Associate Prof University of Arizona Tucson, Arizona, United States
Introduction: : Continuous physiological interrogation and modulation using wireless, battery-free implants enable detailed characterization of biological processes at an organism level. Recent advances have demonstrated the feasibility of real-time multimodal sensing and closed-loop neuromodulation in freely moving subjects. Building on this, our latest studies introduce a distributed ecosystem of miniaturized wireless implants that integrate electrochemical sensing, electrical, and optogenetic neuromodulation. Crucially, we have scaled these technologies from initial small animal validations to extensive large animal models, illustrating their capability to provide clinically relevant physiological insights over chronic timescales. Here, we summarize these developments, emphasizing the scalable wireless powering strategies, system-level integration, and their implications for eventual translation to human health monitoring and intervention.
Materials and
Methods: : Implantable devices were fabricated on flexible polyimide substrates and encapsulated in biocompatible silicone and parylene-C, suitable for chronic implantation. The implants integrated multimodal biosensors and stimulation, specifically including three-electrode electrochemical sensors for catecholamine detection, micro-LED arrays for optogenetic neuromodulation, and electrical stimulation electrodes optimized for spinal cord and neuromuscular applications. Wireless power and data transfer were implemented via resonant near-field communication (NFC) at 13.56 MHz, facilitating concurrent operation of multiple implants with operational distances around 20 mm. Electrochemical sensing and optogenetic modulation were initially validated in rodent models, while electrical stimulation implants were engineered to be capable to deliver sustained, high-power outputs (up to 15 mW) for spinal cord neuromodulation and functional neuromuscular stimulation. Further, we demonstrated clinical scalability through extended large animal studies (duration up to 11 months), employing wearable biosymbiotic hubs recharged wirelessly via far-field power transfer (915 MHz). These wearable hubs provided uninterrupted data acquisition and implant powering without manual intervention, enabling real-time monitoring of clinically relevant biomarkers such as bone strain during fracture healing. All animal experiments were conducted following institutionally approved IACUC protocols.
Results, Conclusions, and Discussions:: To address the need for organism-level physiological interrogation and modulation, we have developed wireless, battery-free implants capable of distributed multimodal sensing and neuromodulation. Initially demonstrated in small animal models, these implants exhibited robust electrochemical sensing of catecholamines with high temporal (sub-500 ms) and chemical resolution ( < 50 nM), coupled with optogenetic modulation, enabling precise behavioral interventions (Stuart et al., ACS Nano, 2023). Expanding to larger animal models (rats), we demonstrated chronic neuromodulatory implants capable of delivering sustained electrical stimulation at power levels exceeding 15 mW, suitable for long-term therapeutic interventions (Widman et al., Advanced Science, 2025). Crucially, we have validated the scalability of our wireless power approach, within operational distances spanning cages, confirming feasibility for distributed physiological monitoring and modulation across multiple anatomical sites (Burton et al., Nature Communications, 2023). Most recently, we translated this approach to clinically relevant large animal studies over extended timescales (up to 11 months), employing wearable biosymbiotic hubs capable of wirelessly powering and communicating with implanted devices, thus enabling continuous data streaming without user intervention. These large animal experiments demonstrated seamless operation, clinical compatibility, and direct translational potential, significantly advancing the viability of this technology for human deployment (Kasper et al., Science Advances, 2025). Collectively, these studies highlight a clear trajectory for the application of battery-free wireless implant ecosystems, from fundamental neuroscience to clinical diagnostics and therapeutic interventions.
Acknowledgements and/or References (Optional):: 1. Stuart, T. et al. ACS Nano 2023, 17(1), 561–574. 2. Widman, A. et al. Advanced Science 2025. 3. Burton, A. et al. Nature Communications 2023, 14, 7887. 4. Kasper, K. A. et al. Science Advances 2025, 11, eadt7488. 5. Bhatia, A. et al. Chemical Reviews 2024.
