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GSK First to Buy HTP, Automated Cell-Culture System from MatriCal

MatriCal last week announced that it has shipped its first automated cell-culture system, or MACCS, to GlaxoSmithKline’s oncology biology facility in Collegeville, Penn.
The automated technology, launched in March, enables scientists to culture a frozen stock of cells and grow them for assay-ready drug-discovery research, according to MatriCal CEO and co-founder Daniel Roark.
The firm sold the unit after around 10 pharma companies, including GSK, provided “very good feedback” into its development, said Roark.
According to Roark, GSK told MatriCal before it began developing the system that it “was looking for alternatives [to manual cell culture] in the marketplace, and did not see a system that was flexible enough to work with some of the cultureware that they felt would be beneficial for their research efforts.”
Ronald Wegrzyn, assistant director of oncology at GSK, told CBA News that he suggested to Roark and MatriCal co-founder and President Kevin Oldenburg that they develop the MACCS “because of a need that we would have in our high-throughput-screening organization. I actually walked up to them and proposed the idea, based on one of their other products, the MiniStore.” The MiniStore is MatriCal’s automated sample storage and management unit.
What Wegrzyn wanted was an automated cell-culture system that he suggested could be created by converting the MiniStore into an incubator, and an add-on system that cultures and plates cells. The resulting MACCS system can perform both tasks.
Current cell culture procedures are primarily manual, and require researchers or technicians to sit under hoods and passage microtiter plates. The Automation Partnership, a MatriCal rival, manufactures automated cell-culture systems, but Wegrzyn described them as “very inflexible as far as what operations they could perform.”

“With our specifications on this machine, we had a very flexible and user-friendly system.”

Wegrzyn said that he wanted an automated system that could passage and seed cell cultures, and that could passage cells out of flasks and transfer them after counting 96- and 384-well microtiter plates. In addition, his team at GSK wanted to be able to use liquid nitrogen vials to freeze cells and be able to thaw them, count them, and seed them into either flasks or microtiter plates.
GSK’s facility has as many as 300 tumor cell lines, so “I need plenty of storage capacity for plates and flasks that are growing cells within the system,” Wegrzyn said. “With our specifications on this machine, we had a very flexible and user-friendly system.”
MatriCal will soon install a system at Danish drug maker NovoNordisk, which will use it primarily for protein production, Roark said.
NovoNordisk is also working with shaker flasks, said Roark, and added that the MACCS system is so far the first [of the company’s systems] to implement shaker flasks.
In addition, NovoNordisk is doing hybridoma work, for which MatriCal has developed a new pipettor.
MACCS-imum Flexibility
The MACCS system was launched in March (see CBA News, 3/28/08). “After you are in the industry for a while, you get to know people, and if you have built good automation in the past, it gives you an opportunity to maybe think about doing something new for someone in the future,” Roark said. “That is how this opportunity with GSK arose.”
While it was developing the MACCS system, MatriCal received feedback from 10 pharmas. Among those who provided feedback were researchers who work with shaker flasks, and MatriCal has said the company will enable the system to read the flasks. The MACCS currently has the ability to store cell culture flasks in “high capacity,” Roark said.
“We also have our own spinner flask [the MatriMix], so we can work with [shaker and spinner] flasks within the system now, which is a big advantage over what exists in the marketplace, which is not very automation-friendly” said Roark.  
Many pharmaceutical researchers want to be able to split cells in real time and monitor cell growth in order to culture the cells to the correct density and screen them. One capability of the MACCS system is that it enables scientists to reseed cultures from mother stock and freeze cells back down.
“As your cell line gets depleted, you need to refreeze and store your mother sample, and we have the ability within the system to do that, which is something that other systems cannot do,” said Roark.
MatriCal’s MiniStore product enables scientists to manipulate tubes on a robot that comprises three axes. But in an environment that includes cell culture, researchers are manipulating flasks, vials, and other lab ware, and need a 6-axis articulated robot that can pour, mix, and handle many types of consumables, from flasks to plates to pipette tips to cannula. This is where the modular MACCS system comes in.
“We just have a lot more variety in [the MACCS] system,” said Roark. “You are actually storing cells, so now you have an incubator, and have to deal with the question of how to get cells in and out of the incubator and into the robotic environment. And, of course, you have to deal with sterility issues.”
Also, based on the capacity required by groups working with the MACCS system, MatriCal can expand the incubator module to accommodate the number of samples that they may want to process, said Roark.
“A lot of different options within the software and database are also being added, in terms of adding image acquisition, that sort of thing, so you can look at cell morphology in addition to getting viability data from a cell sorter,” he added.
The company is also looking at adapting the MACCS system to work with stem cells. 
MatriCal has built a software and support team to deal with the different types of applications, said Roark. For example, the company built its MatriMix spinner flask, for which it has a patent pending.
One issue MatriCal had with some of the currently available spinner flasks is that they are not automation-friendly. “We needed to develop a flask that allowed our automation to orient the flask and also to aspirate from it,” Roark said.
Researchers also want to maintain a homogeneous mixture of cells, so that when they are plating them, they get an even distribution with each aspiration and dispense. “The benefit of this is that we have an aspiration port while we continue to mix,” Roark said.
The system features built-in alerts that reminds operators by e-mail to load enough media for weekend runs, so that the scheduled production can occur as planned.

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