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Sample records for 300i magnetic cell

  1. Magnetic needles and superparamagnetic cells

    PubMed Central

    Bryant, H C; Sergatskov, D A; Lovato, Debbie; Adolphi, Natalie L; Larson, Richard S; Flynn, Edward R

    2007-01-01

    Superparamagnetic nanoparticles can be attached in great numbers to pathogenic cells using specific antibodies so that the magnetically-labeled cells themselves become superparamagnets. The cells can then be manipulated and drawn out of biological fluids, as in a biopsy, very selectively using a magnetic needle. We examine the origins and uncertainties in the forces exerted on magnetic nanoparticles by static magnetic fields, leading to a model for trajectories and collection times of dilute superparamagnetic cells in biological fluids. We discuss the design and application of such magnetic needles and the theory of collection times. We compare the mathematical model to measurements in a variety of media including blood. PMID:17664592

  2. First cell magnet system tests

    SciTech Connect

    Schneider, W.J.; Brown, D.P.; Briggs, J.J.; Foerster, C.L.; Halama, H.J.; Schlafke, A.P.; Werner, A.P.

    1981-01-01

    The ISABELLE refrigeration system utilizes compressed liquid helium to supply refrigeration to nearly 1100 superconducting bending and focusing magnets. These magnets steer the proton orbits of the accelerator and are arranged into two interlocking rings. The total heat load that the refrigerator must provide is made up of the heat load of the magnets, magnet leads and vessels and the interconnecting piping to the refrigerator. The design and test results of the magnet system during various operating conditions in use on the ISABELLE prototype, the First Cell, are described.

  3. Multitarget magnetic activated cell sorter

    PubMed Central

    Adams, Jonathan D.; Kim, Unyoung; Soh, H. Tom

    2008-01-01

    Magnetic selection allows high-throughput sorting of target cells based on surface markers, and it is extensively used in biotechnology for a wide range of applications from in vitro diagnostics to cell-based therapies. However, existing methods can only perform separation based on a single parameter (i.e., the presence or absence of magnetization), and therefore, the simultaneous sorting of multiple targets at high levels of purity, recovery, and throughput remains a challenge. In this work, we present an alternative system, the multitarget magnetic activated cell sorter (MT-MACS), which makes use of microfluidics technology to achieve simultaneous spatially-addressable sorting of multiple target cell types in a continuous-flow manner. We used the MT-MACS device to purify 2 types of target cells, which had been labeled via target-specific affinity reagents with 2 different magnetic tags with distinct saturation magnetization and size. The device was engineered so that the combined effects of the hydrodynamic force produced from the laminar flow and the magnetophoretic force produced from patterned ferromagnetic structures within the microchannel result in the selective purification of the differentially labeled target cells into multiple independent outlets. We demonstrate here the capability to simultaneously sort multiple magnetic tags with >90% purity and >5,000-fold enrichment and multiple bacterial cell types with >90% purity and >500-fold enrichment at a throughput of 109 cells per hour. PMID:19015523

  4. Cell labeling with magnetic nanoparticles: Opportunity for magnetic cell imaging and cell manipulation

    PubMed Central

    2013-01-01

    This tutorial describes a method of controlled cell labeling with citrate-coated ultra small superparamagnetic iron oxide nanoparticles. This method may provide basically all kinds of cells with sufficient magnetization to allow cell detection by high-resolution magnetic resonance imaging (MRI) and to enable potential magnetic manipulation. In order to efficiently exploit labeled cells, quantify the magnetic load and deliver or follow-up magnetic cells, we herein describe the main requirements that should be applied during the labeling procedure. Moreover we present some recommendations for cell detection and quantification by MRI and detail magnetic guiding on some real-case studies in vitro and in vivo. PMID:24564857

  5. Magnetic levitation of single cells.

    PubMed

    Durmus, Naside Gozde; Tekin, H Cumhur; Guven, Sinan; Sridhar, Kaushik; Arslan Yildiz, Ahu; Calibasi, Gizem; Ghiran, Ionita; Davis, Ronald W; Steinmetz, Lars M; Demirci, Utkan

    2015-07-14

    Several cellular events cause permanent or transient changes in inherent magnetic and density properties of cells. Characterizing these changes in cell populations is crucial to understand cellular heterogeneity in cancer, immune response, infectious diseases, drug resistance, and evolution. Although magnetic levitation has previously been used for macroscale objects, its use in life sciences has been hindered by the inability to levitate microscale objects and by the toxicity of metal salts previously applied for levitation. Here, we use magnetic levitation principles for biological characterization and monitoring of cells and cellular events. We demonstrate that each cell type (i.e., cancer, blood, bacteria, and yeast) has a characteristic levitation profile, which we distinguish at an unprecedented resolution of 1 × 10(-4) g ⋅ mL(-1). We have identified unique differences in levitation and density blueprints between breast, esophageal, colorectal, and nonsmall cell lung cancer cell lines, as well as heterogeneity within these seemingly homogenous cell populations. Furthermore, we demonstrate that changes in cellular density and levitation profiles can be monitored in real time at single-cell resolution, allowing quantification of heterogeneous temporal responses of each cell to environmental stressors. These data establish density as a powerful biomarker for investigating living systems and their responses. Thereby, our method enables rapid, density-based imaging and profiling of single cells with intriguing applications, such as label-free identification and monitoring of heterogeneous biological changes under various physiological conditions, including antibiotic or cancer treatment in personalized medicine. PMID:26124131

  6. Magnetic levitation of single cells

    PubMed Central

    Durmus, Naside Gozde; Tekin, H. Cumhur; Guven, Sinan; Sridhar, Kaushik; Arslan Yildiz, Ahu; Calibasi, Gizem; Davis, Ronald W.; Steinmetz, Lars M.; Demirci, Utkan

    2015-01-01

    Several cellular events cause permanent or transient changes in inherent magnetic and density properties of cells. Characterizing these changes in cell populations is crucial to understand cellular heterogeneity in cancer, immune response, infectious diseases, drug resistance, and evolution. Although magnetic levitation has previously been used for macroscale objects, its use in life sciences has been hindered by the inability to levitate microscale objects and by the toxicity of metal salts previously applied for levitation. Here, we use magnetic levitation principles for biological characterization and monitoring of cells and cellular events. We demonstrate that each cell type (i.e., cancer, blood, bacteria, and yeast) has a characteristic levitation profile, which we distinguish at an unprecedented resolution of 1 × 10−4 g⋅mL−1. We have identified unique differences in levitation and density blueprints between breast, esophageal, colorectal, and nonsmall cell lung cancer cell lines, as well as heterogeneity within these seemingly homogenous cell populations. Furthermore, we demonstrate that changes in cellular density and levitation profiles can be monitored in real time at single-cell resolution, allowing quantification of heterogeneous temporal responses of each cell to environmental stressors. These data establish density as a powerful biomarker for investigating living systems and their responses. Thereby, our method enables rapid, density-based imaging and profiling of single cells with intriguing applications, such as label-free identification and monitoring of heterogeneous biological changes under various physiological conditions, including antibiotic or cancer treatment in personalized medicine. PMID:26124131

  7. Rapid Characterization of Magnetic Moment of Cells for Magnetic Separation.

    PubMed

    Ooi, Chinchun; Earhart, Christopher M; Wilson, Robert J; Wang, Shan X

    2013-07-01

    NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen were previously shown to be captured at high efficiencies by a microfabricated magnetic sifter. If fine control and optimization of the magnetic separation process is to be achieved, it is vital to be able to characterize the labeled cells' magnetic moment rapidly. We have thus adapted a rapid prototyping method to obtain the saturation magnetic moment of these cells. This method utilizes a cross-correlation algorithm to analyze the cells' motion in a simple fluidic channel to obtain their magnetophoretic velocity, and is effective even when the magnetic moments of cells are small. This rapid characterization is proven useful in optimizing our microfabricated magnetic sifter procedures for magnetic cell capture. PMID:24771946

  8. Rapid Characterization of Magnetic Moment of Cells for Magnetic Separation

    PubMed Central

    Ooi, Chinchun; Earhart, Christopher M.; Wilson, Robert J.; Wang, Shan X.

    2014-01-01

    NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen were previously shown to be captured at high efficiencies by a microfabricated magnetic sifter. If fine control and optimization of the magnetic separation process is to be achieved, it is vital to be able to characterize the labeled cells’ magnetic moment rapidly. We have thus adapted a rapid prototyping method to obtain the saturation magnetic moment of these cells. This method utilizes a cross-correlation algorithm to analyze the cells’ motion in a simple fluidic channel to obtain their magnetophoretic velocity, and is effective even when the magnetic moments of cells are small. This rapid characterization is proven useful in optimizing our microfabricated magnetic sifter procedures for magnetic cell capture. PMID:24771946

  9. Microfluidic Magnetic Bead Assay for Cell Detection.

    PubMed

    Liu, Fan; KC, Pawan; Zhang, Ge; Zhe, Jiang

    2016-01-01

    We present a novel cell detection device based on a magnetic bead cell assay and microfluidic Coulter counting technology. The device cannot only accurately measure cells size distribution and concentration but also detect specific target cells. The device consists of two identical micro Coulter counters separated by a fluid chamber where an external magnetic field is applied. Antibody-functionalized magnetic beads were bound to specific antigens expressed on the target cells. A high-gradient magnetic field was applied to the chamber closer to the second counter via an external cylindrical magnet. Because of the magnetic interaction between the magnetic beads and the magnetic field, target cells were retarded by the magnetic field; transit time of a target cell (bound with magnetic beads) passing through the second counter was longer than that through the first counter. In comparison, transit times of a nontarget cell remained nearly the same when it passed through both counters. Thus, from the transit time delay we can identify target cells and quantify their concentration in a cell suspension. The transit time and the size of each cell were accurately measured in terms of the width and amplitude of the resistive pulses generated from the two Coulter counters. Experiments demonstrated that for mixed cells with various target cell ratios, the transit time delay increased approximately linearly with the increasing target cell ratio. The limit of detection (LOD) of the assay was estimated to be 5.6% in terms of target cell ratio. Cell viability tests further demonstrated that most cells were viable after the detection. With the simple device configuration and easy sample preparation, this rapid and reliable method is expected to accurately detect target cells and could be applied to facilitate stem cell isolation and characterization. PMID:26636715

  10. Segmented magnetic nanofibers for single cell manipulation

    NASA Astrophysics Data System (ADS)

    Liu, Jun; Shi, Jian; Jiang, Lianmei; Zhang, Fan; Wang, Li; Yamamoto, Shinpei; Takano, Mikio; Chang, Mengjie; Zhang, Haoli; Chen, Yong

    2012-07-01

    We report a simple but straightforward approach to fabricate magnetic nanofiber segments for cell manipulation. Electrospinning was used to produce nanofibers from a magnetic nanoparticles containing polymethylglutarimide (PMGI) precursor solution. After sonication, the fabricated nanofibers were uniformly segmented. When dispersed in an aqueous solution, the orientation of the fiber segments could easily be controlled by an external magnetic field. NIH 3T3 cells were then cultured in a medium containing magnetic fibers, resulting in stable cell-nanofiber hybrids which can be conveniently manipulated with a magnet.

  11. Magnetic tweezers for manipulation of magnetic particles in single cells

    NASA Astrophysics Data System (ADS)

    Ebrahimian, H.; Giesguth, M.; Dietz, K.-J.; Reiss, G.; Herth, S.

    2014-02-01

    Magnetic tweezers gain increasing interest for applications in biology. Here, a setup of magnetic tweezers is introduced using micropatterned conducting lines on transparent glass slides. Magnetic particles of 1 μm diameter were injected in barley cell vacuoles using a microinject system under microscopic control. Time dependent tracking of the particles after application of a magnetic field was used to determine the viscosity of vacuolar sap in vivo relative to water and isolated vacuolar fluid. The viscosity of vacuolar sap in cells was about 2-fold higher than that of extracted vacuolar fluid and 5 times higher than that of water.

  12. Magnetic actuation of hair cells

    PubMed Central

    Rowland, David; Roongthumskul, Yuttana; Lee, Jae-Hyun; Cheon, Jinwoo; Bozovic, Dolores

    2011-01-01

    The bullfrog sacculus contains mechanically sensitive hair cells whose stereociliary bundles oscillate spontaneously when decoupled from the overlying membrane. Steady-state offsets on the resting position of a hair bundle can suppress or modulate this native motility. To probe the dynamics of spontaneous oscillation in the proximity of the critical point, we describe here a method for mechanical actuation that avoids loading the bundles or contributing to the viscous drag. Magnetite beads were attached to the tips of the stereocilia, and a magnetic probe was used to impose deflections. This technique allowed us to observe the transition from multi-mode to single-mode state in freely oscillating bundles, as well as the crossover from the oscillatory to the quiescent state. PMID:22163368

  13. Magnetic actuation of hair cells.

    PubMed

    Rowland, David; Roongthumskul, Yuttana; Lee, Jae-Hyun; Cheon, Jinwoo; Bozovic, Dolores

    2011-11-01

    The bullfrog sacculus contains mechanically sensitive hair cells whose stereociliary bundles oscillate spontaneously when decoupled from the overlying membrane. Steady-state offsets on the resting position of a hair bundle can suppress or modulate this native motility. To probe the dynamics of spontaneous oscillation in the proximity of the critical point, we describe here a method for mechanical actuation that avoids loading the bundles or contributing to the viscous drag. Magnetite beads were attached to the tips of the stereocilia, and a magnetic probe was used to impose deflections. This technique allowed us to observe the transition from multi-mode to single-mode state in freely oscillating bundles, as well as the crossover from the oscillatory to the quiescent state. PMID:22163368

  14. Magnetic resonance investigation of magnetic-labeled baker's yeast cells

    NASA Astrophysics Data System (ADS)

    Godoy Morais, J. P. M.; Azevedo, R. B.; Silva, L. P.; Lacava, Z. G. M.; Báo, S. N.; Silva, O.; Pelegrini, F.; Gansau, C.; Buske, N.; Safarik, I.; Safarikova, M.; Morais, P. C.

    2004-05-01

    In this study, the interaction of DMSA-coated magnetite nanoparticles (5 and 10 nm core-size) with Saccharomyces cerevisae was investigated using magnetic resonance (MR) and transmission electron microscopy (TEM). The TEM micrographs revealed magnetite nanoparticles attached externally to the cell wall. The MR data support the strong interaction among the nanoparticles supported by the cells. A remarkable shift in the resonance field was used as signature of particle attachment to the cell wall.

  15. Optical magnetic imaging of living cells

    PubMed Central

    Le Sage, D.; Arai, K.; Glenn, D. R.; DeVience, S. J.; Pham, L. M.; Rahn-Lee, L.; Lukin, M. D.; Yacoby, A.; Komeili, A.; Walsworth, R. L.

    2013-01-01

    Magnetic imaging is a powerful tool for probing biological and physical systems. However, existing techniques either have poor spatial resolution compared to optical microscopy and are hence not generally applicable to imaging of sub-cellular structure (e.g., magnetic resonance imaging [MRI]1), or entail operating conditions that preclude application to living biological samples while providing sub-micron resolution (e.g., scanning superconducting quantum interference device [SQUID] microscopy2, electron holography3, and magnetic resonance force microscopy [MRFM]4). Here we demonstrate magnetic imaging of living cells (magnetotactic bacteria) under ambient laboratory conditions and with sub-cellular spatial resolution (400 nm), using an optically-detected magnetic field imaging array consisting of a nanoscale layer of nitrogen-vacancy (NV) colour centres implanted at the surface of a diamond chip. With the bacteria placed on the diamond surface, we optically probe the NV quantum spin states and rapidly reconstruct images of the vector components of the magnetic field created by chains of magnetic nanoparticles (magnetosomes) produced in the bacteria, and spatially correlate these magnetic field maps with optical images acquired in the same apparatus. Wide-field sCMOS acquisition allows parallel optical and magnetic imaging of multiple cells in a population with sub-micron resolution and >100 micron field-of-view. Scanning electron microscope (SEM) images of the bacteria confirm that the correlated optical and magnetic images can be used to locate and characterize the magnetosomes in each bacterium. The results provide a new capability for imaging bio-magnetic structures in living cells under ambient conditions with high spatial resolution, and will enable the mapping of a wide range of magnetic signals within cells and cellular networks5, 6. PMID:23619694

  16. Optical magnetic imaging of living cells.

    PubMed

    Le Sage, D; Arai, K; Glenn, D R; DeVience, S J; Pham, L M; Rahn-Lee, L; Lukin, M D; Yacoby, A; Komeili, A; Walsworth, R L

    2013-04-25

    Magnetic imaging is a powerful tool for probing biological and physical systems. However, existing techniques either have poor spatial resolution compared to optical microscopy and are hence not generally applicable to imaging of sub-cellular structure (for example, magnetic resonance imaging), or entail operating conditions that preclude application to living biological samples while providing submicrometre resolution (for example, scanning superconducting quantum interference device microscopy, electron holography and magnetic resonance force microscopy). Here we demonstrate magnetic imaging of living cells (magnetotactic bacteria) under ambient laboratory conditions and with sub-cellular spatial resolution (400 nanometres), using an optically detected magnetic field imaging array consisting of a nanometre-scale layer of nitrogen-vacancy colour centres implanted at the surface of a diamond chip. With the bacteria placed on the diamond surface, we optically probe the nitrogen-vacancy quantum spin states and rapidly reconstruct images of the vector components of the magnetic field created by chains of magnetic nanoparticles (magnetosomes) produced in the bacteria. We also spatially correlate these magnetic field maps with optical images acquired in the same apparatus. Wide-field microscopy allows parallel optical and magnetic imaging of multiple cells in a population with submicrometre resolution and a field of view in excess of 100 micrometres. Scanning electron microscope images of the bacteria confirm that the correlated optical and magnetic images can be used to locate and characterize the magnetosomes in each bacterium. Our results provide a new capability for imaging bio-magnetic structures in living cells under ambient conditions with high spatial resolution, and will enable the mapping of a wide range of magnetic signals within cells and cellular networks. PMID:23619694

  17. Biological cell manipulation by magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Gertz, Frederick; Khitun, Alexander

    2016-02-01

    We report a manipulation of biological cells (erythrocytes) by magnetite (Fe3O4) nanoparticles in the presence of a magnetic field. The experiment was accomplished on the top of a micro-electromagnet consisting of two magnetic field generating contours. An electric current flowing through the contour(s) produces a non-uniform magnetic field, which is about 1.4 mT/μm in strength at 100 mA current in the vicinity of the current-carrying wire. In responses to the magnetic field, magnetic nanoparticles move towards the systems energy minima. In turn, magnetic nanoparticles drag biological cells in the same direction. We present experimental data showing cell manipulation through the control of electric current. This technique allows us to capture and move cells located in the vicinity (10-20 microns) of the current-carrying wires. One of the most interesting results shows a periodic motion of erythrocytes between the two conducting contours, whose frequency is controlled by an electric circuit. The obtained results demonstrate the feasibility of non-destructive cell manipulation by magnetic nanoparticles with micrometer-scale precision.

  18. Manipulating Cells with Static Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Valles, J. M.; Guevorkian, K.

    2005-07-01

    We review our investigations of the use of static magnetic fields, B, for manipulating cells and cellular processes. We describe how B fields modify the cell division pattern of frog embryos and consequently can be used to probe the pattern determinants. We also observe that magnetic fields modify the swimming behavior of Paramecium Caudatum. We describe these modifications and their potential application to investigations of their swimming behavior.

  19. Visualizing Magnetism with Optical Ferrofluid Cells

    NASA Astrophysics Data System (ADS)

    Snyder, Michael

    2015-05-01

    a novel technique for the visualization of magnetic fields. The ferrofluid cells are made up of two optically flat windows with a layer of Fe3O4/Fe2O3 ferrofluid between the glass. Using different magnet configurations and lighting, highly structured pictures are obtained of one of the universes forces. Characterized as the magneto-optic Kerr/displacement current effect on self assembled micrometer sized helical rods of Fe304/Fe203.

  20. Stem cell labeling for magnetic resonance imaging.

    PubMed

    Himmelreich, Uwe; Hoehn, Mathias

    2008-01-01

    In vivo applications of cells for the monitoring of their cell dynamics increasingly use non-invasive magnetic resonance imaging. This imaging modality allows in particular to follow the migrational activity of stem cells intended for cell therapy strategies. All these approaches require the prior labeling of the cells under investigation for excellent contrast against the host tissue background in the imaging modality. The present review discusses the various routes of cell labeling and describes the potential to observe both cell localization and their cell-specific function in vivo. Possibilities for labeling strategies, pros and cons of various contrast agents are pointed out while potential ambiguities or problems of labeling strategies are emphasized. PMID:18465447

  1. Multistage Magnetic Separator of Cells and Proteins

    NASA Technical Reports Server (NTRS)

    Barton, Ken; Ainsworth, Mark; Daily, Bruce; Dunn, Scott; Metz, Bill; Vellinger, John; Taylor, Brock; Meador, Bruce

    2005-01-01

    The multistage electromagnetic separator for purifying cells and magnetic particles (MAGSEP) is a laboratory apparatus for separating and/or purifying particles (especially biological cells) on the basis of their magnetic susceptibility and magnetophoretic mobility. Whereas a typical prior apparatus based on similar principles offers only a single stage of separation, the MAGSEP, as its full name indicates, offers multiple stages of separation; this makes it possible to refine a sample population of particles to a higher level of purity or to categorize multiple portions of the sample on the basis of magnetic susceptibility and/or magnetophoretic mobility. The MAGSEP includes a processing unit and an electronic unit coupled to a personal computer. The processing unit includes upper and lower plates, a plate-rotation system, an electromagnet, an electromagnet-translation system, and a capture-magnet assembly. The plates are bolted together through a roller bearing that allows the plates to rotate with respect to each other. An interface between the plates acts as a seal for separating fluids. A lower cuvette can be aligned with as many as 15 upper cuvette stations for fraction collection during processing. A two-phase stepping motor drives the rotation system, causing the upper plate to rotate for the collection of each fraction of the sample material. The electromagnet generates a magnetic field across the lower cuvette, while the translation system translates the electromagnet upward along the lower cuvette. The current supplied to the electromagnet, and thus the magnetic flux density at the pole face of the electromagnet, can be set at a programmed value between 0 and 1,400 gauss (0.14 T). The rate of translation can be programmed between 5 and 2,000 m/s so as to align all sample particles in the same position in the cuvette. The capture magnet can be a permanent magnet. It is mounted on an arm connected to a stepping motor. The stepping motor rotates the arm to

  2. Magnetic alignment of plant cell microfibrils and their anisotropic elasticity

    NASA Astrophysics Data System (ADS)

    Fujimura, Yuu; Sakaida, Hidetaka; Iino, Masaaki

    2010-06-01

    The magnetic alignment of microfibrils on a single regenerated plant cell surface subjected to magnetic fields and its anisotropic cell surface area expansivity modulus (area modulus) were studied. The magnetic alignment around the equator of the cell (the polar axis parallel to the magnetic field) was confirmed by a 2-dim Fourier analysis of images from a scanning electron microscope, and these were expressed by a theoretical magnetic order parameter for anisotropic relative magnetic permeability of 3×10-27, while the microfibrils near the pole did not show any such magnetic alignment. The magnetic field anisotropically stiffened the cell surface. The stiffness around the equator was greater than that around the pole. The magnetic field dependences of the area modulus agreed with the mechanical model.

  3. Remote Control of T Cell Activation Using Magnetic Janus Particles.

    PubMed

    Lee, Kwahun; Yi, Yi; Yu, Yan

    2016-06-20

    We report a strategy for using magnetic Janus microparticles to control the stimulation of T cell signaling with single-cell precision. To achieve this, we designed Janus particles that are magnetically responsive on one hemisphere and stimulatory to T cells on the other side. By manipulating the rotation and locomotion of Janus particles under an external magnetic field, we could control the orientation of the particle-cell recognition and thereby the initiation of T cell activation. This study demonstrates a step towards employing anisotropic material properties of Janus particles to control single-cell activities without the need of complex magnetic manipulation devices. PMID:27144475

  4. Life on magnets: stem cell networking on micro-magnet arrays.

    PubMed

    Zablotskii, Vitalii; Dejneka, Alexandr; Kubinová, Šárka; Le-Roy, Damien; Dumas-Bouchiat, Frédéric; Givord, Dominique; Dempsey, Nora M; Syková, Eva

    2013-01-01

    Interactions between a micro-magnet array and living cells may guide the establishment of cell networks due to the cellular response to a magnetic field. To manipulate mesenchymal stem cells free of magnetic nanoparticles by a high magnetic field gradient, we used high quality micro-patterned NdFeB films around which the stray field's value and direction drastically change across the cell body. Such micro-magnet arrays coated with parylene produce high magnetic field gradients that affect the cells in two main ways: i) causing cell migration and adherence to a covered magnetic surface and ii) elongating the cells in the directions parallel to the edges of the micro-magnet. To explain these effects, three putative mechanisms that incorporate both physical and biological factors influencing the cells are suggested. It is shown that the static high magnetic field gradient generated by the micro-magnet arrays are capable of assisting cell migration to those areas with the strongest magnetic field gradient, thereby allowing the build up of tunable interconnected stem cell networks, which is an elegant route for tissue engineering and regenerative medicine. PMID:23936425

  5. Magnetic Nanoparticles for Imaging Dendritic Cells

    PubMed Central

    Kobukai, Saho; Baheza, Richard; Cobb, Jared G.; Virostko, Jack; Xie, Jingping; Gillman, Amelie; Koktysh, Dmitry; Kerns, Denny; Does, Mark; Gore, John C.; Pham, Wellington

    2015-01-01

    We report the development of superparamagnetic iron oxide (SPIOs) nanoparticles and investigate the migration of SPIO-labeled dendritic cells (DCs) in a syngeneic mouse model using magnetic resonance (MR) imaging. The size of the dextran-coated SPIO is roughly 30 nm, and the DCs are capable of independent uptake of these particles, although not at levels comparable to particle uptake in the presence of a transfecting reagent. On average, with the assistance of polylysine, the particles were efficiently delivered inside DCs within one hour of incubation. The SPIO particles occupy approximately 0.35% of cell surface and are equivalent to 34.6 pg of iron per cell. In vivo imaging demonstrated that the labeled cells migrated from the injection site in the footpad to the corresponding popliteal lymph node. The homing of labeled cells in the lymph nodes resulted in a signal drop of up to 79%. Furthermore, labeling DCs with SPIO particles did not compromise cell function, we demonstrated that SPIO-enhanced MR imaging can be used to track the migration of DCs effectively in vivo. Magn Reson Med 63:1383–1390, 2010. PMID:20432309

  6. DNA and cell resonance: magnetic waves enable cell communication.

    PubMed

    Meyl, Konstantin

    2012-04-01

    DNA generates a longitudinal wave that propagates in the direction of the magnetic field vector. Computed frequencies from the structure of DNA agree with those of the predicted biophoton radiation. The optimization of efficiency by minimizing the conduction losses leads to the double-helix structure of DNA. The vortex model of the magnetic scalar wave not only covers many observed structures within the nucleus perfectly, but also explains the hyperboloid channels in the matrix when two cells communicate with each other. Potential vortexes are an essential component of a scalar waves, as discovered in 1990. The basic approach for an extended field theory was confirmed in 2009 with the discovery of magnetic monopoles. For the first time, this provides the opportunity to explain the physical basis of life not only from the biological discipline. Nature covers the whole spectrum of known scientific fields of research, and interdisciplinary understanding is required to explain its complex relationships. The characteristics of the potential vortex are significant. With its concentration effect, it provides for miniaturization down to a few nanometers, which allows enormously high information density in the nucleus. With this first introduction of the magnetic scalar wave, it becomes clear that such a wave is suitable to use genetic code chemically stored in the base pairs of the genes and electrically modulate them, so as to "piggyback" information from the cell nucleus to another cell. At the receiving end, the reverse process takes place and the transported information is converted back into a chemical structure. The necessary energy required to power the chemical process is provided by the magnetic scalar wave itself. PMID:22011216

  7. Magnetic characterization of isolated candidate vertebrate magnetoreceptor cells.

    PubMed

    Eder, Stephan H K; Cadiou, Hervé; Muhamad, Airina; McNaughton, Peter A; Kirschvink, Joseph L; Winklhofer, Michael

    2012-07-24

    Over the past 50 y, behavioral experiments have produced a large body of evidence for the existence of a magnetic sense in a wide range of animals. However, the underlying sensory physiology remains poorly understood due to the elusiveness of the magnetosensory structures. Here we present an effective method for isolating and characterizing potential magnetite-based magnetoreceptor cells. In essence, a rotating magnetic field is employed to visually identify, within a dissociated tissue preparation, cells that contain magnetic material by their rotational behavior. As a tissue of choice, we selected trout olfactory epithelium that has been previously suggested to host candidate magnetoreceptor cells. We were able to reproducibly detect magnetic cells and to determine their magnetic dipole moment. The obtained values (4 to 100 fAm(2)) greatly exceed previous estimates (0.5 fAm(2)). The magnetism of the cells is due to a μm-sized intracellular structure of iron-rich crystals, most likely single-domain magnetite. In confocal reflectance imaging, these produce bright reflective spots close to the cell membrane. The magnetic inclusions are found to be firmly coupled to the cell membrane, enabling a direct transduction of mechanical stress produced by magnetic torque acting on the cellular dipole in situ. Our results show that the magnetically identified cells clearly meet the physical requirements for a magnetoreceptor capable of rapidly detecting small changes in the external magnetic field. This would also explain interference of ac powerline magnetic fields with magnetoreception, as reported in cattle. PMID:22778440

  8. Separating Magnetically Labeled and Unlabeled Biological Cells within Microfluidic Channels

    NASA Astrophysics Data System (ADS)

    Byvank, Tom; Vieira, Greg; Miller, Brandon; Yu, Bo; Chalmers, Jeffrey; Lee, L. James; Sooryakumar, R.

    2011-03-01

    The transport of microscopic objects that rely on magnetic forces have numerous advantages including flexibility of controlling many design parameters and the long range magnetic interactions generally do not adversely affect biological or chemical interactions. We present results on the use of magnetic micro-arrays imprinted within polydimethylsiloxane (PDMS) microfluidic channels that benefit from these features and the ability to rapidly reprogram the magnetic energy landscape for cell manipulation and sorting applications. A central enabling feature is the very large, tunable, magnetic field gradients (> 10 4) that can be designed within the microfluidic architecture. Through use of antibody-conjugated magnetic microspheres to label biological cells, results on the transport and sorting of heterogeneous cell populations are presented. The effects of micro-array and fluid channel design parameters, competition between magnetic forces and hydrodynamic drag forces, and cell-labeling efficiency on cell separation are discussed.

  9. Magnetic nanoparticles as bimodal tools in magnetically induced labelling and magnetic heating of tumour cells: an in vitro study

    NASA Astrophysics Data System (ADS)

    Kettering, M.; Winter, J.; Zeisberger, M.; Bremer-Streck, S.; Oehring, H.; Bergemann, C.; Alexiou, C.; Hergt, R.; Halbhuber, K. J.; Kaiser, W. A.; Hilger, I.

    2007-05-01

    Localized magnetic heating treatments (hyperthermia, thermal ablation) using superparamagnetic iron oxide nanoparticles continue to be an active area of cancer research. The present study uses magnetic nanoparticles (MNP) as bimodal tools and combines magnetically induced cell labelling and magnetic heating. The main focus was to assess if a selective and higher MNP accumulation within tumour cells due to magnetic labelling (max. 56 and 83 mT) and consequently a larger heating effect occurs after exposure to an alternating magnetic field (magnetic heating: frequency 400 kHz, amplitude 24.6 kA m-1) in order to eliminate labelled tumour cells effectively. The results demonstrate that the magnetically based cellular MNP uptake by human adenocarcinoma cells is due to suitable magnetic field gradients in vitro which intensify the temperature increase generated during magnetic heating. A significantly (P<=0.05) enhanced MNP cell uptake due to 83 mT labelling compared to controls or to 56 mT labelling was observed. Our experiments required the following conditions, namely a cell concentration of 2.5 × 107 cells ml-1, a minimum MNP concentration of 0.32 mg Fe ml-1 culture medium, and an incubation time of 24 h, to reach this effect as well as for the significantly enlarged heating effects to occur.

  10. Effect of Magnetic Field Gradient on Effectiveness of the Magnetic Sifter for Cell Purification.

    PubMed

    Ooi, Chinchun; Earhart, Christopher M; Wilson, Robert J; Wang, Shan X

    2013-01-01

    In our experiments with NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen, we demonstrate capture efficiencies above 90% even at sample flow rates of 5 ml/h through our microfabricated magnetic sifter. We also improve the elution efficiencies from between 50% and 60% to close to 90% via optimization of the permanent magnet size and position used to magnetize the sifter. We then explain our observations via the use of finite element software for magnetic field and field gradient distributions, and a particle tracing algorithm, illustrating the impact of magnetic field gradients on the performance of the magnetic sifter. The high capture and elution efficiencies observed here is especially significant for magnetic separation of biologically interesting but rare moieties such as cancer stem cells for downstream analysis. PMID:23515873

  11. Effect of Magnetic Field Gradient on Effectiveness of the Magnetic Sifter for Cell Purification

    PubMed Central

    Ooi, Chinchun; Earhart, Christopher M.; Wilson, Robert J.; Wang, Shan X.

    2013-01-01

    In our experiments with NCI-H1650 lung cancer cell lines labeled with magnetic nanoparticles via the Epithelial Cell Adhesion Molecule (EpCAM) antigen, we demonstrate capture efficiencies above 90% even at sample flow rates of 5 ml/h through our microfabricated magnetic sifter. We also improve the elution efficiencies from between 50% and 60% to close to 90% via optimization of the permanent magnet size and position used to magnetize the sifter. We then explain our observations via the use of finite element software for magnetic field and field gradient distributions, and a particle tracing algorithm, illustrating the impact of magnetic field gradients on the performance of the magnetic sifter. The high capture and elution efficiencies observed here is especially significant for magnetic separation of biologically interesting but rare moieties such as cancer stem cells for downstream analysis. PMID:23515873

  12. Three-dimensional tissue culture based on magnetic cell levitation

    NASA Astrophysics Data System (ADS)

    Souza, Glauco R.; Molina, Jennifer R.; Raphael, Robert M.; Ozawa, Michael G.; Stark, Daniel J.; Levin, Carly S.; Bronk, Lawrence F.; Ananta, Jeyarama S.; Mandelin, Jami; Georgescu, Maria-Magdalena; Bankson, James A.; Gelovani, Juri G.; Killian, T. C.; Arap, Wadih; Pasqualini, Renata

    2010-04-01

    Cell culture is an essential tool in drug discovery, tissue engineering and stem cell research. Conventional tissue culture produces two-dimensional cell growth with gene expression, signalling and morphology that can be different from those found in vivo, and this compromises its clinical relevance. Here, we report a three-dimensional tissue culture based on magnetic levitation of cells in the presence of a hydrogel consisting of gold, magnetic iron oxide nanoparticles and filamentous bacteriophage. By spatially controlling the magnetic field, the geometry of the cell mass can be manipulated, and multicellular clustering of different cell types in co-culture can be achieved. Magnetically levitated human glioblastoma cells showed similar protein expression profiles to those observed in human tumour xenografts. Taken together, these results indicate that levitated three-dimensional culture with magnetized phage-based hydrogels more closely recapitulates in vivo protein expression and may be more feasible for long-term multicellular studies.

  13. Concentric Magnetic Structures for Magnetophoretic Bead Collection, Cell Trapping and Analysis of Cell Morphological Changes Caused by Local Magnetic Forces

    PubMed Central

    Huang, Chen-Yu; Wei, Zung-Hang

    2015-01-01

    Concentric magnetic structures (ring and square) with domain wall (DW) pinning geometry are designed for biological manipulation. Magnetic beads collection was firstly demonstrated to analyse the local magnetic field generated by DWs and the effective regions to capture magnetic targets of size 1 μm. Primary mouse embryonic fibroblasts (MEFs) are magnetically labeled by internalizing poly (styrene sulfonic acid) stabilized magnetic nanoparticles (PSS-MNPs) and then are selectively trapped by head-to-tail DWs (HH DWs) or tail-to-tail DWs (TT DWs) to be arranged into linear shape or cross shape. The morphologies and the nuclear geometry of the cells growing on two kinds of concentric magnetic structures are shown to be distinctive. The intracellular magnetic forces generated by the local magnetic field of DWs are found to influence the behaviour of cells. PMID:26270332

  14. Effect of Static Magnetic Field on Cell Migration

    NASA Astrophysics Data System (ADS)

    Hashimoto, Yuichiro; Kawasumi, Masashi; Saito, Masao

    The effect of magnetic field on cell has long been investigated, but there are few quantitative investigations of the migration of cells. Cell-migration is important as one of the fundamental activities of the cell. This study proposes a method to evaluate quantitatively the cell-diffusion constant and the effect of static magnetic field on cell migration. The cell-lines are neuroblastoma (NG108-15), fibroblastoma (NIH/3T3) and osteoblastoma (MC3T3-E1). The static magnetic field of 30 mT or 120 mT is impressed by a permanent magnet in vertical or horizontal direction to the dish. It is shown that the cell-diffusion constant can represent the cell migration as the cell activity. It is found that the cell migration is enhanced by exposure to the magnetic field, depending on the kind of cell. It is conjectured that the effect of static magnetic field affects the cell migration, which is at the downstream of the information transmission.

  15. Varying the effective buoyancy of cells using magnetic force

    NASA Astrophysics Data System (ADS)

    Guevorkian, Karine; Valles, James M.

    2004-06-01

    We introduce a magnetic force buoyancy variation (MFBV) technique that employs intense inhomogeneous magnetic fields to vary the effective buoyancy of cells and other diamagnetic systems in solution. Nonswimming Paramecia have been suspended, forced to sediment and driven to rise in solution using MFBV. Details of their response to MFBV have been used to determine the magnetic susceptibility of a single Paramecium. The use of MFBV as a means by which to suspend cell cultures indefinitely is also described.

  16. Magnetic Cobalt Ferrite Nanocrystals For an Energy Storage Concentration Cell.

    PubMed

    Dai, Qilin; Patel, Ketan; Donatelli, Greg; Ren, Shenqiang

    2016-08-22

    Energy-storage concentration cells are based on the concentration gradient of redox-active reactants; the increased entropy is transformed into electric energy as the concentration gradient reaches equilibrium between two half cells. A recyclable and flow-controlled magnetic electrolyte concentration cell is now presented. The hybrid inorganic-organic nanocrystal-based electrolyte, consisting of molecular redox-active ligands adsorbed on the surface of magnetic nanocrystals, leads to a magnetic-field-driven concentration gradient of redox molecules. The energy storage performance of concentration cells is dictated by magnetic characteristics of cobalt ferrite nanocrystal carriers. The enhanced conductivity and kinetics of redox-active electrolytes could further induce a sharp concentration gradient to improve the energy density and voltage switching of magnetic electrolyte concentration cells. PMID:27440206

  17. Modeling the Efficiency of a Magnetic Needle for Collecting Magnetic Cells

    PubMed Central

    Butler, Kimberly S; Adolphi, Natalie L.; Bryant, H C; Lovato, Debbie M; Larson, Richard S; Flynn, Edward R

    2014-01-01

    As new magnetic nanoparticle-based technologies are developed and new target cells are identified, there is a critical need to understand the features important for magnetic isolation of specific cells in fluids, an increasingly important tool in disease research and diagnosis. To investigate magnetic cell collection, cell-sized spherical microparticles, coated with superparamagnetic nanoparticles, were suspended in 1) glycerine-water solutions, chosen to approximate the range of viscosities of bone marrow, and 2) water in which 3, 5, 10 and 100 % of the total suspended microspheres are coated with magnetic nanoparticles, to model collection of rare magnetic nanoparticle-coated cells from a mixture of cells in a fluid. The magnetic microspheres were collected on a magnetic needle, and we demonstrate that the collection efficiency vs. time can be modeled using a simple, heuristically-derived function, with three physically-significant parameters. The function enables experimentally-obtained collection efficiencies to be scaled to extract the effective drag of the suspending medium. The results of this analysis demonstrate that the effective drag scales linearly with fluid viscosity, as expected. Surprisingly, increasing the number of non-magnetic microspheres in the suspending fluid results increases the collection of magnetic microspheres, corresponding to a decrease in the effective drag of the medium. PMID:24874577

  18. Modeling the efficiency of a magnetic needle for collecting magnetic cells.

    PubMed

    Butler, Kimberly S; Adolphi, Natalie L; Bryant, H C; Lovato, Debbie M; Larson, Richard S; Flynn, Edward R

    2014-07-01

    As new magnetic nanoparticle-based technologies are developed and new target cells are identified, there is a critical need to understand the features important for magnetic isolation of specific cells in fluids, an increasingly important tool in disease research and diagnosis. To investigate magnetic cell collection, cell-sized spherical microparticles, coated with superparamagnetic nanoparticles, were suspended in (1) glycerine-water solutions, chosen to approximate the range of viscosities of bone marrow, and (2) water in which 3, 5, 10 and 100% of the total suspended microspheres are coated with magnetic nanoparticles, to model collection of rare magnetic nanoparticle-coated cells from a mixture of cells in a fluid. The magnetic microspheres were collected on a magnetic needle, and we demonstrate that the collection efficiency versus time can be modeled using a simple, heuristically-derived function, with three physically-significant parameters. The function enables experimentally-obtained collection efficiencies to be scaled to extract the effective drag of the suspending medium. The results of this analysis demonstrate that the effective drag scales linearly with fluid viscosity, as expected. Surprisingly, increasing the number of non-magnetic microspheres in the suspending fluid results increases the collection of magnetic microspheres, corresponding to a decrease in the effective drag of the medium. PMID:24874577

  19. Modeling the efficiency of a magnetic needle for collecting magnetic cells

    NASA Astrophysics Data System (ADS)

    Butler, Kimberly S.; Adolphi, Natalie L.; Bryant, H. C.; Lovato, Debbie M.; Larson, Richard S.; Flynn, Edward R.

    2014-07-01

    As new magnetic nanoparticle-based technologies are developed and new target cells are identified, there is a critical need to understand the features important for magnetic isolation of specific cells in fluids, an increasingly important tool in disease research and diagnosis. To investigate magnetic cell collection, cell-sized spherical microparticles, coated with superparamagnetic nanoparticles, were suspended in (1) glycerine-water solutions, chosen to approximate the range of viscosities of bone marrow, and (2) water in which 3, 5, 10 and 100% of the total suspended microspheres are coated with magnetic nanoparticles, to model collection of rare magnetic nanoparticle-coated cells from a mixture of cells in a fluid. The magnetic microspheres were collected on a magnetic needle, and we demonstrate that the collection efficiency versus time can be modeled using a simple, heuristically-derived function, with three physically-significant parameters. The function enables experimentally-obtained collection efficiencies to be scaled to extract the effective drag of the suspending medium. The results of this analysis demonstrate that the effective drag scales linearly with fluid viscosity, as expected. Surprisingly, increasing the number of non-magnetic microspheres in the suspending fluid results increases the collection of magnetic microspheres, corresponding to a decrease in the effective drag of the medium.

  20. Quantitative Magnetic Separation of Particles and Cells Using Gradient Magnetic Ratcheting.

    PubMed

    Murray, Coleman; Pao, Edward; Tseng, Peter; Aftab, Shayan; Kulkarni, Rajan; Rettig, Matthew; Di Carlo, Dino

    2016-04-13

    Extraction of rare target cells from biosamples is enabling for life science research. Traditional rare cell separation techniques, such as magnetic activated cell sorting, are robust but perform coarse, qualitative separations based on surface antigen expression. A quantitative magnetic separation technology is reported using high-force magnetic ratcheting over arrays of magnetically soft micropillars with gradient spacing, and the system is used to separate and concentrate magnetic beads based on iron oxide content (IOC) and cells based on surface expression. The system consists of a microchip of permalloy micropillar arrays with increasing lateral pitch and a mechatronic device to generate a cycling magnetic field. Particles with higher IOC separate and equilibrate along the miropillar array at larger pitches. A semi-analytical model is developed that predicts behavior for particles and cells. Using the system, LNCaP cells are separated based on the bound quantity of 1 μm anti-epithelial cell adhesion molecule (EpCAM) particles as a metric for expression. The ratcheting cytometry system is able to resolve a ±13 bound particle differential, successfully distinguishing LNCaP from PC3 populations based on EpCAM expression, correlating with flow cytometry analysis. As a proof-of-concept, EpCAM-labeled cells from patient blood are isolated with 74% purity, demonstrating potential toward a quantitative magnetic separation instrument. PMID:26890496

  1. On-chip cell sorting via patterned magnetic traps

    NASA Astrophysics Data System (ADS)

    Byvank, Tom; Prikockis, Michael; Chen, Aaron; Miller, Brandon; Chalmers, Jeffrey; Sooryakumar, Ratnasingham

    2015-03-01

    Due to their importance in research for the diagnosis and treatment of cancer, numerous schemes have been developed to sort rare cell populations, e.g., circulating tumor cells (CTCs), from a larger ensemble of cells. Here, we improve upon a previously developed microfluidic device (Lab Chip 13, 1172, (2013)) to increase throughput and sorting purity of magnetically labeled cells. The separation mechanism involves controlling magnetic forces by manipulating the magnetic domain structures of embedded permalloy microdisks with weak external fields. These forces move labeled cells from the input flow stream into an adjacent buffer flow stream. Such magnetically activated transfer separates the magnetic entities from their non-magnetic counterparts as the two flow streams split apart and move toward their respective outputs. Purity of the magnetic output is modulated by the withdrawal rate of the non-magnetic output relative to the inputs. A proof of concept shows that CTCs from metastatic breast cancer patients can be sorted, recovered from the device, and confirmed as CTCs using separate immunofluorescence staining and analysis. With further optimizations, the channel could become a useful device for high purity final sorting of enriched patient cell samples.

  2. Magnetically shaped cell aggregates: from granular to contractile materials.

    PubMed

    Frasca, G; Du, V; Bacri, J-C; Gazeau, F; Gay, C; Wilhelm, C

    2014-07-28

    In recent decades, significant advances have been made in the description and modelling of tissue morphogenesis. By contrast, the initial steps leading to the formation of a tissue structure, through cell-cell adhesion, have so far been described only for small numbers of interacting cells. Here, through the use of remote magnetic forces, we succeeded at creating cell aggregates of half million cells, instantaneously and for several cell types, not only those known to form spheroids. This magnetic compaction gives access to the cell elasticity, found in the range of 800 Pa. The magnetic force can be removed at any time, allowing the cell mass to evolve spontaneously thereafter. The dynamics of contraction of these cell aggregates just after their formation (or, in contrast, their spreading for non-interacting monocyte cells) provides direct information on cell-cell interactions and allows retrieving the adhesion energy, in between 0.05 and 2 mJ m(-2), depending on the cell type tested, and in the case of cohesive aggregates. Thus, we show, by probing a large number of cell types, that cell aggregates behave like complex materials, undergoing a transition from a wet granular to contractile network, and that this transition is controlled by cell-cell interactions. PMID:24710948

  3. Effects of Magnetic Field on Biological Cells and Applications

    NASA Astrophysics Data System (ADS)

    Chen, Ching-Jen

    2001-03-01

    While there has been extensive research performed in the physics of magnetic fields and the physics and chemistry in life sciences, independent of each other, there has been a paucity of scientific research and development investigating the possible applications of magnetic fields in life sciences. The focus of this presentation is to present the stimulation mechanism by which magnetic fields affect (a) yeast cells (b) plant cells and (c) mammalian normal and cancer cells. Recently we have found that the Saccharomyces Cerevsa yeast growth increases by about 30to a 1 tesla field and the production of CO2 increases by about 30of yeast metabolism may be due to an increase in intercellular interaction and protein channel alignment, the introduction of an alteration in the DNA from the magnetic field exposure or a combination of these mechanisms. We also have found that the application of high magnetic fields (1 tesla and above) can have marked effects on the germination and growth of plants, especially corn, beans and peas. This finding has opened up the possibility of technology developments in botanical growth systems to accelerate seed germination and crop harvesting. Most recently we have investigated the application of high magnetic fields on leukemia, CaCoII and HEP G2 cancer cell lines. We found that when leukemia are exposed to a 12 tesla field for 2 hours has an increase in cell death by about 30that were not exposed to the magnetic field. Viability of CaCoII cells sandwiched between permanent magnets of maximum strength of 1.2 tesla was measured. A decrease in viable cells by 33unexposed cells. HSP 70 was measured for HEPG2 cells that were exposed to permanent magnetic field of 1.2 tesla for 40 minutes and for unexposed cells. It was found that the exposed cells produce 19 times more HSP70 compared to unexposed cells. Our results together with other investigators report suggest a strong evidence of a reduction in the cell growth rate for cancer cells when

  4. Micro-magnet arrays for specific single bacterial cell positioning

    NASA Astrophysics Data System (ADS)

    Pivetal, Jérémy; Royet, David; Ciuta, Georgeta; Frenea-Robin, Marie; Haddour, Naoufel; Dempsey, Nora M.; Dumas-Bouchiat, Frédéric; Simonet, Pascal

    2015-04-01

    In various contexts such as pathogen detection or analysis of microbial diversity where cellular heterogeneity must be taken into account, there is a growing need for tools and methods that enable microbiologists to analyze bacterial cells individually. One of the main challenges in the development of new platforms for single cell studies is to perform precise cell positioning, but the ability to specifically target cells is also important in many applications. In this work, we report the development of new strategies to selectively trap single bacterial cells upon large arrays, based on the use of micro-magnets. Escherichia coli bacteria were used to demonstrate magnetically driven bacterial cell organization. In order to provide a flexible approach adaptable to several applications in the field of microbiology, cells were magnetically and specifically labeled using two different strategies, namely immunomagnetic labeling and magnetic in situ hybridization. Results show that centimeter-sized arrays of targeted, isolated bacteria can be successfully created upon the surface of a flat magnetically patterned hard magnetic film. Efforts are now being directed towards the integration of a detection tool to provide a complete micro-system device for a variety of microbiological applications.

  5. Scaffold-independent Patterning of Cells using Magnetic Nanoparticles

    NASA Astrophysics Data System (ADS)

    Ghosh, Suvojit; Biswas, Moanaro; Elankumaran, Subbiah; Puri, Ishwar

    2013-03-01

    Spatial patterning of cells in vitro relies on direct contact of cells on to solid surfaces. Scaffold independent patterning of cells has never been achieved so far. Patterning of cells has wide applications including stem cell biology, tissue architecture and regenerative medicine besides fundamental biology. Magnetized cells in a suspension can be manipulated using an externally applied magnetic field enabling directed patterning. We magnetized mammalian cells by internalization of superparamagnetic nanoparticles coated with bovine serum albumin (BSA). A magnetic field is then used to arrange cells in a desired pattern on a substrate or in suspension. The control strategy is derived from the self-assembly of magnetic colloids in a liquid considering magnetostatic interactions. The range of achievable structural features promise novel experimental methods investigating the influence of tissue shape and size on cell population dynamics wherein Fickian diffusion of autocrine growth signals are known to play a significant role. By eliminating the need for a scaffold, intercellular adhesion mechanics and the effects of temporally regulated signals can be investigated. The findings can be applied to novel tissue engineering methods.

  6. Identification of Lectins from Metastatic Cancer Cells through Magnetic Glyconanoparticles

    PubMed Central

    Kavunja, Herbert W.; Voss, Patricia G.

    2016-01-01

    Cancer cells can have characteristic carbohydrate binding properties. Previously, it was shown that a highly metastatic melanoma cell line B16F10 bound to galacto-side-functionalized nanoparticles much stronger than the corresponding less metastatic B16F1 cells. To better understand the carbohydrate binding properties of cancer cells, herein, we report the isolation and characterization of endogenous galactose binding proteins from B16F10 cells using magnetic glyconanoparticles. The galactose-coated magnetic glyconanoparticles could bind with lectins present in the cells and be isolated through magnet-mediated separation. Through Western blot and mass spectrometry, the arginine/serine rich splicing factor Sfrs1 was identified as a galactose-selective endogenous lectin, overexpressed in B16F10 cells, compared with B16F1 cells. In addition, galactin-3 was found in higher amounts in B16F10 cells. Finally, the glyconanoparticles exhibited a superior efficiency in lectin isolation, from both protein mixtures and live cells, than the corresponding more traditional microparticles functionalized with carbohydrates. Thus, the magnetic glyconanoparticles present a useful tool for discovery of endogenous lectins, as well as binding partners of lectins, without prior knowledge of protein identities. PMID:27110035

  7. Single cell magnetic imaging using a quantum diamond microscope

    PubMed Central

    Park, H.; Weissleder, R.; Yacoby, A.; Lukin, M. D.; Lee, H.; Walsworth, R. L.; Connolly, C. B.

    2015-01-01

    We apply a quantum diamond microscope to detection and imaging of immunomagnetically labeled cells. This instrument uses nitrogen-vacancy (NV) centers in diamond for correlated magnetic and fluorescence imaging. Our device provides single-cell resolution and two orders of magnitude larger field of view (~1 mm2) than previous NV imaging technologies, enabling practical applications. To illustrate, we quantify cancer biomarkers expressed by rare tumor cells in a large population of healthy cells. PMID:26098019

  8. Magnetic liposomes for colorectal cancer cells therapy by high-frequency magnetic field treatment

    NASA Astrophysics Data System (ADS)

    Hardiansyah, Andri; Huang, Li-Ying; Yang, Ming-Chien; Liu, Ting-Yu; Tsai, Sung-Chen; Yang, Chih-Yung; Kuo, Chih-Yu; Chan, Tzu-Yi; Zou, Hui-Ming; Lian, Wei-Nan; Lin, Chi-Hung

    2014-09-01

    In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes ( ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 μM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.

  9. Magnetic liposomes for colorectal cancer cells therapy by high-frequency magnetic field treatment

    PubMed Central

    2014-01-01

    In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 μM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells. PMID:25246875

  10. Optimization of magnetic switches for single particle and cell transport

    NASA Astrophysics Data System (ADS)

    Abedini-Nassab, Roozbeh; Murdoch, David M.; Kim, CheolGi; Yellen, Benjamin B.

    2014-06-01

    The ability to manipulate an ensemble of single particles and cells is a key aim of lab-on-a-chip research; however, the control mechanisms must be optimized for minimal power consumption to enable future large-scale implementation. Recently, we demonstrated a matter transport platform, which uses overlaid patterns of magnetic films and metallic current lines to control magnetic particles and magnetic-nanoparticle-labeled cells; however, we have made no prior attempts to optimize the device geometry and power consumption. Here, we provide an optimization analysis of particle-switching devices based on stochastic variation in the particle's size and magnetic content. These results are immediately applicable to the design of robust, multiplexed platforms capable of transporting, sorting, and storing single cells in large arrays with low power and high efficiency.

  11. Optimization of magnetic switches for single particle and cell transport

    SciTech Connect

    Abedini-Nassab, Roozbeh; Yellen, Benjamin B.; Murdoch, David M.; Kim, CheolGi

    2014-06-28

    The ability to manipulate an ensemble of single particles and cells is a key aim of lab-on-a-chip research; however, the control mechanisms must be optimized for minimal power consumption to enable future large-scale implementation. Recently, we demonstrated a matter transport platform, which uses overlaid patterns of magnetic films and metallic current lines to control magnetic particles and magnetic-nanoparticle-labeled cells; however, we have made no prior attempts to optimize the device geometry and power consumption. Here, we provide an optimization analysis of particle-switching devices based on stochastic variation in the particle's size and magnetic content. These results are immediately applicable to the design of robust, multiplexed platforms capable of transporting, sorting, and storing single cells in large arrays with low power and high efficiency.

  12. Activation of Schwann cells in vitro by magnetic nanocomposites via applied magnetic field

    PubMed Central

    Liu, Zhongyang; Huang, Liangliang; Liu, Liang; Luo, Beier; Liang, Miaomiao; Sun, Zhen; Zhu, Shu; Quan, Xin; Yang, Yafeng; Ma, Teng; Huang, Jinghui; Luo, Zhuojing

    2015-01-01

    Schwann cells (SCs) are attractive seed cells in neural tissue engineering, but their application is limited by attenuated biological activities and impaired functions with aging. Therefore, it is important to explore an approach to enhance the viability and biological properties of SCs. In the present study, a magnetic composite made of magnetically responsive magnetic nanoparticles (MNPs) and a biodegradable chitosan–glycerophosphate polymer were prepared and characterized. It was further explored whether such magnetic nanocomposites via applied magnetic fields would regulate SC biological activities. The magnetization of the magnetic nanocomposite was measured by a vibrating sample magnetometer. The compositional characterization of the magnetic nanocomposite was examined by Fourier-transform infrared and X-ray diffraction. The tolerance of SCs to the magnetic fields was tested by flow-cytometry assay. The proliferation of cells was examined by a 5-ethynyl-2-deoxyuridine-labeling assay, a PrestoBlue assay, and a Live/Dead assay. Messenger ribonucleic acid of BDNF, GDNF, NT-3, and VEGF in SCs was assayed by quantitative real-time polymerase chain reaction. The amount of BDNF, GDNF, NT-3, and VEGF secreted from SCs was determined by enzyme-linked immunosorbent assay. It was found that magnetic nanocomposites containing 10% MNPs showed a cross-section diameter of 32.33±1.81 µm, porosity of 80.41%±0.72%, and magnetization of 5.691 emu/g at 8 kOe. The 10% MNP magnetic nanocomposites were able to support cell adhesion and spreading and further promote proliferation of SCs under magnetic field exposure. Interestingly, a magnetic field applied through the 10% MNP magnetic scaffold significantly increased the gene expression and protein secretion of BDNF, GDNF, NT-3, and VEGF. This work is the first stage in our understanding of how to precisely regulate the viability and biological properties of SCs in tissue-engineering grafts, which combined with additional

  13. On-chip Magnetic Separation and Cell Encapsulation in Droplets†

    PubMed Central

    Chen, Aaron; Byvank, Tom; Chang, Woo-Jin; Bharde, Atul; Vieira, Greg; Miller, Brandon; Chalmers, Jeffrey J.; Bashir, Rashid; Sooryakumar, Ratnasingham

    2014-01-01

    The demand for high-throughput single cell assays is gaining importance because of the heterogeneity of many cell suspensions, even after significant initial sorting. These suspensions may display cell-to-cell variability at the gene expression level that could impact single cell functional genomics, cancer, stem-cell research and drug screening. The on-chip monitoring of individual cells in an isolated environment would prevent cross-contamination, provide high recovery yield, and enable study of biological traits at a single cell level. These advantages of on-chip biological experiments is a significant improvement for myriad of cell analyses over conventional methods, which require bulk samples providing only averaged information on cell metabolism. We report on a device that integrates mobile magnetic trap array with microfluidic technology to provide, combined functionality of separation of immunomagnetically labeled cells or magnetic beads and their encapsulation with reagents into pico-liter droplets. This scheme of simultaneous reagent delivery and compartmentalization of the cells immediately after sorting, all performed seamlessly within the same chip, offers unique advantages such as the ability to capture cell traits as originated from its native environment, reduced chance of contamination, minimal use and freshness of the reagent solution that reacts only with separated objects, and tunable encapsulation characteristics independent of the input flow. In addition to the demonstrated preliminary cell viability assay, the device can potentially be integrated with other up- or downstream on-chip modules to become a powerful single-cell analysis tool. PMID:23370785

  14. Instant magnetic labeling of tumor cells by ultrasound in vitro

    NASA Astrophysics Data System (ADS)

    Mo, Runyang; Yang, Jian; Wu, Ed X.; Lin, Shuyu

    2011-09-01

    Magnetic labeling of living cells creates opportunities for numerous biomedical applications. Here we describe an instantly cell magnetic labeling method based on ultrasound. We present a detailed study on the ultrasound performance of a simple and efficient labeling protocol for H-22 cells in vitro. High frequency focus ultrasound was investigated as an alternative method to achieve instant cell labeling with the magnetic particles without the need for adjunct agents or initiating cell cultures. Mean diameter of 168 nm dextran-T40 coated superparamagnetic iron oxide (SPIO) nanoparticles were prepared by means of classical coprecipitation in solution in our laboratory. H-22 tumor cells suspended in phosphate-buffered saline (PBS, pH=7.2) were exposed to ultrasound at 1.37 MHz for up to 120 s in the presence of SPIOs. The cellular uptake of iron oxide nanoparticles was detected by prussion blue staining. The viability of cells was determined by a trypan blue exclusion test. At 2 W power and 60 s ultrasound exposure in presence of 410 μg/ml SPIOs, H-22 cell labeling efficiency reached 69.4±6.3% and the labeled cells exhibited an iron content of 10.38±2.43 pg per cell. Furthermore, 95.2±3.2% cells remained viable. The results indicated that the ultrasound protocol could be potentially applied to label cells with large-sized magnetic particles. We also calculated the shear stress at the 2 W power and 1.37 MHz used in experiments. The results showed that the shear stress threshold for ultrasonically induced H-22 cell reparable sonoporation was 697 Pa. These findings provide a quantitative guidance in designing ultrasound protocols for cell labeling.

  15. Functionalization of whole‐cell bacterial reporters with magnetic nanoparticles

    PubMed Central

    Zhang, Dayi; Fakhrullin, Rawil F.; Özmen, Mustafa; Wang, Hui; Wang, Jian; Paunov, Vesselin N.; Li, Guanghe; Huang, Wei E.

    2011-01-01

    Summary We developed a biocompatible and highly efficient approach for functionalization of bacterial cell wall with magnetic nanoparticles (MNPs). Three Acinetobacter baylyi ADP1 chromosomally based bioreporters, which were genetically engineered to express bioluminescence in response to salicylate, toluene/xylene and alkanes, were functionalized with 18 ± 3 nm iron oxide MNPs to acquire magnetic function. The efficiency of MNPs functionalization of Acinetobacter bioreporters was 99.96 ± 0.01%. The MNPs‐functionalized bioreporters (MFBs) can be remotely controlled and collected by an external magnetic field. The MFBs were all viable and functional as good as the native cells in terms of sensitivity, specificity and quantitative response. More importantly, we demonstrated that salicylate sensing MFBs can be applied to sediments and garden soils, and semi‐quantitatively detect salicylate in those samples by discriminably recovering MFBs with a permanent magnet. The magnetically functionalized cells are especially useful to complex environments in which the indigenous cells, particles and impurities may interfere with direct measurement of bioreporter cells and conventional filtration is not applicable to distinguish and harvest bioreporters. The approach described here provides a powerful tool to remotely control and selectively manipulate MNPs‐functionalized cells in water and soils. It would have a potential in the application of environmental microbiology, such as bioremediation enhancement and environment monitoring and assessment. PMID:21255376

  16. Magnetically Targeted Stem Cell Delivery for Regenerative Medicine.

    PubMed

    Cores, Jhon; Caranasos, Thomas G; Cheng, Ke

    2015-01-01

    Stem cells play a special role in the body as agents of self-renewal and auto-reparation for tissues and organs. Stem cell therapies represent a promising alternative strategy to regenerate damaged tissue when natural repairing and conventional pharmacological intervention fail to do so. A fundamental impediment for the evolution of stem cell therapies has been the difficulty of effectively targeting administered stem cells to the disease foci. Biocompatible magnetically responsive nanoparticles are being utilized for the targeted delivery of stem cells in order to enhance their retention in the desired treatment site. This noninvasive treatment-localization strategy has shown promising results and has the potential to mitigate the problem of poor long-term stem cell engraftment in a number of organ systems post-delivery. In addition, these same nanoparticles can be used to track and monitor the cells in vivo, using magnetic resonance imaging. In the present review we underline the principles of magnetic targeting for stem cell delivery, with a look at the logic behind magnetic nanoparticle systems, their manufacturing and design variants, and their applications in various pathological models. PMID:26133387

  17. A Unit Cell Laboratory Experiment: Marbles, Magnets, and Stacking Arrangements

    ERIC Educational Resources Information Center

    Collins, David C.

    2011-01-01

    An undergraduate first-semester general chemistry laboratory experiment introducing face-centered, body-centered, and simple cubic unit cells is presented. Emphasis is placed on the stacking arrangement of solid spheres used to produce a particular unit cell. Marbles and spherical magnets are employed to prepare each stacking arrangement. Packing…

  18. An efficient magnetically modified microbial cell biocomposite for carbazole biodegradation

    NASA Astrophysics Data System (ADS)

    Li, Yufei; Du, Xiaoyu; Wu, Chao; Liu, Xueying; Wang, Xia; Xu, Ping

    2013-12-01

    Magnetic modification of microbial cells enables to prepare smart biocomposites in bioremediation. In this study, we constructed an efficient biocomposite by assembling Fe3O4 nanoparticles onto the surface of Sphingomonas sp. XLDN2-5 cells. The average particle size of Fe3O4 nanoparticles was about 20 nm with 45.5 emu g-1 saturation magnetization. The morphology of Sphingomonas sp. XLDN2-5 cells before and after Fe3O4 nanoparticle loading was verified by scanning electron microscopy and transmission electronic microscopy. Compared with free cells, the microbial cell/Fe3O4 biocomposite had the same biodegradation activity but exhibited remarkable reusability. The degradation activity of the microbial cell/Fe3O4 biocomposite increased gradually during recycling processes. Additionally, the microbial cell/Fe3O4 biocomposite could be easily separated and recycled by an external magnetic field due to the super-paramagnetic properties of Fe3O4 nanoparticle coating. These results indicated that magnetically modified microbial cells provide a promising technique for improving biocatalysts used in the biodegradation of hazardous compounds.

  19. An efficient magnetically modified microbial cell biocomposite for carbazole biodegradation

    PubMed Central

    2013-01-01

    Magnetic modification of microbial cells enables to prepare smart biocomposites in bioremediation. In this study, we constructed an efficient biocomposite by assembling Fe3O4 nanoparticles onto the surface of Sphingomonas sp. XLDN2-5 cells. The average particle size of Fe3O4 nanoparticles was about 20 nm with 45.5 emu g-1 saturation magnetization. The morphology of Sphingomonas sp. XLDN2-5 cells before and after Fe3O4 nanoparticle loading was verified by scanning electron microscopy and transmission electronic microscopy. Compared with free cells, the microbial cell/Fe3O4 biocomposite had the same biodegradation activity but exhibited remarkable reusability. The degradation activity of the microbial cell/Fe3O4 biocomposite increased gradually during recycling processes. Additionally, the microbial cell/Fe3O4 biocomposite could be easily separated and recycled by an external magnetic field due to the super-paramagnetic properties of Fe3O4 nanoparticle coating. These results indicated that magnetically modified microbial cells provide a promising technique for improving biocatalysts used in the biodegradation of hazardous compounds. PMID:24330511

  20. Magnetically Targeted Stem Cell Delivery for Regenerative Medicine

    PubMed Central

    Cores, Jhon; Caranasos, Thomas G.; Cheng, Ke

    2015-01-01

    Stem cells play a special role in the body as agents of self-renewal and auto-reparation for tissues and organs. Stem cell therapies represent a promising alternative strategy to regenerate damaged tissue when natural repairing and conventional pharmacological intervention fail to do so. A fundamental impediment for the evolution of stem cell therapies has been the difficulty of effectively targeting administered stem cells to the disease foci. Biocompatible magnetically responsive nanoparticles are being utilized for the targeted delivery of stem cells in order to enhance their retention in the desired treatment site. This noninvasive treatment-localization strategy has shown promising results and has the potential to mitigate the problem of poor long-term stem cell engraftment in a number of organ systems post-delivery. In addition, these same nanoparticles can be used to track and monitor the cells in vivo, using magnetic resonance imaging. In the present review we underline the principles of magnetic targeting for stem cell delivery, with a look at the logic behind magnetic nanoparticle systems, their manufacturing and design variants, and their applications in various pathological models. PMID:26133387

  1. Noninvasive assessment of magnetic nanoparticle-cancer cell interactions

    PubMed Central

    Giustini, Andrew J.; Perreard, Irina; Rauwerdink, Adam M.; Hoopes, P. Jack; Weaver, John B.

    2012-01-01

    The success of magnetic nanoparticle (mNP)-based diagnostic and therapeutic techniques is dependent upon how the mNP are distributed in vivo. The potential efficacy and timing of a given magnetic nanoparticle treatment or diagnostic test is largely determined by the number of nanoparticles in each tissue and microscopic compartment: e.g., in the intravascular and extravascular spaces, in the interstitial space, cell surface and in cell cytoplasm. Techniques for monitoring these cell-level interactions generally require the harvesting and destruction of tissues or cells at each time point of interest. We present a method (magnetic spectroscopy of Brownian motion, MSB) for longitudinally monitoring nanoparticle binding to cell surface proteins and uptake by cancer cells in vitro using the harmonics of the magnetization produced by the nanoparticles. These harmonics can be measured rapidly and noninvasively without the need for nanoparticle modifications and without damaging the cells. We demonstrate sensitivity of this harmonic signal to the nanoparticles’ microenvironment and use this technique to monitor the nanoparticle binding activities of different cell lines. PMID:22945022

  2. High gradient magnetic field microstructures for magnetophoretic cell separation.

    PubMed

    Abdel Fattah, Abdel Rahman; Ghosh, Suvojit; Puri, Ishwar K

    2016-08-01

    Microfluidics has advanced magnetic blood fractionation by making integrated miniature devices possible. A ferromagnetic microstructure array that is integrated with a microfluidic channel rearranges an applied magnetic field to create a high gradient magnetic field (HGMF). By leveraging the differential magnetic susceptibilities of cell types contained in a host medium, such as paramagnetic red blood cells (RBCs) and diamagnetic white blood cells (WBCs), the resulting HGMF can be used to continuously separate them without attaching additional labels, such as magnetic beads, to them. We describe the effect of these ferromagnetic microstructure geometries have on the blood separation efficacy by numerically simulating the influence of microstructure height and pitch on the HGMF characteristics and resulting RBC separation. Visualizations of RBC trajectories provide insight into how arrays can be optimized to best separate these cells from a host fluid. Periodic microstructures are shown to moderate the applied field due to magnetic interference between the adjacent teeth of an array. Since continuous microstructures do not similarly weaken the resultant HGMF, they facilitate significantly higher RBC separation. Nevertheless, periodic arrays are more appropriate for relatively deep microchannels since, unlike continuous microstructures, their separation effectiveness is independent of depth. The results are relevant to the design of microfluidic devices that leverage HGMFs to fractionate blood by separating RBCs and WBCs. PMID:27294532

  3. Influence on cell death of high frequency motion of magnetic nanoparticles during magnetic hyperthermia experiments

    NASA Astrophysics Data System (ADS)

    Hallali, N.; Clerc, P.; Fourmy, D.; Gigoux, V.; Carrey, J.

    2016-07-01

    Studies with transplanted tumors in animals and clinical trials have provided the proof-of-concept of magnetic hyperthermia (MH) therapy of cancers using iron oxide nanoparticles. Interestingly, in several studies, the application of an alternating magnetic field (AMF) to tumor cells having internalized and accumulated magnetic nanoparticles (MNPs) into their lysosomes can induce cell death without detectable temperature increase. To explain these results, among other hypotheses, it was proposed that cell death could be due to the high-frequency translational motion of MNPs under the influence of the AMF gradient generated involuntarily by most inductors. Such mechanical actions of MNPs might cause cellular damages and participate in the induction of cell death under MH conditions. To test this hypothesis, we developed a setup maximizing this effect. It is composed of an anti-Helmholtz coil and two permanent magnets, which produce an AMF gradient and a superimposed static MF. We have measured the MNP heating power and treated tumor cells by a standard AMF and by an AMF gradient, on which was added or not a static magnetic field. We showed that the presence of a static magnetic field prevents MNP heating and cell death in standard MH conditions. The heating power of MNPs in an AMF gradient is weak, position-dependent, and related to the presence of a non-zero AMF. Under an AMF gradient and a static field, no MNP heating and cell death were measured. Consequently, the hypothesis that translational motions could be involved in cell death during MH experiments is ruled out by our experiments.

  4. Diffusion of magnetic elements in a supergranular cell

    SciTech Connect

    Giannattasio, F.; Berrilli, F.; Del Moro, D.; Stangalini, M.; Rubio, L. Bellot

    2014-06-20

    Small scale magnetic fields (magnetic elements) are ubiquitous in the solar photosphere. Their interaction can provide energy to the upper atmospheric layers, and contribute to heat the solar corona. In this work, the dynamic properties of magnetic elements in the quiet Sun are investigated. The high number of magnetic elements detected in a supergranular cell allowed us to compute their displacement spectrum ((Δr){sup 2})∝τ{sup γ} (with γ > 0, and τ the time since the first detection), separating the contribution of the network (NW) and the internetwork (IN) regions. In particular, we found γ = 1.27 ± 0.05 and γ = 1.08 ± 0.11 in NW (at smaller and larger scales, respectively), and γ = 1.44 ± 0.08 in IN. These results are discussed in light of the literature on the topic, as well as the implications for the build-up of the magnetic network.

  5. Magnetic micro-device for manipulating PC12 cell migration and organization.

    PubMed

    Alon, N; Havdala, T; Skaat, H; Baranes, K; Marcus, M; Levy, I; Margel, S; Sharoni, A; Shefi, O

    2015-05-01

    Directing neuronal migration and growth has an important impact on potential post traumatic therapies. Magnetic manipulation is an advantageous method for remotely guiding cells. In the present study, we have generated highly localized magnetic fields with controllable magnetic flux densities to manipulate neuron-like cell migration and organization at the microscale level. We designed and fabricated a unique miniaturized magnetic device composed of an array of rectangular ferromagnetic bars made of permalloy (Ni80Fe20), sputter-deposited onto glass substrates. The asymmetric shape of the magnets enables one to design a magnetic landscape with high flux densities at the poles. Iron oxide nanoparticles were introduced into PC12 cells, making the cells magnetically sensitive. First, we manipulated the cells by applying an external magnetic field. The magnetic force was strong enough to direct PC12 cell migration in culture. Based on time lapse observations, we analysed the movement of the cells and estimated the amount of MNPs per cell. We plated the uploaded cells on the micro-patterned magnetic device. The cells migrated towards the high magnetic flux zones and aggregated at the edges of the patterned magnets, corroborating that the cells with magnetic nanoparticles are indeed affected by the micro-magnets and attracted to the bars' magnetic poles. Our study presents an emerging method for the generation of pre-programmed magnetic micro-'hot spots' to locate and direct cellular growth, setting the stage for implanted magnetic devices. PMID:25792133

  6. Microfabricated atomic vapor cell arrays for magnetic field measurements

    SciTech Connect

    Woetzel, S.; Schultze, V.; IJsselsteijn, R.; Schulz, T.; Anders, S.; Stolz, R.; Meyer, H.-G.

    2011-03-15

    We describe a method for charging atomic vapor cells with cesium and buffer gas. By this, it is possible to adjust the buffer gas pressure in the cells with good accuracy. Furthermore, we present a new design of microfabricated vapor cell arrays, which combine silicon wafer based microfabrication and ultrasonic machining to achieve the arrays of thermally separated cells with 50 mm{sup 3} volume. With cells fabricated in the outlined way, intrinsic magnetic field sensitivities down to 300 fT/Hz{sup 1/2} are reached.

  7. Detection of molecules and cells using nuclear magnetic resonance with magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Rümenapp, Christine; Gleich, Bernhard; Mannherz, Hans Georg; Haase, Axel

    2015-04-01

    For the detection of small molecules, proteins or even cells in vitro, functionalised magnetic nanoparticles and nuclear magnetic resonance measurements can be applied. In this work, magnetic nanoparticles with the size of 5-7 nm were functionalised with antibodies to detect two model systems of different sizes, the protein avidin and Saccharomyces cerevisiae as the model organism. The synthesised magnetic nanoparticles showed a narrow size distribution, which was determined using transmission electron microscopy and dynamic light scattering. The magnetic nanoparticles were functionalised with the according antibodies via EDC/NHS chemistry. The binding of the antigen to magnetic nanoparticles was detected through the change in the NMR T2 relaxation time at 0.5 T (≈21.7 MHz). In case of a specific binding the particles cluster and the T2 relaxation time of the sample changes. The detection limit in buffer for FITC-avidin was determined to be 1.35 nM and 107 cells/ml for S. cerevisiae. For fluorescent microscopy the avidin molecules were labelled with FITC and for the detection of S. cerevisiae the magnetic nanoparticles were additionally functionalised with rhodamine. The binding of the particles to S. cerevisiae and the resulting clustering was also seen by transmission electron microscopy.

  8. Magnetic particle motions within living cells. Physical theory and techniques.

    PubMed Central

    Valberg, P A; Butler, J P

    1987-01-01

    Body tissues are not ferromagnetic, but ferromagnetic particles can be present as contaminants or as probes in the lungs and in other organs. The magnetic domains of these particles can be aligned by momentary application of an external magnetic field; the magnitude and time course of the resultant remanent field depend on the quantity of magnetic material and the degree of particle motion. The interpretation of magnetometric data requires an understanding of particle magnetization, agglomeration, random motion, and both rotation and translation in response to magnetic fields. We present physical principles relevant to magnetometry and suggest models for intracellular particle motion driven by thermal, elastic, or cellular forces. The design principles of instrumentation for magnetizing intracellular particles and for detecting weak remanent magnetic fields are described. Such magnetic measurements can be used for noninvasive studies of particle clearance from the body or of particle motion within body tissues and cells. Assumptions inherent to this experimental approach and possible sources of artifact are considered and evaluated. PMID:3676435

  9. Rapid magnetic cell delivery for large tubular bioengineered constructs.

    PubMed

    Gonzalez-Molina, J; Riegler, J; Southern, P; Ortega, D; Frangos, C C; Angelopoulos, Y; Husain, S; Lythgoe, M F; Pankhurst, Q A; Day, R M

    2012-11-01

    Delivery of cells into tubular tissue constructs with large diameters poses significant spatial and temporal challenges. This study describes preliminary findings for a novel process for rapid and uniform seeding of cells onto the luminal surface of large tubular constructs. Fibroblasts, tagged with superparamagnetic iron oxide nanoparticles (SPION), were directed onto the luminal surface of tubular constructs by a magnetic field generated by a k4-type Halbach cylinder device. The spatial distribution of attached cells, as measured by the mean number of cells, was compared with a conventional, dynamic, rotational cell-delivery technique. Cell loading onto the constructs was measured by microscopy and magnetic resonance imaging. The different seeding techniques employed had a significant effect on the spatial distribution of the cells (p < 0.0001). The number of attached cells at defined positions within the same construct was significantly different for the dynamic rotation technique (p < 0.05). In contrast, no significant differences in the number of cells attached to the luminal surface were found between the defined positions on the construct loaded with the Halbach cylinder. The technique described overcomes limitations associated with existing cell-delivery techniques and is amenable to a variety of tubular organs where rapid loading and uniform distribution of cells for therapeutic applications are required. PMID:22696487

  10. On-chip Magnetic Separation and Cell Encapsulation in Droplets

    NASA Astrophysics Data System (ADS)

    Chen, A.; Byvank, T.; Bharde, A.; Miller, B. L.; Chalmers, J. J.; Sooryakumar, R.; Chang, W.-J.; Bashir, R.

    2012-02-01

    The demand for high-throughput single cell assays is gaining importance because of the heterogeneity of many cell suspensions, even after significant initial sorting. These suspensions may display cell-to-cell variability at the gene expression level that could impact single cell functional genomics, cancer, stem-cell research and drug screening. The on-chip monitoring of individual cells in an isolated environment could prevent cross-contamination, provide high recovery yield and ability to study biological traits at a single cell level These advantages of on-chip biological experiments contrast to conventional methods, which require bulk samples that provide only averaged information on cell metabolism. We report on a device that integrates microfluidic technology with a magnetic tweezers array to combine the functionality of separation and encapsulation of objects such as immunomagnetically labeled cells or magnetic beads into pico-liter droplets on the same chip. The ability to control the separation throughput that is independent of the hydrodynamic droplet generation rate allows the encapsulation efficiency to be optimized. The device can potentially be integrated with on-chip labeling and/or bio-detection to become a powerful single-cell analysis device.

  11. Magnetic field-guided cell delivery with nanoparticle-loaded human corneal endothelial cells.

    PubMed

    Moysidis, Stavros N; Alvarez-Delfin, Karen; Peschansky, Veronica J; Salero, Enrique; Weisman, Alejandra D; Bartakova, Alena; Raffa, Gabriella A; Merkhofer, Richard M; Kador, Karl E; Kunzevitzky, Noelia J; Goldberg, Jeffrey L

    2015-04-01

    To improve the delivery and integration of cell therapy using magnetic cell guidance for replacement of corneal endothelium, here we assess magnetic nanoparticles' (MNPs') effects on human corneal endothelial cells (HCECs) in vitro. Biocompatible, 50 nm superparamagnetic nanoparticles endocytosed by cultured HCECs induced no short- or long-term change in viability or identity. Assessment of guidance of the magnetic HCECs in the presence of different magnet shapes and field strengths showed a 2.4-fold increase in delivered cell density compared to gravity alone. After cell delivery, HCECs formed a functional monolayer, with no difference in tight junction formation between MNP-loaded and control HCECs. These data suggest that nanoparticle-mediated magnetic cell delivery may increase the efficiency of cell delivery without compromising HCEC survival, identity or function. Future studies may assess the safety and efficacy of this therapeutic modality in vivo. From the clinical editor: The authors show in this article that magnetic force facilitates the delivery of human corneal endothelial cells loaded by superparamagnetic nanoparticles to cornea, without changing their morphology, identity or functional properties. This novel idea can potentially have vast impact in the treatment of corneal endothelial dystrophies by providing self-endothelial cells after ex-vivo expansion. PMID:25596075

  12. Tracking immune cells in vivo using magnetic resonance imaging

    PubMed Central

    Ahrens, Eric T.; Bulte, Jeff W. M.

    2013-01-01

    The increasing complexity of in vivo imaging technologies, coupled with the development of cell therapies, has fuelled a revolution in immune cell tracking in vivo. Powerful magnetic resonance imaging (MRI) methods are now being developed that use iron oxide- and 19F-based probes. These MRI technologies can be used for image-guided immune cell delivery and for the visualization of immune cell homing and engraftment, inflammation, cell physiology and gene expression. MRI-based cell tracking is now also being applied to evaluate therapeutics that modulate endogenous immune cell recruitment and to monitor emerging cellular immunotherapies. These recent uses show that MRI has the potential to be developed in many applications to follow the fate of immune cells in vivo. PMID:24013185

  13. Magnetic field-magnetic nanoparticle culture system used to grow in vitro murine embryonic stem cells.

    PubMed

    de Freitas, Erika Regina Leal; Soares, Paula Roberta Otaviano; de Santos, Rachel Paula; dos Santos, Regiane Lopes; Porfírio, Elaine Paulucio; Báo, Sônia N; Lima, Emília Celma Oliveira; Guillo, Lídia Andreu

    2011-01-01

    The in vitro growth of embryonic stem cells (ESCs) is usually obtained in the presence of murine embryonic fibroblasts (MEF), but new methods for in vitro expansion of ESCs should be developed due to their potential clinical use. This study aims to establish a culture system to expand and maintain ESCs in the absence of MEF by using murine embryonic stem cells (mECS) as a model of embryonic stem cell. Magnetic nanoparticles (MNPs) were used for growing mESCs in the presence of an external magnetic field, creating the magnetic field-magnetic nanoparticle (MF-MNP) culture system. The growth characteristics were evaluated showing a doubling time slightly higher for mESCs cultivated in the presence of the system than in the presence of the MEF. The undifferentiated state was characterized by RT-PCR, immunofluorescence, alkaline phosphatase activity and electron microscopy. Murine embryonic stem cells cultivated in presence of the MF-MNP culture system exhibited Oct-4 and Nanog expression and high alkaline phosphatase activity. Ultrastructural morphology showed that the MF-MNP culture system did not interfere with processes that cause structural changes in the cytoplasm or nucleus. The MF-MNP culture system provides a tool for in vitro expansion of mESCs and could contribute to studies that aim the therapeutic use of embryonic stem cells. PMID:21446404

  14. Magnetic resonance imaging of transplanted stem cell fate in stroke

    PubMed Central

    Aghayan, Hamid Reza; Soleimani, Masoud; Goodarzi, Parisa; Norouzi-Javidan, Abbas; Emami-Razavi, Seyed Hasan; Larijani, Bagher; Arjmand, Babak

    2014-01-01

    Nowadays, scientific findings in the field of regeneration of nervous system have revealed the possibility of stem cell based therapies for damaged brain tissue related disorders like stroke. Furthermore, to achieve desirable outcomes from cellular therapies, one needs to monitor the migration, engraftment, viability, and also functional fate of transplanted stem cells. Magnetic resonance imaging is an extremely versatile technique for this purpose, which has been broadly used to study stroke and assessment of therapeutic role of stem cells. In this review we searched in PubMed search engine by using following keywords; “Stem Cells”, “Cell Tracking”, “Stroke”, “Stem Cell Transplantation”, “Nanoparticles”, and “Magnetic Resonance Imaging” as entry terms and based on the mentioned key words, the search period was set from 1976 to 2012. The main purpose of this article is describing various advantages of molecular and magnetic resonance imaging of stem cells, with focus on translation of stem cell research to clinical research. PMID:25097631

  15. Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting

    PubMed Central

    Cheng, Ke; Shen, Deliang; Hensley, M. Taylor; Middleton, Ryan; Sun, Baiming; Liu, Weixin; De Couto, Geoffrey; Marbán, Eduardo

    2014-01-01

    Stem cell transplantation is a promising strategy for therapeutic cardiac regeneration, but current therapies are limited by inefficient interaction between potentially beneficial cells (either exogenously transplanted or endogenously recruited) and the injured tissue. Here we apply targeted nanomedicine to achieve in vivo cell-mediated tissue repair, imaging and localized enrichment without cellular transplantation. Iron nanoparticles are conjugated with two types of antibodies (one against antigens on therapeutic cells and the other directed at injured cells) to produce magnetic bifunctional cell engager (MagBICE). The antibodies link the therapeutic cells to the injured cells, whereas the iron core of MagBICE enables physical enrichment and imaging. We treat acute myocardial infarction by targeting exogenous bone marrow-derived stem cells (expressing CD45) or endogenous CD34-positive cells to injured cardiomyocytes (expressing myosin light chain. Targeting can be further enhanced by magnetic attraction, leading to augmented functional benefits. MagBICE represents a generalizable platform technology for regenerative medicine. PMID:25205020

  16. Large area magnetic micropallet arrays for cell colony sorting.

    PubMed

    Cox-Muranami, Wesley A; Nelson, Edward L; Li, G P; Bachman, Mark

    2016-01-01

    A new micropallet array platform for adherent cell colony sorting has been developed. The platform consisted of thousands of square plastic pallets, 270 μm by 270 μm on each side, large enough to hold a single colony of cells. Each pallet included a magnetic core, allowing them to be collected with a magnet after being released using a microscope mounted laser system. The micropallets were patterned from 1002F epoxy resist and were fabricated on translucent, gold coated microscope slides. The gold layer was used as seed for electroplating the ferromagnetic cores within every individual pallet. The gold layer also facilitated the release of each micropallet during laser release. This array allows for individual observation, sorting and collection of isolated cell colonies for biological cell colony research. In addition to consistent release and recovery of individual colonies, we demonstrated stable biocompatibility and minimal loss in imaging quality compared to previously developed micropallet arrays. PMID:26606460

  17. Biofunctionalized magnetic vortex microdisks for targeted cancer cell destruction.

    SciTech Connect

    Kim, D.-H.; Rozhkova, E. A.; Ulasov, I. V.; Bader, S. D.; Rajh, T.; Lesniak, M. S.; Novosad, V.; Univ. of Chicago Pritzker School of Medicine

    2010-01-01

    Nanomagnetic materials offer exciting avenues for probing cell mechanics and activating mechanosensitive ion channels, as well as for advancing cancer therapies. Most experimental works so far have used superparamagnetic materials. This report describes a first approach based on interfacing cells with lithographically defined microdiscs that possess a spin-vortex ground state. When an alternating magnetic field is applied the microdisc vortices shift, creating an oscillation, which transmits a mechanical force to the cell. Because reduced sensitivity of cancer cells toward apoptosis leads to inappropriate cell survival and malignant progression, selective induction of apoptosis is of great importance for the anticancer therapeutic strategies. We show that the spin-vortex-mediated stimulus creates two dramatic effects: compromised integrity of the cellular membrane, and initiation of programmed cell death. A low-frequency field of a few tens of hertz applied for only ten minutes was sufficient to achieve {approx}90% cancer-cell destruction in vitro.

  18. Recent patents and advances on applications of magnetic nanoparticles and thin films in cell manipulation.

    PubMed

    Abedini-Nassab, Roozbeh; Eslamian, Morteza

    2014-01-01

    Cell manipulation is instrumental in most biological applications. One of the most promising methods in handling cells and other biological particles is the magnetic manipulation technique. In this technique, magnetic nanoparticles are employed to magnetize cells. Such cells then can be manipulated, sorted, or separated by applying an external magnetic field. In this work, first recent works and patents on the synthesis methods used for producing magnetic nanoparticles are investigated. These methods include co-precipitation, solvothermal, electrical wire explosion, microemulsion, laser pyrolysis, spray pyrolysis and carbon reduction. Then recent patents and articles on surface modification and functionalization of magnetic nanoparticles using polymers, dithiocarbamate, superparamagnetic shells, antibodies, graphene shells, and fluorescent materials are reviewed. Finally, different techniques on magnetic cell manipulation, such as direct attaching of magnetic particles to cells, employing intercellular markers or extra support molecules, as well as magnetic thin films, microfluidic channels and magnetic beads, are studied. PMID:25336173

  19. Biosorption of water-soluble dyes on magnetically modified Saccharomyces cerevisiae subsp. uvarum cells.

    PubMed

    Safaríková, M; Ptácková, L; Kibriková, I; Safarík, I

    2005-05-01

    Brewer's yeast (bottom yeast, Saccharomyces cerevisiae subsp. uvarum) cells were magnetically modified using water based magnetic fluid stabilized with perchloric acid. Magnetically modified yeast cells efficiently adsorbed various water soluble dyes. The dyes adsorption can be described by the Langmuir adsorption model. The maximum adsorption capacity of the magnetic cells differed substantially for individual dyes; the highest value was found for aniline blue (approx. 220 mg per g of dried magnetic adsorbent). PMID:15811411

  20. Morphological effect of oscillating magnetic nanoparticles in killing tumor cells

    NASA Astrophysics Data System (ADS)

    Cheng, Dengfeng; Li, Xiao; Zhang, Guoxin; Shi, Hongcheng

    2014-04-01

    Forced oscillation of spherical and rod-shaped iron oxide magnetic nanoparticles (MNPs) via low-power and low-frequency alternating magnetic field (AMF) was firstly used to kill cancer cells in vitro. After being loaded by human cervical cancer cells line (HeLa) and then exposed to a 35-kHz AMF, MNPs mechanically damaged cell membranes and cytoplasm, decreasing the cell viability. It was found that the concentration and morphology of the MNPs significantly influenced the cell-killing efficiency of oscillating MNPs. In this preliminary study, when HeLa cells were pre-incubated with 100 μg/mL rod-shaped MNPs (rMNP, length of 200 ± 50 nm and diameter of 50 to 120 nm) for 20 h, MTT assay proved that the cell viability decreased by 30.9% after being exposed to AMF for 2 h, while the cell viability decreased by 11.7% if spherical MNPs (sMNP, diameter of 200 ± 50 nm) were used for investigation. Furthermore, the morphological effect of MNPs on cell viability was confirmed by trypan blue assay: 39.5% rMNP-loaded cells and 15.1% sMNP-loaded cells were stained after being exposed to AMF for 2 h. It was also interesting to find that killing tumor cells at either higher (500 μg/mL) or lower (20 μg/mL) concentration of MNPs was less efficient than that achieved at 100 μg/mL concentration. In conclusion, the relatively asymmetric morphological rod-shaped MNPs can kill cancer cells more effectively than spherical MNPs when being exposed to AMF by virtue of their mechanical oscillations.

  1. Magnetic field-controlled gene expression in encapsulated cells

    PubMed Central

    Ortner, Viktoria; Kaspar, Cornelius; Halter, Christian; Töllner, Lars; Mykhaylyk, Olga; Walzer, Johann; Günzburg, Walter H.; Dangerfield, John A.; Hohenadl, Christine; Czerny, Thomas

    2012-01-01

    Cell and gene therapies have an enormous range of potential applications, but as for most other therapies, dosing is a critical issue, which makes regulated gene expression a prerequisite for advanced strategies. Several inducible expression systems have been established, which mainly rely on small molecules as inducers, such as hormones or antibiotics. The application of these inducers is difficult to control and the effects on gene regulation are slow. Here we describe a novel system for induction of gene expression in encapsulated cells. This involves the modification of cells to express potential therapeutic genes under the control of a heat inducible promoter and the co-encapsulation of these cells with magnetic nanoparticles. These nanoparticles produce heat when subjected to an alternating magnetic field; the elevated temperatures in the capsules then induce gene expression. In the present study we define the parameters of such systems and provide proof-of-principle using reporter gene constructs. The fine-tuned heating of nanoparticles in the magnetic field allows regulation of gene expression from the outside over a broad range and within short time. Such a system has great potential for advancement of cell and gene therapy approaches. PMID:22197778

  2. Local viscoelasticity of living cells measured by rotational magnetic spectroscopy.

    PubMed

    Berret, J-F

    2016-01-01

    When submitted to a magnetic field, micron-size wires with superparamagnetic properties behave as embedded rheometers and represent interesting sensors for microrheology. Here we use rotational magnetic spectroscopy to measure the shear viscosity of the cytoplasm of living cells. We address the question of whether the cytoplasm is a viscoelastic liquid or an elastic gel. The main result of the study is the observation of a rotational instability between a synchronous and an asynchronous regime of rotation, found for murine fibroblasts and human cancer cells. For wires of susceptibility 3.6, the transition occurs in the range 0.01-1 rad s(-1). The determination of the shear viscosity (10-100 Pa s) and elastic modulus (5-20 Pa) confirms the viscoelastic character of the cytoplasm. In contrast to earlier studies, it is concluded that the interior of living cells can be described as a viscoelastic liquid, and not as an elastic gel. PMID:26729062

  3. Local viscoelasticity of living cells measured by rotational magnetic spectroscopy

    NASA Astrophysics Data System (ADS)

    Berret, J.-F.

    2016-01-01

    When submitted to a magnetic field, micron-size wires with superparamagnetic properties behave as embedded rheometers and represent interesting sensors for microrheology. Here we use rotational magnetic spectroscopy to measure the shear viscosity of the cytoplasm of living cells. We address the question of whether the cytoplasm is a viscoelastic liquid or an elastic gel. The main result of the study is the observation of a rotational instability between a synchronous and an asynchronous regime of rotation, found for murine fibroblasts and human cancer cells. For wires of susceptibility 3.6, the transition occurs in the range 0.01-1 rad s-1. The determination of the shear viscosity (10-100 Pa s) and elastic modulus (5-20 Pa) confirms the viscoelastic character of the cytoplasm. In contrast to earlier studies, it is concluded that the interior of living cells can be described as a viscoelastic liquid, and not as an elastic gel.

  4. Non-Temperature Induced Effects of Magnetized Iron Oxide Nanoparticles in Alternating Magnetic Field in Cancer Cells

    PubMed Central

    Hapuarachchige, Sudath; Kato, Yoshinori; Ngen, Ethel J.; Smith, Barbara; Delannoy, Michael; Artemov, Dmitri

    2016-01-01

    This paper reports the damaging effects of magnetic iron-oxide nanoparticles (MNP) on magnetically labeled cancer cells when subjected to oscillating gradients in a strong external magnetic field. Human breast cancer MDA-MB-231 cells were labeled with MNP, placed in the high magnetic field, and subjected to oscillating gradients generated by an imaging gradient system of a 9.4T preclinical MRI system. Changes in cell morphology and a decrease in cell viability were detected in cells treated with oscillating gradients. The cytotoxicity was determined qualitatively and quantitatively by microscopic imaging and cell viability assays. An approximately 26.6% reduction in cell viability was detected in magnetically labeled cells subjected to the combined effect of a static magnetic field and oscillating gradients. No reduction in cell viability was observed in unlabeled cells subjected to gradients, or in MNP-labeled cells in the static magnetic field. As no increase in local temperature was observed, the cell damage was not a result of hyperthermia. Currently, we consider the coherent motion of internalized and aggregated nanoparticles that produce mechanical moments as a potential mechanism of cell destruction. The formation and dynamics of the intracellular aggregates of nanoparticles were visualized by optical and transmission electron microscopy (TEM). The images revealed a rapid formation of elongated MNP aggregates in the cells, which were aligned with the external magnetic field. This strategy provides a new way to eradicate a specific population of MNP-labeled cells, potentially with magnetic resonance imaging guidance using standard MRI equipment, with minimal side effects for the host. PMID:27244470

  5. Magnetic levitating polymeric nano/microparticular substrates for three-dimensional tumor cell culture.

    PubMed

    Lee, Woong Ryeol; Oh, Kyung Taek; Park, So Young; Yoo, Na Young; Ahn, Yong Sik; Lee, Don Haeng; Youn, Yu Seok; Lee, Deok-Keun; Cha, Kyung-Hoi; Lee, Eun Seong

    2011-07-01

    Herein, we describe magnetic cell levitation models using conventional polymeric microparticles or nanoparticles as a substrate for the three-dimensional tumor cell culture. When the magnetic force originating from the ring-shaped magnets overcame the gravitational force, the magnetic field-levitated KB tumor cells adhered to the surface area of magnetic iron oxide (Fe(3)O(4))-encapsulated nano/microparticles and concentrated clusters of levitated cells, ultimately developing tumor cells to tumor spheroids. These simple cell culture models may prove useful for the screening of anticancer drugs and their formulations. PMID:21420837

  6. Magnetic microfluidic system for isolation of single cells

    NASA Astrophysics Data System (ADS)

    Mitterboeck, Richard; Kokkinis, Georgios; Berris, Theocharis; Keplinger, Franz; Giouroudi, Ioanna

    2015-06-01

    This paper presents the design and realization of a compact, portable and cost effective microfluidic system for isolation and detection of rare circulating tumor cells (CTCs) in suspension. The innovative aspect of the proposed isolation method is that it utilizes superparamagnetic particles (SMPs) to label CTCs and then isolate those using microtraps with integrated current carrying microconductors. The magnetically labeled and trapped CTCs can then be detected by integrated magnetic microsensors e.g. giant magnetoresistive (GMR) or giant magnetoimpedance (GMI) sensors. The channel and trap dimensions are optimized to protect the cells from shear stress and achieve high trapping efficiency. These intact single CTCs can then be used for additional analysis, testing and patient specific drug screening. Being able to analyze the CTCs metastasis-driving capabilities on the single cell level is considered of great importance for developing patient specific therapies. Experiments showed that it is possible to capture single labeled cells in multiple microtraps and hold them there without permanent electric current and magnetic field.

  7. Easily fabricated magnetic traps for single-cell applications

    NASA Astrophysics Data System (ADS)

    Koschwanez, John H.; Carlson, Robert H.; Meldrum, Deirdre R.

    2007-04-01

    We describe a simple and inexpensive method of fabricating single cell magnetic traps within a polydimethylsiloxane (PDMS) device. These traps were developed as part of an automated system that captures individual yeast cells in a microfluidic device and analyzes each cell as it buds. To make the traps, PdCl2 catalyst is rubbed with vinyl foam onto plasma-patterned PDMS, and then Co-Ni-B alloy is electrolessly deposited onto the catalyst at a moderate temperature. We demonstrate individual yeast cell capture and estimate the capture force (1.9-4.4 pN) by measuring the flow speed required to remove the cell from its trap in a microfluidic channel.

  8. Cell Targeting and Magnetically Induced Hyperthermia

    NASA Astrophysics Data System (ADS)

    Duguet, Etienne; Hardel, Lucile; Vasseur, Sébastien

    With the recent development of efficient and reproducible methods for synthesis, stable aqueous dispersions of individual particles can be prepared, in which the particle sizes can be accurately adjusted from a few nanometers to a few tens of nanometers [1]. Provided that their physical and chemical surface properties can be suitably adapted, these objects are small enough to circulate within the human body without risk of causing an embolus, since the finest capillaries (those of the lungs) have a minimal internal diameter of 5 μm. They can also escape from the blood compartment by windows of diameter around 100 nm in certain epithelia with permeability defects, such as those located in tumours and centers of infection, whereby they may then accumulate in such tissues. Furthermore, the smallest particles can migrate from the cardiovascular system into the lymph system. Finally, under the right conditions, they can enter cells and their various compartments. They should quickly become indispensable in the field of biological labelling, image contrast enhancement, the delivery of active principles, and the treatment of many different pathologies, by virtue of their novel physical properties [2, 3].

  9. Magnetic and fluorescence-encoded polystyrene microparticles for cell separation

    NASA Astrophysics Data System (ADS)

    Bradbury, Diana; Anglin, Emily J.; Bailey, Sheree; Macardle, Peter J.; Fenech, Michael; Thissen, Helmut; Voelcker, Nicolas H.

    2008-12-01

    Materials assisting with the efforts of cell isolation are attractive for numerous biomedical applications including tissue engineering and cell therapy. Here, we have developed surface modification methods on microparticles for the purposes of advanced cell separation. Iron oxide nanoparticles were incorporated into 200 ım polystyrene microparticles for separation of particle-bound cells from non-bound cells in suspension by means of a permanent magnet. The polystyrene microparticles were further encoded with fluorescent quantum dots (QD) as identification tags to distinguish between specific microparticles in a mixture. Cluster of differentiation (CD) antibodies were displayed on the surface of the microparticles through direct adsorption and various methods of covalent attachment. In addition, a protein A coating was used to orientate the antibodies on the microparticle surface and to maximise accessibility of the antigen-binding sites. Microparticles which carried CD antibodies via covalent attachment showed greater cell attachment over those modifications that were only adsorbed to the surface through weak electrostatic interactions. Greatest extent of cell attachment was observed on microparticles modified with protein A - CD antibody conjugates. B and T lymphocytes were successfully isolated from a mixed population using two types of microparticles displaying B and T cell specific CD antibodies, respectively. Our approach will find application in preparative cell separation from tissue isolates and for microcarrier-based cell expansion.

  10. In vitro cytotoxicity of Selol-loaded magnetic nanocapsules against neoplastic cell lines under AC magnetic field activation

    NASA Astrophysics Data System (ADS)

    Falqueiro, A. M.; Siqueira-Moura, M. P.; Jardim, D. R.; Primo, F. L.; Morais, P. C.; Mosiniewicz-Szablewska, E.; Suchocki, P.; Tedesco, A. C.

    2012-04-01

    The goals of this study are to evaluate invitro compatibility of magnetic nanomaterials and their therapeutic potential against cancer cells. Highly stable ionic magnetic fluid sample (maghemite, γ-Fe2O3) and Selol were incorporated into polymeric nanocapsules by nanoprecipitation method. The cytotoxic effect of Selol-loaded magnetic nanocapsules was assessed on murine melanoma (B16-F10) and oral squamous cell carcinoma (OSCC) cell lines following AC magnetic field application. The influence of different nanocapsules on cell viability was investigated by colorimetric MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In the absence of AC magnetic field Selol-loaded magnetic nanocapsules, containing 100 µg/mL Selol plus 5 × 1012 particle/mL, showed antitumoral activity of about 50% on B16-F10 melanoma cells while OSCC carcinoma cells demonstrated drug resistance at all concentrations of Selol and magnetic fluid (range of 100-500 µg/mL Selol and 5 × 1012-2.5 × 1013 particle/mL). On the other hand, under AC applied fields (1 MHz and 40 Oe amplitude) B16-F10 cell viability was reduced down to 40.5% (±3.33) at the highest concentration of nanoencapsulated Selol. The major effect, however, was observed on OSCC cells since the cell viability drops down to about 33.3% (±0.38) under application of AC magnetic field. These findings clearly indicate that the Selol-loaded magnetic nanocapsules present different toxic effects on neoplastic cell lines. Further, the cytotoxic effect was maximized under AC magnetic field application on OSCC, which emphasizes the effectiveness of the magnetohyperthermia approach.

  11. Microrheology of cells with magnetic force modulation atomic force microscopy.

    PubMed

    Rebêlo, L M; de Sousa, J S; Mendes Filho, J; Schäpe, J; Doschke, H; Radmacher, M

    2014-04-01

    We propose a magnetic force modulation method to measure the stiffness and viscosity of living cells using a modified AFM apparatus. An oscillating magnetic field makes a magnetic cantilever oscillate in contact with the sample, producing a small AC indentation. By comparing the amplitude of the free cantilever motion (A0) with the motion of the cantilever in contact with the sample (A1), we determine the sample stiffness and viscosity. To test the method, the frequency-dependent stiffness of 3T3 fibroblasts was determined as a power law k(s)(f) = α + β(f/f¯)(γ) (α = 7.6 × 10(-4) N m(-1), β = 1.0 × 10(-4) N m(-1), f¯ = 1 Hz, γ = 0.6), where the coefficient γ = 0.6 is in good agreement with rheological data of actin solutions with concentrations similar to those in cells. The method also allows estimation of the internal friction of the cells. In particular we found an average damping coefficient of 75.1 μN s m(-1) for indentation depths ranging between 1.0 μm and 2.0 μm. PMID:24651941

  12. Noninvasive Tracking of Encapsulated Insulin Producing Cells Labelled with Magnetic Microspheres by Magnetic Resonance Imaging

    PubMed Central

    Yim, Mandy M. W.; Foster, Jayne L.; Oberholzer, Jose

    2016-01-01

    Microencapsulated islets are usually injected free-floating into the peritoneal cavity, so the position of the grafts remains elusive after transplantation. This study aims to assess magnetic resonance imaging (MRI) as a noninvasive means to track microencapsulated insulin producing cells following transplantation. Encapsulated insulin producing cells (MIN6 and human islets) were labelled with magnetic microspheres (MM), assessed for viability and insulin secretion, and imaged in vitro using a clinical grade 3 T MRI and in vivo using both clinical grade 3 T and research grade 11.7 T MRI. Fluorescent imaging demonstrated the uptake of MM by both MIN6 and human islets with no changes in cell morphology and viability. MM labelling did not affect the glucose responsiveness of encapsulated MIN6 and islets in vitro. In vivo encapsulated MM-labelled MIN6 normalized sugar levels when transplanted into diabetic mice. In vitro MRI demonstrated that single microcapsules as well as clusters of encapsulated MM-labelled cells could be visualised clearly in agarose gel phantoms. In vivo encapsulated MM-labelled MIN6 could be visualised more clearly within the peritoneal cavity as discrete hypointensities using the high power 11.7 T but not the clinical grade 3 T MRI. This study demonstrates a method to noninvasively track encapsulated insulin producing cells by MM labelling and MRI.

  13. Quantification of Non-Specific Binding of Magnetic Micro and Nano particles using Cell Tracking Velocimetry: Implication for magnetic cell separation and detection

    PubMed Central

    Chalmers, J.J.; Xiong, Y.; Jin, X.; Shao, M.; Tong, X.; Farag, S.; Zborowski, M.

    2012-01-01

    The maturation of magnetic cell separation technology places increasing demands on magnetic cell separation performance. While a number of factors can cause suboptimal performance, one of the major challenges can be non-specific binding of magnetic nano or micro particles to non-targeted cells. Depending on the type of separation, this non-specific binding can have a negative effect on the final purity, the recovery of the targeted cells, or both. In this work, we quantitatively demonstrate that non-specific binding of magnetic nanoparticles can impart a magnetization to cells such that these cells can be retained in a separation column and thus negatively impact the purity of the final product and the recovery of the desired cells. Through experimental data and theoretical arguments, we demonstrate that the number of MACS magnetic particles needed to impart a magnetization that is sufficient to causes non-targeted cells to be retained in the column to be on the order of 500 to 1,000 nanoparticles. This number of non-specifically bound particles was demonstrated experimentally with an instrument, cell tracking velocimeter, CTV, and it is demonstrated that the sensitivity of the CTV instrument for Fe atoms contained in magnetic nanoparticles on the order of 1 × 10−15 g/mL of Fe. PMID:20014141

  14. Non-chemotoxic induction of cancer cell death using magnetic nanowires.

    PubMed

    Contreras, Maria F; Sougrat, Rachid; Zaher, Amir; Ravasi, Timothy; Kosel, Jürgen

    2015-01-01

    In this paper, we show that magnetic nanowires with weak magnetic fields and low frequencies can induce cell death via a mechanism that does not involve heat production. We incubated colon cancer cells with two concentrations (2.4 and 12 μg/mL) of nickel nanowires that were 35 nm in diameter and exposed the cells and nanowires to an alternating magnetic field (0.5 mT and 1 Hz or 1 kHz) for 10 or 30 minutes. This low-power field exerted a force on the magnetic nanowires, causing a mechanical disturbance to the cells. Transmission electron microscopy images showed that the nanostructures were internalized into the cells within 1 hour of incubation. Cell viability studies showed that the magnetic field and the nanowires separately had minor deleterious effects on the cells; however, when combined, the magnetic field and nanowires caused the cell viability values to drop by up to 39%, depending on the strength of the magnetic field and the concentration of the nanowires. Cell membrane leakage experiments indicated membrane leakage of 20%, suggesting that cell death mechanisms induced by the nanowires and magnetic field involve some cell membrane rupture. Results suggest that magnetic nanowires can kill cancer cells. The proposed process requires simple and low-cost equipment with exposure to only very weak magnetic fields for short time periods. PMID:25834430

  15. Non-chemotoxic induction of cancer cell death using magnetic nanowires

    PubMed Central

    Contreras, Maria F; Sougrat, Rachid; Zaher, Amir; Ravasi, Timothy; Kosel, Jürgen

    2015-01-01

    In this paper, we show that magnetic nanowires with weak magnetic fields and low frequencies can induce cell death via a mechanism that does not involve heat production. We incubated colon cancer cells with two concentrations (2.4 and 12 μg/mL) of nickel nanowires that were 35 nm in diameter and exposed the cells and nanowires to an alternating magnetic field (0.5 mT and 1 Hz or 1 kHz) for 10 or 30 minutes. This low-power field exerted a force on the magnetic nanowires, causing a mechanical disturbance to the cells. Transmission electron microscopy images showed that the nanostructures were internalized into the cells within 1 hour of incubation. Cell viability studies showed that the magnetic field and the nanowires separately had minor deleterious effects on the cells; however, when combined, the magnetic field and nanowires caused the cell viability values to drop by up to 39%, depending on the strength of the magnetic field and the concentration of the nanowires. Cell membrane leakage experiments indicated membrane leakage of 20%, suggesting that cell death mechanisms induced by the nanowires and magnetic field involve some cell membrane rupture. Results suggest that magnetic nanowires can kill cancer cells. The proposed process requires simple and low-cost equipment with exposure to only very weak magnetic fields for short time periods. PMID:25834430

  16. Using Magnetic Nanoparticles for Gene Transfer to Neural Stem Cells: Stem Cell Propagation Method Influences Outcomes

    PubMed Central

    Pickard, Mark R.; Adams, Christopher F.; Barraud, Perrine; Chari, Divya M.

    2015-01-01

    Genetically engineered neural stem cell (NSC) transplants offer a key strategy to augment neural repair by releasing therapeutic biomolecules into injury sites. Genetic modification of NSCs is heavily reliant on viral vectors but cytotoxic effects have prompted development of non-viral alternatives, such as magnetic nanoparticle (MNPs). NSCs are propagated in laboratories as either 3-D suspension “neurospheres” or 2-D adherent “monolayers”. MNPs deployed with oscillating magnetic fields (“magnetofection technology”) mediate effective gene transfer to neurospheres but the efficacy of this approach for monolayers is unknown. It is important to address this issue as oscillating magnetic fields dramatically enhance MNP-based transfection in transplant cells (e.g., astrocytes and oligodendrocyte precursors) propagated as monolayers. We report for the first time that oscillating magnetic fields enhanced MNP-based transfection with reporter and functional (basic fibroblast growth factor; FGF2) genes in monolayer cultures yielding high transfection versus neurospheres. Transfected NSCs showed high viability and could re-form neurospheres, which is important as neurospheres yield higher post-transplantation viability versus monolayer cells. Our results demonstrate that the combination of oscillating magnetic fields and a monolayer format yields the highest efficacy for MNP-mediated gene transfer to NSCs, offering a viable non-viral alternative for genetic modification of this important neural cell transplant population. PMID:25918990

  17. Cell-Based Therapy in TBI: Magnetic Retention of Neural Stem Cells In Vivo.

    PubMed

    Shen, Wei-Bin; Plachez, Céline; Tsymbalyuk, Orest; Tsymbalyuk, Natalya; Xu, Su; Smith, Aaron M; Michel, Sarah L J; Yarnell, Deborah; Mullins, Roger; Gullapalli, Rao P; Puche, Adam; Simard, J Marc; Fishman, Paul S; Yarowsky, Paul

    2016-01-01

    Stem cell therapy is under active investigation for traumatic brain injury (TBI). Noninvasive stem cell delivery is the preferred method, but retention of stem cells at the site of injury in TBI has proven challenging and impacts effectiveness. To investigate the effects of applying a magnetic field on cell homing and retention, we delivered human neuroprogenitor cells (hNPCs) labeled with a superparamagnetic nanoparticle into post-TBI animals in the presence of a static magnetic field. We have previously devised a method of loading hNPCs with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles Molday ION Rhodamine B (MIRB™). Labeling of hNPCs (MIRB-hNPCs) does not affect hNPC viability, proliferation, or differentiation. The 0.6 tesla (T) permanent magnet was placed ∼4 mm above the injured parietal cortex prior to intracarotid injection of 4 × 10(4) MIRB-hNPCs. Fluorescence imaging, Perls' Prussian blue histochemistry, immunocytochemistry with SC121, a human-specific antibody, and T2-weighted magnetic resonance imaging ex vivo revealed there was increased homing and retention of MIRB-hNPCs in the injured cortex as compared to the control group in which MIRB-hNPCs were injected in the absence of a static magnetic field. Fluoro-Jade C staining and immunolabeling with specific markers confirmed the viability status of MIRB-hNPCs posttransplantation. These results show that increased homing and retention of MIRB-hNPCs post-TBI by applying a static magnetic field is a promising technique to deliver cells into the CNS for treatment of neurological injuries and neurodegenerative diseases. PMID:26395573

  18. Magnetic resonance imaging in pediatric sickle cell anemia

    PubMed Central

    Zhang, Xinxian; Li, Chenglong; Li, Qiancheng

    2016-01-01

    Sickle cell disease is the result of altered genetic make up due to hereditary encounter and its form as homozygous sickle cell anemia is the most common and severe. The disease is characterized by chronic anemia, recurrent pain crises and vascular occlusion. Neurologically, there is a high incidence of stroke in childhood, as well as cognitive dysfunction. Newborn screening programmes and preventative treatments have allowed a much longer lifespan. However, recently, neurological research has shifted to characterizing more subtle aspects of brain development and functioning that may be critically important to the individual's quality of life. The present review article examines the neurological and neurocognitive complications of sickle cell disease, and discusses the importance of magnetic resonance imaging scans in the management of the disease. PMID:27446243

  19. Magnetic Manipulation of Nanorods in the Nucleus of Living Cells

    PubMed Central

    Celedon, Alfredo; Hale, Christopher M.; Wirtz, Denis

    2011-01-01

    The organization of chromatin in the cell nucleus is crucial for gene expression regulation. However, physically probing the nuclear interior is challenging because high forces have to be applied using minimally invasive techniques. Here, magnetic nanorods embedded in the nucleus of living cells are subjected to controlled rotational forces, producing micron-sized displacements in the nuclear interior. The resulting time-dependent rotation of the nanorods is analyzed in terms of viscoelastic parameters of the nucleus, in wild-type and Lamin A/C deficient cells. This method and analysis reveal that Lamin A/C knockout, together perhaps with other changes that result from the knockout, induce significant decreases in the nuclear viscosity and elasticity. PMID:22004741

  20. Biomedical Applications of Magnetic Nanoparticles: Delivering Genes and Remote Control of Cells

    NASA Astrophysics Data System (ADS)

    Dobson, Jon

    2013-03-01

    The use of magnetic micro- and nanoparticles for biomedical applications was first proposed in the 1920s as a way to measure the rehological properties of the cell's cytoplasm. Since that time, magnetic micro- and nanoparticle synthesis, coating and bio-functionalization have advanced significantly, as have the applications for these particles. Magnetic micro- and nanoparticles are now used in a variety of biomedical techniques such as targeted drug delivery, MRI contrast enhancement, gene transfection, immno-assay and cell sorting. More recently, magnetic micro- and nanoparticles have been used to investigate and manipulate cellular processes both in vitro and in vivo. This talk will focus on magnetic nanoparticle targeting to and actuation of cell surface receptors to control cell signaling cascades to control cell behavior. This technology has applications in disease therapy, cell engineering and regenerative medicine. The use of magnetic nanoparticles and oscillating magnet arrays for enhanced gene delivery will also be discussed.

  1. Local viscoelasticity of living cells measured by rotational magnetic spectroscopy

    PubMed Central

    Berret, J.-F.

    2016-01-01

    When submitted to a magnetic field, micron-size wires with superparamagnetic properties behave as embedded rheometers and represent interesting sensors for microrheology. Here we use rotational magnetic spectroscopy to measure the shear viscosity of the cytoplasm of living cells. We address the question of whether the cytoplasm is a viscoelastic liquid or an elastic gel. The main result of the study is the observation of a rotational instability between a synchronous and an asynchronous regime of rotation, found for murine fibroblasts and human cancer cells. For wires of susceptibility 3.6, the transition occurs in the range 0.01–1 rad s−1. The determination of the shear viscosity (10–100 Pa s) and elastic modulus (5–20 Pa) confirms the viscoelastic character of the cytoplasm. In contrast to earlier studies, it is concluded that the interior of living cells can be described as a viscoelastic liquid, and not as an elastic gel. PMID:26729062

  2. Individual Mammalian Cell Magnetic Measurements with a Superconducting Quantum Interference Device

    NASA Astrophysics Data System (ADS)

    Palmstrom, Johanna C.; Brewer, Kimberly; Tee, Sui Seng; Theis, Eric; Rutt, Brian; Moler, Kathryn A.

    2015-03-01

    Magnetism can be introduced into otherwise nonmagnetic cells by the uptake of superparamagnetic iron oxide (SPIO) nanoparticles. SPIO nanoparticles are used in numerous biomedical applications including cellular therapies and targeted drug delivery. Currently there are few tools capable of characterizing individual magnetic nanoparticles and the magnetic properties of individual mammalian cells loaded with SPIO. Our scanning superconducting quantum interference devices (SQUIDs) are good candidates for these measurements due to their high sensitivity to magnetic dipole moments (approx. 200 μb/ √Hz) In this study, we use a scanning SQUID to image the magnetic flux from SPIO loaded H1299 lung cancer cells. We find that the magnetic moment spatially varies inside the cell with each cell having a unique distribution of moments. We also correlate these magnetic images with optical and scanning electron microscope images. These results show that the SQUID is a useful tool for imaging biological magnetism. The visualization of single cell magnetism and the quantification of magnetic dipole moments in magnetically labeled cells can be used to optimize conventional biological magnetic imaging techniques, such as MRI.

  3. Analysis of cell mechanics in single vinculin-deficient cells using a magnetic tweezer

    NASA Technical Reports Server (NTRS)

    Alenghat, F. J.; Fabry, B.; Tsai, K. Y.; Goldmann, W. H.; Ingber, D. E.

    2000-01-01

    A magnetic tweezer was constructed to apply controlled tensional forces (10 pN to greater than 1 nN) to transmembrane receptors via bound ligand-coated microbeadswhile optically measuring lateral bead displacements within individual cells. Use of this system with wild-type F9 embryonic carcinoma cells and cells from a vinculin knockout mouse F9 Vin (-/-) revealed much larger differences in the stiffness of the transmembrane integrin linkages to the cytoskeleton than previously reported using related techniques that measured average mechanical properties of large cell populations. The mechanical properties measured varied widely among cells, exhibiting an approximately log-normal distribution. The median lateral bead displacement was 2-fold larger in F9 Vin (-/-) cells compared to wild-type cells whereas the arithmetic mean displacement only increased by 37%. We conclude that vinculin serves a greater mechanical role in cells than previously reported and that this magnetic tweezer device may be useful for probing the molecular basis of cell mechanics within single cells. Copyright 2000 Academic Press.

  4. Fundamentals and Application of Magnetic Particles in Cell Isolation and Enrichment

    PubMed Central

    Plouffe, Brian D.; Murthy, Shashi K.; Lewis, Laura H.

    2014-01-01

    Magnetic sorting using magnetic beads has become a routine methodology for the separation of key cell populations from biological suspensions. Due to the inherent ability of magnets to provide forces at a distance, magnetic cell manipulation is now a standardized process step in numerous processes in tissue engineering, medicine, and in fundamental biological research. Herein we review the current status of magnetic particles to enable isolation and separation of cells, with a strong focus on the fundamental governing physical phenomena, properties and syntheses of magnetic particles and on current applications of magnet-based cell separation in laboratory and clinical settings. We highlight the contribution of cell separation to biomedical research and medicine and detail modern cell separation methods (both magnetic and non-magnetic). In addition to a review of the current state-of-the-art in magnet-based cell sorting, we discuss current challenges and available opportunities for further research, development and commercialization of magnetic particle-based cell separation systems. PMID:25471081

  5. Magnetic Resonance Imaging as a Biomarker for Renal Cell Carcinoma

    PubMed Central

    Wu, Yan; Kwon, Young Suk; Labib, Mina; Foran, David J.; Singer, Eric A.

    2015-01-01

    As the most common neoplasm arising from the kidney, renal cell carcinoma (RCC) continues to have a significant impact on global health. Conventional cross-sectional imaging has always served an important role in the staging of RCC. However, with recent advances in imaging techniques and postprocessing analysis, magnetic resonance imaging (MRI) now has the capability to function as a diagnostic, therapeutic, and prognostic biomarker for RCC. For this narrative literature review, a PubMed search was conducted to collect the most relevant and impactful studies from our perspectives as urologic oncologists, radiologists, and computational imaging specialists. We seek to cover advanced MR imaging and image analysis techniques that may improve the management of patients with small renal mass or metastatic renal cell carcinoma. PMID:26609190

  6. Release of Magnetic Nanoparticles from Cell-Encapsulating Biodegradable Nanobiomaterials

    PubMed Central

    Xu, Feng; Inci, Fatih; Mullick, Omer; Gurkan, Umut Atakan; Sung, Yuree; Kavaz, Doga; Li, Baoqiang; Denkbas, Emir Baki; Demirci, Utkan

    2013-01-01

    The future of tissue engineering requires development of intelligent biomaterials using nanoparticles. Magnetic nanoparticles (MNPs) have several applications in biology and medicine; one example is Food and Drug Administration (FDA)-approved contrast agents in magnetic resonance imaging. Recently, MNPs have been encapsulated within cell-encapsulating hydrogels to create novel nanobiomaterials (i.e., M-gels), which can be manipulated and assembled in magnetic fields. The M-gels can be used as building blocks for bottom-up tissue engineering to create 3D tissue constructs. For tissue engineering applications of M-gels, it is essential to study the release of encapsulated MNPs from the hydrogel polymer network and the effect of MNPs on hydrogel properties, including mechanical characteristics, porosity, swelling behavior, and cellular response (e.g., viability, growth). Therefore, we evaluated the release of MNPs from photocrosslinkable gelatin methacrylate hydrogels as the polymer network undergoes biodegradation using inductively coupled plasma atomic emission spectroscopy. MNP release correlated linearly with hydrogel biodegradation rate with correlation factors (Pearson product moment correlation coefficient) of 0.96 ± 0.03 and 0.99 ± 0.01 for MNP concentrations of 1% and 5%, respectively. We also evaluated the effect of MNPs on hydrogel mechanical properties, porosity, and swelling behavior, as well as cell viability and growth in MNP-encapsulating hydrogels. Fibroblasts encapsulated with MNPs in hydrogels remained viable (>80% at t = 144 h) and formed microtissue constructs in culture (t = 144 h). These results indicated that MNP-encapsulating hydrogels show promise as intelligent nanobiomaterials, with great potential to impact broad areas of bioengineering, including tissue engineering, regenerative medicine, and pharmaceutical applications. PMID:22680777

  7. Removal of malaria-infected red blood cells using magnetic cell separators: A computational study.

    PubMed

    Kim, Jeongho; Massoudi, Mehrdad; Antaki, James F; Gandini, Alberto

    2012-02-15

    High gradient magnetic field separators have been widely used in a variety of biological applications. Recently, the use of magnetic separators to remove malaria-infected red blood cells (pRBCs) from blood circulation in patients with severe malaria has been proposed in a dialysis-like treatment. The capture efficiency of this process depends on many interrelated design variables and constraints such as magnetic pole array pitch, chamber height, and flow rate. In this paper, we model the malaria-infected RBCs (pRBCs) as paramagnetic particles suspended in a Newtonian fluid. Trajectories of the infected cells are numerically calculated inside a micro-channel exposed to a periodic magnetic field gradient. First-order stiff ordinary differential equations (ODEs) governing the trajectory of particles under periodic magnetic fields due to an array of wires are solved numerically using the 1(st) -5(th) order adaptive step Runge-Kutta solver. The numerical experiments show that in order to achieve a capture efficiency of 99% for the pRBCs it is required to have a longer length than 80 mm; this implies that in principle, using optimization techniques the length could be adjusted, i.e., shortened to achieve 99% capture efficiency of the pRBCs. PMID:22345827

  8. Erythrocyte Enrichment in Hematopoietic Progenitor Cell Cultures Based on Magnetic Susceptibility of the Hemoglobin

    PubMed Central

    Jin, Xiaoxia; Abbot, Stewart; Zhang, Xiaokui; Kang, Lin; Voskinarian-Berse, Vanessa; Zhao, Rui; Kameneva, Marina V.; Moore, Lee R.; Chalmers, Jeffrey J.; Zborowski, Maciej

    2012-01-01

    Using novel media formulations, it has been demonstrated that human placenta and umbilical cord blood-derived CD34+ cells can be expanded and differentiated into erythroid cells with high efficiency. However, obtaining mature and functional erythrocytes from the immature cell cultures with high purity and in an efficient manner remains a significant challenge. A distinguishing feature of a reticulocyte and maturing erythrocyte is the increasing concentration of hemoglobin and decreasing cell volume that results in increased cell magnetophoretic mobility (MM) when exposed to high magnetic fields and gradients, under anoxic conditions. Taking advantage of these initial observations, we studied a noninvasive (label-free) magnetic separation and analysis process to enrich and identify cultured functional erythrocytes. In addition to the magnetic cell separation and cell motion analysis in the magnetic field, the cell cultures were characterized for cell sedimentation rate, cell volume distributions using differential interference microscopy, immunophenotyping (glycophorin A), hemoglobin concentration and shear-induced deformability (elongation index, EI, by ektacytometry) to test for mature erythrocyte attributes. A commercial, packed column high-gradient magnetic separator (HGMS) was used for magnetic separation. The magnetically enriched fraction comprised 80% of the maturing cells (predominantly reticulocytes) that showed near 70% overlap of EI with the reference cord blood-derived RBC and over 50% overlap with the adult donor RBCs. The results demonstrate feasibility of label-free magnetic enrichment of erythrocyte fraction of CD34+ progenitor-derived cultures based on the presence of paramagnetic hemoglobin in the maturing erythrocytes. PMID:22952572

  9. Disruptive effect of Dzyaloshinskii-Moriya interaction on the magnetic memory cell performance

    NASA Astrophysics Data System (ADS)

    Sampaio, J.; Khvalkovskiy, A. V.; Kuteifan, M.; Cubukcu, M.; Apalkov, D.; Lomakin, V.; Cros, V.; Reyren, N.

    2016-03-01

    In order to increase the thermal stability of a magnetic random access memory cell, materials with high spin-orbit interaction are often introduced in the storage layer. As a side effect, a strong Dzyaloshinskii-Moriya interaction (DMI) may arise in such systems. Here, we investigate the impact of DMI on the magnetic cell performance, using micromagnetic simulations. We find that DMI strongly promotes non-uniform magnetization states and non-uniform switching modes of the magnetic layer. It appears to be detrimental for both the thermal stability of the cell and its switching current, leading to considerable deterioration of the cell performance even for a moderate DMI amplitude.

  10. Magnetic assembly-mediated enhancement of differentiation of mouse bone marrow cells cultured on magnetic colloidal assemblies

    NASA Astrophysics Data System (ADS)

    Sun, Jianfei; Liu, Xuan; Huang, Jiqing; Song, Lina; Chen, Zihao; Liu, Haoyu; Li, Yan; Zhang, Yu; Gu, Ning

    2014-05-01

    Here we reported an interesting phenomenon that the field-induced assemblies of magnetic nanoparticles can promote the differentiation of primary mouse bone marrow cells into osteoblasts. The reason was thought to lie in the remnant magnetic interaction inside the assemblies which resulted from the magnetic field-directed assembly. Influence of the assemblies on the cells was realized by means of interface effect rather than the internalization effect. We fabricated a stripe-like assemblies array on the glass plate and cultured cells on this surface. We characterized the morphology of assemblies and measured the mechanic property as well as the magnetic property. The cellular differentiation was measured by staining and quantitative PCR. Finally, Fe uptake was excluded as the reason to cause the phenomenon.

  11. Magnetic assembly-mediated enhancement of differentiation of mouse bone marrow cells cultured on magnetic colloidal assemblies

    PubMed Central

    Sun, Jianfei; Liu, Xuan; Huang, Jiqing; Song, Lina; Chen, Zihao; Liu, Haoyu; Li, Yan; Zhang, Yu; Gu, Ning

    2014-01-01

    Here we reported an interesting phenomenon that the field-induced assemblies of magnetic nanoparticles can promote the differentiation of primary mouse bone marrow cells into osteoblasts. The reason was thought to lie in the remnant magnetic interaction inside the assemblies which resulted from the magnetic field-directed assembly. Influence of the assemblies on the cells was realized by means of interface effect rather than the internalization effect. We fabricated a stripe-like assemblies array on the glass plate and cultured cells on this surface. We characterized the morphology of assemblies and measured the mechanic property as well as the magnetic property. The cellular differentiation was measured by staining and quantitative PCR. Finally, Fe uptake was excluded as the reason to cause the phenomenon. PMID:24874764

  12. Tracking of iron-labeled human neural stem cells by magnetic resonance imaging in cell replacement therapy for Parkinson's disease

    PubMed Central

    Ramos-Gómez, Milagros; Martínez-Serrano, Alberto

    2016-01-01

    Human neural stem cells (hNSCs) derived from the ventral mesencephalon are powerful research tools and candidates for cell therapies in Parkinson's disease. However, their clinical translation has not been fully realized due, in part, to the limited ability to track stem cell regional localization and survival over long periods of time after in vivo transplantation. Magnetic resonance imaging provides an excellent non-invasive method to study the fate of transplanted cells in vivo. For magnetic resonance imaging cell tracking, cells need to be labeled with a contrast agent, such as magnetic nanoparticles, at a concentration high enough to be easily detected by magnetic resonance imaging. Grafting of human neural stem cells labeled with magnetic nanoparticles allows cell tracking by magnetic resonance imaging without impairment of cell survival, proliferation, self-renewal, and multipotency. However, the results reviewed here suggest that in long term grafting, activated microglia and macrophages could contribute to magnetic resonance imaging signal by engulfing dead labeled cells or iron nanoparticles dispersed freely in the brain parenchyma over time. PMID:26981077

  13. The effect of nonuniform magnetic targeting of intracoronary-delivering mesenchymal stem cells on coronary embolisation.

