Index-agnostic oblique plane light sheet microscopy of centimetre-scale cleared tissues at subcellular resolution

Lamb, J. R.; Cardoso Mestre, M.; Fenwyn Longrin, K.; Bhat, P.; Stevenson, M.; Rhodes, A. D. Y.; Gosieniecka, J.; Redmond, L. C.; Higgins, C. A.; Rodriguez-Rodrigues, N.; Lancaster, M. A.; Manton, J. D.

doi:10.64898/2026.06.01.729284

bioRxiv · 10.64898/2026.06.01.729284

Index-agnostic oblique plane light sheet microscopy of centimetre-scale cleared tissues at subcellular resolution

Lamb, J. R.·Cardoso Mestre, M.·Fenwyn Longrin, K.·Bhat, P.·Stevenson, M.·Rhodes, A. D. Y.·Gosieniecka, J.·Redmond, L. C.·Higgins, C. A.·Rodriguez-Rodrigues, N.·Lancaster, M. A.·Manton, J. D.

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Abstract

We present cleared-tissue direct-view oblique plane microscopy (CtDvOPM), which enables optically sectioned subcellular resolution imaging of centimetre-scale tissues at high throughput over the full range of clearing media refractive indices (n = 1.33-1.56). CtDvOPM can image conventionally-mounted expanded, aqueous or non-aqueous cleared tissue samples at up to 2 {micro}m lateral by 14 {micro}m axial resolution over a 10.1 mm x 25.0 mm x 6.8 mm (x x y x z) sample volume without image tiling, at up to 400 million voxels per second.

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Lamb, J. R., Cardoso Mestre, M., Fenwyn Longrin, K., Bhat, P., Stevenson, M., Rhodes, A. D. Y., Gosieniecka, J., Redmond, L. C., Higgins, C. A., Rodriguez-Rodrigues, N., Lancaster, M. A., Manton, J. D.. 2026-06-02. Index-agnostic oblique plane light sheet microscopy of centimetre-scale cleared tissues at subcellular resolution. https://doi.org/10.64898/2026.06.01.729284

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