Surface-enhanced Raman spectroscopy for polychlorinated biphenyl detection: Recent developments and future prospects

Journal Pre-proof Surface-enhanced Raman spectroscopy for polychlorinated biphenyl detection: Recent developments and Future Prospects Jie Cheng, Peilong Wang, Xiao-Ou Su PII:

S0165-9936(19)30295-X

DOI:

https://doi.org/10.1016/j.trac.2020.115836

Reference:

TRAC 115836

To appear in:

Trends in Analytical Chemistry

Received Date: 13 May 2019 Revised Date:

1 February 2020

Accepted Date: 1 February 2020

Please cite this article as: J. Cheng, P. Wang, X.-O. Su, Surface-enhanced Raman spectroscopy for polychlorinated biphenyl detection: Recent developments and Future Prospects, Trends in Analytical Chemistry, https://doi.org/10.1016/j.trac.2020.115836. 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. © 2020 Elsevier B.V. All rights reserved.

1

Surface-enhanced Raman spectroscopy for

2

polychlorinated biphenyl detection: Recent developments

3

and Future Prospects

4

Jie Cheng, Peilong Wang*, Xiao-Ou Su**

5 6

Institute of Quality Standards and Testing Technologies for Agro-products, Chinese Academy of Agricultural

7

Sciences, Beijing, 100081, China

8 9 10

*Corresponding author. Peilong Wang (P. L. Wang); Fax: +86 010 82106580; Email: [email protected]. **Corresponding author. Xiao-Ou Su (X. O. Su); Fax: +86 010 82106580; Email: [email protected].

11 12

1

13

Abstract:

14

Polychlorinated biphenyls (PCBs) have gained much attention for their carcinogenic,

15

teratogenic, and mutagenic properties. Although banned in the 1970s, PCBs are still

16

frequently found worldwide in environment, animal-origin food and natural waters. Therefore,

17

the development of determination methods is an indispensable step for the monitoring of

18

PCBs. Surface-enhanced Raman spectroscopy (SERS) is an emerging technique for the

19

chemical analysis. With the advantages of excellent sensitivity and significant enhancement

20

to identify the target, SERS has become a promising alternative method for PCBs analysis.

21

This paper comprehensively reviews the recent progress of SERS development in the

22

determination of PCBs, mainly focusing on the preparation of SERS substrates. As the

23

current SERS research on PCBs analysis is still in an early stage, there are several hurdles for

24

further advancing SERS for complex samples. This review includes our discussion on the

25

current challenges and outlook on real-word applications of SERS in PCBs analysis.

26 27 28

Keywords: surface-enhanced Raman spectroscopy; polychlorinated biphenyl; substrates; matrix; detection

29

2

30

1. Introduction

31

Polychlorinated biphenyls (PCBs), which are synthetic organic chemicals consisting of two

32

phenyl rings with substitution of hydrogen with chlorine at any of the 10 hydrogen sites, have

33

209 different possible congeners. These compounds are used as coolants, lubricants, paint

34

additives, carbonless copy paper, plastics, and in electric transformers and capacitors. PCBs

35

are classified as persistent organic pollutants (POPs) as they exhibit significant toxicity,

36

bioaccumulation, environmental persistence, and long-distance migration. Several reports

37

have shown that a large number of people have been exposed to PCBs via food

38

contamination. Consumption of PCB contaminated rice oil in Japan in 1968 and Taiwan in

39

1979 caused nail and mucous membrane pigmentation as well as eyelid swelling, fatigue,

40

nausea, and vomiting. PCBs can also persist in the environment, bioaccumulate through the

41

food chain, and pose a constant threat to human health and the overall ecosystem [1]. Thus,

42

PCBs were banned by the United States Congress in 1979 and were listed as a POP at the

43

Stockholm Convention (managed by the United Nations Environment Program (UNEP)) in

44

2001. Depending on the number and position of the chlorine atoms, PCB congeners have

45

been assigned IUPAC numbers ranging from 1 to 209. Among these compounds, co-planar

46

and non-planar PCBs are distinguished based on whether the two benzene rings exist in the

47

same plane. Co-planar PCBs adopt a configuration similar to those of polychlorinated

48

dibenzodioxins (PCDDs) and are commonly referred to as “dioxin-like” PCBs (DL-PCBs)

49

demonstrating similar toxicity. DL-PCBs have been assigned toxic equivalency factors (TEFs)

50

by comparing their toxicity to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD),

51

which is the most toxic dioxin with an assigned TEF value of 1 (Table 1) [2].

52

Table 1. Dioxin-like PCBs (non-ortho PCBs + mono-ortho PCBs) and their respective TEF values. IUPAC No.

IUPAC Name

TEF values

non-ortho PCBs 77

3,3’,4,4’-tetrachlorobiphenyl

0.0001

81

3,4,4’,5-tetrachlorobiphenyl

0.0003

126

3,3’,4,4’,5-pentachlorobiphenyl

0.1

169

3,3’,4,4’,5,5’-hexachlorobiphenyl

0.03

mono-ortho PCBs 105

2,3,3’,4,4’-pentachlorobiphenyl 3

0.00003

53

114

2,3,4,4’,5-pentachlorobiphenyl

0.00003

118

2,3’,4,4’,5-pentachlorobiphenyl

0.00003

123

2’,3,4,4’,5-pentachlorobiphenyl

0.00003

156

2,3,3’,4,4’,5-hexachlorobiphenyl

0.00003

157

2,3,3’,4,4’,5’-hexachlorobiphenyl

0.00003

167

2,3’,4,4’,5,5’-hexachlorobiphenyl

0.00003

189

2,3,3’,4,4’,5,5’-hepachlorobiphenyl

0.00003

In addition to DL-PCBs, so-called “indicator PCBs” (Table 2) are often selected as suitable

54

representatives for risk assessments of foodstuffs and environmental samples. For example,

55

six indicator PCBs (PCB 28, 52, 101, 138, 153, 180) are target compounds for the risk

56

assessments of food and foodstuffs as prescribed by the European Food Safety Authority

57

(EFSA) [3]. In China, the maximum residue limit (MRL) of seven indicator PCBs, including

58

PCB 28, 52, 101, 118, 138, 153, and 180, in aquatic animals and products has been set as 0.5

59

mg/kg [4], which is the same level selected by Global Environmental Monitoring Scheme

60

(GEMS). The focus on the constant threat to human health and the strict regulation about

61

MRL have indicated the necessary of developing highly sensitive quantification and

62

confirmation methods for the monitoring of PCBs. Table 2. Names of the indicator PCBs.

63 IUPAC No.

IUPAC Name

28

2,4,4’-trichlorobiphenyl

52

2,2’,5,5’-tetrachlorobiphenyl

101

2,2’,4,5,5’-pentachlorobiphenyl

118

2,3’,4,4’,5-pentachlorobiphenyl

138

2,2’,3,4,4’,5’-hexachlorobiphenyl

153

2,2’,4,4’,5,5’-hexachlorobiphenyl

180

2,2’,3,4,4’,5,5’-heptachlorobiphenyl

64

Generally, high resolution gas chromatography combined with high resolution mass

65

spectrometry (HRGC-HRMS) is the gold standard for PCB determination and laboratory

66

confirmation. Other confirmation methods include two-dimensional gas chromatography with

67

time-of-flight mass spectrometry (GC×GC-TOF/MS) [5], gas chromatography coupled to a

68

triple quadruple mass spectrometer (GC-QQQ-MS/MS) [6], and atmospheric-pressure

69

chemical ionization gas chromatography coupled with a tandem quadruple mass spectrometry 4

70

(APGC-MS/MS) [7]. These conventional detection methods are very accurate, but require

71

time-consuming sample pretreatment steps, expensive instrumentation, and sophisticated

72

technical operators, which are unsuitable for on-site and rapid detection. To reduce the cost of

73

monitoring PCBs, other bioanalytical screening methods have been developed, including

74

enzyme-linked immunosorbent assay (ELISA) [8] and ethoxyresorufin-O-deethylase (EROD)

75

[9], which can detect dioxins (polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated

76

dibenzofurans (PCDFs)) and DL-PCBs simultaneously. In addition, a detection method based

77

on chemical reporter gene assays [10] has also been developed. The testing results are usually

78

calculated as 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) toxic equivalents. Despite

79

the success of these rapid and simple bio-analytical screening methods, many challenges

80

remain. The ELISA technique depends on the specific interaction between antibodies and

81

antigens, but has a high rate of “false positives” for PCB detection. The preparation of

82

PCB-antibodies to identify multiple of PCBs simultaneously is difficult. For the EROD

83

method, the actual PCB concentrations could not be directly obtained and detection recovery

84

is impossible. In addition, other emerging fast detection techniques have recently been

85

developed to detect trace amounts of PCBs, including fluorescence probes [11], biomimetic

86

sensors [12], fluorescence quantitative PCR [13], electrochemical sensors [14], and

87

surface-enhanced Raman spectroscopy (SERS) [15]. These novel detection methods have

88

improved existing screening methods and attracted increasing amounts of attention.

89

The SERS technique has been developed over the past two decades and is considered to be

90

a promising analytical tool for label-free molecular diagnostics. As a powerful analytical tool

91

for trace detection, the SERS technique has been widely used in drug discovery [16], food

92

safety [17], environment monitoring [18], and biomedical diagnostics [19]. So far, a few

93

reviews about the SERS detection of harmful compounds have been published in the past.

94

For instance, Jiang described a general process for SERS-based common harmful chemical

95

residues [20]. Pang, Yang, and He reviewed the SERS detection of synthetic chemical

96

pesticides [21]. Recently, Yaseen and his co-workers focused on the functionalization

97

techniques for improving SERS substrates [22]. However, these reviews mainly focused on

98

the common harmful chemical residues in the area of food safety. No review is available on 5

99

advanced SERS techniques for the detection of POPs, especially PCBs. Therefore, in the

100

current review, the principles of SERS are discussed first. Then the current developments of

101

SERS for PCBs detection including the critical technique points are discussed. Furthermore,

102

the future use, limitations, and development trends of SERS for PCB detection are

103

emphasized.

104 105 106

2. Theoretical basis of SERS The Raman signal intensity can be significantly amplified when the target molecules are

107

adsorbed or come into close proximity to the nanostructured noble metal surfaces, a

108

phenomenon first observed in the early 1970s [23] (Fig. 1). The nanostructure-induced

109

enhancement can reach as high as 14 to 15 orders of magnitude compared to that of the

110

corresponding bulk Raman signal. In the stimulation of the two enhancement mechanisms

111

analytes at the extremely low concentration can be detected by SERS even down to the level

112

of a single molecule [24]. The first mechanism called electromagnetic (EM) enhancement

113

dominated the SERS effect by an enhancement of more than 105 in most cases, which is

114

caused by the local surface plasmon resonances (LSPR) and depends on the shape and size of

115

the nanostructures [25]. The other mechanism is chemical enhancement (CM), which is

116

caused by a resonance Raman like process associated with the charge transfer (CT) between

117

the surface of a metallic nanostructure and the molecule analytes by the enhancement factor

118

of 102 [26]. The CT state increases the polarizability of analytes, resulting in a higher degree

119

of Raman transition. Generally, SERS is simultaneously generated from both EM and CT

120

mechanisms.

121

The remarkable characteristics of its rapid response, ultra-sensitivity, specificity, and

122

simple operation make SERS particularly well suited for PCBs monitoring, especially for

123

field tests. This method can be used to screen large numbers of samples to verify presumptive

124

positive samples.

125

3. Current advancement of SERS in PCBs detection

126

In SERS detection procedure, the metal nanostructured substrate and sample cleanup are

127

fundamental components, which mainly includes substrate preparation, sample pretreatment,

128

and Raman instrument analysis. However, the current research is still at an early stage and the 6

129

reported target PCBs are largely based on a pure format without spiking into any matrix or

130

real samples from the field. There were few reports about the sample cleanup before SERS

131

detection of PCBs. In contrast, significant progress has been made towards the preparation of

132

SERS substrates in the past few years (Table 3). In summary, four kinds of substrates have

133

been prepared to enhance the Raman signal of PCBs. Table 3. The substrates preparation for SERS detection of PCBs in recent years.

134

SERS Substrates

Targets

Matrixes

Sensitivity (LOD)

Ref.

50 pM

[36]

/

[37]

Modified with alkanethiol and perfluoroalkanethiol

PCB-47, PCB-77

standard solution

β-CD modified gold nanoparticles (AuNPs)

PCB-40, PCB-54, PCB-65, PCB-80

agriculture soil

Ag-nanowire tip array and modified with β-CD

PCB-77

standard solution

10-10 M

[38]

β-CD coated SiO2 @ Au @ Ag core-shell nanoparticles

PCB-3, PCB-77

standard solution

10-6 M

[39]

Ag nanosheet-assembled micro-hemispheres modified with HS-β-CD

PCB-77

standard solution

10-7 M

[40]

glutathione (GSH) functionalized Au NPs

PCB-47

rangeland extract

/

[41]

rGO-AgNPs

PCB-47, PCB-77

standard solution

10-7 M

[52]

GO wrapped flower-like Ag microparticles (Ag @ GO)

PCB-3, PCB-77

standard solution

10-4 M

[53]

AgNPs @ PAN-nanohump

PCB-77

standard solution

10-5 M

[30]

Ag-nanosheet-grafted polyamide-nanofibers modified with

PCB-3, PCB-77

standard solution

1.6×10-5 M

[32]

ZnO-NRs decorated with Ag-NRs and Ag spheres

PCB-77

standard solution

10-11 M

[33]

AgNPs modified with Fe3O4

PCB-77

standard solution

10-8 M

[34]

Modified with a –SH3 group

PCB-77

standard solution

10-8 M

[42]

Ag-nanorod modified with aptamers

PCB-77

standard solution

1.0×10-8 M

[75]

PCB-29,

PCB-52,

7

land

soil

Ag-nanorod modified with aptamers

PCB-77

standard solution

3.3×10-8 M

[76]

DNA aptamer modified SiO2 @ Au core shell nanoparticles

PCB-77

standard solution

1 µM

[77]

135 136

3.1 Substrates possess high density of “hot spots”

137

As is known to us, the EM enhancement mechanism dominates the SERS effect, showing

138

an enhancement of ˃105 in most cases, arising from LSPR depending on the shape and size of

139

the nanostructures. The LSPR is usually present at the gaps between the nanostructures,

140

resulting in so called “hot spots” that stimulate the SERS effects. A good substrate possesses

141

a high density of “hot spots” to achieve high sensitivity for SERS detection. The design and

142

preparation of a high density of “hot spots” is key for sensitive SERS detection. A variety of

143

substrates besides gold and silver nanoparticles (Au and Ag NPs) have been successfully

144

prepared and applied as SERS substrates (Fig. 2), including flower-like Ag nanoparticles [27],

145

Ag nanoparticle hierarchical structures [28], sea urchin-like Au micro-particles [29], Ag

146

nanoparticles decorated on nanohumps [30], and gecko-inspired nano tentacle [31]. The hot

147

spots reside within the nano-sized gaps in the inter space of the abovementioned

148

nanostructures and the SERS signals of the target molecules are largely governed by their

149

capture by the hot spots. Li et al. developed a facile SERS fabrication method using large

150

scale films, with one surface consisting of Ag NP decorated polyacrylonitrile (PAN)

151

nanohumps (Ag NPs @ PAN-nanohump) [30]. The designed 3D hybrid exhibited a high

152

density of hot spots and large surface area, demonstrating good SERS performance for

153

sensing a congener of PCBs (Fig. 3(A)). In the same manner, a high-density hot spot 3D

154

SERS substrate consisting of polyamide nanofibers was grafted with vertical Ag-nanosheets

155

[32]. Homogeneous nanoscale gaps between neighboring Ag-nanosheets were formed,

156

resulting in a high density of 3D SERS hotspots and demonstrating high SERS activity (Fig.

157

3(B)). Similarly, the 3D SERS substrate can be fabricated via simultaneous assembly of small

158

Ag NPs and large Ag spheres on the side surface and top ends of large scale vertically aligned

159

cone shaped ZnO nanorods [33] (Fig. 3(C)). Another method combined a traditional SERS

160

substrate (Ag NPs) with a magnetomotive enrichment compound (Fe3O4) to detect PCB-77

161

[34]. The authors increased the EM field enhancement of the substrates by modulating the

162

magnetic response of Fe3O4 to dynamically adjust the distances of neighboring Ag NPs. This

163

method created more effective “hot spots” and resulted in an improved SERS detection limit 8

164

for PCBs (Fig. 3(D)). However, the preparation of the sophisticated substrates requires long

165

synthesis times.

166

3.2 Substrates with modified surfaces

167

According to the CM mechanism, the charge transfer between the substrate and analyte

168

PCBs increases the polarizability of the analytes, resulting in a higher degree of Raman

169

transition. The close proximity of target PCBs to the surface of the substrate is regarded as

170

the premise for the phenomenon of CT take place [35]. However, bare Au or Ag NPs

171

experience are difficulty in obtaining SERS signals because of the strong hydrophobicity of

172

PCBs. Thus, significant efforts have been made to modify the surface of the substrates.

173

Modifying the surface with appropriate functional groups has become quite popular and three

174

major types of modification have been developed. (1) Alkanethiols and perfluoroalkanethiol

175

can be coupled with the substrate surface to concentrate analytes and facilitate SERS

176

detection (Fig. 4(A)) [36]. Through Van der Waal interaction with PCBs, the straight chain

177

alkanethiol can be used to modify the substrate surface and capture the hydrophobic PCBs. (2)

178

Cyclodextrins (CDs) are also effective modification agents, as they contain a hydrophobic

179

inner cavity and hydrophilic outer part. They can trap water-insoluble molecules in the cavity

180

to form stable host-guest inclusion complexes. CDs coated on the surface of the core shell

181

nanostructures or nanosheets has demonstrated significantly improved sensitivity of detection.

