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

Objective We 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 (IrO_x) for the electrodes, and are designed to interface small autonomic and somatic nerves (e.g. mouse vagus nerve).

Approach Flex 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 °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 IrO_x electrodes, respectively. Flex electrodes efficacy was demonstrated by stimulating the mouse vagus nerve (∼100 µm) and measuring heart and respiratory rate changes as biomarkers.

Results Cost 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 for Flex electrodes.

Significance Flex electrodes offer demonstrated efficacy, low impedance (443 ± 32 Ω 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.