Vacuum-Assisted Microneedle Platforms for Dermal Interstitial Fluid Sampling

Background: Dermal interstitial fluid (ISF) contains both plasma-derived biomarkers and biomarkers unique to ISF, making it a promising biofluid for painless, scalable, and decentralized liquid biopsy and continuous health monitoring. However, efficient ISF collection remains challenging due to the small accessible fluid volume in the dermis, slow physiological turnover, and stratum corneum. Methods: This review reframes dermal ISF sampling as a pressure gradient engineering problem using Darcy's law. We examine how vacuum-assisted microneedle platforms can effectively drive ISF through the dermal extracellular matrix in a minimally invasive manner. We compare the two architectures: micropore-based and hollow microneedle approaches. Results: In the micropore approach, a vacuum chamber is placed over the transient micropores left by withdrawn microneedles, supporting off-device, multi-omic downstream analyses of the collected ISF. The hollow microneedle approach retains the microneedles in the skin and applies vacuum through internal lumens, allowing integration of the vacuum source, microneedles, and biosensors into a single wearable platform for in situ biomarker detection. Comparative studies across these architectures identify the vacuum seal between the device and the skin as the major engineering bottleneck shared by both architectures. Conclusions: Vacuum-assisted microneedle platforms provide a practical route for generating pressure gradient-driven ISF transport while preserving minimally invasive skin access. Future development should prioritize device-skin vacuum seal robustness, reproducible ISF recovery across users and skin sites, integrated vacuum sources, scalable fabrication, and usability in clinical or at-home settings.