Stolovitzky’s group designed

a nanopore with a metal-dielectric sandwich structure capable of controlling the DNA translocation process with a single-base accuracy by tuning the trapping electric fields inside the nanopore [20–22]. This design is verified by molecular dynamics (MD) simulations, but there is no device reported so far due to its difficulty in fabrication. Applying an external force in the opposite direction of the electric field force on DNA could control a DNA strand through a nanopore at a very slow speed. It can be achieved using optical tweezer [23] or magnetic tweezer [24] technologies. However, it is hard to extend these methods to sequence DNA in parallel [25], such as employing thousands of nanopores on a chip concurrently [26]. As we know, counterions in solutions can bind to see more www.selleckchem.com/products/sgc-cbp30.html DNA molecules, which may provide a drag force on the DNA and reduce the translocation speed. Dekker’s group found that DNA translocation time in LiCl salt solution is longer than that in KCl or NaCl solutions. Through MD simulation, they elucidated that the root of this effect is attributed to the stronger Li+ ion binding DNA than that of K+ and Na+[27]. The DNA electrophoretic mobility depends on its surface charge density and the applied voltage. If we can adjust the DNA

surface charge density, it is possible to actively control the DNA translocation through a nanopore. It has been found that Mg2+ could reduce electrophoretic mobility of DNA molecule more than Na+ at the same concentration without Amoxicillin worrying about changing the DNA molecule charge to a positive value [28]. It is also known that Mg2+ is regularly used in selleck compound adhering the DNA to inorganic surfaces, which may also reduce the DNA mobility. Inspired by the process of reducing effective surface charge density of a DNA molecule

and that increasing the attractive force between DNA molecule and nanopore inner surface can retard DNA molecule translocation, we employed bivalent salt solution such as MgCl2 to observe the DNA translocation event through nanopores. We hope the two kinds of phenomena occur at the same time, thus extending the translocation time further more. Methods The fabrication process of a solid-state nanopore is shown in Figure 1a. It starts with the fabrication of a 100-nm thick, low-stress Si3N4 window (75 × 75 μm2) supported by a silicon chip using lithography and wet etching processes. Then, we mill the membrane in a small window with size of 500 × 500 nm2 to reduce the membrane thickness to approximately 20 nm. Following the milling process, a nanopore with diameter in several nanometers is drilled on the milled region in the Si3N4 film. Both the milling and drilling processes are completed by focused ion beams in a dual beam microscope (Helios 600i NanoLab, FEI Company, Hillsboro, USA).