Research Progress on Epidemic Virus Detection Based on Surface‑Enhanced Raman Spectroscopy

Yi Liu; Nan Wang; Shaohua He; Jun Zhang; Shangyuan Feng; Duo Lin

doi:10.3788/CJL231604

Journals >Chinese Journal of Lasers >Volume 51 >Issue 9 >Page 0907006 > Article

Chinese Journal of Lasers
Vol. 51, Issue 9, 0907006 (2024)

Research Progress on Epidemic Virus Detection Based on Surface‑Enhanced Raman Spectroscopy

Yi Liu, Nan Wang, Shaohua He, Jun Zhang, Shangyuan Feng, and Duo Lin^*

Author Affiliations

Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Photonic and Electronic Engineering, Fujian Normal University, Fuzhou 350007, Fujian , China

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DOI: 10.3788/CJL231604 Cite this Article Set citation alerts

Yi Liu, Nan Wang, Shaohua He, Jun Zhang, Shangyuan Feng, Duo Lin. Research Progress on Epidemic Virus Detection Based on Surface‑Enhanced Raman Spectroscopy[J]. Chinese Journal of Lasers, 2024, 51(9): 0907006 Copy Citation Text

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Fig. 1. Schematic diagram of virus detection based on SERS technology

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SERS sensors and platforms are designed in a variety of diverse ways for label-free detection of SARS-CoV-2. (a) Schematic diagram of the design and operation process of the COVID-19 SERS sensor[36]; (b) flexible substrate combined with SERS metal-insulator-metal nanostructures and machine learning-based label-free detection platform[42]; (c) schematic diagram of SnS2 microsphere substrates design[44]; (d) Raman enhancement mechanism of Cu2O nanoarray with significant enhancement factor[45]

Fig. 2. SERS sensors and platforms are designed in a variety of diverse ways for label-free detection of SARS-CoV-2. (a) Schematic diagram of the design and operation process of the COVID-19 SERS sensor^[36]; (b) flexible substrate combined with SERS metal-insulator-metal nanostructures and machine learning-based label-free detection platform^[42]; (c) schematic diagram of SnS₂ microsphere substrates design^[44]; (d) Raman enhancement mechanism of Cu₂O nanoarray with significant enhancement factor^[45]

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Fig. 3. Machine learning techniques are applied to SARS-CoV-2 label-free detection. (a) Identification of pure S protein standard samples by SERS spectroscopy using PCA^[47]; (b) SERS biosensors are engineered with 3D porous Ag nanoparticle-based microplasma-engineered nanoassemblies (denoted as AgMEN) deposited on cellulose paper (left) and functionalized with antibodies (AgMEN@Ab)(center part) to detect the corresponding antigens by analyzing the SERS response (right)^[48]

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Fig. 4. Application of SERS nanoprobes in label detection and differentiation of SARS-CoV-2. （a) Schematic of the SERS assay based on one-step aptamer recognition for rapid point-of-care detection of SARS-CoV-2 virus within 5 min^[51]; (b) stepwise reactions of RBD probe for SARS-CoV-2 capture and detection with SERS nanotags, for virus and variant identification based on the average Raman spectrum results^[54]

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Fig. 5. Application of SERS label detection method for the detection of RNA and proteins from SARS-CoV-2 virus lysates.(a) Schematic illustrations of the preparation of SERS tags and the signal amplification strategy for SERS detection of SARS-CoV-2 RNA^[55]; (b) preparation of Au@4MBN@Ag NPs and fabrication of two-dimensional SERS sensing chip for SARS-CoV-2 RNA detection^[56]; (c) schematic illustration of the quantitative evaluation of SARS-CoV-2 using the SERS-based aptasensor^[57]

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Fig. 6. Multi-mode virus detection scheme incorporating SERS technology. (a) Schematic of the triple-mode biosensors for COVID-19 virus RNA detection^[59]; (b) PCR amplification process for bridge DNAs and SERS detections for bridge DNAs^[60]

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Fig. 7. SERS labeling method applied to the detection of influenza A virus. (a) Schematic diagram of using SERS assisted with pre-filtering to sensitively detect influenza A virus ^[64]; (b)schematic of the IMBSIs@Ag-SERS method for H5N1 influenza virus detection^[65]

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Fig. 8. SERS labeling method applied to the detection and differentiation of multiple respiratory viruses. (a) Working principle of dual aptamer-immobilized Au nanopopcorn substrate for virus assays^[69]; (b) collection of throat swab sample and operating procedure for the simultaneous quantitative detection of three respiratory viruses via the Fe₃O₄@Au-based SERS LFA strip^[70]

