Novel DNA sensing technology could revolutionize modern medicine

Imagine a visit to a doctor where a simple blood test provides the key to your genetic code, and with that information, the doctor can base your care precisely on the treatment that will work best for you. No longer will it be one medicine, dosage, or treatment plan fits all—each patient will get the care that best fits his or her genetic makeup.

Accurately, quickly, and cheaply sequencing an individual’s DNA is one way that medicine can personalize care for each patient. Based on sophisticated computational modeling, researcher Jean-Pierre Leburton, along with several collaborators at the Beckman Institute, believes that the use of semiconductor nanotechnology has the potential to revolutionize individual healthcare by providing DNA sequencing on a scale that has not been reached previously.

After 10 years of research, Leburton, a professor of electrical and computer engineering, has found a way to exploit the electrical properties of graphene—a mono-atomic layer material obtained from carbon graphite—to create a solid-state transistor with a nanopore that has the ability to sequence the human genome electronically, which opens the door to high performance sequencing.

Current methods of sequencing DNA use various kinds of biochemical processes that are expensive and tedious. In Leburton’s recently published paper in Proceedings of the National Academy of Sciences (PNAS), entitled “Graphene quantum point contact transistor for DNA sensing,” he and collaborators Klaus Schulten, Anuj Girdhar, and Chaitanya Sathe describe a novel methodology that exploits the high electrical conductivity of graphene in a very tiny transistor that allows an electrically charged DNA strand to push through a nanopore within the solid-state device. As the molecule threads through the nanopore, each nucleotide passing in front of the graphene’s mono-layer scatters the current in graphene differently, which identifies the base sequence.

“There are two main reasons why this technology is revolutionary,” Leburton said. “It is a new paradigm for sequencing DNA, which uses an electrical constriction around a nanopore in graphene to sense and detect passing DNA nucleotides with the highest possible resolution.

“Secondly, the graphene layer is embedded into a transistor structure containing an electrical gate that modulates the electrical sensitivity of the graphene layer, and corrects it from the detrimental influences of the edge roughness of the graphene constriction as well as from neighboring charges in the insulating layers of the solid-state membrane. This is a completely new way of approaching DNA sequencing, and one that can be done quickly, reliably, and cheaply, once the technology could be developed into mass production.”

The first proposal for sequencing DNA with nanopores utilized ion channels in biological membranes of living cells to measure the variations of the blocking ionic current for each nucleotide passing through the channel with a specific signature. However, this method still lacks temporal and spatial resolution due to the finite thickness of the membrane. Moreover, ion channels designed by nature lack the flexibility and material versatility of semiconductor technology to control the sequencing process. Here, electronics through the transistor operation enables optimal sequencing control, which could lead to faster, cheaper, and more reliable DNA sequencing.

“We knew we could do things differently than by using biological membranes to sequence DNA,” Leburton said. “With semiconductor nanotechnology, we could fabricate a membrane with several electrically active layers, and assign a different function to each layer, so that translocating DNA would be efficiently controlled and detected with different electrodes.”

Oxford Nanopore Technologies, a company that develops nanopore equipment to sequence DNA, funds part of the research on this new graphene-based approach. Leburton joined forces with Beckman researchers Rashid Bashir and Aleksei Aksimentiev to integrate their theoretical and experimental efforts, and establish this new technology on real ground.

“This project fits very well in the Beckman Institute because it brings together scientists with different expertise,” Leburton said. “Bashir is a bioengineer, Aksimentiev is a theoretical biophysicist, and I am an electrical engineer with a physics background. This is why Beckman is so wonderful. People, who otherwise would have pursued their research in their own department, can work on a project at the crossroad among different disciplines. In this particular case, it merges biology and basic nanoelectronics, which are completely separate disciplines, each with its own concepts, methodology, and language.”

The next step for the technology is to implement the group’s high-resolution simulation of the transistor structure into an operational computer model, to provide directions as well as feedback to the experimental effort.

“Our hope is to establish our ideas into a viable technology that can be ported to industry and advance medical practices,” Leburton said. “Because of its compactness, and reduced number of operations, our sequencing scheme has great potential for portable medicine. It can be used out in the field rather than in the lab where it could be a long and expensive process. If you can rapidly sequence DNA, you have quick access to your own genetic information and determine if you’ve been exposed to external hazards or if you are ill. Then the doctor will provide, effectively and quickly, the appropriate treatment or medicine. This technology has the potential to revolutionize modern medicine.”

The paper detailing this technology, published in PNAS, can be viewed online. It was selected as a paper making an impact on scientific knowledge in the Nanotechnology category by The Latest Science.