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Forssén, Patrik
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Publications (10 of 36) Show all publications
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: 2019-08-16Bibliographically 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: 2019-03-28Bibliographically approved
Forssen, P. & Fornstedt, T. (2015). A model free method for estimation of complicated adsorption isotherms in liquid chromatography. Journal of Chromatography A, 1409, 108-115
Open this publication in new window or tab >>A model free method for estimation of complicated adsorption isotherms in liquid chromatography
2015 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1409, p. 108-115Article in journal (Refereed) Published
Abstract [en]

Here we show that even extremely small variations in the adsorption isotherm can have a tremendous effect on the shape of the overloaded elution profiles and that the earlier in the adsorption isotherms the variation take place, the larger its impact on the shape of the elution profile. These variations are so small that they can be "hidden" by the discretization and in the general experimental noise when using traditional experimental methods, such as frontal analysis, to measure adsorption isotherms. But as the effects of these variations are more clearly visible in the elution profiles, the Inverse Method (IM) of adsorption isotherm estimation is an option. However, IM usually requires that one selects an adsorption isotherm model prior to the estimation process. Here we show that even complicated models might not be able to estimate the adsorption isotherms with multiple inflection points that small variations might give rise to. We therefore developed a modified IM that, instead of fixed adsorption isotherm models, uses monotone piecewise interpolation. We first validated the method with synthetic data and showed that it can be used to estimate an adsorption isotherm, which accurately predicts an extremely "strange" elution profile. For this case it was impossible to estimate the adsorption isotherm using IM with a fixed adsorption model. Finally, we will give an example of a real chromatographic system where adsorption isotherm with inflection points is estimated by the modified IM.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Adsorption isotherms; Chromatography; Finite volume method; Interpolation; Inverse problems; Liquid chromatography, Adsorption isotherm model; Chromatographic systems; Equilibrium dispersive model; Estimation process; Experimental methods; Inflection points; Inverse methods; Piecewise interpolation, Adsorption, omeprazole, adsorption isotherm; analytic method; Article; high performance liquid chromatography; inverse method; isotherm; liquid chromatography; mathematical computing; mathematical model; measurement accuracy; priority journal; simulation; validation study; adsorption; liquid chromatography; procedures; theoretical model; thermodynamics, Adsorption; Chromatography, Liquid; Models, Theoretical; Thermodynamics
National Category
Chemical Engineering
Research subject
Chemical Engineering
Identifiers
urn:nbn:se:kau:diva-42433 (URN)10.1016/j.chroma.2015.07.030 (DOI)000359882600011 ()2-s2.0-84938738464 (Scopus ID)
Funder
Swedish Research Council, 621-2012-3978Knowledge Foundation, 20140179
Available from: 2016-05-27 Created: 2016-05-23 Last updated: 2017-09-09Bibliographically approved
Enmark, M., Samuelsson, J., Forss, E., Forssén, P. & Fornstedt, T. (2014). Investigation of plateau methods for adsorption isotherm determination in supercritical fluid chromatography. Journal of Chromatography A, 1354, 129-138
Open this publication in new window or tab >>Investigation of plateau methods for adsorption isotherm determination in supercritical fluid chromatography
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2014 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1354, p. 129-138Article in journal (Refereed) Published
Abstract [en]

The Perturbation Peak (PP) method and Frontal analysis (FA) are considered as the most accurate methods for adsorption isotherms determination in liquid chromatography. In this study we investigate and explain why this is not the case in Supercritical Fluid Chromatography (SFC), where the PP method does not work at all, using a modern analytical system. The main reason was found to be that the solute to be studied must be dissolved in the MeOH reservoir before it is mixed with CO2. Since the solute occupies a certain partial volume in the reservoir, the larger the solute content the larger this fractional volume will be, and the final MeOH fraction in the mobile phase will then be smaller compared to the bulk mobile phase without solute in the modifier. If the retention of small injections on the concentration plateaus, i.e., “analytical-size” perturbation peaks, is sensitive to small variations of MeOH in the eluent, this will seriously decrease the accuracy of the PP method. This effect was verified and compensated for and we also demonstrated that the same problem will occur in frontal analysis, another concentration plateau method.

