Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting

Abstract

Plasmonic metasurfaces (PMs) functionalized with the monoclonal antibody (mAb) are promising biophotonic sensors for biomolecular interaction analysis and convenient immunoassay of various biomarkers, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Previous PM biosensing suffers from the slow affinity detection rate and lack of sufficient immunoassay studies on various SARS-CoV-2 variants. Here, we develop a high-efficiency affinity testing method based on label-free PM sensors with mAbs and demonstrate their binding characteristics to 12 spike receptor binding domain (RBD) variants of SARS-CoV-2. In addition to the research of plasmonic near-field influence on surface biomolecule sensing, we provide a comprehensive report about the Langmuir binding equilibrium of molecular kinetics between 12 SARS-CoV-2 RBD variants and mAb-functionalized PMs, which plays a crucial role in label-free immunosensing. A high-affinity mAb can be combined with the highly sensitive propagating plasmonic mode to boost the detection of SARS-CoV-2 variants. Owing to a better understanding of molecular dynamics on PMs, we develop an ultrasensitive biosensor of the SARS-CoV-2 Omicron variant. The experiments show great distinguishment of P < 0.0001 from respiratory diseases induced by other viruses, and the limit of detection is 2 orders smaller than the commercial colloidal gold immunoassay. Our study shows the label-free biosensing by low-cost wafer-scale PMs, which will provide essential information on biomolecular interaction and facilitate high-precision point-of-care testing for emerging SARS-CoV-2 variants in the future.

Machine-learning-aided multiplexed nanobiosensor for COVID-19 population immunity profiling

“…This outcome is expected as the measured samples were collected before the emergence of the Omicron variant. Also, our findings align with a recent work where variant-dependent antibody binding was shown using kinetic affinity measurements [42] . Notably, this trend did not apply to the blind samples, some of which presented similar antibody levels against RBD_WT and RBD_Om (Fig.…”

Machine-learning-aided multiplexed nanoplasmonic biosensor for COVID-19 population immunity profiling

“…Also, our findings align with a recent work where variant-dependent antibody binding was shown using kinetic affinity measurements. 47 Notably, this trend did not apply to the blind samples, some of which presented similar antibody levels against RBD_WT and RBD_Om (Fig. 5(d)).…”

Metasurface‐Driven and Nanomaterial‐Coupled Plasmonic Biosensor for the Rapid and Quantitative Clinical Identification of Neutralizing Antibodies against SARS‐CoV‐2 Variants

“…The MetaSPR chip comprises a uniform nanocup array and has parameters D and P as the primary factors affecting the sensitivity of the MetaSPR sensor (Figure 3A). [26,34] The performance of the MetaSPR sensor is typically evaluated using the figure of merit (FOM), defined as the ratio of the sensitivity to the width of the spectral peak (the full width at half maximum [FWHM] at the resonant peak). To find a MetaSPR chip with high sensitivity and strong specificity, we first verified the chips by two aspects, including its refractive index (RI) and FOM from Equation (1).…”

“…[24,25] Li et al constructed a biophysical model of the plasmonic metasurface and compared it with the BIAcore 8K commercial device. [26] In this study, we prepared five kinds of portable biosensor chips and verified the chip with the highest performance through chipsensitive and biophysical experiments, which were used in the follow-up experiments after parallel experiments with the Bio-Layer Interferometry (BLI) commercial molecular interaction instrument. However, MetaSPR cannot accurately read limited values when used on complex sera containing many foreign proteins or low-concentration samples.…”