Molecularly imprinted polymer (MIP)-based electrochemical sensors for the protein α-synuclein (a marker for Parkinson's disease) were developed using a peptide epitope from the protein. MIPs doped with various concentrations and species of transition metal dichalcogenides (TMDs) to enhance conductivity were electropolymerized with and without template molecules. The current during the electropolymerization was compared with that associated with the electrochemical response (at 0.24~0.29 V vs. ref. electrode) to target peptide molecules in the finished sensor. We found that this relationship can aid in the rational design of conductive MIPs for the recognition of biomarkers in biological fluids. The sensing range and limit of detection of TMD-doped imprinted poly(AN-co-MSAN)-coated electrodes were 0.001-100 pg/mL and 0.5 fg/mL (SNR = 3), respectively. To show the potential applicability of the MIP electrochemical sensor, cell culture medium from PD patient-specific midbrain organoids generated from induced pluripotent stem cells was analyzed. α-Synuclein levels were found to be significantly reduced in the organoids from PD patients, compared to those generated from age-matched controls. The relative standard deviation and recovery are less than 5% and 95-115%, respectively. Preparation of TMD-doped α-synuclein (SNCA) peptide-imprinted poly(AN-co-MSAN)-coated electrodes.
Keywords: Electrochemical sensing; Peptide imprinting; Transition metal dichalcogenides; α-Synuclein.