Exploring Single-Molecule Biophotonics for Ultrahigh-Resolution Spatiotemporal-Multiplexed Optical Microscopy

探索用于超高分辨率时空多重光学显微镜的单分子生物光子学

• 批准号: 10251215
• 负责人: Shu Jia
• 金额: $ 36.8万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10251215
• 关键词: 3-Dimensional; Address; Aging; Architecture; Biocompatible Materials; Biological; Biomedical Research; Biomedical Technology; Biophotonics; Brain; Brain imaging; Complex; Development; Disease; Engineering; Foundations; Future; Health; Homeostasis; Human; Image; Imaging technology; Immune system; Investigation; Light; Microglia; Microscopy; Mission; Molecular; National Institute of General Medical Sciences; Neuroimmune; Optics; Organism; Pathway interactions; Personal Satisfaction; Public Health; Research; Research Support; Resolution; Role; Specificity; Speed; Technology; Time; Tissues; Translating; Work; bioimaging; biological systems; complex biological systems; computer framework; high throughput technology; innovation; insight; instrumentation; light microscopy; multiplexed imaging; nanoscale; next generation; optical imaging; programs; single molecule; spatiotemporal; tool

Project Summary / Abstract The distribution and interactions of molecules in three-dimensionally organized cellular networks are fundamen- tal to the function of living systems. However, to date, a complete understanding of how local molecular mecha- nisms are integrated over larger scales to support tissue functions, or contribute to disease initiation, is still lacking. The challenges are mainly due to the limitations in imaging technology to provide molecular specificity, nanometer-scale resolution, ultrafast speed across larger volumes of tissue. To address the challenge, the pro- posed research program investigates the physical and engineering principles underlying optical imaging in com- plex biological materials, and utilizes these principles to develop new biophotonic tools for next-generation light microscopy. The objective of this proposal is to establish a research program on transformative bioimaging tech- nology for high-throughput extraction of single-molecule information in biological systems. Specifically, the pro- posed research program proceeds in three major directions to develop and apply enabling technologies for un- derstanding the ultrastructural architecture, fast dynamics, and spatiotemporal-multiplexed molecular information in complex biological systems: 1) Wavefront-engineered super-resolution microscopy to allow nanometer-scale imaging at and beyond the tis- sue level with isotropic 3D resolution and large imaging depth; 2) High-resolution light-field microscopy and computational super-resolution imaging to enable ultrafast, live im- aging of large-scale, volumetric biological dynamics and activities; and 3) Spatiotemporal-multiplexed imaging and a proof-of-principle investigation of the brain immune system. The research integrates and translates innovations in physical concepts, computational frameworks, and ad- vanced optical engineering and instrumentation into enabling technologies for biomedical investigations. The significant impact of the work will advance the imaging power across unexplored regimes in both space and time for a better understanding of the molecular basis for the functions of tissues and organisms. The spatiotemporal- multiplexed imaging of the brain immune system will lay the technological foundation for future systematic inves- tigations of the role of microglia in brain homeostasis, circuit formation, and disease initiation and protection. In the long term, the proposed program is expected to not only provide new insights for brain study, but also open up many new pathways to a broad range of biomedical research, and ultimately enable new discoveries to ad- dress challenges in human well-being.

项目概要/摘要 三维组织的细胞网络中分子的分布和相互作用是基础 与生命系统的功能有关。然而，迄今为止，对局部分子机制如何的完整理解 Nisms 在更大范围内整合以支持组织功能或有助于疾病的发生，仍然是 缺乏。挑战主要是由于成像技术提供分子特异性的限制， 纳米级分辨率，超快速度穿过更大体积的组织。为了应对这一挑战，亲 提出的研究计划调查了计算机中光学成像的物理和工程原理 复合生物材料，并利用这些原理开发用于下一代光的新生物光子工具 显微镜。该提案的目标是建立一个关于变革性生物成像技术的研究计划 生物系统中单分子信息高通量提取的科学。具体来说，亲 提出的研究计划在三个主要方向上进行，以开发和应用联合国的使能技术 了解超微结构、快速动力学和时空多重分子信息 在复杂的生物系统中： 1) 波前设计的超分辨率显微镜可实现纳米级成像 具有各向同性3D分辨率和大成像深度的苏级水平； 2）高分辨率光场显微镜和计算超分辨率成像，以实现超快、实时成像 大规模、体积生物动力学和活动的老化；和 3）时空多重成像和大脑免疫系统的原理验证研究。 该研究整合并转化了物理概念、计算框架和广告方面的创新。 将光学工程和仪器先进到生物医学研究的支持技术中。这 这项工作的重大影响将提高在空间和时间上未探索的区域的成像能力 更好地了解组织和生物体功能的分子基础。时空—— 脑免疫系统的多重成像将为未来的系统研究奠定技术基础 小胶质细胞在大脑稳态、回路形成以及疾病发生和保护中的作用。在 从长远来看，拟议的计划不仅有望为大脑研究提供新的见解，而且还将开放 为广泛的生物医学研究开辟许多新途径，并最终使新发现能够应用于 着装对人类福祉的挑战。