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  • 1.
    Barnkob, Rune
    et al.
    Tech Univ Denmark, Lyngby, Denmark .
    Iranmanesh, Ida
    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.
    Bruus, Henrik
    Tech Univ Denmark, Lyngby, Denmark .
    Measuring acoustic energy density in microchannel acoustophoresis using a simple and rapid light-intensity method2012In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 12, no 13, p. 2337-2344Article in journal (Refereed)
    Abstract [en]

    We present a simple and rapid method for measuring the acoustic energy density in microchannel acoustophoresis based on light-intensity measurements of a suspension of particles. The method relies on the assumption that each particle in the suspension undergoes single-particle acoustophoresis. It is validated by the single-particle tracking method, and we show by proper re-scaling that the re-scaled light intensity plotted versus re-scaled time falls on a universal curve. The method allows for analysis of moderate-resolution images in the concentration range encountered in typical experiments, and it is an attractive alternative to particle tracking and particle image velocimetry for quantifying acoustophoretic performance in microchannels.

  • 2. Bruus, Henrik
    et al.
    Dual, Jürg
    Hawkes, Jeremy
    Hill, Martyn
    Laurell, Thomas
    Nilsson, Johan
    Radel, Stefan
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Forthcoming lab on a chip tutorial series on acoustofluidics: Acoustofluidics - Exploiting ultrasonic standing wave forces and acoustic streaming in microfluidic systems for cell and particle manipulation2011In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 11, no 21, p. 3579-3580Article in journal (Other academic)
  • 3. Carannante, Valentina
    et al.
    Olofsson, Karl
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Van Oojen, Hanna
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Edwards, Steven
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Lundqvist, Andreas
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Novel platform for studying infiltration, migration and cytotoxicity of human Natural Killer cells in solid tumors2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 315-315Article in journal (Other academic)
  • 4.
    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).

  • 5.
    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.

  • 6.
    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.

  • 7.
    Christakou, Athanasia E.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Ohlin, Mathias
    KTH, School of Engineering Sciences (SCI), Applied 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.
    Solid tumor spheroid formation by temperature-controlled high voltage ultrasound in a multi-well microdevice2014In: 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014, Chemical and Biological Microsystems SocietyChemical and Biological Microsystems Society , 2014, p. 573-575Conference paper (Refereed)
    Abstract [en]

    In the present work we demonstrate effective 3D growth of human hepatocellular carcinoma (HCC) HepG2 cell spheroids in parallel in a multi-well microdevice actuated with high voltage ultrasound in a temperature-controlled system. We compare the spheroid formation during continuous ultrasound exposure for one week where we formed spheroids in 59% of the wells, with the spheroid formation without ultrasound actuation, where we obtained 0% spheroids. Furthermore, we present an application of the tumor spheroids for investigating natural killer (NK) cells behavior against solid tumors.

  • 8.
    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.
    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.
    Ultrasonic three-dimensional cell culture on chip for dynamic studies of tumor immune surveillance by natural killer cellsManuscript (preprint) (Other academic)
  • 9.
    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.
    Önfelt, Björn
    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.
    Ultrasound-assisted three-dimensional tumor formation in a multi well microplate for monitoring natural killer cell functional behaviorManuscript (preprint) (Other academic)
  • 10.
    Christakou, Athanasia
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ohlin, Mathias
    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.
    Characterization of natural killer cell immune surveillance against solid liver tumors2015In: MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Chemical and Biological Microsystems Society , 2015, p. 915-917Conference paper (Refereed)
    Abstract [en]

    We demonstrate a method for investigating natural killer (NK) cell aggression against ultrasound-assisted human hepatocellular carcinoma (HCC) HepG2 solid tumors in a multi-well microdevice. We quantify the activity of human primary IL-2 activated NK cells against HepG2 tumors for up to five days and we present the correlation between NK cell numbers versus average tumor volume and final tumor outcome (growth or defeat). We suggest future applications on formation of tumors originated from primary tumors cells and other tumor components as well as primary NK originating from the patient for use in personalized immunotherapy.

  • 11.
    Christakou, Athanasia
    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.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Ultrasonic three-dimensional on-chip cell culture for dynamic studies of tumor immune surveillance by natural killer cells2015In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 15, no 15, p. 3222-31Article in journal (Refereed)
    Abstract [en]

    We demonstrate a simple method for three-dimensional (3D) cell culture controlled by ultrasonic standing waves in a multi-well microplate. The method gently arranges cells in a suspension into a single aggregate in each well of the microplate and, by this, nucleates 3D tissue-like cell growth for culture times between two and seven days. The microplate device is compatible with both high-resolution optical microscopy and maintenance in a standard cell incubator. The result is a scaffold- and coating-free method for 3D cell culture that can be used for controlling the cellular architecture, as well as the cellular and molecular composition of the microenvironment in and around the formed cell structures. We demonstrate the parallel production of one hundred synthetic 3D solid tumors comprising up to thousands of human hepatocellular carcinoma (HCC) HepG2 cells, we characterize the tumor structure by high-resolution optical microscopy, and we monitor the functional behavior of natural killer (NK) cells migrating, docking and interacting with the tumor model during culture. Our results show that the method can be used for determining the collective ability of a given number of NK cells to defeat a solid tumor having a certain size, shape and composition. The ultrasound-based method itself is generic and can meet any demand from applications where it is advantageous to monitor cell culture from production to analysis of 3D tissue or tumor models using microscopy in one single microplate device.

