Change search
Refine search result
12 1 - 50 of 54
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Christakou, Athanasia E.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ohlin, Mathias
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Kadri, N.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics. Karolinska Institute, Sweden.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Characterization of natural killer cells' cytotoxic heterogeneity using an array of sono-cages2012In: Proceedings of the 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2012, Chemical and Biological Microsystems Society , 2012, p. 1555-1557Conference paper (Refereed)
    Abstract [en]

    Using a multi-well device as an array of sono-cages for single cell analysis, we quantify for the first time the heterogeneity of natural killer (NK) cells' cytotoxic response against cancer cells. We report a fraction of inactive NK cells within the tested population (36%), as well as the existence of few 'serial killers' that eliminate up to six targets during 4 hours. We also characterize the multi-well acoustic device in terms of trapping efficiency at different actuation voltages, using adherent and non-adherent cell lines. We show that the acoustic forces applied on the cells can be compared to forces of biological processes (i.e. cell adherence).

  • 2.
    Christakou, Athanasia. E.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ohlin, Mathias
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Khorshidi, Mohammad Ali
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Aggregation and long-term positioning of cells by ultrasound in a multi-well microchip for high-resolution imaging of the natural killer cell immune synapse2011In: 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2011, MicroTAS 2011, 2011, p. 329-331Conference paper (Refereed)
    Abstract [en]

    In this study we investigate the ability of Natural Killer (NK) cells to form ultrasound-mediated intercellular contacts with target cells in a multi-well microdevice by high-resolution confocal-microscopy imaging of inhibitory immune synapses. Furthermore, we compare the NK-Target cell cluster migration with and without ultrasound actuation. Experiments indicate that clusters of cells are positioned and maintained centered in the wells for 17 hours when they are exposed continuously to ultrasound. Our system can be used for both screening high numbers of events in low resolution and also for high resolution imaging of long term cell-cell interactions.

  • 3.
    Christakou, Athanasia E.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Ohlin, Mathias
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Khorshidi, Mohammad Ali
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Kadri, Nadir
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Live cell imaging in a micro-array of acoustic traps facilitates quantification of natural killer cell heterogeneity2013In: Integrative Biology, ISSN 1757-9694, E-ISSN 1757-9708, Vol. 5, no 4, p. 712-719Article in journal (Refereed)
    Abstract [en]

    Natural killer (NK) cells kill virus-infected or cancer cells through the release of cytotoxic granules into a tight intercellular contact. NK cell populations comprise individual cells with varying sensitivity to distinct input signals, leading to disparate responses. To resolve this NK cell heterogeneity, we have designed a novel assay based on ultrasound-assisted cell-cell aggregation in a multiwell chip allowing high-resolution time-lapse imaging of one hundred NK-target cell interactions in parallel. Studying human NK cells' ability to kill MHC class I deficient tumor cells, we show that approximately two thirds of the NK cells display cytotoxicity, with some NK cells being particularly active, killing up to six target cells during the assay. We also report that simultaneous interaction with several susceptible target cells increases the cytotoxic responsiveness of NK cells, which could be coupled to a previously unknown regulatory mechanism with implications for NK-mediated tumor elimination.

  • 4.
    Dånmark, Staffan
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Gladnikoff, Micha
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Zelenina, Marina
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Mustafa, Kamal
    Russom, Aman
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Finne-Wistrand, Anna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Development of a novel microfluidic device for long-term in situ monitoring of live cells in 3-dimensional matrices2012In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 14, no 5, p. 885-893Article in journal (Refereed)
    Abstract [en]

    Using the latest innovations in microfabrication technology, 3-dimensional microfluidic cell culture systems have been developed as an attractive alternative to traditional 2-dimensional culturing systems as a model for long-term microscale cell-based research. Most microfluidic systems are based on the embedding of cells in hydrogels. However, physiologically realistic conditions based on hydrogels are difficult to obtain and the systems are often too complicated. We have developed a microfluidic cell culture device that incorporates a biodegradable rigid 3D polymer scaffold using standard soft lithography methods. The device permits repeated high-resolution fluorescent imaging of live cell populations within the matrix over a 4 week period. It was also possible to track cell development at the same spatial location throughout this time. In addition, human primary periodontal ligament cells were induced to produce quantifiable calcium deposits within the system. This simple and versatile device should be readily applicable for cell-based studies that require long-term culture and high-resolution bioimaging.

  • 5.
    Dånmark, Staffan
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Gladnikoff, Micha
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Zelenina, Marina
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Mustafa, Kamal
    Insititutt for klinisk Odontologi, Medicinska och Odontologiska Fakulteten, Universitetet i Bergen, Norge.
    Russom, Aman
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Finne-Wistrand, Anna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Development of Novel Microfluidic Device for Long-Term in situ Monitoring of Live Cells in 3-dimensional MatricesManuscript (preprint) (Other academic)
  • 6. Forslund, E.
    et al.
    Guldevall, Karolin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Olofsson, Per E.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Christakou, Athanasia E.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Novel microchip-based tools facilitating live cell imaging and assessment of functional heterogeneity within NK cell populations2012In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 3, no OCT, p. 300-Article in journal (Refereed)
    Abstract [en]

    Each individual has a heterogeneous pool of NK cells consisting of cells that may be specialized towards specific functional responses such as secretion of cytokines or killing of tumor cells. Many conventional methods are not fit to characterize heterogeneous populations as they measure the average response of all cells. Thus, there is a need for experimental platforms that provide single cell resolution. In addition, there are transient and stochastic variations in functional responses at the single cell level, calling for methods that allow studies of many events over extended periods of time. This paper presents a versatile microchip platform enabling long-term microscopic studies of individual NK cells interacting with target cells. Each microchip contains an array of microwells, optimized for medium or high-resolution time-lapse imaging of single or multiple NK and target cells, or for screening of thousands of isolated NK-target cell interactions. Individual NK cells confined with target cells in small microwells is a suitable setup for high-content screening and rapid assessment of heterogeneity within populations, while microwells of larger dimensions are appropriate for studies of NK cell migration and sequential interactions with multiple target cells. By combining the chip technology with ultrasonic manipulation, NK and target cells can be forced to interact and positioned with high spatial accuracy within individual microwells.This setup effectively and synchronously creates NK-target conjugates at hundreds of parallel positions in the microchip. Thus, this facilitates assessment of temporal aspects of NK-target cell interactions, e.g., conjugation, immune synapse formation, and cytotoxic events.The microchip platform presented here can be used to effectively address questions related to fundamental functions of NK cells that can lead to better understanding of how the behavior of individual cells add up to give a functional response at the population level.

