MXene/Au nanorods synergized electrochemical interface for sensitive DDC detection in serum from Parkinson's disease patients

Ternary MXene/AuNRs/pSC4 interface enables oriented antibody immobilization. • 1.15 ng mL −1 detection limit in serum, 10–200 ng mL −1 linear range. • Hydrophilic MXene/AuNRs surface resists biofouling without serum pretreatment. • 5.7× signal gain over single-component devices via synergistic amplification. • Clinically distinguishes PD patients from healthy controls ( p  < 0.001). Parkinson's disease (PD) management requires point-of-care accessible tools for personalized monitoring of levodopa therapy. Plasma dopa decarboxylase (DDC), a drug-responsive biomarker, has emerged as a promising target to guide dosing and anticipate adverse effects. However, current DDC assays rely on costly, labor intensive platforms that preclude rapid, sensitive detection in complex biological fluids. Here we report an electrochemical biosensor based on a novel ternary supramolecular interface combining MXene, Au nanorods, and p-sulfonatocalix[4]arene (pSC₄). In this design, pSC₄ serves as a supramolecular adapter to orient anti DDC antibodies via host–guest recognition, while the MXene/AuNRs hybrid provides synergistic signal amplification and contributes to reduced nonspecific adsorption. The sensor achieves a detection limit of 1.15 ng mL −1 and a linear range of 10–200 ng mL −1 in undiluted human serum, representing an approximately 5.7 fold signal amplification over single component devices. In an exploratory study of 12 subjects (6 PD patients under chronic dopaminergic therapy, 6 healthy controls), sera from PD patients showed a significantly higher ΔRct than controls (approximately threefold, P  < 0.001). This work establishes an analytical proof-of-concept for DDC detection by integrating supramolecular chemistry with nanomaterials, providing a foundation for future clinical studies. Download: Download high-res image (109KB) Download: Download full-size image