Opto-fluidic ring resonator (OFRR) is a photonic technology originally invented in the PI's lab. The OFRR integrates the optical cavity of extremely high Q-factors (>107) with microfluidics, enabling efficient sample delivery and control of light through fluids. Because of these novel characteristics, the OFRR has broad applications in many fields, including bio/chemical sensors, photonic devices, and fundamental physics. In the proposed research, in particular, the PI wilo expand the OFRR study into fluorescence resonant energy transfer (FRET). FRET has been extensively employed in biological and chemical sensors. However, extremely low energy transfer efficiency beyond the Forster distance (2-10 nm) has severely deteriorated the FRET sensing capability, especially for large biomolecules. The PI's recent studies, along with those conducted earlier by other groups, have shown that FRET efficiency can be drastically enhanced by an optical cavity through long-range cavity assisted energy transfer and nonlinear lasing action. These properties can be exploited to overcome the limitations of the traditional FRET-based biosensing. The overall aim of the proposed research is to conduct a fundamental investigation into FRET processes in the OFRR and to harness the powerful OFRR and FRET technologiesto develop a novel miniaturized and highly sensitive photonic biosensing system that can be operated at even the single molecule level.
Intellectual merits: The objective of the proposed research is to conduct a fundamental investigation into fluorescence resonance energy transfer (FRET) processes in a high-Q laser cavity and to harness the powerful cavity and FRET to develop a novel miniaturized and highly sensitive photonic biosensing system. Basically we need to understand how the cavity can enhance FRET and how FRET affects the emission from the cavity. The project has the following merits: (1) Although FRET in a cavity has been employed in various applications, its application in biosensing has not been systematically investigated. Through theoretical analysis and modeling, and through experiments using DNA as an accurate nano-sized ruler to control the energy transfer, the proposed research will elucidate energy transfer processes in the high-Q cavity (in particular, optofluidic ring resonator – OFRR, developed in-house) and provide a thorough understanding of the fundamental and technical issues in the OFRR-FRET-based bio/chemical sensor. (2) The OFRR-FRET-based sensor uniquely combines the advantages of the OFRR and FRET. It will feature tremendously enhanced energy transfer efficiency, excellent detection sensitivity and selectivity, integrated microfluidics, and extremely low sample volume, which is a significant advancement over the existing FRET sensors. In addition, the donor/acceptor interaction distance will be drastically extended, making the OFRR-FRET-based sensor a promising test-bed for studying many biological processes that cannot be examined with the traditional FRET method. Broader Impacts: The project has laid a solid foundation for further exploration of OFFR-related and FRET-related optical bio/chemical sensors. It has also significantly benefitted the development of other photonic devices such as microfluidic lasers, opto-fluidic components, and solar cells. Moreover, the insights gained from the proposed research are applicable to fundamental physics such as cavity-QED, single molecule lasers and optical switches, and nonlinear optics. This proposal also consists of strong educational and outreach plans that include (1) development of undergraduate biophotonic lab modules incorporating knowledge derived from the proposed research; (2) expansion of student educational experiences via an "Industrial Biophotonics Keynote Speaker" program; (3) involvement of undergraduate students in research and industry internships; and (4) outreach to other universities/colleges, K-12 schools, the general public, and international institutions. Major activities and findings: In the past 6 years, under the support of this NSF grant, we have published approximately 20 peer-reviewed journal articles, 1 book, 3 book chapters, 1 patent, and numerous conference presentations, invited talk, and articles in popular scientific magazines. In addition, we trained 2 post-doctors, 6 graduate students, nearly 10 undergraduate students, and several high school students. 2 courses were developed for undergraduate and graduate students. According to our theoretical analysis and experimental work, we found that the cavity can significantly enhance the FRET efficiency. Particularly, in the presence of the laser emission, the FRET signal can be increased 10-100 times, as compared to the fluorescence case in the absence of a cavity. On the other hand, the laser emission from the cavity can be sensitively modulated by the FRET which is in turn controlled by the underlying biological processes. This opens a door for us to develop biologically controlled optofluidic lasers, which are currently being investigated under other funding supports.