  • 12.
    Faridi, M. A.
    et al.
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ramachandraiah, H.
    KTH, School of Biotechnology (BIO).
    Iranmanesh, I. S.
    KTH, School of Biotechnology (BIO). KTH, School of Engineering Sciences (SCI), Applied Physics.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Microbubble assisted cell sorting by acoustophoresis2016In: 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016, Chemical and Biological Microsystems Society , 2016, p. 1677-1678Conference paper (Refereed)
    Abstract [en]

    Polymer shelled gas microbubbles (MBs) are used to sort cells in a microfluidic chip under acoustic standing waves (SW). When particles are subjected to SW based on their acoustic contrast factor (ACF) they migrate to nodes (positive contrast factor particles; PACP) or antinodes (negative acoustic contrast particles; NACP)[1]. We have bounded functionalized MBs with cells such that, they can be selectively migrated to antinodes under SW and sorted from unbounded cell both in no flow and flow conditions. Here we demonstrate acoustic mediated microbubble tagged cell sorting with 75% efficiency.

  • 13.
    Faridi, Muhammad Asim
    et al.
    KTH. mafaridi@kth.se.
    Iranmanesh, Ida Sadat
    KTH.
    Ramachandraiah, Harisha
    Vanderleyden, Els
    Dubruel, Peter
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Glass Capillary based cavity resonator for particle trapping study and bacteria up-concentrationIn: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781Article in journal (Refereed)
    Abstract [en]

    We have performed particle aggregation characterization on the basis of their material and suspending

    medium in a capillary-based cavity resonator used for acoustophoresis. We have investigated the experimental

    aggregation time of 5μm polystyrene and silica particles, size of aggregate, number of trapped particles and upconcentration

    factor in water, 0.01M phosphate buffered saline (PBS) and 0.005M PBS at 1.97MHz and with

    actuation voltages between 4, 8 and 12Vpp. We have found that there is little difference between using water and

    PBS as suspension medium, approximately 5-10% longer trapping times with PBS compared with water.

    However we get approx. 5.5 times faster trapping time for silica than for polystyrene. It is also observed and

    calculated that silica particle aggregates have 3.4 times larger area than the polystyrene aggregates using the same

    starting particle concentrations, revealing similar amount of difference in trapped number of particles. The upconcentration

    factor for silica is also about 3.2 times higher than that of polystyrene due to larger aggregate area

    of silica particles. Based on theoretical predictions and experimental characterization of the particle aggregation

    pattern, we note that the particle-particle interaction force contribution to the total acoustic radiation force is more

    pronounced for silica than for polystyrene. Finally as a proof of principle for biomedical sample preparation

    application we demonstrate the capillary-based silica particles mediated bacteria acoustophoretic upconcentration.

    This setup could potentially be utilized not only for sample preparation application but also for

    bead based affinity immunoassays.

  • 14.
    Faridi, Muhammad Asim
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. mafaridi@kth.se.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Iranmanesh, Ida Sadat
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    MicroBubble Activated Acoustic Cell Sorting: BAACSIn: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781Article in journal (Refereed)
    Abstract [en]

    Acoustophoresis, the ability to acoustically manipulate particles and cells inside a microfluidic channel, is a critical enabling technology for cell-sorting applications. However, one of the major impediments for routine use of acoustophoresis at clinical laboratory has been the reliance on the inherent physical properties of cells for separation. Here, we present a microfluidic-based microBubble-Activated Acoustic Cell Sorting (BAACS) method that rely on the specific binding of target cells to microbubbles conjugated with specific antibodies on their surface for continuous cell separation using ultrasonic standing wave. In acoustophoresis, cells being positive acoustic contrast particles migrate to pressure nodes. On the contrary we show that air-filled polymer-shelled microbubbles being strong negative acoustic contrast particles migrate to pressure antinodes at acoustic pressure amplitudes as low as 60 kPa. As a proof of principle, using the BAACS strategy, we demonstrate the separation of cancer cell line in a suspension with better than 75% efficiency. Moreover, 100% of the microbubble-cell conjugates migrated to the anti-node. Hence a better upstream affinity-capture has the potential to provide higher sorting efficiency. The BAACS technique may potentially provide a simplistic approach for similar sized selective isolation of cells, and is suited for applications in point of care.

  • 15.
    Faridi, Muhammad Asim
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. mafaridi@kth.se.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Iranmanesh, Ida Sadat
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    MicroBubble Activated Acoustic Cell Sorting: BAACS2017In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 19, no 2Article in journal (Refereed)
    Abstract [en]

    Acoustophoresis, the ability to acoustically manipulate particles and cells inside a microfluidic channel, is a critical enabling technology for cell-sorting applications. However, one of the major impediments for routine use of acoustophoresis at clinical laboratory has been the reliance on the inherent physical properties of cells for separation. Here, we present a microfluidic-based microBubble-Activated Acoustic Cell Sorting (BAACS) method that rely on the specific binding of target cells to microbubbles conjugated with specific antibodies on their surface for continuous cell separation using ultrasonic standing wave. In acoustophoresis, cells being positive acoustic contrast particles migrate to pressure nodes. On the contrary we show that air-filled polymer-shelled microbubbles being strong negative acoustic contrast particles migrate to pressure antinodes at acoustic pressure amplitudes as low as 60 kPa. As a proof of principle, using the BAACS strategy, we demonstrate the separation of cancer cell line in a suspension with better than 75% efficiency. Moreover, 100% of the microbubble-cell conjugates migrated to the anti-node. Hence a better upstream affinity-capture has the potential to provide higher sorting efficiency. The BAACS technique may potentially provide a simplistic approach for similar sized selective isolation of cells, and is suited for applications in point of care.

