| 1. |
- Fornstedt, Torgny, et al.
(författare)
-
HPLC vs UHPLC - a comparison of peak asymmetry and plan to step forward using Quality by Design (QbD) related to analytical methods
- 2012
-
Konferensbidrag (refereegranskat)abstract
- The purpose of this study is to demonstrate, with experiments and with computer simulations based on a firm chromatographic theory, that the wide spread perception of that the United States Pharmacopeia tailing factor must be lower than 2 (Tf < 2) is questionable when using the latest generation of LC equipment. It is shown that highly efficient LC separations like those obtained with sub-2 ïm porous and 2.7 ïm superficially porous particles (UHPLC) produce significantly higher Tf-values than the corresponding separation based on 3 ïm porous particles (HPLC) when the same amount of sample is injected. Still UHPLC separations provide a better resolution to adjacent peaks. Expressions have been derived that describe how the Tf-value changes with particle size or number of theoretical plates. Expressions have also been derived that can be used to scale the injection volume based on particle size or number of theoretical plates to maintain the Tf-value when translating a HPLC separation to the corresponding UHPLC separation. This aspect has been ignored in previous publications. Finally, data obtained from columns with different age/condition indicate that Tf-values should be complemented by a peak width measure to provide a more objective quality measure. A plan to take a further step for using Quality by Design (QbD) related to analytical methods will also be presented [Ref 1]. Continuous improvement of an original HPLC method to an UHPLC method will be the used as a case study. The capability of the two methods will be deeply studied using mechanistic comparisons. Method criteria that must be fulfilled for the two chromatographic methods will be stated. [1] 2012 PDA Europe Workshop Quality by Design The Role of Analytical Science in Implementing QbD − Technical and Regulatory Aspects, Liverpool UK 6-7 March. This is an industrial – academic cooperation in the Fundamental Separation S
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| 2. |
- Fornstedt, Torgny, et al.
(författare)
-
Why UHPLC Produces More Tailing Peaks Than HPLC, Why it Does Not Matter and How it Can be Addressed
- 2012
-
Konferensbidrag (refereegranskat)abstract
- The purpose of this study is to demonstrate, with experiments and with computer simulations based on a firm chromatographic theory, that the wide spread perception of that the United States Pharmacopeia tailing factor must be lower than 2 (Tf < 2) is questionable when using the latest generation of LC equipment. It is shown that highly efficient LC separations like those obtained with sub-2 ÎŒm porous and 2.7 ÎŒm superficially porous particles (UHPLC) produce significantly higher Tf -values than the corresponding separation based on 3 ÎŒm porous particles (HPLC) when the same amount of sample is injected. Still UHPLC separations provide a better resolution to adjacent peaks. Expressions have been derived that describe how the Tf-value changes with particle size or number of theoretical plates. Expressions have also been derived that can be used to scale the injection volume based on particle size or number of theoretical plates to maintain the Tf-value when translating a HPLC separation to the corresponding UHPLC separation. An aspect that has been ignored in previous publications. Finally, data obtained from columns with different age/condition indicate that Tf-values should be complemented by a peak width measure to provide a more objective quality measure.
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| 3. |
- Petersson, Patrik, et al.
(författare)
-
Why ultra high performance liquid chromatography produces more tailing peaks than high performance liquid chromatography, why it does not matter and how it can be addressed
- 2011
-
Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X .- 0021-9673 .- 1873-3778. ; 1218:39, s. 6914-6921
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to demonstrate, with experiments and with computer simulations based on a firm chromatographic theory, that the wide spread perception of that the United States Pharmacopeia tailing factor must be lower than 2 (Tf < 2) is questionable when using the latest generation of LC equipment. It is shown that highly efficient LC separations like those obtained with sub-2 μm porous and 2.7 μm superficially porous particles (UHPLC) produce significantly higher Tf-values than the corresponding separation based on 3 μm porous particles (HPLC) when the same amount of sample is injected. Still UHPLC separations provide a better resolution to adjacent peaks. Expressions have been derived that describe how the Tf-value changes with particle size or number of theoretical plates. Expressions have also been derived that can be used to scale the injection volume based on particle size or number of theoretical plates to maintain the Tf-value when translating a HPLC separation to the corresponding UHPLC separation. An aspect that has been ignored in previous publications. Finally, data obtained from columns with different age/condition indicate that Tf-values should be complemented by a peak width measure to provide a more objective quality measure.
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| 4. |
- Agmo Hernández, Víctor, et al.
(författare)
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Enhanced interpretation of adsorption data generated by liquid chromatography and by modern biosensors
- 2013
-
Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1317, s. 22-31
-
Tidskriftsartikel (refereegranskat)abstract
- In this study we demonstrate the importance of proper data processing in adsorption isotherm estimations. This was done by investigating and reprocessing data from five cases on two closely related platforms: liquid chromatography (LC) and biosensors. The previously acquired adsorption data were reevaluated and reprocessed using a three-step numerical procedure: (i) preprocessing of adsorption data, (ii) adsorption data analysis and (iii) final rival model fit. For each case, we will discuss what we really measure and what additional information can be obtained by numerical processing of the data. These cases clearly demonstrate that numerical processing of LC and biosensor data can be used to gain deeper understanding of molecular interactions with adsorption media. This is important because adsorption data, especially from biosensors, is often processed using old and simplified methods. (C) 2013 Elsevier B.V. All rights reserved.
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| 5. |
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| 6. |
- Arnell, Robert, et al.
(författare)
-
Adsorption behaviour of a quinidine carbamate-based chiral stationary phase : Role of the additive
- 2009
-
Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1216:16, s. 3480-3487
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we incorporate the additive properties into the theoretical model of a general preparative chromatographic system; this is normally not done and this limits a proper process optimization. As a model phase system, we used the adsorption of 9H-fluoren-9-ylmethoxycarbonyl-allylglycine (Fmoc-allylglycine) enantiomers on a quinidine carbamate-based chiral stationary phase (anion exchanger) together with a methanol-glacial acetic acid-ammonium acetate eluent. The inverse method was used to measure the competitive adsorption isotherms of both the Fmoc-allylglycine enantiomers as well as the non-detectable additive acetic acid. It was concluded that this enantioselective preparative system is well described by a non-heterogeneous adsorption model and that the loading capacity is very high. The proposed model is valid over a wide range of additive concentrations, which is important for process optimization.
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| 7. |
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| 8. |
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| 9. |
- Bergman, Penny, 1982, et al.
