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Carbon dots derived fluorescent nanosensors as versatile tools for food quality and safety assessment: A review
Journal Pre-proof Carbon dots derived fluorescent nanosensors as versatile tools for food quality and safety assessment: A review Xueli Luo, Yong Han, Xiumei Chen, Wenzhi Tang, Tianli Yue, Zhonghong Li PII:
S0924-2244(19)30211-0
DOI:
https://doi.org/10.1016/j.tifs.2019.11.017
Reference:
TIFS 2666
To appear in:
Trends in Food Science & Technology
Received Date: 19 March 2019 Revised Date:
26 September 2019
Accepted Date: 16 November 2019
Please cite this article as: Luo, X., Han, Y., Chen, X., Tang, W., Yue, T., Li, Z., Carbon dots derived fluorescent nanosensors as versatile tools for food quality and safety assessment: A review, Trends in Food Science & Technology (2019), doi: https://doi.org/10.1016/j.tifs.2019.11.017. 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 Published by Elsevier Ltd.
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Bacteria
Veterinary drug residues
t a R
c
Banned additives
Off
FL intensity
Toxins
i r t e m io
FL intensity
Pesticide residues
FL intensity
GRAPHICAL ABSTRACT
Analyte concentration
Functional components
Heavy metal
On
FL intensity
λ/nm
Analyte concentration
λ/nm
CDs based sensors
Analytes in food samples
Fluorescence response
1
Carbon dots derived fluorescent nanosensors as versatile
2
tools for food quality and safety assessment: a review
3
Xueli Luo a, Yong Han a, Xiumei Chen a, Wenzhi Tang a, Tianli Yue a, b, c, Zhonghong
4
Li a, b, c*
5
a
6
Shaanxi 712100, PR China
7
b
8
Ministry of Agriculture, Yangling, Shaanxi 712100, PR China
9
c
10
College of Food Science and Engineering, Northwest A&F University, Yangling,
Laboratory of Quality & Safety Risk Assessment for Agro-products (YangLing),
National Engineering Research Center of Agriculture Integration Test(Yangling),
Yangling, Shaanxi 712100, PR China
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
*
Corresponding author. Tel: +86 29 8703 8857; E-mail: [email protected]; [email protected].
1
32
Abstract
33
Background: Food analysis is essential in monitoring food quality for risk
34
assessment regarding public health. Traditional techniques can meet the requirement
35
of routine food analysis in laboratory. However, serious food safety situations
36
urgently demand rapid, time-saving, low-cost analysis methods even on-site, portable
37
and household testing kits. Fluorescence analysis exhibits immense potential for food
38
safety owing to its remarkable advantages of high sensitivity, ease of operation, low
39
cost and rapid result outputs.
40
Scope and approach: Carbon dots (CDs) are novel 0D carbonic nanomaterials
41
recently emerging as potential substitutes for traditional fluorescent materials.
42
Compared with the conventional fluorescent materials, e.g. organic fluorescent dyes,
43
metal nanoparticles/nanoclusters and quantum dots (QDs), CDs possess many
44
appealing merits such as ease of preparation, low cost, non-blinking, low cytotoxicity,
45
excellent biocompatibility and high resistance to photo-bleaching. As a result
46
CDs-based fluorescence sensing provides excellent analysis platforms for monitoring
47
food-related analytes. This review provides a comprehensive overview of the
48
state-of-the-art synthesis methods and the fluorescence properties of CDs along with
49
the sensing mechanisms and designing principles of CDs-based fluorescent sensors
50
for food analysis. Possible challenges and appealing prospects of CDs-based
51
fluorescent sensors are also discussed.
52
Key findings and conclusions: CDs have been widely applied in bio-imaging,
53
sensing, drug delivery, catalysis and optronics. Integration of CDs into food science 2
54
and engineering for food safety control and risk assessment exhibits a bright future.
55
Keywords: Carbon nanomaterials; Nanosensors; Analysis of Food contaminants;
56
Optical sensors; Fluorescence assay; Food safety
3
57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83
Contents 1. 2.
3.
4.
5.
6. 7.
Introduction ............................................................................................................................... 5 Synthesis of CDs ....................................................................................................................... 8 2.1. Size-tuning .................................................................................................................... 8 2.2. Surface chemistry tuning............................................................................................... 9 2.2.1. Surface passivation/functionalization................................................................ 9 2.2.2. Heteroatom doping .......................................................................................... 11 Fluorescent properties ............................................................................................................. 13 3.1. Photoluminescence mechanism................................................................................... 13 3.2. Fluorescent properties ................................................................................................. 14 3.3. Phosphorescence ......................................................................................................... 15 Fluorescence response mechanisms ........................................................................................ 16 4.1. Direct fluorescence quenching .................................................................................... 17 4.2. Direct fluorescence enhancement................................................................................ 20 4.3. Ratiometric response ................................................................................................... 20 4.4. Wavelength shifts ........................................................................................................ 21 Design principles for food analysis ......................................................................................... 21 5.1. Ligand-free sensors ..................................................................................................... 21 5.2. Ligand-functionalized sensors..................................................................................... 22 5.2.1. Covalent conjugation....................................................................................... 23 5.2.2. Noncovalent modification ............................................................................... 25 5.3. Molecule imprinting polymers (MIPs) ........................................................................ 26 5.4. Switchable sensors ...................................................................................................... 28 5.5. Ratiometric fluorescence sensors ................................................................................ 29 5.6. Flexible microdevices ................................................................................................. 31 Spectral analysis and quality control....................................................................................... 32 Conclusions and trends ........................................................................................................... 33
84 85 86 87 88
4
89
1. Introduction
90
Food safety is emerging as a global human health issue. The continuing
91
development of modern industry, agriculture and food processing has resulted in
92
chemical contamination, biological pollutants and food adulteration (Aragay, Pino, &
93
Merkoci, 2012; Potorti, et al., 2018; Salvo, et al., 2018; Salvo, et al., 2019). Food
94
analysis and quality assessment play central roles in food safety control by providing
95
risk pre-warning and consumers protecting from the threats of adulteration, spoilage
96
and contamination. However, food matrices are too complicated to be analyzed
97
without proper pretreatments because of the interference of co-existing substances.
98
Conventional food analysis methods, e.g. spectroscopy, immunoassay, culture and
99
colony counting, enzymatic, electrochemical, nuclear magnetic resonance and
100
chromatography, offer powerful trace analysis with high reproducibility, good
101
sensitivity and selectivity. However, they require specific instrumentations, skilled
102
personnel and tedious sample preparation. Feasible and facile analysis, especially for
103
in situ and real-time monitoring, is urgently required for quick pre-warning of serious
104
food safety threats.
105
Compared with conventional analysis methods, the fluorescence-based food
106
analysis is very promising. It possesses intrinsic simplicity, high sensitivity, easy
107
operation, low cost and simple equipment requirement. Organic fluorescent dyes,
108
metallic nanoparticles/nanoclusters, quantum dots (QDs) and rare earth up-conversion
109
nanomaterials are classical fluorescent nanomaterials, but they suffer from inevitable 5
110
disadvantages which restrict their practical applications for food analysis. Heavy
111
metal-based semiconductors QDs such as CdSe/CdTe are inevitably involved in
112
complicated
113
stability/biocompatibility (Y. Liu, et al., 2017). The high cost of noble metal
114
nanoparticles/nanoclusters
115
nanoparticles/nanoclusters together with low stability limit their wide applications.
116
Rhodamine, fluorescein, cyanine and coumarin are the common organic molecular
117
dyes that have been widely used in fluorescence sensing. These organic fluorescent
118
dyes usually show poor solubility, severe photobleaching and poor bio-availability.
119
Furthermore, the narrow excitation of dyes is undesirable for sensing due to the
120
requirement of different wavelength lights to excite dyes. Herein, developing
121
eco-friendly fluorescence sensing materials with desirable fluorescence properties,
122
low cost and adequate sensitivity is urgently essential and promising for designing
123
novel fluorescent sensors.
and
harsh
synthesis
and
along
the
high
with
high
toxicity
toxicity
of
and
heavy
poor
metal
124
Carbons dots (CDs), also called as carbon nanoparticles or carbon nanodots,
125
were firstly discovered in 2004 by Xu et al during the electrophoresis purification of
126
single-walled carbon nanotubes (X. Xu, et al., 2004). As the emerging 0D carbonic
127
nanomaterials, CDs have been defined as discrete, spherical or quasi-spherical
128
nanoparticles with particle sizes less than 10 nm (Baker & Baker, 2010). The structure
129
of CDs is considered as sp2 conjugated carbon cores embedded in amorphous shells
130
(mainly
131
oxygen/nitrogen-based groups or polymeric aggregations (L. B. Li & Dong, 2018; S.
sp3
hybridized
carbon
matrices)
6
containing
considerable
132
J. Zhu, et al., 2015). CDs emerge as eco-friendly and promising sensory nanomaterials
133
owing to their attractive merits for fluorescence sensing, including facile synthesis,
134
excellent solubility, cost-effectiveness, low toxicity, biocompatibility and unique
135
fluorescence properties. The fluorescence properties of CDs mainly refer to their (1)
136
excitation spectrum, i.e. the changes of the fluorescence intensity versus different
137
excitation wavelength at a fixed emission wavelength; (2) emission spectrum, i.e. the
138
change of fluorescence intensity versus emission wavelength at a certain excitation
139
wavelength, and the emission peak intensity is often used as a quantitative parameter
140
to determine analyte content; (3) fluorescence life, i.e. the required time for
141
fluorescence intensity to decrease to 1/e of the maximum intensity after withdrawing
142
the excitation light; (4) fluorescence quantum yield (FLQY), i.e. the ratio of the
143
number of excited molecules returned to the ground state by fluorescence emission
144
and the number of all excited molecules; (5) Stokes shift, i.e. the difference between
145
the maximum fluorescence emission wavelength and the maximum absorption
146
wavelength.
147
Reviews on the synthesis, properties and applications of CDs have been
148
published (Du & Guo, 2016; Lim, Shen, & Gao, 2015; J. Wang & Qiu, 2016; Zuo, Lu,
149
Sun, Guo, & He, 2015), but a more focused overview regarding food analysis is still
150
lacking. This is likely because of the challenge to research presented by interferents
151
existing in extremely complex food matrices. In this review, we briefly present the
152
synthesis and fluorescence properties of CDs. We also emphatically describe the
153
fluorescence sensing mechanisms and designing principles of CDs-based sensors for 7
154
food analysis. In conclusion, current challenges and new trends in CDs sensing
155
applications for food analysis are highlighted.
156
2. Synthesis of CDs
157
The synthesis approaches of CDs can be grouped into size tuning and surface
158
chemistry tuning. Size tuning can be used to synthesize CDs and regulate their
159
fluorescence properties by controlling their sizes. Surface chemistry tuning strategies
160
can be used to tailor surface groups of CDs to induce different surface states. A
161
schematic illustration of the two synthesis methods is shown in Fig. 1.
162
2.1. Size-tuning
163
Fluorescence properties of CDs predominantly depend on their size owing to the
164
quantum-confinement effect and the variation in density and nature of sp2 domain.
165
Herein, size-tuning via shortening or prolonging the reaction time can be used to
166
modulate the energy band gap of CDs.
167
According to the chosen carbonaceous precursor, the size-tuning synthesis routes
168
are mainly divided into ‘‘top-down’’ (Fig. 1A) and ‘‘bottom-up’’ (Fig. 1B). The
169
former method involves exfoliating larger carbon materials such as nanodiamonds,
170
graphite rods, carbon nanotubes, carbon soot, and graphite oxide into smaller carbon
171
nanoparticles via arc discharge (X. Xu, et al., 2004), laser ablation (Sun, et al., 2006)
172
and electrochemical (Zhou, et al., 2007). The as-prepared CDs with a perfect sp2
173
carbon structure lack an efficient band gap to generate fluorescence. A surface
174
modification is often required to improve their luminous efficiency (S. J. Zhu, et al., 8
175
2015). In another respect, the yield of the method is too low to synthesize CDs in
176
large scale, which is not conducive to their wide applications. The “bottom-up” route
177
carbonizes carbon-rich molecular precursors, such as citrate, amino acids,
178
carbohydrates, polymer-silica nanocomposites and even biomass, into CDs through
179
hydrothermal/solvothermal, microwave and ultrasonic oscillation methods.
180
2.2. Surface chemistry tuning
181
Two urgent challenges regarding sensing applications of raw CDs are the low
182
FLQY and the lack of functional groups for surface grafting/bio-conjugation of
183
recognition units. Surface chemistry tuning approaches (Fig.1 C, D) can tailor the
184
fluorescence behaviors by modulating the surface chemical groups or π-π conjugated
185
network as well as by adjusting the degree of surface oxidation. Surface
186
passivation/functionalization and heteroatom doping are the two major ways to tune
187
surface chemistry of CDs.
188
2.2.1. Surface passivation/functionalization
189
Surface functionalization (Fig. 1C) introduces various organic, inorganic,
190
polymeric or biological species via functional groups or π-π conjugated network to
191
CDs. Three main purposes for surface functionalization include improving the
192
solubility, tuning the fluorescence properties especially for improving the FLQY and
193
increasing the selectivity for analytes. For example, the FLQY of CDs has been
194
significantly improved via modifying with amino-containing compounds. Amino
195
relevant moieties have been confirmed to give higher FLQY and more tunable
196
fluorescence caused by non-local π orbital and molecular orbital resonance structures 9
197
(F. Y. Yan, et al., 2018). Oxygen-containing groups (e.g. carboxyl, hydroxyl and
198
epoxy), which can be easily obtained by different methods such as strong acids
199
oxidation, endow CDs with desirable water solubility and facile functionalization.
200
CDs are generally functionalized by covalent coupling (Y. Yang, et al., 2012),
201
coordination (Yin, Liu, Jiang, Chen, & Yao, 2013), electrostatic absorption, π-π
202
interaction (H. L. Li, Zhang, Wang, Tian, & Sun, 2011), sol-gel technology (F. Wang,
203
Xie, Zhang, Liu, & Zhang, 2011), hydrophobic interactions and host-guest
204
interactions. More fundamental and detailed functionalization approaches would be
205
discussed in Section 5.
206
Surface passivation is necessary to endow CDs with desirable fluorescence
207
properties. Surface passivation methods include (1) oxidizing the surface carbons to
208
carboxylic acid groups using nitric acid, (2) doping the oxidized CDs by inorganic
209
salts (e.g. ZnS, ZnO) and (3) capping the pristine CDs with organic polymers (e.g.,
210
polyethylene glycol) (Esteves da Silva & Gonçalves, 2011). Organic molecules (also
211
considered as precursors) and polymers, including polyethylene glycols (e.g. PEG900N,
212
PEG1500N) and amine molecules (e.g. thiourea, 4,7,10-trioxa-1,13-tridecanediamine
213
and 1-hexadecylamine) are predominant passivation agents. PEG-passivated CDs
214
have been prepared by connecting -OH of PEG to -COOH of CDs. Such
215
modifications are complicated and also additional purifications are inevitably required
216
to collect the modified CDs. In some cases surface passivating agents (mainly organic
217
molecules) could act as functionalizing agents to modify physical/fluorescence
218
properties of CDs and therefore additional modifications could be omitted (Dong, et 10
219
al., 2012). Two main explanations for the passivation mechanisms are: (1) filling
220
defects on the surface of CDs and (2) generating energy traps by organic polymers (L.
221
B. Li & Dong, 2018).
222
2.2.2. Heteroatom doping
223
Heteroatoms doping (Fig. 1D) improves fluorescence properties by doping
224
heteroatoms into the carbon skeleton of CDs. The method changes the Fermi level to
225
modulate electronic characteristics and provides more active sites such as -OH,
226
-COOH, and -NH2 on the CDs surface which can serve as energy traps to improve the
227
fluorescence properties (Lai, et al., 2013). Both the types and the content of dopants
228
have great effects on the fluorescence properties of CDs. For example, the FLQY of
229
CDs without doping is 5.3%, much lower than 73% of the N,S co-doped CDs (Y.
230
Dong, et al., 2013). In another example, the fluorescence emission of N doped CDs
231
shows a gradual red-shift with increasing content of N dopants (Y.-Q. Zhang, et al.,
232
2012). Furthermore, additional passivation or modification could be unnecessary for
233
doped CDs. The mainly reported dopants include metal ions (e.g. Mn, Co, Cu, Mg)
234
and nonmetallic dopants (e.g. nitrogen (N), boron (B), sulfur (S), phosphorus (P),
235
fluorine (F) and chlorine (Cl)). These dopants can be independently applied or
236
combined with one or more other dopants, i.e. the process of co-doping. N is the most
237
prominent doping candidate due to its matchable atomic size and five valence
238
electrons available to bond with C atoms (Du & Guo, 2016; Y.-Q. Zhang, et al., 2012).
239
N can change the electronic and transport properties of CDs by infusing electrons into
240
carbon-based materials (Ma, Ming, Huang, Liu, & Kang, 2012). Several reports have 11
241
demonstrated that the performance of N dopants for improving the FLQYs following
242
the order of primary amine>secondary amine (tertiary amines are rarely applied to
243
produce CDs) and diamine>monoamine (Zhai, et al., 2012).
244
According to the charge carriers (i.e., holes or electrons), the doping types
245
include n-type and p-type. The n-type (e.g. N, P, S, Cl doping) donates extra electrons
246
while p-type (e.g. B doping) introduces extra holes to the hosts (L. B. Li & Dong,
247
2018). The introduction of new energy levels by incorporating impurities in the
248
forbidden band will change the Fermi level. For n-type doping, the electron
249
concentration will increase while the minority carrier-hole concentration will decrease
250
when more dopants are incorporated. Accordingly, the Fermi level will be much
251
closer to the bottom of the conduction band. In terms of p-type doping the Fermi level
252
will gradually approach to the top of the valence band and even enter the valence band.
253
These changes induce the radiative recombination of electron-hole pairs, resulting in
254
significant changes of the fluorescence properties. In addition, the introduction of
255
dopants will change the surface groups and the micro-structures of CDs, thus inducing
256
surface defective emission including trap states and molecular states. The
257
conventional synthesis methods for undoped CDs are also applicable to prepare doped
258
CDs although extra doping procedures or other precursors containing doping elements
259
are needed. One-step methods can be used to prepare doped CDs via chemical
260
reactions between the carbon source and the dopants using common procedures. In
261
multi-step approaches, undoped CDs are firstly prepared followed by doping via
262
hydrothermal reaction, strong acid treatment, chemical vapor deposition or 12
263
photochemistry synthesis. The successful doping can be evidenced by XPS
264
characterizations of doped CDs which can reveal valence states of all elements,
265
chemical bonds and atomic ratios of C atoms to the doping heteroatoms.
266
Most CDs have been synthesized via complicated systems/media, and resultant
267
purifications are unavoidably required to collect CDs. Several purification techniques
268
including centrifugation, dialysis and/or extraction, high-performance liquid
269
chromatography (HPLC) (X. J. Gong, et al., 2014), polyacrylamide gel
270
electrophoresis (H. Liu, et al., 2007), and column chromatography separation (Jia, Li,
271
& Wang, 2012) have been reported.
272
3. Fluorescent properties
273
3.1. Photoluminescence mechanism
274
The photoluminescence mechanism of CDs includes (a) intrinsic emission,
275
involving the quantum-confinement effect of size-dependent sp2 conjugated π-domain
276
(Ye, et al., 2013) together with the recombination of localized electron-hole pairs and
277
(b) surface states emission including molecule states and trap states (Schneider, et al.,
278
2017; L. Wang, et al., 2013). Molecule states mainly account for the fluorescence
279
origin of CDs derived from citric acid as the carbon source. Trap states induced
280
emissions are related to special edge states on sp3 carbon framework and functional
281
groups. The band gaps of σ and σ* states of sp3 matrix have been proven to influence
282
π and π* electronic levels of sp2 domain (F. Li, Yang, & Xu, 2019). At present the
283
fluorescence origin of CDs is assumed to be a synergistic effect of intrinsic state 13
284
emission and defect emission, but more research should be done to reveal the exact
285
origins of the fluorescence emissions.
286
3.2. Fluorescent properties
287
pH The pH-dependent behavior is relevant to electronic transition changes of
288
π-π* and n-π* in graphite nanodomains which refill or deplete their valence bands via
289
protonation-deprotonation. This implies that the surface defects may serve as
290
capturing centers for carriers which results in correlated luminescence. Pyridine N
291
accepts protons and is gradually protonated with the decrease of pH. Electrons are
292
transferred from the protonated N to the adjacent C with conjugated structure, leading
293
to the increase of fluorescence intensity.
294
Excitation Excitation-dependent emission might result from the quantum effect
295
and/or the different emissive traps on the CDs surface (Y. Wang, et al., 2013). It is
296
considered that the excitation-dependent properties may be related to the aromatic
297
C=C and the surface defects from C-OH and C=O groups (Zheng, et al., 2015). CDs
298
synthesized by using ammonium citrate and ethylenediamine as precursors present the
299
excitation-dependent property. The surface defects and the narrower size distribution
300
of CDs may contribute to the excitation-dependent property (Z. Li, et al., 2015). Some
301
reported CDs show excitation independent emissions which may be attributed to their
302
uniform size and surface state.
303
Tunable emissions Tunable emissions involve modulating CDs emissions by
304
adjusting condensation reactions, synthesis operations, doping (Y.-Q. Zhang, et al.,
305
2012) and reaction solvents (Miao, et al., 2017). Biological auto-fluorescence 14
306
substrates such as proteins, amino acids, bio-tissues and cells usually emit blue
307
fluorescence. This tunable property can be used to synthesize CDs with long
308
wavelength emission which is helpful in reducing food matrix interference such as the
309
spontaneous blue fluorescence of biomass and ion absorption.
310
Up-conversion Up-conversion fluorescence is an anti-Stokes luminescence
311
phenomenon wherein the emission wavelength is shorter than the selected excitation
312
wavelength (Y.-Q. Zhang, et al., 2012). Most reported CDs and biological tissues
313
normally emit blue fluorescence when excited by ultraviolet light. This obviously
314
interferes with accurate fluorescence analysis within organisms. The up-conversion
315
property paves a way to avoid the auto-fluorescence of organisms or food matrices
316
containing proteins or amino acids. Furthermore, the synthesis of CDs with
317
up-conversion emissions is simple and without complicated modifications required for
318
traditional lanthanide doped up-conversion nanoparticles.
319
3.3. Phosphorescence
320
Phosphorescence is a phenomenon of delayed photoluminescence that
321
corresponds to the radiative decay of the molecular triplet state. Room-temperature
322
phosphoresce sensors with long lifetime eliminate the interference of short-lived
323
background fluorescence such as the bioluminescence of tryptophan, tyrosine and
324
guanylate. More importantly, most detection matrices show no phosphorescence
325
emission. Herein, endowing CDs with excellent phosphorescence would open a
326
promising horizon for bio-sensing because of the longer lifetime of observable
327
emissions, the lower fluorescence interference and the more sensitive response to 15
328
small molecules. But realizing a long-lifetime room-temperature phosphoresce of CDs
329
is difficult because of the deficient triplet excitons and the non-radiative deactivations.
330
The reported CDs-based phosphorescent materials were obtained by embedding CDs
331
into various polymer matrices, e.g. polyvinyl alcohol, layered double hydroxides,
332
potash alum, aluminum sulfate, zeolites, urea/biuret, polyurethane and silica gel.
333
These matrix molecules can protect phosphors from being quenched by molecular
334
vibrations, oxygen molecules, and high temperatures. These host matrices only allow
335
specific CDs to possess room-temperature phosphoresce. Hence, choosing an
336
appropriate background matrix is critical to achieve phosphorescence. In addition,
337
these CDs mainly exhibit phosphorescence with short wavelengths (blue- to
338
green-light spectrum). These unfavorable limitations largely hinder the developments
339
and applications of CD-based room-temperature phosphorescence materials (Li, et al.,
340
2019). CDs with room-temperature phosphorescence properties have recently been
341
readily synthesized by the one-pot solvothermal method via the elemental doping
342
strategy instead of using the matrix-assisted oxygen-barrier method (Long, et al.,
343
2018). More interestingly, a universal host matrix (boric acid) has been novelly
344
exploited to activate long lifetime and multi-color (blue, green, green-yellow and
345
orange) room-temperature phosphorescence of CDs (Li, et al., 2019).
346
4. Fluorescence response mechanisms
347
The basic analytical principles of fluorescence sensors can be summarized as the
348
interaction between recognition components and targets which induces the changes of 16
349
the fluorescence properties of CDs and the changes quantitatively relate to the
350
concentration or structure of the target analytes. Additionally, recognition components
351
should have insignificant influence on the excitation/emission of CDs. The four main
352
fluorescence signal outputs are fluorescence quenching, fluorescence enhancement,
353
the emission wavelength shift and the fluorescence lifetime. They are summarized as
354
follows.
355
4.1. Direct fluorescence quenching
356
The target-trigged quenching mechanisms are mainly divided into static
357
quenching effect (SQE), dynamic quenching effect (DQE), photo-induced electron
358
transfer (PET), Förster resonance energy transfer (FRET) and inner filter effect (IFE),
359
which are shown in Fig. 2.
360
SQE (Fig. 2A) is closely related to the formation of a non-fluorescent
361
ground-state complex between ground-state molecules of CDs and quenchers. A
362
quenching process can be explained as SQE when coincidences happen with (a) the
363
insignificant change of fluorescence life in the absence (τ0) and the presence of a
364
quencher (τ), i.e. τ0/τ =1, (b) the changes of the absorption spectrum upon introduction
365
of a quencher, and (c) the gradually fluorescence increase owing to a
366
rising-temperature induced instability of ground-state complex. Chemical interactions
367
between CDs and quenchers are necessary for a SQE process, thereby it is
368
indispensable to modify or functionalize CDs (Zu, et al., 2017). For instance,
369
tartrazine can quench the fluorescence of CDs via SQE because of the formation of a
370
ground-state complex (H. Xu, Yang, Li, Zhao, & Liao, 2015). 17
371
DQE (Fig. 2B) involves the collision between the excited state of CDs and
372
quencher. Different characteristics are presented as (a) τ0/τ≠1, (b) insignificant
373
changes of the absorption spectrum, and (c) the gradual increase of quenching effect
374
in terms of a rising temperature (Zu, et al., 2017).
375
The PET (Fig. 2C) quenching mechanism is related to an electron transfer
376
process between the excited stage of the electron donor/receptor and the quencher.
377
The quencher can coordinate with groups on the surface of CDs to form a complex
378
which would initiate non-radiative emissions when the excited electrons return to the
379
ground state. Depending on the role of CDs, PET can be classified into reductive and
380
oxidative PET. As the electron receptor, CDs receive electrons from the donor in the
381
reductive PET process which is driven by the energy gap between the lowest
382
unoccupied molecular orbitals (LUMO) of the quencher and the highest occupied
383
molecular orbitals (HOMO) of CDs. In the oxidative PET process electrons are
384
donated by the activated CDs to the quencher. The oxidative PET is driven by the
385
energy gap between the LUMO of the CDs and the LUMO of the quencher (Zu, et al.,
386
2017).
387
The FRET (Fig. 2D) mechanism is characterized by non-radiative energy
388
transfer when an energy donor (denoted as ‘D’ in Fig. 2D) transmits its excited state
389
energy directly to an acceptor (denoted as ‘A’ in Fig. 2D) via a non-radiative
390
‘dipole-dipole’ coupling instead of emitting photons for absorption by the acceptor.
391
The occurrence of FRET relies on the premises that the donor is the independent
392
luminescent center and that the acceptor may not necessarily emit light but have an 18
393
independent absorption spectrum overlapping the donor emission spectrum (Sapsford,
394
Berti, & Medintz, 2006). Moreover, FRET processes are distance-dependent, and the
395
distance between D and A of 1-10 nm is required for an effective FRET. The
396
calculation method of the CDs-quencher distance (r) and Förster distance (R0) could
397
refer to the literature (J. Liu, et al., 2016)..
398
IFE (Fig. 2E) refers to the fluorescence quenching of fluorophores due to that the
399
co-existing other light-absorbing substances in the sensing system absorb the
400
excitation and/or emission light. In the IFE process the absorption peaks and
401
fluorescence lifetime of CDs will not change because no new substance is generated.
402
IFE is a well-known interference in spectrofluorometry studies, and the Parker
403
equation (Eq. 1) is often utilized to correct the fluorescence intensities. Some
404
IFE-based fluorescence sensors have been recently developed under the prerequisites:
405
(a) the absorption spectrum of the quencher overlaps the excitation/emission spectrum
406
of CDs and (b) the distance between CDs and the quencher is more than 10 nm. Many
407
fluorescence sensors targeted to both inorganic and organic analytes have been
408
successfully exploited by utilizing IFE quenching mechanism. For instance, the
409
fluorescence of CDs can be quenched by silver nanoparticles (AgNPs) and Cr(VI),
410
while the fluorescence would be restored by certain analytes due to their stronger
411
affinity to the quenchers. Hence switchable sensors have been designed to determine
412
pesticides in spiked apple juice (Zhao, Chen, Sun, & Yang, 2016) and ascorbic acid in
413
fresh fruits and commercial fruit juices (X. Gong, et al., 2017).
414
Fcor 2.3dAex gAem 2.3sAem = 10 Fobsd 1-10-dAex 1-10-sAem 19
(1)
415
where Fobsd and Fcor represent the observed fluorescence and the corrected
416
fluorescence after deducting IFE from Fobsd; Aex and Aem are UV absorbance at the
417
maximum excitation and emission wavelength. S is the thickness of the excitation
418
beam, d is the cuvette width and g is the distance between the edge of the excitation
419
beam and the edge of the cuvette.
420
4.2. Direct fluorescence enhancement
421
Directly enhanced fluorescence sensors are developed when (1) the CDs show
422
weak fluorescence or no fluorescence in the absence of the analytes and (2) the
423
fluorescence can be enhanced by analytes. Two main mechanisms of the
424
aggregation-induced enhancement (AIE) and the metal-enhanced fluorescence (MEF)
425
explain the analyte-trigged fluorescence enhancement phenomenon. In the AIE
426
mechanism, the analyte can coordinate with groups on the surface of the fluorophore
427
which results in surface charge changes. MEF is usually based on the surface plasmon
428
resonance (SPR) phenomenon of metallic nanostructures such as Au/Ag NPs which
429
enhances the local electromagnetic field and leads to the increased fluorescence of
430
nearby fluorophores. For example, Ag+-induced fluorescence enhancement can be
431
used to detect Ag+ (Gao, et al., 2015).
432
4.3. Ratiometric response
433
Single-emission fluorescence sensors usually suffer from low sensitivity and low
434
selectivity because fluorescence intensities can be affected by analyte-independent
435
factors such as concentration of the sensor, chemical environment, spectrometer
436
parameters and light scattering caused by the sample matrices (Amjadi & Jalili, 20
437
2017; Lee, Kim, & Sessler, 2015). Ratiometric fluorescence sensors endow
438
themselves with self-calibrations by calculating the fluorescence intensity ratio of
439
two or more well-resolved emissions. In other words, ratiometric sensing provides
440
excellent accuracy and reliability which could diminish environmental effect and
441
false signals (K. Wang, et al., 2015; X. Wang, et al., 2016; Zhuang, Ding, Zhu, &
442
Tian, 2014). Dual-emitting sensing systems can be constructed by either hybridizing
443
CDs with other fluorophores or designing CDs with inherent dual emissions. The
444
detail design will be discussed in Section 5.
