Microfluidic particle dam for direct visualization of SARS-CoV-2 antibody levels in COVID-19 vaccinees

Abstract

Various COVID-19 vaccines are currently deployed, but their immunization varies and decays with time. Antibody level is a potent correlate to immune protection, but its quantitation relies on intensive laboratory techniques. Here, we report a decentralized, instrument-free microfluidic device that directly visualizes SARS-CoV-2 antibody levels. Magnetic microparticles (MMPs) and polystyrene microparticles (PMPs) can bind to SARS-CoV-2 antibodies simultaneously. In a microfluidic chip, this binding reduces the incidence of free PMPs escaping from magnetic separation and shortens PMP accumulation length at a particle dam. This visual quantitative result enables use in either sensitive mode [limit of detection (LOD): 13.3 ng/ml; sample-to-answer time: 70 min] or rapid mode (LOD: 57.8 ng/ml; sample-to-answer time: 20 min) and closely agrees with the gold standard enzyme-linked immunosorbent assay. Trials on 91 vaccinees revealed higher antibody levels in mRNA vaccinees than in inactivated vaccinees and their decay in 45 days, demonstrating the need for point-of-care devices to monitor immune protection.

Utilization of a Glucometer Test Strip and Enzymatic Reactions to Quantify Anti-SARS-CoV-2 Spike RBD IgG Antibody and SARS-CoV-2 Virus in Saliva and Serum

“…A recent study that assessed antibody titers in COVID-19 patients showed that the spike RBD-specific IgG was ∼11.4 μg/mL in most patients even after 41 days of infection . In addition, a study of 91 healthy but vaccinated people without a history SARS-CoV-2 infection showed that mRNA-vaccinated persons have 1.1 μg/mL as the mean range of anti-SARS-CoV-2 spike RBD IgG . This indicates our sensor is sufficiently sensitive (LOD: 0.42 ng/mL) to quantify anti-SARS-CoV-2 spike RBD IgG antibodies in both COVID-19 patients and vaccinated healthy individuals.…”

“…This dilution is advantageous because it minimizes matrix effects and is usually done in immunoassays to decrease background noise. Our method provided a better LOD than a similar fluorescence-based antibody detection method (50 ng/mL) 16 and a microfluidic device-based method (13.3 ng/mL), 29 and a comparable LOD (0.3 ng/mL) to an enzyme immunoassay for quantification of anti-SARS-CoV-2 IgG. 30 There are also methods that have been reported with lower LODs than this method, such as 0.24 pg/mL using a Simoa HD-X Analyzer for SARS-CoV-2 antibody detection.…”

Development of nucleocapsid-specific monoclonal antibodies for SARS-CoV-2 and their ELISA diagnostics on an automatic microfluidic device

“…We summarized the comparative evaluation of our platform with the previously reported systems in Table S4 . Compared with the previous results, our system shows similar LOD value with easy colorimetric analysis by naked eye, cost-effective automatic operation, versatile nucleocapsid-specific monoclonal antibodies capable of distinguishing four kinds of SARS-CoV-2 variants [26] , [27] , [28] , [29] .…”

Hand-powered centrifugal micropipette-tip with distance-based quantification for on-site testing of SARS-CoV-2 virus

“…The antigen-antibody binding was carried out within a test tube, enabling an immediate and synchronal contact of antigen- and antibody-conjugated beads and achieving a low detection limit of less than 100 copies mL −1 within 30 s. The detection signal was then obtained by the naked-eye reading of the red color intensity, which was potentially affected by subjective interpretation. Subsequently, to fulfill quantitative measurement while maintaining a simple and user-friendly interface, Wu et al demonstrated a novel microfluidic chip with a particle dam for quantitative visualization of SARS-CoV-2 antibody levels from the accumulation length of the microparticles functionalized with antibodies [ 16 ]. However, despite promising progress, most of these POC platforms enable naked-eye qualitative detection or additional instrument-assisted quantitative detection.…”