On-Demand Delivery of Single DNA Molecules Using Nanopipets

Abstract

Understanding the behavioral properties of single molecules or larger scale populations interacting with single molecules is currently a hotly pursued topic in nanotechnology. This arises from the potential such techniques have in relation to applications such as targeted drug delivery, early stage detection of disease, and drug screening. Although label and label-free single molecule detection strategies have existed for a number of years, currently lacking are efficient methods for the controllable delivery of single molecules in aqueous environments. In this article we show both experimentally and from simulations that nanopipets in conjunction with asymmetric voltage pulses can be used for label-free detection and delivery of single molecules through the tip of a nanopipet with "on-demand" timing resolution. This was demonstrated by controllable delivery of 5 kbp and 10 kbp DNA molecules from solutions with concentrations as low as 3 pM.

Selective single molecule nanopore sensing of proteins using DNA aptamer-functionalised gold nanoparticles

“…39–41 Nanopipettes exhibit a number of advantages over conventional solid-state nanopores including quick and low-cost fabrication, good mechanical stability and low noise. 40,42–47 The nanopipettes used had a conical geometry at the tip with a nanopore of 21 ± 4 nm in diameter, as determined by the SEM imaging (Fig. 1B).…”

Characterization of Nanopipettes

“…Nanoelectrodes can also be fabricated by electrochemically plating nanopipettes with a variety of different metals. 12 Applications of nanopipettes include as tools for sizing, counting, [13][14][15][16][17] and sequencing of single particles or molecules. [18][19][20] These applications use the changes in ionic current through the end of the nanopipette (with an applied bias), as a single entity passes through the end of the probe, to provide diagnostic information.…”

“…[18][19][20] These applications use the changes in ionic current through the end of the nanopipette (with an applied bias), as a single entity passes through the end of the probe, to provide diagnostic information. Furthermore, these probes constitute powerful tools for the delivery of molecules, including drugs and other stimuli, 16,21,22 to surfaces and interfaces. Nanopipettes have also been used extensively as chemical sensors, detecting, for example, pH, 9 sodium, 23 potassium 24 and other ions as well as dopamine 25 and DNA molecules.…”

Nanopore Sensing

“…Controllable voltage-driven delivery/sampling of biomolecules by a nanopipette has been demonstrated in a number of different experiments. 74, 233, 234 The deposition/ capture of molecules is controlled by amplitude and polarity of the applied potential to the pipet electrode.…”