Actively Controlled Photonic Force Microscopy

描述（由申请人提供）：建立在设计，动力学，测量和控制的工程基础上，PI旨在开发一种主动控制的光子力显微镜（AC-PFM）系统，并实现活细胞中活性生物分子的力探测和操纵的新能力。提出的光子力显微系统的基本构建块是一个三维（3D）的探测系统，其中一个功能化的纳米珠被光学捕获周围的最小的场电位作为测量探针，而随机的热力往往会使它不稳定。提出了一种新的非线性控制方案，沿着采用三轴转向系统，根据测量探针的绝对位置有效地改变场电位，提高光阱的稳定性，降低所需的激光功率，从而降低探针和被测样品的温升。理论和实验研究，提出了估计探头样本的相互作用，噪声，导致实施基于模型的估计三维动态力传感。感测3D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。力反馈控制将有助于在细胞内操纵探针并实现自动扫描以进行细胞内可视化。如果成功开发，拟议的仪器将开辟新的前沿研究活动的生物分子。 公共卫生相关性声明：拟议的技术发展将导致一个主动控制的光子力显微镜系统，使科学家能够研究活细胞中的生物分子，在可视化和力探测方面具有新的能力。它将对生物学、药理学以及医学的许多方面产生重大影响。

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.