Third Generation DNA Sequencing with a Nanopore - Nanopores: Sensing and Fundamental Biological Interactions - page 294

resolution, provided that the membrane capacitance is minimized using
conventional nanofabrication practices to reduce the area.

12.2 Single Molecule Sequencing with a Synthetic Nanopore

12.2.1 Nanopore Fabrication

We have developed methods for producing nanometer diameter pores in robust
membranes as illustrated in Fig. 12.2 . Pores in solid-state membranes offer vastly
improved chemical stability over phosphor-lipid layers. They are resilient in the

Fig. 12.2 Silicon nanotechnology is a key innovation for nanopore sequencing. (a) A TEM cross-
section through the membrane structure. SiO 2 membranes are formed by depositing a sacrificial
silicon layer on a substrate. A thin oxide < 5 nm thick shown in (b) is grown by RTO and
subsequently a thin layer of polysilicon is deposited on top and polished back using CMP. With
DUV lithography and a combination of wet and dry etching a membrane is revealed. (c) Optical
micrograph of a membrane showing a (2 m m) 2 top silicon layer with a 1 m m via through it and a
(10 m m) 2 bottom Si layer. The nitride layer on the top and bottom are transparent. The top and
bottom Si layers act as etch stops. (d) After revealing the membrane, a pore is sputtered using a
tightly focused, high energy electron beam. The TEM micrograph shows a ~0.7 nm diameter pore.
(e) Scanning TEM (STEM) micrograph of a 0.9

2.4 nm 2 slit produced with Titan at 300 kV. (f)
An “L” shaped pattern indicating the stability of the 1 nm beam (

< 1 nm drift/30 min). Adapted

from references [ 33 - 35 ]