Skin's Interstitial Fluid, Sampling Device Could Yield New Source Of Biomarkers

An array of tiny needles allowed researchers to sample the skin's interstitial fluid, a largely unexplored bodily liquid that could potentially yield diagnostic biomarkers not found in blood and measurements of environmental toxin exposure, a new study suggests.

Because the dermal interstitial fluid doesn't clot like blood does, the microneedle-based extraction also could offer a new approach to continuous monitoring of key health indicators, such as glucose, researchers report in Science Translational Medicine.

"We currently get our information about health status largely from blood," said study coauthor Mark Prausnitz, Regents Professor of Chemical and Biomolecular Engineering at the Georgia Institute of Technology in Atlanta. "But there are many other fluids in the body. We have developed a method that involves microneedles to access interstitial fluid, which opens the door to new kinds of medical diagnostics as well as new research."

Interstitial fluid originates in the blood and then leaks out of capillaries to bring nutrients to cells in the body's tissues, Prausnitz explained. It should have information about the tissues themselves beyond what can be measured from testing the blood.

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One advantage of using interstitial fluid rather than blood is that it contains more information than blood, Prausnitz said. "There are metabolic processes that happen in tissue that are not specific to the skin, but are the result of activity in the tissues," he said.

Another advantage, Prausnitz said, is that monitoring with interstitial fluid wouldn't have the big drawback, clotting, that blood does. "We can envision a patch that continuously samples fluid from the skin and makes measurements from it," he said.

Other researchers have found ways to access interstitial fluid, but they are not minimally invasive, like the one developed by Georgia Tech, Prausnitz said. Some have used surgically implanted tubing and vacuum-created blisters to extract interstitial fluid through the skin, but these techniques are not suitable for routine clinical diagnostic use, he added.

The new method of collecting interstitial fluid uses a patch containing five solid stainless steel microneedles one hundredth of an inch in length. To test their new device, the researchers recruited 50 volunteers to participate in a series of experiments.

By pressing the patch onto a volunteer's skin at an angle, the researchers were able to create shallow micropores that reached only into the outer layer of skin. When suction was applied to the area of skin with micropores, Prausnitz and his colleagues were able to obtain enough fluid for their analyses. Overall, the interstitial extraction took about 20 minutes for each volunteer and was well tolerated. The researchers also collected blood from the volunteers for comparison.

To identify the chemical species contained in the fluid, the researchers analyzed it with chromatography-mass spectrometry. They found the fluid contained 10,000 unique compounds, most of which (79%) were also found in the blood samples.

In another experiment, the researchers tracked caffeine levels in the body with both blood samples and interstitial fluid samples, while volunteers consumed a caffeinated soda. The interstitial fluid levels of caffeine correlated well with those from blood samples.

You can look at the skin "as a window to the body," said Dr. Lou Falo, a professor and chair of the department of dermatology at the University of Pittsburgh School of Medicine. "The novel approach (described in the study) can be used to gain insight into a broad range of metabolic changes and disease indicators," Dr. Falo said. "It could be a great tool for systemic monitoring and also a unique tool for dermatologic monitoring."

The new research is "very timely and important," said Netz Arroyo, an assistant professor of pharmacology and molecular sciences at the Johns Hopkins University School of Medicine. "There is an ongoing race to develop wearable technology that will non-invasively monitor molecular targets in the body," he added.

While this type of research may one day lead to a biosensor patch, "that may be a ways away," Arroyo said. "The technique they presented is not directly translated into a wearable format," he added.

—Linda Carroll

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