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

Abstract

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.

Deformable, transparent, high‐performance, room‐temperature oxygen sensors based on ion‐conductive, environment‐tolerant, and green organohydrogels

“…Flexible and stretchable chemical sensors have attracted increasing research interest because of their great application promise in emerging fields such as electronic skin, healthcare, wearable medical device, soft robotics, environmental monitoring 1–9 . Oxygen (O 2 ) is an essential gas with significant applications in many fields, such as biology, oceanography, medicine, environmental, and life sciences 10–12 . Recently, numerous COVID‐19 patients suffer from hypoxia, so convenient and continuous O 2 monitoring can provide potent aid to the real‐time evaluation of the COVID‐19 patients' health condition for thereafter timely treatments 13 .…”

“…[1][2][3][4][5][6][7][8][9] Oxygen (O 2 ) is an essential gas with significant applications in many fields, such as biology, oceanography, medicine, environmental, and life sciences. [10][11][12] Recently, numerous COVID-19 patients suffer from hypoxia, so convenient and continuous O 2 monitoring can provide potent aid to the real-time evaluation of the COVID-19 patients' health condition for thereafter timely treatments. 13 Among various sensing materials, ionic conductive hydrogels have become one of the most promising candidates as flexible wearable sensors owing to their tunable material composition and sensing performance, intrinsic stretchability, transparency, biocompatibility, self-healability, facile and costeffective synthesis process, and so on.…”

A flexible, stretchable system for simultaneous acoustic energy transfer and communication

“…Recently, state-of-the-art ultrasoundpowered devices can substantially reduce the dimensions of implants so that they have decreased implantation risk and show promising implantable medical applications of wireless acoustic energy transfer and communication (65)(66)(67)(68). Sonmezoglu et al developed a miniaturized ultrasound-powered implant (3 mm by 4.5 mm by 1.2 mm) that could wirelessly monitor deep-tissue oxygenation (tested at centimeter-scale depths in sheep) (69). Piech et al developed a tiny ultrasound-powered implantable neural stimulator (3.1 mm by 1.9 mm by 0.8 mm) with bidirectional communication function that may facilitate closed-loop neurostimulation for therapeutic interventions (18).…”

Scandium-Doped Aluminum Nitride PMUT Arrays for Wireless Ultrasonic Powering of Implantables

“…Within ultrasonic power receivers, a fair amount of work has utilized bulk thickness-extensional mode transducers [2] resulting in high power outputs but having the caveat of being invasive due to their minimum dimensions required. A further step within these kind of transducers has been the demonstration of minute Lead Zirconate Titanate (PZT) cubes allowing to power implantable Application-Specific Integrated Circuits (ASICs) for optogenetic stimulation [3], wireless recording of bio-signals [4], deep-tissue oxygenation monitoring [5] and bi-directional data links [6].…”