Current nanopore technologies for direct DNA sequencing are limited in their detection sensitivity by the fast translocation speed of DNA molecules (~1 μs base−1). An international research group led by Charles M. Lieber of Harvard University has developed a silicon nanowire field-effect transistor-integrated nanopore sensor to tackle the challenge of providing high bandwidth detection to match the fast DNA translocation speeds. The novel nanowire-nanopore sensor exploits the localized electrical potential developed near the nanopore during DNA translocation, to provide a highly sensitive DNA sequencing method. Lieber, P. Xie, and Q. Qing of Harvard; Q. Xiong of Nanyang Technological University in Singapore; and Y. Fang of the National Center for Nanoscience and Technology in China published their findings in the December 11, 2011 issue of Nature Nanotechnology (DOI: 10.1038/NNANO.2011.217).
Chemical vapor deposition (CVD)-synthesized p-type silicon nanowires were deposited onto SiNx membranes, with nickel contacts defined by electron-beam lithography. The nanopores were drilled with a focused electron beam in a transmission electron microscope. The FET-integrated sensor is electrically connected to a printed circuit board chip carrier, which in turn is sandwiched between two poly(dimethylsiloxane) (PDMS) solution chambers with buffer solutions. The double strand DNA molecule is then injected into the bottom PDMS chamber to translocate through the nanopore. However, the researchers had to change the relative ionic strengths of the top and bottom PDMS chambers, with the bottom chamber having a higher ionic strength, in order to successfully produce the localized potential and detect FET conductance signals correlated in time to the ionic currents.
The researchers report a constant ratio between the orders of magnitude larger FET signal and corresponding ionic current signal. Such a correlation is a unique advantage of this new sensing method. This feature in principle ensures the compatibility of this much faster sensing scheme with all previous ionic current-based nanopore base-differentiation methods. Furthermore, the FET-integrated nanopore sensors have the potential to be integrated and multiplexed into large-scale DNA detection systems for higher throughput without complex microfluidics.
Experimental values of the field-effect transistor (FET) signal (black data points) and FET signal/ionic current signal ratio (red data points) under different voltages. Reproduced with permission from Nature Nanotech, DOI: 10.1038/NNANO.2011.217. © 2011 Macmillan Publishers Ltd.
