SARS-CoV-2 Variant Screening Using a Virus-Receptor-Based Electrical Biosensor

Abstract

SARS-CoV-2 variants are of particular interest because they can potentially increase the transmissibility and virulence of COVID-19 or reduce the effectiveness of available vaccines. However, screening SARS-CoV-2 variants is a challenge because biosensors target viral components that can mutate. One promising strategy is to screen variants via angiotensin-converting enzyme 2 (ACE2), a virus receptor shared by all known SARS-CoV-2 variants. Here we designed a highly sensitive and portable COVID-19 screening biosensor based on the virus receptor. We chose a dual-gate field-effect transistor to overcome the low sensitivity of virus-receptor-based biosensors. To optimize the biosensor, we introduced a synthetic virus that mimics the important features of SARS-CoV-2 (size, bilayer structure, and composition). The developed biosensor successfully detected SARS-CoV-2 in 20 min and showed sensitivity comparable to that of molecular diagnostic tests (∼165 copies/mL). Our results indicate that a virus-receptor-based biosensor can be an effective strategy for screening infectious diseases to prevent pandemics.

Sensitive detection of SARS-CoV-2 spike protein using vertically-oriented silicon nanowire array-based biosensor

“…The Δ I D % is close to zero at 100 ng/mL or 575 pM (ng/mL to pM conversion is explained above in Section 2.1 ) of spike protein, which defines the limit-of-detection (LOD) for our biosensor. This LOD is significantly higher than some other reported works [ 15 ] for ACE2 receptor-based biosensors and lower than others [ 13 ]. Therefore, we have successfully demonstrated a proof-of-principle for a vSiNW based biosensor platform for sensitive and selective detection of SARS-CoV-2.…”

“…Alternatively, recently there has been increasing efforts in the development of angiotensin-converting enzyme 2 (ACE2) receptor-based biosensors by multiple research groups around the world [ [12] , [13] , [14] , [15] , [16] ]. This is because ACE2 is the main receptor used by SARS-CoV-2 for cellular entry, and infection of SARS-CoV-2 begins when the spike protein binds to ACE2 [ 17 ].…”

“…Recently Park et al [ 13 ] demonstrated a high sensitivity (~165 virus copies/mL) dual-gate field-effect transistor (FET) using ACE2 as the receptor. However, the dual-gate FET architecture was rather complex to manufacture and based on non-CMOS compatible materials, such as tin oxide, titanium nitride, among others; all of which can make it challenging to scale up this biosensor architecture for global monitoring of the pandemic.…”

Research progress of biosensors for detection of SARS-CoV-2 variants based on ACE2

“… Type of Biosensor Testing Sample Assay Time (min) LOD Ref. Electrochemical saliva 6.5 229 fg mL −1 [ 80 ] Electrochemical saliva 4 2.8 fg mL −1 [ 81 ] Electrochemical saliva 60 0.35 ag mL −1 [ 82 ] Colorimetric NP/OP 5 0.154 pg mL −1 [ 83 ] Colorimetricr NP/OP 30 4.98 ng mL −1 [ 84 ] Colorimetric NP/OP 5 100 pfu mL −1 [ 85 ] SERS – – 300 nM [ 89 ] SERS urines 5 80 copies mL −1 [ 90 ] Nano biofluids 0.08 12.6 nM [ 93 ] FET PBS 20 165 copies mL −1 [ ...…”

“…They synthesized a SARS-CoV-2 analog virus and optimized the FET biosensor. The biosensor can be detected in 20 min with sensitivity comparable to molecular diagnostic tests (165 copies mL −1 ) [ 94 ].

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