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Cell line development solutions with automated clone screening

The ClonePix® 2 Mammalian Colony Picker is a fully automated system for the selection of high-value clones used in antibody discovery and cell line development. Hybridoma, CHO cells, and other cell types are imaged and selected based on user-defined parameters. Plate handling, barcode reading, and picking are all fully integrated. All data, including images, are saved for downstream analysis. The picker increases the probability of finding optimally produced cell lines and significantly reduces time and labor.

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    Screen more clones in less time

    ClonePix 2 picker is 10x faster than labor-intensive limiting dilution and FACS. Our sophisticated software and integrated robotics enables a picking speed of > 10,000 clones per day.

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    Select cells with desirable attributes

    Easily screen and select clones based on protein productivity, antigen-specificity, cell viability, and expression levels of tagged recombinant proteins.

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    Pick colonies with accuracy

    Picking accuracy < 1 mm. Robotic picking reduces risk of colony disturbance. Images of picked clones are stored with data.

ClonePix 2 System

ClonePix 2

Features

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    Multiple detection methods

    White light identifies and measures clone morphology, size and proximity. Fluorescence indicates expression level and/or specificity. Up to five fluorescent filters are available for multiplexing.

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    Sterility maintenance

    A host of sterility features and options including a UV light process for sanitizing the interior of the instrument, as well as pin washing and halogen drying are standard.

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    Integrated plate storage

    Includes two storage stacks for source and destination plates, each with a capacity of 10 plates.

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    Discrete colony formation

    Semi-solid CloneMediaTM encourages single cells to grow into discreet colonies, and allows for ease of plating. The media allows for a higher density of clones to be screened.

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    Animal-free media and reagents

    Chemically defined and animal-free, CloneMedia cell-culture media, is optimized to increase productivity and aid in visualizing secreted antibodies when used with the CloneDetectTM detection agent.

  • Automation Icon

    Custom automation options*

    The Advanced Workflow Engineering Solutions Team can customize the monoclonality system and offer added services such as integrated verification of monoclonality.

*Price, time to deliver, and specifications will vary based on mutually agreed technical requirements. Solution requirements may cause adjustment to standard performance.
 

Applications of ClonePix 2 Mammalian Colony Picker

  • Cell Line Development

    Cell Line Development for Recombinant Proteins

    Cell line development is a critical step in the process of generating biopharmaceutical molecules, such as monoclonal antibodies. The process often begins with transfecting the host cell type with the DNA encoding the therapeutic protein of interest allowing for random or directed integration of target DNA into the host cell genome. Thousands of clones are screened to isolate the rare high producing cells, a manual and time-consuming process.

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    Cell surface expression screening

    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.

  • Clone productivity screening and titer

    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.

    Hybridoma Screening

    Hybridoma Screening

    Antibody discovery typically refers to the screening and identification of monoclonal antibodies (mAbs) that target a specific epitope for the diagnosis and treatment of diseases. A common approach to generating monoclonal antibodies involves the fusion of a pre-mitotic cancer cell with a post-mitotic and terminal antibody-expressing B-cell from the spleen. The resulting fused cell is called a hybridoma and has the advantage of producing mAbs while dividing to regenerate itself. Screening hybridomas for binding specificity or productivity can be automated using the ClonePix 2 System.

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  • Monoclonal Antibody Discovery

    Antigen-Specific Screening

    Antibody discovery typically refers to the screening and identification of specific antibodies that target an antigen molecule for the diagnosis and treatment of diseases. The specificity of the antibody is based on its ability to bind the epitope, a unique region on the antigen molecule. Therapeutic antibodies are typically monoclonal, single cell-derived and target a unique epitope region on the antigen. The ClonePix 2 System automates screening and rapid detection of antigen-specific clones from a heterogenous population of cells.

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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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Specifications & Options of ClonePix 2 Mammalian Colony Picker

Resources of ClonePix 2 Mammalian Colony Picker

Presentations
Videos & Webinars
Stable Cell Line Development Generation

Stable Cell Line Development Workflow

Hybridoma Workflow

Hybridoma Workflow

mammalian cells secreting non-mAb proteins workflow

Selection of high producing mammalian cells secreting non-mAb proteins workflow - SynBioBeta Lightning Talk

Rapid identification of Neutralizing Antibodies

Optimized workflow for rapid identification of neutralizing antibodies against viral particles

Selection GPCR Cell Line

Identification and Selection of GPCR Cell Lines with ClonePix 2

ClonePix 2 System

ClonePix 2

  • Citation
    Dated: Dec 01, 2017
    Publication Name: Journal of Immunological Methods

    Sequential screening by ClonePix FL and intracellular staining facilitate isolation of high producer cell lines for monoclonal antibody manufacturing

