Integrated nanophotonic biosensors for quantitative molecular diagnostics

In order to realize precise diagnostics of human diseases at molecular level, we have to tackle all the challenges in functional genomics and proteomics. Although human genome has been fully sequenced, it is still far from the complete understanding of all the genetic functions and the complicated gene regulation processes. Despite of many existing diagnostic or probing tools, we are still ill-equipped with novel scientific apparatus to measure dynamic genetic processes at a molecular dimension. Besides of genetic process, various protein functions are also the key to the conduction of normal cellular processes. Many protein functions are sequentially cascaded to form signaling pathways which lead to particular cellular functions. Although the technologies are available for profiling the molecule events in these signaling pathways such as proteolysis and phosphorylation at a fixed moment, people are still investigating methods to track the dynamic protein functions in a living system. Not only beneficial to diagnostics, a dynamic biomolecular based probing tool can also facilitate the drug development and screening process. It will be an excellent economical pre-validation test to in vivo drug testing. We have to invent new detection technologies for real time in vivo or in vitro detections of dynamic biomolecular reactions with nanoscale spatial resolution and adequate temporal resolutions.; As demonstrated in my dissertation, new physical, chemical and biological phenomena can be created by shedding light onto hybrid nanostructures with artificial nanophotonic subunits and endogenous biomolecular subunits. The light-matter interactions at the nanoscale physical/life system interface can provide us a new way to communicate with mysterious biological systems optically. I established such communications by constructing effective nanobiophotonic hybrid structures including nanoplasmonic devices to track dynamic genetic processes such as hybridization, nucleolysis and DNA-protein interactions, SERS nanosubstrates to monitor real time protein activities such as proteolysis and kinase phosphorylation, and electronic energy transfer interfaces between nanoplasmonic system and biomolecular system. The above novel bio-nano hybrid engineering tools permit the near single molecular level studies of functional and dynamic genomics and proteomics with nanoscale spatial resolution. Furthermore these nanoscale engineering tools are integrated to microfluidics biochips by using novel integration methods presented in my dissertation, which makes the "infinitesimal" nanobiophotonic devices available for the wide applications in conventional bench and portable disease diagnostic instruments.