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Understand the efficiency of simulating bioreactor operations for faster growth, reduced costs, and cell culture optimization. Analyzing different impeller effects on growth and integrating ISF to balance oxygen delivery and cell damage.
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What is a Bioreactor? • Experimental device used to culture cells • Provides nutrient media, oxygen support, fluid environment, area to grow • Used both in laboratories and in industry-- specifically used in the lab portion of the BME 281: Biotechnology class
BME 281: Biotechnology • Course goal: to integrate cellular and molecular biology with process bioengineering to describe the manufacture of products derived from mammalian cells
Why Simulate? • based on initial lab results • quicker, more efficient, and less expensive
Laboratory 22 days to prepare cells for bioreactor 5 days to obtain a significant amount of growth TOTAL: 27 days Simulation approximately 1 minute to enter experimental data and get results TOTAL: 1 minute Experimental Time Comparison
Cell Types • HeLa--common in research labs • ECV304--endothelial cells • 293--used in BME 282 lab • can be distinguished based on specific growth constants & the extent to which they are affected by local environmental limitations
Past Work • Modeled simple exponential growth based only on cell-specific growth constant • Accounted for oxygen delivery limitation • Introduced different impeller types
Simple Exponential Growth • unlimited growth • cell types distinguished based on k
Impeller • different types influencing the amount of power that is delivered to the bioreactor system • increases oxygen dispersal throughout the system, thereby increasing delivery • forces imposed on cells due to stirring causes mechanical damage and cell death
Impeller Types Rushton turbine Marine Propeller Paddle Anchor Helical ribbon
Current Work • Incorporation of impeller effects on growth • Integration of ISF to balance oxygen delivery capabilities with cell death due to mechanical damage • Validation of model with actual lab results • Literature search to investigate other cell culture models
Integrated Shear Factor • Cell growth under different shear conditions can be correlated to an ISF factor
Stirring Speed Effects via ISF • ISF related to speed of impeller and its distance from the walls of the bioreactor
Experimental Comparisons • Given a time lag, model correlates with BME 282 data
Other Models • No other model attempted to integrate several interrelated factors that affect cell growth • Instead, focused on one parameter or determining event • None incorporated oxygen delivery limitations
Future Work • 1. Slight alterations to the program to make it more user-friendly • 2. Specific documentation of program procedure and functions