IDBR: RUI: Development of a Cantilever Based Optical Interfacial Force Microscope

基于悬臂梁的光学界面力显微镜（COIFM）是本项目开发的一种研究生物分子亚稳态能态的新工具。生物分子系统在达到具有最低能量的稳定状态之前会经过几个亚稳态。探索亚稳态及其形状或构象对于理解生物分子功能至关重要。然而，亚稳态由于其相对短的寿命和其在溶液相中的非平衡性质而难以观察。COIFM？COIFM的敏感距离和力控制能力将允许研究沿着反应坐标的亚稳态。通过将传统的界面力显微镜（IFM）和原子力显微镜（AFM）类型的悬臂梁及其光学检测方案相结合，COIFM将实质性地改进 测量精度IFM的力反馈技术将被采用，以消除快速折断过程，固有的机械不稳定性与传统的设备，这将阻止探测亚稳态生物分子激活过程中。悬臂的较小探针尺寸将使 与传统技术相比，将力分辨率提高至少一个数量级。改进的COIFM能力将通过在单分子水平上探测生物系统的生物分子活化过程中的亚稳态来证明。这些COIFM修改具有在各种分子水平上定量测量生物相互作用的潜力，不仅对于单分子，而且对于病毒，细菌和细胞系统。为了使这一发展尽可能广泛地提供给其他实验室，所有的细节，包括电子电路和规格的COIFM机械头，将有充分的记录和公开访问。对于生物系统的广泛应用，将鼓励制造商将COIFM能力纳入其现有系统。研究活动的结果将通过以下方式传播和评估：（一）在国家/国际科学会议上的演讲;（二）在同行评审的期刊上发表文章;（三）创建交互式物理实验室网站;以及（四）向实验室访问者演示。该项目每年将有一名本科生和一名研究生参加研究和培训活动，从而在三年内为多达六名物理，化学，生物和工程专业的学生提供前所未有的研究机会。这项研究将是博伊西州立大学强大和不断发展的多学科本科研究计划的重要补充，也是其计划中的生物分子科学博士课程的重要补充。

The cantilever based optical interfacial force microscope (COIFM) is a new tool to be developed, through this project, for the study bio-molecular metastable energy states. A bio-molecular system passes through several metastable states before it reaches a stable state with the lowest energy. Probing the metastable states and their shape, or conformation, is crucial for understanding bio-molecular function. However, metastable states are difficult to observe because of their relatively short lifetime and their non-equilibrium nature in a solution phase. The COIFM?s sensitive distance and force control capability will allow for investigating the metastable states along the reaction coordinates.By combining a conventional interfacial force microscope (IFM) and an atomic force microscope (AFM) type cantilever and its optical detection scheme, the COIFM will substantive improve measurement accuracy .. A force feedback technique for the IFM will be adopted to remove the rapid snap-off process, an intrinsic mechanical instability associated with conventional devices, which prevents probing metastable states during bio-molecular activations. The smaller probe size of the cantilever will enable inproving the force resolution, over conventional techniques, by at least an order of magnitude. The improved COIFM capability will be demonstrated by probing metastable states during bio-molecular activations of a biological system at the single molecule level.These COIFM modifications have the potential to quantitatively measure biological interactions at various molecular levels, not only for single molecules, but also for viral, bacterial, and cellular systems. To make this development as widely available to other laboratories as possible, all details, including electronic circuits and specifications of the COIFM mechanical head, will be well-documented and openly accessible. For wide applications to biological systems, manufacturers will be encouraged to incorporate COIFM capability into their existing systems. Results of the research activities will be disseminated through, and evaluated by, (i) presentations at national/international scientific conferences; (ii) publications in peer-reviewed journals; (iii) creation of an interactive physics lab website; and (iv) demonstrations to lab visitors. This project will engage one undergraduate student and one graduate student in research and training activities each year, thus providing unprecedented research opportunities for as many as six physics, chemistry, biology, and engineering students over a three-year period. This research will be an important addition to the strong and growing multi-disciplinary undergraduate research program at Boise State University, and to its planned Biomolecular Sciences PhD program.