SLICE: A Turnkey, Low-Cost Light-Sheet Fluorescence Microscope for Sub-Cellular Imaging of Cleared Tissues at Mesoscale Volumes

Abstract Light-sheet fluorescence microscopy (LSFM) has transformed biological imaging, yet its cost and complexity limits accessibility to the scientific community. SLICETM—a turnkey light sheet imaging system—builds on the projected light-sheet microscopy (pLSM) framework to democratize high-performance LSFM. By integrating cost-effective scanned laser pico projectors, optimized optics, a precision nanopositioning XYZ stage, and the intuitive BrightSLICETM software, SLICE achieves sub-cellular resolution and rapid volumetric imaging of cleared tissues at a fraction of the cost of other commercial LSFM systems. Performance benchmarks confirm imaging quality comparable, or exceeding, that of systems 4–10 times more expensive. SLICE enables high-throughput imaging across diverse tissue-clearing protocols and fluorophores, with robust resolution and minimal photobleaching. Its streamlined, benchtop design makes advanced 3D microscopy accessible to a wider range of laboratories, setting a new standard for affordability, usability, and performance in mesoscale imaging. SLICE has been honored with the 2025 ­Microscopy Today Innovation Award.