Despite the expanding presence of microscale technology in chemical synthesis and energy production as well as in biomedical devices and analytical and diagnostic tools, its potential in biocatalytic processes for pharmaceutical and fine chemicals, as well as related industries, has not yet been fully exploited. The aim of the scientific review paper is to shed light on the strategic advantages of the promising technology for the development and realization of biocatalytic processes and subsequent product recovery steps, demonstrated with examples from the literature. Constraints, opportunities, and the future outlook for the implementation of key green engineering methods and the role of supporting tools such as mathematical models to establish sustainable production processes are discussed. The review was published in a prestige scientific journal, which fits in top 5% (3/161) journals in the field of biotechnology and applied technology. The paper presents an exceptional contribution to research in the field of microprocess engineering and biotechnology, and for technological development in the field of production process intensification. The article has been cited 85 times. Review article is a part of the basic orientation of the program group and presents fundaments for further research within P2-0191 (RS1).
COBISS.SI-ID: 1536258243
A mathematical model comprising transport phenomena and enzyme-catalysed reaction performed on the inner walls of the continuously operated microreactor with surface-immobilized-transaminase was developed. Oriented enzyme immobilization enabling unhindered accessibility of enzyme active sites was obtained by using fusion protein N-SBM-ATA-wt consisting of selected x-transaminase ATA-wt and the positively charged Zbasic2 tag, which established ionic interactions with silicon/glass microchannel surface. Enzyme-catalyzed transamination of methylbenzylamine and pyruvate to acetophenone and L-alanine was described by surface kinetics based on a ping-pong bi-bi mechanism. Reaction kinetic parameters were preliminarily defined in a batch system using various initial substrates concentrations and further applied in the surface reaction description. The results are published in one of the leading and recognized scientific journals in the field of chemical engineering. The results represent a significant contribution to the science and enable further researches in the field of enzymatic reactions in microreactors. The article has been cited 12 times. This article is part of a wider research presented in: Novak et al., Microfluid. Nanofluidics, 2015, 19, 75–83, Novak et al., J. Environ. Eng., 2016, 6, 33–38; Miložič et al., N. Biotechnol., 2018, 47, 18–24. Results are fundaments for further research within P2-0191 (RS1).
COBISS.SI-ID: 1537316803
Droplet-based liquid–liquid extraction in a microchannel was studied, both theoretically and experimentally. A full 3D mathematical model, incorporating convection and diffusion in all spatial directions along with the velocity profile, was developed to depict the governing transport characteristics of droplet-based microfluidics. The finite elements method, as the most common macroscale simulation technique, was used to solve the set of differential equations regarding conservation of moment, mass and solute concentration in a two-domain system coupled by interfacial surface of droplet-based flow pattern. The model was numerically verified and validated online by following the concentrations of a solute in two phases within the microchannel. The relative azobenzene concentration profiles in a methanol/n-octane two-phase system at different positions along the channel length were retrieved by means of a thermal lens microscopic (TLM) technique coupled to a microfluidic system, which gave results of high spatial and temporal resolution. Very good agreement between model calculations and online experimental data was achieved without applying any fitting procedure to the model parameters. Research findings have been published in a recognized scientific journal in the field of biochemical research methods. The results represent an important scientific contribution in the field of liquid-liquid extraction in microfluidic devices and as such contribute to further progress. Results are important for further research within P2-0191 (RS1).
COBISS.SI-ID: 1536245187
A micro packed-bed reactor (µPBR) based on two-parallel-plates configuration with immobilized Candida antarctica lipase B in the form of porous particles (Novozym® 435) was theoretically and experimentally characterized. A residence time distribution (RTD) within µPBRs comprising various random distributions of particles placed in one layer was computationally predicted by a mesoscopic lattice Boltzmann (LB) method. Numerical simulations were compared with measurements of RTD, obtained by stimulus-response experiment with a pulse input using glucose as a tracer, monitored by an electrochemical glucose oxidase microbiosensor integrated with the reactor. The model was validated by a good agreement between the experimental data and predictions of LB model at different conditions. The developed µPBR was scaled-up in length and width comprising either a single or two layers of Novozym® 435 particles and compared regarding the selected enzyme-catalyzed transesterification. A linear increase in the productivity with the increase in all dimensions of the µPBR between two-plates demonstrated very efficient and simple approach for the capacity rise. Further characterization of µPBRs of various sizes using the piezoresistive pressure sensor revealed very low pressure drops as compared to their conventional counterparts and thereby great applicability for production systems based on numbering-up approach. The results were published in a reputable and established journal in the field of chemical engineering. The article is of an essential role in in-depth understanding transport phenomena and microkinetics using highly controlled conditions in microflow device and multiscale modelling. This article is the result of some preliminary research in the field: Bajič et al., Process Biochem., 2017, 52, 63–72; Žnidaršič Plazl, J. Flow Chem., 2017, 7, 111–117; Prašnikar et al., Chemistry today, 2017, 35, 18–20. Results are important for further research within P2-0191 (RS1).
COBISS.SI-ID: 1537783747
The kinetics of enzymatic aldol reaction catalyzed by DERA (2-deoxyribose- 5-phosphate aldolase) was studied. The reaction between acetyloxyacetaldehyde/acetaldehyde and chloroacetaldehyde/acetaldehyde in the presence of DERA produces chiral lactol intermediates, which are useful in the synthesis of optically pure super-statins. A three-step kinetic model was proposed including the formation of the intermediate product, synthesis of the main desired product and the synthesis of the side product by parallel non-desired secondary reaction. The kinetics of enzyme inactivation caused by reactants was also included in kinetic model design. The establishment of the kinetic model based on the two-substrates binding assuming random mechanism. The highest concentrations of the desired main product were produced in the case of fed-batch experiments applying such feeding regime that minimal surplus of reactants in the reaction mixture was attained, which consequently led to lower losses in the enzyme activity. To our knowledge, this is the first developed kinetic model describing the DERA catalyzed reaction of 2-substituted acetaldehydes to corresponding lactols. Obtained kinetic model can be used in further reactor design in the manner of optimizing the process by lowering the loss of enzyme activity in order to achieve higher amounts of the desired main product. Results are published in one of the leading and recognized scientific journals in the field of chemical engineering. The results represent an important contribution to the understanding of enzymatic reactions and allow further improvement and intensification of the processes in pharmaceutical industry. A theme studied by PhD student Aleš Ručigaj was awarded by The Krka Award for an exceptional dissertation. Other results were presented in Ručigaj et al., Org. Process Res. Dev., 2013, 17, 854–862. Results are fundaments for further research within P2-0191 (RS1&2).
COBISS.SI-ID: 1752623
The study concerns the development/kinetics of rheological properties of aqueous TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl)-oxidized nanofibrillated cellulose (NFC) suspensions prepared from a commercially available TEMPO-NFC powder. Ageing of hydrogels with concentrations from 1 to 3 wt% of TEMPO-NFC was investigated by monitoring shear flow and linear viscoelastic properties after different days from sample preparation. For quantitative representation of the results time dependencies of zero shear viscosity and storage modulus are given. The increase of rheological parameters is described by a sigmoidal mathematical model. By superposition of individual data sets master curves displaying reduced values of the most significant parameters are constructed, showing the effect of ageing kinetics. The reduced storage modulus and zero-shear viscosity values increase for 2 and 3 decades, respectively, before reaching final values. Obtained results are useful for several applications of nanocellulose hydrogels, especially for those, where pumping, mixing, coating or injecting is necessary. For example, in biomedical field, a less viscous suspension can be injected to the spot of interest, where the final gel properties are developed. The results of the research were published in the scientific journal ranked first in the field of paper and wood materials science. The results represent an important scientific contribution to the understanding of the rheological properties of nanofibrillic cellulose hydrogels and as such has an important impact on the progress in the development of new biomedical products. Results are important for further research within P2-0191 (RS1&2).
COBISS.SI-ID: 1538034371
Both Laponite and scleroglucan can find several applications in various fields (from industrial to biomedical one) in virtue of their peculiar features and rheological properties displayed in aqueous phases. Structural states of Laponite dispersions strongly depend on concentration and ionic strength. When attractive and repulsive interparticle interactions are so effective that they lead to arrested states (attractive gel or repulsive glass), the rheological behaviour of the dispersion undergoes a sharp transition, from quasi-Newtonian to markedly shear thinning and viscoelastic. Conversely, scleroglucan solutions gradually change to weak gels with increasing polymer concentration. The present work is concerned with aqueous Laponite-scleroglucan mixed systems, obtained according to different preparation modes, and is aimed at examining how much the content and proportion of both components affect the viscoelastic and flow properties of the mixed system. Research results are published in one of the leading and recognized scientific journals in the field of applied chemistry and polymer science. Results are important for further research within P2-0191 (RS1).
COBISS.SI-ID: 1537400003
A new innovative synthetic approach for the preparation of maleimidobenzoxazines was developed. For the first time the phenolic diversity in maleimidobenzoxazine compounds was enabled, opening many possibilities for tailoring properties of maleimidobenzoxazines through phenolic diversity. The key in a successful implementation of a novel synthetic approach was utilization of aminomaleimide compound prepared by modified synthetic path, without the need for chromatographic purification. Yields of prepared maleimidobenzoxazines reached up to 95%, which is a significant improvement prior to previous studies dealing with the maleimidobenzoxazines. Aminomaleimide and all novel maleimidobenzoxazine substances were characterized by 1H NMR, 13C NMR and FTIR spectroscopies. The curing behaviour of prepared maleimidobenzoxazines was investigated by DSC analysis and mechanical properties by DMA analysis. Novel maleimidobenzoxazines showed similar properties comparing to the already presented in the literature showing high glass transition temperature values over 240 °C. Thermogravimetric analysis proved improved thermal stability of maleimidobenzoxazines compared to anilinobenzoxazines. Finally, the use of prepared maleimidobenzoxazines was investigated by the means of Diels-Alder reaction as a possible benzoxazine bearing maleimide group precursor for self-healing purposes. A new approach to the synthesis of maleimidobenzoxazines was published in a respectable scientific journal in the field of polymer science. The proposed synthesis path allows further development and synthesis of new maleimidobenzoxazines with desired applicative properties. The results are an important contribution to the field of benzoxazines and will affect further research. This article is a part of a more extensive study presented in: Ručigaj et al., Express Polym. Lett., 2015, 9, 647–657; Ambrožič et al., Polymer, 2015, 76, 203–212; Štirn et al., Express Polym. Lett., 2016, 10, 537–547; Štirn et al., Macromol. Mat. Eng., 2018, 303, 1800284. Results are fundamental for further research within P2-0191 (RS2).
COBISS.SI-ID: 1537432771
Presence of nonharmful natural organic species in drinking water treated by the commonly applied chlorine disinfection is highly undesirable since they are converted to halogenated hydrocarbons, which are proven to have adverse effects to human health, during the treatment. The use of hydrodynamic cavitation in combination with the ozone, hydrogen peroxide and the UV-based oxidation processes is proposed. Humic acid as a source of dissolved organic carbon (DOC) was used. The hydrodynamic cavitation effectiveness for DOC removal was proven for low amounts of applied oxidants and high UV absorbance of the samples. The findings of the research were published in the leading scientific journal in the field. The cavitation-assisted advanced oxidation processes have been proven as a perspective approach in the field of drinking water disinfection. The article has been cited 14 times. Research results were published also in: Čehovin et al., Acta Chim. Slov., 2016, 63, 837–849; Marques et al., Chem. Eng. J., 2018, 345, 669–678. Results are fundaments for further research within P2-0191 (RS3).
COBISS.SI-ID: 1537341379
The aim of this study was to evaluate the importance of wastewater treatment on the release of microplastics into the environment. This is the first study reporting on the sizes and distribution of microbeads, which are actually released into the environment. It was first shown, that the existing researches have reported results only for the particles of larger sizes and thus missed the most abundant fraction of microplastics, which represents the majority in the particle size distribution. It has been proven that wastewater treatment plant cannot capture all the microplastics, especially smaller particles as those used in cosmetic products. The results of the study are important for understanding the behaviour of microplastics in the environment, their fate and effects on various organisms. The article has been cited 16 times and is a part of a more extensive study presented also in: Kalčikova et al., Environ. Pollut., 2017, 203, 1108–1115; Kalčikova et al., N. Biotechnol., 2018, 47, 67–72; Žgajnar Gotvajn et al., J. Environ. Manage., 2018, 228, 165–168. Results are important for further research within P2-0191 (RS3).
COBISS.SI-ID: 1537587395