  • 16. 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.

  • 17.
    Girnyk, Maksym A.
    et al.
    KTH, School of Electrical Engineering (EES), Communication Theory.
    Vehkapera, Mikko
    Rasmussen, Lars Kildehoj
    Christakou, Athanasia
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Onfelt, Bjorn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Orange, Jordan
    Lytic granule convergence is essential for NK cells to promote targeted killing while preventing collateral damage2016In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196Article in journal (Other academic)
  • 18.
    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)
  • 19.
    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.

  • 20. Hsu, Hsiang-Ting
    et al.
    Mace, Emily M.
    Carisey, Alexandre F.
    Viswanath, Dixita I.
    Christakou, Athanasia
    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, Bjorn
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Orange, Jordan S.
    NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing2016In: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 215, no 6, p. 875-889Article in journal (Refereed)
    Abstract [en]

    Natural killer (NK) cell activation triggers sequential cellular events leading to destruction of diseased cells. We previously identified lytic granule convergence, a dynein-and integrin signal-dependent movement of lysosome-related organelles to the microtubule-organizing center, as an early step in the cell biological process underlying NK cell cytotoxicity. Why lytic granules converge during NK cell cytotoxicity, however, remains unclear. We experimentally controlled the availability of human ligands to regulate NK cell signaling and promote granule convergence with either directed or nondirected degranulation. By the use of acoustic trap microscopy, we generated specific effector-target cell arrangements to define the impact of the two modes of degranulation. NK cells with converged granules had greater targeted and less nonspecific "bystander" killing. Additionally, NK cells in which dynein was inhibited or integrin blocked under physiological conditions demonstrated increased nondirected degranulation and bystander killing. Thus, NK cells converge lytic granules and thereby improve the efficiency of targeted killing and prevent collateral damage to neighboring healthy cells.

  • 21.
    Hultström, Jessica
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Manneberg, Otto
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Dopf, Katja
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Brismar, Hjalmar
    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.
    Proliferation and viability of adherent cells manipulated by standing-wave ultrasound in a microfluidic chip2007In: Ultrasound in Medicine and Biology, ISSN 0301-5629, E-ISSN 1879-291X, Vol. 33, p. 145-151Article in journal (Refereed)
    Abstract [en]

    Ultrasonic-standing-wave (USW) technology has potential to become a standard method for gentle and contactless cell handling in microfluidic chips. We investigate the viability of adherent cells exposed to USWs by studying the proliferation rate of recultured cells following ultrasonic trapping and aggregation of low cell numbers in a microfluidic chip. The cells form 2-D aggregates inside the chip and the aggregates are held against a continuous flow of cell culture medium perpendicular to the propagation direction of the standing wave. No deviations in the doubling time from expected values (24 to 48 h) were observed for COS-7 cells held in the trap at acoustic pressure amplitudes up to 0.85 MPa and for times ranging between 30 and 75 min. Thus, the results demonstrate the potential of ultrasonic standing waves as a tool for gentle manipulation of low cell numbers in microfluidic systems.

  • 22.
    Iranmanesh, Ida
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ohlin, Mathias
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Acoustic micro-vortexing of fluids, beads and cells in disposible microfluidic chips2015In: MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Chemical and Biological Microsystems Society , 2015, p. 1005-1007Conference paper (Refereed)
    Abstract [en]

    In this paper we demonstrate a multi-functional platform using ultrasound for vortexing of 20-μl volumes of different samples in polymer-based disposable chips. The method enables different vortexing functions such as mixing laminar flows, resuspension of a micro-pellet of magnetic beads as well as cell lysis for DNA extraction. The device consists of an inexpensive low-frequency, high power, horn-shaped langevin transducer which is typically used for cell disruption in larger volumes. By controlling the operating time of this device (from fractions of a second up to a minute) different functions can be achieved. In addition, to avoid the high-power-induced heating, a simple cooling system is used as a chip holder consisting of a PC fan-cooled aluminum heat sink. To demonstrate a sample preparation application, we perform on-chip cell lysis and DNA extraction.

  • 23.
    Iranmanesh, Ida
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ohlin, Mathias
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ye, Simon
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Acoustic micro-vortexing of fluids, particles and cells in disposable microfluidic chips2016In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 18, no 4, article id 71Article in journal (Refereed)
    Abstract [en]

    We demonstrate an acoustic platform for microvortexing in disposable polymer microfluidic chips with small-volume (20 mu l) reaction chambers. The described method is demonstrated for a variety of standard vortexing functions, including mixing of fluids, re-suspension of a pellet of magnetic beads collected by a magnet placed on the chip, and lysis of cells for DNA extraction. The device is based on a modified Langevin-type ultrasonic transducer with an exponential horn for efficient coupling into the microfluidic chip, which is actuated by a low-cost fixed-frequency electronic driver board. The transducer is optimized by numerical modelling, and different demonstrated vortexing functions are realized by actuating the transducer for varying times; from fractions of a second for fluid mixing, to half a minute for cell lysis and DNA extraction. The platform can be operated during 1 min below physiological temperatures with the help of a PC fan, a Peltier element and an aluminum heat sink acting as the chip holder. As a proof of principle for sample preparation applications, we demonstrate on-chip cell lysis and DNA extraction within 25 s. The method is of interest for automating and chip-integrating sample preparation procedures in various biological assays.

