Validation of an optical sensor-based high-throughput bioreactor system for mammalian cell culture.

Abstract:

:Cell culture optimization is a labor-intensive process requiring a large number of experiments to be conducted under varying conditions. Here we describe a high-throughput bioreactor system that allows 12 mini stirred-tank bioreactors to be operated simultaneously. All bioreactors are monitored by low-cost minimally invasive optical sensors for pH and dissolved oxygen. The sensors consist of single-use patches affixed inside the bioreactors and monitored optically from the outside. Experimental results show that different sensing patches with the same composition respond consistently. The discrepancy between different pH sensors is less than 0.1 pH units over most of their responsive range. The discrepancy between different dissolved oxygen sensors is less than 10% over the whole range from 0% to 100% dissolved oxygen. The consistency of the sensing system ensures that only an initial one-time calibration is required for the sensing patches. After that, a calibration code is generated and sensing patches of the same composition can be used directly. This greatly reduces the time and cost required for monitored multi-bioreactor operations. We used SP2/0 myeloma/mouse hybridoma cell cultures to demonstrate reactor performance consistency. Transcriptional profiling, HPLC analysis, viable cell count, and viability inspection show that the presence of sensing patches and the use of optical monitoring have no apparent effect on the metabolism of the cells.

journal_name

J Biotechnol

journal_title

Journal of biotechnology

authors

Ge X,Hanson M,Shen H,Kostov Y,Brorson KA,Frey DD,Moreira AR,Rao G

doi

10.1016/j.jbiotec.2005.12.009

subject

Has Abstract

pub_date

2006-04-10 00:00:00

pages

293-306

issue

3

eissn

0168-1656

issn

1873-4863

pii

S0168-1656(05)00763-7

journal_volume

122

pub_type

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