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Fig. 9. SERS technology applied to the detection of human immunodeficiency virus (HIV-1) and norovirus (NoV). (a) Schematic diagram demonstrating rapid handheld SERS platform for HIV detection^[73]; (b) the stepwise dual-modality NoV detection^[77]

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Fig. 10. SERS technology applied to the detection of dengue virus (DENV). (a) Schematic of platform for DENV2 NS1 detection in a single infected mosquito sample with the integration of nanoyeast scFvs affinity probes and nanobox-based SERS nanotags^[83]; (b) schematic illustration of SERS assay of DENV gene via a cascade enzyme-free signal amplification strategy of LCHA and HCR^[84]

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Fig. 11. SERS technology used for the detection of DNA viruses such as hepatitis B virus(HBV) and monkeypox virus(MPXV).(a) Schematic illustration showing the integration of a microfluidic device with the SERS-active substrate based on Au-Ag coated GaN surface^[92]; (b) schematic diagram of CRISPR/Cas12a-SERS principle analysis^[93]; (c) the principle of MPXV detection by colorimetric-SERS dual-mode ICA^[97]

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Fig. 12. CRISPR/Cas-SERS platform applied to the detection of viral genetic material. (a) Schematic diagram of the gene detection by using the CRISPR/dCas9-based SERS method, assisted with HRP-Catalyzed signal amplification^[111]; (b) schematic diagram of the proposed CRISPR/Cas12a-SERS platform for amplification-free ASFV dsDNA detection^[112]

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Fig. 13. Portable Raman spectrometer devices applied to SERS virus detection schemes. (a) Schematic illustration of SERS based immunoassay platform(with a portable Raman spectrometer)^[115]; (b) schematic diagram of the detection of influenza A virus H1N1 by SERS and gold electrodeposition nanostructure^[116]; (c) schematic diagram of a SERS detection method based on one-step aptamer identification using a portable Raman spectrometer for rapid and point-of-care detection of SARS-CoV-2 virus in less than 5 minutes^[51]