182

Jency et al. performed early studies using a highly sensitive SERS platform for trace

183

detection of PCBs in agricultural soil based on β-CD modified AuNPs [37]. When

184

contaminated soil was added to the detection system, the binding of the soil contents with

185

β-CD resulted in the aggregation of AuNPs, and a Raman signal of the target PCBs molecules

186

was obtained. A similar method was developed by Xu et al [38]. To increase the efficiency of

187

capturing PCB-77, β-CD was modified on an Ag-nanowire tip array, achieving a limit of

188

detection as low as 1×10-10 M and demonstrating that the sensitivity and selectivity for SERS

189

detection of PCBs can be significantly improved (Fig. 4(B). Hybrid substrates have been

190

fabricated by SH-β-CD via thiol binding. However, the thiolated modifier occupies the active

191

site of the metal surface and interferes with substrate uniformity [39, 40] (Fig. 4(C, D)). In

192

addition, this method is not selective since the other interferents with similar sizes and shapes

193

can be identified by the β-CD. (3) The third type is glutathione (GSH) modification, which

194

can be easily adsorb onto the substrate surface by its thiol groups and the GSH-AuNPs

195

composites have been extensively applied for PCB detection [41].

196

3.3 Indirect measurement 9

197

Besides the modification of the surface of the substrates, the target analytes can also be

198

converted into analogues through addition or substitution reactions for realizing indirect

199

measurements (Fig. 5). Rindzevicius et al. developed an improved procedure for the

200

analytical detection of PCB-77 through modification with a –SH3 group. The vibrational

201

modes of PCB-77 and PCB-77-SCH3 were very similar, but the vibrational intensity of

202

PCB-77-SCH3 was much stronger than that of PCB-77. The experiments showed improved

203

sensitivity towards the detection to PCB-77-SCH3 (10-8 M) over that of PCB-77 (10-5 M) [42].

204

Thus, chemical variations improved the SERS sensitivity, but the selectivity must also be

205

considered. The functional groups interact with the target and other molecules that interfere

206

with the process due to their similar structures and properties.

207

3.4 Substrates with high stability

208

Metal nanoparticle colloids are widely used as SERS substrates due to the hot spots formed

209

between the nanoparticles. However, metal nanoparticle aggregation in colloidal solutions is

210

difficult to control, leading to the random formation of hot spots. When the target molecules

211

exist near the hot spots, the intensities of the enhanced Raman signals were unstable. Other

212

factors influenced by the chemical adsorption such as vibration, charge transfer, and the

213

deformation or distortion of molecules also affect the Raman signals [43]. It is of significant

214

interest to improve substrates from a randomly rough surface to obtain highly ordered

215

nanostructures. Thus, many researches have attempted to control hot spot formation by the

216

modulation of pH [44], temperature [45], and DNA aptamers [46]. Cleaning of the glass

217

sample vials, vortexing time used for sample mixing, and vortexing duration of the enhanced

218

solution significantly influence the aggregation of the metal nanoparticles and affect the

219

reproducibility of the associated analytical method [47]. In addition, the metal nanoparticles

220

decorated on supporting materials, such as graphene sheets, have demonstrated improved

221

stability. Graphene can be used as a platform for molecular decoration and quench

222

fluorescence to provide Raman enhancement. Meanwhile, the sp2 hybridized structure of the

223

carbon atoms constituted a large π bond network, allowing the target molecules to

224

homogeneously adsorb on the surface through π-π interactions, improving the stability of the

225

hybrid substrates [48-50]. This function of graphene has been called the graphene-enhanced

226

Raman scattering (GERS) effect [51]. Shanta et al. described the fabrication of reduced

227

graphene oxide (rGO) assemblies with Ag nanoprisms for improved SERS detection of three

228

tetrachlorobiphenyl isomers from a mixture. The hybrid substrate offered remarkable trace

229

detection ability for PCB-77 [52]. The fabricated periodic nanoprism array on top of the GO 10

230

layers attracted the aromatic rings of the PCBs to the surface via π-π stacking interactions and

231

the captured PCBs showed enhanced SERS signals due the increased charge transfer (Fig.

232

7(A)). The GO structure may also improve the reproducibility of SERS detection. For

233

example, an effective SERS substrate based on GO wrapped flower-like Ag microparticles

234

(Ag @ GO) exhibited higher stability over 50 days of exposure to ambient conditions and

235

demonstrated excellent enrichment and SERS effect for target PCBs molecules [53] (Fig.

236

7(B)). Another method focuses on the fabrication of uniform nanostructures using various

237

advanced nanofabrication techniques [54, 55]. Among these techniques, oblique angle

238

deposition (OAD), which is a physical vapor deposition technique based on a shadowing

239

effect and surface diffusion, has been widely used. The vapor atoms are deposited on a

240

substrate at a large incident angle with respect to the substrate surface normal. Under these

241

conditions, typical Ag nanorod arrays (Ag NRs) can be prepared [56]. By controlling the

242

deposition conditions, including deposition angle, deposition time, growth rate, and

243

temperature, the morphology of the Ag NRs can be easily controlled. In addition, the SERS

244

enhancement factors are mainly dependent on the metal nanorod length [57], incident angle

245

[58], and polarization of the excitation light [59]. Through rigorous control of the above

246

parameters, the nanorod array demonstrated good uniformity and reproducibility [60].

247 248

4. Challenges and perspectives

249

As a sensitive and prominent tool for on-site detection, SERS has been made significant

250

progress towards PCBs detection in the past few years. However, some challenges remain,

251

including the narrow focus of the sensors; the current target PCBs are mainly focused on only

252

PCB-77. Additional PCBs, such as the 12 DL-PCBs and 7 indicator PCBs, should be

253

considered. The current research is still at an early stage and the reported target PCBs are

254

largely based on a pure format without spiking into any matrix or real samples from the field.

255

And the sensitivity of SERS detection for PCBs is relatively low (LOD＞10-8 M). Therefore,

256

moreresearch is needed as shown in Fig. 8.

257

4.1 Technology integration

258

SERS is often used as detection tool rather than a separation method. Multiple

259

interferences from structural analogs in the complex matrices exhibit their own characteristic

260

Raman peaks that contribute to SERS spectral patterns. Thus, it is difficult to establish

261

reliable SERS spectral features for target compounds. The integration of effective separation

262

or concentration techniques with further SERS detection are therefore necessary. In past 11

263

studies, many advanced separation techniques have been combined with SERS. However,

264

their applications in PCBs analysis are still very limited. And more research can be conducted

265

from this part.

266

4.1.1 Antibody-based SERS

267

Because of the high selectivity and specificity, antibody-based SERS has attracted

268

increasing attention. Antibodies with a high affinity and specificity for target antigen

269

recognition can be used to capture the target molecules from the complex matrices. The

270

traditional method is based on a sandwich structure consisting of antibodies, target molecules,

271

and tags. The tags are usually composed of the substrates and antibodies called

272

immune-nanoparticles. Typically, a three-step method is used to develop the

273

sandwich-structure. First, the antibodies are immobilized on a metal substrate surface or

274

magnetic beads. Second, the immobilized antibodies specifically capture target molecules

275

(antigens) and finally the antibody-antigen complexes bound with tags are formed into a

276

sandwich structure. To remove the interference originating from the complex matrices, the

277

sandwich structure can be separated via washing or magnetic field application. Compounds

278

that are not bound with the antibodies are eliminated during this step. In the detection step,

279

some substrates exhibit their own characteristic SERS signals, which can be used as an

280

internal standard to decrease the variation of the resulting quantitative calculations [61].

281

Generally, sandwich-structured SERS immunoassays are known as label-free detection, a

282

type of indirect detection. Considering the interaction between target antigens and substrates,

283

Raman reporter molecules are introduced. The Raman reporter is used to characterize the

284

concentration of large proteins composed of repeating units, because the signal intensity of

285

the Raman reporter is correlated to the concentration of the antigen [62]. This detection

286

system can be used for multi-target detection if the corresponding antibodies and different

287

tags can be immobilized or labeled. Magnetic beads used for the separation and enrichment

288

of the target compounds have allowed for remarkable progress in the field of antibody-based

289

SERS detection. In addition to indirect detection, direct immunoassay SERS detection

290

methods have also been developed [63, 64]. These methods usually use antibodies

291

immobilized on the surface of immunomagnetic beads to capture target molecules from the

292

matrices. Elution solutions are used to break the non-covalent bonds between the target

293

molecule and antibodies, which can be subsequently separated and the isolated molecules

294

detected in presence of the SERS substrate. In addition to the classical metallic nanospheres,

295

Raman active nanoparticles including gold nanorods [65], gold nanostars [66], gold 12

296

nanocubes [67], and Au @ Ag NPs [68] have been developed as tags. To improve the stability

297

of the self-aggregating substrates, more stable SERS tags have been fabricated and include

298

core-Raman reporter-shell substrates [69], metal-organic framework (MOF) @ Au tetrapods

299

(Au TPs) immobilized Raman reporter or antibodies [70], and Ag NPs @

300

antibody-functionalized polyethyleneglycol coatings [71]. Some research about the

301

antibody-based SERS used in PCBs detection have been carried out in our research group.

302

We found that the main hurdle remains in preparing antibodies and more research is needed.

