RT Journal Article
SR Electronic
T1 Label-free adaptive optics single-molecule localization microscopy for whole animals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.18.469175
DO 10.1101/2021.11.18.469175
A1 Sanghyeon Park
A1 Yonghyeon Jo
A1 Minsu Kang
A1 Jin Hee Hong
A1 Sangyoon Ko
A1 Suhyun Kim
A1 Sangjun Park
A1 Hae-Chul Park
A1 Sang-Hee Shim
A1 Wonshik Choi
YR 2022
UL http://biorxiv.org/content/early/2022/10/26/2021.11.18.469175.abstract
AB The specimen-induced aberration has been a major factor limiting the imaging depth of single-molecule localization microscopy (SMLM). Here, we report the application of label-free wavefront sensing adaptive optics to SMLM for deep-tissue super-resolution imaging. The proposed system measures complex tissue aberrations from intrinsic reflectance rather than fluorescence emission and physically corrects the wavefront distortion more than three-fold stronger than the previous limit. This enables us to resolve sub-diffraction morphologies of cilia and oligodendrocytes in whole intact zebrafish as well as dendritic spines in thick mouse brain tissues at the depth of up to 102 μm with localization number enhancement by up to 37 times and localization precision comparable to aberration-free samples. The proposed approach can expand the application range of SMLM to intact animals that cause the loss of localization points owing to severe tissue aberrations.Competing Interest StatementThe authors have declared no competing interest.