Lipid bilayer coated Al₂O₃ nanopore sensors: Towards a hybrid biological solid-state nanopore

Solid-state nanopore sensors are highly versatile platforms for the rapid, label-free electrical detection and analysis of single molecules, applicable to next generation DNA sequencing. The versatility of this technology allows for both large scale device integration and interfacing with biological systems. Here we report on the development of a hybrid biological solid-state nanopore platform that incorporates a highly mobile lipid bilayer on a single solid-state Al₂O₃ nanopore sensor, for the potential reconstitution of ion channels and biological nanopores. Such a system seeks to combine the superior electrical, thermal, and mechanical stability of Al₂O ₃ solid-state nanopores with the chemical specificity of biological nanopores. Bilayers on Al₂O₃ exhibit higher diffusivity than those formed on TiO₂ and SiO₂ substrates, attributed to the presence of a thick hydration layer on Al₂O₃, a key requirement to preserving the biological functionality of reconstituted membrane proteins. Molecular dynamics simulations demonstrate that the electrostatic repulsion between the dipole of the DOPC headgroup and the positively charged Al₂O₃ surface may be responsible for the enhanced thickness of this hydration layer. Lipid bilayer coated Al ₂O₃ nanopore sensors exhibit excellent electrical properties and enhanced mechanical stability (GΩ seals for over 50 h), making this technology ideal for use in ion channel electrophysiology, the screening of ion channel active drugs and future integration with biological nanopores such as α-hemolysin and MspA for rapid single molecule DNA sequencing. This technology can find broad application in bio-nanotechnology.