Dual-Mode Bio-CM2: Multimodal Computational Miniature Mesoscope for Fluorescence and Label-Free Imaging
- 1Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, USA; Department of Biomedical Engineering, Boston University,
Abstract
Understanding biological function often requires complementary information on molecular identity, morphology, behavior, and physiology acquired simultaneously from the same specimen. Achieving this capability in miniature microscopes remains challenging because integrating multiple imaging contrasts typically increases optical complexity while compromising field of view (FOV), spatial resolution, or form factor. Here we present dual-mode Bio-CM2, a multimodal computational miniature mesoscope that simultaneously captures fluorescence and label-free reflectance through a shared optical architecture based on distributed computational optics. The system enables frame-interleaved, co-registered dual-mode imaging over a [~]7.5 x 10 mm2 FOV with [~]6 m lateral resolution. We demonstrate the versatility of dual-mode Bio-CM2 across diverse biological systems. In freely moving Caenorhabditis elegans, reflectance captures body posture and locomotor behavior that contextualize fluorescently labeled protein aggregates. In freely swimming larval zebrafish, reflectance captures whole-body morphology and swimming behavior, while fluorescence visualizes cardiac activity. In head-fixed mice, simultaneous fluorescence and reflectance imaging across the bilateral dorsal cortex provides complementary measurements of neuronal calcium activity and intrinsic hemodynamic signals. By integrating molecularly specific fluorescence with complementary reflectance contrast, dual-mode Bio-CM2 extends distributed computational optics into a scalable platform for multimodal miniature imaging.
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BibTeX
@misc{deng2026dualmode,
title = {{Dual-Mode Bio-CM2: Multimodal Computational Miniature Mesoscope for Fluorescence and Label-Free Imaging}},
author = {Q. Deng and G. Hu and B. C. Rauscher and M. Villafuerte and B. Weinberg and Z. Chen and H. Feng and A. Devor and M. Thunemann and L. Tian},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.08.750281},
url = {https://www.biorxiv.org/content/10.64898/2026.09.08.750281v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Dual-Mode Bio-CM2: Multimodal Computational Miniature Mesoscope for Fluorescence and Label-Free Imaging
AU - Q. Deng
AU - G. Hu
AU - B. C. Rauscher
AU - M. Villafuerte
AU - B. Weinberg
AU - Z. Chen
AU - H. Feng
AU - A. Devor
AU - M. Thunemann
AU - L. Tian
PY - 2026
DA - 2026/09/08
PB - bioRxiv
DO - 10.64898/2026.09.08.750281
UR - https://www.biorxiv.org/content/10.64898/2026.09.08.750281v1
AB - Understanding biological function often requires complementary information on molecular identity, morphology, behavior, and physiology acquired simultaneously from the same specimen. Achieving this capability in miniature microscopes remains challenging because integrating multiple imaging contrasts typically increases optical complexity while compromising field of view (FOV), spatial resolution, or form factor. Here we present dual-mode Bio-CM2, a multimodal computational miniature mesoscope that simultaneously captures fluorescence and label-free reflectance through a shared optical architecture based on distributed computational optics. The system enables frame-interleaved, co-registered dual-mode imaging over a [~]7.5 x 10 mm2 FOV with [~]6 m lateral resolution. We demonstrate the versatility of dual-mode Bio-CM2 across diverse biological systems. In freely moving Caenorhabditis elegans, reflectance captures body posture and locomotor behavior that contextualize fluorescently labeled protein aggregates. In freely swimming larval zebrafish, reflectance captures whole-body morphology and swimming behavior, while fluorescence visualizes cardiac activity. In head-fixed mice, simultaneous fluorescence and reflectance imaging across the bilateral dorsal cortex provides complementary measurements of neuronal calcium activity and intrinsic hemodynamic signals. By integrating molecularly specific fluorescence with complementary reflectance contrast, dual-mode Bio-CM2 extends distributed computational optics into a scalable platform for multimodal miniature imaging.
ER -