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

宾夕法尼亚州立大学（Pennsylvania State University）获得了一项奖励，以开发集成等离子流体显微镜（PFM），该显微镜可以以简单、紧凑、经济、用户友好的格式进行高通量、高灵敏度的单分子研究。以其前所未有的高灵敏度和高通量的能力，同时使用相对简单，低成本的格式，所提出的PFM有可能改变单分子研究领域，并加速生物学，生物化学和医学等许多学科的发现。这项技术有望有许多不同的应用，具有直接的积极影响。例子包括远离平衡的分子动力学研究，分子特性的表征，如蛋白质构象变化和折叠，或蛋白质-蛋白质或蛋白质- dna相互作用动力学和动力学的研究。拟议的PFM将通过以下方式传播：1)录制和分发实验过程的视频；2)招募beta测试实验室；3)在会议上举办演示会议；4)与行业合作伙伴合作。女性和代表性不足的少数民族学生将广泛参与拟议的研究项目。所提出的PFM利用了等离子体（即光与纳米材料之间的相互作用）和微流体所提供的独特特性。它将传统纳米孔传感器的灵敏度提高了20-120倍。除了提高灵敏度外，所提出的PFM技术提供了更精确的流体控制，最大限度地减少了样品和试剂的消耗，并降低了设备成本。该项目将在微/纳米尺度上提高对光、流体和分子相互作用的理解，为等离子体流体学的新兴领域做出贡献。提出的基于pfm的T4复制体单分子研究也将提高对DNA复制过程的理解，这不仅将阐明生物学和生物化学的基本过程，而且将为许多疾病的治疗提供启示，如癌症和传染病。

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.