Monitoring hippocampus electrical activity in vitro on an elastically deformable microelectrode array

Interfacing electronics and recording electrophysiological activity in mechanically active biological tissues is challenging. This challenge extends to recording neural function of brain tissue in the setting of traumatic brain injury (TBI), which is caused by rapid (within hundreds of milliseconds) and large (greater than 5% strain) brain deformation. Interfacing electrodes must be biocompatible on multiple levels and should deform with the tissue to prevent additional mechanical damage. We describe an elastically stretchable microelectrode array (SMEA) that is capable of undergoing large, biaxial, 2-D stretch while remaining functional. The new SMEA consists of elastically stretchable thin metal films on a silicone membrane. It can stimulate and detect electrical activity from cultured brain tissue (hippocampal slices), before, during, and after large biaxial deformation. We have incorporated the SMEA into a well-characterized in vitro TBI research platform, which reproduces the biomechanics of TBI by stretching the SMEA and the adherent brain slice culture. Mechanical injury parameters, such as strain and strain rate, can be precisely controlled to generate specific levels of damage. The SMEA allowed for quantification of neuronal function both before and after injury, without breaking culture sterility or repositioning the electrodes for the injury event, thus enabling serial and long-term measurements. We report tests of the SMEA and an initial application to study the effect of mechanical stimuli on neuron function, which could be employed as a high-content, drug-screening platform for TBI.