Keywords
Adsorption isotherms, Antipyrine, Elution by Characteristic Points, Perturbation Peak method, Supercritical fluid chromatography
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kau:diva-34392 (URN)10.1016/j.chroma.2014.05.070 (DOI)000339144000015 ()24931444 (PubMedID)
Available from: 2014-10-15 Created: 2014-10-15 Last updated: 2019-07-12Bibliographically approved
Forssén, P., Samuelsson, J. & Fornstedt, T. (2014). Relative importance of column and adsorption parameters on the productivity in preparative liquid chromatography II: Investigation of separation systems with competitive Langmuir adsorption isotherms. Journal of Chromatography A, 1347, 72-79
Open this publication in new window or tab >>Relative importance of column and adsorption parameters on the productivity in preparative liquid chromatography II: Investigation of separation systems with competitive Langmuir adsorption isotherms
2014 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1347, p. 72-79Article in journal (Refereed) Published
Abstract [en]

In this study we investigated how the maximum productivity for commonly used, realistic separation system with a competitive Langmuir adsorption isotherm is affected by changes in column length, packing particle size, mobile phase viscosity, maximum allowed column pressure, column efficiency, sample concentration/solubility, selectivity, monolayer saturation capacity and retention factor of the first eluting compound. The study was performed by generating 1000 random separation systems whose optimal injection volume was determined, i.e., the injection volume that gives the largest achievable productivity. The relative changes in largest achievable productivity when one of the parameters above changes was then studied for each system and the productivity changes for all systems were presented as distributions. We found that it is almost always beneficial to use shorter columns with high pressure drops over the column and that the selectivity should be greater than 2. However, the sample concentration and column efficiency have very limited effect on the maximum productivity. The effect of packing particle size depends on the flow rate limiting factor. If the pumps maximum flow rate is the limiting factor use smaller packing, but if the pressure of the system is the limiting factor use larger packing up to about 40μm.

Keywords
Numerical optimization, Preparative chromatography, Process optimization, Productivity
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kau:diva-34386 (URN)10.1016/j.chroma.2014.04.059 (DOI)000336872800009 ()24831425 (PubMedID)00219673 (ISBN)
Available from: 2014-10-15 Created: 2014-10-15 Last updated: 2019-07-12Bibliographically approved
Enmark, M., Forssén, P., Samuelsson, J. & Fornstedt, T. (2013). Determination of adsorption isotherms in supercritical fluid chromatography. Journal of Chromatography A, 1312, 124-133
Open this publication in new window or tab >>Determination of adsorption isotherms in supercritical fluid chromatography
2013 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1312, p. 124-133Article in journal (Refereed) Published
Abstract [en]

Abstract In this study we will demonstrate the potential of modern integrated commercial analytical SFC-systems for rapid and reliable acquisition of thermodynamic data. This will be done by transferring the following adsorption isotherm determination methods from liquid chromatography (LC) to supercritical fluid chromatography (SFC): Elution by Characteristic Points (ECP), the Retention Time Method (RTM), the Inverse Method (IM) and the Perturbation Peak (PP) method. In order to transfer these methods to SFC in a reliable, reproducible way we will demonstrate that careful system verification using external sensors of mass flow, temperature and pressure are needed first. The adsorption isotherm data generated by the different methods were analyzed and compared and the adsorption isotherms ability to predict new experimental elution profiles was verified by comparing experiments with simulations. It was found that adsorption isotherm data determined based on elution profiles, i.e., ECP, IM and RTM, were able to accurately predict overloaded experimental elution profiles while the more tedious and time-consuming PP method, based on small injections on concentration plateaus, failed in doing so.

Keywords
Adsorption isotherms, Elution by Characteristic Points, Inverse method, Perturbation Peak method, Retention Time Method, Supercritical fluid chromatography
National Category
Physical Chemistry
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-34380 (URN)10.1016/j.chroma.2013.09.007 (DOI)000325123200016 ()24041510 (PubMedID)
Available from: 2014-10-15 Created: 2014-10-15 Last updated: 2019-07-12Bibliographically approved
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