Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 92) Show all publications
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
Show others...
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
Lin, G., Zhang, Y., Cheng, X., Gulliksson, M., Forssén, P. & Fornstedt, T. (2018). A regularizing Kohn-Vogelius formulation for the model-free adsorption isotherm estimation problem in chromatography. Applicable Analysis, 97(1), 13-40
Open this publication in new window or tab >>A regularizing Kohn-Vogelius formulation for the model-free adsorption isotherm estimation problem in chromatography
Show others...
2018 (English)In: Applicable Analysis, ISSN 0003-6811, E-ISSN 1563-504X, Vol. 97, no 1, p. 13-40Article in journal (Refereed) Published
Abstract [en]

Competitive adsorption isotherms must be estimated in order to simulate and optimize modern continuous modes of chromatography in situations where experimental trial-and-error approaches are too complex and expensive. The inverse method is a numeric approach for the fast estimation of adsorption isotherms directly from overloaded elution profiles. However, this identification process is usually ill-posed. Moreover, traditional model-based inverse methods are restricted by the need to choose an appropriate adsorption isotherm model prior to estimate, which might be very hard for complicated adsorption behavior. In this study, we develop a Kohn-Vogelius formulation for the model-free adsorption isotherm estimation problem. The solvability and convergence for the proposed inverse method are studied. In particular, using a problem-adapted adjoint, we obtain a convergence rate under substantially weaker and more realistic conditions than are required by the general theory. Based on the adjoint technique, a numerical algorithm for solving the proposed optimization problem is developed. Numerical tests for both synthetic and real-world problems are given to show the efficiency of the proposed regularization method.

National Category
Chemical Sciences Geophysics Analytical Chemistry
Research subject
Chemistry; Physics
Identifiers
urn:nbn:se:kau:diva-65938 (URN)10.1080/00036811.2017.1284311 (DOI)000417831700003 ()
Available from: 2018-01-25 Created: 2018-01-25 Last updated: 2018-06-29Bibliographically approved
Zhang, Y., Forssén, P., Fornstedt, T., Gulliksson, M. & Dai, X. (2018). An adaptive regularization algorithm for recovering the rate constant distribution from biosensor data. Inverse Problems in Science and Engineering, 26(10), 1464-1489
Open this publication in new window or tab >>An adaptive regularization algorithm for recovering the rate constant distribution from biosensor data
Show others...
2018 (English)In: Inverse Problems in Science and Engineering, ISSN 1741-5977, E-ISSN 1741-5985, Vol. 26, no 10, p. 1464-1489Article in journal (Refereed) Published
Abstract [en]

We present here the theoretical results and numerical analysis of a regularization method for the inverse problem of determining the rate constant distribution from biosensor data. The rate constant distribution method is a modern technique to study binding equilibrium and kinetics for chemical reactions. Finding a rate constant distribution from biosensor data can be described as a multidimensional Fredholm integral equation of the first kind, which is a typical ill-posed problem in the sense of J. Hadamard. By combining regularization theory and the goal-oriented adaptive discretization technique, we develop an Adaptive Interaction Distribution Algorithm (AIDA) for the reconstruction of rate constant distributions. The mesh refinement criteria are proposed based on the a posteriori error estimation of the finite element approximation. The stability of the obtained approximate solution with respect to data noise is proven. Finally, numerical tests for both synthetic and real data are given to show the robustness of the AIDA.

Place, publisher, year, edition, pages
Oxon, UK: Taylor & Francis, 2018
Keywords
Rate constant distribution, inverse problem, regularization, adaptive finite element, a posteriori error estimation
National Category
Computational Mathematics Geophysics Chemical Engineering
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-68754 (URN)10.1080/17415977.2017.1411912 (DOI)000438638300005 ()
Note