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Label method	Type of virus	Virus species	SERS platform	Target	Dynamic range	Methods used	Sample solution	Time	LoD	Reference
Label free	RNA virus	SARS-CoV-2	gold-nanoneedles array	S-protein		PCA & DA	saliva urines	5 min	80 copies/mL	［36］
Label free	RNA virus	SARS-CoV-2	SERS-active surfaces	S-protein			PBS		<1 pg/mL	［39］
Label free	RNA virus	SARS-CoV-2	Au nanoplate film/MgF2/Au mirror/glass	S-protein	1.25×10^-6‒4.7×10^-3 g/mL	VTM， PCA PLS-DA	saliva		2.8× 10^-11 g/mL	［40］
Label free	RNA virus	SARS-CoV-2 Omicron	Ag platform	ssRNA			PBS			［41］
Label free	RNA virus	SARS-CoV-2 influenza A H1N1	metal-insulator-metal nanostructures	S protein HA protein		PCA random forest algorithm	saliva	25 min	10³ copies/mL	［42］
Label free	RNA virus	SARS-CoV-2	GAgNPs paper sensor	S-protein			saliva	2 min	2.4 pg/µL	［43］
Label free	RNA virus	SARS-CoV-2	spherical SnS₂ structure	S protein RNA	10‒ 10¹⁰copies/mL	PCA	saliva， stool， urine， blood， items	5 min	80 copies/mL	［44］
Label free	RNA virus	SARS-CoV-2	Cu₂O nanoarray	RNA	100‒ 10⁶ copies/mL		respiratory swab RNA extracts	5 min	80 copies/mL	［45］
Label free	RNA virus	SARS-CoV-2 Beta，Delta，Wuhan， Omicron	Ag INPs	S protein		PCA， logistic regression algorithm	saliva nasal swab	15 min		［47］
Label free	RNA virus	SARS-CoV-1 SARS-CoV-2	Au nano-pyramids	single-particle		LDA， HCA Modle training	saliva	5 h		［46］
Label free	RNA virus	SARS-CoV-2 wild-type， Alpha， Delta， Omicron	3D porous AgMEN	S protein N protein	1.0 fg/mL‒ 1 mg/mL 1.0 pg/mL‒ 1 mg/mL 1.0 pg/mL‒ 1 mg/mL		saliva		1.0 fg/mL 1000 fg/mL 100 fg/mL	［48］
Label free	RNA virus	MERS-CoV SARS-CoV SARS-CoV-2 HCoVHKU1 HCoV-OC43	Ag-coated Si substrates	S-protein		MLP	PBS			［49］
4-MBA	RNA virus	SARS-CoV-2	Ag-LFA	N-protein	10‒ 1000 ng/mL		saliva	15 min	0.03 ng/mL	［50］
Nile BlueA	RNA virus	SARS-CoV-2	Magnetic beads	viral particles	250‒ 10000 TU/μL		PBS， swab samples	5 min	124 TU/μL	［51］
GNPs	RNA virus	SARS-CoV-2	magnetic nanoparticles	S-protein	4.1×10⁴ genomes/mL		saliva	30 min	257 fg/mL	［52］
4-MBA	RNA virus	SARS-CoV-2	Au NPs	S-protein	1 fg/mL‒ 1ng/mL 10 fg/mL ‒ 10 ng/mL		PBS saliva serum blood		0.77 fg/mL 6.07 fg/mL 7.60 fg/mL 0.10 pg/mL	［53］
MMC DTNB TFMBA MBA	RNA virus	SARS-CoV-2 Delta，Omicron	Au-Ag nanobox-based SERS barcodes	S protein N protein			nasal swab		20 virus/μL or 50 pg/mL	［54］
DTNB	RNA virus	SARS-CoV-2	Ag NRs	RNA	10²‒ 10⁶ copies/mL		PBS	50 min	51.38 copies/mL	［55］
4-MBN	RNA virus	SARS-CoV-2	Au@4MBN@Ag NPs	RNA	10^-6‒10^-12M		PBS	10 min	7.61× 10^-14 mol	［56］
4-MBA	RNA virus	SARS-CoVM-2	Au nanopopcorn	S-protein	0‒ 1000 PFU/mL		PBS	15 min	10 PFU/mL	［57］
DTNB	RNA virus	SARS-CoV-2	AuNP-rGO-SW	N-protein	1 fmol‒ 100 amol		PBS		1 fmol	［58］
Label free	RNA virus	SARS-CoV-2	Au NPs	RNA	160 fmol‒ 1 nmol	Colorimetric fluorescenc	PBS	40 min	395 fmol	［59］
MGITC	RNA virus	SARS-CoV-2	Au NDs	RdRp genes		SERS-PCR	PBS		‒	［60］
Label free	RNA virus	Influenza A Influenza B	Ag NPs	viral particles		SVM	PBS		0.05 µg/mL	［61］
Label free	RNA virus	Influenza A	Ag NPs	viral particles	2×10⁵‒2× 10⁶ VP/mL		PBS	15 min	2× 10⁵ VP/mL	［62］
Label free	RNA virus	Influenza A	Ag NPs	viral particles	10³‒5×10¹⁰virus Particles/mL		PBS		10³ particles/mL	［64］
Label free	RNA virus	Influenza A H5N1	IMBSIs@Ag	viral particles			PBS		5.0×10⁶ TCID₅₀/mL	［65］
Cy3	RNA virus	Influenza A	Ag NPs	viral particles			PBS		10 VP/mL or 2 VP/mL per probe	［66］
MGITC	RNA virus	Influenza A SARS-CoV-2	Au NPs	N-protein	0‒ 8064 HAU/mL 50‒ 1000 PFU/mL		nasopharyngeal samples		23 HAU/mL 5.2 PFU/mL	［67］
Label free	RNA virus	Influenza A SARS-CoV-2 hCoV-229E	Gold particles	viral particles		AI，RVM，PCA	PBS			［68］
Cy3 RRX 4-MBA	RNA virus	SARS-CoV-2 Influenza A	Au nanopopcorn substrate	S-Protein hemagglutinin	0.32‒ 200 PFU/ml 0.13‒ 80.6 HAU/mL		PBS	15 min	0.62 HAU/mL 0.78 PFU/mL	［69］
DTNB	RNA virus	influenzaA SARS-CoV-2 RSV	Fe₃O₄@Au core–shell MNPs	viral antigen			throat swab samples	15 min	85 copies/mL 8 pg/mL 8 pg/mL	［70］
4-ATP	RNA virus	influenza A influenza B SARS-CoV-2	Au^4-ATP@Ag NPs	N-protein		Photothermal effect	pharyngeal swab samples	<20 min	31.25 pg/mL 93.75 pg/m： 31.25 pg/mL	［71］
Label free	RNA virus	HIV	Au NCs	HIV-1 DNA			Millipore water			［72］
Label free	RNA virus	HIV（A，B，C，D， CRF02_AG）	Ag nanorods	viral particles	10²‒ 10⁶ copies/mL	PCA	plasma			［73］
Label free	RNA virus	HIV（A，B，C，D）	Au sputtered Ag nanorods	viral particles		PCA	plasma			［74］
MoO₃-QDs	RNA virus	HEV，NoV	nanogels （NGs）	viral particles	10²‒ 10⁸ copies/mL		PBS		6.5 fg/mL 8.2 fg/mL	［76］
S-agCDs	RNA virus	NoV	Poly（DOP）-MNPs-Ag NCs	viral particles	1 fg/mL‒ 1 ng/mL	FL-SER	PBS	5 min	10 RNA copies /mL	［77］
Label free	RNA virus	HCV	Ag NPs	viral particles		PLSR， RMSECV， R²	serum			［79］
Label free	RNA virus	HCV	Ag NPs	RNA		PLSR， PCA	serum			［80］
Label free	RNA virus	DENV-2	NANOBOX	DENV2-NS1			PBS			［83］
Label free	RNA virus	DENV	Ag NRs array	RNA	1 fmol‒10 nmol		serum		0.49 fmol	［84］
Label free	RNA virus	DENV	Au NPs	RNA	‒		serum		1 pg/μL	［85］
Label free	RNA virus	Zika virus	Ag NIs	Zika antigen	5‒1000 ng/mL		PBS		0.11 ng/mL	［86］
Label free	RNA virus	WNV	Au@Ag NPs	WNV-NS1 inactivated WNV virions			PBS		0.1 ng/mL 0.2×10² copies/μL	［88］
Label free	RNA virus	EMCV influenza A	triangular Au nano-cavities array	virus particles			PBS		10⁶ PFU/ mL 10⁴ PFU/ mL	［106］
4-MBA	RNA virus	SARS-CoV-2	DVD	VLP protein S-Protein	100 pg/mL‒1000 ng/mL		PBS saliva	20 min	50 pg/mL 400 pg/mL	［115］
4-ATP	RNA virus	SARS-CoV-2	Au NPs	virus particle S-Protein			PBS	5 min	18 Vp/mL 4 pg/mL	［117］
4-ATP	RNA virus	SARS-CoV-2	SERS-CRISPR/ Cas12a	SARS-CoV-2 N gene			nasopharyngeal swab samples	40 min	1 fmol	［113］
4-MBA	RNA virus	SARS-CoV-2	CRISPR/Cas12a-OVER-SARS-CoV-2	SARS-CoV-2 gene			nasopharyngeal swab samples	45 min	1.9 copies/mL	［109］
Cy3	RNA virus	SARS-CoV-2 influenza A RSV	Si substrates	antigens			Nasal swabs	17 min		［95］
Label free	RNA virus DNA virus	SARS-CoV-2 influenza A	clustered silver nanoparticles	virus particle		LDA	PBS saliva		10 PFU/test	［51］