303

4.1.2 Aptamer-based SERS

304

In 1990, the first report of an in vitro selection technique was published and used to find

305

specific nucleic acid sequences that bind non-nucleic acid targets with high affinity and

306

specificity [72, 73]. Unlike interactions between antibodies and antigens, aptamer-based

307

sensors operate based on the selectivity between an aptamer and a corresponding aptamer

308

modified with a reporter. Aptamers are oligonucleotides or peptides that bind specific target

309

molecules for the separation, recognition, and enrichment of target analytes. The most

310

common aptamers are composed nucleic acid ligands such as single standard

311

deoxyribonucleic acid (ssDNA) or ribonucleic acid (RNA), obtained by repeated rounds of in

312

vitro selection or equivalently, SELEX (systematic evolution of ligands by exponential

313

enrichment) [74]. These oligonucleotides can recognize target molecules because of their

314

three-dimensional structures. Once the target PCBs are captured, the ssDNA molecules can

315

fold themselves into three-dimensional formations such as hairpin loops, T-junctions, or

316

G-quadruplexes. For example, an ssDNA oligomer PCB-77 binding aptamer containing the

317

sequence (5’-3’)

318

SH-(CH2)6-GGCGGGGCTACGAAGTAGTGATTTTTTCCGATGGCCCGTG (40 bases)

319

was used for many detections and confirmed to be effective [75-77]. By changing the DNA

320

structure formed upon conjugation with the target molecules, selective and quantitative

321

determination can be realized because of the high affinity and specificity toward the target.

322

Another method involves the change of conformation of the probe when the target gets close

323

to substrate, leading SERS signal changes. The specific recognition of aptamers has the

324

potential to improve the selectivity of SERS detection in complex matrices. A third method is

325

using aptamer-modified metal nanostructures for trace detection of PCBs (Fig. 6). These

326

aptamers are usually composed of single-stranded DNA (ssDNA) oligomers where one end of

327

ssDNA is anchored covalently to an Ag surface via a thiol linker.

328

ssDNA used in aptamer-based SERS is usually selected from a large and random pool of 13

329

nucleotides by the SELEX method, which is time-consuming and exhibits some degree of

330

randomness in the final results. The use of aptamer-based SERS applications remains at an

331

early stage and more research are required.

332

4.1.3 Molecularly imprinted polymer-based SERS

333

Molecularly imprinted polymers (MIPs) are highly selective and sensitive for separating

334

target analytes from complicated matrices. Typical MIPs include template molecules,

335

functional monomers, and cross-linking reagents. The recognition and capture of target

336

molecules are realized by creating template-shaped cavities in the polymer matrices. The

337

target analytes act as the templates and interact with functional monomers via covalent or

338

non-covalent bonds in solution. The formed covalent complex then inter-act with

339

cross-linking reagents. After removal of the template molecules from the polymers,

340

microcavities with complementary 3D structures conforming to the shape and chemical

341

functionality of the templates are generated. These polymers exhibit excellent capabilities for

342

specifically and sensitively rebinding targets with the similar shapes and microstructures to

343

the original template [78]. MIPs are often referred to as “artificial antibodies” and the target

344

molecule will form a “lock and key” combination with the artificial antibody when reacted

345

with the MIP. The selective MIP method was developed to separate targets from a

346

complicated matrix or for the selective removal of pollutions from environmental matrices

347

[79]. The combination of MIPs with SERS has been validated as a promising platform for the

348

simultaneous separation and determination of trace levels of analytes [80, 81]. For instance,

349

MIP can be doped with AuNPs (AuNPs @ MIPs) via one-pot precipitation polymerization as

350

a template and was successfully applied for chemical sensing [82]. Moreover, novel

351

surface-imprinted core-shell AuNPs were fabricated and applied for the sensitive and

352

selective detection of bisphenol A (BPA) by SERS in real samples. The BPA imprinted MIP

353

layer was fabricated on the AuNPs using a sol-gel process. The formed MIP-AuNPs

354

containing specific recognition sites were used to rebind the BPA molecules [83]. Before

355

MIP-based SERS detection, the selectivity of MIPs for the target compounds and their

356

affinity towards the substrates surface must be evaluated or only weak SERS signals will be

357

obtained.

358

4.1.4 Other techniques combined with SERS

359

Other advanced separation techniques have been used to remove matrix interference and

360

improve SERS detection selectivity [84, 85]. Chemical separation methods such as thin layer

361

chromatography [86, 87, 88], phase separation (liquid-liquid extraction [89], gas-solid 14

362

extraction [90, 91], column chromatography [92, 93]), transmission electron microscopy [94]

363

and electrochemical impedance spectroscopy [95] have shown that sample pretreatment can

364

condense the target analytes, reduce interferences, and enhance SERS detection selectivity.

365

And many techniques that have not yet been used in combination with SERS could be

366

attempted.

367

4.2 Expanding the detection range and realizing of the high-throughput detection

368

Most reported methods focused primarily on PCB-77 or PCB-3 detection and expanding

369

the scope of the target PCBs should be addressed. For example, 12 congeners of DL-PCB

370

that show dioxin-like toxicity and 7 indicator PCBs as representative POPs for monitoring

371

should be used in the development of novel methods. TEFs and toxic equivalency quantity

372

(TEQ) values are used by the World Health Organization (WHO), scientists, and regulators as

373

a consistent method to evaluate the toxicities of individual dioxin compounds and their

374

mixtures, respectively. The concentration of one of these PCBs is insufficient for estimating

375

the TEQ level. Therefore, research regarding the capacity of SERS detection should continue.

376

The target scope should be expanded to include the entire family of PCBs. Hence, various

377

SERS-active substrates should be further designed. For example, complex 2D or 3D

378

nanostructures could be used, and the shape and structure of substrates could be adjusted

379

according to the scope requirements.

380

One the other hand is the realizing of high-throughput detection. Novel multi-channel

381

SERS active devices should be developed to enable high-throughput detection. Most reported

382

SERS detection methods for PCBs focused on only a single analyte in a single test. The

383

simultaneous detection integrated into one system is a developing trend. Another way is the

384

use of capturer units modified on the surface of SERS substrates. Currently, some MIP

385

materials have been used for the class specific recognition of structural analogs in complex

386

matrices [96]. The multi-target PCBs with similar chemical structures can be simultaneously

387

captured through MIP. In the case, with the multiple recognition from MIP and the Raman

388

enhancement from SERS substrates, the core-shell nanoparticles consisting of metal core and

389

a MIP shell can be used for the identification of a variety of PCBs. Further, the chemometric

390

resolution methods such as principal component analysis (PCA) can be used to calculate the

391

composition of chemical mixtures [97]. One way is to calculate the adsorption kinetics factor

392

for each component using a standard sample as the reference, with which one could correct

393

the predictions given by PCA [98]. In this situation the determination of multi-target PCBs

394

may be realized. 15

395 396

4.3 Improving the feasibility of SERS substrates

397

The different kinds of substrates for SERS detection of PCBs have been developed.

398

However, the current sensitivity of SERS detection for PCBs is relatively low (LOD＞10-8

399

M), which cannot meet the requirements of detection for actual samples. The sensitivity of

400

SERS detection is primarily attributed to the “hot spots” on nano-substrate. These hot spots

401

are generated at the interstitial gaps between metallic nanoparticles. Therefore, increasing the

402

number and location of hot spots can improve the sensitivity of detection. One example is the

403

pre-concentrations of nanoparticles through physical means such as filtration, which can be

404

used to improve the limit of detection. Another example is the coupling of electrokinetic

405

pre-concentration with SERS, which was developed to detect antibiotics and phenols [99,

406

100]. Besides increasing the number of hot spots, alternations of the shape of the

407

nanoparticles can also increase of localized electromagnetic field and increase the likelihood

408

of the contact of target compounds with the hot spots. Nanoparticle with the shape of sea

409

urchin-like [29], and gecko-inspired nano tentacle [31] have been applied. However, their

410

applications in PCBs detection are still very limited, and future studies can be conducted in

411

this way. In addition, during the immobilization of aptamer on the surface of SERS substrate,

412

nonspecific binding of PCBs due to the difficulty of full coverage of the aptamer on the

413

SERS substrate can greatly interfere with the sensitivity of the analysis. The optimization of

414

the surface modification by adding blocker molecules to backfill the empty spaces on the

415

substrates may be the future direction.

416

Meanwhile, the stability and portability of substrates have to be improved further to realize

417

the commercial applications. Traditional colloidal substrates have not been used on a

418

large-scale due to issues concerning their stability and reproducibility. Hence, solid substrates

419

are more suitable for portable on-site detection and fiber-based SERS facilitates the used of

420

solid substrates in field applications [101]. And nanotechnology is often used to fabricate

421

solid metal nanostructures. By adjusting the preparation parameters, different substrates with

422

different morphological characteristics can be fabricated. Higher reproducibility and

423

homogeneity of the substrates will result in precise quantitative detection of PCBs. Therefore,

424

future research efforts should be devoted to developing novel nanotechnologies and exploring

425

the relation between the preparation parameters and structural characteristics. However, the

426

background level of the fiber material may interfere with the detection, limiting the

427

application of the fiber-based SERS. In contrast, paper-based SERS offers a promising 16

428

platform for field detection. Due to its low cost, portability, and feasibility, paper-based SERS

429

platforms have just been developed. Generally, submicron size metal is deposited on filter

430

paper using a spinning device and the paper-based substrate mounted on a holder inside a

431

vacuum chamber, where metal is then allowed to thermally evaporate onto the substrate [102].

432

The deposited metal particles are usually composed of Au NPs [103] or Ag NPs [104].

