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A microneedle device for rapid dermal interstitial fluid sampling

Hung, Andy1; Kamat, Netra1; Bermudez, Abel1; Boczek, Stephanie1; Garcia-Marques, Fernando1; Tan, Yee Lin1; Hwang, Jihyun (Luna)1; Sinawang, Prima Dewi1; Ilyn, Dan1; Jacobson, Gunilla1; Demirci, Utkan1; Poplack, Steven1; Pitteri, Sharon1; DeSimone, Joseph1

Research facility: Stanford University School of Medicine
Published Sep 05, 2025 on Dryad. https://doi.org/10.5061/dryad.c2fqz61p1

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Abstract

Dermal interstitial fluid (ISF) offers a promising alternative to invasive blood tests and opportunities for novel skin diagnostics. Progress in both the understanding and adoption of ISF tests is hindered by sampling challenges, including lengthy collection times, non-negligible failure rates, variable collection volumes, and inconsistent bioanalyte levels. The causes of many of these issues are not well understood. We demonstrate a microneedle device that is several times faster than state-of-the-art, collecting an average of 15.5 mg of ISF in 5 minutes in humans with a near-zero failure rate. This improvement was achieved by designing the spatial pressure gradient driving ISF flow. The influence of penetration depth, collection time, pressure, and age on ISF collection was elucidated, with Darcy's law explaining multiple observations. A data-driven acceptance criterion of <1% blood contamination for ISF is proposed. The device and findings presented will empower researchers to better conduct robust studies in the development of ISF diagnostics.