| 1. |
- Enmark, Martin, 1984-, et al.
(författare)
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Investigation of robustness for supercritical fluid chromatography separation of peptides : Isocratic vs gradient mode
- 2018
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Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1568, s. 177-187
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Tidskriftsartikel (refereegranskat)abstract
- We investigated and compared the robustness of supercritical fluid chromatography (SFC) separations of the peptide gramicidin, using either isocratic or gradient elution. This was done using design of experiments in a design space of co-solvent fraction, water mass fraction in co-solvent, pressure, and temperature. The density of the eluent (CO2-MeOH-H2O) was experimentally determined using a Coriolis mass flow meter to calculate the volumetric flow rate required by the design. For both retention models, the most important factor was the total co-solvent fraction and water mass fraction in co-solvent. Comparing the elution modes, we found that gradient elution was more than three times more robust than isocratic elution. We also observed a relationship between the sensitivity to changes and the gradient steepness and used this to draw general conclusions beyond the studied experimental system. To test the robustness in a practical context, both the isocratic and gradient separations were transferred to another laboratory. The gradient elution was highly reproducible between laboratories, whereas the isocratic system was not. Using measurements of the actual operational conditions (not the set system conditions), the isocratic deviation was quantitatively explained using the retention model. The findings indicate the benefits of using gradient elution in SFC as well as the importance of measuring the actual operational conditions to be able to explain observed differences between laboratories when conducting method transfer.
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| 2. |
- Kaczmarski, J., et al.
(författare)
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Transparent Ru–Si–O/In–Ga–Zn–O MESFETs on flexible polymer substrates
- 2018
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Ingår i: IEEE Transactions on Electron Devices. - 1557-9646 .- 0018-9383. ; 65:1, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- With the development of novel device applications, e.g., in the field of Internet of Things or point-of-care personalized diagnostic systems, came an increased demand for MESFETs for fast and low-power consumption integrated circuits and active-matrix displays. In this paper, we present fabrication and characterization of transparent Ru–Si–O/In–Ga–Zn–O MESFETs on flexible substrates. The use of transparent conducting oxide, namely, Ru–Si–O, as Schottky gate electrode, allows for processing the devices at room temperature, enabling the utilization of such low-temperature substrates as polyethylene terephthalate foil and paper. It was shown that tuning the device geometry allows realization of transistors providing on-current up to 2 mA, while the highest on-to-off current ratio equals 2 × 105, with off-current below 1 nA, carrier mobility in the channel exceeds 9 cm2·V−1·s−1, and subthreshold swing is below 250 mV·decade−1
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| 3. |
- Lesko, Marek, et al.
(författare)
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Choice of Model for Estimation of Adsorption Isotherm Parameters in Gradient Elution Preparative Liquid Chromatography
- 2015
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Ingår i: Chromatographia. - : Springer Berlin/Heidelberg. - 0009-5893 .- 1612-1112. ; 78:19-20, s. 1293-1297
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Tidskriftsartikel (refereegranskat)abstract
- The inverse method is a numerical method for fast estimation of adsorption isotherm parameters directly from a few overloaded elution profiles and it was recently extended to adsorption isotherm acquisition in gradient elution conditions. However, the inverse method in gradient elution is cumbersome due to the complex adsorption isotherm models found in gradient elution. In this case, physicochemically correct adsorption models have very long calculation times. The aim of this study is to investigate the possibility of using a less complex adsorption isotherm model, with fewer adjustable parameters, but with preserved/acceptable predictive abilities. We found that equal or better agreement between experimental and predicted elution profiles could be achieved with less complex models. By being able to select a model with fewer adjustable parameters, the calculation times can be reduced by at least a factor of 10.
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| 4. |
- Samuelsson, Jörgen, 1971-, et al.
(författare)
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Optimizing Column Length and Particle Size in Preparative Batch Chromatography Using Enantiomeric Separations of Omeprazole and Etiracetam as Models : Feasibility of Taguchi Empirical Optimization
- 2018
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Ingår i: Chromatographia. - Heidelberg : Springer. - 0009-5893 .- 1612-1112. ; 81:6, s. 851-860
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Tidskriftsartikel (refereegranskat)abstract
- The overreaching purpose of this study is to evaluate new approaches for determining the optimal operational and column conditions in chromatography laboratories, i.e., how best to select a packing material of proper particle size and how to determine the proper length of the column bed after selecting particle size. As model compounds, we chose two chiral drugs for preparative separation: omeprazole and etiracetam. In each case, two maximum allowed pressure drops were assumed: 80 and 200 bar. The processes were numerically optimized (mechanistic modeling) with a general rate model using a global optimization method. The numerical predictions were experimentally verified at both analytical and pilot scales. The lower allowed pressure drop represents the use of standard equipment, while the higher allowed drop represents more modern equipment. For both compounds, maximum productivity was achieved using short columns packed with small-particle size packing materials. Increasing the allowed backpressure in the separation leads to an increased productivity and reduced solvent consumption. As advanced numerical calculations might not be available in the laboratory, we also investigated a statistically based approach, i.e., the Taguchi method (empirical modeling), for finding the optimal decision variables and compared it with advanced mechanistic modeling. The Taguchi method predicted that shorter columns packed with smaller particles would be preferred over longer columns packed with larger particles. We conclude that the simpler optimization tool, i.e., the Taguchi method, can be used to obtain “good enough” preparative separations, though for accurate processes, optimization, and to determine optimal operational conditions, classical numerical optimization is still necessary
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| 5. |
- Åsberg, Dennis, 1988-, et al.
