pH-assisted ratiometric surface-enhanced Raman scattering for reliable creatinine quantification in serum

Abnormal serum creatinine levels are a key clinical biomarker for kidney dysfunction, making its accurate monitoring essential for early diagnosis and prevention. Current commercial kits based on the creatine kinase method are often affected by matrix interference, limiting their reliability in clinical settings. To address this issue, we developed a pH- assisted ratiometric surface-enhanced Raman scattering (SERS) approach for precise creatinine detection in biological samples. We synthesized core-shell nanoparticles (Au@MPA@Ag NPs) with 3-mercaptopropionic acid (MPA) as the internal standard. Under optimized alkaline conditions (pH = 9), the adsorption of creatinine onto the substrate was significantly enhanced, leading to a strong and reproducible SERS response. Moreover, the internal standard-calibrated Raman intensity exhibited a strong linear correlation with creatinine concentration, achieving the limit of detection as 3.3   μM. As a proof of concept, this method was successfully applied to quantify creatinine in human serum. The recovery rates ranged from 98% to 107%, demonstrating high consistency with results obtained using a commercial creatinine assay kit. This method provides a clinically accurate and reliable for creatinine monitoring, offering strong potential for point-of-care testing.