Marcel Ottens's research while affiliated with Delft University of Technology and other places

Publications (110)

Article
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 development...
Article
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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 due to...
Article
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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 effecti...
Article
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 start...
Article
Full-text available
Process development in the biotech industry leads to investments around hundred‐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 start ma...
Article
Full-text available
Continuous manufacturing is an indicator of a maturing industry, as can be seen by the example of 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 had signifi...
Article
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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 chromatography....
Article
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The article brings an analysis on published models used to calculate phase separation in aqueous two-phase systems (ATPS) based on Flory-Huggins (FH) theory, in terms of problem formulation and mathematical solving algorithm. An integrated algorithm is presented, showing different mathematical approaches of using the FH theory. The algorithm involv...
Article
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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 the proc...
Article
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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 limite...
Article
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 type zeo...
Article
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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 model s...
Article
While packed bed chromatography, known as conventional chromatography, has been serving the biopharmaceutical industry for decades as the bioseparation method of choice, alternative approaches are likely to take an increasing leading role in the next few years. The high number of new biological drugs under development, and the need to make biopharm...
Article
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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 reagen...
Article
Full-text available
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 identify...
Article
A common sensory deficiency of alcohol-free beers (AFB) is caused by the presence of worty aldehydes. The aim of this study was to develop and proof the concept of a selective adsorption step, facilitating the removal of aldehydes from AFB. Therefore, the performance of 21 adsorbents (amine-functionalized polymers, hydrophobic resins and zeolites)...
Article
Sinapic acid is a potential valuable compound to be recovered from rapeseed meal extracts as it processes antioxidant and antimicrobial properties. However, the concentration of this compound might be low and the presence of other low value compounds could complicate its downstream processing. Adsorption is an alternative technique that might allow...
Article
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 and mi...
Article
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 processes. Ho...
Article
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 differ...
Article
Edible berries are considered to be among nature’s treasure chests as they contain a large number of (poly)phenols with potentially health-promoting properties. However, as berries contain complex (poly)phenol mixtures, it is challenging to associate any interesting pharmacological activity with a single compound. Thus, identification of pharmacolo...
Article
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Liquid-liquid extraction (LLE) can be an effective strategy for the purification of polyphenols from a fermentation broth. However, solvents need to be chosen to assure high extraction capacity and selectivity. For that purpose, a systematic study is here presented, where the partition of different polyphenols - naringin, naringenin, p-coumaric aci...
Article
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Recovery of volatile flavor-active aroma compounds which are key components of processed liquid food streams is of utmost concern to food industry, as these compounds contribute to the quality of the final product. This review paper highlights the recently published research on different techniques that can be applied for recovery of the key flavor...
Article
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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 prediction...
Article
Full-text available
Flavor-active esters, produced during fermentation, are vital components and important contributors to the aroma of beer. In order to separate trace amounts of esters, their adsorption behavior in the presence of high concentrations of ethanol and their thermodynamic behavior under the influence of temperature needs to be understood. This study rep...
Article
The application of mechanistic models for chromatography requires accurate model parameters. Especially for complex feedstocks such as a clarified cell harvest, this can still be an obstacle limiting the use of mechanistic models. Another commonly encountered obstacle is a limited amount of sample material and time to determine all needed parameter...
Article
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BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel h...
Article
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Adsorption can be an effective way of purifying polyphenols from complex mixtures. However, polyphenols may be present in small concentrations, making it difficult to selectively adsorb them onto standard hydrophobic resins and obtain appreciable adsorption. In this work, non-functionalized hydrophobic resins (Amberlite® XAD-7HP, XAD-16) are compar...
Article
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Expanded bed adsorption (EBA) emerged in the early 1990’s in an attempt to integrate the clarification, capture and initial product concentration/purification process. Several mathematical models have been put forward to describe its operation. However, none of the models developed specifically for EBA allow simultaneous prediction of bed hydrodyna...
Article
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A microfluidic device for pH gradient chromatofocusing is presented, which performs creation of a micro-column, pH gradient generation, and fraction collection in a single device. Using a sieve micro-valve, anion exchange particles were packed into a microchannel in order to realize a solid-phase absorption column. To fractionate proteins according...
