The National Institutes of Health has awarded GMS Biotech a phase I Small Business Innovation Research grant worth $115,762 to help it develop an array-based blood-screening device that the firm hopes will replace existing serological techniques used in blood banks.
Entitled "The transfusion chip: a simple, low cost microarray for DNA-based blood typing," the grant was awarded on Aug. 1 and is set to expire on Jan. 30, 2012.
GMS Biotech CEO Krishna Jayaraman told BioArray News this week that there is a "huge, unmet need" for an inexpensive genotyping method to address changes in the blood-typing arena.
"For nearly a century, ABO blood-group typing has been based on serology" techniques such as agglutination, Jayaraman said. At the same time, the "science of transfusion medicine has rapidly expanded beyond the need to perform ABO typing by serology.
"The requirement for high-resolution Rh typing and the addition of newer markers like Duffy as a malaria marker makes serology less and less practical as a test panel," he added.
According to Jayaraman, while the use of gene-based blood-group markers is well documented, the cost of making blood-group testing "well suited for microarray analysis" may hinder its adoption.
He said that Inverness, Ill.-based GMS believes it can offer blood-group testing for about $10 per analysis on its platform, as opposed to $300 for other array-based options.
Founded in 2004, GMS has to date accumulated $6 million in SBIR grants to develop a system for human leukocyte antigen testing. The privately held firm is officially registered as Genomics USA, but began doing business last year as GMS, which stands for "genomics made simple." Jamarayan said the company will eventually change its official name to GMS Biotech.
In 2007, Doylestown, Penn.-based biotech QuantRx announced a plan to acquire Genomics USA, but according to Jamarayan, the deal fell through (BAN 1/23/2007).
On its website GMS claims that its core technology, developed while its founders were at Baylor College of Medicine, 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 GMS, its array fabrication method does not require modifying the DNA and needs only minimal modification of the surface, which allows it to offer chips at a lower price than its competitors.
Chief Scientific Officer Michael Hogan told BioArray News that the firm's platform is "relatively straightforward microarray technology," consisting of synthetic oligonucleotides bound in a surface targeting fluorescently tagged PCR amplicons.
He said that the firm's platform departs from traditional array technology when it comes to fabrication. Unmodified oligos are adsorbed to the cationic surface via an electric charge, enabling the oligos to electrostatically link to the surface.
Hogan added that the company can assay "absolutely raw samples," bypassing DNA purification steps. The assays can be run on "any liquid-handling instrument," including those sold by Tecan and Beckman Coulter, Hogan said.
"Our business model is very open source," he said. Labs equipped with liquid-handling instruments require only a thermal cycler to perform the PCR reactions and an imager to scan the assay results.
He said that it is "too early to say" how much the firm's assays will cost per sample, but that "the market will not accept a $30 blood-typing test" as most serological tests cost about $5. "The cost of the test has to be closer to $10," he said.
According to the grant abstract, the new funding will help it modify its HLA-typing platform to support blood-group typing by using an array that the firm has dubbed the "Transfusion Chip." Over the next six months, the company aims to design and validate between 13 and 15 PCR reactions for use with it.
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All informative sites among the seven blood-marker genes will be amplified in parallel in order to generate a dye-labeled amplicon set ready for microarray hybridization.
GMS will then design and fabricate a Transfusion Chip prototype to interrogate the informative sequence variations that define blood-group variations among the seven loci, according to its grant abstract.
If successful, Jayaraman said, the firm will pursue a two-year, phase II SBIR grant worth around $2 million. That funding "would be sufficient to take Transfusion Chip development to the stage where it would be ready for final validation and for product launch into the unregulated R&D markets," he said.
According to the grant abstract, phase II will focus on refining the PCR and array designs, scaling up manufacturing, fabricating preliminary PCR kits, and delivering those materials to beta testers. These include the "three or four top blood labs," which will compare the Transfusion Chip against existing serological typing and competing array and PCR-based tests.
In parallel, GMS said it plans to seek additional funding to perform validation tests required for a US Food and Drug Administration 510(k) review of the Transfusion Chip.
Jayaraman estimated that this process would require an additional two years and about $3 million of additional funding from the NIH or private sources. He did not say where this additional capital will come from, but noted that GMS has already obtained similar funding to validate its HLAChip and expects FDA to review that device for clinical use next year.
In the phase I SBIR grant abstract, the company claimed that the availability of an FDA-cleared blood-typing chip would "reduce the cost of blood-supply testing in the US" and "enable a new generation of enhanced, DNA-based blood-group typing in the developing world."
Other companies have similar ambitions. Progenika, located in Derio, Spain, with a US office outside of Boston, currently offers a blood-group genotyping test it claims can detect more than 100 genetic variants in the nine blood-group systems that are most relevant to transfusion safety.
The assay has been offered as a service through Salt Lake City-based ARUP Laboratories since 2009 (BAN 11/3/2009).
Jayaraman noted that the Progenika service costs about $300 per sample and claimed that, if successful, GMS' Transfusion Chip would be sold at at around $10. E-mails to Progenika seeking to confirm the cost of its test were not returned in time for this publication.
Because between 12 and 16 tests can be conducted per slide, GMS' chips would cost between $120 and $160, based on Jayaraman's one-tenth estimate. Using the firm's existing automated-instrumentation and -analysis software, Transfusion Chip-based blood-group typing could be performed at a rate of 2,000 samples per day per workstation, he said.
Jayaraman said GMS can offer lower prices because its technology is "unique in its ability to use raw samples, bypassing expensive DNA preparation." Additionally, he said that microarray hybridization in the GMS platform occurs at room temperature on array slides.
"That combination of raw-sample genotyping, low-cost microarrays, and room-temperature processing is unique to GMS and we think uniquely suited to the requirements for simplified, low-cost, population-scale transfusion-marker analysis," he said.
If GMS manages to bring the Transfusion Chip to market, it will be targeting blood banks, transplantation labs where blood-group typing augments HLA typing, and, in the longer term, point-of-collection sites such as clinics, Jayaraman said.
"It is especially interesting to note that once the transition has been made to DNA-based blood group typing, the analysis can be performed without a blood draw — a cheek swab will work just as well," he added.
The major barrier for the transfusion community to adopt the new platform will be convincing it that the genetics of the transfusion markers are well-enough linked to the serological phenotype, and that DNA analysis is safe enough to replace serology, Jayaraman said. Still, he is optimistic.
This is "analogous to the transition which occurred 15 years ago for HLA typing in transplantation medicine," Jayaraman said. "The result [is] that DNA-based HLA typing is now regarded as the gold standard in the field, replacing serology."
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