GOALI: Nonlinear, Multi-modal, and Stochastic Dynamics of Low-stiffness Microcantilevers in Liquid Environment Atomic Force Microscopy

该奖项由2009年美国复苏和再投资法案(公共法律111-5)资助。该项目旨在研究微悬臂梁的非线性、多模式和随机动力学，利用液体中的样品来显著改进用于生物和医学的下一代动态原子力显微镜(DAFM)。这项拟议的工作将开发新的成像模式和悬臂设计，以大大增强纳米材料在液体中的性质对比度，如分子弹性和识别，同时对脆弱的生物样本施加柔和的力，包括细胞、膜、病毒和蛋白质。通过系统地考虑流体动力耦合效应、随机朗之万力、针尖-样品的非线性相互作用(如化学键合力)和多个悬臂梁的特征模式，建立了精确的数学模型来模拟液体中低刚度AFM微悬臂梁的动力学。研究将集中在瞬间激发，非共振模式相互作用，依赖于：局部弹性和分子识别，以及从单次敲击振荡到多次敲击振荡的分叉。基于这些模式耦合现象，将开发缓冲溶液中新的DAFM模式，以实验解决缓冲溶液中生物分子的局部弹性和分子识别的变化。DAFM已经成为纳米分辨率成像和材料性能表征的主要科学技术。为液体中生物样品的DAFM开发新的高分辨率、温和的作用力和材料对比模式将使生物学和医学广泛受益，例如，通过提供癌细胞上的蛋白质标记或细胞上的药物受体位置的敏感地图，从而使早期疾病检测和药物发现成为可能。这些结果还可以深入了解更广泛类别的系统的动力学，这些系统受到非线性、流体动力学和朗之万力的强烈影响，例如，光学陷阱中的粒子、用于液体中生化检测的纳米机械悬臂传感器、DNA、生物聚合物以及真核细胞的纤毛和鞭毛。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).This project seeks to study the nonlinear, multi-modal, and stochastic dynamics of microcantilevers tapping on samples in liquids to significantly improve next generation dynamic Atomic Force Microscopy (dAFM) for biology and medicine. The proposed work will develop new imaging modes and cantilever designs to greatly enhance nanoscale material property contrast, such as molecular elasticity and recognition, in liquids while applying gentle forces on fragile biological samples including cells, membranes, viruses, and proteins. Accurate mathematical models will be developed to simulate the dynamics of low-stiffness AFM microcantilevers in liquids by systematically including hydrodynamic coupling effects, stochastic Langevin forces, nonlinear tip-sample interactions such as chemical bond forces, and multiple cantilever eigenmodes. Investigations will focus on the dependence of momentary excitation, a non-resonant modal interaction, on: local elasticity and molecular recognition, and bifurcations from single to multiple tapping oscillations. New dAFM modes in buffer solutions will be developed based on these mode coupling phenomena to experimentally resolve variations in local elasticity and molecular recognition on biological molecules in buffer solutions. dAFM has become a major scientific technique for nanometer resolution imaging and materials property characterization. The development of new high-resolution, gentle force, material contrast modes for dAFM of biological samples in liquids would broadly benefit biology and medicine, for example, by providing sensitive maps of protein markers on a cancer cell or drug receptor sites on a cell, thus enabling discoveries in early disease detection and drug discovery. The results could also provide insight into the dynamics of a wider class of systems that are strongly affected by nonlinearities, hydrodynamics and Langevin forces, for example, particles in optical traps, nanomechanical cantilever sensors for biochemical detection in liquids, DNA, biopolymers, and cilia and flagella of eukaryotic cells.