SIMULATION OF A BIOREACTOR Tiffany Tarrant Todd Giorgio

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

Experimental Time Comparison 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

Typical Cell Culture

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 Cell Types

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

Oxygen Limitation Effects

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 Paddle Marine Propeller 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

Impeller Effects

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

Program Flowchart

Parameter Effects on Growth

Future Work 1. Slight alterations to the program to make it more user-friendly 2. Specific documentation of program procedure and functions