(författare)
-
Perceptual validation of auralized heavy-duty vehicles
- 2015
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Ingår i: Euronoise 2015. ; , s. 769-774
-
Konferensbidrag (refereegranskat)abstract
- Auralization is a valuable tool when evaluating the effect of traffic noise on people. The present study focuses on the validation of auralization of heavy-duty vehicles with a diesel engine. To capture the characteristics of the diesel engine a granular approach has been used. The granular approach has proven to be successful in a previous validation test examining two microphone positions around a still-standing truck. In the present study a granular approach was used to achieve pass-by noise at an artificial listening position alongside a Volvo truck (experiment 1) and pass-by noise inside an apartment (experiment 2). The aim of experiment 1 was to determine the number of interpolated sets of grains needed, in order to create a perceptually valid auralized signal. The results were used in the auralization of pass-by noise in an apartment in experiment 2. 20 and 15 participants respectively rated original recordings and auralized signals on four different attributes: realism, annoyance, and emotional response measured by valence and arousal. The results of both experiments suggest that auralizations of heavy-duty vehicles are successful and usable. It further indicates that what distinguish the auralized signals from the original recordings is mostly the arousal responses.
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| 10. |
- Dashti, Fatemeh, 1991, et al.
(författare)
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Finite Element Modelling of Tunnel Shielding in Vibration Measurements of Ground-Borne Noise
- 2024
-
Ingår i: Lecture Notes in Mechanical Engineering. - 2195-4356 .- 2195-4364. ; 14th International Work-shop on Railway Noise, IWRN 2022, s. 723-730
-
Konferensbidrag (refereegranskat)abstract
- Several factors can affect vibration levels during transmission from a tunnel to the ground surface. This study investigates the effect of a tunnel cavity in bedrock with force excitation at the tunnel floor. The tunnel geometry affects the wave propagation around the tunnel and the directivity pattern of waves propagating to the ground surface. For instance, there is no direct propagation path of ground waves from the excitation in the tunnel floor to positions on the tunnel walls. The waves reaching the walls have been diffracted at the tunnel corners. This tunnel shielding effect is here investigated regarding sensor position and direction and directivity of wave propagation up to 1 kHz using the finite element method. An underground tunnel is modelled in 2D and 3D for a bedrock ground typical for Swedish conditions. The results show that the velocity levels at the tunnel floor are higher than at the tunnel wall. It is also shown that the tunnel shielding effect causes decreased vibration levels at mid-frequencies above the tunnel and significant level fluctuations, especially at higher frequencies. The results from the 3D modeling support the 2D results.
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| 11. |
- Enmark, Martin, et al.
(författare)
-
A systematic investigation of algorithm impact in preparative chromatography with experimental verifications
- 2011
-
Ingår i: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673 .- 1873-3778. ; 1218:5, s. 662-672
-
Tidskriftsartikel (refereegranskat)abstract
- Computer-assisted optimization of chromatographic separations requires finding the numerical solution of the Equilibrium-Dispersive (ED) mass balance equation. Furthermore, the competitive adsorption isotherms needed for optimization are often estimated numerically using the inverse method that also solves the ED equations. This means that the accuracy of the estimated adsorption isotherm parameters explicitly depends on the numerical accuracy of the algorithm that is used to solve the ED equations. The fast and commonly used algorithm for this purpose, the Rouchon Finite Difference (RFD) algorithm, has often been reported not to be able to accurately solve the ED equations for all practical preparative experimental conditions, but its limitations has never been completely and systematically investigated. In this study, we thoroughly investigate three different algorithms used to solve the ED equations: the RFD algorithm, the Orthogonal Collocation on Finite Elements (OCFE) method and a Central Difference Method (CDM) algorithm, both for increased theoretical understanding and for real cases of industrial interest. We identified discrepancies between the conventional RFD algorithm and the more accurate OCFE and CDM algorithms for several conditions, such as low efficiency, increasing number of simulated components and components present at different concentrations. Given high enough efficiency, we experimentally demonstrate good prediction of experimental data of a quaternary separation problem using either algorithm, but better prediction using OCFE/CDM for a binary low efficiency separation problem or separations when the compounds have different efficiency. Our conclusion is to use the RFD algorithm with caution when such conditions are present and that the rule of thumb that the number of theoretical plates should be greater than 1000 for application of the RFD algorithm is underestimated in many cases
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| 12. |
- Enmark, Martin, et al.
(författare)
-
A systematic investigation on the accuracy of computer simulations for optical isomers in industrial settings
- 2010
-
Konferensbidrag (refereegranskat)abstract
- Predicting the band profiles of typical chromatographic separations using the approach of the inverse method (IM) [2] requires finding the numerical solution of the Equilibrium-Dispersive (ED) mass balance equation [1]. The accuracy of the determination of the competitive adsorption isotherms is therefore explicitly dependent on the choice of algorithm to solve the ED model. Earlier studies have shown that the well known RFD algorithm [3] has limitations in its accuracy for certain simulated conditions such as column efficiency and adsorption isotherm type [5]. In this study, we thoroughly investigate three different algorithms, the rapid and well known Rouchon Finite Difference (RFD) algorithm [3], the Orthogonal Collocation on Finite Elements (OCFE) method [4] and the Central Difference Method (CDM) algorithm developed by us. Firstly, a systematic investigation is made, comparing the different algorithms under a broad range of different synthetic conditions. Secondly, we apply all three algorithms using the IM on real experimental systems; (I) one high efficiency quaternary separation and (II) one pharmaceutical industry application with a chiral intermediate separation. We have found discrepancies between the conventional (RFD) and the more accurate (OCFE and CDM) algorithms for several synthetic conditions such as low efficiency, increasing number of simulated components and components present at different concentrations. Given high enough efficiency, we experimentally demonstrate good prediction of experimental data of a quaternary separation problem using either algorithm but better prediction of OCFE/CDM for a binary low efficiency separation problem. Our conclusion is to use the RFD algorithm with caution when any of the particular conditions we have investigated is valid. When the highest accuracy is sought, there is no doubt that OCFE or CDM should be the algorithms of choice. However, given the computational speed of RFD, we also recommend it for preliminary parameter fitting. For conditions where we have shown the algorithms to produce practically identical solutions, RFD can be applied with greater certainty. It remains to be thoroughly investigated the effect on the particular shape of the adsorption isotherm on the obtained solution, for example type III having inflection points.
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| 13. |
- Enmark, Martin, et al.
(författare)
-
Adsorption Isotherm Determination for Reliable Phase System Characterization in SFC : Challenges and Pitfalls
- 2012
-
Konferensbidrag (refereegranskat)abstract
- Recently the pharmaceutical industry has started to replace HPLC with SFC because of incentives to lower the environmental impact and as well as increasing performance. Reliable characterization of the adsorption processes in SFC, is therefore of utmost importance. The key thermodynamic phase system information is obtained by rigorous determination of adsorption isotherms over a broad concentration range. If properly processed, this data gives not only correct information about the degree of heterogeneity but also the values of the energy of interactions and monolayer capacities of each individual type of adsorption site in the phase system; ultimately, this can result in identification of the types of interactions (dipole-dipole, van der Waals interactions etc.). In this study, we will present the transfer of LC adsorption characterization methods to SFC conditions using several model compounds with several different methods for adsorption isotherm determination traditionally applied with success in LC, and now modified for SFC. We have limited our investigation to methanol as modifier and used the operational conditions, temperature and backpressure most typically observed in industrial settings; in addition, we have used commercial standard SFC-equipment. The results clearly shows that adsorption isotherm determinations in SFC are considerably more complicated than in LC; we will go through the most important pitfalls and give guidelines for more rigorous determinations of adsorption data in SFC. This is an industrial – academic cooperation in the Fundamental Separation Science Group www.separationscience.se
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| 14. |
- Enmark, Martin, et al.
