Opportunities and challenges in the diagnostic utility of dermal interstitial fluid

The volume of interstitial fluid (ISF) in the human body is three times that of blood. Yet, collecting diagnostically useful ISF is more challenging than collecting blood because the extraction of dermal ISF disrupts the delicate balance of pressure between ISF, blood and lymph, and because the triggered local inflammation further skews the concentrations of many analytes in the extracted fluid. In this Perspective, we overview the most meaningful differences in the make-up of ISF and blood, and discuss why ISF cannot be viewed generally as a diagnostically useful proxy for blood. We also argue that continuous sensing of small-molecule analytes in dermal ISF via rapid assays compatible with nanolitre sample volumes or via miniaturized sensors inserted into the dermis can offer clinically advantageous utility, particularly for the monitoring of therapeutic drugs and of the status of the immune system.