SBIR Phase II: A Cell Analysis Platform for Low-cost, Rapid Diagnosis of Sepsis Using Microfluidic Technologies

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is in detecting sepsis early in its course, before end organ damage when it is most treatable. Sepsis, an uncontrolled systemic response to local infection by bacteria or fungi, is responsible for more deaths than prostate cancer, breast cancer, and AIDS combined and is associated with ~$17B in annual U.S. healthcare expenditures. We anticipate that providing emergency department physicians with an earlier diagnostic will profoundly influence clinical outcomes (currently ~40% mortality), costs (>$22,000/case), and the quality of life for survivors and their families. Accumulating evidence connects systemic immune activation ? a key process in sepsis ? with single-cell architectural changes that are mechanically measured by high-speed mechanical phenotyping technology. This technology is well-suited for adult sepsis screening in the emergency department (market size of $1.5B) due to: (1) the functional analysis of cell state the mechanical measurement provides, (2) its high achievable throughput and therefore statistical accuracy, (3) exceedingly short turnaround time, (4) low cost of goods, and (5) the clinically-actionable information it provides. Beyond the adult sepsis screening market, several additional indications include neonatal sepsis, bladder cancer detection, academic research tools, and drug development. The proposed project brings an innovative new class of biomarkers to bear on a problem that has been intractable with current biomarkers. Briefly, the physical properties of cells have been known to be important for decades, but only with the advent of breakthrough microfluidic technology have we been able to measure these parameters in a high-throughput manner capable of diagnosing disease. This Small Business Innovation Research (SBIR) Phase II award will be used to develop and validate innovative sample preparation and image analysis modules for a sepsis screening technology as well as performance of proof-of-concept clinical studies that would be a flagship offering in using biomechanical biomarkers to diagnose disease. The technical objectives are designed to improve sensitivity to white blood cells, activated during sepsis, by microfluidic automation of sample preparation and optimization of the microscopic imaging optics. In addition to preparing the test for practical implementation in the emergency department, the test will be validated with a proof-of-concept clinical study, and a clinical scoring system will be devised.