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Modeling and control of amino acid starvation-induced apoptosis in CHO cell cultures

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Abstract

Advanced process control theories are usually tested in a simulated environment. This article shows how a non-classical control algorithm can be implemented in a discrete fashion on a real biological process with satisfactory results. Kalman filters and model predictive controllers were implemented to delay starvation-induced apoptosis in CHO cell cultures. Apoptosis was mostly caused by deprivation of glutamine and asparagine in the medium. The concentrations of the state variables were estimated every 15 hours by forward integration of the system equations. The off-line measured concentrations of viable cells, lactate, and glucose were used to update the state estimates. Neural Network and Kalman filter techniques were then used to approximate the concentration of apoptotic cells in the bioreactor based on the concentrations of viable cells, glutamine and asparagine. This information was then fed to a model based predictive controller that was activated when the apoptotic cell estimate reached a concentration of 0.1 million cells per ml. This resulted in improved protein productivity and a reduced final apoptotic cell concentration.

Original languageEnglish (US)
Title of host publicationProceedings of the 2002 American Control Conference, ACC 2002
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages1579-1584
Number of pages6
ISBN (Print)0780372980
DOIs
StatePublished - 2002
Event2002 American Control Conference, ACC 2002 - Anchorage, AK, United States
Duration: May 8 2002 → May 10 2002

Publication series

NameProceedings of the American Control Conference
Volume2

Conference

Conference2002 American Control Conference, ACC 2002
Country/TerritoryUnited States
CityAnchorage, AK
Period5/8/02 → 5/10/02

ASJC Scopus subject areas

  • Electrical and Electronic Engineering

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