  • 7.
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    MEMS Interfaces for Bioanalysis Systems2008Doctoral thesis, comprehensive summary (Other scientific)
    Abstract [en]

    This thesis deals with various aspects of using open microfluidic interfaces. Three specific areas of application are studied.

    The first is air-to-liquid interfacing in biosensors with possibilities for component inte­gration. A micromachined interface for airborne sample-to-liquid and droplet-to-liquid adsorption is discussed. It enables a robust sheet liquid flow serving as adsorption site. The inter­face properties are presented. Along with the interface, a novel method and system for rapid detection of dust and vapour-based narcotics and explosives traces is introduced. The QCM sensor detection principle with antibody immunoassay is described. Having shown the working principles of molecular adsorption to liquid surface and molecular detection with QCM technology, an integrated device is introduced. Diffusion as an effective transport mechanism in this microfluidic device is discussed. By holding the two components (inter­face and QCM) together with a double-sided adhesive, anisotropically vertically conductive tape, we achieve three functions, namely fixation, electrical connection and liquid sealing. Finally, enhanced electrostatic trapping of small particles to the liquid interface is demon­strated.

    The second area concerns open microfluidics for the integration of capillary electropho­resis and mass spectroscopy. A technique for hyphenation between CE and MALDI-MS is presented. Two closed fused-silica capillaries were connected via a silicon chip comprising an open microcanal. The influence of the capillary-to-microcanal connection is discussed, as well as a simple technique to control evaporation from the open microcanal.

    The third area concerns microfluidics enabling studies of single cells in asymmetric en­vironments. Using extracellular matrix or synthetic gel-embedding cells in an assay chamber, cells thrive and proliferate. This makes it possible to carry out medium to long term cultiva­tion of cells in a more physiological, controlled 3D environment than in traditional 2D cul­tures. The gels are discussed in terms of handling as well as their properties. A gel and micro­fluidic device for three dimensional cell culture with microgradient environments is pre­sented. Finally, a method for studying cilia-forming cells in asymmetric microfluidic environments is presented. Bending the primary cilium with a fluid flow will give rise to a response, but sensitivity to flow direction has only been sparsely studied. Design considerations are presented and discussed.

  • 8.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Eng, Lars
    Biosensor Applications AB, Sundbyberg, Sweden.
    Guo, Shaohua
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    A MINIATURISED INTEGRATED QCM-BASED ELECTRONIC NOSE MICROSYSTEM2007In: 20th IEEE International Conference on Micro Electro Mechanical Systems (IEEE MEMS 2007), New York: IEEE conference proceedings, 2007, p. 417-420Conference paper (Refereed)
    Abstract [en]

    We designed, fabricated and successfully tested an integrated miniaturised Quartz Crystal Microbalance (QCM) based electronic nose microsystem. The microsystem. is an assembly of four parts: 1. a micromachined gas-liquid interface with integrated fluid channels and electrical conductors, 2. an anisotropically conductive double-sided adhesive film, 3. a QCM crystal and 4. a polymer cap with fluid and electrical ports. The choice of the multifunctional materials and the geometric features of the four-component microsystem allow a functional integration of a QCM crystal, electrical contacts, fluidic contacts and a sample interface in a single system with minimal assembly effort, a potential for low-cost manufacturing, and a few orders of magnitude reduction in system size (12*12*4 mm(3)) and weight compared to commercially available instruments. The system detected ecstasy in the 100 ng range within 30 seconds.

  • 9.
    Frisk, Thomas
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Khorshidi, Mohammad Ali
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Guldevall, Karolin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    A silicon-glass microwell platform for high-resolution imaging and high-content screening with single cell resolution2011In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 13, no 4, p. 683-693Article in journal (Refereed)
    Abstract [en]

    We present a novel microwell array platform suited for various cell-imaging assays where single cell resolution is important. The platform consists of an exchangeable silicon-glass microchip for cell biological applications and a custom made holder that fits in conventional microscopes. The microchips presented here contain arrays of miniature wells, where the well sizes and layout have been designed for different applications, including single cell imaging, studies of cell-cell interactions or ultrasonic manipulation of cells. The device has been designed to be easy to use, to allow long-term assays (spanning several days) with read-outs based on high-resolution imaging or high-content screening. This study is focused on screening applications and an automatic cell counting protocol is described and evaluated. Finally, we have tested the device and automatic counting by studying the selective survival and clonal expansion of 721.221 B cells transfected to express HLA Cw6-GFP compared to untransfected 721.221 B cells when grown under antibiotic selection for 3 days. The device and automated analysis protocol make up the foundation for development of several novel cellular imaging assays.

  • 10.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Roxhed, Niclas
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    MEMS for medical technology applications2007In: MEMS Adaptive Optics / [ed] Olivier, S.S., Bifano T.G., Kubby J.A., 2007, Vol. 6467, p. 46513-46513Conference paper (Refereed)
    Abstract [en]

    This paper gives an in-depth description of two recent projects at the Royal Institute of Technology (KTH) which utilize MEMS and microsystem technology for realization of components intended for specific applications in medical technology and diagnostic instrumentation. By novel use of the DRIE fabrication technology we have developed side-opened out-of-plane silicon microneedles intended for use in transdermal drug delivery applications. The side opening reduces clogging probability during penetration into the skin and increases the up-take area of the liquid in the tissue. These microneedles offer about 200 mu m deep and pain-free skin penetration. We have been able to combine the microneedle chip with an electrically and heat controlled liquid actuator device where expandable microspheres are used to push doses of drug liquids into the skin. The entire unit is made of low cost materials in the form of a square one cm-sized patch. Finally, the design, fabrication and evaluation of an integrated miniaturized Quartz Crystal Microbalance (QCM) based "electronic nose" microsystem for detection of narcotics is described. The work integrates a novel environment-to-chip sample interface with the sensor element. The choice of multifunctional materials and the geometric features of a four-component microsystem allow a functional integration of a QCM crystal, electrical contacts, fluidic contacts and a sample interface in a single system with minimal assembly effort, a potential for low-cost manufacturing, and a few orders of magnitude reduced in system size (12*12*4 mm) and weight compared to commercially available instruments. The sensor chip was successfully used it for the detection of 200 ng of narcotics sample.

