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Cytoo, Buoyed by Nature Methods Study, to Debut New Cell-Screening Plates, Chips

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By Justin Petrone

Cytoo, a French startup specializing in high-content cell analysis, later this year plans to debut new chips and plates to support its growing customer base, according to a company official.

Bill Sharp, CEO of the company's Framingham, Mass.-based subsidiary, told BioArray News this week that the company in September will begin selling 96-well CytooPlates, which will soon be followed by 384-well plates that contain cells patterned using its technology. Both plates will initially be sold as catalog products, but will eventually be customizable, he said.

Sharp added that Cytoo also plans to expand its line of CytooChips to support fluorescence labeling, including a line of chips specifically targeted for immunofluorescence applications, and is "growing our commercial organization around the world," especially into "geographies beyond Europe and North America."

Grenoble-based Cytoo has been encouraged to expand its offerings by a recent paper in Nature Methods in which researchers demonstrated that the company's adhesive micropattern technology can quantify cell-wide internal organization.

The micropattern technology is designed to enable users to control internal cell organization, and to decipher protein redistribution following drug treatment, which was undetectable using conventional cell-culture conditions.

The study, performed by researchers at the Institut Curie, "shows dramatic improvements in quantitative cell analysis when using micropatterns that control internal cell organization," said Sharp. In particular, he noted that the study delivered "statistically significant results with 20 cells versus thousands normally required in standard culture ware."

The Institut Curie is one of 15 private and public laboratories that have been assessing the company's CytooPlates ahead of their planned September debut, according to Sharp.

Founded in 2008 to continue developing technology licensed from the Institut Curie and France's Centre National de la Recherche Scientifique, Cytoo last year began selling chips that make use of its adhesive cell micropatterning platform.

The chips control the adhesion of cells in predetermined patterns, including disc, crossbow, H, Y, and L shapes, in small, medium, and large sizes, to reduce cell-to-cell variability in high-throughput, cell-based assays.

Cytoo's current generation of chips are 2 cm-by-2-cm, 170-micrometer glass substrates covered with an organized grid of 144 micropattern arrays that provide 20,000 micropatterns. And according to the company, each well of its planned CytooPlates will hold an array of over 3,000 identical micropatterns.

Sharp said that Cytoo's first 96-well CytooPlates will be available in a "Starter's" configuration that will enable customers to experiment with five different patterns in two sizes to help them "identify what pattern works best for their particular application or cell type." Customers will also have access to standard plates, where the same pattern is present throughout the plate, he added.

CytooPlates may also be manufactured to a customer's specific design, "either with a single micropattern throughout or with a family of micropatterns in the layout chosen by the customer in collaboration with Cytoo's experts," said Sharp.

Cytoo's arrays and chips are imaged via the company's CytooChambers, which fit into standard microscope instruments. To enhance this imaging process, the company plans eventually to introduce a series of fluorophor-labeled CytooChips that include Alexa 546, the equivalent of Cy3 dye; Alexa 674, the equivalent to Cy5; and Alexa 488, which is equivalent to FITC, Sharp said.

And later this year it will also launch "smaller footprint" CytooChips that are "specifically targeted for immunofluorescence applications," he added, without elaborating on the design of the new chips.

Nature Methods

In the recent Nature Methods paper, Institut Curie researchers discussed a computational imaging approach that can be used with micropatterned, three-dimensional, spatially organized endomembranes from micromanipulation-normalized mammalian cells.

Applied to several well-known marker proteins, the approach showed the average steady state organization of early endosomes, multivesicular bodies or lysosomes, endoplasmic reticulum exit sites, the Golgi apparatus, and Golgi-derived transport carriers in crossbow-shaped cells, the researchers said.

According to the paper's authors, the steady-state organization of each tested endomembranous population was "well-defined, unique, and in some cases depended on the cellular adhesion geometry."

Furthermore, density maps of all endomembrane populations "became stable when pooling several tens of cells only and were reproducible in independent experiments, allowing construction of a standardized cell model," they wrote.

The authors also detected "subtle changes in steady-state organization induced by disruption of the cellular cytoskeleton, with statistical significance observed for just 20 cells."

The authors determined that combining Cytoo's micropattern chips with the construction of endomembrane density maps allows the "systematic study of intracellular trafficking determinants."

They also suggested that the technology could be used to highlight pathological disorders during malignant development and argued that the technology could be used in high-throughput analyses of phenotypic alteration upon chemical compound or short interfering RNA treatments in large populations.

Indeed, study co-author Bruno Goud, a research director of the subcellular structure and cellular dynamics lab at Curie, told BioArray News that the institute is currently using 96-well plates provided by Cytoo to set up an assay for an siRNA-based screen.

Sharp said that an undisclosed number of customers in Europe and the US are using Cytoo's micropattern technology with siRNA-transfected cells and that the company is also partnering with EMBL/Bioquant to further develop such approaches.

US Operations

Sharp joined Cytoo last year when the company established an office near Boston with a focus on sales, marketing, and customer support. According to Sharp, sales in North America already represent 30 percent of the company’s total worldwide revenue during for its most recent fiscal quarter.

"We are taking a measured approach to growing our commercial organization around the world and are exploring a number of options for expanding our reach into and penetration of both the academic research market as well as geographies beyond Europe and North America," Sharp said.

Cytoo raised $4.7 million last year to support the expansion, which followed a $1.5 million seed funding round in 2008 (BAN 12/1/2009). Investors include Auriga Partners, CEA Valorisation, Rhône-Alpes-Creation, and Expansinvest as well as private investors.

At around that time, Cytoo President and co-CEO François Chatelain told BioArray News that the firm stands to benefit from conducting sales and marketing out of the US as opposed to France.

"Not only do we want a subsidiary in the United States, [but] we want our marketing to be directed from the US, because to address the worldwide market, US marketing is better, and is more universal or generic than French marketing," Chatelain said.

Chatelain also said that one of the aims of the US expansion was to position the company for further rounds of financing. This week Sharp said there are a "number of paths we will be exploring relative to supporting and funding the planned growth of our business." He did not elaborate.

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