Biophysics study makes exciting advancements for the future of DNA sequencing

September 11, 2017
Sequencing single DNA molecules in nano-wells. Credit: Ella Maru Studio

A Northeastern research team has developed new technology that optimizes DNA sequencing using nanophysics and electric currents. In a paper published in Nature Nanotechnology, Northeastern Professor of Biological Physics Meni Wanunu, in partnership with Pacific Biosciences, a biotechnology company with a focus on DNA sequencing, developed a method for loading DNA into sequencing wells with orders of magnitude higher efficiencies.

"Apart from being a multi-billion dollar a year market, DNA sequencing is one avenue where incremental improvements in research, like discovery of a new gene, for example, can have immediate clinical consequences," said Wanunu.

Our human DNA is a genome composed of 23 pairs of chromosomes, which breaks down into six billion pieces that all come together to give each person their unique characteristics and properties. While we have the ability to sequence important parts of the genome, the ability to know the entire sequence has the potential to make huge strides in the area of understanding and predicting disease, and more importantly, to personalize medicine.

"Right now, piecing together the entire sequence through traditional methods is like stitching together a giant puzzle, and the error rate can get so enormous that after the first few hundred bases, the sequence is gibberish," said Wanunu. "That's why there's a fundamental limit for second-generation sequencing methods, which we want to move past."

This is why technology has evolved to bring forward a new method for sequencing DNA: single-molecule sequencing.

Pacific Biosciences has developed an optical technology for single-molecule DNA sequencing that relies on nano-wells. These wells localize the sequencing signal and allow single molecule sequencing to be carried out. However, the methods used by the company to load the DNA into the wells favors shorter DNA , rather than longer ones.

Wanunu's lab has redesigned the wells to incorporate nanopores at their bases, which allows them to attract larger segments of DNA using an electric field. By simply applying a voltage, the charged DNA molecules efficiently enter the wells, and longer DNA molecules become preferred over shorter ones.

"Large DNA molecules need just a small push to get into the sequencing volume, but once we apply this force, we can capture enormous sample fragments easily. The system will enable totally new sequencing experiments," said Joe Larkin, first author of this paper.

To further this research, Wanunu and his lab are working on preparing this technology for more large-scale use, specifically with equipment at Pacific Biosciences. The team is testing a porous substrate to replace the metal wells currently being used to attract and sequence DNA. As they continue in this research, Wanunu hopes to even further increase the fundamental length of DNA that can be sequenced.

"We would like to have a platform, some day, that sequences every nucleic acid molecule in a single cell, without the need for making many copies of these molecules prior to sequencing, just reading the native DNA," Wanunu said.

Explore further: Nanopores promise cost savings in gene sequencing

More information: Joseph Larkin et al, Length-independent DNA packing into nanopore zero-mode waveguides for low-input DNA sequencing, Nature Nanotechnology (2017). DOI: 10.1038/nnano.2017.176

Related Stories

Nanopores promise cost savings in gene sequencing

September 20, 2012

(Phys.org)—In the last five years, next-​​generation gene sequencing has brought down the cost of unlocking a single genome from $10 mil­lion to $10,000. While the sav­ings is unprece­dented, more can still be done ...

Gene sequencing at warp speed

March 20, 2012

(PhysOrg.com) -- One million vocalists singing the same song will sound cacophonous to an audience member if the singers belt out the tune at different tempos.

Recommended for you

The microscopic origin of efficiency droop in LEDs

November 21, 2017

Light-emitting diodes—or LEDs, as they are commonly known—have been slowly replacing incandescent light bulbs in applications ranging from car taillights to indicators on electronics since their invention in the 1960s.

Borophene shines alone as 2-D plasmonic material

November 20, 2017

An atom-thick film of boron could be the first pure two-dimensional material able to emit visible and near-infrared light by activating its plasmons, according to Rice University scientists.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.