A solid-state nanopore can electrophoretically capture a DNA molecule and pull it through in a folded configuration. The resulting ionic current signal indicates where along its length the DNA was captured. A statistical study using an 8 nm wide nanopore reveals a strong bias favoring the capture of molecules near their ends. A theoretical model shows that bias to be a consequence of configurational entropy, rather than a search by the polymer for an energetically favorable configuration. We also quantified the fluctuations and length-dependence of the speed of simultaneously translocating polymer segments from our study of folded DNA configurations.

Nanopores with one or two embedded nanoelectrodes can be fabricated by high resolution, milling-based methods. We first demonstrate how a focused ion beam, whose sputtering mechanism is well understood, can create a nanopore containing an annular electrode of an arbitrary metal, and with a regular perimeter. The inner surface of the nanopore can be insulated, and its diameter can be reduced with nanometer precision, by conformally coating a dielectric material by atomic layer deposition. We then investigate the mechanism of pore formation using a transmission electron microscope (TEM) through studies of the milling rate, and its dependence on the flux of electrons and on the atomic number of different target metals. Sputtering from the surface is identified as the dominant mechanism. Accordingly, light element conductors should be chosen to enhance the rate and resolution of TEM milling, which we demonstrate by articulating a nanopore with transverse carbon nanotube electrodes. Finally, we electrochemically verify that TEM milling preserves the quality of an annular gold electrode through cyclic voltammetry measurements performed at various stages of the fabrication.

Solid-state nanopores have emerged as powerful new tools for electrically characterizing single DNA molecules. When DNA molecules are made to rapidly translocate a nanopore by electrophoresis, the resulting ionic current blockage provides information about the molecular length and folding conformation. A solid-state nanopore can also be integrated with nanofabricated actuators and sensors, such as an embedded gate electrode or transverse tunneling electrodes, to enhance its functionality. Here we describe detailed methods for fabricating passive solid-state nanopores and using them to detect DNA translocations. We also describe procedures for integrating electrodes into the nanopore membrane in order to create an electrically active structure. Finally, we describe how to modulate the ionic conductance through a pore whose inner surface is surrounded by an embedded annular gate electrode.