Fast DNA Sequencing via Transverse Electronic Transport
18 Apr, 2006 06:37 pm
Currently it costs millions of dollars and takes months to sequence the entire genome of a human. In order to realize the goal of personalized medicine, the cost and time would have to come down. A fast and cheap sequencing method could revolutionize the way medicine works.
With recent advances in manufacturing processes, it is now possible to manufacture structures about the size of the individual bases in DNA. This, for example, allows researchers to manufacture tiny nanopores with a diameter about the size of a DNA base, or about 10,000 times smaller than the diameter of a human hair.
If one were to put a positively charged plate on one side of such a pore and a negatively charged plate on the other side of the pore, a DNA molecule can be pulled through the pore. This happens as DNA[1] is acidic, and hence negatively charged; negative charges repel each other, while they are attracted to positive charges. As the DNA is present inside the pore, it will block other objects from passing through. It has been suggested that by analyzing the blockade of ions, as the DNA is present in the pore, the DNA strand can be sequenced[2]. However, up until date the resolution of the measurements has not been good enough for sequencing.
In a recent paper[3] has been suggested that by embedding electrodes in the sides of the nanopore, an electric current can be injected through each nucleotide and the resistance of it can be measured. As the resistance of the four bases, in perfectly oriented DNA, is unique from each other[4], one can then sequence the DNA by looking at its resistance. Numerical simulations in this paper show that the wiggling and twisting of the DNA, as it translocates through a pore, causes the resistance of the nucleotides to vary enough such that a single current measurement is not enough to distinguish which base it is, despite that the electrodes would induce an electric field which would reduce these movements. However by measuring the resistance more than once, one can with higher and higher certainty determine if the base is an A,T, C or G, that is sequence the DNA. For example, for a particular geometry of the pore it was shown that the DNA could be sequenced with 99.9% accuracy using 70 measurements per base. Without the electric field induced by the electrodes, the DNA would move around so much that, even with multiple current measurements, it would be impossible to sequence the DNA.
The exact number of measurements would vary depending on the geometry of the pore, but as one can do millions of measurements per second, all 3 billion bases in a human could be sequenced in a matter of hours, or about 100 times faster than current state of the art methods. Not only does this method have the potential of of being much faster than current
methods, but it would also be order of magnitudes cheaper.
Figure 1 (http://ucsdnews.ucsd.edu/graphics/images/2006/poredna_sm.jpg)
View from above as the DNA propagates through the pore.
[1] DNA is an acronym for Deoxyribonucleic acid
[2] J. J. Kasianowicz, E. Brandin, D. Branton and D. W. Deamer; Natl.
Acad. Sci. USA 93, 13770, 1996
[3] J. Lagerqvist, M. Zwolak and M. Di Ventra; Nano Letters 6, 779, 2006
[4] M. Zwolak and M. Di Ventra; Nano Letters 5, 421, 2005
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