Silicon chip could enable rapid genome sequencing

New DNA-reading technology could help create a device for sequencing a person’s entire genetic code in minutes, according to its UK-based inventors.

Scientists from Imperial College London have created a silicon chip that can detect an individual strand of DNA between two tiny electrodes.

They hope to use it to create a cheap and easily manufactured device that will allow doctors to perform rapid genome sequencing and use this data to prescribe drugs or make health predictions based on a patient’s DNA.

‘Our initial experiments suggest that you could theoretically do a complete scan of the 3,165 million bases in the human genome within minutes.’

Dr Joshua Edel

‘With our platform, point-of-care diagnostic is realistic,’ Dr Joshua Edel, one of the scientists behind the technology, told The Engineer.

‘The technology we’re using is identical to what’s used in CPUs [central processing units in computers],’ he said, adding that this should make it relatively easy to incorporate the technology into a mass-produced device.

The chip detects DNA strands by propelling them at high speed through a tiny 50-nanometre (nm) hole, known as a nanopore, in a silicon membrane.

A 2nm ‘tunnelling electrode junction’ then reads the strand with an electrical current that interacts with the different base molecules that form DNA. Eventually, a computer should be able to use this data to construct the genome sequence.

‘We haven’t tried it on a whole genome yet but our initial experiments suggest that you could theoretically do a complete scan of the 3,165 million bases in the human genome within minutes,’ said Edel.

‘It should be significantly faster and more reliable, and would be easy to scale up to create a device 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.’

A grid of genome-sequencing chips
A grid of genome-sequencing chips

Nanopores are widely seen as the next step for rapidly detecting and reading DNA because they avoid the need to break the strands into fragments or add chemical labels to identify the base molecules, as is common with current techniques.

UK firm Oxford Nanopore Technologies has been working to commercialise research from Oxford and Harvard universities, among others, on both biological and silicon-based membranes for the last few years.

But the Imperial team claims designs for an accurate and fast silicon reader have not been demonstrated until now.

‘Getting the DNA strand through the nanopore is a bit like sucking up spaghetti,’ said Dr Emanuele Instuli, co-author of the team’s latest paper in the journal Nano Letters.

‘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.

‘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.’

Dr Joshua Edel shows the prototype genome-sequencing chips
Dr Joshua Edel shows the prototype genome-sequencing chips

Oxford Nanopore Technologies is working on similar technology, but spokesperson Zoe McDougall told The Engineer that it was company policy not to comment on the progress of its work because of its collaborations with listed firms.

She said a solid-state device was the ‘holy grail’ of nanopore research but that building one was a lot more complicated than just creating a detector chip, because a technology needs to be highly scalable and there are still challenges in fabrication techniques at this time.

The next step for the Imperial team will be to use the chip to identify strands of DNA. They hope to begin a follow-up project in 18 months to identify the base molecules and sequence the genome. A reader device could be developed within a few years, said Edel.

The research, which also included Aleksandar Ivanov and Dr Tim Albrecht, was funded by more than £500,000 from the Wellcome Trust and a fellowship award from the Corrigan Foundation.