Efficient, large-FOV volumetric imaging with slanted grating oblique plane microscopy (sgOPM)

• Applicant: Professor Benjamin Judkewitz, Ph.D.
• Subject Area: Measurement Systems ; Experimental and Theoretical Network Neuroscience ; Medical Physics, Biomedical Technology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 581568557

High-resolution volumetric imaging of neuronal activity across large fields of view (FOV) is a crucial technological milestone for understanding vertebrate brain function. However, it remains challenging due to inherent limitations in currently available microscopy techniques. Conventional methods like two-photon microscopy provide excellent spatial resolution but are hindered by slow scanning rates that preclude large-FOV volumetric imaging. On the other hand, oblique plane microscopy (OPM) achieves fast volumetric rates, but faces a fundamental trade-off between light efficiency and resolution – which becomes prohibitive for high-resolution imaging beyond ~1 mm FOV. This presents a critical gap: current volumetric imaging methods cannot simultaneously achieve high resolution, large field of view, and efficient light collection. As a result, there is still no solution that enables light-efficient, high-speed, high-resolution imaging across brain-scale volumes in adult vertebrates, including fish. Overcoming this limitation requires a new optical strategy. As we outline in the proposal, recent advances in nanoscale photonics – specifically the development of slanted transmission gratings – now make it possible to achieve high-resolution volumetric microscopy with wide FOV and high light efficiency. Preliminary data, including finite-difference time-domain simulations and pilot whole-brain imaging experiments in the adult fish Danionella cerebrum, indicate that this approach could achieve diffraction efficiencies exceeding 80%, surpassing the light efficiency of alternatives by a factor of 5x-10x, nearly an order of magnitude. In summary, this proposal aims to develop a volumetric microscopy system capable of imaging the entire brain of small vertebrates at cellular resolution with high speed and minimal light loss. Such a tool would open new frontiers in functional neuroimaging, allowing detailed study of neuronal dynamics across brain-wide circuits.

• DFG Programme: New Instrumentation for Research