445
4.4. Wavelength shifts
446
The emission wavelength shift or the changes of Stokes shift can also be utilized
447
to design fluorescence sensors. The shift distance of emission wavelength or Stokes
448
shift is linearly proportional to the analyte concentration in the fitted range. Spectral
449
analysis and data processing could refer to the literature (Lavkush Bhaisare, Pandey,
450
Shahnawaz Khan, Talib, & Wu, 2015).
451
5. Design principles for food analysis
452
CDs sensing approaches can be generally divided into three major classes: (1)
453
ligand-free sensors, (2) post-functionalized sensors, and (3) integrating CDs with
454
quenchers, fluorophores, molecule imprinting polymers (MIPs) and substrates.
455
5.1. Ligand-free sensors
456
For the ligand-free strategy, active groups (e.g. hydroxyl, carboxyl, amino and
457
phenolic hydroxyl) obtained during the synthesis process directly act as recognition
458
units. The surface groups of CDs are different because of various precursors, reaction 21
459
reagents and carbonization conditions (temperature, time, pH, etc.), resulting in
460
different binding ability of CDs to analytes. The basic detection principle of pristine
461
CDs sensors is based on the strong coordination of the active groups on CDs’ surface
462
with the target analytes, leading to changes of fluorescence properties. Ligand-free
463
CDs based fluorescence sensors have been successfully developed for detecting metal
464
ions (e.g. Fe3+ (Edison, et al., 2016), Hg2+ (J. J. Liu, et al., 2016), Ag+ (Qian, et al.,
465
2014)) and anions (e.g. ClO- (Hu, Yang, Jia, & Yu, 2015)) in different food samples.
466
Organic molecules and pathogens, e.g. pesticides residues in agricultural products
467
(Chang, Ginjom, & Ng, 2017), food additives (H. Xu, et al., 2015; H. Yang, He, Pan,
468
Liu, & Hu, 2019; Yuan, et al., 2016) and bacteria (N. Wang, et al., 2016), can also be
469
detected by ligand-free CDs sensors. Ligand-free sensors are simple and convenient
470
for direct sensing, but they present low specific recognition which results in poor
471
sensitivity and poor selectivity toward analytes.
472
5.2. Ligand-functionalized sensors
473
Surface functionalization of nanomaterials using highly specific receptors, such
474
as organic molecules and biomolecules (proteins, amino acids, peptides, aptamers,
475
antibody others biomolecules), has become a major focus for improving selectivity of
476
fluorescence nanosensors for bio-/chemical analysis in complex matrices (Z. Zhang,
477
et al., 2014). CDs prepared by treating oxygen-containing and/or nitrogen-containing
478
organic precursors usually possess carboxyl, hydroxyl and amino groups on their
479
surface which provide wonderful opportunities for grafting ligands via covalent and
480
non-covalent modification. 22
481
5.2.1. Covalent conjugation
482
Amide coupling reaction The method (Fig. 3A, using carboxyl-terminated CDs
483
as an example) involves forming amide linkage via chemical reactions between amino
484
groups and acylating reagents (e.g. acid chloride or carboxylic acid) with catalysis of
485
carbodiimide
486
1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), dicyclohexylcarbodiimide
487
(DCC), N,N'-diisopropylcarbodiimide (DIC) and N-hydroxysuccinimide (NHS). The
488
simple preparation of carboxyl-terminated CDs (CDs-COOH) and amino-terminated
489
CDs (CDs-NH2) provides feasibility to functionalize CDs with acyl/amino
490
compounds
491
fluorescence sensors for detecting pathogens can be designed by carbodiimide
492
chemistry because either bio-ligands contain abundant carboxyl/amino groups or the
493
bio-ligands can be easily modified with carboxyl or amino. Aptamers are artificially
494
selected oligonucleotide or peptide molecules which can selectively bind to analytes
495
by folding into three-dimensional structures. Bioligands-functionalized CDs have
496
been designed as fluorescence sensors for assaying food-borne pathogens such as
497
Salmonella typhimurium (R. J. Wang, Xu, Zhang, & Jiang, 2015) and Staphylococcus
498
aureus (Zhong, Zhuo, Feng, & Yang, 2015) in food samples. CDs-COOH can also be
499
covalently modified using chemical ligands containing amino groups via amide
500
coupling.
501
([N-(2-aminoethyl)-N,N,N0-tris(pyridin-2-ylmethyl) ethane-1,2-diamine]) can be
502
bonded onto the surface of CDs by amide linkages, and both the functionalized CDs
reagents.
or
acyl/amino
Branched
Common
carbodiimide
modified
molecules.
polyethyleneimine
23
reagents
include
Biomolecules-labeled
and
amino
CDs
TPEA
503
show good affinity to Cu2+ (Yongqiang Dong, et al., 2012; Qu, Zhu, Shao, Shi, &
504
Tian, 2012). Amide coupling principles can also be used to hybrid CDs with other
505
nanomaterials. For example, amino-passivated CdTe QDs have been grafted onto
506
CDs-COOH via EDC/NHS coupling to develop a ratiometric fluorescence sensor for
507
detecting Hg2+ (H. Y. Xu, Zhang, Liu, Liu, & Xie, 2017). Similarly, CDs-NH2 can also
508
be grafted with acyl compounds via the principle.
509
Esterification reaction Esterification methods (Fig. 3B) can introduce different
510
functional moieties because CDs are usually rich in -COOH or -OH in terms of
511
treating oxygenate compounds as organic precursors. Mannose modified CDs
512
(Man-CDs) have been synthesized by anchoring mannose onto the CDs surfaces
513
through a dehydration reaction using dry heating. The Man-CDs can selectively detect
514
Escherichia coli (E. coli) as low as 100 CFU/mL in drinking water and in apple juice
515
(Irving Po-Jung Lai & Yu-Jia Li, 2016).
516
Silylation reaction Silylation modification is a reaction between silane and
517
active hydrogen on the surface of CDs. Silanization reagents such as
518
3-aminopropyltriethoxysilane (APTES), 3-mercaptopropyltriethoxysilane (MPTS),
519
and tetraethyl orthosilicate (TEOS) can be hydrolyzed in acid or alkali to produce
520
Si-O-Si bonds which can be then polymerized to form a SiO2 shell coating on the
521
surface of CDs to provide silanol-rich groups. Organosilane-functionalized CDs can
522
be obtained by hydrothermally treating citric acid and APTES (Poshteh Shirani,
523
Rezaei, & Ensafi, 2019). CDs-NH2 has been encapsulated in a silica shell using TEOS
524
and APTES via silylation reaction and then covalently conjugated with thioglycolic 24
525
acid modified CdTe QDs via EDC/NHS coupling to develop a ratiometric sensor for
526
detecting Cu2+ in spiked vegetable and fruit samples (Rao, et al., 2016).
527
Thiol functionalized CDs Thiol or thiol derivatives modified molecules such as
528
glutathione, thioethers, dithiocarbamate alkanethiolates, DNA peptides, and proteins
529
can be coupled on the surface of CDs for Hg2+, Cu2+ and arsenite assays due to the
530
strong affinity of sulfhydryl to these analytes.
531
5.2.2. Noncovalent modification
532
Electrostatic immobilization CDs usually present positive/negative charge due
533
to the existence of amino, carboxyl and hydroxyl on their surfaces. Electrostatic
534
adsorption assembles reverse charged ligands or fluorophores onto CDs (Fig. 3C).
535
The positive charged N-doped CDs can be assembled on aptamer modified gold
536
nanoparticles (Aptamer/AuNPs) with negative charge via electrostatic interactions,
537
resulting in fluorescence quenching of CDs. In the presence of aflatoxin B1 (AFB1),
538
the fluorescence of CDs can be restored because AFB1 can competitively bind to the
539
aptamer to release the CDs. Based on the principle, a “turn-on” sensor has been
540
developed to determine AFB1 in peanut and corn with the detection limit of 5 pg/mL
541
(B. Wang, et al., 2016). A dual-emitting sensor fabricated by covalent coupling of
542
polyethyleneimine modified CDs and fluorescein isothiocyanate via electrostatic
543
interactions and thiourea bonds can selectively detect Cu2+ in yogurt (B. Wang, et al.,
544
2016). Electrostatic coupling is sensitive to medium pH and is not desirable when
545
used alone.
546
π-π stacking Some aromatic molecules can be anchored to CDs containing 25
547
extended π systems via π interaction (Fig. 3D). The fluorescence of dye-labeled
548
single-stranded DNA (ss-DNA) probe can be quenched when the ss-DNA is adsorbed
549
onto the surface of CDs via π interaction. When the target DNA matches with the
550
dye-labeled DNA to form double-stranded DNA (ds-DNA), the ss-DNA is separated
551
from the surface of CDs and thereby inducing the fluorescence recovery (H. L. Li, Y.
552
W. Zhang, et al., 2011). Based on this strategy, metal ions such as Hg2+ and Ag+ can
553
be respectively determined through T-Hg2+-T and C-Ag+-C base pairs (H. Li, Zhai,
554
Tian, Luo, & Sun, 2011; H. L. Li, Zhai, & Sun, 2011).
555
Other ligands have also been used to modify CDs to improve sensitivity and
556
selectivity of CDs-based sensors in complicated food matrices (Table 1).
557
5.3. Molecule imprinting polymers (MIPs)
558
Owing to their favorable selectivity, biological recognition elements are
559
considered as the most important part of sensing platforms. Along with the high cost
560
for wide in-field application of biological-entities based sensors other challenges still
561
exist. Firstly, most biological receptors exhibit poor physical and chemical stability
562
toward extreme environments (e.g. strong acidic or basic media, organic solvents,
563
high temperatures, etc.). Antibodies and enzymes are easily denatured, thus resulting
564
in the variation of the interaction capacity of the recognition sites. Secondly, the
565
preparation of high-affinity bioreceptors is rather difficult and tedious. As an example,
566
antibodies are produced in tissue culture or animals and it might take a year or more
567
to develop highly specific antibodies due to complicated steps required. As promising
568
artificial receptors, aptamers are DNA or RNA oligonucleotides which can 26
569
specifically bind to target molecules. However, screening appropriate aptamers for
570
certain analytes is complicated and lengthy. Thirdly, even no commercial antibodies
571
are available for certain small molecules (molecular weights <1 KDa, e.g. toxins and
572
pesticides) because such small molecules cannot generate immunogenic reactions
573
alone. Therefore artificial antigens are required to be in prior synthesized (Aragay, et
574
al., 2012). Under such circumstances the development of low-cost synthetic affinity
575
agents as substitutes for those biological origins has become a research hotspot.
576
MIPs have been known as ‘‘artificial antibodies”. They can mimic the specific
577
binding characteristics of natural antibodies and can be deservedly used to selectively
578
recognize specific analytes via tailor-made sites (Ren, Liu, & Chen, 2015). As
579
depicted in Fig. 4A, the preparation of MIPs involves several procedures of
580
self-assembly, copolymerization and removing templates (target molecules or
581
analogs). Template molecules and functional monomers self-assemble by covalent,
582
non-covalent or coordinate bonds to form prepolymers in reaction solvents. Upon
583
introduction of cross-linkers and initiators, the copolymerization process is triggered
584
by light or heat leading to the forming of highly cross-linked ‘‘host-guest” polymers
585
around the prepolymers. MIPs are obtained after eluting the template with a strong
586
polar solvent, an acid, a base, a salt or a complex solvent based on the principles of
587
static electricity, hydrogen bonding, ionic bonding, etc. The as-prepared MIPs possess
588
tailored nanocavities with matchable size, shape, and corresponding functional groups
589
capable of capturing target analytes. MIPs show high mechanical strength, stable
590
physical and chemical properties in terms of high temperature, strong acid/alkali and 27
591
organic solvents. MIPs capped CDs (MIP-CDs) sensors have inspired tremendous
592
research interests owing to the integration of desirable fluorescence properties of CDs
593
with predictable structures, specific selectivity and universal application of MIPs.
594
MIPs show excellent analysis performance with good selectivity for small
595
molecules such as toxins and pesticides compared with other interfering substances
596
and analogs. Several MIP-CDs sensors have been designed to detect pesticides,
597
mycotoxins, antibiotics and other food contaminants in food samples, including
598
acetamiprid (Poshteh Shirani, et al., 2019), sterigmatocystin (L. H. Xu, Fang, Pan,
599
Wang, & Wang, 2016), zearalenone (Shao, Yao, Saeger, Yan, & Song, 2018),
600
tetracycline (J. Hou, H. Y. Li, et al., 2016) and 3-monochloropropane-1,2-diol (Fang,
601
Zhou, Zhang, Liu, & Gong, 2019). MIPs and other host-guest receptors possess
602
greater stability, better cost-effectiveness and easier engineering operations over
603
biological receptors, but they are confronted with problems such as template leakage,
604
incompatibility in aqueous media, low binding capacity and slow mass transfer
605
(Aragay, et al., 2012). New trends toward improving the sensing performance of MIP
606
sensors include (1) upgrading the hierarchical architecture of the sensors such as
607
core-shell, hollow and mesoporous structures, (2) post-imprinting modifications and
608
(3) ratiometric fluorescence (Yang, et al., 2018).
609
5.4. Switchable sensors
610
The current CDs-based sensing platforms are constructed upon the fluorescence
611
“turn-off” model in which the change of fluorescence intensity is proportional to the
612
concentration of analytes. This direct quenching analysis is susceptible to 28
613
environmental stimulus which may debase the analytical performances. Incorporating
614
CDs with fluorescence quenchers can develop novel switchable sensors in which the
615
original fluorescence of the CDs is firstly quenched by quenchers and then recovered
616
by analytes (Fig. 4B). These indirect sensors with higher analytical sensitivity than
617
the “on-off” sensors have been successfully developed to detect different targets such
618
as nutrients, heavy metals, toxins, pesticides and banned additives in food samples.
619
Table 2 gives a summary of four common switchable detection principles. In the
620
redox principle, analytes reduce/oxidize quenchers into other substances weakening
621
the quenching of the quencher and resulting in fluorescence recovery of CDs. For the
622
affinity principle, analytes can restore fluorescence of CDs by competitively capturing
623
the quencher on account of their stronger affinity to the quencher. The
624
aggregation/depolymerization principle is mainly applicable to nanoquenchers such as
625
AgNPs
626
aggregation/depolymerization of quenchers. In the principle of enzyme activity
627
inhibiting, quenchers are usually the products of the corresponding substrates
628
catalyzed by a specific enzyme. The analytes (mainly pesticides) can inhibit enzyme
629
activity, resulting in the decrease of the concentration of the quencher in the sensing
630
systems. As a result, the fluorescence of the CDs can be recovered.
631
5.5. Ratiometric fluorescence sensors
where
analytes
trigger
colloidal
stability
and
induce
632
Ratiometric fluorescence sensors involve simultaneously measuring the
633
analyte-induced fluorescence intensity changes of two or more well-resolved emission
634
and then calculating their intensity ratio. A dual-emission system includes CDs with
635
intrinsic dual-emission or a hybrid of CDs (donors) with other emitters (receptors). 29
636
For a hybrid dual-emitting system, CDs are usually coupled with QDs, organic dye
637
molecules and metal-organic frameworks (MOFs) via two main strategies. The first
638
strategy is energy transfer-based fluorescent ratiometry in which the emission of CDs
639
can excite receptors, i.e. the emission of CDs overlaps the adsorption of the receptor.
