Interfacing Biological and Solid-State Nanopores for Scalable Single-Molecule Sensing

Biological nanopores can read biomolecules with exceptional resolution. This capability has revolutionized DNA sequencing and is widely expected to enable a similar breakthrough in protein sequencing in the coming years. Their performance stems from an atomically defined nanoscale aperture that can be engineered with extraordinary precision. However, integrating biological nanopores into large-scale sensing arrays remains challenging, limiting the ability to generate ever larger volumes of biological data at lower cost. In contrast, solid-state nanopores offer excellent robustness and scalability, benefiting from established semiconductor fabrication processes and natural enablement of highly dense sensor arrays. Yet, they currently lack the molecular resolution achieved by biological nanopores. This PhD project aims to marry the strengths of both approaches by embedding a biological pore within a solid-state host structure to create a hybrid nanopore technology. The goal is to achieve high-resolution biomolecular sensing without relying on a fragile lipid membrane while enabling smooth integration with semiconductor technology. 

To realize this vision, the project will establish a framework for the site-selective placement and functional integration of biological nanopores within solid-state nanopores. Nanoscale surface-functionalization strategies will be developed to create localized capture sites at the pore rim or within the pore wall, while passivating surrounding surfaces to suppress nonspecific interactions. Self-assembly and field-driven transport will be explored to enable the deterministic capture, orientation, and insertion of biological nanopores and protein nanostructures into predefined apertures with nanometer-scale precision. Strategies will be developed to improve the long-term functionality and stability of protein-solid-state hybrid architectures, minimize parasitic leakage pathways around the sensing channel, and maximize hybrid pore assembly yield. 

These hybrid nanopores combine the molecular resolution of biological pores with the manufacturability and scalability of CMOS technology. Such devices could enable robust single-molecule sensing platforms and provide a scalable route toward next-generation DNA and protein sequencing technologies.