Federal Grant Award Summary

The National Institute of General Medical Sciences (NIGMS) awarded The Leland Stanford Junior University a $1.73 million Project Grant under the Biomedical Research and Research Training program (CFDA 93.859) beginning July 1, 2026, and extending through June 30, 2030. The award supports the development of a multi-resolution open-top light-sheet expansion microscopy system designed to achieve ultra-high resolution three-dimensional (3D) imaging capabilities. The deliverable represents a significant advancement over prior generations of open-top light-sheet (OTLS) microscopes, achieving lateral resolutions below 100 nanometers and axial resolutions below 350 nanometers through a combination of enhanced optical design (0.3 × 0.3 × 1 μm³ resolution) and moderate tissue expansion techniques (3–4×).

The research addresses a longstanding challenge in biomedical imaging by enabling high-throughput, ultra-high-resolution 3D visualization of large tissue specimens over millimeter-scale depth ranges and centimeter-scale lateral fields of view. This capability will facilitate critical biological investigations, including quantitative RNA transcription mapping for cellular atlases of large organs and characterization of ultrastructural morphology in expanded tissues. By leveraging camera-based light-sheet imaging rather than slower point-scanning approaches, the system reduces photobleaching and improves optical efficiency, making it well-suited for imaging optically cleared, hydrogel-embedded tissues. The work builds upon the Principal Investigator's established expertise in OTLS microscope development and represents a progression toward clinical and research applications requiring both high resolution and large-volume imaging capabilities.