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Peer-reviewedCC BY-NCScience Advances

MIMAS: An open-source microlens-array miniature microscope for accessible large-field cortical imaging in freely behaving mice

  • Mian Xie1,2,3,4
  • Jingyi Ma1,2
  • Baoyi Zhang1,2,5
  • Jian Lu6,7
  • Hongda Yin2,8
  • Yuanpeng Jiang1,2
  • Yuxi Zhao1,2,5
  • Yongjun Qian2,8
  • Zengcai V. Guo6,7
  • Wenhao Liu9
  • Qiang Fu10,11,12
  • Changliang Guo1,2
1 more authors
  • Liangyi Chen1,2
12 affiliations
  1. 1State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, National Biomedical Imaging Center, Peking University, Beijing, China.
  2. 2School of Future Technology, Peking University, Beijing, China.
  3. 3School of Life Sciences, Tsinghua University, Beijing, China.
  4. 4Peking University–Tsinghua University–National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Tsinghua University, Beijing, China.
  5. 5Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
  6. 6IDG/McGovern Institute for Brain Research, School of Basic Medical Sciences, Tsinghua University, 100084, Beijing, China.
  7. 7Tsinghua-Peking Center for Life Sciences, 100084, Beijing, China.
  8. 8The State Key Laboratory of Gene Function and Modulation Research, Peking-Tsinghua Center for Life Sciences, IDG/McGovern Institute for Brain Research, Beijing Advanced Center of RNA Biology, Peking University, Beijing, China.
  9. 9Innovation Photonics and Imaging Center, School of Instrumentation Science and Engineering, State Key Laboratory of Matter Behaviors in Space Environment, Frontier Science Center for Interaction between Space Environment and Matter, Harbin Institute of Technology; Harbin, China.
  10. 10Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.
  11. 11University of Chinese Academy of Sciences, Beijing 100049, China.
  12. 12State Key Laboratory of Advanced Manufacturing for Optical Systems, Changchun 130033, China.
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Abstract

Large-scale cortical dynamics during natural behavior are difficult to measure because head-mounted imaging systems must balance field of view, spatial resolution, weight, and optical complexity. Existing wide-field miniature microscopes often rely on compound or custom-corrected optical assemblies, which increase device complexity and limit accessibility for laboratories without specialized optics expertise. Here, we present the Miniature Integrated Microlens Array System (MIMAS), an open-source head-mounted fluorescence microscope that replaces conventional multi-element optics with a 4 × 5 microlens array as its sole imaging element. By combining modular subfield acquisition with computational registration and stitching, MIMAS achieves cellular-resolution imaging across an approximately 4 × 4.5 mm 2 field of view while weighing only 2.31 g. In freely behaving mice with sparse labeling of layer 2/3 cortical neurons, MIMAS enabled simultaneous calcium imaging across multiple dorsal cortical regions, with signals extracted from thousands of neurons. This broad sampling captured distributed cortical activity related to locomotor state and sparse position-modulated responses during open-field exploration without detectable disruption of locomotion or loss of signal quality over 30 min of recording. Beyond neuronal imaging, MIMAS also supported wide-field vascular imaging and resolved vessel caliber-dependent hemodynamic responses to isoflurane. These results establish MIMAS as a lightweight, accessible, and versatile platform for large-scale fluorescence imaging in freely behaving mice and demonstrate an alternative strategy for wide-field cortical imaging that lowers the optical complexity barrier for individual laboratories.

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Cite

BibTeXRIS
BibTeX
@article{xie2026mimas,
  title = {{MIMAS: An open-source microlens-array miniature microscope for accessible large-field cortical imaging in freely behaving mice}},
  author = {Mian Xie and Jingyi Ma and Baoyi Zhang and Jian Lu and Hongda Yin and Yuanpeng Jiang and Yuxi Zhao and Yongjun Qian and Zengcai V. Guo and Wenhao Liu and Qiang Fu and Changliang Guo and Liangyi Chen},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aei8743},
  url = {https://www.science.org/doi/10.1126/sciadv.aei8743},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - MIMAS: An open-source microlens-array miniature microscope for accessible large-field cortical imaging in freely behaving mice
AU  - Mian Xie
AU  - Jingyi Ma
AU  - Baoyi Zhang
AU  - Jian Lu
AU  - Hongda Yin
AU  - Yuanpeng Jiang
AU  - Yuxi Zhao
AU  - Yongjun Qian
AU  - Zengcai V. Guo
AU  - Wenhao Liu
AU  - Qiang Fu
AU  - Changliang Guo
AU  - Liangyi Chen
PY  - 2026
DA  - 2026/10/09
JO  - Science Advances
DO  - 10.1126/sciadv.aei8743
UR  - https://www.science.org/doi/10.1126/sciadv.aei8743
AB  - Large-scale cortical dynamics during natural behavior are difficult to measure because head-mounted imaging systems must balance field of view, spatial resolution, weight, and optical complexity. Existing wide-field miniature microscopes often rely on compound or custom-corrected optical assemblies, which increase device complexity and limit accessibility for laboratories without specialized optics expertise. Here, we present the Miniature Integrated Microlens Array System (MIMAS), an open-source head-mounted fluorescence microscope that replaces conventional multi-element optics with a 4 × 5 microlens array as its sole imaging element. By combining modular subfield acquisition with computational registration and stitching, MIMAS achieves cellular-resolution imaging across an approximately 4 × 4.5 mm 2 field of view while weighing only 2.31 g. In freely behaving mice with sparse labeling of layer 2/3 cortical neurons, MIMAS enabled simultaneous calcium imaging across multiple dorsal cortical regions, with signals extracted from thousands of neurons. This broad sampling captured distributed cortical activity related to locomotor state and sparse position-modulated responses during open-field exploration without detectable disruption of locomotion or loss of signal quality over 30 min of recording. Beyond neuronal imaging, MIMAS also supported wide-field vascular imaging and resolved vessel caliber-dependent hemodynamic responses to isoflurane. These results establish MIMAS as a lightweight, accessible, and versatile platform for large-scale fluorescence imaging in freely behaving mice and demonstrate an alternative strategy for wide-field cortical imaging that lowers the optical complexity barrier for individual laboratories.
SN  - 2375-2548
ER  -