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.

Cell Line Development Process

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

Optima Ultracentrifuges

Optima ultracentrifugation
Biomek iSeries Automated Liquid Handlers

Biomek i-Series

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.

Echo 525

Echo 525 call-outs

Access Solutions Systems

Discover a comprehensive suite of high-throughput automation platforms that are easily integrated to meet each critical step of your cell line development workflow.
Avanti JXN 26

Avanti JXN Series

High performance centrifugation for cell culture harvest and purification optimization
MoFlo Astrios EQ

MoFlo Astrios

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
Vi-CELL MetaFLEX

Vi-CELL MetaFLEX

Vi-CELL MetaFLEX for bioreactor media analysis

Vi-CELL BLU

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

Avanti J-15R

Separate cells from culture media for antibody titer assays, quantification. Pellet cells for media exchanges.

SRT

CytoFLEX SRT

CytoFLEX SRT

Helpful Links

Content and Resources

Choosing the Right Instrument for Cell Counting and Particle Characterization
Cell Line Development Automating the cell line development workflow increases throughput and optimizes media conditions which are critical for cell lines needed for vaccines, antibody production, recombinant therapies and drug screening
Vi-CELL® XR Cell Type Tutorial Introduce users to the Cell Type Feature in the Vi-CELL XR software
Automated Solutions for Cell Line Development Your Guide to Workflow Intelligence
Automating Cell Line Development for Biologics Cell line development is a highly-involved, multi-week workflow that involves the plating, screening, and expansion of single cell-derived clones to establish a protein-expression cell line