There is an urgent need for diagnostic technologies that can rapidly inform a healthcare professional on the appropriate management strategy for patients with infectious diseases. Recent epidemics of flu and Ebola have crucially highlighted the importance for rapid detection solutions. However, point-of-care (POC) diagnostic devices are currently limited to a narrow range of abundant biomarkers principally due to (1) the low detection levels they achieve, (2) the rudimentary level of sample preparation they accomplish, and (3) the impossibility of performing nucleic acid tests or other cellular readouts. Utilizing advances made by Tasso Inc., researchers at the University of Wisconsin-Madison, and researchers at the NIH, we propose the development of a diagnostics platform that will enable new readouts at the point-of-care previously unachievable, namely nucleic acid and cellular quantification. The pursuit of cutting edge technology in the fields of biomedical engineering and chemistry will enable levels of detection on par with blood laboratory analysis. As a result, Tasso will integrate into the same platform the ability to quantify levels of viral antigen, viral RNA, and leukocyte count. The resulting paired genomic and proteomic diagnostic platform (PGP-Dx) will provide information rich diagnosis allowing the healthcare professional to adapt immediately to the status and risk factor of the patient. The combination of multiple orthogonal readouts will provide information on the time of infection, the advancement of the disease, and the physiological conditions of the patient, all of which lead to different measures and urgencies of response. To achieve this project, Tasso is uniquely positioned through three key collaborations: 1) Professor David Beebe as an expert consultant for sample preparation and clinical microfluidics with startup and commercialization experience in four different companies, 2) Dr. Daniel Appella as an expert and co-Investigator in the field of synthetic chemistry and peptide nucleic acids, 3) Dr. Frank Graziano as an expert consultant for diagnostics in low-resource settings with a special affiliation with the Joint Clinical Research Centre (JCRC) in Uganda, and 4) Dr. Valerie Ng, MD, as the director of a blood analysis department in Alameda Health System in Oakland that will provide a beta testing site for the PGP-Dx platform to obtain essential human trial data and feedback of healthcare professions. The proposal consists of three Aims. First, the physical components of the PGP-Dx platform will be developed: a modified HemoLink device able to collect 250 uL of blood; a disposable cartridge able to perform precise sample purification and analysis; and a proof-of-concept base reader operating the cartridge and performing the electronics for the readout. Secondly, the chemistry and reagents utilized in the workflow (the PNA, enzymatic color change, etc) will be optimized to further increase the limit of detection of viral RNA as well as an increase in manufacturability for plastic injection molding. Finally, human pre-clinical trials will be performd to quantify the clinical utility and performance of the PGP-Dx platform in real-life use conditions This last aim will also focus around establishing the pathway towards regulatory clearance and initiating the product master file. Beyond Phase II, we will leverage the strong FDA position and the clinical utility data to raise a series A funding towards industrial designing, clinical trials and FDA approval.
Current POC solutions for infectious diseases suffer from a very limited sensitivity and range of tests that can be performed. Tasso,Inc. is proposing to develop a system that will bring tests previously only performed in expensive centralized labs to the point-of- care. This will enable more rapid and affordable diagnostics, more relevant clinical information, and better management of patients with infectious diseases. The device will open multiple windows on important biomarkers of the disease in the same test. What this will provide the patient and the clinician is a snapshot of the overall infection and the overall health of the patient through monitoring the state of viral infection/viral load, the status of immune response (antibody levels), and the overall health of the patient (white blood cell counts).
