Smartphone-Validated Portable Paper-Based Device Integrated with an Electropolymerized Molecularly Imprinted Polymer for Serotonin Detection in Serum Samples

Abstract

Accurate and decentralized quantification of serotonin, also known as 5-hydroxytryptamine (5-HT), in biological fluids is critically important for the diagnosis, prognosis, and therapeutic monitoring of neurological and psychiatric disorders. However, conventional analytical methods generally rely on centralized laboratory infrastructure, skilled personnel, and labor-intensive sample processing, which restrict their applicability in rapid near-patient and point-of-care settings. Herein, we report a portable molecularly imprinted polymer (MIP)-based electrochemical sensing platform for selective and on-site detection of serotonin using screen-printed carbon electrodes (SPCEs). The biomimetic recognition interface was fabricated through direct electropolymerization of a polydopamine recognition layer in the presence of serotonin as the template molecule, followed by template extraction to generate complementary recognition cavities for selective rebinding. The sensor fabrication parameters, including monomer concentration, electropolymerization cycles, template-to-monomer stoichiometry, and electrolyte pH, were systematically optimized to achieve improved sensitivity, selectivity, and signal stability. Under optimized conditions, the MIP/SPCE sensor exhibited a broad linear response from 10 pM -10 {micro}M in phosphate buffer, with a correlation coefficient of R2 = 0.974 and an ultralow limit of detection of 0.16 pM. The analytical applicability of the platform was further validated in spiked artificial serum, where the sensor achieved an LOD of 0.12 pM, satisfactory recovery values of 88.66-96.02%, and acceptable precision with RSD values [≤] 8.43% (n=3), confirming its reliability in a complex biological matrix. The developed sensor demonstrated excellent selectivity toward serotonin against physiologically relevant interferents, maintaining signal retention between 99% and 101%. In addition, the platform showed high operational repeatability with an RSD of 0.45%, good inter-electrode reproducibility with an RSD of 6.3%, and long-term storage stability, retaining 90-110% of its initial response over 28 days. Importantly, cross-platform validation using a smartphone-coupled potentiostat demonstrated strong analytical agreement with laboratory-grade instrumentation, as evidenced by R2 = 0.9967 and a slope of 1.023. These findings establish the proposed MIP/SPCE platform as a simple, low-cost, portable, and smartphone-compatible electrochemical device for field-deployable serotonin monitoring in clinically relevant samples.