In Situ Nanopore Fabrication and Single-Molecule Sensing with Microscale Liquid Contacts

Abstract

In this article, we introduce a flexible technique for high-throughput solid-state nanopore analysis of single biomolecules. By confining the electrolyte to a micron-scale liquid meniscus at the tip of a glass micropipette, we enable automation and reuse of a single solid-state membrane chip for measurements with hundreds of distinct nanopores per day. In addition to overcoming important experimental bottlenecks, the microscale liquid contact dramatically reduces device capacitance, which is a key limiting factor to the speed and fidelity of solid-state nanopore sensor recordings.

Scanning electrochemical cell microscopy: New perspectives on electrode processes in action

“…The imaging techniques described in this article are of wide applicability to contemporary problems in electrochemistry and electrochemical technology, and will be powerful in studies of electrocatalysis, understanding battery electrodes and designing electrochemical sensors. We should also point out that the SECCM technique, and closely related methods, can also be used to pattern surfaces with new composite materials [40,41] and create nano-devices [42], whose activity can be investigated with the same probe.…”

Nanopore Formation via Tip‐Controlled Local Breakdown Using an Atomic Force Microscope

“…We believe the final nanopore diameter can be adjusted via careful tuning of either of these two parameters (or a combination of both). Alternatively, as reported in previous studies, application of voltage pulses across the nanopore after the initial pore formation can enlarge the nanopore. Such a strategy might also be used together with TCLB.…”

“…In Figure d we compare the average time‐to‐breakdown for our tip‐controlled approach versus classical dielectric breakdown. We find that our approach gives pore formation times two orders of magnitude lower than classical breakdown, by comparison with a wide‐range of experimental studies exploring classical breakdown for different film thickness (10–30 nm, 75 nm), pH (2–13.5), and voltage (1–24 V).…”

“…Nanopore fabrication time (time‐to‐breakdown, t BD ) can provide insight into the pore formation mechanism. Nanopores fabricated via classic dielectric breakdown have a time‐to‐breakdown following a Weibull probability distribution . The Weibull distribution is used extensively to model the time‐to‐failure of semiconductor devices .…”

“…[12,13,23] Critically, the breakdown approach may also inadvertently produce more than one nanopore over the membrane area, [24][25][26][27] leading to a drastic loss of signal-to-noise and inability to resolve single-molecule translocation events. A recent variation of the breakdown approach uses a pipette tip to control voltage application, [28] increasing pore positioning precision to the micron scale (the pipette tip opening diameter is 2 μm),…”