433

However, the deposited metal particles are exposed on the paper and subject to oxidation,

434

which may decrease their SERS activity. Finally, to improve the feasibility of the SERS

435

detection methods the standardized operation protocols should also be developed.

436

4.4 Reduction of the cost of the procedure

437

Uniform SERS substrates are usually fabricated by relatively new nanotechnology methods.

438

Based on the properties of PCBs molecules, these substrates are often modified with various

439

functional groups for SERS detection. For a wider range of applications, the SERS cost

440

should be reduced by lowering the cost of substrate production and the price of portable

441

Raman spectrometers. Specifically, the source materials of the SERS substrates, optical

442

design, laser devices, charge-coupled devices, and software design will be the improved in

443

the future, leading to significant cost savings.

444 445 446

5. Conclusions The remarkable characteristics of its rapid response, ultra-sensitivity, and simple operation

447

make SERS particularly well suited for PCBs monitoring, especially for on-site detection.

448

The current review presents the rapid advances in the preparation of SERS substrates for the

449

detection of PCBs in the past few years. And some critical technology points have been

450

discussed. However, some challenges still remain. The current target PCBs are mainly

451

focused on only PCB-77. The reported target PCBs are largely based on a pure format rather

452

than the real samples. And the sensitivity of SERS detection for PCBs is relatively low.

453

Future studies should focus on the integration of SERS with other techniques, broadening the

454

detection range, improving the feasibility of SERS substrates, realizing of the

455

high-throughput detection, reduction of the cost of the procedure. Continued efforts and

456

achievements in this field will significantly improve the practical application of SERS for

457

PCBs detection.

458 459 460

Acknowledgment The project was supported in 13th five-year development plan of China by the National 17

461

Key Research and Development Program (2017YFC1600301), the Fundamental Research

462

Funds for Central Non-profit Scientific Institution, Chinese Academy of Agricultural

463

Sciences (NO. 1610072017006) and a special fund for the innovation project for the Chinese

464

Academy of Agricultural Sciences (The innovation team of testing and evaluation for feed

465

quality & safety).

466 467

References

468

[1] F. Wania, D. Mackay, Tracking the Distribution of Persistent Organic Pollutants, Environ. Sci.

469

Technol. 30 (1996) 390-396.

470

[2] M. Van den Berg, L.S. Birnbaum, M. Denison, M. De Vito, W. Feeley, H. Fiedler, et al., The 2005

471

World Health Organisation Re-evaluation of Human and Mammalian Toxic Equivalency Factors for

472

Dioxins and Dioxins-like Compounds. Toxicol. Sci. 93 (2006) 223-241.

473

[3] Commission desicion 277/2012/EC, Off. J. Eur. Commun. L91 1-7.

474

[4] National Food Safety Standard, GB/T 2762, China, 2017.

475

[5] D. Xia, L. Gao, M. Zheng, S. Wang, G. Liu, Simultaneous analysis of polychlorinated biphenyls and

476

polychlorinated

naphthalenes

by

isotope

dilution

comprehensive

two-dimensional

gas

477

chromatography high-resolution time-of-flight mass spectrometry, Anal. Chim. Acta 937 (2016)

478

160-167.

479

[6] G.D. Dam, I.C. Pussente, G. Scholl, G. Eppe, A. Schaechtele, S.V. Leeuwen, The performance of

480

atmospheric pressure gas chromatography - tandem mass spectrometry compared to gas

481

chromatography - high resolution mass spectrometry for the analysis of polychlorinated dioxins and

482

polychlorinated biphenyls in food and feed samples, J. Chromatogr. A 1477 (2016) 76-90.

483

[7] D. Geng, P. Kukucka, I.E. Jogsten, Analysis of brominated flame retardants and their derivatives by

484

atmospheric

pressure

chemical

ionization

using gas chromatography coupled

485

quadrupole mass spectrometry, Talanta 162 (2016) 618-624.

to tandem

486

[8] L. Ching, B. Eric, L. James, Z. Wei, Optimized efficiency of mapping a site contaminated with

487

dioxins by immunoassay compared to gas chromatography-high resolution mass spectrometry, Anal.

488

Bioanal. Chem. 408 (2016) 1095-1105.

489

[9] D. Crump, A. Farhat, S. Chiu, K.L. Williams, S.P. Jones, V.S. Langlois, Use of a Novel

490

Double-Crested Cormorant ToxChip PCR Array and the EROD Assay to Determine Effects of

491

Environmental Contaminants in Primary Hepatocytes, Environ. Sci. Technol. 50 (2016) 3265-3274.

492

[10] H. Kojima, S. Takeuchi, M. Iida, S.F. Nakayama, T. Shiozaki, A sensitive, rapid, and simple

493

DR-EcoScreen bioassay for the determination of PCDD/Fs and dioxin-like PCBs in environmental

494

and food samples, Environ. Sci. Pollut. Res. 25 (2018) 7101-7112. 18

495

[11] I. Ahmad, J.Y. Weng, A.J. Stromberg, J.Z. Hilt, T.D. Dziubla, Fluorescence based detection of

496

polychlorinated biphenyls (PCBs) in water using hydrophobic interactions, Analyst 144 (2019):

497

677-684.

498

[12] M. Mascini, A. Macagnano, G. Scortichini, M.D. Carlo, G. Diletti, A.D. Amico, C.D. Natele, D.

499

Compagnone, Biomimetic sensors for dioxins detection in food samples, Sens. Actuators B Chem.

500

111 (2005) 376-384.

501

[13] G. Yang, H. Zhuang, H. Chen, X. Ping, B. Du, A gold nanoparticle based immunosorbent bio-barcode

502

assay combined with real-time immuno-PCR for the detection of polychlorinated biphenyls, Sens.

503

Actuators B Chem. 214 (2015) 152-158.

504 505

[14] X. Zheng, H. Li, F. Xia, D. Tian, X. Hua, X. Qiao, C. Zhou, An electrochemical sensor for ultrasensitive determination the polychlorinated biphenyls, Electrochimica Acta 194 (2016) 413-421.

506

[15] C.Y. Zhang, R. Hao, Y.Z. Fu, H.J. Zhang, S. Moeendarbari, C.S. Peckering, Y.W. Hao, Y.Q. Liu,

507

Graphene oxide-wrapped flower-like sliver particles for surface-enhanced Raman spectroscopy and

508

their applications in polychlorinated biphenyls detection, Appl. Surf. Sci. 400 (2017) 49-56.

509 510 511 512 513 514

[16] G.B. Adam, M.R. Stephen, M.W. Ian, Vertical-flow paper SERS system for therapeutic drug monitoring of flucytosine in serum, Ana. Chim. Acta. 949 (2017) 59-66. [17] Y.F. Jiang, D.W. Sun, H.B. Pu, Q.Y. Wei, Ultrasensitive analysis of kanamycin residue in milk by SERS-based aptasensor, Talanta 197 (2019) 151-158. [18] J.J. Du, C.Y. Jing, One-step fabrication of dopamine-inspired Au for SERS sensing of Cd2+ and polycyclic aromatic hydrocarbons, Anal. Chim. Acta 1062 (2019) 131-139.

515

[19] J. Cheng, X.O. Su, C.Q. Han, S. Wang, P.L. Wang, S. Zhang, J.C. Xie, Ultrasensitive detection of

516

salbutamol in animal urine by immunomagnetic bead treatment couping with surface-enhanced

517

Raman spectroscopy, Sens. Actuators B Chem. 255 (2018) 2329-2338.

518

[20] Y.F. Jiang, D.W. Sun, H.B. Pu, Q.Y. Wei, Surface enhanced Raman spectroscopy (SERS): A novel

519

reliable technique for rapid detection of common harmful chemical residues, Trends Food Sci. Tech.

520

75 (2018) 10-22.

521 522

[21] S. Pang, T.X. Yang, L.L. He, Review of surface enhanced Raman spectroscopic (SERS) detection of synthetic chemical pesticides, Trend. Anal. Chem. 85 (2016) 73-82.

523

[22] T. Yaseen, H.B. Pu, D.W. Sun, Functionalization techniques for improving SERS substrates and their

524

applications in food safety evaluation: A review of recent research trends, Trends Food Sci. Tech. 72

525

(2018) 162-174.

526 527 528

[23] M. Fleischmann, P.J. Hendra, A.J. McQuillan, Raman spectra of pyridine adsorbed at a silver electrode, Chem. Phys. Lett. 26 (1974) 163-166. [24] M. Moskovits, Surface enhanced spectroscopy, Rev. Mod. Phys. 57 (1985) 783-826. 19

529

[25] E.C.L. Ru, E. Blackie, M. Meyer, P.G. Etchegoin, Surface Enhanced Raman Scattering Enhancement

530 531

Factors: A comprehensive study, J. Phys. Chem. C 111 (2007) 13794-13803. [26] Y.S. Yamamoto, T. Itoh, Why and how do the shapes of surface-enhanced Ramsn scattering spectra

532

change? Recent progress from mechanistic studies, J. Raman Spectrosc. 47 (2016) 78-88.

533

[27] H.Y. Liang, Z.P. Li, W.Z. Wang, Y.S. Wu, H.X. Xu, Highly surface-roughened “flower-like” silver

534

nanoparticles for extremely sensitive substrates of surface-enhanced Raman scattering, Adv. Mater. 21

535

(2009) 4614-4618.

