liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Bergström, Gunnar
Publications (10 of 12) Show all publications
Johansson, L. B. G., Simon, R., Bergström, G., Eriksson, M., Prokop, S., Mandenius, C.-F., . . . Nilsson, P. (2015). An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates. Biosensors & bioelectronics, 63, 204-211
Open this publication in new window or tab >>An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates
Show others...
2015 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 63, p. 204-211Article in journal (Refereed) Published
Abstract [en]

Ligands for identifying protein aggregates are of great interest as such deposits are the pathological hallmark of a wide range of severe diseases including Alzheimers and Parkinsons disease. Here we report the synthesis of an azide functionalized fluorescent pentameric oligothiophene that can be utilized as a ligand for multimodal detection of disease-associated protein aggregates. The azide functionalization allows for attachment of the ligand to a surface by conventional click chemistry without disturbing selective interaction with protein aggregates and the oligothiophene-aggregate interaction can be detected by fluorescence or surface plasmon resonance. In addition, a methodology where the oligothiophene ligand is employed as a capturing molecule selective for aggregated proteins in combination with an antibody detecting a distinct peptide/protein is also presented. We foresee that this methodology will offer the possibility to create a variety of multiplex sensing systems for sensitive and selective detection of protein aggregates, the pathological hallmarks of several neurodegenerative diseases.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Protein aggregates; Oligothiophene; Fluorescence; Surface plasmon resonance; Click chemistry
National Category
Chemical Sciences Biological Sciences
Identifiers
urn:nbn:se:liu:diva-112169 (URN)10.1016/j.bios.2014.07.042 (DOI)000343337000030 ()25089818 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research; Ehrling Persson Foundation; ERC Starting Independent Researcher grant (Project: MUMID)

Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2019-01-22
Bergström, G., Kuusk, A. & Mandenius, C.-F. (2015). Capacitive biosensor for detection of toxicity biomarkers.
Open this publication in new window or tab >>Capacitive biosensor for detection of toxicity biomarkers
2015 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Microfluidic devices are rapidly gaining importance for in vitro toxicity testing. Biomarker detection in microfluidic assays are however challenging due to small sample sizes and low analyte concentration. Capacitive electrochemical biosensors have been reported to have high sensitivity and properties that are amenable for implementation into microfluidic devices.

In this work a biosensor application for troponin T (TnT) is presented. The sensor showed linear response to analyte over five orders of magnitude with the lowest detectable signal at 10-13 M. The sensor proved to be able to detect TnT spiked in cell culture media at concentrations relevant for cell cultures.

National Category
Biological Sciences Physical Sciences
Identifiers
urn:nbn:se:liu:diva-118293 (URN)
Available from: 2015-05-26 Created: 2015-05-26 Last updated: 2019-01-22
Bergström, G. (2015). Microfluidic biosensor systems for cardiotoxicity assaying. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Microfluidic biosensor systems for cardiotoxicity assaying
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Toxicity screening is an important part of pharmaceutical development and early detection of toxic side effects provide the opportunity for early redesign or termination of unfeasible projects. Today toxicity testing is relying on experiments on animals. Ethical concerns, high costs and problems with interspecies variability in animal experiments have introduced incentives for cell-based toxicity assays. The recent development of stem cell technology have raised the hope for toxicity testing with higher predictivity that can reduce the amount of animals sacrificed, increase the patient safety and reduce the costs in pharmaceutical development.

Cell development and behavior is to a large extent dependent on the microenvironment. Microfluidic techniques can be used to build small-sized structures that provide the opportunity to introduce a high degree of control of the cell culture environment with features in cell sizes. In this thesis is demonstrated two different methods for infusing cells into microfluidic cell culture devices using either cells clustered in cardiac bodies during differentiation or cells pre-seeded in microporous carriers prior to infusion.

Microfluidic cell culture devices are well suited for optical  evaluation. Demonstrated in this thesis is fluorescent staining in combination with confocal microscopy as well as automated imaging with evaluation of beating frequency of cardiomyocyte cell clusters can be used to assess toxicity of cells cultured in microfluidic devices.

