Cell Culture Technology

Pörtner, Ralf; Jandt, Uwe; Zeng, An‐Ping

doi:10.1002/9783527807833.ch4

Cited by 4 publications

(4 citation statements)

References 127 publications

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“…Τhe culture was inserted in concentration of 5% ( v / v ) achieving maximum C max value after 12 h, signaling the fermentation apex. Glucose carbon source in concentration of 8 g/L was infused and cellular density > 10 7 cell/mL was documented by the S-101 supernatant optical density sensor [ 43 ]. Suspension pumping introduces complexity referring to the cellular viability condition [ 44 ], while filtering offers dual function removing metabolic debris between filtrate and medium, increasing the obtained culture density.…”

Section: Resultsmentioning

confidence: 99%

Pharma 4.0 Continuous mRNA Drug Products Manufacturing

2021

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Continuous mRNA drugs manufacturing is perceived to nurture flow processes featuring quality by design, controlled automation, real time validation, robustness, and reproducibility, pertaining to regulatory harmonization. However, the actual adaptation of the latter remains elusive, hence batch-to-continuous transition would a priori necessitate holistic process understanding. In addition, the cost related to experimental, pilot manufacturing lines development and operations thereof renders such venture prohibitive. Systems-based Pharmaceutics 4.0 digital design enabling tools, i.e., converging mass and energy balance simulations, Monte-Carlo machine learning iterations, and spatial arrangement analysis were recruited herein to overcome the aforementioned barriers. The primary objective of this work is to hierarchically design the related bioprocesses, embedded in scalable devices, compatible with continuous operation. Our secondary objective is to harvest the obtained technological data and conduct resource commitment analysis. We herein demonstrate for first time the feasibility of the continuous, end-to-end production of sterile mRNA formulated into lipid nanocarriers, defining the equipment specifications and the desired operational space. Moreover, we find that the cell lysis modules and the linearization enzymes ascend as the principal resource-intensive model factors, accounting for 40% and 42% of the equipment and raw material, respectively. We calculate MSPD 1.30–1.45 €, demonstrating low margin lifecycle fluctuation.

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Section: Resultsmentioning

confidence: 99%

Pharma 4.0 Continuous mRNA Drug Products Manufacturing

2021

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“…For fast and efficient bioprocess development, it is essential to monitor DO and pH at early stages of development to detect oxygen limitations and critical changes in pH early on [12]. Additionally, one of the most essential parameters in bioprocesses is biomass, which provides information about the progress of the process and determines the time point for induction and harvest [12,13]. In order to overcome the challenges of small working volumes and limited space inside the vessel, non-invasive optical measurement techniques are often used instead of invasive probes which are generally applied in bench-scale bioreactors [14] By means of recombinant protein technology, expression of protein-based biopharmaceuticals has been achieved by using several organisms such as bacteria, yeast, or mammalian cells [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Investigation and evaluation of a 3D‐printed optical modified cultivation vessel for improved scattered light measurement of biotechnologically relevant organisms

Rehfeld,

Kuhnke,

Ude

et al. 2023

Engineering in Life Sciences

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In the field of bioprocess development miniaturization, parallelization and flexibility play a key role reducing costs and time. To precisely meet these requirements, additive manufacturing (3D‐printing) is an ideal technology. 3D‐printing enables rapid prototyping and cost‐effective fabrication of individually designed devices with complex geometries on demand. For successful bioprocess development, monitoring of process‐relevant parameters, such as pH, dissolved oxygen (DO), and biomass, is crucial. Online monitoring is preferred as offline sampling is time‐consuming and leads to loss of information. In this study, 3D‐printed cultivation vessels with optical prisms are evaluated for the use in upstream processes of different industrially relevant microorganisms and cell lines. It was shown, that the 3D‐printed optically modified well (OMW) is of benefit for a wide range of biotechnologically relevant microorganisms and even for mammalian suspension cells. Evaluation tests with Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, and Chinese hamster ovary (CHO) cells were performed, providing highly reproducible results. Growth behavior of OMW cultures was comparable to behavior of shake flask (SF) cultivations and the signal to noise ratio in online biomass measurement was shown to be reduced up to 95.8% by using the OMW. Especially the cultivation phases with low turbidity respective optical densities below 1.0 rel.AU could be monitored accurately for the first time. Furthermore, it was demonstrated that the 3D‐printed optics are transferable to different well geometries and sizes, enabling efficient biomass monitoring for individual requirements with tailor‐made 3D‐printed cultivation vessels in small scale.

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“…In biomedical applications, most of the aspects of cell function, such as spreading, migration, proliferation, and differentiation, are significantly determined by substrates materials ruling adhesion control of cells to surfaces. Key material features like surface chemistry and topography are known to affect cell behavior, and the relationship between cell size and surface properties, or more generally, cellsurface interaction, has been widely investigated [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Super Liquid-repellent Surfaces and 3D Spheroids Growth

Ferrari¹,

Cirisano²,

Morán³

2022

Front. Biosci. (Landmark Ed)

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Substrates composition and surface features of materials rule adhesion control of cells to surfaces. As a result, most of the aspects of cell functions, such as spreading, migration, proliferation, and differentiation, can be significantly influenced in biomedical applications. Cell cultures make possible to understand cell biology, tissue morphology, mechanisms of diseases, drug action, and tissue engineering development, among others. Recent techniques related to culturing 3D cell aggregates in the presence of very low wettable surfaces represent an innovative field for in vitro experimentation aimed at more reliable conditions to investigate both tumor and non-tumor cell lines. Matching in particular cell biology to innovative materials, this work reviews the recent literature available on promoting cell aggregates formation strongly influenced by the high surface hydrophobicity. In particular, for spheroid formation, the highest water repellent coatings seem to be required for the significant effectiveness of the process. In this way, 3D cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions.

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Cell Culture Technology

Cited by 4 publications

References 127 publications

Pharma 4.0 Continuous mRNA Drug Products Manufacturing

Pharma 4.0 Continuous mRNA Drug Products Manufacturing

Investigation and evaluation of a 3D‐printed optical modified cultivation vessel for improved scattered light measurement of biotechnologically relevant organisms

Super Liquid-repellent Surfaces and 3D Spheroids Growth

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