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Beckman Coulter and NPE to Further Develop Flow-Based Cell Analyzer Tool

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Citing a “fundamental shift” in the flow cytometry and cellular analysis marketplace, Beckman-Coulter has forged a strategic alliance with NPE Systems to license and further develop NPE’s benchtop flow-based cell counting and sizing instrument, Quanta.

Under the agreement, Beckman will now take over the Quanta line from NPE, of Pembroke Pines, Fla., and incorporate it with some modifications into its Cell Lab suite of flow-based cellular analysis tools. A more robust version of the product will likely be available next month, said Ian Ley, cellular analysis strategic business manager for Beckman Coulter, and the company will introduce a second updated version with additional capabilities early next year.

The deal is part of a blanket strategy by the company to offer a range of flow-based cellular analysis products to fit a variety of tastes and budgets, according to Ley. Beckman, he said, recently previewed its newest, soon-to-be-released multi-color, high-end sorting system in May at the International Society of Analytical Cytology meeting in Montpellier, France. In addition, he said that the company will soon be revealing some changes to its mid-level XC-500 series of cytometers that will “make them more amenable to the research market.”

“We’ll go from literally a $10,000 cell counter, all the way up to a $300,000 research-grade cytometer system,” Ley said. “And I think we’ll then be in a unique position where we’ll have price points and a capable entry at every single grade and level you want.”

The Quanta product helps Beckman fill a product niche where until now it had been lacking — that of a push-button flow cytometry-based system for running simple cell assays on a basic laboratory bench top.

“The reason we’ve taken on the deal with NPE … is that we’ve got the technology, but the marketplace has fundamentally shifted,” Ley said. “Up until [recently], all flow cytometry systems were typically placed in core facilities … and they would supply the service. We’ve clearly seen that if you can get the price structure right, you can have this distributed system where many of the simpler assays — apoptosis, cell-cycle — can be carried out in the lab by the researcher instead of wasting a day or two, or even a week to get answers from a core facility.”

Although Beckman has “somewhat tapped in” to this niche with its compact Vi-Cell cell viability analyzer, Ley said, he sees fledgling companies Guava Technologies and Luminex as having already made significant headway in this area.

Guava markets the benchtop PCA cellular analysis system as a platform on which to conduct simple viability and cell-count assays, while Luminex’ screening system uses bead-based technology to conduct a variety of assays.

NPE’s Quanta was attractive to Beckman Coulter, Ley said, for two primary reasons: its flexibility and ability to accurately count and size cells. The flexibility is afforded by an arc lamp coupled with appropriate filters that can produce excitation wavelengths of 405, 434, 546, and 578 nm — sometimes simultaneously — which allows analysis of more than one fluorescence marker or cell type at the same time. The instrument is also equipped with a pair of photomultiplier tubes for fluorescence detection. These capabilities allow researchers to conduct assays such as apoptosis and cell-cycle.

Quanta’s cell-counting and sizing ability is based on the widely accepted Coulter principle. In this method, as described on Beckman-Coulter’s website, particles are sized and counted “based on measurable changes in electrical resistance produced by nonconductive particles suspended in an electrolyte. A small opening (aperture) between electrodes is the sensing zone through which suspended particles pass. In the sensing zone each particle displaces its own volume of electrolyte. Volume displaced is measured as a voltage pulse; the height of each pulse being proportional to the volume of the particle.” Put simply by Ley, “it literally displaces its own volume of electrolyte so you can determine the size of a cell very accurately.”

Beckman already manufactures a few “Coulter counter” instruments capable of this, but they are strictly for particle counting and sizing, and do not incorporate fluorescence-based assays as do the Quanta or other Beckman flow cytometry systems.

“We should have built it ourselves,” Ley joked. “We actually did build [one] in-house a couple of years ago, and for a variety of reasons, it just never got commercialized. We literally had, more or less, what NPE has got.”

Beckman will be making changes to the Quanta so it better matches its methods and extensive suite of flow cytometry reagents. The most significant change will be the addition of a laser beam to complement the existing light source. Operating at 488 nm, the laser is intended to enable analyses using some of the more popular fluorescent dyes used in flow cytometry, and will provide a better fit with Beckman’s reagent offerings.

“A lot of dyes tend to be excited on the 488 laser,” Ley said, “and because of the special properties of an arc lamp, you can’t get a 488 line out of it. The alternative is, you rebuild your menu of fluorochromes … but we’ve got thousands of products. The other aspect is, in the flow cytometry community, that’s what they use, particularly for immunofluorescence applications.”

This updated version of the instrument will be ready some time next month, Ley said. In the next version, due out early next year, Beckman will be adding more automation features and side-scatter measurement capabilities. Side-scattering is a way for researchers to better characterize cell type or complexity.

And although NPE had working analysis software for the Quanta instrument, Beckman will update that, as well.

“Though it’s a contract deal, essentially, we’re supporting their efforts,” Ley said. “We have a support team in place there. From a software perspective, they’ve got a piece of software in place, and it’s pretty functional, but they’re working with our team now to make sure that it meets our standards and our specifications.”

The bells and whistles will add up to a benchtop system that should glean even more information from cells than those offered by the competition, such as Guava’s PCA. It may not, however, surpass the PCA in cost efficiency.

Keith Olson, director of product commercialization at Guava, said that the PCA’s patented microfluidics and ability to operate without sheath fluid is still what will set the PCA apart from its competitors.

“This eliminates the cost and maintenance associated with a sheath fluid system,” Olson told Inside Bioassays last week. “Also, we can work with much smaller volumes of cells, which is important when you’re dealing with very precious cells, such as stem cells.

“From a sheer size perspective, [the Quanta] is a smaller footprint, and it is low-cost, something they share with us,” he added.

In April, Olson told Inside Bioassays that the PCA, in addition to allowing simple assays to be conducted in basic research labs, will also have pharmaceutical screening applications, such as quality control and initial screening, where pharmaceutical researchers can check cell viability, expression levels, and health before moving on to more high-content screening. (See Inside Bioassays, 4/27/2004).

Beckman said that the instrument is expected to prove useful in the secondary screening and ADME/Tox stages of drug discovery. Ley added that the new Beckman instrument should also serve another purpose, as a “backup system within a core lab.”

“This is where we think we’ll probably win out against Guava to some extent,” he said. “Basically, if you’re a core lab manager, and you’ve got four, five, or six apoptosis studies, or a couple quick cell-cycle analyses, instead of a flow system that does one particular type of assay best, just put them on a simple system, which doesn’t particularly need an advanced operator.”

— BB

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