  • 24.
    Iranmanesh, Ida Sadat
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Barnkob, R.
    Bruus, H.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Tunable-angle wedge transducer for improved acoustophoretic control in a microfluidic chip2013In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 23, no 10, p. 105002-Article in journal (Refereed)
    Abstract [en]

    We present a tunable-angle wedge ultrasound transducer for improved control of microparticle acoustophoresis in a microfluidic chip. The transducer is investigated by analyzing the pattern of aligned particles and induced acoustic energy density while varying the transducer geometry, transducer coupling angle, and transducer actuation method (single-frequency actuation or frequency-modulation actuation). The energy-density analysis is based on measuring the transmitted light intensity through a microfluidic channel filled with a suspension of 5 mu m diameter beads and the results with the tunable-angle transducer are compared with the results from actuation by a standard planar transducer in order to decouple the influence from change in coupling angle and change in transducer geometry. We find in this work that the transducer coupling angle is the more important parameter compared to the concomitant change in geometry and that the coupling angle may be used as an additional tuning parameter for improved acoustophoretic control with single-frequency actuation. Further, we find that frequency-modulation actuation is suitable for diminishing such tuning effects and that it is a robust method to produce uniform particle patterns with average acoustic energy densities comparable to those obtained using single-frequency actuation.

  • 25.
    Iranmanesh, Ida Sadat
    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.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Acoustic micro-vortexing of fluids, beads and cells in disposable microfluidic chipsManuscript (preprint) (Other academic)
  • 26.
    Iranmanesh, Ida Sadat
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ramachandraiah, Harisha
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    On-chip ultrasonic sample preparation for cell based assays2015In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 5, no 91, p. 74304-74311Article in journal (Refereed)
    Abstract [en]

    We demonstrate an acoustophoresis method for size-based separation, isolation, up-concentration and trapping of cells that can be used for on-chip sample preparation combined with high resolution imaging for cell-based assays. The method combines three frequency-specific acoustophoresis functions in a sequence by actuating three separate channel zones simultaneously: zones for pre-alignment, size-based separation, and trapping. We characterize the mutual interference between the acoustic radiation forces between the different zones by measuring the spatial distribution of the acoustic energy density during different schemes of ultrasonic actuation, and use this information for optimizing the driving frequencies and voltages of the three utilized ultrasonic transducers attached to the chip, and the flow rates of the pumps. By the use of hydrodynamic defocusing of the pre-aligned cells in the separation zone, a cell population from a complex sample can be isolated and trapped with very high purity, followed by dynamic fluorescence analysis. We exemplify the method's potential by isolating A549 lung cancer cells from red blood cells with 100% purity, 92% separation efficiency, and 93% trapping efficiency resulting in a 130× up-concentration factor during 15 minutes of continuous sample processing through the chip. Furthermore, we demonstrate an on-chip fluorescence assay of the isolated cancer cells by monitoring the dynamic uptake and release of a fluorescence probe in individual trapped cells. The ability to combine isolation of individual cells from a complex sample with high-resolution image analysis holds great promise for applications in cellular and molecular diagnostics.

  • 27.
    Johansson, Linda
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Enlund, J.
    Johansson, S.
    Katardjiev, I.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Yantchev, V.
    Surface acoustic wave-induced precise particle manipulation in a trapezoidal glass microfluidic channel2012In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 22, no 2, p. 025018-Article in journal (Refereed)
    Abstract [en]

    Surface acoustic wave (SAW) excitation of an acoustic field in a trapezoidal glass microfluidic channel for particle manipulation in continuous flow has been demonstrated. A unidirectional interdigital transducer (IDT) on a Y-cut Z-propagation lithium niobate (LiNbO3) substrate was used to excite a surface acoustic wave at approximately 35 MHz. An SU8 layer was used for adhesive bonding of the superstrate glass layer and the substrate piezoelectric layer. This work extends the use of SAWs for acoustic manipulation to also include glass channels in addition to prior work with mainly poly-di-methyl-siloxane channels. Efficient alignment of 1.9 mu m polystyrene particles to narrow nodal regions was successfully demonstrated. In addition, particle alignment with only one IDT active was realized. A finite element method simulation was used to visualize the acoustic field generated in the channel and the possibility of 2D alignment into small nodal regions was demonstrated.

