Development of Plasmonics-based Optical Nanoprobes for Medical Diagnosis

The development of practical and sensitive techniques for screening early biomarkers such as nucleic acid targets related to medical diseases and cancers is critical for early diagnosis, prevention and effective interventions. Recent advances in molecular profiling technology have made significant progress in the discovery of various biomarkers that could serve as important predictors of cancer risk and progression. Fast and precise measurement of biomarkers will help identify molecular signatures critical for the evaluation of cancer risk and early detection. Recently, there has been great interest in the design and fabrication of plasmonics-active biosensing platforms for a wide variety of applications ranging from biomedical diagnostics, food safety, environmental monitoring, to homeland defense. In particular, DNA-functionalized metal nanoparticles (e.g. gold and silver) have been utilized in the development of novel plasmonics-based analytical techniques for the detection of nucleic acid targets. In this study, two novel label-free approaches named "molecular sentinel (MS) nanoprobes", and "plasmonic coupling interference (PCI) nanoprobes" have been developed for multiplex detection of disease biomarkers using surface-enhanced Raman scattering (SERS). The MS approach has been further extended into a unique "molecular sentinel-on-chip" (MSC) technology based on a SERS-active nanowire array substrate, leading to the development of a unique diagnostic tool having multiplexing and high-throughput screening capabilities. Finally, a novel nanoparticle-based colorimetric assay has been developed and implemented for the detection of microRNAs (miRNAs). Direct detection of miRNAs in RNA samples from breast cancer cell lines has been demonstrated. Furthermore, the PCI technique has successfully detected miRNA biomarkers in biopsies of gastrointestinal cancer patients and the results are consistent with established techniques such qRT-PCR. The results of this study demonstrate that these plasmonics-based nanoprobes have great potential as useful point-of-care diagnostic tools for medical applications.