Nanopore-Based Single-Molecule Mass Spectrometry on a Lipid Membrane Microarray

We report on parallel high-resolution electrical single-molecule analysis on a chip-based nanopore microarray. Lipid bilayers of <20 μm diameter containing single alpha-hemolysin pores were formed on arrays of subpicoliter cavities containing individual microelectrodes (microelectrode cavity array, MECA), and ion conductance-based single molecule mass spectrometry was performed on mixtures of poly(ethylene glycol) molecules of different length. We thereby demonstrate the function of the MECA device as a chip-based platform for array-format nanopore recordings with a resolution at least equal to that of established single microbilayer supports. We conclude that devices based on MECAs may enable more widespread analytical use of nanopores by providing the high throughput and ease of operation of a high-density array format while maintaining or exceeding the precision of state-of-the-art microbilayer recordings.