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Vera, C. M., Samuelsson, J., Fornstedt, T., Dennis, G. R. & Shalliker, R. A. (2019). Visualisation of axial temperature gradients and heat transfer process of different solvent compositions in ultra high performance liquid chromatography using thermography. Microchemical journal (Print), 145, 927-935
Open this publication in new window or tab >>Visualisation of axial temperature gradients and heat transfer process of different solvent compositions in ultra high performance liquid chromatography using thermography
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2019 (English)In: Microchemical journal (Print), ISSN 0026-265X, E-ISSN 1095-9149, Vol. 145, p. 927-935Article in journal (Refereed) Published
Abstract [en]

Thermal imaging was used to visualise axial temperature gradients in chromatography columns running solvents of water, methanol and acetonitrile at various compositions. The non-monotonic relationship between solvent composition and viscosity enabled the testing of solvent conditions with equivalent viscosities, but with different percentages of water. It was observed that at equivalent power the increase in water composition leads to an increase in the magnitude of the axial temperature gradients (Delta T-A). Observing the change in temperature at defined points (Delta T-p) with increasing power indicates that the relationship between Delta T-p and power is not linear but deviates at higher power. The degree of this deviation depends on what point along the column axis is observed as well what solvent composition is used. Being able to monitor the entire length of the column using thermography also allowed for the observation of different rates of heat transfer through to the bulky stainless steel end fittings from solvent to solvent. Revealing that water is able to transfer heat to the stainless steel surface in such a way that the temperature profile of transition point between columns to end fitting is more gradual compared to when methanol or acetonitrile is used. This evidence plus video data collected indicates that at constant flow rate an equilibrium between heat generated and heat dissipated through the stainless steel is formed, which differs from solvent to solvent. Moreover any disruption to this equilibrium, i.e. a change in flow rate will momentarily change the shape of the temperature profile.

Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Physical Chemistry
Research subject
Physics
Identifiers
urn:nbn:se:kau:diva-71232 (URN)10.1016/j.microc.2018.11.037 (DOI)000457513000118 ()
Available from: 2019-02-21 Created: 2019-02-21 Last updated: 2019-03-06Bibliographically approved
Enmark, M., Glenne, E., Leśko, M., Langborg Weinmann, A., Leek, T., Kaczmarski, K., . . . Fornstedt, T. (2018). Investigation of robustness for supercritical fluid chromatography separation of peptides: Isocratic vs gradient mode. Journal of Chromatography A, 1568, 177-187
Open this publication in new window or tab >>Investigation of robustness for supercritical fluid chromatography separation of peptides: Isocratic vs gradient mode
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2018 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1568, p. 177-187Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Gramicidin, Method transfer, Peptide, Robustness, SFC, Water, Design of experiments, Effluent treatment, Gas chromatography, Oceanography, Peptides, Robustness (control systems), Supercritical fluids, Coriolis mass flow meter, Experimental system, Gradient separations, Method transfers, Operational conditions, Super critical fluid chromatography, Volumetric flow rate, Solvents
National Category
Chemical Engineering
Research subject
Chemical Engineering
Identifiers
urn:nbn:se:kau:diva-69063 (URN)10.1016/j.chroma.2018.07.029 (DOI)000443669600019 ()
Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2018-11-22Bibliographically approved
Samuelsson, J., Leśko, M., Enmark, M., Högblom, J., Karlsson, A. & Kaczmarski, K. (2018). Optimizing Column Length and Particle Size in Preparative Batch Chromatography Using Enantiomeric Separations of Omeprazole and Etiracetam as Models: Feasibility of Taguchi Empirical Optimization. Chromatographia, 81(6), 851-860
Open this publication in new window or tab >>Optimizing Column Length and Particle Size in Preparative Batch Chromatography Using Enantiomeric Separations of Omeprazole and Etiracetam as Models: Feasibility of Taguchi Empirical Optimization
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2018 (English)In: Chromatographia, Vol. 81, no 6, p. 851-860Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Preparative chromatography, Omeprazole, Etiracetam, Optimization of productivity, Taguchi optimization, Equilibrium–dispersive model
National Category
Biochemistry and Molecular Biology Analytical Chemistry
Identifiers
urn:nbn:se:kau:diva-67311 (URN)10.1007/s10337-018-3519-z (DOI)2-s2.0-85046036669 (Scopus ID)
Available from: 2018-05-11 Created: 2018-05-11 Last updated: 2018-07-10Bibliographically approved
Vera, C. M., Samuelsson, J., Fornstedt, T., Dennis, G. R. & Shalliker, R. A. (2018). Protocol for the visualisation of axial temperature gradients in ultra high performance liquid chromatography using infrared cameras. Microchemical journal (Print), 141, 141-147
Open this publication in new window or tab >>Protocol for the visualisation of axial temperature gradients in ultra high performance liquid chromatography using infrared cameras
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2018 (English)In: Microchemical journal (Print), ISSN 0026-265X, E-ISSN 1095-9149, Vol. 141, p. 141-147Article in journal (Refereed) Published
Abstract [en]