640
The second strategy is hybridizing two independent fluorophores that possess the
641
same excitation wavelength by either chemically connecting or simply physical
642
mixing. These hybridized ratiometric sensors are usually constructed by encapsulating
643
two different fluorescent components, one as the reference signal and the other as the
644
recognition unit, into a SiO2 shell using silane. The intrinsic dual-emitting systems are
645
designed by metal doping to insert new energy levels of transition metals (Wu, Hou,
646
Xu, & Chen, 2016). This model may have two dynamic fluorophores which increase,
647
decrease, or shift their signals in the opposite directions in the presence of analytes.
648
More attractively, different colors with characteristic color tonalities are usually
649
generated in ratiometric approaches. The color changes of the ratiometric sensing
650
systems typically comprise three scenarios. The color of the sensor gradually changes
651
from the intermediate color to that of the reference fluorophore when the reference
652
signal is inert to the analyte while the other emission is simultaneously quenched. In
653
contrast, a gradual color changing from the initial emission color of the reference to
654
the final mixing color of the reference and sensitive fluorophore is observed when the
655
fluorescence intensity of the sensitive fluorophore is increased and the reference
656
emission remains unchanged. In the case of two dynamic fluorophores, the color will
657
close to the fluorophore with stronger fluorescence intensity upon addition of the 30
658
analyte. This unique phenomenon presents a winning strategy for precise visual
659
quantitative assay.
660
Owing to the built-in self-calibration and potential visual detection, ratiometric
661
sensors are quite promising and suitable for food analysis in resource-constrained
662
areas. Ratiometric sensors for detecting nitrite (Xiang, et al., 2018), biothiols (Fu, et
663
al., 2017), feed additives (L. Chen, et al., 2018), heavy metals (Rao, et al., 2016), pH
664
(X. Zhu, Jin, Gao, Gui, & Wang, 2017) and biomarker (M. L. Liu, et al., 2019) have
665
been developed by integrating CDs with organic fluorescent dyes, QDs and rare earth
666
metals ions. Overall, the synergy of the desired fluorescence properties of CDs and
667
the analysis advantages of ratiometric fluorescence sensing holds great promise in
668
food safety sensing fields.
669
5.6. Flexible microdevices
670
Food analysis by unskilled personnels, staff of quality supervision department
671
and even homemakers requires convenient, rapid and on-site assaying targets by
672
naked eyes or available smart devices. Most reported CDs sensors are solution-based,
673
while incorporating CDs sensors into solid materials could be utilized to develop
674
more convenient portable sensing devices. Testing kits, filter papers (M. L. Liu, et al.,
675
2019) or strips and smartphone colorimetric-based analysis have been introduced for
676
CDs-based sensors. The smartphone-based analysis technique has attracted
677
tremendous attentions. It offers use of smartphone camera with high-resolution
678
imaging, manual or auto exposure and focus control. Smartphone-based analysis has
679
the obvious benefits of ease of use, portability and programmability. Both the 31
680
development of new Applications (Apps) and smartphone electronics can facilitate
681
broad designing and applications of smartphone biosensors.
682
6. Spectral analysis and quality control
683
Fluorescence signals are collected upon the interaction between sensors and
684
analytes. For fluorescence quenching/enhancing response sensors, the net difference
685
of fluorescence intensities (F0-F or F0/F, where F0 and F represent the fluorescence
686
intensity of CDs in the absence and presence of analytes) should be fitted with the
687
concentration [C] of analytes. For the ratiometric sensors, the ratio of the two
688
emission peaks intensities is used as an indicator to assay the concentration [C] of
689
analytes. In fluorescence emission shift based sensors, the shift distances of the
690
emission peak (nm) are collected as a quantitative parameter to quantify the analyte
691
concentration.
692
Food samples analysis Food matrices are so complex that nutrition
693
compositions undoubtedly interfere with the accuracy and practical applications of
694
detection sensors. Appropriate sample pretreatments such as filtration, centrifugation,
695
ultrasound and soxhlet extraction are necessary. It should be noted that these simple
696
treatments are inevitably required for complex food matrices, but they are much easier
697
than the sample pretreatments of chromatography, atomic absorption spectrometer and
698
other methods requiring column separation and digestion. The expectation of novel
699
fluorescent sensors is that they will simplify the pre-treatment of food samples,
700
eliminate matrix effects, and achieve in-situ non-destructive testing. 32
701
A linear range can be obtained by fitting the fluorescence spectra data against the
702
concentrations of analytes using normalized intensity, relative fluorescence intensity
703
(Fr) and empirical equations such as Stern-volume equation. The limit of detection
704
(LOD) is estimated according to 3σ IUPAC criteria (Eq. 2). Precisions are evaluated
705
by replicating detection of a certain analyte standard solutions. Accuracy of these
706
fluorescence sensors based methods is estimated by the variation analysis (e.g. T-test)
707
between routine methods (HPLC, GC-MS, atom absorption, ELISA, ICP-MS,
708
ICP-AES, etc.) and the developed methods. For real samples without target analytes, a
709
series of recovery experiments in spiked real samples should be carried out and the
710
recovery rate can be estimated by Eq. 3. LOD=3σ/k
711 712 713 714
(2)
Where k is the slop of the calibration curve and σ was the standard deviation of bank signals of the sensing systems (n=9). Recovery= (Cmeasured-Cinitial)/Cadded
(3)
715
Where Cmeasured is the concentration determined by sensors; Cinitial reprents the
716
background content of analytes in real samples; Cadded is the spiked concentration.
717
7. Conclusions and trends
718
In this review the synthesis and fluorescence properties of CDs, sensing
719
mechanisms and designing principles of CDs-based fluorescent sensors for food
720
analysis have been comprehensively summarized. We have discussed ligand-free
721
sensors, functionalized CDs based sensors and CDs integrated with other ligands or 33
722
sensing models. Regarding interference of autofluorescence in food matrices,
723
near-infrared and upconversion fluorescent CDs can efficiently avoid spontaneous
724
fluorescence of biomass which usually emits blue emission under deep ultraviolet
725
excitation. Phosphorescence behavior of CDs is rarely reported, but CDs-based room
726
temperature phosphorescence sensors would be a promising platform for avoiding
727
background fluorescence and scattered light from substrates. The complexity of food
728
matrices inspires researchers to develop varieties of ligands which can specifically
729
recognize analytes with good anti-interference. Coupling CDs-based sensors with
730
other techniques (immunoassay, electrochemical sensors and MIPs) will broaden the
731
implementation of CDs by improving their sensitive and selectivity. Multi-modes
732
sensing that coupling various fluorescence signals such as fluorescence intensity,
733
spectra shift, lifetime change and ratiometric with other signal outputs (e.g.
734
electrochemisrtry, quartz crystal microbalance and UV-vis adsorption) is a promising
735
research hotpot for improving the analysis performance of CDs-based sensors. Most
736
CDs-based sensors are currently developed and tested in laboratory. It is still an urgent
737
demand to design standardized CDs-based fluorescence sensors such as lab-on-chip
738
devices for commercial and industrial applications to realize more significant sensing
739
(e.g. global security, early detection of diseases, public safety). Portable sensors
740
including kits, strips, filter papers based sensors, and Apps on smartphones should be
741
developed instead of solution-based sensors. After solving problems of selectivity,
742
anti-interference and in-situ/non-destructive determination in food matrices,
743
CDs-based sensors will be promising platforms to provide new approaches and 34
744
technologies for food safety supervision.
745
Acknowledgements
746
This work was supported by the National Natural Science Foundation of China
747
(No.31801628) and Shaanxi Social Development Project (2018SF-401).
748
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749
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1081
with vancomycin for assaying Gram-positive bacteria like Staphylococcus
1082
aureus. Biosensors and Bioelectronics, 74, 546-553.
1083
Zhou, J., Booker, C., Li, R., Zhou, X., Sham, T. K., Sun, X., & Ding, Z. (2007). An
1084
electrochemical avenue to blue luminescent nanocrystals from multiwalled
1085
carbon nanotubes (MWCNTs). Journal of the American Chemical Society,
1086
129, 744-745.
1087
Zhu, S. J., Song, Y. B., Zhao, X. H., Shao, J. R., Zhang, J. H., & Yang, B. (2015). The
1088
photoluminescence mechanism in carbon dots (graphene quantum dots, carbon
1089
nanodots, and polymer dots): current state and future perspective. Nano
1090
Research, 8, 355-381.
1091
Zhu, X., Jin, H., Gao, C., Gui, R., & Wang, Z. (2017). Ratiometric, visual, dual-signal
1092
fluorescent sensing and imaging of pH/copper ions in real samples based on
1093
carbon dots-fluorescein isothiocyanate composites. Talanta, 162, 65-71.
1094
Zhuang, M., Ding, C. Q., Zhu, A. W., & Tian, Y. (2014). Ratiometric Fluorescence
1095
Probe for Monitoring Hydroxyl Radical in Live Cells Based on Gold 50
1096
Nanoclusters. Analytical Chemistry, 86, 1829-1836.
1097
Zu, F., Yan, F., Bai, Z., Xu, J., Wang, Y., Huang, Y., & Zhou, X. (2017). The
1098
quenching of the fluorescence of carbon dots: A review on mechanisms and
1099
applications. Microchimica Acta, 184, 1899-1914.
1100
Zuo, P., Lu, X., Sun, Z., Guo, Y., & He, H. (2015). A review on syntheses, properties,
1101
characterization and bioanalytical applications of fluorescent carbon dots.
1102
Microchimica Acta, 183, 519-542.
51
Table 1 Various ligands modified CDs for food analysis Analytes
Ligands
Linear range
LOD
Real samples
References
Salmonella typhimurium
Aptamers
103-105 cfu/mL
50 cfu/mL
egg
(R. J. Wang, et al., 2015)
glyphosate
0.06-473 µM
4.7×10–5 µM
Pearl River water, tea, and soil samples
(D. Wang, Lin, Cao, Guo, & Yu, 2016)
IgG
E. coli
103-108 cfu/mL
450 cfu/mL
tap water, apple juice, human urine
(Weng, et al., 2015)
Mannose
E. coli
amikacin
3.904×105-7.625×102 cfu/mL
552 cfu/mL
fruit juice (apple, pineapple and orange)
(Chandra, Chowdhuri, Mahto, Samui, & Sahu, 2016)
E. coli
colistin
3.81×102–2.44×104 cfu/mL
460 cfu/mL
human urine, apple juice, and tap water
(Chandra, Mahto, Chowdhuri, Das, & Sahu, 2017)
S. aureus
Vancomycin
3.18×105-1.59×108 cfu/mL
9.40×104 cfu/mL
orange juice
(Zhong, et al., 2015)
E. coli
Mannose
0-108cfu/mL
100 cfu/mL
drinking water, apple juice
tannic acid
PEGA
0.1-10mg/L
0.018 mg/L
PEGA: polyethyleneglycol bis(3-aminopropyl)
(Irving Po-Jung Lai & Yu-Jia Li, 2016)
red and white wine
(Ahmed, Laino, Calzon, & Garcia, 2015)
Table 2 The CDs based switchable FL sensors Type
Analytes
Quenchers
Principles
Cr(VI) Ascorbic acid
Redox reaction
Affinity
MnO2
Linear range
LOD
5.0-200 µM
1.35 µM
0.18-90 µM
42 nM
AA reduce those quenchers
Real samples fresh fruits, vegetables, commercial fruit juices
Dichlorvos
Cu2+
thiocholine reduced Cu2+ to Cu+
6.0×109-6.0×108 M
3.8×109 M
cabbage, fruit
90 fM
Protoporphyrin
Sudan red III oxidize protoporphyrin into aromatic amines
9.9 pM-0.37 nM
Sudan red III
tomato ketchup, red chili sauce
AFB1
AuNPs
aptamer showed higher special binding ability to AFB1
0.005-2 ng/mL
5 pg/mL
peanut, corn
GSH
Hg2+
the stronger affinity between thiol and Hg2+
0.08-60 µM
20 nM
Hg2+
GO
CDs were released from GO due to the formation of T-Hg2+-T duplex
5-200 nM
2.6 nM
Al3+
Dopamine
dopamine has high affinity towards Al3+ at the ratio of 2:1 at pH 7.4
4-40 µM
0.0329 µM
kanamycin
MoS2
the strong specificity between the aptamer and kanamycin
4-25 µM
1.1 µM.
tomatoes, bananas and cucumbers citrus leaf fried bread stick, bread, chips, steamed bread milk
References (X. Gong, et al., 2017) (J. Liu, et al., 2016) (J. Hou, G. Dong, et al., 2016) (Jahan, Mansoor, Naz, Lei, & Kanwal, 2013) (B. Wang, et al., 2016) (Fu, et al., 2017) (Xin Cui, 2015) (F. Yan, et al., 2016) (Y. Wang, et al., 2016)
AuNPs melamine Hg2+
Aggregation and depolymerization
Inhibiting enzyme activity
melamine reduce FRET effect between CDs and AuNPs via binding to AuNPs melamine binds to Hg2+ via multi-nitrogen heterocyclic ring and reduces the interaction between Hg2+ and CDs oxytetracycline showed stronger 3+ coordination ability to Fe
oxytetracycline
Fe3+
glyphosate
AgNPs
glyphosate induce the aggregation of Ag NPs
methyl parathion
Quinone
methyl parathion inhibit tyrosinase activity
carbaryl
AgNPs
carbaryl
H2O2
dichlorvos
TNB
analytes inhibit the activity of AChE
50-500 nM
36 nM
raw milk, milk
(Dai, et al., 2014)
1-20 µM
0.3 µM
powder
(C. H. Lei, 2016)
0.1-2.7 µM
22.8 nM
milk
0.025-2.5 µg/mL
12 ng/mL
1.0×10-10-1.0×10-4 M
1×10-8-1×10-4 g/L
0.006 µg/L
apple juice
6.3×10-9-6.3×10-4 g/L
5.4×10-9 g/L
apples
5.0×10-11-1.0×10-7 M
1.9×10-11 M
fruit juice
MnO2/MoS2: MoS2 nanosheets; AuNPs: gold nanoparticle; AgNPs: silver nanoparticle; TNB: 5-thio-2-nitrobenzoic acid; AFB1： aflatoxin B1； AChE：Acetylcholinesterase; GO: graphene oxide
4.8×10−11 M
rice, millet, wheat flour, maize flour cabbage, milk, fruit juice
(An, Zhuo, Zhang, & Zhu, 2015) (L. Wang, et al., 2016) (J. Y. Hou, et al., 2015) (Zhao, et al., 2016) (H.Li, et al., 2016) (J.Hou, et al., 2016)
Size tuning Arc discharge
Laser ablation
Electrochemical
A)Top-down Electrode Laser Beam
Insert Gas Chamber
Carbon target
Insert Gas Chamber
Pt grid
MWCNT Carbon target immersed in water or PEG200
V Pt grid
Graphite electrode
Laser Beam and Carrier Gas
Electrode
Soot Deposition
MWCNT
Raw CDs
B)Bottom-up Microwave irradiation
Carbon precursor Adequate solvent
Thermal carbonization
Carbon precursor Adequate solvent
Microwave
Sonication
Precursor
CDs
Ultrasonic oscillation
Surface chemistry C) Surface passivation/functionalization Surface passivation Neutralization
Functionalizing negative/positive charge for electronic coupling
Nitric acid reflux
Organic polymer reflux
Raw CDs other functional groups for coupling
Inorganic salt doping
Electron energy
D)Doping Before doping Conduction band
After doping
Conduction band
Before doping
Conduction band
After doping
Conduction band
Fermi level
Valence band
Valence band
Valence band
Valence band
p-type doping n-type doping Fig.1. The schematic illustration of the synthesis methods of based on size-tuning and surface chemistry tuning strategies
(C)PET
LUMO E
LUMO
HOMO
eHOMO
E LUMO
HOMO
HOMO
Reductive PET
Oxidative PET
FRET
D
r
A
1-10nm
FL intensity
(A)SQE
Donor emission
Through-space energy transfer
(B)DQE
Wavelength (nm) (E) IFE
Fig. 2. The quenching mechanisms of fluorescent CDs
Adsorption
Acceptor adsorption
(D)FRET
Quencher
LUMO
e-
A) Amide reaction
Carbodiimide reagents ligands
B) Esterification reaction
C) Electrostatic immobilization
D) π-π stacking
Fig. 3. Schematic functionalization of CDs motif.