    PubMed

    Huang, Zheyong; Shen, Yunli; Pei, Ning; Sun, Aijun; Xu, Jianfeng; Song, Yanan; Huang, Gangyong; Sun, Xiaoning; Zhang, Shuning; Qin, Qing; Zhu, Hongming; Yang, Shan; Yang, Xiangdong; Zou, Yunzeng; Qian, Juying; Ge, Junbo

    2013-12-01

    Magnetic targeting has been recently introduced to enhance cell retention in animals with acute myocardial infarction. However, it is unclear whether the magnetic accumulation of intravascular cells increases the risk of coronary embolism. Upon finite element analysis, we found that the permanent magnetic field was nonuniform, manifestated as attenuation along the vertical axis and polarisation along the horizontal axis. In the in vitro experiments, iron-labelled mesenchymal stem cells (MSCs) were accumulated in layers predominantly at the edge of the magnet. In an ischaemic rat model subjected to intracavitary MSCs injection, magnetic targeting induced unfavourable vascular embolisation and an inhomogeneous distribution of the donor cells, which prevented the enhanced cell retention from translating into additional functional benefit. These potential complications of magnetic targeting should be thoroughly investigated and overcome before clinical application. PMID:24055521

  14. Hydrodynamic instability in a magnetically driven suspension of paramagnetic red blood cells.

    PubMed

    Kashevsky, B E; Zholud, A M; Kashevsky, S B

    2015-09-01

    We investigate the magnetically driven motion in suspensions of paramagnetic particles. Our object is diluted deoxygenated whole blood with paramagnetic red blood cells (RBCs). We use direct observations in a closed vertical Hele-Shaw channel, and a well-defined magnetic force field applied horizontally in the channel plane. At very low cell concentrations, we register single-particle motion mode, track individual cells and determine their hydrodynamic and magnetic characteristics. Above 0.2 volume percent concentration, we observe local swirls and a global transient quasi-periodic vortex structure, intensifying with increasing cell concentration, but surprisingly this does not influence the time and purity of the magnetic extraction of RBCs. Our observations shed light on the behavioral complexity of magnetically driven submagnetic suspensions, an important issue for the emerging microfluidic technology of direct magnetic cell separation and intriguing for the mechanics of particulate soft matter. PMID:26212385

  15. Harvesting of Dunaliella tertiolecta cells by magnetic filtration

    NASA Astrophysics Data System (ADS)

    Manousakis, Emmanouil; Manariotis, Ioannis D.

    2015-04-01

    The rising cost and reduced reserves of fossil fuels have enhanced the interest for finding alterative energy sources. Microalgae are considered to be the only sustainable option in biodiesel production for two key points. The energy yield from microalgae is much higher than that of oil producing crops, and the cultivation of algae it is not antagonistic with food supply chain. Because of the small size of microalgae and the dilute nature of algal cultures, the harvesting cost of microalgae is so far a limiting step for the scale up of microalgal biofuel production. It is estimated that the algal harvesting cost is at least 20-30% of the total biomass production cost. Traditional methods, which have been employed for the recovery of microalgal biomass, include centrifugation, gravity separation, filtration, flocculation, and flotation. Alternative approaches, other than conventional methods, capable of processing large cultures volume at a low cost, and reducing effluent toxicity are essential for microalgal biomass production. Magnetic separation is a promising technology and has been applied for algal removal in the mid of 1970s. The aim of this study was to investigate the harvesting of microalgae cells using magnetic microparticles (MPs). Dunaliella tertiolecta was selected as a representative for marine microalgae. The cultivation of microalgae was conducted under continuous artificial light, in 20 L flasks. Iron oxide microparticles were prepared by microwave irradiation of FeSO4 7H2O in an alkaline solution. Samples were taken at different operation intervals to conduct harvesting studies. Batch and flow-through experiments were conducted in order to investigate the effect of the magnetic material on microalgae removal. Algal removal in flow through experiments ranged from 70 to 85% depending on the initial MPs concentration even at very short hydraulic retention times (i.e. 2 min). In batch tests, algal removal was up to 97% at MPs concentration of 490 mg/L.

  16. Magnetically driven spinning nanowires as effective materials for eradicating living cells

    NASA Astrophysics Data System (ADS)

    Choi, Daniel S.; Hopkins, Xiaoping; Kringel, Rosemarie; Park, Jungrae; Jeon, In Tak; Keun Kim, Young

    2012-04-01

    We present a method to inflame cells, in vitro, by applying an alternating current (ac) magnetic field to ferromagnetic nanowires (NWs) internalized by living cells. Nickel (Ni) NWs were internalized by human embryonic kidney cells (HEK-293). The application of ac magnetic field to the cells induced spinning of the cells via the motion of internalized NWs. This resulted in cell death by physically causing damage. A study of the response of cytokine to cells with spinning NWs shows increased interleukin-6 effects when compared with responses from non-spinning cells. The spinning effect of cells caused by the application of magnetic field can be used to target and inflame the cells. Such experiments suggest the possibility of inflaming cells for the treatment of cancer.

  17. Magnetic Relaxometry with an Atomic Magnetometer and SQUID Sensors on Targeted Cancer Cells

    PubMed Central

    Johnson, Cort; Adolphi, Natalie L.; Butler, Kimberly L.; Debbie M, Lovato; Larson, Richard; Schwindt, Peter D.D.; Flynn, Edward R.

    2012-01-01

    Magnetic relaxometry methods have been shown to be very sensitive in detecting cancer cells and other targeted diseases. Superconducting Quantum Interference Device (SQUID) sensors are one of the primary sensor systems used in this methodology because of their high sensitivity with demonstrated capabilities of detecting fewer than 100,000 magnetically-labeled cancer cells. The emerging technology of atomic magnetometers (AM) represents a new detection method for magnetic relaxometry with high sensitivity and without the requirement for cryogens. We report here on a study of magnetic relaxometry using both AM and SQUID sensors to detect cancer cells that are coated with superparamagnetic nanoparticles through antibody targeting. The AM studies conform closely to SQUID sensor results in the measurement of the magnetic decay characteristics following a magnetization pulse. The AM and SQUID sensor data are well described theoretically for superparamagnetic particles bound to cells and the results can be used to determine the number of cells in a cell culture or tumor. The observed fields and magnetic moments of cancer cells are linear with the number of cells over a very large range. The AM sensor demonstrates very high sensitivity for detecting magnetically labeled cells does not require cryogenic cooling and is relatively inexpensive. PMID:22773885

  18. The measurement of small magnetic signals from magnetic nanoparticles attached to the cell surface and surrounding living cells using a general-purpose SQUID magnetometer

    NASA Astrophysics Data System (ADS)

    Hashimoto, S.; Oda, T.; Yamada, K.; Takagi, M.; Enomoto, T.; Ohkohchi, N.; Takagi, T.; Kanamori, T.; Ikeda, H.; Yanagihara, H.; Kita, E.; Tasaki, A.

    2009-04-01

    Magnetic nanoparticles have recently been widely applied in the bio-medical field. Responding to the demand for a simple and sensitive magnetic assay system for bio-liquid samples, we employed a general-purpose superconducting quantum interference device (SQUID) magnetometer. Strips of filter paper were used as a liquid-specimen sample holder possessing a very small magnetic background signal. An aqueous solution of superparamagnetic iron-oxide nanoparticles (Resovist®) was dropped in a tiny blot-like spot in the middle of the filter paper and the magnetization was measured. Magnetic moments of a dilution series of Resovist® solutions versus the number of particles provided a linear graph, revealing that the magnetic moment per Resovist® particle was 8.25 × 10-17 emu. 1 × 105 cancer cells were incubated with Resovist®, and the number of Resovist® particles attached to the cell surface and surrounding a living cell was calculated to be 1.02 ± 0.14 × 107 particles/cell. Our system using a commercial SQUID magnetometer should be more than enough to determine the number of magnetic nanoparticles biologically reacting with living cells, contributing to the application of magneto nanomaterials to the life-science field.

  19. Bifunctional magnetic-fluorescent nanoparticles: synthesis, characterization, and cell imaging.

    PubMed

    Lu, Yanjiao; Zheng, Yang; You, Shusen; Wang, Feng; Gao, Zhuo; Shen, Jie; Yang, Wantai; Yin, Meizhen

    2015-03-11

    A new type of bifunctional magnetic-fluorescent Fe3O4@SiO2-PDI-PAA/Ca(2+) nanoparticles has been prepared by coating PDI-cored star polymers (PDI-PAA) onto the surface of Fe3O4@SiO2 core-shell nanostructures. The morphology and properties of the composite nanoparticles are investigated by transmission electron microscopy, ultraviolet-visible spectrometry, fluorescence spectrometry, and vibrating sample magnetometry. The composite nanoparticles display a strong red emission and superparamagnetic behavior at room temperature. The cell viability and uptake assays reveal good biocompatibility of these hybrid nanoparticles. Hence, the composite nanoparticles are of potential to be further explored as therapeutic vector in biomedical field. PMID:25691125

  20. Highly efficient magnetic targeting of mesenchymal stem cells in spinal cord injury

    PubMed Central

    Vaněček, Václav; Zablotskii, Vitalii; Forostyak, Serhiy; Růřička, Jiří; Herynek, Vít; Babič, Michal; Jendelová, Pavla; Kubinová, Šárka; Dejneka, Alexandr; Syková, Eva

    2012-01-01

    The transplantation of mesenchymal stem cells (MSC) is currently under study as a therapeutic approach for spinal cord injury, and the number of transplanted cells that reach the lesioned tissue is one of the critical parameters. In this study, intrathecally transplanted cells labeled with superparamagnetic iron oxide nanoparticles were guided by a magnetic field and successfully targeted near the lesion site in the rat spinal cord. Magnetic resonance imaging and histological analysis revealed significant differences in cell numbers and cell distribution near the lesion site under the magnet in comparison to control groups. The cell distribution correlated well with the calculated distribution of magnetic forces exerted on the transplanted cells in the subarachnoid space and lesion site. The kinetics of the cells’ accumulation near the lesion site is described within the framework of a mathematical model that reveals those parameters critical for cell targeting and suggests ways to enhance the efficiency of magnetic cell delivery. In particular, we show that the targeting efficiency can be increased by using magnets that produce spatially modulated stray fields. Such magnetic systems with tunable geometric parameters may provide the additional level of control needed to enhance the efficiency of stem cell delivery in spinal cord injury. PMID:22888231

  1. Yeast cells proliferation on various strong static magnetic fields and temperatures

    NASA Astrophysics Data System (ADS)

    Otabe, E. S.; Kuroki, S.; Nikawa, J.; Matsumoto, Y.; Ooba, T.; Kiso, K.; Hayashi, H.

    2009-03-01

    The effect of strong magnetic fields on activities of yeast cells were investigated. Experimental yeast cells were cultured in 5 ml of YPD(Yeast extract Peptone Dextrose) for the number density of yeast cells of 5.0 ±0.2 x 106/ml with various temperatures and magnetic fields up to 10 T. Since the yeast cells were placed in the center of the superconducting magnet, the effect of magnetic force due to the diamagnetism and magnetic gradient was negligibly small. The yeast suspension was opened to air and cultured in shaking condition. The number of yeast cells in the yeast suspension was counted by a counting plate with an optical microscope, and the time dependence of the number density of yeast cells was measured. The time dependence of the number density of yeast cells, ρ, of initial part is analyzed in terms of Malthus equation as given by ρ = ρo exp(kt), where k is the growth coefficient. It is found that, the growth coefficient under the magnetic field is suppressed compared with the control. The growth coefficient decreasing as increasing magnetic field and is saturated at about 5 T. On the other hand, it is found that the suppression of growth of yeast cells by the magnetic field is diminished at high temperatures.

  2. Biological effects of strong static magnetic fields on insulin-secreting cells

    NASA Astrophysics Data System (ADS)

    Sakurai, T.; Miyakoshi, J.

    2009-03-01

    The magnetic flux density of MRI for clinical diagnosis has been increasing. However, there remains very little biological data regarding the effect of strong static magnetic fields (SMFs) on human health. To evaluate the biological effects of strong SMFs, we cultured INS-1 cells under exposure to sham and SMF conditions for 1 or 2 h, and analyzed insulin secretion, mRNA expression, cell proliferation and cell number. Exposure to SMF with a high magnetic field gradient for 1 h significantly increased insulin secretion and insulin 1 mRNA expression. Exposure to SMF did not affect cell proliferation and cell number. Our results suggested that MRI systems with a higher magnetic flux density might not cause cell proliferative or functional damages on insulin-secreting cells.

  3. Isolation and manipulation of living adherent cells by micromolded magnetic rafts

    PubMed Central

    Gach, Philip C.; Wang, Yuli; Phillips, Colleen; Sims, Christopher E.; Allbritton, Nancy L.

    2011-01-01

    A new strategy for magnetically manipulating and isolating adherent cells with extremely high post-collection purity and viability is reported. Micromolded magnetic elements (termed microrafts) were fabricated in an array format and used as culture surfaces and carriers for living, adherent cells. A poly(styrene-co-acrylic acid) polymer containing well dispersed magnetic nanoparticles was developed for creating the microstructures by molding. Nanoparticles of γFe2O3 at concentrations up to 1% wt.∕wt. could be used to fabricate microrafts that were optically transparent, highly magnetic, biocompatible, and minimally fluorescent. To prevent cellular uptake of nanoparticles from the magnetic polymer, a poly(styrene-co-acrylic acid) layer lacking γFe2O3 nanoparticles was placed over the initial magnetic microraft layer to prevent cellular uptake of the γFe2O3 during culture. The microraft surface geometry and physical properties were altered by varying the polymer concentration or layering different polymers during fabrication. Cells plated on the magnetic microrafts were visualized using standard imaging techniques including brightfield, epifluorescence, and confocal microscopy. Magnetic microrafts possessing cells of interest were dislodged from the array and efficiently collected with an external magnet. To demonstrate the feasibility of cell isolation using the magnetic microrafts, a mixed population of wild-type cells and cells stably transfected with a fluorescent protein was plated onto an array. Microrafts possessing single, fluorescent cells were released from the array and magnetically collected. A post-sorting single-cell cloning rate of 92% and a purity of 100% were attained. PMID:22007266

  4. Water Permeability of Chlorella Cell Membranes by Nuclear Magnetic Resonance

    PubMed Central

    Stout, Darryl G.; Steponkus, Peter L.; Bustard, Larry D.; Cotts, Robert M.

    1978-01-01

    Measurement by two nuclear magnetic resonance (NMR) techniques of the mean residence time τa of water molecules inside Chlorella vulgaris (Beijerinck) var. “viridis” (Chodot) is reported. The first is the Conlon and Outhred (1972 Biochim Biophys Acta 288: 354-361) technique in which extracellular water is doped with paramagnetic Mn2+ ions. Some complications in application of this technique are identified as being caused by the affinity of Chlorella cell walls for Mn2+ ions which shortens the NMR relaxation times of intra- and extracellular water. The second is based upon observations of effects of diffusion on the spin echo of intra- and extracellular water. Echo attenuation of intracellular water is distinguished from that of extracellular water by the extent to which diffusive motion is restricted. Intracellular water, being restricted to the cell volume, suffers less echo attenuation. From the dependence of echo amplitude upon gradient strength at several values of echo time, the mean residence time of intracellular water can be determined. From the mean residence time of intracellular water, the diffusional water permeability coefficient of the Chlorella membrane is calculated to be 2.1 ± 0.4 × 10−3 cm sec−1. PMID:16660456

  5. Magnetic Labelling of Mesenchymal Stem Cells with Iron-Doped Hydroxyapatite Nanoparticles as Tool for Cell Therapy.

    PubMed

    Panseri, Silvia; Montesi, Monica; Iafisco, Michele; Adamiano, Alessio; Ghetti, Martina; Cenacchi, Giovanna; Tampieri, Anna

    2016-05-01

    Superparamagnetic nanoparticles offer several opportunities in nanomedicine and magnetic cell targeting. They are considered to be an extremely promising approach for the translation of cell-based therapies from the laboratory to clinical studies. In fact, after injection, the magnetic labeled cells could be driven by a static magnetic field and localized to the target site where they can perform their specific role. In this study, innovative iron-doped hydroxyapatite nanoparticles (FeHA NPs) were tested with mesenchymal stem cells (MSCs) as tools for cell therapy. Results showed that FeHA NPs could represent higher cell viability in'respect to commercial superparamagnetic iron oxide nanoparticles (SPION) at four different concentrations ranging from 10 μg/ml up to 200 μg/ml and would also upregulate an early marker involved in commitment and differentiation of MSCs. Moreover, FeHA NPs were uptaken without negatively affecting the cell behavior and their ultrastructure. Thus obtained magnetic cells were easily guided by application of a static magnetic field. This work demonstrates the promising opportunities of FeHA NPs in MSCs labeling due to the unique features of fast degradation and very low iron content of FeHA NPs compared to SPIONs. Likewise, due to the intrinsic properties of FeHA NPs, this approach could be simply transferred to different cell types as an effective magnetic carrier of drugs, growth factors, miRNA, etc., offering favorable prospects in nanomedicine. PMID:27305814

  6. Controlled Payload Release by Magnetic Field Triggered Neural Stem Cell Destruction for Malignant Glioma Treatment.

    PubMed

    Muroski, Megan E; Morshed, Ramin A; Cheng, Yu; Vemulkar, Tarun; Mansell, Rhodri; Han, Yu; Zhang, Lingjiao; Aboody, Karen S; Cowburn, Russell P; Lesniak, Maciej S

    2016-01-01

    Stem cells have recently garnered attention as drug and particle carriers to sites of tumors, due to their natural ability to track to the site of interest. Specifically, neural stem cells (NSCs) have demonstrated to be a promising candidate for delivering therapeutics to malignant glioma, a primary brain tumor that is not curable by current treatments, and inevitably fatal. In this article, we demonstrate that NSCs are able to internalize 2 μm magnetic discs (SD), without affecting the health of the cells. The SD can then be remotely triggered in an applied 1 T rotating magnetic field to deliver a payload. Furthermore, we use this NSC-SD delivery system to deliver the SD themselves as a therapeutic agent to mechanically destroy glioma cells. NSCs were incubated with the SD overnight before treatment with a 1T rotating magnetic field to trigger the SD release. The potential timed release effects of the magnetic particles were tested with migration assays, confocal microscopy and immunohistochemistry for apoptosis. After the magnetic field triggered SD release, glioma cells were added and allowed to internalize the particles. Once internalized, another dose of the magnetic field treatment was administered to trigger mechanically induced apoptotic cell death of the glioma cells by the rotating SD. We are able to determine that NSC-SD and magnetic field treatment can achieve over 50% glioma cell death when loaded at 50 SD/cell, making this a promising therapeutic for the treatment of glioma. PMID:26734932

  7. Controlled Payload Release by Magnetic Field Triggered Neural Stem Cell Destruction for Malignant Glioma Treatment

    PubMed Central

    Muroski, Megan E.; Morshed, Ramin A.; Cheng, Yu; Vemulkar, Tarun; Mansell, Rhodri; Han, Yu; Zhang, Lingjiao; Aboody, Karen S.; Cowburn, Russell P.; Lesniak, Maciej S.

    2016-01-01

    Stem cells have recently garnered attention as drug and particle carriers to sites of tumors, due to their natural ability to track to the site of interest. Specifically, neural stem cells (NSCs) have demonstrated to be a promising candidate for delivering therapeutics to malignant glioma, a primary brain tumor that is not curable by current treatments, and inevitably fatal. In this article, we demonstrate that NSCs are able to internalize 2 μm magnetic discs (SD), without affecting the health of the cells. The SD can then be remotely triggered in an applied 1 T rotating magnetic field to deliver a payload. Furthermore, we use this NSC-SD delivery system to deliver the SD themselves as a therapeutic agent to mechanically destroy glioma cells. NSCs were incubated with the SD overnight before treatment with a 1T rotating magnetic field to trigger the SD release. The potential timed release effects of the magnetic particles were tested with migration assays, confocal microscopy and immunohistochemistry for apoptosis. After the magnetic field triggered SD release, glioma cells were added and allowed to internalize the particles. Once internalized, another dose of the magnetic field treatment was administered to trigger mechanically induced apoptotic cell death of the glioma cells by the rotating SD. We are able to determine that NSC-SD and magnetic field treatment can achieve over 50% glioma cell death when loaded at 50 SD/cell, making this a promising therapeutic for the treatment of glioma. PMID:26734932

  8. Magnetic stromal layers for enhanced and unbiased recovery of co-cultured hematopoietic cells.

    PubMed

    Savvateeva, Maria V; Demin, Alexander M; Krasnov, Victor P; Belyavsky, Alexander V

    2016-09-15

    Cell co-culture systems have a long history of application in hematology and hold promise for successful hematopoietic stem and progenitor cell expansion. Here we report that various types of stromal cells used in such co-cultures can be rapidly and efficiently labeled with l-lysine-modified Fe3O4 magnetic nanoparticles. Hematopoiesis-supporting activity does not seem to be compromised after magnetic labeling of stromal cells, and the loss of the label by stromal layers during extended culturing is negligible. Magnetic labeling allows for simple and efficient removal of stromal component, yielding unbiased hematopoietic cell populations. When Lin(-) bone mouse marrow fraction was co-cultured with magnetic stromal layers and resulting cell populations were harvested by trypsinization, the yields of total nucleated cells, colony forming cells, and phenotypically primitive Lin(-)Sca-1(+)c-kit(+) subset were substantially higher as compared with nonadherent cell fractions harvested after conventional stromal co-culture. The advantage offered by the magnetic stroma approach over the traditional one was even more significant after a second round of co-culture and was more dramatic for more primitive hematopoietic cells. We conclude that magnetic stromal layers represent a simple, efficient, and convenient tool for co-culturing and subsequent recovery of sufficiently pure unbiased populations of hematopoietic cells. PMID:27318238

  9. Magnetic field effects on viscous fingering of a ferrofluid in an anisotropic Hele-Shaw cell

    NASA Astrophysics Data System (ADS)

    Ballou, R.; Molho, P.

    2005-12-01

    When a viscous fluid is pushed into a more viscous one in a Hele-Shaw cell, the interface between the two fluids may become unstable, leading to fingering and ramified patterns. Anisotropy can be introduced by engraving a grid in one plate of the cell, allowing one to obtain dendritic patterns. The use of a ferrofluid as one of the viscous fluid is a way to introduce magnetism in the problem, especially the magnetic field as a control parameter. Magnetic field effects on viscous fingering of ferrofluids have already been studied: in a rectangular Hele-Shaw cell, a magnetic field applied in the cell plane is stabilizing when parallel to the interface between the two fluids and destabilizing when normal to the interface. A magnetic field perpendicular to the plane of a radial Hele-Shaw cell has the same destabilizing effect as the pressure. We have studied the effect of a magnetic field, normal to and in the plane of anisotropic radial Hele-Shaw cells te{5}, to characterize the competing effects of hydrodynamics, magnetic field and dipolar energy, and anisotropy. Here we study more precisely the effect of a magnetic field normal to a radial anisotropic Hele-Shaw cell. Figs 8, Refs 9.

  10. Influence of strong static magnetic field on human cancer HT 1080 cells

    NASA Astrophysics Data System (ADS)

    Rodins, Juris; Korhovs, Vadims; Freivalds, Talivaldis; Buikis, Indulis; Ivanova, Tatjana

    2001-10-01

    The aim of this study was to investigate strong uniform magnetic field influence on the human cancer cells HT 1080. The cells were treated with magnetic field of intensity 1,16 Tesla and with anticancer agent - cis-platinum 0.025 mg/ml or vincristinum 2-3 ng/ml. The intact and the treated cell samples were incubated in a medium with acridine orange (AO). The magnetic field after 15 minutes of influence significantly increased cytoplasmic red fluorescence. Increased AO accumulation in lysosomes suggested to cancer cell metabolic activity stimulation.

  11. Detection of circulating tumor cells using targeted surface-enhanced Raman scattering nanoparticles and magnetic enrichment

    NASA Astrophysics Data System (ADS)

    Shi, Wei; Paproski, Robert J.; Moore, Ronald; Zemp, Roger

    2014-05-01

    While more than 90% of cancer deaths are due to metastases, our ability to detect circulating tumor cells (CTCs) is limited by low numbers of these cells in the blood and factors confounding specificity of detection. We propose a magnetic enrichment and detection technique for detecting CTCs with high specificity. We targeted both magnetic and surface-enhanced Raman scattering (SERS) nanoparticles to cancer cells. Only cells that are dual-labeled with both kinds of nanoparticles demonstrate an increasing SERS signal over time due to magnetic trapping.

  12. Response of animal and vegetative cells to the effect of a typical magnetic storm

    NASA Astrophysics Data System (ADS)

    Talikina, M. G.; Izyumov, Yu. G.; Krylov, V. V.

    2013-12-01

    Experimentally reproduced fluctuations of a low-frequency magnetic field in a nanotesla range (magnetic storm) affect the mitosis of animals and vegetative cells. Action of this factor during twenty four hours leads to a significant increase in the proliferative activity of embryo cells in roach ( Rutilus rutilus L.) and meristem cells of onion rootlets ( Allium cepa). The clastogenic effect statistically confirmed only in the Allium test seems to reflect the species specificity of the response and higher sensitivity of the cell association of the onion meristem to magnetic storm.

  13. Magnetic Resonance Imaging Features of a Juxtaglomerular Cell Tumor

    PubMed Central

    Kang, Suhai; Guo, Aitao; Wang, Haiyi; Ma, Lu; Xie, Zongyu; Li, Jinglong; Tonge, Xinyuan; Ye, Huiyi

    2015-01-01

    Objective: To retrospectively determine whether magnetic resonance imaging (MRI) findings can help differentiate a juxtaglomerular cell tumor (JCT) from clear cell renal cell carcinoma (ccRCC). Materials and Methods: Eight patients with JCTs and 24 patients with pathologically proven ccRCC were included for image analysis. All patients underwent unenhanced MRI and dynamic contrast-enhanced MRI. Fat-suppressed T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), in- and opposed-phase imaging, and fat-suppressed preliver acquisitions with volume acceleration sequences were performed before enhancement. After the administration of contrast, dynamic imaging was performed in the corticomedullary, nephrographic, and excretory phases. Student's t-test, t′-test, Chi-square test, and nonparametric Kruskal–Wallis H-test were used to determine the significance of the difference between the two groups. The sensitivity and specificity of the MRI findings were calculated. Results: In patients with a JCT, a cystic part of the lesion of <10%, isointensity or mild hyperintensity on T2WI, heterogeneous hyperintensity on DWI, less signal drop (<10%) in in- and opposed-phase imaging, and a degree of enhancement <200% in the corticomedullary phase showed statistically significant differences compared with those of ccRCC (P < 0.05). After combining a lower apparent diffusion coefficient (ADC) value (heterogeneous hyperintensity) on DWI and a degree of enhancement <200% in the corticomedullary phase using a parallel test, the sensitivity and specificity were 90.9% and 91.7%, respectively. Conclusions: Isointensity or mild hyperintensity on T2WI, a lower ADC value (heterogeneous hyperintensity) on DWI, and a degree of enhancement <200% in the corticomedullary phase are the major MRI findings for JCTs, combined with relative clinical manifestations and excluding other renal masses. A main solid tumor, less signal drop (<10%) in in- and opposed-phase imaging, and a less

  14. High-throughput magnetic flow sorting of human cells selected on the basis of magnetophoretic mobility

    NASA Astrophysics Data System (ADS)

    Reece, Lisa M.; Sanders, Lehanna; Kennedy, David; Guernsey, Byron; Todd, Paul; Leary, James F.

    2010-02-01

    We have shown the potential of a new method for optimizing the separation of human stem cell subsets from peripheral blood based on a novel cell labeling technique that leverages the capabilities of a new commercially available high speed magnetic cell sorting system (IKOTECH LLC, New Albany, IN). This new system sorts cells in a continuously flowing manner using a Quadrupole Magnetic cell Sorter (QMS). The sorting mechanism is based upon the magnetophoretic mobility of the cells, a property related to the relative binding distributions of magnetic particles per cell, as determined by the utilization of a Magnetic Cell Tracking Velocimeter (MCTV). KG-1 cells were competitively labeled with anti-CD34 magnetic beads and anti-CD34 FITC to obtain an optimal level of magnetophoretic mobility as visualized by the MCTV for high throughput sort recovery in the QMS. In QMS sorting, the concept of split-flow thin channel (SPLITT) separation technology is applied by having a sample stream enter a vertical annular flow channel near the channel's interior wall followed by another sheath flow entering near the exterior wall. The two flows are initially separated by a flow splitter. They pass through the bore of a Halbach permanent quadrupole magnet assembly, which draws magnetized cells outward and deflects them into a positive outflow, while negative cells continue straight out via the inner flow lamina. QMS sorts cells based upon their magnetophoretic mobility, or the velocity of a cell per unit ponderomotive force, the counterpart of fluorescence intensity in flow cytometry. The magnetophoretic mobility distribution of a cell population, measured by automated MCTV, is used as input data for the algorithmic control of sample, sheath, and outlet flow velocities of the QMS. In this study, the relative binding distributions of magnetic particles per cell were determined by MCTV using novel sorting and sizing algorithms. The resulting mobility histograms were used to set the QMS

  15. Microscale Magnetic Field Modulation for Enhanced Capture and Distribution of Rare Circulating Tumor Cells

    PubMed Central

    Chen, Peng; Huang, Yu-Yen; Hoshino, Kazunori; Zhang, John X.J.

    2015-01-01

    Immunomagnetic assay combines the powers of the magnetic separation and biomarker recognition and has been an effective tool to perform rare Circulating Tumor Cells detection. Key factors associated with immunomagnetic assay include the capture rate, which indicates the sensitivity of the system, and distributions of target cells after capture, which impact the cell integrity and other biological properties that are critical to downstream analyses. Here we present a theoretical framework and technical approach to implement a microscale magnetic immunoassay through modulating local magnetic field towards enhanced capture and distribution of rare cancer cells. Through the design of a two-dimensional micromagnet array, we characterize the magnetic field generation and quantify the impact of the micromagnets on rare cell separation. Good agreement is achieved between the theory and experiments using a human colon cancer cell line (COLO205) as the capture targets. PMID:25735563

  16. Detection of single mammalian cells by high-resolution magnetic resonance imaging.

    PubMed Central

    Dodd, S J; Williams, M; Suhan, J P; Williams, D S; Koretsky, A P; Ho, C

    1999-01-01

    This study reports the detection of single mammalian cells, specifically T cells (T lymphocytes) labeled with dextran-coated superparamagnetic iron oxide particles, using magnetic resonance microscopy. Size amplification due to sequestration of the superparamagnetic particles in vacuoles enhances contrast in localized areas in high-resolution magnetic resonance imaging. Magnetic resonance images of samples containing differing concentrations of T cells embedded in 3% gelatin show a number of dark regions due to the superparamagnetic iron oxide particles, consistent with the number predicted by transmission electron microscopy. Colabeling of T cell samples with a fluorescent dye leads to strong correlations between magnetic resonance and fluorescence microscopic images, showing the presence of the superparamagnetic iron oxide particles at the cell site. This result lays the foundation for our approach to tracking the movement of a specific cell type in live animals and humans. PMID:9876127

  17. Imaging of magnetic microfield distortions allows sensitive single-cell detection.

    PubMed

    Lindquist, Randall L; Papazoglou, Sebastian; Scharlach, Constantin; Waiczies, Helmar; Schnorr, Jörg; Taupitz, Matthias; Hamm, Bernd; Schellenberger, Eyk

    2013-01-01

    Cell tracking with magnetic resonance imaging (MRI) is mostly performed using superparamagnetic iron oxide (SPIO) nanoparticle-labeled cells. However, negative contrast in T2*-weighted imaging is inherently problematic as a homogeneous background signal is required to visualize the negative signal. In a magnetic field, SPIO-labeled cells develop their own magnetization, distorting the main field. We show here a method to visualize these distortions and use them to identify single cells with increased sensitivity and certainty compared to T2* images. We labeled HeLa cells with SPIOs, suspended labeled cells in agarose to make phantoms, and performed high-resolution gradient-echo MRI. Phase images were processed to enhance the visibility of single cells. To quantify SPIO content, we generated a map of frequency differences. MRI of cell phantoms showed that single cells could be detected at concentrations ranging from 200 to 10,000 cells mL(-1). Postprocessing of the magnetic resonance phase images reveals characteristic microfield distortions, increasing dramatically the sensitivity of cell recognition, compared to unprocessed T2* images. Calculating frequency shifts and comparing microfield distortions to simulations permit estimation of the nanoparticle load of single cells. We expect the ability to detect and quantify the iron load of single cells to prove useful in studies of cell trafficking, especially in rare cell populations. PMID:23415396

  18. An effective strategy of magnetic stem cell delivery for spinal cord injury therapy

    NASA Astrophysics Data System (ADS)

    Tukmachev, Dmitry; Lunov, Oleg; Zablotskii, Vitalii; Dejneka, Alexandr; Babic, Michal; Syková, Eva; Kubinová, Šárka

    2015-02-01

    Spinal cord injury (SCI) is a condition that results in significant mortality and morbidity. Treatment of SCI utilizing stem cell transplantation represents a promising therapy. However, current conventional treatments are limited by inefficient delivery strategies of cells into the injured tissue. In this study, we designed a magnetic system and used it to accumulate stem cells labelled with superparamagnetic iron oxide nanoparticles (SPION) at a specific site of a SCI lesion. The loading of stem cells with engineered SPIONs that guarantees sufficient attractive magnetic forces was achieved. Further, the magnetic system allowed rapid guidance of the SPION-labelled cells precisely to the lesion location. Histological analysis of cell distribution throughout the cerebrospinal channel showed a good correlation with the calculated distribution of magnetic forces exerted onto the transplanted cells. The results suggest that focused targeting and fast delivery of stem cells can be achieved using the proposed non-invasive magnetic system. With future implementation the proposed targeting and delivery strategy bears advantages for the treatment of disease requiring fast stem cell transplantation.Spinal cord injury (SCI) is a condition that results in significant mortality and morbidity. Treatment of SCI utilizing stem cell transplantation represents a promising therapy. However, current conventional treatments are limited by inefficient delivery strategies of cells into the injured tissue. In this study, we designed a magnetic system and used it to accumulate stem cells labelled with superparamagnetic iron oxide nanoparticles (SPION) at a specific site of a SCI lesion. The loading of stem cells with engineered SPIONs that guarantees sufficient attractive magnetic forces was achieved. Further, the magnetic system allowed rapid guidance of the SPION-labelled cells precisely to the lesion location. Histological analysis of cell distribution throughout the cerebrospinal

  19. Magnetic field effects in dye-sensitized solar cells controlled by different cell architecture

    PubMed Central

    Klein, M.; Pankiewicz, R.; Zalas, M.; Stampor, W.

    2016-01-01

    The charge recombination and exciton dissociation are generally recognized as the basic electronic processes limiting the efficiency of photovoltaic devices. In this work, we propose a detailed mechanism of photocurrent generation in dye-sensitized solar cells (DSSCs) examined by magnetic field effect (MFE) technique. Here we demonstrate that the magnitude of the MFE on photocurrent in DSSCs can be controlled by the radius and spin coherence time of electron-hole (e-h) pairs which are experimentally modified by the photoanode morphology (TiO2 nanoparticles or nanotubes) and the electronic orbital structure of various dye molecules (ruthenium N719, dinuclear ruthenium B1 and fully organic squaraine SQ2 dyes). The observed MFE is attributed to magnetic-field-induced spin-mixing of (e-h) pairs according to the Δg mechanism. PMID:27440452

  20. Magnetic field effects in dye-sensitized solar cells controlled by different cell architecture

    NASA Astrophysics Data System (ADS)

    Klein, M.; Pankiewicz, R.; Zalas, M.; Stampor, W.

    2016-07-01

    The charge recombination and exciton dissociation are generally recognized as the basic electronic processes limiting the efficiency of photovoltaic devices. In this work, we propose a detailed mechanism of photocurrent generation in dye-sensitized solar cells (DSSCs) examined by magnetic field effect (MFE) technique. Here we demonstrate that the magnitude of the MFE on photocurrent in DSSCs can be controlled by the radius and spin coherence time of electron-hole (e-h) pairs which are experimentally modified by the photoanode morphology (TiO2 nanoparticles or nanotubes) and the electronic orbital structure of various dye molecules (ruthenium N719, dinuclear ruthenium B1 and fully organic squaraine SQ2 dyes). The observed MFE is attributed to magnetic-field-induced spin-mixing of (e-h) pairs according to the Δg mechanism.

  1. Magnetic field effects in dye-sensitized solar cells controlled by different cell architecture.

    PubMed

    Klein, M; Pankiewicz, R; Zalas, M; Stampor, W

    2016-01-01

    The charge recombination and exciton dissociation are generally recognized as the basic electronic processes limiting the efficiency of photovoltaic devices. In this work, we propose a detailed mechanism of photocurrent generation in dye-sensitized solar cells (DSSCs) examined by magnetic field effect (MFE) technique. Here we demonstrate that the magnitude of the MFE on photocurrent in DSSCs can be controlled by the radius and spin coherence time of electron-hole (e-h) pairs which are experimentally modified by the photoanode morphology (TiO2 nanoparticles or nanotubes) and the electronic orbital structure of various dye molecules (ruthenium N719, dinuclear ruthenium B1 and fully organic squaraine SQ2 dyes). The observed MFE is attributed to magnetic-field-induced spin-mixing of (e-h) pairs according to the Δg mechanism. PMID:27440452

  2. Structural responses of cells to intracellular magnetic force induced by superparamagnetic iron oxide nanoparticles

    PubMed Central

    Shen, Han; Tong, Sheng; Bao, Gang; Wang, Biao

    2014-01-01

    In this paper, we study the effects of intracellular force on human umbilical vein endothelial cells. We generated intracellular force on endothelial cells under different magnetic fields using the cell uptake of superparamagnetic iron oxide nanoparticles. Cell responses to intracellular force were observed using fluorescent microscopy. Our results indicated that nanoparticles were taken up by the cell by endocytosis and were deposited in lysosomes. Nanoparticles and lysosomes inside the cell could be relocated by the application of a magnetic force. The intracellular magnetic force could also be used to accelerate cell migration by adjusting the magnetic fields and giving the cell free culture space. No cytotoxicity of nanoparticles was found in our experiments. By comparing intracellular relocalization with migration of the whole cell, we obtained a better understanding of the self-defence mechanisms of cells based on their mechanical properties. Based on the promising mechanical properties and low cytotoxicity of our magnetic nanoparticles, their potential applications in cytomechanics and cell patterning are discussed. PMID:24336693

  3. Cell and membrane lipid analysis by proton magnetic resonance spectroscopy in five breast cancer cell lines.

    PubMed

    Le Moyec, L; Tatoud, R; Eugène, M; Gauvillé, C; Primot, I; Charlemagne, D; Calvo, F

    1992-10-01

    The lipid composition of five human breast cancer cell lines (MCF-7, T47D, ZR-75-1, SKBR3 and MDA-MB231) was assessed by proton magnetic resonance spectroscopy (MRS) in whole cells and membrane-enriched fractions. The proportions of the three main lipid resonances in 1D spectra were different for each cell line. These resonances included mobile methyl and methylene functions from fatty acids of triglycerides and phospholipids and N-trimethyl from choline of phospholipids. T47D and ZR-75-1 cells presented a high methylene/methyl ratio (6.02 +/- 0.35 and 6.28 +/- 0.90). This ratio was significantly lower for SKBR3, MCF-7 and MDA-MB231 cells (2.76 +/- 0.22, 2.27 +/- 0.57 and 1.39 +/- 0.39). The N-trimethyl/methyl ratio was high for MDA-MB231 and SKBR3 cells (1.38 +/- 0.54 and 0.86 +/- 0.32), but lower for MCF-7, T47D and ZR-75-1 cells (0.49 +/- 0.11, 0.16 +/- 0.07 and 0.07 +/- 0.03). 2D COSY spectra confirmed these different proportions in mobile lipids. From 1D spectra obtained on membrane preparations, T47D and ZR-75-1 were the only cell lines to retain a signal from mobile methylene functions. These differences might be related to the heterogeneity found for several parameters of these cells (tumorigenicity, growth rate, hormone receptors); an extended number of cases from fresh samples might enable clinical correlations. PMID:1329906

  4. Pulsed taut-wire measurement of the magnetic alignment of the ITS induction cells

    SciTech Connect

    Melton, J.G.; Burns, M.J.; Honaberger, D.J.

    1993-06-01

    The mechanical and magnetic alignment of the first eight induction-cell, solenoid magnets of the Integrated Test Stand (ITS) for the Dual-Axis Radiographic Hydrodynamic Test (DARHT) facility were measured by observing the deflection of a fine, taut wire carrying a pulsed current. To achieve the required alignment (less than 0.25 mm offset and less than 5 mrad tilt), the magnet design uses quadrufilar windings and iron field-smoothing rings. After detailed measurements of each solenoid magnet, the cells are assembled and then mechanically aligned using a laser and an alignment target moved along the cell centerline. After the cells are in final position, the pulsed wire method is used to verify the magnetic alignment. The measurements show an average offset of the magnetic axes from the mechanical axis of 0. 15 mm, with a maximum offset of 0.3 mm. The average tilt of the magnetic axis was 0.7 mrad with a maximum tilt of 1.4 mrad. Tilts are corrected to less than 0.3 mrad, using dipole trim magnets assembled into each cell. Correction is limited noise.

  5. Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

    PubMed Central

    Jiang, Quan

    2016-01-01

    Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury, substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic. PMID:26981068

  6. Spatial control of chromosomal location in a live cell with functionalized magnetic particles.

    PubMed

    Hong, Juhee; Purwar, Prashant; Cha, Misun; Lee, Junghoon

    2015-12-01

    Long-range chromosomal travel is a phenomenon unique to cell division. Methods for non-invasive, artificial manipulation of chromosomes, such as optical or magnetic tweezers, have difficulty in producing the motion of whole chromosomes in live cells. Here, we report the spatial control of chromosomes over 10 μm in a live mouse oocyte using magnetic particles driven by an external magnetic field. Selective capture of the chromosomes was achieved using antibodies specific for histone H1 in the chromosome that were conjugated to magnetic particles (H1-BMPs). When an external magnetic field was applied, the chromosomes captured by the H1-BMPs traveled through the cytosol and accumulated near the cell membrane though the movement of the chromosomes captured by H1-BMPs was strongly disturbed by the distribution of the cytoskeleton (e.g. actin filaments). Being non-invasive in nature, our approach will enable new opportunities in the remote manipulation of subcellular elements. PMID:26524004

  7. Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting.

    PubMed

    Muthana, Munitta; Kennerley, Aneurin J; Hughes, Russell; Fagnano, Ester; Richardson, Jay; Paul, Melanie; Murdoch, Craig; Wright, Fiona; Payne, Christopher; Lythgoe, Mark F; Farrow, Neil; Dobson, Jon; Conner, Joe; Wild, Jim M; Lewis, Claire

    2015-01-01

    Cell-based therapy exploits modified human cells to treat diseases but its targeted application in specific tissues, particularly those lying deep in the body where direct injection is not possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic iron oxide nanoparticles and apply pulsed magnetic field gradients in the direction of the tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into tumours, resulting in increased tumour macrophage infiltration and reduction in tumour burden and metastasis. Our study indicates that clinical MRI scanners can not only track the location of magnetically labelled cells but also have the potential to steer them into one or more target tissues. PMID:26284300

  8. Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting

    PubMed Central

    Muthana, Munitta; Hughes, Russell; Fagnano, Ester; Richardson, Jay; Paul, Melanie; Murdoch, Craig; Wright, Fiona; Payne, Christopher; Lythgoe, Mark F.; Farrow, Neil; Dobson, Jon; Conner, Joe; Wild, Jim M; Lewis, Claire

    2015-01-01

    Cell-based therapy exploits modified human cells to treat diseases but its targeted application in specific tissues, particularly those lying deep in the body where direct injection is not possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic iron oxide nanoparticles (SPIOs) and apply pulsed magnetic-field gradients in the direction of the tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into tumors, resulting in increased tumour macrophage infiltration and reduction in tumor burden and metastasis. Our study indicates that clinical MRI scanners can not only track the location of magnetically labelled cells but also have the potential to steer them into one or more target tissues. PMID:26284300

  9. [Determination of the nucleic acids in pig embryonic kidney cells by magnetic cytaphoresis].

    PubMed

    Chikov, V M; Maksimova, E V

    1989-01-01

    Gallocyanine-chrome alum-stained pig embryonic kidney cells have paramagnetic properties. They move under the influence of gradient magnetic field (magnetophoresis). The velocity of magnetophoresis is proportional to the content of nucleic acids in cells. This allows to estimate the content of nucleic acids per cell dry weight by magnetophoresis and analytical centrifugation. PMID:2473104

  10. ACTION OF 50 HZ MAGNETIC FIELDS ON NEURITE OUTGROWTH IN PHEOCHROMOCYTOMA CELLS

    EPA Science Inventory

    This study tests the capacity of 50-Hz magnetic and electric fields to stimulate neurite outgrowth in PC-12D cells, a cell line which originated from a pheochromocytoma in rat adrenal medulla. he cells were plated on collagen-coated plastic petri dishes and exposed to sinusoidal ...

  11. Particle-in-cell simulations of electron energization in laser-driven magnetic reconnection

    NASA Astrophysics Data System (ADS)

    Lu, San; Lu, Quanming; Guo, Fan; Sheng, Zhengming; Wang, Huanyu; Wang, Shui

    2016-01-01

    Electrons can be energized during laser-driven magnetic reconnection, and the energized electrons form three super-Alfvénic electron jets in the outflow region (Lu et al 2014 New J. Phys. 16 083021). In this paper, by performing two-dimensional particle-in-cell simulations, we find that the electrons can also be significantly energized before magnetic reconnection occurs. When two plasma bubbles with toroidal magnetic fields expand and squeeze each other, the electrons in the magnetic ribbons are energized through betatron acceleration due to the enhancement of the magnetic field, and an electron temperature anisotropy {T}{{e}\\perp }\\gt {T}{{e}| | } develops. Meanwhile, some electrons are trapped and bounced repeatedly between the two expanding/approaching bubbles and get energized through a Fermi-like process. The energization before magnetic reconnection is more significant (or important) than that during magnetic reconnection.

  12. Antibody Conjugated Magnetic Iron Oxide Nanoparticles for Cancer Cell Separation in Fresh Whole Blood

    PubMed Central

    Xu, Hengyi; Aguilar, Zoraida P.; Yang, Lily; Kuang, Min; Duan, Hongwei; Xiong, Yonghua; Wei, Hua; Wang, Andrew

    2011-01-01

    A highly efficient process using iron oxide magnetic nanoparticles (IO)-based immunomagnetic separation of tumor cells from fresh whole blood has been developed. The process involved polymer coated 30 nm IO that was modified with antibodies (Ab) against human epithelial growth factor receptor 2 (anti-HER2 or anti-HER2/neu) forming IO-Ab. HER2 is a cell membrane protein that is over expressed in several types of human cancer cells. Using a HER2/neu over expressing human breast cancer cell line, SK-BR3, as a model cell, the IO-Ab was used to separate 73.6 % (with a maximum capture of 84%) of SK-BR3 cells that were spiked in 1 mL of fresh human whole blood. The IO-Ab preferentially bound to SK-BR3 cells over normal cells found in blood due to the high level of HER2/neu receptor on the cancer cells unlike the normal cell surfaces. The results showed that the nanosized magnetic nanoparticles exhibited an enrichment factor (cancer cells over normal cells) of 1:10,000,000 in a magnetic field (with gradient of 100 T/m) through the binding of IO-Ab on the cell surface that resulted in the preferential capture of the cancer cells. This research holds promise for efficient separation of circulating cancer cells in fresh whole blood. PMID:21920599

  13. Bio-Nano-Magnetic Materials for Localized Mechanochemical Stimulation of Cell Growth and Death.

    PubMed

    Kilinc, Devrim; Dennis, Cindi L; Lee, Gil U

    2016-07-01

    Magnetic nanoparticles are promising new tools for therapeutic applications, such as magnetic nanoparticle hyperthermia therapy and targeted drug delivery. Recent in vitro studies have demonstrated that a force application with magnetic tweezers can also affect cell fate, suggesting a therapeutic potential for magnetically modulated mechanical stimulation. The magnetic properties of nanoparticles that induce physical responses and the subtle responses that result from mechanically induced membrane damage and/or intracellular signaling are evaluated. Magnetic particles with various physical, geometric, and magnetic properties and specific functionalization can now be used to apply mechanical force to specific regions of cells, which permit the modulation of cellular behavior through the use of spatially and time controlled magnetic fields. On one hand, mechanochemical stimulation has been used to direct the outgrowth on neuronal growth cones, indicating a therapeutic potential for neural repair. On the other hand, it has been used to kill cancer cells that preferentially express specific receptors. Advances made in the synthesis and characterization of magnetic nanomaterials and a better understanding of cellular mechanotransduction mechanisms may support the translation of mechanochemical stimulation into the clinic as an emerging therapeutic approach. PMID:26780501

  14. Ectoenzyme switches the surface of magnetic nanoparticles for selective binding of cancer cells.

    PubMed

    Du, Xuewen; Zhou, Jie; Xu, Bing

    2015-06-01

    Enzymatic switch, such as phosphorylation and dephosphorylation of proteins, is the most important mechanism for cellular signal transductions. Inspired by Nature and encouraged by our recent unexpected observation of the dephosphorylation of d-tyrosine phosphate-contain small peptides, we modify the surface of magnetic nanoparticles (MNP) with d-tyrosine phosphate that is a substrate of alkaline phosphatase (ALP). Our studies find that ALP is able to remove the phosphate groups from the magnetic nanoparticles. Most importantly, placental alkaline phosphatase (ALPP), an ectoenzyme that locates on cell surface with catalytic domains outside the plasma membrane and is overexpressed on many cancer cells, dephosphorylate the d-tyrosine phosphates on the surface of the magnetic nanoparticle and enable the magnetic nanoparticles to adhere selectively to the cancer cells, such as HeLa cells. Unlikely commonly used antibodies, the selectivity of the magnetic nanoparticles to cancer cells originates from the enzymatic reaction catalyzed by ALPP. The use of enzymatic reaction to modulate the surface of various nanostructures may lead to a general method to broadly target cancer cells without relying on specific ligand-receptor interactions (e.g., antibodies). This work, thus, illustrates a fundamentally new concept to allow cells to actively engineer the surface of colloids materials, such as magnetic nanoparticles, for various applications. PMID:25586118

  15. Enhanced leukemia cell detection using a novel magnetic needle and nanoparticles

    PubMed Central

    Jaetao, Jason E.; Butler, Kimberly S.; Adolphi, Natalie L.; Lovato, Debbie M.; Bryant, Howard C.; Rabinowitz, Ian; Winter, Stuart S.; Tessier, Trace E.; Hathaway, Helen J.; Bergemann, Christian; Flynn, Edward R.; Larson, Richard S.

    2009-01-01

    Acute leukemia is a hematopoietic malignancy for which the accurate measurement of minimal residual disease is critical to determining prognosis and treatment. While bone marrow aspiration and light microscopy remain the current standard of care for detecting residual disease, these approaches cannot reliably discriminate less than 5% lymphoblast cells. To improve the detection of leukemia cells in the marrow, we developed a novel apparatus that employs antibodies conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) and directed against the acute leukemia antigen CD34, coupled with a “magnetic needle” biopsy. Leukemia cell lines expressing high or minimal CD34 were incubated with anti-CD34-conjugated SPIONs. Three separate approaches including microscopy, Superconducting Quantum Interference Device (SQUID) magnetometry, and in vitro magnetic needle extraction were then employed to assess cell sampling. We found that CD34-conjugated nanoparticles preferentially bind high CD34-expressing cell lines. Furthermore, the magnetic needle enabled identification of both cell line and patient leukemia cells diluted into normal blood at concentrations below those normally found in remission marrow samples. Finally, the magnetic needle enhanced the percentage of lymphoblasts detectable by light microscopy by ten-fold in samples of fresh bone marrow aspirate approximating minimal residual disease. These data suggest that bone marrow biopsy using antigen-targeted magnetic nanoparticles and a magnetic needle for the evaluation of minimal residual disease in CD34-positive acute leukemias can significantly enhance sensitivity compared to the current standard of care. PMID:19808954

  16. THE INFLUENCE OF MAGNETIC FIELDS ON INHIBITION OF MCF-7 CELL GROWTH BY TAMOXIFEN

    EPA Science Inventory

    THE INFLUENCE OF MAGNETIC FIELDS ON INHIBITION OF MCF-7 CELL GROWTH BY TAMOXIFEN.
    Harland and Liburdy (1) reported that 1.2-uT, 60-Hz magnetic fields could significantly block the inhibitory action of pharmacological levels of tamoxifen (10-7 M) on the growth of MCF-7 human br...

  17. Studies of cell toxicity of complexes of magnetic fluids and biological macromolecules

    NASA Astrophysics Data System (ADS)

    Macaroff, Patrícia P.; Oliveira, Daniela M.; Ribeiro, Karina F.; Lacava, Zulmira G. M.; Lima, Emília C. D.; Morais, Paulo C.; Tedesco, Antonio C.

    2005-05-01

    In this study, we performed a comparative investigation of the binding properties of two surface-coated (carboxymethyldextran/glucuronic acid), magnetite-based biocompatible magnetic fluids with different biological macromolecules (BSA, HSA, and LDL). We also investigated the in vitro toxicity of the complex formed between the magnetic fluid and the biological macromolecule in the neoplastic cell line J774-A.

  18. Ultrasensitive detection of microbial cells using magnetic focus enhanced lateral flow sensors.

    PubMed

    Ren, Wen; Cho, Il-Hoon; Zhou, Zhongwu; Irudayaraj, Joseph

    2016-04-01

    We report on an improved lateral flow immunoassay (LFIA) sensor with a magnetic focus for ultrasensitive naked-eye detection of pathogenic microorganisms at a near single cell limit without any pre-enrichment steps, by allowing the magnetic probes to focus the labelled pathogens to the target zone of the LF strip. PMID:26978736

  19. Magnetic Resonance Imaging Characteristics of Ovarian Clear Cell Carcinoma

    PubMed Central

    Wang, Wei; Ding, Jianhui; Zhu, Xiaoli; Li, Yuan; Gu, Yajia; Peng, Weijun

    2015-01-01

    Purpose To probe the magnetic resonance imaging (MRI) features of ovarian clear cell carcinoma (OCCC). Methods This study retrospectively collected MRI data for 21 pathology-confirmed OCCCs from 19 female patients. The MRI findings were analyzed to determine the tumor size, shape/edge, shape and number of protrusions within the cyst, cystic or necrotic components, signal intensity (SI) and enhancement features. Results The age of the 19 patients ranged from 28 to 63 years (mean age: 53 years). Unilateral tumors were found in 17 patients (17/19, 89%); the average size of all tumors was 10.8 cm. The tumors on MRI were classified into two categories: (a) “cystic adnexal mass with solid protrusions” in 12 (57%) and (b) “solid adnexal mass with cystic areas or necrosis” in 9 (43%). For group a, high to very high SI was observed for most tumors (10/12, 83%) on T1-weighted images (T1WIs), and very high SI was observed on T2-weighted images (T2WIs) for all 12 tumors. Most solid protrusions were irregular and few in number and exhibited heterogeneous intermediate SI on T1WIs and T2WIs and prolonged enhanced SI in the contrast study. All 9 OCCCs in group b were predominantly solid masses with unequally sized necrotic or cystic areas in which some cysts were located at the periphery of the tumor (4/9, 44%). The solid components in all 9 tumors showed iso- or slightly high SI on T1WIs, heterogeneous iso-high SI on T2WIs and heterogeneous prolonged enhancement. According to FIGO classification, 14 tumors (14/19, 74%) were stages I-II, and 5 (5/19, 26%) were stages III-IV. Conclusions On MRI, OCCCs present as large unilateral multilocular or unilocular cystic masses with irregular intermediate SI solid protrusions or predominantly solid masses with cysts or necrosis at an early FIGO stage. PMID:26161555

  20. METHOD FOR CALCULATING ELECTRIC AND MAGNETIC FIELDS IN TEM CELLS AT ELF (JOURNAL VERSION)

    EPA Science Inventory

    A method is presented whereby the electric and magnetic field distributions within rectangular strip transmission lines (TEM cells) can be calculated. Quasi-static approximations are employed, thereby restricting the validity of the results to operational frequencies well below t...

  1. Can Lucifer Yellow Indicate Correct Permeability of Biological Cell Membrane under An Electric and Magnetic Field?

    PubMed

    Pourmirjafari Firoozabadi, Tahereh; Shankayi, Zeinab; Izadi, Azam; Pourmirjafari Firoozabadi, Seyed Mohammad

    2015-01-01

    The effect of external magnetic and electric fields, in the range of electroporation and magnetoporation, on Lucifer Yellow (LY) fluorescence in the absence of cells is studied. Electric-field-induced quenching and magnetic field-induced increase are observed for fluorescence intensity of LY. Regard to the fact that the variation of field-induced fluorescence, even in the absence of cells, can be observed, the application of LY, as a marker, is debatable in electroporation and magnetoporation techniques. PMID:25685747

  2. Microwave-synthesized magnetic chitosan microparticles for the immobilization of yeast cells.

    PubMed

    Safarik, Ivo; Pospiskova, Kristyna; Maderova, Zdenka; Baldikova, Eva; Horska, Katerina; Safarikova, Mirka

    2015-01-01

    An extremely simple procedure has been developed for the immobilization of Saccharomyces cerevisiae cells on magnetic chitosan microparticles. The magnetic carrier was prepared using an inexpensive, simple, rapid, one-pot process, based on the microwave irradiation of chitosan and ferrous sulphate at high pH. Immobilized yeast cells have been used for sucrose hydrolysis, hydrogen peroxide decomposition and the adsorption of selected dyes. PMID:24753015

  3. Magnetic trapping with simultaneous photoacoustic detection of molecularly targeted rare circulating tumor cells

    NASA Astrophysics Data System (ADS)

    Wei, Chen-Wei; Xia, Jinjun; Pelivanov, Ivan M.; Hu, Xiaoge; Gao, Xiaohu; O'Donnell, Matthew

    2013-03-01

    Photoacoustic (PA) imaging has been widely used in molecular imaging to detect diseased cells by targeting them with nanoparticle-based contrast agents. However, the sensitivity and specificity are easily degraded because contrast agent signals can be masked by the background. Magnetomotive photoacoustic imaging uses a new type of multifunctional composite particle combining an optically absorptive gold nanorod core and magnetic nanospheres, which can potentially accumulate and concentrate targeted cells while simultaneously enhancing their specific contrast compared to background signals. In this study, HeLa cells molecularly targeted using nanocomposites with folic acid mimicking targeted rare circulating tumor cells (CTCs) were circulated at a 6 ml/min flow rate for trapping and imaging studies. Preliminary results show that the cells accumulate rapidly in the presence of an externally applied magnetic field produced by a dual magnet system. The sensitivity of the current system can reach up to 1 cell/ml in clear water. By manipulating the trapped cells magnetically, the specificity of detecting cells in highly absorptive ink solution can be enhanced with 16.98 dB background suppression by applying motion filtering on PA signals to remove unwanted background signals insensitive to the magnetic field. The results appear promising for future preclinical studies on a small animal model and ultimate clinical detection of rare CTCs in the vasculature.

  4. Vortex fluidic entrapment of functional microalgal cells in a magnetic polymer matrix

    NASA Astrophysics Data System (ADS)

    Eroglu, Ela; D'Alonzo, Nicholas J.; Smith, Steven M.; Raston, Colin L.

    2013-03-01

    Composite materials based on superparamagnetic magnetite nanoparticles embedded in polyvinylpyrrolidone (PVP) are generated in a continuous flow vortex fluidic device (VFD). The same device is effective in entrapping microalgal cells within this material, such that the functional cells can be retrieved from aqueous dispersions using an external magnet.Composite materials based on superparamagnetic magnetite nanoparticles embedded in polyvinylpyrrolidone (PVP) are generated in a continuous flow vortex fluidic device (VFD). The same device is effective in entrapping microalgal cells within this material, such that the functional cells can be retrieved from aqueous dispersions using an external magnet. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr33813d

  5. Contactless dielectrophoretic manipulation of biological cells using pulsed magnetic fields.

    PubMed

    Novickij, Vitalij; Grainys, Audrius; Novickij, Jurij

    2014-06-01

    Contactless method for manipulation of polar or polarisable micro and nanoscale particles based on the dielectrophoresis force exerted by the induced electric field in high pulsed magnetic field is presented in this study. Finite element method analysis of the magnetic and resulting induced electric fields is carried out. The structure of the magnetic field generator that was based on a controlled frequency spark gap, and the structure of the coil that was used as a load are described. Experimental data showing positive dielectrophoresis on the Jurkat T-lymphoblasts is presented. The study discusses further developments of the technique, its limitations and possible applications. PMID:25014083

  6. Magnetic-field-induced DNA strand breaks in brain cells of the rat.

    PubMed Central

    Lai, Henry; Singh, Narendra P

    2004-01-01

    In previous research, we found that rats acutely (2 hr) exposed to a 60-Hz sinusoidal magnetic field at intensities of 0.1-0.5 millitesla (mT) showed increases in DNA single- and double-strand breaks in their brain cells. Further research showed that these effects could be blocked by pretreating the rats with the free radical scavengers melatonin and N-tert-butyl-alpha-phenylnitrone, suggesting the involvement of free radicals. In the present study, effects of magnetic field exposure on brain cell DNA in the rat were further investigated. Exposure to a 60-Hz magnetic field at 0.01 mT for 24 hr caused a significant increase in DNA single- and double-strand breaks. Prolonging the exposure to 48 hr caused a larger increase. This indicates that the effect is cumulative. In addition, treatment with Trolox (a vitamin E analog) or 7-nitroindazole (a nitric oxide synthase inhibitor) blocked magnetic-field-induced DNA strand breaks. These data further support a role of free radicals on the effects of magnetic fields. Treatment with the iron chelator deferiprone also blocked the effects of magnetic fields on brain cell DNA, suggesting the involvement of iron. Acute magnetic field exposure increased apoptosis and necrosis of brain cells in the rat. We hypothesize that exposure to a 60-Hz magnetic field initiates an iron-mediated process (e.g., the Fenton reaction) that increases free radical formation in brain cells, leading to DNA strand breaks and cell death. This hypothesis could have an important implication for the possible health effects associated with exposure to extremely low-frequency magnetic fields in the public and occupational environments. PMID:15121512

  7. Sliced Magnetic Polyacrylamide Hydrogel with Cell-Adhesive Microarray Interface: A Novel Multicellular Spheroid Culturing Platform.

    PubMed

    Hu, Ke; Zhou, Naizhen; Li, Yang; Ma, Siyu; Guo, Zhaobin; Cao, Meng; Zhang, Qiying; Sun, Jianfei; Zhang, Tianzhu; Gu, Ning

    2016-06-22

    Cell-adhesive properties are of great significance to materials serving as extracellular matrix mimics. Appropriate cell-adhesive property of material interface can balance the cell-matrix interaction and cell-cell interaction and can promote cells to form 3D structures. Herein, a novel magnetic polyacrylamide (PAM) hydrogel fabricated via combining magnetostatic field induced magnetic nanoparticles assembly and hydrogel gelation was applied as a multicellular spheroids culturing platform. When cultured on the cell-adhesive microarray interface of sliced magnetic hydrogel, normal and tumor cells from different cell lines could rapidly form multicellular spheroids spontaneously. Furthermore, cells which could only form loose cell aggregates in a classic 3D cell culture model (such as hanging drop system) were able to be promoted to form multicellular spheroids on this platform. In the light of its simplicity in fabricating as well as its effectiveness in promoting formation of multicellular spheroids which was considered as a prevailing tool in the study of the microenvironmental regulation of tumor cell physiology and therapeutic problems, this composite material holds promise in anticancer drugs or hyperthermia therapy evaluation in vitro in the future. PMID:27258682

  8. Disaggregation of stacked red blood cells under strong pulse magnetic field

    NASA Astrophysics Data System (ADS)

    Hwang, Do-Guwn; Park, Hyeji; Kim, Woori; Lee, Jinyoung; Lee, Hyun Sook

    2015-05-01

    We have investigated the dependence of magnetic field intensity and stimulation time on stacking formation of red blood cells (RBCs) to study blood circulation in human body. The pulse magnetic field with the maximum intensity of 0.27-0.07 T, pulse transition time of 0.102 ms, and pulse intervals of 1 s was applied to the distal end of palm for 5-20 min. The aggregation of RBCs was measured using microscopy. After the magnetic stimulation for 10 min, the fully stacked RBCs were almost separated from each other and moved much faster than those in unstimulated state. The disaggregation was maintained at a decreasing intensity of 0.19 T, and a few cells were stacked at the weak intensity of 0.07 T. In this work, we investigated the degree of RBCs aggregation and activity time by varying the intensity and time of magnetic stimulation to get the optimum condition of pulse magnetic field stimulus.

  9. Geometrically pinned magnetic domain wall for multi-bit per cell storage memory

    NASA Astrophysics Data System (ADS)

    Bahri, M. Al; Sbiaa, R.

    2016-06-01

    Spintronic devices currently rely on magnetic switching or controlled motion of domain walls (DWs) by an external magnetic field or a spin-polarized current. Controlling the position of DW is essential for defining the state/information in a magnetic memory. During the process of nanowire fabrication, creating an off-set of two parts of the device could help to pin DW at a precise position. Micromagnetic simulation conducted on in-plane magnetic anisotropy materials shows the effectiveness of the proposed design for pinning DW at the nanoconstriction region. The critical current for moving DW from one state to the other is strongly dependent on nanoconstricted region (width and length) and the magnetic properties of the material. The DW speed which is essential for fast writing of the data could reach values in the range of hundreds m/s. Furthermore, evidence of multi-bit per cell memory is demonstrated via a magnetic nanowire with more than one constriction.

  10. Particle-In-Cell Simulations of the Solar Wind Interaction with Lunar Crustal Magnetic Anomalies: Magnetic Cusp Regions

    NASA Technical Reports Server (NTRS)

    Poppe, A. R.; Halekas, J. S.; Delory, G. T.; Farrell, W. M.

    2012-01-01

    As the solar wind is incident upon the lunar surface, it will occasionally encounter lunar crustal remanent magnetic fields. These magnetic fields are small-scale, highly non-dipolar, have strengths up to hundreds of nanotesla, and typically interact with the solar wind in a kinetic fashion. Simulations, theoretical analyses, and spacecraft observations have shown that crustal fields can reflect solar wind protons via a combination of magnetic and electrostatic reflection; however, analyses of surface properties have suggested that protons may still access the lunar surface in the cusp regions of crustal magnetic fields. In this first report from a planned series of studies, we use a 1 1/2-dimensional, electrostatic particle-in-cell code to model the self-consistent interaction between the solar wind, the cusp regions of lunar crustal remanent magnetic fields, and the lunar surface. We describe the self-consistent electrostatic environment within crustal cusp regions and discuss the implications of this work for the role that crustal fields may play regulating space weathering of the lunar surface via proton bombardment.

  11. Optical Pumping Spin Exchange {sup 3}He Gas Cells for Magnetic Resonance Imaging

    SciTech Connect

    Kim, W.; Stepanyan, S. S.; Kim, A.; Jung, Y.; Woo, S.; Yurov, M.; Jang, J.

