The National Hearth Lung and Blood Institute has awarded GMS Biotech $105,000 and given the firm access to a large repository of umbilical cord blood samples to validate the company's microarray-based human leukocyte antigen typing platform.
GMS believes the project could demonstrate the potential of its technology for use in routine newborn genotyping as well as HLA typing of umbilical cord blood for transplantation and stem cell therapy.
Indeed, GMS Chief Scientific Officer Michael Hogan told BioArray News that the company is already beginning to make contacts toward a follow-up prospective validation.
Under the current grant, set to end in March 2013, the company plans to further optimize and validate its process for HLA testing of raw cord blood samples stored as dried blood spots on filter paper.
"We really feel this is going to go rapidly," said Hogan. He said that most of the firm's core technology is "all ready to go" and that the new project "puts all the pieces together: the filter cards, adding water, sending samples straight into the raw sample genotyping and the high-throughput, inexpensive microarray analysis."
As GMS moves ahead with its validation project, it also plans to release its HLA chips this summer for research use only. The company has been working under a phase II Small Business Innovation Research grant to support a submission to the US Food and Drug Administration for its HLA arrays. Hogan said current plans are to begin meeting with the agency in the next few months and to submit for 510(k) review before the end of this year.
Founded in 2004, GMS has to date accumulated several million dollars in SBIR grants to develop its microarray technology for HLA typing. GMS' technology is based on the spontaneous assembly of an orderly DNA monolayer on the microarray surface and the resulting novel duplex form that is created when it binds to it, according to the firm.
Integral to the cord blood project, Hogan said, is the ability of GMS' technology to analyze raw samples, and allow the use of rehydrated blood spots.
"What we showed in preliminary results is that we could use the raw sample [ability] coupled to the HLA chips as a very inexpensive way to do HLA typing on umbilical cord blood samples," he said.
"A small amount of blood would be spotted onto filter paper much like other newborn screening done almost universally at birth … and we showed we can turn that into the basis for a very high-throughput way to obtain HLA types on that high scale."
Hogan explained that the company has developed preliminary technology to pipette a small amount of fluid onto dried blood spots on standard Guthrie cards so that a small bubble forms. A microliter sample from this bubble then becomes the input for the company's raw sample and HLA microarray technology.
"It creates a workflow model where you could collect samples on these cards in principle from every baby born, but certainly from that fraction that has consented to give cord blood, and you completely take the refrigerated cold chain out of the process, you take DNA purification out of the process, and you … basically go straight to the PCR and microarray analysis, so it cuts out many, many steps."
Under the NHLBI funding, GMS plans to optimize this process, and validate its preliminary results, using a sample cohort from the NHLBI-funded Cord Blood Transplantation Study, or COBLT. According to the grant description, the study will be carried out using 480 raw, enriched UCB samples.
Hogan said GMS has some defined plans to streamline the sample-to-result process as a first step under the grant, by optimizing the rehydration method as well as dividing filter cards into isolated wells to better enable robotic or multiple channel pipetting.
He said the company also plans to work on "ramping up the automation" of its raw sample genotyping and HLA chip microarray analysis. "We have developed a way to make these chips in an ordinary microscope slide format, except to put either 16 or 48 different [wells] in the same 1 inch by 3 inch microscope slide in a way that is relatively inexpensive," he said.
"In the 48-well format, depending on the resolution you want for HLA typing, or if you're working with a simpler test, we can actually make those for about $1 per array," he explained. The next step, he said, would then be to set up an automated workstation to demonstrate that the firm's workflow could be expanded to thousands of tests per day.
Hogan said the company is trying to be "very serious about the idea that some day soon the concept of doing complex genetic analysis on every newborn will be very real."
Around 12,000 babies are born in the US every day, but only a small portion of those families currently consent to cord blood donation. However, Hogan said there is growing interest in cord blood as a source of stem cells for transplantation and therapeutics, and technology will be needed to scale up HLA typing if and when the donation and use of UCB grows.
"The argument is that… to the extent that you believe the umbilical cord blood is a robust source, there needs to be a way to provide the HLA type at a scale much larger than currently implemented."
Under the NHBLI grant, the company is focused on umbilical cord blood, but GMS believes that the project could also serve as a demonstration of how its technology and dried blood spot approach could serve as a platform for routine HLA typing or other genetic testing on all babies.
While GMS's technology might not show many advantages over other methods for HLA typing in current areas like solid organ transplant, Hogan said the company believes it is the only group pursuing a low-cost microarray approach.
"The data we get is no better than what you can get from sequencing and maybe just a little better than Luminex beads, but I think where we shine is the way we've simplified the path from a raw specimen to getting this data," he said. "We believe that as the need for this kind of testing moves from being a niche market in support of very high value-added medical procedures like transplantation into something that is the next step up from that — in support of large-scale UCB sampling or attaining HLA typing of everyone at birth — we think we shine in that as the scale gets larger and larger, all of a sudden what we do starts to look more and more distinctive."
Right now, "testing for things like BRCA 2 or HLA typing for organ transplant, that's the sort of thing where one isn't necessarily all that worried about workflow or even cost, in getting that valuable information for people who are sick," Hogan said.
"On the other hand, if you start doing that testing on every baby, or some fraction of babies, you're talking about a flow of material orders of magnitude larger. So that's really what we're trying to address. We really are taking seriously the question of what happens when you start to enter a world where a reasonable fraction of everyone born every day has a complex genetic test associated with them."
After the company completes its validation work using the COBLT samples, Hogan said the team hopes to be able to move toward prospective validation by partnering with a group that already performs HLA typing on cord blood to gain prospectively collected samples.
He said GMS has made initial contact with a Red Cross facility that currently does about one third of all UCB testing in the US. "If we're successful in optimizing in this initial phase, our intention is to work to contact the Red Cross and others to do a larger prospective version of what we're doing with these archived materials."
Hogan said this is all somewhat forward looking. "We're not launching product this summer for national UCB screening, it's for organ transplant. But down the line, if you can show that it's economically feasible to obtain that information, all of a sudden it's worth talking about."
Blood Typing Update
Last year the National Institutes of Health awarded GMS Biotech a phase I SBIR grant for a separate project to develop a simple, low-cost microarray for DNA-based blood typing (BAN 8/9/2011).
Hogan said last week that the company successfully completed the Phase I project and recently submitted a phase II grant request to support additional development of its transfusion chips.
The company's advances in further miniaturizing the way it makes its microarrays, to allow 48 isolated wells, will also have relevance for the blood-typing project, Hogan said.
The plan, he explained, is to split blood markers between two chips: one covering ABO and Rh typing, which are more commonly used in clinical practice; and another with newer markers like Duffy that are measured more often in the research setting.
"It turns out all the probe content that would go into the ABO and Rh version can fit into one of these 48 per slide wells, and all the rest will fit into another," Hogan said. "So for this phase II that's what we're hoping to do."
Since ABO and Rh types are commonly used in clinical practice, he said the company would seek FDA review for that chip first, leaving the other as an RUO product until the clinical community "made a decision that some fraction of the rest of them should be folded into the ordinary practice of medicine."
Additionally, Hogan said the company hopes to investigate using raw saliva as a sample type. "We found that a really, really nice sample to use is raw saliva. So one thing we'll be doing is to focus not only on raw blood, but raw saliva. It sounds odd at first – but you don't really need blood to do blood typing, it's just genetics," he said.