One-Step Rapid Quantification of SARS-CoV-2 Virus Particles via Low-Cost Nanoplasmonic Sensors in Generic Microplate Reader and Point-of-Care Device

Abstract

The spread of SARS-CoV-2 virus in the ongoing global pandemics has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is crucial for controlling and stopping the pandemics. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples.Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. We demonstrate that we can detect as few as 30 virus particles in one step within 15 minutes and can quantify the virus concentration linearly in the range of 10 3 vp/ml to 10 6 vp/ml. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.

Diagnostics for SARS-CoV-2 infections

“…Recently, researchers have devised a single-step, optical S-protein-specific nanoplasmonic resonance sensor that requires minimal sample preparation and provides fast and direct virus detection. In such a system, highly specific antibodies to SARS-CoV-2 were immobilized on nanosensor chip surfaces to which intact coronavirus particles bind through S protein, leading to plasmon resonance or intensity changes that can be optically measured through a sensing system 49,50 . For this assay, the lower limit of detection is 30 virus particles.…”

“…On analysing the specificity of the sensor for binding SARS-CoV-2 in comparison to SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV) and vesicular stomatitis pseudoviruses, nanoplasmonic sensor chips demonstrated very high specificity (>1,000:1) in detecting the SARS-CoV-2 (ref. 49 ). The nanoplasmonic sensor chips have the advantage of being low cost and scalable while maintaining uniformity and repeatability.…”

“…A low-cost, portable device controlled using a smartphone application can analyse SARS-CoV-2 in one step within 15 min with sensitive viral detection. Although the detection limit is 370, the virus can be quantified linearly from 0 to 10 7 virus particles per millilitre and it may find application in clinics, roadside screening sites and homes 49 . AuNP-based sensors coupled with artificial intelligence can detect volatile organic compounds associated with SARS-CoV-2 in exhaled breaths.…”

Current status, advances, challenges and perspectives on biosensors for COVID-19 diagnosis in resource-limited settings

“…The assay time was only 15 min with a linear detection range up to 10 7 viral particles (vp)/ml and a LOD of about 370 vp/ml. Moreover, it showed a high specificity to SARS-CoV-2 when compared with SARS, MERS, and VSV viruses [93] . However, this device has not been tested with real samples.…”

“…(c) Schematic of SARS-CoV-2 pseudovirus detection with an AuNP enhanced plasmonic sensor chip and analyzed through a handheld optical readout device. Reproduced with permission from [93] . …”