June 28, 2023 – A smartwatch can tell you a lot about your health, but for guarding against big threats like diabetes and heart disease, blood tests remain the gold standard – for now. 

Someday, a wearable patch could give you the same information, minus the poke in the arm and the schlep to the doctor’s office. 

The patch will track markers in fluid under your skin, between and around your cells, called interstitial fluid. 

If you’ve ever seen or used a continuous glucose monitor, then you’ve already glimpsed this future. These skin patches, typically worn on the back of the upper arm,  use interstitial fluid to track blood sugar levels in real time. 

Now scientists are asking: What else could this tech help us measure? 

“The vision is eventually to develop a lab under the skin,” said Joseph Wang, PhD, a professor of nanoengineering at the University of California San Diego.

The result: All your lab work – cholesterol, hormones, electrolytes, and more – could become do-it-yourself, easing burdens on the health care system and empowering you with real-time, clinical-grade information about your health. 

How Does It Work?

Sweat and saliva may be easier to get to, but interstitial fluid is a better mirror for blood. It leaks from tiny blood vessels (capillaries), and it carries nutrients to and removes waste from your skin.

To capture this fluid, each monitor has either a tiny wire or an array of less-than-a-millimeter-long microneedles that penetrate the skin for days, weeks, or however long you wear it. “You don’t feel it,” Wang said. “Once you place it on the skin, you forget about it.”

The microneedles or wires are made from a polymer that sucks up the fluid, which flows to a biochemical sensor targeting the marker you want to measure.

The earliest patents for this technology date back to the 1990s (the first wearable glucose monitors for home use rolled out in the 2000s), but sensors have come a long way since then, becoming smaller, more accurate, and more sophisticated.

Glucose sensors use an enzyme that reacts to glucose to reveal its concentration in the blood. Some researchers – like Jason Heikenfeld, PhD, and his team at the University of Cincinnati – focus on “aptamers,” short single strands of DNA that bind to target molecules. “You can leverage the body’s own ability to generate stuff to grab a needle in a haystack,” he said.   

The Bigger Picture

As our population ages and health care costs spiral, and our medical infrastructure and labor force are stretched thin, we’re seeing a push for decentralized medicine, Heikenfeld said. Like other at-home monitoring technologies, interstitial fluid sensing promises convenience and better access to care. 

“There’s a lot you can do over telemedicine, over the phone,” said Justin T. Baca, MD, PhD, an associate professor at the University of New Mexico. “But we still haven’t figured out how to collect reliable biosamples and analyze them remotely.”

Unlike a traditional blood test, which gives a health snapshot for a single point in time, these devices track data continuously, revealing trends and helping doctors spot oncoming threats earlier. 

Take ketones, for example, a chemical made in the liver as it breaks down fats. High levels in diabetes patients can lead to a life-threatening condition called diabetic ketoacidosis, which often builds slowly and can be overlooked in early stages. 

Baca and others are using interstitial fluid to continuously detect ketone levels in the blood. 

“It’s potentially like an early warning sign that somebody needs to get either checked out or get rehydrated or get some insulin,” Baca said, “kind of an early diagnostic to avoid hospital visits later on.” 

Here’s what else this tech could help us do:

Chronic Disease Management

Seeing the health impact of medication and diet in real time could motivate patients to stick to their treatment plans, Heikenfeld said. Researchers in Taiwan are developing a test that could help people with chronic kidney disease track levels of cystatin C, a protein that goes up as kidney function declines. Heart disease patients could watch their cholesterol levels drop over time, and of course, diabetes patients can already track glucose. 

Prescription Drug Monitoring

Providers could monitor drug levels in a patient’s body – like antibiotics for an infection – to see how it’s being metabolized, and adjust the dose as needed, Heikenfeld said. 

Stress and Hormone Therapy

Interstitial fluid could help us measure hormone levels, such as the stress hormone cortisol. 

Scientists in the U.K. and Norway developed a waist-worn device that collects interstitial fluid samples continuously for up to 3 days. In their study, samples were sent out for analysis, but someday the device could be equipped with a sensor to monitor a single hormone in real time, said study author Thomas Upton, PhD, a clinical research fellow at the University of Bristol in England. “There is a lot of interest in real-time cortisol monitoring,” he said. 

Among those who could benefit: patients with hormone deficiencies, night shift workers with messed-up circadian rhythms, or anyone who wants to keep tabs on their stress response. 

Human Performance and Wellness

Athletes could use glucose and lactate monitors to optimize training, recovery time, and diet. On the keto diet? A monitor could help you adjust your carb intake based on your ketone levels. Abbott’s Analyte Ventures group is working on blood alcohol sensors, helpful to anyone who wants to avoid overindulging.  

When Can You Get One? 

Early research has been promising, but much more is needed before interstitial fluid sensors can be verified and approved. 

Manufacturing will be a challenge. Producing these sensors at scale, without sacrificing consistency or quality, won’t be cheap, said Heikenfeld. Today’s continuous glucose monitors took decades and hundreds of millions of dollars to develop. 

Still, the groundwork has been laid. 

“As we all pivot more towards interstitial fluid, there’s a proven roadmap of success that the big diagnostic companies over decades have cut their teeth on,” said Heikenfeld. 

For now, scientists are refining sensors and figuring out how to protect them from other body fluids while in use, Wang said. But if it all comes together, the result could be game-changing.

Wang’s lab is developing a system that can monitor glucose and lactate or glucose and alcohol – which could become available in as little as 2 years, he said. 

In the next decade, Wang predicted, we’ll be able to measure a dozen markers with one simple patch.

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