3D-Printed Hollow Microneedle Potentiometric Sensors: A Modular Approach

Microneedle sensors represent a genuine approach to continuous health monitoring with minimally invasive access to skin interstitial fluid. However, their clinical deployment is hindered by complex fabrication and functionalization processes that compromise reproducibility and scalability. Truly, recent advancements in additive manufacturing have diminished certain obstacles; yet, single-modality techniques continue to encounter a significant trade-off between attaining high resolution and including electrochemical functionality. Accordingly, we introduce herein a novel modular hollow microneedle (HMN) architecture that separates insertion mechanics from ion sensing functionality. This new strategy synergistically integrates two complementary 3D printing modalities: high-resolution masked stereolithography (MSLA) to produce a robust, HMN shell, and fused filament fabrication (FFF) to fabricate a conductive pillar electrode to be modified with the ion-sensing role. The modularity of the sensor allows the pillar electrode to be functionalized prior to seamless assembly, protecting the sensing layer and ensuring robust and consistent potentiometric performance while addressing former drawbacks of the involved fabrication method: MSLA offers high-resolution hollow structures but is deficient in conductivity, whereas FFF facilitates conductive printing but suffers from restricted resolution. As a proof of concept, we have developed a potentiometric pH-HMN sensor that demonstrates excellent analytical performance, including a near-Nernstian response of -55.35 ± 0.54 mV/pH, high repeatability (RSD = 0.61%), reproducibility (RSD = 1.16%), and stability (0.37 mV/h) during in vitro testing. A complete sensing architecture comprising a single 3D-printed patch with two HMN to house both the pH sensing pillar electrode and a reference pillar electrode has demonstrated high accuracy in ex vivo tests using rat skin samples, showing a mean absolute difference of less than 0.05 pH units compared to a commercial pH electrode. The developed modular platform streamlines manufacturing, enabling the rapid, low-cost, and scalable production of reliable microneedle sensors, paving the way for their widespread use to other ions and analytes as well as future testing in live subjects.