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 a narrow dynamic range that limits 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 with 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 set point tracking of gene expression in batch cultures within a standard microplate reader and show how growth dynamics complicate controller selection and tuning. Together, this platform reduces setup overhead and speeds up iteration, enabling accurate real-time optogenetic feedback control.