Functional Infectious Nanoparticle Detector: Finding Viruses by Detecting Their Host Entry Functions Using Organic Bioelectronic Devices.

Emerging viruses will continue to be a threat to human health and wellbeing into the foreseeable future. The COVID-19 pandemic revealed the necessity for rapid viral sensing and inhibitor screening in mitigating viral spread and impact. Here, we present a platform that uses a label-free electronic readout as well as a dual capability of optical (fluorescence) readout to sense the ability of a virus to bind and fuse with a host cell membrane, thereby sensing viral entry. This approach introduces a hitherto unseen level of specificity by distinguishing fusion-competent viruses from fusion-incompetent viruses. The ability to discern between competent and incompetent viruses means that this device could also be used for applications beyond detection, such as screening antiviral compounds for their ability to block virus entry mechanisms. Using optical means, we first demonstrate the ability to recapitulate the entry processes of influenza virus using a biomembrane containing the viral receptor that has been functionalized on a transparent organic bioelectronic device. Next, we detect virus membrane fusion, using the same, label-free devices. Using both reconstituted and native cell membranes as materials to functionalize organic bioelectronic devices, configured as electrodes and transistors, we measure changes in membrane properties when virus fusion is triggered by a pH drop, inducing hemagglutinin to undergo a conformational change that leads to membrane fusion.

Microphysiological Systems: Next Generation Systems for Assessing Toxicity and Therapeutic Effects of Nanomaterials.

Microphysiological systems, also known as organ-on-a-chip platforms, show promise for the development of new testing methods that can be more accurate than both conventional two-dimensional cultures and costly animal studies. The development of more intricate microphysiological systems can help to better mimic the human physiology and highlight the systemic effects of different drugs and materials. Nanomaterials are among a technologically important class of materials used for diagnostic, therapeutic, and monitoring purposes; all of which and can be tested using new organ-on-a-chip systems. In addition, the toxicity of nanomaterials which have entered the body from ambient air or diet can have deleterious effects on various body systems. This in turn can be studied in newly developed microphysiological systems. While organ-on-a-chip models can be useful, they cannot pick up secondary and systemic toxicity. Thus, the utilization of multi-organ-on-a-chip systems for advancing nanotechnology will largely be reflected in the future of drug development, toxicology studies and precision medicine. Various aspects of related studies, current challenges, and future perspectives are discussed in this paper.