SARS-CoV-2 multi-variant graphene biosensor based on engineered dimeric ACE2 receptor

Abstract

Fast, reliable and point-of-care systems to detect the SARS-CoV-2 infection are crucial to contain viral spreading and to adopt timely clinical treatments. Many of the rapid detection tests currently in use are based on antibodies that bind viral proteins. However, newly appearing virus variants accumulate mutations in their RNA sequence and produce proteins, such as Spike, that may show reduced binding affinity to these diagnostic antibodies, resulting in less reliable tests and in the need for continuous update of the sensing systems. Here we propose a graphene field-effect transistor (gFET) biosensor which exploits the key interaction between the Spike protein and the human ACE2 receptor. This interaction is one of the determinants of host infections and indeed recently evolved Spike variants were shown to increase affinity for this receptor. Through extensive computational analyses we show that a chimeric ACE2-Fc construct mimics the ACE2 dimer, normally present on host cells membranes, better than its soluble truncated form. We demonstrate that ACE2-Fc functionalized gFET is effective for in vitro detection of Spike and outperforms the same chip functionalized with either a diagnostic antibody or the soluble ACE2. Our sensor is implemented in a portable, wireless, point-of-care device and successfully detected both alpha and gamma virus variants in patient clinical samples. As incomplete immunization, due to vaccine roll-out, may offer new selective grounds for antibody-escaping virus variants, our biosensor opens to a class of highly sensitive and variant-robust SARS-CoV-2 detection systems.

Two-Dimensional Field-Effect Transistor Sensors: The Road toward Commercialization

“…Data acquisition is the process of signals transferring from real-world phenomena to digital forms that can be analyzed by a computer. , Multiple approaches have been developed to meet requirements for data acquisition in reliable and real-time sensing applications. , The following section will discuss the technologies for acquiring raw data from 2D FET sensors with high quality.…”

“…12,249 Multiple approaches have been developed to meet requirements for data acquisition in reliable and real-time sensing applications. 577,616 The following section will discuss the technologies for acquiring raw data from 2D FET sensors with high quality.…”