Diverse Approaches to Workflows

On a basic level, a workflow is a sequence of steps necessary to complete a designated task. In a laboratory, there are many workflows. For example, a workflow may consist of the specific procedures for preparing a sample for analysis. Another workflow may encompass sample preparation as well as sample analysis.

Laboratory product and instrument companies serve many of these workflows, depending on their product offerings, application expertise and market focus. Increasingly, these companies are offering complete workflows. That is, products that are used in each step of a given laboratory process.

However, creating a workflow entails more than simply offering products for each workflow step. It also involves integrating these products in order to simplify and accelerate the process, and improve the quality and reliability of results. New products from Thermo Fisher Scientific, QIAGEN and Roche Applied Sciences demonstrate the varied approaches to workflow solutions that are possible and how such workflows can meet end-users’ needs.

Capitalizing on the 2006 merger of Thermo Electron and Fisher Scientific (see IBO 5/15/06), Thermo Fisher Scientific launched its Cell Culture Excellence Program in May. The Program provides laboratory reagents, consumables, equipment and instruments for cell culture processes. For reagent and cell storage, Thermo Fisher Scientific’s offerings include Revco freezers and Nunc vials. For cell growth and passage, the company can provide Heraeus incubators and Hyclone growth media, among other products. Microplates and Finnpipette Novus pipettes, and other products, are available for cell culture and experimentation applications. For cell harvest, Heraeus centrifuges and Nalgene bottles are among the products offered. For recovery, Thermo provides the Slide-A-Lyzer MWCO dialysis cassettes, among other products, while for analysis, it offers microplate readers.

Jeff Goldman, Strategic Marketing manager for Thermo Fisher Scientific, described how the program is not simply another sales technique: “It’s not a one-stop shop kind of offering. We’re not saying you have to buy everything from us.” Mr. Goldman also emphasized how customization and support distinguish the program. “We have such a broad offering that we have the ability to tailor that offering to the exact needs to all of the customers in the market,” he said. “We have the ability to ask our customers broad questions, such as, what are you trying to do with this lab? What are you trying to do with this experiment? Then, we customize our offering based on what their needs are.”

The program also facilitates product development and customer partnerships as Thermo receives input from researchers. “Technology advances as research advances, and our customers are eager to engage in this partnership,” Mr. Goldman noted. “Something else we’ve learned is that there hasn’t been a company that has had the ability to address the entire market,” he said. And the service and products that Thermo provides extend beyond its own products. “It seems that we don’t have a lot of gaps in the [Cell Culture] portfolio, except for microscopy, but we do have the opportunity to offer those products and cell sorters, which is another product not in the portfolio. Thermo Fisher has the capabilities to sell both of those separately.”

The Cell Culture Excellence Program follows Thermo’s creation of another workflow solution, the Stem Cell Excellence Program, in December of 2007. “Our portfolio of products for the stem cell excellence and the cell culture excellence program are tightly linked. Thermo has put together groups of resources to serve both of those markets,” said Mr. Goldman.

The Programs also further encourages Thermo Fisher Scientific’s product groups to collaborate on applications. Discussing the program from the perspective of Thermo Fisher Scientific’s Hyclone group, which supplies culture media, Alain Fairbank, research market manager for Cell Culture Products, explained: “We reach out and work with our sister organizations. . . . Our stem cell team not only does product development, but works with other Thermo Fisher Scientific teams on application-focused work.”

In contrast to Thermo Fisher Scientific, which links its products for the cell culture workflow through customization and support, QIAGEN’s new workflow solution targets a more specific workflow with a standardized solution that combines new product offerings. In June, QIAGEN launched five new products that fill gaps in the company’s epigenetics workflow. QIAGEN’s epigenetics workflow consists of products for DNA methylation studies, from DNA purification to bisulfite treatment and analysis.

