A high density micro-electrode array includes a transistor layer including a plurality of access transistors and a substrate in operable communication with the transistor layer including, wherein at least a portion of the substrate includes a plurality of trenches. The system includes a plurality of electrodes at least partially located in the plurality of trenches, wherein each of the plurality of electrodes is connected to at least one of the plurality of access transistors and wherein each of the electrodes is separated by a distance less than approximately one microns.