Cell Retention Devices for Suspended-Cell Perfusion Cultures

Castilho, Leda R.; Medronho, Ricardo de Andrade

doi:10.1007/3-540-45736-4_7

Cited by 93 publications

(98 citation statements)

References 100 publications

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“…Spin-filters (SF) have been proposed as cell retention devices for animal cell culture several decades ago (Himmelfarb et al 1969) and became a popular device for perfusion cultivations both for small-scale studies and large-scale processes (Castilho and Medronho 2002;Chu and Robinson 2001;Figueredo et al 2005). They can be either placed inside the bioreactor (internal spin-filters) or in an external recirculation loop.…”

Section: Introductionmentioning

confidence: 99%

CFD simulation of an internal spin-filter: evidence of lateral migration and exchange flow through the mesh

et al. 2009

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In the present work Computational Fluid Dynamics (CFD) was used to study the flow field and particle dynamics in an internal spin-filter (SF) bioreactor system. Evidence of a radial exchange flow through the filter mesh was detected, with a magnitude up to 130-fold higher than the perfusion flow, thus significantly contributing to radial drag. The exchange flow magnitude was significantly influenced by the filter rotation rate, but not by the perfusion flow, within the ranges evaluated. Previous reports had only given indirect evidences of this exchange flow phenomenon in spin-filters, but the current simulations were able to quantify and explain it. Flow pattern inside the spinfilter bioreactor resembled a typical Taylor-Couette flow, with vortices being formed in the annular gap and eventually penetrating the internal volume of the filter, thus being the probable reason for the significant exchange flow observed. The simulations also showed that cells become depleted in the vicinity of the mesh due to lateral particle migration. Cell concentration near the filter was approximately 50% of the bulk concentration, explaining why cell separation achieved in SFs is not solely due to size exclusion. The results presented indicate the power of CFD techniques to study and better understand spin-filter systems, aiming at the establishment of effective design, operation and scale-up criteria.

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Section: Introductionmentioning

confidence: 99%

CFD simulation of an internal spin-filter: evidence of lateral migration and exchange flow through the mesh

et al. 2009

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“…Cell retention devices are employed for the separation of cells from spent medium. Thus, the combination of continuous nutrient feeding, metabolites removal and cell retention allows high-cell-density cultures (greater than 10 7 cells/mL) and high productivities (usually at least 10-fold higher than in batch cultures) to be obtained (Woodside et al 1998;Castilho and Medronho 2002). However, the main concern in perfusion cultures is the technique employed to separate cells from the spent medium.…”

Section: Introductionmentioning

confidence: 99%

“…These separation devices present several advantages for use in the biotechnology industry, such as their simplicity and reliability, as well as the absence of moving parts. Furthermore, for cell separation applications, hydrocyclones would require no maintenance, allowing long-term continuous operation of perfusion bioreactors (Castilho and Medronho 2002).…”

Section: Introductionmentioning

confidence: 99%

Separation of CHO cells using hydrocyclones

2007

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Hydrocyclones are simple and robust separation devices with no moving parts. In the past few years, their use in animal cell separation has been proposed. In this work, the use of different hydrocyclone configurations for Chinese hamster ovary (CHO) cell separation was investigated following an experimental design. It was shown that cell separation efficiencies for cultures of the wildtype CHO.K1 cell line and of a recombinant CHO cell line producing granulocyte-macrophage colony stimulating factor (GM-CSF) were kept above 97%. Low viability losses were observed, as measured by trypan blue exclusion and by determination of intracellular lactate dehydrogenase (LDH) released to the culture medium. Mathematical models were proposed to predict the flow rate, flow ratio and separation efficiency as a function of hydrocyclone geometry and pressure drop. When cells were monitored for any induction of apoptosis upon passage through the hydrocyclones, no increase in apoptotic cell concentration was observed within 48 h of hydrocycloning. Thus, based on the high separation efficiencies, the robustness of the equipment, and the absence of apoptosis induction, hydrocyclones seem to be specially suited for use as cell retention devices in long-term perfusion runs.

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“…Spin-filters (SF) were proposed as cell retention devices for animal cell culture several decades ago [15] and became a popular device for perfusion cultivations both for small-scale studies and large-scale processes [16][17][18].…”

Section: Introductionmentioning

confidence: 99%