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  • 1.
    Bergström, Gunnar
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Christoffersson, Jonas
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Schwanke, Kristin
    Hannover Medical School, Leibniz Research Laboratories for Biotechnology and Artificial Organs -LEBAO-, Hannover, Germany.
    Zweigerdt, Robert
    Hannover Medical School, Leibniz Research Laboratories for Biotechnology and Artificial Organs -LEBAO-, Hannover, Germany.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging2015In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 15, no 15, p. 3242-3249Article in journal (Refereed)
    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.

  • 2.
    Bergström, Gunnar
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Nilsson, K.
    Percell Biolytica AB, Åstorp, Sweden.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Robinson, Nathaniel D
    Linköping University, Department of Physics, Chemistry and Biology, Surface Physics and Chemistry. Linköping University, The Institute of Technology.
    Macroporous microcarriers for introducing cells into a microfluidic chip2014In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 14, no 18, p. 3502-3504Article in journal (Refereed)
    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.

  • 3.
    Comina, German
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Suska, Anke
    Linköping University, Department of Physics, Chemistry and Biology, Chemical and Optical Sensor Systems. Linköping University, The Institute of Technology.
    Filippini, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Chemical and Optical Sensor Systems. Linköping University, The Institute of Technology.
    Low cost lab-on-a-chip prototyping with a consumer grade 3D printer2014In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 14, no 16, p. 2978-2982Article in journal (Refereed)
    Abstract [en]

    Versatile prototyping of 3D printed lab-on-a-chip devices, supporting different forms of sample delivery, transport, functionalization and readout, is demonstrated with a consumer grade printer, which centralizes all critical fabrication tasks. Devices cost 0.57US$ and are demonstrated in chemical sensing and micromixing examples, which exploit established principles from reference technologies.

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  • 4.
    Comina, German
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemical and Optical Sensor Systems. Linköping University, Faculty of Science & Engineering.
    Suska, Anke
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Filippini, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    PDMS lab-on-a-chip fabrication using 3D printed templates2014In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 14, no 2, p. 424-430Article in journal (Refereed)
    Abstract [en]

    The fabrication of conventional PDMS on glass lab-on-a-chip (LOC) devices, using templates printed with a commercial (2299 US$) micro-stereo lithography 3D printer, is demonstrated. Printed templates replace clean room and photolithographic fabrication resources and deliver resolutions of 50 mu m, and up to 10 mu m in localized hindrances, whereas the templates are smooth enough to allow direct transfer and proper sealing to glass substrates. 3D printed templates accommodate multiple thicknesses, from 50 mu m up to several mm within the same template, with no additional processing cost or effort. This capability is exploited to integrate silicone tubing easily, to improve micromixer performance and to produce multilevel fluidics with simple access to independent functional surfaces, which is illustrated by time-resolved glucose detection. The templates are reusable, can be fabricated in under 20 min, with an average cost of 0.48 US$, which promotes broader access to established LOC configurations with minimal fabrication requirements, relieves LOC fabrication from design skills and provides a versatile LOC development platform.

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  • 5. Corrie, S R
    et al.
    Fernando, G J P
    Crichton, M L
    Brunck, M E G
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Kendall, M A F
    Surface-modified microprojection arrays for intradermal biomarker capture, with low non-specific protein binding2010In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 10, p. 2655-2658Article in journal (Refereed)
    Abstract [en]

    Minimally invasive biosensors are of great interest for rapid detection of disease biomarkers for diagnostic screening at the point-of-care. Here we introduce a device which extracts disease-specific biomarkers directly from the upper dermis, without the needle and syringe or resource-intensive blood processing. Using antigen-specific antibodies raised in mice as a model system, we confirm the analytical specificity and sensitivity of the antibody capture and extraction in comparison to the conventional methods based on needle/syringe blood draw followed by processing and antigen-specific ELISAs.

