Beyond point of care diagnostics: Low-dimensional nanomaterials for electronic virus sensing

Influenza results in tens of thousands of deaths annually in the USA and hundreds of thousands worldwide. COVID-19, caused by the SARS-Cov-2 virus, is even more devastating in terms of patient mortality. At the time of this writing, the nanoscopic SARS-Cov-2 virus has paralyzed the world economy and resulted in what are likely permanent changes in our expectations of society and daily life. New technology is needed to reduce the economic and social impacts of diseases such as COVID-19 and prevent additional negative consequences resulting from subsequent pandemics. As viruses such as Influenza A and SARS-Cov-2 are transmitted from person to person by exposure to infected secretions, inexpensive at-home or workplace tests for the analysis of the virus content within those secretions, such as saliva or mucus from the nasopharynx (as in a swab-based test) or oropharynx (as in a saliva-based test), will be critical for a safe return to work, school, and cultural activities. The most reliable approaches for viral sensing are polymerase chain reaction and protein detection via enzyme-linked immunosorbent assay; however, these approaches require extensive sample handling, laboratory infrastructure, and long sample-to-result time. Advances are leading to increased point-of-care capability for these testing methods, but even this effort is insufficient for curbing the impact of the current pandemic. There are many options for alternative virus (or antigen) detection currently in development. These novel approaches are more amenable for testing in home or workplace without specialized equipment and training and include measurements of mass changes, heat of adsorption, electrochemical changes, changes in optical properties, and changes in electronic properties. Of these transduction mechanisms, electronic property measurements of materials as they interact with virus-containing secretions offer the greatest potential for simplicity, selectivity, and sensitivity needed to revolutionize traditional laboratory assays for at-home pathogen detection. We have, therefore, focused this review on the operation and architecture of electronic antigen sensors, specifically those demonstrating a change in electrical conductivity when interacting with a specific antigen, with hopes that a brief summary of over five decades of research in this area will be beneficial to those developing alternative, user-friendly routes for detection of viruses at this or any time. A key element in electronic virus sensing with useful sensitivity is the use of nanomaterials with ultrahigh surface-to-volume ratios, maximizing the change in charge carrier density upon adsorption events. So-called “low-dimensional materials” are materials characterized by nanoscopic length scales in at least one dimension. One-dimensional nanomaterials such as nanowires and nanotubes are well-established as effective sensing materials with potential for high sensitivity; however, their realization on a large scale has been challenging. Two-dimensional materials are planar materials with thicknesses of one or a few molecular layers and represent the ultimate limit of the surface-to-volume ratio with promising demonstrations of large-scale production and sensitive, selective virus sensing with many options for functionalization. All aspects of 2D sensor fabrication, functionalization, and use are addressed.