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A note on the modelling of lubrication forces in unresolved simulations

Nijssen, T.M.J. (author), Ottens, M. (author), Padding, J.T. (author)

Lubrication forces play a major role in the behaviour of fluid–solid systems, where they affect the collisions between particles. Current implementations of lubrication forces in unresolved simulations often suffer from shortcomings, such as neglecting parts of the physics or relying on arbitrarily defined parameters. In this short...

journal article 2023

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Design of a microfluidic mixer channel: First steps into creating a fluorescent dye-based biosensor for mAb aggregate detection

Neves Sao Pedro, M. (author), Silva dos Santos, M. (author), Eppink, Michel H.M. (author), Ottens, M. (author)

A major challenge in the transition to continuous biomanufacturing is the lack of process analytical technology (PAT) tools which are able to collect real-time information on the process and elicit a response to facilitate control. One of the critical quality attributes (CQAs) of interest during monoclonal antibodies production is aggregate...

journal article 2022

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Small, smaller, smallest: Miniaturization of chromatographic process development

Picanço Castanheira Da Silva, T. (author), Eppink, Michel (author), Ottens, M. (author)

Biopharmaceuticals are becoming increasingly important in modern healthcare. Monoclonal antibodies (mAb) are one of the most widely used therapeutic proteins and are important for the treatment of cancer and autoimmune diseases, among others. After cell culture there are still large amounts of other impurities (e.g. host cell proteins) in...

journal article 2022

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Recent advances to accelerate purification process development: A review with a focus on vaccines

Keulen, D. (author), Geldhof, Geoffroy (author), Bussy, Olivier Le (author), Pabst, Martin (author), Ottens, M. (author)

The safety requirements for vaccines are extremely high since they are administered to healthy people. For that reason, vaccine development is time-consuming and very expensive. Reducing time-to-market is key for pharmaceutical companies, saving lives and money. Therefore the need is raised for systematic, general and efficient process...

journal article 2022

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Process analytical technique (PAT) miniaturization for monoclonal antibody aggregate detection in continuous downstream processing

Neves Sao Pedro, M. (author), Klijn, M.E. (author), Eppink, Michel H.M. (author), Ottens, M. (author)

The transition to continuous biomanufacturing is considered the next step to reduce costs and improve process robustness in the biopharmaceutical industry, while also improving productivity and product quality. The platform production process for monoclonal antibodies (mAbs) is eligible for continuous processing to lower manufacturing costs...

review 2021

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High throughput process development for the purification of rapeseed proteins napin and cruciferin by ion exchange chromatography

Moreno Gonzalez, M. (author), Chuekitkumchorn, Pattra (author), Silva, Marcelo (author), Groenewoud, Roos (author), Ottens, M. (author)

Proteins derived from plant resources such as oilseed meals, canola and sunflower, are considered a viable alternative to animal proteins for food consumption. This work presents a rational methodology, using high throughput experimentation (HTE), for the separation of cruciferin and napin, the two major proteins of canola meal, by...

journal article 2021

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White paper on high-throughput process development for integrated continuous biomanufacturing

Neves Sao Pedro, M. (author), Picanço Castanheira Da Silva, T. (author), Patil, Rohan (author), Ottens, M. (author)

Continuous manufacturing is an indicator of a maturing industry, as can be seen by the example of the petrochemical industry. Patent expiry promotes a price competition between manufacturing companies, and more efficient and cheaper processes are needed to achieve lower production costs. Over the last decade, continuous biomanufacturing has...

journal article 2021

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A Structured Approach to Recover Valuable Compounds from Agri-food Side Streams

Moreno Gonzalez, M. (author), Ottens, M. (author)

Food side streams contain useful compounds such as proteins, sugars, polyphenols, and amino acids that might get discarded during processing. The concentration of these components may be low (e.g., fruit side streams are mainly composed by water, around 90%, while polyphenol content in rapeseed meal is less than 3% dry weight) and therefore...

review 2021

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Automation and miniaturization: Enabling tools for fast, high-throughput process development in integrated continuous biomanufacturing

Picanço Castanheira Da Silva, T. (author), Eppink, Michel (author), Ottens, M. (author)

Process development in the biotech industry leads to investments around hundred of millions of dollars. It is important to mitigate costs without neglecting the quality of process development. Biopharmaceutical process development is important for companies to develop new processes and be first to market, improve a pre-established process, or...

review 2021

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Continuous adsorption in food industry: The recovery of sinapic acid from rapeseed meal extract

Moreno Gonzalez, M. (author), Keulen, D. (author), Gomis-Fons, Joaquín (author), Lopez Gomez, M.G. (author), Nilsson, Bernt (author), Ottens, M. (author)

Efficient recovery and utilization of valuable components from industrial food side streams is a main driver towards a circular economy. Among different available purification techniques, adsorption can effectively recover these components. However, the conventional batch mode of operation can limit its applicability in food processes due to...

journal article 2021

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A critical assessment of the Flory-Huggins (FH) theory to predict aqueous two-phase behaviour

Consorti Bussamra, B. (author), Sietaram, D.L. (author), Verheijen, Peter J.T. (author), Mussatto, Solange (author), Carvalho da Costa, Aline (author), van der Wielen, L.A.M. (author), Ottens, M. (author)

This article provides an analysis on published models used to calculate phase separation in aqueous two-phase<br/>systems (ATPS) based on Flory-Huggins (FH) theory, in terms of problem formulation and mathematical solving<br/>algorithm. An integrated algorithm is presented, showing different mathematical approaches of using the FH<br/>theory....

