A major challenge facing the clinical diagnostics industry in the years ahead is the need for new assay platforms capable of rapid, accurate evaluation of low-abundance biomarkers for early detection of disease and risk for diseases such as cancer, cardiovascular, and infectious diseases, as well as rapid evaluation of traumas, such as heart attack, stroke, and injury. Thus, new assay platforms are urgently needed which permit real-time quantitative evaluation of low-abundance therapeutic targets and biomarkers in clinical specimens with minimal sample processing. Ideally, such new assay platforms should be endowed with: (1) superior sensitivity to permit early detection and evaluation of risk, (2) suitability for kits for rapid analysis at points of care by non-specialists using simple equipment, (3) adaptability to standard automated high-throughput microfluidic systems. For many years immunosorbent assay platforms, such as RIA, and ELISA, have formed the basis of most biomarker assays, but as clinical medicine has evolved, increasing demand for sensitivity, accuracy, speed, and versatility have rendered these platforms sub-optimal for many important applications. To address the need for a quantitative clinical assay platform that overcomes the limitations of the immunosorbent platforms, and meets the requirements listed above for the ideal assay platform, a proprietary target recognition-mediated enzyme reactivation sensor based on the reactivation of an auto-inhibited 2- lactamase has been developed, called TRAIL. The TRAIL system is completely homogeneous, and has the potential for rapid, accurate measurement of any macromolecular species at picomolar concentrations in most biological fluids in standard laboratory settings with minimal sample processing and standard detection equipment. In addition, the system permits sensitive detection in minutes at points of care by non- professionals. The system utilizes universal reporter activation components that can be readily combined with standard target-binders such as antibody fragments for rapid generation of new assays. In Phase I, human cardiac Troponin I (cTnI) will be used as a model biomarker for validation and optimization of the TRAIL assay platform. The appearance of cTnI in the circulation has become a preferred indicator of heart attack in patients presenting with chest pain in the ER. A TRAIL assay for cTnI could allow rapid confirmation of acute myocardial infarction (AMI) sooner after onset of ischemia than is possible with current immunosorbent tests. The Phase I goal is to optimize a TRAIL assay which can quantify cTnI in human serum down to 1.0 picomolar or less in less than 30 minutes. In Phase II, the TRAIL cTnI assay will be validated for accuracy, sensitivity, and reproducibility on pre-clinical and clinical samples, and compared to standard commercial assays. FDA approval will be sought, and a corporate partner will be engaged for commercial development of the assay. Additional assays will be developed and validated for other biomarkers of disease and trauma in collaboration with corporate partners in the pharmaceutical and diagnostics industries.
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