Monitoring of Traumatically Injured Organotypic Hippocampal Cultures with Stretchable Microelectrode Arrays
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Monitoring of Traumatically Injured Organotypic Hippocampal Cultures with Stretchable Microelectrode Arrays Zhe Yu1, Candice Tsay2, Stéphanie P. Lacour3, Sigurd Wagner2, and Barclay Morrison III1 1 Biomedical Engineering, Columbia University, New York, NY, 10027 2 Electrical Engineering, Princeton University, Princeton, NJ, 08544 3 NanoScience, University of Cambridge, Cambridge, CB3 0FF, United Kingdom
ABSTRACT Traumatic brain injury (TBI) can be caused by motor vehicle accidents, falls and firearms, and approximately 2% of the US population lives with disabilities cause by TBI. To discover mechanisms of functional deficits underlying TBI, and to develop strategies to restore lost function with neural interfaces, we developed a stretchable microelectrode array (SMEA), which can be used for continuous recording of neuronal function, pre-, during, and post-stretch injury. The SMEAs were fabricated on elastomeric substrates, consisting of stretchable 100µm wide, 25nm thick gold electrodes patterned on a polydimethylsiloxane (PDMS) substrate, and encapsulated with a 10-20µm thick, photo-patternable silicone insulation layer. The SMEA was packaged between two printed circuit boards and mounted in a commercial Multi Channel Systems amplifier. Combined with our TBI model, which can generate precise and reproducible injuries in cultured hippocampus, the SMEAs will make possible extracellular field potential recording pre-, during, and post-stretch injury. Previous biocompatibility tests have showed no overt necrosis or cell death caused by the SMEAs after 2 weeks in culture [2]. The electrical performance of the SMEAs was tested in electrophysiological saline before, during and after biaxial stretching. The initial electrode impedance at 1kHz was ~2kΩ. The SMEA was stretched to 8.5% biaxial strain, and the microelectrode impedance increased with the strain to reach 833kΩ at 8.5% strain. Upon relaxation, the impedance recovered to 2kΩ. New designs of microelectrode array, the choice of materials and a new fabrication technology were tested on gold microelectrode arrays supported on glass. Using the prototype arrays, population spikes were recorded from organotypic hippocampal slice cultures of brain tissue. The prototype arrays have electrical performance compatible with existing multielectrode array systems. Moreover, the results indicate the ability of the prototype arrays to record neuronal activity from hippocampal slices. Stretchable microelectrode arrays will enable new studies to understand injury mechanisms leading to post-traumatic neuronal dysfunction.
INTRODUCTION Traumatic brain injury causes disabilities through disrupting the function of the brain. To identify therapeutic targets and develop strategies to mitigate and prevent post-traumatic damage, understanding the mechanisms how mechanical injury induces functional pathology is important. Major initial pathophysiologic process is caused by deformation of brain tissue during traumatic injury. To mimic induced brain deformation during TBI, our
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