Rapid Prediction of Sudden Death Using Fluorescent Nanoparticles

摘要

Sudden cardiac death (SCD) is a major, unsolved public health issue in the United States, claiming 300,000-400,000 deaths annually. The time and mode of death is highly unexpected, stimulating a great interest in improving the predictive mechanism for sudden death prevention. Since the most common cause for SCD is cardiac arrhythmias such as ventricular fibrillation, interests have intensified in developing biochemical markers (e.g., troponins and CK-MB) to predict susceptibility to cardiac events and aid in the early diagnosis and patient management. Experimental and clinical studies have demonstrated that nerve growth factor (NGF) up-regulation is an indicative of cardiac nerve sprouting which is believed to be the underlying mechanism of many cardiac arrhythmias and SCD. However, the standard analytical method with ELISA for NGF assay in hospital central lab is time-consuming (3 days) and technically complicated. For this reason, we developed a more rapid (~ 5 min), point-of-care, and cost-effective fiber-optic biosensor (FOB) for sudden death prevention. FOB employs fluorophore-mediated sandwich immunoassay on the surface of an optical fiber. To enhance the sensitivity, stability, and reliability of the FOB system, we investigated the effect of doping thousands of fluorophore (Alexa Fluor 647) inside silica nanoparticles (20-100 nm) and the applications of the highly fluorescent nanoparticles in NGF assay. Monodispersed silica nanoparticles were fabricated using a reverse microemulsion process. Characterization of the fluorescent silica nanoparticles in terms of size, shape, distribution, and fluorescent intensities were performed. A significant enhancement of the biosensing performance of the fiber-optic biosensor is achieved.