Biosensors use biological recognition elements to measure the presence of a chemical substance, for example low concentrations of biomarkers secreted by cells in a toxicity assay. Especially capacitive biosensors have shown very low limit of detection. In addition, protein G is demonstrated as an affinity ligand to capture IgG antibodies used as recognition element in a biosensor application or used for antibody screening.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. p. 49
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1678
National Category
Biological Sciences Physical Sciences
Identifiers
urn:nbn:se:liu:diva-118295 (URN)978-91-7519-046-4 (ISBN)
Public defence
2015-06-12, Visionen, B-huset, Campus Valla, Linköping, 14:00 (Swedish)
Opponent
Supervisors
Available from: 2015-05-26 Created: 2015-05-26 Last updated: 2019-01-22Bibliographically approved
Wickham, A., Sjölander, D., Bergström, G., Wang, E., Rajendran, V., Hildesjö, C., . . . Aili, D. (2015). Near-Infrared Emitting and Pro-Angiogenic Electrospun Conjugated Polymer Scaffold for Optical Biomaterial Tracking. Advanced Functional Materials, 25(27), 4274-4281
Open this publication in new window or tab >>Near-Infrared Emitting and Pro-Angiogenic Electrospun Conjugated Polymer Scaffold for Optical Biomaterial Tracking
Show others...
2015 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 25, no 27, p. 4274-4281Article in journal (Refereed) Published
Abstract [en]

Noninvasive tracking of biomaterials is vital for determining the fate and degradation of an implant in vivo, and to show its role in tissue regeneration. Current biomaterials have no inherent capacity to enable tracing but require labeling with, for example, fluorescent dyes, or nanoparticles. Here a novel biocompatible fully conjugated electrospun scaffold is described, based on a semiconducting luminescent polymer that can be visualized in situ after implantation using fluorescence imaging. The polymer, poly [2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8-diyl-alt -thiophene-2,5-diyl] (TQ1), is electrospun to form a fibrous mat. The fibers display fluorescence emission in the near-infrared region with lifetimes in the sub-nanosecond range, optimal for in situ imaging. The material shows no cytotoxic behaviors for embryonic chicken cardiomyocytes and mouse myoblasts, and cells migrate onto the TQ1 fibers even in the presence of a collagen substrate. Subcutaneous implantations of the material in rats show incorporation of the TQ1 fibers within the tissue, with limited inflammation and a preponderance of small capillaries around the fibers. The fluorescent properties of the TQ1 fibers are fully retained for up to 90 d following implantation and they can be clearly visualized in tissue using fluorescence and lifetime imaging, thus making it both a pro-angiogenic and traceable biomaterial.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
Keywords
biomaterials, conjugated polymers, near-infrared, angiogenesis, electrospinning
National Category
Biomaterials Science Polymer Chemistry
Identifiers
urn:nbn:se:liu:diva-120449 (URN)10.1002/adfm.201500351 (DOI)000357996600011 ()
Note

Funding Agencies|Linkoping University; Swedish Foundation for Strategic Research; Swedish Research Council

Available from: 2015-08-12 Created: 2015-08-11 Last updated: 2017-12-04
Bergström, G., Christoffersson, J., Schwanke, K., Zweigerdt, R. & Mandenius, C.-F. (2015). Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging. Lab on a Chip, 15(15), 3242-3249
Open this publication in new window or tab >>Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging
Show others...
2015 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 15, no 15, p. 3242-3249Article in journal (Refereed) Published
Abstract [en]

Beating in vivo-like human cardiac bodies (CBs) were used in a microfluidic device for testing cardiotoxicity. The CBs, cardiomyocyte cell clusters derived from induced pluripotent stem cells, exhibited typical structural and functional properties of the native human myocardium. The CBs were captured in niches along a perfusion channel in the device. Video imaging was utilized for automatic monitoring of the beating frequency of each individual CB. The device allowed assessment of cardiotoxic effects on the 3D clustered cardiomyocytes from the drug substances doxorubicin, verapamil and quinidine. Beating frequency data recorded over a period of 6 hours are presented and compared to literature data. The results indicate that this microfluidic setup with imaging of CB characteristics provides a new opportunity for label-free, non-invasive investigation of toxic effects in a 3D microenvironment.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2015
National Category
Biological Sciences Physical Sciences
Identifiers
urn:nbn:se:liu:diva-118294 (URN)10.1039/c5lc00449g (DOI)000358022900017 ()
Available from: 2015-05-26 Created: 2015-05-26 Last updated: 2019-01-22Bibliographically approved
Duong-Thi, M.-D., Bergström, G., Mandenius, C.-F., Bergstrom, M., Fex, T. & Ohlson, S. (2014). Comparison of weak affinity chromatography and surface plasmon resonance in determining affinity of small molecules. Analytical Biochemistry, 461, 57-59
Open this publication in new window or tab >>Comparison of weak affinity chromatography and surface plasmon resonance in determining affinity of small molecules
Show others...
2014 (English)In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 461, p. 57-59Article in journal (Refereed) Published
Abstract [en]

