Tiny reader makes fast, cheap DNA sequencing feasible

March 26, 2012
The various levels of electrical signal from the sequence of a DNA strand pulled through a nanopore reader (top) corresponds to specific DNA nucleotides, thymine, adenine, cytosine and guanine (bottom). Credit: University of Washington

Researchers have devised a nanoscale sensor to electronically read the sequence of a single DNA molecule, a technique that is fast and inexpensive and could make DNA sequencing widely available.

The technique could lead to affordable personalized medicine, potentially revealing predispositions for afflictions such as cancer, diabetes or addiction.

"There is a clear path to a workable, easily produced sequencing platform," said Jens Gundlach, a University of Washington physics professor who leads the research team. "We augmented a protein we developed for this purpose with a molecular motor that moves a DNA strand through the a nucleotide at a time."

The researchers previously reported creating the nanopore by genetically engineering a pore from a . The nanopore, from Mycobacterium smegmatis porin A, has an opening 1 billionth of a meter in size, just large enough for a single DNA strand to pass through.

To make it work as a reader, the nanopore was placed in a membrane surrounded by potassium-chloride solution, with a small voltage applied to create an ion current flowing through the nanopore. The electrical signature changes depending on the type of nucleotide traveling through the nanopore. Each type of DNA nucleotide – cytosine, guanine, adenine and thymine – produces a distinctive signature.

The researchers attached a molecular motor, taken from an enzyme associated with replication of a virus, to pull the through the nanopore reader. The motor was first used in a similar effort by researchers at the University of California, Santa Cruz, but they used a different pore that could not distinguish the different nucleotide types.

Gundlach is the corresponding author of a paper published online March 25 by Nature Biotechnology that reports a successful demonstration of the new technique using six different strands of DNA. The results corresponded to the already known DNA sequence of the strands, which had readable regions 42 to 53 nucleotides long.

"The motor pulls the strand through the pore at a manageable speed of tens of milliseconds per nucleotide, which is slow enough to be able to read the current signal," Gundlach said.

Gundlach said the nanopore technique also can be used to identify how DNA is modified in a given individual. Such modifications, referred to as epigenetic DNA modifications, take place as chemical reactions within cells and are underlying causes of various conditions.

"Epigenetic modifications are rather important for things like cancer," he said. Being able to provide DNA sequencing that can identify epigenetic changes "is one of the charms of the nanopore sequencing method."

Coauthors of the Nature Biotechnology paper are Elizabeth Manrao, Ian Derrington, Andrew Laszlo, Kyle Langford, Matthew Hopper and Nathaniel Gillgren of the UW, and Mikhail Pavlenok and Michael Niederweis of the University of Alabama at Birmingham.

The work was funded by the National Human Genome Research Institute in a program designed to find a way to conduct individual DNA sequencing for less than $1,000. When that program began, Gundlach said, the cost of such sequencing was likely in the hundreds of thousands of dollars, but "with techniques like this it might get down to a 10-dollar or 15-minute genome project. It's moving fast."

Explore further: Nanopore Sequencing Could Slash DNA Analysis Costs

Related Stories

Nanopore Sequencing Could Slash DNA Analysis Costs

March 27, 2009

(PhysOrg.com) -- Over the past 5 years, researchers have been exploring the use of nanoscale pores as nucleic acid sequencing tools. In theory, such pores should generate a unique response characteristic of each of the four ...

DNA through graphene nanopores

July 12, 2010

A team of researchers from Delft University of Technology (The Netherlands) announces a new type of nanopore devices that may significantly impact the way we screen DNA molecules, for example to read off their sequence. In ...

Whole-Genome sequencing simulated on supercomputers

February 25, 2011

(PhysOrg.com) -- The Human Genome Project paved the way for genomics, the study of an organism's genome. Personalized genomics can establish the relationship between DNA sequence variations among individuals and their health ...

Recommended for you

Physicists develop new technique to fathom 'smart' materials

November 26, 2015

Physicists from the FOM Foundation and Leiden University have found a way to better understand the properties of manmade 'smart' materials. Their method reveals how stacked layers in such a material work together to bring ...

Mathematicians identify limits to heat flow at the nanoscale

November 24, 2015

How much heat can two bodies exchange without touching? For over a century, scientists have been able to answer this question for virtually any pair of objects in the macroscopic world, from the rate at which a campfire can ...

New sensor sends electronic signal when estrogen is detected

November 24, 2015

Estrogen is a tiny molecule, but it can have big effects on humans and other animals. Estrogen is one of the main hormones that regulates the female reproductive system - it can be monitored to track human fertility and is ...


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.