Depth-enhanced molecular imaging with two-photon oblique plane microscopy.

ABSTRACT: High-numerical-aperture (NA) oblique plane microscopy enables noninvasive fluorescence imaging of subcellular dynamics without requiring radical sample modification. However, performance degrades at depth in multicellular specimens as scattering and refractive-index heterogeneity raise out-of-focus background. We report a two-photon oblique plane microscope that improves resolution at depth by combining high-NA single-objective detection with multiphoton plane illumination. The microscope achieves $\sim\!300$ nm lateral and $\sim\!650$ nm axial resolution, with single-molecule sensitivity in vivo. Compared with two-photon point scanning, the lower illumination NA delivers an order of magnitude lower peak intensity, enabling $>\!5\times$ faster volumetric acquisition (up to $3.25 \times 10^

SUBMITTER: Keomanee-Dizon K 

PROVIDER: S-EPMC12642766 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature