Gut Microbiome Redox Sensors With Ultrasonic Wake-Up and Galvanic Coupling Wireless Links.

Tools to measure in vivo redox activity of the gut microbiome and its influence on host health are lacking. In this paper, we present the design of new in vivo gut oxidation-reduction potential (ORP) sensors for rodents, to study host-microbe and microbe-environment interactions throughout the gut. These are the first in vivo sensors to combine ultrasonic wake-up and galvanic coupling telemetry, allowing for sensor miniaturization, experiment flexibility, and robust wireless measurements in live rodents. A novel study of in situ ORP along the intestine reveals biogeographical redox features that the ORP sensors can uniquely access in future gut microbiome studies.

On-demand electrochemically controlled compound release from an ultrasonically powered implant.

On-demand drug delivery systems are promising for a wide range of therapeutic applications. When combined with wireless implants for controlled drug delivery, they can reduce overall dosage and side effects. Here, we demonstrate release of fluorescein from a novel on-demand release system for negatively charged compounds. The release system is based on a modified electroresponsive polypyrrole nanoparticulate film designed to minimize ion exchange with the stored compound - a major passive leakage mechanism. We further designed an ultrasonically powered mm-sized implant to electronically control the on-demand drug delivery system in vivo. Release kinetics are characterized both in vitro and in vivo in mice using fluorescein as a model drug, demonstrating the feasibility of wireless, controllable drug release using an ultrasonically powered implant.

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.

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.