Nanometal particle reagents for sensitive, MEMS based fiber-optic, multi-analyte, immuno-biosensing

Integration of nanotechnology to medical diagnostics has brought a new era to public health practice. An excellent example is the utilization of unique optoelectronic properties of nanoparticles to develop highly sensitive biosensing devices for point-of-care (POC) disease diagnosis/prognosis. Fluorophore mediated, immuno-biosensors are important disease detection tools. The property of intra-molecular fluorescence quenching of most fluorophores, however, limits the sensitivity of this type of sensors. A plasmon-rich nanometal particle (NMP) can transfer the lone pair electrons of a fluorophore, which normally participate in the fluorescence self-quenching, to its surface plasmon field, resulting in artificial fluorescence enhancement. The enhancement was found to depend on the metal type, the particle size, the distance between a particle and a fluorophore, and the quantum yield of a fluorophore.;Some biocompatible solvents were also found to increase the fluorescence emission efficiency via effective dipole coupling between the fluorophore and the solvent molecule. The application of solvents in inmuno-sensing could additionally improve the fluorescence light retrieval by the conformational change of the protein complexes in solvent. The mixture of the NMP and the solvent, which we defined as nanometal particle reagent (NMPR), provided even higher enhancements.;Cardiovascular diseases (CVDs) kill 1 person in every 6 seconds. Among the CVDs, acute myocardial infarction (AMI; commonly known as heart attack) is the most dangerous and time-sensitive killer. A rapid and accurate AMI diagnosis is crucial for saving many lives. For this purpose, a fluorophore mediated, immuno-reaction based, multi-cardiac-marker sensing device was developed, to quantify four myocardium-specific proteins simultaneously, accurately, rapidly, and user-friendly. The four cardiac markers of our choice were myoglobin (MG), C-reactive protein (CRP), cardiac troponin I (cTnI), and B-type natriuretic peptide (BNP). Two of these cardiac markers, cTnI and BNP, were rather difficult to sense due to their low concentrations (tens of picomolar) in blood plasma immediately after the AMI. The NMPRs that we have developed enhanced the sensor signals as high as 8 times, accomplishing a sensitive and accurate quantification of all four markers in 7 minutes with an average signal-to-noise ratio of 35.;As a promising POC sensing device, system portability, sensing reliability, and user-friendly operation are important. Micro-electro-mechanical system (MEMS) technology was, therefore, integrated to the immuno-sensing device with microfluidic control and microfabrication. A LabVIEW(TM) computer code was also written for a "one-click" automated immunoassay and a real-time data analysis.;Our four-cardiac-marker immuno-sensing device incorporated with nanotechnology and MEMS technology is capable of simultaneous quantification at a near-real time, which can save many lives. This device can be also used for measuring any disease-representing biomarkers (e.g., cancer markers) for rapid and accurate disease diagnosis/prognosis.