(författare)
-
Computer-assisted optimization in preparative SFC, Challenges, Pitfalls and Solutions
- 2010
-
Konferensbidrag (refereegranskat)abstract
- Preparative packed column SFC (pSFC) is an environmentally favorable alternative to normal phase HPLC. We are participating in a larger research project where the overreaching goal is to make an impact in the recovery of high-value compounds from agricultural byproducts and waste materials using environmentally sustainable techniques. Our specific task is to isolate large amounts of valuable compounds from discarded biomaterials using pSFC. It is still not possible to accurately model, simulate and optimize a preparative SFC proess, although SFC has been in use for almost fifty years. This is mainly because of the compressibility of the mobile phase and how this influences the physical parameters of the system. More particular, if pSFC is operated under combinations of back pressures and flow rates that give negligible pressure drop, it has been demonstrated and implied, that the tools developed and used within HPLC, can be transferred and used successfully [1, 2]. However, when the pressure drop becomes noticeable, the induced density gradient significantly increases the complexity. An earlier study has clearly described the effect of this pressure gradient on the retention factor, and also the column efficiency [3]. However, it remains to be investigated how the entire adsorption isotherm depends on the density.In this study we will investigate the use of the inverse and the perturbation peak methods, originally developed within LC, to determine the nonlinear adsorption isotherm for i) negligible, and ii) non-negligible pressure drop conditions respectively. To do this, we will use a simple racemic substance and a cellulose based CSP with a column equipped with pressure sensors at the inlet and outlet. Using obtained parameters we will validate the methods by simulating the separation using a variable coefficient version of the Equilibrium-Dispersive model for cases i and ii. [1] S. Ottiger, J. Kluge, A. Rajendran , M. Mazzotti, J. Chromatogr., A 1162 (2007) 74-82[2] C. Wenda, A. Rajendran, J. Chromatogr., A 1216 (2009) 8750-8758[3]A. Rajendran, O. Kräuchi, M. Mazzotti, M. Morbidelli, J Chromatogr., A, 1092 (2005) 149-160[4] G. Guiochon, A. Felinger, D. G. Shirazi, A. M. Katti, Fundamentals of Preparative and Nonlinear Chromatography 2nd Ed, Elsevier Academic Press (2006).
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| 15. |
- Enmark, Martin, et al.
(författare)
-
Computer Assisted Optimization of Pharmaceutical Purification - The Impact of Algorithms and Experimental Approach
- 2010
-
Konferensbidrag (refereegranskat)abstract
- Computer assisted process optimization of chromatographic separations requires the selection of computer algorithms and measurement of relevant parameters. In this study, we will investigate how the choice of algorithms and the number of performed initial experiments affect the estimated optimal separations conditions. We will focus on conditions typically encountered for slurry packing coated 20 µm CSP in large-scale columns used for pharmaceutical intermediate purification.Probably the most essential for parameters in this context are the adsorption isotherm parameters for the components. The rapid "inverse method" is commonly used and this method requires that one numerically solve the mass balance equations describing the chromatographic process. Here we thoroughly investigate how different algorithms that solve the Equilibrium-Dispersive (ED) mass balance equations will affect the estimated adsorption isotherm parameters.Furthermore, we will investigate and compare how different strategies affect the prediction of the optimal separation conditions. First, we will use a more rapid approach that requires a minimum of experiments and uses standard algorithms to estimate optimal conditions. Secondly, we will use a more exact approach that requires more experiments and uses more advanced simulation- and optimization algorithms
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| 16. |
- Enmark, Martin, 1984-, et al.
(författare)
-
Determination of adsorption isotherms in supercritical fluid chromatography
- 2013
-
Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1312, s. 124-133
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract In this study we will demonstrate the potential of modern integrated commercial analytical SFC-systems for rapid and reliable acquisition of thermodynamic data. This will be done by transferring the following adsorption isotherm determination methods from liquid chromatography (LC) to supercritical fluid chromatography (SFC): Elution by Characteristic Points (ECP), the Retention Time Method (RTM), the Inverse Method (IM) and the Perturbation Peak (PP) method. In order to transfer these methods to SFC in a reliable, reproducible way we will demonstrate that careful system verification using external sensors of mass flow, temperature and pressure are needed first. The adsorption isotherm data generated by the different methods were analyzed and compared and the adsorption isotherms ability to predict new experimental elution profiles was verified by comparing experiments with simulations. It was found that adsorption isotherm data determined based on elution profiles, i.e., ECP, IM and RTM, were able to accurately predict overloaded experimental elution profiles while the more tedious and time-consuming PP method, based on small injections on concentration plateaus, failed in doing so.
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| 17. |
- Enmark, Martin, et al.
(författare)
-
Enantioseparation of omeprazole effect of different packing particle size on productivity
- 2012
-
Ingår i: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673. ; 1240:1, s. 123-131
-
Tidskriftsartikel (refereegranskat)abstract
- Enantiomeric separation of omeprazole has been extensively studied regarding both product analysis and preparation using several different chiral stationary phases. In this study, the preparative chiral separation of omeprazole is optimized for productivity using three different columns packed with amylose tris (3,5-dimethyl phenyl carbamate) coated macroporous silica (5, 10 and 25 Όm) with a maximum allowed pressure drop ranging from 50 to 400 bar. This pressure range both covers low pressure process systems (50–100 bar) and investigates the potential for allowing higher pressure limits in preparative applications in a future. The process optimization clearly show that the larger 25 Όm packing material show higher productivity at low pressure drops whereas with increasing pressure drops the smaller packing materials have substantially higher productivity. Interestingly, at all pressure drops, the smaller packing material result in lower solvent consumption (L solvent/kg product); the higher the accepted pressure drop, the larger the gain in reduced solvent consumption. The experimental adsorption isotherms were not identical for the different packing material sizes; therefore all calculations were recalculated and reevaluated assuming identical adsorption isotherms (with the 10 Όm isotherm as reference) which confirmed the trends regarding productivity and solvent consumption.
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| 18. |
- Enmark, Martin, 1984-, et al.
