Sampling interstitial fluid from human skin using a microneedle patch

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Science Translational Medicine  25 Nov 2020:
Vol. 12, Issue 571, eaaw0285
DOI: 10.1126/scitranslmed.aaw0285

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Metabolite monitoring

Biofluids such as saliva, blood, urine, tears, and interstitial fluid (the fluid that surrounds cells) contain proteins and can be isolated for health monitoring. Samant and colleagues developed a microneedle-based method that used mild suction to isolate interstitial fluid from skin. Mass spectrometry was used to compare metabolites in interstitial fluid, suction blister fluid, and plasma from healthy individuals and to look at glucose pharmacodynamics in children with diabetes. Microneedle sampling could provide a minimally invasive method for biomarker analysis from interstitial fluid.


Tissue interstitial fluid (ISF) surrounds cells and is an underutilized source of biomarkers that complements conventional sources such as blood and urine. However, ISF has received limited attention due largely to lack of simple collection methods. Here, we developed a minimally invasive, microneedle-based method to sample ISF from human skin that was well tolerated by participants. Using a microneedle patch to create an array of micropores in skin coupled with mild suction, we sampled ISF from 21 human participants and identified clinically relevant and sometimes distinct biomarkers in ISF when compared to companion plasma samples based on mass spectrometry analysis. Many biomarkers used in research and current clinical practice were common to ISF and plasma. Because ISF does not clot, these biomarkers could be continuously monitored in ISF similar to current continuous glucose monitors but without requiring an indwelling subcutaneous sensor. Biomarkers distinct to ISF included molecules associated with systemic and dermatological physiology, as well as exogenous compounds from environmental exposures. We also determined that pharmacokinetics of caffeine in healthy adults and pharmacodynamics of glucose in children and young adults with diabetes were similar in ISF and plasma. Overall, these studies provide a minimally invasive method to sample dermal ISF using microneedles and demonstrate human ISF as a source of biomarkers that may enable research and translation for future clinical applications.

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