(författare)
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A practical approach for predicting retention time shifts due to pressure and temperature gradients in ultra-high-pressure liquid chromatography
- 2017
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Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1479, s. 107-120
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Tidskriftsartikel (refereegranskat)abstract
- Large pressure gradients are generated in ultra-high-pressure liquid chromatography (UHPLC) using sub–2 μm particles causing significant temperature gradients over the column due to viscous heating. These pressure and temperature gradients affect retention and ultimately result in important selectivity shifts. In this study, we developed an approach for predicting the retention time shifts due to these gradients. The approach is presented as a step-by-step procedure and it is based on empirical linear relationships describing how retention varies as a function of temperature and pressure and how the average column temperature increases with the flow rate. It requires only four experiments on standard equipment, is based on straightforward calculations, and is therefore easy to use in method development. The approach was rigorously validated against experimental data obtained with a quality control method for the active pharmaceutical ingredient omeprazole. The accuracy of retention time predictions was very good with relative errors always less than 1% and in many cases around 0.5% (n = 32). Selectivity shifts observed between omeprazole and the related impurities when changing the flow rate could also be accurately predicted resulting in good estimates of the resolution between critical peak pairs. The approximations which the presented approach are based on were all justified. The retention factor as a function of pressure and temperature was studied in an experimental design while the temperature distribution in the column was obtained by solving the fundamental heat and mass balance equations for the different experimental conditions. We strongly believe that this approach is sufficiently accurate and experimentally feasible for this separation to be a valuable tool when developing a UHPLC method. After further validation with other separation systems, it could become a useful approach in UHPLC method development, especially in the pharmaceutical industry where demands are high for robustness and regulatory oversight.
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| 6. |
- Åsberg, Dennis, 1988-, et al.
(författare)
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Combining Chemometric Models with Adsorption Isotherm Measurements to Study Omeprazole in RP-LC
- 2016
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Ingår i: Chromatographia. - : Springer Berlin/Heidelberg. - 0009-5893 .- 1612-1112. ; 79:19, s. 1283-1291
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of the proton-pump inhibitor omeprazole was investigated using RP-LC with chemometric models combined with adsorption isotherm modelling to study the effect of pH and type of organic modifier (i.e., acetonitrile or methanol). The chemometric approach revealed that omeprazole was tailing with methanol and fronting with acetonitrile along with increased fronting at higher pH. The increased fronting with higher pH for acetonitrile was explored using a pH-dependent adsorption isotherm model that was determined using the inverse method and it agreed well with the experimental data. The model indicated that the peaks exhibit more fronting at high pH due to a larger fraction of charged omeprazole molecules. This model could accurately predict the shape of elution profiles at arbitrary pH levels in the studied interval. Using a two-layer adsorption isotherm model, the difference between acetonitrile and methanol was studied at the lowest pH at which almost all omeprazole molecules are neutral. Omeprazole had adsorbate–adsorbate interactions that were similar in strength for the acetonitrile and methanol mobile phases, while the solute–adsorbent interactions were almost twice as strong with methanol. The difference in the relative strengths of these two interactions likely explains the different peak asymmetries (i.e., tailing/fronting) in methanol and acetonitrile. In conclusion, thermodynamic modelling can complement chemometric modeling in HPLC method development and increase the understanding of the separation.
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| 7. |
- Åsberg, Dennis, 1988-, et al.