  • 11.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Rydholm, Susanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Andersson, Helene
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Cultivation of COS7-cells using extracellular matrix in 3D microfluidic surface enlarged structure2005In: Micro Total Analysis Systems 2004, 2005, no 297, p. 261-263Conference paper (Refereed)
    Abstract [en]

    This paper presents a novel method to cultivate cells in a controlled 3D surface enlarged micro-environment. The 3D environment is achieved by insertion of a gel-like extracellular matrix (ECM) mixed with cells into a micromachined silicon fluid structure. Shrinking of the gel enables further flow through the channel. Due to the structure design the shrinking is non-uniform, which results in an increased surface area. With the proposed design cells are alive and viable after 72 h of incubation within the chip.

  • 12.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Rydholm, Susanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Andersson, Helene
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Three dimensional asymmetric microenvironment for cell biological studies2005In: Proceedings of µTAS 2005 Conference, 2005, p. 915-917Conference paper (Refereed)
    Abstract [en]

    We report on a method for three-dimensional cultivation of cells in a microstructured asymmetric environment. In the system an asymmetric environment is created by using diffusion through a gel of extra cellular matrix proteins surrounded by microfluidic flow channels. Individual cells embedded in the gel react on the concentration gradient. The system has been evaluated both for diffusion properties and based on the cellular response.

  • 13.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Rydholm, Susanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Andersson, Helene
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    A concept for miniaturized 3-D cell culture using an extracellular matrix gel2005In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 26, no 24, p. 4751-4758Article in journal (Refereed)
    Abstract [en]

    This paper presents a novel method to embed, anchor, and cultivate cells in a controlled 3-D flow-through microenvironment. This is realized using an etched silicon pillar flow chamber filled with extracellular matrix (ECM) gel mixed with cells. At 4 degrees C, while in liquid form, ECM gel is mixed with cells and injected into the chamber. Raising the temperature to 37 degrees C results in a gel, with cells embedded. The silicon pillars both stabilize and increase the surface to volume ratio of the gel. During polymerization the gel shrinks, thus creating channels, which enables perfusion through the chip. The pillars increase the mechanical stability of the gel permitting high surface flow rates without surface modifications. Within the structure cells were still viable and proliferating after 6 days of cultivation. Our method thus makes it possible to perform medium- to long-term cultivation of cells in a controlled 3-D environment. This concept opens possibilities to perform studies of cells in a more physiological environment compared to traditional 2-D cultures on flat substrates.

  • 14.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Rydholm, Susanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Andersson Svahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Three dimensional asymmetric microenvironment for cell biologigal studies2005In: Proceedings Micro Total Analysis Systems (muTAS) 2005, 2005Conference paper (Refereed)
  • 15.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Rydholm, Susanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Liebmann, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Andersson-Svahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    A microfluidic device for parallel 3-D cell cultures in asymmetric environments2007In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 28, no 24, p. 4705-4712Article in journal (Refereed)
    Abstract [en]

    We demonstrate a concept for how a miniaturized 3-D cell culture in biological extracellular matrix (ECM) or synthetic gels bridges the gap between organ-tissue culture and traditional 2-D cultures. A microfluidic device for 3-D cell culture including microgradient environments has been designed, fabricated, and successfully evaluated. In the presented system stable diffusion gradients can be generated by application of two parallel fluid flows with different composition against opposite sides of a gel plug with embedded cello. Culture for up to two weeks was performed showing cells still viable and proliferating. The cell tracer dye calcein was used to verify gradient formation as the fluorescence intensity in exposed cells was proportional to the position in the chamber. Cellular response to an applied stimulus was demonstrated by use of an adenosine triphosphate gradient where the onset of a stimulated intracellular calcium release also depended on cell position.

  • 16.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Rönnholm, David
    Biosensor Applications Sweden AB.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    A micromachined interface for airborne sample-to-liquid transfer and its application in a biosensor system2006In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 6, no 12, p. 1504-1509Article in journal (Refereed)
    Abstract [en]

    A novel micromachined interface for airborne sample-to-liquid adsorption and droplet-to-liquid transfer was designed and fabricated. It enables a robust sheet liquid flow serving as an adsorption site. The interface was characterised for flow and pressure properties and tested successfully for the transfer/adsorption of different samples. A qualitative theoretical model of the device characteristics is presented. We also used the interface to introduce a novel method and system for fast detection of dust- and vapour-based narcotics and explosives traces. The microfluidic vapour-to-liquid adsorption interface was coupled to a set of downstream QCM sensors. The system was tested successfully, with 50 ng cocaine samples rendering 15 Hz frequency shifts and with 100 ng heroine samples rendering 50 Hz frequency shifts. Gravitation invariance of the open liquid interface was demonstrated successfully, with the interface mounted upside down as well as vertically. The detection time was reduced to half of the time needed in previous systems. Machine size, weight and cost were reduced.

  • 17.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Rönnholm, David
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Fast narcotics and explosives detection using a microfluidic sample interface2005Conference paper (Refereed)
    Abstract [en]

    We introduce a novel method and system for fast detection of dust- and vapour-based narcotics and explosives traces. A micro fluidic vapour-to-liquid adsorption interface was built-in to an existing electronic nose instrument, reducing the detection time, machine size, weight, and cost. The system was successfully tested with 50 ng cocaine samples rendering 15 Hz frequency shifts and with 100 ng heroine samples rendering 50 Hz frequency shifts. Also the gravity invariance of the open liquid interface was successfully tested with the interface mounted up side down as well as vertically. The detection time was reduced to half of the time needed in commercial systems.

