Axially swept light-sheet microscopy (ASLM) enables fast volumetric imaging with reduced photodamage, yet its performance is often limited by inherent coupling between lateral field of view and axial resolution. Conventional ASLM imaging systems are constrained by fixed optical geometries, where isotropic imaging with muti-scale axial resolution is not efficient and improving signal collection typically requires higher laser power at the cost of increased photodamage. We present a dynamic light-sheet waist control strategy that enhances signal collection efficiency without increasing excitation power while enabling imaging with tunable, multi-scale axial resolution. By employing a variable beam expander to adjust the incident beam diameter, the system modulates the thickness of light-sheet waist to image the specimen efficiently across a diverse range of specimens. This approach directly addresses the signal-starvation problem inherent to ASLM and provides a flexible framework to image large biological samples.
Sain et al. (2026) studied this question.