Single-Cell Optogenetic Control of Calcium Signaling with a High-Density Micro-LED Array.

Precise optogenetic control, ideally down to single cells in dense cell populations, is essential in understanding the heterogeneity of cell networks. Devices with such capability, if built in a chip scale, will advance optogenetic studies at cellular levels in a variety of experimental settings. Here we demonstrate optogenetic control of intracellular Ca2+ dynamics at the single cell level using a 16-μm pitched micro-light emitting diode (LED) array that features high brightness, small spot size, fast response, and low voltage operation. Individual LED pixels are able to reliably trigger intracellular Ca2+ transients, confirmed by fluorescence microscopy and control experiments and cross-checked by two genetically coded Ca2+ indicators. Importantly, our array can optogenetically address individual cells that are sub-10 μm apart in densely packed cell populations. These results suggest the possible use of the micro-LED array toward a lab-on-a-chip for single-cell optogenetics, which may allow for pharmaceutical screening and fundamental studies on a variety of cell networks.