  • 18.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Sandström, Niklas
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Eng, Lars
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Månsson, Per
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    A miniaturised QCM-based integrated electronic nose system2007Conference paper (Other academic)
  • 19.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Sandström, Niklas
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Eng, Lars
    Biosensor Applications AB, Solna.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Månsson, Per
    Biosensor Applications AB, Solna.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    An integrated QCM-based narcotics sensing microsystem2008In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 8, no 10, p. 1648-1657Article in journal (Refereed)
    Abstract [en]

    We present the design, fabrication and successful testing of a 14 x 14 x 4 mm(3) integrated electronic narcotics sensing system which consists of only four parts. The microsystem absorbs airborne narcotics molecules and performs a liquid assay using an integrated quartz crystal microbalance (QCM). A vertically conductive double-sided adhesive foil (VCAF) was used and studied as a novel material for LOC and MEMS applications and provides easy assembly, electrical contacting and liquid containment. The system was tested for measuring cocaine and ecstasy, with successful detection of amounts as small as 100 ng and 200 ng, respectively These levels are of interest in security activities in customs, prisons and by the police.

  • 20.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Fast Narcotics Detection with a Microfluidic Sample Interface2006In: Microsystems Technology Workshop, 2006Conference paper (Other academic)
  • 21.
    Frisk, Thomas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Fast Narcotics Detection With a Microfluidic Sample Interface2006In: Medicinteknikdagarna, 2006Conference paper (Other academic)
  • 22.
    Guldevall, Karolin
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brandt, Ludwig
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Forslund, Elin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Sweden.
    Olofsson, Karl
    Frisk, Thomas W.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Olofsson, Per E.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Karin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Manneberg, Otto
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Karre, Klas
    Uhlin, Michael
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Microchip screening Platform for single cell assessment of NK cell cytotoxicity2016In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 7, article id 119Article in journal (Refereed)
    Abstract [en]

    Here, we report a screening platform for assessment of the cytotoxic potential of individual natural killer (NK) cells within larger populations. Human primary NK cells were distributed across a silicon-glass microchip containing 32,400 individual microwells loaded with target cells. Through fluorescence screening and automated image analysis, the numbers of NK and live or dead target cells in each well could be assessed at different time points after initial mixing. Cytotoxicity was also studied by time-lapse live-cell imaging in microwells quantifying the killing potential of individual NK cells. Although most resting NK cells (approximate to 75%) were non-cytotoxic against the leukemia cell line K562, some NK cells were able to kill several (>= 3) target cells within the 12-h long experiment. In addition, the screening approach was adapted to increase the chance to find and evaluate serial killing NK cells. Even if the cytotoxic potential varied between donors, it was evident that a small fraction of highly cytotoxic NK cells were responsible for a substantial portion of the killing. We demonstrate multiple assays where our platform can be used to enumerate and characterize cytotoxic cells, such as NK or T cells. This approach could find use in clinical applications, e.g., in the selection of donors for stem cell transplantation or generation of highly specific and cytotoxic cells for adoptive immunotherapy.

  • 23.
    Guldevall, Karolin
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Khorsidi, Mohammed Ali
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Manneberg, Otto
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Christakou, Athanasia
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Imaging immune surveillance by individual Natural Killer cells isolated in arrays of nanoliter wells2010Conference paper (Refereed)
  • 24.
    Guldevall, Karolin
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Karin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Forslund, Elin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Manneberg, Otto
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Olofsson, Per E.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Tauriainen, Johanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Stikvoort, Arwen
    Karolinska Institute.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mattsson, Jonas
    Karolinska Institute.
    Kärre, Klas
    Karolinska Institute.
    Uhlin, Michael
    Karolinska Institute.
    Önfelt, Bjorn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Microchip screening platform for assessment of cytotoxic effector cellsManuscript (preprint) (Other academic)
    Abstract [en]

    Here we report a screening platform for assessment of the cytotoxic potential of individual natural killer (NK) or T cells within larger populations. Human primary NK cells or human Epstein-Barr virus (EBV)- specific T cells were distributed across a silicon-glass microchip containing 32 400 individual microwells loaded with target cells. Through fluorescence screening and automated image analysis the numbers of effector and live or dead target cells in each well could be assessed at different time-points after initial mixing. Cytotoxicity was also studied by time-lapse live-cell imaging in microwells quantifying the killing potential of individual NK cells. Although most resting NK cells (≈75%) were non-cytotoxic to the leukemia cell line K562, some NK cells were able to kill several (≥3) target cells within the 12 hours long experiment. We demonstrate that this assay can be used to enumerate and characterize cytotoxic cells, something that could find clinical applications, e.g. in the selection of donors for stem cell transplantation or generation of highly specific and cytotoxic cells for adoptive immunotherapy.

  • 25.
    Guldevall, Karolin
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.
    Hurtig, Johan
    Department of Chemsitry, University of Washington, Seattle, USA.
    Christakou, Athanasia
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Manneberg, Otto
    Department of Environmental Health, Harvard School of Public Health, Boston, USA.
    Lindström, Sara
    KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    Andersson-Svahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Imaging Immune Surveillance of Individual Natural Killer Cells Confined in Microwell Arrays2010In: PLOS ONE, ISSN 1932-6203, Vol. 5, no 11, p. e15453-Article in journal (Refereed)
    Abstract [en]

    New markers are constantly emerging that identify smaller and smaller subpopulations of immune cells. However, there is a growing awareness that even within very small populations, there is a marked functional heterogeneity and that measurements at the population level only gives an average estimate of the behaviour of that pool of cells. New techniques to analyze single immune cells over time are needed to overcome this limitation. For that purpose, we have designed and evaluated microwell array systems made from two materials, polydimethylsiloxane (PDMS) and silicon, for high-resolution imaging of individual natural killer (NK) cell responses. Both materials were suitable for short-term studies (<4 hours) but only silicon wells allowed long-term studies (several days). Time-lapse imaging of NK cell cytotoxicity in these microwell arrays revealed that roughly 30% of the target cells died much more rapidly than the rest upon NK cell encounter. This unexpected heterogeneity may reflect either separate mechanisms of killing or different killing efficiency by individual NK cells. Furthermore, we show that high-resolution imaging of inhibitory synapse formation, defined by clustering of MHC class I at the interface between NK and target cells, is possible in these microwells. We conclude that live cell imaging of NK-target cell interactions in multi-well microstructures are possible. The technique enables novel types of assays and allow data collection at a level of resolution not previously obtained. Furthermore, due to the large number of wells that can be simultaneously imaged, new statistical information is obtained that will lead to a better understanding of the function and regulation of the immune system at the single cell level.