(författare)
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Estimation of Nonlinear Adsorption Isotherms in Gradient Elution RP-LC of Peptides in the Presence of an Adsorbing Additive
- 2017
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Ingår i: Chromatographia. - : Springer. - 0009-5893 .- 1612-1112. ; 80:6, s. 961-966
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Tidskriftsartikel (refereegranskat)abstract
- In electrostatic repulsive interaction chromatography, using a charged surface hybrid sorbent carrying positive charges can improve the peak shape of peptides in reversed-phase liquid chromatography (RP-LC), especially in overloaded conditions, compared with standard C-18 sorbents. However, the positive surface charges can interact with anionic additives commonly used in peptide separations, e.g., trifluoroacetic acid (TFA), complicating adsorption isotherm estimation. We investigated how the competition for available adsorption sites between TFA and two peptides influenced the adsorption isotherm in gradient elution. A model accounting for the competition with TFA was compared with a model neglecting TFA adsorption. We found that the two models predicted elution profiles with the same accuracy. We also found that the adsorption isotherms were extremely similar in shape, leading to the conclusion that neglecting the competition with TFA is a valid approximation enabling faster and more robust adsorption isotherm estimation for the studied type of sorbent.
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| 8. |
- Åsberg, Dennis, et al.
(författare)
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Method transfer from high-pressure liquid chromatography to ultra-high-pressure liquid chromatography. II. Temperature and pressure effects
- 2015
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Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1401, s. 52-59
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Tidskriftsartikel (refereegranskat)abstract
- The importance of the generated temperature and pressure gradients in ultra-high-pressure liquid chromatography (UHPLC) are investigated and compared to high-pressure liquid chromatography (HPLC). The drug Omeprazole, together with three other model compounds (with different chemical characteristics, namely uncharged, positively and negatively charged) were used. Calculations of the complete temperature profile in the column at UHPLC conditions showed, in our experiments, a temperature difference between the inlet and outlet of 16 degrees C and a difference of 2 degrees C between the column center and the wall. Through van't Hoff plots, this information was used to single out the decrease in retention factor (k) solely due to the temperature gradient. The uncharged solute was least affected by temperature with a decrease in k of about 5% while for charged solutes the effect was more pronounced, with k decreases up to 14%. A pressure increase of 500 bar gave roughly 5% increase in k for the uncharged solute, while omeprazole and the other two charged solutes gave about 25, 20 and 15% increases in k, respectively. The stochastic model of chromatography was applied to estimate the dependence of the average number of adsorption/desorption events (n) and the average time spent by a molecule in the stationary phase (tau(s)) on temperature and pressure on peak shape for the tailing, basic solute. Increasing the temperature yielded an increase in n and decrease in tau(s) which resulted in less skew at high temperatures. With increasing pressure, the stochastic modeling gave interesting results for the basic solute showing that the skew of the peak increased with pressure. The conclusion is that pressure effects are more pronounced for both retention and peak shape than the temperature effects for the polar or charged compounds in our study. (C) 2015 Elsevier B.V. All rights reserved.
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| 9. |
- Åsberg, Dennis, 1988-, et al.
(författare)
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The importance of ion-pairing in peptide purification by reversed-phase liquid chromatography
- 2017
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Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1496, s. 80-91
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption mechanism for three peptides was studied under overloaded conditions through adsorption isotherm measurements in the presence of an ion-pairing reagent, trifluoroacetic acid (TFA), on an end-capped C18-bonded stationary phase. The overall aim of the study was to obtain a better understanding of how the acetonitrile and the TFA fractions in the eluent affected the overloaded elution profiles and the selectivity between peptides using mechanistic modelling and multivariate design of experiments. When studying the effect of TFA, direct evidence for ion pair formation between a peptide and TFA in acetonitrile-water solutions was provided by fluorine-proton nuclear Overhauser NMR enhancement experiments and the adsorption of TFA on the stationary phase was measured by frontal analysis. The adsorption isotherms for each peptide were then determined by the inverse method at eight TFA concentrations ranging from 2.6 mM to 37.3 mM (0.02–0.29 vol-%) in isocratic elution. The equilibrium between the peptide ion and the peptide-TFA complex was modelled by coupling the mass-balance to reaction kinetics and determining separate adsorption isotherms for the two species. We found that a Langmuir isotherm described the elution profile of peptide-TFA complex well while the peptide ion was described by a bi-Langmuir adsorption isotherm since it exhibited strong secondary interactions. The elution profiles had an unfavorable shape at low TFA concentrations consisting of a spike in their front and a long tailing rear due to the secondary interactions for the peptide ion having very low saturation capacity. The acetonitrile dependence on the adsorption isotherms was studied by determination of adsorption isotherms directly from elution profiles obtained in gradient elution which enabled a broad acetonitrile interval to be studied. Here, it was found that the column saturation capacity was quickly reached at very low acetonitrile fractions and that there were significant variations in adsorption with the molecular weight. Finally, practical implications for method development are discussed based on an experimental design where gradient slope and TFA concentrations are used as factors. (c) 2017 Published by Elsevier B.V.
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