Enhanced extraction of human interstitial fluid using microneedles and laser-induced fluid recruitment

Dermal interstitial fluid (ISF) contains biomarkers with potential use in medical diagnostics, but current systems extract insufficient ISF for many applications. We tested the hypothesis that increased skin water content can increase ISF extraction due to enlarged dermal pore structure. Increasing skin water content <i>ex vivo</i> increased dermal pore size >5-fold, dermal hydraulic conductivity 1.5-fold, and ISF extraction 7-fold. We next developed an <i>in vivo</i> ISF extraction method involving laser pretreatment of skin to increase water content, microneedle puncture of skin to create pathways for ISF flow, and suction to drive ISF flow. This method yielded ISF volumes of up to 55 μL in human subjects, an 8-fold increase compared to extraction without laser and 4-fold increase in ISF volume per microneedle compared to prior studies. Overall, microneedles with laser-induced fluid recruitment provide a new mechanism to increase ISF sampling from skin, advancing the study of ISF biomarkers and ISF-based diagnostics.