IDBR: Type A: Development of Plasmofluidic Microscopy (PFM) for High-Sensitivity, High-Throughput Single-Molecule Studies

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An award is made to The Pennsylvania State University to develop integrated plasmofluidic microscopy (PFM) that can conduct high-throughput, high-sensitivity single-molecule studies in a simple, compact, cost-effective, user-friendly format. With its unprecedented ability to achieve high sensitivity and high throughput simultaneously while using a relatively simple, low-cost format, the proposed PFM has the potential to transform the field of single-molecule studies and accelerate discoveries in many disciplines in biology, biochemistry, and medicine. This technology would be expected to have numerous diverse applications with immediate, positive implications. Examples include the study of molecular dynamics far from equilibrium, the characterization of molecular properties such as protein conformational changes and folding, or the investigation of protein-protein or protein-DNA interaction kinetics and dynamics. The proposed PFM will be disseminated through 1) recording and distributing videos on experimental procedures, 2) recruiting beta-testing labs, 3) hosting demo sessions at conferences, and 4) collaborating with industry partners. Female and underrepresented minority students will participate extensively in the proposed research projects. The proposed PFM takes advantage of unique features offered by both plasmonics (i.e., the interaction between light and nanomaterials) and microfluidics. It improves the sensitivity of traditional nanoaperture-based sensors by 20-120 times. In addition to improved sensitivity, the proposed PFM technique provides more precise fluidic control, minimizes consumption of samples and reagents, and reduces equipment costs. This project will improve understanding on the interactions of light, fluid, and molecules at the micro/nano scale, contributing to the emerging field of plasmofluidics. The proposed PFM-based single-molecule studies on the T4 replisome will also improve understanding of the DNA replication process, which will not only elucidate fundamental processes of biology and biochemistry but also shed light on the therapeutics of many diseases, such as cancer and infectious diseases.