Table 1. Comparison table of RNA viral detection protocols

Label method	Type of virus	Virus species	SERS platform	Target	Dynamic range	Methods used	Sample solution	Time	LoD	Reference
FC	DNA virus	HBV	GaN/Au-Ag SERS substrate	HBsAg	0.0125‒ 60 IU/ml		plasma		0.01 IU/mL	［92］
4-ATP	DNA virus	HBV	Au NPs@4-ATP	HBV DNA	1 pmol‒ 1 nmol	PCA	serum	50 min	0.67 pM	［93］
Label free	DNA virus	HBV	Ag NPs	HBV DNA		PCA， PLS-DA	Blood			［94］
Label free	DNA virus	MPXV	Ag@cit	M1R proteins		PCA	serum		100 copies/mL	［96］
DTNB	DNA virus	MPXV	MoS₂@Au-Au	MPXV antigens	100‒ 0.01 ng/mL	colorimetry	throat swab specimens	<20 min	0.002 ng/mL	［97］
Label free	DNA virus	EBV		RBV Infection		PCA， Mann-Whitney U test， IPA， IPKB	Glial Cells			［100］
R6G TMB	DNA virus	EBV	PS/Au NPs	EBV IgG	10^-1‒ 10⁵ pg/mL		blood	10 min	0.045 pg/mL	［101］
Label free	DNA virus	HSV-1，EBV	nanoparticles	antigens		PCA	cell confluence			［103］
Label free	DNA virus	Adenovirus	triangular Au nano-cavities array	virus particles			PBS		10⁶ PFU/mL	［106］
Cy3	DNA virus	Adenovirus	Si substrates	antigens			Nasal swabs	17 min		［95］
Label free	DNA virus	Adenovirus 7	clustered silver nanoparticles	virus particle		LDA	PBS， saliva		10 PFU/test	［51］
MBN	DNA virus	HPV	CRISPR/Cas-SERS platform	HPV16/ 18 dsDNA	6.72×10^-12 mol‒6.72×10^-7 mol		serum	40 min		［110］
TMB	DNA virus	HPV	CRISPR/dCas9-SERS AuNC@SiO₂	HPV 16 pseudovirus genes	30 ng‒190 ng		H₂O			［111］
4-MBA	DNA virus	ASFV	CRISPR/Cas12a-SERS platform	ASFV dsDNA	100 nmol‒10 fmol		serum	2 h	10 fmol	［112］

Table 2. Comparison table of DNA viral detection protocols

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