A)
+
Covalent/non-covalent / coordinate bonds
+
Self-assembly Prepolymers
Cross linker
Polymerization
Template Functional monomers
Rebind template Remove template
B)
Fig.4. (A) A general scheme of molecules imprinted CDs sensors preparation and detection principles; (B) The basic principle of “on-off-on” switchable CDs-based fluorescence sensors.
Highlights 1. Fluorescence properties for reducing interferences to food safety screening. 2. Fluorescence response mechanisms of CDs-based fluorescent sensors. 3. Designing and analysis principles of CDs sensors for food analysis. 4. Selectivity improving and interference reducing for practical applications. 5. New trends in material, ligands and portable sensors designing.
S0924-2244(19)30211-0
DOI:
https://doi.org/10.1016/j.tifs.2019.11.017
Reference:
TIFS 2666
To appear in:
Trends in Food Science & Technology
Received Date: 19 March 2019 Revised Date:
26 September 2019
Accepted Date: 16 November 2019
Please cite this article as: Luo, X., Han, Y., Chen, X., Tang, W., Yue, T., Li, Z., Carbon dots derived fluorescent nanosensors as versatile tools for food quality and safety assessment: A review, Trends in Food Science & Technology (2019), doi: https://doi.org/10.1016/j.tifs.2019.11.017. 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 Published by Elsevier Ltd.
+
Bacteria
Veterinary drug residues
t a R
c
Banned additives
Off
FL intensity
Toxins
i r t e m io
FL intensity
Pesticide residues
FL intensity
GRAPHICAL ABSTRACT
Analyte concentration
Functional components
Heavy metal
On
FL intensity
λ/nm
Analyte concentration
λ/nm
CDs based sensors
Analytes in food samples
Fluorescence response
1
Carbon dots derived fluorescent nanosensors as versatile
2
tools for food quality and safety assessment: a review
3
Xueli Luo a, Yong Han a, Xiumei Chen a, Wenzhi Tang a, Tianli Yue a, b, c, Zhonghong
4
Li a, b, c*
5
a
6
Shaanxi 712100, PR China
7
b
8
Ministry of Agriculture, Yangling, Shaanxi 712100, PR China
9
c
10
College of Food Science and Engineering, Northwest A&F University, Yangling,
Laboratory of Quality & Safety Risk Assessment for Agro-products (YangLing),
National Engineering Research Center of Agriculture Integration Test(Yangling),
Yangling, Shaanxi 712100, PR China
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
*
Corresponding author. Tel: +86 29 8703 8857; E-mail: [email protected]; [email protected].
1
32
Abstract
33
Background: Food analysis is essential in monitoring food quality for risk
34
assessment regarding public health. Traditional techniques can meet the requirement
35
of routine food analysis in laboratory. However, serious food safety situations
36
urgently demand rapid, time-saving, low-cost analysis methods even on-site, portable
37
and household testing kits. Fluorescence analysis exhibits immense potential for food
38
safety owing to its remarkable advantages of high sensitivity, ease of operation, low
39
cost and rapid result outputs.
40
Scope and approach: Carbon dots (CDs) are novel 0D carbonic nanomaterials
41
recently emerging as potential substitutes for traditional fluorescent materials.
42
Compared with the conventional fluorescent materials, e.g. organic fluorescent dyes,
43
metal nanoparticles/nanoclusters and quantum dots (QDs), CDs possess many
44
appealing merits such as ease of preparation, low cost, non-blinking, low cytotoxicity,
45
excellent biocompatibility and high resistance to photo-bleaching. As a result
46
CDs-based fluorescence sensing provides excellent analysis platforms for monitoring
47
food-related analytes. This review provides a comprehensive overview of the
48
state-of-the-art synthesis methods and the fluorescence properties of CDs along with
49
the sensing mechanisms and designing principles of CDs-based fluorescent sensors
50
for food analysis. Possible challenges and appealing prospects of CDs-based
51
fluorescent sensors are also discussed.
52
Key findings and conclusions: CDs have been widely applied in bio-imaging,
53
sensing, drug delivery, catalysis and optronics. Integration of CDs into food science 2
54
and engineering for food safety control and risk assessment exhibits a bright future.
55
Keywords: Carbon nanomaterials; Nanosensors; Analysis of Food contaminants;
56
Optical sensors; Fluorescence assay; Food safety
3
57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83
Contents 1. 2.
3.
4.
5.
6. 7.
Introduction ............................................................................................................................... 5 Synthesis of CDs ....................................................................................................................... 8 2.1. Size-tuning .................................................................................................................... 8 2.2. Surface chemistry tuning............................................................................................... 9 2.2.1. Surface passivation/functionalization................................................................ 9 2.2.2. Heteroatom doping .......................................................................................... 11 Fluorescent properties ............................................................................................................. 13 3.1. Photoluminescence mechanism................................................................................... 13 3.2. Fluorescent properties ................................................................................................. 14 3.3. Phosphorescence ......................................................................................................... 15 Fluorescence response mechanisms ........................................................................................ 16 4.1. Direct fluorescence quenching .................................................................................... 17 4.2. Direct fluorescence enhancement................................................................................ 20 4.3. Ratiometric response ................................................................................................... 20 4.4. Wavelength shifts ........................................................................................................ 21 Design principles for food analysis ......................................................................................... 21 5.1. Ligand-free sensors ..................................................................................................... 21 5.2. Ligand-functionalized sensors..................................................................................... 22 5.2.1. Covalent conjugation....................................................................................... 23 5.2.2. Noncovalent modification ............................................................................... 25 5.3. Molecule imprinting polymers (MIPs) ........................................................................ 26 5.4. Switchable sensors ...................................................................................................... 28 5.5. Ratiometric fluorescence sensors ................................................................................ 29 5.6. Flexible microdevices ................................................................................................. 31 Spectral analysis and quality control....................................................................................... 32 Conclusions and trends ........................................................................................................... 33
84 85 86 87 88
4
89
1. Introduction
90
Food safety is emerging as a global human health issue. The continuing
91
development of modern industry, agriculture and food processing has resulted in
92
chemical contamination, biological pollutants and food adulteration (Aragay, Pino, &
93
Merkoci, 2012; Potorti, et al., 2018; Salvo, et al., 2018; Salvo, et al., 2019). Food
94
analysis and quality assessment play central roles in food safety control by providing
95
risk pre-warning and consumers protecting from the threats of adulteration, spoilage
96
and contamination. However, food matrices are too complicated to be analyzed
97
without proper pretreatments because of the interference of co-existing substances.
98
Conventional food analysis methods, e.g. spectroscopy, immunoassay, culture and
99
colony counting, enzymatic, electrochemical, nuclear magnetic resonance and
100
chromatography, offer powerful trace analysis with high reproducibility, good
101
sensitivity and selectivity. However, they require specific instrumentations, skilled
102
personnel and tedious sample preparation. Feasible and facile analysis, especially for
103
in situ and real-time monitoring, is urgently required for quick pre-warning of serious
104
food safety threats.
105
Compared with conventional analysis methods, the fluorescence-based food
106
analysis is very promising. It possesses intrinsic simplicity, high sensitivity, easy
107
operation, low cost and simple equipment requirement. Organic fluorescent dyes,
108
metallic nanoparticles/nanoclusters, quantum dots (QDs) and rare earth up-conversion
109
nanomaterials are classical fluorescent nanomaterials, but they suffer from inevitable 5
110
disadvantages which restrict their practical applications for food analysis. Heavy
111
metal-based semiconductors QDs such as CdSe/CdTe are inevitably involved in
112
complicated
113
stability/biocompatibility (Y. Liu, et al., 2017). The high cost of noble metal
114
nanoparticles/nanoclusters
115
nanoparticles/nanoclusters together with low stability limit their wide applications.
116
Rhodamine, fluorescein, cyanine and coumarin are the common organic molecular
117
dyes that have been widely used in fluorescence sensing. These organic fluorescent
118
dyes usually show poor solubility, severe photobleaching and poor bio-availability.
119
Furthermore, the narrow excitation of dyes is undesirable for sensing due to the
120
requirement of different wavelength lights to excite dyes. Herein, developing
121
eco-friendly fluorescence sensing materials with desirable fluorescence properties,
122
low cost and adequate sensitivity is urgently essential and promising for designing
123
novel fluorescent sensors.
and
harsh
synthesis
and
along
the
high
with
high
toxicity
toxicity
of
and
heavy
poor
metal
124
Carbons dots (CDs), also called as carbon nanoparticles or carbon nanodots,
125
were firstly discovered in 2004 by Xu et al during the electrophoresis purification of
126
single-walled carbon nanotubes (X. Xu, et al., 2004). As the emerging 0D carbonic
127
nanomaterials, CDs have been defined as discrete, spherical or quasi-spherical
128
nanoparticles with particle sizes less than 10 nm (Baker & Baker, 2010). The structure
129
of CDs is considered as sp2 conjugated carbon cores embedded in amorphous shells
130
(mainly
131
oxygen/nitrogen-based groups or polymeric aggregations (L. B. Li & Dong, 2018; S.
sp3
hybridized
carbon
matrices)
6
containing
considerable
132
J. Zhu, et al., 2015). CDs emerge as eco-friendly and promising sensory nanomaterials
133
owing to their attractive merits for fluorescence sensing, including facile synthesis,
134
excellent solubility, cost-effectiveness, low toxicity, biocompatibility and unique
135
fluorescence properties. The fluorescence properties of CDs mainly refer to their (1)
136
excitation spectrum, i.e. the changes of the fluorescence intensity versus different
137
excitation wavelength at a fixed emission wavelength; (2) emission spectrum, i.e. the
138
change of fluorescence intensity versus emission wavelength at a certain excitation
139
wavelength, and the emission peak intensity is often used as a quantitative parameter
140
to determine analyte content; (3) fluorescence life, i.e. the required time for
141
fluorescence intensity to decrease to 1/e of the maximum intensity after withdrawing
142
the excitation light; (4) fluorescence quantum yield (FLQY), i.e. the ratio of the
143
number of excited molecules returned to the ground state by fluorescence emission
144
and the number of all excited molecules; (5) Stokes shift, i.e. the difference between
145
the maximum fluorescence emission wavelength and the maximum absorption
146
wavelength.
147
Reviews on the synthesis, properties and applications of CDs have been
148
published (Du & Guo, 2016; Lim, Shen, & Gao, 2015; J. Wang & Qiu, 2016; Zuo, Lu,
149
Sun, Guo, & He, 2015), but a more focused overview regarding food analysis is still
150
lacking. This is likely because of the challenge to research presented by interferents
151
existing in extremely complex food matrices. In this review, we briefly present the
152
synthesis and fluorescence properties of CDs. We also emphatically describe the
153
fluorescence sensing mechanisms and designing principles of CDs-based sensors for 7
154
food analysis. In conclusion, current challenges and new trends in CDs sensing
155
applications for food analysis are highlighted.
156
2. Synthesis of CDs
157
The synthesis approaches of CDs can be grouped into size tuning and surface
158
chemistry tuning. Size tuning can be used to synthesize CDs and regulate their
159
fluorescence properties by controlling their sizes. Surface chemistry tuning strategies
160
can be used to tailor surface groups of CDs to induce different surface states. A
161
schematic illustration of the two synthesis methods is shown in Fig. 1.
162
2.1. Size-tuning
163
Fluorescence properties of CDs predominantly depend on their size owing to the
164
quantum-confinement effect and the variation in density and nature of sp2 domain.
165
Herein, size-tuning via shortening or prolonging the reaction time can be used to
166
modulate the energy band gap of CDs.
167
According to the chosen carbonaceous precursor, the size-tuning synthesis routes
168
are mainly divided into ‘‘top-down’’ (Fig. 1A) and ‘‘bottom-up’’ (Fig. 1B). The
169
former method involves exfoliating larger carbon materials such as nanodiamonds,
170
graphite rods, carbon nanotubes, carbon soot, and graphite oxide into smaller carbon
171
nanoparticles via arc discharge (X. Xu, et al., 2004), laser ablation (Sun, et al., 2006)
172
and electrochemical (Zhou, et al., 2007). The as-prepared CDs with a perfect sp2
173
carbon structure lack an efficient band gap to generate fluorescence. A surface
174
modification is often required to improve their luminous efficiency (S. J. Zhu, et al., 8
175
2015). In another respect, the yield of the method is too low to synthesize CDs in
176
large scale, which is not conducive to their wide applications. The “bottom-up” route
177
carbonizes carbon-rich molecular precursors, such as citrate, amino acids,
178
carbohydrates, polymer-silica nanocomposites and even biomass, into CDs through
179
hydrothermal/solvothermal, microwave and ultrasonic oscillation methods.
180
2.2. Surface chemistry tuning
181
Two urgent challenges regarding sensing applications of raw CDs are the low
182
FLQY and the lack of functional groups for surface grafting/bio-conjugation of
183
recognition units. Surface chemistry tuning approaches (Fig.1 C, D) can tailor the
184
fluorescence behaviors by modulating the surface chemical groups or π-π conjugated
185
network as well as by adjusting the degree of surface oxidation. Surface
186
passivation/functionalization and heteroatom doping are the two major ways to tune
187
surface chemistry of CDs.
188
2.2.1. Surface passivation/functionalization
189
Surface functionalization (Fig. 1C) introduces various organic, inorganic,
190
polymeric or biological species via functional groups or π-π conjugated network to
191
CDs. Three main purposes for surface functionalization include improving the
192
solubility, tuning the fluorescence properties especially for improving the FLQY and
193
increasing the selectivity for analytes. For example, the FLQY of CDs has been
194
significantly improved via modifying with amino-containing compounds. Amino
195
relevant moieties have been confirmed to give higher FLQY and more tunable
196
fluorescence caused by non-local π orbital and molecular orbital resonance structures 9
197
(F. Y. Yan, et al., 2018). Oxygen-containing groups (e.g. carboxyl, hydroxyl and
198
epoxy), which can be easily obtained by different methods such as strong acids
199
oxidation, endow CDs with desirable water solubility and facile functionalization.
200
CDs are generally functionalized by covalent coupling (Y. Yang, et al., 2012),
201
coordination (Yin, Liu, Jiang, Chen, & Yao, 2013), electrostatic absorption, π-π
202
interaction (H. L. Li, Zhang, Wang, Tian, & Sun, 2011), sol-gel technology (F. Wang,
203
Xie, Zhang, Liu, & Zhang, 2011), hydrophobic interactions and host-guest
204
interactions. More fundamental and detailed functionalization approaches would be
205
discussed in Section 5.
206
Surface passivation is necessary to endow CDs with desirable fluorescence
207
properties. Surface passivation methods include (1) oxidizing the surface carbons to
208
carboxylic acid groups using nitric acid, (2) doping the oxidized CDs by inorganic
209
salts (e.g. ZnS, ZnO) and (3) capping the pristine CDs with organic polymers (e.g.,
210
polyethylene glycol) (Esteves da Silva & Gonçalves, 2011). Organic molecules (also
211
considered as precursors) and polymers, including polyethylene glycols (e.g. PEG900N,
212
PEG1500N) and amine molecules (e.g. thiourea, 4,7,10-trioxa-1,13-tridecanediamine
213
and 1-hexadecylamine) are predominant passivation agents. PEG-passivated CDs
214
have been prepared by connecting -OH of PEG to -COOH of CDs. Such
215
modifications are complicated and also additional purifications are inevitably required
216
to collect the modified CDs. In some cases surface passivating agents (mainly organic
217
molecules) could act as functionalizing agents to modify physical/fluorescence
218
properties of CDs and therefore additional modifications could be omitted (Dong, et 10
219
al., 2012). Two main explanations for the passivation mechanisms are: (1) filling
220
defects on the surface of CDs and (2) generating energy traps by organic polymers (L.
