Closed-loop Optogenetic Control in a Microplate Reader

Abstract Optogenetics integrates living cells and electronics into powerful cell–silicon systems, but prototyping their dynamics remains challenging. Current tools either require robotic liquid transfers into flow cytometers or rely on custom sensors with narrow dynamic range that limit controller performance. Additionally, current successful optogenetic feedback controllers only operate in chemostats or microfluidic devices that enforce constant growth, because models for growth-aware controller design in batch culture are lacking. Here we present LEMOS, a low-cost LED-embedded microplate that runs inside a commercial microplate reader. Coupled to a growth-aware multiscale model of gene expression for controller tuning, this platform enables rapid design-build-test-learn cycles for cell-silicon systems. We demonstrate closed loop setpoint tracking of gene expression in batch cultures within a standard microplate reader and show how growth dynamics complicates controller selection and tuning. Together, this platform reduces setup overhead and speed up iteration, enabling accurate real-time optogenetic feedback control. Competing Interest Statement The authors have declared no competing interest. Footnotes The main results did not change; we made the manuscript shorter and easier to read.