A novel monitoring platform for airborne virus harvesting, enrichment, and diagnostics

Y. Cao, H.C. Shum
The University of Hong Kong,
China

Keywords: airborne virus monitoring, liquid-liquid phase separation, biomarker enrichment

Summary:

The COVID-19 pandemic has posed significant threats to the global economy and human welfare over the past three years. The SARS-CoV-2 is transmitted through respiratory droplets and direct contact, which has been well identified and confirmed. Meanwhile, the airborne transmission of the virus is becoming a critical factor in future outbreaks and other potential infectious diseases. However, the study of airborne viruses is still underdeveloped – mainly caused by the ultra-low concentration of airborne viral analytes and the inefficient sampling and harvesting methods – which is considered a major challenge to the full control of airborne diseases. Inspired by the liquid-liquid phase separation mechanism, we propose developing novel techniques for airborne virus harvesting, enrichment, and detection. First, the airborne virus will be harvested and concentrated via phase separation. Then the enriched samples will be detected online by immunosorbent bioassays integrated with flexible microfluidic systems. Moreover, the viral load of the enriched samples will be diagnosed at a single-virus level by digital droplet microfluidics. This pioneering technology promises high efficiency and biocompatibility, paving the way for advanced airborne virus studies, enhancing our understanding of transmission mechanisms, and facilitating community environmental safety monitoring. Based on our developed techniques, we have successfully enriched the viral antigens of SARS-CoV-2 and influenza virus to more than 30-fold and enriched the viral RNA of SARS-CoV-2 to more than 28-fold. Additionally, we have applied our techniques to develop ultrasensitive rapid antigen tests and successfully improve the limit of detection (10-fold) of four commercially available test kits. Moreover, our enrichment protocols have been validated using the clinical specimens from patients directly, showcasing the great translation potential. Meanwhile, we have developed protocols for single-virus encapsulation, detection, and diagnostics based on digital droplet microfluidics. With the rapid development of micro and nano-fabrication techniques, the in-lab research outputs can be miniaturized into portable devices. The technical routes and processing pipelines for airborne virus enrichment, online detection, and off-line diagnostics can be encapsulated and packaged into a single desktop platform. The user-friendly analysis software and operation interface will be designed so that the products can be used by more customers. For example, doctors and nurses can deploy desktop platforms to screen patients; airport security guards, ticket sellers, or other people who must stay in public sites with large population shifts, can utilize the online detection devices to protect themselves from potential infection. The proposed project can bring long-term impact in preventing the potential outbreak of unknown diseases. With further research on the structures of different viral nucleic acids and proteins, and the partitioning and enriching capability of various phase-separation solutions, the phase separation-based harvesting and enrichment techniques can be applicable for detecting more types of airborne diseases (e.g. the common cold, influenza, and SARS). Combined with much higher detection sensitivity and efficiency, a real-time monitoring system for the spreading of airborne virus-induced outbreaks or even pandemics can be established by deploying portable devices in public sites (e.g. classrooms, supermarkets, airports, and metro stations.).