An ultrasensitive virus identification method for acute respiratory virus infections using carbon nanotube arrays-integrated microdevice - SUMMARY
Acute respiratory tract infections are the leading cause of infectious-related mortality, the fifth-leading cause of
death overall. In particular, rare unrecognized acute respiratory virus (ARV) infection outbreaks caused many
human diseases of unknown etiology, particularly in less developed countries. If active ARV infection can be
accurately detected and effectively vaccinated or treated with the right therapy, the outbreak can be prevented
or controlled. However, current clinical assays are mainly based on PCR panels, which miss rare or highly
mutated emerging ARVs and can’t distinguish high-risk infections harboring active virions from bare viral nucleic
acids from previous or latent infections. Additionally, there is no FDA approved comprehensive diagnostic tool
compatible with rare ARV or rare ARV subtype infection. To meet this urgent and unmet clinical challenge, we
hypothesize that the isolation and analysis of viable ARV virions with high purity would provide an accurate,
effective and low-cost solution for clinical applications. Captis Diagnostics has developed a new IP-pending
carbon nanotube size tunable enrichment microdevice (CNT-STEM) technology that performs label-free virion
capture from clinical and environmental samples. The CNT-STEM system can maintain virus viability/infectivity
and has been demonstrated to identify an emerging H11N9 avian influenza virus (AIV) from swab samples of
wild ducks and a new infectious bursa disease virus (IBDV) strain from turkey eyelid tissue that was previously
unidentifiable by common serological and molecular methods. Furthermore, CNT-STEM captures viruses with
over 90% efficiency and boosts the detection limits virus isolation by 100 times. It also increases the ratio of viral
reads in next generation sequencing by more than 1,000 times. In this proposal, we propose to further optimize
our proprietary CNT-STEM technology for virus isolation and coupled with high throughput sequencing to detect
ARV in nasopharyngeal swab samples with high sensitivity and specificity. For Aim 1, Captis Diagnostics will
optimize and validate CNT-STEM technology to develop it to a research device for ARV capture that can achieve
high isolation efficiency of whole virions. Aim 2 will develop a proof-of-concept clinical assay to detect whole
ARV virions by coupling efficient high throughput sequencing technology with CNT-STEM-based viable virion
isolation. Successful completion of these Aims will yield a proprietary advanced technology that can isolate rare
ARVs and position Captis Diagnostics to pursue clinical validation of the technology in patients of ARV infection.
Phase II study will focus on clinical performance of ARV diagnosis, in which CNT-STEM-based virus isolation
technology will be tested with samples from ARV infection patients to validate its clinical utility with the ultimate
goal of its clinical adoption and FDA clearance.
