New sensing system could enable faster, cheaper DNA sequencing

A sensing system developed at the University of Cambridge in England for use in rapid, low-cost DNA sequencing could make disease detection and diagnosis more efficient and individualized treatment more affordable.

A sensing system developed at the University of Cambridge in England for use in rapid, low-cost DNA sequencing could make disease detection and diagnosis more efficient and individualized treatment more affordable.

Ulrich Keyser, Ph.D., of the Cavendish Laboratory at the University of Cambridge, along with PhD student Nick Bell and other colleagues, has developed a system that combines a solid-state nanopore with a technique known as DNA origami for use in DNA sequencing, protein sensing, and other applications. The technology has been licensed for development and commercialization to Oxford Nanopore Technologies (Oxford, England), which is developing portable, low-cost DNA analysis sequencing devices.

Related: 'DNA origami' technology boosts labeling options for fluorescence microscopy

A nanopore is a hole that measures between 1 and 100 nm in diameter, and is typically contained in a membrane between two chambers containing a salt solution and the molecule of interest. When the molecules pass through the nanopores, they disrupt an ionic current through the nanopore and this difference in electrical signals allows researchers to determine certain properties of those molecules.

In collaboration with researchers at Ludwig Maximilian University (Munich, Germany), Keyser and his team have developed a hybrid nanopore that combines a solid-state material, such as silicon or graphene, and DNA origami—small, well-controlled shapes made of DNA.

“The DNA origami structures can be formed into any shape, allowing highly accurate control of the size and shape of the pore, so that only molecules of a certain shape can pass through,” says Keyser. “This level of control allows for far more detailed analysis of the molecule, which is particularly important for applications such as phenotyping or gene sequencing.”

Since complementary sequences of DNA can bind to one another, the origami structures can be customized so that functional groups, fluorescent compounds, and other molecular adapters can be added to the DNA strands with sub-nanometer precision, improving sensitivity and reliability. Additionally, hundreds of billions of self-assembling origami structures can be produced at the same time, with yields of up to 90 percent.

Recent research by the team, published in the journal Lab on a Chip, has shown that up to 16 measurements can be taken simultaneously, allowing for much higher data throughput and screening of different DNA origami structures.

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