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Minimally invasive devices to detect molecules in dermal interstitial fluid (ISF) are desirable for point-of-care diagnostic and monitoring applications. In this study, we developed a microneedle (MN) patch that collects ISF for on-patch biomarker analysis by surface-enhanced Raman scattering (SERS). The micrometer-scale MNs create micropores in the skin surface, through which microliter quantities of ISF are collected onto plasmonic paper on the patch backing. The plasmonic paper was prepared by immobilizing poly(styrenesulfonate) (PSS) coated gold nanorods (AuNRs) on a thin strip of filter paper using plasmonic calligraphy. Negatively charged PSS was used to bind positively charged rhodamine 6G (R6G), which served as a model compound, and thereby localize R6G on AuNR surface. R6G bound on the AuNR surface was detected and quantified by acquiring SERS spectra from the plasmonic paper MN patch. This approach was used to measure pharmacokinetic profiles of R6G in ISF and serum from rats in vivo. This proof-of-concept study indicates that a plasmonic paper MN patch has the potential to enable on-patch measurement of molecules in ISF for research and future medical applications.

Minimally invasive point-of-care diagnostic devices are of great interest for rapid detection of biomarkers in diverse settings. Although blood is the most common source of biomarkers, interstitial fluid (ISF) is an alternate body fluid that does not clot or contain red blood cells that often complicate analysis. However, ISF is difficult to collect. In this study, we assessed the utility of a microneedle patch to sample microliter volumes of ISF in a simple and minimally invasive manner. We demonstrated the use of ISF collected in this way 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. These studies demonstrate the potential utility of ISF collected by microneedle patch in therapeutic drug monitoring and immunodiagnostic applications.

Interstitial fluid (ISF) that surrounds cells in tissues of the body is a novel source of biomarkers that complements conventional sources like blood, urine and saliva. To overcome difficulties in harvesting ISF, we developed a minimally invasive, rapid, simple-to-use and cost-effective method to collect ISF from the skin involving a microneedle (MN) patch. By pressing 650 μm long MNs at an angle just below the skin surface, blood-free ISF flowed through micropores to the skin surface and was absorbed into a thin strip of paper on the MN patch backing for subsequent analysis. An optimized method in rat skin in vivo was well tolerated and able to collect >2 μl of ISF within 1 min. Brief skin pre-treatment with MNs followed by a 5 min delay dramatically increased subsequent ISF collection by a mechanism believed to involve increased skin hydration. ISF collection using a MN patch has the potential to simplify access to biomarkers in ISF for research and future medical diagnostic and monitoring applications.