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bioRxiv · 10.64898/2026.01.13.699198

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.
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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.

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Kaltenschnee, N., Dietz, M. S., Kessler, L. F., Li, Y., Kaufmann, J., Heckel, A., Heilemann, M.. 2026-01-13. Wash-Free Multi-Target Super-Resolution Microscopy with Photocaged DNA Labels. https://doi.org/10.64898/2026.01.13.699198

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