Surface-Enhanced Raman Spectroscopy-Based Detection of SARS-CoV-2 Antibodies with a Portable Raman Spectrometer

In recent years, both portable Raman spectroscopy and surface-enhanced Raman spectroscopy (SERS) have become crucial techniques in medical diagnostics and point-of-care testing. Researchers in China have developed a SERS-based test for the ultra-low detection of antibodies for SARS-CoV-2- the pathogen that causes the COVID-19 disease- in clinical samples.1 A collaborative study between the Anhui Agricultural University, Beijing Institute of Radiation Medicine, Hebei Medical University, and the Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control published their results in Sensors and Actuators: B. Chemical.

Detecting antibodies in patients can help to control the spread of the COVID-19 disease. Lateral flow immunoassays (LFIAs) have proven to be valuable point-of-care tests due to their simplicity, low-cost, and rapid effectiveness. Although several colorimetric-based LFIAs have been developed for the simultaneous detection of anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG), they often provide poor sensitivity and little ability for quantification. To increase the sensitivity of the antibody detection, the researchers developed a SERS-based LFIA. A SERS spectrum provides a unique molecular fingerprint and can also be used to develop a quantitative model.

The researchers fabricated a SiO2@Ag SERS nanotag made of three parts: an SiO2 core, dual layers of the Raman reporter molecule 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB), and a SARS-CoV-2 spike (S) protein that binds to anti-SARS-CoV-2 IgM (/IgG. The principal of the LFIA test is based on the reactions between antigen and antibody (the full test scheme is shown in Scheme 1). The clinical sample is dropped onto a sample pad and flows through the strip via capillary forces. As the solution reaches the conjugate pad, the IgG and IgM are captured by the nanotag to form a complex containing the SiO2@Ag-S protein and the IgG/IgM. If present, the complexes are captured by the IgM/IgG lines and their SERS spectra can be measured and their SERS signals can be related to the concentrations of IgG/IgM. An i-Raman Plus 785 nm system with a video microscope and 20x objective was used for the data collection.

The detection limits of the test were found to be 800 times higher than the standard LFIA test for IgM and IgG using Au nanoparticles. The test results of clinical serum samples showed high accuracy and specificity. The use of a portable Raman system allows for the test to be easily performed at multiple points-of-care.

Read the full open-access journal article here.

1. H. Liu, E. Dai, R. Xiao, Z. Zhou, M. Zhang, Z. Bai, Y. Shao, K. Qi, J. Tu, C. Wang,  and S. Wang, Sens Actuators B Chem. 329, 129196 (2021).


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