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Forssén, Patrik
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Publications (10 of 42) Show all publications
Glenne, E., Samuelsson, J., Leek, H., Forssén, P., Klarqvist, M. & Fornstedt, T. (2020). Systematic investigations of peak distortions due to additives in supercritical fluid chromatography. Journal of Chromatography & Separation Techniques, Article ID 461048.
Open this publication in new window or tab >>Systematic investigations of peak distortions due to additives in supercritical fluid chromatography
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2020 (English)In: Journal of Chromatography & Separation Techniques, E-ISSN 2157-7064, article id 461048Article in journal (Refereed) In press
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Supercritical fluid chromatography, Peak performance Peak distortions, Additives, Basic components, Overloaded peaks
National Category
Analytical Chemistry
Research subject
Chemical Engineering
Identifiers
urn:nbn:se:kau:diva-75764 (URN)10.1016/j.chroma.2020.461048 (DOI)
Note

This article was published as manuscript in Emelie Glennes PhD dissertation.

Available from: 2019-11-18 Created: 2019-11-18 Last updated: 2020-03-19
Liangsupree, T., Multia, E., Metso, J., Jauhiainen, M., Forssén, P., Fornstedt, T., . . . Riekkola, M.-L. (2019). Rapid affinity chromatographic isolation method for LDL in human plasma by immobilized chondroitin-6-sulfate and anti-apoB-100 antibody monolithic disks in tandem. Scientific Reports, 9, Article ID 11235.
Open this publication in new window or tab >>Rapid affinity chromatographic isolation method for LDL in human plasma by immobilized chondroitin-6-sulfate and anti-apoB-100 antibody monolithic disks in tandem
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 11235Article in journal (Refereed) Published
Abstract [en]

Low-density lipoprotein (LDL) is considered the major risk factor for the development of atherosclerotic cardiovascular diseases (ASCVDs). A novel and rapid method for the isolation of LDL from human plasma was developed utilising affinity chromatography with monolithic stationary supports. The isolation method consisted of two polymeric monolithic disk columns, one immobilized with chondroitin-6-sulfate (C6S) and the other with apolipoprotein B-100 monoclonal antibody (anti-apoB-100 mAb). The first disk with C6S was targeted to remove chylomicrons, very-low-density lipoprotein (VLDL) particles, and their remnants including intermediate-density lipoprotein (IDL) particles, thus allowing the remaining major lipoprotein species, i.e. LDL, lipoprotein(a) (Lp(a)), and high-density lipoprotein (HDL) to flow to the anti-apoB-100 disk. The second disk captured LDL particles via the anti-apoB-100 mAb attached on the disk surface in a highly specific manner, permitting the selective LDL isolation. The success of LDL isolation was confirmed by different techniques including quartz crystal microbalance. In addition, the method developed gave comparable results with ultracentrifugation, conventionally used as a standard method. The reliable results achieved together with a short isolation time (less than 30 min) suggest the method to be suitable for clinically relevant LDL functional assays.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
Keywords
IMMUNOAFFINITY CHROMATOGRAPHY; FAST SEPARATION; LIPOPROTEINS; INSIGHTS; COLUMNS
National Category
Engineering and Technology
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-74335 (URN)10.1038/s41598-019-47750-z (DOI)000478575000022 ()31375727 (PubMedID)
Available from: 2019-08-15 Created: 2019-08-15 Last updated: 2020-01-16Bibliographically 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
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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: 2019-03-28Bibliographically 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
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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: 2019-03-28Bibliographically 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
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
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
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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: 2019-12-09Bibliographically approved
Fornstedt, T., Forssén, P. & Samuelsson, J. (2017). Chapter 24 - Modeling of preparative liquid chromatography. In: Fanali, Salvatore; Haddad, Paul R.; Poole, Colin F.; Riekkola, Marja-Liisa (Ed.), Liquid Chromatography (Second Edition): (pp. 573-592). Elsevier
Open this publication in new window or tab >>Chapter 24 - Modeling of preparative liquid chromatography
2017 (English)In: Liquid Chromatography (Second Edition) / [ed] Fanali, Salvatore; Haddad, Paul R.; Poole, Colin F.; Riekkola, Marja-Liisa, Elsevier, 2017, p. 573-592Chapter in book (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Preparative liquid chromatography, Adsorption isotherm, Modeling, Optimization, Injection profile, Additive, Gradient elution
National Category
Chemical Sciences
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-75538 (URN)10.1016/B978-0-12-805393-5.00024-5 (DOI)978-0-12-805393-5 (ISBN)
Available from: 2019-11-07 Created: 2019-11-07 Last updated: 2019-11-07Bibliographically approved
Zhang, Y., Lin, G.-L., Forssén, P., Gulliksson, M., Fornstedt, T. & Cheng, X.-L. (2016). A regularization method for the reconstruction of adsorption isotherms in liquid chromatography. Inverse Problems, 32(10), Article ID 105005.
Open this publication in new window or tab >>A regularization method for the reconstruction of adsorption isotherms in liquid chromatography
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2016 (English)In: Inverse Problems, ISSN 0266-5611, E-ISSN 1361-6420, Vol. 32, no 10, article id 105005Article in journal (Refereed) Published
Abstract [en]

Determining competitive adsorption isotherms is an open problem in liquid chromatography. Since traditional experimental trial-and-error approaches are too complex and expensive, a modern technique of obtaining adsorption isotherms is to solve the inverse problem so that the simulated batch separation coincides with actual experimental results. This is a typical ill-posed problem. Moreover, in almost all cases the observed concentration at the outlet is the total response of all components, which makes the problem more difficult. In this work, we tackle the ill-posedness with a new regularization method, which is based on the fact that the adsorption isotherms do not depend on the injection profile. The proposed method transfers the original problem to an optimization problem with a time-dependent convection-diffusion equation constraint. Iterative algorithms for solving constraint optimization problems for both the equilibrium-dispersive and the transport-dispersive models are developed. The mass transfer resistance is also estimated by the proposed inverse method. A regularization parameter selection method and the convergence property of the proposed algorithm are discussed. Finally, numerical tests for both synthetic problems and real-world problems are given to show the efficiency and feasibility of the proposed regularization method.

Place, publisher, year, edition, pages
IOP PUBLISHING LTD, 2016
Keywords
chromatography, adsorption isotherm, inverse problem, regularization, convection-diffusion equation, adjoint problem
National Category
Chemical Engineering
Identifiers
urn:nbn:se:kau:diva-65078 (URN)10.1088/0266-5611/32/10/105005 (DOI)000402976000005 ()
Available from: 2017-11-02 Created: 2017-11-02 Last updated: 2019-12-09Bibliographically approved
Fornstedt, T., Forssén, P. & Westerlund, D. (2016). System peaks and their impact in liquid chromatography. TrAC. Trends in analytical chemistry, 81, 42-50
Open this publication in new window or tab >>System peaks and their impact in liquid chromatography
2016 (English)In: TrAC. Trends in analytical chemistry, ISSN 0165-9936, E-ISSN 1879-3142, Vol. 81, p. 42-50Article, review/survey (Refereed) Published
Abstract [en]

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. 

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Liquid chromatography, System peaks, Perturbation peaks, Indirect detection, Peak distortions, Peak compression, Peak deformations, Linear chromatography, Nonlinear chromatography
National Category
Chemical Engineering
Research subject
Chemical Engineering
Identifiers
urn:nbn:se:kau:diva-46237 (URN)10.1016/j.trac.2016.01.008 (DOI)000380603600006 ()
Available from: 2016-09-21 Created: 2016-09-21 Last updated: 2019-11-04Bibliographically approved
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