美国北卡罗来纳大学教堂山分校Wesley R. Legant等研究人员合作开发出用于罕见复杂细胞事件成像的智能晶格光片显微镜。2024年1月2日，《自然—方法学》杂志在线发表了这项成果。

据介绍，光片显微镜可对生物标本进行快速高分辨率成像；然而，生物过程跨越时空尺度。此外，长期表型往往是由罕见或转瞬即逝的生物事件引发的，难以用单一成像模式捕捉。

为了克服这一局限性，研究人员展示了智能光片显微镜（smartLLSM），这是一种结合了基于人工智能的仪器控制的显微镜，可以在荧光倒置成像和晶格光片显微镜（LLSM）之间自主切换。研究人员将这种方法应用于两个独特的过程：细胞分裂和免疫突触形成。在每种情况下，smartLLSM都能提供数千个细胞的群体级统计数据，并能自主捕捉多色三维数据集或罕见事件的四维延时电影，其速度大大超过人类的能力。

由此，研究人员量化了紫杉醇剂量对分裂细胞纺锤体结构和动粒动态的影响，以及抗原强度对细胞毒性T淋巴细胞参与和免疫突触淋巴颗粒极化的影响。总之，smartLLSM能有效检测异质细胞群中的罕见事件，并通过高时空四维成像对这些过程进行统计意义上的重复记录。

附：英文原文

Title: Smart lattice light-sheet microscopy for imaging rare and complex cellular events

Author: Shi, Yu, Tabet, Jimmy S., Milkie, Daniel E., Daugird, Timothy A., Yang, Chelsea Q., Ritter, Alex T., Giovannucci, Andrea, Legant, Wesley R.

Issue&Volume: 2024-01-02

Abstract: Light-sheet microscopes enable rapid high-resolution imaging of biological specimens; however, biological processes span spatiotemporal scales. Moreover, long-term phenotypes are often instigated by rare or fleeting biological events that are difficult to capture with a single imaging modality. Here, to overcome this limitation, we present smartLLSM, a microscope that incorporates artificial intelligence-based instrument control to autonomously switch between epifluorescent inverted imaging and lattice light-sheet microscopy (LLSM). We apply this approach to two unique processes: cell division and immune synapse formation. In each context, smartLLSM provides population-level statistics across thousands of cells and autonomously captures multicolor three-dimensional datasets or four-dimensional time-lapse movies of rare events at rates that dramatically exceed human capabilities. From this, we quantify the effects of Taxol dose on spindle structure and kinetochore dynamics in dividing cells and of antigen strength on cytotoxic T lymphocyte engagement and lytic granule polarization at the immune synapse. Overall, smartLLSM efficiently detects rare events within heterogeneous cell populations and records these processes with high spatiotemporal four-dimensional imaging over statistically significant replicates.

DOI: 10.1038/s41592-023-02126-0

Source: https://www.nature.com/articles/s41592-023-02126-0