In this study, we compared affinity data from surface plasmon resonance (SPR) and weak affinity chromatography (WAC), two established techniques for determination of weak affinity (mM-mu M) small molecule-protein interactions. In the current comparison, thrombin was used as target protein. In WAC the affinity constant (K-D) was determined from retention times, and in SPR it was determined by Langmuir isotherm fitting of steady-state responses. Results indicate a strong correlation between the two methods (R-2 = 0.995, P less than 0.0001).

Place, publisher, year, edition, pages
Elsevier Masson, 2014
Keywords
Affinity determination; Fragment-based drug discovery; Surface plasmon resonance; Thrombin; Weak affinity chromatography
National Category
Biological Sciences
Identifiers
urn:nbn:se:liu:diva-110266 (URN)10.1016/j.ab.2014.05.023 (DOI)000340077600009 ()24915639 (PubMedID)
Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2019-01-22
Bergström, G., Nilsson, K., Mandenius, C.-F. & Robinson, N. D. (2014). Macroporous microcarriers for introducing cells into a microfluidic chip. Lab on a Chip, 14(18), 3502-3504
Open this publication in new window or tab >>Macroporous microcarriers for introducing cells into a microfluidic chip
2014 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 14, no 18, p. 3502-3504Article in journal (Refereed) Published
Abstract [en]

Macroporous gelatin beads (CultiSpher™ microcarriers) provide a convenient method for rapidly and reliably introducing cells cultured ex situ into a microfluidic device, where the spheres create a 3D environment for continued cell proliferation. We demonstrate the usefulness of this technique with a proof-of-concept viability analysis of cardiac cells after treatment with doxorubicin. © 2014 the Partner Organisations.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2014
National Category
Biological Sciences Physical Sciences
Identifiers
urn:nbn:se:liu:diva-109971 (URN)10.1039/c4lc00693c (DOI)000340474300008 ()25068539 (PubMedID)2-s2.0-84905837163 (Scopus ID)
Funder
Swedish Research Council, 2008-7537 2011-6404
Note

Acknowledgements

The primary embryonic cardiomyocytes were provided byJordi Altimiras, Department of Physics, Chemistry andBiology, Linköping University. The authors thank the SwedishResearch Council (Vetenskapsrådet) for fundingviagrants 2008-7537 and 2011-6404

Available from: 2014-08-29 Created: 2014-08-29 Last updated: 2019-01-22Bibliographically approved
Bergström, G. (2012). Exploring the SPR methodology for monitoring of critical attributes in toxicity testing and bioproduction. (Licentiate dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Exploring the SPR methodology for monitoring of critical attributes in toxicity testing and bioproduction
2012 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Analysis of biological components is central in bioprocess monitoring, process control, product quality control and cell based toxicity assaying. One of these themes that is pursued in this thesis is the use of biosensors for monitoring of molecular markers, exploiting the natural selectivity of biomolecules. Another is the use of glycoconjugates to monitor the activity of biomolecules in a flu vaccine process is studied and were the sensor is based on the concept of weak affinity giving fast response time for the sensor.

A third theme is monitoring of cell cultures used for toxicity testing different protein markers is of interest.

When developing biosensor surfaces for new antigens commercial preparations of antibodies are often used. In this work we have chosen to look at lactate dehydrogenase (LDH) and describe the preparation and characterisation of antibody used in biosensor surface development.

The design of a sensor surface is important for the characteristics of a sensor. By binding antibodies in an oriented manner to the surface a better control of the properties of the antibodies is achieved. The demonstrated method also has the advantage of in situ purification and provides a flexible platform for antibody evaluation and sensor development.

In one sentence this thesis explores the possibility of utilizing recognition elements of a biosensor surface. In particular, surface plasmon resonance (SPR) is used as the primary biosensing tool, however most findings in are relevant for other biosensors.