  • 28.
    Kothapalli, Satya V. V. N.
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Janerot-Sjöberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering. Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Paradossi, Gaio
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering. Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Investigation of polymer-shelled microbubble motions in acoustophoresis2016In: Ultrasonics, ISSN 0041-624X, E-ISSN 1874-9968, Vol. 70, p. 275-283Article in journal (Refereed)
    Abstract [en]

    The objective of this paper is to explore the trajectory motion of microsize (typically smaller than a red blood cell) encapsulated polymer-shelled gas bubbles propelled by radiation force in an acoustic standing-wave field and to compare the corresponding movements of solid polymer microbeads. The experimental setup consists of a microfluidic chip coupled to a piezoelectric crystal (PZT) with a resonance frequency of about 2.8 MHz. The microfluidic channel consists of a rectangular chamber with a width, w, corresponding to one wavelength of the ultrasound standing wave. It creates one full wave ultrasound of a standing-wave pattern with two pressure nodes at w/4 and 3w/4 and three antinodes at 0, w/2, and w. The peak-to-peak amplitude of the electrical potential over the PZT was varied between 1 and 10 V. The study is limited to no-flow condition. From Gor'kov's potential equation, the acoustic contrast factor, Phi, for the polymer-shelled microbubbles was calculated to about -60.7. Experimental results demonstrate that the polymer-shelled microbubbles are translated and accumulated at the pressure antinode planes. This trajectory motion of polymer-shelled microbubbles toward the pressure antinode plane is similar to what has been described for other acoustic contrast particles with a negative Phi. First, primary radiation forces dragged the polymer-shelled microbubbles into proximity with each other at the pressure antinode planes. Then, primary and secondary radiation forces caused them to quickly aggregate at different spots along the channel. The relocation time for polymer-shelled microbubbles was 40 times shorter than that for polymer microbeads, and in contrast to polymer microbeads, the polymer-shelled microbubbles were actuated even at driving voltages (proportional to radiation forces) as low as 1 V. In short, the polymer-shelled microbubbles demonstrate the behavior attributed to the negative acoustic contrast factor particles and thus can be trapped at the antinode plane and thereby separated from particles having a positive acoustic contrast factor, such as for example solid particles and cells. This phenomenon could be utilized in exploring future applications, such as bioassay, bioaffinity, and cell interaction studies in vitro in a well-controlled environment.

  • 29.
    Kothapalli, Satya V.V.N.
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Janerot Sjöberg, Birgitta
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden .
    Paradossi, Gaio
    Diapartimento di Chimica, Università di Roma Tor Vergata.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Grishenkov, Dmitry
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden .
    Investigation of Polymer-Shelled Microbubble Motions in AcoustophoresisManuscript (preprint) (Other academic)
    Abstract [en]

    The objective of this paper is to explore the trajectory motion of microsize (typically smaller than a redblood cell) encapsulated polymer-shelled gas bubbles propelled by radiation force in an acousticstanding-wave field and to compare the corresponding movements of solid polymer microbeads. Theexperimental setup consists of a microfluidic chip coupled to a piezoelectric crystal (PZT) with aresonance frequency of about 2.8 MHz. The microfluidic channel consists of a rectangular chamberwith a width, w, corresponding to one wavelength of the ultrasound standing wave. It creates one fullwave ultrasound of a standing-wave pattern with two pressure nodes at4w and43w and threeantinodes at 0,2w , and w. The peak-to-peak amplitude of the electrical potential over the PZT wasvaried between 1 and 10 volts. From Gor’kov’s potential equation, the acoustic contrast factor, Φ, forthe polymer-shelled microbubbles was calculated to about -60.7. Experimental results demonstratethat the polymer-shelled microbubbles are translated and accumulated at the pressure antinode planes.This trajectory motion of polymer-shelled microbubbles toward the pressure antinode plane is similarto what has been described for other acoustic contrast particles with a negative Φ. First, primaryradiation forces dragged the polymer-shelled microbubbles into proximity with each other at thepressure antinode planes. Then, secondary radiation forces caused them to aggregate at different spotsalong the channel. The relocation time for polymer-shelled microbubbles was 40 times shorter thanthat for polymer microbeads, and in contrast to polymer microbeads, the polymer-shelledmicrobubbles were actuated even at driving voltages (proportional to radiation forces) as low as 1 volt.In short, the polymer-shelled microbubbles demonstrate the behavior attributed to the negativeacoustic contrast factor particles and thus can be trapped at the antinode plane and thereby seperatedfrom solid particles, such as cells. This phenomenon could be utilized in exploring future applications,such as bioassay, bioaffinity, and cell interaction studies in vitro in a well-controlled environment.

  • 30. Lemor, Robert
    et al.
    Günther, Christian
    Fuhr, Günther
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Metod och anordning för akustisk manipulering av partiklar, celler och virus2005Patent (Other (popular science, discussion, etc.))
  • 31.
    Manneberg, Otto
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Hagsäter, S. Melker
    Svennebring, Jessica
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Hertz, Hans M.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Kutter, Jörg P.
    Bruus, Henrik
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Spatial confinement of ultrasonic force fields in microfluidic chips2009In: Ultrasonics, ISSN 0041-624X, E-ISSN 1874-9968, Vol. 49, p. 112-119Article in journal (Refereed)
    Abstract [en]

    We demonstrate and investigate multiple localized ultrasonic manipulation functions in series in microfluidic chips. The manipulation functions are based on spatially separated and confined ultrasonic primary radiation force fields, obtained by local matching of the resonance condition of the microfluidic channel. The channel segments are remotely actuated by the use of frequency-specific external transducers with refracting wedges placed on top of the chips. The force field in each channel segment is characterized by the use of micrometer-resolution particle image velocimetry ( micro-PIV). The confinement of the ultrasonic fields during single-or dual-segment actuation, as well as the cross-talk between two adjacent. fields, is characterized and quantified. Our results show that the field confinement typically scales with the acoustic wavelength, and that the cross-talk is insignificant between adjacent. fields. The goal is to define design strategies for implementing several spatially separated ultrasonic manipulation functions in series for use in advanced particle or cell handling and processing applications. One such proof-of-concept application is demonstrated, where. flow-through-mode operation of a chip with. flow splitting elements is used for two-dimensional pre-alignment and addressable merging of particle tracks.

