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

A novel electrochemical sensor for α-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 α-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 nanostructures 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.