221
B. Li & Dong, 2018).
222
2.2.2. Heteroatom doping
223
Heteroatoms doping (Fig. 1D) improves fluorescence properties by doping
224
heteroatoms into the carbon skeleton of CDs. The method changes the Fermi level to
225
modulate electronic characteristics and provides more active sites such as -OH,
226
-COOH, and -NH2 on the CDs surface which can serve as energy traps to improve the
227
fluorescence properties (Lai, et al., 2013). Both the types and the content of dopants
228
have great effects on the fluorescence properties of CDs. For example, the FLQY of
229
CDs without doping is 5.3%, much lower than 73% of the N,S co-doped CDs (Y.
230
Dong, et al., 2013). In another example, the fluorescence emission of N doped CDs
231
shows a gradual red-shift with increasing content of N dopants (Y.-Q. Zhang, et al.,
232
2012). Furthermore, additional passivation or modification could be unnecessary for
233
doped CDs. The mainly reported dopants include metal ions (e.g. Mn, Co, Cu, Mg)
234
and nonmetallic dopants (e.g. nitrogen (N), boron (B), sulfur (S), phosphorus (P),
235
fluorine (F) and chlorine (Cl)). These dopants can be independently applied or
236
combined with one or more other dopants, i.e. the process of co-doping. N is the most
237
prominent doping candidate due to its matchable atomic size and five valence
238
electrons available to bond with C atoms (Du & Guo, 2016; Y.-Q. Zhang, et al., 2012).
239
N can change the electronic and transport properties of CDs by infusing electrons into
240
carbon-based materials (Ma, Ming, Huang, Liu, & Kang, 2012). Several reports have 11
241
demonstrated that the performance of N dopants for improving the FLQYs following
242
the order of primary amine>secondary amine (tertiary amines are rarely applied to
243
produce CDs) and diamine>monoamine (Zhai, et al., 2012).
244
According to the charge carriers (i.e., holes or electrons), the doping types
245
include n-type and p-type. The n-type (e.g. N, P, S, Cl doping) donates extra electrons
246
while p-type (e.g. B doping) introduces extra holes to the hosts (L. B. Li & Dong,
247
2018). The introduction of new energy levels by incorporating impurities in the
248
forbidden band will change the Fermi level. For n-type doping, the electron
249
concentration will increase while the minority carrier-hole concentration will decrease
250
when more dopants are incorporated. Accordingly, the Fermi level will be much
251
closer to the bottom of the conduction band. In terms of p-type doping the Fermi level
252
will gradually approach to the top of the valence band and even enter the valence band.
253
These changes induce the radiative recombination of electron-hole pairs, resulting in
254
significant changes of the fluorescence properties. In addition, the introduction of
255
dopants will change the surface groups and the micro-structures of CDs, thus inducing
256
surface defective emission including trap states and molecular states. The
257
conventional synthesis methods for undoped CDs are also applicable to prepare doped
258
CDs although extra doping procedures or other precursors containing doping elements
259
are needed. One-step methods can be used to prepare doped CDs via chemical
260
reactions between the carbon source and the dopants using common procedures. In
261
multi-step approaches, undoped CDs are firstly prepared followed by doping via
262
hydrothermal reaction, strong acid treatment, chemical vapor deposition or 12
263
photochemistry synthesis. The successful doping can be evidenced by XPS
264
characterizations of doped CDs which can reveal valence states of all elements,
265
chemical bonds and atomic ratios of C atoms to the doping heteroatoms.
266
Most CDs have been synthesized via complicated systems/media, and resultant
267
purifications are unavoidably required to collect CDs. Several purification techniques
268
including centrifugation, dialysis and/or extraction, high-performance liquid
269
chromatography (HPLC) (X. J. Gong, et al., 2014), polyacrylamide gel
270
electrophoresis (H. Liu, et al., 2007), and column chromatography separation (Jia, Li,
271
& Wang, 2012) have been reported.
272
3. Fluorescent properties
273
3.1. Photoluminescence mechanism
274
The photoluminescence mechanism of CDs includes (a) intrinsic emission,
275
involving the quantum-confinement effect of size-dependent sp2 conjugated π-domain
276
(Ye, et al., 2013) together with the recombination of localized electron-hole pairs and
277
(b) surface states emission including molecule states and trap states (Schneider, et al.,
278
2017; L. Wang, et al., 2013). Molecule states mainly account for the fluorescence
279
origin of CDs derived from citric acid as the carbon source. Trap states induced
280
emissions are related to special edge states on sp3 carbon framework and functional
281
groups. The band gaps of σ and σ* states of sp3 matrix have been proven to influence
282
π and π* electronic levels of sp2 domain (F. Li, Yang, & Xu, 2019). At present the
283
fluorescence origin of CDs is assumed to be a synergistic effect of intrinsic state 13
284
emission and defect emission, but more research should be done to reveal the exact
285
origins of the fluorescence emissions.
286
3.2. Fluorescent properties
287
pH The pH-dependent behavior is relevant to electronic transition changes of
288
π-π* and n-π* in graphite nanodomains which refill or deplete their valence bands via
289
protonation-deprotonation. This implies that the surface defects may serve as
290
capturing centers for carriers which results in correlated luminescence. Pyridine N
291
accepts protons and is gradually protonated with the decrease of pH. Electrons are
292
transferred from the protonated N to the adjacent C with conjugated structure, leading
293
to the increase of fluorescence intensity.
294
Excitation Excitation-dependent emission might result from the quantum effect
295
and/or the different emissive traps on the CDs surface (Y. Wang, et al., 2013). It is
296
considered that the excitation-dependent properties may be related to the aromatic
297
C=C and the surface defects from C-OH and C=O groups (Zheng, et al., 2015). CDs
298
synthesized by using ammonium citrate and ethylenediamine as precursors present the
299
excitation-dependent property. The surface defects and the narrower size distribution
300
of CDs may contribute to the excitation-dependent property (Z. Li, et al., 2015). Some
301
reported CDs show excitation independent emissions which may be attributed to their
302
uniform size and surface state.
303
Tunable emissions Tunable emissions involve modulating CDs emissions by
304
adjusting condensation reactions, synthesis operations, doping (Y.-Q. Zhang, et al.,
305
2012) and reaction solvents (Miao, et al., 2017). Biological auto-fluorescence 14
306
substrates such as proteins, amino acids, bio-tissues and cells usually emit blue
307
fluorescence. This tunable property can be used to synthesize CDs with long
308
wavelength emission which is helpful in reducing food matrix interference such as the
309
spontaneous blue fluorescence of biomass and ion absorption.
310
Up-conversion Up-conversion fluorescence is an anti-Stokes luminescence
311
phenomenon wherein the emission wavelength is shorter than the selected excitation
312
wavelength (Y.-Q. Zhang, et al., 2012). Most reported CDs and biological tissues
313
normally emit blue fluorescence when excited by ultraviolet light. This obviously
314
interferes with accurate fluorescence analysis within organisms. The up-conversion
315
property paves a way to avoid the auto-fluorescence of organisms or food matrices
316
containing proteins or amino acids. Furthermore, the synthesis of CDs with
317
up-conversion emissions is simple and without complicated modifications required for
318
traditional lanthanide doped up-conversion nanoparticles.
319
3.3. Phosphorescence
320
Phosphorescence is a phenomenon of delayed photoluminescence that
321
corresponds to the radiative decay of the molecular triplet state. Room-temperature
322
phosphoresce sensors with long lifetime eliminate the interference of short-lived
323
background fluorescence such as the bioluminescence of tryptophan, tyrosine and
324
guanylate. More importantly, most detection matrices show no phosphorescence
325
emission. Herein, endowing CDs with excellent phosphorescence would open a
326
promising horizon for bio-sensing because of the longer lifetime of observable
327
emissions, the lower fluorescence interference and the more sensitive response to 15
328
small molecules. But realizing a long-lifetime room-temperature phosphoresce of CDs
329
is difficult because of the deficient triplet excitons and the non-radiative deactivations.
330
The reported CDs-based phosphorescent materials were obtained by embedding CDs
331
into various polymer matrices, e.g. polyvinyl alcohol, layered double hydroxides,
332
potash alum, aluminum sulfate, zeolites, urea/biuret, polyurethane and silica gel.
333
These matrix molecules can protect phosphors from being quenched by molecular
334
vibrations, oxygen molecules, and high temperatures. These host matrices only allow
335
specific CDs to possess room-temperature phosphoresce. Hence, choosing an
336
appropriate background matrix is critical to achieve phosphorescence. In addition,
337
these CDs mainly exhibit phosphorescence with short wavelengths (blue- to
338
green-light spectrum). These unfavorable limitations largely hinder the developments
339
and applications of CD-based room-temperature phosphorescence materials (Li, et al.,
340
2019). CDs with room-temperature phosphorescence properties have recently been
341
readily synthesized by the one-pot solvothermal method via the elemental doping
342
strategy instead of using the matrix-assisted oxygen-barrier method (Long, et al.,
343
2018). More interestingly, a universal host matrix (boric acid) has been novelly
344
exploited to activate long lifetime and multi-color (blue, green, green-yellow and
345
orange) room-temperature phosphorescence of CDs (Li, et al., 2019).
346
4. Fluorescence response mechanisms
347
The basic analytical principles of fluorescence sensors can be summarized as the
348
interaction between recognition components and targets which induces the changes of 16
349
the fluorescence properties of CDs and the changes quantitatively relate to the
350
concentration or structure of the target analytes. Additionally, recognition components
351
should have insignificant influence on the excitation/emission of CDs. The four main
352
fluorescence signal outputs are fluorescence quenching, fluorescence enhancement,
353
the emission wavelength shift and the fluorescence lifetime. They are summarized as
354
follows.
355
4.1. Direct fluorescence quenching
356
The target-trigged quenching mechanisms are mainly divided into static
357
quenching effect (SQE), dynamic quenching effect (DQE), photo-induced electron
358
transfer (PET), Förster resonance energy transfer (FRET) and inner filter effect (IFE),
359
which are shown in Fig. 2.
360
SQE (Fig. 2A) is closely related to the formation of a non-fluorescent
361
ground-state complex between ground-state molecules of CDs and quenchers. A
362
quenching process can be explained as SQE when coincidences happen with (a) the
363
insignificant change of fluorescence life in the absence (τ0) and the presence of a
364
quencher (τ), i.e. τ0/τ =1, (b) the changes of the absorption spectrum upon introduction
365
of a quencher, and (c) the gradually fluorescence increase owing to a
366
rising-temperature induced instability of ground-state complex. Chemical interactions
367
between CDs and quenchers are necessary for a SQE process, thereby it is
368
indispensable to modify or functionalize CDs (Zu, et al., 2017). For instance,
369
tartrazine can quench the fluorescence of CDs via SQE because of the formation of a
370
ground-state complex (H. Xu, Yang, Li, Zhao, & Liao, 2015). 17
371
DQE (Fig. 2B) involves the collision between the excited state of CDs and
372
quencher. Different characteristics are presented as (a) τ0/τ≠1, (b) insignificant
373
changes of the absorption spectrum, and (c) the gradual increase of quenching effect
374
in terms of a rising temperature (Zu, et al., 2017).
375
The PET (Fig. 2C) quenching mechanism is related to an electron transfer
376
process between the excited stage of the electron donor/receptor and the quencher.
377
The quencher can coordinate with groups on the surface of CDs to form a complex
378
which would initiate non-radiative emissions when the excited electrons return to the
379
ground state. Depending on the role of CDs, PET can be classified into reductive and
380
oxidative PET. As the electron receptor, CDs receive electrons from the donor in the
381
reductive PET process which is driven by the energy gap between the lowest
382
unoccupied molecular orbitals (LUMO) of the quencher and the highest occupied
383
molecular orbitals (HOMO) of CDs. In the oxidative PET process electrons are
384
donated by the activated CDs to the quencher. The oxidative PET is driven by the
385
energy gap between the LUMO of the CDs and the LUMO of the quencher (Zu, et al.,
386
2017).
387
The FRET (Fig. 2D) mechanism is characterized by non-radiative energy
388
transfer when an energy donor (denoted as ‘D’ in Fig. 2D) transmits its excited state
389
energy directly to an acceptor (denoted as ‘A’ in Fig. 2D) via a non-radiative
390
‘dipole-dipole’ coupling instead of emitting photons for absorption by the acceptor.
391
The occurrence of FRET relies on the premises that the donor is the independent
392
luminescent center and that the acceptor may not necessarily emit light but have an 18
393
independent absorption spectrum overlapping the donor emission spectrum (Sapsford,
394
Berti, & Medintz, 2006). Moreover, FRET processes are distance-dependent, and the
395
distance between D and A of 1-10 nm is required for an effective FRET. The
396
calculation method of the CDs-quencher distance (r) and Förster distance (R0) could
397
refer to the literature (J. Liu, et al., 2016)..
398
IFE (Fig. 2E) refers to the fluorescence quenching of fluorophores due to that the
399
co-existing other light-absorbing substances in the sensing system absorb the
400
excitation and/or emission light. In the IFE process the absorption peaks and
401
fluorescence lifetime of CDs will not change because no new substance is generated.
402
IFE is a well-known interference in spectrofluorometry studies, and the Parker
403
equation (Eq. 1) is often utilized to correct the fluorescence intensities. Some
404
IFE-based fluorescence sensors have been recently developed under the prerequisites:
405
(a) the absorption spectrum of the quencher overlaps the excitation/emission spectrum
406
of CDs and (b) the distance between CDs and the quencher is more than 10 nm. Many
407
fluorescence sensors targeted to both inorganic and organic analytes have been
408
successfully exploited by utilizing IFE quenching mechanism. For instance, the
409
fluorescence of CDs can be quenched by silver nanoparticles (AgNPs) and Cr(VI),
410
while the fluorescence would be restored by certain analytes due to their stronger
411
affinity to the quenchers. Hence switchable sensors have been designed to determine
412
pesticides in spiked apple juice (Zhao, Chen, Sun, & Yang, 2016) and ascorbic acid in
413
fresh fruits and commercial fruit juices (X. Gong, et al., 2017).
414
Fcor 2.3dAex gAem 2.3sAem = 10 Fobsd 1-10-dAex 1-10-sAem 19
(1)
415
where Fobsd and Fcor represent the observed fluorescence and the corrected
416
fluorescence after deducting IFE from Fobsd; Aex and Aem are UV absorbance at the
417
maximum excitation and emission wavelength. S is the thickness of the excitation
418
beam, d is the cuvette width and g is the distance between the edge of the excitation
419
beam and the edge of the cuvette.
420
4.2. Direct fluorescence enhancement
421
Directly enhanced fluorescence sensors are developed when (1) the CDs show
422
weak fluorescence or no fluorescence in the absence of the analytes and (2) the
423
fluorescence can be enhanced by analytes. Two main mechanisms of the
424
aggregation-induced enhancement (AIE) and the metal-enhanced fluorescence (MEF)
425
explain the analyte-trigged fluorescence enhancement phenomenon. In the AIE
426
mechanism, the analyte can coordinate with groups on the surface of the fluorophore
427
which results in surface charge changes. MEF is usually based on the surface plasmon
428
resonance (SPR) phenomenon of metallic nanostructures such as Au/Ag NPs which
429
enhances the local electromagnetic field and leads to the increased fluorescence of
430
nearby fluorophores. For example, Ag+-induced fluorescence enhancement can be
431
used to detect Ag+ (Gao, et al., 2015).