  • 6.
    Faxälv, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Bolin, Maria
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Electronic control of platelet adhesion using conducting polymer microarrays2014In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 14, no 16, p. 3043-3049Article in journal (Refereed)
    Abstract [en]

    We hereby report a method to fabricate addressable micropatterns of e-surfaces based on the conducting polymer poly(3,4-ethylenedioxythiophene) doped with the anion tosylate (PEDOT:Tos) to gain dynamic control over the spatial distribution of platelets in vitro. With thin film processing and microfabrication techniques, patterns down to 10 mu m were produced to enable active regulation of platelet adhesion at high spatial resolution. Upon electronic addressing, both reduced and oxidized surfaces were created within the same device. This surface modulation dictates the conformation and/or orientation, rather than the concentration, of surface proteins, thus indirectly regulating the adhesion of platelets. The reduced electrode supported platelet adhesion, whereas the oxidized counterpart inhibited adhesion. PEDOT:Tos electrode fabrication is compatible with most of the classical patterning techniques used in printing as well as in the electronics industry. The first types of tools promise ultra-low-cost production of low-resolution (greater than30 mu m) electrode patterns that may combine with traditional substrates and dishes used in a classical analysis setup. Platelets play a pronounced role in cardiovascular diseases and have become an important drug target in order to prevent thrombosis. This clinical path has in turn generated a need for platelet function tests to monitor and assess platelet drug efficacy. The spatial control of platelet adherence presented here could prove valuable for blood cell separation or biosensor microarrays, e.g. in diagnostic applications where platelet function is evaluated.

  • 7.
    Gabrielsson, Erik O.
    et al.
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Tybrandt, Klas
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Ion diode logics for pH control2012In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 12, no 14, p. 2507-2513Article in journal (Refereed)
    Abstract [en]

    Electronic control over the generation, transport, and delivery of ions is useful in order to regulate reactions, functions, and processes in various chemical and biological systems. Different kinds of ion diodes and transistors that exhibit non-linear current versus voltage characteristics have been explored to generate chemical gradients and signals. Bipolar membranes (BMs) exhibit both ion current rectification and water splitting and are thus suitable as ion diodes for the regulation of pH. To date, fast switching ion diodes have been difficult to realize due to accumulation of ions inside the device structure at forward bias – charges that take a long time to deplete at reverse bias. Water splitting occurs at elevated reverse voltage bias and is a feature that renders high ion current rectification impossible. This makes integration of ion diodes in circuits difficult. Here, we report three different designs of micro-fabricated ion bipolar membrane diodes (IBMDs). The first two designs consist of single BM configurations, and are capable of either splitting water or providing high current rectification. In the third design, water-splitting BMs and a highly-rectifying BM are connected in series, thus suppressing accumulation of ions. The resulting IBMD shows less hysteresis, faster off-switching, and also a high ion current rectification ratio as compared to the single BM devices. Further, the IBMD was integrated in a diode-based AND gate, which is capable of controlling delivery of hydroxide ions into a receiving reservoir.

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  • 8.
    Jonsson, C.
    et al.
    Jönsson, C., Åmic AB, Uppsala, Sweden, Biomedical Diagnostics Institute, NCSR Building, Dublin City University, Glasnevin Dublin 9, Ireland.
    Aronsson, M.
    Åmic AB, Uppsala, Sweden.
    Rundstrom, G.
    Rundström, G., Åmic AB, Uppsala, Sweden.
    Pettersson, C.
    Åmic AB, Uppsala, Sweden.
    Mendel-Hartvig, I.
    Åmic AB, Uppsala, Sweden.
    Bakker, J.
    Åmic AB, Uppsala, Sweden, Biomedical Diagnostics Institute, NCSR Building, Dublin City University, Glasnevin Dublin 9, Ireland.
    Martinsson, Erik
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    MacCraith, B.
    Biomedical Diagnostics Institute, NCSR Building, Dublin City University, Glasnevin Dublin 9, Ireland.
    Ohman, O.
    Öhman, O., Åmic AB, Uppsala, Sweden.
    Melin, J.
    Åmic AB, Uppsala, Sweden, Biomedical Diagnostics Institute, NCSR Building, Dublin City University, Glasnevin Dublin 9, Ireland.
    Silane-dextran chemistry on lateral flow polymer chips for immunoassays2008In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 8, no 7, p. 1191-1197Article in journal (Refereed)
    Abstract [en]

    The prognosis for patients suffering from cardiovascular and many other diseases can be substantially improved if diagnosed at an early stage. High performance diagnostic testing using disposable microfluidic chips can provide a platform for realizing this vision. Åmic AB (Uppsala, Sweden) has developed a new microfluidic test chip for sandwich immunoassays fabricated by injection molding of the cycloolefin-copolymer Zeonor™. A highly ordered array of micropillars within the fluidic chip distributes the sample solution by capillary action. Since wetting of the pillar array surface is the only driving force for liquid distribution precise control of the surface chemistry is crucial. In this work we demonstrate a novel protocol for surface hydrophilization and antibody immobilization on cycloolefin-copolymer test chips, based on direct silanisation of the thermoplastic substrate. Dextran is subsequently covalently coupled to amino groups, thus providing a coating with a low contact angle suitable for antibody immobilization. The contact angle of dextran coated chips is stable for at least two months, which enables production of large batches that can be stored for extended periods of time. We demonstrate the utility of the presented platform and surface chemistry in a C-reactive protein assay with a detection limit of 2.6 ng ml-1, a dynamic range of 102 and a coefficient of variance of 15%. © The Royal Society of Chemistry.

