Single-Molecule Reliable Detections with a Large-Area Electronic Interface

A large millimeter-wide electronic interface can detect at a single-molecule/entity limit-of-detection. The technology is called SiMoT - Single-Molecule with a large Transistor.¹ So far, antigens (Immunoglobulins, C-reactive proteins, spike 1, HIV p-24), antibodies (anti-immunoglobulins, anti-spike1), peptides, viruses (SARS-Cov-2), bacteria (Xylella fastidiosa), and even DNA strands (KRAS, miR-182) have been detected. Selectivity is assured by covering the gate electrode with a large number (10¹¹-10¹²/cm²) of recognition elements to affinity binding the target element.<br/><br/>SiMoT detects directly in a droplet (0.1 mL) of a real fluid such as saliva from COVID-19 patients, blood serum, pancreatic cysts juice, and olive saps from infected trees. Relevantly Brownian diffusion enables the entity to statistically hit the millimeter-wide interface in a few minutes.²Considering the footprint of a molecule on a millimeter-wide interface, it is like spotting a droplet of water falling on the surface of a 1 Km wide lake as depicted in the graphical abstract.<br/><br/>The applications span from a handheld intelligent single-molecule binary bioelectronic system for fast and reliable immunometric point-of-care testing of COVID-19 patients³ and Xylella fastidiosa single bacterium detected in infected plants sap. The phenomenon enabling such outstanding performance level was discovered in 2018.⁴ While still under investigation, it is supposed to involve an amplification that starts from the single affinity binding that triggers a propagating collaborative response.<br/><br/>Future actions include the deepening of our understanding of the sensing mechanism and the engagement in a campaign of thousands of clinical trials that will bring SiMoT beyond TRL5.<br/><br/><i>References</i><br/>1. E. Macchia <i>et al. </i><i>Chemical Review</i> 2022, 122, 4636 DOI: 10.1021/acs.chemrev.1c00290<br/>2. E. Macchia <i>et al.</i> <i>Advanced Science</i> 2022, 2104381 DOI: DOI: 10.1002/advs.2021043811<br/>3. E. Macchia <i>et al., Science Advances</i> 2022, 8 (27) DOI: 10.1126/sciadv.abo0881<br/>4. E. Macchia <i>et al.,</i> <i>Nature Communication</i> 2018, DOI: 10.1038/s41467-018-05235-z