Microbioreactors for Process Development and Cell-Based Screening Studies

Frey, Lasse Jannis; Krull, Rainer

doi:10.1007/10_2020_130

Cited by 6 publications

(4 citation statements)

References 173 publications

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“…This leads to the conclusion that for process development with modern production cell lines, where cell densities far above 10 7 cells mL −1 are common, as far as possible for the final steps of cell line screening, it is advisable to use bioreactor systems with the highest levels of process control. There are review articles available that provide a detailed overview of microbioreactors that can be used for this purpose [33,34].…”

Section: Discussionmentioning

confidence: 99%

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

Ott,

Eibl

et al. 2024

Processes

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Modern production processes for biopharmaceuticals often work with very high cell densities. Moreover, there is a trend towards moving from fed-batch to continuous perfusion processes; a development that is influencing the requirements for bioreactor design and process control. In this study, the transfer of fed-batch and perfusion experiments between different cylindrical stirred lab-scale bioreactors and Thermo Scientific’sTM (Waltham, MA, USA) cubical HyPerformaTM DynaDriveTM Single-Use Bioreactor was investigated. Different scaling parameters were used, which were selected based on the requirements of the respective processes. Peak cell densities of up to 49 × 106 cells mL−1 and antibody titers of up to 5.2 g L−1 were achieved in 15- to 16-day fed-batch experiments. In 50-day perfusion cultivations, a viable cell volume of >100 mm3 mL−1 was maintained and more than 1 g L−1 d−1 of antibodies were harvested. The perfusion processes were automated with both cell bleed control and glucose concentration control. Cell retention was performed using Repligen’s (Waltham, MA, USA) XCell® ATF perfusion systems and single-use devices. In summary, approaches for successfully scaling highly productive fed-batch and perfusion processes between geometrically dissimilar lab and pilot scale bioreactors were demonstrated. The advantages of perfusion in comparison to fed-batch processes were also observed.

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Section: Discussionmentioning

confidence: 99%

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

Ott,

Eibl

et al. 2024

Processes

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“…It is scalable, easy to handle and monitor, 39 allows the study of several parameters that affect cell functions, and provides more sensitive analyses due to the surface-to-volume ratio. 40 Micro-bioreactors can be divided into stirred systems or spinner flasks, rotating wall vessel, hollow fibre micro-bioreactors, micro-bioreactors for mechanical stimulation and microfluidic bioreactors. For a better understanding, their schematic structures are depicted in Figure 4 .…”

Section: Advanced In Vitro Systemsmentioning

confidence: 99%

A comprehensive overview of advanced dynamic in vitro intestinal and hepatic cell culture models

Leal¹,

Zeiringer

Jeitler

et al. 2023

Tissue Barriers

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Orally administered drugs pass through the gastrointestinal tract before being absorbed in the small intestine and metabolised in the liver. To test the efficacy and toxicity of drugs, animal models are often employed; however, they are not suitable for investigating drug-tissue interactions and making reliable predictions, since the human organism differs drastically from animals in terms of absorption, distribution, metabolism and excretion of substances. Likewise, simple static in vitro cell culture systems currently used in preclinical drug screening often do not resemble the native characteristics of biological barriers. Dynamic models, on the other hand, provide in vivo -like cell phenotypes and functionalities that offer great potential for safety and efficacy prediction. Herein, current microfluidic in vitro intestinal and hepatic models are reviewed, namely single- and multi-tissue micro-bioreactors, which are associated with different methods of cell cultivation, i.e ., scaffold-based versus scaffold-free.

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“…They provide an alternative to closed microfluidic systems, such as flow channels, yet offer similar benefits: low sample consumption, high throughput, automation possibilities, and, most importantly, flexibility and versatility [1][2][3] . Furthermore, the sessile droplet offers additional advantages that include simplicity of fabrication and surface modification, feasibility of operation without a pump, elimination of device failures from channel blockage, and more compliance for unskilled users [4][5][6] . Sessile droplets on a solid substrate are used in a myriad of microfluidic applications, such as chemical synthesis 7,8 , polymerase chain reaction (PCR) 9,10 , immunoassay 11,12 , electrochemical sensing 13,14 , particle and cell separation and agglomeration [15][16][17] , and cell culturing 18,19 .…”

Section: Introductionmentioning

confidence: 99%

Internal flow in sessile droplets induced by substrate oscillation: towards enhanced mixing and mass transfer in microfluidic systems

Zhang,

Zhou,

Simon

et al. 2024

Microsyst Nanoeng

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The introduction of flows within sessile droplets is highly effective for many lab-on-a-chip chemical and biomedical applications. However, generating such flows is difficult due to the typically small droplet volumes. Here, we present a simple, non-contact strategy to generate internal flows in sessile droplets for enhancing mixing and mass transport. The flows are driven by actuating a rigid substrate into oscillation with certain amplitude distributions without relying on the resonance of the droplet itself. Substrate oscillation characteristics and corresponding flow patterns are documented herein. Mixing indices and mass transfer coefficients of sessile droplets on the substrate surface are measured using optical and electrochemical methods. They demonstrate complete mixing within the droplets in 1.35 s and increases in mass transfer rates of more than seven times static values. Proof of concept was conducted with experiments of silver nanoparticle synthesis and with heavy metal ion sensing employing the sessile droplet as a microreactor for synthesis and an electrochemical cell for sensing. The degrees of enhancement of synthesis efficiency and detection sensitivity attributed to the internal flows are experimentally documented.

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Microbioreactors for Process Development and Cell-Based Screening Studies

Cited by 6 publications

References 173 publications

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

Scaling Fed-Batch and Perfusion Antibody Production Processes in Geometrically Dissimilar Stirred Bioreactors

A comprehensive overview of advanced dynamic in vitro intestinal and hepatic cell culture models

Internal flow in sessile droplets induced by substrate oscillation: towards enhanced mixing and mass transfer in microfluidic systems

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