Microfluidic device for detection of infectious prion proteins

Project Abstract Transmissible Spongiform Encephalopathies (TSEs) are 100% fatal neurodegenerative disorders caused by prion protein misfolding. These diseases, including Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy in cattle, scrapie in sheep and goats, and chronic wasting disease in cervids, pose significant public health risks due to their transmissibility, especially through medical procedures (organ transplants and blood transfusions). The rising incidence of CJD in the United States, and the potential for animal to human infection, further intensifies these concerns. Diagnosis of TSEs is challenging, with autopsy often being the gold standard for confirmation in humans. Current molecular detection methods for misfolded proteins, such as Real-Time Quaking Induced Conversion (RT-QuIC), are limited in availability and not well-suited for point-of-care use. In response to this critical need, Priogen Corp. has developed and patented an advanced point-of-care microfluidic device, Micro-QuIC, which leverages microfluidic channels and acoustic wave technology to rapidly detect misfolded prion proteins using fluorescent dyes such as thioflavin T. This approach builds upon proven principles of fluorescent detection of TSEs through solution agitation. However, current Micro-QuIC prototypes depend on bulky lab equipment, are not feasible for commercial production and have only been demonstrated with one TSE. In this Phase I STTR proposal, Priogen Corp. will partner with the University of Minnesota to refine Micro-QuIC into a scalable, rapid, portable, point-of-care microfluidic device for TSE detection. The project will be achieved through the following Specific Aims: (1) to optimize the Micro-QuIC assay to distinguish between native and misfolded prions within 6 hours, (2) to develop a self-contained Micro-QuIC device by integrating an acoustic frequency generator and a fluorescence detection system into a portable docking station, and (3) to demonstrate the utility of Micro-QuIC across various TSEs. The successful implementation of the Micro-QuIC system will revolutionize TSE detection, offering rapid, accessible, and reliable testing. This innovation holds immense potential for improving public health safety by enabling early detection and management of TSEs in both human and animal populations.