    2009-08-04

    We present a device for spin-exchange optical pumping system to produce large quantities of polarized noble gases for Magnetic Resonance Imaging (MRI). A method and design of apparatus for pumping the polarization of noble gases is described. The method and apparatus enable production, storage and usage of hyperpolarized noble gases for different purposes, including Magnetic Resonance Imaging of human and animal subjects. Magnetic imaging agents breathed into lungs can be observed by the radio waves of the MRI scanner and report back physical and functional information about lung's health and desease. The technique known as spin exchange optical pumping is used. Nuclear magnetic resonance is implemented to measure the polarization of hyperpolarized gas. The cells prepared and sealed under high vacuum after handling Alkali metals into the cell and filling with the {sup 3}He-N{sub 2} mixture. The cells could be refilled. The {sup 3}He reaches around 50% polarization in 5-15 hours.

  12. Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity.

    PubMed Central

    Valberg, P A; Feldman, H A

    1987-01-01

    Submicrometer magnetic particles, ingested by cells and monitored via the magnetic fields they generate, provide an alternative to optical microscopy for probing movement and viscosity of living cytoplasm, and can be used for cells both in vitro and in vivo. We present methods for preparing lung macrophages tagged with magnetic particles for magnetometric study. Interpretation of the data involves fitting experimental remanent-field decay curves to nonlinear mechanistic models of intracellular particle motion. The model parameters are sensitive to mobility and apparent cytoplasmic viscosity experienced by particle-containing organelles. We present results of parameter estimation for intracellular particle behavior both within control cells and after (a) variable magnetization duration, (b) incubation with cytochalasin D, and (c) particle twisting by external fields. Magnetometric analysis showed cytoplasmic elasticity, dose-dependent motion inhibition by cytochalasin D, and a shear-thinning apparent viscosity. Images FIGURE 1 FIGURE 2 PMID:3676436

  13. Intracellular Delivery by Shape Anisotropic Magnetic Particle-Induced Cell Membrane Cuts.

    PubMed

    Lin, Ming-Yu; Wu, Yi-Chien; Lee, Ji-Ann; Tung, Kuan-Wen; Zhou, Jessica; Teitell, Michael A; Yeh, J Andrew; Chiou, Pei Yu

    2016-08-01

    Introducing functional macromolecules into a variety of living cells is challenging but important for biology research and cell-based therapies. We report a novel cell delivery platform based on rotating shape anisotropic magnetic particles (SAMPs), which make very small cuts on cell membranes for macromolecule delivery with high efficiency and high survivability. SAMP delivery is performed by placing commercially available nickel powder onto cells grown in standard cell culture dishes. Application of a uniform magnetic field causes the magnetic particles to rotate because of mechanical torques induced by shape anisotropic magnetization. Cells touching these rotating particles are nicked, which generates transient membrane pores that enable the delivery of macromolecules into the cytosol of cells. Calcein dye, 3 and 40 kDa dextran polymers, a green fluorescence protein (GFP) plasmid, siRNA, and an enzyme (β-lactamase) were successfully delivered into HeLa cells, primary normal human dermal fibroblasts (NHDFs), and mouse cortical neurons that can be difficult to transfect. The SAMP approach offers several advantages, including easy implementation, low cost, high throughput, and efficient delivery of a broad range of macromolecules. Collectively, SAMP delivery has great potential for a broad range of academic and industrial applications. PMID:26882924

  14. [Comparison of sorting of fluorescently and magnetically labelled dental pulp stem cells].

    PubMed

    Kerényi, Farkas; Tarapcsák, Szabolcs; Hrubi, Edit; Baráthne, Szabó Ágnes; Hegedüs, Viktória; Balogh, Sára; Bágyi, Kinga; Varga, Gábor; Hegedüs, Csaba

    2016-03-01

    Stem cells are present in many tissues, such as dental pulp. Stem cells can be easily isolated from dental pulp because third molars are often removed from patients. Stem cells could be separated from the tissue derived heterogeneous cell population. There are two main methods to separate a cell type from the other ones: the fluorescence activated cell sorting (FACS) and the magnetic activated cell sorting (MACS). The aim of this study was to compare these methods' effect on cell surviving and population growth after sorting on dental pulp cells. The anti-STRO-1 antibody was used as primary antibody to specifically label stem cells. Two secondary antibodies were used: magnetic or fluorescent labelled. We sorted the cells by MACS or by FACS or by combination of both (MACS-FACS). Our results show that the effectivity of MACS and FACS sorting are comparable while of MACS-FACS was significantly higher (MACS 79.53 ± 5.78%, FACS 88.27 ± 3.70%, MACS-FACS 98.43 ± 0.67%). The cell surviving and the post-sorting population growth, on the contrary, are very different. The cell population is growing on first week after MACS but after FACS did not. Moreover, after MACS-FACS, on first week the cell number of population decreased. Taken together, our results suggest to use MACS instead of FACS, at least in case of sorting dental pulp stem cells with anti-STRO-1 antibody. PMID:27188159

  15. Differential blood cell separation using a high gradient magnetic field.

    PubMed

    Paul, F; Roath, S; Melville, D

    1978-02-01

    A technique for the separation of erythrocytes from whole blood is described which exploits the magnetic property of haemoglobin in the reduced state. The technique is characterized by the use of a filter consisting of a cylinder, containing stainless steel wire mesh, placed between the jaws of an electro magnet. When activated, the electromagnet induces a magnetic field gradient in the vicinity of each of the constituent wires, sufficient to attract and trap erythrocytes in suspension. The number of erythrocytes captured varies with the applied field (0-1.4 Tesla in these experiments) and flow rate (1.9-12.9 x 10(-4) m s-1). The capture process does not cause haemolysis or observable surface damage to the erythrocytes and neither leucocytes nor platelets are retained by the filter. PMID:638075

  16. Synthesis of bacterial magnetic particles during cell cycle of Magnetospirillum magneticum AMB-1.

    PubMed

    Yang, C D; Takeyama, H; Tanaka, T; Hasegawa, A; Matsunaga, T

    2001-01-01

    We investigated the relationship between the synthesis of bacterial magnetic particles (BMPs) and the transcription of magA gene-encoding iron transport protein using synchronous culture of Magnetospirillum magneticum AMB-1. Synchronously cultured cells were subjected to transmission electron microscopic observation and fluorescence in situ hybridization. The average number of BMPs slowly increased in the cell with increasing cell size. A sharp increase in BMPs occurred just before cell division and resulted in maximum BMP production of 30 particles/cell. The transcription of magA was regulated immediately before and after cell division. PMID:11963844

  17. ORIENTATION REQUIREMENT TO DETECT MAGNETIC FIELD-INDUCTED ALTERATION OF GAP JUNCTION COMMUNICATION IN EPITHELIAL CELLS

    EPA Science Inventory

    ORIENTATION REQUIREMENT TO DETECT MAGNETIC FIELD-INDUCED ALTERATION OF GAP JUNCTION COMMUNICATION IN EPITHELIAL CELLS.
    OBJECTIVE: We have shown that functional gap junction communication as measured by Lucifer yellow dye transfer (DT) in Clone-9 rat liver epithelial cells, c...

  18. GAP JUNCTION COMMUNICATON IN A TRANSFECTED HUMAN CELL LINE: ACTION OF MELATONIN AND MAGNETIC FIELDS

    EPA Science Inventory

    GAP JUNCTION COMMUNICTION IN TRANSFECTED HUMAN CELL LINE: ACTION OF MELATONIN AND MAGNETIC FIELDS.

    OBJECTIVE: We previously showed that functional gap junction communication (GJC), as monitored by dye transfer (DT), could be enhanced in mouse C3H 10T112 cells and in mouse...

  19. INFLUENCE OF 50-HZ ELECTRIC AND MAGNETIC FIELDS ON NEURITE OUTGROWTH IN PHEOCHROMOCYTOMA CELLS

    EPA Science Inventory

    This study describes the ability of electric and magnetic fields to substitute for nerve growth factor in the stimulation of trite growth in a subline of PC-12 cells, derived from a pheochromocytoma in rat adrenal medulla. he cells were plated on collagen-coated, 60-mm plastic di...

  20. [Synergistic inhibitory effect of static magnetic field and antitumor drugs on Hepa1-6 cells].

    PubMed

    Xu, Lingling; Guo, Wei; Liu, Ying; Zhang, Xueqing; Yu, Juntao; Wu, Wencai; Zhao, Tiejun

    2015-09-01

    Chemotherapy as a routine method for clinical treatment of cancer has disadvantages such as significant toxicity and strong resistance. In order to improve the efficacy of the drugs and reduce the by-effects, we tried to combine static magnetic field (SMF) with cisplatin or adriamycin. The growth of Hepa1-6 cells treated with the static magnetic field (SMF) combined with cisplatin or adriamycin was significantly inhibited, as detected with MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) test. Combined treatment group cells underwent significant morphological changes as observed by HE (Hematoxylin and eosin) staining under optical microscope. Cell cycle analysis indicated that SMF increased the ratio of cells arrested in G2/M phase caused by cisplatin, and when treated with SMF combined with adriamycin, cells were almost arrested in G1 and G2/M phase. SCGE test showed that SMF can enhance the ability of cisplatin or adriamycin to promote cell DNA damage. Atomic force microscope observation found that the combination of antitumor drugs and magnetic field treatment induced larger and deeper holes on the cell membrane, and surface structure damage is serious. The combination of antitumor drugs and magnetic field technology effectively inhibits the growth of tumor cells, and reduces drug doses. The results implicate this method as potential cancer therapy. PMID:26955714

  1. Study on Axially Distributed Divertor Magnetic Field Configuration in a Mirror Cell

    SciTech Connect

    Islam, M.K.; Nakashima, Y.; Higashizono, Y.; Katanuma, I.; Cho, T

    2005-01-15

    A mirror magnetic field configuration (MFC) is studied in which a divertor is distributed axially using multipole coils. Both configurations of divertor and minimum-B are obtained in a mirror cell. Magnetohydrodynamic (MHD) instability of a mirror cell can be eliminated in this way. Concept of the design and properties of the MFC are discussed.

  2. Observation of magnetic field-induced contraction of fission yeast cells using optical projection microscopy

    NASA Astrophysics Data System (ADS)

    Yang, Xi; Beckwith, Andrew; Miller, John; Wood, Lowell

    2004-12-01

    The charges in live cells interact with or produce electric fields, which results in enormous dielectric responses, flexoelectricity, and related phenomena. Here we report on a contraction of Schizosaccharomyces pombe (fission yeast) cells induced by magnetic fields, as observed using a phase-sensitive projection imaging technique. Unlike electric fields, magnetic fields only act on moving charges. The observed behavior is therefore quite remarkable, and may result from a contractile Lorentz force acting on diamagnetic screening currents. This would indicate extremely high intracellular charge mobilities. Besides, we observed a large electro-optic response from fission yeast cells.

  3. Observation of magnetic field-induced contraction of fission yeast cells using optical projection microscopy

    NASA Astrophysics Data System (ADS)

    Yang, Xi; Beckwith, A. W.

    2005-03-01

    The charges in live cells interact with or produce electric fields, which results in enormous dielectric responses, flexoelectricity, and related phenomena. Here we report on a contraction of Schizosaccharomyces pombe (fission yeast) cells induced by magnetic fields, as observed using a phase-sensitive projection imaging technique. Unlike electric fields, magnetic fields only act on moving charges. The observed behavior is therefore quite remarkable, and may result from a contractile Lorentz force acting on diamagnetic screening currents. This would indicate extremely high intracellular charge mobilities. Besides, we observed a large electro-optic response from fission yeast cells.

  4. Increasing the sensitivity for stem cell monitoring in system-function based magnetic particle imaging

    NASA Astrophysics Data System (ADS)

    Them, Kolja; Salamon, J.; Szwargulski, P.; Sequeira, S.; Kaul, M. G.; Lange, C.; Ittrich, H.; Knopp, Tobias

    2016-05-01

    The use of superparamagnetic iron oxide nanoparticles (SPIONs) has provided new possibilities in biophysics and biomedical imaging technologies. The magnetization dynamics of SPIONs, which can be influenced by the environment, are of central interest. In this work, different biological SPION environments are used to investigate three different calibration methods for stem cell monitoring in magnetic particle imaging. It is shown that calibrating using SPIONs immobilized via agarose gel or intracellular uptake results in superior stem cell image quality compared to mobile SPIONs in saline. This superior image quality enables more sensitive localization and identification of a significantly smaller number of magnetically labeled stem cells. The results are important for cell tracking and monitoring of future SPION based therapies such as hyperthermia based cancer therapies, targeted drug delivery, or tissue regeneration approaches where it is crucial to image a sufficiently small number of SPIONs interacting with biological matter.

  5. Moissanite anvil cell design for giga-pascal nuclear magnetic resonance

    SciTech Connect

    Meier, Thomas; Herzig, Tobias; Haase, Jürgen

    2014-04-15

    A new design of a non-magnetic high-pressure anvil cell for nuclear magnetic resonance (NMR) experiments at Giga-Pascal pressures is presented, which uses a micro-coil inside the pressurized region for high-sensitivity NMR. The comparably small cell has a length of 22 mm and a diameter of 18 mm, so it can be used with most NMR magnets. The performance of the cell is demonstrated with external-force vs. internal-pressure experiments, and the cell is shown to perform well at pressures up to 23.5 GPa using 800 μm 6H-SiC large cone Boehler-type anvils. {sup 1}H, {sup 23}Na, {sup 27}Al, {sup 69}Ga, and {sup 71}Ga NMR test measurements are presented, which show a resolution of better than 4.5 ppm, and an almost maximum possible signal-to-noise ratio.

  6. Moissanite anvil cell design for giga-pascal nuclear magnetic resonance

    NASA Astrophysics Data System (ADS)

    Meier, Thomas; Herzig, Tobias; Haase, Jürgen

    2014-04-01

    A new design of a non-magnetic high-pressure anvil cell for nuclear magnetic resonance (NMR) experiments at Giga-Pascal pressures is presented, which uses a micro-coil inside the pressurized region for high-sensitivity NMR. The comparably small cell has a length of 22 mm and a diameter of 18 mm, so it can be used with most NMR magnets. The performance of the cell is demonstrated with external-force vs. internal-pressure experiments, and the cell is shown to perform well at pressures up to 23.5 GPa using 800 μm 6H-SiC large cone Boehler-type anvils. 1H, 23Na, 27Al, 69Ga, and 71Ga NMR test measurements are presented, which show a resolution of better than 4.5 ppm, and an almost maximum possible signal-to-noise ratio.

  7. Increasing the sensitivity for stem cell monitoring in system-function based magnetic particle imaging.

    PubMed

    Them, Kolja; Salamon, J; Szwargulski, P; Sequeira, S; Kaul, M G; Lange, C; Ittrich, H; Knopp, Tobias

    2016-05-01

    The use of superparamagnetic iron oxide nanoparticles (SPIONs) has provided new possibilities in biophysics and biomedical imaging technologies. The magnetization dynamics of SPIONs, which can be influenced by the environment, are of central interest. In this work, different biological SPION environments are used to investigate three different calibration methods for stem cell monitoring in magnetic particle imaging. It is shown that calibrating using SPIONs immobilized via agarose gel or intracellular uptake results in superior stem cell image quality compared to mobile SPIONs in saline. This superior image quality enables more sensitive localization and identification of a significantly smaller number of magnetically labeled stem cells. The results are important for cell tracking and monitoring of future SPION based therapies such as hyperthermia based cancer therapies, targeted drug delivery, or tissue regeneration approaches where it is crucial to image a sufficiently small number of SPIONs interacting with biological matter. PMID:27032447

  8. USING CORONAL CELLS TO INFER THE MAGNETIC FIELD STRUCTURE AND CHIRALITY OF FILAMENT CHANNELS

    SciTech Connect

    Sheeley, N. R. Jr.; Warren, H. P.; Martin, S. F.; Panasenco, O.

    2013-08-01

    Coronal cells are visible at temperatures of {approx}1.2 MK in Fe XII coronal images obtained from the Solar Dynamics Observatory and Solar Terrestrial Relations Observatory spacecraft. We show that near a filament channel, the plumelike tails of these cells bend horizontally in opposite directions on the two sides of the channel like fibrils in the chromosphere. Because the cells are rooted in magnetic flux concentrations of majority polarity, these observations can be used with photospheric magnetograms to infer the direction of the horizontal field in filament channels and the chirality of the associated magnetic field. This method is similar to the procedure for inferring the direction of the magnetic field and the chirality of the fibril pattern in filament channels from H{alpha} observations. However, the coronal cell observations are easier to use and provide clear inferences of the horizontal field direction for heights up to {approx}50 Mm into the corona.

  9. Magnetic nanoparticles for ultrafast mechanical control of inner ear hair cells.

    PubMed

    Lee, Jae-Hyun; Kim, Ji-wook; Levy, Michael; Kao, Albert; Noh, Seung-Hyun; Bozovic, Dolores; Cheon, Jinwoo

    2014-07-22

    We introduce cubic magnetic nanoparticles as an effective tool for precise and ultrafast control of mechanosensitive cells. The temporal resolution of our system is ∼1000 times faster than previously used magnetic switches and is comparable to the current state-of-the-art optogenetic tools. The use of a magnetism-gated switch reported here can address the key challenges of studying mechanotransduction in biological systems. The cube-shaped magnetic nanoparticles are designed to bind to components of cellular membranes and can be controlled with an electromagnet to exert pico-Newtons of mechanical force on the cells. The cubic nanoparticles can thus be used for noncontact mechanical control of the position of the stereocilia of an inner ear hair cell, yielding displacements of tens of nanometers, with sub-millisecond temporal resolution. We also prove that such mechanical stimulus leads to the influx of ions into the hair cell. Our study demonstrates that a magnetic switch can yield ultrafast temporal resolution, and has capabilities for remote manipulation and biological specificity, and that such magnetic system can be used for the study of mechanotransduction processes of a wide range of sensory systems. PMID:25004005

  10. A Magnetic Nanoparticle-Based Multiple-Gene Delivery System for Transfection of Porcine Kidney Cells

    PubMed Central

    Wang, Yan; Cui, Haixin; Li, Kui; Sun, Changjiao; Du, Wei; Cui, Jinhui; Zhao, Xiang; Chen, Wenjie

    2014-01-01

    Superparamagnetic nanoparticles are promising candidates for gene delivery into mammalian somatic cells and may be useful for reproductive cloning using the somatic cell nuclear transfer technique. However, limited investigations of their potential applications in animal genetics and breeding, particularly multiple-gene delivery by magnetofection, have been performed. Here, we developed a stable, targetable and convenient system for delivering multiple genes into the nuclei of porcine somatic cells using magnetic Fe3O4 nanoparticles as gene carriers. After surface modification by polyethylenimine, the spherical magnetic Fe3O4 nanoparticles showed strong binding affinity for DNA plasmids expressing the genes encoding a green (DNAGFP) or red (DNADsRed) fluorescent protein. At weight ratios of DNAGFP or DNADsRed to magnetic nanoparticles lower than or equal to 10∶1 or 5∶1, respectively, the DNA molecules were completely bound by the magnetic nanoparticles. Atomic force microscopy analyses confirmed binding of the spherical magnetic nanoparticles to stretched DNA strands up to several hundred nanometers in length. As a result, stable and efficient co-expression of GFP and DsRed in porcine kidney PK-15 cells was achieved by magnetofection. The results presented here demonstrate the potential application of magnetic nanoparticles as an attractive delivery system for animal genetics and breeding studies. PMID:25048709

  11. Cell type-specific response to high intracellular loading of polyacrylic acid-coated magnetic nanoparticles.

    PubMed

    Lojk, Jasna; Bregar, Vladimir B; Rajh, Maruša; Miš, Katarina; Kreft, Mateja Erdani; Pirkmajer, Sergej; Veranič, Peter; Pavlin, Mojca

    2015-01-01

    Magnetic nanoparticles (NPs) are a special type of NP with a ferromagnetic, electron-dense core that enables several applications such as cell tracking, hyperthermia, and magnetic separation, as well as multimodality. So far, superparamagnetic iron oxide NPs (SPIONs) are the only clinically approved type of metal oxide NPs, but cobalt ferrite NPs have properties suitable for biomedical applications as well. In this study, we analyzed the cellular responses to magnetic cobalt ferrite NPs coated with polyacrylic acid (PAA) in three cell types: Chinese Hamster Ovary (CHO), mouse melanoma (B16) cell line, and primary human myoblasts (MYO). We compared the internalization pathway, intracellular trafficking, and intracellular fate of our NPs using fluorescence and transmission electron microscopy (TEM) as well as quantified NP uptake and analyzed uptake dynamics. We determined cell viability after 24 or 96 hours' exposure to increasing concentrations of NPs, and quantified the generation of reactive oxygen species (ROS) upon 24 and 48 hours' exposure. Our NPs have been shown to readily enter and accumulate in cells in high quantities using the same two endocytic pathways; mostly by macropinocytosis and partially by clathrin-mediated endocytosis. The cell types differed in their uptake rate, the dynamics of intracellular trafficking, and the uptake capacity, as well as in their response to higher concentrations of internalized NPs. The observed differences in cell responses stress the importance of evaluation of NP-cell interactions on several different cell types for better prediction of possible toxic effects on different cell and tissue types in vivo. PMID:25733835

  12. Cell type-specific response to high intracellular loading of polyacrylic acid-coated magnetic nanoparticles

    PubMed Central

    Lojk, Jasna; Bregar, Vladimir B; Rajh, Maruša; Miš, Katarina; Kreft, Mateja Erdani; Pirkmajer, Sergej; Veranič, Peter; Pavlin, Mojca

    2015-01-01

    Magnetic nanoparticles (NPs) are a special type of NP with a ferromagnetic, electron-dense core that enables several applications such as cell tracking, hyperthermia, and magnetic separation, as well as multimodality. So far, superparamagnetic iron oxide NPs (SPIONs) are the only clinically approved type of metal oxide NPs, but cobalt ferrite NPs have properties suitable for biomedical applications as well. In this study, we analyzed the cellular responses to magnetic cobalt ferrite NPs coated with polyacrylic acid (PAA) in three cell types: Chinese Hamster Ovary (CHO), mouse melanoma (B16) cell line, and primary human myoblasts (MYO). We compared the internalization pathway, intracellular trafficking, and intracellular fate of our NPs using fluorescence and transmission electron microscopy (TEM) as well as quantified NP uptake and analyzed uptake dynamics. We determined cell viability after 24 or 96 hours’ exposure to increasing concentrations of NPs, and quantified the generation of reactive oxygen species (ROS) upon 24 and 48 hours’ exposure. Our NPs have been shown to readily enter and accumulate in cells in high quantities using the same two endocytic pathways; mostly by macropinocytosis and partially by clathrin-mediated endocytosis. The cell types differed in their uptake rate, the dynamics of intracellular trafficking, and the uptake capacity, as well as in their response to higher concentrations of internalized NPs. The observed differences in cell responses stress the importance of evaluation of NP–cell interactions on several different cell types for better prediction of possible toxic effects on different cell and tissue types in vivo. PMID:25733835

  13. Tracking Transplanted Stem Cells Using Magnetic Resonance Imaging and the Nanoparticle Labeling Method in Urology

    PubMed Central

    Kim, Jae Heon; Lee, Hong J.; Song, Yun Seob

    2015-01-01

    A reliable in vivo imaging method to localize transplanted cells and monitor their viability would enable a systematic investigation of cell therapy. Most stem cell transplantation studies have used immunohistological staining, which does not provide information about the migration of transplanted cells in vivo in the same host. Molecular imaging visualizes targeted cells in a living host, which enables determining the biological processes occurring in transplanted stem cells. Molecular imaging with labeled nanoparticles provides the opportunity to monitor transplanted cells noninvasively without sacrifice and to repeatedly evaluate them. Among several molecular imaging techniques, magnetic resonance imaging (MRI) provides high resolution and sensitivity of transplanted cells. MRI is a powerful noninvasive imaging modality with excellent image resolution for studying cellular dynamics. Several types of nanoparticles including superparamagnetic iron oxide nanoparticles and magnetic nanoparticles have been used to magnetically label stem cells and monitor viability by MRI in the urologic field. This review focuses on the current role and limitations of MRI with labeled nanoparticles for tracking transplanted stem cells in urology. PMID:26413510

  14. Retinoic acid inhibits the cytoproliferative response to weak 50-Hz magnetic fields in neuroblastoma cells

    PubMed Central

    TRILLO, MARÍA ÁNGELES; MARTÍNEZ, MARÍA ANTONIA; CID, MARÍA ANTONIA; ÚBEDA, ALEJANDRO

    2012-01-01

    We previously reported that intermittent exposure to a 50-Hz magnetic field (MF) at 100 μT stimulates cell proliferation in the human neuroblastoma cell line NB69. The present study aimed to investigate whether the magnetic field-induced growth promotion also occurs at a lower magnetic flux density of 10 μT. To this purpose, NB69 cells were subjected for 42 h to intermittent exposure, 3 h on/3 h off, to a 50-Hz MF at a 10 or 100 μT magnetic flux density. The field exposure took place either in the presence or in the absence of the antiproliferative agent retinoic acid. At the end of the treatment and/or incubation period, the cell growth was estimated by hemocytometric counting and spectrophotometric analysis of total protein and DNA contents. Potential changes in DNA synthesis were also assessed through proliferating cell nuclear antigen (PCNA) immunolabeling. The results confirmed previously reported data that a 42-h exposure to a 50-Hz sine wave MF at 100 μT promotes cell growth in the NB69 cell line, and showed that 10 μT induces a similar proliferative response. This effect, which was significantly associated and linearly correlated with PCNA expression, was abolished by the presence of retinoic acid in the culture medium. PMID:23292364

  15. Endothelialization of Magnetic Graft Materials using SPION-labeled Endothelial Cells

    NASA Astrophysics Data System (ADS)

    Newman, Brant R.; Dragomir-Daescu, Dan; Harbuzariu, Adriana; McIntosh, Malcolm; Harburn, J. Jonathan; Parakka, Anthony; Kalra, Manju; Holmes, David; Simari, Robert D.; Sandhu, Gurpreet S.

    2010-12-01

    Seeding vascular grafts with autologous endothelial cells (EC) has been shown to improve in vivo patency, but high cost and development time have prevented widespread clinical use. A technique for loading EC with superparamagnetic iron-oxide nanospheres (SPIONs) was recently described. SPION-loaded EC experience magnetic attractive forces in the presence of sufficient magnetic field gradients. Using a multi-factorial design of experiments approach, the quantity and spatial distribution of magnetizable metal particles within a poly (ether urethane) matrix were systematically varied to produce unique material specimens. Specimens were seeded with SPION-loaded ECs, and cell coverage was quantified at various post-seeding time intervals using micrographic image analysis. The effects of changing design parameters on cell capture and sustained cell viability on magnetic substrates were statistically examined. Magnetized ferrites and samarium cobalt demonstrated cell capture, though cytotoxicity prevented sustained cell growth. Cobalt chromium substrates showed effective cell capture and growth to near complete confluence for up to one month.

  16. Mechanical anisotropy and adaptation of metastatic cells probed by magnetic microbeads

    NASA Astrophysics Data System (ADS)

    Zhang, Zhipeng; Shi, Yanhui; Jhiang, Sissy M.; Menq, Chia-Hsiang

    2010-02-01

    Metastatic cells have the ability to break through the basal lamina, enter the blood vessels, circulate through the vasculature, exit at distant sites, and form secondary tumors. This multi-step process, therefore, clearly indicates the inherent ability of metastatic cells to sense, process, and adapt to the mechanical forces in different surrounding environments. We describe a magnetic probing device that is useful in characterizing the mechanical properties of cells along arbitrary two-dimensional directions. Magnetic force, with the advantages of biocompatibility and specificity, was produced by magnetic poles placed in an octupole configuration and applied to fibronectin-coated magnetic microbeads attached on cell membrane. Cell deformation in response to the applied force was then recorded through the displacement of the microbeads. The motion of the beads was measured by computer processing the video images acquired by a high-speed CMOS camera. Rotating force vectors with constant magnitude while pointing to directions of all 360 degrees were applied to study the mechanical anisotropy of metastatic breast cancer cells MDA-MB-231. The temporal changes in magnitude and directionality of the cellular responses were then analyzed to investigate the cellular adaptation to force stimulation. This probing technology thus has the potential to provide us a better understanding of the mechano-signatures of cells.

  17. A long-lasting concentration cell based on a magnetic electrolyte.

    PubMed

    Yan, Yong; Timonen, Jaakko V I; Grzybowski, Bartosz A

    2014-11-01

    A concentration cell is composed of two equivalent half-cells made of the same material but differing in the concentration of reactants. As these concentrations equilibrate, the increase in entropy is converted into a flow of electricity with the voltage output determined by the Nernst equation and proportional to the logarithm of the concentration ratios. However, as diffusion constantly strives to erase all concentration gradients, concentration cells produce only moderate voltages (typically tens of millivolts at room temperature) over relatively short times and, consequently, such devices have not been regarded as promising for energy storage. Here, we report a concentration cell that produces significantly higher voltages (∼ 0.5 V) for over 100 h. The key to our design is that the citric acid molecules involved in the electrode reactions are tethered onto magnetic nanoparticles, and a sharp gradient (10(7)-10(11) anode/cathode concentration ratio) is maintained at one of the electrodes by a permanent magnet external to the cell. Our cell does not result in corrosion of the electrodes, produces no harmful by-products, and can be regenerated by recoating used nanoparticles with fresh citric acid. We show that a series of such centimetre-sized cells produces enough electricity to power small electronic devices (timers and calculators) for several tens of hours. Our results illustrate how redox-active molecules that are, in themselves, non-magnetic can be effectively concentrated by magnetic fields to produce electrical energy. PMID:25262332

  18. A long-lasting concentration cell based on a magnetic electrolyte

    NASA Astrophysics Data System (ADS)

    Yan, Yong; Timonen, Jaakko V. I.; Grzybowski, Bartosz A.

    2014-11-01

    A concentration cell is composed of two equivalent half-cells made of the same material but differing in the concentration of reactants. As these concentrations equilibrate, the increase in entropy is converted into a flow of electricity with the voltage output determined by the Nernst equation and proportional to the logarithm of the concentration ratios. However, as diffusion constantly strives to erase all concentration gradients, concentration cells produce only moderate voltages (typically tens of millivolts at room temperature) over relatively short times and, consequently, such devices have not been regarded as promising for energy storage. Here, we report a concentration cell that produces significantly higher voltages (˜0.5 V) for over 100 h. The key to our design is that the citric acid molecules involved in the electrode reactions are tethered onto magnetic nanoparticles, and a sharp gradient (107-1011 anode/cathode concentration ratio) is maintained at one of the electrodes by a permanent magnet external to the cell. Our cell does not result in corrosion of the electrodes, produces no harmful by-products, and can be regenerated by recoating used nanoparticles with fresh citric acid. We show that a series of such centimetre-sized cells produces enough electricity to power small electronic devices (timers and calculators) for several tens of hours. Our results illustrate how redox-active molecules that are, in themselves, non-magnetic can be effectively concentrated by magnetic fields to produce electrical energy.

  19. Local mechanical response of cells to the controlled rotation of magnetic nanorods.

    PubMed

    Castillo, Matias; Ebensperger, Roberto; Wirtz, Denis; Walczak, Magdalena; Hurtado, Daniel E; Celedon, Alfredo

    2014-11-01

    The mechanical response of the cytoplasm was investigated by the intracellular implantation of magnetic nanorods and exposure to low-frequency rotatory magnetic fields. Nanorods (Pt-Ni, ∼200 nm diameter) fabricated by electrodeposition in templates of porous alumina with lengths of approximately 2 and 5 µm were inserted into NIH/3T3 fibroblasts and manipulated with a rotational magnetic field. Nanorod rotation was observed only for torques greater than 3.0 × 10(-16) Nm, suggesting a Bingham-type behavior of the cytoplasm. Higher torques produced considerable deformation of the intracellular material. The cell nucleus and cell membrane were significantly deformed by nanorods actuated by 4.5 × 10(-15) Nm torques. Our results demonstrate that nanorods under magnetic fields are an effective tool to mechanically probe the intracellular environment. We envision that our findings may contribute to the noninvasive and direct mechanical characterization of the cytoplasm. PMID:24700696

  20. Sub-Kelvin magnetic and electrical measurements in a diamond anvil cell with in situ tunability

    NASA Astrophysics Data System (ADS)

    Palmer, A.; Silevitch, D. M.; Feng, Yejun; Wang, Yishu; Jaramillo, R.; Banerjee, A.; Ren, Y.; Rosenbaum, T. F.

    2015-09-01

    We discuss techniques for performing continuous measurements across a wide range of pressure-field-temperature phase space, combining the milli-Kelvin temperatures of a helium dilution refrigerator with the giga-Pascal pressures of a diamond anvil cell and the Tesla magnetic fields of a superconducting magnet. With a view towards minimizing remnant magnetic fields and background magnetic susceptibility, we characterize high-strength superalloy materials for the pressure cell assembly, which allows high fidelity measurements of low-field phenomena such as superconductivity below 100 mK at pressures above 10 GPa. In situ tunability and measurement of the pressure permit experiments over a wide range of pressure, while at the same time making possible precise steps across abrupt phase transitions such as those from insulator to metal.

  1. Magnetic Flattening of Stem-Cell Spheroids Indicates a Size-Dependent Elastocapillary Transition

    NASA Astrophysics Data System (ADS)

    Mazuel, Francois; Reffay, Myriam; Du, Vicard; Bacri, Jean-Claude; Rieu, Jean-Paul; Wilhelm, Claire

    2015-03-01

    Cellular aggregates (spheroids) are widely used in biophysics and tissue engineering as model systems for biological tissues. In this Letter we propose novel methods for molding stem-cell spheroids, deforming them, and measuring their interfacial and elastic properties with a single method based on cell tagging with magnetic nanoparticles and application of a magnetic field gradient. Magnetic molding yields spheroids of unprecedented sizes (up to a few mm in diameter) and preserves tissue integrity. On subjecting these spheroids to magnetic flattening (over 150 g ), we observed a size-dependent elastocapillary transition with two modes of deformation: liquid-drop-like behavior for small spheroids, and elastic-sphere-like behavior for larger spheroids, followed by relaxation to a liquidlike drop.

  2. Sub-Kelvin magnetic and electrical measurements in a diamond anvil cell with in situ tunability.

    PubMed

    Palmer, A; Silevitch, D M; Feng, Yejun; Wang, Yishu; Jaramillo, R; Banerjee, A; Ren, Y; Rosenbaum, T F

    2015-09-01

    We discuss techniques for performing continuous measurements across a wide range of pressure-field-temperature phase space, combining the milli-Kelvin temperatures of a helium dilution refrigerator with the giga-Pascal pressures of a diamond anvil cell and the Tesla magnetic fields of a superconducting magnet. With a view towards minimizing remnant magnetic fields and background magnetic susceptibility, we characterize high-strength superalloy materials for the pressure cell assembly, which allows high fidelity measurements of low-field phenomena such as superconductivity below 100 mK at pressures above 10 GPa. In situ tunability and measurement of the pressure permit experiments over a wide range of pressure, while at the same time making possible precise steps across abrupt phase transitions such as those from insulator to metal. PMID:26429451

  3. Sub-Kelvin magnetic and electrical measurements in a diamond anvil cell with in situ tunability

    SciTech Connect

    Palmer, A; Silevitch, D M; Feng, Yejun; Wang, Y; Jaramillo, R.; Banerjee, A.; Ren, Y.; Rosenbaum, T. F.

    2015-09-01

    We discuss techniques for performing continuous measurements across a wide range of pressure–field–temperature phase space, combining the milli-Kelvin temperatures of a helium dilution refrigerator with the giga-Pascal pressures of a diamond anvil cell and the Tesla magnetic fields of a superconducting magnet. With a view towards minimizing remnant magnetic fields and background magnetic susceptibility, we characterize high-strength superalloy materials for the pressure cell assembly, which allows high fidelity measurements of low-field phenomena such as superconductivity below 100 mK at pressures above 10 GPa. In situ tunability and measurement of the pressure permit experiments over a wide range of pressure, while at the same time making possible precise steps across abrupt phase transitions such as those from insulator to metal.

  4. High-Resolution Proton Nuclear Magnetic Resonance Analysis of Metastatic Cancer Cells

    NASA Astrophysics Data System (ADS)

    Mountford, Carolyn E.; Wright, Lesley C.; Holmes, Kerry T.; MacKinnon, Wanda B.; Gregory, Patricia; Fox, Richard M.

    1984-12-01

    High-resolution proton nuclear magnetic resonance (NMR) studies of intact cancer cells revealed differences between cells with the capacity to metastasize and those that produce locally invasive tumors. The NMR resonances that characterize the metastatic cells were associated with an increased ratio of cholesterol to phospholipid and an increased amount of plasma membrane--bound cholesterol ester. High-resolution NMR spectroscopy could therefore be used to assess the metastatic potential of primary tumors.

  5. Electrical performance of a string of magnets representing a half-cell of the LHC machine

    SciTech Connect

    Rodriguez-Mateos, F.; Coull, L.; Dahlerup-Petersen, K.; Hagedorn, D.; Krainz, G.; Rijllart, A.; McInturff, A.

    1995-06-21

    Tests have been carried out on a string prototype superconducting magnets, consisting of one double-quadrupole and two double-dipoles forming the major part of a half-cell of the LHC machine. The magnets are protected individually by ``cold diodes`` and quench heaters. The electrical aspects of these tests are described here. The performance during quench of the protection diodes and the associated interconnections was studied. Tests determined the magnet quench performance in training and at different ramp-rates, and investigated the inter-magnet propagation of quenches. Current lead and inter-magnet contact resistances were controlled and the performance of the power converter and the dump switches assessed.

  6. Design features of the solenoid magnets for the central cell of the MFTF-B

    SciTech Connect

    Wohlwend, J.W.; Tatro, R.E.; Ring, D.S.

    1981-10-23

    The 14 superconducting solenoid magnets which form the central cell of the MFTF-B are being designed and fabricated by General Dynamics for the Lawrence Livermore National Laboratory. Each solenoid coil has a mean diameter of five meters and contains 600 turns of a proven conductor type. Structural loading resulting from credible fault events, cooldown and warmup requirements, and manufacturing processes consistent with other MFTF-B magnets have been considered in the selection of 304 LN as the structural material for the magnet. The solenoid magnets are connected by 24 intercoil beams and 20 solid struts which resist the longitudinal seismic and electromagnetic attractive forces and by 24 hanger/side supports which react magnet dead weight and seismic loads. A modular arrangement of two solenoid coils within a vacuum vessel segment allow for sequential checkout and installation.

  7. Magnetic Levitation of MC3T3 Osteoblast Cells as a Ground-Based Simulation of Microgravity.

    PubMed

    Hammer, Bruce E; Kidder, Louis S; Williams, Philip C; Xu, Wayne Wenzhong

    2009-11-01

    Diamagnetic samples placed in a strong magnetic field and a magnetic field gradient experience a magnetic force. Stable magnetic levitation occurs when the magnetic force exactly counter balances the gravitational force. Under this condition, a diamagnetic sample is in a simulated microgravity environment. The purpose of this study is to explore if MC3T3-E1 osteoblastic cells can be grown in magnetically simulated hypo-g and hyper-g environments and determine if gene expression is differentially expressed under these conditions. The murine calvarial osteoblastic cell line, MC3T3-E1, grown on Cytodex-3 beads, were subjected to a net gravitational force of 0, 1 and 2 g in a 17 T superconducting magnet for 2 days. Microarray analysis of these cells indicated that gravitational stress leads to up and down regulation of hundreds of genes. The methodology of sustaining long-term magnetic levitation of biological systems are discussed. PMID:20052306

  8. Light narrowing of rubidium magnetic-resonance lines in high-pressure optical-pumping cells

    NASA Astrophysics Data System (ADS)

    Appelt, S.; Ben-Amar Baranga, A.; Young, A. R.; Happer, W.

    1999-03-01

    We report on some unusual magnetic-resonance phenomena of optically pumped Rb vapor in high-pressure gas cells. When Rb-Rb spin exchange is the fastest spin-relaxation rate, we observe a considerable narrowing of the magnetic-resonance linewidths with increasing pump-laser power. The experimentally measured Rb magnetic-resonance linewidths are in excellent agreement with a theoretical model, which includes the processes of Rb-He and Rb-Xe spin destruction, Rb-Rb spin exchange, and Rb optical pumping.

  9. Magnetic field effects in RF magnetron sputtering of CdS/CdTe solar cells

    SciTech Connect

    Compaan, A.D.; Shao, M.; Tabory, C.N.; Feng, Z.; Fischer, A.; Shen, F.; Narayanswami, C.; Bohn, R.G.

    1996-01-01

    We have studied effects of magnetic field strength and configuration on rf planar magnetron sputtering of CdS and CdTe. This study was carried out with one sputter gun having an unbalanced magnetic field and a second gun having an approximately balanced magnetic field. The unbalanced field gun produces significantly higher ion and electron bombardment of the film during growth and slightly higher electron kinetic energies. Films produced with the unbalanced gun show much stronger photoluminescence and cell performance is much better when the CdTe is deposited with the unbalanced gun. {copyright} {ital 1996 American Institute of Physics.}

  10. Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Nonsmall Cell Lung Cancer.

    PubMed

    Munaweera, Imalka; Shi, Yi; Koneru, Bhuvaneswari; Saez, Ruben; Aliev, Ali; Di Pasqua, Anthony J; Balkus, Kenneth J

    2015-10-01

    Lung cancer is the leading cause of cancer-related death in the United States and approximately 85% of all lung cancers are classified as nonsmall cell (NSCLC). We here use an innovative approach that may ultimately allow for the clinician to target tumors and aggressively reduce tumor burden in patients with NSCLC. In this study, a platinum (Pt)-based chemotherapeutic (cisplatin, carboplatin, or oxaliplatin) and holmium-165 (Ho), which can be neutron-activated to produce the holmium-166 radionuclide, have been incorporated together in a garnet magnetic nanoparticle (HoIG-Pt) for selective delivery to tumors using an external magnet. The synthesized magnetic HoIG nanoparticles were characterized using PXRD, TEM, ICP-MS, and neutron-activation. Platinum(II) drugs were incorporated onto HoIG, and these were characterized using FTIR, EDX, ICP-MS, and zeta potential measurements, and in vitro and in vivo studies were performed using a HoIG-platinum system. Results indicate that neutron-activated (166)HoIG-cisplatin is more toxic toward NSCLC A549 cells than is blank (166)HoIG and free cisplatin, and that when an external magnetic field is applied in vivo, higher tumor to liver ratios of Ho are observed than when no magnet is applied, suggesting that magnetic targeting is achieved using this system. Furthermore, an efficacy study demonstrated the inhibition of tumor growth by chemoradiotherapeutic magnetic nanoparticles, compared to no treatment controls. PMID:26325115

  11. Magneto-impedance based detection of magnetically labeled cancer cells and bio-proteins

    NASA Astrophysics Data System (ADS)

    Devkota, J.; Howell, M.; Mohapatra, S.; Nhung, T. H.; Mukherjee, P.; Srikanth, H.; Phan, M. H.

    2015-03-01

    A magnetic biosensor with enhanced sensitivity and immobilized magnetic markers is essential for a reliable analysis of the presence of a biological entity in a fluid. Based on conventional approaches, however, it is quite challenging to create such a sensor. We report on a novel magnetic biosensor using the magneto-impedance (MI) effect of a Co-based amorphous ribbon with a microhole-patterned surface that fulfils these requirements. The sensor probe was fabricated by patterning four microholes, each of diameter 2 μm and depth 2 μm, on the ribbon surface using FIB lithography. The magnetically labeled Luis Lung Carcinoma (LLC) cancer cells and Bovine serum albumin (BSA) proteins were drop-casted on the ribbon surface, and MI was measured over 0.1 - 10 MHz frequency range. As the analytes were trapped into the microholes, their physical motion was minimized and interaction among the magnetic fields was strengthened, thus yielding a more reliable and sensitive detection of the biological entities. The presence of magnetically labeled LLC cells (8.25x105 cells/ml, 10 μl) and BSA proteins (2x1011 particles/ml, 10 μl) were found to result in a ~ 2% change in MI with respect to the reference signal.

  12. Experimental determination of the magnetic dipole moment of candidate magnetoreceptor cells in trout

    NASA Astrophysics Data System (ADS)

    Winklhofer, M.; Eder, S.; Cadioiu, H.; McNaughton, P. A.; Kirschvink, J. L.

    2011-12-01

    Based on histological, physiological, and physical evidence, Walker et al (1997) and Diebel et al (2000) have identified distinctive cells in the olfactory epithelium of the rainbow trout (Onchorynchus mykiss) that contain magnetite and are closely associated with neurons that respond to changes in magnetic field. To put biophysical constraints on the possible transduction mechanism of magnetic signals, and in particular, to find out if the intracellular magnet is free to rotate or rather firmly anchored within the cell body, we have studied the magneto-mechanical response of isolated candidate receptor cells in suspension using a light microscope equipped with two pairs of Helmholtz coils. From the characteristic re-orientation time of suspended cells after a change in magnetic field direction, we have determined the magnitude of the magnetic dipole moment of the cells in function of the external field strength (0.4 mT to 3.2 mT) in order to find out whether or not the natural magnetic moment is remanence-based or induced (i.e., single-domain vs. superparamagnetic/multi-domain). Results: 1) The mechanical response of isolated cells to a change in magnetic field direction was always immediate, irrespective of the direction of change, which implies that the intracellular magnet is not free to rotate in the cell, but rather rigidly attached, probably to the plasma membrane, which is also suggested by our confocal fluorescence-microscope studies. 2) The cellular dipole moment turned out to be independent of the external field strength. Thus, the natural magnetic dipole moment is based on magnetic remanence, which points to single-domain particles and corroborates the results by Diebel et al (2000), who obtained switching fields consistent with single-domain magnetite. 3). The magnetic dipole moment is found to be of the order of several tens of fAm2, which greatly exceeds previous estimates (0.5 fAm2), and thus is similar to values reported for the most strongly

  13. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells.

    PubMed

    Galanzha, Ekaterina I; Shashkov, Evgeny V; Kelly, Thomas; Kim, Jin-Woo; Yang, Lily; Zharov, Vladimir P

    2009-12-01

    The spread of cancer cells between organs, a process known as metastasis, is the cause of most cancer deaths. Detecting circulating tumour cells -- a common marker for the development of metastasis -- is difficult because ex vivo methods are not sensitive enough owing to limited blood sample volume and in vivo diagnosis is time-consuming as large volumes of blood must be analysed. Here, we show a way to magnetically capture circulating tumour cells in the bloodstream of mice followed by rapid photoacoustic detection. Magnetic nanoparticles, which were functionalized to target a receptor commonly found in breast cancer cells, bound and captured circulating tumour cells under a magnet. To improve detection sensitivity and specificity, gold-plated carbon nanotubes conjugated with folic acid were used as a second contrast agent for photoacoustic imaging. By integrating in vivo multiplex targeting, magnetic enrichment, signal amplification and multicolour recognition, our approach allows circulating tumour cells to be concentrated from a large volume of blood in the vessels of tumour-bearing mice, and this could have potential for the early diagnosis of cancer and the prevention of metastasis in humans. PMID:19915570

  14. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells

    NASA Astrophysics Data System (ADS)

    Galanzha, Ekaterina I.; Shashkov, Evgeny V.; Kelly, Thomas; Kim, Jin-Woo; Yang, Lily; Zharov, Vladimir P.

    2009-12-01

    The spread of cancer cells between organs, a process known as metastasis, is the cause of most cancer deaths. Detecting circulating tumour cells-a common marker for the development of metastasis-is difficult because ex vivo methods are not sensitive enough owing to limited blood sample volume and in vivo diagnosis is time-consuming as large volumes of blood must be analysed. Here, we show a way to magnetically capture circulating tumour cells in the bloodstream of mice followed by rapid photoacoustic detection. Magnetic nanoparticles, which were functionalized to target a receptor commonly found in breast cancer cells, bound and captured circulating tumour cells under a magnet. To improve detection sensitivity and specificity, gold-plated carbon nanotubes conjugated with folic acid were used as a second contrast agent for photoacoustic imaging. By integrating in vivo multiplex targeting, magnetic enrichment, signal amplification and multicolour recognition, our approach allows circulating tumour cells to be concentrated from a large volume of blood in the vessels of tumour-bearing mice, and this could have potential for the early diagnosis of cancer and the prevention of metastasis in humans.

  15. Graphite-coated magnetic nanoparticle microarray for few-cells enrichment and detection.

    PubMed

    Chen, Zhuo; Hong, Guosong; Wang, Hailiang; Welsher, Kevin; Tabakman, Scott M; Sherlock, Sarah P; Robinson, Joshua T; Liang, Yongye; Dai, Hongjie

    2012-02-28

    Graphite-coated, highly magnetic FeCo core-shell nanoparticles were synthesized by a chemical vapor deposition method and solubilized in aqueous solution through a unique polymer mixture modification, which significantly improved the biocompatibility and stability of the magnetic nanoparticles (MNPs). Such functionalized MNPs were proven to be very stable in different conditions which would be significant for biological applications. Cell staining, manipulation, enrichment, and detection were developed with these MNPs. Under external magnetic manipulation, the MNP-stained cells exhibited directed motions. Moreover, MNPs were printed on substrates to modulate the magnetic field distribution on the surface. Capture and detection of sparse populations of cancer cells spiked into whole blood has been explored in a microarray fashion. Cancer cells from hundreds down to only two were able to be simply and efficiently detected from 1 mL of whole blood on the MNP microarray chips. Interestingly, the cells captured through the MNP microarray still showed viability and adhered to the MNP spots after incubation, which could be utilized for cancer cell detection, localized growth, and proliferation. PMID:22229344

  16. Digitized quantitative electroencephalographic patterns applied as magnetic fields inhibit melanoma cell proliferation in culture.

    PubMed

    Karbowski, Lukasz M; Harribance, Sean L; Buckner, Carly A; Mulligan, Bryce P; Koren, Stanley A; Lafrenie, Robert M; Persinger, Michael A

    2012-08-15

    Weak (1 μT) physiologically patterned magnetic fields produce changes in behavioral, physiological, and cellular activity. In the present experiments 12 temporal samples of the electroencephalographic anomaly and normal activity of a person (SLH) whose proximity reliably affected the brain activity of others were extracted from QEEG data, digitized, and presented as equivalent magnetic field patterns to B16 mouse melanoma cells. Only two of the patterns, both originating from the primary source (right temporal lobe) of the EEG anomaly reduced the cell growth by one-third compared to the other patterns extracted from his QEEG or sham field exposures. In previous experiments these EEG transients were also associated with marked increases in photon emissions from the right side of SLH's head. The results suggest that the intrinsic complexity of electroencephalographic patterns of some people, when amplified appropriately and applied as computer-generated magnetic fields in the three spatial planes, could diminish cancer cell growth. PMID:22750152

  17. Effect of extremely low frequency magnetic fields on cell proliferation and gene expression.

    PubMed

    Lee, Hyung Chul; Hong, Mi-Na; Jung, Seung Hee; Kim, Bong Cho; Suh, Young Ju; Ko, Young-Gyu; Lee, Yun-Sil; Lee, Byeong-Yoon; Cho, Yeun-Gyu; Myung, Sung-Ho; Lee, Jae-Seon

    2015-10-01

    Owing to concerns regarding possible effects of extremely low frequency magnetic fields (ELF-MF) on human health, many studies have been conducted to elucidate whether ELF-MF can induce modifications in biological processes. Despite this, controversies regarding effects of ELF-MF are still rife. In this study, we investigated biological effects of ELF-MF on MCF10A, MCF7, Jurkat, and NIH3T3 cell lines. ELF-MF with a magnetic flux density of 1 mT at 60 Hz was employed to stimulate cells for 4 or 16 h, after which the effects of ELF-MF on cell proliferation, cell death, cell viability, and DNA synthesis rates were assessed. Whereas Jurkat and NIH3T3 cells showed no consistent variation in cell number, cell viability, and DNA synthesis rate, MCF10A and MCF7 cells showed consistent and significant decreases in cell number, cell viability, and DNA synthesis rates. However, there was no effect of ELF-MF on cell death in any of tested cell lines. Next, to investigate the effect of ELF-MF on gene expression, we exposed MCF7 cells to 2 mT at 60 Hz for 16 h and examined transcriptional responses by using gene expression array. We found a gene, PMAIP1, that exhibited statistically significant variation using two-fold cut-off criteria and certified its expression change by using semi-quantitative and quantitative reverse transcription polymerase chain reaction. From these results, we concluded that ELF-MF could induce the delay of cell cycle progression in MCF7 and MCF10A cells in a cell context-specific manner and could up-regulate PMAIP1 in MCF7 cells. PMID:26239017

  18. Molecular extraction in single live cells by sneaking in and out magnetic nanomaterials

    PubMed Central

    Yang, Zhen; Deng, Liangzi; Lan, Yucheng; Zhang, Xiaoliu; Gao, Zhonghong; Chu, Ching-Wu; Cai, Dong; Ren, Zhifeng

    2014-01-01

    Extraction of intracellular molecules is crucial to the study of cellular signal pathways. Disruption of the cellular membrane remains the established method to release intracellular contents, which inevitably terminates the time course of biological processes. Also, conventional laboratory extractions mostly use bulky materials that ignore the heterogeneity of each cell. In this work, we developed magnetized carbon nanotubes that can be sneaked into and out of cell bodies under a magnetic force. Using a testing model with overexpression of GFP, the nanotubes successfully transported the intracellular GFP out at the single-cell level. The confined nanoscale invasiveness did not change cell viability or proliferation. This study presents the proof of concept of a previously unidentified real-time and single-cell approach to investigate cellular biology, signal messengers, and therapeutic effects with nanomaterials. PMID:25030447

  19. Magnetic poly(lactide-co-glycolide) and cellulose particles for MRI-based cell tracking.

    PubMed

    Nkansah, Michael K; Thakral, Durga; Shapiro, Erik M

    2011-06-01

    Biodegradable, superparamagnetic microparticles and nanoparticles of poly(lactide-co-glycolide) (PLGA) and cellulose were designed, fabricated, and characterized for magnetic cell labeling. Monodisperse nanocrystals of magnetite were incorporated into microparticles and nanoparticles of PLGA and cellulose with high efficiency using an oil-in-water single emulsion technique. Superparamagnetic cores had high magnetization (72.1 emu/g). The resulting polymeric particles had smooth surface morphology and high magnetite content (43.3 wt % for PLGA and 69.6 wt % for cellulose). While PLGA and cellulose nanoparticles displayed highest r 2* values per millimole of iron (399 sec(-1) mM(-1) for cellulose and 505 sec(-1) mM(-1) for PLGA), micron-sized PLGA particles had a much higher r 2* per particle than either. After incubation for a month in citrate buffer (pH 5.5), magnetic PLGA particles lost close to 50% of their initial r 2* molar relaxivity, while magnetic cellulose particles remained intact, preserving over 85% of their initial r 2* molar relaxivity. Lastly, mesenchymal stem cells and human breast adenocarcinoma cells were magnetically labeled using these particles with no detectable cytotoxicity. These particles are ideally suited for noninvasive cell tracking in vivo via MRI and due to their vastly different degradation properties, offer unique potential for dedicated use for either short (PLGA-based particles) or long-term (cellulose-based particles) experiments. PMID:21404328

  20. Selection of nonapoptotic sperm by magnetic-activated cell sorting in Senegalese sole (Solea senegalensis).

    PubMed

    Valcarce, D G; Herráez, M P; Chereguini, O; Rodríguez, C; Robles, V

    2016-09-15

    Senegalese sole (Solea senegalensis) is a promising species in aquaculture. However, owing to decreased sperm quality in F1 generations and the absence of courtship in those individuals born in captivity, artificial fertilization is being used to generate new progenies. The objective of this study was to implement a sperm selection method for nonapoptotic sperm subpopulation recovery before sperm cryopreservation. In particular, magnetic-activated cell sorting is used to eliminate apoptotic spermatozoa. This study represents the proof-of-concept for magnetic-activated cell sorting applicability in teleost species relevant in aquaculture. Apoptotic cell population was studied by flow cytometry using YO-PRO-1 and a caspase detection kit. Also, reactive oxygen species were measured in sperm samples. Our data demonstrated that caspase detection is more specific than YO-PRO-1 in the identification of apoptotic cells in S senegalensis seminal samples. The results showed that the percentage of apoptotic cells (caspase positive) was significantly higher (P = 0.04) in seminal samples from F1 than that from wild individuals. Magnetic-activated cell sorting removed a significant number of apoptotic cells from the samples (54% and 75% in wild and F1 individuals, respectively), decreasing the level of cells positive for reactive oxygen species (P = 0.17). In conclusion, this technique reduces the percentage of nonfunctional spermatozoa in a seminal sample before cryopreservation. This novel technique can be applied directly in the aquaculture industry. PMID:27173958

  1. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    NASA Astrophysics Data System (ADS)

    de Paula, Leonardo B.; Primo, Fernando L.; Pinto, Marcelo R.; Morais, Paulo C.; Tedesco, Antonio C.

    2015-04-01

    The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×1013 or 1.50×1013 particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×1013 or 1.50×1013 magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments.

  2. A simple cell patterning method using magnetic particle-containing photosensitive poly (ethylene glycol) hydrogel blocks: a technical note.

    PubMed

    Fu, Chien-Yu; Lin, Chun-Yen; Chu, Wen-Chen; Chang, Hwan-You

    2011-08-01

    All human organs consist of multiple types of cells organized in a complex pattern to meet specific functional needs. One possible approach for reconstructing human organs in vitro is to generate cell sheets of a specific pattern and later stack them systematically by layer into a three-dimensional organoid. However, many commonly used cell patterning techniques suffer drawbacks such as dependence on sophisticated instruments and manipulation of cells under suboptimal growth conditions. Here, we describe a simple cell patterning method that may overcome these problems. This method is based on magnetic force and photoresponsive poly (ethylene glycol) diacrylate (PEG-DA) hydrogels. The PEG-DA hydrogel was magnetized by mixing with iron ferrous microparticles and then fabricated into blocks with a specific pattern by photolithography. The resolution of the hydrogel empty space pattern was approximately 150  μm and the generated hydrogel blocks can be remotely manipulated with a magnet. The magnetic PEG-DA blocks were used as a stencil to define the area for cell adhesion in the cell culture dish, and the second types of cells could be seeded after the magnetic block was removed to create heterotypic cell patterns. Cell viability assay has demonstrated that magnetic PEG-DA and the patterning process produced negligible effects on cell growth. Together, our results indicate that this magnetic hydrogel-based cell patterning method is simple to perform and is a useful tool for tissue surrogate assembly for disease mechanism study and drug screening. PMID:21486199

  3. Proton nuclear magnetic resonance studies of mast cell histamine

    SciTech Connect

    Rabenstein, D.L.; Ludowyke, R.; Lagunoff, D.

    1987-11-03

    The state of histamine in mast cells was studied by /sup 1/H NMR spectroscopy. Spectra were measured for histamine in situ in intact mast cells, for histamine in suspensions of mast cell granule matrices that had been stripped of their membranes, and for histamine in solutions of heparin. The /sup 1/H NMR spectrum of intact mast cells is relatively simple, consisting predominantly of resonances for intracellular histamine superimposed on a weaker background of resonances from heparin and proteins of the cells. All of the intracellular histamine contributes of the NMR signals, indicating it must be relatively mobile and not rigidly associated with the negatively charged granule matrix. Spectra for intracellular histamine and for histamine in granule matrices are similar, indicating the latter to be a reasonable model for the in situ situation. The dynamics of binding of histamine by granule matrices and by heparin are considerably different; exchange of histamine between the bulk water and the granule matrices is slow on the /sup 1/H NMR time scale, whereas exchange between the free and bound forms in heparin solution is fast. The chemical shifts of resonances for histamine in mast cells are pH dependent, decreasing as the intragranule pH increases without splitting or broadening. The results are interpreted to indicate that histamine in mast cells is relatively labile, with rapid exchange between histamine and pools of free histamine in water compartments confined in the granule matrix.

  4. Synergistic enhancement effect of magnetic nanoparticles on anticancer drug accumulation in cancer cells

    NASA Astrophysics Data System (ADS)

    Zhang, Renyun; Wang, Xuemei; Wu, Chunhui; Song, Min; Li, Jingyuan; Lv, Gang; Zhou, Jian; Chen, Chen; Dai, Yongyuan; Gao, Feng; Fu, Degang; Li, Xiaomao; Guan, Zhiqun; Chen, Baoan

    2006-07-01

    Three kinds of magnetic nanoparticle, tetraheptylammonium capped nanoparticles of Fe3O4, Fe2O3 and Ni have been synthesized, and the synergistic effect of these nanoparticles on the drug accumulation of the anticancer drug daunorubicin in leukaemia cells has been explored. Our observations indicate that the enhancement effect of Fe3O4 nanoparticles is much stronger than that of Fe2O3 and Ni nanoparticles, suggesting that nanoparticle surface chemistry and size as well as the unique properties of the magnetic nanoparticles themselves may contribute to the synergistic enhanced effect of the drug uptake of targeted cancer cells.

  5. Contribution of a 300 kHz alternating magnetic field on magnetic hyperthermia treatment of HepG2 cells.

    PubMed

    Wang, Xiaowen; Chen, Youping; Huang, Changshuo; Wang, Xufei; Zhao, Linyun; Zhang, Xiaodong; Tang, Jintian

    2013-02-01

    We investigated the relative contributions of temperature and a 300 kHz alternating magnetic field (AMF) on magnetic hyperthermia treatment (MHT). Our system consisted of an induction coil, which generated AMF by electric current flow, and a newly developed, temperature-controlled circulating water-jacketed glass bottle placed inside the coil. The AMF generator operated at a frequency of 300 kHz with variable field strength ranging from 0 to 11 mT. Four treatment conditions were employed: (A) control (37 °C, 0 mT), (B) AMF exposure (37 °C, 11 mT), (C) hyperthermia (46 °C, 0 mT), and (D) hyperthermia plus AMF exposure (46 °C, 11 mT) for 30 min. Cell viability and apoptotic death rate were estimated. The relative contributions or interactions of hyperthermia (46 °C) and AMF (11 mT) on MHT were evaluated using 2 × 2 factorial experiment analysis. Group A was statistically different (P < 0.05) from each of the other treatments. The observed effects on both cell viability and apoptotic cell death were influenced by temperature (97.36% and 92.15%, respectively), AMF (1.78% and 4.99%, respectively), and the interactions between temperature and AMF (0.25% and 2.36%, respectively). Thus, the effect of hyperthermia was significant. Also, AMF exposure itself might play a role in MHT, although these observations were made in vitro. These findings suggest a possible presence of an AMF effect during clinical magnetic hyperthermia. PMID:23059525

  6. Magnetic Particle Spectroscopy Reveals Dynamic Changes in the Magnetic Behavior of Very Small Superparamagnetic Iron Oxide Nanoparticles During Cellular Uptake and Enables Determination of Cell-Labeling Efficacy.

    PubMed

    Poller, Wolfram C; Löwa, Norbert; Wiekhorst, Frank; Taupitz, Matthias; Wagner, Susanne; Möller, Konstantin; Baumann, Gert; Stangl, Verena; Trahms, Lutz; Ludwig, Antje

    2016-02-01

    In vivo tracking of nanoparticle-labeled cells by magnetic resonance imaging (MRI) crucially depends on accurate determination of cell-labeling efficacy prior to transplantation. Here, we analyzed the feasibility and accuracy of magnetic particle spectroscopy (MPS) for estimation of cell-labeling efficacy in living THP-1 cells incubated with very small superparamagnetic iron oxide nanoparticles (VSOP). Cell viability and proliferation capacity were not affected by the MPS measurement procedure. In VSOP samples without cell contact, MPS enabled highly accurate quantification. In contrast, MPS constantly overestimated the amount of cell associated and internalized VSOP. Analyses of the MPS spectrum shape expressed as harmonic ratio A₅/A₃ revealed distinct changes in the magnetic behavior of VSOP in response to cellular uptake. These changes were proportional to the deviation between MPS and actual iron amount, therefore allowing for adjusted iron quantification. Transmission electron microscopy provided visual evidence that changes in the magnetic properties correlated with cell surface interaction of VSOP as well as with alterations of particle structure and arrangement during the phagocytic process. Altogether, A₅/A₃-adjusted MPS enables highly accurate, cell-preserving VSOP quantification and furthermore provides information on the magnetic characteristics of internalized VSOP. PMID:27305767

  7. Application of a Halbach magnetic array for long-range cell and particle separations in biological samples

    NASA Astrophysics Data System (ADS)

    Kang, Joo H.; Driscoll, Harry; Super, Michael; Ingber, Donald E.

    2016-05-01

    Here, we describe a versatile application of a planar Halbach permanent magnet array for an efficient long-range magnetic separation of living cells and microparticles over distances up to 30 mm. A Halbach array was constructed from rectangular bar magnets using 3D-printed holders and compared to a conventional alternating array of identical magnets. We theoretically predicted the superiority of the Halbach array for a long-range magnetic separation and then experimentally validated that the Halbach configuration outperforms the alternating array for isolating magnetic microparticles or microparticle-bound bacterial cells at longer distances. Magnetophoretic velocities (ymag) of magnetic particles (7.9 μm diameter) induced by the Halbach array in a microfluidic device were significantly higher and extended over a larger area than those induced by the alternating magnet array (ymag = 178 versus 0 μm/s at 10 mm, respectively). When applied to 50 ml tubes (˜30 mm diameter), the Halbach array removed >95% of Staphylococcus aureus bacterial cells bound with 1 μm magnetic particles compared to ˜70% removed using the alternating array. In addition, the Halbach array enabled manipulation of 1 μm magnetic beads in a deep 96-well plate for ELISA applications, which was not possible with the conventional magnet arrays. Our analysis demonstrates the utility of the Halbach array for the future design of devices for high-throughput magnetic separations of cells, molecules, and toxins.

  8. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells

    PubMed Central

    Galanzha, Ekaterina I.; Shashkov, Evgeny V.; Kelly, Thomas; Kim, Jin-Woo; Yang, Lily; Zharov, Vladimir P.

