PFI-TT: High-Throughput Digital Biosensing: Future Of Molecular Diagnostics

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is in the development of a practical and fast diagnostic technology platform. Areas like precision medicine and liquid biopsies hold great promise in the field of healthcare. They rely on very sensitive technologies that can detect tiny molecules in human bodies. One exciting advancement is called "digital detection," which can analyze individual molecules with incredible accuracy, even better than older methods. The proposed single-molecule counting technology has the potential to revolutionize disease diagnosis because it could make advanced diagnostic tools more affordable and widely available. The project will create a practical and cost-effective platform for detecting diseases early on, which will be incredibly beneficial for various medical applications, like accurate and early diagnosis using small samples from liquid biopsies. The team has a proven track record of prototyping, technology translation, and commercialization. The project will make a contribution to workforce creation by training 2 PhD students and 2 undergraduate students in technology development and entrepreneurship. The proposed project builds on more than a decade-long cutting-edge basic and applied research effort and develops a new paradigm of Digital Biosensing that is affordable, practical, and broadly adaptable by exploiting multiple innovations. The technology is based on Interferometric Reflectance Imaging Sensor (IRIS), which can dynamically detect thousands of individual biological nanoparticles (viruses, exosomes) or single biomolecules labeled with plasmonic gold nanoparticles as they are captured on the sensor surface. Perhaps the most significant innovation relevant to this Technology Translation effort is the invention to address the limitations of the conventional interferometric detection that requires acquisition of a stack of images, thus, necessitating moving parts, to distinguish individual nanoparticles. The new modality of digital detection, ʻpixel-diversityʻ (PD)-IRIS, that introduces encoding the necessary optical signatures of target particles within a single image frame rather than an image stack. This innovation eliminates moving parts and drastically reduces the complexity of the reader enabling digital detection directly in ubiquitous microwell plates – an industry standard for automation – achieving an unprecedented capability of High-throughput Digital Biosensing. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.