    Screening and characterization of cell lines for stable production are critical tasks in identifying suitable recombinant cell lines for the manufacture of protein therapeutics. To aid this essential function we have developed a methodology for the selection of antibody expressing cells using fluorescence based ClonePix FL colony isolation and… View more

    Screening and characterization of cell lines for stable production are critical tasks in identifying suitable recombinant cell lines for the manufacture of protein therapeutics. To aid this essential function we have developed a methodology for the selection of antibody expressing cells using fluorescence based ClonePix FL colony isolation and flow cytometry analysis following intracellular staining for immunoglobulin G (IgG). Our data show that characterization of cells by flow cytometry early in the clone selection process enables the identification of cell lines with the potential for high productivity and helps to eliminate unstable cell lines. We further demonstrate a correlation between specific productivity (qP) and intracellular heavy chain (HC) content with final productivity. The unique combination of screening using ClonePix FL and the flow cytometry approaches facilitated more efficient isolation of clonal cell lines with high productivity within a 15 week timeline and which can be applied across NS0 and CHO host platforms. Furthermore, in this study we describe the critical parameters for the ClonePix FL colony based selection and the associated calculations to provide an assessment of the probability of monoclonality of the resulting cell lines.

    Contributors: Gargi Roya, Guillermo Miro-Quesadab, Li Zhuanga, Tom Martina, Jie Zhub, Herren Wua, Marcello Marellia, Michael A.Bowena  
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  • Citation
    Dated: Dec 14, 2015
    Publication Name: 24th European Society for Animal Cell Technology (ESACT) Meeting: C2P2: Cells, Culture, Patients, Products

    CHO-DHFR cell line development platform: Application of Clonepix and Automated Mini Bioreactor (AMBR) technologies to meet accelerated timelines

    The Holy Grail sought by all Bioprocess Cell Line Development (CLD) groups is achieving high yields from easily-cultured, robustly-growing cells in timelines measured in weeks rather than months. As the first bottleneck in process development, CLD must first birth its product for upstream and downstream groups to initiate their own reproductive… View more

    The Holy Grail sought by all Bioprocess Cell Line Development (CLD) groups is achieving high yields from easily-cultured, robustly-growing cells in timelines measured in weeks rather than months. As the first bottleneck in process development, CLD must first birth its product for upstream and downstream groups to initiate their own reproductive cycles. To facilitate shortened CLD timelines, scientists have turned to new technologies and automation platforms. Emerging high-throughput instrumentation such as Clonepix and Automated MicroBioreactors (AMBR) have been enthusiastically integrated into stable cell line generation platforms; however, application of these methodologies among users is divergent.

    Contributors: Venkata R Mangalampalli, Dyane Wycuff, Mingzhong Chen, David Berlinger, Elizabeth H Scheideman, Amritha Menon, Guilia Fabozzi, Althaf Hussain & Richard M Schwartz  
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  • Citation
    Dated: May 25, 2014
    Publication Name: New Biotechnology

    High-throughput ClonePix FL analysis of mAb-expressing clones using the UCOE expression system

    Therapeutic recombinant monoclonal antibodies (mAbs) are commonly produced by high-expressing, clonal, mammalian cells. Creation of these clones for manufacturing remains heavily reliant on stringent selection and gene amplification, which in turn can lead to genetic instability, variable expression, product heterogeneity and prolonged development… View more

    Therapeutic recombinant monoclonal antibodies (mAbs) are commonly produced by high-expressing, clonal, mammalian cells. Creation of these clones for manufacturing remains heavily reliant on stringent selection and gene amplification, which in turn can lead to genetic instability, variable expression, product heterogeneity and prolonged development timelines. Inclusion of cis-acting ubiquitous chromatin opening elements (UCOE™) in mammalian expression vectors has been shown to improve productivity and facilitate high-level gene expression irrespective of the chromosomal integration site without lengthy gene amplification protocols. In this study we have used high-throughput robotic clone selection in combination with UCOE™ containing expression vectors to develop a rapid, streamlined approach for early-stage cell line development and isolation of high-expressing clones for mAb production using Chinese hamster ovary (CHO) cells. Our results demonstrate that it is possible to go from transfection to stable clones in only 4 weeks, while achieving specific productivities exceeding 20 pg/cell/day. Furthermore, we have used this approach to quickly screen several process-crucial parameters including IgG subtype, enhancer-promoter combination and UCOE™ length. The use of UCOE™-containing vectors in combination with automated robotic selection provides a rapid method for the selection of stable, high-expressing clones.

    Contributors: Jeff Jia Cheng Hou, Ben S. Hughes, Matthew Smede, Kar Man Leung, Kara Levine, Susan Rigby, Peter P. Gray, Trent P.Munro  
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