    2012-01-01

    The spread of cancer cells between organs, a process known as metastasis, is the cause of most cancer deaths1,2. Detecting circulating tumour cells—a common marker for the development of metastasis3,4—is difficult because ex vivo methods are not sensitive enough owing to limited blood sample volume and in vivo diagnosis is time-consuming as large volumes of blood must be analysed5–7. Here, we show a way to magnetically capture circulating tumour cells in the bloodstream of mice followed by rapid photoacoustic detection. Magnetic nanoparticles, which were functionalized to target a receptor commonly found in breast cancer cells, bound and captured circulating tumour cells under a magnet. To improve detection sensitivity and specificity, gold-plated carbon nanotubes conjugated with folic acid were used as a second contrast agent for photoacoustic imaging. By integrating in vivo multiplex targeting, magnetic enrichment, signal amplification and multicolour recognition, our approach allows circulating tumour cells to be concentrated from a large volume of blood in the vessels of tumour-bearing mice, and this could have potential for the early diagnosis of cancer and the prevention of metastasis in humans. PMID:19915570

  9. Formation and properties of magnetic chains for 100 nm nanoparticles used in separations of molecules and cells

    PubMed Central

    Wilson, Robert J.; Hu, Wei; Fu, Cheryl Wong Po; Koh, Ai Leen; Gaster, Richard S.; Earhart, Christopher M.; Fu, Aihua; Heilshorn, Sarah C.; Sinclair, Robert; Wang, Shan X.

    2009-01-01

    Optical observations of 100 nm metallic magnetic nanoparticles are used to study their magnetic field induced self assembly. Chains with lengths of tens of microns are observed to form within minutes at nanoparticle concentrations of 1010 per mL. Chain rotation and magnetophoresis are readily observed, and SEM reveals that long chains are not simple single particle filaments. Similar chains are detected for several 100 nm commercial bio-separation nanoparticles. We demonstrate the staged magnetic condensation of different types of nanoparticles into composite structures and show that magnetic chains bind to immunomagnetically labeled cells, serving as temporary handles which allow novel magnetic cell manipulations. PMID:20161001

  10. Crystalline magnetic carbon nanoparticle assisted photothermal delivery into cells using CW near-infrared laser beam

    PubMed Central

    Gu, Ling; Koymen, Ali R.; Mohanty, Samarendra K.

    2014-01-01

    Efficient and targeted delivery of impermeable exogenous material such as small molecules, proteins, and plasmids into cells in culture as well as in vivo is of great importance for drug, vaccine and gene delivery for different therapeutic strategies. Though advent of optoporation by ultrafast laser microbeam has allowed spatial targeting in cells, the requirement of high peak power to create holes on the cell membrane is not practical and also challenging in vivo. Here, we report development and use of uniquely non-reactive crystalline magnetic carbon nanoparticles (CMCNPs) for photothermal delivery (PTD) of impermeable dyes and plasmids encoding light-sensitive proteins into cells using low power continuous wave near-infrared (NIR) laser beam. Further, we utilized the magnetic nature of these CMCNPs to localize them in desired region by external magnetic field, thus minimizing the required number of nanoparticles. We discovered that irradiation of the CMCNPs near the desired cell(s) with NIR laser beam leads to temperature rise that not only stretch the cell-membrane to ease delivery, it also creates fluid flow to allow mobilization of exogenous substances to the delivery. Due to significant absorption properties of the CMCNPs in the NIR therapeutic window, PTD under in vivo condition is highly possible. PMID:24870227

  11. Crystalline magnetic carbon nanoparticle assisted photothermal delivery into cells using CW near-infrared laser beam

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Koymen, Ali R.; Mohanty, Samarendra K.

    2014-05-01

    Efficient and targeted delivery of impermeable exogenous material such as small molecules, proteins, and plasmids into cells in culture as well as in vivo is of great importance for drug, vaccine and gene delivery for different therapeutic strategies. Though advent of optoporation by ultrafast laser microbeam has allowed spatial targeting in cells, the requirement of high peak power to create holes on the cell membrane is not practical and also challenging in vivo. Here, we report development and use of uniquely non-reactive crystalline magnetic carbon nanoparticles (CMCNPs) for photothermal delivery (PTD) of impermeable dyes and plasmids encoding light-sensitive proteins into cells using low power continuous wave near-infrared (NIR) laser beam. Further, we utilized the magnetic nature of these CMCNPs to localize them in desired region by external magnetic field, thus minimizing the required number of nanoparticles. We discovered that irradiation of the CMCNPs near the desired cell(s) with NIR laser beam leads to temperature rise that not only stretch the cell-membrane to ease delivery, it also creates fluid flow to allow mobilization of exogenous substances to the delivery. Due to significant absorption properties of the CMCNPs in the NIR therapeutic window, PTD under in vivo condition is highly possible.

  12. Genotoxic Effects of Superconducting Static Magnetic Fields (SMFs) on Wheat (Triticum aestivum) Pollen Mother Cells (PMCs)

    NASA Astrophysics Data System (ADS)

    Zhang, Pingping; Yin, Ruochun; Chen, Zhiyou; Wu, Lifang; Yu, Zengliang

    2007-04-01

    The effects of superconducting static magnetic fields (SMFs) on the pollen mother cells (PMCs) of wheat were investigated in order to evaluate the possible genotoxic effect of such non-ionizing radiation. The seeds of wheat were exposed to static magnetic fields with either different magnetic flux densities (0, 1, 3, 5 and 7 Tesla) for 5 h or different durations (1, 3 and 5 h) at a magnetic flux density of 7 Tesla. The seeds were germinated at 23oC after exposure and the seedlings were transplanted into the field. The PMCs from young wheat ears were taken and slides were made following the conventional method. The genotoxic effect was evaluated in terms of micronucleus (MN), chromosomal bridge, lagging chromosome and fragments in PMCs. Although the exposed groups of a low field intensity (below 5 Tesla) showed no statistically significant difference in the aberration frequency compared with the unexposed control groups and sham exposed groups, a significant increase in the chromosomal bridge, lagging chromosome, triple-polar segregation or micronucleus was observed at a field strength of 5 Tesla or 7 Tesla, respectively. The analysis of dose-effect relationships indicated that the increased frequency of meiotic abnormal cells correlated with the flux density of the magnetic field and duration, but no linear relationship was observed. Such statistically significant differences indicated a potential genotoxic effect of high static magnetic fields above 5 T.

  13. Does Magnetic Field Affect Malaria Parasite Replication in Human Red Blood Cells?

    NASA Technical Reports Server (NTRS)

    Chanturiya, Alexandr N.; Glushakova, Svetlana; Yin, Dan; Zimmerberg, Joshua

    2004-01-01

    Digestion of red blood cell (RBC) hemoglobin by the malaria parasite results in the formation of paramagnetic hemazoin crystals inside the parasite body. A number of reports suggest that magnetic field interaction with hamazoin crystals significantly reduces the number of infected cells in culture, and thus magnetic field can be used to combat malaria. We studies the effects of magnetic filed on the Plasmodium falciparum asexual life cycle inside RBCs under various experimental conditions. No effect was found during prolonged exposure of infected RBCs to constant magnetic fields up to 6000 Gauss. Infected RBCs were also exposed, under temperature-controlled conditions, to oscillating magnetic fields with frequencies in the range of 500-20000 kHz, and field strength 30-600 Gauss. This exposure often changed the proportion of different parasite stages in treated culture compared to controls. However, no significant effect on parasitemia was observed in treated cultures. This result indicates that the magnetic field effect on Plasmodium falciparum is negligible, or that hypothetical negative and positive effects on different stages within one 48-hour compensate each other.

  14. Magnetic field effects in a polymer/fullerene blend photovoltaic cell

    NASA Astrophysics Data System (ADS)

    Jang, Hyuk-Jae; Basham, James I.; Gundlach, David J.; Richter, Curt A.

    Organic photovoltaic (OPV) systems based on blends of conjugated polymers and fullerene derivatives have shown great promise for low-cost and efficient photovoltaic applications. Recent findings suggest that a weak external magnetic field can disturb the spin configuration of excited states and subsequently change properties of OPV cells such as photocurrent. These changes are referred to as magnetic field effects (MFEs). In order to have a better understanding of the underlying mechanisms responsible for the MFEs in polymer/fullerene blend photovoltaic systems, we fabricated poly-3-hexylthiophene (P3HT):phenyl-C61-butyric acid methyl ester (PC61BM) cells and carried out photovoltaic device performance and impedance spectroscopy measurements with and without an externally applied magnetic field. A significant reduction in short circuit current (JSC) as well as open circuit voltage (VOC) was observed with an applied magnetic field of a 0.1 tesla compared to those measured without a magnetic field under the same intensity of illumination. Impedance spectroscopy data gives insights into the influence of an external magnetic field on charge generation and recombination near normal photovoltaic operating conditions.

  15. The protective effect of a constant magnetic field. [reduction of molecular cell pathology

    NASA Technical Reports Server (NTRS)

    Sosunov, A. V.; Tripuzov, A. N.

    1974-01-01

    The protective effect of a constant magnetic field sharply reduced spontaneous lysis of E. coli cells when subjected to ultraviolet radiation. A protective effect of a CMF was found in a study of tissue cultures of normally growing cells (kidney epithelium) and cancer cells (cells from a cancer of the larynx). The protective effect of a CMF is also seen in a combined exposure of tissue cultures to X-rays and CMF energy (strength of the CMF was 2000 oersteds with a gradient of 500 oersteds/cm). The data obtained are of interest to experimental oncology (development of new methods of treating malignant tumors).

  16. Binding kinetics of magnetic nanoparticles on latex beads and yeast cells studied by magnetorelaxometry

    NASA Astrophysics Data System (ADS)

    Eberbeck, Dietmar; Bergemann, Christian; Hartwig, Stefan; Steinhoff, Uwe; Trahms, Lutz

    2005-03-01

    The ion exchange mediated binding of magnetic nanoparticles (MNP) to modified latex spheres and yeast cells was quantified using magnetorelaxometry. By fitting subsequently recorded relaxation curves, the kinetics of the binding reactions was extracted. The signal of MNP with weak ion exchanger groups bound to latex and yeast cells scales linearly with the concentration of latex beads or yeast cells whereas that of MNP with strong ion exchanger groups is proportional to the square root of concentration. The binding of the latter leads to a much stronger aggregation of yeast cells than the former MNP.

  17. Innovative Strategy for MicroRNA Delivery in Human Mesenchymal Stem Cells via Magnetic Nanoparticles

    PubMed Central

    Schade, Anna; Delyagina, Evgenya; Scharfenberg, Dorothee; Skorska, Anna; Lux, Cornelia; David, Robert; Steinhoff, Gustav

    2013-01-01

    Bone marrow derived human mesenchymal stem cells (hMSCs) show promising potential in regeneration of defective tissue. Recently, gene silencing strategies using microRNAs (miR) emerged with the aim to expand the therapeutic potential of hMSCs. However, researchers are still searching for effective miR delivery methods for clinical applications. Therefore, we aimed to develop a technique to efficiently deliver miR into hMSCs with the help of a magnetic non-viral vector based on cationic polymer polyethylenimine (PEI) bound to iron oxide magnetic nanoparticles (MNP). We tested different magnetic complex compositions and determined uptake efficiency and cytotoxicity by flow cytometry. Additionally, we monitored the release, processing and functionality of delivered miR-335 with confocal laser scanning microscopy, real-time PCR and live cell imaging, respectively. On this basis, we established parameters for construction of magnetic non-viral vectors with optimized uptake efficiency (~75%) and moderate cytotoxicity in hMSCs. Furthermore, we observed a better transfection performance of magnetic complexes compared to PEI complexes 72 h after transfection. We conclude that MNP-mediated transfection provides a long term effect beneficial for successful genetic modification of stem cells. Hence, our findings may become of great importance for future in vivo applications. PMID:23702843

  18. Multi-bits memory cell using degenerated magnetic states in a synthetic antiferromagnetic reference layer

    NASA Astrophysics Data System (ADS)

    Fukushima, Akio; Yakushiji, Kay; Konoto, Makoto; Kubota, Hitoshi; Imamura, Hiroshi; Yuasa, Shinji

    2016-02-01

    We newly developed a magnetic memory cell having multi-bit function. The memory cell composed of a perpendicularly magnetized magnetic tunnel junction (MB-pMTJ) and a synthetic antiferromagnetic reference layer. The multi-bit function is realized by combining the freedom of states of the magnetic free layer and that in the antiferromagnetically coupled reference layer. The structure of the reference layer is (FeB/Ta/[Co/Pt]3)/Ru/([Co/Pt]6); the top and the bottom layers are coupled through Ru layer where the reference layer has two degrees of freedom of a head-to-head and a bottom-to-bottom magnetic configuration. A four-state memory cell is realized by combination of both degrees of freedom. The states in the reference layer however is hardly detected by the total resistance of MB-pMTJ, because the magnetoresistance effect in the reference layer is negligibly small. That implies that the resistance values for the different states in the reference layer are degenerated. On the other hand, the two different states in the reference layer bring different stray fields to the free layer, which generate two different minor loop with different switching fields. Therefore, the magnetic states in the reference layer can be differentiated by the two-step reading, before and after applying the appropriately pulsed magnetic field which can identify the initial state in the reference layer. This method is similar to distinguishing different magnetic states in an in-plane magnetized spin-valve element. We demonstrated that four different states in the MB-pMTJ can be distinguished by the two-step read-out. The important feature of the two-step reading is a practically large operation margins (large resistance change in reading) which is equal to that of a single MTJ. Even though the two-step reading is a destructive method by which 50% of the magnetic state is changed, this MB-pMTJ is promising for high density non-volatile memory cell with a minor cost of operation speed.

  19. Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates.

    PubMed

    Franken, Lars; Klein, Marika; Spasova, Marina; Elsukova, Anna; Wiedwald, Ulf; Welz, Meike; Knolle, Percy; Farle, Michael; Limmer, Andreas; Kurts, Christian

    2015-01-01

    A main function of splenic red pulp macrophages is the degradation of damaged or aged erythrocytes. Here we show that these macrophages accumulate ferrimagnetic iron oxides that render them intrinsically superparamagnetic. Consequently, these cells routinely contaminate splenic cell isolates obtained with the use of MCS, a technique that has been widely used in immunological research for decades. These contaminations can profoundly alter experimental results. In mice deficient for the transcription factor SpiC, which lack red pulp macrophages, liver Kupffer cells take over the task of erythrocyte degradation and become superparamagnetic. We describe a simple additional magnetic separation step that avoids this problem and substantially improves purity of magnetic cell isolates from the spleen. PMID:26260698

  20. Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates

    PubMed Central

    Franken, Lars; Klein, Marika; Spasova, Marina; Elsukova, Anna; Wiedwald, Ulf; Welz, Meike; Knolle, Percy; Farle, Michael; Limmer, Andreas; Kurts, Christian

    2015-01-01

    A main function of splenic red pulp macrophages is the degradation of damaged or aged erythrocytes. Here we show that these macrophages accumulate ferrimagnetic iron oxides that render them intrinsically superparamagnetic. Consequently, these cells routinely contaminate splenic cell isolates obtained with the use of MCS, a technique that has been widely used in immunological research for decades. These contaminations can profoundly alter experimental results. In mice deficient for the transcription factor SpiC, which lack red pulp macrophages, liver Kupffer cells take over the task of erythrocyte degradation and become superparamagnetic. We describe a simple additional magnetic separation step that avoids this problem and substantially improves purity of magnetic cell isolates from the spleen. PMID:26260698

  1. Electrostatically Stabilized Magnetic Nanoparticles - An Optimized Protocol to Label Murine T Cells for in vivo MRI.

    PubMed

    Wuerfel, Eva; Smyth, Maureen; Millward, Jason M; Schellenberger, Eyk; Glumm, Jana; Prozorovski, Timour; Aktas, Orhan; Schulze-Topphoff, Ulf; Schnorr, Jörg; Wagner, Susanne; Taupitz, Matthias; Infante-Duarte, Carmen; Wuerfel, Jens

    2011-01-01

    We present a novel highly efficient protocol to magnetically label T cells applying electrostatically stabilized very small superparamagnetic iron oxide particles (VSOP). Our long-term aim is to use magnetic resonance imaging (MRI) to investigate T cell dynamics in vivo during the course of neuroinflammatory disorders such as experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Encephalitogenic T cells were co-incubated with VSOP, or with protamine-complexed VSOP (VProt), respectively, at different conditions, optimizing concentrations and incubation times. Labeling efficacy was determined by atomic absorption spectrometry as well as histologically, and evaluated on a 7 T MR system. Furthermore, we investigated possible alterations of T cell physiology caused by the labeling procedure. T cell co-incubation with VSOP resulted in an efficient cellular iron uptake. T2 times of labeled cells dropped significantly, resulting in prominent hypointensity on T2*-weighted scans. Optimal labeling efficacy was achieved by VProt (1 mM Fe/ml, 8 h incubation; T2 time shortening of ∼80% compared to untreated cells). Although VSOP promoted T cell proliferation and altered the ratio of T cell subpopulations toward a CD4(+) phenotype, no effects on CD4 T cell proliferation or phenotypic stability were observed by labeling in vitro differentiated Th17 cells with VProt. Yet, high concentrations of intracellular iron oxide might induce alterations in T cell function, which should be considered in cell tagging studies. Moreover, we demonstrated that labeling of encephalitogenic T cells did not affect pathogenicity; labeled T cells were still capable of inducing EAE in susceptible recipient mice. PMID:22203815

  2. Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips†

    PubMed Central

    Earhart, Christopher M.; Hughes, Casey E.; Gaster, Richard S.; Ooi, Chin Chun; Wilson, Robert J.; Zhou, Lisa Y.; Humke, Eric W.; Xu, Lingyun; Wong, Dawson J.; Willingham, Stephen B.; Schwartz, Erich J.; Weissman, Irving L.; Jeffrey, Stefanie S.; Neal, Joel W.; Rohatgi, Rajat; Wakelee, Heather A.; Wang, Shan X.

    2014-01-01

    Detection and characterization of circulating tumor cells (CTCs) may reveal insights into the diagnosis and treatment of malignant disease. Technologies for isolating CTCs developed thus far suffer from one or more limitations, such as low throughput, inability to release captured cells, and reliance on expensive instrumentation for enrichment or subsequent characterization. We report a continuing development of a magnetic separation device, the magnetic sifter, which is a miniature microfluidic chip with a dense array of magnetic pores. It offers high efficiency capture of tumor cells, labeled with magnetic nanoparticles, from whole blood with high throughput and efficient release of captured cells. For subsequent characterization of CTCs, an assay, using a protein chip with giant magnetoresistive nanosensors, has been implemented for mutational analysis of CTCs enriched with the magnetic sifter. The use of these magnetic technologies, which are separate devices, may lead the way to routine preparation and characterization of “liquid biopsies” from cancer patients. PMID:23969419

  3. Characterization and Insights Into the Nano Liposomal Magnetic Gene Vector Used for Cell Co-Transfection.

    PubMed

    Chen, Wenjie; Cui, Haixin; Zhao, Xiang; Cui, Jinhui; Wang, Yan; Sun, Chaojiao; Cui, Bo; Lei, Feng

    2015-08-01

    The development of magnetofection technology has brought a promising method for gene delivery. Here, we develop a novel liposomal magnetofection system, consisted of magnetic nanoparticle and liposome through molecular assembly, was applied to introduce double genes into porcin somatic cells with high co-transfection efficiency. The performace of liposomal magnetic gene nanovectors has been evaluated by involving the micro morphology, diameters distribution, zeta potentials and the capacity of loading DNA molecules. The assembly way among magnetic gene nanovectors and DNA molecules was investigated by atomic force microscopy. Liposomal nano magnetic gene vectors complexes displayed nanoscale assembly and formed compact "fishing-net structure" after combining with plasmid DNA, which is favorable to enhance the loading capacity of DNA molecules. PMID:26369113

  4. IS MAGNETIC RECONNECTION THE CAUSE OF SUPERSONIC UPFLOWS IN GRANULAR CELLS?

    SciTech Connect

    Borrero, J. M.; Schmidt, W.; Martinez Pillet, V.; Quintero Noda, C.; Bonet, J. A.

    2013-05-01

    In a previous work, we reported on the discovery of supersonic magnetic upflows on granular cells in data from the SUNRISE/IMaX instrument. In the present work, we investigate the physical origin of these events employing data from the same instrument but with higher spectral sampling. By means of the inversion of Stokes profiles we are able to recover the physical parameters (temperature, magnetic field, line-of-sight velocity, etc.) present in the solar photosphere at the time of these events. The inversion is performed in a Monte-Carlo-like fashion, that is, repeating it many times with different initializations and retaining only the best result. We find that many of the events are characterized by a reversal in the polarity of the magnetic field along the vertical direction in the photosphere, accompanied by an enhancement in the temperature and by supersonic line-of-sight velocities. In about half of the studied events, large blueshifted and redshifted line-of-sight velocities coexist above/below each other. These features can be explained in terms of magnetic reconnection, where the energy stored in the magnetic field is released in the form of kinetic and thermal energy when magnetic field lines of opposite polarities coalesce. However, the agreement with magnetic reconnection is not perfect and, therefore, other possible physical mechanisms might also play a role.

  5. Is Magnetic Reconnection the Cause of Supersonic Upflows in Granular Cells?

    NASA Astrophysics Data System (ADS)

    Borrero, J. M.; Martínez Pillet, V.; Schmidt, W.; Quintero Noda, C.; Bonet, J. A.; del Toro Iniesta, J. C.; Bellot Rubio, L. R.

    2013-05-01

    In a previous work, we reported on the discovery of supersonic magnetic upflows on granular cells in data from the SUNRISE/IMaX instrument. In the present work, we investigate the physical origin of these events employing data from the same instrument but with higher spectral sampling. By means of the inversion of Stokes profiles we are able to recover the physical parameters (temperature, magnetic field, line-of-sight velocity, etc.) present in the solar photosphere at the time of these events. The inversion is performed in a Monte-Carlo-like fashion, that is, repeating it many times with different initializations and retaining only the best result. We find that many of the events are characterized by a reversal in the polarity of the magnetic field along the vertical direction in the photosphere, accompanied by an enhancement in the temperature and by supersonic line-of-sight velocities. In about half of the studied events, large blueshifted and redshifted line-of-sight velocities coexist above/below each other. These features can be explained in terms of magnetic reconnection, where the energy stored in the magnetic field is released in the form of kinetic and thermal energy when magnetic field lines of opposite polarities coalesce. However, the agreement with magnetic reconnection is not perfect and, therefore, other possible physical mechanisms might also play a role.

  6. Magnetically Responsive Biodegradable Nanoparticles Enhance Adenoviral Gene Transfer in Cultured Smooth Muscle and Endothelial Cells

    PubMed Central

    Chorny, Michael; Fishbein, Ilia; Alferiev, Ivan; Levy, Robert J.

    2012-01-01

    Replication-defective adenoviral (Ad) vectors have shown promise as a tool for gene delivery-based therapeutic applications. Their clinical use is however limited by therapeutically suboptimal transduction levels in cell types expressing low levels of Coxsackie-Ad receptor (CAR), the primary receptor responsible for the cell entry of the virus, and by systemic adverse reactions. Targeted delivery achievable with Ad complexed with biodegradable magnetically responsive nanoparticles (MNP) may therefore be instrumental for improving both the safety and efficiency of these vectors. Our hypothesis was that magnetically driven delivery of Ad affinity-bound to biodegradable MNP can substantially increase transgene expression in CAR deficient vascular cells in culture. Fluorescently labeled MNP were formulated from polylactide with inclusion of iron oxide and surface-modified with the D1 domain of CAR as an affinity linker. MNP cellular uptake and GFP reporter transgene expression were assayed fluorimetrically in cultured endothelial and smooth muscle cells using λex/λem of 540 nm/575 nm and 485 nm/535 nm, respectively. Stable vector-specific association of Ad with MNP resulted in formation of MNP–Ad complexes displaying rapid cell binding kinetics following a brief exposure to a high gradient magnetic field with resultant gene transfer levels significantly increased compared to free vector or nonmagnetic control treatment. Multiple regression analysis suggested a mechanism of MNP–Ad mediated transduction distinct from that of free Ad, and confirmed the major contribution of the complexes to the gene transfer under magnetic conditions. The magnetically enhanced transduction was achieved without compromising the cell viability or growth kinetics. The enhancement of adenoviral gene delivery by affinity complexation with biodegradable MNP represents a promising approach with a potential to extend the applicability of the viral gene therapeutic strategies. PMID:19496618

  7. Bulk magnetic susceptibility induced broadening in the 19F NMR of suspended leukemic cells.

    PubMed

    Adebodun, F; Post, J F

    1993-01-01

    The relevance of bulk magnetic susceptibility (BMS) induced broadening to in vivo NMR studies of intact cells has been examined and the significance of the contribution of BMS difference to the resolution of intra- and extracellular resonances was demonstrated. BMS difference between intra- and extracellular compartments was found to limit the resolution of intra- and extracellular 19F resonances of fluoro compounds in leukemic cells. PMID:8499242

  8. Magnetically levitated nano-robots: an application to visualization of nerve cells injuries.

    PubMed

    Lou, Mingji; Jonckheere, Edmond

    2007-01-01

    This paper proposes a swarm of magnetically levitated nano-robots with high sensitivity nano-sensors as a mean to detect chemical sources, specifically the chemical signals released by injured nervous cells. In the aftermath of the process, further observation by these nano-robots would be used to monitor the healing process and assess the amount of regeneration, if any, or even the repair, of the injured nervous cells. PMID:17377291

  9. Fluorescent magnetic bead-based mast cell biosensor for electrochemical detection of allergens in foodstuffs.

    PubMed

    Jiang, Donglei; Zhu, Pei; Jiang, Hui; Ji, Jian; Sun, Xiulan; Gu, Wenshu; Zhang, Genyi

    2015-08-15

    In this study, a novel electrochemical rat basophilic leukemia cell (RBL-2H3) cell sensor, based on fluorescent magnetic beads, has been developed for the detection and evaluation of different allergens in foodstuffs. Fluorescein isothiocyanate (FITC) was successfully fused inside the SiO2 layer of SiO2 shell-coated Fe3O4 nanoparticles, which was superior to the traditional Fe3O4@SiO2@FITC modification process. The as-synthesized fluorescent magnetic beads were then encapsulated with lipidosome to form cationic magnetic fluorescent nanoparticles (CMFNPs) for mast cell magnetofection. The CMFNPs were then characterized by SEM, TEM, VSM, FTIR, and XRD analyses, and transfected into RBL-2H3 cells through a highly efficient, lipid-mediated magnetofection procedure. Magnetic glassy carbon electrode (MGCE), which possesses excellent reproducibility and regeneration qualities, was then employed to adsorb the CMFNP-transfected RBL-2H3 cells activated by an allergen antigen for electrochemical assay. Results show that the exposure of model antigen-dinitrophenol-bovine serum albumin (DNP-BSA) to anti-DNP IgE-sensitized mast cells induced a robust and long-lasting electrochemical impedance signal in a dose-dependent manner. The detection limit was identified at 3.3×10(-4) ng/mL. To demonstrate the utility of this mast cell-based biosensor for detection of real allergens in foodstuffs, Anti-Pen a1 IgE and Anti-PV IgE-activated cells were employed to quantify both shrimp allergen tropomyosin (Pen a 1) and fish allergen parvalbumin (PV). Results show high detection accuracy for these targets, with a limit of 0.03 μg/mL (shrimp Pen a 1) and 0.16 ng/mL (fish PV), respectively. To this effect, we conclude the proposed method is a facile, highly sensitive, innovative electrochemical method for the evaluation of food allergens. PMID:25889258

  10. Structural and function changes in organelles of liver cells in rats exposed to magnetic fields

    SciTech Connect

    Gorczynska, E. ); Wegrzynowicz, R. )

    1991-08-01

    Exposure of rats to magnetic fields of 10{sup {minus}3} and 10{sup {minus}2} T for 1 hr daily generated structural changes in hepatocytes mitochondria, endoplasmic reticulum, and ribosomes. Simultaneously there was an increase in the activities of the mitochondrial respiratory enzymes: NADH dehydrogenase, succinic dehydrogenase, and cytochrome oxidase. The extent of the changes in liver cell properties following exposure depend on the duration of exposure to and the strength of the applied magnetic fields. Ultrastructural studies did not reveal any changes in external membranes of hepatocytes or in the membranes of cell nuclei. An increase in the amount of glycogen in hepatocytes of rats exposed to both 10{sup {minus}3} and 10{sup {minus}2} T was noted. The high level of cortisol in serum of exposed rats suggests that magnetic field may be a stress generating factor.

  11. Transferrin Decorated Thermoresponsive Nanogels as Magnetic Trap Devices for Circulating Tumor Cells.

    PubMed

    Asadian-Birjand, Mazdak; Biglione, Catalina; Bergueiro, Julian; Cappelletti, Ariel; Rahane, Chinmay; Chate, Govind; Khandare, Jayant; Klemke, Bastian; Strumia, Miriam C; Calderón, Marcelo

    2016-03-01

    A rational design of magnetic capturing nanodevices, based on a specific interaction with circulating tumor cells (CTCs), can advance the capturing efficiency and initiate the development of modern smart nanoformulations for rapid isolation and detection of these CTCs from the bloodstream. Therefore, the development and evaluation of magnetic nanogels (MNGs) based on magnetic nanoparticles and linear thermoresponsive polyglycerol for the capturing of CTCs with overexpressed transferrin (Tf(+) ) receptors has been presented in this study. The MNGs are synthesized using a strain-promoted "click" approach which has allowed the in situ surface decoration with Tf-polyethylene glycol (PEG) ligands of three different PEG chain lengths as targeting ligands. An optimal value of around 30% of cells captures is achieved with a linker of eight ethylene glycol units. This study shows the potential of MNGs for the capture of CTCs and the necessity of precise control over the linkage of the targeting moiety to the capturing device. PMID:26691543

  12. Diode/magnetic tunnel junction cell for fully scalable matrix-based biochip

    NASA Astrophysics Data System (ADS)

    Cardoso, F. A.; Ferreira, H. A.; Conde, J. P.; Chu, V.; Freitas, P. P.; Vidal, D.; Germano, J.; Sousa, L.; Piedade, M. S.; Costa, B. A.; Lemos, J. M.

    2006-04-01

    Magnetoresistive biochips have been recently introduced for the detection of biomolecular recognition. In this work, the detection site incorporates a thin-film diode in series with a magnetic tunnel junction (MTJ), leading to a matrix-based biochip that can be easily scaled up to screen large numbers of different target analytes. The fabricated 16×16 cell matrix integrates hydrogenated amorphous silicon (a-Si:H) diodes with aluminum oxide barrier MTJ. Each detection site also includes a U-shaped current line for magnetically assisted target concentration at probe sites. The biochip is being integrated in a portable, credit card size electronics control platform. Detection of 250 nm diameter magnetic nanoparticles by one of the matrix cells is demonstrated.

  13. Methods to Characterize Vapor Cell Performance for Nuclear Magnetic Resonance Applications

    NASA Astrophysics Data System (ADS)

    Mirijanian, James; Larsen, Michael

    2012-06-01

    The Advanced Sensors Development team at Northrop Grumman, Navigation Systems Division is developing a Nuclear Magnetic Resonance Gyroscope (NMRG). Various methods to measure atomic spin lifetimes in vapor cells for predicting NMRG performance have been investigated. Certain methods show clear advantages over others by reducing required testing times and improving test data resolution. New modifications of methods were also developed to study and improve the precision and repeatability of test results. These methods help correlate vapor cell performance to cell filling and sealing methods for cell fabrication process improvement. The vapor cells produced in conjunction with these techniques have exhibited significant and consistent increases in both the noble gas spin lifetimes and the NMR signal strengths compared to previous cell fabrication processes, providing more precise insight into cell development techniques.

  14. Effects of strong magnetic fields on cell growth and radiation response of human T-lymphocytes in culture.

    PubMed

    Norimura, T; Imada, H; Kunugita, N; Yoshida, N; Nikaido, M

    1993-06-01

    Experiments were undertaken in order to verify whether or not a strong magnetic field would have any biological effects on the cell growth, viability and radiation response of mammalian cells. Magnetic field exposures were conducted using a superconducting magnet with freshly-isolated human peripheral blood T-lymphocytes maintained at their normal growing temperature of 37 degrees C. The static magnetic fields with intensities up to 6.3-tesla (T) exerted little influence on the cell growth and viability of actively-growing T-lymphocytes under normal cell-culture conditions. On the other hand, the T cells exposed to the magnetic fields (4 T-6.3 T) during PHA stimulation were inhibited in their cell growth when compared to controls. The effects of the magnetic fields with intensities up to 2 T on cell growth properties, however, were minimal in this system. Also, the radiosensitivity of T-lymphocytes previously exposed to the strong magnetic fields was more sensitive than that of control cells. These results suggest that exposure to a static magnetic field of 4 T or stronger might lead to physiological and growth abnormalities at the cellular level. PMID:8316709

  15. Cell nucleus targeting for living cell extraction of nucleic acid associated proteins with intracellular nanoprobes of magnetic carbon nanotubes.

    PubMed

    Zhang, Yi; Hu, Zhengyan; Qin, Hongqiang; Liu, Fangjie; Cheng, Kai; Wu, Ren'an; Zou, Hanfa

    2013-08-01

    Since nanoparticles could be ingested by cells naturally and target at a specific cellular location as designed, the extraction of intracellular proteins from living cells for large-scale analysis by nanoprobes seems to be ideally possible. Nucleic acid associated proteins (NAaP) take the crucial position during biological processes in maintaining and regulating gene structure and gene related behaviors, yet there are still challenges during the global investigation of intracellular NAaP, especially from living cells. In this work, a strategy to extract intracellular proteins from living cells with the magnetic carbon nanotube (oMWCNT@Fe3O4) as an intracellular probe is developed, to achieve the high throughput analysis of NAaP from living human hepatoma BEL-7402 cells with a mass spectrometry-based proteomic approach. Due to the specific intracellular localization of the magnetic carbon nanotubes around nuclei and its strong interaction with nucleic acids, the highly efficient extraction was realized for cellular NAaP from living cells, with the capability of identifying 2383 intracellular NAaP from only ca. 10,000 living cells. This method exhibited potential applications in dynamic and in situ analysis of intracellular proteins. PMID:23815738

  16. CHARACTERISTICS OF TRANSVERSE ELECTRIC AND MAGNETIC FIELD TRANSMISSION CELLS AT EXTREMELY LOW FREQUENCIES

    EPA Science Inventory

    Transverse electric and magnetic field cells are often designed to subject samples to electromagnetic radiation of intrinsic impedance (E/H) that is the same as in free space, 377 ohms. Earlier work has shown this value to be correct for the RF region. In the study, measurements ...

  17. Magnetic Nano- and Micro- Particles in Living Cells: Kinetics and Fluctuations

    NASA Astrophysics Data System (ADS)

    Pease, C.; Chiang, N.; Pierce, C.; Muthusamy, N.; Sooryakumar, R.

    2015-03-01

    Functional nano and micro materials have recently been used not only as diagnostic tools for extracellular studies but also as intracellular drug delivery vehicles and as internal probes of the cell. To realize proper cellular applications, it is important not only to achieve efficient delivery of these materials to targeted cells, but also to control their movement and activity within the confines of the cell. In this presentation, superparamagnetic nano and micro particles are utilized as probes, with their responses to weak external magnetic fields enabling them to be maneuvered within a cell. In order to generate the required local magnetic fields needed for manipulation, the fields emanating from microscopic domain walls stabilized on patterned surface profiles are used in conjunction with weak external magnetic fields to create mobile traps that can localize and transport the internalized particle. Preliminary findings on creating the mobile traps suitable for applications to probe the interior of cells, and the responses, both Brownian fluctuations and directed motion, of particles ranging in size from 200 nm to 1 micron within HS-5 cells will be presented. Future applications to probe cellular behavior within the framework of emerging biomaterials will be discussed.

  18. SERS-fluorescence joint spectral encoded magnetic nanoprobes for multiplex cancer cell separation.

    PubMed

    Wang, Zhuyuan; Zong, Shenfei; Chen, Hui; Wang, Chunlei; Xu, Shuhong; Cui, Yiping

    2014-11-01

    A new kind of cancer cell separation method is demonstrated, using surface-enhanced Raman scattering (SERS) and fluorescence dual-encoded magnetic nanoprobes. The designed nanoprobes can realize SERS-fluorescence joint spectral encoding (SFJSE) and greatly improve the multiplexing ability. The nanoprobes have four main components, that is, the magnetic core, SERS generator, fluorescent agent, and targeting antibody. These components are assembled with a multi-layered structure to form the nanoprobes. Specifically, silica-coated magnetic nanobeads (MBs) are used as the inner core. Au core-Ag shell nanorods (Au@Ag NRs) are employed as the SERS generators and attached on the silica-coated MBs. After burying these Au@Ag NRs with another silica layer, CdTe quantum dots (QDs), that is, the fluorescent agent, are anchored onto the silica layer. Finally, antibodies are covalently linked to CdTe QDs. SFJSE is fulfilled by using different Raman molecules and QDs with different emission wavelengths. By utilizing four human cancer cell lines and one normal cell line as the model cells, the nanoprobes can specifically and simultaneously separate target cancer cells from the normal ones. This SFJSE-based method greatly facilitates the multiplex, rapid, and accurate cancer cell separation, and has a prosperous potential in high-throughput analysis and cancer diagnosis. PMID:24862088

  19. Three-dimensional cell culturing by magnetic levitation for evaluating efficacy/toxicity of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Sabino, Luis G.; Menezes, Priscila F. C.; Bagnato, Vanderlei S.; Souza, Glauco; Killian, Thomas C.; Kurachi, Cristina

    2014-03-01

    We used three dimensional cell cultures (3D) based on the magnetic levitation method (MLM) to evaluate cytotoxicity of photodynamic therapy (PDT). First, we decorated Hep G2 and MDA-MB-321 cells with NanoShuttle by introducing it in the media and incubated overnight. Next day, we transferred the cells to a 6-well plate and placed a magnetic driver on the top of the plate to start levitation. We monitored the formation of the 3D cell culture by optical microscopy and after four days, we added the photosensitizer Photogem (PG) in the culture media in concentrations of 50, 25, 12.5, 6.25μg/ml. We incubated them for 24 hours, after that we washed the cultures with PBS and added fresh media. Samples were then illuminated for 600s using a 630nm LED-based device, generating light intensities of 30 mW/cm2 in a total light fluence of 18 J/cm2. Following the illumination, we added fresh media, and 30 hours later, the 3D structures were broken using a pipettor and the cells seeded in 96 well plates, 105 cells per well, with a magnetic drive placed on the bottom of the plate to create cell culture dots. After 24 hours, we used a MTT assay to evaluate PDT cytotoxicity. The PDT effect, evaluated by the half maximal effective concentration (EC50), in MDA-MB-231 cells (EC50 =3.14 μg/ml) is more aggressive compared to the effect of PDT in Hep G2 cells (EC50 = 7.48 μg/ml). It suggests that the cell culture structure and its interaction facilitated the PG uptake and consequently elevated the Photodynamic effect for MDA-MB-231.

  20. MAGNETS

    DOEpatents

    Hofacker, H.B.

    1958-09-23

    This patent relates to nmgnets used in a calutron and more particularly to means fur clamping an assembly of magnet coils and coil spacers into tightly assembled relation in a fluid-tight vessel. The magnet comprises windings made up of an assembly of alternate pan-cake type coils and spacers disposed in a fluid-tight vessel. At one end of the tank a plurality of clamping strips are held firmly against the assembly by adjustable bolts extending through the adjacent wall. The foregoing arrangement permits taking up any looseness which may develop in the assembly of coils and spacers.

  1. Biotechnological promises of Fe-filled CNTs for cell shepherding and magnetic fluid hyperthermia applications

    NASA Astrophysics Data System (ADS)

    Pineux, Florent; Marega, Riccardo; Stopin, Antoine; La Torre, Alessandro; Garcia, Yann; Devlin, Eamonn; Michiels, Carine; N. Khlobystov, Andrei; Bonifazi, Davide

    2015-12-01

    Fe-filled carbon nanotubes (Fe@CNTs) recently emerged as an effective class of hybrid nanoparticles for biotechnological applications, such as magnetic cell sorting and magnetic fluid hyperthermia. Aiming at studying the effects of both the Fe loading and the magnetocrystalline characteristics in these applications, we describe herein the preparation of Fe@CNTs containing different Fe phases that, upon functionalization with the antibody Cetuximab (Ctxb), allow the targeting of cancer cells. Our experimental findings reveal that an optimal Ctxb/Fe weight ratio of 1.2 is needed for efficient magnetic cell shepherding, whereas enhanced MFH-induced mortality (70 vs. 15%) can be reached with hybrids enriched in the coercive Fe3C phase. These results suggest that a synergistic effect between the Ab loading and the Fe distribution in each nanotube exists, for which the maximum shepherding and hyperthermia effects are observed when higher densities of Fe@CNTs featuring the more coercive phase are interfaced with the cells.Fe-filled carbon nanotubes (Fe@CNTs) recently emerged as an effective class of hybrid nanoparticles for biotechnological applications, such as magnetic cell sorting and magnetic fluid hyperthermia. Aiming at studying the effects of both the Fe loading and the magnetocrystalline characteristics in these applications, we describe herein the preparation of Fe@CNTs containing different Fe phases that, upon functionalization with the antibody Cetuximab (Ctxb), allow the targeting of cancer cells. Our experimental findings reveal that an optimal Ctxb/Fe weight ratio of 1.2 is needed for efficient magnetic cell shepherding, whereas enhanced MFH-induced mortality (70 vs. 15%) can be reached with hybrids enriched in the coercive Fe3C phase. These results suggest that a synergistic effect between the Ab loading and the Fe distribution in each nanotube exists, for which the maximum shepherding and hyperthermia effects are observed when higher densities of Fe

  2. Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

    NASA Astrophysics Data System (ADS)

    Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

    2015-04-01

    Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time.

  3. An Assessment of Gadonanotubes as Magnetic Nanolabels for Improved Stem Cell Detection and Retention in Cardiomyoplasty

    NASA Astrophysics Data System (ADS)

    Tran, Lesa A.

    In this work, gadolinium-based carbon nanocapsules are developed as a novel nanotechnology that addresses the shortcomings of current diagnostic and therapeutic methods of stem cell-based cardiomyoplasty. With cardiovascular disease (CVD) responsible for approximately 30% of deaths worldwide, the growing need for improved cardiomyoplasty has spurred efforts in nanomedicine to develop innovative techniques to enhance the therapeutic retention and diagnostic tracking of transplanted cells. Having previously been demonstrated as a high-performance T1-weighted magnetic resonance imaging (MRI) contrast agent, Gadonanotubes (GNTs) are shown for the first time to intracellularly label pig bone marrow-derived mesenchymal stem cells (MSCs). Without the use of a transfection agent, micromolar concentrations of GNTs deliver up to 109 Gd3+ ions per cell, allowing for MSCs to be visualized in a 1.5 T clinical MRI scanner. The cellular response to the intracellular incorporation of GNTs is also assessed, revealing that GNTs do not compromise the viability, differentiation potential, or phenotype characteristics of the MSCs. However, it is also found that GNT-labeled MSCs exhibit a decreased response to select cell adhesion proteins and experience a nonapoptotic, non-proliferative cell cycle arrest, from which the cells recover 48 h after GNT internalization. In tandem with developing GNTs as a new stem cell diagnostic agent, this current work also explores for the first time the therapeutic application of the magnetically-active GNTs as a magnetic facilitator to increase the retention of transplanted stem cells during cardiomyoplasty. In vitro flow chamber assays, ex vivo perfusion experiments, and in vivo porcine injection procedures all demonstrate the increased magnetic-assisted retention of GNT-labeled MSCs in the presence of an external magnetic field. These studies prove that GNTs are a powerful 'theranostic' agent that provides a novel platform to simultaneously monitor

  4. Magnetic Resonance Detection of CD34+ Cells from Umbilical Cord Blood Using a 19F Label

    PubMed Central

    Duinhouwer, Lucia E.; van Rossum, Bernard J. M.; van Tiel, Sandra T.; van der Werf, Ramon M.; Doeswijk, Gabriela N.; Haeck, Joost C.; Rombouts, Elwin W. J. C.; ter Borg, Mariëtte N. D.; Kotek, Gyula; Braakman, Eric; Cornelissen, Jan J.; Bernsen, Monique R.

    2015-01-01

    Impaired homing and delayed recovery upon hematopoietic stem cell transplantation (HSCT) with hematopoietic stem cells (HSC) derived from umbilical cord blood (UCB) is a major problem. Tracking transplanted cells in vivo will be helpful to detect impaired homing at an early stage and allows early interventions to improve engraftment and outcome after transplantation. In this study, we show sufficient intracellular labeling of UCB-derived CD34+ cells, with 19F-containing PLGA nanoparticles which were detectable with both flow cytometry and magnetic resonance spectroscopy (MRS). In addition, labeled CD34+ cells maintain their capacity to proliferate and differentiate, which is pivotal for successful engraftment after transplantation in vivo. These results set the stage for in vivo tracking experiments, through which the homing efficiency of transplanted cells can be studied. PMID:26394043

  5. Vortex or whorl formation of cultured human corneal epithelial cells induced by magnetic fields.

    PubMed

    Dua, H S; Singh, A; Gomes, J A; Laibson, P R; Donoso, L A; Tyagi, S

    1996-01-01

    The terms 'vortex keratopathy' and 'hurricane keratopathy' describe two similar conditions affecting the corneal surface. In the former, a vortex or whorl pattern is seen on the corneal surface and is due to the deposition of substances such as pigment, iron or drugs in the epithelial cells. In the latter, a similar pattern is presented by migrating epithelial cells but, unlike the former, the pattern is rendered more visible by fluorescein staining. Both represent the migratory pattern of normal epithelial cells which is otherwise not visible due to the slow rate of epithelial turnover and migration. The whorl pattern has a clockwise predisposition in the majority of cases and is hypothesised to be due to the influence of ocular electro-magnetic fields on the migrating epithelial cells. In this study we tested in vitro the effect of static magnetic fields on corneal epithelial cells. We were able to reproduce dramatic vortex or whorl patterns in response to magnetic fields, but without preferential migration towards the North or South Pole. PMID:8944095

  6. In Situ Tissue Engineering Using Magnetically Guided Three-Dimensional Cell Patterning

    PubMed Central

    Grogan, Shawn P.; Pauli, Chantal; Chen, Peter; Du, Jiang; Chung, Christine B.; Kong, Seong Deok; Colwell, Clifford W.; Lotz, Martin K.; Jin, Sungho

    2012-01-01

    Manipulation of cell patterns in three dimensions in a manner that mimics natural tissue organization and function is critical for cell biological studies and likely essential for successfully regenerating tissues—especially cells with high physiological demands, such as those of the heart, liver, lungs, and articular cartilage.1,2 In the present study, we report on the feasibility of arranging iron oxide-labeled cells in three-dimensional hydrogels using magnetic fields. By manipulating the strength, shape, and orientation of the magnetic field and using crosslinking gradients in hydrogels, multi-directional cell arrangements can be produced in vitro and even directly in situ. We show that these ferromagnetic particles are nontoxic between 0.1 and 10 mg/mL; certain species of particles can permit or even enhance tissue formation, and these particles can be tracked using magnetic resonance imaging. Taken together, this approach can be adapted for studying basic biological processes in vitro, for general tissue engineering approaches, and for producing organized repair tissues directly in situ. PMID:22224660

  7. Microfluidic Synthesis of Microfibers for Magnetic-Responsive Controlled Drug Release and Cell Culture

    PubMed Central

    Lin, Yung-Sheng; Huang, Keng-Shiang; Yang, Chih-Hui; Wang, Chih-Yu; Yang, Yuh-Shyong; Hsu, Hsiang-Chen; Liao, Yu-Ju; Tsai, Chia-Wen

    2012-01-01

    This study demonstrated the fabrication of alginate microfibers using a modular microfluidic system for magnetic-responsive controlled drug release and cell culture. A novel two-dimensional fluid-focusing technique with multi-inlets and junctions was used to spatiotemporally control the continuous laminar flow of alginate solutions. The diameter of the manufactured microfibers, which ranged from 211 µm to 364 µm, could be well controlled by changing the flow rate of the continuous phase. While the model drug, diclofenac, was encapsulated into microfibers, the drug release profile exhibited the characteristic of a proper and steady release. Furthermore, the diclofenac release kinetics from the magnetic iron oxide-loaded microfibers could be controlled externally, allowing for a rapid drug release by applying a magnetic force. In addition, the successful culture of glioblastoma multiforme cells in the microfibers demonstrated a good structural integrity and environment to grow cells that could be applied in drug screening for targeting cancer cells. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of generating functional microfibers with the potential for biomedical applications, such as drug controlled release and cell culture. PMID:22470443

  8. Labeling pluripotent stem cell-derived neural progenitors with iron oxide particles for magnetic resonance imaging.

    PubMed

    Sart, Sébastien; Bejarano, Fabian Calixto; Yan, Yuanwei; Grant, Samuel C; Li, Yan

    2015-01-01

    Due to the unlimited proliferation capacity and the unique differentiation ability of pluripotent stem cells (PSCs), including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), large numbers of PSC-derived cell products are in demand for applications in drug screening, disease modeling, and especially cell therapy. In stem cell-based therapy, tracking transplanted cells with magnetic resonance imaging (MRI) has emerged as a powerful technique to reveal cell survival and distribution. This chapter illustrated the basic steps of labeling PSC-derived neural progenitors (NPs) with micron-sized particles of iron oxide (MPIO, 0.86 μm) for MRI analysis. The protocol described PSC expansion and differentiation into NPs, and the labeling of the derived cells either after replating on adherent surface or in suspension. The labeled cells can be analyzed using in vitro MRI analysis. The methods presented here can be easily adapted for cell labeling in cell processing facilities under current Good Manufacturing Practices (cGMP). The iron oxide-labeled NPs can be used for cellular monitoring of in vitro cultures and in vivo transplantation. PMID:25304204

  9. [Preparation of Biological Functional Magnetic Nanoparticles and Study on the Effect of Guiding Endothelial Progenitor Cells In Vitro].

    PubMed

    Ma, Baolong; Yan, Wei; Chen, Jialong; Qi, Pengkai; Li, Jianhui; Huang, Nan

    2016-02-01

    Coprecipitation method was used to prepare triiron tetroxide magnetic nanoparticles enclosed in L-DOPA, and then EDC was used to activate the carboxyl group of L-DOPA after the nanoparticles were synthesized. The carboxyl group of L-DOPA formed amide bond with specific amino on the aptamer by dehydration condensation reaction. The surfaces of magnetic nanoparticles were modified with aptamer and L-DOPA. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), nanoparticle size analysis (SEM), magnetic measurement (VSM) and other testing methods were used to detect the magnetic nanoparticles in different stages. The endothelial progeni-tor cells (EPCs) were cocultured with the surface modified magnetic nanoparticles to evaluate cell compatibility and the combination effect of nanoparticles on EPCs in a short period of time. Directional guide of the surface-modified magnetic nanoparticles to endothelial progenitor cells (EPCs) was evaluated under an applied magnetic field and simulated dynamic blood flow condition. The results showed that the prepared magnetic nanoparticles had good magnetic response, good cell compatibility within a certain range of the nanoparticle concentrations. The surface modified nanoparticles could combine with EPCs effectively in a short time, and those nanoparticles combined EPCs can be directionally guided on to a stent surface under the magnetic field in the dynamic flow environment. PMID:27382754

  10. Geometrically pinned magnetic domain wall for multi-bit per cell storage memory.

    PubMed

    Bahri, M Al; Sbiaa, R

    2016-01-01

    Spintronic devices currently rely on magnetic switching or controlled motion of domain walls (DWs) by an external magnetic field or a spin-polarized current. Controlling the position of DW is essential for defining the state/information in a magnetic memory. During the process of nanowire fabrication, creating an off-set of two parts of the device could help to pin DW at a precise position. Micromagnetic simulation conducted on in-plane magnetic anisotropy materials shows the effectiveness of the proposed design for pinning DW at the nanoconstriction region. The critical current for moving DW from one state to the other is strongly dependent on nanoconstricted region (width and length) and the magnetic properties of the material. The DW speed which is essential for fast writing of the data could reach values in the range of hundreds m/s. Furthermore, evidence of multi-bit per cell memory is demonstrated via a magnetic nanowire with more than one constriction. PMID:27334038

  11. Geometrically pinned magnetic domain wall for multi-bit per cell storage memory

    PubMed Central

    Bahri, M. Al; Sbiaa, R.

    2016-01-01

    Spintronic devices currently rely on magnetic switching or controlled motion of domain walls (DWs) by an external magnetic field or a spin-polarized current. Controlling the position of DW is essential for defining the state/information in a magnetic memory. During the process of nanowire fabrication, creating an off-set of two parts of the device could help to pin DW at a precise position. Micromagnetic simulation conducted on in-plane magnetic anisotropy materials shows the effectiveness of the proposed design for pinning DW at the nanoconstriction region. The critical current for moving DW from one state to the other is strongly dependent on nanoconstricted region (width and length) and the magnetic properties of the material. The DW speed which is essential for fast writing of the data could reach values in the range of hundreds m/s. Furthermore, evidence of multi-bit per cell memory is demonstrated via a magnetic nanowire with more than one constriction. PMID:27334038

  12. Probing protein quinary interactions by in-cell nuclear magnetic resonance spectroscopy.

    PubMed

    Majumder, Subhabrata; Xue, Jing; DeMott, Christopher M; Reverdatto, Sergey; Burz, David S; Shekhtman, Alexander

    2015-05-01

    Historically introduced by McConkey to explain the slow mutation rate of highly abundant proteins, weak protein (quinary) interactions are an emergent property of living cells. The protein complexes that result from quinary interactions are transient and thus difficult to study biochemically in vitro. Cross-correlated relaxation-induced polarization transfer-based in-cell nuclear magnetic resonance allows the characterization of protein quinary interactions with atomic resolution inside live prokaryotic and eukaryotic cells. We show that RNAs are an important component of protein quinary interactions. Protein quinary interactions are unique to the target protein and may affect physicochemical properties, protein activity, and interactions with drugs. PMID:25894651

  13. A newly designed experimental system for exposure of mammalian cells to extremely low frequency magnetic fields.

    PubMed

    Miyakoshi, J; Ohtsu, S; Tatsumi-Miyajima, J; Takebe, H

    1994-03-01

    To examine the biological effects of extremely low frequency magnetic field (ELFMF), we have designed and manufactured a new equipment for long-term and high-density exposure of cells to ELFMF. The ELFMF exposure system consists of a generator of magnets with a built-in CO2 incubator, an alternating current (AC) power supply, a gas compressor and a thermocontroller for the incubator, and a cooling unit for the magnets. The CO2 incubator made of acrylic resin is inserted into the inner-space of the silicon steel strip-cores. In this system, the temperature of the incubator is maintained at 37 +/- 0.5 degrees C. The maximum magnetic flux density on the exposure area of the incubator is 500 mT (T; tesla) at a current of 556 Arms (rms; root mean square) at 50 Hz. The long-term (up to 120 hr) exposure of 400 mT ELFMF did not affect the growth of both HL60RG and CCRF-CEM cells originated from human leukemia. The post-X-irradiation exposure of 400 mT ELFMF for 2 hr also did not affect the radiation sensitivity of GM0637 and TAT2SF cells originated from a normal human and an ataxia telangiectasia patient. PMID:8057268

  14. Assessment of direct versus indirect magnetic bead-based T-cell isolation procedures followed by magnetic bead-based DNA isolation

    PubMed Central

    Rosenbaum, Anna; Bleck, Ellen; Schneider, Matthias; Pongratz, Georg; Vordenbäumen, Stefan

    2016-01-01

    Objective To compare direct and indirect bead-based T-cell isolation followed by magnetic bead-based DNA isolation. Methods T-cells were isolated by direct or indirect selection with magnetic bead coated antbiodies followed by magnetic bead-based automated DNA isolation in 10 healthy subjects. Purity of T-cells, purity of DNA (by A260/A280 ratio measurement) and DNA concentration were assessed. Results Direct and indirect labelling resulted in comparable T-cell purity (93.11±1.47% vs. 94.99±1.54%, p= 0.125) and DNA concentration per cell (50.97±14.15 ng/(mlxcell) vs. 49.53±13.62 ng/(mlxcell), p=0.492), while DNA purity was significantly higher after direct labelling (1.82±0.05 vs. 1.78±0.03, p=0.0488). Conclusions Both direct and indirect magnetic bead-based T-cell selection may be used prior to magnetic bead-based DNA isolation procedures. PMID:27547441

  15. Use of an advanced composite material in construction of a high pressure cell for magnetic ac susceptibility measurements

    NASA Astrophysics Data System (ADS)

    Wang, X.; Misek, M.; Jacobsen, M. K.; Kamenev, K. V.

    2014-10-01

    The applicability of fibre-reinforced polymers for fabrication of high pressure cells was assessed using finite element analysis and experimental testing. Performance and failure modes for the key components of the cell working in tension and in compression were evaluated and the ways for optimising the designs were established. These models were used in construction of a miniature fully non-metallic diamond anvil cell for magnetic ac susceptibility measurements in a magnetic property measurement system. The cell is approximately 14 mm long, 8.5 mm in diameter and was demonstrated to reach a pressure of 5.6 GPa. AC susceptibility data collected on Dy2O3 demonstrate the performance of the cell in magnetic property measurements and confirm that there is no screening of the sample by the environment which typically accompanies the use of conventional metallic high pressure cells in oscillating magnetic fields.

  16. Magnetic-field tunable defect modes in a photonic-crystal/liquid-crystal cell.

    PubMed

    Zyryanov, Victor Ya; Myslivets, Sergey A; Gunyakov, Vladimir A; Parshin, Alexander M; Arkhipkin, Vasily G; Shabanov, Vasily F; Lee, Wei

    2010-01-18

    Light transmission spectrum of a multilayer photonic crystal with a central liquid-crystal defect layer placed between crossed polarizers has been studied. Transmittance was varied due to the magnetically induced reorientation of the nematic director from homeotropic to planar alignment. Two notable effects were observed for this scheme: the spectral shift of defect modes corresponding to the extraordinary light wave and its superposition with the ordinary one. As a result, the optical cell allows controlling the intensity of interfering defect modes by applied magnetic field. PMID:20173953

  17. Particle-in-cell simulations on spontaneous thermal magnetic field fluctuations

    SciTech Connect

    Simões, F. J. R. Jr.; Pavan, J.; Gaelzer, R.; Ziebell, L. F.; Yoon, P. H.

    2013-10-15

    In this paper an electromagnetic particle code is used to investigate the spontaneous thermal emission. Specifically we perform particle-in-cell simulations employing a non-relativistic isotropic Maxwellian particle distribution to show that thermal fluctuations are related to the origin of spontaneous magnetic field fluctuation. These thermal fluctuations can become seed for further amplification mechanisms and thus be considered at the origin of the cosmological magnetic field, at microgauss levels. Our numerical results are in accordance with theoretical results presented in the literature.

  18. MPQ-cytometry: a magnetism-based method for quantification of nanoparticle-cell interactions

    NASA Astrophysics Data System (ADS)

    Shipunova, V. O.; Nikitin, M. P.; Nikitin, P. I.; Deyev, S. M.

    2016-06-01

    Precise quantification of interactions between nanoparticles and living cells is among the imperative tasks for research in nanobiotechnology, nanotoxicology and biomedicine. To meet the challenge, a rapid method called MPQ-cytometry is developed, which measures the integral non-linear response produced by magnetically labeled nanoparticles in a cell sample with an original magnetic particle quantification (MPQ) technique. MPQ-cytometry provides a sensitivity limit 0.33 ng of nanoparticles and is devoid of a background signal present in many label-based assays. Each measurement takes only a few seconds, and no complicated sample preparation or data processing is required. The capabilities of the method have been demonstrated by quantification of interactions of iron oxide nanoparticles with eukaryotic cells. The total amount of targeted nanoparticles that specifically recognized the HER2/neu oncomarker on the human cancer cell surface was successfully measured, the specificity of interaction permitting the detection of HER2/neu positive cells in a cell mixture. Moreover, it has been shown that MPQ-cytometry analysis of a HER2/neu-specific iron oxide nanoparticle interaction with six cell lines of different tissue origins quantitatively reflects the HER2/neu status of the cells. High correlation of MPQ-cytometry data with those obtained by three other commonly used in molecular and cell biology methods supports consideration of this method as a prospective alternative for both quantifying cell-bound nanoparticles and estimating the expression level of cell surface antigens. The proposed method does not require expensive sophisticated equipment or highly skilled personnel and it can be easily applied for rapid diagnostics, especially under field conditions.Precise quantification of interactions between nanoparticles and living cells is among the imperative tasks for research in nanobiotechnology, nanotoxicology and biomedicine. To meet the challenge, a rapid method

  19. Magnetic Shielding Accelerates the Proliferation of Human Neuroblastoma Cell by Promoting G1-Phase Progression

    PubMed Central

    Liu, Ying; Bartlett, Perry F.; He, Rong-qiao

    2013-01-01

    Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF. PMID:23355897

  20. Development of Multifunctional Magnetic Nanoparticles for Genetic Engineering and Tracking of Neural Stem Cells.

    PubMed

    Adams, Christopher; Israel, Liron Limor; Ostrovsky, Stella; Taylor, Arthur; Poptani, Harish; Lellouche, Jean-Paul; Chari, Divya

    2016-04-01

    Genetic modification of cell transplant populations and cell tracking ability are key underpinnings for effective cell therapies. Current strategies to achieve these goals utilize methods which are unsuitable for clinical translation because of related safety issues, and multiple protocol steps adding to cost and complexity. Multifunctional magnetic nanoparticles (MNPs) offering dual mode gene delivery and imaging contrast capacity offer a valuable tool in this context. Despite their key benefits, there is a critical lack of neurocompatible and multifunctional particles described for use with transplant populations for neurological applications. Here, a systematic screen of MNPs (using a core shown to cause contrast in magnetic resonance imaging (MRI)) bearing various surface chemistries (polyethylenimine (PEI) and oxidized PEI and hybrids of oxidized PEI/alginic acid, PEI/chitosan and PEI/polyamidoamine) is performed to test their ability to genetically engineer neural stem cells (NSCs; a cell population of high clinical relevance for central nervous system disorders). It is demonstrated that gene delivery to NSCs can be safely achieved using two of the developed formulations (PEI and oxPEI/alginic acid) when used in conjunction with oscillating magnetofection technology. After transfection, intracellular particles can be detected by histological procedures with labeled cells displaying contrast in MRI (for real time cell tracking). PMID:26867130

  1. Magnetic Resonance Imaging (MRI) of PEM Dehydration and Gas Manifold Flooding During Continuous Fuel Cell Operation

    SciTech Connect

    Minard, Kevin R.; Vishwanathan, Vilanyur V.; Majors, Paul D.; Wang, Li Q.; Rieke, Peter C.

    2006-10-27

    The methods, apparatus, and results are reported for in-situ, near real time, magnetic resonance imaging (MRI) of MEA dehydration and gas manifold flooding in an operating PEM fuel cell. To acquire high-resolution, artifact-free images for visualizing water distribution, acquisition parameters for a standard, two-dimensional (2D), spin-echo sequence were first optimized for the measured magnetic field heterogeneity induced by fuel cell components. 2D images of water inside the fuel cell were then acquired every 128 seconds during 11.4 hours of continuous operation under constant load. Collected images revealed that MEA dehydration proceeded non-uniformly across its plane, starting from gas inlets and ending at gas outlets, and that upon completion of this dehydration process manifold flooding began. To understand these observations, acquired images were correlated to the current output and operating characteristics of the fuel cell. Results demonstrate the power of MRI for in-situ, near real-time imaging of water distribution and non-uniformity in operating PEM fuel cells, and highlight its utility for understanding PEM fuel cell operation, the causes of cell failure, and for developing new strategies of water management.

  2. Magnetic shielding accelerates the proliferation of human neuroblastoma cell by promoting G1-phase progression.

    PubMed

    Mo, Wei-chuan; Zhang, Zi-jian; Liu, Ying; Bartlett, Perry F; He, Rong-qiao

    2013-01-01

    Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF. PMID:23355897

  3. Electrochemical cell for in situ electrodeposition of magnetic thin films in a superconducting quantum interference device magnetometer

    SciTech Connect

    Topolovec, Stefan Würschum, Roland; Krenn, Heinz

    2015-06-15

    An electrochemical cell is designed and applied for in situ electrodeposition of magnetic thin films in a commercial SQUID magnetometer system. The cell is constructed in such a way that any parasitic contribution of the cell and of the substrate for electrodeposition to the magnetic moment of the deposited film is reduced to a minimum. A remanent minor contribution is readily taken into account by a proper analysis of the detected signal. Thus, a precise determination of the absolute magnetic moment of the electrodeposited magnetic film during its growth and dissolution is achieved. The feasibility of the cell design is demonstrated by performing Co electrodeposition using cyclic voltammetry. For an average Co film thickness of (35.6 ± 3.0) atomic layers, a magnetic moment per Co atom of (1.75 ± 0.11) μ{sub B} was estimated, in good agreement with the literature bulk value.

  4. MPQ-cytometry: a magnetism-based method for quantification of nanoparticle-cell interactions.

    PubMed

    Shipunova, V O; Nikitin, M P; Nikitin, P I; Deyev, S M

    2016-07-01

    Precise quantification of interactions between nanoparticles and living cells is among the imperative tasks for research in nanobiotechnology, nanotoxicology and biomedicine. To meet the challenge, a rapid method called MPQ-cytometry is developed, which measures the integral non-linear response produced by magnetically labeled nanoparticles in a cell sample with an original magnetic particle quantification (MPQ) technique. MPQ-cytometry provides a sensitivity limit 0.33 ng of nanoparticles and is devoid of a background signal present in many label-based assays. Each measurement takes only a few seconds, and no complicated sample preparation or data processing is required. The capabilities of the method have been demonstrated by quantification of interactions of iron oxide nanoparticles with eukaryotic cells. The total amount of targeted nanoparticles that specifically recognized the HER2/neu oncomarker on the human cancer cell surface was successfully measured, the specificity of interaction permitting the detection of HER2/neu positive cells in a cell mixture. Moreover, it has been shown that MPQ-cytometry analysis of a HER2/neu-specific iron oxide nanoparticle interaction with six cell lines of different tissue origins quantitatively reflects the HER2/neu status of the cells. High correlation of MPQ-cytometry data with those obtained by three other commonly used in molecular and cell biology methods supports consideration of this method as a prospective alternative for both quantifying cell-bound nanoparticles and estimating the expression level of cell surface antigens. The proposed method does not require expensive sophisticated equipment or highly skilled personnel and it can be easily applied for rapid diagnostics, especially under field conditions. PMID:27279427

  5. Combining magnetic sorting of mother cells and fluctuation tests to analyze genome instability during mitotic cell aging in Saccharomyces cerevisiae.

