A Novel Ultrasonic Resonance Field Device for the Retention of Animal Cells

Doblhoff-Dier, O.; Gaida, T.; Katinger, Hermann; Bürger, Wolfgang; Groschl, M.; Benes, E.

doi:10.1021/bp00028a600

Cited by 115 publications

(64 citation statements)

References 13 publications

(4 reference statements)

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“…Doblhoff-Dier et al (1994) demonstrated that a higher input power was required to maintain a constant separation efficiency at high flow-rates. This trend is explained by the increased ultrasonic force required to retain the aggregated cells against the fluid drag, and by the lower mean fluid residence time.…”

Section: Ultrasonic Cell Retentionmentioning

confidence: 99%

Mammalian cell retention devices for stirred perfusion bioreactors

Woodside¹,

Bowen²,

Piret³

1998

Current Applications of Cell Culture Engineering

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Within the spectrum of current applications for cell culture technologies, efficient large-scale mammalian cell production processes are typically carried out in stirred fed-batch or perfusion bioreactors. The specific aspects of each individual process that can be considered when determining the method of choice are presented. A major challenge for perfusion reactor design and operation is the reliability of the cell retention device. Current retention systems include cross-flow membrane filters, spin-filters, inclined settlers, continuous centrifuges and ultrasonic separators. The relative merits and limitations of these technologies for cell retention and their suitability for large-scale perfusion are discussed.

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Section: Ultrasonic Cell Retentionmentioning

confidence: 99%

Mammalian cell retention devices for stirred perfusion bioreactors

Woodside¹,

Bowen²,

Piret³

1998

Current Applications of Cell Culture Engineering

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“…Planar USW systems may employ resonators that are larger than a wavelength and contain multiple pressure nodal planes [12,13], but for microfluidic scale devices, a resonant cavity with an axial dimension that is lower than the operating wavelength may be employed [14][15][16]. Such sub-wavelength resonators typically rely for their operation on precise positioning of the pressure node, to which particles will migrate.…”

Section: Introductionmentioning

confidence: 99%

Modelling for the robust design of layered resonators for ultrasonic particle manipulation

2008

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a b s t r a c t Several approaches have been described for the manipulation of particles within an ultrasonic field. Of those based on standing waves, devices in which the critical dimension of the resonant chamber is less than a wavelength are particularly well suited to microfluidic, or ''lab on a chip" applications. These might include pre-processing or fractionation of samples prior to analysis, formation of monolayers for cell interaction studies, or the enhancement of biosensor detection capability. The small size of microfluidic resonators typically places tight tolerances on the positioning of the acoustic node, and such systems are required to have high transduction efficiencies, for reasons of power availability and temperature stability. Further, the expense of many microfabrication methods precludes an iterative experimental approach to their development. Hence, the ability to design sub-wavelength resonators that are efficient, robust and have the appropriate acoustic energy distribution is extremely important. This paper discusses one-dimensional modelling used in the design of ultrasonic resonators for particle manipulation and gives example of their uses to predict and explain resonator behaviour. Particular difficulties in designing quarter wave systems are highlighted, and modelling is used to explain observed trends and predict performance of such resonators, including their performance with different coupling layer materials.

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“…In addition, the temperature difference between the recirculation flow and the resonator chamber is proven to be an important parameter for the stability of the acoustic field. In a previous study it is shown that an increase of the temperature difference, resulted in a decrease of the stability of the acoustic field and a decrease in the separation efficiency (Doblhoff-Dier et al, 1994;Gorenflo et al, 2002). Here the temperature in the conus of the acoustic separator increased from 34.2 to 34.9 due to the increase in the recirculation rate (Fig.…”

Section: Acoustic-separator Performancementioning

confidence: 75%

Stable hybridoma cultivation in a pilot‐scale acoustic perfusion system: Long‐term process performance and effect of recirculation rate

Dalm

Jansen²,

Keijzer³

et al. 2005

Biotech & Bioengineering

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Perfusion systems have the possibility to be operated continuously for several months. It is important that the performance of the cell retention device does not limit the operation time of a perfusion process used in the production of active pharmaceutical ingredients. Therefore, the aim of this study was to investigate the reliability and long-term stability of an acoustic perfusion process using the 200 L/d BioSep. As the BioSep is an external device, it is possible that dependent on the recirculation rate nutrient gradients occur in the external loop, which could affect the cell metabolism. Therefore, the effect of possible nutrient gradients on cell metabolism, viability and productivity was studied by varying the recirculation rate. In this study, it is shown that a perfusion process using a pilot-scale acoustic cell-retention device (200 L/ d) is reliable and simple to operate, resulting in a stable 75-day cultivation of a hybridoma cell line producing a monoclonal antibody. The recirculation rate had a significant effect on the oxygen concentration in the external loop, with oxygen being depleted within the cell-retention device at recirculation rates below 6 mThe oxygen depletion at low circulation rates correlated with a slightly increased lactate production rate. For all other parameters no effect of the recirculation rate was observed, including cell death measured through the release of lactate dehydrogenase and specific productivity. A maximum specific productivity of 12 pg/cell Á d was reached. ß 2005 Wiley Periodicals, Inc.

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A Novel Ultrasonic Resonance Field Device for the Retention of Animal Cells

Cited by 115 publications

References 13 publications

Mammalian cell retention devices for stirred perfusion bioreactors

Mammalian cell retention devices for stirred perfusion bioreactors

Modelling for the robust design of layered resonators for ultrasonic particle manipulation

Stable hybridoma cultivation in a pilot‐scale acoustic perfusion system: Long‐term process performance and effect of recirculation rate

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