  • 32.
    Manneberg, Otto
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Svennebring, Jessica
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    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.
    Wedge transducer design for two-dimensional ultrasonic manipulation in a microfluidic chip2008In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 18, p. 095025-Article in journal (Refereed)
    Abstract [en]

    We analyze and optimize the design of wedge transducers used for the excitation of resonances in the channel of a microfluidic chip in order to efficiently manipulate particles or cells in more than one dimension. The design procedure is based on (1) theoretical modeling of acoustic resonances in the transducer-chip system and calculation of the force fields in the fluid channel, (2) full-system resonance characterization by impedance spectroscopy and (3) image analysis of the particle distribution after ultrasonic manipulation. We optimize the transducer design in terms of actuation frequency, wedge angle and placement on top of the chip, and we characterize and compare the coupling effects in orthogonal directions between single- and dual-frequency ultrasonic actuation. The design results are verified by demonstrating arraying and alignment of particles in two dimensions. Since the device is compatible with high-resolution optical microscopy, the target application is dynamic cell characterization combined with improved microfluidic sample transport.

  • 33.
    Manneberg, Otto
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Svennebring, Jessica
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    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.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    A three-dimensional ultrasonic cage for characterization of individual cells2008In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 93, p. 063901-Article in journal (Refereed)
    Abstract [en]

    We demonstrate enrichment, controlled aggregation, and manipulation of microparticles and cells by an ultrasonic cage integrated in a microfluidic chip compatible with high-resolution optical microscopy. The cage is designed as a dual-frequency resonant filleted square box integrated in the fluid channel. Individual particles may be trapped three dimensionally, and the dimensionality of one-dimensional to three-dimensional aggregates can be controlled. We investigate the dependence of the shape and position of a microparticle aggregate on the actuation voltages and aggregate size, and demonstrate optical monitoring of individually trapped live cells with submicrometer resolution.

  • 34.
    Manneberg, Otto
    et al.
    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.
    Flow-free transport of cells in microchannels by frequency-modulated ultrasound2009In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 9, p. 833-837Article in journal (Refereed)
    Abstract [en]

    We demonstrate flow-free transport of cells and particles by the use of frequency-modulated ultrasonic actuation of a microfluidic chip. Two different modulation schemes are combined: A rapid (1 kHz) linear frequency sweep around similar to 6.9 MHz is used for two-dimensional spatial stabilization of the force field over a 5 mm long inlet channel of constant cross section, and a slow (0.2-0.7 Hz) linear frequency sweep around similar to 2.6 MHz is used for flow-free ultrasonic transport and positioning of cells or particles. The method is used for controlling the motion and position of cells monitored with high-resolution optical microscopy, but can also be used more generally for improving the robustness and performance of ultrasonic manipulation micro-devices.

  • 35. Nilsson, H.
    et al.
    Wiklund, Martin
    KTH, Superseded Departments, Physics.
    Johansson, T.
    Hertz, Hans M.
    KTH, Superseded Departments, Physics.
    Nilsson, S.
    Microparticles for selective protein determination in capillary electrophoresis2001In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 22, no 12, p. 2384-2390Article in journal (Refereed)
    Abstract [en]

    A system for detection of trace amounts of protein was developed. Two different monoclonal antibodies against human chorionic gonadotropin (hCG) were covalently bound to latex particles. When the latex particles were mixed with a sample containing hCG, a latex-protein-latex complex (immunocomplex) was formed. The complex was separated from the single latex particles using capillary electrophoresis and detected using UV-Vis detection. Limit of detection was 8 amol hCG. The separation was also monitored in real time using laser induced fluorescence - charge coupled device (LIF-CCD) imaging detection. However, a limitation of the method is the restriction to detection of proteins for which monoclonal antibodies are available.

  • 36.
    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.

  • 37.
    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.

  • 38.
    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.

  • 39.
    Ohlin, Mathias
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Iranmanesh, Ida Sadat
    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.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Temperature-controlled MPa-pressure ultrasonic cell manipulation in a microfluidic chip2015In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 15, no 16, p. 3341-3349Article in journal (Refereed)
    Abstract [en]

    We study the temperature-independent impact on cell viability of relevant physical parameters during long-term, high-acoustic-pressure ultrasonic exposure in a microfluidic chip designed for ultrasonic-standing-wave trapping and aggregation of cells. We use a light-intensity method and 5 mum polymer beads for accurate acoustic pressure calibration before injecting cells into the device, and we monitor the viability of A549 lung cancer cells trapped during one hour in an ultrasonic standing wave with 1 MPa pressure amplitude. The microfluidic chip is actuated by a novel temperature-controlled ultrasonic transducer capable of keeping the temperature stable around 37 °C with an accuracy better than ±0.2 °C, independently on the ultrasonic power and heat produced by the system, thereby decoupling any temperature effect from other relevant effects on cells caused by the high-pressure acoustic field. We demonstrate that frequency-modulated ultrasonic actuation can produce acoustic pressures of equally high magnitudes as with single-frequency actuation, and we show that A549 lung cancer cells can be exposed to 1 MPa standing-wave acoustic pressure amplitudes for one hour without compromising cell viability. At this pressure level, we also measure the acoustic streaming induced around the trapped cell aggregate, and conclude that cell viability is not affected by streaming velocities of the order of 100 mum s(-1). Our results are important when implementing acoustophoresis methods in various clinical and biomedical applications.

