Capture and Translocation of Nucleic Acids into Sub-5 nm Solid-State Nanopores - Nanopores: Sensing and Fundamental Biological Interactions - page 231

Fig. 10.2 (a) Schematic illustration of a solid-state nanopore setup. A silicon wafer contains a thin
solid state membrane, where a single ~4 nm pore is fabricated. This membrane separates two tiny
fluid chambers ( cis and trans ). A pair of electrodes immersed in these chambers are used to apply
voltage and measure the ionic current through the pore. (b) Ion-current trace just before and after
the addition of double-stranded DNA molecules to the negatively biased cis chamber. The linear
passage of the DNA molecules through the pore causes discrete current blockades .(c) Magnified
view of several current blockades. Reproduced with permission from Wanunu et al. [ 50 ],
copyright Nature Publishing Group, and from Wanunu et al. [ 49 ], copyright Elsevier Inc

10.2 The Problem of DNA Capture

While nanopore sensing involves reading the properties of biopolymers as they move
through the pore, the initial process of threading a molecule into the nanopore
governs the overall throughput of the method, as described above. DNA capture
consists of two steps: arrival of a molecule from the bulk to the mouth of the pore, and
threading one end of that polymer into the pore. Studies investigating the capture of
single-stranded DNA into lipid-embedded -hemolysin channels indicate that there

is a significant free energy barrier for DNA entry into the pore, which is associated
with threading of the first few bases [ 17 , 36 , 37 ]. However, such a barrier was not

a