Cell Line Development
Reducing timelines in generating clonal cell lines for therapeutic protein production.
Introduction
In order to produce high yields of recombinant proteins for therapeutic applications, stable producer cell lines need to be developed. Mammalian host cell lines, such as CHO or HEK 293, are typically the system of choice because of the importance of consistent post-translational modifications.

Proof of clonality
Clear and traceable evidence of single-cell deposition

SINGLE-CELL CLONING AND PROOF OF CLONALITY
Following transfection, single cells need to be isolated from transfected pools. Traditionally, this crucial step has been performed by limiting dilution. Based on early regulatory guidelines released by the U.S. Food and Drug Administration (FDA) and others, the production cell line of recombinant products is to be cloned from a single progenitor cell in order to minimize population heterogeneity and facilitate isolation and subsequent selection of high producing clones.

Our solution
To ensure that cell lines are clonally derived, multiple rounds of limiting dilutions are required, a time- and labor-intensive process. Our single-cell printer™ dispensing technology allows for deterministic single-cell isolation, offers documented image-based proof of clonality, and provides efficient and fast single-cell seeding combined with excellent cell viability and zero risk of cross-contamination.
Featured workflow
Our extensive product portfolio offers a range of innovative technologies and instruments for significantly increasing the speed, quality and efficiency of your cell line development workflows.

1. Transfection

6. Selection of high producer clones
Early suspension culture
After single-cell cloning, cells are typically cultured under static conditions for several weeks before well-growing clones are transferred to shaken deep well or 24-well plates. After additional cultivation, selected clones are then transferred to larger volumes and finally to shake flasks or mini bioreactors. Hence, during the first weeks after cloning, cells are cultured under static conditions, which do not match the culture environment the cells experience in later stages of the process and during production. Our innovative microbioreactor platform, the c.bird™, was developed to enable suspension culture early in the cell line development process.

Related application notes
Streamlined Workflow for the Generation of CRISPR-edited Mesenchymal Stem Cell Clones for Regenerative Medicine Applications
f.sight – Fluorescence intensity-based isolation of single cells with assured clonality for CLD workflows
Downloadc.bird – A microbioreactor that enables suspension culture in 96-well plates for improved cell growth and recombinant protein yield
Providing Optimal Suspension Culture Conditions in 96-well Plates and Superior Comparability with Large-scale Shaker-flask Culture Environments
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c.sight™
Isolate single cells in 96- & 384-well plates Bright field nozzle imaging with 10x magnification. Cell line development and single-cell genomics.

f.sight™
Isolate green fluorescent eukaryotic cells in well plates. Bright field and fluorescence imaging. Fully tunable to enable even low intensity samples.

CASY
Comprehensive cell status monitoring.

SOLARIS bioreactors
Flexible and scalable platforms for R&D and product development applications.