  • 26.
    Jacksén, Johan
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Redeby, Theres
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Parmar, Varun
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Emmer, Åsa
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Analytical Chemistry.
    Off-line integration of CE and MALDI-MS using a closed-open-closed microchannel system2007In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 28, no 14, p. 2458-2465Article in journal (Refereed)
    Abstract [en]

    In this work, a new technique for off-line hyphenation between CE and MALDI-MS is presented. Two closed fused-silica capillaries were connected via a silicon chip comprising an open microcanal. The EOF in the system was evaluated using mesityloxide or leucine-enkephalin as a sample and with a running buffer that rendered the analyte neutrally charged. Comparison was made between the EOF in a closed system (first capillary solely included in the electrical circuit) and in a closed-open system (first capillary and microcanal included in the electrical circuit). It was concluded that the experimental values of the EOF agreed with the theory. The influence of the capillary outer diameter on the peak dispersion was investigated using a closed-open-closed system (first capillary, microcanal and second capillary included in the electrical circuit). It was clearly seen that a capillary with 375 mu m od induced considerably higher peak dispersion than a 150 mu m od capillary, due to a larger liquid dead volume in the connection between the first capillary outlet and the microcanal. Mass spectrometric analysis has also been performed following CE separation runs in a closed-open-closed system with cytochrome c and lysozyme as model proteins. It was demonstrated that a signal distribution profile of the separated analytes could be recorded over a 30 mm long microcanal.

  • 27.
    Kianirad, Hoda
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Zukauskas, Andrius
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Canalias, Carlota
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Laurell, Fredrik
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Contact poling of Rb:KTiOPO4 using a micro-structured silicon electrode2015In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 23, no 2, p. 636-641Article in journal (Refereed)
    Abstract [en]

    A contact poling technique for domain engineering of ferroelectrics using a micro-structured silicon electrode is demonstrated on Rb:KTiOPO4. High quality QPM gratings were reproducibly fabricated. The silicon electrode is reusable and the technique potentially suitable when complex structures with sub-mu m features are to be domain engineered, which otherwise is incompatible with conventional photolithography. A non-negligible domain broadening was seen and attributed to a low nucleation rate using this type of electrode. However, under the appropriate poling conditions, this could be exploited to obtain a QPM grating with a short pitch (2 mu m), equal to half of the electrode period.

  • 28.
    Kianirad, Hoda
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Zukauskas, Andrius
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Canalias, Carlota
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Laurell, Fredrik
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Contact poling of RKTP using a micro-structured silicon electrode2014Conference paper (Other academic)
  • 29.
    Kianirad, Hoda
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Zukauskas, Andrius
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Canalias, Carlota
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Laurell, Fredrik
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Contact poling of RKTP with silicon pillars2013In: 2013 Conference on Lasers and Electro-Optics Europe and International Quantum Electronics Conference, CLEO/Europe-IQEC 2013, IEEE Computer Society, 2013, p. 6800873-Conference paper (Refereed)
    Abstract [en]

    Quasi-phase-matching (QPM) is a method to get tailored efficient second order nonlinear interactions [1]. Several techniques exist for fabrication of periodic domain structures in ferroelectric crystals for QPM frequency conversion. By far, electric field poling using lithographically patterned electrodes on the z-face of the crystal is the most common one [2]. High-quality periodically inverted ferroelectric domain structures in flux grown KTiOP 4 (KTP) crystals were fabricated already in the late 90's using this technique [3], and recently periodic domain sizes of few hundred nanometers were fabricated in 1 mm thick samples thanks to the quasi-one dimensional structure of KTP. It has recently also been shown that a slight Rb doping of the KTP crystal (RKTP) facilitates the periodic poling [4]. However, fabrication of two-dimensional (2D) domain structures in RKTP has not yet been investigated. A disadvantage with the lithographic patterning is that each sample needs to be patterned individually, which is tedious and time consuming. Moreover, when it comes to the small domain features, which are required by the next generation of nonlinear optical devices, a more versatile poling technique has to be developed due to the limitations of conventional photolithography. Structured silicon has been investigated as an alternative electrode for formation of 1D domains by contact poling in LiNb3 [5]. However, these electrodes were fabricated by wet etching and the sample thickness was limited to ∼200 μm.

  • 30.
    Ohlin, Mathias
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Christakou, Athanasia E.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Analysis of trapping and streaming in an ultrasoundactuated multi-well microplate for single-cell studies2012In: Proceedings of the 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2012, Chemical and Biological Microsystems Society , 2012, p. 497-499Conference paper (Refereed)
    Abstract [en]

    The dynamics of the acoustic streaming and the acoustic positioning performance in an ultrasound-actuated multiwell microplate are investigated by two different ultrasonic frequency actuation schemes: Frequency-modulation and single- frequency actuation. Our results show a significant decrease in size of the field of view when using frequencymodulation compared to single-frequency actuation, which can be used for improving the scanning time for 3D highresolution confocal microscopy by almost one order of magnitude. Furthermore, in the ultrasound-actuated multi-well microplate the high-voltage acoustic streaming show a complex time and temperature dependence and could gain stability by the use of temperature control.

