Benefits of Automated Cell Culture Monitoring

Successfully growing cells in culture—especially precious, rare, or difficult cell types—is both an art and a science. But the benefits of automated cell culture monitoring are clear and numerous. It saves researchers hands-on lab time that is usually mind-numbingly repetitive, freeing them for more advanced and creative work. This results in happier researchers, and reduces the risks of human error and contamination. Automation offers better documentation of cultures, and optimal conditions that yield more consistent data. Overall, these benefits can cut costs by preventing the loss of important cell cultures, or the need to repeat experiments. This article discusses the benefits of automated cell culture monitoring, with examples of different systems available today.

Built-in monitoring functions

Automated monitoring systems can vary in the number and type of variables measured. Many platforms incorporate built-in cell culture monitoring functions. For example, ImageXpress^® High-Content Imaging Systems from Molecular Devices can monitor and control environmental factors such as humidity, O₂, and CO₂ levels throughout multi-day imaging experiments. In addition, their Organoid Innovation Center offers expertise to researchers interested in automating their 3D cell culture workflow, using label-free imaging to monitor the development of 3D models over time. Cell culture maintenance, and the addition of treatment compounds to media, are handled by precision robots with automated liquid handling.

Molecular Devices is investing time and resources into setting up automation for 3D cell cultures. Organoids can take weeks to culture, so to save time, Angeline Lim, Senior Applications Scientist at Molecular Devices, and her team use colorectal cancer organoids from Cellesce, which they mix with Matrigel and grow with automated cell culture monitoring. They aim to help researchers use organoids as model systems in drug discovery. “It's still pretty small to medium throughput in most places, so we're hoping to address some of these bottlenecks so labs can scale faster,” she says. “Right now, we’re trying to automate the process of expanding organoids, which is a very tedious process involving a lot of repetitive pipetting to break up the organoids.”

In general, researchers can be hesitant to trust automated systems to monitor these precious cells—understandably—because errors can be costly. However, any errors in the system also arise from humans, so proper set-up can ensure success. “Most people don’t have the time for testing to figure out the right automation for a 3D culture,” says Lim. “My team and I do the cell culture and figure out the best way to automate the process so that other scientists can spend more time in the actual drug discovery.”

Monitoring by LC/MS

Some systems monitor O₂ and CO₂ levels, temperature, and pH, while others measure many more parameters. Thus, it’s important to think about what your particular cell cultures and experiments require. For example, monitoring components of cell media can reveal important indicators of the cells’ metabolic states. “Simultaneous analysis of medium substrate (i.e., amino acids, nucleic acids, metabolites, vitamins, and sugars) that provides essential nutrients to the cells is vital in ensuring product quality,” says Evelyn Wang, Application Scientist Team Leader at Shimadzu Scientific Instruments.

Shimadzu offers the C2MAP™ System to automate cell culture monitoring, displaying graphs of changes in various components over time. It is also integrated with Shimadzu’s liquid chromatography mass spectrometer (LC/MS) for automatic sampling and comprehensive media composition analysis. “The system can be used for the optimization of culture conditions by monitoring the consumption and depletion of media components during culturing, as well as the variation in metabolites secreted from cells,” says Wang. In addition, Shimadzu offers a cell culture profiling method package for analyzing 144 compounds from culture media simultaneously in less than 20 minutes using an LC/MS.

Wang suggests that reports generated from automated monitoring use a graphical format to make it easy and quick for researchers to take in the information. “In addition to the traditional bar graphs or scatter plots, statistical results such as volcano plots, principal component analysis, and hierarchical clustering are preferred,” she says. “The scientists should be able to use the data to monitor the progress of cell growth, and intervene if modification is necessary to increase the cells’ quality and quantity in real-time.”

Monitoring with imaging

Some systems use imaging to monitor and document cells. Avi Smith, Associate Product Manager at Evident Scientific, sees an automated cell culture monitoring system as akin to a lab assistant, albeit one who can improve the consistency and reproducibility of repetitive tasks. Evident Scientific’s Olympus Provi CM20 Incubation Monitoring System uses epi-oblique illumination, which situates the illumination and imaging optics beneath the specimen and allows researchers to use their own culture vessels. The CM20’s epi-oblique illumination uses a red LED to minimize phototoxicity, and its compact, flat design means the device can be completely sealed, and is easy to sanitize or sterilize.

Researchers have expressed to Smith the value of having access to more data. “Culture monitors are able to collect more data than may be realistic for a person—for example, in scratch assays, where it’s important to image at the right time to see variability between conditions,” says Smith. “With culture monitoring, images can be taken automatically on a consistent basis, including overnight and on weekends, so there is less risk of missing cells at a critical moment.”

Culture monitoring can also help researchers to pinpoint problems that might otherwise remain unsolved. “We had a researcher using our CM20 monitoring system with precious primary neural cells, who noticed a slightly reduced proliferation rate in one of her cultures,” says Smith. The lab figured out the problem was in the culture vessel matrix, and made appropriate changes. “Had they not identified this problem during early stages of culture, they could have wasted thousands of dollars on media and reagents, as well as lost some of their stock of rare cells,” he says.

Culture monitoring also offers predictive power. For example, CM20 monitoring data was used to correlate the proliferation rates of iPS cells with their likelihood of differentiation to liver organoids. “Using this information, the lab can now use the CM20 to predict whether their iPS cells will differentiate, according to their specifications earlier in the process,” he adds.

Lim emphasizes that human thinking and brainpower are things that cannot be automated. “Postdocs are very well trained—instead of carrying out mundane tasks like media changes, they can think more about the resulting data and plan the next steps in the research,” she says. “That’s why we should have scientists do the thinking, and a robot for the tedious routine work like manual pipetting.” She cites burnout (including weekend lab sessions to change cell culture media) as a significant factor in academic attrition. With automated cell culture monitoring, going into the lab on weekends to change culture media is no longer necessary. “Assuming that the system is set up correctly with no technical issues, researchers can actually have a better work-life balance,” adds Lim.