Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

Abstract

Serological tests are essential for the control and management of COVID-19 pandemic (diagnostics and surveillance, and epidemiological and immunity studies). We introduce a direct serological biosensor assay employing proprietary technology based on plasmonics, which offers rapid (<15 min) identification and quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in clinical samples, without signal amplification. The portable plasmonic device employs a custom-designed multiantigen (RBD peptide and N protein) sensor biochip and reaches detection limits in the low ng mL –1 range employing polyclonal antibodies. It has also been implemented employing the WHO-approved anti-SARS-CoV-2 immunoglobulin standard. A clinical validation with COVID-19 positive and negative samples ( n = 120) demonstrates its excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor as an accurate and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the disease management and for the evaluation of immunological status during vaccination or treatment.

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

“…Noble metal NPs possess remarkable plasmonic properties [ 76 , 77 ], which can be modified with bioreceptors and show plasmonic resonance change after interacting with the antigen of SARS-CoV-2 [ 78 ]. For instance, Olalla Calvo-Lozano et al employed an electron beam-deposition system and fabricated 1 nm of titanium (Ti) and 49 nm of gold (Au) sensor chips by metal evaporation [ 79 ]. With surface cleaning, modification biofunctionalization, immobilization, etc., a serological biosensor assay was prepared for analysis of multiantigen (RBD peptide and NP).…”

“…(b) Sensor signal distribution, sensitivity (Sens), specificity (Spec), positive predictive value (PPV), negative predictive value (NPV), and threshold of 100 COVID-19 positive (PS) and 20 negative (NG) clinical samples; the right axis is the total immunoglobulins (Ig) concentration calculated based on the WHO standard; Reprinted with permission from Ref. [ 79 ], Copyright 2022, American Chemical Society. Nanoplasmonic sensor chips for analysis of SARS-CoV-2 pseudovirus.…”

A Framework for Biosensors Assisted by Multiphoton Effects and Machine Learning

“…Plasmon-based technologies, such as SPR biosensors, have outstanding performance and versatility, and they are one kind of biosensor that is able to detect COVID-19 [ 21 ]. An SPR biosensor is capable of completing a reliable COVID-19 test in a matter of minutes compared to other long PCR or antigen tests that patients must perform in medical centers or hospitals [ 22 ].…”

Asymmetric Mach–Zehnder Interferometric Biosensing for Quantitative and Sensitive Multiplex Detection of Anti-SARS-CoV-2 Antibodies in Human Plasma

“…To improve POC biomarker detection, different types of sensitive and real-time measuring biosensors have been suggested for implementation in POC devices [ 5 , 17 , 18 , 19 ] such as electrochemical sensors and optical sensors based on surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS), fluorescence, and chemiluminescence. Photonic biosensing technologies that have been explored for the possible use in SARS-CoV-2 serology include SPR [ 20 , 21 , 22 , 23 , 24 ], biolayer interferometry (BLI) [ 25 ], and microring resonators (MRRs) [ 26 , 27 ]. The last mentioned is a member of a special group of sensors called the photonic integrated circuit (PIC) biosensors.…”