1. Calorimetric insight into coupling between functionalized primary alkyl halideand vinylic organocuprate reagent : experimental determination of reaction enthalpies in the synthesis of (R)-ethyl 3-(tert-butyldimethylsilyloxy)hex-5-enoate - a key lactonized statinside chain precursorZdenko Časar, Marko Tramšek, Andreja Goršek, 2010, original scientific article Abstract: The first calorimetric study of coupling between organocuprate, derived from Grignard reagent (vinyl magnesium chloride), and primary alkyl halide (e.g. (S)-ethyl 3-(tert-butyldimethylsilyloxy)-4-iodobutanoate) has been conducted. This transformation is paramountly important for efficient preparation of (R)-ethyl 3-(tert-butyldimethylsilyloxy)hex-5-enoate – a key lactonized statin side chain precursor. The results obtained give thorough calorimetric insight into this complex low-temperature synthesis as well as a new understanding of the suggested reductive elimination of the final intermediates in the coupling reaction. Namely, the surprising unexpected spontaneous three-step exothermal event has been observed during controlled progressive heating of the mixture of the final intermediates to the room temperature. This phenomenon confirms that coupling between functionalized primary alkyl halide and vinylic organocuprate reagent is not a simple $S_N2$ substitution reaction. The presented study provides among others the first reported values of reaction enthalpies and corresponding adiabatic temperature rises of reaction mixture for all exothermic events that occurred in the (R)-ethyl 3-(tert-butyldimethylsilyloxy)hex-5-enoate synthesis. The obtained results ensure consequential thermal process safety knowledge which can be incorporated into safe process scale-up as well as design of reactor system with sufficient cooling capacity for industrial production of (R)-ethyl 3-(tert-butyldimethylsilyloxy)hex-5-enoate. Moreover, the results provide a basic guidance for other organocuprate coupling reaction systems.
Keywords: Grignard reagents, organocuprates, coupling reaction, reaction calorimetry, statins
Published in DKUM: 17.08.2017; Views: 1134; Downloads: 104
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3. Kefir grains production - An approach for volume optimization of two stage bioreactor systemAndreja Goršek, Marko Tramšek, 2008, original scientific article Abstract: The main objective of the present study was to design a continuous two-stage bioreactor system for kefir grains production. Based on the experimental data of time-depended kefir grain mass increase and average pH profile during kefir grains batch propagation, parameters of predictive growth and exponential pH models were initially estimated. Afterwards, the non-linear programming (NLP) optimization problem for estimating the optimal volumes of two unequal in series connected continuously stirred tank bioreactors (CSTB) has been developed. The NLP problem is based on criterion of minimal total holding time (MTHT), kefir grain mass balances in CSTB and parameters of the growth and pH models. The results showed that novel kefir grains production plant with two-stage continuous operation, at capacity, qm,KG,pr=3 kgh-1 and conversion, Xo,2=0.980, would primarily require investment in two CSTB with V1=5.93 m3 and V2=5.62 m3, respectively. Technological and economical authorization for a two-stage continuous bioreactor system was mainly confirmed with a more than five times lower total bioreactor volume compared to one-stage plant.
Keywords: chemical processing, bioprocesses, milk products, kefir grains production, bioreactor design, modeling, optimization
Published in DKUM: 31.05.2012; Views: 3283; Downloads: 126
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4. Analysis of growth models for batch kefir grain biomass production in RC1 reaction systemMarko Tramšek, Andreja Goršek, 2008, original scientific article Abstract: This work describes the statistical analysis of three mathematical models, modified for describing the kefir grain biomass growth curve. Experimental data of time-dependent kefir grain mass increase were used. The propagation was performed in RC1 batch reaction system under optimal bioprocess parameters (temperature, rotational frequency of stirrer, glucose mass concentration) using traditional cultivation in fresh, high-temperature, pasteurized whole fat cow's milk. We compared values of biological parameters obtained by applying the nonlinear regression of experimental data in logistic, Gompertz and Richards models. The most statistically appropriate model was determined using the seven statistical indicators. We established that the kefir grain biomass growth curve during batch propagation under optimal bioprocess conditions can be most successfully described using the Gompertz growth model.