536

[28] B. Zhang, P. Xu, X.M. Xie, H. Wei, Z.P. Li, N.H. Mack, X.J. Han, H.X. Xu, H.L. Wang, Acid-directed

537

synthesis of SERS-active hierarchical assemblies of silver nanostructures, J. Mater. Chem. 21 (2011)

538

2495-2501.

539

[29] X.S. Wang, D.P. Yang, P. Huang, M. Li, D. Chen, D.X. Cui, Hierarchically assembled Au

540

microspheres and sea urchin-like architectures: formation mechanism and SERS study, Nanoscale 24

541

(2012) 7766-7772.

542

[30] Z.B. Li, G.W. Meng, Q. Huang, X.Y. Hu, X. He, H.B. Tang, Z.W. Wang, F.D. Li, Ag

543

nanoparticles-grafted PAN-nanohump array films with 3D high-density hot spots as flexible and

544

reliable SERS substrates, Small 40 (2015) 5452-5459.

545

[31] P. Wang, L. Wu, Z.C. Lu, Q. Li, W.M. Yin, F. Ding, H.Y. Han, Gecko-inspired nanotentacle

546

surface-enhanced raman spectroscopy substrate for sampling and reliable detection of pesticide

547

residues in fruits and vegetables, Anal. Chem. 89 (2017) 2424-2431.

548

[32]

Y. Qian, G.W. Meng, Q. Huang, C.H. Zhu, Z.L. Huang, K.X. Sun, B. Chen, Flexible membranes of

549

Ag-nanosheet-grafted polyamide-nanofibers as effective 3D SERS substrates, Nanoscale 6 (2014)

550

4781-4788.

551

[33]

H.B. Tang, G.W. Meng, Q. Huang, Z. Zhang, Z.L. Huang, C.H. Zhu, Arrays of cone-shaped ZnO

552

nanorods decorated with Ag nanoparticles as 3D surface-enhanced raman scattering substrates for

553

rapid detection of trace polychlorinated biphenyls, Adv. Funct. Mater. 22 (2012) 218-224.

554

[34]

Z.Y. Bao, X. Liu, Y. Chen, Y.C. Wu, H.L.W. Chan, J.Y. Dai, D.Y. Lei, Quantitative SERS detection

555

of low-concentration aromatic polychlorinated biphenyl-77 and 2,4,6-trinitrotoluene, J. Hazard. Mater.

556

280 (2014) 706-712.

557

[35] K. Zhang, Y. Wang, M. Wu, Y. Liu, D. Shi, B. Liu, On-demand quantitative SERS bioassays

558 559

facilitated by surface-tethered ratiometric probes, Chem. Sci. 9 (2018) 8089-8093. [36] K.C. Bantz, C.L. Haynes, Surface-enhanced Raman scattering detection and discrimination of

560 561 562

polychlorinated biphenyls, Vib. Spectrosc. 50 (2009) 29-35. [37]

D.A. Jency, M. Umadevi, G.V. Sathe, SERS detection of polychlorinated biphenyls using β-cyclodextrin functionalized gold nanoparticles on agriculture land soil, J. Raman Spectrosc. 46 20

563 564

(2015) 377-383. [38]

W. Xu, G.W. Meng, Q. Huang, X.Y. Hu, Z.L. Huang, H.B. Tang, J.X. Zhang, Large-scale uniform

565

Ag-NW tip array with enriched sub-10-nm gaps as SERS substrates of rapid determination of trace

566

PCB77, Appl. Surf. Sci. 271 (2013) 125-130.

567

[39] Y.L. Lu, G.H. Yao, K.X. Sun, Q. Huang, β-Cyclodextrin coated SiO2@Au@Ag core-shell

568

nanoparticles for SERS detection of PCBs, Phys. Chem. Chem. Phys. 17 (2015) 21149-21157.

569

[40] C. Zhu, G.W. Meng, Q. Huang, Z.B. Li, Z.L. Huang, M.L. Wang, J.P. Yuan, Large-scale

570

well-separated Ag assembled micro-hemispheres modified with HS-β-CD as effective SERS

571

substrates for trace detection of PCBs, J. Mater Chem. 22 (2012) 2271-2278.

572

[41]

J.D. Arocikia, R. Parimaladevi, S.G. Vasant, M. Umadevi, Glutathione functionalized gold

573

nanoparticles as efficient surface enhanced Raman scattering substrate for poly chlorinated biphenyl

574

detection, J. Clust. Sci. 29 (2018) 281-287.

575

[42] T. Rindzevicius, J. Barten, M. Vorobiev, M.S. Schmidt, J.J. Castillo, A. Boisen, Detection of

576

surface-linked polychlorinated biphenyls using surface-enhanced Raman scattering spectroscopy, Vib.

577

Spectrosc. 90 (2017) 1-6.

578

[43] J.F. Li, Y.F. Huang, Y. Ding, Z.L. Yang, S.B. Li, Z X.S. hou, F.R. Fan, W. Zhang, Z.Y. Zhou, D.Y. Wu,

579

B. Ren, Z.L. Wang, Z.Q. Tian, Shell-isolated nanoparticle-enhanced raman spectroscopy, Nature 464

580

(2010) 392-395.

581

[44] T.B. Patricia, J.B. Niklaas, R.L. Laura, P.J. Jorge, M.L.M. Luis, H. Pablo, Reversible assembly of

582

metal nanoparticles induced by penicillamine. Dynamic formation of SERS hot spots, J. Mater. Chem.

583

21 (2011) 16880-16887.

584

[45] A. Bonyár, I. Csarnovics, M. Veres, L. Himics, A. Csik, J. Kámán, L. Balázs, S. Kökényesi,

585

Investigation of the performance of thermally generated gold nanoislands for LSPR and SERS

586

applications, Sens. Actuators B 255 (2018) 433-439.

587 588

[46] N.H. King, S.J. Lee, M. Moskovits, Reversible tuning of SERS hot spots with aptamers, Adv. Mater. 23 (2011) 4152-4156.

589

[47] J. Cheng, X.O. Su, C.Q. Han, S. Wang, P.L. Wang, S. Zhang, J.C. Xie, Ultrasensitive detection of

590

salbutamol in animal urine by immunomagnetic bead treatment couping with surface-enhanced

591

Raman spectroscopy, Sens. Actuators B Chem. 255 (2018) 2329-2338.

592 593

[48] C.T. Zhang, K. Lin, Y.Q. Huang, J.H. Zhang, Graphene-Ag hybrids on laser-textured Si surface for SERS detection, Sensor 17 (2017) 1462.

594

[49] J. Guo, S.C. Xu, X.Y. Liu, Z. Li, L.T. Hu, Z. Li, P.X. Chen, Y. Ma, S.Z. Jiang, T.Y. Ning, Graphene

595

oxide-Ag nanoparticles-pyramidal silicon hybrid system for homogeneous, long-term stable and

596

sensitive SERS activity, Appl. Surf. Sci. 396 (2017) 1130-1137. 21

597 598 599 600 601 602

[50] H.H. Tian, N. Zhang, L.M. Tong, J. Zhang, In situ quantitative graphene-based surface-enhanced Raman spectroscopy, Small Methods 1 (2017) 1700126. [51] W.G. Xu, N.N. Mao, J. Zhang, Graphene: A platform for surface-enhanced Raman spectroscopy, Small 8 (2013) 1206-1224. [52] P.V. Shanta, Q. Cheng, Graphene oxide nanoprims for sensitive detection of environmentally important aromatic compounds with SERS, ACS Sensors 1 (2017) 817-827.

603

[53] C.Y. Zhang, R. Hao, Y.Z. Fu, H.J. Zhang, S. Moeendarbari, C.S. Peckering, Y.W. Hao, Y.Q. Liu,

604

Graphene oxide-wrapped flower-like sliver particles for surface-enhanced Raman spectroscopy and

605

their applications in polychlorinated biphenyls detection, Appl. Surf. Sci. 400 (2017) 49-56.

606 607

[54] B.A. Heman, K. Jan, K. Andrzej, Modification of surfaces of silver nanoparticles for controlled deposition of silicon, manganese, and titanium dioxides, Appl. Surf. Sci. 427 (2018) 334-339.

608

[55] C.Q. Han, Y. Yao, W. Wang, L.L. Qu, L. Bradley, S.L. Sun, Y.P. Zhao, Rapid and sensitive detection

609

of sodium saccharin in soft drinks by silver nanorod array SERS substrates, Sens. Actuators B 251

610

(2017) 272-279.

611 612

[56] Y. He, Y.P. Zhao, Advanced multi-component nanostructures designed by dynamic shadowing growth, Nanoscale 3 (2011) 2361-2375.

613

[57] J.D. Driskell, S. Shanmukh, Y.J. Liu, S.B. Chaney, X.J. Tang, Y.P. Zhao, R.A. Dluhy, The Use of

614

Aligned Silver Nanorod Arrays Prepared by Oblique Angle Deposition as Surface Enhanced Raman

615

Scattering Substrates, J. Phys. Chem. C 112 (2008) 895-901.

616 617

[58] Y.J. Liu, J.G. Fan, Y.P. Zhao, S. Shanmukh, R.A. Dluhy, Angle dependent surface enhanced Raman scattering obtained from a Ag nanorod array substrate, Appl. Phys. Lett. 89 (2006) 173134.

