IDBR: Type A. Far-field optical thermal wave nanoscopy.

阿肯色大学医学科学学院获得了一项奖项，以开发一种远场超分辨率光热纳米显微镜（PTN），用于对弱荧光细胞纳米结构和纳米颗粒进行三维、无标签成像，这在目前是不可能的。PTN的应用将包括活细胞分子的高分辨率成像，以及研究蛋白质的错误折叠、降解和聚集。PTN可以提供控制和优化激光的生物应用，如组织解剖和消融。PTN将是现有显微技术的一种有价值的替代或补充，与它们结合起来，可以为以细胞为重点的生物研究提供一种强大而通用的工具。该项目将使各种生物研究团体和科学领域受益，包括细胞生物学、蛋白质组学、神经科学、纳米技术、等离子体纳米传感、老年学和癌症治疗。这项涉及物理学家、生物学家和计算机工程师的跨学科研究包括一个关于先进光学成像的培训计划，该计划将培训和教育来自代表性不足群体的本科生和研究生。本项目的目标是：1)开发具有增强灵敏度的光热共聚焦纳米显微镜平台；2)探索非线性和光电开关现象，提高空间和光谱分辨率；3)探索PTN的独特应用，包括对不同纳米结构、蛋白质聚集体和图像引导分解的无标记和靶向成像。该项目的智力优势在于远场显微镜的新概念，集成了共聚焦设计，高脉冲速率激光器，高速扫描和时间分辨检测，以显着改善当前的衍射和光谱限制。由于许多细胞成分在天然状态下具有较低的荧光，并且是纳米级的尺寸，因此明确需要一种具有高分辨率，高吸收灵敏度，时间分辨率和快速采集时间的成像技术来研究它们。提出的PTN将提供前所未有的分辨率和增强的吸收灵敏度，从而为与细胞代谢活性、氧化、内吞作用、吞噬作用、黑素生成和凋亡相关的未开发生物学研究领域打开新的窗口。

An award is made to the University of Arkansas for Medical Sciences to develop a far-field super resolution photothermal nanoscope (PTN) for three-dimensional, label-free imaging of weakly fluorescent cellular nanostructures and nanoparticles that is currently not possible. Applications of PTN will include high-resolution imaging of molecules in live cells as well as investigating protein misfolding, degradation, and aggregation. PTN can provide control and optimization of biological applications of lasers such as tissue dissection and ablation. PTN would be a valuable alternative or supplement to existing microscopic techniques and, in combination with them, could provide a powerful and versatile tool for biological research with a focus on cells. The project will benefit variety of biological research communities and scientific areas including cell biology, proteomics, neuroscience, nanotechnology, plasmonic nanosensing, gerontology, and cancer therapy. This interdisciplinary research involving physicists, biologists, and computer engineers includes a training program on advanced optical imaging that will train and educate undergraduate and graduate students from underrepresented groups. This project has the following goals: 1) develop a photothermal confocal nanosocopy platform with enhanced sensitivity; 2) explore nonlinear and photoswitching phenomena to improve both spatial and spectral resolution; and 3) explore the unique applications of PTN including label-free and targeted imaging of different nanostructures, protein aggregates and image-guided disaggregation. The intellectual merit of the project lies in the new concept of a far-field microscopy integrating a confocal design, high pulse-rate lasers, high-speed scanning, and time-resolved detection, to significantly improve on current diffraction and spectral limitations. Because many cellular components in the native state have low fluorescence, and are nano-scale in size, there is a clear need for an imaging technique to study them with high resolution, high absorption sensitivity, temporal resolution and fast acquisition time. The proposed PTN will provide unprecedented resolution with enhanced absorption sensitivity, thus opening new windows into unexplored areas of biological research associated with cell metabolic activity, oxidization, endocytosis, phagocytosis, melanogenesis, and apoptosis.