Speed Matters: Human Genome Sequencing with a Nano-Mechanical Twist

DNA in a bottle.jpg Imagine genome sequencing technologies that approach the speed of that seen in the movies, in the futuristic film GATTACA, for example. In the future, a person need only wait a few minutes for important information to be retrieved from their genes for purposes of medical diagnosing and disease prevention. Nanotechnology, the science and technology of objects in the range of 1 billionth of a meter, may be just the key to upping the ante in DNA sequencing speed and accessible personalized medicine. Mechanical engineers familiar with nanofabrication may be just the people to get us there.

Jiahao Wu, a graduate student in the Department of Mechanical Engineering at Louisiana State University, is working on one groundbreaking innovation to reading the human genome, a process known as nanoscale DNA sequencing, under the guidance of award-winning Professor Dr. Steven Soper. Wu believes that cheap ‘microchips’ equipped with tiny channels, channels small enough to allow single DNA molecules to be manipulated and analyzed individually, could revolutionize point-of-care genetic testing.

Nano-scale DNA sequencing could potentially be much cheaper and faster than conventional methods, allowing researchers to ‘read’ parts of the human genome in seconds instead of hours. Faster and cheaper approaches to DNA sequencing are of vast importance in genetic studies and personalized medicine, especially in developing countries.

DNA sequencing involves determining the order of DNA bases – A, G, C, or T – like four different colored pearls, along a string of DNA. Sequencing technologies have allowed researchers to decode the human genome, the entire collection of DNA material that exists in each cell of the human body and which is passed from parents to offspring. The order of A, G, C, or T bases in the human genome is unique for each individual person, allowing DNA sequencing techniques to differentiate between you and your other family members, for example.

Traditional approaches to DNA sequencing, including the Sanger method, are slow, expensive, and often prone to error for long strings of DNA. Wu is attempting to harness very small channels, known as nanochannels, to capture pieces of DNA and read these pieces at a faster pace and at lower cost than the Sanger method requires.

Nanoscale DNA sequencing is cheaper because it operates microchip.png on a smaller scale – the size of a computer microchip – and uses cheaper materials – plastics. Most traditional microchips, made out of silicon, take hours or days to create. “I can make a chip in one minute,” Wu says. His microchip designs are simply ‘stamped’ into pieces of plastic. This process allows for nanoscale DNA sequencing microchips to be created cheaply, quickly, and in high numbers, making them essentially disposable after a one-time use.

Microchannel and ‘funnel’ nanochannel structures being ‘stamped’ into a plastic chip (blue).

The microchips that Wu designs have tiny channels, called nanochannels, grooved into their surfaces. These channels are so small – 100 times smaller around than a strand of human hair – that their width approaches the size of a single strand of DNA, Wu said.

One particular type of channel that Wu has designed looks like a funnel, catching pieces of DNA at the wide end of the funnel and causing them to stretch out as they travel down a narrowing path. Once a string of DNA is fully stretched inside the nanochannel, like a piece of curly human hair stretched out to its longest length, it becomes easier to read the A, G, C, or T ‘pearls’ along the DNA string.

This stretching, or uncoiling, of pieces of DNA is the premise of Dr. Soper’s pioneering approach to DNA sequencing. If pieces of DNA could be uncoiled and ‘read’ inside the nanochannels of a disposable plastic microchip, many more individuals could take advantage of cheap and fast diagnosis of genetic diseases, for example.

Soper’s nanoscale DNA sequencing research incorporates a variety of research fields, including chemistry, biology, and engineering. Graduate students from a variety of disciplines collaborate on this project.

Wu said that being an engineer in Dr. Soper’s research group has been a great advantage. Wu is intimately familiar with the mechanical design of his microchips. “When the other students in our group have an instrument fail or a microchip go bad, they may be able to recognize that there is a problem, but they don’t know where to start in fixing it. For me, when a microchip fails, I just walk back to the clean room to make another chip.”

Wu believes that students need a diverse academic background to succeed on such a multi-disciplinary project as Dr. Soper’s nanoscale DNA sequencing project. “Working on such a unique, high-tech project, you are going to run into problems such that only one background is not enough to solve them,” Wu said. He pointed out that his background in mechanical engineering and physics has allowed him to problem-solve in ways that other students cannot.

Engineering our way to a better future.

Jiahao Wu in his laboratory (above).

Image Credits:

DNA in a Bottle Image Prepared by the Biological and Environmental Research Information System, Oak Ridge National Laboratory, genomicscience.energy.gov/ and genomics.energy.gov/.

Microchip images and DNA movement video property of Jiahao Wu, Dr. Steven Soper, LSU.

Jiahao Wu, Rattikan Chantiwas,, & Alborz Amirsadeghi, Steven A. Soper, Sunggook Park (2011). Complete plastic nanofluidic devices for DNA analysis via direct imprinting
with polymer stamps Lab on a Chip, 11,