618

[59] Y.P. Zhao, S.B. Chaney, S. Shanmukh, R.A. Dluhy, Polarized Surface Enhanced Raman and

619

Absorbance Spectra of Aligned Silver Nanorod Arrays, J. Phys. Chem. B 110 (2006) 3153-3157.

620

[60] A. Barranco, A. Borras, A.R. Gonzalez-Elipe, A. Palmero, Perspectives on oblique angle deposition of

621

thin films: from fundamentals to devices, Progress in materials science 76 (2016) 59-153.

622

[61] Y. Wang, M. Salehi, M. Schütz, S. Schlücker, Femtogram detection of cytokines in a direct dot-blot

623

assay using SERS microspectroscopy and hydrophilically stabilized Au-Ag nanoshells, Chem.

624

Commun. 50 (2014) 2711-2714.

625 626

[62] S. Laing, K. Gracie, K. Faulds, Multiplex in vitro detection using SERS, Chem. Soc. Rev. 45 (2016) 1901-1918.

627

[63] J. Cheng, X.O. Su, S. Wang, Y.P. Zhao, Highly sensitive detection of clenbuterol in animal urine using

628

immunomagnetic bead treatment and surface-enhanced raman spectroscopy, Sci. Rep. 6 (2016)

629

32637.

22

630

[64] A. Lopez, F. Lovato, S.H. Oh, Y.H. Lai, S. Filbrun, E.A. Driskell, J.D. Driskell, SERS immunoassay

631

based on the capture and concentration of antigen-assembled gold nanoparticles, Talanta 146 (2016)

632

388-393.

633

[65] M.E. Pekdemir, D. Ertürkan, H. Külah, I.H. Boyacı, C. Özgen, U. Tamer, Ultrasensitive and selective

634

homogeneous sandwich immunoassay detection by Surface Enhanced Raman Scattering (SERS),

635

Analyst 137 (2012) 4834-4840.

636

[66] Y.W. Pei, Z.Y. Wang, S.F. Zong, Y.P. Cui, Highly sensitive SERS-based immunoassay with

637

simultaneous utilization of self-assembled substrates of gld nanostars and aggregates of gold

638

nanostars, J. Mater. Chem. B 1 (2013) 3992-3998.

639

[67] A. Phranot, R. Patcharee, I. Wishulada, P. Thantrira, I. Numpon, Synthesis, characterization, drug

640

release and transdentinal delivery studies of magnetic nanocubes coated with biodegradable poly (2-

641

(dimethyl amino) ethyl methacrylate), J. Magn. Magn. Mater. 427 (2017) 235-240.

642

[68] Y. Xie, H.F. Chang, K. Zhao, J.G. Li, H. Yang, L.Y. Mei, S.M. Xu, A.P. Deng, A novel

643

immunochromatographic assay (ICA) based on surface-enhaned Raman scattering for the sensitive

644

and quantitative determination of clenbuterol, Anal. Methods 7 (2015) 513-520.

645

[69] Y.W. Chen, T.Y. Liu, P.J. Chen, P.H. Chang, S.Y. Chen, A High-Sensitivity and Low-Power

646

Theranostic Nanosystem for Cell SERS Imaging and Selectively Photothermal Therapy Using

647

Anti-EGFR-Conjugated Reduced Graphene Oxide/Mesoporous Silica/AuNPs Nanosheets, Small 12

648

(2016) 1458-1468.

649

[70] Y. He, Y. Wang, X. Yang, S.B. Xie, R. Yuan, Y.Q. Chai, Metal organic frameworks combing CoFe2O4

650

magnetic nanoparticles as highly efficient SERS sensing platform for ultrasensitive detection of

651

N-Terninal pro-brain natriuretic peptide, ACS Appl. Mater. Interfaces 8 (2016) 7683-7690.

652 653 654 655 656 657 658 659

[71] N. Guarrotxena, G.C. Bazan, Antibody-functionalized SERS tags with improved sensitivity, Chem. Commun. 47 (2011) 8784-8786. [72] A.D. Ellington, J.W. Szostak, In vitro selection of RNA molecules that bind specific ligands, Nature 346 (1990) 818-822. [73] C. Tuerk, L. Gold, Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase, Science 249 (1990) 505-510. [74] M. Famulok, J.W. Szostak, In Vitro Selection of Specific Ligand-binding Nucleic Acids, Angew. Chem. Int. Ed. 31 (2010) 979-988.

660

[75] C.C. Fu, Y. Wang, G. Chen, L.Y. Yang, S.P. Xu, W.Q. Xu, Aptamer-based surface-enhanced Raman

661

scattering-Microfluidic sensor for sensitive and selective polychlorinated biphenyls detection, Anal.

662

Chem. 87 (2015) 9555-9558.

663

[76] K. Sun, Q. Huang, G.W. Meng, Y.L. Lu, Highly sensitive selective surface enhanced raman 23

664

spectroscopy label detection of 3,3’,4,4’-tetrachlorobiphenyl using DNA aptamer-modified

665

Ag-nanorod arrays, ACS Appl. Mater. Interfaces 8 (2016) 5723-5728.

666

[77]

based on DNA aptamer modified SiO2@Au core/shell nanoparticles, Analyst 139 (2014) 3083-3087.

667 668

Y.L. Lu, Q. Huang, G.W. Meng, L.J. Wu, J.J. Zhang, Label-free selective SERS detection of PCB-77

[78] R.J. Gui, H. Jin, H.J.Guo, Z.H. Wang, Recent advances and future prospects in molecularly imprinted

669

polymers-based electrochemical biosensors, Biosens. Bioelectron. 100 (2018) 56-70.

670

[79] D.S. Mkhize, H. Nyoni, L.P. Quinn, B.B. Mamba, T.A.M. Msagati, Molecularly imprinted

671

membranes (MIMs) for selective removal of polychlorinated biphenyls (PCBs) in environmental

672

waters: fabrication and characterization, Environ. Sci. Pollut. R. 24 (2017) 11694-11707.

673

[80] H. Li, X. Wang, Z. Wang, J. Jiang, Y. Qiao, M. Wei, Y. Yan, C. Li, A high-performance

674

SERS-imprinted sensor doped with silver particles of different surface morphologies for selective

675

detection of pyrethroids in rivers, Mew J. Chem. 41 (2017) 14342-14350.

676

[81] Y. Xie, M. Zhao, Q. Hu, Y. Cheng, Y. Guo, H. Qian, W. Yao, Selective detection of chloramphenicol

677

in milk based on molecularly imprinted polymer surface-enhanced Raman spectroscopic nanosensor,

678

J. Raman. Spectrosc. 48 (2017) 204-210.

679

[82] T. Shahar, T. Sicron, D. Mandler, Nanosphere molecularly imprinted polymers doped with gold

680

nanoparticles for high selectivity molecular sensors, Nano Res. 10 (2017) 1056-1063.

681

[83] J.Q. Xue, D.W. Li, L.L. Qu, Y.T. Long, Surface-imprinted core-shell Au nanoparticles for selective

682

detection of bisphenol A based on surface-enhanced Raman scattering, Anal. Chim. Acta 777 (2013)

683

57-62.

684

[84] Y. Zhang, S.J. Zhao, J.K. Zheng, L.L. He, Surface-enhanced Raman spectroscopy (SERS) combined

685

techniques for high-performance detection and characterization, Trend. Anal. Chem. 90 (2017) 1-13.

686

[85] W. Liao, X.N. Lu, Determination of chemical hazards in foods using surface-enhanced Raman

687

spectroscopy coupled with advanced separation techniques, Trends Food Sci. Tech. 54 (2016)

688

103-113.

689

[86] F. Fang, Y. Qi, F. Lu, L. Yang, Highly sensitive on-site detection of drugs adulterated in botanical

690

dietary supplements using thin layer chromatography combined with dynamic surface enhanced

691

Raman spectroscopy, Talanta 146 (2016) 351-357.

692

[87] Y.C. Ho, W.W.Y. Lee, S.E.J. Bell, Investigation of the chemical origin and evidential value of

693 694

differences in the SERS spectra of blue gel inks, Analyst 141 (2016) 5152-5158. [88]

Q. Zhu, Y. Zhao, Y. Cao, Y. Chai, F. Lu, Rapid on-site TLC-SERS detection of four antidiabetes

695

drugs used as adulterants in botanical dietary supplements. Anal. Bioanal. Chem. 406 (2014) 1877.

696

[89] M. Zhang, X. Zhang, Y. Shi, Z. Liu, J. Zhan, Surface enhanced Raman spectroscopy hyphenated with

697

surface microextraction for in-situ detection of polycyclic aromatic hydrocarbons on food contact 24

698

materials, Talanta 158 (2016) 322-329.

699

[90] Y. Chen, Y. Zhang, F. Pan, J. Liu, K. Wang, C. Zhang, S. Cheng, L. Lu, W. Zhang, Z. Zhang, X. Zhi,

700

Q. Zhang, G. Alfranca, J.M. De la Fuente, D. Chen, D. Cui, Breath analysis based on

701

surface-enhanced Raman scattering sensor distinguishes early and advanced gastric cancer patients

702

from healthy persons, ACS Nano 10 (2016) 8169-8179.

