A simple apparatus for measuring cell settling velocity

Wang, Zhaowei; Belovich, Joanne M.

doi:10.1002/btpr.432

Cited by 32 publications

(18 citation statements)

References 35 publications

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“…Viability of the perfusate samples at maximum viable cell concentration (93.1 ± 4.8%) was consistently higher than that of the homogenous microscale cultures (86.2 ± 5.5%; n = 16, p < 0.001). Although cell viability was reported to affect settling velocity in early reports (Searles et al, ), with nonviable cells moving 30–50% slower than viable cells (Wang & Belovich, ), this was not observed in the cultures investigated here. However, given the difference in size, the cells removed were more likely those, which displayed lower specific productivity due to their stage in cell cycle, as reported earlier (Lloyd, Holmes, Jackson, Emery, & Al‐Rubeai, ).…”

Section: Resultscontrasting

confidence: 54%

Enhancing the functionality of a microscale bioreactor system as an industrial process development tool for mammalian perfusion culture

Sewell

Turner²,

Field³

et al. 2019

Biotech & Bioengineering

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Without a scale‐down model for perfusion, high resource demand makes cell line screening or process development challenging, therefore, potentially successful cell lines or perfusion processes are unrealized and their ability untapped. We present here the refunctioning of a high‐capacity microscale system that is typically used in fed‐batch process development to allow perfusion operation utilizing in situ gravity settling and automated sampling. In this low resource setting, which involved routine perturbations in mixing, pH and dissolved oxygen concentrations, the specific productivity and the maximum cell concentration were higher than 3.0 × 106 mg/cell/day and 7 × 10 7 cells/ml, respectively, across replicate microscale perfusion runs conducted at one vessel volume exchange per day. A comparative analysis was conducted at bench scale with vessels operated in perfusion mode utilizing a cell retention device. Neither specific productivity nor product quality indicated by product aggregation (6%) was significantly different across scales 19 days after inoculation, thus demonstrating this setup to be a suitable and reliable platform for evaluating the performance of cell lines and the effect of process parameters, relevant to perfusion mode of culturing.

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Section: Resultscontrasting

confidence: 54%

Enhancing the functionality of a microscale bioreactor system as an industrial process development tool for mammalian perfusion culture

Sewell

Turner²,

Field³

et al. 2019

Biotech & Bioengineering

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“…At 36 ll/min they travel from inlet to the trapping region in 4.4 s on average and at a sedimentation rate of 7.8 lm/s. 51 Their vertical position is between 6 lm (average radius) and 10 lm from the floor of the device. Two particles with the same sign of the Clausius-Mossotti factor are attracted to each other when the pair is aligned along the electric field and they repel when the pair is aligned perpendicularly to the field.…”

Section: Resultsmentioning

confidence: 99%

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

et al. 2016

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We designed a new microfluidic device that uses pillars on the same order as the diameter of a cell (20 lm) to isolate and enrich rare cell samples from background. These cell-scale microstructures improve viability, trapping efficiency, and throughput while reducing pearl chaining. The area where cells trap on each pillar is small, such that only one or two cells trap while fluid flow carries away excess cells. We employed contactless dielectrophoresis in which a thin PDMS membrane separates the cell suspension from the electrodes, improving cell viability for off-chip collection and analysis. We compared viability and trapping efficiency of a highly aggressive Mouse Ovarian Surface Epithelial (MOSE) cell line in this 20 lm pillar device to measurements in an earlier device with the same layout but pillars of 100 lm diameter. We found that MOSE cells in the new device with 20 lm pillars had higher viability at 350 V RMS , 30 kHz, and 1.2 ml/h (control 77%, untrapped 71%, trapped 81%) than in the previous generation device (untrapped 47%, trapped 42%). The new device can trap up to 6 times more cells under the same conditions. Our new device can sort cells with a high flow rate of 2.2 ml/h and throughput of a few million cells per hour while maintaining a viable population of cells for off-chip analysis. By using the device to separate subpopulations of tumor cells while maintaining their viability at large sample sizes, this technology can be used in developing personalized treatments that target the most aggressive cancerous cells. V C 2016 AIP Publishing LLC. [http://dx

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“…6 The particle settling velocity of a given suspension can be measured directly 29 or can be calculated based on the expression derived from Stokes' law for low particle concentrations and low Reynolds number:…”

Section: Settler Characterization Methodsmentioning

confidence: 99%

“…29 The mean diameter of the microspheres was selected to be 16 lm with a density of 1.05 g/mL to mimic typical single mammalian cell properties. Bulk solutions of copolymer microsphere suspensions were purchased from Duke Scientific Corporation (Catalog number 7516C, Palo Alto, CA).…”

Section: Experimental Materials and Setupmentioning

confidence: 99%

CFD‐aided cell settler design optimization and scale‐up: Effect of geometric design and operational variables on separation performance

Shen

Yanagimachi

2011

Biotechnology Progress

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The inclined multiplate (lamella) gravity settler has proven to be an effective cell retention device in industrial perfusion cell culture applications. Investigations on the effects of geometric design and operational variables of the cell settler are crucial to understanding how to best improve the settler performance. Maximizing the harvest/perfusion flow rate while minimizing viable cell loss out of the harvest is the primary challenge for optimization of the settler design. This study demonstrated that computational fluid dynamics (CFD) can be utilized to accurately model and evaluate the settler separation performance for near-monodisperse suspensions and therefore aid in the design optimization of the settler under these baseline conditions. With the preferred geometric features that were identified from CFD modeling results, we proposed design guidelines for the scale-up of these multiplate settler systems. With these guidelines and performance verification using the CFD model, a new large-scale settler was designed and fabricated for a perfusion cell culture process using a minimally aggregating production cell line. Perfusion cell culture runs with this particular cell line were performed with this settler, and the CFD model was able to predict the initial ramp-up performance, proving it to be a valuable scale-up design tool for this production process.

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A simple apparatus for measuring cell settling velocity

Cited by 32 publications

References 35 publications

Enhancing the functionality of a microscale bioreactor system as an industrial process development tool for mammalian perfusion culture

Enhancing the functionality of a microscale bioreactor system as an industrial process development tool for mammalian perfusion culture

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

CFD‐aided cell settler design optimization and scale‐up: Effect of geometric design and operational variables on separation performance

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