Visualized molecularly-imprinted hydrogel chips for point-of-care SERS assay of N-nitrosodiethylamine contamination in antihypertensive drugs

This study presents a dual-mode colorimetric and surface enhanced Raman scattering (SERS) platform for the highly sensitive and selective assay of N-nitrosodiethylamine (NDEA) in antihypertensive drugs. A polydopamine embedded molecularly-imprinted agarose hydrogel (MIAG) chip was developed, serving as a multifunctional sensing substrate. Upon exposure to NDEA, the chip facilitates specific target adsorption and enrichment, simultaneously triggering a Griess reaction that yields a deep-red azo compound. This reaction provides the basis for both colorimetric readout and generates a strong Raman signal through azo-enhanced scattering for quantification. This design allows the MIAG chip to function not only as a naked-eye indicator but also as a platform for smartphone-based colorimetric analysis by directly translating color responses into digital barcodes. Furthermore, the in-situ synthesized gold nanoparticles (AuNPs) within the hydrogel matrix generate enhanced SERS activity, leveraging the porous network to create abundant hotspots for ultra-sensitive detection, achieving a limit of detection as low as 2.3 × 10 −14  M. The synergistic combination of dual-mode output offers robust and cross-verification results, significantly improving detection reliability. This integrated smartphone-compatible platform holds great promise for point-of-care testing of drug safety, making accurate screening accessible from regulatory laboratories to the public