnCo2O4 showed a stronger oxidase-like catalytic activity, and efficiently catalyze the oxidation
411
of colorimetric substrate (TMB) to produce a blue color. However, the oxidase-like catalytic
412
activity of MnCo2O4 was able to be inhibited by the aptamer strands due to the attachment of the
413
aptamer strands on the surface of MnCo2O4 through the binding of aptamer and target. Fortunately,
414
the toxic ochratoxin A (OTA) could selectively combined with the aptamer to lead to the
415
restoration of MnCo2O4 nanozyme catalysis. Accordingly, a simple “turn-on” colorimetric
416
biosensor was constructed for selectively detecting OTA in maize samples ranging from 0.1 to 10
417
ng/mL, and with a low LOD of 0.08 ng/mL [103]. In a very recent study, on the basis of the
418
inhibition of zearalenone (ZEN) Apt on the peroxidase-mimicking performance of AuNPs, Xie’s
419
group developed a rapid, simple, colorimetric biosensor for the sensitive and specific
420
determination of zearalenone (ZEN). It was found that the ZEN Apt could inhibit the
421
peroxidase-like activity of AuNPs. However, the ZEN Apt could be bound with ZEN, and
422
therefore the presence of ZEN could lead to the restoration of the peroxidase-like performance of
423
AuNPs. The color variation of the solution was related to the concentration of ZEN and observed
424
by naked eyes. The proposed colorimetric biosensor could be used to detect the ZEN in real corn 17
425
and oil samples with a concentration ranging from 10 to 250 ng/mL, and with a low LOD of 10
426
ng/mL [42].
427
3.2 Antibiotics
428
Antibiotics as the human and veterinary drugs have been extensively applied in the therapy of
429
bacterial infection and the prevention of diseases of livestock. However, the residues of these
430
antibiotic drugs and metabolites may accumulate in some livestock products, including eggs, meat,
431
milk, and so on. Owing to an increasing threat from the antibiotic abuse, the construction of new
432
strategies for the accurate detection of antibiotic drug and metabolite residues in complex food
433
matrices has become increasingly important [104-109]. Recently, some nanozymes-based
434
biosensors have been successfully established for determination of antibiotics [82, 109-113]. For
435
example, based on the enhanced catalytic activity of AuNPs, Wang et al. developed a new
436
colorimetric approach (Fig.6a) with high selectivity and sensitivity for the detection of Kana. In
437
this study, interestingly, the peroxidase-mimicking performance of citrate-capped AuNPs could be
438
enhanced by Kana due to the attachment of Kana on the surface of AuNPs through the interaction
439
between -COOH on AuNPs and -NH2 on Kana and the interaction between AuNPs and the
440
glucoside on Kana (which could change the surface property of AuNPs, and generated the Au3+
441
and •OH radicals in the solution, catalyzing the oxidation of TMB to produce a blue color in the
442
presence of H2O2.) The established colorimetric biosensor could be used for sensitive detection of
443
Kana in meat and milk samples with a wide linear range of 0.1-20 nM and 20-300 nM,
444
respectively, and yielded a low LOD of 0.1 nM [110]. In another study, Govindasamy et al.
445
innovatively established a novel simple electrochemical biosensor with excellent selectivity and
446
sensitivity for detection of chloramphenicol (CAP) using a new nanocomposite material
447
synthesized by the molybdenum disulfide nanosheets (MoS2) coated on the functionalized
448
multiwalled carbon nanotubes (f-MWCNTs) via a hydrothermal strategy. The as-prepared
449
MoS2/f-MWCNTs nanocomposite showed excellent electrochemical performances and an
450
excellent electrocatalytic ability for CAP. The obtained electrochemical biosensor (Fig.6b) could
451
be applied to detect the CAP in food samples like milk, honey, and powdered milk samples with a
452
wide linear range of 0.08-1392 µM, and a low LOD was 0.015 µM [111]. Based on chitosan 18
453
modified AgI/TiO2 nanozymes, Chang et al. developed a new photoresponsive colorimetric
454
immunoassay for highly sensitive detection of chloramphenicol (CAP). Using this method, the
455
CAP in the real food samples could be detected in the linear range of 0.03 -12.53 nM with a LOD
456
of 0.03 nM [114]. By utilizing polyaniline nanowires-functionalized graphene oxide framework,
457
Zeng et al. successfully developed a novel pressure-based bioassay based on Pt
458
nanozyme-catalyzed gas generation for the Kana detection. The proposed method showed
459
excellent specificity, good reproducibility, and outstanding precision, which could be used to
460
detect the Kana within a dynamic working range of 0.2-50 pM at a LOD of 0.063 pM [113]. In a
461
recent study, Chen et al. developed a novel electrochemical biosensor for the ultrasensitive
462
determination of Kana by the combination between the signal transduction of the horseradish
463
peroxidase (HRP)-functionalized AuNPs (AuNP/HRP nanoprobe) and the highly specific
464
Kana-aptamer biorecognition. This biosensor was built based on following procedures. First of all,
465
the hybridization of the biotinylated Kana-aptamers was achieved at the electrode modified by
466
their complementary oligonucleotide strand and then methylene blue (MB) was intercalated into
467
the produced dsDNA. After that, the high-content AuNP/HRP NPs probes and streptavidin were
468
bound to the sensor. A sensitive electrochemical signal was generated through the MB-mediated
469
HRP-catalytic reaction, and the aptamer-biorecognition for Kana could lead to the quantitative
470
decline of nanoprobe capture due to the decrease of MB intercalation, achieving a simple and
471
convenient electrochemical signal transduction. The biosensor exhibited ultrahigh sensitivity
472
owing to the enhancement of the electrochemical signal through the AuNP/HRP NPs-catalytic
473
reaction and the amplification of nanoprobe signal. Moreover, the intercalation of MB into dsDNA
474
could provide an important electron mediator for the AuNP/HRP NPs-catalytic reaction and
475
simplify the electrochemical measurement. In addition, the developed biosensor for detection of
476
Kana antibiotic exhibited a wide linear range more than four-order of magnitude, and possessed a
477
low LOD of 0.88 pg/mL[112].
478
3.3 Pesticides
479
Pesticides as critical compounds have been widely applied in the agricultural field to reduce
480
the losses in agricultural production caused through pests and insects [115]. However, the 19
481
pesticides can heavily accumulate in air, soil, water, and ultimately food, most of which are
482
carcinogenic and difficult to be digested in organs, leading to a remarkable damage and increasing
483
threat to public health. Traditional methods such as capillary electrophoresis and GC/LC
484
combined with MS have been widely developed for the detection of pesticide residues.
485
Nevertheless, these strategies possess some defects of short storage time, complicated
486
pretreatment, time consuming, and requirement of expensive equipment with skilled experts. Thus,
487
the development of simple, sensitive, and on-site monitoring strategies is urgently needed to
488
protect human form the risk of exposure to the pesticides [2, 6]. Recently, to break the limits of
489
conventional strategies, some emerging nanozymes-based biosensors have been successfully
490
established for the detection of pesticides [44, 56, 62, 116]. For example, Biswas et al. developed
491
a colorimetric biosensor based on Gold nanorods (GNRs) with peroxidase-mimicking activity for
492
the determination of malathion. In this study, the prepared GNRs as nanozymes or enzyme
493
mimetics were studied, and the catalytic activity of GNRs was compared with that of HRP and
494
other Au nanostructures. It was found that the peroxidase-like activity of GNRs was 2.5 times
495
higher than that of HRP and AuNPs. The obtained GNRs exhibited good stability and excellent
496
catalytic activity, which was used to catalyze the oxidation of TMB to produce a blue color in the
497
presence of H2O2. However, malathion showed an inhibitory effect on the peroxidase-like activity
498
of GNRs, and the catalytic activity of GNRs gradually decreased with the increase of malathion
499
concentration. On this basis, a new, simple, and cheaper colorimetric biosensor was constructed
500
for the detection of malathion using GNR nanozymes. The malathion could be specifically and
501
sensitively detected by this colorimetric biosensor with a low LOD of 1.78 µg/mL[117]. Similarly,
502
by employing palladium-gold nanorod (Pd@AuNR) as nanozyme, Singh et al. developed a new,
503
simple, selective, and sensitive label free colorimetric biosensor for the detection of malathion
504
(Fig.7a). The as-fabricated Pd@AuNR nanozyme showed an excellent peroxidase-like activity for
505
OPD with the existence of H2O2. Nevertheless, the peroxidase-like activity of Pd@AuNR
506
nanozyme could be selectively quenched by malathion. Accordingly, a novel colorimetric
507
biosensor was constructed for the detection of malathions with a lowest LOD of 60 ng/mL and no
508
cross-reaction with metal salts/other similar organophosphates [118]. In another study, a novel
509
facile, simple, and sensitive AgNPs-based CL biosensor was developed for the detection of
510
carbamate pesticides and OPs on the basis of simultaneous use of the triple-channel performances 20
511
of the Lum-AgNP and H2O2 CL system (Fig.7b). The established CL biosensor could be used to
512
detect five carbamate pesticides and OPs (including carbofuran, dimethoate, carbaryl, dipterex,
513
and chlorpyrifos) with a low LOD of 24 µg/mL[61]. Recently, Zhao et al. innovatively proposed a
514
new biosensor based on the coupling of lateral-flow test strip with a smartphone for the first time
515
(Fig.7c). The proposed biosensor was developed for measuring butyrylcholinesterase (BChE)
516
activity. In this biosensor, the BChE served as a model enzyme, and the ethyl paraoxon was used
517
as the analyte representing OPs. The total amount of BChE was quantified through a sensitive
518
colorimetric signal originating from a sandwich immunochromatographic assay. In this sandwich
519
immunochromatographic assay, PtPd NPs were employed as a colorimetric probe, which showed
520
an excellent catalytic activity for phenols. The catalytic activity of BChE could be determined
521
through another colorimetric signal utilizing the Ellman assay. The colorimetric signals generated
522
from two separated test strips could be measured using the smartphone-based ambient light sensor.
523
Moreover, this portable, low-cost, and easy-operation biosensor possessed a huge potential for the
524
sensitive online determination of OP exposure [119]. In a very recent study, Qiu et al. developed a
525
new electrochemical biosensor for the determination of OPs on the basis of the electrodes
526
modified by the amino acids conjugated nanozymes. It was found that the glutamic acid (E),
527
histamine (H), and amino acids (AAs), serine (S) attached nanozymes could be used to catalyze
528
hydrolysis of OPs to produce the electroactive p-nitrophenol (pNP). Based on this principle, a
529
novel electrochemical biosensor for the detection of OPs utilizing the electrode modified by S, H,
530
and E conjugated TiO2 NPs was successfully established. The TiO2 NPs served as carriers and the
531
attached AAs, S, H, and E showed the hydrolyzing activity for the hydrolysis of OPs, so the TiO2
532
NPs-AAs showed nanozymes-like hydrolysis activity. The electrode was modified by
533
TiO2@DA@S/H/E nanozyme composites through dip-coating for the first time. The OPs
534
(including ethyl paraoxon, methyl paraoxon, and methyl parathion) could be catalyzed by
535
TiO2@DA@S/H/E nanozymes to produce the redox active pNP on the surface of nanozymes
536
modified electrode, and OPs could be detected by the electrochemical signal produced from the
537
pNP. With this electrochemical biosensor, the ethyl paraoxon, methyl paraoxon, and methyl
538
parathion could be determined with a linear range of 0.5-100 µM at a low LOD of 0.24 µM [120].
21
539
3.4 Pathogens
540
Owing to the high incidence of foodborne illnesses, the foodborne pathogens as the major
541
threat to the public health have caused the worldwide attentions. The foodborne pathogens
542
contaminated food will lead to some severe diseases of human, such as acute abdominalgia and
543
acute emesis. Furthermore, it is reported that the percentage of the population suffering from the
544
foodborne diseases has been as high as 30% every year in some industrialized countries, which is
545
mainly ascribed to the drinking water or food contaminated by the foodborne pathogens [2, 6,
546
121]. Among these foodborne pathogens, the Listeria monocytogenes (L. monocytogenes), S.
547
aureus, Escherichia coli O157:H7 (E. coli O157:H7), and Salmonella generally caused the
548
majority of foodborne pathogen outbreaks [122]. Recently, some nanozymes-based biosensors
549
have been developed for the detection of foodborne pathogens [36, 99, 123]. For example, on the
550
basis of the signal amplification catalyzed by nanoparticle cluster (NPC), Zhang et al. developed a
551
novel biosensor for the visual and rapid determination of L. monocytogenes (Fig.8a). In this
552
biosensor, a glycopeptide antibiotic (vancomycin (Van)) against Gram-positive bacteria was
553
employed as the first molecular recognition agent for the capture of L. monocytogenes. The
554
aptamer modified by Fe3O4 NPC served as the nanoprobe for the signal amplification, especially
555
recognizing the cell wall on the L. monocytogenes. Due to the recognition of Van and aptamer to
556
the L. monocytogenes at various sites, the formed sandwich recognition could lead to an excellent
557
specificity. By using the Fe3O4 NP cross-linking with the poly-L-lysine, Fe3O4 NPC with a higher
558
catalytic activity could be successfully fabricated to catalyze the oxidation of TMB to generate a
559
color reaction in the presence of H2O2 compared to the individual Fe3O4 NP, which was due to a
560
collective effect of NPC. The concentration of analytes could be measured by the variation of
561
color or absorbance. The proposed biosensor with simplicity, labor-saving, and high sensitivity
562
could be used to directly determine the L. monocytogenes whole cells linearly ranging from
563
5.4×103 to 5.4×108 cfu/mL with a low LOD of 5.4×10 3 cfu/mL[121]. By utilizing Cu-MOF NPs
564
with enzyme-mimicking performance, Wang et al. successfully developed a new sensitive
565
colorimetric biosensor for the determination of S. aureus (Fig.8b). The Cu-MOF NPs were
566
prepared by Cu(NO3)2 and 2-aminoterephthalic acid through a mixed solvothermal strategy, which
567
possessed a diameter of approximately 550 nm and exhibited an excellent peroxidase-like activity 22
568
that could catalyze the oxidation of TMB to produce a yellow color reaction with the existence of
569
H2O2. The S. aureus aptamer could be facilely modified on the surfaces of Cu-MOF NPs due to
570
the existence of a great many amine groups on the surface of Cu-MOF NPs, endowing Cu-MOF
571
NPs with the selectivity for recognition of S. aureus. Moreover, the Cu-MOF NPs with the
572
uniform size and regular morphology could make each bacterial cell link with the same amount of
573
Cu-MOF NPs, leading to a good linearity for the determination of S. aureus. Based on the
574
combination of chromogenic reaction catalyzed by Cu-MOF NPs with the aptamer recognition
575
and the magnetic separation (using aptamer modified magnetic NPs), a novel colorimetric
576
biosensor with simplicity, good selectivity, and high sensitivity was constructed for S. aureus assay.
577
With this colorimetric biosensor, S. aureus was detected with a linear range of 50-10000 cfu/mL at
578
a low LOD of 20 cfu/mL in milk samples [124]. In another study, by the integration of
579
nanozyme-mediated dual lateral flow immunoassay (LFIA) with a smartphone, Cheng et al.
580
creatively constructed a novel sensitive biosensor for simultaneous determination of pathogens for
581
the first time. In proposed biosensor, the prepared mesoporous core-shell palladium@platinum
582
(Pd@Pt) nanozymes with an excellent peroxidase-like catalytic activity for signal enhancement
583
were employed as a signal reporter. And the smartphone was used as a result recorder. Moreover,
584
the synthesized Pd@Pt nanozymes for the signal amplification and the parallel design of
585
simultaneous determination could eliminate the cross-interference, achieving a high sensitivity of
586
dual detection. With the developed biosensor, the Salmonella Enteritidis and E. coli O157:H7
587
could be simultaneously detected with the LODs of ∼20 cfu/mL and ∼34 cfu/mL, respectively. In
588
addition, the estimated recoveries of dual LFIA using milk and ice cream samples showed a range
589
of 91.44-117.00%, which demonstrated that the proposed strategy could be used to detect the live
590
pathogens in food samples[125]. Similarly, by employing the Pd-Pt nanozymes as probes, Han et
591
al. constructed a sensitive lateral flow assay (LFA) on the basis of the sandwich format to
592
qualitatively and quantitatively detect E. coli O157:H7 in milk. The prepared Pd-Pt nanozyme
593
with a high peroxidase-like catalytic activity could catalyze the oxidation of TMB to greatly
594
improve the signal intensity of test line, leading to an enhanced sensitivity of the LFA. The
595
developed nanozymes-based LFA with high sensitivity could be employed to detect E. coli
596
O157:H7 in PBS and milk with the LODs of 0.87 × 102 cfu/mL and 9.0 ×102 cfu/mL, respectively.
597
Moreover, the proposed method was 111-fold higher sensitivity than the conventional colloidal 23
598
Au-based LFA [126].
599
3.5 Intentional adulteration
600
The misuse or overuse of illegal food additives has resulted in the frequent emergence of a
601
series of food safety incidents, which has caused a huge threat to the public health and aroused
602
widespread concerns for food safety. Due to the poisonousness and carcinogenicity of these illegal
603
food additives, the monitoring of illegal food additives is of great importance for food safety [2,
604
127]. Common illegal food additives such as Sudan I, clenbuterol (CLB), and nitrite have caused
605
widespread concerns in many countries. To rapidly and sensitively detect these illegal food
606
additives, some novel nanozymes-based biosensors have been successfully established [71,
607
127-129]. Owing to its low cost and attractive red, Sudan I has been extensively employed as food
608
additives, particularly in the chili powder. However, Sudan I has been proved to be carcinogenic,
609
and could cause the damage to genetic material due to the reaction with a specific DNA sequence
610
in vitro [130]. Using the electrode modified via the PtNPs decorated graphene-β-cyclodextrin
611
(graphene/β-CD/PtNPs), Palanisamy et al. for the first time developed a novel, reliable, and
612
sensitive electrochemical biosensor for the determination of Sudan I in food samples. The
613
electrochemical performances of various modified electrodes for Sudan I were evaluated through
614
cyclic voltammetry. Among these modified electrodes, the prepared graphene/β-CD/PtNPs
615
composites modified electrode showed the highest electrocatalytic activity for Sudan I. Moreover,
616
the as-prepared nanocomposite modified electrode could increase the sensitivity of Sudan I assay,
617
and leading to a linear response range enhancement of the electrochemical biosensor. The
618
proposed electrochemical biosensor could be used to detect Sudan I in food samples (including
619
chili powder, chili sauce, tomato sauce, and ketchup) with a linear range of 0.005-68.68 µM, and
620
the LOD was 1.6 nM[131]. In another study, Tajik and co-workers for the first time constructed an
621
ultrasensitive and highly selective electrochemical biosensor utilizing the La3+-doped Co3O4
622
nanocubes for the detection of sudan I in food samples (including ketchup sauce, chili powder, and
623
tomato paste). The as-prepared La3+-doped Co3O4 nanocubes could be used to modify screen
624
printed electrode (SPE). The voltammetry method was employed to evaluate the electrocatalytic
625
activity of La3+-doped Co3O4 nanocubes/SPE towards the oxidation of Sudan I. The proposed 24
626
biosensor with good sensitivity and excellent accuracy could be used to determine Sudan I in food
627
samples in the linear response ranging from 0.3 to 300 µM with a low LOD of 0.05 µM [127].
628
Recently, based on the CuO NPs-modified 3D N-doped porous carbon (CuO/3DNPC), Ye et al.
629
developed a new electrochemical biosensor with high sensitivity and selectivity for the accurate
630
determination of Sudan I. The 3DNPC was for the first time synthesized through the calcination of
631
the precursor of 3D integrated polysaccharide. Following that, the prepared 3DNPC was modified
632
with CuO NPs through hydrothermal strategy. Owing to the outstanding electrocatalytic
633
performance of CuO NPs and the accelerated electron transfer via 3DNPC, the CuO/3DNPC
634
decorated electrode was endowed with a wide linear range and high sensitivity for the
635
determination of Sudan I. In addition, the developed CuO/3DNPC also showed the advantages of
636
high stability, good selectivity, and high reproducibility for the determination of Sudan I in food
637
samples such as ketchup and chilli sauces [132]. CLB as a β2-adrenergic agonist has been applied
638
in the therapy of veterinary and human pulmonary illness such as asthma. Nevertheless, in the past
639
decades, the CLB has been extensively misused as a nutrient repartitioning agent for the meat
640
production animals due to its characteristics of improving growth-rate, increasing protein
641
accretion, and reducing fat deposition, which will lead to some huge hazards to human health such
642
as dizziness, headache, muscle tremors, and heart palpitations, when the CLB resides in some
643
edible tissues of livestock products [2, 133-135]. By using the Prussian blue nanoparticles
644
(PBNPs), Zhao et al. developed a new and simple biosensor for the ultrasensitive detection of
645
CLB based on lateral flow assay (Fig.9a). The CLB in pork, bacon, and pork kidney samples
646
could be sensitively detected by the proposed PBNP-based LFA with a low LOD of 1ng/mL, and
647
with a dynamic linear range of 0.5-5 ng/mL [133]. In a very recent study, Zhang et al. developed a
648
novel rapid, and convenient electrochemical biosensor with good stability and high sensitivity on
649
the basis of the double signal amplification produced by the zirconium dioxide nanocomposites
650
hybrids material (ZrO2) nanocomposites and the polyoxometalate (NH4)5PV8Mo4O40 (NPVMo)
651
for the simultaneous determination of ractopamine (RAC) and CLB (Fig.9b). The ZrO2NPs with a
652
larger surface area and needle-like nanostructure was employed as POM carrier to construct an
653
electrochemical biosensor for the first time. The prepared NPVMo/ ZrO2/GCE showed the merits
654
of electrocatalytic actives, fast response, high stability, and good conductivity, resulting in the
655
enhancement of peak current and the negative shift of oxidation potentials of RAC and CLB. 25
656
Based on the synergistic effect between the ZrO2NPs and NPVMo, the oxidation of RAC and
657
CLB on NPVMo/ZrO2/GCE was determined through the differential pulse voltammetry (DPV)
658
with low LODs of 9.3×10-1 and 5.03×10-3 µM, respectively. Moreover, the RAC could be detected
659
in the linear response ranging from 3.0 to 50 µM, and the CLB could be detected with a wide
660
range of 0.1-1000 µM [135]. Nitrite as a color former and food preservative has been widely
661
applied in food processing. Nevertheless, the potential toxicity of nitrite produces a huge threat for
662
public health. The small amounts of nitrite are inhaled possibly leading to the acute poisoning, and
663
the nitrite with long-term intake can result in the cancer [136]. To monitor and control the use of
664
nitrite in food processing, nanozymes-based biosensors has been constructed for detection of
665
nitrite in food samples [71, 129]. For example, Liu et al. proposed a new, reliable, convenient, and
666
facile strategy for electrochemical and colorimetric assay of nitrite based on the histidine-capped
667
gold nanoclusters (His@AuNCs) with an excellent oxidase-mimicking activity. The prepared
668
His@AuNCs could catalyze the oxidation of TMB to generate the blue colored oxTMB in the
669
absence of H2O2. The oxidase-mimicking activity of His@AuNCs could be further enhanced by
670
the assembly between His@AuNCs and reduced graphene oxide (RGO). The as-prepared
671
His@AuNCs/RGO nanocomposites not only possessed a higher catalytic constant (Kcat) and
672
lower Michaelis constant (Km) for the oxidation of TMB, but also showed a stronger
673
electrocatalytic performance toward the TMB. However, the nitrite could inhibit the oxidase-like
674
catalytic activity and electrocatalytic activity of His@AuNCs/RGO toward the oxidation of TMB.
675
On this basis, a novel, convenient, reliable, and facile electrochemical and colorimetric biosensor
676
was successfully established by using the His@AuNCs/RGO nanocomposites as oxidase mimics
677
for the detection of nitrite in sausage samples with wide linear ranges of 2.5-5700 µM and 10-500
678
µM, respectively [129].
679
3.6 Metal ions
680
Currently，the toxic heavy metal ions such as Hg2+, Pb2+, and Cd2+ have caused wide
681
attentions due to their huge threat to the public health. Long-term exposure to the hazardous heavy
682
metal ions (even trace amount hazardous metal ions present in food) will lead to some severe
683
diseases, such as cognitive deficits, reproductive disorders, minamata, kidney failure, 26
684
cardiovascular disorders, and neurological disorders[2, 137, 138]. In addition to heavy metal ions,
685
some other metal ions such as Cu2+ also could bring about the toxic effect on human [139]. It was
686
reported that the USA Environmental Protection Agency had built the maximum residue limits for
687
Cu2+ and Hg2+ in drinking water at 20 µM and10 nM, respectively [6]. In order to rapidly, simply,
688
economically, and sensitively detect the hazardous metal ions, some emerging nanozymes-based
689
biosensors have been developed for detection of hazardous metal ions [140-142].
