ADD bioreactor scale-up stuff

tex/thesis.tex

@@ -747,6 +747,42 @@ compared to state-of-the-art systems.
 
 \subsection{methods to scale T cells}
 
+In order to scale T cell therapies to meet clinical demands, automation and
+bioreactors will be necessary. To this end, there are several choices that have
+found success in the clinic.
+
+The WAVE bioreactor (GE Healthcare) is the choice of expansion for many clinical
+applications [5,45,64]. It is part of a broader class of bioreactors that
+consist of rocking platforms that agitate a bag filled with media and cells.
+Importantly, it has built-in sensors for measuring media flow rate, carbon
+dioxide, oxygen, pH, and nutrient consumption which enables automation.
+Unfortunately, in some settings this is not considered scalable as only one bag
+per bioreactor is allowed at once\cite{Roddie2019}.
+
+% BACKGROUND find clinical trials (if any) that use this
+Alternatively, the CliniMACS Prodigy (Miltenyi) is an all-in-one system that is
+a fully closed system that removes the need for expensive cleanrooms and
+associated personnel. It contains modules to perform transduction, expansion,
+and washing. This setup also implies that fewer mistakes and handling errors
+will be made, since many of the steps are internal to the machine. Initial
+investigations have shown that it can yield T cells doses required for clinical
+use.
+% https://reader.elsevier.com/reader/sd/pii/S1465324917307041?token=CF7C833CF6E0A7D5E003703A845A51066D028D5BF605792595DCF8D540B23933F4B856A0A9881C6DDEFE0C38D220A768&originRegion=us-east-1&originCreation=20210802022804
+At the time of writing, several clinical trial are underway which use the
+CliniMACS, although mostly for stem-cell based cell treatments.
+
+Finally, another option that has been investigated for T cell expansion is the
+Grex bioreactor (Wilson Wolf). This is effectively a tall tissue-culture plate
+with a porous membrane at the bottom, which allows gas exchange to the active
+cell culture at the bottom of the plate while permitting large volumes of media
+to be loaded on top without suffocating the cells. While this is quite similar
+to plates and flasks normally used for small-scale research, the important
+difference is that its larger size requires fewer interactions and keeps the
+cells at a higher nutrient concentration for longer periods of time. However, it
+is still a an open system and requires manual (by default) interaction from an
+operator to load, feed, and harvest the cell product. Grex bioreactors have
+been using to grow \glspl{til} [58] and virus-specific T cells [61].
+
 \subsection{overview of T cell quality}
 
 % memory