    PubMed

    Patterson, Melissa N; Maxwell, Patrick H

    2014-01-01

    Saccharomyces cerevisiae has been an excellent model system for examining mechanisms and consequences of genome instability. Information gained from this yeast model is relevant to many organisms, including humans, since DNA repair and DNA damage response factors are well conserved across diverse species. However, S. cerevisiae has not yet been used to fully address whether the rate of accumulating mutations changes with increasing replicative (mitotic) age due to technical constraints. For instance, measurements of yeast replicative lifespan through micromanipulation involve very small populations of cells, which prohibit detection of rare mutations. Genetic methods to enrich for mother cells in populations by inducing death of daughter cells have been developed, but population sizes are still limited by the frequency with which random mutations that compromise the selection systems occur. The current protocol takes advantage of magnetic sorting of surface-labeled yeast mother cells to obtain large enough populations of aging mother cells to quantify rare mutations through phenotypic selections. Mutation rates, measured through fluctuation tests, and mutation frequencies are first established for young cells and used to predict the frequency of mutations in mother cells of various replicative ages. Mutation frequencies are then determined for sorted mother cells, and the age of the mother cells is determined using flow cytometry by staining with a fluorescent reagent that detects bud scars formed on their cell surfaces during cell division. Comparison of predicted mutation frequencies based on the number of cell divisions to the frequencies experimentally observed for mother cells of a given replicative age can then identify whether there are age-related changes in the rate of accumulating mutations. Variations of this basic protocol provide the means to investigate the influence of alterations in specific gene functions or specific environmental conditions on

  6. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

    NASA Astrophysics Data System (ADS)

    Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

    2013-08-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific

  7. Size-Dependent Photodynamic Anticancer Activity of Biocompatible Multifunctional Magnetic Submicron Particles in Prostate Cancer Cells.

    PubMed

    Choi, Kyong-Hoon; Nam, Ki Chang; Malkinski, Leszek; Choi, Eun Ha; Jung, Jin-Seung; Park, Bong Joo

    2016-01-01

    In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe₂O₄-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting of cancer cells and destruction of cancer cell functionality, basic cobalt ferrite (CoFe₂O₄) particles were covalently bonded with a photosensitizer (PS), which comprises hematoporphyrin (HP), and folic acid (FA) molecules. The magnetic properties of the CoFe₂O₄ particles were finely adjusted by controlling the size of the primary CoFe₂O₄ nanograins, and secondary superstructured composite particles were formed by aggregation of the nanograins. The prepared CoFe₂O₄-HP-FA exhibited high water solubility, good MR-imaging capacity, and biocompatibility without any in vitro cytotoxicity. In particular, our CoFe₂O₄-HP-FA exhibited remarkable photodynamic anticancer efficiency via induction of apoptotic death in PC-3 prostate cancer cells in a particle size- and concentration-dependent manner. This size-dependent effect was determined by the specific surface area of the particles because the number of HP molecules increased with decreasing size and increasing surface area. These results indicate that our CoFe₂O₄-HP-FA may be applicable for photodynamic therapy (PDT) as a PS delivery material and a therapeutic agent for MR-imaging based PDT owing to their high saturation value for magnetization and superparamagnetism. PMID:27607999

  8. Energetic constraints on the creation of cell membrane pores by magnetic particles.

    PubMed Central

    Vaughan, T E; Weaver, J C

    1996-01-01

    Naturally occurring and contaminant ferromagnetic and ferrimagnetic particles have been found within or near cells, and might allow pulsed magnetic fields to create transient cell membrane opening ("pores"). We show that this possibility is significantly constrained by the maximum rotational energy that can be transferred to the cell membrane. For single biologically synthesized magnetosomes (radius rmag approximately 10(-7) m, magnetic moment mu approximately 2 x 10(-15) A m2) and typical cell membranes, the estimated pulse magnitude must exceed Bo approximately 6 x 10(-3) to 7 x 10(-2) T, and the optimal pulse durations are in the range 10(-5) s < tpulse < 10(-1) s. For larger contaminant particles with larger net magnetic moments, the pulse magnitudes could be only somewhat smaller, and the optimal durations are about the same. Very large pulses that exceed the coercive force of a particle are predicted to have a smaller effective magnitude and shorter effective duration. PMID:8842201

  9. Carbon-covered magnetic nanomaterials and their application for the thermolysis of cancer cells.

    PubMed

    Xu, Yang; Mahmood, Meena; Fejleh, Ashley; Li, Zhongrui; Watanabe, Fumiya; Trigwell, Steve; Little, Reginald B; Kunets, Vasyl P; Dervishi, Enkeleda; Biris, Alexandru R; Salamo, Gregory J; Biris, Alexandru S

    2010-01-01

    Three types of graphitic shelled-magnetic core (Fe, Fe/Co, and Co) nanoparticles (named as C-Fe, C-Fe/Co, and C-Co NPs) were synthesized by radio frequency-catalytic chemical vapor deposition (RF-cCVD). X-ray diffraction and X-ray photoelectron spectroscopy analysis revealed that the cores inside the carbon shells of these NPs were preserved in their metallic states. Fluorescence microscopy images indicated effective penetrations of the NPs through the cellular membranes of cultured cancer HeLa cells, both inside the cytoplasm and the nucleus. Low RF radiation of 350 kHz induced localized heating of the magnetic NPs, which triggered cell death. Apoptosis inducement was found to be dependent on the RF irradiation time and NP concentration. It was showed that the Fe-C NPs had a much higher ability of killing the cancer cells (over 99%) compared with the other types of NPs (C-Co or C-Fe/Co), even at a very low concentration of 0.83 microg/mL. The localized heating of NPs inside the cancer cells comes from the hysteresis heating and resistive heating through eddy currents generated under the RF radiation. The RF thermal ablation properties of the magnetic NPs were correlated with the analysis provided by a superconducting quantum interference device (SQUID). PMID:20463932

  10. Carbon-covered magnetic nanomaterials and their application for the thermolysis of cancer cells

    PubMed Central

    Xu, Yang; Mahmood, Meena; Fejleh, Ashley; Li, Zhongrui; Watanabe, Fumiya; Trigwell, Steve; Little, Reginald B; Kunets, Vasyl P; Dervishi, Enkeleda; Biris, Alexandru R; Salamo, Gregory J; Biris, Alexandru S

    2010-01-01

    Three types of graphitic shelled-magnetic core (Fe, Fe/Co, and Co) nanoparticles (named as C-Fe, C-Fe/Co, and C-Co NPs) were synthesized by radio frequency-catalytic chemical vapor deposition (RF-cCVD). X-ray diffraction and X-ray photoelectron spectroscopy analysis revealed that the cores inside the carbon shells of these NPs were preserved in their metallic states. Fluorescence microscopy images indicated effective penetrations of the NPs through the cellular membranes of cultured cancer HeLa cells, both inside the cytoplasm and the nucleus. Low RF radiation of 350 kHz induced localized heating of the magnetic NPs, which triggered cell death. Apoptosis inducement was found to be dependent on the RF irradiation time and NP concentration. It was showed that the Fe-C NPs had a much higher ability of killing the cancer cells (over 99%) compared with the other types of NPs (C-Co or C-Fe/Co), even at a very low concentration of 0.83 μg/mL. The localized heating of NPs inside the cancer cells comes from the hysteresis heating and resistive heating through eddy currents generated under the RF radiation. The RF thermal ablation properties of the magnetic NPs were correlated with the analysis provided by a superconducting quantum interference device (SQUID). PMID:20463932

  11. Dual-Color Fluorescence Imaging of Magnetic Nanoparticles in Live Cancer Cells Using Conjugated Polymer Probes

    PubMed Central

    Sun, Minjie; Sun, Bin; Liu, Yun; Shen, Qun-Dong; Jiang, Shaojun

    2016-01-01

    Rapid growth in biological applications of nanomaterials brings about pressing needs for exploring nanomaterial-cell interactions. Cationic blue-emissive and anionic green-emissive conjugated polymers are applied as dual-color fluorescence probes to the surface of negatively charged magnetic nanoparticles through sequentially electrostatic adsorption. These conjugated polymers have large extinction coefficients and high fluorescence quantum yield (82% for PFN and 62% for ThPFS). Thereby, one can visualize trace amount (2.7 μg/mL) of fluorescence-labeled nanoparticles within cancer cells by confocal laser scanning microscopy. Fluorescence labeling by the conjugated polymers is also validated for quantitative determination of the internalized nanoparticles in each individual cell by flow cytometry analysis. Extensive overlap of blue and green fluorescence signals in the cytoplasm indicates that both conjugated polymer probes tightly bind to the surface of the nanoparticles during cellular internalization. The highly charged and fluorescence-labeled nanoparticles non-specifically bind to the cell membranes, followed by cellular uptake through endocytosis. The nanoparticles form aggregates inside endosomes, which yields a punctuated staining pattern. Cellular internalization of the nanoparticles is dependent on the dosage and time. Uptake efficiency can be enhanced three-fold by application of an external magnetic field. The nanoparticles are low cytotoxicity and suitable for simultaneously noninvasive fluorescence and magnetic resonance imaging application. PMID:26931282

  12. Magnetic domain wall tweezers: a new tool for mechanobiology studies on individual target cells.

    PubMed

    Monticelli, M; Conca, D V; Albisetti, E; Torti, A; Sharma, P P; Kidiyoor, G; Barozzi, S; Parazzoli, D; Ciarletta, P; Lupi, M; Petti, D; Bertacco, R

    2016-08-01

    In vitro tests are of fundamental importance for investigating cell mechanisms in response to mechanical stimuli or the impact of the genotype on cell mechanical properties. In particular, the application of controlled forces to activate specific bio-pathways and investigate their effects, mimicking the role of the cellular environment, is becoming a prominent approach in the emerging field of mechanobiology. Here, we present an on-chip device based on magnetic domain wall manipulators, which allows the application of finely controlled and localized forces on target living cells. In particular, we demonstrate the application of a magnetic force in the order of hundreds of pN on the membrane of HeLa cells cultured on-chip, via manipulation of 1 μm superparamagnetic beads. Such a mechanical stimulus produces a sizable local indentation of the cellular membrane of about 2 μm. Upon evaluation of the beads' position within the magnetic field originated by the domain wall, the force applied during the experiments is accurately quantified via micromagnetic simulations. The obtained value is in good agreement with that calculated by the application of an elastic model to the cellular membrane. PMID:27364187

  13. Dual-Color Fluorescence Imaging of Magnetic Nanoparticles in Live Cancer Cells Using Conjugated Polymer Probes.

    PubMed

    Sun, Minjie; Sun, Bin; Liu, Yun; Shen, Qun-Dong; Jiang, Shaojun

    2016-01-01

    Rapid growth in biological applications of nanomaterials brings about pressing needs for exploring nanomaterial-cell interactions. Cationic blue-emissive and anionic green-emissive conjugated polymers are applied as dual-color fluorescence probes to the surface of negatively charged magnetic nanoparticles through sequentially electrostatic adsorption. These conjugated polymers have large extinction coefficients and high fluorescence quantum yield (82% for PFN and 62% for ThPFS). Thereby, one can visualize trace amount (2.7 μg/mL) of fluorescence-labeled nanoparticles within cancer cells by confocal laser scanning microscopy. Fluorescence labeling by the conjugated polymers is also validated for quantitative determination of the internalized nanoparticles in each individual cell by flow cytometry analysis. Extensive overlap of blue and green fluorescence signals in the cytoplasm indicates that both conjugated polymer probes tightly bind to the surface of the nanoparticles during cellular internalization. The highly charged and fluorescence-labeled nanoparticles non-specifically bind to the cell membranes, followed by cellular uptake through endocytosis. The nanoparticles form aggregates inside endosomes, which yields a punctuated staining pattern. Cellular internalization of the nanoparticles is dependent on the dosage and time. Uptake efficiency can be enhanced three-fold by application of an external magnetic field. The nanoparticles are low cytotoxicity and suitable for simultaneously noninvasive fluorescence and magnetic resonance imaging application. PMID:26931282

  14. Dual-responsive magnetic core-shell nanoparticles for nonviral gene delivery and cell separation.

    PubMed

    Majewski, Alexander P; Schallon, Anja; Jérôme, Valérie; Freitag, Ruth; Müller, Axel H E; Schmalz, Holger

    2012-03-12

    We present the synthesis of dual-responsive (pH and temperature) magnetic core-shell nanoparticles utilizing the grafting-from approach. First, oleic acid stabilized superparamagnetic maghemite (γ-Fe(2)O(3)) nanoparticles (NPs), prepared by thermal decomposition of iron pentacarbonyl, were surface-functionalized with ATRP initiating sites bearing a dopamine anchor group via ligand exchange. Subsequently, 2-(dimethylamino)ethyl methacrylate (DMAEMA) was polymerized from the surface by ATRP, yielding dual-responsive magnetic core-shell NPs (γ-Fe(2)O(3)@PDMAEMA). The attachment of the dopamine anchor group on the nanoparticle's surface is shown to be reversible to a certain extent, resulting in a grafting density of 0.15 chains per nm(2) after purification. Nevertheless, the grafted NPs show excellent long-term stability in water over a wide pH range and exhibit a pH- and temperature-dependent reversible agglomeration, as revealed by turbidimetry. The efficiency of γ-Fe(2)O(3)@PDMAEMA hybrid nanoparticles as a potential transfection agent was explored under standard conditions in CHO-K1 cells. Remarkably, γ-Fe(2)O(3)@PDMAEMA led to a 2-fold increase in the transfection efficiency without increasing the cytotoxicity, as compared to polyethyleneimine (PEI), and yielded on average more than 50% transfected cells. Moreover, after transfection with the hybrid nanoparticles, the cells acquired magnetic properties that could be used for selective isolation of transfected cells. PMID:22296556

  15. Synthesis, Characterization, and Preliminary Investigation of Cell Interaction of Magnetic Nanoparticles with Catechol-Containing Shells

    SciTech Connect

    Wagner, Kerstin; Seemann, Thomas; Wyrwa, Ralf; Schnabelrauch, Matthias; Clement, Joachim H.; Mueller, Robert; Nietzsche, Sandor

    2010-12-02

    Superparamagnetic iron oxide cores were synthesized by co-precipitation of Fe(II) and Fe(III) salts and subsequently stabilized by coating with different catechols (levodopa, dopamine, hydrocaffeic acid, dopamine-containing carboxymethyl dextran) known to act as high-affinity, bidentate ligands for Fe(III). The prepared stable magnetic fluids were characterized with regard to their chemical composition (content of iron and shell material, Fe(II)/Fe(III) ratio) and their physical properties (size, surface charge, magnetic parameters). The nanoparticles showed no or only slight cytotoxic effects within 1 and 4 days of incubation with 3T3 fibroblast cells. Preliminary experiments were performed to study the interaction of the prepared nanoparticles with human MCF-7 breast cancer cells and leukocytes. An intense interaction of the MCF-7 cells with these particles was found whereas the leukocytes showed a lower tendency of interaction. Based on these finding, the novel magnetic nanoparticles possess the potential for use in depletion of tumor cells from peripheral blood.

  16. Effect of different magnetic nanoparticle coatings on the efficiency of stem cell labeling

    NASA Astrophysics Data System (ADS)

    Horák, Daniel; Babič, Michal; Jendelová, Pavla; Herynek, Vít; Trchová, Miroslava; Likavčanová, Katarina; Kapcalová, Miroslava; Hájek, Milan; Syková, Eva

    2009-05-01

    Maghemite nanoparticles with various coatings were prepared by the coprecipitation method and characterized by transmission electron microscopy, dynamic light scattering and IR in terms of morphology, size, polydispersity and surface coating. The labeling efficiency and the viability of both rat and human mesenchymal stem cells labeled with Endorem ®, poly( L-lysine) (PLL)-modified Endorem ®, uncoated γ-Fe 2O 3, D-mannose-, PLL- or poly( N,N-dimethylacrylamide) (PDMAAm)-coated γ-Fe 2O 3 nanoparticles were compared. Coated γ-Fe 2O 3 nanoparticles labeled cells better than did Endorem ®. High relaxation rates and in vitro magnetic resonance imaging of cells labeled with coated nanoparticles showed clearly visible contrast compared with unlabeled cells or cells labeled with Endorem ®.

  17. Magnetic resonance tracking of nanoparticle labelled neural stem cells in a rat's spinal cord

    NASA Astrophysics Data System (ADS)

    Wang, F. H.; Lee, I. H.; Holmström, N.; Yoshitake, T.; Kim, D. K.; Muhammed, M.; Frisén, J.; Olson, L.; Spenger, C.; Kehr, J.

    2006-04-01

    Neural stem cells isolated from an adult rat's spinal cord were loaded with superparamagnetic gold-coated monocrystalline iron oxide nanoparticles (Au-MION) intended for use as contrast enhancers in magnetic resonance imaging (MRI). A dose-dependent attenuation of MRI signals was observed for Au-MION down to 0.001 µg Fe/µl and for nanoparticle-loaded clusters of only 20 cells. The labelled cells were infused into the spinal cord of anaesthetized rats and tracked by MRI at 1 h, 48 h and 1 month post-injection. Histological analysis revealed that MRI signals correlated well with gold-positive staining of transplanted cells. The present results show that Au-MION exerts powerful contrast-enhancing properties and may represent novel MRI labels for labelling and tracking the transplanted cells in vivo.

  18. Particle distributions in collisionless magnetic reconnection: An implicit Particle-In-Cell (PIC) description

    SciTech Connect

    Hewett, D.W.; Francis, G.E.; Max, C.E.

    1990-06-29

    Evidence from magnetospheric and solar flare research supports the belief that collisionless magnetic reconnection can proceed on the Alfven-wave crossing timescale. Reconnection behavior that occurs this rapidly in collisionless plasmas is not well understood because underlying mechanisms depend on the details of the ion and electron distributions in the vicinity of the emerging X-points. We use the direct implicit Particle-In-Cell (PIC) code AVANTI to study the details of these distributions as they evolve in the self-consistent E and B fields of magnetic reconnection. We first consider a simple neutral sheet model. We observe rapid movement of the current-carrying electrons away from the emerging X-point. Later in time an oscillation of the trapped magnetic flux is found, superimposed upon continued linear growth due to plasma inflow at the ion sound speed. The addition of a current-aligned and a normal B field widen the scope of our studies.

  19. Highly efficient mesenchymal stem cell proliferation on poly-ε-caprolactone nanofibers with embedded magnetic nanoparticles.

    PubMed

    Daňková, Jana; Buzgo, Matej; Vejpravová, Jana; Kubíčková, Simona; Sovková, Věra; Vysloužilová, Lucie; Mantlíková, Alice; Nečas, Alois; Amler, Evžen

    2015-01-01

    In this study, we have developed a combined approach to accelerate the proliferation of mesenchymal stem cells (MSCs) in vitro, using a new nanofibrous scaffold made by needleless electrospinning from a mixture of poly-ε-caprolactone and magnetic particles. The biological characteristics of porcine MSCs were investigated while cultured in vitro on composite scaffold enriched with magnetic nanoparticles. Our data indicate that due to the synergic effect of the poly-ε-caprolactone nanofibers and magnetic particles, cellular adhesion and proliferation of MSCs is enhanced and osteogenic differentiation is supported. The cellular and physical attributes make this new scaffold very promising for the acceleration of efficient MSC proliferation and regeneration of hard tissues. PMID:26677321

  20. Model of the influence of magnetic fields on a plasma electrode Pockels cell

    SciTech Connect

    Boley, C.D.; Rhodes, M.A.

    1996-10-01

    We describe a model which gives the effects of magnetic fields on a plasma electrode Pockels cell. The fields arise from the return currents to the cathode as well as from neighboring devices such as amplifier flashlamps. In effect, electrons are treated as a static, planar fluid moving under the influence of magnetic fields, the electric field of the discharge, electron pressure gradients, and electron-atom elastic collisions. This leads to a closed two- dimensional equation for the electron density, which is solved subject to appropriate boundary collisions. The model is applied to four cases-. the baseline NIF configuration with magnetic fields due to balanced return currents; a case with unbalanced return currents; the reverser configuration containing an external field parallel to the main plasma current; and a configuration with a field perpendicular to both the current and the optical direction.

  1. Highly efficient mesenchymal stem cell proliferation on poly-ε-caprolactone nanofibers with embedded magnetic nanoparticles

    PubMed Central

    Daňková, Jana; Buzgo, Matej; Vejpravová, Jana; Kubíčková, Simona; Sovková, Věra; Vysloužilová, Lucie; Mantlíková, Alice; Nečas, Alois; Amler, Evžen

    2015-01-01

    In this study, we have developed a combined approach to accelerate the proliferation of mesenchymal stem cells (MSCs) in vitro, using a new nanofibrous scaffold made by needleless electrospinning from a mixture of poly-ε-caprolactone and magnetic particles. The biological characteristics of porcine MSCs were investigated while cultured in vitro on composite scaffold enriched with magnetic nanoparticles. Our data indicate that due to the synergic effect of the poly-ε-caprolactone nanofibers and magnetic particles, cellular adhesion and proliferation of MSCs is enhanced and osteogenic differentiation is supported. The cellular and physical attributes make this new scaffold very promising for the acceleration of efficient MSC proliferation and regeneration of hard tissues. PMID:26677321

  2. Evidence of magnetic field switch-off in Particle In Cell simulations of collisionless magnetic reconnection with guide field

    NASA Astrophysics Data System (ADS)

    Innocenti, M. E.; Goldman, M. V.; Newman, D. L.; Markidis, S.; Lapenta, G.

    2015-12-01

    The long term evolution of large domain Particle In Cell simulations of collisionless magnetic reconnection is investigated following observations that show two possible outcomes for collisionless reconnection: towards a Petschek-like configuration (Gosling 2007) or towards multiple X points (Eriksson et al. 2014). In the simulations presented here and described in [Innocenti2015*], a mixed scenario develops. At earlier time, plasmoids are emitted, disrupting the formation of Petschek-like structures. Later, an almost stationary monster plasmoid forms, preventing the emission of other plasmoids. A situation reminding of Petschek's switch-off then ensues. Switch-off is obtained through a slow shock / rotational discontinuity (SS/RD) compound structure, with the rotation discontinuity downstreamthe slow shock. Two external slow shocks located in correspondence of the separatrices reduce the in plane tangential component of the magnetic field, but not to zero. Two transitions reminding of rotational discontinuities in the internal part of the exhausts then perform the final switch-off. Both the slow shocks and the rotational discontinuities are characterized as such through the analysis of their Rankine-Hugoniot jump conditions. A moderate guide field is used to suppress the development of the firehose instability in the exhaust that prevented switch off in [Liu2012]. Compound SS/RD structures, with the RD located downstream the SS, have been observed in both the solar wind and the magnetosphere in Wind and Geotail data respectively [Whang1998, Whang2004]. Ion trajectiories across the SS/RD structure are followed and the kinetic origin of the SS/RD structure is investigated. * Innocenti, Goldman, Newman, Markidis, Lapenta, Evidence of magnetic field switch-off in collisionless magnetic reconnection, accepted in Astrophysical Journal Letters, 2015 Acknowledgements: NERSC, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of

  3. Magnetic resonance imaging findings in giant cell arteritis.

    PubMed

    D'Souza, N M; Morgan, M L; Almarzouqi, S J; Lee, A G

    2016-05-01

    PurposeGiant cell arteritis (GCA) is a systemic vasculitis that affects medium-to-large-caliber arteries. Early diagnosis and treatment is essential as involvement of the ophthalmic artery or its branches may cause blindness. Radiographic findings may be variable and non-specific leading to delay in diagnosis. We conducted a review of the literature on neuroimaging findings in GCA and present a retrospective case series from tertiary-care ophthalmic referral centers of three patients with significant neuroimaging findings in biopsy-proven GCA.MethodsRetrospective case series of biopsy-proven GCA cases with neuroimaging findings at the Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital between 2010-2015 were included in this study. Literature search was conducted using Google Scholar and Medline search engines between the years 1970 and 2015.ResultsWe report findings of optic nerve enhancement, optic nerve sheath enhancement, and the first description in the English-language ophthalmic literature, to our knowledge, of chiasmal enhancement in biopsy-proven GCA. We describe four main categories of neuroimaging findings that may be seen in GCA from our series and from past cases in the literature.DiscussionIt is essential that clinicians be aware of the possible radiographic findings in GCA. Appropriate and prompt treatment should not be delayed based upon these findings. PMID:26915748

  4. Antibody-Free Magnetic Cell Sorting of Genetically Modified Primary Human CD4+ T Cells by One-Step Streptavidin Affinity Purification

    PubMed Central

    Matheson, Nicholas J.; Peden, Andrew A.; Lehner, Paul J.

    2014-01-01

    Existing methods for phenotypic selection of genetically modified mammalian cells suffer disadvantages of time, cost and scalability and, where antibodies are used to bind exogenous cell surface markers for magnetic selection, typically yield cells coated with antibody-antigen complexes and beads. To overcome these limitations we have developed a method termed Antibody-Free Magnetic Cell Sorting in which the 38 amino acid Streptavidin Binding Peptide (SBP) is displayed at the cell surface by the truncated Low Affinity Nerve Growth Receptor (LNGFRF) and used as an affinity tag for one-step selection with streptavidin-conjugated magnetic beads. Cells are released through competition with the naturally occurring vitamin biotin, free of either beads or antibody-antigen complexes and ready for culture or use in downstream applications. Antibody-Free Magnetic Cell Sorting is a rapid, cost-effective, scalable method of magnetic selection applicable to either viral transduction or transient transfection of cell lines or primary cells. We have optimised the system for enrichment of primary human CD4+ T cells expressing shRNAs and exogenous genes of interest to purities of >99%, and used it to isolate cells following Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing. PMID:25360777

  5. Multifunctional nanoprobe for cancer cell targeting and simultaneous fluorescence/magnetic resonance imaging.

    PubMed

    Wei, Zhenzhen; Wu, Yafeng; Zhao, Yuewu; Mi, Li; Wang, Jintao; Wang, Jimin; Zhao, Jinjin; Wang, Lixin; Liu, Anran; Li, Ying; Wei, Wei; Zhang, Yuanjian; Liu, Songqin

    2016-09-28

    Multifunctional nanoprobes with distinctive magnetic and fluorescent properties are highly useful in accurate and early cancer diagnosis. In this study, nanoparticles of Fe3O4 core with fluorescent SiO2 shell (MFS) are synthesized by a facile improved Stöber method. These nanoparticles owning a significant core-shell structure exhibit good dispersion, stable fluorescence, low cytotoxicity and excellent biocompatibility. TLS11a aptamer (Apt1), a specific membrane protein for human liver cancer cells which could be internalized into cells, is conjugated to the MFS nanoparticles through the formation of amide bond working as a target-specific moiety. The attached TLS11a aptamers on nanoparticles are very stable and can't be hydrolyzed by DNA hydrolytic enzyme in vivo. Both fluorescence and magnetic resonance imaging show significant uptake of aptamer conjugated nanoprobe by HepG2 cells compared to 4T1, SGC-7901 and MCF-7 cells. In addition, with the increasing concentration of the nanoprobe, T2-weighted MRI images of the as-treated HepG2 cells are significantly negatively enhanced, indicating that a high magnetic field gradient is generated by MFS-Apt1 which has been specifically captured by HepG2 cells. The relaxivity of nanoprobe is calculated to be 11.5 mg(-1)s(-1). The MR imaging of tumor-bearing nude mouse is also confirmed. The proposed multifunctional nanoprobe with the size of sub-100 nm has the potential to provide real-time imaging in early liver cancer cell diagnosis. PMID:27619098

  6. Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device.

    PubMed

    Talasaz, AmirAli H; Powell, Ashley A; Huber, David E; Berbee, James G; Roh, Kyung-Ho; Yu, Wong; Xiao, Wenzhong; Davis, Mark M; Pease, R Fabian; Mindrinos, Michael N; Jeffrey, Stefanie S; Davis, Ronald W

    2009-03-10

    The enumeration of rare circulating epithelial cells (CEpCs) in the peripheral blood of metastatic cancer patients has shown promise for improved cancer prognosis. Moving beyond enumeration, molecular analysis of CEpCs may provide candidate surrogate endpoints to diagnose, treat, and monitor malignancy directly from the blood samples. Thorough molecular analysis of CEpCs requires the development of new sample preparation methods that yield easily accessible and purified CEpCs for downstream biochemical assays. Here, we describe a new immunomagnetic cell separator, the MagSweeper, which gently enriches target cells and eliminates cells that are not bound to magnetic particles. The isolated cells are easily accessible and can be extracted individually based on their physical characteristics to deplete any cells nonspecifically bound to beads. We have shown that our device can process 9 mL of blood per hour and captures >50% of CEpCs as measured in spiking experiments. We have shown that the separation process does not perturb the gene expression of rare cells. To determine the efficiency of our platform in isolating CEpCs from patients, we have isolated CEpCs from all 47 tubes of 9-mL blood samples collected from 17 women with metastatic breast cancer. In contrast, we could not find any circulating epithelial cells in samples from 5 healthy donors. The isolated CEpCs are all stored individually for further molecular analysis. PMID:19234122

  7. Mesenchymal stem cell in vitro labeling by hybrid fluorescent magnetic polymeric particles for application in cell tracking.

    PubMed

    Supokawej, Aungkura; Nimsanor, Natakarn; Sanvoranart, Tanwarat; Kaewsaneha, Chariya; Hongeng, Suradej; Tangboriboonrat, Pramuan; Jangpatarapongsa, Kulachart

    2015-12-01

    Mesenchymal stem cells (MSCs) are a type of adult stem cell that contains multi-differentiation and proliferative properties and that shows high treatment implications for many clinical problems. The outcome of stem cell transplantation is still limited due to many factors, especially their survival and their interaction with the microenvironment after transplantation. Molecular imaging is a challenging technique that has been used to overcome this limitation and is based on the concept of labeling cells with tractable, visible, and non-toxic materials to track the cells after transplantation. In this study, magnetic polymeric nanoparticles (MPNPs) were used to directly label Wharton's jelly-derived MSCs (WJ-MSCs). After labeling, the growth rate and the viability of the MSCs as well as the time of exposure were determined. The 3D images of WJ-MSCs labeled with MPNPs for 24 h were created using confocal microscopy. The results showed that, after incubation with fluorescent MPNPs for over 8 h, the growth rate and cell viability of the WJ-MSCs was similar to those of the control. Three-dimensional imaging revealed that the fluorescent MPNPs could infiltrate into the cells and spread into the cytoplasm, which suggests that the synthesized fluorescent MPNPs could possibly label MSCs for cell tracking study and be further developed for in vivo applications. PMID:25893425

  8. Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device

    PubMed Central

    Talasaz, AmirAli H.; Powell, Ashley A.; Huber, David E.; Berbee, James G.; Roh, Kyung-Ho; Yu, Wong; Xiao, Wenzhong; Davis, Mark M.; Pease, R. Fabian; Mindrinos, Michael N.; Jeffrey, Stefanie S.; Davis, Ronald W.

    2009-01-01

    The enumeration of rare circulating epithelial cells (CEpCs) in the peripheral blood of metastatic cancer patients has shown promise for improved cancer prognosis. Moving beyond enumeration, molecular analysis of CEpCs may provide candidate surrogate endpoints to diagnose, treat, and monitor malignancy directly from the blood samples. Thorough molecular analysis of CEpCs requires the development of new sample preparation methods that yield easily accessible and purified CEpCs for downstream biochemical assays. Here, we describe a new immunomagnetic cell separator, the MagSweeper, which gently enriches target cells and eliminates cells that are not bound to magnetic particles. The isolated cells are easily accessible and can be extracted individually based on their physical characteristics to deplete any cells nonspecifically bound to beads. We have shown that our device can process 9 mL of blood per hour and captures >50% of CEpCs as measured in spiking experiments. We have shown that the separation process does not perturb the gene expression of rare cells. To determine the efficiency of our platform in isolating CEpCs from patients, we have isolated CEpCs from all 47 tubes of 9-mL blood samples collected from 17 women with metastatic breast cancer. In contrast, we could not find any circulating epithelial cells in samples from 5 healthy donors. The isolated CEpCs are all stored individually for further molecular analysis. PMID:19234122

  9. Magnetic targeting of mechanosensors in bone cells for tissue engineering applications.

    PubMed

    Hughes, Steven; Dobson, Jon; El Haj, Alicia J

    2007-01-01

    Mechanical signalling plays a pivotal role in maintaining bone cell function and remodelling of the skeleton. Our previous work has highlighted the potential role of mechano-induction in tissue engineering applications. In particular, we have highlighted the potential for using magnetic particle techniques for tissue engineering applications. Previous studies have shown that manipulation of integrin attached magnetic particles leads to changes in intracellular calcium signalling within osteoblasts. However, due to the phenomenon of particle internalisation, previous studies have typically focused on short-term stimulation experiments performed within 1-2 h of particle attachment. For tissue engineering applications, bone tissue growth occurs over a period of 3-5 weeks. To date, no study has investigated the cellular responses elicited from osteoblasts over time following stimulation with internalised magnetic particles. Here, we demonstrate the long-term biocompatibility of 4.5 microm RGD-coated particles with osteoblasts up to 21 days in culture, and detail a time course of responses elicited from osteoblasts following mechanical stimulation with integrin attached magnetic particles (<2h post attachment) and internalised particles (>48h post attachment). Mechanical manipulation of both integrin attached and internalised particles were found to induce intracellular calcium signalling. It is concluded that magnetic particles offer a tool for applying controlled mechanical forces to osteoblasts, and can be used to stimulate intracellular calcium signalling over prolonged periods of time. Magnetic particle technology presents a potentially valuable tool for tissue engineering which permits the delivery of highly localised mechano-inductive forces directly to cells. PMID:17532323

  10. Labeling of stem cells with monocrystalline iron oxide for tracking and localization by magnetic resonance imaging

    PubMed Central

    Calzi, Sergio Li; Kent, David L.; Chang, Kyung-Hee; Padgett, Kyle R.; Afzal, Aqeela; Chandra, Saurav B.; Caballero, Sergio; English, Denis; Garlington, Wendy; Hiscott, Paul S.; Sheridan, Carl M.; Grant, Maria B.; Forder, John R.

    2013-01-01

    Precise localization of exogenously delivered stem cells is critical to our understanding of their reparative response. Our current inability to determine the exact location of small numbers of cells may hinder optimal development of these cells for clinical use. We describe a method using magnetic resonance imaging to track and localize small numbers of stem cells following transplantation. Endothelial progenitor cells (EPC) were labeled with monocrystalline iron oxide nanoparticles (MIONs) which neither adversely altered their viability nor their ability to migrate in vitro and allowed successful detection of limited numbers of these cells in muscle. MION-labeled stem cells were also injected into the vitreous cavity of mice undergoing the model of choroidal neovascularization, laser rupture of Bruch’s membrane. Migration of the MION-labeled cells from the injection site towards the laser burns was visualized by MRI. In conclusion, MION labeling of EPC provides a non-invasive means to define the location of small numbers of these cells. Localization of these cells following injection is critical to their optimization for therapy. PMID:19345699

  11. Labeling of stem cells with monocrystalline iron oxide for tracking and localization by magnetic resonance imaging.

    PubMed

    Li Calzi, Sergio; Kent, David L; Chang, Kyung-Hee; Padgett, Kyle R; Afzal, Aqeela; Chandra, Saurav B; Caballero, Sergio; English, Denis; Garlington, Wendy; Hiscott, Paul S; Sheridan, Carl M; Grant, Maria B; Forder, John R

    2009-06-01

    Precise localization of exogenously delivered stem cells is critical to our understanding of their reparative response. Our current inability to determine the exact location of small numbers of cells may hinder optimal development of these cells for clinical use. We describe a method using magnetic resonance imaging to track and localize small numbers of stem cells following transplantation. Endothelial progenitor cells (EPC) were labeled with monocrystalline iron oxide nanoparticles (MIONs) which neither adversely altered their viability nor their ability to migrate in vitro and allowed successful detection of limited numbers of these cells in muscle. MION-labeled stem cells were also injected into the vitreous cavity of mice undergoing the model of choroidal neovascularization, laser rupture of Bruch's membrane. Migration of the MION-labeled cells from the injection site towards the laser burns was visualized by MRI. In conclusion, MION labeling of EPC provides a non-invasive means to define the location of small numbers of these cells. Localization of these cells following injection is critical to their optimization for therapy. PMID:19345699

  12. Magnetic-field-assisted photothermal therapy of cancer cells using Fe-doped carbon nanoparticles

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Vardarajan, Vijaylakshmi; Koymen, Ali R.; Mohanty, Samarendra K.

    2012-01-01

    Photothermal therapy with assistance of nanoparticles offers a solution for the destruction of cancer cells without significant collateral damage to otherwise healthy cells. However, minimizing the required number of injected nanoparticles is a major challenge. Here, we introduce the use of magnetic carbon nanoparticles (MCNPs), localizing them in a desired region by applying an external magnetic-field, and irradiating the targeted cancer cells with a near-infrared laser beam. The MCNPs were prepared in benzene, using an electric plasma discharge, generated in the cavitation field of an ultrasonic horn. The CNPs were made ferromagnetic by use of Fe-electrodes to dope the CNPs, as confirmed by magnetometry. Transmission electron microscopy measurements showed the size distribution of these MCNPs to be in the range of 5 to 10 nm. For photothermal irradiation, a tunable continuous wave Ti: Sapphire laser beam was weakly focused on to the cell monolayer under an inverted fluorescence microscope. The response of different cell types to photothermal irradiation was investigated. Cell death in the presence of both MCNPs and laser beam was confirmed by morphological changes and propidium iodide fluorescence inclusion assay. The results of our study suggest that MCNP based photothermal therapy is a promising approach to remotely guide photothermal therapy.

  13. Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer.

    PubMed

    Yin, Perry T; Shah, Shreyas; Pasquale, Nicholas J; Garbuzenko, Olga B; Minko, Tamara; Lee, Ki-Bum

    2016-03-01

    Stem cell-based gene therapies, wherein stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential for cancer applications owing to their innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by our current inability to control when the therapeutic genes are actually turned on, thereby resulting in detrimental side effects. Here, we report the novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in adipose-derived mesenchymal stem cells (AD-MSCs). By combining the tumor tropism of the AD-MSCs with the spatiotemporal MCNP-based delivery and activation of TRAIL expression, this platform provides an attractive means with which to enhance our control over the activation of stem cell-based gene therapies. In particular, we found that these engineered AD-MSCs retained their innate ability to proliferate, differentiate, and, most importantly, home to tumors, making them ideal cellular carriers. Moreover, exposure of the engineered AD-MSCS to mild magnetic hyperthermia resulted in the selective expression of TRAIL from the engineered AD-MSCs and, as a result, induced significant ovarian cancer cell death in vitro and in vivo. PMID:26720500

  14. A smart fully integrated micromachined separator with soft magnetic micro-pillar arrays for cell isolation

    NASA Astrophysics Data System (ADS)

    Dong, Tao; Su, Qianhua; Yang, Zhaochu; Zhang, Yulong; Egeland, Eirik B.; Gu, Dan D.; Calabrese, Paolo; Kapiris, Matteo J.; Karlsen, Frank; Minh, Nhut T.; Wang, K.; Jakobsen, Henrik

    2010-11-01

    A smart fully integrated micromachined separator with soft magnetic micro-pillar arrays has been developed and demonstrated, which can merely employ one independent lab-on-chip to realize cell isolation. The simulation, design, microfabrication and test for the new electromagnetic micro separator were executed. The simulation results of the electromagnetic field in the separator show that special soft magnetic micro-pillar arrays can amplify and redistribute the electromagnetic field generated by the micro-coils. The separator can be equipped with a strong magnetic field to isolate the target cells with a considerably low input current. The micro separator was fabricated by micro-processing technology. An electroplating bath was hired to deposit NiCo/NiFe to fabricate the micro-pillar arrays. An experimental system was set up to verify the function of the micro separator by isolating the lymphocytes, in which the human whole blood mixed with Dynabeads® FlowComp Flexi and monoclonal antibody MHCD2704 was used as the sample. The results show that the electromagnetic micro separator with an extremely low input current can recognize and capture the target lymphocytes with a high efficiency, the separation ratio reaching more than 90% at a lower flow rate. For the electromagnetic micro separator, there is no external magnetizing field required, and there is no extra cooling system because there is less Joule heat generated due to the lower current. The magnetic separator is totally reusable, and it can be used to separate cells or proteins with common antigens.

  15. A Peltier cell calorimeter for the direct measurement of the isothermal entropy change in magnetic materials.

    PubMed

    Basso, Vittorio; Küpferling, Michaela; Sasso, Carlo P; Giudici, Laura

    2008-06-01

    We developed a calorimetric technique to measure the isothermal magnetocaloric entropy change. The method consists in the use of Peltier cells as heat flow sensor and heat pump at the same time. In this paper, we describe the setup, the constitutive equations of the Peltier cell as sensor and actuator, and the calibration procedure. The Peltier heat is used to keep the sample isothermal when magnetic field is changed. The temperature difference between the sample and the thermal reservoir is kept by a digital control within 5 mK for a magnetic field rate of 20 mT s(-1). The heat flux sensitivity around 1 microW. With this method, it is possible to measure the magnetocaloric effect in magnetic materials by tracing the curves of the exchanged entropy Delta(e)s as a function of the magnetic field H. The method proves to be, in particular, suitable to reveal the role of the entropy production Delta(i)s, which is connected with hysteresis. Measurement examples are shown for Gd, BaFe(12)O(19) ferrite, and Gd-Si-Ge. PMID:18601417

  16. Modular design for narrow scintillating cells with MRS photodiodes in strong magnetic field for ILC detector

    NASA Astrophysics Data System (ADS)

    Beznosko, D.; Blazey, G.; Dyshkant, A.; Rykalin, V.; Schellpffer, J.; Zutshi, V.

    2006-08-01

    The experimental results for the narrow scintillating elements with effective area about 20 cm 2 are reported. The elements were formed from the single piece of scintillator and were read out via wavelength shifting (WLS) fibers with the Metal/Resistor/Semiconductor (MRS) photodiodes on both ends of each fiber. The count rates were obtained using radioactive source 90Sr, with threshold at about three photoelectrons in each channel and quad coincidences (double coincidences between sensors on each fiber and double coincidences between two neighboring fibers). The formation of the cells from the piece of scintillator by using grooves is discussed, and their performances were tested using the radioactive source by measuring the photomutiplier current using the same WLS fiber. Because effective cell area can be readily enlarged or reduced, this module may be used as an active element for calorimeter or muon system for the design of the future electron-positron linear collider detector. Experimental verification of the performance of the MRS photodiode in a strong magnetic field of 9 T, and the impact a magnet quench at 9.5 T are reported. The measurement method used is described. The results confirm the expectations that the MRS photodiode is insensitive to a strong magnetic field and therefore applicable to calorimetry in the presence of magnetic field. The overall result is of high importance for large multi-channel systems.

  17. Generation of magnetized olfactory ensheathing cells for regenerative studies in the central and peripheral nervous tissue.

    PubMed

    Riggio, Cristina; Nocentini, Sara; Catalayud, Maria Pilar; Goya, Gerardo Fabian; Cuschieri, Alfred; Raffa, Vittoria; del Río, José Antonio

    2013-01-01

    As olfactory receptor axons grow from the peripheral to the central nervous system (CNS) aided by olfactory ensheathing cells (OECs), the transplantation of OECs has been suggested as a plausible therapy for spinal cord lesions. The problem with this hypothesis is that OECs do not represent a single homogeneous entity, but, instead, a functionally heterogeneous population that exhibits a variety of responses, including adhesion and repulsion during cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. In this paper, we report a system based on modified OECs carrying magnetic nanoparticles as a proof of concept experiment enabling specific studies aimed at exploring the potential of OECs in the treatment of spinal cord injuries. Our studies have confirmed that magnetized OECs (i) survive well without exhibiting stress-associated cellular responses; (ii) in vitro, their migration can be modulated by magnetic fields; and (iii) their transplantation in organotypic slices of spinal cord and peripheral nerve showed positive integration in the model. Altogether, these findings indicate the therapeutic potential of magnetized OECs for CNS injuries. PMID:23708092

  18. Magnetic Particle Imaging tracks the long-term fate of in vivo neural cell implants with high image contrast

    PubMed Central

    Zheng, Bo; Vazin, Tandis; Goodwill, Patrick W.; Conway, Anthony; Verma, Aradhana; Ulku Saritas, Emine; Schaffer, David; Conolly, Steven M.

    2015-01-01

    We demonstrate that Magnetic Particle Imaging (MPI) enables monitoring of cellular grafts with high contrast, sensitivity, and quantitativeness. MPI directly detects the intense magnetization of iron-oxide tracers using low-frequency magnetic fields. MPI is safe, noninvasive and offers superb sensitivity, with great promise for clinical translation and quantitative single-cell tracking. Here we report the first MPI cell tracking study, showing 200-cell detection in vitro and in vivo monitoring of human neural graft clearance over 87 days in rat brain. PMID:26358296

  19. The Effect of Iron Oxide Magnetic Nanoparticles on Smooth Muscle Cells

    NASA Astrophysics Data System (ADS)

    Zhang, Song; Chen, Xiangjian; Gu, Chunrong; Zhang, Yu; Xu, Jindan; Bian, Zhiping; Yang, Di; Gu, Ning

    2009-01-01

    Recently, magnetic nanoparticles of iron oxide (Fe3O4, γ-Fe2O3) have shown an increasing number of applications in the field of biomedicine, but some questions have been raised about the potential impact of these nanoparticles on the environment and human health. In this work, the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) with the same crystal structure, magnetic properties, and size distribution was designed, prepared, and characterized by transmission electronic microscopy, powder X-ray diffraction, zeta potential analyzer, vibrating sample magnetometer, and Fourier transform Infrared spectroscopy. Then, we have investigated the effect of the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) on smooth muscle cells (SMCs). Cellular uptake of nanoparticles by SMC displays the dose, the incubation time and surface property dependent patterns. Through the thin section TEM images, we observe that DMSA-Fe2O3 is incorporated into the lysosome of SMCs. The magnetic nanoparticles have no inflammation impact, but decrease the viability of SMCs. The other questions about metabolism and other impacts will be the next subject of further studies.

  20. Multifunctional magnetic-hollow gold nanospheres for bimodal cancer cell imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Bai, Ling-Yu; Yang, Xiao-Quan; An, Jie; Zhang, Lin; Zhao, Kai; Qin, Meng-Yao; Fang, Bi-Yun; Li, Cheng; Xuan, Yang; Zhang, Xiao-Shuai; Zhao, Yuan-Di; Ma, Zhi-Ya

    2015-08-01

    Multifunctional nanocomposites combining imaging and therapeutic functions have great potential for cancer diagnosis and therapy. In this work, we developed a novel theranostic agent based on hollow gold nanospheres (HGNs) and superparamagnetic iron oxide nanoparticles (SPIO). Taking advantage of the excellent magnetic properties of SPIO and strong near-infrared (NIR) absorption property of HGNs, such nanocomposites were applied to targeted magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) of cancer cells. In vitro results demonstrated they displayed significant contrast enhancement for T2-weighted MRI and strong PAI signal enhancement. Simultaneously, the nanocomposites exhibited a high photothermal effect under the irradiation of the near-infrared laser and can be used as efficient photothermal therapy (PTT) agents for selective killing of cancer cells. All these results indicated that such nanocomposites combined with MRI-PAI and PTT functionality can have great potential for effective cancer diagnosis and therapy.

  1. Multifunctional magnetic-hollow gold nanospheres for bimodal cancer cell imaging and photothermal therapy.

    PubMed

    Bai, Ling-Yu; Yang, Xiao-Quan; An, Jie; Zhang, Lin; Zhao, Kai; Qin, Meng-Yao; Fang, Bi-Yun; Li, Cheng; Xuan, Yang; Zhang, Xiao-Shuai; Zhao, Yuan-Di; Ma, Zhi-Ya

    2015-08-01

    Multifunctional nanocomposites combining imaging and therapeutic functions have great potential for cancer diagnosis and therapy. In this work, we developed a novel theranostic agent based on hollow gold nanospheres (HGNs) and superparamagnetic iron oxide nanoparticles (SPIO). Taking advantage of the excellent magnetic properties of SPIO and strong near-infrared (NIR) absorption property of HGNs, such nanocomposites were applied to targeted magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) of cancer cells. In vitro results demonstrated they displayed significant contrast enhancement for T2-weighted MRI and strong PAI signal enhancement. Simultaneously, the nanocomposites exhibited a high photothermal effect under the irradiation of the near-infrared laser and can be used as efficient photothermal therapy (PTT) agents for selective killing of cancer cells. All these results indicated that such nanocomposites combined with MRI-PAI and PTT functionality can have great potential for effective cancer diagnosis and therapy. PMID:26177713

  2. Functional magnetic resonance microscopy at single-cell resolution in Aplysia californica

    PubMed Central

    Radecki, Guillaume; Nargeot, Romuald; Jelescu, Ileana Ozana; Le Bihan, Denis; Ciobanu, Luisa

    2014-01-01

    In this work, we show the feasibility of performing functional MRI studies with single-cell resolution. At ultrahigh magnetic field, manganese-enhanced magnetic resonance microscopy allows the identification of most motor neurons in the buccal network of Aplysia at low, nontoxic Mn2+ concentrations. We establish that Mn2+ accumulates intracellularly on injection into the living Aplysia and that its concentration increases when the animals are presented with a sensory stimulus. We also show that we can distinguish between neuronal activities elicited by different types of stimuli. This method opens up a new avenue into probing the functional organization and plasticity of neuronal networks involved in goal-directed behaviors with single-cell resolution. PMID:24872449

  3. Estimation of localized current anomalies in polymer electrolyte fuel cells from magnetic flux density measurements

    NASA Astrophysics Data System (ADS)

    Nara, Takaaki; Koike, Masanori; Ando, Shigeru; Gotoh, Yuji; Izumi, Masaaki

    2016-05-01

    In this paper, we propose novel inversion methods to estimate defects or localized current anomalies in membrane electrode assemblies (MEAs) in polymer electrolyte fuel cells (PEFCs). One method is an imaging approach with L1-norm regularization that is suitable for estimation of focal anomalies compared to Tikhonov regularization. The second is a complex analysis based method in which multiple pointwise current anomalies can be identified directly and algebraically from the measured magnetic flux density.

  4. PDMAEMA-grafted core-shell-corona particles for nonviral gene delivery and magnetic cell separation.

    PubMed

    Majewski, Alexander P; Stahlschmidt, Ullrich; Jérôme, Valérie; Freitag, Ruth; Müller, Axel H E; Schmalz, Holger

    2013-09-01

    Monodisperse, magnetic nanoparticles as vectors for gene delivery were successfully synthesized via the grafting-from approach. First, oleic acid stabilized maghemite nanoparticles (γ-Fe2O3) were encapsulated with silica utilizing a reverse microemulsion process with simultaneous functionalization with initiating sites for atom transfer radical polymerization (ATRP). Polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA) from the core-shell nanoparticles led to core-shell-corona hybrid nanoparticles (γ-Fe2O3@silica@PDMAEMA) with an average grafting density of 91 polymer chains of DP(n) = 540 (PDMAEMA540) per particle. The permanent attachment of the arms was verified by field-flow fractionation. The dual-responsive behavior (pH and temperature) was confirmed by dynamic light scattering (DLS) and turbidity measurements. The interaction of the hybrid nanoparticles with plasmid DNA at various N/P ratios (polymer nitrogen/DNA phosphorus) was investigated by DLS and zeta-potential measurements, indicating that for N/P ≥ 7.5 the complexes bear a positive net charge and do not undergo secondary aggregation. The hybrids were tested as transfection agents under standard conditions in CHO-K1 and L929 cells, revealing transfection efficiencies >50% and low cytotoxicity at N/P ratios of 10 and 15, respectively. Due to the magnetic properties of the hybrid gene vector, it is possible to collect most of the cells that have incorporated a sufficient amount of magnetic material by using a magnetic activated cell sorting system (MACS). Afterward, cells were further cultivated and displayed a transfection efficiency of ca. 60% together with a high viability. PMID:23889326

  5. Motion and Magnetic Flux Changes of Coronal Bright Points Relative to Supergranular Cell Boundaries

    NASA Astrophysics Data System (ADS)

    Yousefzadeh, M.; Safari, H.; Attie, R.; Alipour, N.

    2016-01-01

    To calculate the magnetic flux and the horizontal movement of coronal bright points (CBPs) in relation to supergranular cell boundaries, the time series of the SDO/HMI visible-light continuum images and SDO/AIA EUV images for 13 February 2011 have been studied. The supergranular lanes were detected in HMI continuum images using the automatic supergranular cell recognition method. The automatic identification and tracking method was applied for detecting the CBPs in AIA 193 Å images. By applying the ball-tracking method on HMI continuum images, the underlying flow fields were determined. By using the velocity fields and the automatic supergranular cell recognition method, the lanes and boundaries were detected. The locations of CBPs were projected on the photospheric co-spatial and co-temporal images. We found that about 90 % of the locations of CBPs correspond to the lane of the supergranular cell boundaries (network CBPs or NCBPs) of which about 40 % of them appeared at junctions. The remaining 10 % appeared within the supergranular regions (internetwork CBPs or INCBPs). The horizontal velocities for NCBPs and INCBPs were about 1.6±0.1 km s^{-1} and 1.7±0.1 km s^{-1}, respectively. Using the magnetic field extrapolation, we were able to detect the bipoles underlying CBPs, and we studied their magnetic evolution. The orientation of CBPs observed in the 171, 193, and 211 Å images and the orientation of their magnetic bipoles are positively correlated. For out of 50 INCBPs, 54 % showed cancellation, 32 % emergence, and 12 % complex flux changes. Out of 90 NCBPs, 60 % presented cancellation, 20 % showed emergence, and 20 % showed complex flux changes.

  6. Model experiments for immunomagnetic elimination of leukemic cells from human bone marrow. Presentation of a novel magnetic separation system.

    PubMed

    Gruhn, B; Häfer, R; Müller, A; Andrä, W; Danan, H; Zintl, F

    1991-11-01

    Optimal conditions for removing leukemic cells from human bone marrow with monoclonal antibodies (mAb) and magnetic immunobeads were investigated. Monodisperse 3 microns polystyrene microspheres containing magnetite were coated with affinity-purified rabbit antimouse IgG at 4 degrees C, pH 9.6 for 18 h. SKW-3 cells (T-CLL cell line) were marked with the supravital DNA stain Hoechst 33342, seeded into normal human bone marrow, and then incubated with the mAb CD1, CD6, and CD8 at 4 degrees C for 30 min. In preliminary experiments REH cells (cALL cells) and mouse anti-REH cell antibodies were used to find the most favorable conditions for the binding of magnetic beads to tumor cells. Optimal formation of cell-bead rosettes was achieved by rotating beads and tumor cells together at room temperature at a concentration of 1 x 10(7) cells/ml, a bead: tumor cell ratio of 100:1 and an incubation time of one hour. The novel magnetic separation apparatus consists of three polystyrene chambers connected by silicone rubber tubing. The chambers contain four steel inserts each equipped with 32 nickel wires, which are magnetized by permanent magnets in such a way that the inhomogeneous high gradient magnetic field could be established within the cell suspension containing the cells to be depleted. The fluid flow was established by a peristaltic pump. At a flow rate of 1.5 ml/min and a field strength of 160 kA/m, no beads could be detected in the purged marrow. A cocktail of the three mAb was more effective than any single antibody in forming bead-cell rosettes. Two sequential purging cycles were superior to one. The marrow recovered was highly viable as assessed by trypan blue dye exclusion and by growth of CFU-GM. PMID:1786986

  7. Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays.

    PubMed

    Saliba, Antoine-Emmanuel; Saias, Laure; Psychari, Eleni; Minc, Nicolas; Simon, Damien; Bidard, François-Clément; Mathiot, Claire; Pierga, Jean-Yves; Fraisier, Vincent; Salamero, Jean; Saada, Véronique; Farace, Françoise; Vielh, Philippe; Malaquin, Laurent; Viovy, Jean-Louis

    2010-08-17

    We propose a unique method for cell sorting, "Ephesia," using columns of biofunctionalized superparamagnetic beads self-assembled in a microfluidic channel onto an array of magnetic traps prepared by microcontact printing. It combines the advantages of microfluidic cell sorting, notably the application of a well controlled, flow-activated interaction between cells and beads, and those of immunomagnetic sorting, notably the use of batch-prepared, well characterized antibody-bearing beads. On cell lines mixtures, we demonstrated a capture yield better than 94%, and the possibility to cultivate in situ the captured cells. A second series of experiments involved clinical samples--blood, pleural effusion, and fine needle aspirates--issued from healthy donors and patients with B-cell hematological malignant tumors (leukemia and lymphoma). The immunophenotype and morphology of B-lymphocytes were analyzed directly in the microfluidic chamber, and compared with conventional flow cytometry and visual cytology data, in a blind test. Immunophenotyping results using Ephesia were fully consistent with those obtained by flow cytometry. We obtained in situ high resolution confocal three-dimensional images of the cell nuclei, showing intranuclear details consistent with conventional cytological staining. Ephesia thus provides a powerful approach to cell capture and typing allowing fully automated high resolution and quantitative immunophenotyping and morphological analysis. It requires at least 10 times smaller sample volume and cell numbers than cytometry, potentially increasing the range of indications and the success rate of microbiopsy-based diagnosis, and reducing analysis time and cost. PMID:20679245

  8. Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays

    PubMed Central

    Saliba, Antoine-Emmanuel; Saias, Laure; Psychari, Eleni; Minc, Nicolas; Simon, Damien; Bidard, François-Clément; Mathiot, Claire; Pierga, Jean-Yves; Fraisier, Vincent; Salamero, Jean; Saada, Véronique; Farace, Françoise; Vielh, Philippe; Malaquin, Laurent; Viovy, Jean-Louis

    2010-01-01

    We propose a unique method for cell sorting, “Ephesia,” using columns of biofunctionalized superparamagnetic beads self-assembled in a microfluidic channel onto an array of magnetic traps prepared by microcontact printing. It combines the advantages of microfluidic cell sorting, notably the application of a well controlled, flow-activated interaction between cells and beads, and those of immunomagnetic sorting, notably the use of batch-prepared, well characterized antibody-bearing beads. On cell lines mixtures, we demonstrated a capture yield better than 94%, and the possibility to cultivate in situ the captured cells. A second series of experiments involved clinical samples—blood, pleural effusion, and fine needle aspirates— issued from healthy donors and patients with B-cell hematological malignant tumors (leukemia and lymphoma). The immunophenotype and morphology of B-lymphocytes were analyzed directly in the microfluidic chamber, and compared with conventional flow cytometry and visual cytology data, in a blind test. Immunophenotyping results using Ephesia were fully consistent with those obtained by flow cytometry. We obtained in situ high resolution confocal three-dimensional images of the cell nuclei, showing intranuclear details consistent with conventional cytological staining. Ephesia thus provides a powerful approach to cell capture and typing allowing fully automated high resolution and quantitative immunophenotyping and morphological analysis. It requires at least 10 times smaller sample volume and cell numbers than cytometry, potentially increasing the range of indications and the success rate of microbiopsy-based diagnosis, and reducing analysis time and cost. PMID:20679245

  9. Magnetic manipulation and spatial patterning of multi-cellular stem cell aggregates†

    PubMed Central

    Bratt-Leal, Andrés M.; Kepple, Kirsten L.; Carpenedo, Richard L.; Cooke, Marissa T.; McDevitt, Todd C.

    2015-01-01

    The controlled assembly and organization of multi-cellular systems to mimic complex tissue structures is critical to the engineering of tissues for therapeutic and diagnostic applications. Recent advances in micro-scale technologies to control multi-cellular aggregate formation typically require chemical modification of the interface between cells and materials and lack multi-scale flexibility. Here we demonstrate that simple physical entrapment of magnetic microparticles within the extracellular space of stem cells spheroids during initial formation enables scaffold-free immobilization, translocation and directed assembly of multi-cellular aggregates across multiple length and time scales, even under dynamic suspension culture conditions. The response of aggregates to externally applied magnetic fields was a direct function of microparticle incorporation, allowing for rapid and transient control of the extracellular environment as well as separation of heterogeneous populations. In addition, spatial patterning of heterogeneous spheroid populations as well as individual multi-cellular aggregates was readily achieved by imposing temporary magnetic fields. Overall, this approach provides novel routes to examine stem cell differentiation and tissue morphogenesis with applications that encompass the creation of new model systems for developmental biology, scaffold-free tissue engineering strategies and scalable bioprocessing technologies. PMID:22076329

  10. Serially Ordered Magnetization of Nanoclusters via Control of Various Transition Metal Dopants for the Multifractionation of Cells in Microfluidic Magnetophoresis Devices.

    PubMed

    Kang, Byunghoon; Cha, Bumjoon; Kim, Bongsoo; Han, Seungmin; Shin, Moo-Kwang; Jang, Eunji; Kim, Hyun-Ouk; Bae, Seo Ryung; Jeong, Unyong; Moon, Il; Son, Hye yeong; Huh, Yong-Min; Haam, Seungjoo

    2016-01-19

    A novel method (i.e., continuous magnetic cell separation in a microfluidic channel) is demonstrated to be capable of inducing multifractionation of mixed cell suspensions into multiple outlet fractions. Here, multicomponent cell separation is performed with three different distinguishable magnetic nanoclusters (MnFe2O4, Fe3O4, and CoFe2O4), which are tagged on A431 cells. Because of their mass magnetizations, which can be ideally altered by doping with magnetic atom compositions (Mn, Fe, and Co), the trajectories of cells with each magnetic nanocluster in a flow are shown to be distinct when dragged under the same external magnetic field; the rest of the magnetic characteristics of the nanoclusters are identically fixed. This proof of concept study, which utilizes the magnetization-controlled nanoclusters (NCs), suggests that precise and effective multifractionation is achievable with high-throughput and systematic accuracy for dynamic cell separation. PMID:26717968

  11. Magnetic resonance imaging of human dental pulp stem cells in vitro and in vivo.

    PubMed

    Struys, T; Ketkar-Atre, A; Gervois, P; Leten, C; Hilkens, P; Martens, W; Bronckaers, A; Dresselaers, T; Politis, C; Lambrichts, I; Himmelreich, U

    2013-01-01

    Recent advances in stem cell research have shown the promising nature of mesenchymal stem cells as plausible candidates for cell-based regenerative medicine. Many studies reported the use of human dental pulp stem cells (hDPSCs), which possess self-renewal capacity, high proliferation potential, and the ability to undergo multilineage differentiation. Together with this therapeutic approach, development of effective, noninvasive and nontoxic imaging techniques for visualizing and tracking the cells in vivo is crucial for the evaluation and improvement of stem cell therapy. Magnetic resonance imaging (MRI) is one of the most powerful diagnostic imaging techniques currently available for in vivo diagnosis and has been proposed as the most attractive modality for monitoring stem cell migration. The aim of this study was to investigate the labeling efficiency of hDPSCs using superparamagnetic iron oxide (SPIO) particles in order to allow visualization using in vitro and in vivo MRI without influencing cellular metabolism. MRI and transmission electron microscopy (TEM) showed optimal uptake with low SPIO concentrations of 15 µg/ml in combination with 0.75 µg/ml poly-L-lysine (PLL) resulting in more than 13 pg iron/cell and an in vitro detection limit of 50 labeled cells/µl. Very low SPIO concentrations in the culture medium resulted in extremely high labeling efficiency not reported before. For these conditions, tetrazolium salt assays showed no adverse effects on cell viability. Furthermore, in vivo MRI was performed to detect labeled hDPSCs transplanted into the brain of Rag 2-γ C immune-deficient mice. Transplanted cells did not show any signs of tumorgenecity or teratoma formation during the studied time course. We have reported on a labeling and imaging strategy to visualize human dental pulp stem cells in vivo using MRI. These data provide a solid base to allow cell tracking in future regenerative studies in the brain longitudinally. PMID:23050936

  12. A magnetic vehicle realized tumor cell-targeted radiotherapy using low-dose radiation.

    PubMed

    Chen, Hsiao-Ping; Tung, Fu-I; Chen, Ming-Hong; Liu, Tse-Ying

    2016-03-28

    Radiotherapy, a common cancer treatment, often adversely affects the surrounding healthy tissue and/or cells. Some tumor tissue-focused radiation therapies have been developed to lower radiation-induced lesion formation; however, achieving tumor cell-targeted radiotherapy (i.e., precisely focusing the radiation efficacy to tumor cells) remains a challenge. In the present study, we developed a novel tumor cell-targeted radiotherapy, named targeted sensitization-enhanced radiotherapy (TSER), that exploits tumor-specific folic acid-conjugated carboxymethyl lauryl chitosan/superparamagnetic iron oxide (FA-CLC/SPIO) micelles to effectively deliver chlorin e6 (Ce6, a sonosensitizer) to mitochondria of HeLa cells under magnetic guidance. For the in vitro tests, the sensitization of Ce6 induced by ultrasound, that could weaken the radiation resistant ability of tumor cells, occurred only in Ce6-internalizing tumor cells. Therefore, low-dose X-ray irradiation, that was not harmful to normal cells, could exert high tumor cell-specific killing ability. The ratio of viable normal cells to tumor cells was increased considerably, from 7.8 (at 24h) to 97.1 (at 72h), after they had received TSER treatment. Our data suggest that TSER treatment significantly weakens tumor cells, resulting in decreased viability in vitro as well as decreased in vivo subcutaneous tumor growth in nude mice, while the adverse effects were minimal. Taken together, TSER treatment appears to be an effective, clinically feasible tumor cell-targeted radiotherapy that can solve the problems of traditional radiotherapy and photodynamic therapy. PMID:26892750

  13. Magnetic fingerprints of rolling cells for quantitative flow cytometry in whole blood.

    PubMed

    Reisbeck, Mathias; Helou, Michael Johannes; Richter, Lukas; Kappes, Barbara; Friedrich, Oliver; Hayden, Oliver

    2016-01-01

    Over the past 50 years, flow cytometry has had a profound impact on preclinical and clinical applications requiring single cell function information for counting, sub-typing and quantification of epitope expression. At the same time, the workflow complexity and high costs of such optical systems still limit flow cytometry applications to specialized laboratories. Here, we present a quantitative magnetic flow cytometer that incorporates in situ magnetophoretic cell focusing for highly accurate and reproducible rolling of the cellular targets over giant magnetoresistance sensing elements. Time-of-flight analysis is used to unveil quantitative single cell information contained in its magnetic fingerprint. Furthermore, we used erythrocytes as a biological model to validate our methodology with respect to precise analysis of the hydrodynamic cell diameter, quantification of binding capacity of immunomagnetic labels, and discrimination of cell morphology. The extracted time-of-flight information should enable point-of-care quantitative flow cytometry in whole blood for clinical applications, such as immunology and primary hemostasis. PMID:27596736

  14. Magnetic fingerprints of rolling cells for quantitative flow cytometry in whole blood

    PubMed Central

    Reisbeck, Mathias; Helou, Michael Johannes; Richter, Lukas; Kappes, Barbara; Friedrich, Oliver; Hayden, Oliver

    2016-01-01

    Over the past 50 years, flow cytometry has had a profound impact on preclinical and clinical applications requiring single cell function information for counting, sub-typing and quantification of epitope expression. At the same time, the workflow complexity and high costs of such optical systems still limit flow cytometry applications to specialized laboratories. Here, we present a quantitative magnetic flow cytometer that incorporates in situ magnetophoretic cell focusing for highly accurate and reproducible rolling of the cellular targets over giant magnetoresistance sensing elements. Time-of-flight analysis is used to unveil quantitative single cell information contained in its magnetic fingerprint. Furthermore, we used erythrocytes as a biological model to validate our methodology with respect to precise analysis of the hydrodynamic cell diameter, quantification of binding capacity of immunomagnetic labels, and discrimination of cell morphology. The extracted time-of-flight information should enable point-of-care quantitative flow cytometry in whole blood for clinical applications, such as immunology and primary hemostasis. PMID:27596736

  15. The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells

    NASA Astrophysics Data System (ADS)

    Villanueva, Angeles; Cañete, Magdalena; Roca, Alejandro G; Calero, Macarena; Veintemillas-Verdaguer, Sabino; Serna, Carlos J; del Puerto Morales, María; Miranda, Rodolfo

    2009-03-01

    The internalization and biocompatibility of iron oxide nanoparticles surface functionalized with four differently charged carbohydrates have been tested in the human cervical carcinoma cell line (HeLa). Neutral, positive, and negative iron oxide nanoparticles were obtained by coating with dextran, aminodextran, heparin, and dimercaptosuccinic acid, resulting in colloidal suspensions stable at pH 7 with similar aggregate size. No intracellular uptake was detected in cells incubated with neutral charged nanoparticles, while negative particles showed different behaviour depending on the nature of the coating. Thus, dimercaptosuccinic-coated nanoparticles showed low cellular uptake with non-toxic effects, while heparin-coated particles showed cellular uptake only at high nanoparticle concentrations and induced abnormal mitotic spindle configurations. Finally, cationic magnetic nanoparticles show excellent properties for possible in vivo biomedical applications such as cell tracking by magnetic resonance imaging (MRI) and cancer treatment by hyperthermia: (i) they enter into cells with high effectiveness, and are localized in endosomes; (ii) they can be easily detected inside cells by optical microscopy, (iii) they are retained for relatively long periods of time, and (iv) they do not induce any cytotoxicity.

