nano 2007-12-02 04:49
IBM: DNA sequencing moves on
[color=blue]【纳米科技世界快讯】A new device that controls the position of DNA molecules inside a nanopore with single nucleotide resolution could revolutionise DNA sequencing claim researchers at IBM Research. The theoretical "DNA transistor", proposed by Stas Polonsky and colleagues of the TJ Watson Research Center in New York, would exploit the interaction of discrete charges on the backbone of DNA with the electric field inside the nanopore[/color].
Present-day DNA sequencing consists of breaking molecules of DNA into fragments of different lengths and adding fluorescent tags to the broken ends. These fragments are then separated using capillary electrophoresis. The problem is that the technique is expensive because large quantities of DNA – in the order of femtomoles – are needed. It is also slow, analysing just tens of base pairs per second.
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[color=gray]Cross-section section of DNA transistor (grey - insulator, yellow - metal, orange - single stranded DNA with discrete charges shown as points, blue electric potential inside the nanaopore). Credit: S Polonsky[/color].
The new technique would overcome these problems: a hundred million times less DNA would be needed and a base pair could be sequenced much quicker. Moreover, the DNA transistor could be fabricated using mainstream microelectronics methods, further reducing sequencing costs.
The technique would work by threading a long DNA molecule through a nanopore a few nanometers wide. The charges on the DNA backbone – which are discrete and are about the same size as charges on single electrons – would be detected as they interact with the electric field inside the nanopore.
The nanopore penetrates a membrane consisting of a sandwich of three nanoscale metal electrodes separated by insulators. The voltage difference between the central and side electrodes establishes an electrostatic trap that confines a DNA molecule (see figure). Oscillating voltage differences in the membrane mean that the position of the DNA molecule can be controlled with single nucleotide accuracy – a first in DNA sequencing.
"Technologies that make reading DNA fast, cheap and widely available could revolutionise biomedical research and herald the era of personalised medicine," Polonsky told nanotechweb.org. "For example, a human genome sequencing capability affordable for individuals is the ultimate goal of the DNA sequencing industry and is commonly referred to as the '$1000 genome'. "
The device could also be important for fundamental science, adds Polonsky. "The ability to move along information-carrying polymers of nucleic acids with single nucleotide precision is vital for the machinery of life," he explained. "DNA polymerase, for example, has to translocate along the DNA molecule with single nucleotide accuracy in order to replicate it correctly. As nanotechnology masters its ability to manipulate single molecules, the question of whether man-made devices can also position themselves along information-carrying polymers with single monomer precision is of practical interest."
The team is now busy working on actually making its DNA transistor in experiments.
The work was published in [url=http://link.aip.org/link/?APPLAB/91/153103/1][color=#0000ff][i]Appl. Phys. Lett.[/i] [b]91[/b] 153103[/color][/url]