In Vivo Wireless Sensors for Gut Microbiome Redox Monitoring.

A perturbed gut microbiome has recently been linked with multiple disease processes, yet researchers currently lack tools that can provide in vivo, quantitative, and real-time insight into these processes and associated host-microbe interactions. We propose an in vivo wireless implant for monitoring gastrointestinal tract redox states using oxidation-reduction potentials (ORP). The implant is powered and conveniently interrogated via ultrasonic waves. We engineer the sensor electronics, electrodes, and encapsulation materials for robustness in vivo, and integrate them into an implant that endures autoclave sterilization and measures ORP for 12 days implanted in the cecum of a live rat. The presented implant platform paves the way for long-term experimental testing of biological hypotheses, offering new opportunities for understanding gut redox pathophysiology mechanisms, and facilitating translation to disease diagnosis and treatment applications.

End-to-End Design of Efficient Ultrasonic Power Links for Scaling Towards Submillimeter Implantable Receivers.

We present an analytical framework for optimizing the efficiency of ultrasonic wireless power links for implantable devices scaled down to sub-mm dimensions. Key design insights and tradeoffs are considered for various parameters including the operating frequency, the transmission depth, the size of the transmitter, the impedance and the aperture efficiency of the miniaturized receiver, and the interface between the receiver and the power recovery chain on the implant. The performance of spherically focused transducers as ultrasonic transmitters is analyzed to study the limits and the tradeoffs. Two optimization methods are presented: "Focal Peak" sets the focus of transducers at target depths, and "Global Maximum" maximizes the efficiency globally with off-focus operation. The results are also compared to phased array implementations. To investigate the efficiency of implants, miniaturized receivers made from single crystalline piezoelectric material, PMN-PT, are used as they have resonances in the derived optimal carrier frequency range (∼1-2 MHz). A methodology to achieve an efficient interface to the power electronics is then provided using an optogenetic stimulator as an example platform. The analytical results are verified through both simulations and measurements. Finally, an example ultrasonic link using a spherical transmitter with a radius of 2 cm is demonstrated; link efficiencies of 1.93-0.23% are obtained at 6-10 cm depths with sub-mm receivers for the optogenetic application.

Thermal analysis of ultrasound-powered miniaturized implants: A tissue-phantom study.

Neurological implants that harvest ultrasound power have the potential to provide long-term stimulation without complications associated with battery power. An important safety question associated with long-term operation of the implant involves the heat generated by the interaction of the device with the ultrasound field. A study was performed in which the temperature rise generated by this interaction was measured. Informed by temperature data from thermocouples outside the ultrasound beam, a mathematical inverse method was used to determine the volume heat source generated by ultrasound absorption within the implant as well as the surface heat source generated within the viscous boundary layer on the surface of the implant. For the test implant used, it was determined that most of the heat was generated in the boundary layer, giving a maximum temperature rise ∼5 times that for absorption in an equivalent volume of soft tissue. This result illustrates that thermal safety guidelines based solely on ultrasound absorption of tissue alone are not sufficient. The method presented represents an alternative approach for quantifying ultrasound thermal effects in the presence of implants. The analysis shows a steady temperature rise of about 0.2 °C for every 100 mW/cm2 for the presented test implant.

A mm-Sized Wireless Implantable Device for Electrical Stimulation of Peripheral Nerves.

A wireless electrical stimulation implant for peripheral nerves, achieving >10× improvement over state of the art in the depth/volume figure of merit, is presented. The fully integrated implant measures just 2 mm × 3 mm × 6.5 mm (39 mm3, 78 mg), and operates at a large depth of 10.5 cm in a tissue phantom. The implant is powered using ultrasound and includes a miniaturized piezoelectric receiver (piezo), an IC designed in 180 nm HV BCD process, an off-chip energy storage capacitor, and platinum stimulation electrodes. The package also includes an optional blue light-emitting diode for potential applications in optogenetic stimulation in the future. A system-level design strategy for complete operation of the implant during the charging transient of the storage capacitor, as well as a unique downlink command/data transfer protocol, is presented. The implant enables externally programmable current-controlled stimulation of peripheral nerves, with a wide range of stimulation parameters, both for electrical (22 to 5000 µA amplitude, ∼14 to 470 µs pulse-width, 0 to 60 Hz repetition rate) and optical (up to 23 mW/mm2 optical intensity) stimulation. Additionally, the implant achieves 15 V compliance voltage for chronic applications. Full integration of the implant components, end-to-end in vitro system characterizations, and results for the electrical stimulation of a sciatic nerve, demonstrate the feasibility and efficacy of the proposed stimulator for peripheral nerves.

Design of Tunable Ultrasonic Receivers for Efficient Powering of Implantable Medical Devices With Reconfigurable Power Loads.

Miniaturized ultrasonic receivers are designed for efficient powering of implantable medical devices with reconfigurable power loads. Design parameters that affect the efficiency of these receivers under highly variable load conditions, including piezoelectric material, geometry, and operation frequency, are investigated. Measurements were performed to characterize electrical impedance and acoustic-to-electrical efficiency of ultrasonic receivers for off-resonance operation. Finally, we propose, analyze, and demonstrate adaptive matching and frequency tuning techniques using two different reconfigurable matching networks for typical implant loads from 10 [Formula: see text] to 1 mW. Both simulations and measurements show a significant increase in total implant efficiency (up to 50 percentage points) over this load power range when operating off-resonance with the proposed matching networks.

An ultrasonically powered implantable device for targeted drug delivery.

A wirelessly powered implantable device is proposed for fully programmable and localized drug delivery. The implant is powered using an external ultrasonic transmitter and operates at <; 5% of the FDA diagnostic ultrasound intensity limit. Drug release is achieved through electrical stimulation of drug-loaded polypyrrole nanoparticles. A design methodology for the implant electronics is presented and experimentally demonstrated to be accurate in predicting the concentration of the released drug. To the best of our knowledge, this is the first ultrasonically powered implantable device platform for targeted drug delivery using electroresponsive polymers. The active area of the implant electronics is just 3 mm × 5 mm.