(författare)
-
Investigation of plateau methods for adsorption isotherm determination in supercritical fluid chromatography
- 2014
-
Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1354, s. 129-138
-
Tidskriftsartikel (refereegranskat)abstract
- The Perturbation Peak (PP) method and Frontal analysis (FA) are considered as the most accurate methods for adsorption isotherms determination in liquid chromatography. In this study we investigate and explain why this is not the case in Supercritical Fluid Chromatography (SFC), where the PP method does not work at all, using a modern analytical system. The main reason was found to be that the solute to be studied must be dissolved in the MeOH reservoir before it is mixed with CO2. Since the solute occupies a certain partial volume in the reservoir, the larger the solute content the larger this fractional volume will be, and the final MeOH fraction in the mobile phase will then be smaller compared to the bulk mobile phase without solute in the modifier. If the retention of small injections on the concentration plateaus, i.e., “analytical-size” perturbation peaks, is sensitive to small variations of MeOH in the eluent, this will seriously decrease the accuracy of the PP method. This effect was verified and compensated for and we also demonstrated that the same problem will occur in frontal analysis, another concentration plateau method.
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| 19. |
- Enmark, Martin, et al.
(författare)
-
Preparative Separation of Chiral Pharmaceutical Compounds - The Effects of Packing Particle Size, Pressure Limit and Column Geometry on Productivity and Solvent Consumption
- 2011
-
Konferensbidrag (refereegranskat)abstract
- In this study, omeprazole was used as a model compound. Omeprazole and other related sulfoxidebenzimidazolesare used against gastric ulcersand have been extensively studied regarding chromatographic resolution techniques using several different chiral stationary phases.First, AstraZeneca launched Losec, a racemic mixture of RS-omeprazole. Facing loss of patent, the more potent S-enantiomer was developed and marketed as Nexium. Now the patent of Nexium is close expiration why methods for isolation of the pure S-enantiomer will be of importance for the generic pharmaceutical companies.The experimental model separation system represents a system with good selectivity and high solubility of the solute in the eluent. In this investigation the productivity optima for three different particle sizes (5, 10 and 25 µm) at maximum system pressure ranging from 50 to 400 bars are studied. Two different optimizations cases were studied in depth. First,a process optimization with fixed column geometry is studied. The results clearly show that larger packing materials have higher productivity at low pressure drops on the analytical size column.With increasing allowed pressure drops, over 200 bar, the smaller packing materials have substantially higher productivity. The results also show that smaller packing material will always have much lower solvent consumption compared to larger particles.The second process optimization was performed with a fixed column volume, but the column geometry was variable. The results shows that the productivity obtained for the smaller packing particles materials was higher compared to the large for all allowed pressure drops. The productivity obtained for the small particle compared to the large increased by 25-300 % while maintaining 50-300 % less solvent consumption for the purification of the first enantiomer.The addition of TEA seems to be unfavorable for all tested conditions.In conclusion, the optimization of the enantioseparation of omeprazole has been shown to be dependent on column packing particle size as well as column geometry. It has been demonstrated that all parameters need to be simultaneously optimized to reach a global productivity optima.
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| 20. |
- Enmark, Martin, et al.
(författare)
-
Preparative Separation of Omeprazole: Predictions of the Optimal Experimental Conditions by Computer Simulations
- 2011
-
Konferensbidrag (refereegranskat)abstract
- In this study, omeprazole was used as a model compound. Omeprazole and other related sulfoxide benzimidazoles are used against gastric ulcers and have been extensively studied regarding chromatographic resolution techniques using several different chiral stationary phases.First, AstraZeneca launched Losec, a racemic mixture of RS-omeprazole. Facing loss of patent, the more potent S-enantiomer was developed and marketed as Nexium. Now the patent of Nexium is close expiration why methods for isolation of the pure S-enantiomer will be of importance for the generic pharmaceutical companies.The experimental model separation system represents a system with good selectivity and high solubility of the solute in the eluent. In this investigation the productivity optima for three different particle sizes (5, 10 and 25 µm) at maximum system pressure ranging from 50 to 400 bars are studied. Two different optimizations cases were studied in depth. First,a process optimization with fixed column geometry is studied. The results clearly show that larger packing materials have higher productivity at low pressure drops on the analytical size column.With increasing allowed pressure drops, over 200 bar, the smaller packing materials have substantially higher productivity.The results also show that smaller packing material will always have much lower solvent consumption compared to larger particles.The second process optimization was performed with a fixed column volume, but the column geometry was variable. The results shows that the productivity obtained for the smaller packing particles materials was higher compared to the large for all allowed pressure drops. The productivity obtained for the small particle compared to the large increased by 25-300 % while maintaining 50-300 % less solvent consumption for the purification of the first enantiomer.The addition of TEA seems to be unfavorable for all tested conditions.In conclusion, the optimization of the enantioseparation of omeprazole has been shown to be dependent on column packing particle size as well as column geometry. It has been demonstrated that all parameters need to be simultaneously optimized to reach a global productivity optima.
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| 21. |
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| 22. |
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| 23. |
- Fornstedt, Torgny, 1957-, et al.
(författare)
-
Chapter 23 - Modeling of preparative liquid chromatography
- 2023. - 3
-
Ingår i: Liquid Chromatography. - : Elsevier. - 9780323999687 ; , s. 603-624
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Preparative chromatography is the best generic method currently available for purifying small drugs and valuable chemical components at the 10-kg level. Progress in computer technology, the development of new non-chiral/chiral stationary phases, and numerous improvements in reliability and economic performance have considerably increased the interest in modeling in academia and industry. This chapter introduces the modeling of preparative liquid chromatography in order to improve the purification process for valuable chemical components such as drugs and chiral components. We review the most important column and adsorption models and the methods for determining the essential thermodynamic adsorption data for both column characterization and process improvement. We also cover important operational modes (e.g., separation in gradient mode), cases involving additives or ion-pair reagents, and operational conditions sometimes neglected in the modeling process, for example, involving the impact of injection profiles.
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| 24. |
- Fornstedt, Torgny, 1957-, et al.
(författare)
-
Chapter 24 - Modeling of preparative liquid chromatography
- 2017
-
Ingår i: Liquid Chromatography (Second Edition). - : Elsevier. - 9780128053935 ; , s. 573-592
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Preparative chromatography is the best generic method today for the purification of small drugs and valuable chemical components at <10-kg level. Recent progress in computer technology and the development of new nonchiral/chiral stationary phases, as well as numerous improvements in reliability and economic performance, have considerably increased the interest in modeling in academic and industrial communities. This chapter serves as an introduction to modeling of preparative liquid chromatography where the aim is to improve process purification of valuable chemical components, such as drugs and chiral components. We go through the most important column and adsorption models and methods for determination of the essential thermodynamic adsorption data for both column characterization and process improvement. We also cover important operational modes, such as separation in gradient mode and cases where additives are present, and operational conditions sometimes neglected in the modeling process, such as the impact of injection profiles.
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| 25. |
- Fornstedt, Torgny, 1957-, et al.
