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\begin{document}

\title{An innovative fixed bed bioreactor platform for linearly scalable,
biomass predictable, single-use adherent cell biomanufacturing}



\author[1]{Vasiliy Goral}%
\author[1]{Yulong Hong}%
\author[2]{Jeffery  Scibek}%
\author[1]{Yujian Sun}%
\author[1]{Lori  Romeo}%
\author[1]{Abhijit  Rao}%
\author[1]{Daniel  Manning}%
\author[2]{Yue Zhou}%
\author[1]{Joel  Schultes}%
\author[1]{Vinalia  Tjong}%
\author[1]{Dragan  Pikula}%
\author[2]{Kathleen  Krebs}%
\author[1]{Ann Ferrie}%
\author[1]{Stefan  Kramel}%
\author[1]{Jennifer Weber}%
\author[1]{Zara Melkoumian}%
\author[2]{Todd Upton}%
\author[1]{Ye Fang}%
\affil[1]{Corning Incorporated}%
\affil[2]{Corning Development Inc}%


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  \date{May 27, 2024}


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\begin{abstract}
Scalable single use adherent cell-based biomanufacturing platforms are
part of solutions to realize the full potential of cell and gene
therapies. Here, we reported the development of an innovative fixed bed
bioreactor platform for the scale-up of adherent cell culture. The
bioreactor platform is centered on a packed bed of woven polyethylene
terephthalate mesh discs that are vertically stacked and sandwiched
between two fluid guide plates. Computational fluid dynamics modeling
was used to direct the design and development of bioreactor series,
targeting uniform flow with minimal shear stress. Residence time
distribution measurements revealed that a pulse injected dye tracer
solution passed through the bioreactors with great uniformity and narrow
distribution of residence time, mimicking plug flow. Periodic media
sampling with an offline analyzer showed that there was minimal gradient
of four important metabolites (glucose, glutamine, lactate, and ammonia)
across the bioreactor throughout cell growth. The bioreactor platform
was further validated in automated cell harvesting with
\textasciitilde{}96\% efficiency and \textasciitilde{}98\% viability, as
well as linear scalability, in terms of both operational parameters and
performance, for cell culture and adeno-associated virus vector
production. Finally, mathematic models based on oxygen uptake rates were
developed and proven effective to model cell growth curves and estimate
biomass in real-time. This study shows that this innovative fixed bed
bioreactor platform enables linearly scalable adherent cell-based
biomanufacturing with high productivity.%
\end{abstract}%



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\textbf{Hosted file}

\verb`FBR manuscript-submitted.docx`  available at \url{https://authorea.com/users/700630/articles/687441-an-innovative-fixed-bed-bioreactor-platform-for-linearly-scalable-biomass-predictable-single-use-adherent-cell-biomanufacturing}

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