690
Zhao et al. developed a sensitive electrochemical biosensor for the determination of Pb2+ on the
691
basis of the high specificity of DNAzymes for the Pb2+ (Fig.10a). The electrochemical signal
692
could be efficiently amplified by the strand replacement reaction-assembly induced catalytic
693
hairpin and the generation of the dendritic structure DNA (DSDNA) through layer-by-layer
694
assembly. The developed electrochemical biosensor was used for the detection of Pb2+ with a liner
695
range of 0.1 pM-200 nM, and with a low LOD of 0.033 pM [143]. In another study, based on the
696
mercury-stimulated peroxidase-like performance of two dimensional reduced Graphene
697
oxide-PEI-Pd nanohybrids (2D rGO/PEI/Pd nanohybrids), Zhang et al. successfully developed a
698
new, general, rapid, and highly selective colorimetric method for the ultratrace naked-eye
699
detection of Hg2+ in water and human serum specimens (Fig.10b). In this study, 2D rGO/PEI/Pd
700
nanohybrids with peroxidase-like performance were prepared for the detection of Hg2+. With the
701
existence of Hg2+, the peroxidase-like activity of 2D rGO/PEI/Pd nanohybrids was discovered to
702
be significantly enhanced, which could effectively catalyze the oxidation of TMB to generate a
703
color change that could be measured by the absorption spectroscopic approach and the naked eyes.
704
The developed colorimetric biosensor coupled with the spectroscopic detection approach exhibited
705
an ultralow LOD of 0.39 nM for Hg2+ in double distilled H2O (ddH2O）and approximately 1nM in
706
serum and water samples, respectively. Based on this colorimetric biosensor, the Hg2+ in human
707
serum and water could be determined by the naked eyes with a low LOD of approximately 10 nM
708
[137]. Interestingly enough, Han et al. innovatively developed a new and facile Au
709
nanozyme-based paper chip (AuNZ-PAD) for the colorimetric determination of Hg2+ in distilled
710
and tap water samples. The established colorimetric biosensor on the AuNZ-PAD was on the basis
711
of the peroxidase-like performance of AuNPs promoted through the production of Au-Hg
712
amalgam (the Hg2+-promoted nanozyme activity of AuNPs). With the introduction of Hg2+ onto
713
the AuNZ-PAD, the catalytic reaction between TMB and H2O2 could be greatly enhanced by the 27
For instance,
714
generation of Au-Hg amalgam, leading to the production of blue staining on the paper chip. On
715
this basis, a novel device was developed for selective and sensitive determination of Hg2+ ions in
716
distilled and tap water samples. Moreover, the developed device with the merits of simplicity,
717
effective cost, feasibility, good sensitivity, high selectivity, and high throughput could be used for
718
the onsite detection with a wide detection dynamic range (approximately 3 orders of magnitude),
719
and with the LODs of 30 µg/L and 1.2 µg/L for a single application and five applications of test
720
samples, respectively [144]. The uptake and accumulation of excess Cu2+ probably lead to some
721
diseases such as neurodegenerative diseases, cardiovascular diseases, cancer, and diabetes. Thus,
722
the development of sensitive methods for the determination of Cu2+ is of great importance. By the
723
surface modification on the Ag/Pt nanoclusters (Ag/Pt NCs) and the tuning of the
724
peroxidase-mimicking performance, Wu et al. successfully developed a sensitive colorimetric
725
biosensor for the determination of Cu2+ in real water samples. The peroxidase-like activity of
726
Ag/Pt NCs could be inhibited by 3-mercaptopropionic acid (MPA). The Cu2+ could catalyze the
727
oxidization of MPA in the presence of oxygen to make MPA lose the inhibition toward
728
peroxidase-mimicking activity of Ag/Pt NCs. On this basis, a new colorimetric biosensor was
729
established for the determination of Cu2+ through measuring the change of colorimetric signal
730
generated by the reaction between TMB and H2O2. The proposed colorimetric biosensor with high
731
selectivity and sensitivity could be used to detect Cu2+ in real water samples ranging from 10 to
732
100 nM with a low LOD of 5.0 nM. In addition, the established method was simple, highly
733
selective and sensitive, and low-cost, which was used for the detection of Cu2+ in food and
734
environmental samples [139]. Recently, Zhang et al. innovatively constructed a novel and facile
735
colorimetric biosensor for the high-performance determination of Ag+ using the tunable
736
peroxidase-mimicking performance of PdNPs mediated by histidine (His). The prepared PdNPs
737
with the intrinsic peroxidase-like activity was able to catalyze the oxidation of colorless TMB to
738
produce a blue oxTMB with the existence of H2O2. However, the peroxidase-like activity of
739
PdNPs could be significantly enhanced by the modification of His on PdNPs owing to the
740
outstanding physicochemical characteristics of the decorated PdNPs including better
741
hydrophilicity, smaller size, and interactions between His and PdNPs, leading to an enhanced
742
color reaction. With the addition of Ag+, the His modifier could be despoiled from the surface of
743
His-Pd via Ag+ due to the specific interaction between His and Ag+, leading to the formation of 28
744
bare PdNPs with a weak peroxidase-like activity. Based on this principle, Ag+ in water samples
745
could be sensitively detected with a linear range of 30-300 nM, and with a low LOD of 4.7 nM
746
[145].
747
3.6 Other food contaminants
748
In addition, there are other food contaminants detected by nanozymes-based biosensors, such
749
as lipopolysaccharide (LPS), arsenic (III), hydroquinone (H2Q), H2O2, and norovirus (NoV) [54,
750
64, 79, 146-148]. For example, Shen et al. established a new ratiometric electrochemical biosensor
751
with high accuracy and sensitivity for the detection of LPS by employing the Cu-MOFs as the
752
catalyst for the signal amplification (Fig.11a). In the proposed biosensor, there were two cycles
753
needed to achieve the detection of LPS. In cycle Ⅰ, with the existence of target LPS, the output
754
DNA could be produced with the help of phi29 DNA polymerase (phi29) due to the conformation
755
variation of the hairpin probes 1 (HP1) with special design triggering the cyclic-induced
756
polymerization of target. In cycle Ⅰ, the produced output DNA could hybridize with the Fc-HP2
757
(HP2 was labeled by ferrocene) immobilized on the AuNFs/GCE to produce a cleavage site of the
758
nicking endonuclease (N.BstNBI). By utilizing the N.BstNBI, the sensing interface modified by
759
single-stranded capture-probe could be obtained when the primitive signal molecules of ferrocene
760
departed from the AuNFs/GCE. The signal probes were produced using the labeled HP3 and
761
AuNPs-functionalized Cu-MOFs (AuNPs/Cu-MOFs). Then, the hybridization of signal probes
762
(HP3/AuNPs/Cu-MOFs) with the capture probes could be used for HP assembly. The prepared
763
AuNPs/Cu-MOFs not only acted as a catalyst for signal output, but also served as nanocarriers for
764
the immobilization of HP3. Based on the target-triggered quadratic cycles and the fracture Fc-HP2
765
cleavage sites, the generated capture probes could be hybridized with HP3/AuNPs/Cu-MOFs,
766
resulting in the decline of ferrocene signal. However, the signal of Cu-MOFs increased due to the
767
closeness of Cu-MOFs to the AuNFs/GCE. With the addition of glucose in solution, the prepared
768
AuNPs/Cu-MOFs with good catalytic activity were able to catalyze the oxidation of glucose to
769
achieve the signal amplification. Through the measurement of the peak current ratio of Cu-MOFs
770
and ferrocene, the LPS could be sensitively and accurately determined by the proposed biosensor
771
in the wide linear response ranging from 1fg/mL to 100 ng/mL with a low LOD of 0.33 29
772
fg/mL[146]. To discriminate the hydroquinone (H2Q) from catechol (CC) and resorcinol (RC),
773
Yang et al. developed a facile colorimetric biosensor for the detection of H2Q. The CeVO4 was for
774
the first time prepared using a simple strategy, which showed both oxidase- and
775
peroxidase-mimicking activity. And CeVO4 could be used to catalyze the oxidation of TMB to
776
produce a blue color with the existence or absence of H2O2. Interestingly enough, H2Q
777
(dihydroxybenzene isomer) could be reduced to generate a visible color variation when the TMB
778
was oxidized by the CeVO4. However, the dihydroxybenzene isomers (RC and CC) could not.
779
Accordingly, a colorimetric biosensor was constructed to discriminate H2Q from CC and RC, and
780
the H2Q could be determined in the linear response ranging from 0.05 to 8 µM with a low LOD of
781
0.04 µM[148]. Due to the serious toxic and low concentration of Arsenic (III)(As(III)) in the
782
drinking water, the development of new ultrasensitive strategy for the detection of As(III) is highly
783
desirable and extremely important. Recently, Li et al. developed a new sensitive sensing interface
784
for the determination of As (III) utilizing the prepared dumbbell-like Au/Fe3O4NPs. Based on the
785
combination of the AuNPs catalyst, the mediation of surface-active Fe (II), and the adsorption of
786
Fe3O4NPs, the electrochemical response for detecting the As(III) was dramatically enhanced. The
787
Au/Fe3O4NPs could be modified on the screen-printed carbon electrode to produce a sensing
788
interface. With the obtained sensing interface, the As (III) could be sensitively detected with a low
789
LOD of 0.0215 ppb [79]. Due to the requirement of the matrix specific concentration of virus and
790
removal of inhibitory compounds, the detection of norovirus (NoV) in food samples is extremely
791
challenging. In a very recent study, Weerathunge et al. successfully developed a new, ultrasensitive,
792
and highly robust colorimetric biosensor for the determination of murine norovirus (MNV) based
793
on the nanozymes (Fig.11b). In the proposed biosensor, the AuNPs with the peroxidase-like
794
activity served as nanozymes for catalyzing the colorless TMB substrate to produce a blue product.
795
However, the MNV-specific AG3 aptamer molecules could inhibit the peroxidase-like activity of
796
nanozymes due to their adsorption onto the surface of AuNPs. With the existence of MNV, the
797
MNV-specific AG3 aptamers were removed from the surface of the AuNPs owing to their specific
798
affinity to MNV, resulting in the recovery of the catalytic activity of AuNPs, again generating a
799
blue product. The color intensity change was proportional to the amount of MNV in the samples.
800
On the contrary, the MNV-specific AG3 aptamers had no affinity to other contaminants, thus the
801
catalytic activity of AuNPs couldn’t be recovered and no color change with the existence of 30
802
nonspecific targets. By the combination between the peroxidase-like activity of AuNPs and high
803
target specificity of MNV-specific AG3 aptamers, an ultrasensitive colorimetric biosensor was
804
established for the rapid and selective detection of MNV. With the proposed colorimetric biosensor,
805
the MNV was detected with a LOD of 20 viruses per assay equivalent to 200 viruses/mL[147].
806
4 Conclusion and prospective
807
Food safety as a hot topic of international concern has attracted more and more attentions
808
around the world. The hazardous substances in food (food contaminants) can cause a huge threat
809
to public health and serious economic loss in food industry [149, 150]. Therefore, the effective
810
detection strategies of food contaminants are of great importance for guarding food safety. To date,
811
a great many traditional strategies have been well constructed for the detection of food
812
contaminants, including HPLC, HPLC-MS, GC-MS, PCR, and so on. Though these methods show
813
high sensitivity, accuracy, and reliability for the detection of food contaminants, they are
814
complicated, laborious, and time consuming, particularly depending on the expensive instruments
815
with well-trained personnel. Thus, they are hard to meet the requirements of the fast and on-site
816
screening of massive samples and apply in some situations like in some developing countries and
817
poor areas without any detection equipment and specialists [2, 6]. Excitingly, recently, the
818
nanozymes as an emerging initiate also has provided some potential opportunities to response
819
some challenges from food safety. Nanozymes for the construction of biosensors has accelerated
820
the development of analytical science for rapid, convenient, efficient, and sensitive determination
821
of food contaminants. In this review, we summarize the advances on nanozymes-based biosensors,
822
including colorimetric biosensors, fluorescence biosensors, chemiluminescent biosensors,
823
electrochemical biosensors, SERS-based biosensors, and other biosensors. Impressively, the
824
applications of the nanozymes-based biosensors in the detection of food contaminants (including
825
mycotoxins, antibiotics, pesticides, pathogens, intentional adulteration, metal ions, and other food
826
contaminants) also have been comprehensively summarized. To promote the development of
827
nanozymes-based biosensors and their applications in the detection of food contaminants, the
828
following challenges and obstacles should be considered in future studies:
829
(1) Nanozyme as an excellent alternative of biological enzyme for signal production and 31
830
amplification play an immense role in the construction of nanozymes-based biosensors.
831
However, compared to the natural enzymes, the catalytic activity of nanozymes is still
832
relatively low. Integrating biological enzymes or nanozymes into the mesoporous
833
nanomaterials such as MOFs, COFs, mesoporous silica, mesoporous carbon, and hydrogels to
834
prepare the integrated nanozymes (INAzymes) maybe a promising strategy to obtain highly
835
active nanozymes [151-156]. In addition, most of nanozymes can hardly catalyze one specific
836
substrate like biological enzymes. Therefore, nanozymes with high catalytic activity, excellent
837
selectivity and specificity remain to be further developed for the construction of
838
nanozymes-based biosensors. Molecular imprinting technology as a potential tool has been
839
used to improve the specificity and selectivity of nanozymes [157-160]. Anchoring the
840
molecularly imprinted polymers onto the nanozymes is a promising method to develop new
841
nanozymes with high selectivity and specificity [161]. In addition, at present, most of the
842
nanozymes only have an oxidase-like activity, which are monotonous compared with
843
biological enzymes. Therefore, the nanozymes with diverse catalytic activity like hydrolase
844
and synthetase remain to be further developed for the construction of nanozymes-based
845
biosensors.
846
(2) To date, plenty of nanozymes-based biosensors have been successfully developed, but these
847
biosensors still need great improvement in detection performances. For instance, the detection
848
accuracy and sensitivity of nanozymes-based colorimetric biosensors are easily influenced by
849
the interference generated from the sample background color. The nanozymes-based
850
fluorescence biosensor, chemiluminescent biosensor, and electrochemical biosensor possess
851
the linear resolution over wide ranges, and can be widely applied to the semi-quantitative and
852
qualitative preliminary screening. Nevertheless, these biosensors all need the dedicated
853
equipment with high precision, accurate functional programs, and professional operators.
854
Moreover, owing to the electrode fouling and the requirement of charging, the electrochemical
855
biosensors suffer from the poor stability and repeatability and the requirement of analytes’
856
outstanding electroactivity. Furthermore, the emerging nanozymes-based SERS biosensors
857
often suffer from the interference from complex samples. Because of the complex food matrix
858
and trace level of food contaminants, the nanozymes-based biosensors for accurate detection
859
of food contaminants in food samples are full of huge challenges. To overcome these 32
860
challenges, the reported nanozymes-based biosensors should be further studied to improve
861
their sensitivity, stability, and repeatability. In addition, the simultaneous emergences of
862
multiple food contaminants in food also bring a great challenge for food safety assay.
863
Therefore, the development of nanozymes-based biosensors with multi-modes for the accurate
864
determination of multiple food contaminants is an extremely promising for food safety assay.
865
For example, the nanozymes can be coupled with the emerging techniques such as
866
electrochemiluminescence (ECL), surface-plasmon resonance (SPR), LAMP, and smartphone
867
to develop new multi-mode nanozymes-based biosensors for the rapid, sensitive, and accurate
868
detection of food contaminants.
869
(3) Currently, a large number of nanozymes-based biosensors have been developed for the
870
detection of food contaminants. However, there are few biosensors used for development of
871
detection devices. To meet the needs of market and customers, some inexpensive, simple,
872
miniaturized, high-throughput, and portable equipment based on nanozymes-based biosensors
873
show great prospective for the rapid determination of food contaminants.
874
Acknowledgement
875
This work was supported by the National R&D Key Programme of China (No.
876
2017YFE0110800), the Natural Science Foundation of Shandong Province (ZR2017JL012), the
877
National Natural Science Foundation of China (21677085 and 31801454), the Science and
878
Technology Nova Plan of Shaanxi Province (2019KJXX-010), the Youth Innovation Team of
879
Shaanxi Universities(Food Quality and Safety), and the Innovation platform for the development
880
and construction of special project of Key Laboratory of Tibetan Medicine Research of Qinghai
881
Province (No. 2017-ZJ-Y11).
882 883 884 885 886 887 888 889 890 891 892
References [1]
J.-M. Liu, Y. Hu, Y.-K. Yang, H. Liu, G.-Z. Fang, X. Lu, S. Wang, Trends Food Sci. Technol. 71 (2018) 94.
[2]
M. Lv, Y. Liu, J. Geng, X. Kou, Z. Xin, D. Yang, Biosens. Bioelectron. 106 (2018) 122.
[3] B. Socas-Rodríguez, J. González-Sálamo, J. Hernández-Borges, M.Á. Rodríguez-Delgado, TrAC Trend. Anal. Chem. 96 (2017) 172. [4] R. Sharma, K.S.M.S. Raghavarao, in: A. López Rubio, M.J. Fabra Rovira, M. martínez Sanz and L.G. Gómez-Mascaraque (Eds.), Chapter 6 - Nanoparticle-Based Aptasensors for Food Contaminant Detection, Elsevier. 2019, pp. 123. [5]
Y. Jiang, D.-W. Sun, H. Pu, Q. Wei, Trends Food Sci. Technol. 75 (2018) 10.
[6]
Y. Li, Z. Wang, L. Sun, L. Liu, C. Xu, H. Kuang, TrAC Trend. Anal. Chem. 113 (2019) 74.
[7]
R. Sharma, K.V. Ragavan, M.S. Thakur, K.S.M.S. Raghavarao, Biosens. Bioelectron. 74 (2015) 612. 33
893 894 895 896 897 898 899 900 901 902 903 904 905 906 907 908 909 910 911 912 913 914 915 916 917 918 919 920 921 922 923 924 925 926 927 928 929 930 931 932 933 934 935 936
[8]
H. Jafarizadeh-Malmiri, Z. Sayyar, N. Anarjan, A. Berenjian, Nano-sensors in Food Nanobiotechnology, Springer International Publishing. Cham, 2019, pp. 81.
[9]
N. Li, D. Wu, X. Li, X. Zhou, G. Fan, G. Li, Y. Wu, Food Chem. (2019) 125455. https://doi.org/10.1016/j.foodchem.2019.125455
[10]
P. Wang, L. Zhang, W. Zheng, L. Cong, Z. Guo, Y. Xie, L. Wang, R. Tang, Q. Feng, Y. Hamada, K. Gonda, Z. Hu, X. Wu, X. Jiang, Angew. Chem. Int. Edit. 57 (2018) 1491.
[11] Y. Lei, L. Tang, Y. Xie, Y. Xianyu, L. Zhang, P. Wang, Y. Hamada, K. Jiang, W. Zheng, X. Jiang, Nat. Commun. 8 (2017) 15130. [12] B. Ran, W. Zheng, M. Dong, Y. Xianyu, Y. Chen, J. Wu, Z. Qian, X. Jiang, Anal. Chem. 90 (2018) 8234. [13] Y. Huang, J. Ren, X. Qu, Chem. Rev. 119 (2019) 4357. [14] J. Wu, X. Wang, Q. Wang, Z. Lou, S. Li, Y. Zhu, L. Qin, H. Wei, Chem. Soc. Rev. 48 (2019) 1004. [15] M. Liang, X. Yan, Acc. Chem. Res. 52 (2019) 2190. [16] Y. Huang, J. Ren, X. Qu, Chem. Rev. (2019). https://doi.org/10.1021/acs.chemrev.8b00672 [17] H. Sun, Y. Zhou, J. Ren, X. Qu, Angew. Chem. Int. Edit. 57 (2018) 9224. [18] Y. Lv, M. Ma, Y. Huang, Y. Xia, Chem. Eur. J. 25 (2019) 954. [19] J. Wu, X. Wang, Q. Wang, Z. Lou, S. Li, Y. Zhu, L. Qin, H. Wei, Chem. Soc. Rev. (2019). 10.1039/C8CS00457A [20] H. Wei, E.K. Wang, Chem. Soc. Rev. 42 (2013) 6060. [21] F. Attar, M.G. Shahpar, B. Rasti, M. Sharifi, A.A. Saboury, S.M. Rezayat, M. Falahati, J. Mol. Liq. 278 (2019) 130. [22] S. Li, X. Liu, H. Chai, Y. Huang, Trac. Trends Anal. Chem. 105 (2018) 391. [23] A. Mohamad, H. Teo, N.A. Keasberry, M.U. Ahmed, Crit. Rev. Biotechnol. 39 (2019) 50. [24] S. Singh, Front. Chem. 7 (2019). [25] D.P. Cormode, L. Gao, H. Koo, Trends Biotechnol. 36 (2018) 15. [26] A.K. Srivastava, A. Dev, S. Karmakar, Environ. Chem. Lett. 16 (2018) 161. [27] L. Hu, H. Liao, L. Feng, M. Wang, W. Fu, Anal. Chem. 90 (2018) 6247. [28] L. Qin, X. Wang, Y. Liu, H. Wei, Anal. Chem. 90 (2018) 9983. [29] H. Wang, K. Wan, X. Shi, Adv. Mater. (2018) 1805368. [30] G. Chen, H.-H. Lan, S.-L. Cai, B. Sun, X.-L. Li, Z.-H. He, S.-R. Zheng, J. Fan, Y. Liu, W.-G. Zhang, ACS Appl. Mater. Interfaces 11 (2019) 12830. [31] X. Zhang, R. Huang, S. Gopalakrishnan, R. Cao-Milán, V.M. Rotello, Trend. Chem. 1 (2019) 90. [32] L. Huang, Q. Zhu, J. Zhu, L. Luo, S. Pu, W. Zhang, W. Zhu, J. Sun, J. Wang, Inorg. Chem. (2019). https://doi.org/10.1021/acs.inorgchem.8b03193 [33] L. Zheng, G. Cai, S. Wang, M. Liao, Y. Li, J. Lin, Biosens. Bioelectron. 124-125 (2019) 143. [34] K. Yin, An Ultrasensitive Colorimetric Biosensor for Copper Ion Detection, Springer Singapore. Singapore, 2020, pp. 37. [35] H. Aldewachi, T. Chalati, M.N. Woodroofe, N. Bricklebank, B. Sharrack, P. Gardiner, Nanoscale 10 (2018) 18. [36] N. Cheng, C. Zhu, Y. Wang, D. Du, M.-J. Zhu, Y. Luo, W. Xu, Y. Lin, J. Anal. Test. 3 (2019) 99. [37] W. Zheng, H. Li, W. Chen, J. Ji, X. Jiang, Anal. Chem.88 (2016) 4140. [38] I.M. Khoris, K. Takemura, J. Lee, T. Hara, F. Abe, T. Suzuki, E.Y. Park, Biosens. Bioelectron. 126 (2019) 425. [39] D. Wu, N. Hu, J. Liu, G. Fan, X. Li, J. Sun, C. Dai, Y. Suo, G. Li, Y. Wu, Talanta 190 (2018) 103. [40] H.-Q. Zheng, C.-Y. Liu, X.-Y. Zeng, J. Chen, J. Lü, R.-G. Lin, R. Cao, Z.-J. Lin, J.-W. Su, Inorg. Chem. 57 34
937 938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953 954 955 956 957 958 959 960 961 962 963 964 965 966 967 968 969 970 971 972 973 974 975 976 977 978 979 980
(2018) 9096. [41] H. Chen, Q. Qiu, S. Sharif, S. Ying, Y. Wang, Y. Ying, ACS Appl. Mater. Interfaces 10 (2018) 24108. [42] S. Sun, R. Zhao, S. Feng, Y. Xie, Microchim. Acta 185 (2018) 535. [43] L. Huang, Q. Zhu, J. Zhu, L. Luo, S. Pu, W. Zhang, W. Zhu, J. Sun, J. Wang, Inorg. Chem. 58 (2019) 1638. [44] L. Huang, D.-W. Sun, H. Pu, Q. Wei, L. Luo, J. Wang, Sensor. Actuator. B Chem. 290 (2019) 573. [45] A. Bigdeli, F. Ghasemi, H. Golmohammadi, S. Abbasi-Moayed, M.A.F. Nejad, N. Fahimi-Kashani, S. Jafarinejad, M. Shahrajabian, M.R. Hormozi-Nezhad, Nanoscale 9 (2017) 16546. [46] M.H. Lee, J.S. Kim, J.L. Sessler, Chem. Soc. Rev. 44 (2015) 4185. [47] S. Hu, J. Yan, X. Huang, L. Guo, Z. Lin, F. Luo, B. Qiu, K.-Y. Wong, G. Chen, Sensor. Actuator. B Chem. 267 (2018) 312. [48] T. Lin, Y. Qin, Y. Huang, R. Yang, L. Hou, F. Ye, S. Zhao, Chem. Commun. 54 (2018) 1762. [49] S. Huang, E. Yang, J. Yao, Y. Liu, Q. Xiao, Microchim. Acta 185 (2018) 394. [50] S. Lu, G. Li, Z. Lv, N. Qiu, W. Kong, P. Gong, G. Chen, L. Xia, X. Guo, J. You, Y. Wu, Biosens. Bioelectron. 85 (2016) 358. [51] G. Li, W. Kong, M. Zhao, S. Lu, P. Gong, G. Chen, L. Xia, H. Wang, J. You, Y. Wu, Biosens. Bioelectron. 79 (2016) 728. [52] M.
Majdinasab,
K.
Mitsubayashi,
J.L.
Marty,
Trends
Biotechnol.
