Multi-immersion oblique plane microscope (miOPM): a reconfigurable platform for high-resolution light-sheet fluorescence microscopy
Year: 2026
Type: article
Abstract: Light-Sheet Fluorescence Microscopy (LSFM) enables gentle, rapid, and efficient volumetric imaging of biological specimens. Despite its potential, LSFM has fragmented into multiple variants, each narrowly optimized for specific samples or imaging regimes, limiting its broad applicability. To overcome this barrier, we introduce the multi-immersion oblique plane microscope (miOPM), an adaptable LSFM platform for high-resolution imaging ranging from subcellular dynamics to whole organisms and cleared tissues. miOPM uniquely supports seamless interchangeability of oil, water, and air objectives, and maintains diffraction limited performance across a refractive index range of 1.33 - 1.51. It is compatible with standard sample mounting, current clearing protocols and high-throughput 3D imaging. We leverage miOPM to image diverse biological specimens at multiple spatial scales. By greatly expanding the adaptability and ease of use of LSFM, miOPM is poised to democratize advanced three-dimensional imaging.
Source: Nature Methods
Authors: Bingying Chen, Alfred Millett-Sikking, Bo-Jui Chang, Seweryn Gałecki, Stephan Daetwyler, Jenny Jiou, Jim Monistrol, Qionghua Shen, Felix Zhou, Hsin-Yu Lin, Edward Jenkins, Miriam C. Stein, Madeleine Marlar-Pavey, Gabriel Sturm, Alexander L. Li, Qiaosi Tang, Brian Y. Feng, Ulises Diaz, Yannan Chen, Aryaman Shalizi, Astrid Gillich, Jonathan R. Friedman, Raju Tomer, Wallace F. Marshall, Sarah Shahmoradian, Kevin M. Dean, Reto Fiolka
Institutions: The University of Texas Southwestern Medical Center, Calico Life Sciences, Silesian University of Technology, Walter and Eliza Hall Institute of Medical Research, Deutsches Elektronen-Synchrotron DESY, Centre for Structural Systems Biology, University of Oxford, Kennedy Institute of Rheumatology, University of California, San Francisco, Princeton University, Columbia University
Language: English
Subfield: Biophysics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: University of Texas Southwestern Medical Center, Center for Strategic Scientific Initiatives, National Cancer Institute, University of Exeter, National Institutes of Health, Medical Research Council, National Institute of Mental Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering
Awards: A comparative approach for decomposing the mammalian brain architectural complexity, Spatial determinants in lipid metabolic organization at the sub-organelle level, Transformative microscopes to image across spatiotemporal scales, UTSW-UNC Center for Cell Signaling Analysis, Dynamic Internal Spatial Organization of Mitochondria, Omni Oblique Plane Microscope to spread light-sheet based imaging in biomedical research, Imaging mechanisms of metastatic tumor formation in situ
OpenAlex ID: W7222930764