Toward Systems Biophotonics: Imaging Biology across High Dimensions and Scales

项目摘要/摘要 PI研究计划的总体研究目标是推动成像科学和技术 改变生物医学研究。到目前为止，还缺乏一个完整的理解来阐明生物分子- 细胞、细胞器和微环境在单个细胞内组装，它们在大种群中的变化-- 以及它们在细胞和组织功能、发育、疾病启动和治疗中的综合作用。 在探索细胞内和多参数复杂性方面，主要成像需求尚未得到满足 细胞和组织中的异质性具有3D纳米级分辨率、体积能力、高通量和敏感度 敏感度和平台通用性。为了满足需求，PI的实验室研究了新的物理， 工程学、仪器原理和系统，并部署它们以说明基本和 医学发现。这项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处于成像创新和生命科学之间的关键界面。 具体地说，PI建议研究方案在三个主要方向上进行，以提供支持 克服空间、时间和可访问性方面的成像挑战的技术，以更深入地了解 生物复杂性：(1)波物理和超分辨率显微镜探测细胞内复杂性和 具有3D超高分辨率、体积能力、高通量和灵敏度的异构性，以及平台 通用性；(2)光场显微镜和计算显微镜，使讯问和超快， 多尺度、体积生物动力学和活动的活体成像；(3)微型显微镜和照相机 物理学改变传统成像平台，提高成像设备的可获得性 成像条件、方式和生物系统。成功地完成和传播了 这项拟议的研究有望(I)承诺并催化发现和翻译影像脊髓损伤-- 科学和技术，(2)提供方法途径，并使受限制的生物医学调查发生革命性变化 通过常规方法，以及(Iii)改造现有的成像基础设施，奠定关键的智力基础- 争取更广泛的科学、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.