Advances in cell line engineering and microfluidic technologies offer substantial opportunities to shorten timelines in cell line development (CLD). However, as with any innovation, optimizing these processes can bring about new challenges and uncertainties that need to be addressed.
This article will explore some of these critical challenges and provides actionable solutions to help enhance your productivity and streamline your workflows.
Key challenges in cell line development
Cell line development faces numerous challenges, including:
- Selection Bias in the Cell Line: Selection bias can arise when clones are chosen based on specific traits like stability or antibody secretion levels, potentially leading to a subset that has not been thoroughly evaluated. Learn strategies to avoid this pitfall by selecting cells based on their future potential.
- Unpredictable Gene Expression: Even with optimization, bottlenecks during gene expression can affect protein yields. Explore techniques such as site-specific integration and refined expression vector design to address these challenges and enhance protein production.
- Issues with Automated Cloning Techniques: While automation can improve efficiency, it may also introduce variability in cell viability and growth. Discover how advanced technologies like Cyto-Mine® can improve cell viability and accelerate cell line development.
- Varying Cell Growth Rates: High-producing cells often exhibit slower growth rates due to higher metabolic demands. Understand how optimizing cell culture media and employing automated bioreactors can support better cell growth and overall productivity.
Addressing selection bias in cell line development
During cell line development, it is essential to avoid selection bias to ensure that clones are chosen based on their long-term stability and productivity. Focusing solely on initial high productivity can be misleading, as it does not always predict future performance.
To mitigate this risk, select a range of high- and medium-producing clones for further evaluation. This approach allows you to account for variations in product quality, stability, and growth. Monitoring these clones throughout their expansion phase helps identify those with the best characteristics for commercial success.
Enhancing gene expression
Optimizing gene expression is crucial for maximizing protein yields in CLD. Techniques like site-specific integration and meticulous expression vector design play a significant role in improving the reliability of gene expression.
Site-specific integration methods, such as CRISPR/Cas9, facilitate precise gene insertion, which helps reduce clonal variation and boost productivity. Additionally, designing expression vectors with strong selection markers and synthetic promoters can enhance both the control and efficiency of gene expression.
Automating cloning techniques
While automation in CLD can be highly beneficial, it does pose some challenges such as reduced cell viability post-sorting. However, the Cyto-Mine® platform offers a solution with its gentle, high-throughput cell processing capabilities.
By encapsulating cells in picodroplets, Cyto-Mine® enables rapid and gentle cell sorting while preserving high cell viability. This advanced technology streamlines the CLD process by integrating multiple steps into a cohesive workflow, effectively reducing timelines and minimizing manual handling.
Optimizing cell growth rates
Supporting the growth of single progenitor cells requires optimized culture conditions. Tailoring media formulations to specific cell lines, including components like plant-based hydrolysates, can significantly improve single-cell survival and colony outgrowth.
Automated bioreactor systems, such as the AMBR® 250, offer precise control over environmental parameters, facilitating better scalability and productivity screening of clones. These advancements help maintain high-producing clones and enhance overall efficiency in the CLD process.
Conclusion
By tackling these challenges with cutting-edge solutions and technologies, you can greatly improve your cell line development process. Sphere Fluidics’ Cyto-Mine® platform, along with its comprehensive article, offers the tools and insights necessary to optimize your workflows and consistently achieve high-quality results.
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About Sphere Fluidics
Our vision
Our philosophy is simple. We combine our knowledge and resources to help you find rare and valuable biological variants, while helping you to save time, reduce costs and stay a step ahead of the competition.
Our novel single cell analysis systems offer the rapid screening and characterization of single cells. These systems are underpinned by our patented picodroplet technology, specifically designed to increase your chances of finding that rare ‘one-in-a-billion’ molecule or cell that could be an industry blockbuster.
We understand that time is of the essence. That’s why our technologies boost throughput and assay sensitivity across a range of applications. Most importantly, our flexible systems evolve alongside your changing research needs, providing an adaptable platform that helps you to meet your goals.
Our history
Founded in 2010, Sphere Fluidics is an established Life Sciences company, originally spun out from the University of Cambridge. We initially developed 25 patented products – biochips and specialist chemicals – which currently assist hundreds of customers globally with their research.
We initially focused on producing novel biochip systems and providing R&D services. We have since extended our expertise and are developing a technology platform that enables discovery in a range of growing markets through single cell analysis. Our systems make the development of new biopharmaceuticals faster and more cost-effective, improve monoclonal antibody screening, cell line development, and overall research efficiency in a number of other applications including synthetic biology, single cell diagnostics, prognostics and single cell genome editing.
The Cyto-Mine® Single Cell Analysis System is our flagship product – the first integrated, benchtop system to automatically analyse, sort and dispense millions of individual cells in just a single day.
Our partnerships
We value and are always open to discussing new collaborative, successful and innovative academic and industry partnerships to further develop and improve our single cell technologies.
Our Technology Access Programmes and Collaborative Services exist to enable academic researchers and companies alike to tap into our application-specific expertise through direct partnerships.
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