(2019).
https://doi.org/10.1016/j.tibtech.2019.01.004 [53] S.M. Yoo, S.Y. Lee, Trends Biotechnol. 34 (2016) 7. [54] C.-W. Lien, B. Unnikrishnan, S.G. Harroun, C.-M. Wang, J.-Y. Chang, H.-T. Chang, C.-C. Huang, Biosens. Bioelectron. 102 (2018) 510. [55] T. Lin, Y. Qin, Y. Huang, R. Yang, L. Hou, F. Ye, S. Zhao, Chem. Commun. 54 (2018) 1762. [56] N. Bagheri, A. Khataee, J. Hassanzadeh, B. Habibi, Spectrochim. Acta A 209 (2019) 118. [57] N. Bagheri, A. Khataee, B. Habibi, J. Hassanzadeh, Talanta 179 (2018) 710. [58] M. Nasir, M.H. Nawaz, U. Latif, M. Yaqub, A. Hayat, A. Rahim, Microchim. Acta 184 (2017) 323. [59] M. Iranifam, Trac. Trends Anal. Chem. 80 (2016) 387. [60] M. Iranifam, Trac. Trends Anal. Chem. 51 (2013) 51. [61] Y. He, B. Xu, W. Li, H. Yu, J. Agric. Food Chem. 63 (2015) 2930. [62] L. He, Z.W. Jiang, W. Li, C.M. Li, C.Z. Huang, Y.F. Li, ACS Appl. Mater. Interfaces 10 (2018) 28868. [63] F. Luo, Y. Lin, L. Zheng, X. Lin, Y. Chi, ACS Appl. Mater. Interfaces 7 (2015) 11322. [64] Y. Li, X. You, X. Shi, Food Anal. Methods 10 (2017) 626. [65] X. Yi, W. Dong, X. Zhang, J. Xie, Y. Huang, Anal. Bioanal. Chem. 408 (2016) 8805. [66] X. Qian Tang, Y. Dan Zhang, Z. Wei Jiang, D. Mei Wang, C. Zhi Huang, Y. Fang Li, Talanta 179 (2018) 43. [67] S. Chaiyo, E. Mehmeti, W. Siangproh, T.L. Hoang, H.P. Nguyen, O. Chailapakul, K. Kalcher, Biosens. Bioelectron. 102 (2018) 113. [68] S. Cinti, R. Cusenza, D. Moscone, F. Arduini, Talanta 187 (2018) 59. [69] Y. Liu, H. Li, L. Lu, B. Sun, L. Huang, H. Chen, W. Qiu, J. Tao, P. Zhao, J. Electrochem. Soc. 166 (2019) B133. [70]
H. Liang, H. Xu, Y. Zhao, J. Zheng, H. Zhao, G. Li, C.-P. Li, Biosens. Bioelectron. 144 (2019) 111691. https://doi.org/10.1016/j.bios.2019.111691
[71] H. Chen, T. Yang, F. Liu, W. Li, Sensor. Actuator. B Chem. 286 (2019) 401. [72] Y. Wei, Y. Li, N. Li, Y. Zhang, T. Yan, H. Ma, Q. Wei, Biosens. Bioelectron. 79 (2016) 482. [73] R. Wang, W.-D. Liu, A.-J. Wang, Y. Xue, L. Wu, J.-J. Feng, Biosens. Bioelectron. 99 (2018) 458. [74]
R. Wang, A.-J. Wang, W.-D. Liu, P.-X. Yuan, Y. Xue, X. Luo, J.-J. Feng, Biosens. Bioelectron. 102 35
981 982 983 984 985 986 987 988 989 990 991 992 993 994 995 996 997 998 999 1000 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 1018 1019 1020 1021 1022 1023 1024
(2018)276. [75] X. Zheng, L. Li, K. Cui, Y. Zhang, L. Zhang, S. Ge, J. Yu, ACS Appl. Mater. Interfaces 10 (2018) 3333. [76] S.S. Menon, S.V. Chandran, A. Koyappayil, S. Berchmans, ChemistrySelect 3 (2018) 8319. [77] W. Meng, Y. Wen, L. Dai, Z. He, L. Wang, Sensor. Actuator. B Chem. 260 (2018) 852. [78] Y. Li, C. Yu, B. Yang, Z. Liu, P. Xia, Q. Wang, Biosens. Bioelectron. 102 (2018) 307. [79] S.-S. Li, W.-Y. Zhou, M. Jiang, Z. Guo, J.-H. Liu, L. Zhang, X.-J. Huang, Anal. Chem. 90 (2018) 4569. [80] X. Tian, L. Liu, Y. Li, C. Yang, Z. Zhou, Y. Nie, Y. Wang, Sensor. Actuator. B Chem. 256 (2018) 135. [81] F. Li, X. Wang, X. Sun, Y. Guo, Rsc Advances 7 (2017) 38981. [82] C. Wang, C. Liu, J. Luo, Y. Tian, N. Zhou, Anal. Chim. Acta 936 (2016) 75. [83] L. Tian, J. Qi, K. Qian, O. Oderinde, Y. Cai, C. Yao, W. Song, Y. Wang, Sensor. Actuator. B Chem. 260 (2018) 676. [84] P. Wu, X. Hou, J.-J. Xu, H.-Y. Chen, Nanoscale 8 (2016) 8427. [85] Z. Wang, S. Zong, L. Wu, D. Zhu, Y. Cui, Chem. Rev. 117 (2017) 7910. [86] H.K. Lee, Y.H. Lee, C.S.L. Koh, G.C. Phan-Quang, X. Han, C.L. Lay, H.Y.F. Sim, Y.-C. Kao, Q. An, X.Y. Ling, Chem. Soc. Rev. (2019). [87] R.A. Tripp, R.A. Dluhy, Y. Zhao, Nano Today 3 (2008) 31. [88] X. Ma, S. Wen, X. Xue, Y. Guo, J. Jin, W. Song, B. Zhao, ACS Appl. Mater. Interfaces 10 (2018) 25726. [89] Y. Hu, H. Cheng, X. Zhao, J. Wu, F. Muhammad, S. Lin, J. He, L. Zhou, C. Zhang, Y. Deng, P. Wang, Z. Zhou, S. Nie, H. Wei, ACS Nano 11 (2017) 5558. [90] M.J. Tan, Z.-Y. Hong, M.-H. Chang, C.-C. Liu, H.-F. Cheng, X.J. Loh, C.-H. Chen, C.-D. Liao, K.V. Kong, Biosens. Bioelectron. 96 (2017) 167. [91] C. Li, Y. Liu, A. Liang, Z. Jiang, Sensor. Actuator. B Chem. 263 (2018) 183. [92] Z. Jiang, P. Gao, L. Yang, C. Huang, Y. Li, Anal. Chem. 87 (2015) 12177. [93] Y. Hu, H. Cheng, X. Zhao, J. Wu, F. Muhammad, S. Lin, J. He, L. Zhou, C. Zhang, Y. Deng, ACS Nano 11 (2017) 5558. [94] J. Wu, K. Qin, D. Yuan, J. Tan, L. Qin, X. Zhang, H. Wei, ACS Appl. Mater. Interfaces 10 (2018) 12954. [95] H. Ouyang, S. Ling, A. Liang, Z. Jiang, Sensor. Actuator. B Chem. 258 (2018) 739. [96] C. Li, H. Wang, Y. Luo, G. Wen, Z. Jiang, Food Chem. 289 (2019) 531. [97] Y. Su, D. Wu, J. Chen, G. Chen, N. Hu, H. Wang, P. Wang, H. Han, G. Li, Y. Wu, Anal. Chem. (2019). https://doi.org/10.1021/acs.analchem.9b02233 [98] F. Zheng, W. Ke, L. Shi, H. Liu, Y. Zhao, Anal. Chem. (2019). https://doi.org/10.1021/acs.analchem.9b02469 [99] L. Zhang, Y. Chen, N. Cheng, Y. Xu, K. Huang, Y. Luo, P. Wang, D. Duan, W. Xu, Anal. Chem. 89 (2017) 10194. [100] J. Chen, Z. Li, J. Ge, R. Yang, L. Zhang, L.-b. Qu, H.-q. Wang, L. Zhang, Talanta 139 (2015) 226. [101]
X. Li, H. Li, X. Li, Q. Zhang, Food Chem. 233 (2017) 290.
[102] S.M. Taghdisi, N.M. Danesh, M. Ramezani, A.S. Emrani, K. Abnous, ACS Appl. Mater. Interfaces 10 (2018) 12504. [103]
L. Huang, K. Chen, W. Zhang, W. Zhu, X. Liu, J. Wang, R. Wang, N. Hu, Y. Suo, J. Wang, Sensor. Actuator. B Chem. 269 (2018) 79.
[104] D. Chudobova, K. Cihalova, S. Skalickova, J. Zitka, M.A.M. Rodrigo, V. Milosavljevic, D. Hynek, P. Kopel, R. Vesely, V. Adam, R. Kizek, Electrophoresis 36 (2015) 457. [105] R.E. Baynes, K. Dedonder, L. Kissell, D. Mzyk, T. Marmulak, G. Smith, L. Tell, R. Gehring, J. Davis, J.E. Riviere, Food Chem. Toxicol. 88 (2016) 112. [106]
Q. Ma, Y. Wang, J. Jia, Y. Xiang, Food Chem. 249 (2018) 98. 36
1025 1026 1027 1028 1029 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068
[107]
Y. Yang, S. Yin, Y. Li, D. Lu, J. Zhang, C. Sun, Trac. Trends Anal. Chem. 95 (2017) 1.
[108]
Z. Khoshbin, A. Verdian, M.R. Housaindokht, M. Izadyar, Z. Rouhbakhsh, Biosens. Bioelectron. 122 (2018) 263.
[109] T.K. Sharma, R. Ramanathan, P. Weerathunge, M. Mohammadtaheri, H.K. Daima, R. Shukla, V. Bansal, Chem. Commun. 50 (2014) 15856. [110]
C. Wang, D. Chen, Q. Wang, R. Tan, Biosens. Bioelectron. 91 (2017) 262.
[111] M. Govindasamy, S.-M. Chen, V. Mani, R. Devasenathipathy, R. Umamaheswari, K. Joseph Santhanaraj, A. Sathiyan, J. Colloid. Interface Sci. 485 (2017) 129. [112] Z. Chen, G. Lai, S. Liu, A. Yu, Sensor. Actuator. B Chem. 273 (2018) 1762. [113] R. Zeng, Z. Luo, L. Zhang, D. Tang, Anal. Chem. 90 (2018) 12299. [114] H. Chang, J. Lv, H. Zhang, B. Zhang, W. Wei, Y. Qiao, Biosens. Bioelectron. 87 (2017) 579. [115]
P. Weerathunge, R. Ramanathan, R. Shukla, T.K. Sharma, V. Bansal, Anal. Chem. 86 (2014) 11937.
[116] L. Zeng, D. Zhou, J. Wu, C. Liu, J. Chen, Anal. Methods 11 (2019) 1168. [117]
S. Biswas, P. Tripathi, N. Kumar, S. Nara, Sensor. Actuator. B Chem. 231 (2016) 584.
[118] S. Singh, P. Tripathi, N. Kumar, S. Nara, Biosens. Bioelectron. 92 (2017) 280. [119] Y. Zhao, M. Yang, Q. Fu, H. Ouyang, W. Wen, Y. Song, C. Zhu, Y. Lin, D. Du, Anal. Chem. 90 (2018) 7391. [120] L. Qiu, P. Lv, C. Zhao, X. Feng, G. Fang, J. Liu, S. Wang, Sensor. Actuator. B Chem. 286 (2019) 386. [121]
L. Zhang, R. Huang, W. Liu, H. Liu, X. Zhou, D. Xing, Biosens. Bioelectron. 86 (2016) 1.
[122] X. Zhao, C.-W. Lin, J. Wang, D.-H. Oh, Advances in Rapid Detection Methods for Foodborne Pathogens, J. Microbiol. Biotechnol 24 (2014) 297. [123] J. Hu, Y.-Z. Jiang, M. Tang, L.-L. Wu, H.-y. Xie, Z.-L. Zhang, D.-W. Pang, Anal. Chem. 91 (2019) 1178. [124] S. Wang, W. Deng, L. Yang, Y. Tan, Q. Xie, S. Yao, ACS Appl. Mater. Interfaces 9 (2017) 24440. [125]
N. Cheng, Y. Song, M.M.A. Zeinhom, Y.-C. Chang, L. Sheng, H. Li, D. Du, L. Li, M.-J. Zhu, Y. Luo, W. Xu, Y. Lin, ACS Appl. Mater. Interfaces 9 (2017) 40671.
[126]
J. Han, L. Zhang, L. Hu, K. Xing, X. Lu, Y. Huang, J. Zhang, W. Lai, T. Chen, J. Dairy Sci. 101 (2018) 5770.
[127]
H. Mahmoudi-Moghaddam, S. Tajik, H. Beitollahi, Food Chem. 286 (2019) 191.
[128]
J. Li, H. Feng, J. Li, Y. Feng, Y. Zhang, J. Jiang, D. Qian, Electrochim. Acta 167 (2015) 226.
[129]
L. Liu, J. Du, W.-e. Liu, Y. Guo, G. Wu, W. Qi, X. Lu, Anal. Bioanal. Chem. 411 (2019) 2189.
[130]
D. Deng, H. Yang, C. Liu, K. Zhao, J. Li, A. Deng, Food Chem. 277 (2019) 595.
[131]
S. Palanisamy, T. Kokulnathan, S.-M. Chen, V. Velusamy, S.K. Ramaraj, J Electroanal Chem 794 (2017) 64.
[132]
Q. Ye, X. Chen, J. Yang, D. Wu, J. Ma, Y. Kong, Food Chem. 287 (2019) 375.
[133]
B. Zhao, Q. Huang, L. Dou, T. Bu, K. Chen, Q. Yang, L. Yan, J. Wang, D. Zhang, Sensor. Actuator. B Chem. 275 (2018) 223.
[134] Y. Chen, Z. Huang, S. Hu, G. Zhang, J. Peng, J. Xia, W. Lai, Anal. Biochem. 577 (2019) 45. [135]
L. Zhang, Q. Wang, Y. Qi, L. Li, S. Wang, X. Wang, Sensor. Actuator. B Chem. 288 (2019) 347.
[136]
X. Li, J. Ping, Y. Ying, Trac. Trends Anal. Chem. 113 (2019) 1.
[137]
S. Zhang, D. Zhang, X. Zhang, D. Shang, Z. Xue, D. Shan, X. Lu, Anal. Chem. 89 (2017) 3538.
[138]
H.N. Kim, W.X. Ren, J.S. Kim, J. Yoon, Chem. Soc. Rev. 41 (2012) 3210.
[139]
L.-L. Wu, Z.-J. Qian, Z.-J. Xie, Y.-Y. Zhang, C.-F. Peng, Chinese J. Anal. Chem. 45 (2017) 471.
[140]
W. Li, B. Chen, H. Zhang, Y. Sun, J. Wang, J. Zhang, Y. Fu, Biosens. Bioelectron.66 (2015) 251.
[141]
H. Li, H. Liu, J. Zhang, Y. Cheng, C. Zhang, X. Fei, Y. Xian, ACS Appl. Mater. Interfaces 9 (2017) 40716. 37
1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112
[142]
Y. Xiong, L. Su, H. Yang, P. Zhang, F. Ye, New J. Chem. 39 (2015) 9221.
[143]
J. Zhao, P. Jing, S. Xue, W. Xu, Biosens. Bioelectron. 87 (2017) 157.
[144]
K.N. Han, J.-S. Choi, J. Kwon, Sci. Rep. 7 (2017) 2806.
[145]
W. Zhang, X. Niu, S. Meng, X. Li, Y. He, J. Pan, F. Qiu, H. Zhao, M. Lan, Sensor. Actuator. B Chem. 273 (2018) 400.
[146]
W.-J. Shen, Y. Zhuo, Y.-Q. Chai, R. Yuan, Anal. Chem. 87 (2015) 11345.
[147]
P. Weerathunge, R. Ramanathan, V.A. Torok, K. Hodgson, Y. Xu, R. Goodacre, B.K. Behera, V. Bansal, Anal. Chem. 91 (2019) 3270.
[148] H. Yang, J. Zha, P. Zhang, Y. Qin, T. Chen, F. Ye, Sensors and Actuators B: Chemical 247 (2017) 469. [149] A.M. Vaidya, U.S. Annapure, in: M. Kuddus (Ed.), Chapter 38 - Enzymes in Biosensors for Food Quality Assessment, Academic Press. 2019, pp. 659. [150]
L. Wu, G. Li, X. Xu, L. Zhu, R. Huang, X. Chen, TrAC Trends in Analytical Chemistry 113 (2019) 140.
[151]
J. Wu, S. Li, H. Wei, Chem. Commun. 54 (2018) 6520.
[152]
H. Cheng, L. Zhang, J. He, W. Guo, Z. Zhou, X. Zhang, S. Nie, H. Wei, Anal. Chem. 88 (2016) 5489.
[153]
Q. Sun, C.-W. Fu, B. Aguila, J. Perman, S. Wang, H.-Y. Huang, F.-S. Xiao, S. Ma, J. Am. Chem. Soc. 140 (2018) 984.
[154] Q. Yang, Q. Xu, H.-L. Jiang, Chem. Soc. Rev. 46 (2017) 4774. [155] X. Lian, Y. Fang, E. Joseph, Q. Wang, J. Li, S. Banerjee, C. Lollar, X. Wang, H.-C. Zhou, Chem. Soc. Rev. 46 (2017) 3386. [156]
X. Shi, Y. Yao, Y. Xu, K. Liu, G. Zhu, L. Chi, G. Lu, ACS Appl. Mater. Interfaces 9 (2017) 7481.
[157]
L. Chen, S. Xu, J. Li, Chem. Soc. Rev. 40 (2011) 2922.
[158]
Z. Zhang, B. Liu, J. Liu, Small 13 (2017).
[159]
L. Fan, D. Lou, H. Wu, X. Zhang, Y. Zhu, N. Gu, Y. Zhang, Adv. Mater. Interfaces 5 (2018) 1801070.
[160]
K. Fan, H. Wang, J. Xi, Q. Liu, X. Meng, D. Duan, L. Gao, X. Yan, Chem. Commun. 53 (2017) 424.
[161]
Z. Zhang, X. Zhang, B. Liu, J. Liu, J. Am. Chem. Soc. 139 (2017) 5412.
[162]
J. Lee, C.H. Jeon, S.J. Ahn, T.H. Ha, Analyst 139 (2014) 1622.
[163]
Y. Wang, Y. Sun, H. Dai, P. Ni, S. Jiang, W. Lu, Z. Li, Z. Li, Sensor. Actuator. B Chem. 236 (2016) 621.
[164]
D. Song, Y. Li, X. Lu, M. Sun, H. Liu, G. Yu, F. Gao, Anal. Chim. Acta 982 (2017) 168.
[165] M. Liang, K. Fan, Y. Pan, H. Jiang, F. Wang, D. Yang, D. Lu, J. Feng, J. Zhao, L. Yang, X. Yan, Anal. Chem. 85 (2013) 308. [166] R. Thiramanas, K. Jangpatarapongsa, P. Tangboriboonrat, D. Polpanich, Anal. Chem. 85 (2013) 5996. [167]
X. Wei, W. Zhou, S.T. Sanjay, J. Zhang, Q. Jin, F. Xu, D.C. Dominguez, X. Li, Anal. Chem. 90 (2018) 9888.
[168]
Z. Zhuang, H. Lin, X. Zhang, F. Qiu, H. Yang, Microchim. Acta 183 (2016) 2807.
[169]
H. Li, H. Liu, J. Zhang, Y. Cheng, C. Zhang, X. Fei, Y. Xian, ACS Appl. Mater. Interfaces 9 (2017) 40716.
38
1113 1114 1115 1116 1117
Graphical abstract
1118 1119
The construction of nanozymes-based biosensors and the applications of nanozymes-based
1120
biosensors in the food safety assay
39
1121 1122
Fig.1. (a) Illustration of the CS-MoSe2 NS-based versatile colorimetric detection of mercury
1123
ions[43]. (b) The colorimetric sensing principle of AChE activity and pesticides based on
1124
degradable MnOOH nanozyme[44].
40
1125 1126
Fig.2. Design for the detection of OPs by AChE inhibition method and peroxidase activity of
1127
magnetic ZIF-8[56].
1128
1129 1130
Fig.3. Schematic illustration for fabricating Cu-MOF and modified electrodes for sensing analysis
1131
of nitrite [71].
41
1132 1133
Fig.4. (a) Schematic illustration of the AuNPs doped COF nanozyme-based SERS immunosorbent
1134
assay [97]. (b) Schematic illustration of the fabrication of Raman IS-aptasensor based on Au-Ag
1135
janus NPs-mxenes assemblies for the detection of OTA [98].
42
1136 1137
Fig.5. (a) (Ⅰ) Schematic image for selective determination of patulin based on its inhibiting effect
1138
on mimetic activity MIP-capped AgNPs@ZnMOF; (Ⅰ) closer look on the location of patulin in
1139
MIP sites and its interaction with specific functional groups[57]. (b) MnCo2O4 oxidase
1140
mimic-based colorimetric assay for OTA detection. (Ⅰ) the principle of the sensing approach. (Ⅰ)
1141
the UV-vis spectra recording the reaction system in the increasing amount of OTA. (Ⅰ) calibration
1142
plots of the absorbance of oxTMB versus the OTA concentration under the optimum conditions
1143
[103]. 43
1144 1145
Fig.6. (a) Schematic illustration of the AuNPs based colorimetric method for detecting kanamycin.
1146
The illustration is not drawn to scale [110]. (b) Determination of chloramphenicol using
1147
MoS2/f-MWCNTs nanocomposite for the determination of CAP in food, biological and
1148
pharmaceutical samples [111].
44
1149 1150
Fig.7. (a) Schematic illustration of the principle of Pd@AuNR nanozyme assay for malathions
1151
[118]. (b) Schematic diagram of the principle of the CL sensor array based on the triple-channel
1152
properties of the Lum-AgNP-H2O2 CL system [61]. (c) Illustration of the principle of nanozyme-
1153
and ambient light-based smartphone platform for simultaneous detection of dual biomarkers from
1154
exposure to OPs [119].
45
1155 1156
Fig.8. (a) Schematic representation for the preparation of Fe3O4 NPC (Ⅰ), the principle of the
1157
Fe3O4 NP-based biosensor (Ⅰ), and the Fe3O4 NPC catalyzed signal amplification biosensor
1158
(Ⅰ)[121]. (b) Schematic illustration of colorimetric detection of target bacteria [124].
46
1159 1160
Fig.9. (a) (i) Schematic illustration of the PBNP-based LFA; (ii) Principle illustration of CL
1161
detection using the LFA strip; (iii) Interpretation of the assay results[133]. (b) Schematic
1162
illustration of the ultrasensitive electrochemical biosensor based on polyoxometalate and
1163
zirconium dioxide nanocomposites hybrids material for simultaneous determination of toxic
1164
clenbuterol and ractopamine [135]. 47
1165
1166 1167
Fig.10. (a) Schematic illustration of the prepared process of the proposed biosensor for Pb2+
1168
detection [143]. (b) Mercury enhanced peroxidase-like activity of rGO/PEI/Pd nanohybrids and
1169
the reaction principle in this system [137].
48
1170 1171
Fig.11. (a) Schematic illustration of the fabrication of the aptasensor: (i) Preparation procedure of
1172
HP3/AuNPs/Cu-MOFs; (ii) Signal amplification strategy and the detection principle for LPS [146].
1173
(b) Working principle of the norovirus nanozyme aptasensor; schematic illustration outlining the
1174
steps involved during norovirus sensing [147].
1175 1176 1177 1178 1179 1180 1181 1182 1183 1184 49
1185 Analytes
Table 1 The reported nanozymes-based biosensors for the determination of food contaminants. Nanozyme-based biosensors
Nanozymes
Linear range
LOD
Food matrix
Ref.
