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  • 1. 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)
  • 2.
    Delsing, Per
    et al.
    Chalmers Univ Technol, Microtechnol & Nanosci, S-41296 Gothenburg, Sweden..
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Westerhausen, Christoph
    Univ Augsburg, Inst Phys, D-86159 Augsburg, Germany.;NIM, Munich, Germany.;Ludwig Maximilians Univ Munchen, Ctr NanoSci CeNS, D-80799 Munich, Germany.;Univ Augsburg, Ctr Interdisciplinary Hlth Res ZIG, D-86135 Augsburg, Germany.;ACIT, D-86159 Augsburg, Germany..
    The 2019 surface acoustic waves roadmap2019In: Journal of Physics D: Applied Physics, ISSN 0022-3727, E-ISSN 1361-6463, Vol. 52, no 35, article id 353001Article, review/survey (Refereed)
    Abstract [en]

    Today, surface acoustic waves (SAWs) and bulk acoustic waves are already two of the very few phononic technologies of industrial relevance and can been found in a myriad of devices employing these nanoscale earthquakes on a chip. Acoustic radio frequency filters, for instance, are integral parts of wireless devices. SAWs in particular find applications in life sciences and microfluidics for sensing and mixing of tiny amounts of liquids. In addition to this continuously growing number of applications, SAWs are ideally suited to probe and control elementary excitations in condensed matter at the limit of single quantum excitations. Even collective excitations, classical or quantum are nowadays coherently interfaced by SAWs. This wide, highly diverse, interdisciplinary and continuously expanding spectrum literally unites advanced sensing and manipulation applications. Remarkably, SAW technology is inherently multiscale and spans from single atomic or nanoscopic units up even to the millimeter scale. The aim of this Roadmap is to present a snapshot of the present state of surface acoustic wave science and technology in 2019 and provide an opinion on the challenges and opportunities that the future holds from a group of renown experts, covering the interdisciplinary key areas, ranging from fundamental quantum effects to practical applications of acoustic devices in life science.

  • 3.
    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.

  • 4.
    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.

  • 5.
    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 2, article id 23Article 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.

  • 6.
    Faridi, Muhammad Asim
    et al.
    KTH.
    Shahzad, Adnan Faqui
    KTH.
    Russom, Aman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Milliliter scale acoustophoresis based bioparticle processing platform2018In: ASME 2018 16th International Conference on Nanochannels, Microchannels, and Minichannels, ICNMM 2018, ASME Press, 2018Conference paper (Refereed)
    Abstract [en]

    Bioparticles such as mammalian cells and bacteria can be manipulated directly or indirectly for multiple applications such as sample preparation for diagnostic applications mainly up-concentration, enrichment & separation as well as immunoassay development. There are various active and passive microfluidic particle manipulation techniques where Acoustophoresis is a powerful technique showing high cell viability. The use of disposable glass capillaries for acoustophoresis, instead of cleanroom fabricated glass-silicon chip can potentially bring down the cost factor substantially, aiding the realization of this technique for real-world diagnostic devices. Unlike available chips and capillary-based microfluidic devices, we report milliliter-scale platform able to accommodate 1ml of a sample for acoustophoresis based processing on a market available glass capillary. Although it is presented as a generic platform but as a demonstration we have shown that polystyrene suspending medium sample can be processed with trapping efficiency of 87% and the up-concentration factor of 10 times in a flow through manner i.e., at 35µl/min. For stationary volume accommodation, this platform practically offers 50 times more sample handling capacity than most of the microfluidic setups. Furthermore, we have also shown that with diluted blood (0.6%) in a flow-through manner, 82% of the white blood cells (WBCs) per ml could be kept trapped. This milliliter platform could potentially be utilized for assisting in sample preparation, plasma separation as well as a flow-through immunoassay assay development for clinical diagnostic applications.