  • 31.
    Ohlin, Mathias
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Christakou, Athanasia E.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Controlling acoustic streaming in a multi-well microplate for improving live cell assays2011In: 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2011, MicroTAS 2011, 2011, p. 1612-1614Conference paper (Refereed)
    Abstract [en]

    Acoustic streaming in a multi-well microplate is investigated using two different ultrasonic actuation frequency-schemes: Single-frequency and frequency-modulation. The streaming is tracked by the use of 1 μm fluorescent polymer beads and micro-particle image velocimetry. The suspension also contained human B cells for studying the acoustic trapping and aggregation performance simultaneously with the acoustic streaming. Our results show a significant difference in the acoustic streaming between the two ultrasonic actuation schemes. A rotational fluid flow speed decreased a factor of 30 when frequency-modulation was applied compared to single-frequency actuation without apparently interfering with the acoustic cell trapping function.

  • 32.
    Ohlin, Mathias
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Christakou, Athanasia E.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Influence of acoustic streaming on ultrasonic particle manipulation in a 100-well ring-transducer microplate2013In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 23, no 3, p. 035008-Article in journal (Refereed)
    Abstract [en]

    We characterize and quantify the performance of ultrasonic particle aggregation and positioning in a 100-well microplate. We analyze the result when operating a planar ultrasonic ring transducer at different single actuation frequencies in the range 2.20-2.40 MHz, and compare with the result obtained from different schemes of frequency-modulated actuation. Compared to our previously used wedge transducer design, the ring transducer has a larger contact area facing the microplate, resulting in lower temperature increase for a given actuation voltage. Furthermore, we analyze the dynamics of acoustic streaming occurring simultaneously with the particle trapping in the wells of the microplate, and we define an adaptive ultrasonic actuation scheme for optimizing both efficiency and robustness of the method. The device is designed as a tool for ultrasound-mediated cell aggregation and positioning. This is a method for high-resolution optical characterization of time-dependent cellular processes at the level of single cells. In this paper, we demonstrate how to operate our device in order to optimize the scanning time of 3D confocal microscopy with the aim to perform high-resolution time-lapse imaging of cells or cell-cell interactions in a highly parallel manner.

  • 33.
    Olofsson, K.
    et al.
    KTH.
    Carannante, V.
    Frisk, T.
    KTH.
    Kushiro, K.
    Takai, M.
    Önfelt, B.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cellular Biophysics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Unanchored micro-tumors in an ultrasonic actuated multi-well microplate with protein repellent coating2016In: 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016, Chemical and Biological Microsystems Society , 2016, p. 409-410Conference paper (Refereed)
    Abstract [en]

    In this paper we demonstrate an improved tissue engineering method producing 100 three-dimensional (3D) HepG2 cell structures in parallel based on a combination of ultrasonic actuation and polymer coating in a multi-well microplate. By the use of a polymer coating in the plates, the method creates non-adherent tumor models of controlled size and shape which introduces both a more flexible 3D culture system as well as improved quality of the 3D tumor relative to previous studies [1].

  • 34.
    Olofsson, Karl
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Carannante, V.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Ohlin, Mathias
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Kushiro, K.
    Univ Tokyo, Dept Bioengn, Tokyo, Japan..
    Takai, M.
    Univ Tokyo, Dept Bioengn, Tokyo, Japan..
    Lundqvist, A.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Önfelt, Björn
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Acoustic formation of multicellular tumor spheroids enabling on-chip functional and structural imaging2018In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 18, no 16, p. 2466-2476Article in journal (Refereed)
    Abstract [en]

    Understanding the complex 3D tumor microenvironment is important in cancer research. This microenvironment can be modelled in vitro by culturing multicellular tumor spheroids (MCTS). Key challenges when using MCTS in applications such as high-throughput drug screening are overcoming imaging and analytical issues encountered during functional and structural investigations. To address these challenges, we use an ultrasonic standing wave (USW) based MCTS culture platform for parallel formation, staining and imaging of 100 whole MCTS. A protein repellent amphiphilic polymer coating enables flexible production of high quality and unanchored MCTS. This enables high-content multimode analysis based on flow cytometry and in situ optical microscopy. We use HepG2 hepatocellular carcinoma, A498 and ACHN renal carcinoma, and LUTC-2 thyroid carcinoma cell lines to demonstrate (i) the importance of the ultrasound-coating combination, (ii) bright field image based automatic characterization of MTCS, (iii) detailed deep tissue confocal imaging of whole MCTS mounted in a refractive index matching solution, and (iv) single cell functional analysis through flow cytometry of single cell suspensions of disintegrated MTCS. The USW MCTS culture platform is customizable and holds great potential for detailed multimode MCTS analysis in a high-content manner.

  • 35.
    Olofsson, Per E.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brandt, Ludwig
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Magnusson, Klas E. G.
    KTH, School of Electrical Engineering (EES), Signal Processing. KTH, School of Electrical Engineering and Computer Science (EECS), Centres, ACCESS Linnaeus Centre.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jaldén, Joakim
    KTH, School of Electrical Engineering (EES), Signal Processing. KTH, School of Electrical Engineering and Computer Science (EECS), Centres, ACCESS Linnaeus Centre.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    A collagen-based microwell migration assay to study NK-target cell interactions2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 10672Article in journal (Refereed)
    Abstract [en]

    Natural killer (NK) cell cytotoxicity in tissue is dependent on the ability of NK cells to migrate through the extracellular matrix (ECM) microenvironment. Traditional imaging studies of NK cell migration and cytotoxicity have utilized 2D surfaces, which do not properly reproduce the structural and mechanical cues that shape the migratory response of NK cells in vivo. Here, we have combined a microwell assay that allows long-term imaging and tracking of small, well-defined populations of NK cells with an interstitial ECM-like matrix. The assay allows for long-term imaging of NK-target cell interactions within a confined 3D volume. We found marked differences in motility between individual cells with a small fraction of the cells moving slowly and being confined to a small volume within the matrix, while other cells moved more freely. A majority of NK cells also exhibited transient variation in their motility, alternating between periods of migration arrest and movement. The assay could be used as a complement to in vivo imaging to study human NK cell heterogeneity in migration and cytotoxicity.

