Label-free surface-enhanced Raman spectroscopy sensing with 3D-Printed Ag-coated Au nanorod microneedles: A Langmuir–Blodgett strategy for on-site pH monitoring

To address the need for highly sensitive yet minimally invasive biomarker detection in deeper tissues, this article presents a high-performance surface-enhanced Raman spectroscopy microneedle sensor that utilizes Ag-coated Au nanorods and a Langmuir–Blodgett multilayer coating on 3D-printed stepped microneedles. The sensor detects rhodamine 6G at concentrations as low as 10⁻¹⁰ M and exhibits excellent durability under repeated insertion-withdrawal tests, showing no observed coating detachment. An agarose-based skin phantom with distinct epidermal and dermal layers confirms its ultratrace detection capability. Furthermore, 4-mercaptobenzoic acid functionalization enables pH monitoring, yielding consistent results in both agarose and ex vivo porcine skin across multiple pH cycles. This minimally invasive platform combines high sensitivity with mechanical robustness, enabling label-free detection of various analytes directly in skin-like tissues. The results of this study underscore its potential for real-time biomedical diagnostics and physiological monitoring, paving the way for broader clinical and translational applications. Therefore, it holds promise as a novel device for advanced biosensing in clinical settings.