03 December 2010

Cyborg nanopores will help speed up DNA analysis

Hybrid nanopores for DNA sequencing are a big step towards personalized medicine
LifeSciencesToday based on materials from Delft University of Technology:
Fitting a biological nanopore into a man-made one, new ways to analyze DNAScientists from Delft University of Technology (Delft University of Technology) and Oxford University (Oxford University) have reported on a new type of nanopore that can help in the development of systems for fast and cheap genetic analysis.

In the journal Nature Nanotechnology, they describe a new method for obtaining tiny holes for measuring and analyzing individual DNA molecules that combine artificial and biological materials (Adam R. Hall et al., Hybrid pore formation by directed insertion of α-haemolysin into solid-state nanopores).

"The first map of the human genome was completed in 2003 and cost about $3 billion. Imagine that the price may drop to the level of several hundred euros, when everyone will be able to undergo such a procedure and get a complete analysis of their genome. This will allow doctors to diagnose and treat diseases even before their symptoms appear," explains Professor Cees Dekker from the Kavli Institute of Nanotechnology in Delft (Kavli Institute of Nanoscience).

One of the promising devices for achieving this goal is called a nanopore. A nanopore is a tiny hole that can be used to "read" information from a single DNA molecule passing through it.

The result of the latest work of the Dekker group, conducted in collaboration with Professor Hagan Bayley from the University of Oxford, was a new, more reliable type of nanopore. It combines biological and artificial building blocks.

"Nanopores are already being used for DNA analysis. To do this, naturally occurring pore-forming proteins are embedded in lipid membranes. A DNA molecule can be "stretched" through such a pore by applying an electrical voltage to it. In this case, its analysis is somewhat similar to the way music is played by an old cassette recorder with its magnetic tape passing through the player. However, one aspect of such biological technology – dependence on a fragile layer of lipids – makes it quite difficult. The new hybrid approach is much more reliable and more suitable for integrating nanopores into readers," Dekker explains the situation.

The figure shows the formation of hybrid pores by direct integration of the natural pore-forming protein alpha-hemolysin (pink) into nanopores made of durable material (holes in the lower green layer). The applied electric field drags the double-stranded DNA molecule (blue, left) through the hole, which leads to the integration of the hemolysin protein into the silicon nitride membrane. After assembly, such hybrid nanopores can be used for sequencing and analysis of single-stranded DNA molecules (blue, in the center).
Credit: Image courtesy of Delft University of Technology

A new study, conducted mainly by Dr. Adam Hall, demonstrates a simple method for integrating pore-forming proteins into a reliable layer in a silicon chip. A large fragment of DNA is stretched through a previously made hole in the silicon nitride membrane, to which a protein molecule is attached. Passing through the hole, the DNA pulls the pore-forming protein behind it, eventually placing it in the hole and thus creating a reliable chip system. Such a system may well be used to create devices for practical use. Scientists have shown that the hybrid device is fully functional and can be used for DNA analysis.

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