The design project entitled “Design of a treatment protocol to improve the health of B12 deficient patients” is carried out as an individual design project of PDEng program in Chemical Product Design. This project is commenced for the B12 Institute, Rotterdam, which aims to improve the diagnosis and treatment of patients with vitamin B12 and folate deficiency. The experience of the B12 Institute showed that the current diagnostic and treatment protocol is not sufficient to improve the health of some severe patients. This design project aims to provide knowledge beyond the classical theories of B12 deficiency, such that an extended protocol can be recommended to enhance the recovery and health of B12 deficient patients. The recommended protocol consists of diagnostic means and subsequent corrective actions. The approach of the project is divided into 4 major steps: 1. study of the biochemistry of vitamin B12 cellular metabolism; 2. generation of hypotheses on disorders related to B12 deficiency according to the biochemistry study; 3. recommendation of biomarkers/diagnostic tools; 4. recommendation of corrective actions. This report discusses the hypotheses of the vitamin B12 cellular inactivity, which extends the theory of the classical B12 deficiency. The hypotheses revolve around the failure of the B12 cellular activation due to enzymes defects and the activation cofactors deficiencies, as well as the failure of B12 co-enzymatic function due to oxidative stress. A series of vicious cycles between the overlooked causes and impacts in B12 inactivity is also described. The highlights of the hypotheses are summarized as follows: • B12 deficiency causes folate cycle block, which leads to glycine deficiency, • Glycine deficiency leads to glutathione deficiency and collagen deficiency, • Glutathione deficiency causes an elevated oxidative stress, and vice versa, • Collagen deficiency leads to intestinal bacterial dysbiosis, • Intestinal bacterial dysbiosis causes the production of bacterial toxins, including formaldehyde, • An excess of formaldehyde exacerbates oxidative stress and damages to the body, and may as well inactivate cellular B12. However, we found that the current knowledge on the mechanisms explaining a lower B12 enzyme activity may still be insufficient to explain the whole condition and issues related to B12 cellular inactivity. Finally, we designed a mini study to obtain evidence on a number of the hypotheses, especially those related to oxidative stress. New biomarkers for the extension of the diagnostic tools are explored. The new biomarkers are expected to provide better tools to explain the condition and symptoms of the patients. In addition, several supplements are recommended as corrective actions of the anticipated issues disclosed by the new biomarkers. The concepts and the results of the project are expected to provide new insights for the medical research and practice of B12 deficiency treatment, as well as to provide major improvement to the health of the patients. @en

Food spoilage has become in the last decades one of the biggest challenges faced by the food industry, with a significant amount of products thrown away at every step of the supply chain. Microbial contamination is listed as one of the major causes of food spoilage and can be at a large extent prevented by application of antimicrobial compounds. Recent trends on the market such as an increasing demand of consumers for natural preservatives and their application in reduced quantities, coupled with the difficulty for industrials to get new antimicrobials approved by health authorities, lead the food industry to a process of reformulation and improvement of functionality and efficiency of already approved ingredients. Natamycin, a naturally-occurring food preservative widely used for the protection of food surfaces, is one of the most popular antifungal agents currently used. This molecule presents several advantages linked to its natural origin, long history of safe use, efficiency at low concentrations and limited modification of food products when applied. Current formulations of the preservative offer however limited specificity or tunability towards applications and little possibilities of controlled/triggered release. This compound also presents a relatively poor aqueous solubility detrimental for its antifungal action and is very sensitive to early-stage degradation by environmental factors such as extreme pH, oxidation and UV exposure. The main goal of this PhD thesis was to determine if the incorporation of this molecule within nano-encapsulation systems could provide benefits for availability, tunability and degradation issues. As a first step, formulation, optimization and characterization of two model nano-encapsulation systems (biodegradable polymeric nanospheres and nano-liposomes) were performed and compared in terms of relative benefit for the encapsulation, delivery, antifungal performance and stability of the antimicrobial. Post-processing of the most promising nano-encapsulation systems in order to obtain commercial products was further evaluated by purification/concentration (tangential flow filtration) or by transformation into redispersible dry products by lyophilization. Nano-liposomes were found overall superior to polymeric nanospheres for the encapsulation and delivery of our molecule and offer higher possible levels of tunability in terms of release rates and antifungal performance. Lyophilization in presence of carbohydrates turned out to be a valuable method for the preparation of dried products with enhanced long-term stability of the antifungal, compared to concentrates prepared by tangential flow filtration, a tedious process that impacted negatively the stability of the preservative.@en

