A wearable 3D-printed hollow microneedle device for pressure-driven interstitial fluid collection and testing

Abstract

Interstitial fluid (ISF) is the extracellular fluid within the dermis that transports biomolecules diffusing from blood vessels to lymphatic vessels. Owing to its blood-like composition and accessibility only a few millimeters beneath the skin surface, ISF has recently attracted considerable attention as a minimally invasive reservoir for biomarker analysis. Conventional ISF collection relies on invasive sampling methods. Microneedle (MN) technology has emerged as a promising approach for developing minimally invasive ISF sampling and analysis systems. We present a design and one-step stereolithography (SLA)-based 3D printing fabrication of a wearable hollow MN device: μHolloSense. The device is capable of negative pressure-assisted ISF collection via its syringe port and is compatible with lateral flow assay (LFA) testing through a dedicated test port. The overall cost was ∼$1 per single-use device, including all components, and $1.50 per SARS-CoV-2 antigen test, used here as a proof-of-concept LFA system. Additionally, a 3D-printed, agarose-based skin-mimicking platform was developed to provide a standardized tool for evaluating MN sampling performance. Beyond this model system, ex vivo skin experiments were conducted to validate the applicability of μHolloSense for ISF collection in biologically relevant tissues. Our results demonstrate that μHolloSense, featuring a refined tip diameter (44.19 ± 2.4 μm) and height (1207.93 ± 11.25 μm), is capable of drawing liquids at a rate sufficient to reach the dermis, exhibiting robust mechanical properties (>0.17 N compressive force per needle) in IgG LFA tests across antigen concentrations of 1, 10, 100, and 250 pg mL⁻¹. Ex vivo experiments on mice skin confirmed ISF extraction of up to 6 μL per sampling, with protein concentrations consistent with physiological levels. Collectively, this work presents a unified strategy for the design, fabrication, and evaluation of 3D-printed hollow MN systems with an integrated negative-pressure approach for ISF-based biomolecule analysis. In the future, further optimization and clinical validation of this platform would enable continuous, minimally invasive monitoring of a wide range of biomarkers, paving the way for point-of-care diagnostic and personalized health applications.