Integrated Microfluidic SERS Sensor Featuring Au NPs@Cu MOF/Hydrogel for Label-Free and Specific Creatinine Detection

Creatinine is a critical biomarker for assessing renal function, and its accurate detection is essential for early diagnosis of kidney diseases. However, real-time and label-free specificity creatinine sensing remains challenging. Herein, we present an integrated microfluidic surface-enhanced Raman scattering (SERS) platform incorporating an in situ polymerized Au NPs@Cu MOF/hydrogel substrate for sensitive and selective creatinine detection. The Au NPs@Cu MOF composite serves as the core SERS active unit, in which Cu MOF provides specific Cu–N coordination sites for direct, label-free specificity creatinine capture. Meanwhile, Au NPs provide electromagnetic enhancement (EM) through localized surface plasmon resonance (LSPR), which synergistically couples with the chemical enhancement (CM) of the Cu MOF to amplify the Raman signal. The hydrogel matrix provides good morphological stability and improves signal reproducibility. In addition, a three-layer microfluidic architecture was designed to prevent hydrogel dehydration and sample cross contamination. This integrated sensor enables creatinine detection using only 10 μL of sample with a 10 min incubation, achieving a low detection limit of 2.54 × 10–4 mg/dL. Further, it exhibited excellent performance in both artificial urine and real human urine, highlighting its potential for practical bioanalytical applications.