  • 36.
    Olofsson, Per
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cellular Biophysics.
    Magnusson, Klas E. G.
    KTH, School of Electrical Engineering (EES), Signal Processing.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cellular Biophysics.
    Jaldén, Joakim
    KTH, School of Electrical Engineering (EES), Signal Processing.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cellular Biophysics.
    A collagen-based microwell migration assay to study NK—target cell interactionsManuscript (preprint) (Other academic)
    Abstract [en]

    Natural killer (NK) cell cytotoxicity is highly dependent on the ability of NK cells to migrate through the extracellular matrix (ECM) microenvironment. Traditional imaging studies of NK cell migration and cytotoxicity have utilized 2-D surfaces, which do not properly reproduce the structural and mechanical cues that shape the migratory response of NK cells in vivo. In addition, current in vivo imaging does not allow for the accurate long-term single-cell imaging required to dissect the functional heterogeneity of NK cell populations, and importantly, it does not allow studies of human cells. Therefore, it is desirable to implement in vitro migration and killing assays that better mimic in vivo conditions.

    We have combined a microwell assay that allows long-term imaging and tracking of small, well-defined populations of NK cells with an interstitial ECM-like matrix to more closely approximate in vivo conditions. The microwells, which are loaded with a gel mixture containing NK and target cells, allows for long-term imaging of NK–target cell interactions within a confined 3-D volume. The microwells were optically sectioned by confocal fluorescence microscopy once every 2 min for 12 h. NK cells were tracked by the Baxter Algorithms to assess motility parameters and interactions with target cells were manually scored for duration and outcome.

    We found marked differences in motility between individual cells with a significant fraction of the cells moving slowly and being confined to a small area within the matrix, while other cells moved more freely, probably reflecting local variations in the matrix structure and inherent difference in motility between individual cells. A majority of NK cells also exhibited transient variation in their mobility alternating between periods of migration arrest and random movement. NK cells that alternated between different modes of migration switched on average once every 3 h.

    NK cells made fewer and shorter contacts with target cells than in comparable 2-D assays. The difference was particularly pronounced for the process of post-conjugation attachment when NK and target cells separate. The timing of this process is likely influenced by a biomechanical component only present in 3-D environments where the cells are offered multiple anchor points with the matrix that can be used to generate the forces needed to pull apart.

    The developed microwell-based assay is suitable for 3-D time-lapse imaging of NK cells migration and cytotoxicity. As it allows for experiments with human cells, it could be used as a complement to in vivo imaging to study the influence of e.g. education and cytokine activation on NK cell heterogeneity in migration and cytotoxicity.

  • 37.
    Rydholm, Susanna
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Andersson, Helene
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Microfluidic device for studies of primary cilium direction sensitivity2005In: Proceedings of µTAS 2005 Conference, 2005, p. 1416-1418Conference paper (Refereed)
    Abstract [en]

    This paper presents a novel method for studying cilia forming cells in asymmetric microfluidic environments. It has previously been shown that bending the primary cilium by a fluid flow will give rise to a calcium signal, but the sensitivity for flow direction has so far not been studied. The microfluidic device presented here was designed for control of the local direction of fluid flow on the cellular level, and thus, enables studies of cellular response to a direction controlled cilium movement. Cells seeded on cover slips form cilia with the average length 2.9 μm after three days in culture and 4.3 μm after four days. Distinct calcium peaks were found after the initiation of flow in the channel. By using a microstructured flow system we have been able to study the sensitivity of confluent COS 7 cells expressing primary cilium to changes in fluid flow.

  • 38.
    Rydholm, Susanna
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Andersson, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Three Dimensional Asymmetric Microenvironment for Cell Biological Studies2006Conference paper (Refereed)
  • 39.
    Rydholm, Susanna
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Andersson Svahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Three Microfluidic Device for Studies of Primary Cilium Direction Sensitivity2006Conference paper (Refereed)
  • 40.
    Rydholm, Susanna
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Kowalewski, Jacob
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Andersson Svahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Controlled stimuli of primary cilia in microfabricated device2008Conference paper (Refereed)
  • 41.
    Rydholm, Susanna
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Kowalewski, Jacob M
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Andersson Svahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Microfluidic devices for studies of primary cilium mediated cellular response to dynamic flow conditions2008In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 10, no 4, p. 555-560Article in journal (Refereed)
    Abstract [en]

    We present the first microfabricated microfluidic devices designed specifically for studies of primary cilium mediated cellular response to dynamic flow. The primary cilium functions as a mechano-sensor in renal tubular epithelium, sensing the extracellular fluid flow. Malfunction of cilia has been implicated in e.g. polycystic kidney disease and other pathological conditions. Bending of the primary cilium by fluid flow has been shown to give rise to an intracellular calcium signal, however little is known about the sensitivity to flow duration, magnitude and direction. This paper presents a novel method for studying cilia forming cells in asymmetric microfluidic environments. The microfluidic devices presented here were designed for a dynamic control of the local fluid flow on a cellular level, and thus, enables studies of cellular responses to an amplitude, frequency and direction controlled cilium movement.

  • 42.
    Rydholm, Susanna
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Zwartz, Gordon
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Kowalewski, Jacob
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Kamali-Zare, Padideh
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Mechanical Properties of Primary Cilia Regulate the Response to Fluid flow2010In: American Journal of Physiology - Renal Physiology, ISSN 0363-6127, E-ISSN 1522-1466, Vol. 298, no 5, p. 1096-1102Article in journal (Refereed)
    Abstract [en]

    The primary cilium is a ubiquitous organelle present on most mammalian cells. Malfunction of the organelle has been associated with various pathological disorders, many of which lead to cystic disorders in liver, pancreas, and kidney. Primary cilia have in kidney epithelial cells been observed to generate intracellular calcium in response to fluid flow, and disruption of proteins involved in this calcium signaling lead to autosomal dominant polycystic kidney disease, implying a direct connection between calcium signaling and cyst formation. It has also been shown that there is a significant lag between the onset of flow and initiation of the calcium signal. The present study focuses on the mechanics of cilium bending and the resulting calcium signal. Visualization of real-time cilium movements in response to different types of applied flow showed that the bending is fast compared with the initiation of calcium increase. Mathematical modeling of cilium and surrounding membrane was performed to deduce the relation between bending and membrane stress. The results showed a delay in stress buildup that was similar to the delay in calcium signal. Our results thus indicate that the delay in calcium response upon cilia bending is caused by mechanical properties of the cell membrane.

