(610d) Extraction of Interstitial Fluid Using Microneedle Patches: Biophysical and Tissue Properties Limiting Dermal Interstitial Fluid Flow (Industry Candidate)

Interstitial fluid (ISF) is a biomarker-rich fluid found in the spaces between the cells in tissues which has potential for use in point-of-care (POC) diagnostic tests. The ISF in the skin can be accessed using microneedle (MN) patches, but the ISF volumes extracted remain low due to slow fluid transport through the dermis.

In this presentation we will discuss the results from two sets of experiments -one ex-vivo and one in humans- that reveal quantitative information about the biophysical tissue factors limiting ISF flow after treating the skin with MN patches and during application of suction to withdraw the ISF. In the first set of experiments we targeted ex-vivo dermis as a porous fibrous matrix to learn about the types of fibers that limit ISF flow through the dermis. When we treated skin ex-vivo with collagenase and hyaluronidase to degrade skin fibers and increase the amount of ISF extracted, we found that treatment with up to 10 mg/ml of collagenase increased ISF flow rates by up to a factor of 5. We attribute this effect to an increase in hydraulic conductivity produced by the degradation of collagen fibers. We also found that similar concentrations of hyaluronidase – an enzyme previously used in drug delivery to reduce the hydraulic conductivity of the dermis- had a smaller effect than collagenase on the amount of ISF collected.

The second set of experiments, done in human subjects, provides insights about fluid flow through the skin as a living organ with the ability to respond physiologically after application of our MN patches and suction treatment. We found that application of suction of 50 kPa on human skin for periods longer than ~1 hours produces blisters, even after creating micropores on the skin with MNs. A theoretical analysis of flow through the skin during blister formation indicates that the hydraulic conductivity of the epidermis is less than 1/10 that of the dermis. We also estimated fluid fluxes from the dermis into blisters, and found that these fluxes may be larger than 1 µl/min/cm², an encouraging finding that suggests it may be possible to mobilize ISF through the dermis at these rates. Altogether, these results provide relevant mechanistic insights about ISF flow that can guide the design of a MN-based systems for extraction of ISF for POC diagnostics tests.