Patulin
Fluorescence biosensor
AgNPs@ZnMOF
0.1-10 µmol/L
0.06 µmol/L
Apple juice, water
[57]
Zearalenone
Colorimetric biosensor
AuNPs
10-250 ng/mL
10 ng/mL
Corn and oil
[42]
Zearalenone
Colorimetric biosensor
AuNPs
20-80000 ng/L
10 ng/L
/
[102]
Ochratoxin A
Colorimetric biosensor
MnCo2O4
0.1-10 ng/mL
0.08 ng/mL
Maize
[103]
Ochratoxin A
Colorimetric biosensor
Hemin
/
0.4 ng/mL
/
[162]
Ochratoxin A
SERS-based biosensor
Au-Ag Janus NPs
/
1.28 pM
Red wine
[98]
Kanamycin
Electrochemical biosensor
AuNPs
0.1-60 nM
0.06 nM
Honey
[82]
Kanamycin
Electrochemical biosensor
AuNPs
10-450 nM
2.85 nM
Milk
[81]
Kanamycin
Colorimetric biosensor
AuNPs
0.1-20 nM, 20-300nM
0.1 nM
Milk and meat
[110]
Kanamycin
Electrochemical biosensor
MoS2/f-MWCNTs
0.08-1392 µM
0.015±0.003 µM
Milk, honey, and powdered milk
[111]
Kanamycin
Electrochemical biosensor
AuNP/HRP NPs
>four-order of magnitude
0.88 pg/mL
Milk
[112]
Kanamycin
Fluorescence biosensor
AuNPs
1-100 nM
1.49 nM
/
[109]
Kanamycin
Electrochemical biosensor
Pt NPs
0.2-50 pM
0.063 pM
Milk
[113]
Tetracyclines
Colorimetric biosensor
Fe3O4 NPs
100-1000 nM
45 nM
/
[163]
Oxytetracycline
Colorimetric biosensor
Fe3O4 NPs
50-1000 nM
26 nM
/
[163]
Toxycycline
Colorimetric biosensor
Fe3O4 NPs
50-1000 nM
48 nM
/
[163]
Chloramphenicol
Electrochemical biosensor
CS-AgI/TiO2
0.03-12.53 nM
0.03 nM
Milk, Honey, Egg
[114]
Malathion
Colorimetric biosensor
GNR nanozyme
/
1.78 µg/mL
Tap water
[117]
Malathion
Colorimetric biosensor
Pd@AuNR
/
60 ng/mL
Water
[118]
Malathion
Electrochemical biosensor
Pd-Cu NWs
5-1000 ppt, 500-3000 ppb
1.5 ppt
Courgettes, carrots, lettuces, and oranges
[164]
Ethoprophos
Chemiluminescent biosensor
AuNPs/MOGs(Fe)
5-800 nM
1 nM
Tap water
[62]
Mycotoxins
Antibiotics
Pesticides
50
Acetamiprid
Colorimetric biosensor
AuNPs
/
0.1 ppm
/
[115]
Acetamiprid
Colorimetric biosensor
DNAzymes
/
10 pM
Chinese cabbage, tomato, eggplant, and cucumber
[116]
Dimethoate
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Dipterex
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Carbofuran
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Chlorpyrifos
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Carbaryl
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Ethyl paraoxon
Electrochemical biosensor
TiO2@DA@S/H/E
0.5-100µM
0.24 µM
Real samples
[120]
Methyl paraoxon
Electrochemical biosensor
TiO2@DA@S/H/E
0.5-100µM
0.24 µM
Real samples
[120]
Methyl parathion
Electrochemical biosensor
TiO2@DA@S/H/E
0.5-100µM
0.24 µM
Real samples
[120]
Methyl paraoxon
Colorimetric biosensor
Fe3O4 MNP
/
10 nM
Water
[165]
Acephate
Colorimetric biosensor
Fe3O4 MNP
/
5 µM
Water
[165]
Sarin
Colorimetric biosensor
Fe3O4 MNP
/
1 nM
Water
[165]
Diazinon
Fluorescence biosensor
Fe3O4 NPs@ZIF-8
0.5-500 nM
0.2 nM
Water, fruit juices
[56]
Omethoate
Colorimetric biosensor
γ-MnOOH
/
0.35 ng/mL in solution state; 10 ng/mL on test paper
Vegetable samples
[44]
Dichlorvos
Colorimetric biosensor
γ-MnOOH
/
0.14 ng/mL in solution state; 3 ng/mL on test paper
Vegetable samples
[44]
Vibrio cholerae
Colorimetric biosensor
MPNP
/
103 cfu/mL
Drinking and tap water
[166]
Enterobacter sakazakii
Other biosensor
Fe3O4NPs
2-10 cfu/mL
10 cfu/mL
Infant powder
[99]
Pathogens
51
Salmonella Enteritidis
Colorimetric biosensor
Fe-MOF NPs
34 cfu/mL
Milk
[36]
Listeria monocytogenes
Colorimetric biosensor
Fe3O4 NPC
5.4×103-108 cfu/mL
5.4×10 3 cfu/mL
Milk
[121]
Staphylococcus aureus
Colorimetric biosensor
Cu-MOF NPs
50-10000 cfu/mL
20 cfu/mL
Milk
[124]
Salmonella Enteritidis
Colorimetric biosensor
Pd@PtNPs
/
∼20 cfu/mL
Milk and ice cream
[125]
Escherichia coli O157:H7
Colorimetric biosensor
Pd@PtNPs
/
∼34 cfu/mL
Milk and ice cream
[125]
Escherichia coli O157:H7
Colorimetric biosensor
Pd@PtNPs
/
9×102 cfu/mL
Milk
[126]
Salmonella enterica
Colorimetric biosensor
PtNPs
/
10 cfu/mL
Apple juice
[167]
Escherichia coli
Colorimetric biosensor
PtNPs
/
10 cfu/mL
Apple juice
[167]
Listeria monocytogenes
Colorimetric biosensor
PtNPs
/
10 cfu/mL
Apple juice
[167]
Intentional adulteration Sudan I
Electrochemical biosensor
PtNPs
0.005-68.68µ M
1.6 nM
Chili powder, chili sauce, tomato sauce, and ketchup
[131]
Sudan I
Electrochemical biosensor
La3+-doped Co3O4 nanocubes
0.3-300 µM
0.05 µM
Chili powder, tomato paste, and ketchup sauce
[127]
Sudan I
Electrochemical biosensor
3DNPC
/
/
Ketchup, and chilli sauces
[132]
Sudan I
Electrochemical biosensor
AuNPs
0.01-70 µmol/L
1 nmol/L
Chili powder, and ketchup sauce
[128]
Nitrite
Electrochemical biosensor
Cu-MOF/Au
0.1-4000 and 4000-10000µ M
82 nM
Water
[71]
Nitrite
Colorimetric biosensor; Electrochemical biosensor
His@AuNCs/RGO
10-500 µM; 2.5-5700 µM
/
Sausage
[129]
Nitrite
Electrochemical biosensor
CD/Au nanohybrid
0.1µmol/L-2 mmol/L
0.06 µmol/L
Water
[168]
Clenbuterol
Other biosensor
PBNPs
0.5-5ng/mL
1.0 ng/mL
Pork, pork kidney and bacon
[133]
Clenbuterol
Electrochemical biosensor
ZrO2NPs
0.1-1000 µM
5.03×10-9 mol/L
Pork
[135]
52
Electrochemical biosensor
ZrO2NPs
3.0-50 µM
9.3×10-7 mol/L
Pork
[135]
Hg2+
Colorimetric biosensor
Pt nanozyme
0-120 nM
7.2 nM
Drinking water
[140]
Hg2+
Colorimetric biosensor
PCuS
/
/
Water
[142]
Hg2+
Colorimetric biosensor
PtNPs@ UiO-66-NH2
0-10 nM
0.35 nM
Water
[169]
Hg2+
Colorimetric biosensor
2D rGO/PEI/Pd nanohybrids
/
1nM by spectrum; 10 nM by naked eyes
Water
[137]
Hg2+
Colorimetric biosensor
Au nanozyme
Approximatel y 3 orders of magnitude
30 µg/L for a test sample; 1.2 µg/L for five test samples
Tap water
[144]
Hg2+
Colorimetric biosensor
CS-MoSe2 NS
/
3.5 nM by ultraviolet-visible spectrophotometer; 8.4 nM by a smartphone
Water
[32]
Pb2+
Electrochemical biosensor
Pt@PdNCs; MnTMPyP
0.1 pM-200 nM
0.033 pM
Water
[143]
Pb2+
SERS-based biosensor
AuNPs(10 nm)
0.13-53.33 nmol/L
0.07 nmol/L
Water
[95]
Cu2+
Colorimetric biosensor
Ag/PtNCs
10 -100 nM
5.0 nM
Water
[139]
Ag+
Colorimetric biosensor
PdNPs
30-300 nM
4.7 nM
Water
[145]
Ractopamine Metal ions
Other food contaminants Hydroquinone
Colorimetric biosensor
CeVO4
0.05-8 µM
0.04 µM
Tap water
[148]
Norovirus
Colorimetric biosensor
AuNPs
/
20 viruses per assay equivalent to 200 viruses/mL
Shellfish
[147]
As(III)
Electrochemical biosensor
Au/Fe3O4NPs
/
0.0215 ppb
Water
[79]
Lipopolysaccharide
Electrochemical biosensor
AuNPs/Cu-MOFs
1fg/mL-100 ng/mL
0.33 fg/mL
/
[146]
H 2O 2
Chemiluminescent biosensor
Fe-MIL-88NH2
0.1-10 µmol/L
0.025 µmol/L
Milk
[64]
1186
Note: /, not reported.
53
Highlights Emerging nanozymes-based biosensors are promising for food safety assay Progress in the construction of nanozymes-based biosensors was reviewed Applications of nanozymes-based biosensors to food safety assay were summarized Challenges and opportunities are discussed and prospected
S0165-9936(19)30347-4
DOI:
https://doi.org/10.1016/j.trac.2019.115668
Reference:
TRAC 115668
To appear in:
Trends in Analytical Chemistry
Received Date: 5 June 2019 Revised Date:
12 September 2019
Accepted Date: 13 September 2019
Please cite this article as: X. Zhang, D. Wu, X. Zhou, Y. Yu, J. Liu, N. Hu, H. Wang, G. Li, Y. Wu, Recent progress on the construction of nanozymes-based biosensors and their applications to food safety assay, Trends in Analytical Chemistry, https://doi.org/10.1016/j.trac.2019.115668. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier B.V. All rights reserved.
1
Recent progress on the construction of nanozymes-based biosensors
2
and their applications to food safety assay
3 4
Xianlong Zhanga, Di Wuf, Xuxia Zhoue, Yanxin Yua, Jichao Liua, Na Huc, Honglun Wangc,
5
Guoliang Li ad* and Yongning Wub
6
a
7
Xi’an 710021, China
8
b
9
Risk Assessment, Beijing 100050, China
School of Food and Biological Engineering, Shaanxi University of Science and Technology,
NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety
10
c
11
Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences，
12
Xining 810001, China
13
d
14
273165, China
15
e
16
310014, China
17
Key Laboratory of Tibetan Medicine Research＆Qinghai Provincial Key Laboratory of Tibetan
Key Laboratory of Life-Organic Analysis of Shandong Province, Qufu Normal University, Qufu
Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou
f
Yangtze Delta Region Institute of Tsinghua University, Zhejiang 314006, China
18
AUTHOR INFORMATION
19
E-mail: [email protected] (Guoliang Li)
20 21 22 1
23
Abstract
24
Food safety as a huge world public health threat has attracted more and more attentions. The
25
effective detection methods are of great importance for guarding food safety. However, the
26
development of reliable and efficient detection methods has been a challenging task due to the
27
complexity of food matrices and trace level of food contaminants. Recently, the emerging
28
nanomaterials with mimetic enzyme activity, namely nanozymes, have been employed for novel
29
biosensor development, which has greatly accelerated the advancement of food safety assay. In
30
this review, we summarize the mechanism and advances on nanozymes-based biosensors
31
including colorimetric biosensors, fluorescence biosensors, chemiluminescent biosensors,
32
electrochemical biosensors, SERS-based biosensors, and other biosensors. Impressively, the
33
applications of nanozymes-based biosensors in food safety screening have also been
34
comprehensively summarized (including mycotoxins, antibiotics, pesticides, pathogens,
35
intentional adulteration, metal ions, and others). In the end, future opportunities and challenges in
36
this promising field are tentatively proposed.
37
Keywords: Colorimetric biosensor
38
Electrochemical biosensor
Fluorescence biosensor
Chemiluminescent biosensor
SERS-based biosensor
Food safety assay
39 40 41 42 43 44 45 46 47 48 2
49
Contents
50
1 Introduction .................................................................................................................................... 6
51
2 Nanozymes-based biosensors ........................................................................................................ 7
52
2.1 Colorimetric biosensors ...................................................................................................... 8
53
2.2 Fluorescence biosensors .................................................................................................... 10
54
2.3 Chemiluminescent biosensors ........................................................................................... 11
55
2.4 Electrochemical biosensors ............................................................................................... 12
56
2.5 SERS-based biosensors ..................................................................................................... 13
57
2.6 Other biosensors ................................................................................................................ 15
58
3 Applications of nanozymes-based biosensors to food safety assay.............................................. 16
59
3.1 Mycotoxins........................................................................................................................ 16
60
3.2 Antibiotics ......................................................................................................................... 18
61
3.3 Pesticides........................................................................................................................... 19
62
3.4 Pathogens .......................................................................................................................... 22
63
3.5 Intentional adulteration ..................................................................................................... 24
64
3.6 Metal ions.......................................................................................................................... 26
65
3.6 Other food contaminants ................................................................................................... 29
66
4 Conclusion and prospective ......................................................................................................... 31
67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 3
84
Abbreviations AAs As(III) AChE APTES AuNZ-PAD ABTS BChE CD CC CN– CLB CL CAP Cu-MOF CuO/3DNPC CoOxH-GO CS-MoSe2 NS ddH2O E ES ECL E. coli O157:H7 ELISA Fe3O4 NPs@ZIF-8 f-MWCNTs GOx GNRs GC-MS H His H 2Q HP1 HRP His@AuNCs HPLC HPLC-MS Kana LPS LOD LFA LFIA L. monocytogenes Lum-AgNPs LAMP MNP MB
amino acids Arsenic (III) acetylcholinesterase 3-aminopropyl triethoxysilane Au nanozyme-based paper chip 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt butyrylcholinesterase carbon dot catechol cyanide clenbuterol chemiluminescent chloramphenicol Cu-based metal-organic framework CuO NPs-modified 3D N-doped porous carbon cobalt hydroxide/oxide-modified graphene oxide chitosan-functionalized molybdenum (IV) selenide nanosheets double distilled H2O glutamic acid Enterobacter sakazakii electrochemiluminescence Escherichia coli O157:H7 enzyme-linked immunosorbent assay Fe3O4 nanoparticles@ZIF-8 functionalized multiwalled carbon nanotubes glucose oxidase Gold nanorods gas chromatography-mass spectrometer histamine histidine hydroquinone hairpin probes 1 horseradish peroxidase histidine-capped gold nanoclusters high performance liquid chromatography liquid chromatography-mass spectrometer kanamycin lipopolysaccharide limit of detection lateral flow assay lateral flow immunoassay Listeria monocytogenes luminol(Lum)-functionalized Ag nanoparticles loop-mediated isothermal amplification magnetic nanoparticle methylene blue 4
MPNP MB-SpinChip MIP MPA MNV NWs NoV NCs NPVMo N.BstNBI OPD OPs OTA PCR POD PMA Pd@AuNR PBNPs PbApt RAC RC RRS RGO SERS SPR S. Enteritidis TMB VBB Van WHO ZEN ZrO2 4-NTP 4-ATP
magnetic polymeric nanoparticle multiplexed bar-chart SpinChip molecularly imprinted polymer 3-mercaptopropionic acid murine norovirus nanowires norovirus nanoclusters (NH4)5PV8Mo4O40 nicking endonuclease o-phenylenediamine organophosphorus pesticides ochratoxin A polymerase chain reactions peroxidase propidium monoazide palladium-gold nanorod Prussian blue nanoparticles Pb2+ aptamer ractopamine resorcinol resonance Rayleigh scattering reduced graphene oxide Surface enhanced Raman scattering surface plasmon resonance Salmonella Enteritidis 3,3’,5,5’-tetramethylbenzidine Victoria blue B vancomycin World Health Organization zearalenone zirconium dioxide 4-nitrothiophenol 4-aminothiophenol
5
85
1 Introduction
86
Food safety as a critical topic of international concern has received worldwide attentions. The
87
hazardous substances in food can cause a huge threat to human health and lead to huge economic
88
losses in food industry around the world. In recent years, food production has made a rapid growth
89
via the Green Revolution with the globalization process. Meanwhile, the potential possibility of
90
food contamination has obviously increased due to the inadvertent entry of trace toxicants [1].
91
Thus, the food safety still remains a great global challenge to human health and development of
92
food industry. To protect the human from the health hazards and risks caused by the food
93
contaminants (the currently common categories of food contaminants leading to the food
94
poisoning mainly include mycotoxins, pathogens, heavy metals, pesticides, metal ions, antibiotics,
95
and so on.), some organizations like World Health Organization (WHO) have developed
96
regulations and legislations for food safety. Furthermore, in last decades, the detection of food
97
contaminants has attracted extensive attentions, because it can be used to identify whether the
98
food is safe [2-4]. So far, a large number of conventional methods have been well established for
99
the detection of food contaminants, such as high-performance liquid chromatography (HPLC),
100
liquid chromatography-mass spectrometer (HPLC-MS), gas chromatography-mass spectrometer
101
(GC-MS), polymerase chain reactions (PCR), and so on. Though these methods show high
102
sensitivity, accuracy, and reliability for food contaminant detection, they are complicated,
103
laborious, and time consuming, particularly depending on the expensive instruments with
104
well-trained personnel. Thus, they are difficult to meet the needs of the fast and on-site screening
105
of massive samples and apply in some situations like in some developing countries and poor areas
106
without detection instruments and specialists [5, 6]. In addition, owing to the complexity of food
107
matrix and the trace level of food contaminants, it is of importance to develop some novel, rapid,
108
and sensitive strategies for the food safety detection. In the last decade, plenty of biosensors have
109
been successfully established as exciting alternatives or as complementary detection tools of
110
traditional methods for rapid and sensitive detection of food contaminants [7].
111
Nanotechnology as an emerging technology has been widely applied in multiple fields, such
112
as transitioning theoretical aspects, medicine, agriculture sector, environment, and so on[8-12].
113
Recently, nanomaterials with enzyme-like catalytic activity, namely nanozyme, have been used to 6
114
develop novel biosensors and improve the sensitivity of biosensors. Nanozymes usually serve as
115
the labels for multi-category signal amplification (e.g. colorimetry, fluorescence, electrochemical,
116
and so on) in the field of analytical chemistry [13-15]. Nanozymes comprise multiple materials
117
(including gold, silver, platinum, molybdenum sulfide, zeolites, and so on) and show the
118
advantages of low cost, simple preparation methods, robust catalytic activity, smooth surface
119
modification, and high stability, which can serve as exciting alternatives to overcome the
120
drawbacks of biological enzymes (such as poor operational stability and low catalytic activity in
121
harsh conditions, the high cost for preparation, isolation, and purification) [16-18]. The great
122
advances have been achieved in the field of the nanozymes in recent years, and some literatures
123
have systematically and comprehensively summarized the progress of nanozymes [16, 19-24].
124
Based on the merits of nanozymes, a great many nanozymes-based biosensors has been
125
successfully developed and widely applied in multiple fields, including biomedical science[25],
126
environmental monitoring[14], agriculture[26], and so on[9, 27-31]. Excitingly, nanozymes as a
127
new initiate also has started providing the opportunities to response some challenges from food
128
safety. Nanozymes for the construction of biosensors has accelerated the development of
129
analytical science for inexpensive, convenient, efficient, rapid and sensitive detection of food
130
contaminants [23]. Compared to conventional methods, nanozymes-based biosensors exhibit some
131
excellent merits such as higher selectivity and sensitivity, more specific target recognition, shorter
132
detection time, and better signal readout [2].
133
To date, the nanozymes-based biosensors for food safety assay are rarely summarized. In this
134
review, we firstly comprehensively summarize the advances of nanozymes-based biosensors,
135
including colorimetric biosensors, fluorescence biosensors, chemiluminescent biosensors,
136
electrochemical biosensors, surface enhanced Raman scattering (SERS)-based biosensors, and
137
other biosensors. Then, attentions are concentrated on the applications of the nanozymes-based
138
biosensors to the determination of food contaminants (including mycotoxins, antibiotics,
139
pesticides, pathogens, intentional adulteration, metal ions, and other food contaminants).
140
2 Nanozymes-based biosensors
141
Recently, nanozyme as an excellent alternative to biological enzyme has been used for signal 7
142
production and amplification in an enzyme-like catalytic manner, which has been applied to
143
construct novel biosensors [25, 32]. To date, a great many nanozymes-based biosensors has been
144
successfully developed based on different modes of nanozymes catalytic mediated signal
145
amplification (e.g. colorimetric sensing, fluorescent sensing, chemiluminescent sensing,
146
electrochemical sensing, and SERS sensing). Herein, we comprehensively summarize the
147
construction of emerging nanozymes-based biosensors, including colorimetric biosensors,
148
fluorescence biosensors, chemiluminescent biosensors, electrochemical biosensors, SERS-based
149
biosensors, and other biosensors.
150
2.1 Colorimetric biosensors
151
Colorimetric biosensors have attracted wide attentions owing to their easy readout and fast
152
visual detection through the naked eyes or low-cost and portable equipment, which can be used to
153
detect the analytes based on the color variation. One of main types of the colorimetric biosensors
154
mainly
155
3,3’,5,5’-tetramethylbenzidine (TMB), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
156
diammonium salt (ABTS), and o-phenylenediamine (OPD) to produce colorimetric output signals
157
[6, 33-37]. However, biological enzymes usually suffer from inherent defects of instabilities and
158
poor sensitivities in disgusting environmental conditions, which greatly hinder the development
159
and applications of colorimetric biosensors. Fortunately, the nanozyme with robust catalytic
160
activity and high stability, as an alternative of biological enzyme, can be used for the construction
161
of colorimetric biosensors to improve the detection selectivity, sensitivity, and stability [13, 38,
162
39]. We selected several typical studies for the mechanism introduction of nanozyme based
163
colorimetric biosensors. For example, Zheng et al. successfully synthesized a new and stable MOF
164
(namely MOF-808) with an excellent peroxidase-like activity under alkaline, neutral, and acidic
165
conditions, which as the catalyst could effectively catalyze the oxidation of TMB to generate a
166
significant color change in the presence of H2O2. On this basis, a novel, facile, and sensitive
167
colorimetric biosensor was constructed [40]. Chen et al. prepared new PtNPs/Cu-TCPP(Fe) hybrid
168
nanosheets by growing the uniform and ultrasmall PtNPs on the novel template ultrathin
169
Cu-TCPP(Fe) nanosheets (the thickness was less than 10 nm) for construction of colorimetric
focuses
on
that
enzymes
catalyze
8
the
chromogenic
substrates
such
as
170
biosensor. Compared to the Cu-TCPP (Fe) nanosheets and PtNPs, the PtNPs/Cu-TCPP(Fe) hybrid
171
nanosheets showed an enhanced peroxidase-like catalytic activity due to the physical mixture
172
between the PtNPs and the PtNPs/Cu-TCPP(Fe) hybrid nanosheets with a good synergistic
173
effect[41]. Using various phosphates to modulate the peroxidase-like activity of the prepared 2D
174
M-TCPP (Fe) nanozymes (M=Cu, Co, or Zn), Qin et al. developed a novel colorimetric biosensor
175
for simultaneously discriminating multiple phosphates [28]. Recently, there are some
176
nanozymes-based biosensors developed for the detection of food contaminants. For example,
177
Cheng et al. successfully prepared a Fe-metal organic framework (MOF) nanoparticle with
178
peroxidase-like activity (named nanozyme). The prepared nanozyme as a signal generation
179
material could be used to catalyze the oxidation of colorimetric substrate (TMB) to produce a blue
180
color. On this basis, a novel nanozyme enhanced colorimetric immunoassay sensor was
181
successfully developed for the detection of Salmonella Enteritidis (S. Enteritidis) in milk samples
182
[36]. In addition, based on the nanozymes with tunable activity, some new colorimetric biosensors
183
have been successfully developed for food safety assay. For example, Sun et al. developed a rapid
184
and sensitive aptamer based colorimetric biosensors for the detection of zearalenone (ZEN) on the
185
basis of the inhibition of AuNPs with the peroxidase-like activity by the ZEN aptamer [42]. In
186
contrast, Wang’s group for the first time developed a novel colorimetric biosensor (Fig.1a) for the
187
determination of mercury (II) (Hg2+) via the activating effect of Hg2+ on the catalytic activities of
188
the chitosan-functionalized molybdenum (IV) selenide nanosheets (CS-MoSe2 NS) nanozyme [43].
189
Recently, based on the degradable γ-MnOOH nanozyme and the domino reaction of
190
acetylcholinesterase (AChE), their group constructed a new colorimetric biosensor (Fig.1b) for
191
sensitive determination of organophosphorus pesticides (OPs). In this biosensor, the γ-MnOOH
192
nanowires (NWs) served as degradable nanozyme and TMB served as a colorimetric substrate,
193
respectively, to achieve a fast and sensitive detection of OPs and monitoring of AChE activity [44].
194
Nanozymes-based colorimetric biosensors have showed some advantages of simplicity,
195
high-speed, portability, and practicality. However, their detection accuracy and sensitivity are
196
easily influenced by the potential interference produced from the sample background color [6, 23].
9
197
2.2 Fluorescence biosensors
198
Fluorescence biosensors are constructed mainly based on the target analytes mediated
199
fluorescence enhancement (“turn-on”) or fluorescence quenching (“turn-off”) [45-51]. Excitingly,
200
the rise of nanozymes has provided a great opportunity for development of fluorescence
201
biosensors. Over the past few years, based on excellent performances of nanozymes for the
202
generation and amplification of fluorescence signals, the nanozymes-based fluorescence
203
biosensors also have attracted widespread research interests, and have been successfully
204
developed for multiple fields, such as biomedical[25], medicine[52], pathogenic microorganisms
205
assay[53], and environmental monitoring[54]. For example, Lin et al. synthesized a MIL-53(Fe)
206
nanozyme with the functions of enzyme-like catalytic activity. The as-prepared MIL-53(Fe)
207
nanozyme was able to catalyze the oxidation of its organic linker terephthalic acid (TA) to produce
208
a fluorescent product (TAOH) by the H2O2 generated from the hydrolysis of glucose with the
209
existence of GOx. On this basis, a label-free fluorescence biosensor was established [55]. In
210
another study, using the bottom-up synthesis method, an amino-functionalized MOF
211
(NH2-Cu-MOF) with peroxidase-like activity was prepared for the construction of fluorescence
212
biosensor [47]. Recently, some nanozymes-based fluorescence biosensors have been developed for
213
food safety assay. On the basis of the novel Fe3O4 nanoparticles@ZIF-8 composites
214
(Fe3O4NPs@ZIF-8) with peroxidase-like catalytic activity, Bagheri et al. constructed a new
215
fluorescence biosensor (Fig.2) for the detection of OPs. The Fe3O4 NPs@ZIF-8 was synthesized
216
by encapsulating magnetic Fe3O4 NPs into ZIF-8, and the catalytic activity of obtained composites
217
was evaluated through the oxidation of substrates [56]. Based on molecular imprinting technique,
218
Bagheri’s group successfully prepared a novel molecularly imprinted polymer (MIP)-capped Ag
219
nanoparticle/Zn-based MOF nanocomposite (AgNPs@ZnMOF) (MIP-capped AgNPs@ZnMOF
220
composite) with an excellent peroxidase mimetic activity for the selective determination of patulin.