Particulate products make up around 80% of chemical products, from all industry sectors. Examples given in this book include the construction materials, fine ceramics and concrete; the delicacies, chocolate and ice cream; pharmaceutical, powders, medical inhalers and sun screen; liquid and powder paints. Size distribution and the shape of the particles provide for different functionalities in these products. Some functions are general, others specific. General functions are powder flow and require – at the typical particulate concentrations of these products – that the particles cause adequate rheological behavior during processing and/or for product performance. Therefore, this book addresses particle packing as well as its relation to powder flow and rheological behavior. Moreover, general relationships to particle size are discussed for e.g. color and sensorial aspects of particulate products. Product-specific functionalities are often relevant for comparable product groups. Particle size distribution and shape provide, for example, the following functionalities: - dense particle packing in relation to sufficient strength is required in concrete construction, ceramic objects and pharmaceutical tablets - good sensorial properties (mouthfeel) to chocolate and ice cream - effective dissolution, flow and compression properties for pharmaceutical powders - adequate hiding power and effective coloring of paints for protection and the desired esthetical appeal of the objects - adequate protection of our body against sun light by sunscreen - effective particle transport and deposition to desired locations for medical inhalers and powder paints. Adequate particle size distribution, shape and porosity of particulate products have to be achieved in order to reach optimum product performance. This requires adequate management of design and development as well as sufficient knowledge of the underlying principles of physics and chemistry. Moreover, flammability, explosivity and other health hazards from powders, during handling, are taken into account. This is necessary, since great risks may be involved. In all aspects, the most relevant parameters of the size distribution (and particle shape) have to be selected. In this book, experts in the different product fields have contributed to the product chapters. This provides optimum information on what particulate aspects are most relevant for behavior and performance within specified industrial products and how optimum results can be obtained. It differs from other books in the way that the critical aspects of different products are reported, so that similarities and differences can be identified. We trust that this approach will lead to improved optimization in design, development and quality of many particulate products. @en

Presently, the majority of the worlds energy supply is dependent on fossil fuels. As these fuels area limited resource and have significant negative side effects, the way humanity uses these is unsustainable and other sources of energy have to be found. One of these sustainable energy sources is plant-derived biomass. However, biomass cannot be efficiently used in its natural form and needs to be converted to other products through processes such as pyrolysis and gasification. Pyrolysis will be the focus of this thesis, as fast pyrolysis of Miscanthus is studied for the BRISK 2 project at Process & Energy (TU Delft). However, the current setup used for pyrolysis research does not provide a complete mass-closure of the experiments, with only 80% of the total mass accounted for in the char, tar and gaseous yields. In order to improve this closure, four different methods were developed and investigated during this thesis. All of the pyrolysis experiments were performed in a Pyroprobe 5200. The pyrolysis parameters were comparable to fast pyrolysis, with a high heating rate of 600°C/s, a low residence time of 10 s and a Final Pyrolysis Temperature between 600°C and 1000°C. The objective of the first adjustment was to improve the purge flow stability, reduce the amount of blockages in the system and increase the accuracy of the experiments. The flow meter, controlling the purge flow, was replaced with a mass-flow controller and a tube in the setup was simplified and shortened. No further blockages were observed and the total mass-closure improved on average by 7.85 wt% over the temperature range of 600-1000°C, with an increase at every temperature. The second considered element was the homogeneity of the biomass. Two biomass feedstocks were investigated, the first feedstock consisted of inhomogeneous pellets grinded down to a size less than 80μm, while the second type was homogenized biomass of a size of less than 200μm. Both biomass types performed comparably to each other and better than the previous data collected with the setup. At 600°C the inhomogeneous biomass performed better, while at 700°C the homogeneous biomass gave a higher yield. The last two experimental series both focused on gravimetrically measuring the tars collected in the condenser of the setup, which was not gravimetrically measured before. The first of these methods removed the condenser in favour of a direct capture in a quartz trap. This gave a maximum yield increase of 1.14 wt% at 700°C. However, concerns of contaminating the gas mixture with tars arose, therefore this method was not investigated at higher temperatures. In the second technique, the 2ml of isopropanol in the condenser was evaporated from a glass Petri dish, leaving the tars behind. This method was explored over a larger temperature range (600-1000°C), yet only provided a maximum increase of 1.5 wt% at 1000°C, while giving significant fluctuations between experiments. Thus proving that neither of these methods is a suitable way of gravimetrically measuring the condenser.

