ADD discussion on process control

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Nathan Dwarshuis 2021-09-03 16:55:55 -04:00
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@ -2768,6 +2768,32 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
publisher = {Elsevier {BV}}, publisher = {Elsevier {BV}},
} }
@Article{Ducker2017,
author = {Gregory S. Ducker and Joshua D. Rabinowitz},
journal = {Cell Metabolism},
title = {One-Carbon Metabolism in Health and Disease},
year = {2017},
month = {jan},
number = {1},
pages = {27--42},
volume = {25},
doi = {10.1016/j.cmet.2016.08.009},
publisher = {Elsevier {BV}},
}
@Article{Parolo2020,
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},
journal = {{ACS} Sensors},
title = {Real-Time Monitoring of a Protein Biomarker},
year = {2020},
month = {jul},
number = {7},
pages = {1877--1881},
volume = {5},
doi = {10.1021/acssensors.0c01085},
publisher = {American Chemical Society ({ACS})},
}
@Comment{jabref-meta: databaseType:bibtex;} @Comment{jabref-meta: databaseType:bibtex;}
@Comment{jabref-meta: grouping: @Comment{jabref-meta: grouping:

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@ -3560,6 +3560,26 @@ More definitive conclusions of metabolic activity across the expanding cell
population can be addressed by a closed system, ideally with on-line process population can be addressed by a closed system, ideally with on-line process
sensors and controls for formate, lactate, along with ethanol and glucose. sensors and controls for formate, lactate, along with ethanol and glucose.
Practically, knowledge of how cytokines and/or metabolites are related to
outcome can be utilized for process control, which involves measuring the
current state of the culture, comparing it to a desired state, and intervening
if it is outside an acceptable range. In the case of lactate and formate, a
benchtop \gls{nmr} can be utilized to sample the media in real time during
culture. This \gls{nmr} can be tuned to automatically quantify the presence of
lactate and formate. Formate is part of the one-carbon pathway, and thus culture
fate may be controlled by altering the inputs to this pathway (glycine, serine,
choline) and/or adding folic acid inhibitors\cite{Ducker2017}. Since lactate is
a direct byproduct of glycolysis, this may be controlled by altering the
concentration of glucose in solution. Each of these control schemes would need
further study to assess if they have enough precision and temporal resolution to
reasonably ensure product quality. In the case of cytokines, there is currently
no analogue to a benchtop \gls{nmr}; however, research is underway to develop
protein-specific sensors using aptamers\cite{Parolo2020}. Even without these
developments, one could still use \gls{elisa} or Luminex to assess protein
levels in a semi-automated manner, but the disadvantage is that these assays are
temporally discrete and impose a significant time lag before the intervention
can be performed.
\chapter{AIM 2B}\label{aim2b} \chapter{AIM 2B}\label{aim2b}
\section{Introduction} \section{Introduction}