Visualizing medium and biodistribution in complex cell culture bioreactors using in vivo imaging
journal contributionposted on 2017-08-21, 10:46 authored by Elizabeth RatcliffeElizabeth Ratcliffe, Rob ThomasRob Thomas, Adrian J. Stacey
There is a dearth of technology and methods to aid process characterization, control and scale-up of complex culture platforms that provide niche micro-environments for some stem cell-based products. We have demonstrated a novel use of 3d in vivo imaging systems to visualize medium flow and cell distribution within a complex culture platform (hollow fiber bioreactor) to aid characterization of potential spatial heterogeneity and identify potential routes of bioreactor failure or sources of variability. This can then aid process characterization and control of such systems with a view to scale-up. Two potential sources of variation were observed with multiple bioreactors repeatedly imaged using two different imaging systems: shortcutting of medium between adjacent inlet and outlet ports with the potential to create medium gradients within the bioreactor, and localization of bioluminescent murine 4T1-luc2 cells upon inoculation with the potential to create variable seeding densities at different points within the cell growth chamber. The ability of the imaging technique to identify these key operational bioreactor characteristics demonstrates an emerging technique in troubleshooting and engineering optimization of bioreactor performance.
This work was funded by Celgene Cellular Therapeutics via the US Defense Advanced Research Projects Agency (DARPA) and the Defense Sciences Office (DSO) Blood Pharming program (Grant number FA9550-08-1-0392).
- Aeronautical, Automotive, Chemical and Materials Engineering
- Chemical Engineering
Published inBiotechnology Progress
Pages256 - 260
CitationRATCLIFFE, E., THOMAS, R. and STACEY, A., 2014. Visualizing medium and biodistribution in complex cell culture bioreactors using in vivo imaging. Biotechnology Progress, 30 (1), pp.256-260.
PublisherJohn Wiley and Sons (© American Institute of Chemical Engineers)
- SMUR (Submitted Manuscript Under Review)
Publisher statementThis work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/
NotesThis is the pre-peer reviewed version of the following article: RATCLIFFE, E., THOMAS, R. and STACEY, A., 2014. Visualizing medium and biodistribution in complex cell culture bioreactors using in vivo imaging. Biotechnology Progress, 30 (1), pp.256-260, which has been published in final form at: http://dx.doi.org/10.1002/btpr.1840. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.