(författare)
-
Injection profiles in liquid chromatography. I. A fundamental investigation
- 2010
-
Ingår i: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673 .- 1873-3778. ; 1217:26, s. 4306-4312
-
Tidskriftsartikel (refereegranskat)abstract
- This is a fundamental experimental and theoretical investigation on how the injection profile depends on important experimental parameters. The experiments revealed that the injection profile becomes more eroded with increased (i) flow rate, (ii) viscosity of the eluent, (iii) size of the solute, (iv) injection volume and (v) inner diameter of the injection loop capillary. These observations cannot be explained by a 1D-convection-diffusion equation, since it does not account for the effect of the parabolic flow and the radial diffusion on the elution profile. Therefore, the 1D model was expanded into a 2D-convection-diffusion equation with cylindrical coordinates, a model that showed a good agreement with the experimental injection profiles dependence on the experimental parameters. For a deeper understanding of the appearance of the injection profile the 2D model is excellent, but to account for injection profiles of various injection volumes and flow rates in preparative and process-chromatography using computer-optimizations, a more pragmatic approach must be developed. The result will give guidelines about how to reduce the extra-column variance caused by the injection profile. This is important both for preparative and analytical chromatography; in particular for modern analytical systems using short and narrow columns
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| 26. |
- Fornstedt, Torgny, 1957-, et al.
(författare)
-
Modeling of Preparative Liquid Chromatography
- 2013
-
Ingår i: Liquid Chromatography. - : Elsevier. - 9780124158078 ; , s. 407-425
-
Bokkapitel (refereegranskat)abstract
- Abstract Preparative chromatography is today the best generic method for the purification of small drugs and valuable chemical components at the <10 kg-level. Recent progress in computer technology and the development of new nonchiral and chiral stationary phases, as well as numerous improvements in reliability and economic performance, have considerably increased the interest in modeling in academic and industrial communities. This chapter serves as an introduction to the field of modeling preparative liquid chromatography in the classical batch mode, aiming at improved process purification of valuable chemical components, drugs, and chiral components. We go through the most important column and adsorption models and methods for determination of the essential thermodynamic adsorption data for both column characterization and process improvement. But, we also cover important operational conditions sometimes neglected in the modeling procedure, such as the impact of injection profiles and accounting for the additive in the modeling procedure.
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| 27. |
- Fornstedt, Torgny, et al.
(författare)
-
New Procedure for Predictions of Overloaded Profiles in Gradient Elution
- 2013
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- To simulate the separation process in liquid chromatography, the competitive adsorption isotherms need to be known. In gradient elution, the adsorption isotherms are determined with isocratic experiments on different mobile-phase plateaus, levels covering the range used in the gradient program. This can lead to extreme retention times for some mobile-phase compositions and therefore it might even be impossible to determine all necessary adsorption data using the traditional isocratic approach. In this talk, we will present a method where single and competitive nonlinear adsorption isotherms are determined directly from overloaded elution profiles in gradient elution. The numerical coefficients in the adsorption isotherms are determined by the inverse method that minimizes the difference between calculated and experimental elution profiles. This is a new method where the need for tedious/impossible isocratic experiments is eliminated. The method is systematically verified using both synthetic and experimental data. Finally the new method is used to successfully predict elution profiles for a two-component mixture in gradient elution. The new method open up the opportunity to study the adsorption of substances whose retention factor vary strongly with the mobile-phase composition, like peptides and proteins, where the classic methods will fail. We also intend to transfer the metholology for SFC in near future; but there are some problems to be solved first (see our SFC posters). This is a contribution from the Fundamental Separation Science Group www.FSSG.se
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| 28. |
- Fornstedt, Torgny, 1957-, et al.
(författare)
-
System peaks and their impact in liquid chromatography
- 2016
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 81, s. 42-50
-
Forskningsöversikt (refereegranskat)abstract
- A sample injected into a chromatographic system can generate extra peaks, called "system peaks", which in general are undetectable. However, for small analytical injections, solute zones eluting with a system zone will often give strongly deformed solute peaks. But, if a solute zone is eluted in a particular region of the system zone it will instead be strongly compressed and well-shaped. For overloaded solute injections, another type of complex band deformation may take place due to large system peaks. This review will present results related to system peak distortions of both small analytical peaks and large preparative ones. Guidelines will be given on how to avoid unwanted distortions and how to utilize the distortions for increased detectability in analytical chromatography, or enhanced production rate in preparative chromatography. The works reviewed here were mainly made by Georges Guiochon, and some of his close colleagues, and is dedicated to his memory.
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| 29. |
- Fornstedt, Torgny, et al.
(författare)
-
Transposing Advanced LC Theory to Modern Biosensors - Estimation of Bio-Molecular Interactions and Drug-Protein Interactions by Transposing LC-Theory to Biosensors
- 2012
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This poster will also serves as background information to the lecture “Deeper insights in retention mechanisms and molecular interactions through improved methods for generating and evaluation adsorption dataâ€. Adsorption isotherms are essential in order to understand the interaction between small molecules such as pharmaceutical compounds and larger biomolecules. An adsorption isotherm describes the relationship of free substance in a solution with adsorbed substance to a surface, at a specific and constant temperature. Adsorption isotherms could be determined using several different method, all method have their pros and cons. In this study we are using two modern but principally different biosensors to determine interactions: quarts micro-balance (QCM) and Surface plasmon resonance (SPR) to determine interactions. For a long time adsorption isotherms has been determined solely by the chromatographic community. In this study we will present transformation of adsorption analysis tools from chromatography to biosensors, especially calculation of adsorption energy distribution prior adsorption model fit. We will also discuss how the experiments should be conducted. Guidelines will be given for the experimental setup and for when the chromatographic or a biosensor technique is to be preferred. This is a contribution from the Fundamental Separation Science Group in Karlstad www.separationscience.se
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| 30. |
- Forssén, Jens, 1968, et al.
(författare)
-
An urban planning tool demonstrator with auralisation and visualisation of the sound environment
- 2020
-
Ingår i: Proceedings of the FA2020 Conference. ; , s. 869-871
-
Konferensbidrag (refereegranskat)abstract
- The paper presents findings from a recent project about the development of a demonstrator of an urban planning tool that includes auralised sounds as well as visualisations of sound propagation and facade noise levels linked to health impact. In urban development projects, the sound environment is one of the key elements, but often enters late in the planning process. As a result, even if the noise regulations are fulfilled, the potentially good sound environment may suffer unnecessary quality reductions. In addition, the standard ways of presenting and analysing the situations, using noise levels and noise maps, has potential for improvement, especially considering the transdisciplinary approaches to planning that are increasing in use. The tool aims to simplify the usage also at early stage planning, including scenario analysis, as well as to facilitate the urban planners' understanding of the sound environment and its effects. The paper presents results from the development of the demonstrator, reflecting on auralisation as well as on multiple aspects of visualisation including grid noise maps, health-related facade noise levels and choice of colour scales.
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| 31. |
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| 32. |
- Forssen, Patrik, et al.
