Ultrasensitive detection of SARS-CoV-2 with graphene sensor

Graphene devices have been used to construct ultrasensitive detectors for SARS-CoV-2, the virus that causes COVID-19. With sensitivity down to several attomoles and potential to use this technology for detecting other pathogens, the latest achievement sets the basis for a new class of analytical platforms.

The highlight of the work, published in the scientific journal Nanoscale, is the use of a novel sensing mechanism for pathogen detection with graphene. The novelty of the detector is in using Angiotensin-converting enzyme 2 (ACE2), a common enzyme produced on the membranes of human cells across many internal organs. When a person is infected with SARS-CoV-2 or another coronavirus, ACE2 interacts with the spike protein of the virus, serving as an entry point into human cells. The sensor makes use of this interaction to detect the presence of a spike protein with unprecedented sensitivity.

Image: GFET S-20 sensor chips.

To make the sensors, researchers attach ACE2 to the surface of graphene devices. The devices are graphene field-effect transistors (GFETs), the Graphenea GFET-S20 product. The GFET-S20 is designed for sensing measurements in a liquid medium, just as required for these novel sensors. GFETs consist of a graphene sheet and electrodes that are used to control and measure electrical currents through the graphene. When a spike protein interacts with ACE2 that is bound to the chip, the electrical properties of graphene change, serving as an indicator of presence of the virus. Signal readout from the GFETs is performed via the Graphenea Cartridge S2X, which is designed for easy interfacing of GFETs to measurement electronics.

An extremely low limit of detection (LOD) is achieved with such an arrangement, down to 3 attomoles (aM). Not only is that orders of magnitude better than previous work with GFETs, but is also a demonstration of a completely new principle. Most platforms for detecting SARS-CoV-2 rely on antibodies as receptors to the spike protein. Antibodies very selectively bind to a specific spike protein, which makes the technique vulnerable to mutations that change parts of the spike. ACE2 is sensitive to a number of pathogens, including various strains of SARS-CoV-2. Furthermore, perhaps even more importantly, in order to obtain antibodies a virus must first be isolated, which requires a large amount of specialist work and is not the case with the method that relies on ACE2 receptors. Thus the ACE2/graphene platform is sensitive, specific to a number of pathogens, compatible with rapid mass deployment, and robust against mutations.

Aside from demonstrating the proof of concept for virus detection with this new method, the scientists performed detailed characterization of the devices and their interactions with the spike protein. This work without doubt paves the way for development of faster, more precise and sensitive diagnostics of existing and future pathogens.