Cell Line Development

Cell surface expression screening

Many proteins that express to the surface of cells are targets for the discovery and development of biopharmaceuticals. For instance, G-protein coupled receptors (GPCRs) are the largest class of cell-surface proteins and are targets for almost 40% of existing drugs. Discovery and selection of high value clones with elevated cell surface expression of GPCRs from a transfected pool of cells can be challenging. The ClonePix 2 System represents an automated method of screening large populations of cells that increases the probability of finding rare high-affinity binder or high producer.

• Rapid automated selection of mammalian cell colonies by cell surface protein expression
• Rapid selection and development of GPCR expressing mammalian cell lines using novel ClonePix Technology
• Rapid and efficient selection of high producing mammalian cells secreting non-mAb proteins

Cell viability

Cell line development requires the discovery of single cell-derived clones that produce high and consistent levels of the target therapeutic protein. A critical first step in the process is the isolation of single, viable cells. Single cells proliferate to form colonies that can then be assessed for productivity of the target therapeutic protein. Viability and growth rates of single cell-derived clones can be characterized on the CloneSelect Imager and the SpectraMax i3x microplate reader and imaging cytometer.

• Confluence and growth curve generation on the CloneSelect Imager
• Measuring cell viability and cytotoxicity with the EarlyTox Cell Integrity Kit
• Luminescent cell viability and cytotoxicity assays
• Brochure: SpectraMax i3x

Clone productivity screening and titer

An important component in identifying high-value clones is determining productivity of single cell-derived colonies. Screening for productivity using traditional approaches is laborious and time consuming, generally consisting of a multistep process that involves isolating single cells from limiting dilution followed by assessment of titer using ELISA. The ClonePix 2 system combines phenotype selection, single-cell isolation and productivity screening into a single step, resulting in dramatically shorter screening times and increased number of candidates.

• Rapid Screening and Selection of Stable High Producing Clones
• Automated optimization of IgG production in CHO Cells
• Enhanced development of virus-specific hybridomas

Comparison of traditional cloning methods vs. f.sight

As regulations for cell line development become increasingly more stringent, researchers will be required to perform single-cell cloning and provide evidence that a cell line is derived from a single cell (proof of clonality). In this study, we conducted six sets of experiments to demonstrate a combined f.sight and CSI workflow with high monoclonality assurance in a single round of cloning. We also compared the cloning eciency of two suspension CHO cell lines on a CloneSelect f.sight single cell printer versus two other accepted traditional cloning methods, flow cytometry and limiting dilution.

• Comparison of traditional cloning methods vs. CloneSelect Single-Cell Printer f.sight using CHO cell lines commonly used for monoclonal antibody production

COVID-19 and Infectious Disease Research

Here we've addressed common applications in infectious disease research including cell line development, binding affinity, viral neutralization, viral titer and more with a focused effort on understanding the SARS-CoV-2 virus in order to develop potential therapies for COVID-19 including vaccines, therapeutics and diagnostics.

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Monoclonality

Cell line development and assurance of monoclonality are critical steps in the process of generating biopharmaceutical molecules, such as monoclonal antibodies. A cell line can be established following the isolation of a single viable cell robustly expressing the protein of interest. A key milestone in this process is documenting evidence of clonality. Documentation of clonality is typically image-based, whereby an image of a single cell is produced and included in regulatory filings.

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Single cell sorting

Cell line development requires the discovery of single cell-derived clones that produce high and consistent levels of the target therapeutic protein. The first step in the process is the isolation of single, viable cells. Limiting dilution is a technique that relies on statistical probability but is time consuming. The CloneSelect Single-Cell Printer enables the gentle isolation of cells in a manner that maximizes cell viability, as well as providing direct evidence of clonality via a series of five images captured as cells dispense.

• A microfluidics-based, single cell printing and microplate imaging workflow optimized for efficiency, viability and monoclonality report generation
• A workflow combining single-cell isolation and microplate imaging improves cloning efficiency with higher assurance of clonality
• Data Sheet: CloneSelect Single-Cell Printer