Article
The growing interest in polyphenols has led to the design of industrial-scale processes able to produce them by fermentation and recover them in a more sustainable way. The goal of this work is to present two integrated approaches for the recovery of resveratrol, obtained through fermentation. The production of resveratrol using Corynebacterium glu...
Article
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BACKGROUND Preferential crystallization is a common technique used in the purification of enantiomers, proving that crystallization may also be applied to the purification of very similar molecules by seeding the solution with the desired compound. Nonetheless, its application to other organic molecules is less widely documented in the literature....
Poster
Sugars derived from lignocellulosic materials are the main carbon sources in bio-based processes aiming to produce renewable fuels and chemicals. One of the major drawbacks during enzymatic hydrolysis of lignocellulosic materials to obtain sugars is the inhibition of enzymes by reaction products (cellobiose and glucose). This effect is even more pr...
Article
A microfluidic platform or “microfluidic batch adsorption device” is presented, which performs two sets of 9 parallel protein incubations with/without adsorbent particles to achieve an adsorption isotherm of a protein in a single experiment. The stepwise concentration gradient of a target protein was created by the integration of microvalves in the...
Article
Chromatographic separation of biopharmaceuticals in general and monoclonal antibodies (mAbs) specifically is the bottleneck in terms of cost and throughput in preparative purification. Still, generalized platform processes are used, neglecting molecule specific characteristics, defining protein-resin interaction terms. Currently used in silico mode...
Chapter
Optimization via high-throughput process development (HTPD) can be done on different aspects of the chromatography unit. The optimal resin out of the huge amount available in the market today differing from each other in particle size, ligand type, and pressure flow characteristics, among others, has to be found while ensuring suitability for scale...
Article
Downstream process development is a major area of importance within the field of bioengineering. During the design of such a downstream process, important decisions have to be made regarding the type of unit operations as well as their sequence and their operating conditions. Current computational approaches addressing these issues either show a hi...
Patent
The invention relates to a fluidic device (1) having a particle trap functionality for a particle (2) in a fluid, the fluidic device (1) comprising a first fluid flow channel (11), a second fluid flow channel (12), and a control channel (13), wherein the first fluid flow channel (11) is in fluid contact with the second fluid flow channel (12) and i...
Article
Quantitative structure-activity relationship (QSAR) modeling for prediction of biomolecule parameters has become an established technique in chromatographic purification process design. Unfortunately available descriptor sets fail to describe the orientation of biomolecules and the effects of ionic strength in the mobile phase on the interaction wi...
Article
This work aims to propose an optimum resin that can be used in industrial adsorption process for tuning flavor-active components or removal of ethanol for producing an alcohol-free beer. A procedure is reported for selective adsorption of volatile aroma components from water/ethanol mixture on synthetic hydrophobic resins. High throughput 96-well m...
Article
Knowledge-based development of chromatographic separation processes requires efficient techniques to determine the physicochemical properties of the product and the impurities to be removed. These characterization techniques are usually divided into approaches that determine molecular properties, such as charge, hydrophobicity and size, or molecula...
Data
Off-chip HRP-catalyzed reactions. (A) Standard curve to quantify the concentration of resorufin according to its fluorescence intensity for tracing the product formation in the HRP-catalyzed reaction. The fluorescence intensity of resorufin was measured at various concentrations of resorufin ranged from 10 μM to 60 μM with an increment of 10 μM (n...
Article
Full-text available
A microfluidic platform or "microfluidic mapper" is demonstrated, which in a single experiment performs 36 parallel biochemical reactions with 36 different combinations of two reagents in stepwise concentration gradients. The volume used in each individual reaction was 36 nl. With the microfluidic mapper, we obtained a 3D enzyme reaction plot of ho...
Data
Photolithographic mask design (Clewin software) of a microfluidic mapper. (TIF)
Data
Image acquisition of 36 reactors. Time interval between two acquisitions of the fluorescent images of neighboring reactors (ΔT) was 3 seconds and between two time-lapse images of the same reactor (Tn+1 –Tn) was 100 seconds for the kinetic study in this work.(A) The moving direction of an automatic stage for scanning 36 reactors, and (B) An example...
