Incorporating a Biologic Nanopore into a Synthetic One Offers New Ways to Analyze DNA

The innovative method that combines synthetic and biologic materials to result in a tiny hole on a chip is able to measure and analyze single DNA molecules.

The investigators involved on the project were from Delft University of Technology (The Netherlands) and Oxford University (UK). "The first mapping of the human genome where the content of the human DNA was read off was completed in 2003 and it cost an estimated 3 billion US dollars. Imagine if that cost could drop to a level of a few 100 euro, where everyone could have their own personal genome sequenced. That would allow doctors to diagnose diseases and treat them before any symptoms arise,” Prof. Cees Dekker of the Kavli Institute of Nanoscience at Delft explained.

One promising device is called a nanopore: a minute hole that can be used to ‘read' data from a single molecule of DNA as it threads through the hole. New research by Dr. Dekker's group in collaboration with Prof. Hagan Bayley of Oxford University, has now demonstrated a new, much more robust type of nanopore device. It combines biologic and artificial building blocks.

Dr. Dekker noted, "Nanopores are already used for DNA analysis by inserting naturally occurring, pore-forming proteins into a liquid-like membrane made of lipids. DNA molecules can be pulled individually through the pore by applying an electrical voltage across it, and analyzed. One feature that makes this biologic technology especially difficult, however, is the reliance on the fragile lipid support layer. This new hybrid approach is much more robust and suitable to integrate nanopores into devices.

The new research, performed mainly by lead author Dr. Adam Hall, is a simple technique that involves implanting the pore-forming proteins into a robust layer in a silicon chip. Essentially, an individual protein is attached to a larger piece of DNA, which is then pulled through a premade opening in a silicon nitride membrane.

When the DNA molecule threads through the hole, it pulls the pore-forming protein behind it, ultimately lodging it in the opening and creating a strong, chip-based system that is custom-made for arrays and device applications. The researchers have shown that the hybrid device is fully functional and can be used to detect DNA molecules.

The scientists published their findings in the November 28, 2010, issue of the journal Nature Nanotechnology.

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Delft University of Technology
Oxford University