diff --git a/tex/references.bib b/tex/references.bib index 5cc2809..f52e9c6 100644 --- a/tex/references.bib +++ b/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: diff --git a/tex/thesis.tex b/tex/thesis.tex index 47f5e53..6457422 100644 --- a/tex/thesis.tex +++ b/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}