  • 7.
    Ghorbani, Morteza
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging. Sabanci Univ, Fac Engn & Nat Sci, Mechatron Engn Program, TR-34956 Istanbul, Turkey.
    Olofsson, Karl
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Benjamins, Jan-Willem
    Research Institute of Sweden (RISE), Chemistry, Materials and Surfaces, Box 5607, SE-114 86 Stockholm, Sweden.
    Loskutova, Ksenia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Paulraj, Thomas
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Polymeric Materials.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Grishenkov, Dmitry
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Svagan, Anna Justina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Unravelling the Acoustic and Thermal Responses of Perfluorocarbon Liquid Droplets Stabilized with Cellulose Nanofibers2019In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 35, no 40, p. 13090-13099Article in journal (Refereed)
    Abstract [en]

    The attractive colloidal and physicochemical properties of cellulose nanofibers (CNFs) at interfaces have recently been exploited in the facile production of a number of environmentally benign materials, e.g. foams, emulsions, and capsules. Herein, these unique properties are exploited in a new type of CNF-stabilized perfluoropentane droplets produced via a straightforward and simple mixing protocol. Droplets with a comparatively narrow size distribution (ca. 1–5 μm in diameter) were fabricated, and their potential in the acoustic droplet vaporization process was evaluated. For this, the particle-stabilized droplets were assessed in three independent experimental examinations, namely temperature, acoustic, and ultrasonic standing wave tests. During the acoustic droplet vaporization (ADV) process, droplets were converted to gas-filled microbubbles, offering enhanced visualization by ultrasound. The acoustic pressure threshold of about 0.62 MPa was identified for the cellulose-stabilized droplets. A phase transition temperature of about 22 °C was observed, at which a significant fraction of larger droplets (above ca. 3 μm in diameter) were converted into bubbles, whereas a large part of the population of smaller droplets were stable up to higher temperatures (temperatures up to 45 °C tested). Moreover, under ultrasound standing wave conditions, droplets were relocated to antinodes demonstrating the behavior associated with the negative contrast particles. The combined results make the CNF-stabilized droplets interesting in cell-droplet interaction experiments and ultrasound imaging.

  • 8. 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.

  • 9.
    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].

  • 10.
    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.

  • 11.
    Olofsson, Karl
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Hammarström, Björn
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Wiklund, Martin
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Ultrasonic Based Tissue Modelling and Engineering2018In: Micromachines, ISSN 2072-666X, E-ISSN 2072-666X, Vol. 9, no 11, article id 594Article, review/survey (Refereed)
    Abstract [en]

    Systems and devices for in vitro tissue modelling and engineering are valuable tools, which combine the strength between the controlled laboratory environment and the complex tissue organization and environment in vivo. Device-based tissue engineering is also a possible avenue for future explant culture in regenerative medicine. The most fundamental requirements on platforms intended for tissue modelling and engineering are their ability to shape and maintain cell aggregates over long-term culture. An emerging technology for tissue shaping and culture is ultrasonic standing wave (USW) particle manipulation, which offers label-free and gentle positioning and aggregation of cells. The pressure nodes defined by the USW, where cells are trapped in most cases, are stable over time and can be both static and dynamic depending on actuation schemes. In this review article, we highlight the potential of USW cell manipulation as a tool for tissue modelling and engineering.

  • 12.
    Saeidi, Davood
    et al.
    Isfahan Univ Technol, Dept Mech Engn, Esfahan, Iran..
    Saghafian, Mohsen
    Isfahan Univ Technol, Dept Mech Engn, Esfahan, Iran..
    Javanmard, Shaghayegh Haghjooy
    Isfahan Univ Med Sci, Dept Physiol, Cardiovasc Res Inst, Appl Physiol Res Ctr, Esfahan, Iran..
    Hammarström, 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.
    Acoustic dipole and monopole effects in solid particle interaction dynamics during acoustophoresis2019In: Journal of the Acoustical Society of America, ISSN 0001-4966, E-ISSN 1520-8524, Vol. 145, no 6, p. 3311-3319Article in journal (Refereed)
    Abstract [en]

    A method is presented for measurements of secondary acoustic radiation forces acting on solid particles in a plain ultrasonic standing wave. The method allows for measurements of acoustic interaction forces between particles located in arbitrary positions such as in between a pressure node and a pressure antinode. By utilizing a model that considers both density- and compressibility-dependent effects, the observed particle-particle interaction dynamics can be well understood. Two differently sized polystyrene micro-particles (4.8 and 25 mu m, respectively) were used in order to achieve pronounced interaction effects. The particulate was subjected to a 2-MHz ultrasonic standing wave in a microfluidic channel, such as commonly used for acoustophoresis. Observation of deflections in the particle pathways shows that the particle interaction force is not negligible under this circumstance and has to be considered in accurate particle manipulation applications. The effect is primarily pronounced when the distance between two particles is small, the sizes of the particles are different, and the acoustic properties of the particles are different relative to the media. As predicted by theory, the authors also observe that the interaction forces are affected by the angle between the inter-particle centerline and the axis of the standing wave propagation direction.

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