The next frontier of continuous health monitoring may be skin deep.
Biomedical engineers at the University of Cincinnati say that interstitial fluid, the watery fluid found between and around the body’s cells, tissues or organs, could provide an excellent means for early diagnosis of disease or long-term health monitoring.
In an article published in the journal Nature Biomedical Engineeringthey outlined the potential advantages and technological challenges of using interstitial fluid.
“The reason we see it as a valuable diagnostic fluid is continuous access. With blood, you can’t easily take continuous readings,” said Mark Friedel, a UC doctoral graduate and co-lead author of the study.
“Can you imagine spending the day with a needle in your vein all day? So we need other tools.”
Researchers are looking for alternatives to monitor a person’s health and well-being. Sweat is a good way to measure things like stress or anxiety because it contains hormones like cortisol. But the body is stingy with other chemicals that aren’t as easily released in sweat, Friedel said.
“Sweat glands are big filters that don’t let everything through,” he said. “So more than half of the things we want to monitor don’t have access to sweat.”
Blood is the gold standard for health monitoring. But people also have liters of interstitial fluid that make up as much as 15% of their body weight.
“The main feature of blood that makes it so advantageous is that we understand blood very well,” Friedel said. “If you have something in your blood, we know what’s going to happen to your heart or your liver,” he said.
The researchers said that interstitial fluid contains many of the same chemicals in the same proportions as blood, offering a potential alternative to expensive and time-consuming lab work.
The study outlined the various ways doctors can collect interstitial fluid samples, from applying suction to the skin to implanting microdialysis.
“As biomedical engineers, one of our biggest goals is to help people better manage their health by making diagnostics more accessible,” said co-author Ian Thompson of Stanford University.
“A major barrier to this accessibility is that most current diagnoses rely on blood sampling, which can be painful and requires trained personnel to perform. So, in recent years, there has been increasing interest in using the interstitial fluid just below skin as a diagnostic specimen that is more accessible and less painful to extract.”
In the New Devices Laboratory of UC College of Engineering and Applied Sciences professor Jason Heikenfeld, students are developing sensors to measure hormones and other chemicals in interstitial fluid. They use microneedles less than 1 millimeter long that pierce the skin through a small patch.
“If you had a splinter, it probably went deeper into your skin than our microneedles did,” Friedel said. “They are usually painless. I don’t feel it most of the time. The most uncomfortable part is removing the tape that holds the device in place.”
But even if you don’t know it’s there, your body does, Friedel said. And this minute reaction can affect the test results.
“There is a Schrödinger observer effect with the interstitial fluid. Whenever you try to collect and measure it, you inherently change the fluid itself,” Friedel said. “If you stick a needle in your skin, your body becomes inflamed and then your [sample] levels change. For continuous biomonitoring, we want to know what those concentrations look like when you’re not being pricked by a tiny needle.
“That’s why it’s such a challenging fluid that it hasn’t been used outside of diabetes monitoring.”
Still, say the researchers, interstitial fluid holds enormous promise for health monitoring through wearable technology. This can help doctors track the effectiveness of medications to ensure proper dosing or provide early diagnosis of disease by monitoring the immune system.
But Friedel said there’s still a lot to learn.
“We’re trying to unlock the box and read the instructions inside to understand what’s in the interstitial fluid and what the potentials are for exploiting it,” he said.
Friedel and Thompson worked with co-author Heikenfeld, UC’s James L. Winkle College of Pharmacy, Sandia National Laboratories in New Mexico, and Southeast Missouri State University.
The study was funded by grants from the National Science Foundation, the US Air Force Office of Scientific Research and the US Office of Naval Research.