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Falling Prices, Higher Throughput Drive Flow Cytometers into Drug Discovery

Start-up biotech Accuri Cytometers’ launch this week of a $25,000 flow cytometer may be occurring at the cusp of what is widely believed to be a re-emergence for the technology in non-traditional application areas.
And, as companies such as Accuri, Guava, and Becton Dickinson, as well as individual researchers, continue to explore ways to exploit flow cytometry’s throughput potential, many believe that drug-discovery applications are right around the corner.
Flow cytometry has been around for decades, and is a well-proven and oft-used technology in clinical applications and basic biomedical research. But over the past 10 years, innovations have also turned flow cytometers into highly sensitive and multiplexed, if costly, tools for drug discovery, especially for high-throughput cellular analysis, assay development, biomarker studies, or bead-based protein-protein interaction analysis, such as Luminex provides.
Flow cytometry is particularly suited for these types of applications on an industrial scale because of its ability to analyze up to 10,000 events per second, blowing away most any plate reader or imager.
Still, for these kinds of applications flow cytometers have faced a major obstacle: their relatively slow sampling rates. Because they generally draw their samples from test tubes, their throughput has not been fast enough for screening applications.
Guava, for one, has attempted to address this shortcoming by offering cellular analyzers that use microfluidics to draw from a 96-well plate. This feature has found Guava’s instrument a home in pharmaceutical and biotechnology labs as a tool for assay development and, in some cases, secondary screening applications.
Other companies and individual researchers are also dabbling in this area, such as San Diego-based drug-discovery firm Novasite Pharmaceuticals, which has developed a proprietary sample-handling technique that allows it to run cell-based functional screens for allosteric modulators of GPCRs from 96-well plates.
In addition, Larry Sklar, a professor at the University of New Mexico Medical School and head of the National Institutes of Health-funded Molecular Libraries Screening Center is attempting to commercialize a sampling technology called HyperCyt for high-throughput, flow-based drug discovery (see CBA News, 5/26/2006).
This week, at the American Society for Cell Biology meeting in San Diego, Accuri launched its ultra-cheap flow cytometer in a move that industry insiders feel may transform the flow cytometery market (see related story, this issue). In addition, Accuri said that it planned to introduce a 96-well-sampling version of its system in 2007.
And later in the week, Beckman Coulter introduced an option that it calls the multi-platform loader (MPL) for its Cell Lab Quanta SC bench-top flow cytometer. According to a statement from Beckman, the instrument enables quick, accurate handling of a range of plate types, including 96- and 384-well plates, chilled plates, or a 24 ViCell sample cup holder (see Products, this issue, for more).
But for now, it remains to be seen whether scientists can create a flow cytometer whose sampling rate can maximize the tool’s ultra-high throughput.
David Olson, Accuri’s chief scientific officer, said that “there will be a point when we’re going to be competing in an industrial marketplace where people are doing cell viability and validation work. We will have to offer a package to those customers that includes not only the instrument, but the software and validated reagents. And we’ll be very competitive at that time.”
In this area, Accuri may have a potential partner in UNM’s Sklar. Jennifer Baird, Accuri’s president and CEO, told CBA News that Accuri is familiar with Sklar’s work, and has had several meaningful conversations with him.
“We agree that it’s exciting to be looking at opportunities to do much faster throughput and sampling rates,” Baird said. “We’ve had some discussions about how that might be accomplished, and there is some potential for synergy between concepts that Larry’s been pursuing, and what our instrument is capable of. We actually have some IP filed related to that and … as part of doing that first 96-well plate reader, we will be incorporating that and expanding that over time.

“There will be a point when we’re going to be competing in an industrial marketplace where people are doing cell viability and validation work.”

“We’re inspired by his ideas, and we are excited about the vision he has for where research can go,” Baird added. “We are not in any formal relationship at this point, however.”
Sklar told CBA News that he has had several conversations with Accuri, and that he is “very interested in working with them in both a research development and commercialization process. I think that I would say right now that the ball is in their court. It’s really up to them to allow the relationship to go forward, and I would very much like it to go forward.”
Accuri will not play in the clinical market near-term, where Becton Dickinson, Beckman Coulter, and other companies such as DakoCytomation have a strong presence. “Eventually,” Baird said. “At this point we are focusing on the research market. We think there are good clinical applications, which we will be sorting out.”
“There are really steps to this,” Olson added. “Unregulated research; unregulated clinical research, such as biomarkers, which gets you in touch with patients; and the next step is clinical research. We’ll eventually have the instrument out in the marketplace.”

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