Herein, we report the fabrication of an ultrasensitive, multiplexing, high-throughput nanoplasmonic-based biosensing platform for the detection of antibody response to SARS-CoV-2.  The biosensing device was fabricated utilizing gold triangular nanoprism (Au TNP) functionalized glass coverslips in a multi-well format.  Previously, we have shown that this biosensing device is capable of detecting IgG antibodies utilizing the localized surface plasmon resonance (LSPR) property of the Au TNPs at a limit of detection in the high aM range.  However, an ultrasensitive biosensing platform with limit of detection in the low aM to zM range is required in order to quantify and differentiate the antibody levels in response to SARS-CoV-2 at different stages of post-symptom onset.  Quantifying the antibody levels at different stages is important to determine whether the antibody levels persist or alternatively decay over time, as well as to determine how long they are present in human biofluids.  To achieve ultra-sensitivity of our LSPR-based biosensors, we optimized the structural parameters through (1) control manipulation of receptor (SARS-CoV-2 spike glycoprotein subunit 1 and a specific peptide sequence), and (2) the geometric dimension of Au TNPs.  These optimization steps provided an ultrasensitive biosensing platform capable of assaying SARS-CoV-2 specific IgG with a limit of detection of high zM.  As a proof of concept, we utilized the biosensing platform to quantify the level of IgG in a cohort of 100 post-infected COVID-19 patients and determined the antibody levels at different stages of infection (post 10 days, 20 days, 30 days), overall showing a stable IgG level for this time period.  Taken together, we believe this ultrasensitive biosensor platform will provide a way to quantify the level of antibodies present post infection of not only COVID-19, but also other viral infections.

Optimization of biosensing platform for the ultrasensitive quantification of SARS-CoV-2 specific IgG antibody response post-infection

ACS Fall 2021

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