Zhang, Yue saknar cas! 20181018

Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-10-18Bibliographically approved
Forssén, P. & Fornstedt, T. (2018). Impact of column and stationary phase properties on the productivity in chiral preparative LC. Journal of Separation Science, 41(6), 1346-1354
Open this publication in new window or tab >>Impact of column and stationary phase properties on the productivity in chiral preparative LC
2018 (English)In: Journal of Separation Science, ISSN 1615-9306, E-ISSN 1615-9314, Vol. 41, no 6, p. 1346-1354Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2018
Keywords
enantiomers, preparative chromatography, process optimization, productivity
National Category
Chemical Sciences
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-67070 (URN)10.1002/jssc.201701435 (DOI)000428797000019 ()29359510 (PubMedID)
Available from: 2018-04-19 Created: 2018-04-19 Last updated: 2018-04-26Bibliographically 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
Show others...
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
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
Show others...
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
Show others...
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
Zhang, Y., Lin, G., Gulliksson, M., Forssén, P., Fornstedt, T. & Cheng, X. (2017). An adjoint method in inverse problems of chromatography. Inverse Problems in Science and Engineering, 25(8), 1112-1137
Open this publication in new window or tab >>An adjoint method in inverse problems of chromatography
Show others...
2017 (English)In: Inverse Problems in Science and Engineering, ISSN 1741-5977, E-ISSN 1741-5985, Vol. 25, no 8, p. 1112-1137Article in journal (Refereed) Published
Abstract [en]

How to determine adsorption isotherms is an issue of significant importance in chromatography. A modern technique of obtaining adsorption isotherms is to solve an inverse problem so that the simulated batch separation coincides with actual experimental results. In this work, as well as the natural least-square approach, we consider a Kohn-Vogelius type formulation for the reconstruction of adsorption isotherms in chromatography, which converts the original boundary fitting problem into a domain fitting problem. Moreover, using the first momentum regularizing strategy, a new regularization algorithm for both the Equilibrium-Dispersive model and the Transport-Dispersive model is developed. The mass transfer resistance coefficients in the Transport-Dispersive model are also estimated by the proposed inverse method. The computation of the gradients of objective functions for both of the two models is derived by the adjoint method. Finally, numerical simulations for both a synthetic problem and a real-world problem are given to show the robustness of the proposed algorithm.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keywords
Chromatography, adsorption isotherm, inverse problem, regularization, convection-diffusion equation, adjoint method
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kau:diva-65526 (URN)10.1080/17415977.2016.1222528 (DOI)000401246500002 ()
Available from: 2018-01-04 Created: 2018-01-04 Last updated: 2018-06-27Bibliographically 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
Show others...
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
Encarnacao, J. C., Barta, P., Fornstedt, T. & Andersson, K. (2017). Impact of assay temperature on antibody binding characteristics in living cells: A case study. BIiomedical reports, 7(5), 400-406
Open this publication in new window or tab >>Impact of assay temperature on antibody binding characteristics in living cells: A case study
2017 (English)In: BIiomedical reports, ISSN 2049-9434, Vol. 7, no 5, p. 400-406Article in journal (Refereed) Published
Abstract [en]

Kinetic and thermodynamic studies of ligand-receptor interactions are essential for increasing the understanding of receptor activation mechanisms and drug behavior. The characterization of molecular interactions on living cells in real-time goes beyond most current binding assays, and provides valuable information about the dynamics and underlying mechanism of the molecules in a living system. The effect of temperature on interactions in cell-based assays is, however, rarely discussed. In the present study, the effect of temperature on binding of monoclonal antibodies, cetuximab and pertuzumab to specific receptors on living cancer cells was evaluated, and the affinity and kinetics of the interactions were estimated at selected key temperatures. Changes in the behavior of the interactions, particularly in the on- and off-rates were observed, leading to greatly extended time to reach the equilibrium at 21 degrees C compared with at 37 degrees C. However, the observed changes in kinetic characteristics were less than a factor of 10. It was concluded that it is possible to conduct real-time measurements with living cells at different temperatures, and demonstrated that influences of the ambient temperature on the interaction behavior are likely to be less than one order of magnitude.

National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:kau:diva-65945 (URN)10.3892/br.2017.982 (DOI)000417416000002 ()29181152 (PubMedID)
Available from: 2018-01-25 Created: 2018-01-25 Last updated: 2018-07-02Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7123-2066

Search in DiVA

Show all publications