Keywords: chemical processing, milk products, kefir grain growth, process parameters, design of experiments, modeling, mathematical models, Gompertz growth model, RC1
Published in DKUM: 31.05.2012; Views: 2990; Downloads: 134
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5. Aerobic digester design for the biodegradation of plant tannins in industrial wastewaterMarko Tramšek, Andreja Goršek, 2008, original scientific article Abstract: This paper describes aerobic digester design for the biodegradation of plant tannins in industrial wastewater. For optimal design, using the criterion of minimal total holding time, some experimental investigations into tannins' biodegradation rate in industrial wastewater were performed in the first part of this research. The chemical oxygen demand method (COD) was applied to follow the tannins degradation rate. The kinetic parameters of a supposed Aiba's inhibition kinetic model were determined using experimental data. In the second part of the study, equations for determining the optimal volumes of two in series connected aerobic digesters were established. Furthermore, a comparison is presented of volumes between one and two in series connected aerobic digester systems regarding wastewater volume flow rate, qV = 120 m3 d-1 and wastewater treatment efficiency, COD = 9 8%.
Keywords: digester design, plant tannins, Aiba's inhibition kinetic model, aerobic digestion, industrial wastewater
Published in DKUM: 31.05.2012; Views: 2113; Downloads: 67
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6. Determination of the process parameters relative influence on k[sub]La value using Taguchi design methodologyMarko Tramšek, Andreja Goršek, 2007, original scientific article Abstract: This article describes experimental determination of the relative impact of significant process parameters that influence volumetric oxygen mass transfer coefficient (kLa) using Taguchi design methodology. For this purpose an automated RC1 reaction calorimeter (Mettler-Toledo), which was originally developed for chemical processes, was modified for the bioprocesses. Simple fermentation using Baker's yeast was studied to illustrate the design procedure. Orthogonal array L25 was selected for the proposed design and ANOVA method was used for recognizing the relative influence of the process parameters. Within the observed range of temperature (?), fermentation media volume (VFM), and yeast mass concentration (?Y), these process parameters were found to be unimportant compared to the volumetric air flow rate (qV,a) and rotational frequency of the stirrer (fm). The qV,a had a substantial effect on the kLa value (89.2 %) and the fm had just a small one (3.6 %), meanwhile the remain fraction to 100 % represents error. The results refer strictly to the selected case study. Anyhow, the proposed procedure shows that application of the Taguchi approach for analyzing the oxygen mass transfer based on the experimental data obtained from a highly-automated laboratory reactor appears to have potential usage in general biopharmaceutical process design.
Keywords: bioprocess parameters, mass transfer, volumetric oxygen mass transfer coefficient, process parameters, Taguchi method, analysis of variance
Published in DKUM: 31.05.2012; Views: 2551; Downloads: 54
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7. A novel approach for assuring and following inoculum activity during kefir grains growth studies : application of dynamic pH profilesMarko Tramšek, Andreja Goršek, 2007, original scientific article Abstract: The profiles of kefir grains growth curves strongly depend on bioprocess conditions and inoculum viability. Therefore, accurate growth curve studies require the use of optimally active kefir grains as inoculum. Accordingly, the main objective of our study was experimental optimization of classic kefir grains activation procedure and afterwards, comparison among growth curves of differently activated kefir grains. For this purpose some experiments were initially performed in computer-controlled RC1 reactor provided data of dynamic pH profiles during batch propagation of differently activated grains. Experimental data were mathematically analyzed and using the special methodology of minimizing the absolute deviation of pH(t) profiles the minimal time for grains activation was determined. We established that optimal inoculum activity could be ensured only by the kefir grains, which were previously activated at least over eleven successive days. In the second part of research the growth curve of optimally activated kefir grains was constructed using experimental measurements and fitted with Gompertz model. The present results were compared with the results obtained by our previous study, where classically activated grains were used. We established that, inspite of equal daily kefir grain mass increase, considerable difference in growth curves of differently activated kefir grains exist.
