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Scientists Gather to Discuss Laboratory Automation; HCS is a Major Component


At last week’s Association for Laboratory Automation’s inaugural LabFusion conference, topics varied from automation solutions in biodefense to robot-human interactions to driving rovers on Mars.

But the conference clearly had a commercial focus, as more than 160 researchers — a majority of them from pharmaceutical or biotechnology companies — gathered in Boston’s Hynes Convention Center to discuss the automation and integration of laboratory instrumentation for drug discovery and development, including technology for cell-based assays and high-content screening.

In addition, LabFusion featured an exhibit hall comprising approximately 100 companies, most of them showing off the latest widgets, gadgets, and gizmos designed to reduce manual labor and alleviate laboratory bottlenecks in the genomic age.

Despite the cornucopia of laboratory instrumentation on display, only a few companies used the meeting as a launching pad for new products — many of the new wares had been introduced at ALA’s LabAutomation conference, held this past February in San Jose, Calif.

On the drug discovery side of things, a modest portion of the podium and poster presentations directly tackled automation in cell-based assays and high-content screening, with about equal numbers focusing on areas such as compound management, high-throughput biochemical screening, proteomics, and informatics. But it was clear that many of the shared experiences and solutions could be directly translated into cellular screening.

Automating Assays

Cindy Sledziona, a scientist with Boehringer Ingelheim pharmaceuticals, presented a poster highlighting “real world examples” of transitioning from assay development to automation, citing areas that require special attention from researchers.

Sledziona told Inside Bioassays that Boehringer in general, and her lab in particular, will be conducting more cell-based assays in the near future for primary drug screening. She also shared some tips developed in her lab to facilitate the switch from a manual to automated assay.

“The first thing to do is to watch a person do an assay on the bench top,” she said. “Also, as assays move toward lower and lower volumes, [you are] worried about evaporation,” she said, adding that temperature and humidity control are crucial for combating this.

Another aspect of automation that is affected by small sample volumes is liquid handling, Seldziona said. Most of the new products introduced at the show fell into this area, with vendors such as Artel and Labcyte plying their new tools for handling smaller and smaller volumes of liquid. Sledziona said, however, that “oftentimes, you can physically see liquid hanging up in pipette tips, regardless of which dispenser you use.”

Lastly, she mentioned a commonly cited problem specific to cell-based assays: the cell culture bottleneck. “In cell-based assays,” she said, “just maintaining cell culture to keep up with the high-throughput assay is a challenge.”

Cell-Picking Robots

In another poster session of note, Chris Mann a biologist with Hampshire, U.K.-based Genetix, discussed a new automation solution intended to alleviate at least part of the cell-culture bottleneck: its ClonePix automated mammalian cell colony imaging and picking robot.

Mann explained that automated systems for isolating bacterial colonies have been available for about a decade. However, as the use of cell-based assays for drug discovery has increased, scientists have not had a comparable instrument for isolating and picking mammalian cells from culture plates.

When researchers transfect mammalian cells to produce antibodies or express a particular receptor protein (drug target), the cells are then often grown on a semi-solid cell culture medium. Each hybridoma grows as a distinct colony in the medium, so researchers can pick monoclonal cells from an appropriate colony for further use.

However, in the past, the culture dishes have typically been examined by eye, explained Mann, and individual cell colonies have been picked manually using a sterile pipette tip — a laborious and time-consuming process.

The ClonePix captures images of culture dishes with a CCD camera, and the images are subsequently analyzed using pre-programmed recognition software. Under sterile conditions, the instrument recognizes appropriate colonies, picks clones with an 8-channel head, and deposits them into microplate wells filled with media for use in cell-based assays. According to the company, the ClonePix can pick cells at a rate of 400 clones per hour.

Other Cell-Based Items

Despite the relative lack of new products, a few companies, such as laboratory equipment manufacturer Corning Life Sciences, demonstrated automation solutions for cell-based assays. Representatives from the company were showing off its RoboFlask cell culture vessels.

