PHILADELPHIA — Scientists at Merck Research Laboratories have found that automating cell cultures can improve the quality and consistency of cell supply, a company official said at a pharmaceutical conference held here this week.
In addition, the absolute reproducibility afforded by automated cell culture protocols can improve the development and robustness of an assay, and analyzing quality control parameters captured by the automated cell culture system can enhance troubleshooting, according to the scientist.
Alison Rush, a senior research associate in the department of automated biotechnology at Merck Research Laboratories in North Wales, Pa., added that automating the cell culture process reduces the number of variables in cell handling, increases the number of cell lines in continuous culture, centralizes cell culture as a core activity, facilitates the transfer of cell lines and assays, and allows researchers to avoid repetitive motion injuries.
Automated cell-culture solutions used in her Merck lab include The Automation Partnership’s SelecT automated plating system and Essen Instrument’s Incucyte automated imaging platform, said Rush, who presented her findings at the Seventh Annual World Pharmaceutical Congress, held here this week. She also said that “automated cell culture releases skilled scientists [to perform] more technically demanding and rewarding activities.”
Appropriate applications for automated cell culture include maintaining multiple cell lines in culture, producing antibodies and hybridomas, and preparing membranes, she said.
Rush also said that researchers that stand to benefit the most from an automated cell culture protocol include core cell-culture facilities, drug metabolism and pharmacokinetics groups, lead optimization groups, and high-throughput screening groups.
“Automated cell culture releases skilled scientists for more technically demanding and rewarding activities.”
Workflows that are amenable to automation are assays that involve 10 million to 100 million cells per assay, and those that use 10 to 30 microplates, said Rush. Automation can also be used to simultaneously culture six to eight divergent cell lines or 10 to 20 similar cell lines. Also, automated cell culture is appropriate for assay quality control and when reproducibility is important.
Not all processes and workflows are appropriate for automated cell-culture systems, however, said Rush. Media lines, process time, resuspension capabilities, and flask formats are all limiting factors in the use of automated cell culture.
Rush said that complex assay protocols and the use of “difficult” cell types such as clumping cells, or loosely adherent cells, also limit the use of automation.
Manual cell culture, on the other hand, is appropriate for high-volume screens involving several billion cells per day, Rush said, and in circumstances of high complexity, “such as when assay development is still ongoing.”
Laboratories and institutions considering automation for all or part of their cell-culture activities should bear several considerations in mind, such as cost and space requirements, said Rush. Some systems cost as much as $500,000, while some systems require a lot of space and access on three sides. In addition, users must have technical support from the manufacturer, and should maintain a back-up system, she said.
Rush also pointed out that, “You have to convince potential users that they want this system.” To earn the trust of cell-culture biologists, Rush said that it is essential to test side-by-side cells cultures that are produced manually and with the help of an automated system. She said that common protestations by cell culture biologists are, “’Only I can grow this cell line,” or “’My cell line is very difficult/picky/sensitive.’”
When training scientists how to use automated cell-supply systems, Rush said that strong cell-culture skills are essential and that the researchers should be comfortable with automation.
In addition, automating the cell supply will ensure consistency in the cell culture process, and facilitate reproducibility of results. Automation will increase productivity by running on nights and weekends.
However, it is not as fast or as flexible as manual production because it can maintain only a limited volume of cells and a limited number of cell lines at a time.