(författare)
-
A model free method for estimation of complicated adsorption isotherms in liquid chromatography
- 2015
-
Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1409, s. 108-115
-
Tidskriftsartikel (refereegranskat)abstract
- Here we show that even extremely small variations in the adsorption isotherm can have a tremendous effect on the shape of the overloaded elution profiles and that the earlier in the adsorption isotherms the variation take place, the larger its impact on the shape of the elution profile. These variations are so small that they can be "hidden" by the discretization and in the general experimental noise when using traditional experimental methods, such as frontal analysis, to measure adsorption isotherms. But as the effects of these variations are more clearly visible in the elution profiles, the Inverse Method (IM) of adsorption isotherm estimation is an option. However, IM usually requires that one selects an adsorption isotherm model prior to the estimation process. Here we show that even complicated models might not be able to estimate the adsorption isotherms with multiple inflection points that small variations might give rise to. We therefore developed a modified IM that, instead of fixed adsorption isotherm models, uses monotone piecewise interpolation. We first validated the method with synthetic data and showed that it can be used to estimate an adsorption isotherm, which accurately predicts an extremely "strange" elution profile. For this case it was impossible to estimate the adsorption isotherm using IM with a fixed adsorption model. Finally, we will give an example of a real chromatographic system where adsorption isotherm with inflection points is estimated by the modified IM.
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| 33. |
- Forssén, Patrik, et al.
(författare)
-
A quest for the optimal additive in chiral preparative chromatography
- 2009
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1216:23, s. 4719-4727
-
Tidskriftsartikel (refereegranskat)abstract
- Traditionally, the choice of acid/base additives used in chiral preparative chromatography has not been considered very important. However, it was recently demonstrate that strongly adsorbing additives can result in the Most unexpected enantiomer band shapes in modern chiral preparative chromatographic systems. In the present study we demonstrate that, depending on the choice of additive, it is actually possible to obtain the following four binary band-shape compositions when a racemic mixture is injected: (i) anti-Langmuir/anti-Langmuir, (ii) anti-Langmuir/Langmuir, (iii) Langmuir/Langmuir and (iv) Langmuir/anti-Langmuir. Further, we made an advanced numerical investigation, in order to ascertain which one of the four band-shape compositions, is the most favourable one in preparative batch chromatography of a racemic mixture. We found that if the target for purification is either the first eluting enantiomer or both ones, the traditional Langmuir/Langmuir band-shape composition should be chosen. But, if only the second eluting enantiomer is to be purified the optimal situation is the anti-Langmuir/Langmuir band-shape composition. Thus, it was concluded that the best choice of additive depends on which enantiomer is of interest and it is useful to perform a thorough additive screening to find the optimal additive, giving the most advantageous peak shape composition and accordingly the best process performance for a particular separation problem. (C) 2009 Elsevier B.V. All rights reserved.
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| 34. |
- Forssén, Patrik, 1966-
(författare)
-
Adsorption Isotherm Parameter Estimation in Nonlinear Liquid Chromatography
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the development and validation of methods for the industrially important area of adsorption isotherm parameter estimation in preparative, nonlinear high performance liquid chromatography (HPLC). Preparative chromatography is a powerful separation method to get pure compounds from more or less complex liquid mixtures, e.g., mixtures of mirror-image molecules. Computer simulations can be used to optimize preparative chromatography, but then competitive adsorption isotherm parameters are usually required. Here two methods to estimate adsorption isotherm parameters are treated: (i) the perturbation peak (PP) method and (ii) the inverse method (IM).A new theory for the PP method was derived and led to a new injection technique which was validated experimentally. This injection technique solved the severe problem with vanishing peaks and enabled us to use the PP method to estimate binary competitive adsorption isotherms valid over a broad concentration range. Also, the injection technique made it possible to estimate competitive adsorption isotherms for a quaternary mixture for the first time. Finally, an interesting perturbation peak phenomenon, known as the “Helfferich Paradox”, was experimentally verified for the first time.The IM is a relatively new method to determine adsorption isotherm parameters. It has the advantage of requiring very small samples, but also requires an advanced computer algorithm. An improved implementation of this computer algorithm was developed and tested experimentally. Also, a variant of the IM called “the inverse method on plateaus” was tested experimentally and the estimated adsorption isotherm parameters were shown to be valid over a broader concentration range than those estimated with the standard IM.
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| 35. |
- Forssén, Patrik, 1966-, et al.
(författare)
-
Advanced Analysis of Biosensor Data for SARS-CoV-2 RBD and ACE2 Interactions
- 2020
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 92:17, s. 11520-11524
-
Tidskriftsartikel (refereegranskat)abstract
- The traditional approach for analyzing interaction data from biosensors instruments is based on the simplified assumption that also larger biomolecules interactions are homogeneous. It was recently reported that the human receptor angiotensin-converting enzyme 2 (ACE2) plays a key role for capturing SARS-CoV-2 into the human target body, and binding studies were performed using biosensors techniques based on surface plasmon resonance and bio-layer interferometry. The published affinity constants for the interactions, derived using the traditional approach, described a single interaction between ACE2 and the SARS-CoV-2 receptor binding domain (RBD). We reanalyzed these data sets using our advanced four-step approach based on an adaptive interaction distribution algorithm (AIDA) that accounts for the great complexity of larger biomolecules and gives a two-dimensional distribution of association and dissociation rate constants. Our results showed that in both cases the standard assumption about a single interaction was erroneous, and in one of the cases, the value of the affinity constant K-D differed more than 300% between the reported value and our calculation. This information can prove very useful in providing mechanistic information and insights about the mechanism of interactions between ACE2 and SARS-CoV-2 RBD or similar systems.
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| 36. |
|
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| 37. |
- Forssén, Patrik, et al.
(författare)
-
Effects of a strongly adsorbed additive on process performance in chiral preparative chromatography
- 2008
-
Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1212:1-2, s. 89-97
-
Tidskriftsartikel (refereegranskat)abstract
- The shapes of elution profiles are often significantly influenced by the presence of strongly adsorbed additives in the mobile phase. This aspect needs to be considered in quantitative optimization of preparative chromatography. The theoretical study carried out here is based on available thermodynamic information for the enantiomers of three beta-blockers, alprenolol, propranolol, and atenolol, on a teicoplanin chiral stationary phase (Chirobiotic T) using methanol/acetonitrile as the mobile phase and acetic acid/triethylamine as the additive. The properties of this strong additive made it possible to tune the binary elution profiles in any combination of the following apparent band shapes: anti-Langmuir/anti-Langmuir, anti-Langmuir/Langmuir and Langmuir/Langmuir. Optimization of the productivity and yield, when performing repetitive batch injections, was investigated using the equilibrium dispersive model. We show that it is important to consider the invisible additive perturbation peak when defining the cycle time and therefore a model-based optimization needs to take this into account. Furthermore, both productivity and yield could be improved for the two unusual shape combinations in comparison to the traditional Langmuir/Langmuir case.
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| 38. |
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| 39. |
- Forssén, Patrik, 1966-, et al.
(författare)
-
Impact of column and stationary phase properties on the productivity in chiral preparative LC
- 2018
-
Ingår i: Journal of Separation Science. - : Wiley-VCH Verlagsgesellschaft. - 1615-9306 .- 1615-9314. ; 41:6, s. 1346-1354
-
Tidskriftsartikel (refereegranskat)abstract
- By generating 1500 random chiral separation systems, assuming two-site Langmuir interactions, we investigated numerically how the maximal productivity (P-R,P-max) was affected by changes in stationary phase adsorption properties. The relative change in P-R,P-max, when one adsorption property changed 10%, was determined for each system and for each studied parameter the corresponding productivity change distribution of the systems was analyzed. We could conclude that there is no reason to have columns with more than 500 theoretical plates and larger selectivity than 3. More specifically, we found that changes in selectivity have a major impact on P-R,P-max if it is below similar to 2 and, interestingly, increasing selectivity when it is above similar to 3 decreases P-R,P-max. Increase in relative saturation capacity will have a major impact on P-R,P-max if it is below similar to 40%, but only modest above this percent. Increasing total monolayer saturation capacity, or decreasing the first eluting enantiomer's retention factor, will have a modest effect on P-R,P-max and increased efficiency will have almost no effect at all on P-R,P-max unless it is below similar to 500 theoretical plates. Finally, we showed that chiral columns with superior analytic performance might have inferior preparative performance, or vice versa. It is, therefore, not possible to assess columns based on their analytical performance alone.
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| 40. |
- Forssén, Patrik, 1966-, et al.
(författare)
-
Injection profiles in liquid chromatography II : Predicting accurate injection-profiles for computer-assisted preparative optimizations
- 2011
-
Ingår i: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673 .- 1873-3778. ; 1218:34, s. 5794-5800
-
Tidskriftsartikel (refereegranskat)abstract
- In computer assisted optimization of liquid chromatography it has been known for some years that it is important to use experimental injection profiles, instead of rectangular ones, in order to calculate accurate elution bands. However, the incorrectly assumed rectangular profiles are still mostly used especially in numerical optimizations. The reason is that the acquisition of injection profiles, for each injection volume and each flow rate considered in a computer-assisted optimization requires a too large number of experiments. In this article a new function is proposed, which enables highly accurate predictions of the injection profiles and thus more accurate computer optimizations, with a minimum experimental effort. To model the injection profiles for any injection volume at a constant flow rate, as few as two experimental injection profiles are required. If it is desirable to also take the effect of flow rate on the injection profiles into account, then just two additional experiments are required. The overlap between fitted and experimental injection profiles at different flow rates and different injection volumes were excellent, more than 90%, using experimental injection profiles from just four different injection volumes at two different flow rates. Moreover, it was demonstrated that the flow rate has a minor influence on the injection profiles and that the injection volume is the main parameter that needs to be accounted for.
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| 41. |
- Forssén, Patrik, 1966-, et al.
(författare)
-
Optimization strategies accounting for the additive in preparative chiral liquid chromatography
- 2012
-
Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1269:SI, s. 279-286
-
Tidskriftsartikel (refereegranskat)abstract
- This study is an in-depth investigation on how numerical optimization strategies that also account for the additive type and concentration, in preparative batch chromatography, should be performed. As a model system, the separation of Z-(R,S)-2-aminobutyric acid enantiomers on a quinidine carbamate-based chiral stationary phase in polar organic mode was used, with different additive strengths of acetic acid or hexanoic acid in methanol. The inverse method was used to determine the competitive adsorption isotherm parameters for the enantiomers and the additives. Three different optimization strategies were examined: (1) injection volume optimization, (2) optimization of injection volume and additive concentration, and (3) full optimization including injection volume, additive concentration, sample concentration and flow rate. It was concluded that (i) it is important to incorporate the additive concentration in the optimization procedure to achieve the highest production rates, (ii) the full optimization strategy had the overall best results, and (iii) the selection of additive is very important (here acetic acid additive was superior to the hexanoic acid additive). By including the additive in the adsorption model and in the numerical optimization it is not only possible to achieve higher production rates but also to properly select the additive that is most advantageous for the specific separation problem.
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| 42. |
- Forssén, Patrik, et al.
(författare)
-
Relative importance of column and adsorption parameters on the productivity in preparative liquid chromatography. I : Investigation of a chiral separation system
- 2013
-
Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1299, s. 58-63
-
Tidskriftsartikel (refereegranskat)abstract
- Starting out from an experimental chiral separation system we have used computer simulations for a systematic investigation on how the maximum productivity depends on changes in column length, packing particle size, column efficiency, back pressure, sample concentration/solubility, selectivity, retention factor of the first eluting component and monolayer saturation capacity. The study was performed by changing these parameters, one at a time, and then calculating the corresponding change in maximum productivity. The three most important parameters for maximum production rate was found to be (i) the selectivity (ii) the retention factor of the first eluting component and (iii) the column length. Surprisingly, the column efficiency and sample concentration/solubility were of minor importance. These findings can be used as rough guidelines for column selection, e.g. a low-efficiency column are more likely perform better, in terms of productivity, than a high-efficiency column that have higher retention factor for the first eluting component.
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| 43. |
- Forssén, Patrik, et al.
(författare)
-
Relative importance of column and adsorption parameters on the productivity in preparative liquid chromatography II : Investigation of separation systems with competitive Langmuir adsorption isotherms
- 2014
-
Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1347, s. 72-79
-
Tidskriftsartikel (refereegranskat)abstract
- In this study we investigated how the maximum productivity for commonly used, realistic separation system with a competitive Langmuir adsorption isotherm is affected by changes in column length, packing particle size, mobile phase viscosity, maximum allowed column pressure, column efficiency, sample concentration/solubility, selectivity, monolayer saturation capacity and retention factor of the first eluting compound. The study was performed by generating 1000 random separation systems whose optimal injection volume was determined, i.e., the injection volume that gives the largest achievable productivity. The relative changes in largest achievable productivity when one of the parameters above changes was then studied for each system and the productivity changes for all systems were presented as distributions. We found that it is almost always beneficial to use shorter columns with high pressure drops over the column and that the selectivity should be greater than 2. However, the sample concentration and column efficiency have very limited effect on the maximum productivity. The effect of packing particle size depends on the flow rate limiting factor. If the pumps maximum flow rate is the limiting factor use smaller packing, but if the pressure of the system is the limiting factor use larger packing up to about 40μm.
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| 44. |
- Forssén, Patrik, 1966-, et al.
