Oxford Gene Technology said last week that it will develop and provide singe-cell analysis technology to the EuroSyStem Consortium, an alliance of European universities and small- and mid-sized businesses focused on advancing knowledge of normal and abnormal stem cells.
The Oxford, UK-based firm is a member of the consortium, which is funded by the EU's 7th Framework Program and provides facilities, resources, and training to the stem cell-research community.
John Anson, OGT’s director of research and development, said that researchers can use the company’s single-cell technology to quantitatively determine gene expression in order to examine the dynamic range of gene expression. In a statement last week, Anson referred to OGT’s method as a “cell population census” approach.
Anson told BioArray News last week that the method, which is being developed specifically for EuroSyStem researchers, relies on OGT-printed cell macroarrays, an internally developed scanner, and bioinformatics tools designed to enable researchers to survey cells on a cell-by-cell basis.
“This is a technology for being able to analyze single cells on a cell-by-cell basis, a cell-population analyzer, if you will,” Anson said. “Cells are effectively fixed onto the surface of a glass slide that contains a macroarray, hybridized in situ, and then specific genes can be viewed using a scanner. So it’s a new way of looking at cell populations on a cell-by-cell basis.”
EuroSyStem researchers will apply the technology to two stem cell systems: erythropoetic stem cells, which are being studied by Tariq Enver in the MRC Molecular Hematology Unit at Oxford University; and mouse embryonic stem cells with the Wellcome Trust Centre for Stem Cell Research, Cambridge, led by Austin Smith.
Anson speculated that if the collaborations with EuroSyStem and others are successful, the single-cell technology could be made commercially available sometime next year.
Founded in 1995 to protect and license the patent estate of array pioneer Sir Edwin Southern, OGT has in recent years taken a more commercial turn under CEO Mike Evans who took the helm of the company in 2005 (see BAN 4/26/2005).
“Many analyses of cells are effectively looking at a population as a whole. This method allows you to avoid going through that pooling stage and it gives you a cell-by-cell analysis.”
Since that time, OGT has commercialized a line of prokaryotic arrays for chromatin immunoprecipitation (ChIP)-on-chip applications, and has launched its CytoSure products and services for comparative genomic hybridization (see BAN 10/3/2006, BAN 6/26/2007).
According to Anson, the single-cell expression technology is the latest to surface from OGT’s pipeline of array applications and the company views its EuroSyStem participation as a way to prepare the technology for eventual commercialization.
“It’s still in development” he said. “We have been working on the technology for some time within OGT and we are at the stage where we want to work with external collaborators. We are also working with collaborators outside the EuroSyStem project in areas such as cancer research” using this technology.
Anson said that such collaborators bring “interesting biology” to OGT’s technology. “They bring questions they want to answer on an individual-cell basis; we take our technology and try to apply it and answer those questions,” he said.
The New Tech
OGT’s new technology is actually a fusion of three R&D areas within OGT related to arrays, optics, and bioinformatics. OGT will use its inkjet in situ synthesis printing technology to produce the arrays for the EuroSyStem project. Because the cell feature size is larger than the typical micron-level features of OGT’s microarrays, the firm’s cell arrays are technically termed “macroarrays.”
The arrays are “based on a lot of knowledge that we have gathered over the years about how hybridization events occur at the surface of an array,” Anson said. “We obviously have got a lot of expertise and knowledge of hybridization kinetics and also labeling. We can use our knowledge and expertise to develop this new technology.”
In terms of optics, Anson said that OGT has been developing a high-resolution, high-sensitivity scanner in-house for the project. “We have evaluated standard array scanners and they don’t have the sensitivity and resolution that we require,” he said. The instrument in development is currently a prototype; OGT hopes that after being streamlined during the EuroSyStem project, it, too, could become a commercial product.
Finally, OGT is developing new software to analyze the quantitative images from screening the cell arrays. “We see this as a next-generation technology and it is where we see arrays going in the future,” said Anson. “We are looking at biology in a slightly different way.”
According to Anson, the approach should be attractive to researchers who are used to running stem cell-expression studies on standard microarrays or RT-PCR. When using those technologies, researchers typically do an RNA preparation step on a cell population, and then run it on the microarray or RT-PCR cartridge. However, that approach offers an average expression of all the cells harvested simultaneously, whereas OGT claims its method allows researchers to view gene expression in each cell.
“Many analyses of cells are effectively looking at a population as a whole,” he said. “This allows you to avoid going through that pooling stage and it gives you a cell-by-cell analysis. That’s useful when you have a population of cells that are heterogeneous in terms of their specific genes of interest.”
According to Anson, stem-cell studies are one area where OGT sees an opportunity for its technology. Still, the company sees potential interest in the market from being able to monitor viral infections or rare events in blood cells.
“Obviously, where you have got things like leukemia and other blood-based disorders, then there is an interest in looking at rare events in what would be a healthy population of cells,” he said. “I think the technology is very useful for those sorts of applications.”