  • 40.
    Ohlin, Mathias
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Iranmanesh, Ida
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Long-term acoustophoresis at 1 MPA do not compromise cell viability2015In: MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Chemical and Biological Microsystems Society , 2015, p. 996-998Conference paper (Refereed)
    Abstract [en]

    In this paper we report on the viability of cells exposed to high acoustic pressure amplitudes (>1 MPa) and long durations (one hour) in a temperature-controlled acoustofluidic microdevice. We demonstrate that A5490 lung cancer cells are not affected by the ultrasound even at pressure levels exceeding what is normally used in acoustophoresis applications, as long as the temperature and fluid streaming around the trapped cells are carefully controlled.

  • 41.
    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].

  • 42.
    Svennebring, Jessica
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Manneberg, Otto
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Skafte-Pedersen, Peder
    Bruus, Henrik
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Selective bioparticle retention and characterization in a chip-integrated confocal ultrasonic cavity2009In: Biotechnology and Bioengineering, ISSN 0006-3592, E-ISSN 1097-0290, Vol. 103, p. 323-328Article in journal (Refereed)
    Abstract [en]

    We demonstrate selective retention and positioning of cells or other bioparticles by ultrasonic manipulation in a microfluidic expansion chamber during microfluidic perfusion. The chamber is designed as a confocal ultrasonic resonator for maximum confinement of the ultrasonic force field at the chamber center, where the cells are trapped. We investigate the resonant modes in the expansion chamber and its connecting inlet channel by theoretical modeling and experimental verification during no-flow conditions. Furthermore, by triple-frequency ultrasonic actuation during continuous microfluidic sample feeding, a set of several manipulation functions performed in series is demonstrated: sample bypass-injection-aggregation and retention-positioning. Finally, we demonstrate transillumination microscopy imaging Of Ultrasonically trapped COS-7 cell aggregates.

  • 43.
    Svennebring, Jessica
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Manneberg, Otto
    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.
    Temperature regulation during ultrasonic manipulation for long-term cell handling in a microfluidic chip2007In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 17, p. 2469-2474Article in journal (Refereed)
    Abstract [en]

    Regulation by the use of ultrasonic standing wave technology in a microfluidic chip. The system is based on a microfabricated silicon structure sandwiched between two glass layers, and an external ultrasonic transducer using a refractive wedge placed on top of the chip for efficient coupling of ultrasound into the microchannel. The chip is fully transparent and compatible with any kind of high-resolution optical microscopy. The temperature regulation method uses calibration data of the temperature increase due to the ultrasonic actuation for determining the temperature of the surrounding air and microscope table, controlled by a warm-air heating unit and a heatable mounting frame. The heating methods are independent of each other, resulting in a flexible choice of ultrasonic actuation voltage and flow rate for different cell and particle manipulation purposes. Our results indicate that it is possible to perform stable temperature regulation with an accuracy of the order of +/- 0.1 degrees C around any physiologically relevant temperature (e.g., 37 degrees C) with high temporal stability and repeatability. The purpose is to use ultrasound for long-term cell and/or particle handling in a microfluidic chip while controlling and maintaining the biocompatibility of the system.

  • 44.
    Vanherberghen, Bruno
    et al.
    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, Biomedical and X-ray Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Ohlin, Mathias
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Hertz, Hans M.
    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.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Ultrasound-controlled cell aggregation in a multi-well chip2010In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 10, no 20, p. 2727-2732Article in journal (Refereed)
    Abstract [en]

    We demonstrate a microplate platform for parallelized manipulation of particles or cells by frequency-modulated ultrasound. The device, consisting of a silicon-glass microchip and a single ultrasonic transducer, enables aggregation, positioning and high-resolution microscopy of cells distributed in an array of 100 microwells centered on the microchip. We characterize the system in terms of temperature control, aggregation and positioning efficiency, and cell viability. We use time-lapse imaging to show that cells continuously exposed to ultrasound are able to divide and remain viable for at least 12 hours inside the device. Thus, the device can be used to induce and maintain aggregation in a parallelized fashion, facilitating long-term microscopy studies of, e.g., cell-cell interactions.

