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

Abstract

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. © Springer Science+Business Media, LLC 2011.