Cell Line Development
Cell line development is the process by which the cellular machinery is co-opted to manufacture therapeutic biologics or other proteins of interest. You can use different expression systems for cell line development: bacterial, plant-based, yeast, mammalian. Most commonly used for the production of the complex protein is Chinese hamster ovary (CHO), cells grown in suspension cultures for eventual use in bioreactors at the manufacturing stage.
The development of these cell lines is a long and arduous process with numerous steps and challenges (Figure 1). Once CHO cells have been transfected with the construct of interest a selection step is required to enrich for those cells that have taken up the construct. Single cells must then be isolated, grown into colonies, and assayed for protein production. Once this production screen has been accomplished, the top candidates are expanded and maintained to test for expression stability. Eventually the top hits are further optimized in different media conditions to enhance expression or other protein attributes (e.g. glycosylation) before scaling up to production levels. Because this process takes months to complete, there are many more challenges than a typical short-term cellular workflow. First, maintaining sterility is essential during various manipulations and throughout the weeks of growth from a single cell. Secondly, as with most screens, the throughput required to identify a handful of optimal clones typically requires thousands of wells. This throughput then tapers off after the hit picking phase, so one should schedule overlapping campaigns to maximize resources. Finally, as clones move through the system and are reformatted into lower density plates during hit picking, all previously recorded data must be tracked as these cell lines are established. We have overcome these challenges by automating the establishment and screening of clones for cell line development.
Products for Cell Line Development
Automate every step of the complex Cell Line Development workflow - from transfection to enrichment to limiting dilution to culture/feeding to assaying to hit-picking and expansion.
Provides an automated, high throughput single cell depositing system. This process is mandatory for master cell bank generation.
- Monochronality verification system (Isolate single cells and expand)
- Validate single cell per well
Used at multiple steps along cell line development. Eliminate human error and user bias when counting cells and determining viability.
- Cell count is critical to determine cell expansion and passaging
- Cell viability- kiow how many cells are live and how many are dead
Separate cells from culture media for antibody titer assays, quantification.
- Separate cells from media for antibody titer
- Pellet cells for media exchanges
- Use of Cells in Therapeutics Product Development
- Early Discovery Target ID
- Hit Generation and Selection
- Lead Optimization
Quality Control for GMP Manufacturing
- Classification and Routine Environmental Monitoring for GMP Cleanrooms
- Active Pharmaceutical Ingredient (API)/ Excipients Powder Granule Sizing
- Bioprocessing Cell Culture
- Clean in Place CIP Processes
- Environmental Monitoring
- Final Product Quality Testing
- Small Molecule Insulin Formulation
- Viral Vector Characterization
- Water Release Testing for GMP Manufacturing
- Echo Liquid Handling for ADME-Tox
Biologics Product Applications
- High-Throughput Screen (HTS)
- Liquid Handling for Gene Expression
- Liquid Handling for Genotyping
- Liquid Handling for Microbial Research
- Acoustic Liquid Handling for Protein Crystallography
- PCR, qPCR, and RT-qPCR
- Next generation Sequencing Library Preparation
- Liquid Handling for Single-Cell Genomics
- Echo Liquid Handling for Synthetic Biology
- Enabling COVID-19 Research
- Echo Liquid Handling for Microsampling
- Small Molecule Product Applications