Detection of protein oligomers with nanopores

Abstract

Powerful single-molecule approaches have been developed for the accurate measurement of protein oligomers, but they are often low throughput and limited to the measurement of specific systems. To overcome this problem, nanopore-based detection holds the promise of providing the high throughput, broad applicability, and accuracy necessary to characterize protein oligomers in a variety of contexts. Nanopores provide accuracy comparable with that of state-of-the-art single-molecule detection methods, but with the added potential for fast and accurate measurements that may be amenable to industrial-scale manufacture. Key to enabling this expansion is combination with other emerging technologies such as DNA nanostructure tagging, machine learning-enabled signal analysis, and innovative detection device manufacture. Together, these technologies could enable widespread adoption of nanopore-based sensing in oligomer detection, revolutionizing diagnostics and biomarker detection in protein misfolding diseases. An overview of the progress and potential of nanopore-based detection of oligomerizing proteins is presented, covering the latest advances and combination with other emerging technologies including device design, DNA nanostructure tagging and machine learning-enabled signal analysis.