The flasks, which are rectangular in shape, are designed for use in automated cell culture systems because of their microplate-sized format, according to the company. Corning markets the flasks as being particularly compatible with Tecan’s Cellerity automated cell culture system — a result of a co-marketing agreement between the companies.

Another area that was heavily discussed on the exhibition floor was liquid handling for both biochemical and cell-based assays. In particular, Artel, of Westbrook, Maine, announced the launch of its MVS (multichannel verification system) for testing and verifying the performance of automated liquid handling equipment.

The company demonstrated its product at a sponsored luncheon, at which product development scientist John Bradshaw described how the MVS’ dual-dye photometric process allows researchers to verify the calibration of liquid handling systems in less than 5 minutes. The company also announced the sales of systems to Merck, Amgen, Biogen, and the Nevada Department of Public Health.

High-Content Automation

During the podium presentations, automated microscopy or other imaging methods for high-content screening formed a major theme. Of note, Jeffrey Price, assistant research scientist at the University of California at San Diego, chaired a session on molecular imaging.

Price’s lab continues to explore automated microscopy only a half-year after his startup company Q3DM — and its flagship automated imaging system — were acquired by Beckman Coulter. Beckman is currently readying a beefed-up version of the instrument for the high-content screening market (see story in this issue, Q3DM’s Cell Imaging System Reborn at Beckman Coulter; Instrument Nears Market).

Feimo Shen, a postdoc in Price’s lab, presented a talk entitled “Automated Functional Proteometrics of RhoA GTPase.” Using automated microscopy instrumentation and image analysis algorithms developed in the UCSD lab, Shen imaged cell motility “to provide some clue about what’s happening inside the cell,” in particular looking at differing expression levels of RhoA GTPase activity. Such studies, Shen said, are important for understanding the function of normal versus stressed, or even cancerous cells.

In the same session, David Basiji, chief technology officer at Seattle-based Amnis, discussed the progression and new applications of that company’s ImageStream high-content cellular analysis system. Somewhere between an automated microscope and a flow cytometer, the instrument is expected to hit the market in Q4 of this year (see Inside Bioassays, 6/1/04).

Amnis seems to be narrowing in on the applications the instrument will be targeting when it finally hits the market. For example, Basiji mentioned identifying apoptotic subsets of cells by examining their morphology; nuclear translocation studies; mechanism of therapeutic antibody action; cell classification in blood and bone marrow; FISH in suspension; and gene expression studies.

Basiji also mentioned that the ImageStream is not really meant to be a high-throughput instrument for primary drug screening. Its rate of 30 samples per day — while impressive for high-content imaging — is most appropriate for basic research and some secondary screening applications, he said.

Also presenting was Brian Healey, head of high-throughput screening at Swiss pharmaceutical company Serono. In his presentation, Healey discussed the implementation of high-content screening for conducting primary drug screens at Serono, and offered Inside Bioassays additional insight as to the drawbacks and benefits of microscopy- and scanner-based instrumentation in high-content screening.

“The issue is, microscopy is based on the intensity of the [fluorophores], and how long [it takes] to acquire an image,” Healey said. “So it’s very challenging to build a fast instrument when you have to do half-second or one-second acquisition times. In a lot of ways, microscopy does not lend itself to the high-throughput world.”

Healy added that if one chooses to switch to scanning-type instruments, throughput can be greatly increased, but at the expense of content. “You lose the Z [axis], and you lose the depth of field,” he said. “So there are drawbacks to both methods.”

Since the ideal primary screening method would be high-content and high-throughput, the topic of lab automation begs the question: Are there any automation improvements that can be made to high-content instrumentation so that it can be used in primary screens?

Healey thinks it’s difficult to peg down one or two improvements because there are “so many different applications.”

“Some of it is assay robustness,” he said. “How stable is your signal? If you’re using primary cells, are they cultureable? I think that people that have been somewhat successful have multiple sets of instruments. Each has their own function and job. Right now I would say that one flavor doesn’t fit all.”


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