Sampling interstitial fluid from human skin using a microneedle patch

• Type of Material: Article
• Authors: Pradnya P. Samant, Georgia Institute of Technology; Megan M. Niedzwiecki, Emory University; Nicholas Raviele, Georgia Institute of Technology; Vilinh Tran, Emory University; Juan Mena-Lapaix, Georgia Institute of Technology; Douglas Walker, Emory University; Eric Felner, Emory University; Dean Jones, Emory University; Gary Miller, Emory University; Mark Prausnitz, Emory University
• Language: English
• Date: 2020-11-25
• Publisher: AMER ASSOC ADVANCEMENT SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
• Final Published Version (URL): http://dx.doi.org/10.1126/scitranslmed.aaw0285
• Title of Journal or Parent Work: SCIENCE TRANSLATIONAL MEDICINE
• Volume: 12
• Issue: 571
• Grant/Funding Information: This work was supported in part by the U.S. National Institutes of Health (U2CES026560, P30ES020953, R01ES023485, P30ES019776, S10OD018006) and Children’s Healthcare of Atlanta.
• Keywords: HUMAN PLASMA; VACCINATION; IN-VIVO; Research & Experimental Medicine; ACID; Medicine, Research & Experimental; Cell Biology; SERUM; SUCTION BLISTER FLUID; Life Sciences & Biomedicine; METABOLOMICS; GLUCOSE; Science & Technology; ACCEPTABILITY; IONTOPHORESIS

Abstract

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.