Data
Michaelis-Menten reaction parameters for AR and H2O2 in the various conditions. (PDF)
Data
Combinations and compositions of reagents for HRP reactions with AR and H2O2. (PDF)
Data
Time-lapse fluorescent images and time courses of HRP reactions. (A) Reactor 1–1 to 1–6, (B) Reactor 2–1 to 2–6, (C) Reactor 3–1 to 3–6, (D) Reactor 4–1 to 4–6, (E) Reactor 5–1 to 5–6, and (F) Reactor 6–1 to 6–6 (200 μm scale bars are shown). (TIF)
Article
Vaccination is one of the most successful public health interventions being a cost-effective tool in preventing deaths among young children. The earliest vaccines were developed following empirical methods, creating vaccines by trial and error. New process development tools, for example mathematical modeling, as well as new regulatory initiatives r...
Article
The correlation between the dimensionless retention times (DRT) of proteins in hydrophobic interaction chromatography (HIC) and their surface properties were investigated. A ternary atomic-level hydrophobicity scale was used to calculate the distribution of local average hydrophobicity across the proteins surfaces. These distributions were characte...
Article
A new microfluidic valve or a "v-type valve" which can be flexibly actuated to focus a fluid flow and block a specific area of a microchannel is demonstrated. Valves with different design parameters were fabricated by multilayer soft lithography and characterized at various operating pressures. To evaluate the functionality of the valve, single mic...
Article
Lower order peak moments of individual peaks in heavily fused peak clusters can be determined by fitting peak models to the experimental data. The success of such an approach depends on two main aspects: the generation of meaningful initial estimates on the number and position of the peaks, and the choice of a suitable peak model. For the detection...
Article
High-throughput batch screening technologies have become an important tool in downstream process development. Although continuative miniaturization saves time and sample consumption, there is yet no screening process described in the 384-well microplate format. Several processes are established in the 96-well dimension to investigate protein-adsorb...
Article
Modified UNIFAC (Mod. UNIFAC) is a proven model for the prediction of activity coefficients of molecules in non-ideal mixtures. However, Mod. UNIFAC is often not accurate when hydrogen bonding or strong hydrophobic interactions are present. An interesting group of molecules called polyphenols presents both types of interactions and therefore, Mod....
Article
Owing to the complexity of food matrices, process synthesis methodologies have not been as widely applied in the food industry as in the chemical industry. Here, we describe the application of a process synthesis methodology to design a system to separate valuable components from a byproduct of the soymilk production. The method yielded a number of...
Article
Okara is a byproduct of the soy milk industry containing valuable phytochemicals, called isoflavones, among other components (i.e., proteins, sugars, fibers, etc.). As a waste product, okara is an interesting source material for obtaining valuable chemicals, and knowledge of the behavior of such components in their complex matrix is a key step for...
Article
This work focuses on the rapid selection of a resin from a defined set of macroporous polymeric resins for the decaffeination of catechins from green tea. High-throughput experimentation and design of experiments are used in order to retrieve as much information as possible from a small set of experiments on the interaction of components with the r...
Article
The purification of biopharmaceuticals is commonly considered the bottleneck of the manufacturing process. Increasing product diversity, along with growing regulatory and economic constraints raise the need to adopt new rational, systematic, and generally applicable process development strategies. Liquid chromatography is the key step in most purif...
Chapter
The objective of this chapter is to present a comprehensive overview of the key aspects of downstream process (DSP) development of proteins and peptides. The chapter opens with a general description of the DSP steps and highlights their objectives and the basic bioseparation techniques employed. After introducing the reader to the general aspects o...
Article
The accelerating growth of the market for proteins and the growing interest in new, more complex molecules are bringing new challenges to the downstream process development of these proteins. This results in a demand for faster, more cost efficient, and highly understood downstream processes. Screening procedures based on high-throughput methods ar...
Article
This article evaluates some of the most used solubility models and their applicability to antioxidants, namely, the family of catechins. From the list of possible catechins, the main four were selected for this study: epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate. Both the enthalpy of fusion and melting temperatur...
Article
The adsorption of bovine serum albumin (BSA) to an immobilized camelid-derived antibody fragment was investigated using six different activated resins, of which two are prototypes. The resins differed in base material, coupling chemistry and particle size. The adsorption, washing and desorption stage of the affinity chromatography process were take...