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Multi-channel high-density single-molecule localization

Sha, H.; Muller, L.-R.; Castillo Duque de Estrada, N. M.; Mathieu, M.; Jaques, A.; Marin, Z.; Zhang, Y.; Macke, J. H.; Ries, J.

2026-07-26 biophysics
10.64898/2026.07.24.740199 bioRxiv
Show abstract

Deep learning has enabled single-molecule localization microscopy (SMLM) at high emitter densities, but only for single channel systems. Here we present DECODE-Plex, a deep-learning-based framework to localize dense single molecules with overlapping point spread functions simultaneously in multiple channels. We showcase DECODE-Plex on experimental ultra-high density dual-color and 3D live-cell data. Packaged for ease of use, it will enable many groups to improve imaging speed and quality of multi-channel SMLM.

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