High-Stability Polyimide-based Flexible Electrodes with IrOx to Interface the Mouse Vagus Nerve

Sun, T.; Falcone, J. D.; Crosfield, C.; Lopez, M. F.; Peragine, J.; Modi, R.; Sharma, R.; Baker, B.; Anderson, G.; Savani, S.; Li, C.; Chang, E. H.; Sohal, H.; Rieth, L.

doi:10.1101/2021.05.10.442867

bioRxiv · 10.1101/2021.05.10.442867

High-Stability Polyimide-based Flexible Electrodes with IrOx to Interface the Mouse Vagus Nerve

Sun, T.·Falcone, J. D.·Crosfield, C.·Lopez, M. F.·Peragine, J.·Modi, R.·Sharma, R.·Baker, B.·Anderson, G.·Savani, S.·Li, C.·Chang, E. H.·Sohal, H.·Rieth, L.

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Abstract

ObjectiveWe developed robust and cost-effective cuff Flex electrodes to facilitate bioelectronic medicine research in mouse models. They utilize polyimide (PI) as a dielectric insulation and iridium oxide (IrOx) for the electrodes, and are designed to interface small autonomic and somatic nerves (e.g. mouse vagus nerve). ApproachFlex electrodes were made using micro-fabrication technology, and innovative integration processes were developed to enable reliable acute and chronic vagus nerve interfaces. The electrochemical properties of Flex electrodes were characterized. Moreover, accelerated aging at 57 {degrees}C and stimulation-stability (Stim-Stab) testing (109 pulses at [~] 1.59 mC/cm2/phase) were performed to evaluate the lifetime of the PI encapsulation and IrOx electrodes, respectively. Flex electrodes efficacy was demonstrated by stimulating the mouse vagus nerve ([~]100 {micro}m) and measuring heart and respiratory rate changes as biomarkers. ResultsCost effective and robust lead and connector integration strategies were demonstrated, including small helical leads that improved the lead elongation by > 7x. PI encapsulation had stable impedance spectra for at least 336 days for interdigitated electrodes. Stim-Stab testing using an aggressive paradigm and rigorous optical and electrical characterization, revealed that half of electrodes showed less than minor damage at the endpoints. A trend of decreasing respiratory rate with stimulation current reached statistical significance at 500 {micro}A, demonstrating efficacy for Flex electrodes. SignificanceFlex electrodes offer demonstrated efficacy, low impedance (443 {+/-} 32 {Omega} at 103 Hz), excellent bench test stability, and cost-effective fabrication. Acute devices are easy to integrate, and mechanically robust chronic devices will be investigated in vivo in future studies. These characteristics make the electrodes well-positioned to advance bioelectronics medicine research by 1) enabling reliable studies with statistically relevant populations of acute mouse models, and 2) offering the potential for a technology that can be used in chronic studies, which scales to very small nerves.

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Sun, T., Falcone, J. D., Crosfield, C., Lopez, M. F., Peragine, J., Modi, R., Sharma, R., Baker, B., Anderson, G., Savani, S., Li, C., Chang, E. H., Sohal, H., Rieth, L.. 2021-05-11. High-Stability Polyimide-based Flexible Electrodes with IrOx to Interface the Mouse Vagus Nerve. https://doi.org/10.1101/2021.05.10.442867

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