432
4.3. Ratiometric response
433
Single-emission fluorescence sensors usually suffer from low sensitivity and low
434
selectivity because fluorescence intensities can be affected by analyte-independent
435
factors such as concentration of the sensor, chemical environment, spectrometer
436
parameters and light scattering caused by the sample matrices (Amjadi & Jalili, 20
437
2017; Lee, Kim, & Sessler, 2015). Ratiometric fluorescence sensors endow
438
themselves with self-calibrations by calculating the fluorescence intensity ratio of
439
two or more well-resolved emissions. In other words, ratiometric sensing provides
440
excellent accuracy and reliability which could diminish environmental effect and
441
false signals (K. Wang, et al., 2015; X. Wang, et al., 2016; Zhuang, Ding, Zhu, &
442
Tian, 2014). Dual-emitting sensing systems can be constructed by either hybridizing
443
CDs with other fluorophores or designing CDs with inherent dual emissions. The
444
detail design will be discussed in Section 5.
445
4.4. Wavelength shifts
446
The emission wavelength shift or the changes of Stokes shift can also be utilized
447
to design fluorescence sensors. The shift distance of emission wavelength or Stokes
448
shift is linearly proportional to the analyte concentration in the fitted range. Spectral
449
analysis and data processing could refer to the literature (Lavkush Bhaisare, Pandey,
450
Shahnawaz Khan, Talib, & Wu, 2015).
451
5. Design principles for food analysis
452
CDs sensing approaches can be generally divided into three major classes: (1)
453
ligand-free sensors, (2) post-functionalized sensors, and (3) integrating CDs with
454
quenchers, fluorophores, molecule imprinting polymers (MIPs) and substrates.
455
5.1. Ligand-free sensors
456
For the ligand-free strategy, active groups (e.g. hydroxyl, carboxyl, amino and
457
phenolic hydroxyl) obtained during the synthesis process directly act as recognition
458
units. The surface groups of CDs are different because of various precursors, reaction 21
459
reagents and carbonization conditions (temperature, time, pH, etc.), resulting in
460
different binding ability of CDs to analytes. The basic detection principle of pristine
461
CDs sensors is based on the strong coordination of the active groups on CDs’ surface
462
with the target analytes, leading to changes of fluorescence properties. Ligand-free
463
CDs based fluorescence sensors have been successfully developed for detecting metal
464
ions (e.g. Fe3+ (Edison, et al., 2016), Hg2+ (J. J. Liu, et al., 2016), Ag+ (Qian, et al.,
465
2014)) and anions (e.g. ClO- (Hu, Yang, Jia, & Yu, 2015)) in different food samples.
466
Organic molecules and pathogens, e.g. pesticides residues in agricultural products
467
(Chang, Ginjom, & Ng, 2017), food additives (H. Xu, et al., 2015; H. Yang, He, Pan,
468
Liu, & Hu, 2019; Yuan, et al., 2016) and bacteria (N. Wang, et al., 2016), can also be
469
detected by ligand-free CDs sensors. Ligand-free sensors are simple and convenient
470
for direct sensing, but they present low specific recognition which results in poor
471
sensitivity and poor selectivity toward analytes.
472
5.2. Ligand-functionalized sensors
473
Surface functionalization of nanomaterials using highly specific receptors, such
474
as organic molecules and biomolecules (proteins, amino acids, peptides, aptamers,
475
antibody others biomolecules), has become a major focus for improving selectivity of
476
fluorescence nanosensors for bio-/chemical analysis in complex matrices (Z. Zhang,
477
et al., 2014). CDs prepared by treating oxygen-containing and/or nitrogen-containing
478
organic precursors usually possess carboxyl, hydroxyl and amino groups on their
479
surface which provide wonderful opportunities for grafting ligands via covalent and
480
non-covalent modification. 22
481
5.2.1. Covalent conjugation
482
Amide coupling reaction The method (Fig. 3A, using carboxyl-terminated CDs
483
as an example) involves forming amide linkage via chemical reactions between amino
484
groups and acylating reagents (e.g. acid chloride or carboxylic acid) with catalysis of
485
carbodiimide
486
1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), dicyclohexylcarbodiimide
487
(DCC), N,N'-diisopropylcarbodiimide (DIC) and N-hydroxysuccinimide (NHS). The
488
simple preparation of carboxyl-terminated CDs (CDs-COOH) and amino-terminated
489
CDs (CDs-NH2) provides feasibility to functionalize CDs with acyl/amino
490
compounds
491
fluorescence sensors for detecting pathogens can be designed by carbodiimide
492
chemistry because either bio-ligands contain abundant carboxyl/amino groups or the
493
bio-ligands can be easily modified with carboxyl or amino. Aptamers are artificially
494
selected oligonucleotide or peptide molecules which can selectively bind to analytes
495
by folding into three-dimensional structures. Bioligands-functionalized CDs have
496
been designed as fluorescence sensors for assaying food-borne pathogens such as
497
Salmonella typhimurium (R. J. Wang, Xu, Zhang, & Jiang, 2015) and Staphylococcus
498
aureus (Zhong, Zhuo, Feng, & Yang, 2015) in food samples. CDs-COOH can also be
499
covalently modified using chemical ligands containing amino groups via amide
500
coupling.
501
([N-(2-aminoethyl)-N,N,N0-tris(pyridin-2-ylmethyl) ethane-1,2-diamine]) can be
502
bonded onto the surface of CDs by amide linkages, and both the functionalized CDs
reagents.
or
acyl/amino
Branched
Common
carbodiimide
modified
molecules.
polyethyleneimine
23
reagents
include
Biomolecules-labeled
and
amino
CDs
TPEA
503
show good affinity to Cu2+ (Yongqiang Dong, et al., 2012; Qu, Zhu, Shao, Shi, &
504
Tian, 2012). Amide coupling principles can also be used to hybrid CDs with other
505
nanomaterials. For example, amino-passivated CdTe QDs have been grafted onto
506
CDs-COOH via EDC/NHS coupling to develop a ratiometric fluorescence sensor for
507
detecting Hg2+ (H. Y. Xu, Zhang, Liu, Liu, & Xie, 2017). Similarly, CDs-NH2 can also
508
be grafted with acyl compounds via the principle.
509
Esterification reaction Esterification methods (Fig. 3B) can introduce different
510
functional moieties because CDs are usually rich in -COOH or -OH in terms of
511
treating oxygenate compounds as organic precursors. Mannose modified CDs
512
(Man-CDs) have been synthesized by anchoring mannose onto the CDs surfaces
513
through a dehydration reaction using dry heating. The Man-CDs can selectively detect
514
Escherichia coli (E. coli) as low as 100 CFU/mL in drinking water and in apple juice
515
(Irving Po-Jung Lai & Yu-Jia Li, 2016).
516
Silylation reaction Silylation modification is a reaction between silane and
517
active hydrogen on the surface of CDs. Silanization reagents such as
518
3-aminopropyltriethoxysilane (APTES), 3-mercaptopropyltriethoxysilane (MPTS),
519
and tetraethyl orthosilicate (TEOS) can be hydrolyzed in acid or alkali to produce
520
Si-O-Si bonds which can be then polymerized to form a SiO2 shell coating on the
521
surface of CDs to provide silanol-rich groups. Organosilane-functionalized CDs can
522
be obtained by hydrothermally treating citric acid and APTES (Poshteh Shirani,
523
Rezaei, & Ensafi, 2019). CDs-NH2 has been encapsulated in a silica shell using TEOS
524
and APTES via silylation reaction and then covalently conjugated with thioglycolic 24
525
acid modified CdTe QDs via EDC/NHS coupling to develop a ratiometric sensor for
526
detecting Cu2+ in spiked vegetable and fruit samples (Rao, et al., 2016).
527
Thiol functionalized CDs Thiol or thiol derivatives modified molecules such as
528
glutathione, thioethers, dithiocarbamate alkanethiolates, DNA peptides, and proteins
529
can be coupled on the surface of CDs for Hg2+, Cu2+ and arsenite assays due to the
530
strong affinity of sulfhydryl to these analytes.
531
5.2.2. Noncovalent modification
532
Electrostatic immobilization CDs usually present positive/negative charge due
533
to the existence of amino, carboxyl and hydroxyl on their surfaces. Electrostatic
534
adsorption assembles reverse charged ligands or fluorophores onto CDs (Fig. 3C).
535
The positive charged N-doped CDs can be assembled on aptamer modified gold
536
nanoparticles (Aptamer/AuNPs) with negative charge via electrostatic interactions,
537
resulting in fluorescence quenching of CDs. In the presence of aflatoxin B1 (AFB1),
538
the fluorescence of CDs can be restored because AFB1 can competitively bind to the
539
aptamer to release the CDs. Based on the principle, a “turn-on” sensor has been
540
developed to determine AFB1 in peanut and corn with the detection limit of 5 pg/mL
541
(B. Wang, et al., 2016). A dual-emitting sensor fabricated by covalent coupling of
542
polyethyleneimine modified CDs and fluorescein isothiocyanate via electrostatic
543
interactions and thiourea bonds can selectively detect Cu2+ in yogurt (B. Wang, et al.,
544
2016). Electrostatic coupling is sensitive to medium pH and is not desirable when
545
used alone.
546
π-π stacking Some aromatic molecules can be anchored to CDs containing 25
547
extended π systems via π interaction (Fig. 3D). The fluorescence of dye-labeled
548
single-stranded DNA (ss-DNA) probe can be quenched when the ss-DNA is adsorbed
549
onto the surface of CDs via π interaction. When the target DNA matches with the
550
dye-labeled DNA to form double-stranded DNA (ds-DNA), the ss-DNA is separated
551
from the surface of CDs and thereby inducing the fluorescence recovery (H. L. Li, Y.
552
W. Zhang, et al., 2011). Based on this strategy, metal ions such as Hg2+ and Ag+ can
553
be respectively determined through T-Hg2+-T and C-Ag+-C base pairs (H. Li, Zhai,
554
Tian, Luo, & Sun, 2011; H. L. Li, Zhai, & Sun, 2011).
555
Other ligands have also been used to modify CDs to improve sensitivity and
556
selectivity of CDs-based sensors in complicated food matrices (Table 1).
557
5.3. Molecule imprinting polymers (MIPs)
558
Owing to their favorable selectivity, biological recognition elements are
559
considered as the most important part of sensing platforms. Along with the high cost
560
for wide in-field application of biological-entities based sensors other challenges still
561
exist. Firstly, most biological receptors exhibit poor physical and chemical stability
562
toward extreme environments (e.g. strong acidic or basic media, organic solvents,
563
high temperatures, etc.). Antibodies and enzymes are easily denatured, thus resulting
564
in the variation of the interaction capacity of the recognition sites. Secondly, the
565
preparation of high-affinity bioreceptors is rather difficult and tedious. As an example,
566
antibodies are produced in tissue culture or animals and it might take a year or more
567
to develop highly specific antibodies due to complicated steps required. As promising
568
artificial receptors, aptamers are DNA or RNA oligonucleotides which can 26
569
specifically bind to target molecules. However, screening appropriate aptamers for
570
certain analytes is complicated and lengthy. Thirdly, even no commercial antibodies
571
are available for certain small molecules (molecular weights <1 KDa, e.g. toxins and
572
pesticides) because such small molecules cannot generate immunogenic reactions
573
alone. Therefore artificial antigens are required to be in prior synthesized (Aragay, et
574
al., 2012). Under such circumstances the development of low-cost synthetic affinity
575
agents as substitutes for those biological origins has become a research hotspot.
576
MIPs have been known as ‘‘artificial antibodies”. They can mimic the specific
577
binding characteristics of natural antibodies and can be deservedly used to selectively
578
recognize specific analytes via tailor-made sites (Ren, Liu, & Chen, 2015). As
579
depicted in Fig. 4A, the preparation of MIPs involves several procedures of
580
self-assembly, copolymerization and removing templates (target molecules or
581
analogs). Template molecules and functional monomers self-assemble by covalent,
582
non-covalent or coordinate bonds to form prepolymers in reaction solvents. Upon
583
introduction of cross-linkers and initiators, the copolymerization process is triggered
584
by light or heat leading to the forming of highly cross-linked ‘‘host-guest” polymers
585
around the prepolymers. MIPs are obtained after eluting the template with a strong
586
polar solvent, an acid, a base, a salt or a complex solvent based on the principles of
587
static electricity, hydrogen bonding, ionic bonding, etc. The as-prepared MIPs possess
588
tailored nanocavities with matchable size, shape, and corresponding functional groups
589
capable of capturing target analytes. MIPs show high mechanical strength, stable
590
physical and chemical properties in terms of high temperature, strong acid/alkali and 27
591
organic solvents. MIPs capped CDs (MIP-CDs) sensors have inspired tremendous
592
research interests owing to the integration of desirable fluorescence properties of CDs
593
with predictable structures, specific selectivity and universal application of MIPs.
594
MIPs show excellent analysis performance with good selectivity for small
595
molecules such as toxins and pesticides compared with other interfering substances
596
and analogs. Several MIP-CDs sensors have been designed to detect pesticides,
597
mycotoxins, antibiotics and other food contaminants in food samples, including
598
acetamiprid (Poshteh Shirani, et al., 2019), sterigmatocystin (L. H. Xu, Fang, Pan,
599
Wang, & Wang, 2016), zearalenone (Shao, Yao, Saeger, Yan, & Song, 2018),
600
tetracycline (J. Hou, H. Y. Li, et al., 2016) and 3-monochloropropane-1,2-diol (Fang,
601
Zhou, Zhang, Liu, & Gong, 2019). MIPs and other host-guest receptors possess
602
greater stability, better cost-effectiveness and easier engineering operations over
603
biological receptors, but they are confronted with problems such as template leakage,
604
incompatibility in aqueous media, low binding capacity and slow mass transfer
605
(Aragay, et al., 2012). New trends toward improving the sensing performance of MIP
606
sensors include (1) upgrading the hierarchical architecture of the sensors such as
607
core-shell, hollow and mesoporous structures, (2) post-imprinting modifications and
608
(3) ratiometric fluorescence (Yang, et al., 2018).
609
5.4. Switchable sensors
610
The current CDs-based sensing platforms are constructed upon the fluorescence
611
“turn-off” model in which the change of fluorescence intensity is proportional to the
612
concentration of analytes. This direct quenching analysis is susceptible to 28
613
environmental stimulus which may debase the analytical performances. Incorporating
614
CDs with fluorescence quenchers can develop novel switchable sensors in which the
615
original fluorescence of the CDs is firstly quenched by quenchers and then recovered
616
by analytes (Fig. 4B). These indirect sensors with higher analytical sensitivity than
617
the “on-off” sensors have been successfully developed to detect different targets such
618
as nutrients, heavy metals, toxins, pesticides and banned additives in food samples.
619
Table 2 gives a summary of four common switchable detection principles. In the
620
redox principle, analytes reduce/oxidize quenchers into other substances weakening
621
the quenching of the quencher and resulting in fluorescence recovery of CDs. For the
622
affinity principle, analytes can restore fluorescence of CDs by competitively capturing
623
the quencher on account of their stronger affinity to the quencher. The
624
aggregation/depolymerization principle is mainly applicable to nanoquenchers such as
625
AgNPs
626
aggregation/depolymerization of quenchers. In the principle of enzyme activity
627
inhibiting, quenchers are usually the products of the corresponding substrates
628
catalyzed by a specific enzyme. The analytes (mainly pesticides) can inhibit enzyme
629
activity, resulting in the decrease of the concentration of the quencher in the sensing
630
systems. As a result, the fluorescence of the CDs can be recovered.
