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

了解小颗粒如何在表面附近的流体中移动对于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。对于纳米尺寸的粒子，捕捉这些运动图像的能力非常有限。液体细胞透射电子显微镜是一种新技术，具有很大的潜力，以克服这一限制，提供它可以首先验证简单的模型系统。本研究项目旨在研究液-固界面附近纳米颗粒的运动，对这些颗粒的运动类型进行分类，并开发基于物理学的理论模型，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靠近表面移动的理解，这在包括生物学，地质学和化学加工在内的许多领域都提出了挑战。通过这个项目，一组不同的本科生将在更高级的项目参与者的指导下合作工作。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图像和视频。了解纳米粒子在流体中和接近表面的运动在物理和化学中具有根本的重要性。一个常见的方法来表征这些运动已经通过光学显微镜，这自然会对动态施加空间分辨率的限制。液体细胞透射电子显微镜的出现使得研究各种表面附近的颗粒在液体环境中的纳米级运动成为可能，并且具有高空间分辨率。本研究项目将研究一个简单的和可调的模型系统的金纳米粒子在水环境中的异常扩散运动附近的氮化硅膜的透射电子显微镜的液体细胞。具体目标包括i）研究电子束剂量率对原位液体池透射电子显微镜中金纳米颗粒异常扩散的影响。这一目标将通过测量大量纳米粒子在不同电子束剂量率下的轨迹来实现; ii）及时利用从粒子轨迹收集的大规模原位显微镜数据，并使用深度神经网络对扩散运动的类型进行分类;和iii）开发Langevin-基于理论模型，以捕捉发生在多个时间尺度上的独特扩散特性，并将局部流变材料特性与在液体细胞环境中的运动。如果成功的话，这项研究将为研究纳米粒子在表面附近的运动提供一种新的方法，从而推进对纳米尺度上物质行为的基本理解。这些知识也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的实验和系统的机制指导设计成为可能。该奖项反映了NSF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.