3D-Printed Hollow Microneedle-Lateral Flow Devices for Rapid Blood-Free Detection of C-Reactive Protein and Procalcitonin

Hollow microneedle devices as a technology for interstitial fluid extraction show promise for the minimally invasive point-of-care detection of analytes. Despite increasing efforts toward on-patch diagnostics, the use of hollow microneedles has been limited due to the complexity caused by integrating hollow microneedles with established point-of-care diagnostic techniques. Herein, a 3D printing method is utilized, to provide low-cost manufacturing of custom-designed hollow microneedle devices, allowing for easy integration with lateral flow assays for rapid and blood-free diagnostics. Microneedle surface modification through PEGylation results in prolonged and enhanced hydrophilicity, enabling passive uptake of small volume samples (≈22.5 µL) and an enhanced shelf life. The hollow microneedle devices are deemed non-cytotoxic to cell types found within the skin following short-term and prolonged exposure in accordance with ISO10993. Furthermore, the devices demonstrate high mechanical strength and successfully penetrate porcine skin grafts without damaging the surrounding skin morphology. This work also demonstrates for the first time the use of hollow microneedles for the simultaneous detection, at clinically relevant concentrations, of C-reactive protein (LoD = 10 µg mL−1) and procalcitonin (LoD = 1 ng mL−1), through porcine skin, ultimately demonstrating the beneficial use of manufactured 3D-printed hollow microneedles towards low-cost blood-free diagnostics of inflammation markers.