Human cardiac Troponin I is one of three subunits of the cardiac Troponin complex that are released into the bloodstream upon injury to cardiac muscle, particularly myocardial infarction, where it is absent under normal conditions. Rapid, sensitive detection of blood borne Troponin I is extremely important for early detection of myocardial infarction. An optical biosensor has been proposed as a versatile, adaptable, and effective method for detection of Troponin I. The biosensor architecture utilizes fluorescence resonance energy transfer (FRET), a distance-dependent chemical signal transduction method that occurs between two fluorescent molecules, termed the donor and acceptor. In order to launch FRET, a donor-labeled protein A molecule is bound to an acceptor-labeled capture antibody. When exposed to the Troponin I antigen, the antibody-antigen binding event initiates a conformational change within the structure of the antibody. As this morphological change in the antibody takes place, the distance between the donor and acceptor changes, resulting in a measurable shift in energy transfer. In this study, quantum dots were utilized as the FRET donors to further increase the efficiency of the biosensor system and organic dyes were utilized as the acceptors. This sensing mechanism was then interfaced in a liquid-core waveguide (LCW) platform that was able to capture the resulting fluorescence to achieve highly sensitive and accurate measurements. The biosensor demonstrated an ample sensitivity to the analyte, achieving a lower limit of detection of approximately 32 nM in phosphate buffered saline and 55 nM in human plasma. A high degree of specificity was also observed when the response to cardiac Troponin I is compared with that of a nonspecific protein. Response time of the biosensor was determined to be less than 1 min; an expeditious time compared with other Troponin diagnostic assays. [ABSTRACT FROM PUBLISHER]