Detection of live SARS-CoV-2 virus and its variants by specially designed SERS-active substrates and spectroscopic analyses

Jaya Sitjar; Jiunn-Der Liao; Han Lee; Huey-Pin Tsai; Jen-Ren Wang; Chien-Hsiung Chen; Hao Wang; Bernard Haochih Liu

doi:10.1016/j.aca.2023.341151

Detection of live SARS-CoV-2 virus and its variants by specially designed SERS-active substrates and spectroscopic analyses

Anal Chim Acta. 2023 May 22:1256:341151. doi: 10.1016/j.aca.2023.341151. Epub 2023 Mar 30.

Authors

Jaya Sitjar¹, Jiunn-Der Liao², Han Lee³, Huey-Pin Tsai⁴, Jen-Ren Wang⁵, Chien-Hsiung Chen⁶, Hao Wang⁷, Bernard Haochih Liu⁸

Affiliations

¹ Engineered Materials for Biomedical Applications Laboratory, Department of Materials Science and Engineering, National Cheng Kung University, Tainan, 701, Taiwan. Electronic address: jaya.sitjar@gmail.com.
² Engineered Materials for Biomedical Applications Laboratory, Department of Materials Science and Engineering, National Cheng Kung University, Tainan, 701, Taiwan. Electronic address: jdliao@mail.ncku.edu.tw.
³ Engineered Materials for Biomedical Applications Laboratory, Department of Materials Science and Engineering, National Cheng Kung University, Tainan, 701, Taiwan. Electronic address: rick594007@hotmail.com.
⁴ Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan. Electronic address: tsaihp@mail.ncku.edu.tw.
⁵ Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan. Electronic address: jrwang@mail.ncku.edu.tw.
⁶ Engineered Materials for Biomedical Applications Laboratory, Department of Materials Science and Engineering, National Cheng Kung University, Tainan, 701, Taiwan. Electronic address: f19980717@gmail.com.
⁷ Engineered Materials for Biomedical Applications Laboratory, Department of Materials Science and Engineering, National Cheng Kung University, Tainan, 701, Taiwan. Electronic address: eddie115923@gmail.com.
⁸ Laboratory for Micro/Nanofabrication and Nanoanalysis, Department of Materials Science and Engineering, National Cheng Kung University, Tainan, 701, Taiwan. Electronic address: hcliu@mail.ncku.edu.tw.

Abstract

A method using label-free surface enhanced Raman spectroscopy (SERS) based on substrate design is provided for an early detection and differentiation of spike glycoprotein mutation sites in live SARS-CoV-2 variants. Two SERS-active substrates, Au nanocavities (Au NCs) and Au NPs on porous ZrO₂ (Au NPs/pZrO₂), were used to identify specific peaks of A.3, Alpha, and Delta variants at different concentrations and demonstrated the ability to provide their SERS spectra with detection limits of 0.1-1.0% (or 10^4-5 copies/mL). Variant identification can be achieved by cross-examining reference spectra and analyzing the substrate-analyte relationship between the suitability of the analyte upon the hotspot(s) formed at high concentrations and the effective detection distance at low concentrations. Mutation sites on the S1 chain of the spike glycoprotein for each variant may be related and distinguishable. This method does not require sample preprocessing and therefore allows for fast screening, which is of high value for more comprehensive and specific studies to distinguish upcoming variants.

Keywords: Fast-screening; Label-free surface-enhanced Raman spectroscopy; Live SARS-CoV-2 variants; Spike glycoprotein mutated sites; Substrate design.

MeSH terms

COVID-19* / diagnosis
Glycoproteins
Gold / chemistry
Humans
Metal Nanoparticles* / chemistry
SARS-CoV-2 / genetics
Spectrum Analysis, Raman / methods

Substances

Gold
Glycoproteins

Supplementary concepts

SARS-CoV-2 variants