Sensitive and Simultaneous Detection of SARS-CoV-2-Specific IgM/IgG Using Lateral Flow Immunoassay Based on Dual-Mode Quantum Dot Nanobeads

Abstract

A rapid and accurate method for detection of virus (SARS-CoV-2)-specific antibodies is important to contain the 2019 coronavirus disease (COVID-19) outbreak, which is still urgently needed. Here, we develop a colorimetric-fluorescent dual-mode lateral flow immunoassay (LFIA) biosensor for rapid, sensitive, and simultaneous detection of SARS-CoV-2-specific IgM and IgG in human serum using spike (S) protein-conjugated SiO2@Au@QD nanobeads (NBs) as labels. The assay only needs 1 μL of the serum sample, can be completed within 15 min, and is 100 times more sensitive than the colloidal gold-based LFIA. Two detection modes of our biosensor are available: the colorimetric mode for rapid screening of the patients with suspected SARS-CoV-2 infection without any special instrument and the fluorescent mode for sensitive and quantitative analyses to determine the concentrations of specific IgM/IgG in human serum and detect the infection early and precisely. We validated the proposed method using 16 positive serum samples from patients with COVID-19 and 41 negative samples from patients with other viral respiratory infections. The results demonstrated that combined detection of virus-specific IgM and IgG via SiO2@Au@QD LFIA can identify 100% of patients with SARS-CoV-2 infection with 100% specificity.

State-of-the-Art of Nanodiagnostics and Nanotherapeutics against SARS-CoV-2

“…(c) Scheme for a dual-mode LFIA using S protein-conjugated SiO 2 @Au@QD NPs. Reprinted in part with permission from ref ( 132 ). Copyright 2020 American Chemical Society.…”

“…In a different SARS-CoV-2 detection approach, Wang et al developed a colorimetric-fluorescent dual-mode lateral flow immunoassay using QD nanobeads ( Figure 6 b). 132 They synthesized SiO 2 @Au@QD nanobeads conjugated with SARS-CoV-2 S protein. The strips containing two test lines (human IgM and IgG) and one control line demonstrated rapid diagnosis (within 15 min) for a little sample volume of 1 μL.…”

Affinity biosensors developed with quantum dots in microfluidic systems

“…Mass transfer in short diffusion distance in the microfluidic system and the large surface area/volume ratio of the QDs enable to reduce response time of the optical sensor and increase sensitivity of sensor [ 27 ]. In this perspective, there are some very recent attempts for Covid-19 detection, such as developing affinity-based optical biosensors with QDs in a lateral flow immunoassay to detect IgG/IgM which are specific for SARS CoV-2 [ 28 , 29 ]. In this review, considering all the advantages of QDs and microfluidic systems, we present a holistic perspective by reporting the related studies on the use of QDs with microfluidic systems and affinity biosensors.…”

Quantitative circular flow immunoassays with trained object recognition to detect antibodies to SARS-CoV-2 membrane glycoprotein

“…However, both Immuno-COV and NeuCOVIX tests are cell-based in vitro assays, which require trained laboratorians and specialized instruments. Designing Immunity Passports, companies, including Sienna (T&D Diagnostics Canada) and Cellex (North Carolina, USA), are developing serological lateral flow immunoassays (LFIAs) to detect human anti-SARS-CoV-2 immunoglobulin G/M (IgM/IgG) by binarily identifying those with antibodies as seropositive, while those without as seronegative [ 9 , 10 ]. However, the application of LFIAs as Immunity Passports faces many problems including 1) antibody titers are not usually quantified nor digitally transformed to portable devices like smartphones for travelers; and 2) “linearly-shaped LFIAs are not able to detect multiple antibody titers in one reaction nor differentiate distinct antibodies such as SARS-CoV-2 from influenza viruses.…”