Outcome-Driven Microscopy: Closed-Loop Optogenetic Control of Cell Biology

Josiah B. Passmore; Alfredo Rates; Jakob Schröder; Menno T. P. van Laarhoven; Vincent J. W. Hellebrekers; Henrik G. van Hoef; Antonius J. M. Geurts; Wendy van Straaten; Wilco Nijenhuis; Florian Berger; Carlas Smith; Ihor Smal; Lukas C. Kapitein

doi:10.1038/s41467-025-67848-5

Cell BiologyNature CommunicationsDec 23, 2025

Peer-reviewed journal article

Outcome-Driven Microscopy: Closed-Loop Optogenetic Control of Cell Biology

Josiah B. Passmore iD, Alfredo Rates iD, Jakob Schröder iD, Menno T. P. van Laarhoven iD, Vincent J. W. Hellebrekers, Henrik G. van Hoef iD, Antonius J. M. Geurts, Wendy van Straaten, Wilco Nijenhuis iD, Florian Berger iD, Carlas Smith iD, Ihor Smal iD, Lukas C. Kapitein iD

Abstract

Smart microscopy is transforming biological imaging by integrating real-time analysis with adaptive acquisition to enhance imaging efficiency. Whereas many emerging implementations are event-driven and focus on on-demand data acquisition to reduce phototoxicity, we here present outcome-driven microscopy, which combines smart microscopy with optogenetics to achieve subcellular spatiotemporal control of biology to predefined outcomes. We validate this approach using light-based control of cell migration and nucleocytoplasmic transport, and demonstrate unprecedented spatiotemporal control over cellular behaviour.

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