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

AbstractObjectiveWe developed robust and cost-effective cuffFlexelectrodes 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).ApproachFlexelectrodes were made using micro-fabrication technology, and innovative integration processes were developed to enable reliable acute and chronic vagus nerve interfaces. The electrochemical properties ofFlexelectrodes were characterized. Moreover, accelerated aging at 57 °C and stimulation-stability (Stim-Stab) testing (109pulses at ∼ 1.59 mC/cm2/phase) were performed to evaluate the lifetime of the PI encapsulation and IrOxelectrodes, respectively.Flexelectrodes efficacy was demonstrated by stimulating the mouse vagus nerve (∼100 µm) 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 µA, demonstrating efficacy forFlexelectrodes.SignificanceFlexelectrodes offer demonstrated efficacy, low impedance (443 ± 32 Ω at 103Hz), excellent bench test stability, and cost-effective fabrication. Acute devices are easy to integrate, and mechanically robust chronic devices will be investigatedin vivoin 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.