Dunn Pilot Project Summary

A point-of-care (POC) analysis platform will be developed that can rapidly quantify amino acid (AA) levels in plasma. The goal is to develop an analysis platform for gastrointestinal bleeds (GIBs) that can guide subsequent endoscopic evaluation and treatment of patients. GIBs account for 20% of all emergency department visits and 2% of all hospital admittances, with mortality rates ranging from 5-10% and inpatient healthcare costs topping $2.5 billion a year. Compelling evidence suggests that AA levels in GI bleeds can differentiate upper and lower GIBs and guide subsequent endoscopic evaluation and care. Endoscopy is usually done within 24 hours of presentation and ideally begun within 4-6 hours or sooner. Most hospitals, however, use external contract laboratories for plasma AA analysis, with turnaround times ranging from 2-5 days making the results obsolete for diagnostics. We propose that a sufficiently rapid, point-of-care (POC) blood test that quantifies AA levels will aid in the real-time diagnosis, risk stratification, and treatment for GIB patients. AAs are a challenging analytical target to separate and detect and conventional analysis usually involves derivatization steps along with complex and expensive instrumentation. These approaches are not sufficient for a rapid, POC diagnostic. Planar capillary electrophoresis (PCE) combined with back-scatter interferometry (BSI), on the other hand, is a relatively simple and inexpensive analysis platform capable of rapidly separating and detecting underivatized AAs. Using PCE-BSI, we recently showed that a mixture of 3 inorganic ions (Na+, K+, Li+) and 8 AAs can be separated and detected in under 40 seconds, illustrating the potential of this approach for rapid GIB diagnostics.

In aim 1, three novel approaches will be developed to extend PCE-BSI figures of merit to meet the diagnostic requirements; while in aim 2 the approach will be tested and validated on model human plasma. The studies proposed in aim 1 will make extensive use of the NIH COBRE CMADP Nanofabrication Core Facility. The successful completion of this pilot project will lead to larger grant applications in collaboration with Dr. Jared Sninsky at Baylor College of Medicine to fully develop and characterize rapid diagnostics for GIB management (real patient samples, additional diagnostic markers like BUN/creatinine, etc.).