Transition to renewable and alternative energy sources has become one of the most important subject of the decade. In The Netherlands today, 11.1% of the primary energy demand is obtained from renewable energy and the biomass accounts for 54% [1]. Another promising material for value added chemical synthesis is carbon dioxide. By utilization of CO2, the production of valuable chemical materials such as methanol, formic acid that can be used as a fuel, heat or power source and reducing the greenhouse gas effect by lowering emission levels will provide industrial and environmental advantages at the same time. Formic acid, used in the agriculture, pharmaceuticals and textile, is a key chemical that can also be used in energy conversion processes. In the current industrial practice, formic acid is produced by carbonylation of methanol with carbon monoxide. However, methanol is another value added chemical that is used in energy production, hence expensive for the process. Therefore, researchers started looking into alternative methods. Biomass and carbon dioxide utilization methods are two of them. In this thesis study, 10 kton and 100 kton annual production of 85 wt.% formic acid from wet oxidation of glucose and catalytic reduction of carbon dioxide, have been modeled and a techno-economic analysis is carried out. Additionally, the processes of obtaining glucose from lignocellulosic biomass and carbon dioxide from syngas by pre-combustion capture are also simulated. ASPEN Plus V8.8 process flowsheeting package program has been used for the simulations. From the results, in energy analysis biomass based formic acid synthesis process showed higher efficiency than CO2 based production. When the hydrogen peroxide and oxygen based biomass wet oxidation routes are compared, it is observed that oxygen based operation is more efficient than hydrogen peroxide based conversion because of lower utility requirements. It was determined that biomass based formic acid production can be economically profitable, but only for large scale wet oxidation via oxygen together with the sale of by-products obtained in pre-treatment process. On the contrary, no profit was obtained by the hydrogen peroxide route. In carbon dioxide utilization route, the breakeven selling price (BSP) of the formic acid was computed to be 7% more than the current market price. In order to improve the process, two case studies were created. In the first case, economically the most suitable reactor amount configuration is determined. However, the process was still not profitable. In the second case study, two times more active catalyst, Au=Al2O3, has been utilized. The process took half the residence time of the previous case and BSP value determined to be 2.6% lower than the current market price. Also, slight increase in efficiency is observed. In conclusion, more research should be done and experiments regarding reaction and intermediate substance performances should be conducted, in order to simulate the process more in detail. However, despite the uncertainties, in this era where the transition to greener energy production through the use of biomass and the reduction of carbon dioxide emissions have been made a definite target by the governments, the synthesis methods studied, will gain importance as the purposes of formic acid use increase.

Our use of pharmaceuticals, pesticides and personal care products leads to an increase of organic micropollutants (OMPs) into the aquatic environment. Conventional wastewater treatment plants are not designed for the removal of OMPs and need to be upgraded to reduce OMP contamination. The adsorption of OMPs to zeolites is proposed as an alternative treatment method. Zeolites are synthesized as powders, however they need to be shaped into pellets to be used in water treatment practice. This research focussed on engineering zeolite pellets and which properties of these pellets are important for the adsorption of OMPs. First the influence of the calcination temperature and binder content on the mechanical stability and porosity of the pellets was analysed. Second, the influence of two different preparation techniques (extrusion and high-shear granulation) and the introduction of a polymer on the mechanical stability, porosity and adsorption kinetics of the pellets was assessed. Third, the effect of the porosity on the breakthrough for an empty bed contact time (EBCT) of 20, 5 and 1 minute(s) was determined according to the linear driving force (LDF) model. It was found that an increasing binder content and calcination temperature increased the wear resistance and porosity of the pellets. However, the effect on the porosity is minimal. The introduction of the polymer had opposite effect on extruded and granulated pellets. For extruded pellets, the introduction of the polymer increased the porosity. However, the granulated pellets showed a decrease in porosity. A relation was found between the porosity and the wear resistance and between the porosity and adsorption kinetics. A larger porosity decreased the wear resistance of the pellets and increased the kinetic rate constant. The porosity was of great importance in relation to the breakthrough. First, the porosity in the zeolite pellets determined to a great extent the bulk density of the filter bed. A higher bulk density resulted in a later breakthrough point. The bulk density was also influenced by the shape of the pellet. Spherically-shaped (granulated) pellets had a higher bulk density than rod-shaped (extruded) pellets. Second, the porosity was related to the kinetic rate constant. At lower EBCTs (5 and 1 minute), the kinetic rate constant had an influence on the breakthrough point. For these EBCTs, a higher kinetic rate constant led to a later breakthrough point. It was recommended to optimize the zeolite pellets by making the extruded pellets in a more spherically-shaped form and to start column experiments to validate the LDF-model.