  16. Quantitatively Resolving Ligand–Receptor Bonds on Cell Surfaces Using Force-Induced Remnant Magnetization Spectroscopy

    PubMed Central

    2016-01-01

    Molecule-specific noncovalent bonding on cell surfaces is the foundation for cellular recognition and functioning. A major challenge in probing these bonds is to resolve the specific bonds quantitatively and efficiently from the nonspecific interactions in a complex environment. Using force-induced remnant magnetization spectroscopy (FIRMS), we were able to resolve quantitatively three different interactions for magnetic beads bearing anti-CD4 antibodies with CD4+ T cell surfaces based upon their binding forces. The binding force of the CD4 antibody–antigen bonds was determined to be 75 ± 3 pN. For comparison, the same bonds were also studied on a functionalized substrate surface, and the binding force was determined to be 90 ± 6 pN. The 15 pN difference revealed by high-resolution FIRMS illustrates the significant impact of the bonding environment. Because the force difference was unaffected by the cell number or the receptor density on the substrate, we attributed it to the possible conformational or local environmental differences of the CD4 antigens between the cell surface and substrate surface. Our results show that the high force resolution and detection efficiency afforded by FIRMS are valuable for studying protein–protein interactions on cell surfaces. PMID:27163031

  17. Magnetic Nanocomposite Scaffold-Induced Stimulation of Migration and Odontogenesis of Human Dental Pulp Cells through Integrin Signaling Pathways.

    PubMed

    Yun, Hyung-Mun; Lee, Eui-Suk; Kim, Mi-joo; Kim, Jung-Ju; Lee, Jung-Hwan; Lee, Hae-Hyoung; Park, Kyung-Ran; Yi, Jin-Kyu; Kim, Hae-Won; Kim, Eun-cheol

    2015-01-01

    Magnetism is an intriguing physical cue that can alter the behaviors of a broad range of cells. Nanocomposite scaffolds that exhibit magnetic properties are thus considered useful 3D matrix for culture of cells and their fate control in repair and regeneration processes. Here we produced magnetic nanocomposite scaffolds made of magnetite nanoparticles (MNPs) and polycaprolactone (PCL), and the effects of the scaffolds on the adhesion, growth, migration and odontogenic differentiation of human dental pulp cells (HDPCs) were investigated. Furthermore, the associated signaling pathways were examined in order to elucidate the molecular mechanisms in the cellular events. The magnetic scaffolds incorporated with MNPs at varying concentrations (up to 10%wt) supported cellular adhesion and multiplication over 2 weeks, showing good viability. The cellular constructs in the nanocomposite scaffolds played significant roles in the stimulation of adhesion, migration and odontogenesis of HDPCs. Cells were shown to adhere to substantially higher number when affected by the magnetic scaffolds. Cell migration tested by in vitro wound closure model was significantly enhanced by the magnetic scaffolds. Furthermore, odontogenic differentiation of HDPCs, as assessed by the alkaline phosphatase activity, mRNA expressions of odontogenic markers (DMP-1, DSPP,osteocalcin, and ostepontin), and alizarin red staining, was significantly stimulated by the magnetic scaffolds. Signal transduction was analyzed by RT-PCR, Western blotting, and confocal microscopy. The magnetic scaffolds upregulated the integrin subunits (α1, α2, β1 and β3) and activated downstream pathways, such as FAK, paxillin, p38, ERK MAPK, and NF-κB. The current study reports for the first time the significant impact of magnetic scaffolds in stimulating HDPC behaviors, including cell migration and odontogenesis, implying the potential usefulness of the magnetic scaffolds for dentin-pulp tissue engineering. PMID:26382272

  18. Magnetic Nanocomposite Scaffold-Induced Stimulation of Migration and Odontogenesis of Human Dental Pulp Cells through Integrin Signaling Pathways

    PubMed Central

    Kim, Mi-joo; Kim, Jung-Ju; Lee, Jung-Hwan; Lee, Hae-Hyoung; Park, Kyung-Ran; Yi, Jin-Kyu; Kim, Hae-Won; Kim, Eun-cheol

    2015-01-01

    Magnetism is an intriguing physical cue that can alter the behaviors of a broad range of cells. Nanocomposite scaffolds that exhibit magnetic properties are thus considered useful 3D matrix for culture of cells and their fate control in repair and regeneration processes. Here we produced magnetic nanocomposite scaffolds made of magnetite nanoparticles (MNPs) and polycaprolactone (PCL), and the effects of the scaffolds on the adhesion, growth, migration and odontogenic differentiation of human dental pulp cells (HDPCs) were investigated. Furthermore, the associated signaling pathways were examined in order to elucidate the molecular mechanisms in the cellular events. The magnetic scaffolds incorporated with MNPs at varying concentrations (up to 10%wt) supported cellular adhesion and multiplication over 2 weeks, showing good viability. The cellular constructs in the nanocomposite scaffolds played significant roles in the stimulation of adhesion, migration and odontogenesis of HDPCs. Cells were shown to adhere to substantially higher number when affected by the magnetic scaffolds. Cell migration tested by in vitro wound closure model was significantly enhanced by the magnetic scaffolds. Furthermore, odontogenic differentiation of HDPCs, as assessed by the alkaline phosphatase activity, mRNA expressions of odontogenic markers (DMP-1, DSPP,osteocalcin, and ostepontin), and alizarin red staining, was significantly stimulated by the magnetic scaffolds. Signal transduction was analyzed by RT-PCR, Western blotting, and confocal microscopy. The magnetic scaffolds upregulated the integrin subunits (α1, α2, β1 and β3) and activated downstream pathways, such as FAK, paxillin, p38, ERK MAPK, and NF-κB. The current study reports for the first time the significant impact of magnetic scaffolds in stimulating HDPC behaviors, including cell migration and odontogenesis, implying the potential usefulness of the magnetic scaffolds for dentin-pulp tissue engineering. PMID:26382272

  19. Dragging human mesenchymal stem cells with the aid of supramolecular assemblies of single-walled carbon nanotubes, molecular magnets, and peptides in a magnetic field.

    PubMed

    de Paula, Ana Cláudia C; Sáfar, Gustavo A M; Góes, Alfredo M; Bemquerer, Marcelo P; Ribeiro, Marcos A; Stumpf, Humberto O

    2015-01-01

    Human adipose-derived stem cells (hASCs) are an attractive cell source for therapeutic applicability in diverse fields for the repair and regeneration of damaged or malfunctioning tissues and organs. There is a growing number of cell therapies using stem cells due to their characteristics of modulation of immune system and reduction of acute rejection. So a challenge in stem cells therapy is the delivery of cells to the organ of interest, a specific site. The aim of this paper was to investigate the effects of a supramolecular assembly composed of single-walled carbon nanotubes (SWCNT), molecular magnets (lawsone-Co-phenanthroline), and a synthetic peptide (FWYANHYWFHNAFWYANHYWFHNA) in the hASCs cultures. The hASCs were isolated, characterized, expanded, and cultured with the SWCNT supramolecular assembly (SWCNT-MA). The assembly developed did not impair the cell characteristics, viability, or proliferation. During growth, the cells were strongly attached to the assembly and they could be dragged by an applied magnetic field of less than 0.3 T. These assemblies were narrower than their related allotropic forms, that is, multiwalled carbon nanotubes, and they could therefore be used to guide cells through thin blood capillaries within the human body. This strategy seems to be useful as noninvasive and nontoxic stem cells delivery/guidance and tracking during cell therapy. PMID:25688350

  20. Dragging Human Mesenchymal Stem Cells with the Aid of Supramolecular Assemblies of Single-Walled Carbon Nanotubes, Molecular Magnets, and Peptides in a Magnetic Field

    PubMed Central

    de Paula, Ana Cláudia C.; Sáfar, Gustavo A. M.; Góes, Alfredo M.; Bemquerer, Marcelo P.; Ribeiro, Marcos A.; Stumpf, Humberto O.

    2015-01-01

    Human adipose-derived stem cells (hASCs) are an attractive cell source for therapeutic applicability in diverse fields for the repair and regeneration of damaged or malfunctioning tissues and organs. There is a growing number of cell therapies using stem cells due to their characteristics of modulation of immune system and reduction of acute rejection. So a challenge in stem cells therapy is the delivery of cells to the organ of interest, a specific site. The aim of this paper was to investigate the effects of a supramolecular assembly composed of single-walled carbon nanotubes (SWCNT), molecular magnets (lawsone-Co-phenanthroline), and a synthetic peptide (FWYANHYWFHNAFWYANHYWFHNA) in the hASCs cultures. The hASCs were isolated, characterized, expanded, and cultured with the SWCNT supramolecular assembly (SWCNT-MA). The assembly developed did not impair the cell characteristics, viability, or proliferation. During growth, the cells were strongly attached to the assembly and they could be dragged by an applied magnetic field of less than 0.3 T. These assemblies were narrower than their related allotropic forms, that is, multiwalled carbon nanotubes, and they could therefore be used to guide cells through thin blood capillaries within the human body. This strategy seems to be useful as noninvasive and nontoxic stem cells delivery/guidance and tracking during cell therapy. PMID:25688350

  1. Improved high gradient magnetic separation for the positive selection of human blood mononuclear cells using ordered wire filters

    NASA Astrophysics Data System (ADS)

    Richards, A. J.; Thomas, T. E.; Roath, O. S.; Watson, J. H. C.; Smith, R. J. S.; Lansdorp, P. M.

    1993-04-01

    CD8 + lymphocytes, fresh and previously cryopreserved, from ficolled human peripheral blood have been enriched to 99% purity with 68% recovery. The CD8 + lymphocytes were labelled with colloidal, magnetisable, Dextran-Iron particles using Tetrameric Antibody complexes. The labelled cells were magnetically separated using High Gradient Magnetic Separation with novel, ordered filters.

  2. A magnetic switch for the control of cell death signalling in in vitro and in vivo systems

    NASA Astrophysics Data System (ADS)

    Cho, Mi Hyeon; Lee, Eun Jung; Son, Mina; Lee, Jae-Hyun; Yoo, Dongwon; Kim, Ji-Wook; Park, Seung Woo; Shin, Jeon-Soo; Cheon, Jinwoo

    2012-12-01

    The regulation of cellular activities in a controlled manner is one of the most challenging issues in fields ranging from cell biology to biomedicine. Nanoparticles have the potential of becoming useful tools for controlling cell signalling pathways in a space and time selective fashion. Here, we have developed magnetic nanoparticles that turn on apoptosis cell signalling by using a magnetic field in a remote and non-invasive manner. The magnetic switch consists of zinc-doped iron oxide magnetic nanoparticles (Zn0.4Fe2.6O4), conjugated with a targeting antibody for death receptor 4 (DR4) of DLD-1 colon cancer cells. The magnetic switch, in its On mode when a magnetic field is applied to aggregate magnetic nanoparticle-bound DR4s, promotes apoptosis signalling pathways. We have also demonstrated that the magnetic switch is operable at the micrometre scale and that it can be applied in an in vivo system where apoptotic morphological changes of zebrafish are successfully induced.

  3. Investigation of superparamagnetic (Fe3O4) nanoparticles and magnetic field exposures on CHO-K1 cell line

    NASA Astrophysics Data System (ADS)

    Coker, Zachary; Estlack, Larry; Hussain, Saber; Choi, Tae-Youl; Ibey, Bennett L.

    2016-03-01

    Rapid development in nanomaterial synthesis and functionalization has led to advanced studies in actuation and manipulation of cellular functions for biomedical applications. Often these actuation techniques employ externally applied magnetic fields to manipulate magnetic nanomaterials inside cell bodies in order to drive or trigger desired effects. While cellular interactions with low-frequency magnetic fields and nanoparticles have been extensively studied, the fundamental mechanisms behind these interactions remain poorly understood. Additionally, modern investigations on these concurrent exposure conditions have been limited in scope, and difficult to reproduce. This study presents an easily reproducible method of investigating the biological impact of concurrent magnetic field and nanoparticle exposure conditions using an in-vitro CHO-K1 cell line model, with the purpose of establishing grounds for in-depth fundamental studies of the mechanisms driving cellular-level interactions. Cells were cultured under various nanoparticle and magnetic field exposure conditions from 0 to 500 μg/ml nanoparticle concentrations, and DC, 50 Hz, or 100 Hz magnetic fields with 2.0 mT flux density. Cells were then observed by confocal fluorescence microscopy, and subject to biological assays to determine the effects of concurrent extreme-low frequency magnetic field and nanoparticle exposures on cellnanoparticle interactions, such as particle uptake and cell viability by MTT assay. Current results indicate little to no variation in effect on cell cultures based on magnetic field parameters alone; however, it is clear that deleterious synergistic effects of concurrent exposure conditions exist based on a significant decrease in cell viability when exposed to high concentrations of nanoparticles and concurrent magnetic field.

  4. A compact bellows-driven diamond anvil cell for high-pressure, low-temperature magnetic measurements

    NASA Astrophysics Data System (ADS)

    Feng, Yejun; Silevitch, D. M.; Rosenbaum, T. F.

    2014-03-01

    We present the design of an efficient bellows-controlled diamond anvil cell that is optimized for use inside the bores of high-field superconducting magnets in helium-3 cryostats, dilution refrigerators, and commercial physical property measurement systems. Design of this non-magnetic pressure cell focuses on in situ pressure tuning and measurement by means of a helium-filled bellows actuator and fiber-coupled ruby fluorescence spectroscopy, respectively. We demonstrate the utility of this pressure cell with ac susceptibility measurements of superconducting, ferromagnetic, and antiferromagnetic phase transitions to pressures exceeding 8 GPa. This cell provides an opportunity to probe charge and magnetic order continuously and with high resolution in the three-dimensional Magnetic Field-Pressure-Temperature parameter space.

  5. A compact bellows-driven diamond anvil cell for high-pressure, low-temperature magnetic measurements

    SciTech Connect

    Feng, Yejun; Silevitch, D. M.; Rosenbaum, T. F.

    2014-03-15

    We present the design of an efficient bellows-controlled diamond anvil cell that is optimized for use inside the bores of high-field superconducting magnets in helium-3 cryostats, dilution refrigerators, and commercial physical property measurement systems. Design of this non-magnetic pressure cell focuses on in situ pressure tuning and measurement by means of a helium-filled bellows actuator and fiber-coupled ruby fluorescence spectroscopy, respectively. We demonstrate the utility of this pressure cell with ac susceptibility measurements of superconducting, ferromagnetic, and antiferromagnetic phase transitions to pressures exceeding 8 GPa. This cell provides an opportunity to probe charge and magnetic order continuously and with high resolution in the three-dimensional Magnetic Field–Pressure–Temperature parameter space.

  6. Effects of maglev-spectrum magnetic field exposure on CEM T-lymphoblastoid human cell growth and differentiation

    SciTech Connect

    Groh, K.R.; Chubb, C.B.; Collart, F.R.; Huberman, E.

    1992-01-01

    Exposure to magnetic fields similar to those produced by maglev vehicles (combined ac and dc components) was studied for the ability to alter cell growth and chemically induced cellular differentiation processes in cultured human CEM Tlymphoblastoid leukemia cells. A series of continuous and intermittent magnetic field (MF) exposures for varying lengths of time were tested at intensities up to 7-fold greater than that produced by the German TR07 maglev vehicle. Phorbol 12-myristate 13-acetate or mycophenolic acid were used to induce cell differentiation. Changes in cell number, morphology, and fluorescence expression of antigenic markers of differentiation were monitored. The results indicated that maglev-spectrum magnetic field exposures up to 2 gauss had little effect on culture growth or chemically induced cellular differentiation when exposed to maglev-spectrum magnetic fields compared to chemically treated but MF-unexposed controls.

  7. Analytical description of 2D magnetic Freedericksz transition in a rectangular cell of a nematic liquid crystal.

    PubMed

    Burylov, S V; Zakhlevnykh, A N

    2016-06-01

    We study the Freedericksz transition induced by a magnetic field in a rectangular cell filled with a nematic liquid crystal. In the initial state the director of the nematic liquid crystal is uniformly aligned in the cross section plane of the cell with rigid anchoring of the director at cell walls: planar on the top and bottom walls, and homeotropic on the left and right ones. The magnetic field is directed perpendicular to the cell cross section plane. We consider two-dimensional (2D) orientational deformations of the nematic liquid crystal in the rectangular cell and determine the critical value of the Freedericksz transition field above which these orientational deformations occur. The 2D expression for the director alignment profile above the threshold of Freedericksz transition is analytically found and the profile shapes as functions of cell sizes, values of the Frank elastic constants of the nematic liquid crystal and the magnetic field are studied. PMID:27349554

  8. How Does Transcranial Magnetic Stimulation Influence Glial Cells in the Central Nervous System?

    PubMed Central

    Cullen, Carlie L.; Young, Kaylene M.

    2016-01-01

    Transcranial magnetic stimulation (TMS) is widely used in the clinic, and while it has a direct effect on neuronal excitability, the beneficial effects experienced by patients are likely to include the indirect activation of other cell types. Research conducted over the past two decades has made it increasingly clear that a population of non-neuronal cells, collectively known as glia, respond to and facilitate neuronal signaling. Each glial cell type has the ability to respond to electrical activity directly or indirectly, making them likely cellular effectors of TMS. TMS has been shown to enhance adult neural stem and progenitor cell (NSPC) proliferation, but the effect on cell survival and differentiation is less certain. Furthermore there is limited information regarding the response of astrocytes and microglia to TMS, and a complete paucity of data relating to the response of oligodendrocyte-lineage cells to this treatment. However, due to the critical and yet multifaceted role of glial cells in the central nervous system (CNS), the influence that TMS has on glial cells is certainly an area that warrants careful examination. PMID:27092058

  9. Relativistic magnetic reconnection in collisionless ion-electron plasmas explored with particle-in-cell simulations

    NASA Astrophysics Data System (ADS)

    Melzani, Mickaël; Walder, Rolf; Folini, Doris; Winisdoerffer, Christophe; Favre, Jean M.

    2014-10-01

    Magnetic reconnection is a leading mechanism for magnetic energy conversion and high-energy non-thermal particle production in a variety of high-energy astrophysical objects, including ones with relativistic ion-electron plasmas (e.g., microquasars or AGNs), a regime where first principle studies are scarce. We present 2D particle-in-cell (PIC) simulations of low β ion-electron plasmas under relativistic conditions, i.e., with inflow magnetic energy exceeding the plasma restmass energy. We identify outstanding properties: (i) For relativistic inflow magnetizations (here 10 ≤ σe ≤ 360), the reconnection outflows are dominated by thermal agitation instead of bulk kinetic energy. (ii) At high inflow electron magnetization (σe ≥ 80), the reconnection electric field is sustained more by bulk inertia than by thermal inertia. It challenges the thermal-inertia paradigm and its implications. (iii) The inflows feature sharp transitions at the entrance of the diffusion zones. These are not shocks but results from particle ballistic motions, all bouncing at the same location, provided that the thermal velocity in the inflow is far lower than the inflow E × B bulk velocity. (iv) Island centers are magnetically isolated from the rest of the flow and can present a density depletion at their center. (v) The reconnection rates are slightly higher than in non-relativistic studies. They are best normalized by the inflow relativistic Alfvén speed projected in the outflow direction, which then leads to rates in a close range (0.14-0.25), thus allowing for an easy estimation of the reconnection electric field.

  10. Generation of iPSCs as a Pooled Culture Using Magnetic Activated Cell Sorting of Newly Reprogrammed Cells

    PubMed Central

    Yang, Wenli; Liu, Ying; Slovik, Katherine J.; Wu, Joseph C.; Duncan, Stephen A.; Rader, Daniel J.; Morrisey, Edward E.

    2015-01-01

    Although significant advancement has been made in the induced pluripotent stem cell (iPSC) field, current methods for iPSC derivation are labor intensive and costly. These methods involve manual selection, expansion, and characterization of multiple clones for each reprogrammed cell sample and therefore significantly hampers the feasibility of studies where a large number of iPSCs need to be derived. To develop higher throughput iPSC reprogramming methods, we generated iPSCs as a pooled culture using rigorous cell surface pluripotent marker selection with TRA-1-60 or SSEA4 antibodies followed by Magnetic Activated Cell Sorting (MACS). We observed that pool-selected cells are similar or identical to clonally derived iPSC lines from the same donor by all criteria examined, including stable expression of endogenous pluripotency genes, normal karyotype, loss of exogenous reprogramming factors, and in vitro spontaneous and lineage directed differentiation potential. This strategy can be generalized for iPSC generation using both integrating and non-integrating reprogramming methods. Our studies provide an attractive alternative to clonal derivation of iPSCs using rigorously selected cell pools and is amenable to automation. PMID:26281015

  11. EGFR-Targeted Hybrid Plasmonic Magnetic Nanoparticles Synergistically Induce Autophagy and Apoptosis in Non-Small Cell Lung Cancer Cells

    PubMed Central

    Kuroda, Shinji; Scott, Ailing W.; Aaron, Jesse; Larson, Tim; Shanker, Manish; Correa, Arlene M.; Kondo, Seiji; Roth, Jack A.; Sokolov, Konstantin; Ramesh, Rajagopal

    2011-01-01

    Background The epidermal growth factor receptor (EGFR) is overexpressed in 80% of non-small cell lung cancer (NSCLC) and is associated with poor survival. In recent years, EGFR-targeted inhibitors have been tested in the clinic for NSCLC. Despite the emergence of novel therapeutics and their application in cancer therapy, the overall survival rate of lung cancer patients remains 15%. To develop more effective therapies for lung cancer we have combined the anti-EGFR antibody (Clone 225) as a molecular therapeutic with hybrid plasmonic magnetic nanoparticles (NP) and tested on non-small cell lung cancer (NSCLC) cells. Methodology/Principal Findings Cell viability was determined by trypan-blue assay. Cellular protein expression was determined by Western blotting. C225-NPs were detected by electron microscopy and confocal microscopy, and EGFR expression using immunocytochemistry. C225-NP exhibited a strong and selective antitumor effect on EGFR-expressing NSCLC cells by inhibiting EGFR-mediated signal transduction and induced autophagy and apoptosis in tumor cells. Optical images showed specificity of interactions between C225-NP and EGFR-expressing NSCLC cells. No binding of C225-NP was observed for EGFR-null NSCLC cells. C225-NP exhibited higher efficiency in induction of cell killing in comparison with the same amount of free C225 antibody in tumor cells with different levels of EGFR expression. Furthermore, in contrast to C225-NP, free C225 antibody did not induce autophagy in cells. However, the therapeutic efficacy of C225-NP gradually approached the level of free antibodies as the amount of C225 antibody conjugated per nanoparticle was decreased. Finally, attaching C225 to NP was important for producing the enhanced tumor cell killing as addition of mixture of free C225 and NP did not demonstrate the same degree of cell killing activity. Conclusions/Significance We demonstrated for the first time the molecular mechanism of C225-NP induced cytotoxic effects in

  12. Chlorotoxin bound magnetic nanovector tailored for cancer cell targeting, imaging, and siRNA delivery.

    PubMed

    Veiseh, Omid; Kievit, Forrest M; Fang, Chen; Mu, Ni; Jana, Soumen; Leung, Matthew C; Mok, Hyejung; Ellenbogen, Richard G; Park, James O; Zhang, Miqin

    2010-11-01

    Ribonucleic acid interference (RNAi) is a powerful molecular tool that has potential to revolutionize the treatment of cancer. One major challenge of applying this technology for clinical application is the lack of site-specific carriers that can effectively deliver short interfering RNA (siRNA) to cancer cells. Here we report the development and assessment of a cancer-cell specific magnetic nanovector construct for efficient siRNA delivery and non-invasive monitoring through magnetic resonance imaging (MRI). The base of the nanovector construct is comprised of a superparamagnetic iron oxide nanoparticle core coated with polyethylene glycol (PEG)-grafted chitosan, and polyethylenimine (PEI). The construct was then further functionalized with siRNA and a tumor-targeting peptide, chlorotoxin (CTX), to improve tumor specificity and potency. Flow cytometry, quantitative RT-PCR, and fluorescence microscopy analyses confirmed receptor-mediated cellular internalization of nanovectors and enhanced gene knockdown through targeted siRNA delivery. The ability of this nanovector construct to generate specific contrast enhancement of glioblastoma cells was demonstrated through MR imaging. These findings suggest that this CTX enabled nanoparticle carrier may be well suited for delivery of RNAi therapeutics to brain cancer cells. PMID:20673683

  13. The influence of particle size and static magnetic fields on the uptake of magnetic nanoparticles into three dimensional cell-seeded collagen gel cultures.

    PubMed

    Lewis, Emily E L; Child, Hannah W; Hursthouse, Andrew; Stirling, David; McCully, Mark; Paterson, David; Mullin, Margaret; Berry, Catherine C

    2015-08-01

    Over recent decades there has been and continues to be major advances in the imaging, diagnosis and potential treatment of medical conditions, by the use of magnetic nanoparticles. However, to date the majority of cell delivery studies employ a traditional 2D monolayer culture. This article aims to determine the ability of various sized magnetic nanoparticles to penetrate and travel through a cell seeded collagen gel model, in the presence or absence of a magnetic field. Three different sized (100, 200, and 500 nm) nanoparticles were employed in the study. The results showed cell viability was unaffected by the presence of nanoparticles over a 24-h test period. The initial uptake of the 100 nm nanoparticle into the collagen gel structure was superior compared to the larger sized nanoparticles under the influence of a magnetic field and incubated for 24 h. Interestingly, it was the 200 nm nanoparticles, which proved to penetrate the gel furthest, under the influence of a magnetic field, during the initial culture stage after 1-h incubation. PMID:25358626

  14. Stray magnetic field influence on the CPT resonance in a coated Rb vacuum cell

    NASA Astrophysics Data System (ADS)

    Taskova, E.; Alipieva, E.; Todorov, G.

    2016-03-01

    Interaction of a resonant laser beam with an atomic absorption medium creates population redistribution and interference between atomic levels. This anisotropy of the medium is experimentally observed as coherent population trapping (CPT) or electromagnetically induced transparency (EIT). Due to the small sub-natural width of the CPT and EIT resonances, they find wide applications in metrology, quantum optics, atom cooling. A non-compensated stray magnetic field (SMF) can change the shape and sign of the resonance or destroy it completely. In this work, we present an experimental and theoretical investigation of the influence of a stray magnetic field on the CPT resonances obtained on Zeeman sublevels of the D1 line of 87Rb in a paraffin-coated vacuum cell. The role is clarified of the polarization moments with different rank in creating the integral registered fluorescent signal in the presence of a stray magnetic field. It is shown that a transverse magnetic field plays an important role in changing the shape of the signal.

  15. The interaction of sterically stabilized magnetic nanoparticles with fresh human red blood cells

    PubMed Central

    Pham, Binh TT; Jain, Nirmesh; Kuchel, Philip W; Chapman, Bogdan E; Bickley, Stephanie A; Jones, Stephen K; Hawkett, Brian S

    2015-01-01

    Sterically stabilized superparamagnetic iron oxide nanoparticles (SPIONs) were incubated with fresh human erythrocytes (red blood cells [RBCs]) to explore their potential application as magnetic resonance imaging contrast agents. The chemical shift and linewidth of 133Cs+ resonances from inside and outside the RBCs in 133Cs nuclear magnetic resonance spectra were monitored as a function of time. Thus, we investigated whether SPIONs of two different core sizes and with three different types of polymeric stabilizers entered metabolically active RBCs, consuming glucose at 37°C. The SPIONs broadened the extracellular 133Cs+ nuclear magnetic resonance, and brought about a small change in its chemical shift to a higher frequency; while the intracellular resonance remained unchanged in both amplitude and chemical shift. This situation pertained over incubation times of up to 90 minutes. If the SPIONs had entered the RBCs, the intracellular resonance would have become broader and possibly even shifted. Therefore, we concluded that our SPIONs did not enter the RBCs. In addition, the T2 relaxivity of the small and large particles was 368 and 953 mM−1 s−1, respectively (three and nine times that of the most effective commercially available samples). This suggests that these new SPIONs will provide a superior performance to any others reported thus far as magnetic resonance imaging contrast agents. PMID:26604741

  16. High resolution in-operando microimaging of solar cells with pulsed electrically-detected magnetic resonance.

    PubMed

    Katz, Itai; Fehr, Matthias; Schnegg, Alexander; Lips, Klaus; Blank, Aharon

    2015-02-01

    The in-operando detection and high resolution spatial imaging of paramagnetic defects, impurities, and states becomes increasingly important for understanding loss mechanisms in solid-state electronic devices. Electron spin resonance (ESR), commonly employed for observing these species, cannot meet this challenge since it suffers from limited sensitivity and spatial resolution. An alternative and much more sensitive method, called electrically-detected magnetic resonance (EDMR), detects the species through their magnetic fingerprint, which can be traced in the device's electrical current. However, until now it could not obtain high resolution images in operating electronic devices. In this work, the first spatially-resolved electrically-detected magnetic resonance images (EDMRI) of paramagnetic states in an operating real-world electronic device are provided. The presented method is based on a novel microwave pulse sequence allowing for the coherent electrical detection of spin echoes in combination with powerful pulsed magnetic-field gradients. The applicability of the method is demonstrated on a device-grade 1-μm-thick amorphous silicon (a-Si:H) solar cell and an identical device that was degraded locally by an electron beam. The degraded areas with increased concentrations of paramagnetic defects lead to a local increase in recombination that is mapped by EDMRI with ∼20-μm-scale pixel resolution. The novel approach presented here can be widely used in the nondestructive in-operando three-dimensional characterization of solid-state electronic devices with a resolution potential of less than 100 nm. PMID:25557860

  17. Hybrid wood materials with magnetic anisotropy dictated by the hierarchical cell structure.

    PubMed

    Merk, Vivian; Chanana, Munish; Gierlinger, Notburga; Hirt, Ann M; Burgert, Ingo

    2014-06-25

    Anisotropic and hierarchical structures are bound in nature and highly desired in engineered materials, due to their outstanding functions and performance. Mimicking such natural features with synthetic materials and methods has been a highly active area of research in the last decades. Unlike these methods, we use the native biomaterial wood, with its intrinsic anisotropy and hierarchy as a directional scaffold for the incorporation of magnetic nanoparticles inside the wood material. Nanocrystalline iron oxide particles were synthesized in situ via coprecipitation of ferric and ferrous ions within the interconnected pore network of bulk wood. Imaging with low-vacuum and cryogenic electron microscopy as well as spectral Raman mapping revealed layered nanosize particles firmly attached to the inner surface of the wood cell walls. The mineralogy of iron oxide was identified by XRD powder diffraction and Raman spectroscopy as a mixture of the spinel phases magnetite and maghemite. The intrinsic structural architecture of native wood entails a three-dimensional assembly of the colloidal iron oxide which results in direction-dependent magnetic features of the wood-mineral hybrid material. This superinduced magnetic anisotropy, as quantified by direction-dependent magnetic hysteresis loops and low-field susceptibility tensors, allows for directional lift, drag, alignment, (re)orientation, and actuation, and opens up novel applications of the natural resource wood. PMID:24873330

  18. High resolution in-operando microimaging of solar cells with pulsed electrically-detected magnetic resonance

    NASA Astrophysics Data System (ADS)

    Katz, Itai; Fehr, Matthias; Schnegg, Alexander; Lips, Klaus; Blank, Aharon

    2015-02-01

    The in-operando detection and high resolution spatial imaging of paramagnetic defects, impurities, and states becomes increasingly important for understanding loss mechanisms in solid-state electronic devices. Electron spin resonance (ESR), commonly employed for observing these species, cannot meet this challenge since it suffers from limited sensitivity and spatial resolution. An alternative and much more sensitive method, called electrically-detected magnetic resonance (EDMR), detects the species through their magnetic fingerprint, which can be traced in the device's electrical current. However, until now it could not obtain high resolution images in operating electronic devices. In this work, the first spatially-resolved electrically-detected magnetic resonance images (EDMRI) of paramagnetic states in an operating real-world electronic device are provided. The presented method is based on a novel microwave pulse sequence allowing for the coherent electrical detection of spin echoes in combination with powerful pulsed magnetic-field gradients. The applicability of the method is demonstrated on a device-grade 1-μm-thick amorphous silicon (a-Si:H) solar cell and an identical device that was degraded locally by an electron beam. The degraded areas with increased concentrations of paramagnetic defects lead to a local increase in recombination that is mapped by EDMRI with ∼20-μm-scale pixel resolution. The novel approach presented here can be widely used in the nondestructive in-operando three-dimensional characterization of solid-state electronic devices with a resolution potential of less than 100 nm.

  19. Red blood cell membrane camouflaged magnetic nanoclusters for imaging-guided photothermal therapy.

    PubMed

    Ren, Xiaoqing; Zheng, Rui; Fang, Xiaoling; Wang, Xiaofei; Zhang, Xiaoyan; Yang, Wuli; Sha, Xianyi

    2016-06-01

    Along with intrinsic magnetic resonance imaging (MRI) advantages, iron oxide nanomaterials capable of photothermal conversion have been reported very recently and have again raised great interest in their designs among biomedical researchers. However, like other inorganic nanomaterials, high macrophage uptake, short blood retention time and unfavorable biodistributions have strongly hampered their applications in vivo. To solve these problems, a rational design of red blood cell (RBC) membrane camouflaged iron oxide magnetic clusters (MNC@RBCs) is presented in this paper. Our data show that by simply introducing an "ultra-stealth" biomimetic coating to iron oxide magnetic nanoclusters (MNCs), MNC@RBCs maintain the imaging and photothermal functionalities inherited from MNCs cores while achieving much lower nonspecific macrophage uptake and dramatically altered fate in vivo. MNC@RBCs with superior prolonged blood retention time, preferred high tumor accumulation and relatively lowered liver biodistribution are demonstrated when injected intravenously in mice, leading to greatly enhanced photothermal therapeutic efficacy by a single treatment without further magnetic force manipulation. Our study illustrates a well prepared integration of MNCs and RBCs, exploiting advantages of both functionalities within a single unit and suggests a promising future for iron-based nanomaterials application in vivo. PMID:27031929

  20. Effects of exposure to gradient magnetic fields emitted by nuclear magnetic resonance devices on clonogenic potential and proliferation of human hematopoietic stem cells.

    PubMed

    Iachininoto, Maria Grazia; Camisa, Vincenzo; Leone, Lucia; Pinto, Rosanna; Lopresto, Vanni; Merla, Caterina; Giorda, Ezio; Carsetti, Rita; Zaffina, Salvatore; Podda, Maria Vittoria; Teofili, Luciana; Grassi, Claudio

    2016-05-01

    This study investigates effects of gradient magnetic fields (GMFs) emitted by magnetic resonance imaging (MRI) devices on hematopoietic stem cells. Field measurements were performed to assess exposure to GMFs of staff working at 1.5 T and 3 T MRI units. Then an exposure system reproducing measured signals was realized to expose in vitro CD34+ cells to GMFs (1.5 T-protocol and 3 T-protocol). CD34+ cells were obtained by Fluorescence Activated Cell Sorting from six blood donors and three MRI-exposed workers. Blood donor CD34+ cells were exposed in vitro for 72 h to 1.5 T or 3 T-protocol and to sham procedure. Cells were then cultured and evaluated in colony forming unit (CFU)-assay up to 4 weeks after exposure. Results showed that in vitro GMF exposure did not affect cell proliferation but instead induced expansion of erythroid and monocytes progenitors soon after exposure and for the subsequent 3 weeks. No decrease of other clonogenic cell output (i.e., CFU-granulocyte/erythroid/macrophage/megakaryocyte and CFU-granulocyte/macrophage) was noticed, nor exposed CD34+ cells underwent the premature exhaustion of their clonogenic potential compared to sham-exposed controls. On the other hand, pilot experiments showed that CD34+ cells exposed in vivo to GMFs (i.e., samples from MRI workers) behaved in culture similarly to sham-exposed CD34+ cells, suggesting that other cells and/or microenvironment factors might prevent GMF effects on hematopoietic stem cells in vivo. Accordingly, GMFs did not affect the clonogenic potential of umbilical cord blood CD34+ cells exposed in vitro together with the whole mononuclear cell fraction. PMID:26992028

  1. Magnetic

    NASA Astrophysics Data System (ADS)

    Aboud, Essam; El-Masry, Nabil; Qaddah, Atef; Alqahtani, Faisal; Moufti, Mohammed R. H.

    2015-06-01

    The Rahat volcanic field represents one of the widely distributed Cenozoic volcanic fields across the western regions of the Arabian Peninsula. Its human significance stems from the fact that its northern fringes, where the historical eruption of 1256 A.D. took place, are very close to the holy city of Al-Madinah Al-Monawarah. In the present work, we analyzed aeromagnetic data from the northern part of Rahat volcanic field as well as carried out a ground gravity survey. A joint interpretation and inversion of gravity and magnetic data were used to estimate the thickness of the lava flows, delineate the subsurface structures of the study area, and estimate the depth to basement using various geophysical methods, such as Tilt Derivative, Euler Deconvolution and 2D modeling inversion. Results indicated that the thickness of the lava flows in the study area ranges between 100 m (above Sea Level) at the eastern and western boundaries of Rahat Volcanic field and getting deeper at the middle as 300-500 m. It also showed that, major structural trend is in the NW direction (Red Sea trend) with some minor trends in EW direction.

  2. High throughput system for magnetic manipulation of cells, polymers, and biomaterials.

    PubMed

    Spero, Richard Chasen; Vicci, Leandra; Cribb, Jeremy; Bober, David; Swaminathan, Vinay; O'Brien, E Timothy; Rogers, Stephen L; Superfine, R

    2008-08-01

    In the past decade, high throughput screening (HTS) has changed the way biochemical assays are performed, but manipulation and mechanical measurement of micro- and nanoscale systems have not benefited from this trend. Techniques using microbeads (particles approximately 0.1-10 mum) show promise for enabling high throughput mechanical measurements of microscopic systems. We demonstrate instrumentation to magnetically drive microbeads in a biocompatible, multiwell magnetic force system. It is based on commercial HTS standards and is scalable to 96 wells. Cells can be cultured in this magnetic high throughput system (MHTS). The MHTS can apply independently controlled forces to 16 specimen wells. Force calibrations demonstrate forces in excess of 1 nN, predicted force saturation as a function of pole material, and powerlaw dependence of F approximately r(-2.7+/-0.1). We employ this system to measure the stiffness of SR2+ Drosophila cells. MHTS technology is a key step toward a high throughput screening system for micro- and nanoscale biophysical experiments. PMID:19044357

  3. High throughput system for magnetic manipulation of cells, polymers, and biomaterials

    PubMed Central

    Spero, Richard Chasen; Vicci, Leandra; Cribb, Jeremy; Bober, David; Swaminathan, Vinay; O’Brien, E. Timothy; Rogers, Stephen L.; Superfine, R.

    2008-01-01

    In the past decade, high throughput screening (HTS) has changed the way biochemical assays are performed, but manipulation and mechanical measurement of micro- and nanoscale systems have not benefited from this trend. Techniques using microbeads (particles ∼0.1–10 μm) show promise for enabling high throughput mechanical measurements of microscopic systems. We demonstrate instrumentation to magnetically drive microbeads in a biocompatible, multiwell magnetic force system. It is based on commercial HTS standards and is scalable to 96 wells. Cells can be cultured in this magnetic high throughput system (MHTS). The MHTS can apply independently controlled forces to 16 specimen wells. Force calibrations demonstrate forces in excess of 1 nN, predicted force saturation as a function of pole material, and powerlaw dependence of F∼r−2.7±0.1. We employ this system to measure the stiffness of SR2+ Drosophila cells. MHTS technology is a key step toward a high throughput screening system for micro- and nanoscale biophysical experiments. PMID:19044357

  4. Label-free magnetic resonance imaging to locate live cells in three-dimensional porous scaffolds

    PubMed Central

    Abarrategi, A.; Fernandez-Valle, M. E.; Desmet, T.; Castejón, D.; Civantos, A.; Moreno-Vicente, C.; Ramos, V.; Sanz-Casado, J. V.; Martínez-Vázquez, F. J.; Dubruel, P.; Miranda, P.; López-Lacomba, J. L.

    2012-01-01

    Porous scaffolds are widely tested materials used for various purposes in tissue engineering. A critical feature of a porous scaffold is its ability to allow cell migration and growth on its inner surface. Up to now, there has not been a method to locate live cells deep inside a material, or in an entire structure, using real-time imaging and a non-destructive technique. Herein, we seek to demonstrate the feasibility of the magnetic resonance imaging (MRI) technique as a method to detect and locate in vitro non-labelled live cells in an entire porous material. Our results show that the use of optimized MRI parameters (4.7 T; repetition time = 3000 ms; echo time = 20 ms; resolution 39 × 39 µm) makes it possible to obtain images of the scaffold structure and to locate live non-labelled cells in the entire material, with a signal intensity higher than that obtained in the culture medium. In the current study, cells are visualized and located in different kinds of porous scaffolds. Moreover, further development of this MRI method might be useful in several three-dimensional biomaterial tests such as cell distribution studies, routine qualitative testing methods and in situ monitoring of cells inside scaffolds. PMID:22442095

  5. GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells

    PubMed Central

    Wang, Ling; An, Yanli; Yuan, Chenyan; Zhang, Hao; Liang, Chen; Ding, Fengan; Gao, Qi; Zhang, Dongsheng

    2015-01-01

    Background Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Methods Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. Results When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. Conclusion The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate

  6. Enrichment of live unlabelled cardiomyocytes from heterogeneous cell populations using manipulation of cell settling velocity by magnetic field

    PubMed Central

    Sofla, Aarash; Cirkovic, Bojana; Hsieh, Anne; Miklas, Jason W.; Filipovic, Nenad; Radisic, Milica

    2013-01-01

    The majority of available cardiomyocyte markers are intercellular proteins, limiting our ability to enrich live cardiomyocytes from heterogeneous cell preparations in the absence of genetic labeling. Here, we describe enrichment of live cardiomyocytes from the hearts of adult mice in a label-free microfluidic approach. The separation device consisted of a vertical column (15 mm long, 700 μm diameter), placed between permanent magnets resulting in a field strength of 1.23 T. To concentrate the field at the column wall, the column was wrapped with 69 μm diameter nickel wire. Before passing the cells through the column, the cardiomyocytes in the cell suspension had been rendered paramagnetic by treatment of the adult mouse heart cell preparation with sodium nitrite (2.5 mM) for 20 min on ice. The cell suspension was loaded into the vertical column from the top and upon settling, the non-myocytes were removed by the upward flow from the column. The cardiomyocytes were then collected from the column by applying a higher flow rate (144 μl/min). We found that by applying a separation flow rate of 4.2 μl/min in the first step, we can enrich live adult cardiomyocytes to 93% ± 2% in a label-free manner. The cardiomyocytes maintained viability immediately after separation and upon 24 h in culture. PMID:24404002

  7. Magnetic particle spectroscopy allows precise quantification of nanoparticles after passage through human brain microvascular endothelial cells.

    PubMed

    Gräfe, C; Slabu, I; Wiekhorst, F; Bergemann, C; von Eggeling, F; Hochhaus, A; Trahms, L; Clement, J H

    2016-06-01

    Crossing the blood-brain barrier is an urgent requirement for the treatment of brain disorders. Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising tool as carriers for therapeutics because of their physical properties, biocompatibility, and their biodegradability. In order to investigate the interaction of nanoparticles with endothelial cell layers in detail, in vitro systems are of great importance. Human brain microvascular endothelial cells are a well-suited blood-brain barrier model. Apart from generating optimal conditions for the barrier-forming cell units, the accurate detection and quantification of SPIONs is a major challenge. For that purpose we use magnetic particle spectroscopy to sensitively and directly quantify the SPION-specific iron content. We could show that SPION concentration depends on incubation time, nanoparticle concentration and location. This model system allows for further investigations on particle uptake and transport at cellular barriers with regard to parameters including particles' shape, material, size, and coating. PMID:27163489

  8. Magnetic particle spectroscopy allows precise quantification of nanoparticles after passage through human brain microvascular endothelial cells

    NASA Astrophysics Data System (ADS)

    Gräfe, C.; Slabu, I.; Wiekhorst, F.; Bergemann, C.; von Eggeling, F.; Hochhaus, A.; Trahms, L.; Clement, J. H.

    2016-06-01

    Crossing the blood–brain barrier is an urgent requirement for the treatment of brain disorders. Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising tool as carriers for therapeutics because of their physical properties, biocompatibility, and their biodegradability. In order to investigate the interaction of nanoparticles with endothelial cell layers in detail, in vitro systems are of great importance. Human brain microvascular endothelial cells are a well-suited blood–brain barrier model. Apart from generating optimal conditions for the barrier-forming cell units, the accurate detection and quantification of SPIONs is a major challenge. For that purpose we use magnetic particle spectroscopy to sensitively and directly quantify the SPION-specific iron content. We could show that SPION concentration depends on incubation time, nanoparticle concentration and location. This model system allows for further investigations on particle uptake and transport at cellular barriers with regard to parameters including particles’ shape, material, size, and coating.

  9. Magnetic measurements at pressures above 10 GPa in a miniature ceramic anvil cell for a superconducting quantum interference device magnetometer

    PubMed Central

    Tateiwa, Naoyuki; Haga, Yoshinori; Matsuda, Tatsuma D.; Fisk, Zachary

    2012-01-01

    A miniature ceramic anvil high pressure cell (mCAC) was earlier designed by us for magnetic measurements at pressures up to 7.6 GPa in a commercial superconducting quantum interference magnetometer [N. Tateiwa , Rev. Sci. Instrum. 82, 053906 (2011)]10.1063/1.3590745. Here, we describe methods to generate pressures above 10 GPa in the mCAC. The efficiency of the pressure generation is sharply improved when the Cu-Be gasket is sufficiently preindented. The maximum pressure for the 0.6 mm culet anvils is 12.6 GPa when the Cu-Be gasket is preindented from the initial thickness of 300–60 μm. The 0.5 mm culet anvils were also tested with a rhenium gasket. The maximum pressure attainable in the mCAC is about 13 GPa. The present cell was used to study YbCu2Si2 which shows a pressure induced transition from the non-magnetic to magnetic phases at 8 GPa. We confirm a ferromagnetic transition from the dc magnetization measurement at high pressure. The mCAC can detect the ferromagnetic ordered state whose spontaneous magnetic moment is smaller than 1 μB per unit cell. The high sensitivity for magnetic measurements in the mCAC may result from the simplicity of cell structure. The present study shows the availability of the mCAC for precise magnetic measurements at pressures above 10 GPa. PMID:22667632

  10. A hybrid magnetic/complementary metal oxide semiconductor three-context memory bit cell for non-volatile circuit design

    SciTech Connect

    Jovanović, B. E-mail: lionel.torres@lirmm.fr; Brum, R. M.; Torres, L.

    2014-04-07

    After decades of continued scaling to the beat of Moore's law, it now appears that conventional silicon based devices are approaching their physical limits. In today's deep-submicron nodes, a number of short-channel and quantum effects are emerging that affect the manufacturing process, as well as, the functionality of the microelectronic systems-on-chip. Spintronics devices that exploit both the intrinsic spin of the electron and its associated magnetic moment, in addition to its fundamental electronic charge, are promising solutions to circumvent these scaling threats. Being compatible with the CMOS technology, such devices offer a promising synergy of radiation immunity, infinite endurance, non-volatility, increased density, etc. In this paper, we present a hybrid (magnetic/CMOS) cell that is able to store and process data both electrically and magnetically. The cell is based on perpendicular spin-transfer torque magnetic tunnel junctions (STT-MTJs) and is suitable for use in magnetic random access memories and reprogrammable computing (non-volatile registers, processor cache memories, magnetic field-programmable gate arrays, etc). To demonstrate the potential our hybrid cell, we physically implemented a small hybrid memory block using 45 nm × 45 nm round MTJs for the magnetic part and 28 nm fully depleted silicon on insulator (FD-SOI) technology for the CMOS part. We also report the cells measured performances in terms of area, robustness, read/write speed and energy consumption.

  11. A hybrid magnetic/complementary metal oxide semiconductor three-context memory bit cell for non-volatile circuit design

    NASA Astrophysics Data System (ADS)

    Jovanović, B.; Brum, R. M.; Torres, L.

    2014-04-01

    After decades of continued scaling to the beat of Moore's law, it now appears that conventional silicon based devices are approaching their physical limits. In today's deep-submicron nodes, a number of short-channel and quantum effects are emerging that affect the manufacturing process, as well as, the functionality of the microelectronic systems-on-chip. Spintronics devices that exploit both the intrinsic spin of the electron and its associated magnetic moment, in addition to its fundamental electronic charge, are promising solutions to circumvent these scaling threats. Being compatible with the CMOS technology, such devices offer a promising synergy of radiation immunity, infinite endurance, non-volatility, increased density, etc. In this paper, we present a hybrid (magnetic/CMOS) cell that is able to store and process data both electrically and magnetically. The cell is based on perpendicular spin-transfer torque magnetic tunnel junctions (STT-MTJs) and is suitable for use in magnetic random access memories and reprogrammable computing (non-volatile registers, processor cache memories, magnetic field-programmable gate arrays, etc). To demonstrate the potential our hybrid cell, we physically implemented a small hybrid memory block using 45 nm × 45 nm round MTJs for the magnetic part and 28 nm fully depleted silicon on insulator (FD-SOI) technology for the CMOS part. We also report the cells measured performances in terms of area, robustness, read/write speed and energy consumption.

  12. Use of a SQUID array to detect T-cells with magnetic nanoparticles in determining transplant rejection

    NASA Astrophysics Data System (ADS)

    Flynn, Edward R.; Bryant, H. C.; Bergemann, Christian; Larson, Richard S.; Lovato, Debbie; Sergatskov, Dmitri A.

    2007-04-01

    Acute rejection in organ transplant is signaled by the proliferation of T-cells that target and kill the donor cells requiring painful biopsies to detect rejection onset. An alternative non-invasive technique is proposed using a multi-channel superconducting quantum interference device (SQUID) magnetometer to detect T-cell lymphocytes in the transplanted organ labeled with magnetic nanoparticles conjugated to antibodies specifically attached to lymphocytic ligand receptors. After a magnetic field pulse, the T-cells produce a decaying magnetic signal with a characteristic time of the order of a second. The extreme sensitivity of this technique, 10 5 cells, can provide early warning of impending transplant rejection and monitor immune-suppressive chemotherapy.

  13. Long-Term MRI Cell Tracking after Intraventricular Delivery in a Patient with Global Cerebral Ischemia and Prospects for Magnetic Navigation of Stem Cells within the CSF

    PubMed Central

    Janowski, Miroslaw; Walczak, Piotr; Kropiwnicki, Tomasz; Jurkiewicz, Elzbieta; Domanska-Janik, Krystyna; Bulte, Jeff W. M.; Lukomska, Barbara; Roszkowski, Marcin

    2014-01-01

    Background The purpose of the study was to evaluate the long-term clinical tracking of magnetically labeled stem cells after intracerebroventricular transplantation as well as to investigate in vitro feasibility for magnetic guidance of cell therapy within large fluid compartments. Method After approval by our Institutional Review Board, an 18-month-old patient, diagnosed as being in a vegetative state due to global cerebral ischemia, underwent cell transplantation to the frontal horn of the lateral ventricle, with umbilical cord blood-derived stem cells labeled with superparamagnetic iron oxide (SPIO) contrast agent. The patient was followed over 33 months with clinical examinations and MRI. To evaluate the forces governing the distribution of cells within the fluid compartment of the ventricular system in vivo, a gravity-driven sedimentation assay and a magnetic field-driven cell attraction assay were developed in vitro. Results Twenty-four hours post-transplantation, MR imaging (MRI) was able to detect hypointense cells in the occipital horn of the lateral ventricle. The signal gradually decreased over 4 months and became undetectable at 33 months. In vitro, no significant difference in cell sedimentation between SPIO-labeled and unlabeled cells was observed (p = NS). An external magnet was effective in attracting cells over distances comparable to the size of human lateral ventricles. Conclusions MR imaging of SPIO-labeled cells allows monitoring of cells within lateral ventricles. While the initial biodistribution is governed by gravity-driven sedimentation, an external magnetic field may possibly be applied to further direct the distribution of labeled cells within large fluid compartments such as the ventricular system. PMID:24919061

  14. Cryopreservation of human embryonic stem cells by a programmed freezer with an oscillating magnetic field.

    PubMed

    Lin, Pei-Yi; Yang, Yao-Chen; Hung, Shih-Han; Lee, Sheng-Yang; Lee, Maw-Sheng; Chu, I-Ming; Hwang, Shiaw-Min

    2013-06-01

    Human embryonic stem cells (hESCs), due to their self-renewal capacity and pluripotency, are an important source of cells for regenerative medicine. The immediate obstacles that need to be addressed are the poor cell survival rate of hESCs and their cell quality after cryopreservation. In this study, we used the Cell Alive System (CAS) which combines a programmed freezer with an oscillating magnetic field to reduce cryo-injury during the freezing process. The hESC clumps suspended in freezing medium were divided into three groups: (i) cells frozen by a conventional freezing container, Mr. Frosty and kept in a -80 °C freezer (MF); (ii) cells frozen to -32 °C by CAS, and then transferred to a -80 °C freezer (CAS); (iii) cells frozen to -32 °C by CAS, and then transferred to a pre-cooled Mr. Frosty and kept in a -80 °C freezer (CAS-MF) for overnight. All cryovials were placed in liquid nitrogen for one week, and hESCs were then thawed and cultured on feeder for 7 days. The results of alkaline phosphatase (AP) staining showed that the attachment efficiency of the cells cryopreserved by CAS and CAS-MF was significantly higher (29.0% and 44.0%) than in the MF method (7.0%). Furthermore, we confirmed the cells cryopreserved using CAS-MF could be subcultured while expressing pluripotent markers, differentiate into three germ layers, and maintain a normal karyotype. These results demonstrate that the use of CAS-MF offers an efficient method of hESC banking. PMID:23466687

  15. The DARPA HUMS program: revolutionizing magnetic field sensors using multiferroic materials and atomic gas vapor cells

    NASA Astrophysics Data System (ADS)

    Coblenz, William S.; Wartenberg, Scott A.

    2012-06-01

    The Heterostructural Uncooled Magnetic Sensors (HUMS) program sponsored by the Defense Advanced Research Projects Agency (DARPA/DSO) is focused on developing magnetic field sensors that operate at room temperature with an ultra-sensitivity to enable applications such as through-wall imaging, perimeter fences, tagging/tracking, and other man-portable operations. Four teams of researchers are participating in the program, with Virginia Tech and University of Maryland leading multiferroic heterostructural materials development and Princeton University and the National Institute of Standards and Technology (NIST) leading atomic vapor cell development. Leveraging the strengths of these two technologies, each team has made advancements towards the program goal of ground-breaking sensitivity, reduced noise, and portability while operating under room temperature conditions. This paper summarizes the program's achievements so far and highlights the accomplishments made by each team.

  16. Effect of magnetic nanoparticles on tobacco BY-2 cell suspension culture.

    PubMed

    Krystofova, Olga; Sochor, Jiri; Zitka, Ondrej; Babula, Petr; Kudrle, Vit; Adam, Vojtech; Kizek, Rene

    2013-01-01

    Nanomaterials are structures whose exceptionality is based on their large surface, which is closely connected with reactivity and modification possibilities. Due to these properties nanomaterials are used in textile industry (antibacterial textiles with silver nanoparticles), electronics (high-resolution imaging, logical circuits on the molecular level) and medicine. Medicine represents one of the most important fields of application of nanomaterials. They are investigated in connection with targeted therapy (infectious diseases, malignant diseases) or imaging (contrast agents). Nanomaterials including nanoparticles have a great application potential in the targeted transport of pharmaceuticals. However, there are some negative properties of nanoparticles, which must be carefully solved, as hydrophobic properties leading to instability in aqueous environment, and especially their possible toxicity. Data about toxicity of nanomaterials are still scarce. Due to this fact, in this work we focused on studying of the effect of magnetic nanoparticles (NPs) and modified magnetic nanoparticles (MNPs) on tobacco BY-2 plant cell suspension culture. We aimed at examining the effect of NPs and MNPs on growth, proteosynthesis - total protein content, thiols - reduced (GSH) and oxidized (GSSG) glutathione, phytochelatins PC2-5, glutathione S-transferase (GST) activity and antioxidant activity of BY-2 cells. Whereas the effect of NPs and MNPs on growth of cell suspension culture was only moderate, significant changes were detected in all other biochemical parameters. Significant changes in protein content, phytochelatins levels and GST activity were observed in BY-2 cells treated with MNPs nanoparticles treatment. Changes were also clearly evident in the case of application of NPs. Our results demonstrate the ability of MNPs to negatively affect metabolism and induce biosynthesis of protective compounds in a plant cell model represented by BY-2 cell suspension culture. The

  17. Effect of Magnetic Nanoparticles on Tobacco BY-2 Cell Suspension Culture

    PubMed Central

    Krystofova, Olga; Sochor, Jiri; Zitka, Ondrej; Babula, Petr; Kudrle, Vit; Adam, Vojtech; Kizek, Rene

    2012-01-01

    Nanomaterials are structures whose exceptionality is based on their large surface, which is closely connected with reactivity and modification possibilities. Due to these properties nanomaterials are used in textile industry (antibacterial textiles with silver nanoparticles), electronics (high-resolution imaging, logical circuits on the molecular level) and medicine. Medicine represents one of the most important fields of application of nanomaterials. They are investigated in connection with targeted therapy (infectious diseases, malignant diseases) or imaging (contrast agents). Nanomaterials including nanoparticles have a great application potential in the targeted transport of pharmaceuticals. However, there are some negative properties of nanoparticles, which must be carefully solved, as hydrophobic properties leading to instability in aqueous environment, and especially their possible toxicity. Data about toxicity of nanomaterials are still scarce. Due to this fact, in this work we focused on studying of the effect of magnetic nanoparticles (NPs) and modified magnetic nanoparticles (MNPs) on tobacco BY-2 plant cell suspension culture. We aimed at examining the effect of NPs and MNPs on growth, proteosynthesis—total protein content, thiols—reduced (GSH) and oxidized (GSSG) glutathione, phytochelatins PC2-5, glutathione S-transferase (GST) activity and antioxidant activity of BY-2 cells. Whereas the effect of NPs and MNPs on growth of cell suspension culture was only moderate, significant changes were detected in all other biochemical parameters. Significant changes in protein content, phytochelatins levels and GST activity were observed in BY-2 cells treated with MNPs nanoparticles treatment. Changes were also clearly evident in the case of application of NPs. Our results demonstrate the ability of MNPs to negatively affect metabolism and induce biosynthesis of protective compounds in a plant cell model represented by BY-2 cell suspension culture. The

  18. Design and experimental demonstration of low-power CMOS magnetic cell manipulation platform using charge recycling technique

    NASA Astrophysics Data System (ADS)

    Niitsu, Kiichi; Yoshida, Kohei; Nakazato, Kazuo

    2016-03-01

    We present the world’s first charge-recycling-based low-power technique of complementary metal-oxide-semiconductor (CMOS) magnetic cell manipulation. CMOS magnetic cell manipulation associated with magnetic beads is a promissing tool for on-chip biomedical-analysis applications such as drug screening because CMOS can integrate control electronics and electro-chemical sensors. However, the conventional CMOS cell manipulation requires considerable power consumption. In this work, by concatenating multiple unit circuits and recycling electric charge among them, power consumption is reduced by a factor of the number of the concatenated unit circuits (1/N). For verifying the effectiveness, test chip was fabricated in a 0.6-µm CMOS. The chip successfully manipulates magnetic microbeads with achieving 49% power reduction (from 51 to 26.2 mW). Even considering the additional serial resistance of the concatenated inductors, nearly theoretical power reduction effect can be confirmed.

  19. Revealing the sub-structures of the magnetic reconnection separatrix via particle-in-cell simulation

    SciTech Connect

    Zhou, M.; Deng, X. H.; Pang, Y.; Xu, X. J.; Yao, M.; Huang, S. Y.; Yuan, Z. G.; Li, H. M.; Wang, D. D.; Wang, Y. H.

    2012-07-15

    Magnetic separatrix is an important boundary layer separating the inflow and outflow regions in magnetic reconnection. In this article, we investigate the sub-structures of the separatrix region by using two-and-half dimensional electromagnetic particle-in-cell simulation. The separatrix region can be divided into two sub-regions in terms of the ion and electron frozen-in conditions. Far from the neutral sheet, ions and electrons are magnetized in magnetic fields. Approaching the neutral sheet, ion frozen-in condition is broken in a narrow region ({approx}c/{omega}{sub pi}) at the edge of a density cavity, while electrons are frozen-in to magnetic fields. In this region, electric field E{sub z} is around zero, and the convective term -(v{sub i} Multiplication-Sign B) is balanced by the Hall term in the generalized Ohm's law because ions carry the perpendicular current. Inside the density cavity, both ion and electron frozen-in conditions are broken. The region consists of two sub-ion or electron-scale layers, which contain intense electric fields. Formation of the two sub-layers is due to the complex electron flow pattern around the separatrix region. In the layer, E{sub z} is balanced by a combination of Hall term and the divergence of electron pressure tensor, with the Hall term being dominant. Our preliminary simulation result shows that the separatrix region in guide field reconnection also contains two sub-regions: the inner region and the outer region. However, the inner region contains only one current layer in contrast with the case without guide field.

  20. In vitro effects of 50 Hz magnetic fields on oxidatively damaged rabbit red blood cells

    SciTech Connect

    Fiorani, M.; Biagiarelli, B.; Vetrano, F.; Guidi, G.; Dacha, M.; Stocchi, V.

    1997-05-01

    The aim of this study was to investigate the effects of 50 Hz magnetic fields on rabbit red blood cells (RBCs) that were exposed simultaneously to the action of an oxygen radical-generating system, Fe(II)/ascorbate. Previous data obtained in the authors` laboratory showed that the exposure of rabbit erythrocytes or reticulocytes to Fe(II)/ascorbate induces hexokinase inactivation, whereas the other glycolytic enzymes do not show any decay. The authors also observed depletion of reduced glutathione (GSH) content with a concomitant intracellular and extracellular increase in oxidized glutathione (GSSG) and a decrease in energy charge. In this work, they investigated whether 50 Hz magnetic fields could influence the intracellular impairments that occur when erythrocytes or reticulocytes are exposed to this oxidant system, namely, inactivation of hexokinase activity, GSH depletion, a change in energy charge, and hemoglobin oxidation. The results obtained indicate that a 0.5 mT magnetic field had no effect on intact RBCs, whereas it increased the damage in an oxidatively stressed erythrocyte system. In fact, exposure of intact erythrocytes incubated with Fe(II)/ascorbate to a 0.5 mT magnetic field induced a significant further decay in hexokinase activity as well as a twofold increase in methemoglobin production compared with RBCs that were exposed to the oxidant system alone. Although further studies will be needed to determine the physiological implications of these data, the results reported in this study demonstrate that the effects of the magnetic fields investigated are able to potentiate the cellular damage induced in vitro by oxidizing agents.

  1. Magnetically Responsive Bone Marrow Mesenchymal Stem Cell-Derived Smooth Muscle Cells Maintain Their Benefits to Augmenting Elastic Matrix Neoassembly.

