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. 

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.

transfection ny2

1. Transfection

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2. Cell counting

upsight in workflow

3. Single-cell cloning and double assurance of clonality

C.BIRD casy workflow

4. Early suspension culture & upscaling

bioreactor casy workflow

5. Bioreactor 0.2-20 l

icon_real time PCR - Pooling library

6. Selection of high producer clones

transfection ny2

Transfection

CASY-frilagd-shadow

Cell counting

upsight in workflow

Single-cell cloning and double assurance of clonality

C.BIRD casy workflow

Early suspension culture & upscaling

bioreactor casy workflow

Bioreactor 0.2-20 l

icon_real time PCR - Pooling library

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

Combined Single-cell Dispensing and 3D Full Well Imaging for Cell Lines with >99.99% Probability of Monoclonality (English)

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

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Download Application Note

Providing Optimal Suspension Culture Conditions in 96-well Plates and Superior Comparability with Large-scale Shaker-flask Culture Environments

Related publication

Related products

UP.SIGHT

Enables nozzle imaging and 3D Full Well Imaging for double assurance of clonality from two independent optical apparatuses, leading to a probability of clonality >99.99%.

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.

C.SIGHT™

Isolate single cells in 96- & 384-well plates Bright field nozzle imaging with 10x magnification. Cell line development and single-cell genomics.

C.BIRD™

Next generation microbioreactor for cell line development.

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