  • 45.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Acoustofluidics 12: Biocompatibility and cell viability in microfluidic acoustic resonators2012In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 12, no 11, p. 2018-2028Article in journal (Other academic)
  • 46.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Affinity-Bead-Mediated Acoustophoresis: A Novel Tool in Cytometry2014In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 85A, no 11, p. 915-917Article in journal (Refereed)
  • 47.
    Wiklund, Martin
    KTH, Superseded Departments, Physics.
    Ultrasonic Enrichment of Microparticles in Bioaffinity Assays2004Doctoral thesis, comprehensive summary (Other scientific)
    Abstract [en]

    This Thesis describes applications of standing-waveultrasonic traps for sensitive biomedical analysis. Two majorapproaches have been investigated where functionalizedmicroparticles are employed in bioaffinity assays. In the firstapproach, a longitudinal flow-through capillary ultrasonic trapis used for size selective separation and retention ofdifferently sized microparticles. This device may be used fordetection of particle pairs, which are formed during theinitial stage of microparticle immunoagglutination. Theperformance of the capillary ultrasonic trap for enrichment andcounting of particle pairs is characterized by a model systemof differently sized homogeneous fluorescent microparticles.The selectivity of this detection method relies on thecharacteristics of the force field inside the narrow borecapillary, which is formed by the competition between acousticradiation forces and viscous drag forces from the fluidflow.

    The second approach is an investigation of the potential forsensitive protein quantification by combining ultrasonicenrichment and confocal laser-scanning fluore-scence detection.Here, the design of the ultrasonic trap is tailor-made for theimaging properties of a confocal microscope, resulting inrearrangement and concentration of suspended microparticlesinto single, dense layers that is scanned by a focused laserbeam. The bioaffinity assay employed is based on detecting thetarget molecules via fluorescent tracer antibodies immobilizedon the surface of each single particle.

    The final part of the work presented in this Thesis is athorough investigation of both the biochemical and the physicalproperties that determine the performance and potentialsensitivity of the particle doublet assay. In thisinvestigation, a novel approach is presented for doubletdetection, namely fluorescence-microscopy-based classificationof doublets and singlets by a pattern recognition algorithm.The experimental results are also compared with the resultsfrom flow cytometry analysis. Furthermore, the initial stage ofimmuno-agglutination is theoretically investigated by a modelbased on diffusion-limited agglutination combined with a stericfactor determined by the geometry of the bio-molecules and theamount of specific and non-specific binding that is present inthe particular assay.

    To conclude, the Thesis presents several approaches wherestanding-wave ultrasonic fields may be used for sensitiveparticle-based biomedical analysis. The best prospect for highsensitivity was found for the confocal laser-scanningfluorescence detection system, with a detection limit of theorder of 10-14M. On the other hand, the agglutination-basedassay may give sensitivity of the order of 10-11-10-10M with very simple and inexpensiveequipment.

  • 48.
    Wiklund, Martin
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Acoustofluidics 18: Microscopy for acoustofluidic micro-devices2012In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 12, no 18, p. 3221-3234Article, review/survey (Refereed)
    Abstract [en]

    In this tutorial review in the thematic series "Acoustofluidics", we discuss the implementation and practice of optical microscopy in acoustofluidic micro-devices. Examples are given from imaging of acoustophoretic manipulation of particles and cells in microfluidic channels, but most of the discussion is applicable to imaging in any lab-on-a-chip device. The discussion includes basic principles of optical microscopy, different microscopy modes and applications, and design criteria for micro-devices compatible with basic, as well as advanced, optical microscopy.

  • 49.
    Wiklund, Martin
    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.
    Iranmanesh, Ida
    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.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    On-chip acoustic sample preparation for cell studies and diagnostics2013In: Proceedings of Meetings on Acoustics: Volume 19, 2013, Acoustical Society of America (ASA), 2013, p. 1-3Conference paper (Refereed)
    Abstract [en]

    We describe a novel platform for acoustic sample preparation in microchannels and microplates. The utilized method is based on generating a multitude of acoustic resonances at a set of different frequencies in microstructures, in order to accurately control the migration and positioning of particles and cells suspended in fluid channels and chambers. The actuation frequencies range from 30 kHz to 7 MHz, which are applied simultaneously and/or in sweeps. We present two devices: A closed microfluidic chip designed for pre-alignment, size-based separation, isolation, up-concentration and lysis of cells, and an open multi-well microplate designed for parallel aggregation and positioning of cells. Both devices in the platform are compatible with high-resolution live-cell microscopy, which is used for fluorescence-based optical characterization. Two bioapplications are demonstrated for each of the devices: The first device is used for size-selective cell isolation and lysis for DNA-based diagnostics, and the second device is used for quantifying the heterogeneity in cytotoxic response of natural killer cells interacting with cancer cells.

  • 50.
    Wiklund, Martin
    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.
    Ohlin, Mathias
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Iranmanesh, Ida
    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.
    Vanherberghen, Bruno
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Önfelt, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Ultrasound-Induced Cell-Cell Interaction Studies in a Multi-Well Microplate2014In: Micromachines, ISSN 2072-666X, E-ISSN 2072-666X, Vol. 5, no 1, p. 27-49Article, review/survey (Refereed)
    Abstract [en]

    This review describes the use of ultrasound for inducing and retaining cell-cell contact in multi-well microplates combined with live-cell fluorescence microscopy. This platform has been used for studying the interaction between natural killer (NK) cells and cancer cells at the level of individual cells. The review includes basic principles of ultrasonic particle manipulation, design criteria when building a multi-well microplate device for this purpose, biocompatibility aspects, and finally, two examples of biological applications: Dynamic imaging of the inhibitory immune synapse, and studies of the heterogeneity in killing dynamics of NK cells interacting with cancer cells.

12 1 - 50 of 59
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