Multiplexed Digital Characterisation of Misfolded Protein Oligomers via Solid-State Nanopores

Misfolded protein oligomers are of central importance in both the detection and treatment of Alzheimer’s and Parkinson’s diseases. However, accurate high-throughput methods to identify and quantify oligomer populations are currently lacking. We present here a single-molecule approach for the detection of oligomeric species. The approach is based on the use of solid state nanopores and multiplexed DNA barcoding to identify and characterise oligomers from multiple samples. We study α-synuclein oligomers in the presence of several small molecule inhibitors of α-synuclein aggregation, as an illustration of the applicability of this method to assist the development of diagnostic and therapeutic methods for Parkinson’s disease.