221
In this study, the AgNPs fixed on the surface of MOF remarkably improved the catalytic activity
222
of AgNPs due to high surface area of MOF. However, the catalytic activity of AgNPs@ZnMOF
223
composite could be strangely reduced by patulin, which may be ascribed to the electron capturing
224
features of patulin. To achieve a selective interaction between AgNPs@ZnMOF composite and
225
patulin molecules, the MIP layer was innovatively capped on the surface of the prepared 10
226
AgNPs@ZnMOF through the co-polymerization reaction between tetraethyl orthosilicate (TEOS)
227
and monomers 3-aminopropyl triethoxysilane (APTES) in which the patulin was used as a
228
template agent. By the combination between novel AgNPs@ZnMOF nanocomposite with
229
outstanding peroxidase-like activity and the MIP with selective identifying feature, a sensitive
230
fluorescence biosensor was successfully developed for the selective detection of patulin [57]. In
231
addition, Lien et al. successfully prepared a well-dispersed and amorphous cobalt
232
hydroxide/oxide-modified graphene oxide (CoOxH-GO) with excellent peroxidase-mimicking
233
catalytic activity through a simple one-step synthesis strategy. Based on the reaction between Co2+
234
and GO at room temperature, CoOxH was produced and deposited in situ on the surface of GO.
235
The as-prepared CoOxH-GO could be applied to the fluorescent detection of cyanide (CN–) ions,
236
glucose, and H2O2 [54]. Nanozymes-based fluorescence biosensors exhibited the merits of good
237
selectivity, outstanding sensitivity, operational simplicity, portability, and real-time detection [58].
238
However, these nanozymes-based fluorescence biosensors still need to improve their sensitivity,
239
stability, and accuracy by eliminating the potential interferences from food matrix.
240
2.3 Chemiluminescent biosensors
241
Chemiluminescent biosensor as one of promising analytical tools has been numerously
242
constructed based on the emission of light generated from the chemical reactions, which has been
243
employed for the detection of various targets owing to its distinguished merits of simple operation,
244
rapidity, simple equipment with no monochromator, low LOD, and wide linear range [59, 60]. The
245
emergence of nanozymes also provides a promising strategy for development of nanozymes-based
246
chemiluminescent biosensors. For instance, AuNPs, AgNPs, and MIL-type MOFs with
247
peroxidase-like catalytic activity have been widely employed as biomimetic components for
248
construction of chemiluminescence biosensor by catalyzing the reaction of H2O2-luminol system
249
to generate fluorescent signal [61, 62]. Recently, Luo et al. developed new MOFs based solid
250
catalysts (Hemin@HKUST-1) through encapsulating the Hemin into HKUST-1. The prepared
251
Hemin@HKUST-1 showed an excellent enzyme-like catalytic activity to catalyze the reaction of
252
H2O2-Luminol system for establishing a selective and sensitive chemiluminescence biosensor [63].
253
It has been reported that some noble metal nanoparticles (NPs) such as AuNPs and AgNPs with 11
254
peroxidase-like catalytic activity have been applied in construction of chemiluminescence
255
biosensor [61, 62]. In addition, some MIL-type MOFs with intrinsic peroxidase-like catalytic
256
activity such as MIL-53, MIL-100, MIL-101 also have been used for catalyzing the reaction of
257
H2O2-Luminol system for construction of the nanozymes-based chemiluminescence biosensors
258
[64-66]. Recently, some nanozymes-based chemiluminescent biosensors have been developed for
259
food safety assay [62]. Based on the luminol(Lum)-functionalized Ag nanoparticles (Lum-AgNPs)
260
and the H2O2 chemiluminescent (CL) system(Lum-AgNP-H2O2 CL system), He et al. constructed
261
a new, facile, simple, and sensitive NPs-based CL sensor for the determination of carbamate
262
pesticides and OPs[61]. Recently, their group for the first time synthesized iron-based MOGs
263
nanosheet hybrids with the immobilization of AuNPs (AuNPs/MOGs (Fe) hybrids) through a
264
facile in situ grown method under ambient conditions. The as-obtained AuNPs/MOGs (Fe)
265
hybrids showed an excellent peroxidase-like activity, which endowed them with the outstanding
266
property in the field of chemiluminescence (CL) with the existence of H2O2. The remarkably
267
enhanced CL via the prepared AuNPs/MOGs (Fe) hybrids was due to the modification of AuNPs
268
on MOGs (Fe) nanosheets, which could speed up the production of O2•−, OH•, and 1O2 for
269
synergistically accelerating the CL reaction. On this basis, a new sensitive CL biosensor was
270
successfully constructed using the AuNPs/MOGs (Fe) hybrids for detection of OPs [62].
271
2.4 Electrochemical biosensors
272
Electrochemical biosensors are mainly based on the change of output-electrical signals
273
produced from the chemical reactions between the target analytes and electrode-immobilized
274
recognition elements. The generation of electrical signals is related to the concentrations of target
275
analytes, which can achieve the qualitative detections and quantitative assays of target molecules
276
[67-69]. So far, due to their simple operation, low cost, remarkable stability, and sensitive
277
response, electrochemical biosensors have been extensively applied in multiple fields, such as
278
pharmacy, environmental monitoring, chemical treat detection, and clinical diagnosis [69, 70]. To
279
further improve the analytical sensitivity of the electrochemical biosensors, the electrodes need be
280
modified by the catalysts with more uniform dispersion and electrocatalytic sites [71]. In recent
281
years, some nanozymes (including AuNPs, AgNPs, PtNPs, Au@PtNPs, AuPd@AuNPs, Cu-MOF, 12
282
and so on) with outstanding catalytic activity have been used as a new catalyst for catalyzing the
283
electrochemistry signal amplification and constructing novel electrochemical biosensors [72-78].
284
Recently, there are some nanozymes-based electrochemical biosensors developed for food safety
285
assay [79-81]. For example, on the basis of the target-induced replacement of aptamer and the
286
peroxidase-like activity of AuNPs, Wang et al. developed an ultrasensitive and enzyme-free
287
electrochemical biosensor for the determination of kanamycin (Kana) residue. The proposed
288
biosensor with an extremely high sensitivity was employed for the determination of Kana in honey
289
samples [82]. It was worth noting Khairy et al. developed a novel, simple, and sensitive
290
nanozyme-based electrochemical biosensor based on nickel oxide nanoplatelets (NPs) modified
291
screen-printed electrodes. The proposed electrochemical biosensor exhibited the excellent
292
electrochemical performances (including good stability, high selectivity and sensitivity) for the
293
determination of OPs (Parathion) in vegetable, water, and human urine samples [70]. Recently,
294
based on Cu-based MOF (Cu-MOF) modified by AuNPs, Chen et al. developed a new
295
electrochemical biosensor (Fig.3) for the sensitive determination of nitrite. The Cu-MOF
296
decorated by the AuNPs with the excellent catalytic activity and high conductivity (Cu-MOF/Au)
297
showed synergetic catalytic activity for the oxidation of nitrite owing to the large porosity and
298
surface area of Cu-MOF that could stop AuNPs from aggregation and enhance the adsorption of
299
nitrite [71]. Nanozymes-based electrochemical biosensors show the linear resolution over wide
300
ranges, and can be widely applied to the semi-quantitative and qualitative preliminary screening
301
[58, 83]. However, all of these biosensors often require the outstanding electroactivity of analytes,
302
and the dedicated equipment with high precision, accurate functional programs, and professional
303
operators. In addition, due to the electrode fouling and the requirement of charging, the
304
electrochemical biosensors suffer from the poor stability and repeatability [84].
305
2.5 SERS-based biosensors
306
SERS as an emerging and powerful analytical technology has attracted wide attention, which
307
has been rapidly developed for the construction of biosensors owing to the outstanding merits of
308
ultrahigh sensitivity, in situ noninvasive detection, and fingerprint information [85-87]. Recently,
309
some SERS-based biosensors have been successfully established for a sensitive determination of 13
310
target molecules by utilizing the nanozymes to improve the SERS activities [88-91]. For example,
311
utilizing in situ fabrication of the (AgNPs) onto the surface of the MIL-101 (Fe) with the
312
peroxidase-like activity, a new, efficient, and outstanding SERS substrate was developed by
313
Jiang’s group. The combination of the obtained SERS substrate with the numerous Raman hot
314
spots between MIL-101 (Fe) and the high-density AgNPs lead to an outstanding SERS substrate
315
for the construction of SERS-based biosensor [92]. Similarly, the nanozyme with peroxidase-like
316
catalytic activity was prepared through in situ growing the AuNPs into thermally stable and highly
317
porous MIL-101. The prepared AuNPs@MIL-101 nanozymes as the peroxidase mimics were not
318
only able to catalyze the oxidation of Raman-inactive reporter leucomalachite green to produce an
319
active malachite green (MG) in the presence of H2O2, but also serve as the SERS substrates for the
320
enhancement of the Raman signal of the generated MG[93]. In another study, by tuning the
321
amount of Pt, the bifunctional nanozymes (Au@Pt NPs) with simultaneous enzyme-like and
322
plasmonic activities were successfully prepared [94]. By using a three-step strategy (including the
323
solvothermal synthesis, Au seed-induced growth, and low-temperature cycling self-assembly), Ma
324
et al. fabricated a new SERS-active magnetic MOF-based nanozyme (Fe3O4@Au@MIL-100 (Fe))
325
with an excellent peroxidase-like activity as a SERS substrate [88]. In addition, the nanozymes for
326
the construction of SERS-based biosensor has been applied in the field of food safety assay. It was
327
worth noting that Ouyang et al. synthesized AuNP nanozyme to catalyze the nanoreaction between
328
HAuCl4 and H2O2 for the production of AuNPs, which showed the strong SERS effect, strong
329
surface plasmon resonance (SPR) absorption, and resonance Rayleigh scattering (RRS) effect with
330
the existence of Victoria blue B (VBB) molecular probes. Interestingly enough, Pb2+ aptamer
331
(PbApt) could inhibit the catalytic activity of AuNP nanozyme by its adsorption on the surface of
332
AuNP nanozyme, leading to the decrease of SERS, SPR absorption, and RRS effect owing to the
333
decrease of redox products of GNP nanoplasmonic effect. With the addition of the Pb2+, the PbApt
334
would be specifically combined with Pb2+ to generate a stable G-quadruplex and the free AuNP
335
nanozymes, which resulted in the restoration of AuNP nanozyme catalysis and the linear increase
336
of the SPR absorbance, SERS, and RRS intensity with the increase of Pb2+ concentration [95].
337
Based on the catalysis of carbon dot (CD), Li et al. developed a new quantitative analysis strategy
338
with simplicity, good selectivity, and high sensitivity using Au nanosol SERS for the trace
339
detection of Na+ [96]. Recently, our group innovatively prepared a new AuNPs doped COFs 14
340
nanozyme with excellent mimic nitroreductase activity and robust stability, which could catalyze
341
the substrate 4-nitrothiophenol (4-NTP) to generate 4-aminothiophenol (4-ATP) with the existence
342
of NaBH4. By the combination between SERS technology and enzyme-linked immunosorbent
343
assay (ELISA), a sensitive SERS-based biosensor (Fig.4a) was successfully developed for the
344
assay of allergenic proteins [97]. In a very recent study, by utilizing Au-Ag Janus NPs with
345
amplified and stable SERS activity, Zheng et al. constructed a novel ratiometric surface-enhanced
346
Raman scattering aptasensor (Fig.4b) for the detection of ochratoxin A [98]. Although these
347
emerging nanozymes-based SERS biosensors possess the merits of ultrahigh sensitivity, in situ
348
noninvasive detection, and fingerprint information, they still suffer from the interference from
349
complex samples [85]. Therefore, nanozymes-based SERS biosensors still need to be further
350
developed to improve their stability and accuracy.
351
2.6 Other biosensors
352
In addition to the above biosensors, there are some other biosensors reported for food safety
353
assay [99]. For example, based on the nanozyme strip, loop-mediated isothermal amplification
354
(LAMP), and propidium monoazide (PMA), Zhang et al. developed a novel, rapid, ultrasensitive,
355
and continual cascade nanozyme biosensor for the determination of viable Enterobacter sakazakii
356
(ES). In this biosensor, BIO- and FITC-modified primers during the LAMP process were
357
employed for determining the ompA gene of ES. And the combination between LAMP and the
358
PMA treatment was used to distinguish the viable ES from the dead. The Fe3O4 magnetic NPs
359
(MNP) served as the nanozyme probes, and a MNP-based immunochromatographic strip
360
(nanozyme strip) could be was further applied for the signal amplification to achieve a simple
361
visual detection and accurate quantification through a strip reader. Moreover, the products
362
generated by LAMP could be sandwiched between the anti-BIO and the anti-FITC, and the
363
accumulation of Fe3O4 MNPs could achieve a rapid, sensitive, and visual determination of ES. The
364
developed biosensor exhibited the advantages of simplicity, high speed, and high sensitivity due to
365
the use of the LAMP assay and PMA. Furthermore, Fe3O4 MNPs as the nanozyme probes
366
replacing colloidal Au for the introduction of enzyme modification into lateral flow biosensor also
367
improved the sensitivity of biosensor. The proposed biosensor was able to detect bacteria at 10 15
368
cfu/mL within 1 h under the optimal condition, and was applied to quantitative detection of the
369
viable ES in infant powder with a simple sample pretreatment. In addition, the biosensor with low
370
cost, rapidity, high efficiency, and portability possessed high potential for detection of other viable
371
microorganisms through replacement of the primers [99].
372
3 Applications of nanozymes-based biosensors to food safety assay
373
To date, there are plenty of nanozymes-based biosensors successfully developed for food
374
safety assay. Herein, we mainly concentrate the attentions on the applications of the
375
nanozymes-based biosensors to the detection of food contaminants (including mycotoxins,
376
antibiotics, pesticides, pathogens, intentional adulteration, metal ions, and other food
377
contaminants). Some reported applications of nanozymes-based biosensors in the detection of
378
food contaminants were illustrated in Table 1.
379
3.1 Mycotoxins
380
The mycotoxin emerges as one of most common food contaminants due to the wide growth
381
of funguses. However, the mycotoxins are hard to be completely eliminated in the general food
382
preparation processes, and the mycotoxins with a low concentration can also lead to some serious
383
diseases, such as liver disease, kidney disease, cancer, and even death owing to their significant
384
virulence. Therefore, the detection of mycotoxins has become extremely important for protecting
385
the human from the health hazards and risks [100, 101]. Due to their high selectivity and
386
sensitivity, specific target recognition, and shorter detection time, nanozymes-based biosensors
387
have been developed for detection of mycotoxins. For instance, Khataee and co-workers
388
developed a new, selective, and sensitive fluorescence biosensor for the selective determination of
389
patulin (Fig.5a) based on the combination between the new AgNPs@ZnMOF nanocomposites
390
with an excellent peroxidase-like activity and the MIP with selective identifying feature. In this
391
fluorescence biosensor, the prepared MIP-capped AgNPs@ZnMOF could be used to catalyze the
392
reaction between the H2O2 and terephthalic acid to produce a strong florescent product. With the
393
addition of patulin, the fluorescence intensity could be decreased proportional to the concentration
394
of patulin. The established fluorescence biosensor could be used to detect patulin with a 16
395
concentration range of 0.1-10 µmol/L and a low LOD of 0.06 µmol/L[57]. To sensitively and
396
precisely detect the zearalenone (ZEN), Abnous et al. developed a novel colorimetric aptasensor
397
for the detection of ZEN by using the catalytic reaction of AuNPs, 4-nitrophenol (pNP) as the
398
colorimetric substrate, exonuclease III (Exo III)-assisted recycling amplification, and
399
nontarget-induced aptamer walker. Interestingly, without the existence of ZEN, the Apt was
400
capable of walking on the surface of AuNPs with the assist of Exo III and binding to their
401
multiplex complementary strands, resulting in the sample color changing from yellow to colorless.
402
In the presence of ZEN, the Apt and its complementary strand could exist as the single-stranded
403
DNAs (ssDNA) on the AuNP surface, leading to the decrease of AuNP catalytic activity and the
404
less amounts of pNP contacting with AuNPs due to the steric hindrance from the Apt/ZEN
405
complexes. And the color of the pNP remained yellow in this case. The developed biosensor could
406
be used for the detection of ZEN with a wide linear range of 20-80000 ng/L, and with a low LOD
407
of 10 ng/L[102]. Recently, on the basis of aptamer-regulated oxidase activity, Huang et al.
408
successfully developed a new and simple “turn-on” colorimetric biosensor for the determination of
409
biomolecular (Fig.5b). Compared to metal oxide-based oxidase nanozymes, the prepared
410
MnCo2O4 showed a stronger oxidase-like catalytic activity, and efficiently catalyze the oxidation
411
of colorimetric substrate (TMB) to produce a blue color. However, the oxidase-like catalytic
412
activity of MnCo2O4 was able to be inhibited by the aptamer strands due to the attachment of the
413
aptamer strands on the surface of MnCo2O4 through the binding of aptamer and target. Fortunately,
414
the toxic ochratoxin A (OTA) could selectively combined with the aptamer to lead to the
415
restoration of MnCo2O4 nanozyme catalysis. Accordingly, a simple “turn-on” colorimetric
416
biosensor was constructed for selectively detecting OTA in maize samples ranging from 0.1 to 10
417
ng/mL, and with a low LOD of 0.08 ng/mL [103]. In a very recent study, on the basis of the
418
inhibition of zearalenone (ZEN) Apt on the peroxidase-mimicking performance of AuNPs, Xie’s
419
group developed a rapid, simple, colorimetric biosensor for the sensitive and specific
420
determination of zearalenone (ZEN). It was found that the ZEN Apt could inhibit the
421
peroxidase-like activity of AuNPs. However, the ZEN Apt could be bound with ZEN, and
422
therefore the presence of ZEN could lead to the restoration of the peroxidase-like performance of
423
AuNPs. The color variation of the solution was related to the concentration of ZEN and observed
424
by naked eyes. The proposed colorimetric biosensor could be used to detect the ZEN in real corn 17
425
and oil samples with a concentration ranging from 10 to 250 ng/mL, and with a low LOD of 10
426
ng/mL [42].
427
3.2 Antibiotics
428
Antibiotics as the human and veterinary drugs have been extensively applied in the therapy of
429
bacterial infection and the prevention of diseases of livestock. However, the residues of these
430
antibiotic drugs and metabolites may accumulate in some livestock products, including eggs, meat,
431
milk, and so on. Owing to an increasing threat from the antibiotic abuse, the construction of new
432
strategies for the accurate detection of antibiotic drug and metabolite residues in complex food
433
matrices has become increasingly important [104-109]. Recently, some nanozymes-based
434
biosensors have been successfully established for determination of antibiotics [82, 109-113]. For
435
example, based on the enhanced catalytic activity of AuNPs, Wang et al. developed a new
436
colorimetric approach (Fig.6a) with high selectivity and sensitivity for the detection of Kana. In
437
this study, interestingly, the peroxidase-mimicking performance of citrate-capped AuNPs could be
438
enhanced by Kana due to the attachment of Kana on the surface of AuNPs through the interaction
439
between -COOH on AuNPs and -NH2 on Kana and the interaction between AuNPs and the
440
glucoside on Kana (which could change the surface property of AuNPs, and generated the Au3+
441
and •OH radicals in the solution, catalyzing the oxidation of TMB to produce a blue color in the
442
presence of H2O2.) The established colorimetric biosensor could be used for sensitive detection of
443
Kana in meat and milk samples with a wide linear range of 0.1-20 nM and 20-300 nM,
444
respectively, and yielded a low LOD of 0.1 nM [110]. In another study, Govindasamy et al.
445
innovatively established a novel simple electrochemical biosensor with excellent selectivity and
446
sensitivity for detection of chloramphenicol (CAP) using a new nanocomposite material
447
synthesized by the molybdenum disulfide nanosheets (MoS2) coated on the functionalized
448
multiwalled carbon nanotubes (f-MWCNTs) via a hydrothermal strategy. The as-prepared
449
MoS2/f-MWCNTs nanocomposite showed excellent electrochemical performances and an
450
excellent electrocatalytic ability for CAP. The obtained electrochemical biosensor (Fig.6b) could
451
be applied to detect the CAP in food samples like milk, honey, and powdered milk samples with a
452
wide linear range of 0.08-1392 µM, and a low LOD was 0.015 µM [111]. Based on chitosan 18
453
modified AgI/TiO2 nanozymes, Chang et al. developed a new photoresponsive colorimetric
454
immunoassay for highly sensitive detection of chloramphenicol (CAP). Using this method, the
455
CAP in the real food samples could be detected in the linear range of 0.03 -12.53 nM with a LOD
456
of 0.03 nM [114]. By utilizing polyaniline nanowires-functionalized graphene oxide framework,
457
Zeng et al. successfully developed a novel pressure-based bioassay based on Pt
458
nanozyme-catalyzed gas generation for the Kana detection. The proposed method showed
459
excellent specificity, good reproducibility, and outstanding precision, which could be used to
460
detect the Kana within a dynamic working range of 0.2-50 pM at a LOD of 0.063 pM [113]. In a
461
recent study, Chen et al. developed a novel electrochemical biosensor for the ultrasensitive
462
determination of Kana by the combination between the signal transduction of the horseradish
463
peroxidase (HRP)-functionalized AuNPs (AuNP/HRP nanoprobe) and the highly specific
464
Kana-aptamer biorecognition. This biosensor was built based on following procedures. First of all,
465
the hybridization of the biotinylated Kana-aptamers was achieved at the electrode modified by
466
their complementary oligonucleotide strand and then methylene blue (MB) was intercalated into
467
the produced dsDNA. After that, the high-content AuNP/HRP NPs probes and streptavidin were
468
bound to the sensor. A sensitive electrochemical signal was generated through the MB-mediated
469
HRP-catalytic reaction, and the aptamer-biorecognition for Kana could lead to the quantitative
470
decline of nanoprobe capture due to the decrease of MB intercalation, achieving a simple and
471
convenient electrochemical signal transduction. The biosensor exhibited ultrahigh sensitivity
472
owing to the enhancement of the electrochemical signal through the AuNP/HRP NPs-catalytic
473
reaction and the amplification of nanoprobe signal. Moreover, the intercalation of MB into dsDNA
474
could provide an important electron mediator for the AuNP/HRP NPs-catalytic reaction and
475
simplify the electrochemical measurement. In addition, the developed biosensor for detection of
476
Kana antibiotic exhibited a wide linear range more than four-order of magnitude, and possessed a
477
low LOD of 0.88 pg/mL[112].
478
3.3 Pesticides
479
Pesticides as critical compounds have been widely applied in the agricultural field to reduce
480
the losses in agricultural production caused through pests and insects [115]. However, the 19
481
pesticides can heavily accumulate in air, soil, water, and ultimately food, most of which are
482
carcinogenic and difficult to be digested in organs, leading to a remarkable damage and increasing
483
threat to public health. Traditional methods such as capillary electrophoresis and GC/LC
484
combined with MS have been widely developed for the detection of pesticide residues.
