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Transformative microscopes to image across spatiotemporal scales

跨时空尺度成像的变革显微镜

基本信息

批准号：
10700160
负责人：
Reto Paul Fiolka
金额：
$ 40.5万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-20 至 2024-07-31
项目状态：
已结题

项目摘要

Project abstract How molecular organization and activity leads to tissue level outcomes is, arguably, one of the big remaining open questions in biology. Bridging these two areas is key to biomedical advances, yet is technically challenging because we cannot observe with molecular precision at the tissue scale. While optical microscopy is the method of choice to observe architecture and dynamics within living cells and organisms, it has fundamental limitations in spatiotemporal resolution and optical penetration depth. Thus our most detailed observations of cellular dynamics and ultrastructure have been limited to single cells that were far removed from their physiological context. Here I propose to significantly expand the reach of super-resolution microscopy to encompass tissues and whole model organisms. This lies far outside of the capabilities of the current state of the art and requires significant progress in volumetric acquisition speed, sensitivity and optical penetration depth. I propose to advance the field by combining three different fields of microscopy. Some of these combinations are non-trivial and thus have not been experimentally tractable so far. I propose novel concepts that can bridge these different fields and overcome technical and fundamental limitations. Furthermore, a novel adaptive sampling approach that only images the most informative voxels at the highest resolution will overcome fundamental barriers to high-resolution imaging over large volumes. I hypothesize that my new instrumentation combined with an intelligent sampling strategt can improve acquisition speed up to 100 fold while reducing phototoxicity and data storage needs. The resulting new microscope technology will dramatically speed up high-resolution imaging over large volumes and hence will enable large volume imaging experiments that have been prohibited by either lack of spatial resolution, optical penetration depth or acquisition speed.

项目摘要分子组织和活动如何导致组织水平的结果，可以说，生物学中尚未解决的大问题。将这两个领域联系起来是生物医学的进步，但在技术上是具有挑战性的，因为我们不能观察与在组织尺度上的分子精确度。虽然光学显微镜是首选的方法，为了观察活细胞和有机体的结构和动力学，时空分辨率和光学穿透深度的基本限制。因此我们对细胞动力学和超微结构的最详细的观察有限，到远离其生理环境的单细胞。在这里，我建议显着扩大超分辨率显微镜的范围，包括组织和整个模式生物。这远远超出了并要求在体积采集方面取得重大进展速度、灵敏度和光学穿透深度。我建议通过以下方式推进该领域结合了三个不同的显微镜领域。其中一些组合是非平凡的因此迄今为止在实验上还不容易处理。我提出了一些新的概念，跨越这些不同的领域，克服技术和基础限制。此外，一种新的自适应采样方法，只图像的信息量最大，最高分辨率的体素将克服高分辨率的基本障碍在大体积上成像。我假设我的新仪器智能采样策略可将采集速度提高100倍，减少光毒性和数据存储需求。由此产生的新显微镜技术将大大加快大体积的高分辨率成像，能够进行大体积成像实验，这些实验由于缺乏空间分辨率、光学穿透深度或采集速度。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Fiji plugin for annotating movies with custom arrows.

DOI：
10.1242/bio.056200
发表时间：
2020-12-01
期刊：
Biology open
影响因子：
2.4
作者：
Daetwyler S;Modes CD;Fiolka R
通讯作者：
Fiolka R

Light-sheet microscopy at high resolution.

DOI：
10.1038/s41587-021-01101-4
发表时间：
2021-11
期刊：
NATURE BIOTECHNOLOGY
影响因子：
46.9
作者：
Fiolka, Reto
通讯作者：
Fiolka, Reto

Light-sheets and smart microscopy, an exciting future is dawning.

DOI：
10.1038/s42003-023-04857-4
发表时间：
2023-05-09
期刊：
COMMUNICATIONS BIOLOGY
影响因子：
5.9
作者：
Daetwyler, Stephan;Fiolka, Reto Paul
通讯作者：
Fiolka, Reto Paul

DaXi-high-resolution, large imaging volume and multi-view single-objective light-sheet microscopy.

DOI：
10.1038/s41592-022-01417-2
发表时间：
2022-04
期刊：
NATURE METHODS
影响因子：
48
作者：
Yang, Bin;Lange, Merlin;Millett-Sikking, Alfred;Zhao, Xiang;Bragantini, Jordao;VijayKumar, Shruthi;Kamb, Mason;Gomez-Sjoberg, Rafael;Solak, Ahmet Can;Wang, Wanpeng;Kobayashi, Hirofumi;McCarroll, Matthew N.;Whitehead, Lachlan W.;Fiolka, Reto P.;Kornberg, Thomas B.;York, Andrew G.;Royer, Loic A.
通讯作者：
Royer, Loic A.