  • 43.
    Sandström, Niklas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Electrohydrodynamic Enhanced Transport and Trapping of Airborne Particles to a Microfluidic Air-Liquid Interface2008In: Micro System Workshop 2008, 2008Conference paper (Other academic)
  • 44.
    Sandström, Niklas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    ELECTROHYDRODYNAMIC ENHANCED TRANSPORT AND TRAPPING OF AIRBORNE PARTICLES TO A MICROFLUIDIC AIR-LIQUID INTERFACE2008In: 21st IEEE International Conference on Micro Electro Mechanical Systems (IEEE MEMS 2008), IEEE conference proceedings, 2008, p. 595-598Conference paper (Refereed)
    Abstract [en]

    We introduce a novel approach for greatly improved transport and trapping of airborne sample to a microfluidic analysis system by integrating an electrohydrodynamic (EHD) air pump with a microfluidic air-liquid interface. In our system, a negative corona discharge partially ionizes the air around a sharp electrode tip while the electrostatic field accelerates airborne particles towards an electrically grounded liquid surface, where they absorb. The air-liquid interface is fixated at the microscale pores of a perforated silicon diaphragm, each pore functioning as a static Laplace valve. Our system was experimentally tested using airborne smoke particles of ammonium chloride and aqueous salt solution as the liquid. We measured that EHD enhanced transport of the particles from the air into the liquid is enhanced over 130 times compared to passive trapping.

  • 45.
    Sandström, Niklas
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Microsystems for Airborne Sample Detection2008In: Mini-symposium on Opto-Microfluidics for Biological Large Scale Integration, 2008Conference paper (Other academic)
  • 46.
    Stemme, Göran
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Rydholm, Susanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Andersson, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    A cell-relevant Microgradient Environment2006In: Proceedings of the 10th International Conference in Miniaturized Systems for Chemistry and Life Sciences (µTas), 2006, p. 1507-1509Conference paper (Refereed)
    Abstract [en]

    With confocal microscopy new knowledge in cell physiology is acquireddaily. However, most cell assays today are carried out either as multiwellplate assays, or in standard petridish assays. These two methods havedifferent features and foci, but they have in common the large amount ofcells submitted for treatment and imaging. In order to study only a few cellson a more detailed level[1, 2] in a relevant context, we have designed, built,and evaluated a microfluidic system. It features 1) immobilization of cells inthree dimensions, 2) transportation of cell nutrients and treatments as wellas removal of residual products, 3) an extremely stable and physiologicallyrelevant gradient of chemical concentration distribution around the cell.Previous efforts in this field by our group revealed a few very importantissues, indicating that microfabrication would be the enabling technologyfor experiments on cells in asymmetricenvironments.

  • 47.
    Stemme, Göran
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Rydholm, Susanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology.
    Andersson, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Microfabricated Device for Controlled Stimuli of Primary Cilia2006In: Proceedings of the 10th International Conference in Miniaturized Systems for Chemistry and Life Sciences (µTas), 2006, p. 1510-1512Conference paper (Refereed)
    Abstract [en]

    We present an improved device and method for studying cellular response onmicrofluidic controlled stimuli of primary cilia. The primary cilium functions as amechano-sensor in renal tubular epithelium. Malfunction of cilia has been implicated inpolycystic kidney decease as well as other kidney abnormalities. Bending of cilia willgive rise to an intracellular calcium signal [1,2,3], but little is known about theimportance of flow direction, magnitude and duration to the calcium response. Ourpreliminary results indicate flow speed sensitivity.

  • 48.
    Stemme, Göran
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    van der Wijngaart, Wouter
    Frisk, Thomas
    Månsson, Per
    ANALYSIS DEVICE2007Patent (Other (popular science, discussion, etc.))
  • 49. Tauriainen, Johanna
    et al.
    Gustafsson, Karin
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Göthlin, Mårten
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gertow, Jens
    Buggert, Marcus
    Frisk, Thomas W.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Karlsson, Annika C.
    Uhlin, Michael
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Institutet, Sweden.
    Single-cell characterization of in vitro migration and interaction dynamics of T cells expanded with IL-2 and IL-72015In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 6, article id 196Article in journal (Refereed)
    Abstract [en]

    T cells are pivotal in the immune defense against cancers and infectious agents. To mount an effector response against cancer cells, T cells need to migrate to the cancer-site, engage in contacts with cancer cells, and perform their effector functions. Adoptive T cell therapy is an effective strategy as treatment of complications such as relapse or opportunistic infections after hematopoietic stem cell transplantations. This requires a sufficient amount of cells that are able to expand and respond to tumor or viral antigens. The cytokines interleukin (IL)-2 and IL-7 drive T cell differentiation, proliferation, and survival and are commonly used to expand T cells ex vivo. Here, we have used microchip-based live-cell imaging to follow the migration of individual T cells, their interactions with allogeneic monocytes, cell division, and apoptosis for extended periods of time; something that cannot be achieved by commonly used methods. Our data indicate that cells grown in IL-7 + IL-2 had similar migration and contact dynamics as cells grown in IL-2 alone. However, the addition of IL-7 decreased cell death creating a more viable cell population, which should be beneficial when preparing cells for immunotherapy.

  • 50.
    van der Wijngaart, Wouter
    et al.
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Frisk, Thomas
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Microsystem Technology (Changed name 20121201).
    A micromachined interface for transfer of liquid or vapour sample to a liquid solution2005In: Solid-State Sensors, Actuators and Microsystems, 2005. Digest of Technical Papers. TRANSDUCERS '05. The 13th International Conference on  (Volume:2 ), NEW YORK: IEEE conference proceedings, 2005, Vol. 2, p. 1276-1279Conference paper (Refereed)
    Abstract [en]

    A novel microfluidic interface for vapour-to-liquid adsorption and droplet-to-liquid transfer was designed and fabricated using silicon micromachining. The interface was characterised and successfully tested.

12 1 - 50 of 54
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf