A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo.

The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating devices limits oxygen availability, leading to hypoxia and cell death in vivo. This is particularly problematic for pancreatic islet cells that have high O2 requirements. Here, we combine bioelectronics with encapsulated cell therapies to develop the first wireless, battery-free oxygen-generating immune-isolating device (O2-Macrodevice) for the oxygenation and immune isolation of cells in vivo. The system relies on electrochemical water splitting based on a water-vapor reactant feed, sustained by wireless power harvesting based on a flexible resonant inductive coupling circuit. As such, the device does not require pumping, refilling, or ports for recharging and does not generate potentially toxic side products. Through systematic in vitro studies with primary cell lines and cell lines engineered to secrete protein, we demonstrate device performance in preventing hypoxia in ambient oxygen concentrations as low as 0.5%. Importantly, this device has shown the potential to enable subcutaneous (SC) survival of encapsulated islet cells, in vivo in awake, freely moving, immune-competent animals. Islet transplantation in Type I Diabetes represents an important application space, and 1-mo studies in immune-competent animals with SC implants show that the O2-Macrodevice allows for survival and function of islets at high densities (~1,000 islets/cm2) in vivo without immune suppression and induces normoglycemia in diabetic animals.

Soft, bioresorbable coolers for reversible conduction block of peripheral nerves.

Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.

Continuous, noninvasive wireless monitoring of flow of cerebrospinal fluid through shunts in patients with hydrocephalus.

Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.

Epidermal electronics for noninvasive, wireless, quantitative assessment of ventricular shunt function in patients with hydrocephalus.

Hydrocephalus is a common and costly neurological condition caused by the overproduction and/or impaired resorption of cerebrospinal fluid (CSF). The current standard of care, ventricular catheters (shunts), is prone to failure, which can result in nonspecific symptoms such as headaches, dizziness, and nausea. Current diagnostic tools for shunt failure such as computed tomography (CT), magnetic resonance imaging (MRI), radionuclide shunt patency studies (RSPSs), and ice pack-mediated thermodilution have disadvantages including high cost, poor accuracy, inconvenience, and safety concerns. Here, we developed and tested a noninvasive, skin-mounted, wearable measurement platform that incorporates arrays of thermal sensors and actuators for precise, continuous, or intermittent measurements of flow through subdermal shunts, without the drawbacks of other methods. Systematic theoretical and experimental benchtop studies demonstrate high performance across a range of practical operating conditions. Advanced electronics designs serve as the basis of a wireless embodiment for continuous monitoring based on rechargeable batteries and data transmission using Bluetooth protocols. Clinical studies involving five patients validate the sensor's ability to detect the presence of CSF flow (P = 0.012) and further distinguish between baseline flow, diminished flow, and distal shunt failure. Last, we demonstrate processing algorithms to translate measured data into quantitative flow rate. The sensor designs, fabrication schemes, wireless architectures, and patient trials reported here represent an advance in hydrocephalus diagnostics with ability to visualize flow in a simple, user-friendly mode, accessible to the physician and patient alike.

Wireless, Battery-Free Epidermal Electronics for Continuous, Quantitative, Multimodal Thermal Characterization of Skin.

Precise, quantitative measurements of the thermal properties of human skin can yield insights into thermoregulatory function, hydration, blood perfusion, wound healing, and other parameters of clinical interest. The need for wired power supply systems and data communication hardware limits, however, practical applicability of existing devices designed for measurements of this type. Here, a set of advanced materials, mechanics designs, integration schemes, and wireless circuits is reported as the basis for wireless, battery-free sensors that softly interface to the skin to enable precise measurements of its temperature and thermal transport properties. Calibration processes connect these parameters to the hydration state of the skin, the dynamics of near-surface flow through blood vessels and implanted catheters, and to recovery processes following trauma. Systematic engineering studies yield quantitative metrics in precision and reliability in real-world conditions. Evaluations on five human subjects demonstrate the capabilities in measurements of skin hydration and injury, including examples of continuous wear and monitoring over a period of 1 week, without disrupting natural daily activities.