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GE Healthcare s Newest HCS Instrument Part of Industry Trend to Make Confocal More Accessible


SAN FRANCISCO — GE Healthcare has launched a new version of the IN Cell Analyzer 1000 and will discontinue the current version as the company falls in line with an emerging trend to make confocal or confocal-like imaging technology more accessible to certain researchers in pharma and academia, GE officials said at the Cambridge Healthtech Institute High-Content Analysis meeting held here this week.

The new version of the IN Cell 1000 will contain optical Z-sectioning ability, which allows the lamp-based widefield microscope to achieve confocal-like imaging and therefore better image quality — a crucial component of high-content screening and analysis.

GE's newest entry into the high-content analysis market is in line with a recent attempt by certain instrument vendors to make confocal or confocal-like imaging technology more accessible to academic researchers or pharmaceutical scientists who want to conduct more image-based assays, but whose budgets won't allow a high-end instrument that costs close to $1 million.

Last week, CBA News reported that Molecular Devices plans to launch a new confocal imaging system called ImageXpress Ultra at the conference here. That system is a true confocal, but Molecular Devices said it has reduced the cost primarily by substituting solid-state lasers for the more expensive laser types typically found in confocal imagers.

"The market is segmented, and we feel that we have to accommodate both segments."

Other vendors have attempted to make confocal-like platforms without the use of lasers, but instead with clever optical tricks and image-processing algorithms. An example of this is BD Biosciences' Pathway HT, which it acquired along with Atto Bioscience. According to the BD-Atto Pathway HT website, the instrument features a module called CARV, which is essentially a spinning disc that helps eliminate all but the desired fluorescence signal, much like a true laser-based confocal does.

Cellomics was one of the earliest vendors to offer such technology: Its ArrayScan instrument is lamp-based but uses a module invented by Zeiss called the Apotome, which achieves confocality using a sliding grid to take three separate images of the same plane, and an image-processing algorithm to reconstruct the image.

The new IN Cell 1000, on the other hand, uses optical grid technology more closely related to the Apotome found in Cellomics' instruments. According to Anne Jones, director of marketing for cellular sciences and lead discovery in GE Healthcare's Discovery Systems division, the technology is licensed from imaging company Improvision, which also sells the technology to researchers wishing to add confocal-like ability to standard laboratory widefield microscopes.

The new system is designed to "play in similar markets" as the BD Pathway HT and Cellomics ArrayScan, Jones said.

"These are designed to be versatile and used for things like assay development, lead profiling, and other similar applications," she said. "But we are also very much focused on making it as modular and versatile as possible. Our system has not only the ability to do live-cell and fixed-cell assays, but you can also image a range of plate types, glass slides, and you can do transmitted light on the system. This last piece we've added further improves the versatility to improve confocal-like imaging."

As detailed in a poster presented by GE Healthcare scientists here at the CHI conference, the optical Z-sectioning ability of the new IN Cell 1000 is comparable to that of the laser-based line-scanning confocal system of the IN Cell 3000.

In addition, according to the GE scientists, the optical-Z sectioning ability may eliminate some of the problems associated with background noise, or auto-fluorescence, in cellular imaging.

"One of the major dilemmas facing investigators performing live-cell imaging is the question of whether to image in the cell's natural medium, or to use a balanced salt solution," the researchers noted in the poster. "The unwanted auto-fluorescence that stems from the presence of medium and serum degrade the quality of their images and potentially compromise image analysis.

"However, removing the cells, even briefly, from their natural medium … can stress the cells and compromise the integrity of the very biological processes being studied," the poster continues.

The poster goes on to present data supporting the notion that the new optical Z-sectioning module on the IN Cell 1000 can reduce loss of contrast due to the presence of auto-fluorescing medium by almost half, allowing for a contrast ratio more than double that of a standard widefield image (5.7 versus 2.6). At a contrast ratio near 1.0, signals can no longer be distinguished from background noise, the researchers explained in the poster.

The upshot of this, according to Jones, is that researchers will be able to conduct low signal-to-noise assays on the less expensive IN Cell 1000 as opposed to a more sensitive confocal instrument such as the IN Cell 3000.

Despite the confocal-like abilities of the IN Cell 1000, it still serves a very different market segment than the 3000.

"The IN Cell 3000 is a true confocal laser-based system, so … it's much more sensitive, it's faster, and designed for high-throughput and high-content cellular screening," Jones said. "It plays at a different price point and space in terms of market segmentation — more in the space of the Evotec Opera, for example.

"The market is segmented, and we feel that we have to accommodate both segments," she added. "One [segment] wants the very versatile system, which may be lower throughput, but wants flexibility in both hardware and software; and one wants the high-end, fast, sensitive instrument that will allow them to do screening."

If Jones' words sound familiar, it's because Mike Sjaastad, Molecular Devices' director of imaging, expressed nearly the same sentiment in an interview with CBA News last week when talking about Molecular Devices' new high-end confocal reader, which was designed to complement its lower-end lamp-based systems used for assay development and secondary screening [see 1/27/2006 CBA News].

And in fact, much of the market seems to be turning that way. Several speakers at the conference discussed how their labs often have two types of instruments — a high-end confocal for true compound library screening, and a lower-end lamp-based system to develop and validate the assays that will eventually be run in high throughput on the confocal systems.

For example, Jonathan Lee, research advisor in the lead generation and optimization biology department at Eli Lilly, said that his lab uses three Cellomics ArrayScans and five TTP Labtech Acumen Explorers. The ArrayScans are used primarily for assay development work, while the Acumen Explorer — though not a confocal system — is a laser-based scanning cytometer that is capable of the type of throughput desired in a compound screening campaign.

GE Healthcare's Jones told CBA News that the new module will not significantly drive up the cost of the IN Cell 1000.

"The pricing of the IN Cell 1000 is highly competitive with other lamp-based systems on the market," she said. "It is designed to be a modular system, so depending on which elements you purchase, there will be a range of prices. It is very much competitively priced with other lamp-based systems, but it not in the same price range as laser-based systems like the [IN Cell] 3000," the Evotec Opera, or Molecular Devices' ImageXpress Ultra, Jones said.

In addition, even though GE Healthcare is discontinuing production of the "old" IN Cell 1000, it plans to continue to support these customers. Furthermore, Jones said, the optical Z-sectioning module can be retrofitted to the old instruments.

— Ben Butkus ([email protected])

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