Automating the Cell Culture Sampling Process

Mike Phipps

Tara Ryan

BME 273

February 11, 2002

Problem

• Cell cultures maintained in bioreactors for Research and Development purposes in pharmaceutical companies must be sampled at least once daily

• methods of manually withdrawing a sample from the bioreactor can be reliable but still come with risks of culture contamination

• lab workers must be trained and experienced in sterile technique

Existing Sampling Methods

Hot plate to maintain temperature

Sampling syringe

ethanol

DO sparger Temperatureprobe

pH probeAgitator

Existing Sampling Methods

ethanol

Sam

plin

g po

rt

Sampling syringe

3-way valve

Water gasket for temperature control

Water inWater out

DO spargerTemperature probe

pH probeagitator

Project Goals

• reduce the risk of contamination that occurs due to sampling

• reduce the time it takes a lab worker to draw a sample from a culture

• reduce the skill and training required by a lab worker

Design IdeasIdea #1

• Continuous flow of medium and cells through tubing loop

• switch 3-way valve to the sampling line in order to draw a sample

• simple

• does not avoid the traditional syringe switch

Design IdeasIdea #2

• Ethanol and wash sterilize the syringe tip (needle)

• Use of septa

• Expand to a set of 4 bioreactors

Design IdeasIdea #3

• Open flame sterilizes the syringe tip (needle)• Use of septa• Water-gasket bioreactor system for better maintenance of the

culture’s temperature• Expand to a set of 4 bioreactors

Design IdeasIdea #4

• Simpler (fewer steps for mechanical arm)

• Reliance on hood to provide sterility

• Expand to a set of 4 bioreactors

Future Work

• Selecting the final design (possibly a combination of the ideas presented)

• Calculations (heat transfers, air flows, etc.) to determine specifications of the final design

• Draw final design using AutoCAD

• Production of a prototype?

References

• ABEC Website, <http://www.abec.com>

• B. Braun Biotech Website, <http://www.bbraunbiotech.com>

• Bailey, James E., and Ollis, David F. Biochemical Engineering Fundamentals. McGraw-Hill Inc.: St. Louis, 1986.

• Balcarcel, R. Robert. Associate Professor of Chemical Engineering, Vanderbilt University.

• New Brunswick Scientific Website, <http://www.nbsc.com>

• Todar, Kenneth. “The Control of Microbial Growth.” 21 September 2000 <http://www.bact.wisc.edu/microtextbook/ControlGrowth/sterilization.html>