Solid state nanopore technology points to the future of DNA sequencing

11/10/2011

Imagine the day when your doctor offers you a test that allows you to look into the future and determine what diseases you may get, enabling early diagnosis and treatment. Sound unbelievable? Researchers in the College of Engineering at Illinois are taking a step in this direction.

Written by

Imagine the day when your doctor offers you a test that allows you to look into the future and determine what diseases you may get, enabling early diagnosis and treatment. Sound unbelievable? Researchers in the College of Engineering at Illinois are taking a step in this direction.

Simulation of the charge contour of a single DNA strand passing through a nanopore in a solid state membrane made of a insulator sandwiched between two nanometer-size semiconductor layers.
Professors Jean-Pierre Leburton (electrical and computer engineering), Aleksei Aksimentiev (physics), and Rashid Bashir (ECE, bioengineering) are developing solid state nanopore technology that has a wide range of applications, including a potential DNA sequencing solution that could make affordable genome sequencing a reality.

While this technology features many adjustable parameters that will encourage numerous adaptations of this technology, one exciting possibility is its ability to sequence DNA quickly and efficiently. Currently, the cost to sequence a complete human genome is tens of thousands of dollars. With more affordable genome sequencing available, it could become a routine diagnostic test and have significant medical impact.

The team’s solid state nanopore technology creates nanopore devices—using a thin semiconductor, the basic material for nanoelectronics and integrated circuits—that can pull single-stranded DNA and double-stranded (ds) DNA through the nanopores in a controlled manner, and provides for the measurement of critical nanopore parameters associated with specific base pairs or degree of methylation.

The geometric elements of the nanopores, such as membrane thickness and diameter, and the material and flexibility of the semiconductor allow for the design of filters adjustable to the customer’s specific needs. For example, the geometry of the nanopore enables the stretching of dsDNA through an undersized pore.

While the majority of other innovations regarding DNA sequencing are chemically prepared or utilize biological membranes, solid state nanopore technology entails a solid semiconductor, which allows a more robust device with more flexibility.

Additionally, bias can be applied to various parts of the nanopore, and changed at will to move and/or trap various entities of interest in the nanopore. Once trapped, scientists can measure the pore and determine which entity has been trapped. This method can be utilized for DNA sequencing by pulling a strand of dsDNA through the nanopore, where the pore geometry allows only one half of each base pair to enter the pore, and to be identified. (See a video describing this nanopore technology--the primary substance of several patent applications.)

Leburton believes that bringing together life science and physical science to create new functionality in nanoscale systems is “one of the greatest challenges for the 21st century,” and will cultivate positive changes in the science world.

“I think solid state nanopores will have tremendous societal impact, especially in medicine, pharmacology, and related disciplines,”

Leburton said. “Because of our ability to make very small, electrically active semiconductors, we can mimic complex functions of the molecules of life.”

Knowing a person’s genome is important because it can indicate what diseases the person might. However, until scientists discover the functions of all genes, it will not be possible to predict all the diseases that are undeveloped in the body. Many diseases are diagnosed only when symptoms appear, which is often too late for effective treatment. Early diagnosis and treatment could lead to fewer deaths, or morbidity, from disease.

Other potential applications of this solid state nanopore technology could include dialysis; drug delivery on demand, for which solid state nanopores could be combined with living cells and artificially control drugs that are produced in biological settings; in vivo diagnostic devices; and as a measurement technique to measure ions in blood vessels.

About five years ago, Leburton and his colleagues –representing a diverse collection of backgrounds and expertise –realized the potential of semiconductor nanopores, and since then, the group has had patent applications filed on their intellectual property portfolio. While the technology has not been used in any specific commercial applications yet, Leburton remarked that patenting is the first step in that direction.

“We can propose new ideas based on modeling; for instance we have seen that some of our predictions on electrically active nanopores have actually been realized,” Leburton said.

Leburton and Aksimentiev are also affiliated with the Beckman Institute for Advanced Science and Technology; Bashir is director of the Micro and Nanotechnology Laboratory at Illinois.
_______________________

Contact: Jean-Pierre Leburton, Department of Electrical and Computer Engineering, 217/333-6813.

Writer: Jillian Forkal, Office of Technology Management.

Photo: Jean-Pierre Leburton

If you have any questions about the College of Engineering, or other story ideas, contact Rick Kubetz, editor, Engineering Communications Office, University of Illinois at Urbana-Champaign, 217/244-7716.

Share this story

This story was published November 10, 2011.