Selective Detection and Ultrasensitive Quantification of SARS-CoV-2 IgG Antibodies in Clinical Plasma Samples Using Epitope-Modified Nanoplasmonic Biosensing Platforms

Abstract

Monitoring the human immune response by assaying (detection and quantification) the antibody level against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important in conducting epidemiological surveillance and immunization studies at a population level. Herein, we present the design and fabrication of a solid-state nanoplasmonic biosensing platform that is capable of quantifying SARS-CoV-2 neutralizing antibody IgG with a limit of detection as low as 30.0 attomolar (aM) and a wide dynamic range spanning seven orders of magnitude. Based on IgG binding constant determination for different biological motifs, we show that the covalent attachment of highly specific SARS-CoV-2 linear epitopes with an appropriate ratio, in contrast to using SARS-CoV-2 spike protein subunits as receptor molecules, to gold triangular nanoprisms (Au TNPs) results in a construction of a highly selective and more sensitive, label-free IgG biosensor. The biosensing platform displays specificity against other human antibodies and no cross reactivity against MERS-CoV antibodies. Furthermore, the nanoplasmonic biosensing platform can be assembled in a multi-well plate format to translate to a high-throughput assay that allowed us to conduct SARS-CoV-2 IgG assays of COVID-19 positive patient ( n = 121) and healthy individual ( n = 65) plasma samples. Most importantly, performing a blind test in an additional cohort of 30 patient plasma samples, our nanoplasmonic biosensing platform successfully identified COVID-19 positive samples with 90% specificity and 100% sensitivity. Very recent studies show that our selected epitopes are conserved in the highly mutated SARS-CoV-2 variant “Omicron”; therefore, the demonstrated high-throughput nanoplasmonic biosensing platform holds great promise for a highly specific serological assay for conducting large-scale COVID-19 testing and epidemiological studies and monitoring the immune response and durability of immunity as part of the global immunization programs.

Two-Way Detection of COVID-19 Spike Protein and Antibody Using All-Dielectric Metasurface Fluorescence Sensors

“…For optical detection of proteins such as Abs, resonant wavelength-shift measurements are often reported. Regarding COVID-19 IgG, a very low LOD of 30 aM has been reported [ 28 ]; such low LODs have sometimes been claimed for other biomolecules as well [ 29 ]. However, the amount of wavelength shift for the COVID-19 IgG is nm for eight-order concentration changes.…”

“…However, the amount of wavelength shift for the COVID-19 IgG is nm for eight-order concentration changes. As a result, similar concentrations are often indistinguishable; for example, the experimental data indicate that the method cannot discriminate 1 nM from 0.1 nM or 0.1 nM from 0.01 nM [ 28 ]. Thus, the technique has a disadvantage in quantifying the target IgG concentrations even at sub-nM ranges as compared with the present metasurface FL sensors.…”

Achieving broad availability of SARS-CoV-2 detections via smartphone-based analysis

“…A designed smartphone app directly calculated the SARS-CoV-2 pseudovirus in spiked samples in one step within 15 min from 0 to 6.0 × 10 6 virus particles (vp)/mL with a quantification limit of about 4000 vp/mL SARS-CoV-2. These nanoplasmonic biosensing platforms may enable amplification-free, accurate, selective, and sensitive detections [ [82] , [83] , [84] ]. Normally, low-cost plasmon-enhanced substrates can be constructed by noble metal nanomaterials such as Au or Ag NPs, nanostars, and nanorods with facile synthetic approaches [ 85 , 86 ].…”

Progress in Biosensors for the Point-of-Care Diagnosis of COVID-19

“…Nanoplasmonic biosensing platforms with immobilized S protein on gold triangular nanoprisms served as anti-SARS-CoV-2 antibodies in the work of Masterson et al [ 86 ]. The device, working on the principle of non-linear optics, exerted a very low limit of detection equal to 30 amol/L for the specific IgG molecules, and 90% specificity and 100% sensitivity were proved when the device was tested on a group of 121 COVID-19-positive patients and 65 healthy individuals.…”