Automated Microscale High‐Throughput Screening for Chromatography Resins

Wierling, P. Schulze; Bensch, Matthias; Schroeder, T.; Hubbuch, Jürgen

doi:10.1002/cite.200590165

Cited by 5 publications

(1 citation statement)

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“…However, the efficient scale‐up of such unit operations is not straightforward. On the microscale, microtiter plates (MTPs) are increasingly used for high throughput screening (HTS) during process development in both upstream and downstream processing of biopharmaceuticals (Diederich et al, 2015 ; Effio & Hubbuch, 2015 ; Feliciano et al, 2016 ; Hubbuch, 2012 ; Micheletti & Lye, 2006 ; Moreno‐González et al, 2021 ; Schulze Wierling et al, 2005 ). They allow experimentation in a parallel fashion while reducing material consumption and enable high flexibility for the selection of operating conditions.…”

Section: Introductionmentioning

confidence: 99%

Characterization of hydrodynamics and volumetric power input in microtiter plates for the scale‐up of downstream operations

Montes‐Serrano

Satzer

Jungbauer

et al. 2021

Biotech & Bioengineering

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Parameter estimation for scale-up of downstream operations from microtiter plates (MTPs) is mostly done empirically because engineering correlations between microplates and stirred tank reactors (STRs) are not yet available. It is challenging to change the operation mode from shaken MTPs to large-scale STRs. For the scale-up of STRs, volumetric power input is well-established although it is unclear whether this parameter can be used to transfer the operations from MTPs. We determine the volumetric power input in MTPs via the temperature increase caused by the motion of the liquid. The hydrodynamics in MTPs are studied with computational fluid dynamics (CFD). Mixing is investigated in 96-, 24-, and 6-well MTPs to cover different geometries, filling volumes, shaking diameters, and shaking frequencies. All CFD simulations are validated by experimental results, which now allows prediction of the volumetric power input and hydrodynamics at various conditions in MTPs without the need for further experiments. We provide a map of the power input achievable in MTPs. Based on this map, from knowing about large-scale conditions, adequate microscale conditions can be adjusted for process development. This enables the direct scale-up of downstream unit operations from MTPs to STRs.

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Section: Introductionmentioning

confidence: 99%

Characterization of hydrodynamics and volumetric power input in microtiter plates for the scale‐up of downstream operations

Montes‐Serrano

Satzer

Jungbauer

et al. 2021

Biotech & Bioengineering

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Mixing at the microscale: Power input in shaken microtiter plates

Dürauer

Hobiger

Walther

et al. 2016

Biotechnology Journal

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Power input and local energy dissipation are crucial parameters for the engineering characterization of mixing and fluid dynamics at the microscale. Since hydrodynamic stress is solely dependent on the maximum power input, we adapted the clay/polymer method to obtain flock destruction kinetics in six-, 24-, and 96-well microtiter plates on orbital shakers. We also determined the specific power input using calorimetry and found that the power input is at the same order of magnitude for the six-and 96-well plates and the laboratory-scale stirred tank reactor, with 40 to 90 W/m 3 (Re' = 180 to 440), 40 to 140 W/m 3 (Re' = 320 to 640), and 30 to 50 W/m 3 (Re = 4000 to 8500), respectively. All of these values are significantly below 450 to 2100 W/m 3 determined for the pilotscale reactor. The hydrodynamic stress differs significantly between the different formats of MTPs, as the 96-well plates showed very low shear stress on the shaker with a shaking amplitude of 3 mm. Thus, the transfer of mixing conditions from the microtiter plate to small-scale and pilot-scale reactors must be undertaken with care. Our findings, especially the power input determined by the calorimetric method, show that the hydrodynamic conditions in laboratory-and pilot-scale reactors cannot be reached.

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Mikro‐Bioverfahrenstechnik

Weuster‐Botz

2006

Chemie Ingenieur Technik

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Mikro‐Bioverfahrenstechnik gibt es bisher nicht als Fachdisziplin. Sie umfasst alle Aspekte der Bioprozesstechnik in kleinen Reaktionsvolumina. Einzelne Aspekte wurden bisher aus unterschiedlichen Fachrichtungen angestoßen: Biotechnologie, Biologie, Medizin, Bioverfahrenstechnik, aber auch Mikroreaktionstechnik. Ein Zusammenführen der unterschiedlichen Ansätze unter dem Dach einer neuen Mikro‐Bioverfahrenstechnik ist in Zukunft zwingend notwendig.

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Automated Microscale High‐Throughput Screening for Chromatography Resins

Cited by 5 publications

References 0 publications

Characterization of hydrodynamics and volumetric power input in microtiter plates for the scale‐up of downstream operations

Characterization of hydrodynamics and volumetric power input in microtiter plates for the scale‐up of downstream operations

Mixing at the microscale: Power input in shaken microtiter plates

Mikro‐Bioverfahrenstechnik

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