SAN FRANCISCO – Millipore is continuing to develop the cell-based screening capabilities it inherited through its Serologicals acquisition last year by entering into a collaboration with GE Healthcare and continuing a relationship that Serologicals unit Chemicon had initiated with Cellumen, CBA News learned this week.
The partnerships with GE Healthcare and Cellumen are in line with other recent moves by Millipore in the cell-based assay arena, such as its October launch of a GPCR screening service. In particular, the new relationships may mark Millipore’s entry into the previously unexplored high-content screening market.
In a presentation at GE Healthcare’s user group meeting during Cambridge Healthtech Institute’s High-Content Analysis meeting held here this week, Matthew Hsu, an R&D director in Millipore’s Chemicon/Upstate division, said that his company purchased an IN Cell Analyzer 1000 from GE Healthcare abut a month ago and is currently using the platform to turn existing cell-based assays into high-content screens.
Hsu said that Millipore’s current drug-discovery strengths are its high-throughput assays and profiling services, which encompass 252 kinases and 29 ion channels; more than 500 cell-based assays for sub-cellular localization, embryonic stem cell characterization, and neurite outgrowth; antibodies; and labware such as its MultiScreen and MilliCell multi-well plates and membranes.
Millipore also has in its toolbox various reagents and cell lines for measuring GPCR activation via calcium mobilization, tools that it pulled together to launch its GPCRProfiler screening service late last year.
But the company had yet to make a serious play in the high-content screening space, an issue it hopes to rectify with the GE Healthcare alliance.
Specifically, Hsu presented details about how Millipore has been attempting to turn a low-throughput neurite outgrowth assay into an industrialized high-content screen. He said that the assay in its current form uses the Millicell well-in-well technology and a bulk fluorescence plate reader, and is in fact a very robust and sensitive assay for neurite outgrowth. Despite this, Hsu said, the assay requires many washing steps and is thus relatively tedious and time consuming.
To adapt the assay to the IN Cell 1000, the company is in the process of developing an immunofluorescence staining method that uses antibodies with high antigen affinity, signal-to-noise, and specificity; and has minimal interactions with other cellular components. He said Millipore is also working with GE to develop appropriate image-analysis software for the task.
Hsu also said that Millipore has developed a GPCR assay adapted for high-content screening that uses the company’s proprietary ChemiScreen GPCR expression system, which expresses a greater number of receptors on the cell surface for FLIPR-type assays; and is attempting to develop a “universal” GPCR assay for HCS that would use an antibody against B-arrestin and possibly be an alternative to Molecular Devices’ popular Transfluor technology.
Ger Brophy, GE Healthcare’s general manager of discovery sciences, further characterized the relationship as the industrialization of Millipore assays that may have traditionally been lower-throughput, bench-top assays — a strategy that GE Healthcare is also exploring with other companies.
“We’re working very closely with them, and helping them develop assays,” Brophy said. “We talked about the industrialization of HCS, and I guess there are two parts to it: There is industrialization of the hardware, but there is also the industrialization of the assays.
Deciphering Cellular Toxicity
Hsu also said that Millipore is collaborating with nascent biotech Cellumen to combine that company’s multi-parameter panel of cell-based assays for cytotoxicity profiling with the IN Cell Analyzer platform.
Cellumen, headed by Cellomics founder Lansing Taylor, has developed its CellCipher cytotox-profiling panel using a variety of cell-based assays that measure multiple cell health parameters.
Cellumen initiated this collaboration with Serologicals’ Chemicon unit last February before Millipore acquired Serologicals [see 4/28/06 CBA News]. At the time, the deal called for Chemicon to provide reagent expertise to Cellumen, which would then develop the cell-based assay panel.
“I’m talking to CROs in general and saying, with a real naïve viewpoint, ‘What are the assays that your researchers are cranking through on a manual basis, and how can we industrialize them and get them on the IN Cell platform?’”
Despite the acquisition, Taylor this week told CBA News that the relationship with Millipore was “ongoing.” He said that Cellumen signed a contract for developing the first panel of cell-based assays, and is continuing to work under that contract. Meanwhile, the companies are considering developing a second panel, though no official contract has yet been signed.
It is likely that the collaboration will continue, however. Dennis Harris, previously the vice president of R&D and business development and chief scientific officer of Serologicals, worked with Taylor to engineer the agreement early last year, and Harris has been appointed corporate vice president and CSO at Millipore following the acquisition.
Kate Johnston, Cellumen’s vice president of discovery programs, also delivered a presentation at the HCA conference that further characterized the goals of the Millipore-Cellumen collaboration.
Specifically, she said that the work is an extension of a notable paper published in 2005 by scientists at Cellomics, Pfizer, and Cerep that showed how high-content screening of various cell-health parameters was highly predictive of toxicity in vivo
(see CBA News, 6/27/2005).
That study, she said, measured only five cellular parameters and was highly predictive. Meanwhile, the cytotoxicity profile being developed by Cellumen and Millipore looks at more than a dozen parameters.