Rapid detection of intact SARS-CoV-2 viral particles using silicon nanomembranes

Abstract

The SARS-CoV-2 pandemic has revealed the need for rapid and inexpensive diagnostic testing to enable population-based screening for active infection. Neither standard diagnostic testing, the detection and measurement of viral RNA (via polymerase chain reaction), or serological testing (via enzyme-linked immunosorbent assay) has the capability to definitively determine active infection. The former due to a lack of ability to distinguish between replicable and inert viral RNA, and the latter due to varying immune responses (ranging from latent to a complete lack of immune response altogether). Despite many companies producing rapid point-of-care (POC) tests, none will address the global scale of testing needed and few help to combat the ever growing issue of testing resource scarcity. Here we discuss our efforts towards the development of a highly manufacturable, microfluidic device that instantly indicates active viral infection status from ~ 20 μL of nasal mucus or phlegm and requires no external power. The device features a biotin functionalized silicon nanomembrane within an acrylic body containing channels and ports for sample introduction and analysis. Virus capture and target confirmation are done using affinity-based capture and size-based occlusion respectively. Modularity of the device is proven with bead and vaccinia virus capture as we work towards testing with both pure SARS-CoV-2 virus and human samples. With success on all fronts, we could achieve an inexpensive POC diagnostic which can determine an individual’s infection status, aiding containment efforts in the current and future pandemics. In addition to direct viral detection, our method can be used as a rapid POC sample preparation tool that limits the application of PCR reagents to those samples which already display viral size and antigen-based positivity through our device.