Summary
A bioRxiv preprint describes Bio-CM2, a miniature mesoscope combining fluorescence and label-free reflectance imaging across a 7.5 × 10 mm² field of view. Demonstrations in worms, zebrafish and mice paired molecular signals with morphology, behaviour and physiology.
Researchers have presented dual-mode Bio-CM2, a computational miniature mesoscope that combines fluorescence and label-free reflectance imaging through a shared optical architecture. In a bioRxiv preprint posted on September 14, 2026, the authors report frame-interleaved, co-registered imaging across a field of view of approximately 7.5 × 10 mm², with approximately 6 μm lateral resolution.
The system was demonstrated in three animal models: freely moving Caenorhabditis elegans, freely swimming larval zebrafish and head-fixed mice. The experiments paired fluorescence, which can provide molecularly specific information, with reflectance, which records light reflected from tissue or the organism without requiring a fluorescent label.
One miniature system, two imaging contrasts
Fluorescence is useful when researchers need to track a selected protein, cell population or physiological signal using fluorescent markers. Reflectance provides a complementary label-free view of structure and movement. Combining the two can link a molecular event to the behaviour, anatomy or broader physiology of the same specimen.
Bio-CM2 uses a shared architecture based on distributed computational optics. In this approach, optical measurement and computational processing work together to support imaging, allowing different contrasts to be collected within the same miniature platform. The preprint describes the two modes as frame-interleaved and co-registered: measurements are acquired in alternating frames, while the resulting images are aligned spatially so that corresponding features can be compared.
The reported field of view is large enough for the demonstrations to capture substantial portions of the organisms or mouse cortex while retaining micrometre-scale lateral resolution. The abstract does not provide a full engineering description of the device’s physical dimensions or operating speed.
Demonstrations in worms, fish and mice
In freely moving C. elegans, reflectance imaging captured body posture and locomotor behaviour. Fluorescence simultaneously tracked labelled protein aggregates. This pairing allowed the fluorescent structures to be interpreted alongside the animal’s movement and physical state.
In freely swimming larval zebrafish, reflectance imaging recorded whole-body morphology and swimming behaviour, while fluorescence visualised cardiac activity. The two contrasts therefore supplied structural and functional information from the same moving animal.
The mouse demonstration used head-fixed animals and covered the bilateral dorsal cortex. Fluorescence provided measurements of neuronal calcium activity, while reflectance captured intrinsic haemodynamic signals. Calcium activity and haemodynamic changes represent different aspects of brain function, so collecting them together can help relate neural activity to accompanying changes in tissue physiology.
Why the combination matters
Biological function is often distributed across several levels: molecular identity, cell activity, tissue structure, behaviour and physiology. Separate instruments can measure these properties, but combining their outputs may require difficult spatial and temporal alignment. Bio-CM2 is intended to collect complementary information within one miniature imaging system and from the same specimen.
The demonstrations show the platform’s potential across different experimental settings rather than a single application. The authors describe dual-mode Bio-CM2 as an extension of distributed computational optics into a scalable platform for multimodal miniature imaging.
The work remains an early-stage research result. It is presented as a bioRxiv preprint, and the reported demonstrations were performed in C. elegans, larval zebrafish and mice rather than in human participants. The findings establish the imaging system’s reported use in these animal experiments; clinical or human imaging applications were not part of the supplied report.