Polyimide-based 3D microelectrode arrays for in vitro testing of human 3D engineered neural tissues

Event Abstract Back to Event Polyimide-based 3D microelectrode arrays for in vitro testing of human 3D engineered neural tissues Marc Heuschkel1*, Flavio M. Mor1 and Luc Stoppini1 1 High School of Landscape Engineering and Architecture, University of Applied Sciences Western Switzerland, Switzerland Human 3D Engineered Neural Tissue (ENT) made of neurons derived from human induced pluripotent stem cells (hiPSC) are among the most promising tools for the next decade in drug discovery and neurotoxicology. It represents a cheaper, faster and more ethical alternative to in vivo animal testing that will likely close the bridge between in vitro animal models and human clinical trials. MEA recordings of spontaneous activity in ENTs offer a non-invasive, real-time and long-term assessment of compounds' effects. However, the use of ENTs (diameter 0.5mm to 1mm) on MicroElectrode Arrays (MEA) involves a series of constraints, such as drastically limited diffusion of oxygen and nutrients due to the lack of vascularization. As a consequence, ENTs are extremely sensitive to experimental conditions and require adequately designed MEA devices that allow the maintenance of an air-liquid interface around ENTs during culture and recording. Past results using 3D glass tip-shaped electrode MEA devices (Heuschkel et al 2002) have demonstrated advantages in the use of 3D versus 2D electrode geometries when monitoring acute brain slices from rodents. In order to improve currently available polyimide-based 2D MEA devices used in combination with ENTs at our laboratory, novel 3D electrode arrays that present electrodes protruding from the porous polyimide substrate have been developed. The manufactured MEA devices are composed of 4 independent wells, where the bottom of each well is made of a porous polyimide membrane (thickness of 8µm) that integrates 8 platinum recording electrodes arranged on a 200µm grid and 2 large reference electrodes. Planar 2D electrodes do have the following characteristics: a circular shape, a diameter of 30µm, and are coated with black platinum material providing low impedance (20-30kΩ @ 1kHz). Based on the same electrode arrangement, the novel 3D electrodes have a square pyramidal or a square truncated pyramidal shape, which are the simplest shapes that can be achieve using microfabrication processes. Obtained electrode heights are 25µm and 35µm for pyramidal electrodes and 25µm for truncated pyramidal electrodes. Resulting platinum electrode impedance is in the range of 300-800kΩ @ 1kHz depending on shape and dimensions of the 3D electrodes. Similar to results from 3D tip-shaped glass electrode arrays, recordings of spontaneous activity from ENTs show that larger signal amplitudes can be recorded with the 3D pyramidal polyimide MEA devices. Furthermore, the recordings from 3D electrodes display a variety of more complex signal shapes (multiple waves) that are less present in planar electrode MEA devices, which suggests that the 3D electrodes configuration reduces the distance between the electrodes and the active cells and neurites within the tissue by slight penetration into the tissue. In conclusion, a novel stand-alone MEA device specifically designed for medium-throughput testing of human 3D engineered neural tissue based on 3D porous polyimide MEA devices has been built and characterized. Acknowledgements The authors thank Laetitia Nikles for excellent technical assistance in human ENTs preparation. The authors acknowledge funding from the Wyss Center for Bio- and Neuro-Engineering TONIC project and HES-SO. References M.O. Heuschkel, M. Fejtl, D. Bertrand, P. Renaud, A three-dimensional multi-electrode array for stimulation and recording in acute brain slices, Journal of Neuroscience Methods, 114 (2002) 135-148 Keywords: Porous polyimide microelectrode array, 3D electrode, hiPSC, 3D engineered neural tissue, spontaneous activity, Drug Discovery, Neurotoxicology Conference: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018. Presentation Type: Poster Presentation Topic: Microelectrode Array Technology Citation: Heuschkel M, Mor FM and Stoppini L (2019). Polyimide-based 3D microelectrode arrays for in vitro testing of human 3D engineered neural tissues. Conference Abstract: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays. doi: 10.3389/conf.fncel.2018.38.00044 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Mar 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Marc Heuschkel, High School of Landscape Engineering and Architecture, University of Applied Sciences Western Switzerland, Geneva, 1202, Switzerland, marc.heuschkel@hesge.ch Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Marc Heuschkel Flavio M Mor Luc Stoppini Google Marc Heuschkel Flavio M Mor Luc Stoppini Google Scholar Marc Heuschkel Flavio M Mor Luc Stoppini PubMed Marc Heuschkel Flavio M Mor Luc Stoppini Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.