SIGNIFICANCE: The long-term impact of stimulation upon visceral organ function remain unknown in many diseases, as acute tethered experiments are confounded by the influence of anesthesia and abnormal patterns of food intake and sleep. Animal handling stress, loss of animals from damage to electrode hardware and connectors, and motion artifacts preclude tethered configurations as a viable alternative for long-term studies. Recent 2016 meetings by SPARC, bioelectronics medicine, and DARPA researchers exemplified a lack of ability to perform long-term continuous stimulation or recordings in small animals. New fully-implantable devices are needed to extend these acute and short-term results from tethered animals to long-term studies and to justify costly therapeutic validation in large animal models. Though the concept of a `closed-loop wireless implantable device' is not novel, a wireless device appropriate for stimulation, recording, and impedance monitoring from small visceral nerves in behaving small animals at this scale is highly innovative. Untethered and freely-behaving operation for multiple animal body weights and implant locations in the rat pose significant miniaturization, power, and heating constraints. Stimulation dosing studies for multiple nerve targets, for example, require programmable bi-phasic current amplitudes up to +/- 5mA (+/-10V compliance), variable pulse-widths, 1-50 kHz frequency blocking waveforms, and electroneurogram (ENG) recordings--each requires a different operating power. Furthermore, ENG recordings require a 5x lower noise than cortical recordings, are difficult even with precision benchtop systems, and noise reduction techniques are too power hungry for implantable operation. An innovative wireless power receiver approach is needed to accommodate the power consumption of a multi-functional circuit, while also not heating the implantable device surface >1 C, and dynamically adapting to variable animal orientation. Lead wire tethering forces on small nerves electrodes must also be reduced. INNOVATION: We will develop a fully-implantable stimulation, recording, blocking, and impedance monitoring fully implantable device (22 x 30 x 8 mm) for >60 day continuous operation from wireless power. An innovative and adaptive mode-switching wireless power receiver is proposed which uses temperature feedback to alternate between resonant and non-resonant coupling modes, to eliminate device heating and to maximize available power for stimulation and recording. A stretchable, micro-helical lead wire is proposed to reduce tethering forces between our novel external urethral sphincter (EUS) electrode and commercial cuff electrode. A novel arrayable and network- connected telemetry base station scalable to a vivarium, is proposed to enable a single computer to stimulate and monitor 5 freely behaving animals over a network. OUTCOMES: This SBIR Phase 1 proposes to develop and commercialize the `Stim-Sense' untethered system which includes (1) an implantable device for bi-phasic stimulation, ENG and EMG recordings, bi-phasic kHz blocking, and impedance monitoring for freely-moving and stress-free animals in a vivarium and (2) validation of the system in a hybrid autonomic interface in overactive bladder. These milestones will enable a focused Phase 2 effort to remotely stimulate and monitor multiple cohorts of dozens of animals.
The Lab-to-Marketplace P1 SBIR proposal seeks to develop and commercialize the first wireless Stim- Sense platform to enable new stimulation therapies of visceral nerves to be performed in freely-moving animals in a vivarium. The proposed wireless technology will reduce the animal mortality in existing neural disease biology studies and improve the data findings from existing animal studies by overcoming the current acute and handling limitations used by tethered and stressed animals. Building upon our existing stimulation and recording prototypes, we will develop the implantable Stim-Sense device and demonstrate 30-day functionality in a bladder dysfunction animal model, with future extension to neuroprosthetics, asthma, and inflammation.
