Borges, H. M. | Search bioRxiv

bioRxiv2025

Feature-Driven Whole-Tissue Imaging with Subcellular Resolution

Understanding how subcellular structures and events shape tissue-wide phenomena remains a central challenge in biology. We present Multiscale Cleared Tissue Axially Swept Light-Sheet Microscopy (MCT-ASLM), a platform combining cm-scale imaging with targeted high-resolution interrogation of intact tissues in human-guided or autonomous modes. Capable of capturing fields of view up to 21 mm at micron-scale resolution, MCT-ASLM can seamlessly transition to submicron (~300 nm) isotropic resolution for targeted imaging. This versatility enables comprehensive studies of hierarchical organization and spatially complex processes, including mapping neuronal circuits in rat brains, visualizing glomerular innervation in mouse kidneys, and examining metastatic tumor microenvironments. By bridging subcellular to tissue-level scales, MCT-ASLM offers a powerful method for unraveling how local events contribute to global biological phenomena.

biophysics↗

bioRxiv2024

Mechanically Sheared Axially Swept Light-Sheet Microscopy

We present a mechanically sheared image acquisition format for upright and open-top light-sheet microscopes that automatically places data in its proper spatial context. This approach, which reduces computational post-processing and eliminates unnecessary interpolation or duplication of the data, is demonstrated on an upright variant of Axially Swept Light-Sheet Microscopy (ASLM) that achieves a field of view, measuring 774 x 435 microns, that is 3.2-fold larger than previous models and a raw and isotropic resolution of [~]420 nm. Combined, we demonstrate the power of this approach by imaging sub-diffraction beads, cleared biological tissues, and expanded specimens.

biophysics↗