A protocol was developed for the visualisation of axial temperature gradients on a Kinetex column (1.3 μm C18 100 Å 50 × 2.1 mm) operated at near maximum pressure of the system (Pmax) using an infrared camera. Real time viscous frictional heating effects across the entire column length was observed, and showed that with increasing flow rate there was an increase in the maximum temperature of the column, and the difference between the inlet and outlet temperatures. Temperature profile data over the entire length of the column revealed the dynamics of heat exchange processes along different parts of the column, and raises the question on potential heating effects on eluents. The axial temperature gradients of eluents such as pure methanol, isopropyl alcohol and acetonitrile near Pmax were compared; finding that acetonitrile which had the highest flow velocity at Pmax gave the highest overall temperature increase for these eluents.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Frictional heating, High pressure, Thermal effects, Thermal imagining, UHPLC
National Category
Biochemistry and Molecular Biology Chemical Sciences
Identifiers
urn:nbn:se:kau:diva-67492 (URN)10.1016/j.microc.2018.05.004 (DOI)2-s2.0-85047094080 (Scopus ID)
Available from: 2018-06-07 Created: 2018-06-07 Last updated: 2018-07-11Bibliographically approved
Forssén, P., Multia, E., Samuelsson, J., Andersson, M., Aastrup, T., Altun, S., . . . Fornstedt, T. (2018). Reliable Strategy for Analysis of Complex Biosensor Data. Analytical Chemistry, 90(8), 5366-5374
Open this publication in new window or tab >>Reliable Strategy for Analysis of Complex Biosensor Data
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2018 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 8, p. 5366-5374Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
Keywords
Biosensors, Dissociation, Kinetics, Molecular biology, Analyte concentration, Complex concentration, Complex formation reactions, Dissociation kinetics, Experimental system, Global fitting procedures, Heterogeneous interactions, Numerical algorithms, Rate constants
National Category
Chemical Sciences Organic Chemistry Biochemistry and Molecular Biology
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-67280 (URN)10.1021/acs.analchem.8b00504 (DOI)000430512200059 ()2-s2.0-85045627010 (Scopus ID)
Available from: 2018-05-04 Created: 2018-05-04 Last updated: 2018-11-22Bibliographically approved
Forss, E., Haupt, D., Stalberg, O., Enmark, M., Samuelsson, J. & Fornstedt, T. (2017). Chemometric evaluation of the combined effect of temperature, pressure, and co-solvent fractions on the chiral separation of basic pharmaceuticals using actual vs set operational conditions. Journal of Chromatography A, 1499, 165-173
Open this publication in new window or tab >>Chemometric evaluation of the combined effect of temperature, pressure, and co-solvent fractions on the chiral separation of basic pharmaceuticals using actual vs set operational conditions
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2017 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1499, p. 165-173Article in journal (Refereed) Published
Abstract [en]

