Cell culturing is integral to diverse research fields including cell therapy, gene therapy, diagnostics, and vaccine development, among others. In addition to the known challenges associated with the technique—controlling contamination sources, improving consistency, and minimizing costs—modern laboratories face increasing output demands, and pressure to maximize yields. Careful consideration when establishing or updating cell culture spaces and protocol scan help to overcome these challenges and ensure efficiency. Planning for growth and change will also save time and money into the future.
CHALLENGES OF SCALING UP WHILE TRIMMING DOWN
Adherent cell culturing is a space intensive task, running the risk of scores of traditional flasks sprawling across lab benches or filling incubators to reach required surface areas. As output needs increase, consistent and timely culture maintenance quickly become a major concern. Laboratory staff must ensure appropriate gas exchange and minimize disruption when adding and removing cell culture fluids. The process is amenable to automation, however proper design and scalability for clinical settings or other large research applications must be considered. An effective approach is to focus on maximizing cell growth capacity and productivity in a small space. Stacked culture vessels are increasing in popularity as an opportunity to dramatically reduce both handling time and spatial footprint, freeing valuable lab resources for increasing scope or other applications.
WHAT TO CONSIDER WHEN PLANNING CELL CULTURE SPACE AND PROTOCOLS
• Determine the current requirements for yield and consider how these may change over time as needs or applications evolve. Planning for future needs can support a more efficient transition and reduce total costs.
• A good understanding of workflows will also improve efficiency. As part of this process, consider how much incubator and bench space is available to support current and future workflows.
• Calculate growth substrate requirements and the associated costs for current and future applications. For example, coated or uncoated flasks, specialized growth substrates, etc.
• While it is important to ensure the laboratory is equipped with the necessary supplies, reagents, and instruments, human resources are essential. Consider how many hours will be devoted to cell culture tasks, how many individuals have the necessary skills and training, and whether additional training or retraining may be required.
• Determine what support will be required for manual or automated workflows, as well as resources and support for technical considerations while adapting protocols and workflows.
Novel technologies have been developed with these considerations in mind to form adaptable, customizable solutions suited to your laboratory. For example, the Corning® HYPERFlask® cell culture vessels are designed to maximize growth capacity with a minimal footprint. They offer 1,720 cm2 growth area in the footprint of a traditional 175 cm2 flask. These high-yielding performance flasks use a multi-layered gas permeable growing surface for efficient gas exchange. The following case studies examine how Corning High Yield PERformance (HYPER) technology can improve yield and facilitate easier scale-up.
INCREASING EFFICIENCY AND PRODUCTIVITY
When biologists from the Cer Groupe immunobiology laboratory in Belgium wanted to improve viral production yields for use in diagnostic kits, they ran a performance comparison for stacked (multi-layer) culture vessels. The diagnostic kits created by the team test for the presence of bovine Parainfluenza 3 virus (PI3V) and require the production of reproducible, large-quantity batches of PI3V.
In the culture vessel comparison, the researchers used a “traditional” large-capacity (6,320 cm2 surface area) 10-layer vessel and Corning HYPER technology allowing for a more compact (1,720 cm2) 10-layer vessel. The latter product stood out in both performance and ease of use.
Viral production numbers with the Corning HYPER technology were on par with traditional cell culture vessels, while using just one-third of the seed culture and spatial footprint. The Corning HYPERFlask vessel also produced twice as much virus per cm2 in surface area. The researchers concluded that this technology allowed for higher productivity with lower space requirements ,allowing them to accommodate more viral culture within the incubator.
Technicians found the smaller flask easier to handle, maintain, exchange fluids, and work with inside the fume hood, reducing both technician time and contamination risk. Overall, the researchers determined that the Corning HYPERFlask cell culture vessel simplified their production of the required reagents for viral diagnostic kits with an economic solution.
IMPROVING TRANSITIONS BETWEEN CLINICAL TRIAL PHASES
Ottawa Hospital Research Institute (OHRI) also found solutions to manageability, consistency, and scaling considerations. The OHRI conducts world-class research programs in cancer therapeutics, chronic disease, clinical epidemiology, neuroscience and regenerative medicine. They prioritize practice changing research and regenerative and biological therapeutics, leading the way in new and innovative patient treatment and care. Being able to transition smoothly from researching and developing new therapies in house to large-scale production for clinical trials is a key consideration in protocol development.
One such project at the OHRI has been the application of stem cell therapy to treating septic shock. They ran clinical trials to determine the safety and efficacy of allogeneic bone marrow-derived mesenchymal stem cells (MSCs) in treating septic shock, a common illness with 20-40 percent mortality rate.
In phase I of the clinical trial, researchers manufactured single doses for new patients as needed in order to determine safety and tolerability. This required researchers to produce a full dose within a six-hour window from notification. To achieve this short response time, the researchers reduced handling time while maximizing yields by adopting the Corning® HYPERFlask® cell culture vessel. By adapting their protocols at this early stage, they were able to effortlessly scale up into higher production in phase II clinical trials using the same technology, with no change to workspaces.
Sherwin Zhu, scientific support specialist with Corning Life Sciences, works with research labs that are facing tech transitions. He notes that the most common consideration for labs considering new technology is hesitancy to change their protocols, due to the time and effort required for revising standard operating procedures. However once labs commit, he sees enormous customer satisfaction with the convenience of streamlined protocols and improved productivity from increased cell adhesion, potency, and viability.
Zhu notes that, ultimately, timing drives tech decisions, “technology sometimes needs to wait for its time.” In one memorable example, a cell bank business was reluctant to change their tech and protocols while they had adequate manpower and space. As the business grew, they rapidly outgrew their methods and space and enlisted Sherwin’s help. In addition to improved manageability of cultures with Corning HYPER technology, they saw boosted cell viability post cryopreservation.
The benefits, in addition to space and time savings, are immediate, according to Zhu. Technicians are easily trained on the tech and protocols, and the improved handling and smaller volume of compact stacked vessels decrease the probability of operational mistakes and reduce the cost of troubleshooting.
Current cell culture applications require increasing yields of reproducible batches, making efficient culture technology more relevant and necessary for modern research labs across diverse fields.
AN EFFICIENT, CUSTOMIZABLE SOLUTION
Minimizing handling time, processing time, and incubator space is a priority for most researchers working with adherent cell cultures. Selecting appropriate high-yield, space-efficient culture vessels can reduce bot effort and space requirements.
Corning HYPER technology incorporates treated gas-permeable growth substrate film to boost productivity and adhesion in a small area, offering 1,720 cm2 of growth area in their Corning HYPERFlask cell culture vessel, the equivalent of 10 traditional culture flasks with the footprint of a single traditional 175 cm2 flask.
Corning HYPER technology offers a highly efficient, customizable solution allowing for automation and scalability.