A tiny wireless implant developed by engineers from the University of California, Berkeley, can offer real-time measurements of tissue oxygen levels deep beneath the skin.
The device is smaller than the average ladybug and driven by ultrasound waves. It could enable doctors to track the health of transplanted tissue or organs and offer an early warning of possible transplant failure.
The technology was developed in collaboration with physicians from the University of California, San Francisco, and opens the door to developing a range of miniaturized sensors with the ability to monitor other crucial biochemical markers in the body, like carbon dioxide or pH.
In the future, these sensors could offer minimally invasive methods for doctors to monitor the biochemistry within functioning tissues and organs.
It’s very difficult to measure things deep inside the body. The device demonstrates how, using ultrasound technology coupled with very clever integrated circuit design, you can create sophisticated implants that go very deep into tissue to take data from organs.
Michel Maharbiz, Professor of Electrical Engineering and Computer Sciences, University of California, Berkeley
Maharbiz, who is also a Chan Zuckerberg Biohub Investigator, is the senior author of a new paper published in the Nature Biotechnology journal and describing the device.
Oxygen is a crucial component crucial for cells to tap energy from the food that humans eat, and almost all tissues in the body need a constant supply to survive. The majority of methods used to measure tissue oxygenation can only offer information related to what occurs close to the surface of the body.
Thisis because these methods depend on electromagnetic waves (for example, infrared light), which can penetrate only a few centimeters into organ tissue or skin. Although other kinds of magnetic resonance imaging can offer information related to deep tissue oxygenation, they need long scanning times and thus cannot offer data in real-time.
From 2013, Maharbiz has been developing miniaturized implants working on ultrasonic waves to wirelessly communicate with the outer world. Ultrasonic waves are a kind of sound that is very high in frequency to be detected by the human ear.
They can penetrate harmlessly through the body at considerably higher distances compared to electromagnetic waves and are already the foundation for the ultrasound imaging technology used in medicine.
Stimdust, a device designed in collaboration with Rikky Muller, a UC Berkeley electrical engineering and computer sciences assistant professor, is one such example with the ability to detect and activate electrical nerve firings in the body.
The effort to increase the capabilities of the implant to include oxygen sensing was led by Soner Sonmezoglu, a postdoctoral researcher in engineering at UC Berkeley. Integrating the oxygen sensor requires building in an LED light source and an optical detector into the tiny device while also putting together a more complex set of electronic controls to run and read out the sensor.
The device was tested by the researchers by monitoring the levels of oxygen within the muscles of live sheep.
Sonmezoglu indicates that an oxygen sensor of this type varies from the pulse oximeters used to measure oxygen saturation in the blood. Pulse oximeters quantify the proportion of hemoglobin in the blood that is oxygenated, whereas the new device can directly measure the amount of oxygen in tissue.
“One potential application of this device is to monitor organ transplants, because in the months after organ transplantation, vascular complications can occur, and these complications may lead to graft dysfunction,” stated Sonmezoglu. “It could be used to measure tumor hypoxia, as well, which can help doctors guide cancer radiation therapy.”
Jeffrey Fineman and Emin Maltepe, co-authors of the study and pediatricians at UCSF and members of the Initiative for Pediatric Drug and Device Development, were involved in the study due to its potential to monitor fetal development and caring for premature babies.
In premature infants, for example, we frequently need to give supplemental oxygen but don’t have a reliable tissue readout of oxygen concentration. Further miniaturized versions of this device could help us better manage oxygen exposure in our preterm infants in the intensive care nursery setting and help minimize some of the negative consequences of excessive oxygen exposure, such as retinopathy of prematurity or chronic lung disease.
Emin Maltepe, Study Co-Author and Pediatrician, University of California, San Francisco
According to Sonmezoglu, the technology can be optimized further by housing the sensor such that it can survive for a long time within the body. Further miniaturization of the device would also ease out the implantation process, which necessitates surgery at present.
He added that the optical platform within the sensor can be readily adapted to quantify other biochemistry in the body.
By just changing this platform that we built for the oxygen sensor, you can modify the device to measure, for example, pH, reactive oxygen species, glucose or carbon dioxide. Also, if we could modify the packaging to make it smaller, you could imagine being able to inject into the body with a needle, or through laparoscopic surgery, making the implantation even easier.
Soner Sonmezoglu, Postdoctoral Researcher in Engineering, University of California, Berkeley
This study was financially supported by the Chan Zuckerberg Biohub and by the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development through grants R44HD094414 and R01HD07245.
Sonmezoglu, S., et al. (2021) Monitoring deep-tissue oxygenation with a millimeter-scale ultrasonic implant. Nature Biotechnology. doi.org/10.1038/s41587-021-00866-y.