Monitoring deep-tissue oxygenation with a millimeter-scale ultrasonic implant

Deep tissue oxygenation monitoring has many potential applications. Vascular complications after solid organ transplantation, for example, frequently lead to graft ischemia, dysfunction or loss, and can occur months after transplantation. While imaging approaches can provide intermittent assessments of graft perfusion, they require highly skilled practitioners, and fail to directly assess graft oxygenation. Existing tissue oxygen monitoring systems have many drawbacks, including the need for wired connections, the inability to provide real-time data, and, crucially, an operation that is limited to surface tissues. Here, we present the first wireless, minimally-invasive deep tissue oxygen monitoring system that provides continuous real-time data from centimeter-scale depths in a clinically-relevant large animal (sheep) model and demonstrates operation at great depths (up to 10 cm) through ex vivo porcine tissue. The system relies on a millimeter-sized, wireless, battery-free, implantable luminescence oxygen sensor that is powered by ultrasound and capable of bi-directional data transfer with an external transceiver. We present various aspects of system and sensor performance and demonstrate the operation of the system in vitro in distilled water, phosphate-buffered saline (PBS) and undiluted human serum, ex vivo through porcine tissue, and in vivo in a sheep model. We believe this technology represents a new class of diagnostic system particularly suitable for organ monitoring, as well as other surgical or critical care indications.