Actively Controlled Photonic Force Microscopy

描述（由申请人提供）：基于设计，动力学，测量和控制的工程基础，PI旨在开发一种主动控制的光子力显微镜（AC-PFM）系统，并实现对活细胞中活性生物分子的力探测和操纵的新能力。所提出的光子力微观系统的基本组成部分是一个三维探测系统，其中一个功能化的纳米珠被光学捕获在最小场势周围作为测量探针，而随机热力倾向于使其不稳定。提出了一种创新的双测量方法来实现反馈控制。提出了一种新颖的非线性控制方案，结合三轴转向系统，根据测量探头的绝对位置有效地改变场势，提高了光阱的稳定性，降低了所需的激光功率，从而降低了探头和被测样品的温升。提出了在噪声中估计探针-样本相互作用的理论和实验研究，从而实现了基于模型的三维动态力传感估计器。探测三维探针-样品相互作用力的能力将使单个分子探测、力映射和力反馈控制成为可能。力反馈控制有助于在细胞内操纵探针，实现细胞内可视化的自动扫描。如果研制成功，该仪器将为活性生物分子的研究开辟新的领域。

DESCRIPTION (provided by applicant): Building on engineering fundamentals in design, dynamics, measurement, and control, PI aims to develop an actively controlled photonic force microscopic (AC-PFM) system and to realize new capabilities for force probing and manipulation of active biomolecules in live cells. The fundamental building block of the proposed photonic force microscopic system is a three-dimensional (3D) probing system, in which a functionalized nano-bead is optically trapped around the minimum of the field potential to serve as the measurement probe, while the random thermal force tends to destabilize it. An innovative dual-measurement approach is proposed to enable feedback control. Novel nonlinear control schemes along with a 3-axis steering system are proposed to effectively change the field potential according to the absolute position of the measurement probe and enhance the stability of the optical trap, lower the required laser power, and thus reduce the temperature rise of the probe as well as that of the sample being probed. Theoretical and experimental investigations are proposed to estimate probe-sample interaction in noise, leading to the implementation of model-based estimators for 3D dynamic force sensing. The ability to sense the 3D probe-sample interaction force will enable individual molecules probing, force mapping, and force feedback control. Force feedback control will help maneuver the probe inside cells and achieve automatic scanning for intracellular visualization. If successfully developed, the proposed instrumentation will open new frontiers in research on active biomolecules. Public Health Relevance Statement: The proposed technological development will result in an actively controlled photonic force microscopic system that enables scientists to study biomolecules in live cells with new capabilities in terms of visualization and force probing. It will have significant impact on many aspects of biology, pharmacology, as well as medicine.