Here, we report advanced materials and devices that enable highefficiency mechanical-to-electrical energy conversion from the natural contractile and relaxation motions of the heart, lung, and diaphragm, demonstrated in several different animal models, each of which has organs with sizes that approach human scales. A cointegrated collection of such energy-harvesting elements with rectifiers and microbatteries provides an entire flexible system, capable of viable integration with the beating heart via medical sutures and operation with efficiencies of ∼2%. Additional experiments, computational models, and results in multilayer configurations capture the key behaviors, illuminate essential design aspects, and offer sufficient power outputs for operation of pacemakers, with or without battery assist.biomedical implants | flexible electronics | transfer printing | wearable electronics | heterogeneous integration N early all classes of active wearable and implantable biomedical devices rely on some form of battery power for operation. Heart rate monitors, pacemakers, implantable cardioverterdefibrillators, and neural stimulators together represent a broad subset of bioelectronic devices that provide continuous diagnostics and therapy in this mode. Although advances in battery technology have led to substantial reductions in overall sizes and increases in storage capacities, operational lifetimes remain limited, rarely exceeding a few days for wearable devices and a few years for implants. Surgical procedures to replace the depleted batteries of implantable devices are thus essential, exposing patients to health risks, heightened morbidity, and even potential mortality. The health burden and costs are substantial, and thus motivate efforts to eliminate batteries altogether, or to extend their lifetimes in a significant way.Investigations into energy-harvesting strategies to replace batteries demonstrate several unusual ways to extract power from chemical, mechanical, electrical, and thermal processes in the human body (1, 2). Examples include use of glucose oxidation (3), electric potentials of the inner ear (4), mechanical movements of limbs, and natural vibrations of internal organs (5-7). Such phenomena provide promising opportunities for power supply to wearable and implantable devices (6-8). A recent example involves a hybrid kinetic device integrated with the heart for applications with pacemakers (7). More speculative approaches, based on analytical models of harvesting from pressure-driven deformations of an artery by magneto-hydrodynamics, also exist (9).Cardiac and lung motions, in particular, serve as inexhaustible sources of energy during the lifespan of a patient. Mechanicalto-electrical transduction mechanisms in piezoelectric materials offer viable routes to energy harvesting in such cases, as demonstrated and analyzed by several groups recently (10-17). For example, proposals exist for devices that convert heartbeat vibrations into electrical energy using resonantly coupled motions of thick (1-2 mm) pi...

The ability to measure subtle changes in arterial pressure using devices mounted on the skin can be valuable for monitoring vital signs in emergency care, detecting the early onset of cardiovascular disease and continuously assessing health status. Conventional technologies are well suited for use in traditional clinical settings, but cannot be easily adapted for sustained use during daily activities. Here we introduce a conformal device that avoids these limitations. Ultrathin inorganic piezoelectric and semiconductor materials on elastomer substrates enable amplified, low hysteresis measurements of pressure on the skin, with high levels of sensitivity (B0.005 Pa) and fast response times (B0.1 ms). Experimental and theoretical studies reveal enhanced piezoelectric responses in lead zirconate titanate that follow from integration on soft supports as well as engineering behaviours of the associated devices. Calibrated measurements of pressure variations of blood flow in near-surface arteries demonstrate capabilities for measuring radial artery augmentation index and pulse pressure velocity.

Mechanical assessment of soft biological tissues and organs has broad relevance in clinical diagnosis and treatment of disease. Existing characterization methods are invasive, lack microscale spatial resolution, and are tailored only for specific regions of the body under quasi-static conditions. Here, we develop conformal and piezoelectric devices that enable in vivo measurements of soft tissue viscoelasticity in the near-surface regions of the epidermis. These systems achieve conformal contact with the underlying complex topography and texture of the targeted skin, as well as other organ surfaces, under both quasi-static and dynamic conditions. Experimental and theoretical characterization of the responses of piezoelectric actuator-sensor pairs laminated on a variety of soft biological tissues and organ systems in animal models provide information on the operation of the devices. Studies on human subjects establish the clinical significance of these devices for rapid and non-invasive characterization of skin mechanical properties.

Recent progress in flexible and stretchable piezoelectric devices for mechanical energy harvesting, sensing and actuation, Extreme Mechanics Letters (2016), http://dx.

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Recent advances in medications for neurodegenerative disorders are expanding opportunities for improving the debilitating symptoms suffered by patients. Existing pharmacologic treatments, however, often rely on systemic drug administration, which result in broad drug distribution and consequent increased risk for toxicity. Given that many key neural circuitries have sub-cubic millimeter volumes and cell-specific characteristics, small-volume drug administration into affected brain areas with minimal diffusion and leakage is essential. We report the development of an implantable, remotely controllable, miniaturized neural drug delivery system permitting dynamic adjustment of therapy with pinpoint spatial accuracy. We demonstrate that this device can chemically modulate local neuronal activity in small (rodent) and large (nonhuman primate) animal models, while simultaneously allowing the recording of neural activity to enable feedback control.

Direct delivery of fluid to brain parenchyma is critical in both research and clinical settings. This is usually accomplished through acutely inserted cannulas. This technique, however, results in backflow and significant dispersion away from the infusion site, offering little spatial or temporal control in delivering fluid. We present an implantable, MRI-compatible, remotely controlled drug delivery system for minimally invasive interfacing with brain microstructures in freely moving animals. We show that infusions through acutely inserted needles target a region more than twofold larger than that of identical infusions through chronically implanted probes due to reflux and backflow. We characterize the dynamics of in vivo infusions using positron emission tomography techniques. Volumes as small as 167 nL of copper-64 and fludeoxyglucose labeled agents are quantified. We further demonstrate the importance of precise drug volume dosing to neural structures to elicit behavioral effects reliably. Selective modulation of the substantia nigra, a critical node in basal ganglia circuitry, via muscimol infusion induces behavioral changes in a volume-dependent manner, even when the total dose remains constant. Chronic device viability is confirmed up to 1-y implantation in rats. This technology could potentially enable precise investigation of neurological disease pathology in preclinical models, and more efficacious treatment in human patients.

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