By Deborah Borfitz
March 10, 2021 | Nanoengineering experts at the University of California (UC), San Diego have succeeded in developing an all-in-one health monitoring device that can reliably measure glucose, lactate, and blood pressure using a soft, stretchy skin patch the size of a postage stamp. It is notoriously difficult to do blood pressure monitoring and metabolite sensing at the same time in the human body due to signal interference when chemical and ultrasound hydrogels intermix, says Juliane Sempionatto, a nanoengineering Ph.D. student in the lab of Joseph Wang.
The problem was overcome by utilizing solid rather than liquid hydrogels and separating the chemical and blood pressure sensors by precisely one centimeter, says Sempionatto, lead author on a study of the epidermal patch that recently published in Nature Biomedical Engineering (DOI: 10.1038/s41551-021-00685-1). It would be “super-easy” to adapt the platform to specific diseases by swapping in the relevant biomarkers.
The wearable will initially be best suited to consumers interested in personal health insights, such as what happens to their blood pressure after they exercise or drink coffee, or how their glucose and blood pressure readings correlate, Sempionatto says. But the research team expects it will ultimately find relevance in medical settings as a device meeting all the regulatory hurdles of the U.S. Food and Drug Administration (FDA).
She envisions an entire line of patches working their way to market tailored to the specific needs of patients. People with chronic health conditions such as high blood pressure and diabetes might slap on a patch to self-monitor their health, Sempionatto says. Physicians might want to add the tool to their remote patient monitoring arsenal to minimize in-person clinic visits.
In the hospital, the device could be used to detect the onset of sepsis, which is characterized by a sudden drop in blood pressure accompanied by a rapid rise in lactate level, she continues. The patch would also be a convenient alternative for patients in intensive care, including babies, in lieu of being tethered to machinery that continuously monitors their blood pressure and other vital signs.
Two pioneering efforts in the UC San Diego Center for Wearable Sensors made the device a reality, Sempionatto says. Wang’s lab came up with wearables capable of monitoring chemical, physical, and electrophysiological signals concurrently, while the lab of nanoengineering professor Sheng Xu developed the stretchy electronic skin patches that can monitor blood pressure deep inside the body.
It has been one of the “greatest partnerships” of her career, enthuses Sempionatto, resulting in the integration of the two technologies into a single device. A thin sheet of polymers that conforms to the skin serves as the substrate.
The blood pressure sensor sits near the center of the device and consists of a set of small ultrasound transducers that are welded to the substrate by a conductive ink, explains Sempionatto. A voltage applied to the transducers causes them to send ultrasound waves into the body and, when they bounce off an artery, the sensor detects the echoes and translates the signals into a blood pressure reading.
The chemical sensors are a pair of electrodes screen-printed on the patch from conductive ink, she says. One electrode can sense either lactate (a biomarker of physical exertion), caffeine, or alcohol, and is printed on the right side of the patch together with the sweat stimulation system, which works by releasing the sweat-inducing drug pilocarpine into the skin for detection of chemical substances in that sweat.
The other electrode, she continues, senses glucose and is printed on the left side of the patch where the interstitial fluid extraction system is located. It works by passing a mild electrical current through the skin to pull out interstitial fluid so glucose can be measured in that fluid.
One of the more challenging and time-consuming tasks was eliminating the “crosstalk effects” between the electrochemical and blood pressure sensors, Sempionatto says. “They both use voltage … so we had to choose our materials carefully.”
The research team did practically everything “from scratch,” says Sempionatto, including fabrication of the stretchy polymers and conductive ink. The enzymes for the chemical sensors were commercially available as was the solid hydrogel, which appears to be scarcely used for any purpose.
For the all-in-one monitoring device, developers needed to use hydrogels with optical properties compatible with human skin, she adds, as well as high densities so they did not interfere with readings from nearby sensors. If a liquid hydrogel is preferred, a bigger device size is required.
Testing of the device has been completed only in a group of healthy consenting volunteers with no previous history of heart conditions, diabetes, or chronic pain. For all on-body evaluations, the patch was placed on their neck. The biomarkers, she notes, all impact blood pressure.
Glucose, lactate, alcohol, and blood pressure signals were validated against a commercial glucometer (ACCU-CHEK), blood-lactate meter (NOVA Biomedical), breathalyzer (BACtrack S80 Pro), and FDA-approved blood pressure cuff (LOVIA), respectively, as detailed in the journal article. Caffeine concentrations were estimated by standard addition methodology using collected sweat. An electrochemical impedance analyzer was used to stimulate sweat and extract interstitial fluid simultaneously.
The version of the patch used for the study was not fully wearable since the blood pressure sensor needed to be connected to a power source and a benchtop machine to display its readings. But the next prototype likely will be completely wireless, says Sempionatto, adding that the research team is now working on the device with doctors in the hospital.
Since only a limited amount of pilocarpine can be loaded into the hydrogel, and gets depleted with use, sweat sensing is only possible for about four hours, Sempionatto says. Extending the monitoring period to 24 hours would be possible with other types of drugs, such as carbachol (used to treat glaucoma), or technologies for sweat stimulation.
The utility of hydrogels is also limited by the fact that they eventually dry. “We’re working on a new formulation of gels in-house… that can last longer without drying [over longer monitoring periods],” she says.
‘Just the Beginning’
Established market players have already started incorporating blood pressure sensing into their activity trackers. Most recently, Samsung Electronics announced that Galaxy smartwatch users can now measure their blood pressure via the Samsung Health Monitor app. Unlike the all-in-one monitoring device of the UC San Diego team, which can continuously and non-invasively monitor blood pressure in patients as deep as four centimeters below the skin, the sensor being used by Samsung is optical, so it might come with “a lot of interference” from neighboring veins.
More than a dozen smartwatches now on the market include blood pressure monitoring via either optical sensors or an actual blood pressure cuff. No word yet on when Fitbit or Apple watches might incorporate such a feature.
To be of value to clinicians, it will be important for the monitoring device to factor in the influence of caffeine, alcohol, and exercise on blood pressure, says Sempionatto. That currently requires a blood pressure cuff and fingerstick device, diagnostic approaches that themselves influence blood pressure readings.
Among the collaborations the research team has with clinicians is a project with a physician utilizing the device for sensing dips in glucose and blood pressure among diabetics experiencing nocturnal hypoglycemia, which can be life-threatening, she says. The wearable is also of potential utility in tracking side effects, including low blood pressure, among patients being treated with certain Parkinson’s drugs.
Xu has a new company, Softsonics, spun off from UC San Diego, which is developing the soft, flexible patch being incorporated into the all-in-one monitoring device. It can be worn on the skin over the carotid artery or jugular vein, and uses pulses of ultrasound to measure blood pressure, providing continuous readings in deep tissue.
The integrated device is newly patented and expected to get the attention of industry partners, Sempionatto says. As detailed in the supplementary information section of the Nature Biomedical Engineering article, the device can be outfitted with an even greater number of anolytes with a few design tweaks.
Sempionatto speculates that the first commercial application of the wearable will be for personal, nondiagnostic use, giving the research team an opportunity to assess consumer acceptance and wearability issues that might limit practical application. But FDA approval for a medical-grade device is on the roadmap, she says. “This is just the beginning.”