Fluorophore mediated, immuno-biosensors have been demonstrated to be effective disease detection tools. To obtain accurate diagnosis, successful sensor must provide high specificity and sensitivity. The sensitivity of fluorophore mediated biosensor highly depends on the intensity of the fluorescence from the target molecules. Therefore, a method to enhance fluorescence emission from a fluorophore can improve the sensitivity of the sensor. Nanometal particle (NMP) placed at an appropriate distance can effectively enhance the fluorescence by transferring the free elections of the fluorophore, normally used for self-quenching, to the strong surface plasmon polariton fields of the nanoparticles. We have found this enhancement depend on the metal type of NMP, NMP size, distance between a fluorophore and an NMP, and quantum yield of a fluorophore. We also found some biocompatible solvents could enhance the fluorescence significantly, possibly via effective dipole coupling between the fluorophore and the solvent molecule, resulting in an increase in the energy gap between the excited and the ground state. Conformational change of the protein complexes in solvent can be another contribution to the enhancement by reducing the distance between fluorophore and sensor surface. To maximize the fluorescence enhancement, we developed nanogold particle reagents (NGPRs) by combining nanogold particles and biocompatible solvents. These NGPRs were tested and optimized in four-cardiac marker fiber-optic biosensing system and found to be able to increase the signal as much as 10 times and accurately quantify cardiac markers at tens of picomolar level. Authors acknowledge the financial support from Kentucky Science and Engineering Foundation (KSEF-148-502-03-55) for fluorescence enhancement studies and National Science Foundation (BES-0330075) for cardiac marker biosensing.