EAGER: Towards molecular scale resolution in studies of the anomalous motion of nanoparticles using liquid phase electron microscopy

了解小颗粒如何在靠近表面的流体中运动对许多科学领域都很重要，例如生物物理学和胶体自组装。这种现象也与许多主要的新兴技术有关，从生物分子分离到三维增材制造。对于纳米大小的粒子，捕捉这些运动图像的能力是非常有限的。液体细胞透射电子显微镜是一种有很大潜力克服这一限制的新技术，前提是它可以首先用简单的模型系统进行验证。该研究项目旨在研究纳米颗粒在液固界面附近的运动，对这些颗粒的运动类型进行分类，并建立基于物理的理论模型来解释这些颗粒在表面附近的运动。从这个研究项目中获得的知识将促进我们对纳米粒子如何接近表面的理解，这在许多领域提出了挑战，包括生物学、地质学和化学加工。通过这个项目，不同的本科生群体将在更资深的项目参与者的指导下协同工作。这些学生将学习如何使用新的数据科学工具来分析收集的显微镜图像和视频。了解纳米颗粒在流体中和靠近表面的运动在物理和化学中具有重要的基础意义。表征这些运动的常用方法是通过光学显微镜，这自然会对动力学施加空间分辨率限制。液体细胞透射电子显微镜的出现使得在液体环境中以高空间分辨率研究各种表面附近粒子的纳米级运动成为可能。本研究项目将研究一个简单可调的金纳米粒子模型系统在靠近透射电子显微镜液体电池氮化硅膜的水环境中的异常扩散运动。具体目的包括：(1)研究电子束剂量率对金纳米粒子在原位液体细胞透射电镜中异常扩散的影响。这一目标将通过测量不同电子束剂量率下大量纳米粒子的轨迹来实现；Ii)利用从粒子轨迹中收集的大规模原位显微镜数据，利用深度神经网络对扩散运动类型进行分类；iii)开发基于朗万的理论模型，以捕捉跨多个时间尺度发生的独特扩散特征，并将局部流变材料特性与液体电池环境中的运动类型联系起来。如果成功，这项研究将为研究纳米粒子靠近表面的运动提供一种新的方法，从而促进对纳米尺度上物质行为的基本理解。这些知识还将使在广泛的科学领域，包括结晶、生物医学药物输送、流变学、化学分离和增材制造研究中，以机制为指导的实验和系统设计成为可能。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Understanding how small particles move in a fluid near a surface is important for many scientific areas, such as biophysics and colloidal self-assembly. This phenomenon is also relevant to many major emerging technologies, from biomolecular separations to three-dimensional additive manufacturing. For nanometer-sized particles, the ability to capture images of these motions has been extremely limited. Liquid cell transmission electron microscopy is a new technique that has great potential to overcome this limitation, provided it can first be validated with simple model systems. This research project aims to study the motion of nanoparticles near a liquid-solid interface, to classify the type of motion of these particles, and to develop physics-based theoretical models that explain the motion of these particles close to a surface. This knowledge gained from this research project will advance our understanding of how nanoparticles move close to a surface, which presents challenges in many fields including biology, geology, and chemical processing. Through this project a diverse group of undergraduate students will work collaboratively under the guidance of the more senior project participants. These students will learn how to use new data science tools to analyze collected microscopy images and videos.Understanding the motions of nanoparticles in a fluid and close to a surface is of fundamental importance in physics and chemistry. A common method to characterize these motions has been through optical microscopy, which naturally imposes spatial resolution limitations on dynamics. The advent of liquid cell transmission electron microscopy has made it possible to study the nanoscale motion of particles near various surfaces, in the liquid environment, and with high spatial resolution. This research project will investigate the anomalous diffusive motion of a simple and tunable model system of gold nanoparticles in aqueous environments near the silicon nitride membrane of a transmission electron microscope’s liquid cell. Specific aims include i) studying the effect of electron beam dose rate on the anomalous diffusion of gold nanoparticles in in-situ liquid cell transmission electron microscopy. This aim will be accomplished by measuring the trajectories of large numbers of nanoparticles at different electron beam dose rates; ii) exploiting the large scale in-situ microscopy data collected from particle trajectories in time and classifying the type of diffusive motion using deep neural networks; and iii) developing Langevin-based theoretical models to capture the distinctive diffusive characteristics that happen across multiple timescales and to relate the local rheological material properties to the type of motion in the liquid cell environment. If successful, this research would facilitate a new way to study the motion of a nanoparticle close to a surface and thereby advance fundamental understanding of the behavior of matter on the nanometer scale. Such knowledge would also enable the mechanism-guided design of experiments and systems in a wide range of scientific fields including crystallization, biomedical drug delivery, rheology, chemical separations, and additive manufacturing research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.