A method is described for fabricating 25−75 μm thick fused quartz membranes containing a single conical shaped nanopore (orifice radius ranging from 10 to 1000 nm). The quartz nanopore membrane (QNM) provides an excellent solid support structure for lipid bilayers in ion channel recordings due to the large electrical resistivity of fused quartz. Electrical measurements demonstrate that the leakage current through 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) bilayers suspended across a 500−1000 nm radius QNM orifice is immeasurably small, corresponding to a bilayer resistance greater than 1012 ohms. Translocation of single-stranded DNA oligomers (poly dA 50-mer and poly dA 20-mer) through a protein ion channel (α-hemolysin) reconstituted in a DPhPC bilayer suspended across the QNM orifice is demonstrated.

Outer membrane protein G is a monomeric β-barrel porin that has seven flexible loops on its extracellular side. Conformational changes of these labile loops induce gating spikes in current recordings that we exploited as the prime sensing element for protein detection. The gating characteristics, open probability, frequency, and current decrease, provide rich information for analyte identification. Here, we show that two antibiotin antibodies each induced a distinct gating pattern, which allowed them to be readily detected and simultaneously discriminated by a single OmpG nanopore in the presence of fetal bovine serum. Our results demonstrate the feasibility of directly profiling proteins in real-world samples with minimal or no sample pretreatment.