I-Corps: A super-resolution optical imaging system for whole cells and tissues

I-Corps：全细胞和组织的超分辨率光学成像系统

• 批准号: 2345637
• 负责人: Fang Huang
• 金额: $ 5万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2345637&HistoricalAwards=false
• 关键词: Corps; super; resolution; optical; imaging

The broader impact/commercial potential of this I-Corps project is the development of a super-resolution microscopy approach designed for detailed 3D imaging in whole cell and tissue samples. Most biological laboratories utilize fluorescence microscopy, with the majority being confocal and having a resolution limit of around 300 nm, which is insufficient for many subcellular structures. While other techniques such as scanning electron microscopy (SEM) and cryogenic electron microscopy offer greater resolution, they come with their own limitations, such as the inability to differentiate protein species. The proposed system, built on the foundational work on super-resolution microscopy, is compatible with live cells, and uses adaptive optics, simultaneous dual-color imaging, and real-time, artifact-free super-resolution image reconstruction. The proposed technology may have broad implications, facilitating advancements in cell biology, biomedical engineering, and therapeutics, and offering granular insights into biological processes and potentially improving diagnostics and treatments.This I-Corps project is based on the development of an integrated single-molecule localization microscopy (SMLM) tailored for 3D tissue imaging. While conventional fluorescence microscopes like confocal reach their limit with a resolution above ~300 nm due to light diffraction, the SMLM provides a distinct methodology. The proposed technology capitalizes on the "blinking" phenomena of individual fluorophores, and pinpoints these events over multiple frames, resulting in an ultra-defined super-resolution image. In addition, this technology integrates artificial intelligence driven adaptive optics into the process facilitating instantaneous adjustments for sample-induced aberrations, which unlocks the capability for deep tissue super-resolution imaging up to 250 µm-cut brain sections. The proposed technology may serve varied research landscapes, specifically lab environments that work on cell biology, neuroscience, and developmental biology.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.

该I-Corps项目的更广泛的影响/商业潜力是开发了用于全细胞和组织样品中详细的3D成像的超分辨率显微镜方法。大多数生物实验室都使用荧光显微镜，其中大多数是共聚焦，并且分辨率极限约为300 nm，这对于许多亚细胞结构不足。尽管其他技术（例如扫描电子显微镜（SEM）和低温电子显微镜）提供了更大的分辨率，但它们具有自身的局限性，例如无法区分蛋白质。所提出的系统建立在超分辨率显微镜基础工作的基础上，与活细胞兼容，并使用自适应光学器件，简单的双色成像和实时的无伪影超级分辨率图像重建。所提出的技术可能具有广泛的影响，支持细胞生物学，生物医学工程和治疗方面的进步，并为生物学过程提供颗粒状见解，并有可能改善诊断和治疗方法。此I-Corps项目基于针对3D组织图像的集成单分子定位微观（SMLM）的综合单分子定位显微镜（SMLM）的开发。虽然像共聚焦这样的常规荧光显微镜达到其极限，而分辨率高于〜300 nm，但SMLM提供了一种独特的方法。所提出的技术利用了单个荧光团的“闪烁”现象，并在多个帧上指定这些事件，从而产生了超定义的超分辨率图像。此外，该技术将人工智能驱动光学器件集成到该过程中，以支持样品诱导的畸变的瞬时调整，从而释放了深层组织超分辨率成像的能力，最高可高达250 µm切割脑切片。拟议的技术可以为各种研究景观提供服务，特别是在细胞生物学，神经科学和发育生物学方面起作用的实验室环境。该奖项反映了NSF的法定任务，并通过使用基金会的智力优点和更广泛的影响来评估NSF的法定任务。