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Wash-Free Multi-Target Super-Resolution Microscopy with Photocaged DNA Labels

Kaltenschnee, N.; Dietz, M. S.; Kessler, L. F.; Li, Y.; Kaufmann, J.; Heckel, A.; Heilemann, M.

2026-01-13 biophysics
10.64898/2026.01.13.699198 bioRxiv
Show abstract

Super-resolution microscopy with DNA-fluorophore labels is primed for multi-target imaging of cell biological samples. However, direct interaction with the sample is required to exchange or add DNA-fluorophore labels in each imaging round, which can impair the accuracy of the imaging data at the nanometer scale. To bypass this requirement, we introduce a wash-free method that employs DNA oligonucleotides equipped with photocaging groups. Irradiation with light removes these photo-modulatable groups and changes the hybridization properties of DNA labels, enabling light-modulated targeting. We demonstrate this concept by imaging various cellular targets with confocal microscopy, single-molecule localization microscopy, and stimulated emission depletion (STED) microscopy.

Published in Angewandte Chemie International Edition (predicted rank #7) · training set

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