703

[91] B. Li, Y. Shi, J. Cui, Z. Liu, X. Zhang, J. Zhan, Au-coated ZnO nanorods on stainless steel fiber for

704

self-cleaning solid phase microextraction-surface enhanced Raman spectroscopy, Anal. Chim. Acta

705

923 (2016) 66-73.

706

[92] W. Wang, M. Xu, Q. Guo, Y. Yuan, R. Gu, J. Yao, Rapid separation and on-line detection by coupling

707

high performance liquid chromatography with surface-enhanced Raman spectroscopy, RSC Adv. 5

708

(2015) 47640-47646.

709

[93] C. Zaffino, G.D. Bedini, G. Mazzola, V. Guglielmi, S. Bruni, Online coupling of high-performance

710

liquid chromatography with surface-enhanced Raman spectroscopy for the identification of historical

711

dyes, J. Raman Spectrosc. 47 (2016) 607-615.

712

[94] E. Cepeda-Pérez, T. López-Luke, G. Plascencia-Villa, L. Perez-Mayen, A. Ceja-Fdez, A. Ponce, et al.

713

SERS and integrative imaging upon internalization of quantum dots into human oral epithelial cells,

714

Journal of Biophotonics, 9 (2016) 683–693.

715 716

[95] A. Convertino, V. Mussi, L. Maiolo, Disordered array of Au covered Silicon nanowires for SERS biosensing combined with electrochemical detection. Scientific Reports 6 (2016) 25099.

717

[96] C. Dougal, M.C. Adam, The use of effective fragment potentials in the design and synthesis of

718

molecularly imprinted polymers for the group recognition of PCBs. Org. Biomol. Chem. 11(2013)

719

4646-4656.

720

[97] H. Luo, Y. Huang, K. Lai, B.A. Rasco, Y. Fan, Surface-enhanced Raman spectroscopy coupled with

721

gold nanoparticles for rapid detection of phosmet and thiabendazole residues in apples. Food control

722

68(2016) 229-235.

723 724

[98] S. Zou, M. Hou, J. Li, Z. Zhang, Semi-quantitative analysis of multiple chemical mixtures in solution at trace level by surface-enhanced Raman scattering. Scientific Reports 7(2017) 6186.

725

[99] Y.T. Li, L.L. Qu, D.W. Li, Q.X. Song, F. Fathi, Y.T. Long, Rapid and sensitive in-situ detection of

726

polar antibiotics in water using a disposable Ag-graphene sensor based on electrophoretic

727

preconcentration and surface-enhanced Raman spectroscopy, Biosens. Bioelectron. 43 (2013) 94-100.

728

[100] D. Li, D.W. Li, J.S. Fossey, Y.T. Long, Portable surface-enhanced Raman scattering sensor for rapid

729

detection of aniline and phenol derivatives by on-site electrostatic preconcentration, Anal. Chem. 82

730

(2010) 9299-9305.

731

[101] X. Yang, C. Gu, F. Qian, Y. Li, J.Z. Zhang, Highly sensitive detection of proteins and bacteria in 25

732

aqueous solution using surface-enhanced Raman scattering and optical fibers, Anal. Chem. 83 (2011)

733

5888-5894.

734 735 736 737 738 739

[102] T. Vodinh, M.Y.K. Hiromoto, G.M. Gegun, R.L. Moody, Surface-enhanced Raman spectrometry for trace organic analysis, Anal. Chem. 56 (1984) 1667-1670. [103] S.W. Hu, S. Qiao, J.B. Pan, B. Kang, J.J. Xu, H.Y. Chen, A paper-based SERS test strip for quantitative detection of Mucin-1 in whole blood, Talanta 179 (2018) 9-14. [104] W.X. Wei, Q.L. Huang, Rapid fabrication of silver nanoparticle-coated filter paper as SERS substrate for low-abundance molecules detection, Spectrochim. Acta. A 179 (2017) 211-215.

740

26

741

Figure captions

742

Fig.1 Illustration of SERS mechanism

743

Fig.2 SEM pictures of (a) “flower”-like Ag nanoparticles [27]; (b, c) Ag nanoparticles

744 745

hierarchical structures [28]; (d) “sea urchin”-like Au micro-particles [29]; (e) Ag nanoparticles decorated on nanohump [30]; (f) gecko-inspired nano tentacle [31].

746 747 748 749 750 751 752 753 754 755 756 757

Fig.3 (A) The fabrication of Ag NPs @ PAN nanohump arrays substrate via Ag sputtering method [30]; (B) Schematic for the fabrication of Ag-nanosheet-grafted PA-nanofiber membranes. Step Ⅰ: a PA-nanofiber membrane is synthesized by electrospinning; Step Ⅰ: Au-nanoparticles are assembled onto the nanofiber as seeds for the growth of Ag-nanosheets; Step Ⅰ: Ag-nanosheets are electrodeposited on the PA nanofibers [32]; (C) Schematic image of the fabrication of an array of ZnO-NRs decorated with Ag NPs (on the NRs side surface) and Ag spheres (on the NRs tops) on Si wafers. There are three kinds of “gaps” between the Ag NPs to form 3D “hot spots” as indicated as 1st, 2nd, and 3rd schematically. “1st” stands for the gaps between the Ag NPs located on the side surface of the same NR; “2nd” stands for the gaps between the two Ag NPs located on the side surface of two neighboring NRs; and “3rd” stands for the gaps between the two large Ag spheres located on the tops of two neighboring NRs [33]; (D) TEM of Ag NPs decorated on Fe3O4 complex and the SERS spectra of PCB-77 with different concentrations [34].

758

Fig.4 (A) The formation of alkanethiol binding layer on SERS substrates for PCBs detection [36]; (B)

759

β-cyclodextrin functionalized gold nanoparticles for the determination of PCB-77 [38]; (C) Schematic

760

representation of β-CD assisted synthesis of uniform SiO2 @ Au @ Ag @ CD NPs for detection of

761

PCB-3, PCB-29, and PCB-77. First, silica NPs are synthesized by the StÖber method, and then Au

762

seeds are conjugated to the silica surface, followed by the formation of the Au shell, and finally, the

763

Ag shell and β-CD capping are achieved simultaneously by using β-CD under alkaline conditions [39].

764

(D) Schematic diagram for the formation of the well separated Ag nanosheet-assembled

765

micro-hemispheres on an ITO substrate. (1) Ag atoms form sparse nuclei on the sparsely distributed

766

and raised tips of the ITO substrate. (2) Newly formed Ag clusters (or particles) attach onto the

767

pre-existing Ag nuclei. (3) Ag particles form nanparticles-assembled hemispheres by oriented

768

attachment. (4) The nanoparticles in the micro-hemispheres fuse together in parallel planes to form

769

rough nanosheets by Ostwald ripening and thus well-separated nanosheet-assembled

770

micro-hemispheres are achieved. (5) The modification of HS-β-CD on the surface of bare Ag

771

nanosheet-assembled micro-hemispheres for PCB-77 detection [40].

772 773 774 775 776 777 778

Fig.5 Schematic comparison of the SERS-based PCB detection principles utilizing ~500nm tall gold-capped Si nanopillars on 200nm thick gold film. Average pillar head dimensions are ~300nm and ~100nm in height and width, respectively. (a) Solvent drying forms nanopillar clusters and encapsulates standard PCB-77; (b) -SCH3 modified PC077 molecules; (c) The SEM images illustrate the clustering step of gold-capped silicon nanopillars; (d) SERS spectra of PCB-77 at concentrations of 5 ×10-3~5 × 10-6 M. (e) SERS spectra of PCB-77-SCH3 at concentrations of 5 ×10-3~5 × 10-8 M [42].

779

Fig.6 (A) SERS measurement of PCB-77 with aptamer capturing in a microfluidic device [75]; (B) 27

780

The label detection of PCB-77 using DNA aptamer-modified Ag-nanorod arrays [76]; (C) Label-free

781

selective SERS detection of PCB-77 based on DNA aptamer modified SiO2@Au core/shell

782

nanoparticles [77].

783 784 785

Fig.7 (A) Fabrication of Ag-nanoprisms on top of GO covered glass slides and the SERS spectra of PCB-47, PCB-52 and PCB-77 [52]; (B) The SERS substrates based on GO wrapped flower-like Ag microparticles (Ag@GO) for the determination of PCB-3 and PCB-77 [53]

786

Fig.8 The trends of SERS for PCBs detection.

787

28

788

Figures

789

Fig.1

790 791

29

792

Fig.2

793 794

30

795

Fig.3

796 797

31

798

Fig.4

799 800

32

801

Fig.5

802 803

33

804

Fig.6

805 806

34

807

Fig.7

808 809

35

810

Fig.8

811 812

36

Highlights

The SERS technical points to the detection of PCBs have been discussed. The rapid advances of SERS substrates preparation for PCBs detection have been presented. The perspectives and the development trends are proposed.

AUTHOR CV Jie Cheng is an associate professor of Agro-products safety in the Institute of Quality Standards and Testing Technology for Agro-products, Chinese Academy of Agricultural Sciences. He received his PhD degree in food safety at the Graduate School of the Chinese Academy of Agricultural Sciences. His research focuses on the synthesis and self-assembly of nanomaterials, and rapid screening methods based on SERS, mainly in the food safety area.

Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: