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Monitoring Cell Development via In Situ Localized Sampling
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  • Mason Chilmonczyk,
  • Gilad Doron,
  • Peter Kottke,
  • Austin Culberson,
  • Kelly Leguineche ,
  • Robert Guldberg,
  • Edwin Horwitz,
  • Andrei Fedorov
Mason Chilmonczyk
Georgia Institute of Technology
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Gilad Doron
Georgia Institute of Technology
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Peter Kottke
Georgia Institute of Technology
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Austin Culberson
Georgia Institute of Technology
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Kelly Leguineche
University of Oregon
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Robert Guldberg
University of Oregon
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Edwin Horwitz
Emory University
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Andrei Fedorov
Georgia Institute of Technology
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Abstract

Nascent advanced therapies, including regenerative medicine and cell and gene therapies, rely on the production of cells in bioreactors that are highly heterogeneous in both space and time. Unfortunately, these promising therapies have failed to reach a wide patient population due to unreliable manufacturing processes that result in batch variability and cost prohibitive production. This can be attributed largely to a void in existing process analytical technologies (PATs) capable of characterizing the secreted critical quality attributes (CQAs) biomolecules that correlate with the final product quality. The Dynamic Sampling Platform (DSP) is a PAT for cell bioreactor monitoring that can be coupled to a suite of sensor techniques to provide real-time feedback on spatial and temporal CQA content in situ. In this study, DSP is coupled with electrospray ionization mass spectrometry (ESI-MS) and direct-from-culture sampling to obtain measures of CQA content in bulk media and the cell microenvironment throughout the entire cell culture process (~3 weeks). Post hoc analysis of this real-time data reveals that DSP output is heavily dependent on spatial context. Importantly, these results demonstrate that an effective PAT must incorporate both spatial and temporal resolution to serve as an effective input f or feedback control in advanced therapy production.

Peer review status:ACCEPTED

10 Jun 2020Submitted to Biotechnology Journal
13 Jun 2020Submission Checks Completed
13 Jun 2020Assigned to Editor
13 Jun 2020Reviewer(s) Assigned
08 Jul 2020Editorial Decision: Revise Major
30 Jul 20201st Revision Received
01 Aug 2020Assigned to Editor
01 Aug 2020Submission Checks Completed
01 Aug 2020Reviewer(s) Assigned
05 Sep 2020Editorial Decision: Revise Minor
09 Sep 20202nd Revision Received
10 Sep 2020Submission Checks Completed
10 Sep 2020Assigned to Editor
10 Sep 2020Reviewer(s) Assigned
18 Sep 2020Editorial Decision: Accept