485
Nevertheless, these strategies possess some defects of short storage time, complicated
486
pretreatment, time consuming, and requirement of expensive equipment with skilled experts. Thus,
487
the development of simple, sensitive, and on-site monitoring strategies is urgently needed to
488
protect human form the risk of exposure to the pesticides [2, 6]. Recently, to break the limits of
489
conventional strategies, some emerging nanozymes-based biosensors have been successfully
490
established for the detection of pesticides [44, 56, 62, 116]. For example, Biswas et al. developed
491
a colorimetric biosensor based on Gold nanorods (GNRs) with peroxidase-mimicking activity for
492
the determination of malathion. In this study, the prepared GNRs as nanozymes or enzyme
493
mimetics were studied, and the catalytic activity of GNRs was compared with that of HRP and
494
other Au nanostructures. It was found that the peroxidase-like activity of GNRs was 2.5 times
495
higher than that of HRP and AuNPs. The obtained GNRs exhibited good stability and excellent
496
catalytic activity, which was used to catalyze the oxidation of TMB to produce a blue color in the
497
presence of H2O2. However, malathion showed an inhibitory effect on the peroxidase-like activity
498
of GNRs, and the catalytic activity of GNRs gradually decreased with the increase of malathion
499
concentration. On this basis, a new, simple, and cheaper colorimetric biosensor was constructed
500
for the detection of malathion using GNR nanozymes. The malathion could be specifically and
501
sensitively detected by this colorimetric biosensor with a low LOD of 1.78 µg/mL[117]. Similarly,
502
by employing palladium-gold nanorod (Pd@AuNR) as nanozyme, Singh et al. developed a new,
503
simple, selective, and sensitive label free colorimetric biosensor for the detection of malathion
504
(Fig.7a). The as-fabricated Pd@AuNR nanozyme showed an excellent peroxidase-like activity for
505
OPD with the existence of H2O2. Nevertheless, the peroxidase-like activity of Pd@AuNR
506
nanozyme could be selectively quenched by malathion. Accordingly, a novel colorimetric
507
biosensor was constructed for the detection of malathions with a lowest LOD of 60 ng/mL and no
508
cross-reaction with metal salts/other similar organophosphates [118]. In another study, a novel
509
facile, simple, and sensitive AgNPs-based CL biosensor was developed for the detection of
510
carbamate pesticides and OPs on the basis of simultaneous use of the triple-channel performances 20
511
of the Lum-AgNP and H2O2 CL system (Fig.7b). The established CL biosensor could be used to
512
detect five carbamate pesticides and OPs (including carbofuran, dimethoate, carbaryl, dipterex,
513
and chlorpyrifos) with a low LOD of 24 µg/mL[61]. Recently, Zhao et al. innovatively proposed a
514
new biosensor based on the coupling of lateral-flow test strip with a smartphone for the first time
515
(Fig.7c). The proposed biosensor was developed for measuring butyrylcholinesterase (BChE)
516
activity. In this biosensor, the BChE served as a model enzyme, and the ethyl paraoxon was used
517
as the analyte representing OPs. The total amount of BChE was quantified through a sensitive
518
colorimetric signal originating from a sandwich immunochromatographic assay. In this sandwich
519
immunochromatographic assay, PtPd NPs were employed as a colorimetric probe, which showed
520
an excellent catalytic activity for phenols. The catalytic activity of BChE could be determined
521
through another colorimetric signal utilizing the Ellman assay. The colorimetric signals generated
522
from two separated test strips could be measured using the smartphone-based ambient light sensor.
523
Moreover, this portable, low-cost, and easy-operation biosensor possessed a huge potential for the
524
sensitive online determination of OP exposure [119]. In a very recent study, Qiu et al. developed a
525
new electrochemical biosensor for the determination of OPs on the basis of the electrodes
526
modified by the amino acids conjugated nanozymes. It was found that the glutamic acid (E),
527
histamine (H), and amino acids (AAs), serine (S) attached nanozymes could be used to catalyze
528
hydrolysis of OPs to produce the electroactive p-nitrophenol (pNP). Based on this principle, a
529
novel electrochemical biosensor for the detection of OPs utilizing the electrode modified by S, H,
530
and E conjugated TiO2 NPs was successfully established. The TiO2 NPs served as carriers and the
531
attached AAs, S, H, and E showed the hydrolyzing activity for the hydrolysis of OPs, so the TiO2
532
NPs-AAs showed nanozymes-like hydrolysis activity. The electrode was modified by
533
TiO2@DA@S/H/E nanozyme composites through dip-coating for the first time. The OPs
534
(including ethyl paraoxon, methyl paraoxon, and methyl parathion) could be catalyzed by
535
TiO2@DA@S/H/E nanozymes to produce the redox active pNP on the surface of nanozymes
536
modified electrode, and OPs could be detected by the electrochemical signal produced from the
537
pNP. With this electrochemical biosensor, the ethyl paraoxon, methyl paraoxon, and methyl
538
parathion could be determined with a linear range of 0.5-100 µM at a low LOD of 0.24 µM [120].
21
539
3.4 Pathogens
540
Owing to the high incidence of foodborne illnesses, the foodborne pathogens as the major
541
threat to the public health have caused the worldwide attentions. The foodborne pathogens
542
contaminated food will lead to some severe diseases of human, such as acute abdominalgia and
543
acute emesis. Furthermore, it is reported that the percentage of the population suffering from the
544
foodborne diseases has been as high as 30% every year in some industrialized countries, which is
545
mainly ascribed to the drinking water or food contaminated by the foodborne pathogens [2, 6,
546
121]. Among these foodborne pathogens, the Listeria monocytogenes (L. monocytogenes), S.
547
aureus, Escherichia coli O157:H7 (E. coli O157:H7), and Salmonella generally caused the
548
majority of foodborne pathogen outbreaks [122]. Recently, some nanozymes-based biosensors
549
have been developed for the detection of foodborne pathogens [36, 99, 123]. For example, on the
550
basis of the signal amplification catalyzed by nanoparticle cluster (NPC), Zhang et al. developed a
551
novel biosensor for the visual and rapid determination of L. monocytogenes (Fig.8a). In this
552
biosensor, a glycopeptide antibiotic (vancomycin (Van)) against Gram-positive bacteria was
553
employed as the first molecular recognition agent for the capture of L. monocytogenes. The
554
aptamer modified by Fe3O4 NPC served as the nanoprobe for the signal amplification, especially
555
recognizing the cell wall on the L. monocytogenes. Due to the recognition of Van and aptamer to
556
the L. monocytogenes at various sites, the formed sandwich recognition could lead to an excellent
557
specificity. By using the Fe3O4 NP cross-linking with the poly-L-lysine, Fe3O4 NPC with a higher
558
catalytic activity could be successfully fabricated to catalyze the oxidation of TMB to generate a
559
color reaction in the presence of H2O2 compared to the individual Fe3O4 NP, which was due to a
560
collective effect of NPC. The concentration of analytes could be measured by the variation of
561
color or absorbance. The proposed biosensor with simplicity, labor-saving, and high sensitivity
562
could be used to directly determine the L. monocytogenes whole cells linearly ranging from
563
5.4×103 to 5.4×108 cfu/mL with a low LOD of 5.4×10 3 cfu/mL[121]. By utilizing Cu-MOF NPs
564
with enzyme-mimicking performance, Wang et al. successfully developed a new sensitive
565
colorimetric biosensor for the determination of S. aureus (Fig.8b). The Cu-MOF NPs were
566
prepared by Cu(NO3)2 and 2-aminoterephthalic acid through a mixed solvothermal strategy, which
567
possessed a diameter of approximately 550 nm and exhibited an excellent peroxidase-like activity 22
568
that could catalyze the oxidation of TMB to produce a yellow color reaction with the existence of
569
H2O2. The S. aureus aptamer could be facilely modified on the surfaces of Cu-MOF NPs due to
570
the existence of a great many amine groups on the surface of Cu-MOF NPs, endowing Cu-MOF
571
NPs with the selectivity for recognition of S. aureus. Moreover, the Cu-MOF NPs with the
572
uniform size and regular morphology could make each bacterial cell link with the same amount of
573
Cu-MOF NPs, leading to a good linearity for the determination of S. aureus. Based on the
574
combination of chromogenic reaction catalyzed by Cu-MOF NPs with the aptamer recognition
575
and the magnetic separation (using aptamer modified magnetic NPs), a novel colorimetric
576
biosensor with simplicity, good selectivity, and high sensitivity was constructed for S. aureus assay.
577
With this colorimetric biosensor, S. aureus was detected with a linear range of 50-10000 cfu/mL at
578
a low LOD of 20 cfu/mL in milk samples [124]. In another study, by the integration of
579
nanozyme-mediated dual lateral flow immunoassay (LFIA) with a smartphone, Cheng et al.
580
creatively constructed a novel sensitive biosensor for simultaneous determination of pathogens for
581
the first time. In proposed biosensor, the prepared mesoporous core-shell palladium@platinum
582
(Pd@Pt) nanozymes with an excellent peroxidase-like catalytic activity for signal enhancement
583
were employed as a signal reporter. And the smartphone was used as a result recorder. Moreover,
584
the synthesized Pd@Pt nanozymes for the signal amplification and the parallel design of
585
simultaneous determination could eliminate the cross-interference, achieving a high sensitivity of
586
dual detection. With the developed biosensor, the Salmonella Enteritidis and E. coli O157:H7
587
could be simultaneously detected with the LODs of ∼20 cfu/mL and ∼34 cfu/mL, respectively. In
588
addition, the estimated recoveries of dual LFIA using milk and ice cream samples showed a range
589
of 91.44-117.00%, which demonstrated that the proposed strategy could be used to detect the live
590
pathogens in food samples[125]. Similarly, by employing the Pd-Pt nanozymes as probes, Han et
591
al. constructed a sensitive lateral flow assay (LFA) on the basis of the sandwich format to
592
qualitatively and quantitatively detect E. coli O157:H7 in milk. The prepared Pd-Pt nanozyme
593
with a high peroxidase-like catalytic activity could catalyze the oxidation of TMB to greatly
594
improve the signal intensity of test line, leading to an enhanced sensitivity of the LFA. The
595
developed nanozymes-based LFA with high sensitivity could be employed to detect E. coli
596
O157:H7 in PBS and milk with the LODs of 0.87 × 102 cfu/mL and 9.0 ×102 cfu/mL, respectively.
597
Moreover, the proposed method was 111-fold higher sensitivity than the conventional colloidal 23
598
Au-based LFA [126].
599
3.5 Intentional adulteration
600
The misuse or overuse of illegal food additives has resulted in the frequent emergence of a
601
series of food safety incidents, which has caused a huge threat to the public health and aroused
602
widespread concerns for food safety. Due to the poisonousness and carcinogenicity of these illegal
603
food additives, the monitoring of illegal food additives is of great importance for food safety [2,
604
127]. Common illegal food additives such as Sudan I, clenbuterol (CLB), and nitrite have caused
605
widespread concerns in many countries. To rapidly and sensitively detect these illegal food
606
additives, some novel nanozymes-based biosensors have been successfully established [71,
607
127-129]. Owing to its low cost and attractive red, Sudan I has been extensively employed as food
608
additives, particularly in the chili powder. However, Sudan I has been proved to be carcinogenic,
609
and could cause the damage to genetic material due to the reaction with a specific DNA sequence
610
in vitro [130]. Using the electrode modified via the PtNPs decorated graphene-β-cyclodextrin
611
(graphene/β-CD/PtNPs), Palanisamy et al. for the first time developed a novel, reliable, and
612
sensitive electrochemical biosensor for the determination of Sudan I in food samples. The
613
electrochemical performances of various modified electrodes for Sudan I were evaluated through
614
cyclic voltammetry. Among these modified electrodes, the prepared graphene/β-CD/PtNPs
615
composites modified electrode showed the highest electrocatalytic activity for Sudan I. Moreover,
616
the as-prepared nanocomposite modified electrode could increase the sensitivity of Sudan I assay,
617
and leading to a linear response range enhancement of the electrochemical biosensor. The
618
proposed electrochemical biosensor could be used to detect Sudan I in food samples (including
619
chili powder, chili sauce, tomato sauce, and ketchup) with a linear range of 0.005-68.68 µM, and
620
the LOD was 1.6 nM[131]. In another study, Tajik and co-workers for the first time constructed an
621
ultrasensitive and highly selective electrochemical biosensor utilizing the La3+-doped Co3O4
622
nanocubes for the detection of sudan I in food samples (including ketchup sauce, chili powder, and
623
tomato paste). The as-prepared La3+-doped Co3O4 nanocubes could be used to modify screen
624
printed electrode (SPE). The voltammetry method was employed to evaluate the electrocatalytic
625
activity of La3+-doped Co3O4 nanocubes/SPE towards the oxidation of Sudan I. The proposed 24
626
biosensor with good sensitivity and excellent accuracy could be used to determine Sudan I in food
627
samples in the linear response ranging from 0.3 to 300 µM with a low LOD of 0.05 µM [127].
628
Recently, based on the CuO NPs-modified 3D N-doped porous carbon (CuO/3DNPC), Ye et al.
629
developed a new electrochemical biosensor with high sensitivity and selectivity for the accurate
630
determination of Sudan I. The 3DNPC was for the first time synthesized through the calcination of
631
the precursor of 3D integrated polysaccharide. Following that, the prepared 3DNPC was modified
632
with CuO NPs through hydrothermal strategy. Owing to the outstanding electrocatalytic
633
performance of CuO NPs and the accelerated electron transfer via 3DNPC, the CuO/3DNPC
634
decorated electrode was endowed with a wide linear range and high sensitivity for the
635
determination of Sudan I. In addition, the developed CuO/3DNPC also showed the advantages of
636
high stability, good selectivity, and high reproducibility for the determination of Sudan I in food
637
samples such as ketchup and chilli sauces [132]. CLB as a β2-adrenergic agonist has been applied
638
in the therapy of veterinary and human pulmonary illness such as asthma. Nevertheless, in the past
639
decades, the CLB has been extensively misused as a nutrient repartitioning agent for the meat
640
production animals due to its characteristics of improving growth-rate, increasing protein
641
accretion, and reducing fat deposition, which will lead to some huge hazards to human health such
642
as dizziness, headache, muscle tremors, and heart palpitations, when the CLB resides in some
643
edible tissues of livestock products [2, 133-135]. By using the Prussian blue nanoparticles
644
(PBNPs), Zhao et al. developed a new and simple biosensor for the ultrasensitive detection of
645
CLB based on lateral flow assay (Fig.9a). The CLB in pork, bacon, and pork kidney samples
646
could be sensitively detected by the proposed PBNP-based LFA with a low LOD of 1ng/mL, and
647
with a dynamic linear range of 0.5-5 ng/mL [133]. In a very recent study, Zhang et al. developed a
648
novel rapid, and convenient electrochemical biosensor with good stability and high sensitivity on
649
the basis of the double signal amplification produced by the zirconium dioxide nanocomposites
650
hybrids material (ZrO2) nanocomposites and the polyoxometalate (NH4)5PV8Mo4O40 (NPVMo)
651
for the simultaneous determination of ractopamine (RAC) and CLB (Fig.9b). The ZrO2NPs with a
652
larger surface area and needle-like nanostructure was employed as POM carrier to construct an
653
electrochemical biosensor for the first time. The prepared NPVMo/ ZrO2/GCE showed the merits
654
of electrocatalytic actives, fast response, high stability, and good conductivity, resulting in the
655
enhancement of peak current and the negative shift of oxidation potentials of RAC and CLB. 25
656
Based on the synergistic effect between the ZrO2NPs and NPVMo, the oxidation of RAC and
657
CLB on NPVMo/ZrO2/GCE was determined through the differential pulse voltammetry (DPV)
658
with low LODs of 9.3×10-1 and 5.03×10-3 µM, respectively. Moreover, the RAC could be detected
659
in the linear response ranging from 3.0 to 50 µM, and the CLB could be detected with a wide
660
range of 0.1-1000 µM [135]. Nitrite as a color former and food preservative has been widely
661
applied in food processing. Nevertheless, the potential toxicity of nitrite produces a huge threat for
662
public health. The small amounts of nitrite are inhaled possibly leading to the acute poisoning, and
663
the nitrite with long-term intake can result in the cancer [136]. To monitor and control the use of
664
nitrite in food processing, nanozymes-based biosensors has been constructed for detection of
665
nitrite in food samples [71, 129]. For example, Liu et al. proposed a new, reliable, convenient, and
666
facile strategy for electrochemical and colorimetric assay of nitrite based on the histidine-capped
667
gold nanoclusters (His@AuNCs) with an excellent oxidase-mimicking activity. The prepared
668
His@AuNCs could catalyze the oxidation of TMB to generate the blue colored oxTMB in the
669
absence of H2O2. The oxidase-mimicking activity of His@AuNCs could be further enhanced by
670
the assembly between His@AuNCs and reduced graphene oxide (RGO). The as-prepared
671
His@AuNCs/RGO nanocomposites not only possessed a higher catalytic constant (Kcat) and
672
lower Michaelis constant (Km) for the oxidation of TMB, but also showed a stronger
673
electrocatalytic performance toward the TMB. However, the nitrite could inhibit the oxidase-like
674
catalytic activity and electrocatalytic activity of His@AuNCs/RGO toward the oxidation of TMB.
675
On this basis, a novel, convenient, reliable, and facile electrochemical and colorimetric biosensor
676
was successfully established by using the His@AuNCs/RGO nanocomposites as oxidase mimics
677
for the detection of nitrite in sausage samples with wide linear ranges of 2.5-5700 µM and 10-500
678
µM, respectively [129].
679
3.6 Metal ions
680
Currently，the toxic heavy metal ions such as Hg2+, Pb2+, and Cd2+ have caused wide
681
attentions due to their huge threat to the public health. Long-term exposure to the hazardous heavy
682
metal ions (even trace amount hazardous metal ions present in food) will lead to some severe
683
diseases, such as cognitive deficits, reproductive disorders, minamata, kidney failure, 26
684
cardiovascular disorders, and neurological disorders[2, 137, 138]. In addition to heavy metal ions,
685
some other metal ions such as Cu2+ also could bring about the toxic effect on human [139]. It was
686
reported that the USA Environmental Protection Agency had built the maximum residue limits for
687
Cu2+ and Hg2+ in drinking water at 20 µM and10 nM, respectively [6]. In order to rapidly, simply,
688
economically, and sensitively detect the hazardous metal ions, some emerging nanozymes-based
689
biosensors have been developed for detection of hazardous metal ions [140-142].
690
Zhao et al. developed a sensitive electrochemical biosensor for the determination of Pb2+ on the
691
basis of the high specificity of DNAzymes for the Pb2+ (Fig.10a). The electrochemical signal
692
could be efficiently amplified by the strand replacement reaction-assembly induced catalytic
693
hairpin and the generation of the dendritic structure DNA (DSDNA) through layer-by-layer
694
assembly. The developed electrochemical biosensor was used for the detection of Pb2+ with a liner
695
range of 0.1 pM-200 nM, and with a low LOD of 0.033 pM [143]. In another study, based on the
696
mercury-stimulated peroxidase-like performance of two dimensional reduced Graphene
697
oxide-PEI-Pd nanohybrids (2D rGO/PEI/Pd nanohybrids), Zhang et al. successfully developed a
698
new, general, rapid, and highly selective colorimetric method for the ultratrace naked-eye
699
detection of Hg2+ in water and human serum specimens (Fig.10b). In this study, 2D rGO/PEI/Pd
700
nanohybrids with peroxidase-like performance were prepared for the detection of Hg2+. With the
701
existence of Hg2+, the peroxidase-like activity of 2D rGO/PEI/Pd nanohybrids was discovered to
702
be significantly enhanced, which could effectively catalyze the oxidation of TMB to generate a
703
color change that could be measured by the absorption spectroscopic approach and the naked eyes.
704
The developed colorimetric biosensor coupled with the spectroscopic detection approach exhibited
705
an ultralow LOD of 0.39 nM for Hg2+ in double distilled H2O (ddH2O）and approximately 1nM in
706
serum and water samples, respectively. Based on this colorimetric biosensor, the Hg2+ in human
707
serum and water could be determined by the naked eyes with a low LOD of approximately 10 nM
708
[137]. Interestingly enough, Han et al. innovatively developed a new and facile Au
709
nanozyme-based paper chip (AuNZ-PAD) for the colorimetric determination of Hg2+ in distilled
710
and tap water samples. The established colorimetric biosensor on the AuNZ-PAD was on the basis
711
of the peroxidase-like performance of AuNPs promoted through the production of Au-Hg
712
amalgam (the Hg2+-promoted nanozyme activity of AuNPs). With the introduction of Hg2+ onto
713
the AuNZ-PAD, the catalytic reaction between TMB and H2O2 could be greatly enhanced by the 27
For instance,
714
generation of Au-Hg amalgam, leading to the production of blue staining on the paper chip. On
715
this basis, a novel device was developed for selective and sensitive determination of Hg2+ ions in
716
distilled and tap water samples. Moreover, the developed device with the merits of simplicity,
717
effective cost, feasibility, good sensitivity, high selectivity, and high throughput could be used for
718
the onsite detection with a wide detection dynamic range (approximately 3 orders of magnitude),
719
and with the LODs of 30 µg/L and 1.2 µg/L for a single application and five applications of test
720
samples, respectively [144]. The uptake and accumulation of excess Cu2+ probably lead to some
721
diseases such as neurodegenerative diseases, cardiovascular diseases, cancer, and diabetes. Thus,
722
the development of sensitive methods for the determination of Cu2+ is of great importance. By the
723
surface modification on the Ag/Pt nanoclusters (Ag/Pt NCs) and the tuning of the
724
peroxidase-mimicking performance, Wu et al. successfully developed a sensitive colorimetric
725
biosensor for the determination of Cu2+ in real water samples. The peroxidase-like activity of
726
Ag/Pt NCs could be inhibited by 3-mercaptopropionic acid (MPA). The Cu2+ could catalyze the
727
oxidization of MPA in the presence of oxygen to make MPA lose the inhibition toward
728
peroxidase-mimicking activity of Ag/Pt NCs. On this basis, a new colorimetric biosensor was
729
established for the determination of Cu2+ through measuring the change of colorimetric signal
730
generated by the reaction between TMB and H2O2. The proposed colorimetric biosensor with high
731
selectivity and sensitivity could be used to detect Cu2+ in real water samples ranging from 10 to
732
100 nM with a low LOD of 5.0 nM. In addition, the established method was simple, highly
733
selective and sensitive, and low-cost, which was used for the detection of Cu2+ in food and
734
environmental samples [139]. Recently, Zhang et al. innovatively constructed a novel and facile
735
colorimetric biosensor for the high-performance determination of Ag+ using the tunable
736
peroxidase-mimicking performance of PdNPs mediated by histidine (His). The prepared PdNPs
737
with the intrinsic peroxidase-like activity was able to catalyze the oxidation of colorless TMB to
738
produce a blue oxTMB with the existence of H2O2. However, the peroxidase-like activity of
739
PdNPs could be significantly enhanced by the modification of His on PdNPs owing to the
740
outstanding physicochemical characteristics of the decorated PdNPs including better
741
hydrophilicity, smaller size, and interactions between His and PdNPs, leading to an enhanced
742
color reaction. With the addition of Ag+, the His modifier could be despoiled from the surface of
743
His-Pd via Ag+ due to the specific interaction between His and Ag+, leading to the formation of 28
744
bare PdNPs with a weak peroxidase-like activity. Based on this principle, Ag+ in water samples
745
could be sensitively detected with a linear range of 30-300 nM, and with a low LOD of 4.7 nM
746
[145].
747
3.6 Other food contaminants
748
In addition, there are other food contaminants detected by nanozymes-based biosensors, such
749
as lipopolysaccharide (LPS), arsenic (III), hydroquinone (H2Q), H2O2, and norovirus (NoV) [54,
750
64, 79, 146-148]. For example, Shen et al. established a new ratiometric electrochemical biosensor
751
with high accuracy and sensitivity for the detection of LPS by employing the Cu-MOFs as the
752
catalyst for the signal amplification (Fig.11a). In the proposed biosensor, there were two cycles
753
needed to achieve the detection of LPS. In cycle Ⅰ, with the existence of target LPS, the output
754
DNA could be produced with the help of phi29 DNA polymerase (phi29) due to the conformation
755
variation of the hairpin probes 1 (HP1) with special design triggering the cyclic-induced
756
polymerization of target. In cycle Ⅰ, the produced output DNA could hybridize with the Fc-HP2
757
(HP2 was labeled by ferrocene) immobilized on the AuNFs/GCE to produce a cleavage site of the
758
nicking endonuclease (N.BstNBI). By utilizing the N.BstNBI, the sensing interface modified by
759
single-stranded capture-probe could be obtained when the primitive signal molecules of ferrocene
760
departed from the AuNFs/GCE. The signal probes were produced using the labeled HP3 and
761
AuNPs-functionalized Cu-MOFs (AuNPs/Cu-MOFs). Then, the hybridization of signal probes
762
(HP3/AuNPs/Cu-MOFs) with the capture probes could be used for HP assembly. The prepared
763
AuNPs/Cu-MOFs not only acted as a catalyst for signal output, but also served as nanocarriers for
764
the immobilization of HP3. Based on the target-triggered quadratic cycles and the fracture Fc-HP2
765
cleavage sites, the generated capture probes could be hybridized with HP3/AuNPs/Cu-MOFs,
766
resulting in the decline of ferrocene signal. However, the signal of Cu-MOFs increased due to the
767
closeness of Cu-MOFs to the AuNFs/GCE. With the addition of glucose in solution, the prepared
768
AuNPs/Cu-MOFs with good catalytic activity were able to catalyze the oxidation of glucose to
769
achieve the signal amplification. Through the measurement of the peak current ratio of Cu-MOFs
770
and ferrocene, the LPS could be sensitively and accurately determined by the proposed biosensor
771
in the wide linear response ranging from 1fg/mL to 100 ng/mL with a low LOD of 0.33 29
772
fg/mL[146]. To discriminate the hydroquinone (H2Q) from catechol (CC) and resorcinol (RC),
773
Yang et al. developed a facile colorimetric biosensor for the detection of H2Q. The CeVO4 was for
774
the first time prepared using a simple strategy, which showed both oxidase- and
775
peroxidase-mimicking activity. And CeVO4 could be used to catalyze the oxidation of TMB to
776
produce a blue color with the existence or absence of H2O2. Interestingly enough, H2Q
777
(dihydroxybenzene isomer) could be reduced to generate a visible color variation when the TMB
778
was oxidized by the CeVO4. However, the dihydroxybenzene isomers (RC and CC) could not.
