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3D printing by two-photon polymerization of hollow microneedles for interstitial fluid extraction

2024/10/15 by Tiago Elias Abi-Ramia Silva, Stephan Köhler, Silva, Tiago Elias Abi-Ramia +7
Engineering · Pharmacology, Toxicology and Pharmaceutics · #Advancements in Transdermal Drug Delivery #FOS: Physical sciences #Medical Physics (physics.med-ph) #Optical Coherence Tomography Applications

paper · pdf · doi:10.48550/arxiv.2410.11631

openalex publication_date 2024/10/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

Dermal interstitial fluid (ISF) is a rich source of biomarkers (e.g., glucose) that can be used for continuous health monitoring with wearable sensors. Hollow microneedle devices are a promising solution to extract ISF on demand by penetrating the skin with minimal pain. However, they rely on inserting bio-incompatible materials (e.g., silicon) into individuals, limiting the application time. Here, the direct 3D printing of polymer hollow microneedles on silicon-based microfluidic devices and the successful in-vivo extraction of ISF are demonstrated. Our additive manufacturing approach enables the versatile combination of materials and rapid prototyping of microneedle geometry. After improving the design through finite element modeling, a hollow microneedle geometry was printed by two-photon polymerization and experimentally characterized with mechanical and fluidic tests. Microneedles were fabricated with high accuracy (i.e., 997 +/- 2 um) and reliably interfaced with the microfluidic chip (i.e., centerline alignment within 5% of diameter). The needles demonstrated sufficient mechanical strength (i.e., 411 +/- 3 mN per needle) to endure at least 10 consecutive insertions into simulated skin. Biocompatibility and ISF extraction were demonstrated in an in-vivo 72-hour test, showing the safety and reliability of our approach. Such a platform is promising for minimally invasive, continuous monitoring of biomarkers in ISF, aiding in medical diagnoses and personalized health treatments.

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