(författare)
-
Reliable Strategy for Analysis of Complex Biosensor Data
- 2018
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 90:8, s. 5366-5374
-
Tidskriftsartikel (refereegranskat)abstract
- When using biosensors, analyte biomolecules of several different concentrations are percolated over a chip with immobilized ligand molecules that form complexes with analytes. However, in many cases of biological interest, e.g., in antibody interactions, complex formation steady-state is not reached. The data measured are so-called sensorgram, one for each analyte concentration, with total complex concentration vs time. Here we present a new four-step strategy for more reliable processing of this complex kinetic binding data and compare it with the standard global fitting procedure. In our strategy, we first calculate a dissociation graph to reveal if there are any heterogeneous interactions. Thereafter, a new numerical algorithm, AIDA, is used to get the number of different complex formation reactions for each analyte concentration level. This information is then used to estimate the corresponding complex formation rate constants by fitting to the measured sensorgram one by one. Finally, all estimated rate constants are plotted and clustered, where each cluster represents a complex formation. Synthetic and experimental data obtained from three different QCM biosensor experimental systems having fast (close to steady-state), moderate, and slow kinetics (far from steady-state) were evaluated using the four-step strategy and standard global fitting. The new strategy allowed us to more reliably estimate the number of different complex formations, especially for cases of complex and slow dissociation kinetics. Moreover, the new strategy proved to be more robust as it enables one to handle system drift, i.e., data from biosensor chips that deteriorate over time.
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| 45. |
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| 46. |
- Glenne, Emelie, et al.
(författare)
-
Systematic investigations of peak distortions due to additives in supercritical fluid chromatography
- 2020
-
Ingår i: Journal of Chromatography & Separation Techniques. - : Elsevier. - 2157-7064. ; 1621, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of eluent components added to improve separation performance in supercritical fluid chromatography was systematically, and fundamentally, investigated. The model system comprised basic pharmaceuticals as solutes and eluents containing three amines (i.e., triethylamine, diethylamine, and isopropylamine) as additives with MeOH as the co-solvent. First, an analytical-scale study was performed, systematically investigating the impact of the additives/co-solvent on solute peak shapes and retentions, using a design of experiments approach; here, the total additive concentration in the eluent ranged between 0.021 and 0.105 % (v/v) and the total MeOH fraction in the eluent between 16 and 26 % (v/v). The co-solvent fraction was found to be the most efficient tool for adjusting retentions, whereas the additive fraction was the prime tool for improving column efficiency and peak analytical performance. Next, the impacts of the amine additives on the shapes of the so-called overloaded solute elution profiles were investigated. Two principal types of preparative peak deformations appeared and were investigated in depth, analyzed using computer simulation with mechanistic modeling. The first type of deformation was due to the solute eluting too close to the additive perturbation peak, resulting in severe peak deformation caused by co-elution. The second type of deformation was also due to additive–solute interactions, but here the amine additives acted as kosmotropic agents, promoting the multilayer adsorption to the stationary phase of solutes with bulkier aryl groups.
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| 47. |
- Gottlieb, David, et al.
(författare)
-
On the Direct Fourier Method for Computer Tomography
- 2000
-
Ingår i: IEEE Transactions on Medical Imaging. - : Institute of Electrical and Electronics Engineers (IEEE). - 0278-0062 .- 1558-254X. ; 19, s. 223-232
-
Tidskriftsartikel (refereegranskat)
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| 48. |
- Gutgsell, Aspen Rene, et al.
(författare)
-
Biosensor-Enabled Deconvolution of the Avidity-Induced Affinity Enhancement for the SARS-CoV-2 Spike Protein and ACE2 Interaction
- 2022
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:2, s. 1187-1194
-
Tidskriftsartikel (refereegranskat)abstract
- Avidity is an effective and frequent phenomenon employed by nature to achieve extremely high-affinity interactions. As more drug discovery efforts aim to disrupt protein-protein interactions, it is becoming increasingly common to encounter systems that utilize avidity effects and to study these systems using surface-based technologies, such as surface plasmon resonance (SPR) or biolayer interferometry. However, heterogeneity introduced from multivalent binding interactions complicates theanalysis of the resulting sensorgram. A frequently applied practice is to fit the data based on a 1:1 binding model, and if the fit does not describe the data adequately, then the experimental setup is changed to favor a 1:1 binding interaction. This reductionistic approach is informative but not always biologically relevant. Therefore, we aimed to develop an SPR-based assay that would reduce the heterogeneity to enable the determination of the kinetic rate constants for multivalent binding interactions using the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human receptor angiotensin-converting enzyme 2 (ACE2) as a model system. We employed a combinatorial approach to generate a sensor surface that could distinguish between monovalent and multivalent interactions. Using advanced data analysis algorithms to analyze the resulting sensorgrams, we found that controlling the surface heterogeneity enabled the deconvolution of theavidity-induced affinity enhancement for the SARS-CoV-2 spike protein and ACE2 interaction.
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| 49. |
- Höstmad, Patrik, 1974, et al.
(författare)
-
Off-peak low noise heavy-duty vehicles, facade insulation and indoor noise disturbance
- 2016
-
Ingår i: Proceedings of the INTER-NOISE 2016 - 45th International Congress and Exposition on Noise Control Engineering. - 9783939296119 ; , s. 5258-5266, s. 5258-5266
-
Konferensbidrag (refereegranskat)abstract
- Off-peak delivery of goods can result in increased transport efficiency, fuel savings, less pollution and increased traffic safety. However, unless carefully managed it causes increased annoyance and health risks for inhabitants exposed to the transportation noise during hours used for recovery and sleep. The presented work focuses on heavy-duty vehicles with Diesel engines during the "last mile" of the transport corridor through densely populated city centers. The aim is to study preconditions, open questions, and problem areas when nighttime soundscapes are altered by low noise vehicles. By using measured and simulated sounds, different driving conditions and acoustical treatments of vehicles and facade were studied at the facade and indoors in terms of 1/3-octaveband levels and judgments in listening tests. The evaluation shows that low-frequency noise of the vehicles is important indoors, while high-frequency noise is the major contributor outdoors. According to the listening tests the low-frequency noise is coupled to the degree of reported arousal, indicating that reduced low-frequency noise is especially important at nighttime. It was concluded that an acceptable indoor environment was achieved with a modified truck that is driven by a responsible driver, and by using "noise proof" windows with higher sound insulation.
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| 50. |
- Höstmad, Patrik, 1974, et al.
(författare)
-
Towards a low noise truck specification
- 2015
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report summarises the most important findings in the research project Quiter Transport for More Efficient Distribution aiming at the outline of a sound characterisation specification for noise improved heavy-duty trucks for nighttime distribution of goods. The focus in the project was on the "last mile" of the transport corridor through densely populated city centres, i.e. transport through rather narrow street canyons lined with residential housings. The noise of the loading or unloading of the goods at the destination is beyond the scope of the project. Section 2 gives the general description of the involved elements; the outdoor truck sound source, the street canyon amplification and reverberation, noise reduction by windows and facades, and the indoor noise levels due to a truck passing by in the street. Section 3 gives some specific results from the project; the results of the modifications of a truck with the purpose to reduce outdoor and indoor noise evaluated by measurements. Section 4 summarises the results of the listening clinics; including fundamental and specific results test subjects evaluating their response to real and synthesised outdoor and indoor sound of a heavy-duty truck, a light-duty van and the modified heavy-duty truck. Section 5 discusses, from various perspectives, sound attributes of a low noise truck suitable for nighttime distribution of goods. Finally, Section 6 gives the conclusions in a concise format.
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