Hung Andy H, Kamat Netra U, Bermudez Abel, Boczek Stephanie M, Garcia-Marqués Fernando J, Tan Yee Lin, Hwang Jihyun Luna, Sinawang Prima Dewi, Ilyin Dan, Jacobson Gunilla B, Demirci Utkan, Poplack Steven P, Pitteri Sharon J, DeSimone Joseph M
Department of Radiology, School of Medicine, Stanford University, CA 94305, USA.
Department of Bioengineering, Stanford University, CA 94305, USA.
Sci Adv. 2025 Sep 26;11(39):eadx5492. doi: 10.1126/sciadv.adx5492. Epub 2025 Sep 24.
Dermal interstitial fluid (ISF) offers a promising alternative to invasive blood tests and opportunities for 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 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.
真皮间质液（ISF）为侵入性血液检测提供了一种有前景的替代方法，也为皮肤诊断带来了机遇。ISF检测在理解和应用方面的进展受到采样挑战的阻碍，包括采集时间长、失败率不可忽视、采集量可变以及生物分析物水平不一致。这些问题中许多的成因尚未得到很好的理解。我们展示了一种微针装置，其速度比现有技术快几倍，在人体中5分钟内平均可采集15.5毫克ISF，失败率近乎为零。这种改进是通过设计驱动ISF流动的空间压力梯度实现的。阐明了穿透深度、采集时间、压力和年龄对ISF采集的影响，达西定律解释了多个观察结果。提出了ISF血液污染<1%的数据驱动接受标准。所展示的装置和研究结果将使研究人员能够在ISF诊断开发中更好地开展稳健的研究。
