Chemosensing of an Autism Biomarker, Gamma-Aminobutyric Acid, by Electropolymerized Molecularly Imprinted Polymers

We electrochemically synthesized molecularly imprinted polymer (MIP) films and simultaneously deposited them onto an interdigitated electrode array (IDEA) and a classical Pt disk electrode to devise chemosensors for the selective determination of gamma-aminobutyric acid (GABA), a biomarker of autism spectrum disorder. <i>p</i>-<i>Bis</i>(2,2'-bithien-5-yl)methyl phenol 2-hydroxy acetamide ether was used as the functional monomer due to its ability to form a stable prepolymerization complex with the GABA template in solution. The highest stability of the prepolymerization complex of GABA with different functional monomers directed the choice of the above functional monomer. The structures of these complexes were optimized using DFT calculations. Potentiodynamic electropolymerization was performed to deposit prepolymerization template and functional monomer complexes on different electrodes. After removing template molecules to generate selective molecular cavities in the resulting MIPs, we evaluated the analytical performance of these MIP films when integrated into electrochemical sensing platforms. We integrated differential pulse voltammetry (DPV) or electrochemical impedance spectroscopy (EIS) transductions with the MIP film-coated electrodes and identified EIS as the most effective for point-of-care GABA determinations. Using EIS, an MIP-film-coated platinum disk electrode detected GABA in a linear dynamic concentration range of 0.19-1.6 μM, with a limit of detection (LOD) of 0.13 μM. The MIP film deposited on the IDEA enabled GABA determination with EIS over a broader range of 8-240 μM, with an LOD of 0.39 μM, highlighting its potential for clinical applications. The EIS-determined imprinting factor was 2.7. The chemosensors were selective with respect to structural analogues of GABA. Finally, we successfully measured GABA concentrations in human serum samples, confirming the clinical applicability of the developed GABA determination method.