High Single-Molecule Read Throughput for Proteomics with Nanopore Field-Effect Transistors: Approach & Roadmap

Abstract

Nanopore technology has revolutionized DNA sequencing, and nascent nanopore-based technology breakthroughs may lead to major strides forward in proteomics. However, the need for recording of pico- to nanoampere ionic currents remains a major challenge for advancing current nanopore technologies. Such low currents limit integrated device array size as well as recording bandwidth. The latter imposes a limit on how quickly a detectable molecule can translocate the pore. Limited integration density and bandwidth severely constrain molecular read throughput while throughput is key to outperforming mass spectroscopy in terms of concentration dynamic range with a single-molecule proteomics technique. The Nanopore Field Effect Transistor (NPFET) is a nanopore coupled to a field-effect transistor (FET). Because the FET relies on much larger currents (e.g., microampere) currents to sense single molecules translocating through the pore, the NPFET enables higher bandwidth and a smaller electronics footprint. Additionally, NPFETs integrate into large arrays more easily because they do not require individual electrolyte contacts. The NPFET promises large integrated high-bandwidth pore arrays to break the nanopore read throughput limit. We will introduce how our nanopore FET technology can benefit proteomics and we will propose a scaling roadmap that aims to incrementally boost NPFET device molecular read throughput. The NPFET promises to enable a single-molecule proteomics concentration dynamic range far beyond what is possible at present.