  • 9.
    Robinson, Linda
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    Hentzell, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    Robinson, Nathaniel D
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    Isaksson, Joakim
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    Berggren, Magnus
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    Electrochemical wettability switches gate aqueous liquids in microfluidic systems2006In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 6, p. 1277-1278Article in journal (Refereed)
    Abstract [en]

     We demonstrate a simple low-voltage technique for gating the flow of aqueous liquids in microfluidic systems employing the electrochemically-controlled surface energy of the conjugated polymer poly(3-hexylthiophene).

  • 10.
    Seitanidou, Maria S
    et al.
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Tybrandt, Klas
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Simon, Daniel T
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Overcoming transport limitations in miniaturized electrophoretic delivery devices2019In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 19, no 8, p. 1427-1435Article in journal (Refereed)
    Abstract [en]

    Organic electronic ion pumps (OEIPs) have been used for delivery of biological signaling compounds, at high spatiotemporal resolution, to a variety of biological targets. The miniaturization of this technology provides several advantages, ranging from better spatiotemporal control of delivery to reduced invasiveness for implanted OEIPs. One route to miniaturization is to develop OEIPs based on glass capillary fibers that are filled with a polyelectrolyte (cation exchange membrane, CEM). These devices can be easily inserted and brought into close proximity to targeted cells and tissues and could be considered as a starting point for other fiber-based OEIP and iontronic technologies enabling favorable implantable device geometries. While characterizing capillary OEIPs we observed deviations from the typical linear current-voltage behavior. Here we report a systematic investigation of these irregularities by performing experimental characterizations in combination with computational modelling. The cause of the observed irregularities is due to concentration polarization established at the OEIP inlet, which in turn causes electric field-enhanced water dissociation at the inlet. Water dissociation generates protons and is typically problematic for many applications. By adding an ion-selective cap that separates the inlet from the source reservoir this effect is then, to a large extent, suppressed. By increasing the surface area of the inlet with the addition of the cap, the concentration polarization is reduced which thereby allows for significantly higher delivery rates. These results demonstrate a useful approach to optimize transport and delivery of therapeutic substances at low concentrations via miniaturized electrophoretic delivery devices, thus considerably broadening the opportunities for implantable OEIP applications.

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  • 11.
    Svennersten, Karl
    et al.
    Karolinska Institutet, Swedish Medical Nanoscience Center, Department of Neuroscience, Stockholm, Sweden.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Richter-Dahlfors, Agneta
    Karolinska Institutet, Swedish Medical Nanoscience Center, Department of Neuroscience, Stockholm, Sweden.
    Jager, Edwin W H
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Mechanical stimulation of epithelial cells using polypyrrole microactuators.2011In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 11, no 19, p. 3287-3293Article in journal (Refereed)
    Abstract [en]

    The importance of mechanotransduction for physiological systems is becoming increasingly recognized. The effect of mechanical stimulation is well studied in organs and tissues, for instance by using flexible tissue culture substrates that can be stretched by external means. However, on the cellular and subcellular level, dedicated technology to apply appropriate mechanical stimuli is limited. Here we report an organic electronic microactuator chip for mechanical stimulation of single cells. These chips are manufactured on silicon wafers using traditional microfabrication and photolithography techniques. The active unit of the chip consists of the electroactive polymer polypyrrole that expands upon the application of a low potential. The fact that polypyrrole can be activated in physiological electrolytes makes it well suited as the active material in a microactuator chip for biomedical applications. Renal epithelial cells, which are responsive to mechanical stimuli and relevant from a physiological perspective, are cultured on top of the microactuator chip. The cells exhibit good adhesion and spread along the surface of the chip. After culturing, individual cells are mechanically stimulated by electrical addressing of the microactuator chip and the response to this stimulation is monitored as an increase in intracellular Ca(2+). This Ca(2+) response is caused by an autocrine ATP signalling pathway associated with mechanical stimulation of the cells. In conclusion, the present work demonstrates a microactuator chip based on an organic conjugated polymer, for mechanical stimulation of biological systems at the cellular and sub-cellular level.

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