(660a) Development of High Throughput Methods for Mammalian Cell System

For the past decade, biopharmaceutical industry had a fast growth, creating a hundred billion dollar market worldwide with the approval of recombinant proteins, monoclonal antibodies and nucleic acid–based drugs. Among all these production systems, the Chinese Hamster Ovary (CHO) cells are the most widely used mammalian cell systems for transfection, expression, and large-scale recombinant protein production, due to its advantage in accurate glycosylation for production of natural proteins in vitro. In recent CHO cell culture technology, significant improvement in recombinant protein production leading to a titer up to 10 g/L was achieved, to meet the high market demand by using stable and high producer together with the optimization of culture process. However, rapid selection for high production of clones is still needed.

In current study, we applied a new screening concept for on line and in situ high throughput screening for mammalian cell system. CHO cell lines producing Herceptin were used as the model mammalian cell system. By measuring the key parameters of the cell culture system on line, the performance of cell line can be predicted, and the high producers can be identified without performing invasive assays. The impact of the research will be very significant in upstream bioprocesses. In cell line development, product titer is a crucial parameter for clone selection. Our method does not require any external reporter, and it is a non-invasive liquid-based assay. We only need to monitor basic information of cell culture in order to calculate the product quantity. High and low producers can be easily identified in a high-throughput manner on-line and in situ using automated handling and aforehand programming. This will be a revolutionary change to current mammalian cell screening system.