Hierarchical 3D-printed electrochemical surface-enhanced Raman spectroscopy (EC-SERS) platform integrated with molecular imprinting for levetiracetam monitoring.

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.