Cell Xpress™ Cell Line Optimization Service Using Laser-Enabled Analysis and Processing (LEAP™) Technology

Angela M. Davis, Genova A. Richardson, Nan Lin, Jennifer R. Cresswell, Matthew V. Caple and Kevin J. Kayser
Cell Sciences and Development, SAFC Biosciences 2909 Laclede Avenue, Saint Louis, MO 63103, USA

Introduction to Cell Xpress Schematic Illustration: Cell XpressCapture and Detection Applications
SAFC Biosciences (SAFCB) Cell Xpress technology combines in situ imaging with laser
Laser Enrichment of A Transfected “Pool” Population C
manipulation to identify, select, and monitor expansion of high recombinant protein
secreting clones. Cell Xpress provides significant advantages over microscope-based A
platforms with respect to throughput, robustness, and automation. Cell Xpress

Normalized Secretion Area

enables rapid analysis of relative secretion heterogeneity and purification of B
transfected or clonal populations. The Cell Xpress technology, when combined with

Average Intensity
SAFCB medium, feed, and process optimization, can result in a significant increase
in productivity from cell culture-based processes. SAFCB uses this integrated process
development platform to develop media and feed for use in the production of a cell
culture-derived therapeutic protein from our customers. SAFCB employs Cell Xpress
to analyze secretion heterogeneity of an initial cell population which may be either
a clonal cell line or a transfected pool. The initial population is laser processed to Normalized Secretion
enrich the population for high producing cells by eliminating low or non-producing
cells in the population. Following two to three rounds of enrichment, single cell
clones are generated from the enriched pool. Clones and enriched populations are
then expanded and screened for growth and productivity performance.
Transfected Pool Cell Xpress Enriched
Transfected Pool
The LEAP Instrument
In situ detection of secreted recombinant IgG: Fluorescent-labeled detection reagent detects
The LEAP Instrument and the Proprietary C-lect™ 384-Well Plate secreted rIgG (red); live cells are stained with viable cell stain (green).

Normalized Secretion Area Average Intensity (Binned)

Methods Single Cell Clone Characterization and Selection

Method Comparison: Cell Xpress vs. Traditional Cell Line Generation

Quantitative Measurement of Clone Secretion
Allows for a more cost-effective and efficient process

More cells from initial population evaluated

Labor -intensive expansion efforts focused on higher

Secretion Area Average

producers
The Benefits of Cell Xpress
Intensity (SAAI)

Traditional Cell Line Generation Cell Xpress Cell Line Generation

• Cell Xpress yields higher secreting cell lines faster
Cloning Secretion Assay
Expansion Cloning – Process 30,000+ clones per single plate
Secretion Assay Expansion – In situ verification of protein secretion prior to labor-intensive clone expansion
efforts
Cell Xpress combines in situ analysis of individual cell secretion with laser-mediated elimination • Provides visual documentation of clones
of poorly-secreting cells
– Image-based validation of clonality and automated tracking of clonal
outgrowth
– Documentation package

Acknowledgements
Correlation of Maximum Volumetric Productivity vs. Normalized Secretion Area Average Intensity
Erika Holroyd, Kathy Roeder
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