Spatially and Chemically Specific Optical Control of Cells via Supervised and Automated Target Selection

The traditional method in biological science to regulate cell functions often employs chemical interventions, which lack precision in space and time. While optical control offers high spatial precision, existing technologies are constrained by limitations in accuracy, response time, and flexibility. Here, we developed a software-assisted real-time precision opto-control (S-RPOC) system by synchronizing galvo scanning with user input, chemical detection, decision-making, and laser activation in real time. It enables both automated target selection and flexible user input. S-RPOC supports the simultaneous creation of diverse optical treatment conditions and monitoring of cellular responses. Applying S-RPOC, we demonstrated selective organelle photoperturbation, activation of compounds solely in selected cells, control of cell division via centrosome perturbation, and label-free blue light treatment of cells. S-RPOC holds the promise to advance our knowledge in site-specific biomolecular activities and offer better approaches to control the functions and responses of biological samples.