The need to determine the actual operational conditions, instead of merely using the set operational conditions, was investigated for in packed supercritical fluid chromatography (SFC) by design of experiments (DoE) using a most important type of compounds, pharmaceutical basics, as models. The actual values of temperature, pressure, and methanol levels were recorded and calculated from external sensors, while the responses in the DoE were the retention factors and selectivity. A Kromasil CelluCoat columh was used as the stationary phase, carbon dioxide containing varying methanol contents as the mobile phase, and the six racemates of alprenolol, atenolol, metoprolol, propranolol, clenbuterol, and mianserin were selected as model solutes. For the retention modeling, the most important term was the methanol fraction followed by the temperature and pressure. Significant differences (p<0.05) between most of the coefficients in the retention models were observed when comparing models from set and actual conditions. The selectivity was much less affected by operational changes, and therefore was not severely affected by difference between set and actual conditions. The temperature differences were usually small, maximum +/- 1.4 degrees C, whereas the pressure differences were larger, typically approximately +10.5 bar. The set and actual fractions of methanol also differed, usually by +/- 0.4 percentage points. A cautious conclusion is that the primary reason for the discrepancy between the models is a mismatch between the set and actual methanol fractions. This mismatch is more serious in retention models at low methanol fractions. The study demonstrates that the actual conditions should almost always be preferred. (C) 2017 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Supercritical fluid chromatography, Basic pharmaceuticals, Chiral separations, Design of experiments, Actual conditions, Set conditions
National Category
Chemical Sciences
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-71672 (URN)10.1016/j.chroma.2017.03.077 (DOI)000401394200017 ()28389095 (PubMedID)
Note

Dan Haupt och Olle Stålberg har affiliering KAU på artikeln men hittar dem inte via personalkatalogen./BHJ

Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2019-04-04Bibliographically approved
Åsberg, D., Lesko, M., Leek, T., Samuelsson, J., Kaczmarski, K. & Fornstedt, T. (2017). Estimation of Nonlinear Adsorption Isotherms in Gradient Elution RP-LC of Peptides in the Presence of an Adsorbing Additive. Chromatographia, 80(6), 961-966
Open this publication in new window or tab >>Estimation of Nonlinear Adsorption Isotherms in Gradient Elution RP-LC of Peptides in the Presence of an Adsorbing Additive
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2017 (English)In: Chromatographia, ISSN 0009-5893, E-ISSN 1612-1112, Vol. 80, no 6, p. 961-966Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Springer, 2017
Keywords
Liquid chromatography · Peptide separation, Charged surface hybrid, Adsorption isotherm, Gradient elution
National Category
Chemical Sciences
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-65567 (URN)10.1007/s10337-017-3298-y (DOI)000402824400014 ()28725083 (PubMedID)
Available from: 2018-01-11 Created: 2018-01-11 Last updated: 2018-11-22Bibliographically approved
Glenne, E., Leek, H., Klarqvist, M., Samuelsson, J. & Fornstedt, T. (2017). Systematic investigations of peak deformations due to co-solvent adsorption in preparative supercritical fluid chromatography. Paper presented at 16th International Symposium on Preparative and Industrial Chromatography and Allied Techniques, OCT 09-12, 2016, Vienna, AUSTRIA. Journal of Chromatography A, 1496, 141-149
Open this publication in new window or tab >>Systematic investigations of peak deformations due to co-solvent adsorption in preparative supercritical fluid chromatography
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2017 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1496, p. 141-149Article in journal (Refereed) Published
Abstract [en]

