, Volume 34, Issue 1–2, pp 27–37 | Cite as

The gel microdrop secretion assay: Identification of a low productivity subpopulation arising during the production of human antibody in CHO cells

  • Linda Hammill
  • Jacqueline Welles
  • Gerald R. CarsonEmail author


The long-term stability of high-level expression is the mostimportant factor to consider when choosing cell lines for the expression of recombinant proteins. Declining volumetricyields in large-scale fermentation can be caused by changes affecting the cell population as a whole such as loss in viability, depletion of nutrients or accumulation of metabolites affecting cell growth. Alternatively, geneticinstability may lead to the outgrowth of a less productive,metabolically favored sub-population. Currently a variety ofparameters are measured to monitor the condition of cells infermenters including glucose uptake, lactate accumulation andoxygen consumption; in addition, periodic viable cell countsallow the determination of the growth rate and viability of the population. All of these methods measure the condition ofthe cell population as a whole and changes must involve a significantly large proportion of the total culture in orderto be detectable. Here we report on a method that allows theevaluation of the productivity of individual cells. Using the gel microdrop secretion assay, we detected the appearance ofa sub-population of cells with lower productivity. Subsequentanalysis of the culture confirmed the existence of lower productivity cells with a lower vector copy number. Therefore,the single cell secretion assay proved to be a rapid method todetect and isolate a low productivity variant of the producer cell line.

CHO cells gel microdrops human antibody population parameters productivity stability 


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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Linda Hammill
    • 1
  • Jacqueline Welles
    • 1
  • Gerald R. Carson
    • 2
    Email author
  1. 1.Department of Molecular BiologyBASF Bioresearch CorporationWorcesterU.S.A.
  2. 2.Department of Molecular BiologyBASF Bioresearch CorporationWorcesterU.S.A.

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