Peptide-Imprinted Poly(hydroxymethyl 3,4-ethylenedioxythiophene) Nanotubes for Detection of α Synuclein in Human Brain Organoids

A novel electrochemical sensor for alpha-synuclein, a marker for Parkinson's disease, has been developed, based on molecularly imprinted electrochemically active polymers. Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, after Alzheimer's disease. A triplication in the alpha-synuclein (SNCA) gene, leading to higher levels of SNCA and subsequent aggregation and neurotoxicity, is a well-described cause for the disease. Thus, the detection of SNCA levels is diagnostically important. In this work, an electrochemical method was used to optimize the synthetic self-assembly of poly(hydroxymethyl 3,4-ethylenedioxythiophene) nanotubes, using a peptide from SNCA as a template molecule, to form peptide-imprinted electrically conductive polymers on sensing electrodes. The tubular nano-structures may increase the effective sensing range. The concentration range of the SNCA peptide sensing was 0.065 pM to 0.65 nM, with a limit of detection as low as 4.0 pM. Finally, the imprinted electrode was used to detect elevated levels of SNCA in culture medium collected from human PD patient-specific midbrain organoids.