(249a) Collecting Interstitial Fluid from the Skin As a Novel Source of Biomarkers

Tissue interstitial fluid (ISF) is a novel source of biomarkers that complements conventional sources like blood and urine. However, ISF has received limited attention due largely to lack of simple collection methods. To address this issue, we have developed methods to sample ISF from skin in a relatively simple manner with minimally invasive microneedles in animals and human participants.

In one study, we used a microneedle patch to create an array of micropores in skin coupled with mild suction to sample ISF from human participants and identified valuable and sometimes unique 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 like current continuous glucose monitors, but without an indwelling subcutaneous sensor. Biomarkers unique 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 (a model biomarker in healthy adults) and pharmacodynamics of glucose (in diabetic children and young adults) were similar in ISF and plasma, indicating that dynamic information of biomarkers could also be captured using ISF.

In another study, we developed a different microneedle-based method to collect ISF from the skin by pressing microneedles at an angle just below the skin surface to collect blood-free ISF through micropores to the skin surface without the need for vacuum, which was absorbed into a thin strip of paper on the microneedle patch backing for subsequent analysis. An optimized method in rat skin in vivo was well tolerated and able to collect microliters of ISF within minutes. Brief skin pre-treatment with microneedles followed by a delay for a few minutes dramatically increased subsequent ISF collection by a mechanism believed to involve increased skin hydration. Using this approach, we demonstrated the use of ISF for therapeutic drug monitoring by showing similar vancomycin pharmacokinetic profiles in ISF and serum from rats. We also measured polio-specific neutralizing antibodies and anti-polio IgG in ISF similar to serum in rats immunized with polio vaccine.

Overall, these studies provide a method to sample ISF in a relatively simple manner with minimally invasive microneedles and demonstrate ISF as a source of biomarkers that can enable further research and translation for future clinical applications.