journal article 2020

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Systematic investigation of insulin fibrillation on a chip

Rho, Hoon Suk (author), Veltkamp, Henk Willem (author), Hanke, A.T. (author), Ottens, M. (author), Breukers, Christian (author), Habibović, Pamela (author), Gardeniers, Han (author)

A microfluidic protein aggregation device (microPAD) that allows the user to perform a series of protein incubations with various concentrations of two reagents is demonstrated. The microfluidic device consists of 64 incubation chambers to perform individual incubations of the protein at 64 specific conditions. Parallel processes of metering...

journal article 2020

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Mass transfer limitations in binderless ZSM-5 zeolite granules during adsorption of flavour compounds from aqueous streams

Gernat, D.C. (author), Rozenbroek, Renzo (author), Brouwer, Eric R. (author), van der Wielen, L.A.M. (author), Ottens, M. (author)

BACKGROUND: Recently, a new process concept has been proposed to selectively adsorb wort off-flavours, i.e. aldehydes, from alcohol-free beers with hydrophobic zeolites. RESULTS: In this work, we investigated the uptake of a mixture of wort flavour compounds (2-methylpropanal, 2-methylbutanal, 3-methylbutanal, furfural, and methional), from a...

journal article 2020

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Enzymatic Hydrolysis of Sugarcane Bagasse in Aqueous Two-Phase Systems (ATPS): Exploration and Conceptual Process Design

Consorti Bussamra, B. (author), Meerman, Paulus (author), Viswanathan, V. (author), Mussatto, Solange I. (author), Carvalho da Costa, Aline (author), van der Wielen, L.A.M. (author), Ottens, M. (author)

The enzymatic conversion of lignocellulosic material to sugars can provide a carbon source for the production of energy (fuels) and a wide range of renewable products. However, the efficiency of this conversion is impaired due to product (sugar) inhibition. Even though several studies investigate how to overcome this challenge, concepts on...

journal article 2020

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Flavour-improved alcohol-free beer – Quality traits, ageing and sensory perception

Gernat, D.C. (author), Brouwer, E. R. (author), Faber-Zirkzee, R. C. (author), Ottens, M. (author)

The increasing popularity of alcohol-free beers (AFBs) fosters the industry interest in delivering the best possible product. Yet, a remaining sensory defect of AFBs is the over-perception of wort flavour, caused by elevated concentrations of small volatile flavour compounds (i.e. aldehydes). Previously, molecular sieves (hydrophobic ZSM-5...

journal article 2020

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Aldehydes as Wort Off-Flavours in Alcohol-Free Beers—Origin and Control

Gernat, D.C. (author), Brouwer, E. (author), Ottens, M. (author)

Although present in concentrations in microgrammes per litre level, aldehydes, in particular those derived from Strecker degradation, are known to majorly contribute to the undesired wort flavour of alcohol-free beers. In order to improve currently available products, one needs to understand the underlying cause for the over-prevalence and...

review 2019

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Column chromatography for separation and fractionation of flavor-active esters on hydrophobic resins and simulation of breakthrough behavior

Saffarionpour, S. (author), de Jong, Tessa F. (author), van der Wielen, L.A.M. (author), Brouwer, Eric (author), Ottens, M. (author)

For simulating an adsorption/elution step for separation and recovery of flavor-active esters in beer in the presence of ethanol at various temperatures, and validating the predicted breakthrough behavior, equilibrium data on concentration of each ester is required. This work evaluates the application of frontal analysis method (FA) for...

journal article 2019

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The Investigation of Protein Diffusion via H-Cell Microfluidics

Yu, M. (author), Picanço Castanheira Da Silva, T. (author), van Opstal, A.W.M. (author), Romeijn, Stefan (author), Every, H.A. (author), Jiskoot, Wim (author), Witkamp, G.J. (author), Ottens, M. (author)

In this study, we developed a microfluidics method, using a so-called H-cell microfluidics device, for the determination of protein diffusion coefficients at different concentrations, pHs, ionic strengths, and solvent viscosities. Protein transfer takes place in the H-cell channels between two laminarly flowing streams with each containing a...

journal article 2019

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A robotic platform to screen aqueous two-phase systems for overcoming inhibition in enzymatic reactions

Consorti Bussamra, B. (author), Gomes, Joana Castro (author), Freitas, Sindelia (author), Mussatto, Solange I. (author), da Costa, Aline Carvalho (author), van der Wielen, L.A.M. (author), Ottens, M. (author)

Aqueous two-phase systems (ATPS) can be applied to enzymatic reactions that are affected by product inhibition. In the biorefinery context, sugars inhibit the cellulolytic enzymes in charge of converting the biomass. Here, we present a strategy to select an ATPS (formed by polymer and salt) that can separate sugar and enzymes. This automated...

journal article 2019

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Model-based optimization of integrated purification sequences for biopharmaceuticals

Pirrung, S.M. (author), Berends, Carmen (author), Backx, Antoon H. (author), van Beckhoven, Ruud F.W.C. (author), Eppink, Michel H.M. (author), Ottens, M. (author)

Finding the best purification process is a challenging task. Recently, mechanistic models that can accelerate the development of chromatographic unit operations, the most important purification units, became widely available. In previous work, several chromatographic models have been linked together to simulate and optimize integrated...

journal article 2019