New horizons in Electrostatic Force Microscopy

与癌症等威胁生命的疾病作斗争需要在分子和细胞水平上深入了解生命系统的功能。因此，对创造探索这些微观生活环境的各种生物化学和生物物理特性的能力的需求很高。生物系统的一个重要但经常被忽视的特性是静电荷，它影响生物化学反应以及细胞分裂，迁移和粘附到细胞外环境的方式。在用于表征静电荷的现有技术中存在许多地板，例如在测量期间需要在样品的表面上拖动尖端，这限制了它们对精细3D生物样品的应用。生物医学研究界最近已经从研究2D细胞样本转向生长3D细胞培养物，这些细胞培养物已被证明可以更好地复制体内环境，使其成为了解疾病的更好模型。工程和物理科学界需要迎头赶上，并提供合适的工具来感知和成像这些更复杂的3D蜂窝环境。显微镜的研究工作旨在建立新的成像方法，不仅是光与样品的相互作用，而且要揭示这些微观世界的化学，机械和电学性质。该提议福尔斯属于这一类别，旨在为生物学家建立一种新的能力，以检测复杂3D环境中亚细胞结构域处的极少量静电荷和力。在这里，我们使用光学捕获-一种提供高灵敏度力转换的显微镜工具-结合定制的电化学配置，可以精确操纵研究中样品的电场。该项目风险很高，但如果成功，它有望提供一种全新的显微镜功能，用于使用非接触式方法在精细的活生物样品周围绘制3D变化的静电荷，使生物医学研究人员能够以目前不可用的方式测试新的假设。

The fight against life-threatening diseases such as cancer requires an in-depth understanding of the functions of living systems at the molecular and cellular levels. Therefore the demand to create capabilities for exploring various biochemical and biophysical characteristics of these microscopic living environments is high. One important but often over-looked property of biological systems is electrostatic charge, which influences biochemical reactions as well as the ways in which cells divide, migrate and adhere to extracellular environments. There are many floors in the existing techniques used to characterize electrostatic charge, such as the requirement to drag a tip across the surface of the sample during measurement, limiting their application to delicate 3D biological samples. The Biomedical Research community has made a relatively recent shift from studying cell samples in 2D to growing 3D cell cultures that have been shown to much better replicate the in vivo environment making them better models for understanding disease. There is a need for the Engineering and Physical Sciences community to catch-up and provide suitable tools for sensing and imaging these much more complex 3D cellular environments. The research efforts in microscopy are directed towards building new ways to image, not just the interactions of light with the sample but to expose insights into chemical, mechanical and electrical nature of these micro worlds. This proposal falls within this category aiming to build a new capability for biologists to detect extremely small quantities of electrostatic charge and force at the subcellular domains in complex 3D environment. Here we use optical trapping - a microscopy tool that offers highly sensitive force transduction - combined with bespoke electrochemical configurations that allows precise manipulation of electric field across the sample under the investigation. This project is high risk, but if successful, it promises to deliver a completely brand new microscopy capability for mapping the changing electrostatic charge in 3D around delicate live biological samples using a non-contact approach, allowing Biomedical researchers to test novel hypothesis in a way that is currently not available.