N. Lei, S. Ramakrishnan, P. Shi, J. Orcutt, R. Yuste, L. Kam, and K.L. Shepard, “An electrically stimulate optically record microsystem based on active CMOS multi-electrode array for dissociated cell cultures“, Proceedings of IEEE/NIH Life Science Systems and Applications Workshop 2011.
Calcium fluorescence-based optical recording combined with patch-clamp stimulation has become the standard technique for analyzing neural network behavior. At best, stimulation is limited to only a few channels in this case. Passive multielectrode arrays for two-dimensional electrophysiology only offer electrode densities of 60 electrodes per mm2. Here, we report an active multielectrode array, constructed with a standard complementary metal-oxide-semiconductor (CMOS) technology, to perform localized extracellular stimulation of dispersed cell cultures. A 256×256 array integrated with in-pixel stimulators on a 4-by-4 mm2 CMOS chip noninvasively stimulate hippocampal cells cultured on chip at cellular resolution. Combined with calcium imaging using high affinity indicators, we demonstrate the ability to observe spatiotemporal dynamics of neural activity.