Moreover, the thesis approaches existing bioanalytical impediments, such as purity and accessibility of the recognition elements on the sensor surface and preparation strategies to achieve this.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. p. 19
Series
Linköping Studies in Science and Technology. Thesis, ISSN 0280-7971 ; 1517
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-73410 (URN)LIU-TEK-LIC-2012:2 (Local ID)978-91-7519-971-9 (ISBN)LIU-TEK-LIC-2012:2 (Archive number)LIU-TEK-LIC-2012:2 (OAI)
Presentation
2012-01-31, Panck, Fysikhuset, Campus Valla, Linköpings Universitet, Linköping, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2012-01-03 Created: 2012-01-03 Last updated: 2019-01-22Bibliographically approved
Bergström, G. & Mandenius, C.-F. (2011). Orientation and capturing of antibody affinity ligands: Applications to surface plasmon resonance biochips. Sensors and actuators. B, Chemical, 158(1), 265-270
Open this publication in new window or tab >>Orientation and capturing of antibody affinity ligands: Applications to surface plasmon resonance biochips
2011 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 158, no 1, p. 265-270Article in journal (Refereed) Published
Abstract [en]

A surface plasmon resonance (SPR) sensor chip with immobilized protein G was used for simultaneously capturing, purifying and orienting antibody ligands. The ligands were further stabilized by chemical cross-linking. This procedure of designing the sensor chip improved efficient use of the ligands and could prolong the analytical use. less thanbrgreater than less thanbrgreater thanThe procedure was evaluated on standard dextran-coated sensor chips onto which commercial semi-purified antibodies towards human serum albumin and human troponin where captured and used for analysing their antigens. less thanbrgreater than less thanbrgreater thanThe procedure demonstrates a general design approach for presenting the biorecognition element on a biosensor surface which enhances sensitivity, stability and selectivity at the same time as an impure ligand is purified.

Place, publisher, year, edition, pages
Elsevier, 2011
Keywords
Biosensor, Affinity interaction, SPR, Biacore, Protein G, Sensor chip
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-71770 (URN)10.1016/j.snb.2011.06.017 (DOI)000295500200037 ()
Note

Funding Agencies|European Commission|LSHB-CT-2007-037636|

Available from: 2011-11-04 Created: 2011-11-04 Last updated: 2019-01-22
Mandenius, C.-F., Wang, R., Aldén, A., Bergström, G., Thébault, S., Lutsch, C. & Ohlson, S. (2008). Monitoring of influenza virus hemagglutinin in process samples using weak affinity ligands and surface plasmon resonance. Analytica Chimica Acta, 623, 66-75
Open this publication in new window or tab >>Monitoring of influenza virus hemagglutinin in process samples using weak affinity ligands and surface plasmon resonance
Show others...
2008 (English)In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 623, p. 66-75Article in journal (Refereed) Published
Abstract [en]

Surface plasmon resonance (SPR) was used to screen the interaction between a variety of affinity ligands and hemagglutinin (HA) from human influenza virus, with the aim of identifying low affinity ligands useful for the development of a rapid bioanalytical sensor. Three sialic acid-based structures and four lectins were evaluated as sensor ligands. The sialic acid-based ligands included a natural sialic acid-containing glycoprotein, human α1-acid glycoprotein (α1-AGP), and two synthetic 6′-sialyllactose-conjugates, with varying degree of substitution. The interaction of HA with the four lectin-based ligands, concanavalin A (Con A), wheat germ agglutinin (WGA), Maackia amurensis lectin (MAL), and Sambucus nigra agglutinin (SNA), showed a wide variation of affinity strengths. Affinity and kinetics data were estimated. Strong affinities were observed for Con A, WGA, α1-AGP, and a 6′-sialyllactose-conjugate with a high substitution degree, and low affinities were observed for MAL and a 6′-sialyllactose-conjugate with low substitution.

The main objective, to identify a low affinity ligand which could be used for on-line monitoring and product quantification, was met by a 6′-sialyllactose–ovalbumin conjugate that had 0.6 mol ligand per mol carrier protein. The apparent affinity of this ligand was estimated to be 1.5 ± 0.03 μM (KD) on the SPR surface. Vaccine process samples containing HA were analyzed in the range 10–100 μg HA mL−1 and correlated with single-radial immunodiffusion. The coefficient of variation on the same chip was between 0.010 and 0.091.

Place, publisher, year, edition, pages
Elsevier, 2008
Keywords
Influenza virus hemagglutinin; Affinity ligand; Surface plasmon resonance; Low affinity; Weak affinity
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-44210 (URN)10.1016/j.aca.2008.06.005 (DOI)76040 (Local ID)76040 (Archive number)76040 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2019-01-22Bibliographically approved
Organisations

Search in DiVA

Show all publications