A microfluidic–SERS platform for real-time monitoring and quantification of antiepileptic drugs

Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is essential for effective seizure control due to their Narrow Therapeutic Index (NTI), high interpatient variability, and complex pharmacokinetics. Despite their analytical accuracy, conventional methods such as HPLC and LC–MS are time-consuming, require specialized infrastructure, and are not suited for rapid or point-of-care applications [1]. To address these limitations, we propose a microfluidic analytical platform integrating surface-enhanced Raman spectroscopy (SERS) with embedded plasmonic gold nanoparticles (AuNPs) for sensitive, label-free, and low-volume detection of clinically relevant AEDs [2]. The platform is based on a laser-etched polydimethylsiloxane (PDMS) microchannel (5 µL) incorporating SERS-active AuNP substrates synthesized via the controlled Turkevich citrate reduction method. This architecture is intended to enable real-time chemical fingerprinting under continuous or semi-continuous flow conditions while maintaining high surface enhancement and reproducibility. Samples are introduced into the microfluidic channel to generate reproducible SERS spectra across clinically relevant concentration ranges. Multivariate chemometric tools, including Principal Component Analysis (PCA) are applied for spectral differentiation, noise reduction, and quantitative model development. This strategy facilitates discrimination of structurally similar molecules and accounts for possible matrix interferences arising from biological fluids or excipients. The proposed microfluidic–SERS system constitutes a versatile proof-of-concept for rapid pharmaceutical analysis and has the potential to form the basis of a compact diagnostic device for personalized antiepileptic therapy. Beyond AEDs, the modularity of the platform makes it adaptable to broader applications, including metabolite profiling, real-time therapeutic monitoring, and the study of drug–matrix or drug–nanoparticle interactions.