Nanopore tech promises genome sequencing ‘in minutes’
Scientists from Imperial College London have taken an important step towards developing breakthrough technology that could sequence a genome in mere minutes, and at a fraction of the cost of current commercial techniques.
Following research published in the peer-reviewed journal Nano Letters this month, the researchers are confident that their finding could lead to an ultrafast commercial DNA sequencing tool in just ten years. They say it would also make important medical tests cheaper and more reliable.
Development of the new technology has been funded in part by a Wellcome Trust Translation Award. It combines two well-documented sequencing techniques for the first time, meaning that an entire genome could eventually be sequenced in a single lab procedure.
An electrical charge propels a DNA strand at high speed through a tiny hole – or nanopore – cut into a silicon chip. As the strand emerges from the back of the chip, its DNA code is read by a ‘tunnelling electrode junction’. This gap between two wires supports an electrical current that interacts with the distinct electrical signal from each of the nucleotide bases – A, T, G or C – in the DNA code. The signal can be interpreted by a powerful computer to construct the genome sequence.
“Getting the DNA strand through the nanopore is a bit like sucking up spaghetti. Until now it has been difficult to precisely align the junction and the nanopore. Furthermore, engineering the electrode wires with such dimensions approaches the atomic scale and is effectively at the limit of existing instrumentation,” says Dr Emanuele Instuli from Imperial College London, who co-authored the paper. “However in this experiment we were able to make two tiny platinum wires into an electrode junction with a gap sufficiently small to allow the electron current to flow between them.”
Nanopore sequencing has long been considered the next big development for DNA technology, thanks to its potential for high speed and high-capacity sequencing. However, designs for an accurate reader that matches this speed have not been demonstrated until now. It has also proven difficult to precisely align the electrode junction with the nanopore at such a small scale.
Co-author Aleksander Ivanov, also from Imperial, says this technology would have several distinct advantages over current techniques.
“Nanopore sequencing would be a fast, simple procedure, unlike available commercial methods, which require time-consuming and destructive chemical processes to break down and replicate small sections of the DNA molecules to determine their sequence. Additionally, these silicon chips are incredibly durable compared with some of the more delicate materials currently used. They can be handled, washed and reused many times over without degrading their performance.”
Another of the Imperial researchers, Dr Joshua Edel, said the development could drastically cut the cost of sequencing, compared with current methods, “just a few pounds, compared with $1m to sequence an entire genome in 2007”.
“It will be significantly faster, more reliable and easily scalable to an array with the capacity to read up to 10 million bases per second, versus the typical 10 bases per second you get with the present day single molecule real-time techniques. Although we haven’t tried it yet, you could theoretically do a complete scan of the 3,165 million bases in the human genome within minutes, providing huge benefits to medical tests or DNA profile for police and security work.”
This work was carried out with support from the Wellcome Trust and the Corrigan Foundation.
- Ivanov AP, Instuli E, McGilvery C, Baldwin G, McComb DW, Albrecht T, & Edel JB (2010). DNA Tunneling Detector Embedded in a Nanopore. Nano letters PMID: 21133389