(620by) A User Friendly Simulator for Antibody Producing Hybridoma Cell Cultures

A User Friendly Simulator for Antibody Producing Hybridoma Cell Cultures

Denizhan Yilmaz, Satish J. Parulekar, and Ali Cinar

Department of Chemical and Biological Engineering

Illinois Institute of Technology, Chicago, IL 60616

(312) 567-3044 (voice), (312) 567-8874 (fax), parulekar@iit.edu

Abstract

The demand for monoclonal antibodies (MAb), produced mostly from hybridoma cells, has proliferated vastly over the last two decades due to their therapeutic and diagnostic applications. The cultivation and development of methods for optimization of cell growth and cell productivity have become a crucial issue to enhance product yield in vitro production. The efficiency and performance of the cell culture systems depend on media optimization, process monitoring and control strategies. Creating these strategies requires understanding of process dynamics affected by cell mechanism in culture environments. Although the experiments provide data to discover underlying biological mechanisms and validate relationships between important cellular variables, acquiring necessary data on the dynamics of cells growth necessitates a broader amount of work. Moreover, the cost of these experiments accumulates with each trial, making these discoveries even more financially intensive. Mathematical models predicting cell growth behavior are becoming more necessary to reduce expensive trial and error experiments. Kinetic models are crucial for mammalian cell cultures as these not only reduce cost but also provide better insight into the process. Kinetic models provide better understanding of cell physiology for optimization and control of animal cell cultures. Demonstrating the most convenient experiments and pointing to strategies to improve process performance, simulation studies enable researchers to eliminate expensive and unnecessary time-consuming experiments. For this reason, we have developed a simulator for investigators without specific expertise in modeling to predict cell growth, cell death, target metabolite productivity, nutrition depletion, and waste product accumulation for different initial conditions, feeding strategies and bioreactor operation modes, such as batch, fed-batch, and perfusion (CSTR).  The Matlab-based simulator is designed as a multifunctional tool incorporating five different kinetic models available in the literature for monoclonal antibody (target metabolite) production by mammalian cells. The user friendly graphical interface allows the user to specify and alter culture conditions - viable and non-viable  cell densities, nutrient (glucose and glutamine) levels, and levels of inhibitory waste products (ammonia and lactate) of cell metabolism. For fed-batch and continuous cultures, the user can specify feeding strategies. The user can experiment by using different kinetic models, adjusting medium composition, and changing feeding strategies to observe their effects on cell growth and cell productivity.