631
5.5. Ratiometric fluorescence sensors
where
analytes
trigger
colloidal
stability
and
induce
632
Ratiometric fluorescence sensors involve simultaneously measuring the
633
analyte-induced fluorescence intensity changes of two or more well-resolved emission
634
and then calculating their intensity ratio. A dual-emission system includes CDs with
635
intrinsic dual-emission or a hybrid of CDs (donors) with other emitters (receptors). 29
636
For a hybrid dual-emitting system, CDs are usually coupled with QDs, organic dye
637
molecules and metal-organic frameworks (MOFs) via two main strategies. The first
638
strategy is energy transfer-based fluorescent ratiometry in which the emission of CDs
639
can excite receptors, i.e. the emission of CDs overlaps the adsorption of the receptor.
640
The second strategy is hybridizing two independent fluorophores that possess the
641
same excitation wavelength by either chemically connecting or simply physical
642
mixing. These hybridized ratiometric sensors are usually constructed by encapsulating
643
two different fluorescent components, one as the reference signal and the other as the
644
recognition unit, into a SiO2 shell using silane. The intrinsic dual-emitting systems are
645
designed by metal doping to insert new energy levels of transition metals (Wu, Hou,
646
Xu, & Chen, 2016). This model may have two dynamic fluorophores which increase,
647
decrease, or shift their signals in the opposite directions in the presence of analytes.
648
More attractively, different colors with characteristic color tonalities are usually
649
generated in ratiometric approaches. The color changes of the ratiometric sensing
650
systems typically comprise three scenarios. The color of the sensor gradually changes
651
from the intermediate color to that of the reference fluorophore when the reference
652
signal is inert to the analyte while the other emission is simultaneously quenched. In
653
contrast, a gradual color changing from the initial emission color of the reference to
654
the final mixing color of the reference and sensitive fluorophore is observed when the
655
fluorescence intensity of the sensitive fluorophore is increased and the reference
656
emission remains unchanged. In the case of two dynamic fluorophores, the color will
657
close to the fluorophore with stronger fluorescence intensity upon addition of the 30
658
analyte. This unique phenomenon presents a winning strategy for precise visual
659
quantitative assay.
660
Owing to the built-in self-calibration and potential visual detection, ratiometric
661
sensors are quite promising and suitable for food analysis in resource-constrained
662
areas. Ratiometric sensors for detecting nitrite (Xiang, et al., 2018), biothiols (Fu, et
663
al., 2017), feed additives (L. Chen, et al., 2018), heavy metals (Rao, et al., 2016), pH
664
(X. Zhu, Jin, Gao, Gui, & Wang, 2017) and biomarker (M. L. Liu, et al., 2019) have
665
been developed by integrating CDs with organic fluorescent dyes, QDs and rare earth
666
metals ions. Overall, the synergy of the desired fluorescence properties of CDs and
667
the analysis advantages of ratiometric fluorescence sensing holds great promise in
668
food safety sensing fields.
669
5.6. Flexible microdevices
670
Food analysis by unskilled personnels, staff of quality supervision department
671
and even homemakers requires convenient, rapid and on-site assaying targets by
672
naked eyes or available smart devices. Most reported CDs sensors are solution-based,
673
while incorporating CDs sensors into solid materials could be utilized to develop
674
more convenient portable sensing devices. Testing kits, filter papers (M. L. Liu, et al.,
675
2019) or strips and smartphone colorimetric-based analysis have been introduced for
676
CDs-based sensors. The smartphone-based analysis technique has attracted
677
tremendous attentions. It offers use of smartphone camera with high-resolution
678
imaging, manual or auto exposure and focus control. Smartphone-based analysis has
679
the obvious benefits of ease of use, portability and programmability. Both the 31
680
development of new Applications (Apps) and smartphone electronics can facilitate
681
broad designing and applications of smartphone biosensors.
682
6. Spectral analysis and quality control
683
Fluorescence signals are collected upon the interaction between sensors and
684
analytes. For fluorescence quenching/enhancing response sensors, the net difference
685
of fluorescence intensities (F0-F or F0/F, where F0 and F represent the fluorescence
686
intensity of CDs in the absence and presence of analytes) should be fitted with the
687
concentration [C] of analytes. For the ratiometric sensors, the ratio of the two
688
emission peaks intensities is used as an indicator to assay the concentration [C] of
689
analytes. In fluorescence emission shift based sensors, the shift distances of the
690
emission peak (nm) are collected as a quantitative parameter to quantify the analyte
691
concentration.
692
Food samples analysis Food matrices are so complex that nutrition
693
compositions undoubtedly interfere with the accuracy and practical applications of
694
detection sensors. Appropriate sample pretreatments such as filtration, centrifugation,
695
ultrasound and soxhlet extraction are necessary. It should be noted that these simple
696
treatments are inevitably required for complex food matrices, but they are much easier
697
than the sample pretreatments of chromatography, atomic absorption spectrometer and
698
other methods requiring column separation and digestion. The expectation of novel
699
fluorescent sensors is that they will simplify the pre-treatment of food samples,
700
eliminate matrix effects, and achieve in-situ non-destructive testing. 32
701
A linear range can be obtained by fitting the fluorescence spectra data against the
702
concentrations of analytes using normalized intensity, relative fluorescence intensity
703
(Fr) and empirical equations such as Stern-volume equation. The limit of detection
704
(LOD) is estimated according to 3σ IUPAC criteria (Eq. 2). Precisions are evaluated
705
by replicating detection of a certain analyte standard solutions. Accuracy of these
706
fluorescence sensors based methods is estimated by the variation analysis (e.g. T-test)
707
between routine methods (HPLC, GC-MS, atom absorption, ELISA, ICP-MS,
708
ICP-AES, etc.) and the developed methods. For real samples without target analytes, a
709
series of recovery experiments in spiked real samples should be carried out and the
710
recovery rate can be estimated by Eq. 3. LOD=3σ/k
711 712 713 714
(2)
Where k is the slop of the calibration curve and σ was the standard deviation of bank signals of the sensing systems (n=9). Recovery= (Cmeasured-Cinitial)/Cadded
(3)
715
Where Cmeasured is the concentration determined by sensors; Cinitial reprents the
716
background content of analytes in real samples; Cadded is the spiked concentration.
717
7. Conclusions and trends
718
In this review the synthesis and fluorescence properties of CDs, sensing
719
mechanisms and designing principles of CDs-based fluorescent sensors for food
720
analysis have been comprehensively summarized. We have discussed ligand-free
721
sensors, functionalized CDs based sensors and CDs integrated with other ligands or 33
722
sensing models. Regarding interference of autofluorescence in food matrices,
723
near-infrared and upconversion fluorescent CDs can efficiently avoid spontaneous
724
fluorescence of biomass which usually emits blue emission under deep ultraviolet
725
excitation. Phosphorescence behavior of CDs is rarely reported, but CDs-based room
726
temperature phosphorescence sensors would be a promising platform for avoiding
727
background fluorescence and scattered light from substrates. The complexity of food
728
matrices inspires researchers to develop varieties of ligands which can specifically
729
recognize analytes with good anti-interference. Coupling CDs-based sensors with
730
other techniques (immunoassay, electrochemical sensors and MIPs) will broaden the
731
implementation of CDs by improving their sensitive and selectivity. Multi-modes
732
sensing that coupling various fluorescence signals such as fluorescence intensity,
733
spectra shift, lifetime change and ratiometric with other signal outputs (e.g.
734
electrochemisrtry, quartz crystal microbalance and UV-vis adsorption) is a promising
735
research hotpot for improving the analysis performance of CDs-based sensors. Most
736
CDs-based sensors are currently developed and tested in laboratory. It is still an urgent
737
demand to design standardized CDs-based fluorescence sensors such as lab-on-chip
738
devices for commercial and industrial applications to realize more significant sensing
739
(e.g. global security, early detection of diseases, public safety). Portable sensors
740
including kits, strips, filter papers based sensors, and Apps on smartphones should be
741
developed instead of solution-based sensors. After solving problems of selectivity,
742
anti-interference and in-situ/non-destructive determination in food matrices,
743
CDs-based sensors will be promising platforms to provide new approaches and 34
744
technologies for food safety supervision.
745
Acknowledgements
746
This work was supported by the National Natural Science Foundation of China
747
(No.31801628) and Shaanxi Social Development Project (2018SF-401).
748
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Table 1 Various ligands modified CDs for food analysis Analytes
Ligands
Linear range
LOD
Real samples
References
Salmonella typhimurium
Aptamers
103-105 cfu/mL
50 cfu/mL
egg
(R. J. Wang, et al., 2015)
glyphosate
0.06-473 µM
4.7×10–5 µM
Pearl River water, tea, and soil samples
(D. Wang, Lin, Cao, Guo, & Yu, 2016)
IgG
E. coli
103-108 cfu/mL
450 cfu/mL
tap water, apple juice, human urine
(Weng, et al., 2015)
Mannose
E. coli
amikacin
3.904×105-7.625×102 cfu/mL
552 cfu/mL
fruit juice (apple, pineapple and orange)
(Chandra, Chowdhuri, Mahto, Samui, & Sahu, 2016)
E. coli
colistin
3.81×102–2.44×104 cfu/mL
460 cfu/mL
human urine, apple juice, and tap water
(Chandra, Mahto, Chowdhuri, Das, & Sahu, 2017)
S. aureus
Vancomycin
3.18×105-1.59×108 cfu/mL
9.40×104 cfu/mL
orange juice
(Zhong, et al., 2015)
E. coli
Mannose
0-108cfu/mL
100 cfu/mL
drinking water, apple juice
tannic acid
PEGA
0.1-10mg/L
0.018 mg/L
PEGA: polyethyleneglycol bis(3-aminopropyl)
(Irving Po-Jung Lai & Yu-Jia Li, 2016)
red and white wine
(Ahmed, Laino, Calzon, & Garcia, 2015)
Table 2 The CDs based switchable FL sensors Type
Analytes
Quenchers
Principles
Cr(VI) Ascorbic acid
Redox reaction
Affinity
MnO2
Linear range
LOD
5.0-200 µM
1.35 µM
0.18-90 µM
42 nM
AA reduce those quenchers
Real samples fresh fruits, vegetables, commercial fruit juices
Dichlorvos
Cu2+
thiocholine reduced Cu2+ to Cu+
6.0×109-6.0×108 M
3.8×109 M
cabbage, fruit
90 fM
Protoporphyrin
Sudan red III oxidize protoporphyrin into aromatic amines
9.9 pM-0.37 nM
Sudan red III
tomato ketchup, red chili sauce
AFB1
AuNPs
aptamer showed higher special binding ability to AFB1
0.005-2 ng/mL
5 pg/mL
peanut, corn
GSH
Hg2+
the stronger affinity between thiol and Hg2+
0.08-60 µM
20 nM
Hg2+
GO
CDs were released from GO due to the formation of T-Hg2+-T duplex
5-200 nM
2.6 nM
Al3+
Dopamine
dopamine has high affinity towards Al3+ at the ratio of 2:1 at pH 7.4
4-40 µM
0.0329 µM
kanamycin
MoS2
the strong specificity between the aptamer and kanamycin
4-25 µM
1.1 µM.
tomatoes, bananas and cucumbers citrus leaf fried bread stick, bread, chips, steamed bread milk
References (X. Gong, et al., 2017) (J. Liu, et al., 2016) (J. Hou, G. Dong, et al., 2016) (Jahan, Mansoor, Naz, Lei, & Kanwal, 2013) (B. Wang, et al., 2016) (Fu, et al., 2017) (Xin Cui, 2015) (F. Yan, et al., 2016) (Y. Wang, et al., 2016)
AuNPs melamine Hg2+
Aggregation and depolymerization
Inhibiting enzyme activity
melamine reduce FRET effect between CDs and AuNPs via binding to AuNPs melamine binds to Hg2+ via multi-nitrogen heterocyclic ring and reduces the interaction between Hg2+ and CDs oxytetracycline showed stronger 3+ coordination ability to Fe
oxytetracycline
Fe3+
glyphosate
AgNPs
glyphosate induce the aggregation of Ag NPs
methyl parathion
Quinone
methyl parathion inhibit tyrosinase activity
carbaryl
AgNPs
carbaryl
H2O2
dichlorvos
TNB
analytes inhibit the activity of AChE
50-500 nM
36 nM
raw milk, milk
(Dai, et al., 2014)
1-20 µM
0.3 µM
powder
(C. H. Lei, 2016)
0.1-2.7 µM
22.8 nM
milk
0.025-2.5 µg/mL
12 ng/mL
1.0×10-10-1.0×10-4 M
1×10-8-1×10-4 g/L
0.006 µg/L
apple juice
6.3×10-9-6.3×10-4 g/L
5.4×10-9 g/L
apples
5.0×10-11-1.0×10-7 M
1.9×10-11 M
fruit juice
MnO2/MoS2: MoS2 nanosheets; AuNPs: gold nanoparticle; AgNPs: silver nanoparticle; TNB: 5-thio-2-nitrobenzoic acid; AFB1： aflatoxin B1； AChE：Acetylcholinesterase; GO: graphene oxide
4.8×10−11 M
rice, millet, wheat flour, maize flour cabbage, milk, fruit juice
(An, Zhuo, Zhang, & Zhu, 2015) (L. Wang, et al., 2016) (J. Y. Hou, et al., 2015) (Zhao, et al., 2016) (H.Li, et al., 2016) (J.Hou, et al., 2016)
Size tuning Arc discharge
Laser ablation
Electrochemical
A)Top-down Electrode Laser Beam
Insert Gas Chamber
Carbon target
Insert Gas Chamber
Pt grid
MWCNT Carbon target immersed in water or PEG200
V Pt grid
Graphite electrode
Laser Beam and Carrier Gas
Electrode
Soot Deposition
MWCNT
Raw CDs
B)Bottom-up Microwave irradiation
Carbon precursor Adequate solvent
Thermal carbonization
Carbon precursor Adequate solvent
Microwave
Sonication
Precursor
CDs
Ultrasonic oscillation
Surface chemistry C) Surface passivation/functionalization Surface passivation Neutralization
Functionalizing negative/positive charge for electronic coupling
Nitric acid reflux
Organic polymer reflux
Raw CDs other functional groups for coupling
Inorganic salt doping
Electron energy
D)Doping Before doping Conduction band
After doping
Conduction band
Before doping
Conduction band
After doping
Conduction band
Fermi level
Valence band
Valence band
Valence band
Valence band
p-type doping n-type doping Fig.1. The schematic illustration of the synthesis methods of based on size-tuning and surface chemistry tuning strategies
(C)PET
LUMO E
LUMO
HOMO
eHOMO
E LUMO
HOMO
HOMO
Reductive PET
Oxidative PET
FRET
D
r
A
1-10nm
FL intensity
(A)SQE
Donor emission
Through-space energy transfer
(B)DQE
Wavelength (nm) (E) IFE
Fig. 2. The quenching mechanisms of fluorescent CDs
Adsorption
Acceptor adsorption
(D)FRET
Quencher
LUMO
e-
A) Amide reaction
Carbodiimide reagents ligands
B) Esterification reaction
C) Electrostatic immobilization
D) π-π stacking
Fig. 3. Schematic functionalization of CDs motif.
A)
+
Covalent/non-covalent / coordinate bonds
+
Self-assembly Prepolymers
Cross linker
Polymerization
Template Functional monomers
Rebind template Remove template
B)
Fig.4. (A) A general scheme of molecules imprinted CDs sensors preparation and detection principles; (B) The basic principle of “on-off-on” switchable CDs-based fluorescence sensors.
Highlights 1. Fluorescence properties for reducing interferences to food safety screening. 2. Fluorescence response mechanisms of CDs-based fluorescent sensors. 3. Designing and analysis principles of CDs sensors for food analysis. 4. Selectivity improving and interference reducing for practical applications. 5. New trends in material, ligands and portable sensors designing.