Hierarchical 3D-printed electrochemical surface-enhanced Raman spectroscopy (EC-SERS) platform integrated with...

Accurate therapeutic drug monitoring of antiepileptic agents is essential for dose optimization, toxicity prevention, and personalized epilepsy management. Here, we report an electrochemical surface-enhanced Raman spectroscopy (EC-SERS) platform for the highly sensitive and selective detection of levetiracetam (LEV). The sensing architecture integrates 3D-printed carbon black-polylactic acid (CB-PLA) electrodes with commercial screen-printed carbon electrodes (SPCEs), preserving the standardized reference and counter electrodes while replacing the commercial working electrode with a reusable, laser-modifiable 3D-printed CB-PLA electrode, thereby enabling advanced surface engineering and post-fabrication customization. Laser ablation was employed to activate the carbon substrate, increasing surface roughness, exposing electroactive domains, and accelerating interfacial electron-transfer kinetics. Subsequent electrodeposition of gold nanoflowers (AuNFs) generated plasmonic hotspots that markedly amplified Raman scattering. To impart molecular selectivity, a molecularly imprinted polymer (MIP) was electropolymerized from pyrrole in the presence of LEV as the template, forming structurally complementary recognition cavities. Under an optimized electrochemical bias of -1 V, electrochemical modulation of the EC-SERS response significantly enhanced SERS intensity while maintaining structural stability, producing distinct molecular fingerprints for unequivocal molecular identification. The integrated 3D-SPCE/Laser/AuNFs/MIP platform achieved a low limit of detection (LOD) of 5.40 ng mL^-1 and a broad dynamic range spanning 10 ng mL^-1 to 1 μg mL^-1. By synergistically integrating additive manufacturing, laser-induced activation, hierarchical plasmonic nanostructuring, electrochemically induced enrichment, and molecular imprinting within a single scalable platform, this work establishes a versatile and portable EC-SERS platform for high-performance drug monitoring. The platform provides a strong foundation for next-generation point-of-care (POC) therapeutic monitoring and antiepileptic drug analysis.