Peer-reviewedCC BY-NC-ND 4.0Nature Methods
Multi-immersion oblique plane microscope (miOPM): a reconfigurable platform for high-resolution light-sheet fluorescence microscopy
13 affiliations
- 1Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX USA
- 2Cecil H. and Ida Green Center for Systems Biology, UT Southwestern Medical Center, Dallas, TX USA
- 3Calico Life Sciences LLC, South San Francisco, CA USA
- 4Department of Systems Biology and Engineering, Silesian University of Technology, Gliwice, Poland
- 5Center for Alzheimer’s and Neurodegenerative Diseases, Peter O’Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX USA
- 6Present Address: Ubiquitin Signalling Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
- 7Present Address: CSSB Centre for Structural Systems Biology, Deutsches Elektronen-Synchrotron DESY, Hamburg, Germany
- 8Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK
- 9Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX USA
- 10Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA USA
- 11Department of Biological Science, Columbia University, New York, NY USA
- 12Present Address: Princeton Neuroscience Institute, Princeton University, Princeton, NJ USA
- 13Department of Biophysics, UT Southwestern Medical Center, Dallas, TX USA
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. Here 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 supports seamless interchangeability of oil, water and air objectives and maintains diffraction-limited performance across a refractive index range of 1.33 to 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 expanding the adaptability and ease of use of LSFM, miOPM is poised to democratize advanced 3D imaging.
Related
- MUFASA: a continuous-time stochastic framework for realistic fluorescence microscopy simulation
- Quantitative Colocalization Analysis in Fluorescence Microscopy
- High-precision correlative fluorescence and electron cryo microscopy using two independent alignment markers
- De novo pan-rhodamine binders for fluorescence microscopy from mammalian cells to extremophiles
- siRNA/mRNA payload of lipid nanoparticles quantified using fluorescence microscopy and correlation spectroscopy
BibTeX
@article{chen2026multiimmersion,
title = {{Multi-immersion oblique plane microscope (miOPM): a reconfigurable platform for high-resolution light-sheet fluorescence microscopy}},
author = {Bingying Chen and Alfred Millett-Sikking and Bo-Jui Chang and Seweryn Gałecki and Stephan Daetwyler and Jenny Jiou and Jim Monistrol and Qionghua Shen and Felix Zhou and Hsin-Yu Lin and Edward Jenkins and Miriam C. Stein and Madeleine Marlar-Pavey and Gabriel Sturm and Alexander L. Li and Qiaosi Tang and Brian Y. Feng and Ulises Diaz and Yannan Chen and Aryaman Shalizi and Astrid Gillich and Jonathan R. Friedman and Raju Tomer and Wallace F. Marshall and Sarah Shahmoradian and Kevin M. Dean and Reto Fiolka},
journal = {Nature Methods},
year = {2026},
month = oct,
doi = {10.1038/s41592-026-03245-0},
url = {https://doi.org/10.1038/s41592-026-03245-0},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Multi-immersion oblique plane microscope (miOPM): a reconfigurable platform for high-resolution light-sheet fluorescence microscopy
AU - Bingying Chen
AU - Alfred Millett-Sikking
AU - Bo-Jui Chang
AU - Seweryn Gałecki
AU - Stephan Daetwyler
AU - Jenny Jiou
AU - Jim Monistrol
AU - Qionghua Shen
AU - Felix Zhou
AU - Hsin-Yu Lin
AU - Edward Jenkins
AU - Miriam C. Stein
AU - Madeleine Marlar-Pavey
AU - Gabriel Sturm
AU - Alexander L. Li
AU - Qiaosi Tang
AU - Brian Y. Feng
AU - Ulises Diaz
AU - Yannan Chen
AU - Aryaman Shalizi
AU - Astrid Gillich
AU - Jonathan R. Friedman
AU - Raju Tomer
AU - Wallace F. Marshall
AU - Sarah Shahmoradian
AU - Kevin M. Dean
AU - Reto Fiolka
PY - 2026
DA - 2026/10/19
JO - Nature Methods
DO - 10.1038/s41592-026-03245-0
UR - https://doi.org/10.1038/s41592-026-03245-0
AB - 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. Here 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 supports seamless interchangeability of oil, water and air objectives and maintains diffraction-limited performance across a refractive index range of 1.33 to 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 expanding the adaptability and ease of use of LSFM, miOPM is poised to democratize advanced 3D imaging.
SN - 1548-7091
SN - 1548-7105
ER -