The increasing use of silver nanoparticles (AgNPs) in various products leads to their presence in the aquatic environment. The dissolution of AgNPs is an important property that has a direct impact on human health and the natural environment. Understanding the dissolution behaviour of nanoparticles in liquid suspensions is essential for predicting their potential toxic effect in organisms, ranging from viruses and bacteria to humans. Moreover, the dissolution rate of nanoparticles can explain some of their disinfecting properties, which are important for sanitation. The objective of this study is to determine the dissolution behaviour of AgNPs in pure water and to improve our understanding of its most fundamental principles. Dissolution constants of AgNPs found in literature span over a wide range, indicating that improvement of the measuring method is needed. AgNPs in this study were produced in a principally impurity-free way, from the gas phase, after which they were transferred into liquid solutions. The purity of the particles produced in this study is in principle higher compared to those used until now, which allows for higher precision in determining the dissolution constant. Measuring the silver ion concentration in the resulting liquid solutions (i.e., after introducing the AgNPs in the solution) with an ICP-MS at specific time intervals gave direct information on the dissolution kinetics. The experiments were repeated with particles having diameters from 7 to 12 nm and, as expected, dissolution kinetics were found to be highly dependent on particle size. The determined dissolution constants are in the same order of magnitude as the values reported in literature. To further improve the reliability of the measurements, the experiment needs to be repeated using different methods for transferring the particles into the liquid, given that the used bubbling method showed deficiencies.

Fermentation processes are considered to be essential to decrease our reliance on fossil fuel based products. However, the scale-up from lab-scale to industrial-scale has proven to be difficult. Computational Fluid Dynamics (CFD) has the potential to be a tool to optimize the scale-up and to help engineers understand the relevant hydrodynamics inside such reactors. However, traditional CFD simulations are computationally intensive and it is not uncommon that simulations can take several months to compute a few minutes of flow-time. Due to the recent development of GPU-based hardware, the Lattice-Boltzmann method (LBM) has been gaining much interest as this meant an orders-of-magnitude decrease of needed computational time compared to conventional CFD methods. In order to calibrate the models underlying the simulations, the obtained results of said simulations should be validated against experimentally obtained data, which is exceptionally scarce for industrial-scaled reactors. Hence the aim of this thesis is to to investigate the applicability of the LBM in high gas-flow, industrial sized reactors by studying three benchmark cases. Using Large Eddy Simulations (LES) and Euler-Lagrangian tracking of bubble parcels, the models provided by M-Star (MStar Simulations, LLC) are validated by replicating a small-scale reactor of which the LBM has already been successfully applied to. The industrial-scaled case consists of the simulation of the 22m3 industrial reactor located in Stavanger, which is an exception regarding the scarcity of experimental data for industrial sized reactors. As this data set did not encompass all the relevant data for aerated stirred tanks, the suitability of the LBM and provided models are also tested for a smaller scaled tank of which the Bubble Size Distribution (BSD) throughout the vessel is known. The applicability of the provided models will be tested by comparing the obtained gas hold-up, BSD and power consumption with experimental data sets. Although the LBM is suitable for industrial-scaled reactors, the provided models by M-Star are not sufficient to predict the gas hold-up and power consumption at high superficial gas velocities. The provided Free Particle drag correlation is not sufficient to describe the dispersion of bubbles throughout the vessel, leading to a significantly under-estimated gas hold-up. In addition, the parcel approach leads to the formation of large bubbles in the vessel. And although enforcing a maximum coalescence diameter does improve the BSD, the gas hold-up is not significantly influenced by the presence of large bubbles. Furthermore, the Euler-Lagrangian way of modeling bubble particles did not lead to the formation of gas cavities, which resulted in an insignificant drop in power consumption. Nevertheless, the current work provides a foundation for subsequent research.