Oxford Nanopore Technologies Ltd is pleased to announce a new agreement to strengthen the Company’s collaboration with the University of Oxford. The Company will fund research in the laboratories of Professor Hagan Bayley and will partner exclusively with the University to develop revolutionary products for molecular analysis from these new discoveries.
Research projects within the Bayley group include methods for the direct sequencing of single stranded DNA (ssDNA). This and other nanopore sequencing techniques may offer substantial performance benefits over currently-available sequencing technologies through improved cost and speed.
“We are delighted to have signed this new agreement to broaden and extend the collaboration between the University of Oxford and Oxford Nanopore Technologies,” said Dr Gordon Sanghera, CEO. “Our core technology is compatible with a broad range of nanopore sensors and so this collaboration enhances the potential of our system, from evolving our first generation of DNA sequencing technology to exploring new applications such as protein sensing.”
Oxford Nanopore is developing a revolutionary platform technology for direct, electrical detection and analysis of single molecules, with a lead application of DNA sequencing. The Company was founded in 2005 on the science of Professor Hagan Bayley of the University of Oxford and has since formed a series of collaborations with other leading institutions including Harvard University and the University of California, Santa Cruz. Oxford Nanopore has licensed or owns more than 200 patents and patent applications that cover all aspects of nanopore sensing including DNA sequencing.
Oxford Nanopore’s modular instrumentation may be combined with different types of nanopore sensor for the analysis of a range of single molecules. The Company’s ‘exonuclease sequencing’ method combines a processive enzyme with a protein nanopore for the identification of individual bases cleaved sequentially from a DNA strand. ‘Strand sequencing’ is a method to identify bases on an intact strand of DNA as it passes through a protein nanopore. Future generations of nanopore sensing technology may use ‘solid-state’ nanopores, holes in synthetic materials.
Sequencing single stranded DNA
Current challenges in sequencing of ssDNA include mechanisms of controlling the translocation of ssDNA through the nanopore and the accurate identification of individual DNA bases on the strand as it passes through the pore. The Bayley laboratory continues to research these methods. Recently published progress includes a 2009 PNAS publication showing that all four DNA bases could be distinguished in immobilized DNA strands and 2010 Angewandte Chemie publication that used two recognition sites in a single protein nanopore to provide additional data for DNA base identification. In a September 2010 Nano Letters publication the group showed that selective mutagenesis of the alpha hemolysin nanopore can weaken or strengthen recognition points within the pore when aiming to identify single nucleobases on ssDNA and can improve the discrimination between the four bases. This methodology provides a structure-function relationship for the enhancement of performance of hemolysin nanopores for DNA sequencing applications.
Array chip for high-throughput single molecule analysis
Oxford Nanopore’s proprietary technology allows parallel measurement of multiple individual channels on a single silicon chip. Each channel measures individual analyses of single molecules using a protein nanopore. In order to provide high-performance single molecule analyses, the technology can therefore be scaled up for the concurrent measurement of multiple channels, from hundreds to tens of thousands of channels depending on the application.
The proprietary array chip creates lipid bilayers across the surface of multiple microwells on a silicon chip and measures the signal from single protein nanopores embedded in the bilayer in individual wells. The Company also has active collaborations in the development of a future generation of ‘solid-state’ nanopores, holes in synthetic materials.
The Bayley laboratory is also researching methods of building and using ligand-nanopore complexes for the analysis of a variety of analytes including proteins. Oxford Nanopore recently announced the start of a research programme in protein analysis, which can be performed on the company’s core technology platform.