Flexible IrOx neural electrode for mouse vagus nerve stimulation

Vagus nerve stimulation (VNS) is being actively explored as a treatment for multiple conditions as part of bioelectronic medicine research. Reliable and safe VNS in mouse models is a critical need for under-standing mechanisms of these. We report on the development and evaluation of a microfabricated cuff electrode (MouseFlex) constructed of polyimide (PI) and with iridium oxide (IrOx) electrodes that is ther-moformed to 86 mu m +/- 12 mu m radius to interface the mouse cervical vagus nerve (r ti 50 mu m). Innovative bench-top methods were used to evaluate the stimulation stability and electrochemical properties of elec-trodes. Our aggressive stimulation stability (Stim-Stab) test utilized 1 billion pulses at a 10 0 0 Hz with a current density of 6.28 A/cm2 (1.51 mC/cm2/phase) delivering 3023 x 10 3 C/cm2 to evaluate electrode lifetimes, and all electrodes remained functional. We also investigated the effects of thermoforming on their impedance, charge storage capacity (CSC), and charge injection capacity (CIC). The modest changes in electrochemical properties indicate that the thermoforming process was well tolerated. Thermoformed electrode safety and efficacy were evaluated in-vivo by performing acute VNS in mice and monitoring their heart and respiration rate as biomarkers. Their electrochemical properties were also measured be-fore, during and after VNS. Bradycardia and bradypnea were reliably induced at stimulation currents of 10 0 to 20 0 mu A, well below the in-vivo CIC of-1250 mu A (-0.5 mC/cm2), supporting their safety and effi-cacy. The electrode impedance increased and CIC decreased during in-vivo use, but largely reversed these changes in in-vitro testing after enzymatic cleaning, supporting their tolerance for surgical use.Statement of significance Vagus nerve stimulation (VNS) is a rapidly growing aspect of healthcare and bioelectronic medicine re-search. Reliable and safe VNS in mice with small diameter (d ti 100 mu m) nerves has been a challenge due to achieving intimate contact with the nerve, and the stimulation stability of commonly used electrodes. We demonstrate a microfabricated (MouseFlex) cuff electrode constructed of polyimide with IrOx elec-trodes that is thermoformed to contact the mouse cervical vagus. Bench studies highlight the stimulation stability exceeded 10 9 pulses at 6.28 A/cm2 and their electrochemical properties were measured before, during, and after bench and nerve stimulation. Nerve stimulation induced bradycardia and bradypnea at currents below the in-vivo charge injection capacity, supporting their safety, efficacy, and tolerance for surgical handling.(c) 2023 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )