ADD discussion on process control

tex/references.bib

@@ -2768,6 +2768,32 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
   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: grouping:

tex/thesis.tex

@@ -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
 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}
 
 \section{Introduction}