779
Accordingly, a colorimetric biosensor was constructed to discriminate H2Q from CC and RC, and
780
the H2Q could be determined in the linear response ranging from 0.05 to 8 µM with a low LOD of
781
0.04 µM[148]. Due to the serious toxic and low concentration of Arsenic (III)(As(III)) in the
782
drinking water, the development of new ultrasensitive strategy for the detection of As(III) is highly
783
desirable and extremely important. Recently, Li et al. developed a new sensitive sensing interface
784
for the determination of As (III) utilizing the prepared dumbbell-like Au/Fe3O4NPs. Based on the
785
combination of the AuNPs catalyst, the mediation of surface-active Fe (II), and the adsorption of
786
Fe3O4NPs, the electrochemical response for detecting the As(III) was dramatically enhanced. The
787
Au/Fe3O4NPs could be modified on the screen-printed carbon electrode to produce a sensing
788
interface. With the obtained sensing interface, the As (III) could be sensitively detected with a low
789
LOD of 0.0215 ppb [79]. Due to the requirement of the matrix specific concentration of virus and
790
removal of inhibitory compounds, the detection of norovirus (NoV) in food samples is extremely
791
challenging. In a very recent study, Weerathunge et al. successfully developed a new, ultrasensitive,
792
and highly robust colorimetric biosensor for the determination of murine norovirus (MNV) based
793
on the nanozymes (Fig.11b). In the proposed biosensor, the AuNPs with the peroxidase-like
794
activity served as nanozymes for catalyzing the colorless TMB substrate to produce a blue product.
795
However, the MNV-specific AG3 aptamer molecules could inhibit the peroxidase-like activity of
796
nanozymes due to their adsorption onto the surface of AuNPs. With the existence of MNV, the
797
MNV-specific AG3 aptamers were removed from the surface of the AuNPs owing to their specific
798
affinity to MNV, resulting in the recovery of the catalytic activity of AuNPs, again generating a
799
blue product. The color intensity change was proportional to the amount of MNV in the samples.
800
On the contrary, the MNV-specific AG3 aptamers had no affinity to other contaminants, thus the
801
catalytic activity of AuNPs couldn’t be recovered and no color change with the existence of 30
802
nonspecific targets. By the combination between the peroxidase-like activity of AuNPs and high
803
target specificity of MNV-specific AG3 aptamers, an ultrasensitive colorimetric biosensor was
804
established for the rapid and selective detection of MNV. With the proposed colorimetric biosensor,
805
the MNV was detected with a LOD of 20 viruses per assay equivalent to 200 viruses/mL[147].
806
4 Conclusion and prospective
807
Food safety as a hot topic of international concern has attracted more and more attentions
808
around the world. The hazardous substances in food (food contaminants) can cause a huge threat
809
to public health and serious economic loss in food industry [149, 150]. Therefore, the effective
810
detection strategies of food contaminants are of great importance for guarding food safety. To date,
811
a great many traditional strategies have been well constructed for the detection of food
812
contaminants, including HPLC, HPLC-MS, GC-MS, PCR, and so on. Though these methods show
813
high sensitivity, accuracy, and reliability for the detection of food contaminants, they are
814
complicated, laborious, and time consuming, particularly depending on the expensive instruments
815
with well-trained personnel. Thus, they are hard to meet the requirements of the fast and on-site
816
screening of massive samples and apply in some situations like in some developing countries and
817
poor areas without any detection equipment and specialists [2, 6]. Excitingly, recently, the
818
nanozymes as an emerging initiate also has provided some potential opportunities to response
819
some challenges from food safety. Nanozymes for the construction of biosensors has accelerated
820
the development of analytical science for rapid, convenient, efficient, and sensitive determination
821
of food contaminants. In this review, we summarize the advances on nanozymes-based biosensors,
822
including colorimetric biosensors, fluorescence biosensors, chemiluminescent biosensors,
823
electrochemical biosensors, SERS-based biosensors, and other biosensors. Impressively, the
824
applications of the nanozymes-based biosensors in the detection of food contaminants (including
825
mycotoxins, antibiotics, pesticides, pathogens, intentional adulteration, metal ions, and other food
826
contaminants) also have been comprehensively summarized. To promote the development of
827
nanozymes-based biosensors and their applications in the detection of food contaminants, the
828
following challenges and obstacles should be considered in future studies:
829
(1) Nanozyme as an excellent alternative of biological enzyme for signal production and 31
830
amplification play an immense role in the construction of nanozymes-based biosensors.
831
However, compared to the natural enzymes, the catalytic activity of nanozymes is still
832
relatively low. Integrating biological enzymes or nanozymes into the mesoporous
833
nanomaterials such as MOFs, COFs, mesoporous silica, mesoporous carbon, and hydrogels to
834
prepare the integrated nanozymes (INAzymes) maybe a promising strategy to obtain highly
835
active nanozymes [151-156]. In addition, most of nanozymes can hardly catalyze one specific
836
substrate like biological enzymes. Therefore, nanozymes with high catalytic activity, excellent
837
selectivity and specificity remain to be further developed for the construction of
838
nanozymes-based biosensors. Molecular imprinting technology as a potential tool has been
839
used to improve the specificity and selectivity of nanozymes [157-160]. Anchoring the
840
molecularly imprinted polymers onto the nanozymes is a promising method to develop new
841
nanozymes with high selectivity and specificity [161]. In addition, at present, most of the
842
nanozymes only have an oxidase-like activity, which are monotonous compared with
843
biological enzymes. Therefore, the nanozymes with diverse catalytic activity like hydrolase
844
and synthetase remain to be further developed for the construction of nanozymes-based
845
biosensors.
846
(2) To date, plenty of nanozymes-based biosensors have been successfully developed, but these
847
biosensors still need great improvement in detection performances. For instance, the detection
848
accuracy and sensitivity of nanozymes-based colorimetric biosensors are easily influenced by
849
the interference generated from the sample background color. The nanozymes-based
850
fluorescence biosensor, chemiluminescent biosensor, and electrochemical biosensor possess
851
the linear resolution over wide ranges, and can be widely applied to the semi-quantitative and
852
qualitative preliminary screening. Nevertheless, these biosensors all need the dedicated
853
equipment with high precision, accurate functional programs, and professional operators.
854
Moreover, owing to the electrode fouling and the requirement of charging, the electrochemical
855
biosensors suffer from the poor stability and repeatability and the requirement of analytes’
856
outstanding electroactivity. Furthermore, the emerging nanozymes-based SERS biosensors
857
often suffer from the interference from complex samples. Because of the complex food matrix
858
and trace level of food contaminants, the nanozymes-based biosensors for accurate detection
859
of food contaminants in food samples are full of huge challenges. To overcome these 32
860
challenges, the reported nanozymes-based biosensors should be further studied to improve
861
their sensitivity, stability, and repeatability. In addition, the simultaneous emergences of
862
multiple food contaminants in food also bring a great challenge for food safety assay.
863
Therefore, the development of nanozymes-based biosensors with multi-modes for the accurate
864
determination of multiple food contaminants is an extremely promising for food safety assay.
865
For example, the nanozymes can be coupled with the emerging techniques such as
866
electrochemiluminescence (ECL), surface-plasmon resonance (SPR), LAMP, and smartphone
867
to develop new multi-mode nanozymes-based biosensors for the rapid, sensitive, and accurate
868
detection of food contaminants.
869
(3) Currently, a large number of nanozymes-based biosensors have been developed for the
870
detection of food contaminants. However, there are few biosensors used for development of
871
detection devices. To meet the needs of market and customers, some inexpensive, simple,
872
miniaturized, high-throughput, and portable equipment based on nanozymes-based biosensors
873
show great prospective for the rapid determination of food contaminants.
874
Acknowledgement
875
This work was supported by the National R&D Key Programme of China (No.
876
2017YFE0110800), the Natural Science Foundation of Shandong Province (ZR2017JL012), the
877
National Natural Science Foundation of China (21677085 and 31801454), the Science and
878
Technology Nova Plan of Shaanxi Province (2019KJXX-010), the Youth Innovation Team of
879
Shaanxi Universities(Food Quality and Safety), and the Innovation platform for the development
880
and construction of special project of Key Laboratory of Tibetan Medicine Research of Qinghai
881
Province (No. 2017-ZJ-Y11).
882 883 884 885 886 887 888 889 890 891 892
References [1]
J.-M. Liu, Y. Hu, Y.-K. Yang, H. Liu, G.-Z. Fang, X. Lu, S. Wang, Trends Food Sci. Technol. 71 (2018) 94.
[2]
M. Lv, Y. Liu, J. Geng, X. Kou, Z. Xin, D. Yang, Biosens. Bioelectron. 106 (2018) 122.
[3] B. Socas-Rodríguez, J. González-Sálamo, J. Hernández-Borges, M.Á. Rodríguez-Delgado, TrAC Trend. Anal. Chem. 96 (2017) 172. [4] R. Sharma, K.S.M.S. Raghavarao, in: A. López Rubio, M.J. Fabra Rovira, M. martínez Sanz and L.G. Gómez-Mascaraque (Eds.), Chapter 6 - Nanoparticle-Based Aptasensors for Food Contaminant Detection, Elsevier. 2019, pp. 123. [5]
Y. Jiang, D.-W. Sun, H. Pu, Q. Wei, Trends Food Sci. Technol. 75 (2018) 10.
[6]
Y. Li, Z. Wang, L. Sun, L. Liu, C. Xu, H. Kuang, TrAC Trend. Anal. Chem. 113 (2019) 74.
[7]
R. Sharma, K.V. Ragavan, M.S. Thakur, K.S.M.S. Raghavarao, Biosens. Bioelectron. 74 (2015) 612. 33
893 894 895 896 897 898 899 900 901 902 903 904 905 906 907 908 909 910 911 912 913 914 915 916 917 918 919 920 921 922 923 924 925 926 927 928 929 930 931 932 933 934 935 936
[8]
H. Jafarizadeh-Malmiri, Z. Sayyar, N. Anarjan, A. Berenjian, Nano-sensors in Food Nanobiotechnology, Springer International Publishing. Cham, 2019, pp. 81.
[9]
N. Li, D. Wu, X. Li, X. Zhou, G. Fan, G. Li, Y. Wu, Food Chem. (2019) 125455. https://doi.org/10.1016/j.foodchem.2019.125455
[10]
P. Wang, L. Zhang, W. Zheng, L. Cong, Z. Guo, Y. Xie, L. Wang, R. Tang, Q. Feng, Y. Hamada, K. Gonda, Z. Hu, X. Wu, X. Jiang, Angew. Chem. Int. Edit. 57 (2018) 1491.
[11] Y. Lei, L. Tang, Y. Xie, Y. Xianyu, L. Zhang, P. Wang, Y. Hamada, K. Jiang, W. Zheng, X. Jiang, Nat. Commun. 8 (2017) 15130. [12] B. Ran, W. Zheng, M. Dong, Y. Xianyu, Y. Chen, J. Wu, Z. Qian, X. Jiang, Anal. Chem. 90 (2018) 8234. [13] Y. Huang, J. Ren, X. Qu, Chem. Rev. 119 (2019) 4357. [14] J. Wu, X. Wang, Q. Wang, Z. Lou, S. Li, Y. Zhu, L. Qin, H. Wei, Chem. Soc. Rev. 48 (2019) 1004. [15] M. Liang, X. Yan, Acc. Chem. Res. 52 (2019) 2190. [16] Y. Huang, J. Ren, X. Qu, Chem. Rev. (2019). https://doi.org/10.1021/acs.chemrev.8b00672 [17] H. Sun, Y. Zhou, J. Ren, X. Qu, Angew. Chem. Int. Edit. 57 (2018) 9224. [18] Y. Lv, M. Ma, Y. Huang, Y. Xia, Chem. Eur. J. 25 (2019) 954. [19] J. Wu, X. Wang, Q. Wang, Z. Lou, S. Li, Y. Zhu, L. Qin, H. Wei, Chem. Soc. Rev. (2019). 10.1039/C8CS00457A [20] H. Wei, E.K. Wang, Chem. Soc. Rev. 42 (2013) 6060. [21] F. Attar, M.G. Shahpar, B. Rasti, M. Sharifi, A.A. Saboury, S.M. Rezayat, M. Falahati, J. Mol. Liq. 278 (2019) 130. [22] S. Li, X. Liu, H. Chai, Y. Huang, Trac. Trends Anal. Chem. 105 (2018) 391. [23] A. Mohamad, H. Teo, N.A. Keasberry, M.U. Ahmed, Crit. Rev. Biotechnol. 39 (2019) 50. [24] S. Singh, Front. Chem. 7 (2019). [25] D.P. Cormode, L. Gao, H. Koo, Trends Biotechnol. 36 (2018) 15. [26] A.K. Srivastava, A. Dev, S. Karmakar, Environ. Chem. Lett. 16 (2018) 161. [27] L. Hu, H. Liao, L. Feng, M. Wang, W. Fu, Anal. Chem. 90 (2018) 6247. [28] L. Qin, X. Wang, Y. Liu, H. Wei, Anal. Chem. 90 (2018) 9983. [29] H. Wang, K. Wan, X. Shi, Adv. Mater. (2018) 1805368. [30] G. Chen, H.-H. Lan, S.-L. Cai, B. Sun, X.-L. Li, Z.-H. He, S.-R. Zheng, J. Fan, Y. Liu, W.-G. Zhang, ACS Appl. Mater. Interfaces 11 (2019) 12830. [31] X. Zhang, R. Huang, S. Gopalakrishnan, R. Cao-Milán, V.M. Rotello, Trend. Chem. 1 (2019) 90. [32] L. Huang, Q. Zhu, J. Zhu, L. Luo, S. Pu, W. Zhang, W. Zhu, J. Sun, J. Wang, Inorg. Chem. (2019). https://doi.org/10.1021/acs.inorgchem.8b03193 [33] L. Zheng, G. Cai, S. Wang, M. Liao, Y. Li, J. Lin, Biosens. Bioelectron. 124-125 (2019) 143. [34] K. Yin, An Ultrasensitive Colorimetric Biosensor for Copper Ion Detection, Springer Singapore. Singapore, 2020, pp. 37. [35] H. Aldewachi, T. Chalati, M.N. Woodroofe, N. Bricklebank, B. Sharrack, P. Gardiner, Nanoscale 10 (2018) 18. [36] N. Cheng, C. Zhu, Y. Wang, D. Du, M.-J. Zhu, Y. Luo, W. Xu, Y. Lin, J. Anal. Test. 3 (2019) 99. [37] W. Zheng, H. Li, W. Chen, J. Ji, X. Jiang, Anal. Chem.88 (2016) 4140. [38] I.M. Khoris, K. Takemura, J. Lee, T. Hara, F. Abe, T. Suzuki, E.Y. Park, Biosens. Bioelectron. 126 (2019) 425. [39] D. Wu, N. Hu, J. Liu, G. Fan, X. Li, J. Sun, C. Dai, Y. Suo, G. Li, Y. Wu, Talanta 190 (2018) 103. [40] H.-Q. Zheng, C.-Y. Liu, X.-Y. Zeng, J. Chen, J. Lü, R.-G. Lin, R. Cao, Z.-J. Lin, J.-W. Su, Inorg. Chem. 57 34
937 938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953 954 955 956 957 958 959 960 961 962 963 964 965 966 967 968 969 970 971 972 973 974 975 976 977 978 979 980
(2018) 9096. [41] H. Chen, Q. Qiu, S. Sharif, S. Ying, Y. Wang, Y. Ying, ACS Appl. Mater. Interfaces 10 (2018) 24108. [42] S. Sun, R. Zhao, S. Feng, Y. Xie, Microchim. Acta 185 (2018) 535. [43] L. Huang, Q. Zhu, J. Zhu, L. Luo, S. Pu, W. Zhang, W. Zhu, J. Sun, J. Wang, Inorg. Chem. 58 (2019) 1638. [44] L. Huang, D.-W. Sun, H. Pu, Q. Wei, L. Luo, J. Wang, Sensor. Actuator. B Chem. 290 (2019) 573. [45] A. Bigdeli, F. Ghasemi, H. Golmohammadi, S. Abbasi-Moayed, M.A.F. Nejad, N. Fahimi-Kashani, S. Jafarinejad, M. Shahrajabian, M.R. Hormozi-Nezhad, Nanoscale 9 (2017) 16546. [46] M.H. Lee, J.S. Kim, J.L. Sessler, Chem. Soc. Rev. 44 (2015) 4185. [47] S. Hu, J. Yan, X. Huang, L. Guo, Z. Lin, F. Luo, B. Qiu, K.-Y. Wong, G. Chen, Sensor. Actuator. B Chem. 267 (2018) 312. [48] T. Lin, Y. Qin, Y. Huang, R. Yang, L. Hou, F. Ye, S. Zhao, Chem. Commun. 54 (2018) 1762. [49] S. Huang, E. Yang, J. Yao, Y. Liu, Q. Xiao, Microchim. Acta 185 (2018) 394. [50] S. Lu, G. Li, Z. Lv, N. Qiu, W. Kong, P. Gong, G. Chen, L. Xia, X. Guo, J. You, Y. Wu, Biosens. Bioelectron. 85 (2016) 358. [51] G. Li, W. Kong, M. Zhao, S. Lu, P. Gong, G. Chen, L. Xia, H. Wang, J. You, Y. Wu, Biosens. Bioelectron. 79 (2016) 728. [52] M.
Majdinasab,
K.
Mitsubayashi,
J.L.
Marty,
Trends
Biotechnol.
(2019).
https://doi.org/10.1016/j.tibtech.2019.01.004 [53] S.M. Yoo, S.Y. Lee, Trends Biotechnol. 34 (2016) 7. [54] C.-W. Lien, B. Unnikrishnan, S.G. Harroun, C.-M. Wang, J.-Y. Chang, H.-T. Chang, C.-C. Huang, Biosens. Bioelectron. 102 (2018) 510. [55] T. Lin, Y. Qin, Y. Huang, R. Yang, L. Hou, F. Ye, S. Zhao, Chem. Commun. 54 (2018) 1762. [56] N. Bagheri, A. Khataee, J. Hassanzadeh, B. Habibi, Spectrochim. Acta A 209 (2019) 118. [57] N. Bagheri, A. Khataee, B. Habibi, J. Hassanzadeh, Talanta 179 (2018) 710. [58] M. Nasir, M.H. Nawaz, U. Latif, M. Yaqub, A. Hayat, A. Rahim, Microchim. Acta 184 (2017) 323. [59] M. Iranifam, Trac. Trends Anal. Chem. 80 (2016) 387. [60] M. Iranifam, Trac. Trends Anal. Chem. 51 (2013) 51. [61] Y. He, B. Xu, W. Li, H. Yu, J. Agric. Food Chem. 63 (2015) 2930. [62] L. He, Z.W. Jiang, W. Li, C.M. Li, C.Z. Huang, Y.F. Li, ACS Appl. Mater. Interfaces 10 (2018) 28868. [63] F. Luo, Y. Lin, L. Zheng, X. Lin, Y. Chi, ACS Appl. Mater. Interfaces 7 (2015) 11322. [64] Y. Li, X. You, X. Shi, Food Anal. Methods 10 (2017) 626. [65] X. Yi, W. Dong, X. Zhang, J. Xie, Y. Huang, Anal. Bioanal. Chem. 408 (2016) 8805. [66] X. Qian Tang, Y. Dan Zhang, Z. Wei Jiang, D. Mei Wang, C. Zhi Huang, Y. Fang Li, Talanta 179 (2018) 43. [67] S. Chaiyo, E. Mehmeti, W. Siangproh, T.L. Hoang, H.P. Nguyen, O. Chailapakul, K. Kalcher, Biosens. Bioelectron. 102 (2018) 113. [68] S. Cinti, R. Cusenza, D. Moscone, F. Arduini, Talanta 187 (2018) 59. [69] Y. Liu, H. Li, L. Lu, B. Sun, L. Huang, H. Chen, W. Qiu, J. Tao, P. Zhao, J. Electrochem. Soc. 166 (2019) B133. [70]
H. Liang, H. Xu, Y. Zhao, J. Zheng, H. Zhao, G. Li, C.-P. Li, Biosens. Bioelectron. 144 (2019) 111691. https://doi.org/10.1016/j.bios.2019.111691
[71] H. Chen, T. Yang, F. Liu, W. Li, Sensor. Actuator. B Chem. 286 (2019) 401. [72] Y. Wei, Y. Li, N. Li, Y. Zhang, T. Yan, H. Ma, Q. Wei, Biosens. Bioelectron. 79 (2016) 482. [73] R. Wang, W.-D. Liu, A.-J. Wang, Y. Xue, L. Wu, J.-J. Feng, Biosens. Bioelectron. 99 (2018) 458. [74]
R. Wang, A.-J. Wang, W.-D. Liu, P.-X. Yuan, Y. Xue, X. Luo, J.-J. Feng, Biosens. Bioelectron. 102 35
981 982 983 984 985 986 987 988 989 990 991 992 993 994 995 996 997 998 999 1000 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 1018 1019 1020 1021 1022 1023 1024
(2018)276. [75] X. Zheng, L. Li, K. Cui, Y. Zhang, L. Zhang, S. Ge, J. Yu, ACS Appl. Mater. Interfaces 10 (2018) 3333. [76] S.S. Menon, S.V. Chandran, A. Koyappayil, S. Berchmans, ChemistrySelect 3 (2018) 8319. [77] W. Meng, Y. Wen, L. Dai, Z. He, L. Wang, Sensor. Actuator. B Chem. 260 (2018) 852. [78] Y. Li, C. Yu, B. Yang, Z. Liu, P. Xia, Q. Wang, Biosens. Bioelectron. 102 (2018) 307. [79] S.-S. Li, W.-Y. Zhou, M. Jiang, Z. Guo, J.-H. Liu, L. Zhang, X.-J. Huang, Anal. Chem. 90 (2018) 4569. [80] X. Tian, L. Liu, Y. Li, C. Yang, Z. Zhou, Y. Nie, Y. Wang, Sensor. Actuator. B Chem. 256 (2018) 135. [81] F. Li, X. Wang, X. Sun, Y. Guo, Rsc Advances 7 (2017) 38981. [82] C. Wang, C. Liu, J. Luo, Y. Tian, N. Zhou, Anal. Chim. Acta 936 (2016) 75. [83] L. Tian, J. Qi, K. Qian, O. Oderinde, Y. Cai, C. Yao, W. Song, Y. Wang, Sensor. Actuator. B Chem. 260 (2018) 676. [84] P. Wu, X. Hou, J.-J. Xu, H.-Y. Chen, Nanoscale 8 (2016) 8427. [85] Z. Wang, S. Zong, L. Wu, D. Zhu, Y. Cui, Chem. Rev. 117 (2017) 7910. [86] H.K. Lee, Y.H. Lee, C.S.L. Koh, G.C. Phan-Quang, X. Han, C.L. Lay, H.Y.F. Sim, Y.-C. Kao, Q. An, X.Y. Ling, Chem. Soc. Rev. (2019). [87] R.A. Tripp, R.A. Dluhy, Y. Zhao, Nano Today 3 (2008) 31. [88] X. Ma, S. Wen, X. Xue, Y. Guo, J. Jin, W. Song, B. Zhao, ACS Appl. Mater. Interfaces 10 (2018) 25726. [89] Y. Hu, H. Cheng, X. Zhao, J. Wu, F. Muhammad, S. Lin, J. He, L. Zhou, C. Zhang, Y. Deng, P. Wang, Z. Zhou, S. Nie, H. Wei, ACS Nano 11 (2017) 5558. [90] M.J. Tan, Z.-Y. Hong, M.-H. Chang, C.-C. Liu, H.-F. Cheng, X.J. Loh, C.-H. Chen, C.-D. Liao, K.V. Kong, Biosens. Bioelectron. 96 (2017) 167. [91] C. Li, Y. Liu, A. Liang, Z. Jiang, Sensor. Actuator. B Chem. 263 (2018) 183. [92] Z. Jiang, P. Gao, L. Yang, C. Huang, Y. Li, Anal. Chem. 87 (2015) 12177. [93] Y. Hu, H. Cheng, X. Zhao, J. Wu, F. Muhammad, S. Lin, J. He, L. Zhou, C. Zhang, Y. Deng, ACS Nano 11 (2017) 5558. [94] J. Wu, K. Qin, D. Yuan, J. Tan, L. Qin, X. Zhang, H. Wei, ACS Appl. Mater. Interfaces 10 (2018) 12954. [95] H. Ouyang, S. Ling, A. Liang, Z. Jiang, Sensor. Actuator. B Chem. 258 (2018) 739. [96] C. Li, H. Wang, Y. Luo, G. Wen, Z. Jiang, Food Chem. 289 (2019) 531. [97] Y. Su, D. Wu, J. Chen, G. Chen, N. Hu, H. Wang, P. Wang, H. Han, G. Li, Y. Wu, Anal. Chem. (2019). https://doi.org/10.1021/acs.analchem.9b02233 [98] F. Zheng, W. Ke, L. Shi, H. Liu, Y. Zhao, Anal. Chem. (2019). https://doi.org/10.1021/acs.analchem.9b02469 [99] L. Zhang, Y. Chen, N. Cheng, Y. Xu, K. Huang, Y. Luo, P. Wang, D. Duan, W. Xu, Anal. Chem. 89 (2017) 10194. [100] J. Chen, Z. Li, J. Ge, R. Yang, L. Zhang, L.-b. Qu, H.-q. Wang, L. Zhang, Talanta 139 (2015) 226. [101]
X. Li, H. Li, X. Li, Q. Zhang, Food Chem. 233 (2017) 290.
[102] S.M. Taghdisi, N.M. Danesh, M. Ramezani, A.S. Emrani, K. Abnous, ACS Appl. Mater. Interfaces 10 (2018) 12504. [103]
L. Huang, K. Chen, W. Zhang, W. Zhu, X. Liu, J. Wang, R. Wang, N. Hu, Y. Suo, J. Wang, Sensor. Actuator. B Chem. 269 (2018) 79.
