Forget Blood—Your Skin Might Know If You’re Sick

A river of biological information flows just beneath the outermost layers of your skin, in which a hodgepodge of proteins squeeze past each other through the interstitial fluid surrounding your cells. This "interstitium" is an expansive and structured space, making it, to some, a newfound “organ.” But its wealth of biomarkers for conditions like tuberculosis, heart attacks, and cancer has attracted growing attention from researchers looking to upend reliance on diagnostic tools they say are inefficient, invasive, and blood-centric.

"Blood is a tiny fraction of the fluid in our body," says Mark Prausnitz, a chemical engineer at Georgia Tech who has been studying drug delivery through the skin since the 1990s. "Other fluids should have something useful—it's just hard to get those fluids."

Biomarkers normally course around your body like molecular records of past challenges to your immune system. Some reach far back in time, like the antibodies from childhood chickenpox; others, such as cytokines, correspond to stressed immune systems in real time. Following a blood draw, doctors have used cytokines as experimental indicators of severe immune response to Covid-19, for example.

Although the interstitial fluid, or ISF, is just a light scratch away, it’s hard to squeeze out even a dozen microliters, roughly a thousandth of a tablespoon, which is hundreds of times smaller than a diagnostic blood draw. Researchers know which biomarkers should be bouncing around in there, but without tools to measure them precisely, establishing baselines of what are normal versus diseased concentrations is essentially impossible. “It’s been a real limitation,” says Prausnitz.
But in a paper published in January in Nature Biomedical Engineering, researchers from Washington University in St. Louis reported catching ISF biomarkers with disposable microneedle patches and measuring them up to about 800 times more sensitively than comparable biomarker tests. These rectangular patches, no wider than a dime, contain hundreds of plastic needles, each prick less than a millimeter long. Press the patch into your finger, then soak the patch into a special nanoparticle solution, and those particles will sense the presence of the predetermined proteins.

Photograph: Srikanth Singamaneni Lab/Washington University in St. Louis
“That is the critical element here,” says Srikanth Singamaneni, a materials scientist who led the study. “We have shown that we can use those particles to significantly improve the sensitivity of immunoassays.”
Relying on blood draws for assays runs into particular barriers in economically developing countries, where health care access and appropriate biological sample storage can be a problem. “A lot of people don't realize that antibodies and so on are kind of unstable, especially when you are storing them in unrefrigerated conditions for a long time,” says Singamaneni. This technical hurdle makes global access to advanced medical tests challenging. “There is a lot of need for bio-diagnostics in low- and middle-income countries—and even in rural parts of the United States,” he continues.