ADD discussion on process control
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@ -2768,6 +2768,32 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
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publisher = {Elsevier {BV}},
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publisher = {Elsevier {BV}},
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}
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}
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@Article{Ducker2017,
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author = {Gregory S. Ducker and Joshua D. Rabinowitz},
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journal = {Cell Metabolism},
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title = {One-Carbon Metabolism in Health and Disease},
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year = {2017},
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month = {jan},
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number = {1},
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pages = {27--42},
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volume = {25},
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doi = {10.1016/j.cmet.2016.08.009},
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publisher = {Elsevier {BV}},
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}
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@Article{Parolo2020,
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author = {Claudio Parolo and Andrea Idili and Gabriel Ortega and Andrew Csordas and Alex Hsu and Netzahualc{\'{o}}yotl Arroyo-Curr{\'{a}}s and Qin Yang and Brian Scott Ferguson and Jinpeng Wang and Kevin W. Plaxco},
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journal = {{ACS} Sensors},
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title = {Real-Time Monitoring of a Protein Biomarker},
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year = {2020},
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month = {jul},
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number = {7},
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pages = {1877--1881},
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volume = {5},
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doi = {10.1021/acssensors.0c01085},
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publisher = {American Chemical Society ({ACS})},
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}
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@Comment{jabref-meta: databaseType:bibtex;}
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@Comment{jabref-meta: databaseType:bibtex;}
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@Comment{jabref-meta: grouping:
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@Comment{jabref-meta: grouping:
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@ -3560,6 +3560,26 @@ More definitive conclusions of metabolic activity across the expanding cell
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population can be addressed by a closed system, ideally with on-line process
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population can be addressed by a closed system, ideally with on-line process
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sensors and controls for formate, lactate, along with ethanol and glucose.
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sensors and controls for formate, lactate, along with ethanol and glucose.
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Practically, knowledge of how cytokines and/or metabolites are related to
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outcome can be utilized for process control, which involves measuring the
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current state of the culture, comparing it to a desired state, and intervening
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if it is outside an acceptable range. In the case of lactate and formate, a
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benchtop \gls{nmr} can be utilized to sample the media in real time during
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culture. This \gls{nmr} can be tuned to automatically quantify the presence of
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lactate and formate. Formate is part of the one-carbon pathway, and thus culture
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fate may be controlled by altering the inputs to this pathway (glycine, serine,
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choline) and/or adding folic acid inhibitors\cite{Ducker2017}. Since lactate is
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a direct byproduct of glycolysis, this may be controlled by altering the
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concentration of glucose in solution. Each of these control schemes would need
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further study to assess if they have enough precision and temporal resolution to
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reasonably ensure product quality. In the case of cytokines, there is currently
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no analogue to a benchtop \gls{nmr}; however, research is underway to develop
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protein-specific sensors using aptamers\cite{Parolo2020}. Even without these
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developments, one could still use \gls{elisa} or Luminex to assess protein
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levels in a semi-automated manner, but the disadvantage is that these assays are
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temporally discrete and impose a significant time lag before the intervention
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can be performed.
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\chapter{AIM 2B}\label{aim2b}
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\chapter{AIM 2B}\label{aim2b}
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\section{Introduction}
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\section{Introduction}
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