The analysis of DNA methylation is dependent on converting isolated DNA using bisulfite to alter the unmethylated cytosine to uracil. Adding to its kits for bisulfite treatment, QIAGEN’s new EpiTect Whole Bisulfitome Kit amplifies the complete bisulfite-converted genome. According to Dr. Dirk Loeffert, QIAGEN’s senior director of Research in North America, this improves methylated-DNA yield during PCR, a problem with other bisulfite treatments. “The EpiTect Bisulfitome Kit overcomes the inherent problem of limited biological material for DNA methylation research, especially when working with valuable patient material. Following bisulfite conversion of the isolated DNA, often there is not sufficient DNA left over to conduct all the required analysis,” he said.

After bisulfite treatment, methylated DNA is detected and analyzed using EpiTect assays and kits, which consist of the new EpiTect MSP (methylation specific PCR) Kit, the EpiTect MethyLight PCR Kit, the EpiTect MethyLight Assay and the EpiTect Control DNA. QIAGEN also offers kits if DNA sequencing is used for analysis.

Together, the new products create QIAGEN’s methylation workflow by standardizing results. “[EpiTect Control DNAs] eliminate any biological variability, as methylation patterns may be strikingly different for various cell lines or tissues commonly used as reference- or process-related variables, e.g., through inefficient chemical conversion of the DNA,” said Dr. Loeffert. “Eventually, the PCR reagent and assay itself can introduce variability depending on the robustness of the assay reagents and the designed assay.” He added, “EpiTect PCR reagents and ready-to-use EpiTect MethyLight Assays overcome this hurdle by providing researchers with standardized assay reagents and protocols for all real-time PCR platforms.”

Roche Applied Science has taken yet another approach to creating a workflow using its products. This April, the company’s NimbleGen business introduced Sequence Capture Technology for targeted gneomic resequencing. Utilizing NimbleGen’s Sequence Capture microarrays and based on a Sequence Capture methodology published last year by researchers at Baylor College of Medicine, the technology utilizes Roche Applied Science’s three technology platforms—DNA microarrays, next-generation sequencing and PCR. Adding to its existing portfolio of PCR products, in 2007, Roche Applied Science acquired DNA microarray company NimbleGen (see IBO 6/30/07) and 454 Life Sciences (see IBO 3/31/07), the maker of the Genome Sequencer FLX System based on pyrosequencing.

The three technologies are standard components of multiple genomics research procedures. As Dr. Burkhard Ziebolz, Roche’s head of Global Communications, stated: “Very roughly, you can position these technologies for discovery (sequencing), analysis (microarray) and validation (real-time PCR). You are going from hypothesis-free analysis to more focused analysis and, finally, you are validating the findings with the best precision possible (PCR).” Roche Applied Science has also integrated the sales process for the three technologies. “The extension to sequencing and arrays does require a good mix of generalists and specialists to work together for maximum presence and impact in the market. This is addressed by key account management approaches.”

The Sequence Capture technology creates a dedicated workflow that integrates all three product platforms. Using the Sequence Capture custom microarray, researchers can amplify selected portions of a genome sequence without PCR. The microarray can capture dispersed and short gene segments, single and long gene segments, and it can enrich fragments in parallel, providing a faster, less costly and more efficient form of sample preparation prior to resequencing than PCR, according to Roche Applied Science. Although initially introduced as a service offering, NimbleGen plans to release Sequence Capture microarrays and kits later this year.

Following sample enrichment, resequencing is performed and then validated using PCR. Although resquencing can be done with other next-generation sequencers besides the FLX System, the use of NimbleGen’s Sequence Capture microarrays with the FLX System has been optimized and validated. As NimbleGen states on its website: “To supply our customers with an affordable, high-quality solution, we have been working closely with our sister Roche business area, 454 Life Sciences, to develop, test, validate, and optimize protocols for obtaining enriched DNA that can be directly and easily integrated into the workflow of the 454 GS FLX instrument. The 454 GS FLX instrument delivers read lengths of 250bp and is the most appropriate sequencing technology for the NimbleGen Sequence Capture solution.” Baylor’s Human Genome Sequence Center plans to use the technology in its sequencing projects and in an effort to resequence the human exome.

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