[104] D. Chudobova, K. Cihalova, S. Skalickova, J. Zitka, M.A.M. Rodrigo, V. Milosavljevic, D. Hynek, P. Kopel, R. Vesely, V. Adam, R. Kizek, Electrophoresis 36 (2015) 457. [105] R.E. Baynes, K. Dedonder, L. Kissell, D. Mzyk, T. Marmulak, G. Smith, L. Tell, R. Gehring, J. Davis, J.E. Riviere, Food Chem. Toxicol. 88 (2016) 112. [106]
Q. Ma, Y. Wang, J. Jia, Y. Xiang, Food Chem. 249 (2018) 98. 36
1025 1026 1027 1028 1029 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068
[107]
Y. Yang, S. Yin, Y. Li, D. Lu, J. Zhang, C. Sun, Trac. Trends Anal. Chem. 95 (2017) 1.
[108]
Z. Khoshbin, A. Verdian, M.R. Housaindokht, M. Izadyar, Z. Rouhbakhsh, Biosens. Bioelectron. 122 (2018) 263.
[109] T.K. Sharma, R. Ramanathan, P. Weerathunge, M. Mohammadtaheri, H.K. Daima, R. Shukla, V. Bansal, Chem. Commun. 50 (2014) 15856. [110]
C. Wang, D. Chen, Q. Wang, R. Tan, Biosens. Bioelectron. 91 (2017) 262.
[111] M. Govindasamy, S.-M. Chen, V. Mani, R. Devasenathipathy, R. Umamaheswari, K. Joseph Santhanaraj, A. Sathiyan, J. Colloid. Interface Sci. 485 (2017) 129. [112] Z. Chen, G. Lai, S. Liu, A. Yu, Sensor. Actuator. B Chem. 273 (2018) 1762. [113] R. Zeng, Z. Luo, L. Zhang, D. Tang, Anal. Chem. 90 (2018) 12299. [114] H. Chang, J. Lv, H. Zhang, B. Zhang, W. Wei, Y. Qiao, Biosens. Bioelectron. 87 (2017) 579. [115]
P. Weerathunge, R. Ramanathan, R. Shukla, T.K. Sharma, V. Bansal, Anal. Chem. 86 (2014) 11937.
[116] L. Zeng, D. Zhou, J. Wu, C. Liu, J. Chen, Anal. Methods 11 (2019) 1168. [117]
S. Biswas, P. Tripathi, N. Kumar, S. Nara, Sensor. Actuator. B Chem. 231 (2016) 584.
[118] S. Singh, P. Tripathi, N. Kumar, S. Nara, Biosens. Bioelectron. 92 (2017) 280. [119] Y. Zhao, M. Yang, Q. Fu, H. Ouyang, W. Wen, Y. Song, C. Zhu, Y. Lin, D. Du, Anal. Chem. 90 (2018) 7391. [120] L. Qiu, P. Lv, C. Zhao, X. Feng, G. Fang, J. Liu, S. Wang, Sensor. Actuator. B Chem. 286 (2019) 386. [121]
L. Zhang, R. Huang, W. Liu, H. Liu, X. Zhou, D. Xing, Biosens. Bioelectron. 86 (2016) 1.
[122] X. Zhao, C.-W. Lin, J. Wang, D.-H. Oh, Advances in Rapid Detection Methods for Foodborne Pathogens, J. Microbiol. Biotechnol 24 (2014) 297. [123] J. Hu, Y.-Z. Jiang, M. Tang, L.-L. Wu, H.-y. Xie, Z.-L. Zhang, D.-W. Pang, Anal. Chem. 91 (2019) 1178. [124] S. Wang, W. Deng, L. Yang, Y. Tan, Q. Xie, S. Yao, ACS Appl. Mater. Interfaces 9 (2017) 24440. [125]
N. Cheng, Y. Song, M.M.A. Zeinhom, Y.-C. Chang, L. Sheng, H. Li, D. Du, L. Li, M.-J. Zhu, Y. Luo, W. Xu, Y. Lin, ACS Appl. Mater. Interfaces 9 (2017) 40671.
[126]
J. Han, L. Zhang, L. Hu, K. Xing, X. Lu, Y. Huang, J. Zhang, W. Lai, T. Chen, J. Dairy Sci. 101 (2018) 5770.
[127]
H. Mahmoudi-Moghaddam, S. Tajik, H. Beitollahi, Food Chem. 286 (2019) 191.
[128]
J. Li, H. Feng, J. Li, Y. Feng, Y. Zhang, J. Jiang, D. Qian, Electrochim. Acta 167 (2015) 226.
[129]
L. Liu, J. Du, W.-e. Liu, Y. Guo, G. Wu, W. Qi, X. Lu, Anal. Bioanal. Chem. 411 (2019) 2189.
[130]
D. Deng, H. Yang, C. Liu, K. Zhao, J. Li, A. Deng, Food Chem. 277 (2019) 595.
[131]
S. Palanisamy, T. Kokulnathan, S.-M. Chen, V. Velusamy, S.K. Ramaraj, J Electroanal Chem 794 (2017) 64.
[132]
Q. Ye, X. Chen, J. Yang, D. Wu, J. Ma, Y. Kong, Food Chem. 287 (2019) 375.
[133]
B. Zhao, Q. Huang, L. Dou, T. Bu, K. Chen, Q. Yang, L. Yan, J. Wang, D. Zhang, Sensor. Actuator. B Chem. 275 (2018) 223.
[134] Y. Chen, Z. Huang, S. Hu, G. Zhang, J. Peng, J. Xia, W. Lai, Anal. Biochem. 577 (2019) 45. [135]
L. Zhang, Q. Wang, Y. Qi, L. Li, S. Wang, X. Wang, Sensor. Actuator. B Chem. 288 (2019) 347.
[136]
X. Li, J. Ping, Y. Ying, Trac. Trends Anal. Chem. 113 (2019) 1.
[137]
S. Zhang, D. Zhang, X. Zhang, D. Shang, Z. Xue, D. Shan, X. Lu, Anal. Chem. 89 (2017) 3538.
[138]
H.N. Kim, W.X. Ren, J.S. Kim, J. Yoon, Chem. Soc. Rev. 41 (2012) 3210.
[139]
L.-L. Wu, Z.-J. Qian, Z.-J. Xie, Y.-Y. Zhang, C.-F. Peng, Chinese J. Anal. Chem. 45 (2017) 471.
[140]
W. Li, B. Chen, H. Zhang, Y. Sun, J. Wang, J. Zhang, Y. Fu, Biosens. Bioelectron.66 (2015) 251.
[141]
H. Li, H. Liu, J. Zhang, Y. Cheng, C. Zhang, X. Fei, Y. Xian, ACS Appl. Mater. Interfaces 9 (2017) 40716. 37
1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112
[142]
Y. Xiong, L. Su, H. Yang, P. Zhang, F. Ye, New J. Chem. 39 (2015) 9221.
[143]
J. Zhao, P. Jing, S. Xue, W. Xu, Biosens. Bioelectron. 87 (2017) 157.
[144]
K.N. Han, J.-S. Choi, J. Kwon, Sci. Rep. 7 (2017) 2806.
[145]
W. Zhang, X. Niu, S. Meng, X. Li, Y. He, J. Pan, F. Qiu, H. Zhao, M. Lan, Sensor. Actuator. B Chem. 273 (2018) 400.
[146]
W.-J. Shen, Y. Zhuo, Y.-Q. Chai, R. Yuan, Anal. Chem. 87 (2015) 11345.
[147]
P. Weerathunge, R. Ramanathan, V.A. Torok, K. Hodgson, Y. Xu, R. Goodacre, B.K. Behera, V. Bansal, Anal. Chem. 91 (2019) 3270.
[148] H. Yang, J. Zha, P. Zhang, Y. Qin, T. Chen, F. Ye, Sensors and Actuators B: Chemical 247 (2017) 469. [149] A.M. Vaidya, U.S. Annapure, in: M. Kuddus (Ed.), Chapter 38 - Enzymes in Biosensors for Food Quality Assessment, Academic Press. 2019, pp. 659. [150]
L. Wu, G. Li, X. Xu, L. Zhu, R. Huang, X. Chen, TrAC Trends in Analytical Chemistry 113 (2019) 140.
[151]
J. Wu, S. Li, H. Wei, Chem. Commun. 54 (2018) 6520.
[152]
H. Cheng, L. Zhang, J. He, W. Guo, Z. Zhou, X. Zhang, S. Nie, H. Wei, Anal. Chem. 88 (2016) 5489.
[153]
Q. Sun, C.-W. Fu, B. Aguila, J. Perman, S. Wang, H.-Y. Huang, F.-S. Xiao, S. Ma, J. Am. Chem. Soc. 140 (2018) 984.
[154] Q. Yang, Q. Xu, H.-L. Jiang, Chem. Soc. Rev. 46 (2017) 4774. [155] X. Lian, Y. Fang, E. Joseph, Q. Wang, J. Li, S. Banerjee, C. Lollar, X. Wang, H.-C. Zhou, Chem. Soc. Rev. 46 (2017) 3386. [156]
X. Shi, Y. Yao, Y. Xu, K. Liu, G. Zhu, L. Chi, G. Lu, ACS Appl. Mater. Interfaces 9 (2017) 7481.
[157]
L. Chen, S. Xu, J. Li, Chem. Soc. Rev. 40 (2011) 2922.
[158]
Z. Zhang, B. Liu, J. Liu, Small 13 (2017).
[159]
L. Fan, D. Lou, H. Wu, X. Zhang, Y. Zhu, N. Gu, Y. Zhang, Adv. Mater. Interfaces 5 (2018) 1801070.
[160]
K. Fan, H. Wang, J. Xi, Q. Liu, X. Meng, D. Duan, L. Gao, X. Yan, Chem. Commun. 53 (2017) 424.
[161]
Z. Zhang, X. Zhang, B. Liu, J. Liu, J. Am. Chem. Soc. 139 (2017) 5412.
[162]
J. Lee, C.H. Jeon, S.J. Ahn, T.H. Ha, Analyst 139 (2014) 1622.
[163]
Y. Wang, Y. Sun, H. Dai, P. Ni, S. Jiang, W. Lu, Z. Li, Z. Li, Sensor. Actuator. B Chem. 236 (2016) 621.
[164]
D. Song, Y. Li, X. Lu, M. Sun, H. Liu, G. Yu, F. Gao, Anal. Chim. Acta 982 (2017) 168.
[165] M. Liang, K. Fan, Y. Pan, H. Jiang, F. Wang, D. Yang, D. Lu, J. Feng, J. Zhao, L. Yang, X. Yan, Anal. Chem. 85 (2013) 308. [166] R. Thiramanas, K. Jangpatarapongsa, P. Tangboriboonrat, D. Polpanich, Anal. Chem. 85 (2013) 5996. [167]
X. Wei, W. Zhou, S.T. Sanjay, J. Zhang, Q. Jin, F. Xu, D.C. Dominguez, X. Li, Anal. Chem. 90 (2018) 9888.
[168]
Z. Zhuang, H. Lin, X. Zhang, F. Qiu, H. Yang, Microchim. Acta 183 (2016) 2807.
[169]
H. Li, H. Liu, J. Zhang, Y. Cheng, C. Zhang, X. Fei, Y. Xian, ACS Appl. Mater. Interfaces 9 (2017) 40716.
38
1113 1114 1115 1116 1117
Graphical abstract
1118 1119
The construction of nanozymes-based biosensors and the applications of nanozymes-based
1120
biosensors in the food safety assay
39
1121 1122
Fig.1. (a) Illustration of the CS-MoSe2 NS-based versatile colorimetric detection of mercury
1123
ions[43]. (b) The colorimetric sensing principle of AChE activity and pesticides based on
1124
degradable MnOOH nanozyme[44].
40
1125 1126
Fig.2. Design for the detection of OPs by AChE inhibition method and peroxidase activity of
1127
magnetic ZIF-8[56].
1128
1129 1130
Fig.3. Schematic illustration for fabricating Cu-MOF and modified electrodes for sensing analysis
1131
of nitrite [71].
41
1132 1133
Fig.4. (a) Schematic illustration of the AuNPs doped COF nanozyme-based SERS immunosorbent
1134
assay [97]. (b) Schematic illustration of the fabrication of Raman IS-aptasensor based on Au-Ag
1135
janus NPs-mxenes assemblies for the detection of OTA [98].
42
1136 1137
Fig.5. (a) (Ⅰ) Schematic image for selective determination of patulin based on its inhibiting effect
1138
on mimetic activity MIP-capped AgNPs@ZnMOF; (Ⅰ) closer look on the location of patulin in
1139
MIP sites and its interaction with specific functional groups[57]. (b) MnCo2O4 oxidase
1140
mimic-based colorimetric assay for OTA detection. (Ⅰ) the principle of the sensing approach. (Ⅰ)
1141
the UV-vis spectra recording the reaction system in the increasing amount of OTA. (Ⅰ) calibration
1142
plots of the absorbance of oxTMB versus the OTA concentration under the optimum conditions
1143
[103]. 43
1144 1145
Fig.6. (a) Schematic illustration of the AuNPs based colorimetric method for detecting kanamycin.
1146
The illustration is not drawn to scale [110]. (b) Determination of chloramphenicol using
1147
MoS2/f-MWCNTs nanocomposite for the determination of CAP in food, biological and
1148
pharmaceutical samples [111].
44
1149 1150
Fig.7. (a) Schematic illustration of the principle of Pd@AuNR nanozyme assay for malathions
1151
[118]. (b) Schematic diagram of the principle of the CL sensor array based on the triple-channel
1152
properties of the Lum-AgNP-H2O2 CL system [61]. (c) Illustration of the principle of nanozyme-
1153
and ambient light-based smartphone platform for simultaneous detection of dual biomarkers from
1154
exposure to OPs [119].
45
1155 1156
Fig.8. (a) Schematic representation for the preparation of Fe3O4 NPC (Ⅰ), the principle of the
1157
Fe3O4 NP-based biosensor (Ⅰ), and the Fe3O4 NPC catalyzed signal amplification biosensor
1158
(Ⅰ)[121]. (b) Schematic illustration of colorimetric detection of target bacteria [124].
46
1159 1160
Fig.9. (a) (i) Schematic illustration of the PBNP-based LFA; (ii) Principle illustration of CL
1161
detection using the LFA strip; (iii) Interpretation of the assay results[133]. (b) Schematic
1162
illustration of the ultrasensitive electrochemical biosensor based on polyoxometalate and
1163
zirconium dioxide nanocomposites hybrids material for simultaneous determination of toxic
1164
clenbuterol and ractopamine [135]. 47
1165
1166 1167
Fig.10. (a) Schematic illustration of the prepared process of the proposed biosensor for Pb2+
1168
detection [143]. (b) Mercury enhanced peroxidase-like activity of rGO/PEI/Pd nanohybrids and
1169
the reaction principle in this system [137].
48
1170 1171
Fig.11. (a) Schematic illustration of the fabrication of the aptasensor: (i) Preparation procedure of
1172
HP3/AuNPs/Cu-MOFs; (ii) Signal amplification strategy and the detection principle for LPS [146].
1173
(b) Working principle of the norovirus nanozyme aptasensor; schematic illustration outlining the
1174
steps involved during norovirus sensing [147].
1175 1176 1177 1178 1179 1180 1181 1182 1183 1184 49
1185 Analytes
Table 1 The reported nanozymes-based biosensors for the determination of food contaminants. Nanozyme-based biosensors
Nanozymes
Linear range
LOD
Food matrix
Ref.
Patulin
Fluorescence biosensor
AgNPs@ZnMOF
0.1-10 µmol/L
0.06 µmol/L
Apple juice, water
[57]
Zearalenone
Colorimetric biosensor
AuNPs
10-250 ng/mL
10 ng/mL
Corn and oil
[42]
Zearalenone
Colorimetric biosensor
AuNPs
20-80000 ng/L
10 ng/L
/
[102]
Ochratoxin A
Colorimetric biosensor
MnCo2O4
0.1-10 ng/mL
0.08 ng/mL
Maize
[103]
Ochratoxin A
Colorimetric biosensor
Hemin
/
0.4 ng/mL
/
[162]
Ochratoxin A
SERS-based biosensor
Au-Ag Janus NPs
/
1.28 pM
Red wine
[98]
Kanamycin
Electrochemical biosensor
AuNPs
0.1-60 nM
0.06 nM
Honey
[82]
Kanamycin
Electrochemical biosensor
AuNPs
10-450 nM
2.85 nM
Milk
[81]
Kanamycin
Colorimetric biosensor
AuNPs
0.1-20 nM, 20-300nM
0.1 nM
Milk and meat
[110]
Kanamycin
Electrochemical biosensor
MoS2/f-MWCNTs
0.08-1392 µM
0.015±0.003 µM
Milk, honey, and powdered milk
[111]
Kanamycin
Electrochemical biosensor
AuNP/HRP NPs
>four-order of magnitude
0.88 pg/mL
Milk
[112]
Kanamycin
Fluorescence biosensor
AuNPs
1-100 nM
1.49 nM
/
[109]
Kanamycin
Electrochemical biosensor
Pt NPs
0.2-50 pM
0.063 pM
Milk
[113]
Tetracyclines
Colorimetric biosensor
Fe3O4 NPs
100-1000 nM
45 nM
/
[163]
Oxytetracycline
Colorimetric biosensor
Fe3O4 NPs
50-1000 nM
26 nM
/
[163]
Toxycycline
Colorimetric biosensor
Fe3O4 NPs
50-1000 nM
48 nM
/
[163]
Chloramphenicol
Electrochemical biosensor
CS-AgI/TiO2
0.03-12.53 nM
0.03 nM
Milk, Honey, Egg
[114]
Malathion
Colorimetric biosensor
GNR nanozyme
/
1.78 µg/mL
Tap water
[117]
Malathion
Colorimetric biosensor
Pd@AuNR
/
60 ng/mL
Water
[118]
Malathion
Electrochemical biosensor
Pd-Cu NWs
5-1000 ppt, 500-3000 ppb
1.5 ppt
Courgettes, carrots, lettuces, and oranges
[164]
Ethoprophos
Chemiluminescent biosensor
AuNPs/MOGs(Fe)
5-800 nM
1 nM
Tap water
[62]
Mycotoxins
Antibiotics
Pesticides
50
Acetamiprid
Colorimetric biosensor
AuNPs
/
0.1 ppm
/
[115]
Acetamiprid
Colorimetric biosensor
DNAzymes
/
10 pM
Chinese cabbage, tomato, eggplant, and cucumber
[116]
Dimethoate
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Dipterex
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Carbofuran
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Chlorpyrifos
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Carbaryl
Chemiluminescent biosensor
Lum-AgNPs
/
24 µg/mL
Water
[61]
Ethyl paraoxon
Electrochemical biosensor
TiO2@DA@S/H/E
0.5-100µM
0.24 µM
Real samples
[120]
Methyl paraoxon
Electrochemical biosensor
TiO2@DA@S/H/E
0.5-100µM
0.24 µM
Real samples
[120]
Methyl parathion
Electrochemical biosensor
TiO2@DA@S/H/E
0.5-100µM
0.24 µM
Real samples
[120]
Methyl paraoxon
Colorimetric biosensor
Fe3O4 MNP
/
10 nM
Water
[165]
Acephate
Colorimetric biosensor
Fe3O4 MNP
/
5 µM
Water
[165]
Sarin
Colorimetric biosensor
Fe3O4 MNP
/
1 nM
Water
[165]
Diazinon
Fluorescence biosensor
Fe3O4 NPs@ZIF-8
0.5-500 nM
0.2 nM
Water, fruit juices
[56]
Omethoate
Colorimetric biosensor
γ-MnOOH
/
0.35 ng/mL in solution state; 10 ng/mL on test paper
Vegetable samples
[44]
Dichlorvos
Colorimetric biosensor
γ-MnOOH
/
0.14 ng/mL in solution state; 3 ng/mL on test paper
Vegetable samples
[44]
Vibrio cholerae
Colorimetric biosensor
MPNP
/
103 cfu/mL
Drinking and tap water
[166]
Enterobacter sakazakii
Other biosensor
Fe3O4NPs
2-10 cfu/mL
10 cfu/mL
Infant powder
[99]
Pathogens
51
Salmonella Enteritidis
Colorimetric biosensor
Fe-MOF NPs
34 cfu/mL
Milk
[36]
Listeria monocytogenes
Colorimetric biosensor
Fe3O4 NPC
5.4×103-108 cfu/mL
5.4×10 3 cfu/mL
Milk
[121]
Staphylococcus aureus
Colorimetric biosensor
Cu-MOF NPs
50-10000 cfu/mL
20 cfu/mL
Milk
[124]
Salmonella Enteritidis
Colorimetric biosensor
Pd@PtNPs
/
∼20 cfu/mL
Milk and ice cream
[125]
Escherichia coli O157:H7
Colorimetric biosensor
Pd@PtNPs
/
∼34 cfu/mL
Milk and ice cream
[125]
Escherichia coli O157:H7
Colorimetric biosensor
Pd@PtNPs
/
9×102 cfu/mL
Milk
[126]
Salmonella enterica
Colorimetric biosensor
PtNPs
/
10 cfu/mL
Apple juice
[167]
Escherichia coli
Colorimetric biosensor
PtNPs
/
10 cfu/mL
Apple juice
[167]
Listeria monocytogenes
Colorimetric biosensor
PtNPs
/
10 cfu/mL
Apple juice
[167]
Intentional adulteration Sudan I
Electrochemical biosensor
PtNPs
0.005-68.68µ M
1.6 nM
Chili powder, chili sauce, tomato sauce, and ketchup
[131]
Sudan I
Electrochemical biosensor
La3+-doped Co3O4 nanocubes
0.3-300 µM
0.05 µM
Chili powder, tomato paste, and ketchup sauce
[127]
Sudan I
Electrochemical biosensor
3DNPC
/
/
Ketchup, and chilli sauces
[132]
Sudan I
Electrochemical biosensor
AuNPs
0.01-70 µmol/L
1 nmol/L
Chili powder, and ketchup sauce
[128]
Nitrite
Electrochemical biosensor
Cu-MOF/Au
0.1-4000 and 4000-10000µ M
82 nM
Water
[71]
Nitrite
Colorimetric biosensor; Electrochemical biosensor
His@AuNCs/RGO
10-500 µM; 2.5-5700 µM
/
Sausage
[129]
Nitrite
Electrochemical biosensor
CD/Au nanohybrid
0.1µmol/L-2 mmol/L
0.06 µmol/L
Water
[168]
Clenbuterol
Other biosensor
PBNPs
0.5-5ng/mL
1.0 ng/mL
Pork, pork kidney and bacon
[133]
Clenbuterol
Electrochemical biosensor
ZrO2NPs
0.1-1000 µM
5.03×10-9 mol/L
Pork
[135]
52
Electrochemical biosensor
ZrO2NPs
3.0-50 µM
9.3×10-7 mol/L
Pork
[135]
Hg2+
Colorimetric biosensor
Pt nanozyme
0-120 nM
7.2 nM
Drinking water
[140]
Hg2+
Colorimetric biosensor
PCuS
/
/
Water
[142]
Hg2+
Colorimetric biosensor
PtNPs@ UiO-66-NH2
0-10 nM
0.35 nM
Water
[169]
Hg2+
Colorimetric biosensor
2D rGO/PEI/Pd nanohybrids
/
1nM by spectrum; 10 nM by naked eyes
Water
[137]
Hg2+
Colorimetric biosensor
Au nanozyme
Approximatel y 3 orders of magnitude
30 µg/L for a test sample; 1.2 µg/L for five test samples
Tap water
[144]
Hg2+
Colorimetric biosensor
CS-MoSe2 NS
/
3.5 nM by ultraviolet-visible spectrophotometer; 8.4 nM by a smartphone
Water
[32]
Pb2+
Electrochemical biosensor
Pt@PdNCs; MnTMPyP
0.1 pM-200 nM
0.033 pM
Water
[143]
Pb2+
SERS-based biosensor
AuNPs(10 nm)
0.13-53.33 nmol/L
0.07 nmol/L
Water
[95]
Cu2+
Colorimetric biosensor
Ag/PtNCs
10 -100 nM
5.0 nM
Water
[139]
Ag+
Colorimetric biosensor
PdNPs
30-300 nM
4.7 nM
Water
[145]
Ractopamine Metal ions
Other food contaminants Hydroquinone
Colorimetric biosensor
CeVO4
0.05-8 µM
0.04 µM
Tap water
[148]
Norovirus
Colorimetric biosensor
AuNPs
/
20 viruses per assay equivalent to 200 viruses/mL
Shellfish
[147]
As(III)
Electrochemical biosensor
Au/Fe3O4NPs
/
0.0215 ppb
Water
[79]
Lipopolysaccharide
Electrochemical biosensor
AuNPs/Cu-MOFs
1fg/mL-100 ng/mL
0.33 fg/mL
/
[146]
H 2O 2
Chemiluminescent biosensor
Fe-MIL-88NH2
0.1-10 µmol/L
0.025 µmol/L
Milk
[64]
1186
Note: /, not reported.
53
Highlights Emerging nanozymes-based biosensors are promising for food safety assay Progress in the construction of nanozymes-based biosensors was reviewed Applications of nanozymes-based biosensors to food safety assay were summarized Challenges and opportunities are discussed and prospected