Recent reports in molecular biology and analytical chemistry have led to a new class of molecular sensors based on transport in biological and artificial pores of nanometer dimensions. In this presentation, we describe a bench-top method for reproducibly fabricating glass nanopore (GNP) electrodes and membranes with pore orifice radii between 2 and 500 nm. Prototype sensors using the GNP electrodes and membranes have been constructed for applications in nanoparticle counting, stochastic single-molecule detection, and in ion selective electrochemistry.

GNP electrodes and membranes are fabricated by sealing an electrochemically sharpened Au or Pt micro-wire into a glass capillary, followed by polishing the glass until a nanometer-sized metal disk is exposed. The key to the success of this methodology is the use of a high-input impedance metal-oxide semiconductor field effect transistor (MOSFET)-based circuit to monitor the radius of the disk electrode during polishing. Proper biasing of the MOSFET circuit, based on consideration of the polishing circuit impedance, enables the routine, bench-top fabrication of Pt nanodisk electrodes of pre-selected radius as small as ~10 nm. In subsequent steps, the fabrication of a GNP electrode is accomplished by etching the metal nanodisk electrode to create a pore in glass, with the remaining metal disk comprising the pore base. Complete removal of the wire yields a glass nanopore membrane, in which a conical shaped pore is embedded in a thin (~50 micrometer) GNP membrane.

The nanopore electrode and membrane can be modified by numerous chemical means including: covalent attachment of molecules to the surfaces; filling the pore volume with polymers and hydrogels; and by deposition of lipid bilayer/proteins across the pore orifice. These modifications impart molecular selectivity and high sensitivity (single molecule) in designing sensors for applications in homeland defense, DNA sequencing, environmental monitoring, and particle counting.