Toward Systems Biophotonics: Imaging Biology across High Dimensions and Scales

项目总结/摘要 PI研究计划的总体研究目标旨在推进成像科学和技术 to transform转变biomedical生物医学research研究.到目前为止，仍然缺乏一个完整的理解，以阐明生物分子- 细胞器、细胞器和微环境在单个细胞内组装，它们在大群体中的变化， 以及它们在细胞和组织功能、发育以及疾病引发和治疗中的综合作用。 存在主要未满足的成像需求，以探测细胞内和多参数复杂性， 细胞和组织中的异质性，具有3D纳米级分辨率、体积能力、高通量和传感能力， 稳定性和平台通用性。为了满足需求，PI的实验室研究了新的物理， 工程，仪器原理和系统，并部署它们来阐明基础和 医学发现这一更新建议旨在继续努力，建立和加强亲， Gram在系统生物光子学领域的领导地位，是成像创新和生命科学之间的关键接口。 具体而言，PI建议研究计划从三个主要方向进行，以提供 技术，克服了空间，时间和可访问性方面的成像挑战， 生物复杂性：（1）波物理学和超分辨率显微镜探测细胞内的复杂性， 具有3D超高分辨率、体积能力、高通量和灵敏度以及平台的异质性 可推广性;（2）光场显微镜和计算显微镜能够进行询问和超快， 多尺度、体积生物动力学和活动的体内成像;（3）微型显微镜和照相机 物理转换传统的成像平台和增强成像设备的可访问性， 成像条件、模态和生物系统。成功完成和传播 预计所提出的研究将（i）承诺并催化成像科学的发现和转化， （二）提供方法途径，并彻底改变生物医学调查限制 通过传统的方法，和（iii）改造现有的成像基础设施，奠定了关键的知识基础- 更广泛的科学，工程和技术突破。

PROJECT SUMMARY / ABSTRACT The overarching research goal of the PI’s research program aims to advance imaging science and technology to transform biomedical research. To date, a complete understanding is still lacking to elucidate how biomole- cules, organelles, and microenvironments are assembled within single cells, their variations over large popula- tions, and their integrated roles in cell and tissue functions, developments, and disease initiation and therapeutics. There have been major unmet imaging needs to probe the intracellular and multi-parametric complexities and heterogeneity in cells and tissues with 3D nanoscale resolution, volumetric capability, high throughput and sen- sitivity, and platform generalizability. To address the demands, the PI’s laboratory investigates the novel physical, engineering, and instrumental principles and systems and deploys them to illuminate both fundamental and medical discoveries. This renewal proposal aims to continue the efforts and establish and strengthen the pro- gram’s leadership in systems biophotonics at the critical interface between imaging innovations and life sciences. Specifically, the PI proposes the research program to proceed in three major directions to provide enabling technologies that overcome imaging challenges in space, time, and accessibility for a deeper understanding of biological complexities: (1) wave physics and super-resolution microscopy to probe intracellular complexities and heterogeneity with 3D ultrahigh-resolution, volumetric capability, high throughput and sensitivity, and platform generalizability; (2) light-field microscopy and computational microscopy to enable the interrogation and ultrafast, in vivo imaging of multi-scale, volumetric biological dynamics and activities; (3) miniature microscopy and camera physics to transform conventional imaging platforms and enhance imaging device accessibility to wide-ranging imaging conditions, modalities, and biological systems. The successful accomplishment and dissemination of the proposed research are anticipated to (i) promise and catalyze the discovery and translation of imaging sci- ence and technology, (ii) provide methodological avenues and revolutionize biomedical investigations restrained by conventional methods, and (iii) transform existing imaging infrastructure, laying a critical intellectual founda- tion for broader science, engineering, and technology breakthroughs.