@article {46957,
	title = {Towards in situ continuous feeding via controlled release of complete nutrients for fed-batch culture of animal cells},
	journal = {Biochemical Engineering Journal},
	volume = {154},
	year = {2020},
	month = {FEB },
	pages = {107436},
	type = {Article},
	abstract = {<p>Small-scale culture of animal cells in suspension is of importance for many applications. At a small-scale, fed-batch is achieved either by manual bolus feeding or the use of liquid handling robots. In this study, we report an alternate application of a hydrogel for in situ continuous delivery of a nutrient feed comprising 18 amino acids, vitamins, antioxidants, and trace elements. We show that amino acid release is sustained for at least seven days. Importantly, release rates of individual amino acids can be independently modulated by changing their loading. We demonstrate the application of this hydrogel for complete in situ feeding of nutrients to a suspension adapted CHO cell line expressing IgG leading to 2.7-fold and 4-fold improvement in integral viable cell density (IVCD) and volumetric productivity respectively. This is similar to improvements obtained by bolus liquid feeding. Further, supplying glucose from the same hydrogel to eliminate manual feeding led to a 1.8-fold increase in IVCD accompanied by a 3-fold increase in volumetric productivity as compared to batch culture. In summary, this study provides a proof-of-concept that hydrogels can enable completely closed in situ feeding for mammalian cell culture requiring no external intervention. Such continuous in situ delivery can potentially enable closed culture systems maintaining nutrients at low levels mimicking physiological concentrations.</p>
},
	keywords = {Amino acids, CHO cells, Closed system, Fed-batch, Hydrogel for continuous feeding, In situ nutrient release},
	issn = {1369-703X},
	doi = {10.1016/j.bej.2019.107436},
	author = {Rawat, Jyoti and Gadgil, Mugdha}
}
@article {47584,
	title = {Trace metals in cellular metabolism and their impact on recombinant protein production},
	journal = {Process Biochemistry},
	volume = {110},
	year = {2021},
	month = {NOV},
	pages = {251-262},
	type = {Review},
	abstract = {Replacement of serum and increasing use of chemically defined media demands optimisation of trace metal components for biomanufacturing applications. Trace metal availability can impact culture performance, productivity and product quality. Several trace metals are cofactors of metabolic and other enzymes, and thus their availability regulates cellular metabolism. Additionally, they can also affect the availability of other trace metals and stability of some medium components. Such factors also need to be considered while formulating trace metal concentrations in the culture medium. Due to their very low concentrations, these components are susceptible to substantial variability arising from contaminants from other raw material and leaching from process equipment and can contribute to process variability. Understanding the role and impact of trace metals will help develop strategies to achieve targeted process parameters and increase process robustness vis-{\textquoteleft}a-vis any lot-to-lot variability in trace metal concentration in culture medium. This review describes the role of trace metals, particularly manganese, copper and zinc, in central carbon metabolism to aid in understanding the basis of metal-mediated effects on culture performance and provides a comprehensive review of the reported impact of trace metals on CHO cell culture performance and recombinant protein quality.},
	keywords = {Chinese hamster ovary cells, glycosylation, Medium formulation, Process variability, Product quality, Recombinant proteins, Trace metals},
	issn = {1359-5113},
	doi = {10.1016/j.procbio.2021.08.006},
	author = {Prabhu, Anuja and Gadgil, Mugdha}
}