Keywords: chemical processing, kefir grains, growth curve, minimal activation time, dynamic pH profiles, Gompertz model
Published in DKUM: 31.05.2012; Views: 2134; Downloads: 119
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8. Quantitative examination of process parameters during kefir grain biomass productionAndreja Goršek, Marko Tramšek, 2007, other scientific articles Abstract: This article examines the propagation of kefir grains in fresh HTP whole fat cows' milk, with some additions (glucose and bakers yeast). The objective of our work was an experimental determination of the various process parameters relative influence on the propagation and daily kefir grain increase mass, using the Taguchi method for experimental design. The effects of medium temperature, glucose mass concentration, bakers yeast mass concentration and the rotational frequency of the stirrer at four levels were studied. Orthogonal array layout of L16 was selected for the proposed experimental design. All experiments were performed in an automated laboratory reaction calorimeter RC1 (Mettler-Toledo) with the same milk (3.5 % fat). The gravimetric method was used to determine daily kefir grain mass increases. Relative contributions of the proposed influencing process parameters on the daily kefir grains increase mass were estimated by analysis of the variance (ANOVA). The highest increase (51.5 %) was found at the rotational frequency of the stirrer 90 (1/min), at glucose mass concentration 20 g/L, and at mediumtemperature 24 °C. Within the observed range of yeast mass concentrationthis process parameter was found to be insignificant compared to others. The rotational frequency of the stirrer has the highest relative influence on the daily kefir grains increase mass (37.3 %) while glucose mass concentration and medium temperature have lower ones, 18.8 % and 9.9 %, respectively. The remaining fraction represents error influence. The main reason for its relatively high value (34.0 %) is that kefir grains are bulky and awkward to handle. This fact confirms the importance of optimal kefir grains production management.
Keywords: chemical processing, milk products, kefir, kefir grain growth, process parameters, design of experiments, Taguchi method, RC1
Published in DKUM: 31.05.2012; Views: 2979; Downloads: 51
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9. Methodology for determination of anaerobic digestion kinetics using a bench top digesterMarko Tramšek, Andreja Goršek, Peter Glavič, 2007, original scientific article Abstract: This paper presents a methodology for determining the microbial growth kinetics of an ideal anaerobic process in a non-ideal laboratory anaerobic digester (Armfield). Some laboratory experiments were performed, to confirm the proposed methodology. Having the same zero biomass concentration, some process parameters were changed and their influence on substrate outlet concentration was monitored. The specific growth rate of the biomass, the saturation constant of the substrate, and the yield coefficient were calculated, on the basis of the measured values. These parameters enabled us to perform a dynamic simulation of an anaerobic process in ideal continuously-stirred tank reactors (CSTR). The results represented the mass concentration profiles for substrate and biomass, from which the time required for reaching the steady state (60 d), where the operation is optimal, could be determined. The laboratory anaerobic digester provided operational process data, which are applicable for wastewater treatment plant design purposes.
Keywords: wastewater treatment, anaerobic digester, kinetics, dynamic simulation
Published in DKUM: 31.05.2012; Views: 2265; Downloads: 108
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10. The aerobic biodegradation kinetics of plant tannins in industrial wastewaterMarko Tramšek, Andreja Goršek, Peter Glavič, 2006, original scientific article Abstract: This paper describes an experimental determination of the biodegradation rate for tannins present in industrial wastewater, after the extraction of chestnut chips. Experiments were performed in a laboratory aerobic reactor (Armfield) by using biomass from an existing industrial wastewater treatment plant. The outlet tannins concentration was determined under various processing conditions. Simultaneously, an optical microscope was used to monitor the mix of microbiological cultures in the biomass. On the basis of data obtained in experiments, non-linear regression was used to perform parametric analysis of various kinetic models, which took into account inhibition, as quoted in literature (Haldane, Edwards, Aiba, Luong). The statistical analysis, based on the P-criterion, F-criterion, adjusted coefficient of determination, Kolmogorov-Smirnov test and root mean squared error, showed that the biodegradation of plant tannins in industrial wastewater under selected conditions for aerobic digestion, can be most successfully described statistically by the Aiba's kinetic model.
Keywords: plant tannins, susbtrate inhibition, kinetic models, statistic analysis, aerobic industrial wastewater digestion
Published in DKUM: 31.05.2012; Views: 1996; Downloads: 50
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