Strangely shaped overloaded bands were recently reported using a standard supercritical fluid chromatographic system comprising a diol column as the stationary phase and carbon dioxide with methanol as the mobile phase, Some of these overloaded elution profiles appeared strongly deformed and even had "anti-Langmuirian" shapes although their solute compounds had "Langmuirian" adsorption. To obtain a more complete understanding of the generality of these effects, the investigation was expanded to cover also other common co-solvents, such as ethanol, 2-propanol, and acetonitrile, as well as various stationary phase materials, such as silica, and 2-ethylpyridine. From this expanded study it could be confirmed that the effects of deformed overloaded solute band shapes, due to co-solvent adsorption, is general phenomena in supercritical fluid chromatographic. It could also be concluded that these effects as well as previously observed "solvent effects" or "plug effects" are entirely due to competition between the solute and solvent molecules for the adsorption sites on the stationary phase surface. Finally, guidelines were given for how to evaluate the risk of deformations occurring for a given solvent-column combination, based simply on testing retention times of solutes and co-solvent. (C) 2017 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Supercritical fluid chromatography, Co-solvent adsorption, Adsorption strength, Langmuir band shape, Anti-Langmuir band shape
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kau:diva-65479 (URN)10.1016/j.chroma.2017.03.053 (DOI)000400222200016 ()28366564 (PubMedID)
Conference
16th International Symposium on Preparative and Industrial Chromatography and Allied Techniques, OCT 09-12, 2016, Vienna, AUSTRIA
Available from: 2017-12-29 Created: 2017-12-29 Last updated: 2018-06-26Bibliographically approved
Asberg, D., Weinmann, A. L., Leek, T., Lewis, R. J., Klarqvist, M., Lesko, M., . . . Fornstedt, T. (2017). The importance of ion-pairing in peptide purification by reversed-phase liquid chromatography. Journal of Chromatography A, 1496, 80-91
Open this publication in new window or tab >>The importance of ion-pairing in peptide purification by reversed-phase liquid chromatography
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2017 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1496, p. 80-91Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Peptide separations, Adsorption isotherm, TFA, Preparative separation, Ion-pair formation, Nuclear Overhauser enhancement
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kau:diva-65480 (URN)10.1016/j.chroma.2017.03.041 (DOI)000400222200010 ()28363419 (PubMedID)
Available from: 2017-12-29 Created: 2017-12-29 Last updated: 2018-06-26Bibliographically approved
Glenne, E., Ohlen, K., Leek, H., Klarqvist, M., Samuelsson, J. & Fornstedt, T. (2016). A closer study of methanol adsorption and its impact on solute retentions in supercritical fluid chromatography. Journal of Chromatography A, 1442, 129-139
Open this publication in new window or tab >>A closer study of methanol adsorption and its impact on solute retentions in supercritical fluid chromatography
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2016 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1442, p. 129-139Article in journal (Refereed) Published
Abstract [en]

Surface excess adsorption isotherms of methanol on a diol silica adsorbent were measured in supercritical fluid chromatography (SFC) using a mixture of methanol and carbon dioxide as mobile phase. The tracer pulse method was used with deuterium labeled methanol as solute and the tracer peaks were detected using APCI-MS over the whole composition range from neat carbon dioxide to neat methanol. The results indicate that a monolayer (4 angstrom) of methanol is formed on the stationary phase. Moreover, the importance of using the set or the actual methanol fractions and volumetric flows in SFC was investigated by measuring the mass flow respective pressure and by calculations of the actual volume fraction of methanol. The result revealed a significant difference between the value set and the actually delivered volumetric methanol flow rate, especially at low modifier fractions. If relying only on the set methanol fraction in the calculations, the Methanol layer thickness should in this system be highly overestimated. Finally, retention times for a set of solutes were measured and related to the findings summarized above concerning methanol adsorption. A strongly non-linear relationship between the logarithms of the retention factors and the modifier fraction in the mobile phase was revealed, prior to the established monolayer. At modifier fractions above that required for establishment of the methanol monolayer, this relationship turns linear which explains why the solute retention factors are less sensitive to changes in modifier content in this region.

Keywords
Supercritical fluid chromatography, SFC, Excess adsorption, Solvent adsorption, Tracer-pulse method, Solute retention
National Category
Chemical Engineering
Research subject
Chemical Engineering
Identifiers
urn:nbn:se:kau:diva-42028 (URN)10.1016/j.chroma.2016.03.006 (DOI)000374083100014 ()26979267 (PubMedID)
Available from: 2016-05-13 Created: 2016-05-13 Last updated: 2017-11-30Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-1819-1709

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