    PubMed

    Swaminathan, Ganesh; Sivaraman, Balakrishnan; Moore, Lee; Zborowski, Maciej; Ramamurthi, Anand

    2016-04-01

    Abdominal aortic aneurysms (AAA) represent abnormal aortal expansions that result from chronic proteolytic breakdown of elastin and collagen fibers by matrix metalloproteases. Poor elastogenesis by adult vascular smooth muscle cells (SMCs) limits regenerative repair of elastic fibers, critical for AAA growth arrest. Toward overcoming these limitations, we recently demonstrated significant elastogenesis by bone marrow mesenchymal stem cell-derived SMCs (BM-SMCs) and their proelastogenesis and antiproteolytic effects on rat aneurysmal SMCs (EaRASMCs). We currently investigate the effects of super paramagnetic iron oxide nanoparticle (SPION) labeling of BM-SMCs, necessary to magnetically guide them to the AAA wall, on their functional benefits. Our results indicate that SPION-labeling is noncytotoxic and does not adversely impact the phenotype and elastogenesis by BM-SMCs. In addition, SPION-BM-SMCs showed no changes in the ability of the BM-SMCs to stimulate elastin regeneration and attenuate proteolytic activity by EaRASMCs. Together, our results are promising toward the utility of SPIONs for magnetic targeting of BM-SMCs for in situ AAA regenerative repair. PMID:26830683

  2. Interventional magnetic resonance imaging-guided cell transplantation into the brain with radially branched deployment.

    PubMed

    Silvestrini, Matthew T; Yin, Dali; Martin, Alastair J; Coppes, Valerie G; Mann, Preeti; Larson, Paul S; Starr, Philip A; Zeng, Xianmin; Gupta, Nalin; Panter, S S; Desai, Tejal A; Lim, Daniel A

    2015-01-01

    Intracerebral cell transplantation is being pursued as a treatment for many neurological diseases, and effective cell delivery is critical for clinical success. To facilitate intracerebral cell transplantation at the scale and complexity of the human brain, we developed a platform technology that enables radially branched deployment (RBD) of cells to multiple target locations at variable radial distances and depths along the initial brain penetration tract with real-time interventional magnetic resonance image (iMRI) guidance. iMRI-guided RBD functioned as an "add-on" to standard neurosurgical and imaging workflows, and procedures were performed in a commonly available clinical MRI scanner. Multiple deposits of super paramagnetic iron oxide beads were safely delivered to the striatum of live swine, and distribution to the entire putamen was achieved via a single cannula insertion in human cadaveric heads. Human embryonic stem cell-derived dopaminergic neurons were biocompatible with the iMRI-guided RBD platform and successfully delivered with iMRI guidance into the swine striatum. Thus, iMRI-guided RBD overcomes some of the technical limitations inherent to the use of straight cannulas and standard stereotactic targeting. This platform technology could have a major impact on the clinical translation of a wide range of cell therapeutics for the treatment of many neurological diseases. PMID:25138755

  3. Labeling Stem Cells with Superparamagnetic Iron Oxide Nanoparticles: Analysis of the Labeling Efficacy by Microscopy and Magnetic Resonance Imaging

    PubMed Central

    Jasmin; Torres, Ana Luiza Machado; Jelicks, Linda; de Carvalho, Antonio Carlos Campos; Spray, David C.; Mendez-Otero, Rosalia

    2013-01-01

    Stem cell therapy has emerged as a potential therapeutic option for cell death-related heart diseases. Application of non-invasive cell tracking approaches is necessary to determine tissue distribution and lifetime of stem cells following their injection and will likely provide knowledge about poorly understood stem cells mechanisms of tissue repair. Magnetic resonance imaging (MRI) is a potentially excellent tool for high-resolution visualization of the fate of cells after transplantation and for evaluation of therapeutic strategies. The application of MRI for in vivo cell tracking requires contrast agents to achieve efficient cell labeling without causing any toxic cellular effects or eliciting any other side effects. For these reasons clinically approved contrast agents (e.g., ferumoxides) and incorporation facilitators (e.g., protamine) are currently the preferred materials for cell labeling and tracking. Here we describe how to use superparamag-netic iron oxide nanoparticles to label cells and to monitor cell fate in several disease models. PMID:22791437

  4. Purification of Immune Cell Populations from Freshly Isolated Murine Tumors and Organs by Consecutive Magnetic Cell Sorting and Multi-parameter Flow Cytometry-Based Sorting.

    PubMed

    Salvagno, Camilla; de Visser, Karin E

    2016-01-01

    It is well established that tumors evolve together with nonmalignant cells, such as fibroblasts, endothelial cells, and immune cells. These cells constantly entangle and interact with each other creating the tumor microenvironment. Immune cells can exert both tumor-promoting and tumor-protective functions. Detailed phenotypic and functional characterization of intra-tumoral immune cell subsets has become increasingly important in the field of cancer biology and cancer immunology. In this chapter, we describe a method for isolation of viable and pure immune cell subsets from freshly isolated murine solid tumors and organs. First, we describe a protocol for the generation of single-cell suspensions from tumors and organs using mechanical and enzymatic strategies. In addition, we describe how immune cell subsets can be purified by consecutive magnetic cell sorting and multi-parameter flow cytometry-based cell sorting. PMID:27581019

  5. Attenuation of Mouse Melanoma by A/C Magnetic Field after Delivery of Bi-Magnetic Nanoparticles by Neural Progenitor Cells

    PubMed Central

    Rachakatla, Raja Shekar; Balivada, Sivasai; Seo, Gwi-Moon; Myers, Carl B; Wang, Hongwang; Samarakoon, Thilani N.; Dani, Raj; Pyle, Marla; Kroh, Franklin O.; Walker, Brandon; Leaym, Xiaoxuan; Koper, Olga B.; Chikan, Viktor; Bossmann, Stefan H.; Tamura, Masaaki; Troyer, Deryl L.

    2010-01-01

    Localized magnetic hyperthermia as a treatment modality for cancer has generated renewed interest, particularly if it can be targeted to the tumor site. We examined whether tumor-tropic neural progenitor cells (NPCs) could be utilized as cell delivery vehicles for achieving preferential accumulation of core/shell iron/iron oxide magnetic nanoparticles (MNPs) within a mouse model of melanoma. We developed aminosiloxane-porphyrin functionalized MNPs, evaluated cell viability and loading efficiency, and transplanted neural progenitor cells loaded with this cargo into mice with melanoma. NPCs were efficiently loaded with core/shell Fe/Fe3O4 MNPs with minimal cytotoxicity; the MNPs accumulated as aggregates in the cytosol. The NPCs loaded with MNPs could travel to subcutaneous melanomas, and after A/C (alternating current) magnetic field (AMF) exposure, the targeted delivery of MNPs by the cells resulted in a measurable regression of the tumors. The tumor attenuation was significant (p<0.05) a short time (24 hours) after the last of three AMF exposures. PMID:21058696

  6. Quantitative “Hot Spot” Imaging of Transplanted Stem Cells using Superparamagnetic Tracers and Magnetic Particle Imaging (MPI)

    PubMed Central

    Bulte, J.W.M.; Walczak, P.; Janowski, M.; Krishnan, K.M.; Arami, H.; Halkola, A.; Gleich, B.; Rahmer, J.

    2015-01-01

    Magnetic labeling of stem cells enables their non-invasive detection by magnetic resonance imaging (MRI). Practically, most MRI studies have been limited to visualization of local engraftment as other sources of endogenous hypointense contrast complicate the interpretation of systemic (whole body) cell distribution. In addition, MRI cell tracking is inherently non-quantitative in nature. We report here on the potential of magnetic particle imaging (MPI) as a novel tomographic technique for non-invasive hot spot imaging and quantification of stem cells using superparamagnetic iron oxide (SPIO) tracers. Neural and mesenchymal stem cells, representing small and larger cell bodies, were labeled with three different SPIO tracer formulations, including two preparations that have previously been used in clinical MRI cell tracking studies (Feridex® and Resovist®). Magnetic particle spectroscopy (MPS) measurements demonstrated a linear correlation between MPI signal and iron content, for both homogeneous solutions of free particles in solution and for internalized and aggregated particles in labeled cells over a wide range of concentrations. The overall MP signal ranged from 1×10-3 - 3×10-4 Am2/g Fe, which was equivalent to 2×10-14 – 1×10-15 Am2 per cell, indicating that cell numbers can be quantified with MPI analogous to the use of radiotracers in nuclear medicine or fluorine tracers in 19F MRI. When SPIO-labeled cells were transplanted in mouse brain, they could be readily detected by MPI at a detection threshold of about 5×104 cells, with MPI/MRI overlays showing an excellent agreement between the hypointense MRI areas and MPI hot spots. The calculated tissue MPI signal ratio for 100,000 vs. 50,000 implanted cells was 2.08. Hence, MPI has potential to be further developed for quantitative and easy-to-interpret, tracer-based non-invasive imaging of cells, preferably with MRI as an adjunct anatomical imaging modality. PMID:26740972

  7. New Approach to High-Pressure Nuclear Magnetic Resonance with Anvil Cells

    NASA Astrophysics Data System (ADS)

    Meissner, T.; Goh, S. K.; Haase, J.; Meier, B.; Rybicki, D.; Alireza, P. L.

    2010-04-01

    A novel approach that uses radio-frequency microcoils in the high-pressure region of anvil cells with Nuclear Magnetic Resonance (NMR) experiments is described. High-sensitivity Al NMR data at 70 kbar for Al metal are presented for the first time. An expected decrease in the Al Knight shift at 70 kbar is observed, as well as an unexpected change in the local charge symmetry at the Al nucleus. The latter is not predicted by chemical structure analysis under high pressure.

  8. Positioning the Flagellum at the Center of a Dividing Cell To Combine Bacterial Division with Magnetic Polarity

    PubMed Central

    Bennet, Mathieu; Klumpp, Stefan

    2015-01-01

    ABSTRACT Faithful replication of all structural features is a sine qua non condition for the success of bacterial reproduction by binary fission. For some species, a key challenge is to replicate and organize structures with multiple polarities. Polarly flagellated magnetotactic bacteria are the prime example of organisms dealing with such a dichotomy; they have the challenge of bequeathing two types of polarities to their daughter cells: magnetic and flagellar polarities. Indeed, these microorganisms align and move in the Earth’s magnetic field using an intracellular chain of nano-magnets that imparts a magnetic dipole to the cell. The paradox is that, after division occurs in cells, if the new flagellum is positioned opposite to the old pole devoid of a flagellum during cell division, the two daughter cells will have opposite magnetic polarities with respect to the positions of their flagella. Here we show that magnetotactic bacteria of the class Gammaproteobacteria pragmatically solve this problem by synthesizing a new flagellum at the division site. In addition, we model this particular structural inheritance during cell division. This finding opens up new questions regarding the molecular aspects of the new division mechanism, the way other polarly flagellated magnetotactic bacteria control the rotational direction of their flagella, and the positioning of organelles. PMID:25714711

  9. The effect of magnetic field during freezing and thawing of rat bone marrow-derived mesenchymal stem cells.

    PubMed

    Shikata, H; Kaku, M; Kojima, S-I; Sumi, H; Kojima, S-T; Yamamoto, T; Yashima, Y; Kawata, T; Tanne, K; Tanimoto, K

    2016-08-01

    Previous studies showed that a programmed freezer with magnetic field can maintain a high survival rate of mesenchymal stem cells (MSCs). The purpose of this study was to evaluate the influences of magnetic field during freezing and thawing on the survival of MSCs isolated from rat bone marrow. The cells were frozen by a normal programmed freezer or a programmed freezer with magnetic field (CAS-LAB1) and cryopreserved for 7 days at -150 °C. Then, the cells were thawed in the presence or absence of magnetic field. Immediately after thawing, the number of surviving or viable cells was counted. The cell proliferation was examined after 1-week culture. Cryopreserved MSCs which were frozen by a normal freezer or a CAS freezer were transplanted into bone defects artificially made in calvaria of 4-week-old rats. Non-cryopreserved MSCs were used as a control. The rats were sacrificed at 8, 16, or 24 weeks after transplantation and the bone regeneration area was measured. Proliferation rates of MSCs after 1 week were significantly higher in the CAS-freezing-thawing group than in the CAS-freezing group. The extent of new bone formation in the CAS-freezing-thawing group tended to be larger than in CAS-freezing group 24 weeks after transplantation. These results suggest that a magnetic field enhances cell survival during thawing as well as freezing. PMID:27346603

  10. Enhanced magnetic resonance imaging and staining of cancer cells using ferrimagnetic H-ferritin nanoparticles with increasing core size

    PubMed Central

    Cai, Yao; Cao, Changqian; He, Xiaoqing; Yang, Caiyun; Tian, Lanxiang; Zhu, Rixiang; Pan, Yongxin

    2015-01-01

    Purpose This study is to demonstrate the nanoscale size effect of ferrimagnetic H-ferritin (M-HFn) nanoparticles on magnetic properties, relaxivity, enzyme mimetic activities, and application in magnetic resonance imaging (MRI) and immunohistochemical staining of cancer cells. Materials and methods M-HFn nanoparticles with different sizes of magnetite cores in the range of 2.7–5.3 nm were synthesized through loading different amounts of iron into recombinant human H chain ferritin (HFn) shells. Core size, crystallinity, and magnetic properties of those M-HFn nanoparticles were analyzed by transmission electron microscope and low-temperature magnetic measurements. The MDA-MB-231 cancer cells were incubated with synthesized M-HFn nanoparticles for 24 hours in Dulbecco’s Modified Eagle’s Medium. In vitro MRI of cell pellets after M-HFn labeling was performed at 7 T. Iron uptake of cells was analyzed by Prussian blue staining and inductively coupled plasma mass spectrometry. Immunohistochemical staining by using the peroxidase-like activity of M-HFn nanoparticles was carried out on MDA-MB-231 tumor tissue paraffin sections. Results The saturation magnetization (Ms), relaxivity, and peroxidase-like activity of synthesized M-HFn nanoparticles were monotonously increased with the size of ferrimagnetic cores. The M-HFn nanoparticles with the largest core size of 5.3 nm exhibit the strongest saturation magnetization, the highest peroxidase activity in immunohistochemical staining, and the highest r2 of 321 mM−1 s−1, allowing to detect MDA-MB-231 breast cancer cells as low as 104 cells mL−1. Conclusion The magnetic properties, relaxivity, and peroxidase-like activity of M-HFn nanoparticles are size dependent, which indicates that M-HFn nanoparticles with larger magnetite core can significantly enhance performance in MRI and staining of cancer cells. PMID:25878496

  11. Enhanced magnetic fluid hyperthermia by micellar magnetic nanoclusters composed of Mn(x)Zn(1-x)Fe(2)O(4) nanoparticles for induced tumor cell apoptosis.

    PubMed

    Qu, Yang; Li, Jianbo; Ren, Jie; Leng, Junzhao; Lin, Chao; Shi, Donglu

    2014-10-01

    Monodispersed MnxZn1-xFe2O4 magnetic nanoparticles of 8 nm are synthesized and encapsulated in amphiphilic block copolymer for development of the hydrophilic magnetic nanoclusters (MNCs). These MNCs exhibit superparamagnetic characteristics, high specific absorption rate (SAR), large saturation magnetization (Ms), excellent stability, and good biocompatibility. MnFe2O4 and Mn0.6Zn0.4Fe2O4 are selected as optimum compositions for the MNCs (MnFe2O4/MNC and Mn0.6Zn0.4Fe2O4/MNC) and employed for magnetic fluid hyperthermia (MFH) in vitro. To ensure biosafety of MFH, the parameters of alternating magnetic field (AMF) and exposure time are optimized with low frequency, f, and strength of applied magnetic field, Happlied. Under optimized conditions, MFH of MnFe2O4/MNC and Mn0.6Zn0.4Fe2O4/MNC result in cancer cell death rate up to 90% within 15 min. The pathway of cancer cell death is identified as apoptosis, which occurs in mild hyperthermia near 43 °C. Both MnFe2O4/MNC and Mn0.6Zn0.4Fe2O4/MNC show similar efficiencies on drug-sensitive and drug-resistant cancer cells. On the basis of these findings, those MnxZn1-xFe2O4 nanoclusters can serve as a promising candidate for effective targeting, diagnosis, and therapy of cancers. The multimodal cancer treatment is also possible as amphiphilic block copolymer can encapsulate, in a similar fashion, different nanoparticles, hydrophobic drugs, and other functional molecules. PMID:25204363

  12. Improved and targeted delivery of bioactive molecules to cells with magnetic layer-by-layer assembled microcapsules

    NASA Astrophysics Data System (ADS)

    Pavlov, Anton M.; Gabriel, Samantha A.; Sukhorukov, Gleb B.; Gould, David J.

    2015-05-01

    Despite our increasing knowledge of cell biology and the recognition of an increasing repertoire of druggable intracellular therapeutic targets, there remain a limited number of approaches to deliver bioactive molecules to cells and even fewer that enable targeted delivery. Layer-by-layer (LbL) microcapsules are assembled using alternate layers of oppositely charged molecules and are potential cell delivery vehicles for applications in nanomedicine. There are a wide variety of charged molecules that can be included in the microcapsule structure including metal nanoparticles that introduce physical attributes. Delivery of bioactive molecules to cells with LbL microcapsules has recently been demonstrated, so in this study we explore the delivery of bioactive molecules (luciferase enzyme and plasmid DNA) to cells using biodegradable microcapsules containing a layer of magnetite nanoparticles. Interestingly, significantly improved intracellular luciferase enzyme activity (25 fold) and increased transfection efficiency with plasmid DNA (3.4 fold) was observed with magnetic microcapsules. The use of a neodymium magnet enabled efficient targeting of magnetic microcapsules which further improved the delivery efficiency of the cargoes as a consequence of increased microcapsule concentration at the magnetic site. Microcapsules were well tolerated by cells in these experiments and only displayed signs of toxicity at a capsule : cell ratio of 100 : 1 and with extended exposure. These studies illustrate how multi-functionalization of LbL microcapsules can improve and target delivery of bioactive molecules to cells.

  13. The effect of two novel amino acid-coated magnetic nanoparticles on survival in vascular endothelial cells, bone marrow stromal cells, and macrophages

    NASA Astrophysics Data System (ADS)

    Wu, Qinghua; Meng, Ning; Zhang, Yanru; Han, Lei; Su, Le; Zhao, Jing; Zhang, Shangli; Zhang, Yun; Zhao, Baoxiang; Miao, Junying

    2014-09-01

    Magnetic nanoparticles (MNPs) have been popularly used in many fields. Recently, many kinds of MNPs are modified as new absorbents, which have attracted considerable attention and are promising to be applied in waste water. In our previous study, we synthesized two novel MNPs surface-coated with glycine or lysine, which could efficiently remove many anionic and cationic dyes under severe conditions. It should be considered that MNP residues in water may exert some side effects on human health. In the present study, we evaluated the potential nanotoxicity of MNPs in human endothelial cells, macrophages, and rat bone marrow stromal cells. The results showed that the two kinds of nanoparticles were consistently absorbed into the cell cytoplasm. The concentration of MNPs@Gly that could distinctly decrease survival was 15 μg/ml in human umbilical vascular endothelial cells (HUVECs) or bone marrow stromal cells (BMSCs) and 10 μg/ml in macrophages. While the concentration of MNPs@Lys that obviously reduced viability was 15 μg/ml in HUVECs or macrophages and 50 μg/ml in BMSCs. Furthermore, cell nucleus staining and cell integrity assay indicated that the nanoparticles induced cell apoptosis, but not necrosis even at a high concentration. Altogether, these data suggest that the amino acid-coated magnetic nanoparticles exert relatively high cytotoxicity. By contrast, lysine-coated magnetic nanoparticles are more secure than glycine-coated magnetic nanoparticles.

  14. Designing 3D Mesenchymal Stem Cell Sheets Merging Magnetic and Fluorescent Features: When Cell Sheet Technology Meets Image-Guided Cell Therapy

    PubMed Central

    Rahmi, Gabriel; Pidial, Laetitia; Silva, Amanda K. A.; Blondiaux, Eléonore; Meresse, Bertrand; Gazeau, Florence; Autret, Gwennhael; Balvay, Daniel; Cuenod, Charles André; Perretta, Silvana; Tavitian, Bertrand; Wilhelm, Claire; Cellier, Christophe; Clément, Olivier

    2016-01-01

    Cell sheet technology opens new perspectives in tissue regeneration therapy by providing readily implantable, scaffold-free 3D tissue constructs. Many studies have focused on the therapeutic effects of cell sheet implantation while relatively little attention has concerned the fate of the implanted cells in vivo. The aim of the present study was to track longitudinally the cells implanted in the cell sheets in vivo in target tissues. To this end we (i) endowed bone marrow-derived mesenchymal stem cells (BMMSCs) with imaging properties by double labeling with fluorescent and magnetic tracers, (ii) applied BMMSC cell sheets to a digestive fistula model in mice, (iii) tracked the BMMSC fate in vivo by MRI and probe-based confocal laser endomicroscopy (pCLE), and (iv) quantified healing of the fistula. We show that image-guided longitudinal follow-up can document both the fate of the cell sheet-derived BMMSCs and their healing capacity. Moreover, our theranostic approach informs on the mechanism of action, either directly by integration of cell sheet-derived BMMSCs into the host tissue or indirectly through the release of signaling molecules in the host tissue. Multimodal imaging and clinical evaluation converged to attest that cell sheet grafting resulted in minimal clinical inflammation, improved fistula healing, reduced tissue fibrosis and enhanced microvasculature density. At the molecular level, cell sheet transplantation induced an increase in the expression of anti-inflammatory cytokines (TGF-ß2 and IL-10) and host intestinal growth factors involved in tissue repair (EGF and VEGF). Multimodal imaging is useful for tracking cell sheets and for noninvasive follow-up of their regenerative properties. PMID:27022420

  15. Efficient treatment of phenolic wastewater with high salinity using a novel integrated system of magnetically immobilized cells coupling with electrodes.

    PubMed

    Jiang, Bei; Shi, Shengnan; Song, Lun; Tan, Liang; Li, Meidi; Liu, Jiaxin; Xue, Lanlan

    2016-10-01

    A novel integrated system in which magnetically immobilized cells coupled with a pair of stainless iron meshes-graphite plate electrodes has been designed and operated to enhance the treatment performance of phenolic wastewater under high salinity. With NaCl concentration increased, phenol, o-cresol, m-cresol, p-cresol and COD removal rates by integrated system increased significantly, which were obviously higher than the sum of removal rates by single magnetically immobilized cells and electrode reaction. This integrated system exhibited higher removal rates for all the compounds than that by single magnetically immobilized cells during six cycles for reuse, and it still performed better, even when the voltage was cut off. These results indicated that there was a coupling effect between biodegradation and electrode reaction. The investigation of phenol hydroxylase activity and cells concentration confirmed that electrode reaction played an important role in this coupling effect. PMID:27347805

  16. Inverse relationship between photon flux densities and nanotesla magnetic fields over cell aggregates: Quantitative evidence for energetic conservation

    PubMed Central

    Persinger, Michael A.; Dotta, Blake T.; Karbowski, Lukasz M.; Murugan, Nirosha J.

    2015-01-01

    The quantitative relationship between local changes in magnetic fields and photon emissions within ∼2 mm of aggregates of 105–106 cells was explored experimentally. The vertical component of the earth’s magnetic field as measured by different magnetometers was ∼15 nT higher when plates of cells removed from incubation were measured compared to plates containing only medium. Additional experiments indicated an inverse relationship over the first ∼45 min between changes in photon counts (∼10−12 W·m−2) following removal from incubation and similar changes in magnetic field intensity. Calculations indicated that the energy within the aqueous volume containing the cells was equivalent for that associated with the flux densities of the magnetic fields and the photon emissions. For every approximately 1 nT increase in magnetic field intensity value there was a decrease of ∼2 photons (equivalent of 10−18 J). These results complement correlation studies and suggest there may be a conservation of energy between expression as magnetic fields that are subtracted or added to the adjacent geomagnetic field and reciprocal changes in photon emissions when aggregates of cells within a specific volume of medium (water) adapt to new environments. PMID:26005634

  17. Magnetic field effects on mitochondrion-activity-related optical properties in slime mold and bone forming cells.

    PubMed

    Mizukawa, Yuri; Iwasaka, Masakazu

    2013-01-01

    In the present study, a cellular level response of Cyto-aa3 oxidation was investigated in real time under both time-varying and strong static magnetic fields of 5 T. Two kinds of cells, a slime mold, Physarum polycephalum, and bone forming cells, MC-3T3-E1, were used for the experiments. The oxidation level of the Cyto-aa3 was calculated by optical absorptions at 690 nm, 780 nm and 830 nm. The sample, fiber-optics and an additional optical fiber for light stimulation were set in a solenoidal coil or the bore of a 5-T superconducting magnet. The solenoidal coil for time-varying magnetic fields produced sinusoidal magnetic fields of 6 mT. The slime mold showed a periodic change in Cyto-aa3 oxidation, and the oxidation-reduction cycle of Cyto-aa3 was apparently changed when visible-light irradiated the slime mold. Similarly to the case with light, time-varying magnetic stimulations changed the oxidation-reduction cycle during and after the stimulation for 10 minutes. The same phenomena were observed in the MC-3T3-E1 cell assembly, although their cycle rhythm was comparatively random. Finally, magnetic field exposure of up to 5 T exhibited a distinct suppression of Cyto-aa3 oscillation in the bone forming cells. Exposure up to 5 T was repeated five times, and the change in Cyto-aa3 oxidation reproducibly occurred. PMID:24109969

  18. Numerical study of induced current perturbations in the vicinity of excitable cells exposed to extremely low frequency magnetic fields

    NASA Astrophysics Data System (ADS)

    Hassan, Noha; Chatterjee, Indira; Publicover, Nelson G.; Craviso, Gale L.

    2003-10-01

    Realistic three-dimensional cell morphologies were modelled to determine the current density induced in excitable cell culture preparations exposed to 60 Hz magnetic fields and to identify important factors that can influence the responses of cells to these fields. Cell morphologies representing single spherical adrenal chromaffin cells, single elongated smooth muscle cells and chromaffin cell aggregates in a Petri dish containing culture medium were modelled using the finite element method. The computations for a spherical cell revealed alterations in the magnitude and spatial distribution of the induced current density in the immediate vicinity of the cell. Maxima occurred at the equatorial sides and minima at the poles. Proximity of cells to each other as well as cell aggregate shape, size and orientation with respect to the induced current influenced the magnitude and spatial distribution of the induced current density. For an elongated cell, effects on the induced current density were highly dependent on cell orientation with respect to the direction of the induced current. These results provide novel insights into the perturbations in induced current that occur in excitable cell culture preparations and lay a foundation for understanding the mechanisms of interaction with extremely low frequency magnetic fields at the tissue level.

  19. Interventional Magnetic Resonance Imaging-guided Cell Transplantation Into the Brain With Radially Branched Deployment

    PubMed Central

    Silvestrini, Matthew T; Yin, Dali; Martin, Alastair J; Coppes, Valerie G; Mann, Preeti; Larson, Paul S; Starr, Philip A; Zeng, Xianmin; Gupta, Nalin; Panter, S S; Desai, Tejal A; Lim, Daniel A

    2015-01-01

    Intracerebral cell transplantation is being pursued as a treatment for many neurological diseases, and effective cell delivery is critical for clinical success. To facilitate intracerebral cell transplantation at the scale and complexity of the human brain, we developed a platform technology that enables radially branched deployment (RBD) of cells to multiple target locations at variable radial distances and depths along the initial brain penetration tract with real-time interventional magnetic resonance image (iMRI) guidance. iMRI-guided RBD functioned as an “add-on” to standard neurosurgical and imaging workflows, and procedures were performed in a commonly available clinical MRI scanner. Multiple deposits of super paramagnetic iron oxide beads were safely delivered to the striatum of live swine, and distribution to the entire putamen was achieved via a single cannula insertion in human cadaveric heads. Human embryonic stem cell–derived dopaminergic neurons were biocompatible with the iMRI-guided RBD platform and successfully delivered with iMRI guidance into the swine striatum. Thus, iMRI-guided RBD overcomes some of the technical limitations inherent to the use of straight cannulas and standard stereotactic targeting. This platform technology could have a major impact on the clinical translation of a wide range of cell therapeutics for the treatment of many neurological diseases. PMID:25138755

  20. Pulsed magnetic field promotes proliferation and neurotrophic genes expression in Schwann cells in vitro

    PubMed Central

    Liu, Liang; Liu, Zhongyang; Huang, Liangliang; Sun, Zhen; Ma, Teng; Zhu, Shu; Quan, Xin; Yang, Yafeng; Huang, Jinghui; Luo, Zhuojing

    2015-01-01

    As one of the most classic supportive cells, Schwann cells (SCs) have been considered as potential candidates for nerve regeneration. However, SCs cultured in vitro are found with attenuated biological activities, which limits their application. Pulsed magnetic field (PMF) has been demonstrated to be safe and efficient to regulate several cells activities. However, it is still unclear the effect of PMF on proliferation and expression of neurotrophic factors in SCs. Therefore, the present study was designed to examine such possible effects. The tolerance of SCs to PMF was examined by flow cytometry and scanning electron microscopy (SEM). The proliferation of cells was detected by an EdU labeling assay and a Prestoblue assay. The expression and secretion of neurotrophic factors in SCs was assayed by RT-PCR and ELISA. We found that 2.0 mT was the optimal intensity that caused relatively little apoptosis with profound proliferation in SCs. The gene expression and protein level of brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF) were up-regulated following PMF stimulation, additionally, the gene expression and protein level of neurotrophin-3 (NT-3) was not enhanced by PMF. Our results suggested that PMF could improve SC proliferation and biological function, which might shed a light on the potential utilization of PMF in nerve regeneration via SC activation. PMID:26045741

  1. Ultrastructure and calcium balance in meristem cells of pea roots exposed to extremely low magnetic fields

    NASA Astrophysics Data System (ADS)

    Belyavskaya, N. A.

    2001-01-01

    Investigations of low magnetic field (LMF) effects on biological systems have attracted attention of biologists due to planned space flights to other planets where the field intensity does not exceed 10 -5 Oe. Pea ( Pisum sativum L.) seeds were grown in an environment of LMF 3 days. In meristem cells of roots exposed to LMF, one could observe such ultrastructural peculiarities as a noticeable accumulation of lipid bodies, development of a lytic compartment (vacuoles, cytosegresomes and paramural bodies), and reduction of phytoferritin in plastids. Mitochondria were the most sensitive organelle to LMF application. Their size and relative volume in cells increased, matrix was electron-transparent, and cristae reduced. Because of the significant role of calcium signalling in plant responses to different environmental factors, calcium participation in LMF effects was investigated using a pyroantimonate method to identify the localization of free calcium ions. The intensity of cytochemical reaction in root cells after LMF application was strong. The Ca 2+ pyroantimonate deposits were observed both in all organelles and in a hyaloplasm of the cells. Data obtained suggest that the observed LMF effects on ultrastructure of root cells were due to disruptions in different metabolic systems including effects on Ca 2+ homeostasis.

  2. A micropreparation of mitochondria from cells using magnetic beads with immunoaffinity.

    PubMed

    Ru, Yawei; Yin, Liang; Sun, Haidan; Yin, Songyue; Pan, Qin; Wei, Hanfu; Wu, Lin; Liu, Siqi

    2012-02-01

    Mitochondrial preparation is a key technique in the study of mitochondria. Growing evidence has demonstrated that mitochondrial proteins are tissue or cell type dependent. Locating the proteins in the global presence of mitochondrial membranes is a primary consideration in adopting antibodies for affinity enrichment of mitochondria on a micro scale. Two proteins located on the outer membrane of mitochondria, cytochrome b5 type B (CYB5B) and synaptojanin-2-binding protein (SYNJ2BP), were selected as candidates based on a survey of databases and the literature. The polyclonal antibodies against the truncated CYB5B and SYNJ2BP exhibited specific recognition to mitochondria and wider sensitivity to several tested mouse tissues and cell lines, whereas the antibody 22-kDa translocase of the outer mitochondrial membrane (TOM22) nearly missed detection of mitochondria in the liver and responded minimally to mitochondria from H9C2 and L-02 cells. Through the affinity enrichment for cellular mitochondria using magnetic beads coated with anti-CYB5B or anti-SYNJ2BP, we found that the anti-CYB5B beads could enrich mitochondria more efficiently even on a scale of 10,000 cultured cells. For the integrity and protein components, the enriched mitochondria on anti-CYB5B were carefully examined and were accepted in further functional study. We propose that an anti-CYB5B immunomagnetic approach is feasible in the micropreparation of mitochondria from cultured cells. PMID:22178913

  3. Electromagnetic particle-in-cell simulations of the solar wind interaction with lunar magnetic anomalies.

    PubMed

    Deca, J; Divin, A; Lapenta, G; Lembège, B; Markidis, S; Horányi, M

    2014-04-18

    We present the first three-dimensional fully kinetic and electromagnetic simulations of the solar wind interaction with lunar crustal magnetic anomalies (LMAs). Using the implicit particle-in-cell code iPic3D, we confirm that LMAs may indeed be strong enough to stand off the solar wind from directly impacting the lunar surface forming a mini-magnetosphere, as suggested by spacecraft observations and theory. In contrast to earlier magnetohydrodynamics and hybrid simulations, the fully kinetic nature of iPic3D allows us to investigate the space charge effects and in particular the electron dynamics dominating the near-surface lunar plasma environment. We describe for the first time the interaction of a dipole model centered just below the lunar surface under plasma conditions such that only the electron population is magnetized. The fully kinetic treatment identifies electromagnetic modes that alter the magnetic field at scales determined by the electron physics. Driven by strong pressure anisotropies, the mini-magnetosphere is unstable over time, leading to only temporal shielding of the surface underneath. Future human exploration as well as lunar science in general therefore hinges on a better understanding of LMAs. PMID:24785022

  4. Nanoparticle encapsulation in red blood cells enables blood-pool magnetic particle imaging hours after injection

    NASA Astrophysics Data System (ADS)

    Rahmer, J.; Antonelli, A.; Sfara, C.; Tiemann, B.; Gleich, B.; Magnani, M.; Weizenecker, J.; Borgert, J.

    2013-06-01

    Magnetic particle imaging (MPI) is a new medical imaging approach that is based on the nonlinear magnetization response of super-paramagnetic iron oxide nanoparticles (SPIOs) injected into the blood stream. To date, real-time MPI of the bolus passage of an approved MRI SPIO contrast agent injected into the tail vein of living mice has been demonstrated. However, nanoparticles are rapidly removed from the blood stream by the mononuclear phagocyte system. Therefore, imaging applications for long-term monitoring require the repeated administration of bolus injections, which complicates quantitative comparisons due to the temporal variations in concentration. Encapsulation of SPIOs into red blood cells (RBCs) has been suggested to increase the blood circulation time of nanoparticles. This work presents first evidence that SPIO-loaded RBCs can be imaged in the blood pool of mice several hours after injection using MPI. This finding is supported by magnetic particle spectroscopy performed to quantify the iron concentration in blood samples extracted from the mice 3 and 24 h after injection of SPIO-loaded RBCs. Based on these results, new MPI applications can be envisioned, such as permanent 3D real-time visualization of the vessel tree during interventional procedures, bleeding monitoring after stroke, or long-term monitoring and treatment control of cardiovascular diseases.

  5. Miniaturized Nuclear Magnetic Resonance Platform for Detection and Profiling of Circulating Tumor Cells

    PubMed Central

    Castro, Cesar M.; Ghazani, Arezou A.; Chung, Jaehoon; Shao, Huilin; Issadore, David; Yoon, Tae-Jong; Weissleder, Ralph; Lee, Hakho

    2013-01-01

    Accurate detection and profiling of circulating tumor cells (CTCs) is a highly sought after technology to improve cancer management. Such “liquid biopsies” could offer a non-invasive, repeatable window into each patient’s tumor, facilitating early cancer diagnosis and treatment monitoring. The rarity of CTCs, approximated at 1 CTC for every billion peripheral blood cells, however, poses significant challenges to sensitive and reliable detection. We have recently developed a new biosensor platform, namely a micro-nuclear magnetic resonance (µNMR). Through the synergistic integration of microfabrication, nanosensors, and novel chemistries, the µNMR platform offers high detection sensitivity and point-of-care operation, overcoming technical barriers in CTC research. We herein review the µNMR technology with emphasis on its application on CTC detection. Recent advances in the sensing technology will be summarized, followed by the description on the dynamic interplay between preclinical and clinical CTC studies. PMID:23835814

  6. Influence of chitosan coating on magnetic nanoparticles in endothelial cells and acute tissue biodistribution.

    PubMed

    Agotegaray, Mariela; Campelo, Adrián; Zysler, Roberto; Gumilar, Fernanda; Bras, Cristina; Minetti, Alejandra; Massheimer, Virginia; Lassalle, Verónica

    2016-08-01

    Chitosan coating on magnetic nanoparticles (MNPs) was studied on biological systems as a first step toward the application in the biomedical field as drug-targeted nanosystems. Composition of MNPs consists of magnetite functionalized with oleic acid and coated with the biopolymer chitosan or glutaraldehyde-cross-linked chitosan. The influence of the biopolymeric coating has been evaluated by in vitro and in vivo assays on the effects of these MNPs on rat aortic endothelial cells (ECs) viability and on the random tissue distribution in mice. Results were correlated with the physicochemical properties of the nanoparticles. Nitric oxide (NO) production by ECs was determined, considering that endothelial NO represents one of the major markers of ECs function. Cell viability was studied by MTT assay. Different doses of the MNPs (1, 10 and 100 μg/mL) were assayed, revealing that MNPs coated with non-cross-linked chitosan for 6 and 24 h did not affect neither NO production nor cell viability. However, a significant decrease in cell viability was observed after 36 h treatment with the highest dose of this nanocarrier. It was also revealed that the presence and dose of glutaraldehyde in the MNPs structureimpact on the cytotoxicity. The study of the acute tissue distribution was performed acutely in mice after 24 h of an intraperitoneal injection of the MNPs and sub acutely, after 28 days of weekly administration. Both formulations greatly avoided the initial clearance by the reticuloendothelial system (RES) in liver. Biological properties found for N1 and N2 in the performed assays reveal that chitosan coating improves biocompatibility of MNPs turning these magnetic nanosystems as promising devices for targeted drug delivery. PMID:27251857

  7. Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model

    PubMed Central

    Basel, Matthew T; Balivada, Sivasai; Wang, Hongwang; Shrestha, Tej B; Seo, Gwi Moon; Pyle, Marla; Abayaweera, Gayani; Dani, Raj; Koper, Olga B; Tamura, Masaaki; Chikan, Viktor; Bossmann, Stefan H; Troyer, Deryl L

    2012-01-01

    Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/ iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/ macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/ iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer. PMID:22287840

  8. Multifunctional Plasmonic Shell–Magnetic Core Nanoparticles for Targeted Diagnostics, Isolation, and Photothermal Destruction of Tumor Cells

    PubMed Central

    Fan, Zhen; Shelton, Melanie; Singh, Anant Kumar; Senapati, Dulal; Khan, Sadia Afrin; Ray, Paresh Chandra

    2012-01-01

    Cancer is the greatest challenge in human healthcare today. Cancer causes 7.6 million deaths and economic losses of around 1 trillion dollars every year. Early diagnosis and effective treatment of cancer are crucial for saving lives. Driven by these needs, we report the development of a multifunctional plasmonic shell–magnetic core nanotechnology-driven approach for the targeted diagnosis, isolation, and photothermal destruction of cancer cells. Experimental data show that aptamer-conjugated plasmonic/magnetic nanoparticles can be used for targeted imaging and magnetic separation of a particular kind of cell from a mixture of different cancer cells. A targeted photothermal experiment using 670-nm light at 2.5 W/cm2 for 10 minutes resulted selective irreparable cellular damage to most of the cancer cells. We also showed that the aptamer-conjugated magnetic/plasmonic nanoparticle-based photothermal destruction of cancer cells is highly selective. We discuss the possible mechanism and operating principle for the targeted imaging, separation, and photothermal destruction using magnetic/plasmonic nanotechnology. PMID:22276857

  9. Multifunctional plasmonic shell-magnetic core nanoparticles for targeted diagnostics, isolation, and photothermal destruction of tumor cells.

    PubMed

    Fan, Zhen; Shelton, Melanie; Singh, Anant Kumar; Senapati, Dulal; Khan, Sadia Afrin; Ray, Paresh Chandra

    2012-02-28

    Cancer is the greatest challenge in human healthcare today. Cancer causes 7.6 million deaths and economic losses of around 1 trillion dollars every year. Early diagnosis and effective treatment of cancer are crucial for saving lives. Driven by these needs, we report the development of a multifunctional plasmonic shell-magnetic core nanotechnology-driven approach for the targeted diagnosis, isolation, and photothermal destruction of cancer cells. Experimental data show that aptamer-conjugated plasmonic/magnetic nanoparticles can be used for targeted imaging and magnetic separation of a particular kind of cell from a mixture of different cancer cells. A targeted photothermal experiment using 670 nm light at 2.5 W/cm(2) for 10 min resulted selective irreparable cellular damage to most of the cancer cells. We also showed that the aptamer-conjugated magnetic/plasmonic nanoparticle-based photothermal destruction of cancer cells is highly selective. We discuss the possible mechanism and operating principle for the targeted imaging, separation, and photothermal destruction using magnetic/plasmonic nanotechnology. PMID:22276857

  10. Transplantation and Magnetic Resonance Imaging of Canine Neural Progenitor Cell Grafts in the Postnatal Dog Brain

    PubMed Central

    Walton, Raquel M.; Magnitsky, Sergey G.; Seiler, Gabriela S.; Poptani, Harish; Wolfe, John H.

    2009-01-01

    Cellular transplantation in the form of bone marrow has been one of the primary treatments of many lysosomal storage diseases (LSDs). Although bone marrow transplantation can help central nervous system manifestations in some cases, it has little impact in many LSD patients. Canine models of neurogenetic LSDs provide the opportunity for modeling central nervous system transplantation strategies in brains that more closely approximate the size and architectural complexity of the brains of children. Canine olfactory bulb-derived neural progenitor cells (NPCs) isolated from dog brains were expanded ex vivo and implanted into the caudate nucleus/thalamus or cortex of allogeneic dogs. Canine olfactory bulb-derived NPCs labeled with micron-sized superparamagnetic iron oxide particles were detected by magnetic resonance imaging both in vivo and postmortem. Grafts expressed markers of NPCs (i.e. nestin and glial fibrillary acidic protein), but not the neuronal markers Map2ab or β-tubulin III. The NPCs were from dogs with the LSD mucopolysaccharidosis VII, which is caused by a deficiency of β-glucuronidase. When mucopolysaccharidosis VII canine olfactory bulb-NPCs that were genetically corrected with a lentivirus vector ex vivo were transplanted into mucopolysaccharidosis VII recipient brains, they were detected histologically by β-glucuronidase expression in areas identified by antemortem magnetic resonance imaging tracking. These results demonstrate the potential for ex vivo stem cell-based gene therapy and noninvasive tracking of therapeutic grafts in vivo. PMID:18800012

  11. Measurement of local viscoelasticity and forces in living cells by magnetic tweezers.

    PubMed

    Bausch, A R; Möller, W; Sackmann, E

    1999-01-01

    We measured the viscoelastic properties of the cytoplasm of J774 macrophages with a recently developed microrheometer. Ferromagnetic beads (1.3 microm in diameter) were used to determine the local viscoelastic moduli. Step-force pulses were applied to the magnetic beads and the displacement was observed by single particle tracking. By analyzing the creep response curves in terms of a triphasic mechanical equivalent circuit, we measured the shear elastic modulus, the effective viscosities, and the strain relaxation time. The values of the shear modulus vary by more than an order of magnitude within the cell population (range, 20-735 Pa; average, 343 Pa) and by a factor of 2 within single cells. The effective viscosity of the cytoplasm exhibits a relatively sharp distribution about an average of eta = 210 Pa s (+/- 143 Pa s). We measured the displacement field generated by the local forces by observing the induced motion of nonmagnetic beads. Even at distances of the order of 1 microm, no induced motion was seen, suggesting that the cytoplasm is composed of clusters of densely packed and cross-linked filaments separated by soft regions. In another series of experiments we analyzed the magnetophoretic motion of the ferromagnetic beads at a constant magnetic force. Measuring the bead velocity parallel and perpendicular to the applied force showed that local active forces on the beads varied from 50 to 900 pN. PMID:9876170

  12. Sub-Kelvin magnetic and electrical measurements in a diamond anvil cell with in-situ tunability

    SciTech Connect

    Palmer, Alexander; Silevitch, Daniel; Feng, Yejun; Wang, Yishu; Jaramillo, R.; Banerjee, Arnab; Ren, Yang; Rosenbaum, Thomas F.

    2015-09-04

    We discuss techniques for performing continuous measurements across a wide range of pressure-field-temperature phase space, combining the milli-Kelvin temperatures of a helium dilution refrigerator with that of the giga-Pascal pressures of a diamond anvil cell and the Tesla magnetic fields of a superconducting magnet. With a view towards minimizing remnant magnetic fields and background magnetic susceptibility, we then characterize high-strength superalloy materials for the pressure cell assembly, which allows high fidelity measurements of low-field phenomena such as superconductivity below 100 mK at pressures above 10 GPa. In situ tunability and measurement of the pressure permit experiments over a wide range of pressure, while at the same time making possible precise steps across abrupt phase transitions such as that from insulator to metal.

  13. Sub-Kelvin magnetic and electrical measurements in a diamond anvil cell with in-situ tunability

    DOE PAGESBeta

    Palmer, Alexander; Silevitch, Daniel; Feng, Yejun; Wang, Yishu; Jaramillo, R.; Banerjee, Arnab; Ren, Yang; Rosenbaum, Thomas F.

    2015-09-04

    We discuss techniques for performing continuous measurements across a wide range of pressure-field-temperature phase space, combining the milli-Kelvin temperatures of a helium dilution refrigerator with that of the giga-Pascal pressures of a diamond anvil cell and the Tesla magnetic fields of a superconducting magnet. With a view towards minimizing remnant magnetic fields and background magnetic susceptibility, we then characterize high-strength superalloy materials for the pressure cell assembly, which allows high fidelity measurements of low-field phenomena such as superconductivity below 100 mK at pressures above 10 GPa. In situ tunability and measurement of the pressure permit experiments over a wide rangemore » of pressure, while at the same time making possible precise steps across abrupt phase transitions such as that from insulator to metal.« less

  14. Quantitative Magnetic Particle Imaging Monitors the Transplantation, Biodistribution, and Clearance of Stem Cells In Vivo

    PubMed Central

    Zheng, Bo; von See, Marc P.; Yu, Elaine; Gunel, Beliz; Lu, Kuan; Vazin, Tandis; Schaffer, David V.; Goodwill, Patrick W.; Conolly, Steven M.

    2016-01-01

    Stem cell therapies have enormous potential for treating many debilitating diseases, including heart failure, stroke and traumatic brain injury. For maximal efficacy, these therapies require targeted cell delivery to specific tissues followed by successful cell engraftment. However, targeted delivery remains an open challenge. As one example, it is common for intravenous deliveries of mesenchymal stem cells (MSCs) to become entrapped in lung microvasculature instead of the target tissue. Hence, a robust, quantitative imaging method would be essential for developing efficacious cell therapies. Here we show that Magnetic Particle Imaging (MPI), a novel technique that directly images iron-oxide nanoparticle-tagged cells, can longitudinally monitor and quantify MSC administration in vivo. MPI offers near-ideal image contrast, depth penetration, and robustness; these properties make MPI both ultra-sensitive and linearly quantitative. Here, we imaged, for the first time, the dynamic trafficking of intravenous MSC administrations using MPI. Our results indicate that labeled MSC injections are immediately entrapped in lung tissue and then clear to the liver within one day, whereas standard iron oxide particle (Resovist) injections are immediately taken up by liver and spleen. Longitudinal MPI-CT imaging also indicated a clearance half-life of MSC iron oxide labels in the liver at 4.6 days. Finally, our ex vivo MPI biodistribution measurements of iron in liver, spleen, heart, and lungs after injection showed excellent agreement (R2 = 0.943) with measurements from induction coupled plasma spectrometry. These results demonstrate that MPI offers strong utility for noninvasively imaging and quantifying the systemic distribution of cell therapies and other therapeutic agents. PMID:26909106

  15. Magnetic Fe₃O₄ nanoparticles and chemotherapy agents interact synergistically to induce apoptosis in lymphoma cells.

    PubMed

    Jing, Hongmei; Wang, Jing; Yang, Ping; Ke, Xiaoyan; Xia, Guohua; Chen, Baoan

    2010-01-01

    The purpose of this study was to investigate the potential effects of combination therapy using magnetic nanoparticles of Fe₃O₄ (MNP-Fe₃O₄) and chemotherapeutic drugs on lymphoma cells. Proliferation, inhibition, and viability of Raji cells were detected by MTT and trypan blue exclusion. The percentage of cells undergoing apoptosis was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. p53 and nuclear factor-κB (NF-κB) protein levels were measured by Western blot. The results showed that proliferation of Raji cells was inhibited by adriamycin or daunorubicin in a dose-and time-dependent manner. Cell sensitivity was improved and the 50% inhibitory concentrations of adriamycin and daunorubicin decreased when combined with a MNP-Fe₃O₄ carrier. Interestingly, increased apoptosis in Raji lymphoma cells was accompanied by upregulation of p53 protein and downregulation of NF-κB protein. Furthermore, the combination of MNP-Fe₃O₄ with adriamycin or daunorubicin increased p53 protein levels and decreased NF-κB protein levels more than adriamycin or daunorubicin alone, indicating that MNP-Fe₃O₄ could enhance the effect of chemotherapeutic drugs on p53 and NF-κB. Similar results for cell apoptosis and protein expression were not observed for the groups treated with dexamethasone ± MNP-Fe₃O₄ (P > 0.05). These findings suggest a potential clinical application for MNP-Fe₃O₄ in combination with daunorubicin or adriamycin in the treatment of lymphoma. PMID:21187919

  16. Multiple effects of glycerol on plant cell metabolism. Phosphorus-31 nuclear magnetic resonance studies.

    PubMed

    Aubert, S; Gout, E; Bligny, R; Douce, R

    1994-08-26

    The effects of glycerol on plant cell metabolism were studied with sycamore (Acer pseudoplatanus L.) cells using 31P nuclear magnetic resonance spectroscopy. After a long period of sucrose starvation, the addition of 50 mM glycerol to the medium did not restore the original glucose-6-P pool and led to a rapid accumulation of sn-glycerol-3-P in the cytoplasmic compartment. The synthesis of sn-glycerol-3-P was rapid and occurred first at the expense of cytoplasmic P(i). Accumulated sn-glycerol-3-P competitively inhibited glucose-6-phosphate isomerase activity when fructose-6-P was the varied substrate. Such a situation prevented the rapid recycling of triose phosphates back to hexose phosphates and led to an arrest of the functioning of the cytosolic and plastidial pentose phosphate pathways. Under these conditions, the flow of carbon to drive cell respiration derived almost exclusively from glycerol, and this polyalcohol was not used as a source of carbon skeletons for biosynthesis. Glycerol also induced the accumulation of O-phosphohomoserine in the cytoplasmic compartment as long as the cell culture medium contained sucrose. Finally glycerol added to sucrose-starved cells stopped the accumulation of phosphocholine (Roby, C., Martin J.-B., Bligny, R., and Douce, R. (1987) J. Biol. Chem. 262, 5000-5007) and prevented a further decline in the uncoupled rate of O2 consumption by the cells (Journet, E. P., Bligny, R., and Douce, R. (1986) J. Biol. Chem. 261, 3193-3199). These last observations strongly suggest that glycerol prevented the triggering of autophagy induced by sucrose starvation in sycamore cells. PMID:8063774

  17. Magnetic Force Nanoprobe for Direct Observation of Audio Frequency Tonotopy of Hair Cells.

    PubMed

    Kim, Ji-Wook; Lee, Jae-Hyun; Ma, Ji-Hyun; Chung, Eunna; Choi, Hongsuh; Bok, Jinwoong; Cheon, Jinwoo

    2016-06-01

    Sound perception via mechano-sensation is a remarkably sensitive and fast transmission process, converting sound as a mechanical input to neural signals in a living organism. Although knowledge of auditory hair cell functions has advanced over the past decades, challenges remain in understanding their biomechanics, partly because of their biophysical complexity and the lack of appropriate probing tools. Most current studies of hair cells have been conducted in a relatively low-frequency range (<1000 Hz); therefore, fast kinetic study of hair cells has been difficult, even though mammalians have sound perception of 20 kHz or higher. Here, we demonstrate that the magnetic force nanoprobe (MFN) has superb spatiotemporal capabilities to mechanically stimulate spatially-targeted individual hair cells with a temporal resolution of up to 9 μs, which is equivalent to approximately 50 kHz; therefore, it is possible to investigate avian hair cell biomechanics at different tonotopic regions of the cochlea covering a full hearing frequency range of 50 to 5000 Hz. We found that the variation of the stimulation frequency and amplitude of hair bundles creates distinct mechanical responsive features along the tonotopic axis, where the kinetics of the hair bundle recovery motion exhibits unique frequency-dependent characteristics: basal, middle, and apical hair bundles can effectively respond at their respective ranges of frequency. We revealed that such recovery kinetics possesses two different time constants that are closely related to the passive and active motilities of hair cells. The use of MFN is critical for the kinetics study of free-standing hair cells in a spatiotemporally distinct tonotopic organization. PMID:27215487

  18. Viking observations of a reverse convection cell developing in response to a northward turning of the interplanetary magnetic field

    SciTech Connect

    Henderson, M.G.; Murphree, J.S.

    1996-04-15

    The authors report the development of a reverse sense convection cell in the polar ionosphere from auroral images coming from UV Viking probes. The cell was observed to grow on the dusk side of the north polar oval, near the transpolar arcs. As it grew it seemed to displace the arc system toward dawn. They compare their observations with a model in which magnetic merging in the magnetopause produces such convection cells, typically associated with horse-collar or teardrop auroral features.

  19. Miniature ceramic-anvil high-pressure cell for magnetic measurements in a commercial superconducting quantum interference device magnetometer.

    PubMed

    Tateiwa, Naoyuki; Haga, Yoshinori; Fisk, Zachary; Ōnuki, Yoshichika

    2011-05-01

    A miniature opposed-anvil high-pressure cell has been developed for magnetic measurement in a commercial superconducting quantum interference device magnetometer. Non-magnetic anvils made of composite ceramic material were used to generate high-pressure with a Cu-Be gasket. We have examined anvils with different culet sizes (1.8, 1.6, 1.4, 1.2, 1.0, 0.8, and 0.6 mm). The pressure generated at low temperature was determined by the pressure dependence of the superconducting transition of lead (Pb). The maximum pressure P(max) depends on the culet size of the anvil: the values of P(max) are 2.4 and 7.6 GPa for 1.8 and 0.6 mm culet anvils, respectively. We revealed that the composite ceramic anvil has potential to generate high-pressure above 5 GPa. The background magnetization of the Cu-Be gasket is generally two orders of magnitude smaller than the Ni-Cr-Al gasket for the indenter cell. The present cell can be used not only with ferromagnetic and superconducting materials with large magnetization but also with antiferromagnetic compounds with smaller magnetization. The production cost of the present pressure cell is about one tenth of that of a diamond anvil cell. The anvil alignment mechanism is not necessary in the present pressure cell because of the strong fracture toughness (6.5 MPa m(1∕2)) of the composite ceramic anvil. The simplified pressure cell is easy-to-use for researchers who are not familiar with high-pressure technology. Representative results on the magnetization of superconducting MgB(2) and antiferromagnet CePd(5)Al(2) are reported. PMID:21639517

  20. RF Power and Magnetic Field Modulation Experiments with Simple Mirror Geometry in the Central Cell of Hanbit Device

    SciTech Connect

    Lee, S.G.; Bak, J.G.; Jhang, H.G.; Kim, S.S.

    2005-01-15

    The radio frequency (RF) stabilization effects to investigate the characteristics of the interchange instability by RF power and magnetic field modulation experiments were performed near {omega}/{omega}{sub i} {approx} = 1 and with low beta ({approx} 0.1%) plasmas in the central cell of the Hanbit mirror device. Temporal behaviors of the interchange mode were measured and analyzed when the interchange mode was triggered by sudden changes of the RF power and magnetic field intensity.

  1. Utility of magnetic cell separation as a molecular sperm preparation technique.

    PubMed

    Said, Tamer M; Agarwal, Ashok; Zborowski, Maciej; Grunewald, Sonja; Glander, Hans-Juergen; Paasch, Uwe

    2008-01-01

    Assisted reproductive techniques (ARTs) have become the treatment of choice in many cases of infertility; however, the current success rates of these procedures remain suboptimal. Programmed cell death (apoptosis) most likely contributes to failed ART and to the decrease in sperm quality after cryopreservation. There is a likelihood that some sperm selected for ART will display features of apoptosis despite their normal appearance, which may be partially responsible for the low fertilization and implantation rates seen with ART. One of the features of apoptosis is the externalization of phosphatidylserine (PS) residues, which are normally present on the inner leaflet of the sperm plasma membrane. Colloidal superparamagnetic microbeads ( approximately 50 nm in diameter) conjugated with annexin V bind to PS and are used to separate dead and apoptotic spermatozoa by magnetic-activated cell sorting (MACS). Cells with externalized PS will bind to these microbeads, whereas nonapoptotic cells with intact membranes do not bind and could be used during ARTs. We have conducted a series of experiments to investigate whether the MACS technology could be used to improve ART outcomes. Our results clearly indicate that integrating MACS as a part of sperm preparation techniques will improve semen quality and cryosurvival rates by eliminating apoptotic sperm. Nonapoptotic spermatozoa prepared by MACS display higher quality in terms of routine sperm parameters and apoptosis markers. The higher sperm quality is represented by an increased oocyte penetration potential and cryosurvival rates. Thus, the selection of nonapoptotic spermatozoa by MACS should be considered to enhance ART success rates. PMID:18077822

  2. Rodent cell transformation and immediate early gene expression following 60-Hz magnetic field exposure.

    PubMed Central

    Balcer-Kubiczek, E K; Zhang, X F; Harrison, G H; McCready, W A; Shi, Z M; Han, L H; Abraham, J M; Ampey, L L; Meltzer, S J; Jacobs, M C; Davis, C C

    1996-01-01

    Some epidemiological studies suggest that exposure to power frequency magnetic fields (MFs) may be associated with an elevated risk of human cancer, but the experimental database remains limited and controversial. We investigated the hypothesis that 60-Hz MF action at the cellular level produces changes in gene expression that can result in neoplastic transformation. Twenty-four hour 200 microT continuous MF exposure produced negative results in two standard transformation systems (Syrian hamster embryo cells and C3H/10T1/2 murine fibroblasts) with or without postexposure to a chemical promoter. This prompted a reexamination of previously reported MF-induced changes in gene expression in human HL60 cells. Extensive testing using both coded and uncoded analyses was negative for an MF effect. Using the same exposure conditions as in the transformation studies, no MF-induced changes in ornithine decarboxylase expression were observed in C3H/10T1/2 cells, casting doubt on a promotional role of MF for the tested cells and experimental conditions. Images Figure 1. Figure 2. A Figure 2. B Figure 2. C Figure 2. D Figure 3. A Figure 3. B Figure 4. Figure 5. A Figure 5. B Figure 5. C Figure 5. D Figure 5. E Figure 6. A Figure 6. B Figure 6. C Figure 6. D Figure 6. E Figure 7. Figure 8. A Figure 8. B Figure 8. C Figure 9. Figure 10. A Figure 10. B PMID:8959408

  3. Dual-Modal Magnetic Resonance/Fluorescent Zinc Probes for Pancreatic β-Cell Mass Imaging

    PubMed Central

    Stasiuk, Graeme J; Minuzzi, Florencia; Sae-Heng, Myra; Rivas, Charlotte; Juretschke, Hans-Paul; Piemonti, Lorenzo; Allegrini, Peter R; Laurent, Didier; Duckworth, Andrew R; Beeby, Andrew; Rutter, Guy A; Long, Nicholas J

    2015-01-01

    Despite the contribution of changes in pancreatic β-cell mass to the development of all forms of diabetes mellitus, few robust approaches currently exist to monitor these changes prospectively in vivo. Although magnetic-resonance imaging (MRI) provides a potentially useful technique, targeting MRI-active probes to the β cell has proved challenging. Zinc ions are highly concentrated in the secretory granule, but they are relatively less abundant in the exocrine pancreas and in other tissues. We have therefore developed functional dual-modal probes based on transition-metal chelates capable of binding zinc. The first of these, Gd⋅1, binds ZnII directly by means of an amidoquinoline moiety (AQA), thus causing a large ratiometric Stokes shift in the fluorescence from λem=410 to 500 nm with an increase in relaxivity from r1=4.2 up to 4.9 mM−1 s−1. The probe is efficiently accumulated into secretory granules in β-cell-derived lines and isolated islets, but more poorly by non-endocrine cells, and leads to a reduction in T1 in human islets. In vivo murine studies of Gd⋅1 have shown accumulation of the probe in the pancreas with increased signal intensity over 140 minutes. PMID:25736590

  4. Quantitative imaging of cell-permeable magnetic resonance contrast agents using x-ray fluorescence.

    PubMed

    Endres, Paul J; Macrenaris, Keith W; Vogt, Stefan; Allen, Matthew J; Meade, Thomas J

    2006-01-01

    The inability to transduce cellular membranes is a limitation of current magnetic resonance imaging probes used in biologic and clinical settings. This constraint confines contrast agents to extracellular and vascular regions of the body, drastically reducing their viability for investigating processes and cycles in developmental biology. Conversely, a contrast agent with the ability to permeate cell membranes could be used in visualizing cell patterning, cell fate mapping, gene therapy, and, eventually, noninvasive cancer diagnosis. Therefore, we describe the synthesis and quantitative imaging of four contrast agents with the capability to cross cell membranes in sufficient quantity for detection. Each agent is based on the conjugation of a Gd(III) chelator with a cellular transduction moiety. Specifically, we coupled Gd(III)-diethylenetriaminepentaacetic acid DTPA and Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with an 8-amino acid polyarginine oligomer and an amphipathic stilbene molecule, 4-amino-4'-(N,N-dimethylamino)stilbene. The imaging modality that provided the best sensitivity and spatial resolution for direct detection of the contrast agents is synchrotron radiation x-ray fluorescence (SR-XRF). Unlike optical microscopy, SR-XRF provides two-dimensional images with resolution 10(3) better than (153)Gd gamma counting, without altering the agent by organic fluorophore conjugation. The transduction efficiency of the intracellular agents was evaluated by T(1) analysis and inductively coupled plasma mass spectrometry to determine the efficacy of each chelate-transporter combination. PMID:17150161

  5. Study on performance of magnetic fluorescent nanoparticles as gene carrier and location in pig kidney cells

    NASA Astrophysics Data System (ADS)

    Wang, Yan; Cui, Haixin; Sun, Changjiao; Du, Wei; Cui, Jinhui; Zhao, Xiang

    2013-03-01

    We evaluated the performance of green fluorescent magnetic Fe3O4 nanoparticles (NPs) as gene carrier and location in pig kidney cells. When the mass ratio of NPs to green fluorescent protein plasmid DNA reached 1:16 or above, DNA molecules can be combined completely with NPs, which indicates that the NPs have good ability to bind negative DNA. Atomic force microscopy (AFM) experiments were carried out to investigate the binding mechanism between NPs and DNA. AFM images show that individual DNA strands come off of larger pieces of netlike agglomerations and several spherical nanoparticles are attached to each individual DNA strand and interact with each other. The pig kidney cells were labelled with membrane-specific red fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate and nucleus-specific blue fluorescent dye 4',6-diamidino-2-phenylindole dihydrochloride. We found that green fluorescent nanoparticles can past the cell membrane and spread throughout the interior of the cell. The NPs seem to locate more frequently in the cytoplasm than in the nucleus.

  6. Surface engineered magnetic nanoparticles for specific immunotargeting of cadherin expressing cells

    NASA Astrophysics Data System (ADS)

    Moros, Maria; Delhaes, Flavien; Puertas, Sara; Saez, Berta; de la Fuente, Jesús M.; Grazú, Valeria; Feracci, Helene

    2016-02-01

    In spite of historic advances in cancer biology and recent development of sophisticated chemotherapeutics, the outlook for patients with advanced cancer is still grim. In this sense nanoparticles (NPs), through their unique physical properties, enable the development of new approaches for cancer diagnosis and treatment. Thus far the most used active targeting scheme involves NPs functionalization with antibodies specific to molecules overexpressed on cancer cell’s surface. Therefore, such active targeting relies on differences in NPs uptake kinetics rates between tumor and healthy cells. Many cancers of epithelial origin are associated with the inappropriate expression of non-epithelial cadherins (e.g. N-, P-, -11) with concomitant loss of E-cadherin. Such phenomenon named cadherin switching favors tumor development and metastasis via interactions of tumor cells with stromal components. That is why we optimized the oriented functionalization of fluorescently labelled magnetic NPs with a novel antibody specific for the extracellular domain of cadherin-11. The obtained Ab-NPs exhibited high specificity when incubated with two cell lines used as models of tumor and healthy cells. Thus, cadherin switching offers a great opportunity for the development of active targeting strategies aimed to improve the early detection and treatment of cancer.

  7. Trapping and dynamic manipulation of polystyrene beads mimicking circulating tumor cells using targeted magnetic/photoacoustic contrast agents

    NASA Astrophysics Data System (ADS)

    Wei, Chen-Wei; Xia, Jinjun; Pelivanov, Ivan; Hu, Xiaoge; Gao, Xiaohu; O'Donnell, Matthew

    2012-10-01

    Results on magnetically trapping and manipulating micro-scale beads circulating in a flow field mimicking metastatic cancer cells in human peripheral vessels are presented. Composite contrast agents combining magneto-sensitive nanospheres and highly optical absorptive gold nanorods were conjugated to micro-scale polystyrene beads. To efficiently trap the targeted objects in a fast stream, a dual magnet system consisting of two flat magnets to magnetize (polarize) the contrast agent and an array of cone magnets producing a sharp gradient field to trap the magnetized contrast agent was designed and constructed. A water-ink solution with an optical absorption coefficient of 10 cm-1 was used to mimic the optical absorption of blood. Magnetomotive photoacoustic imaging helped visualize bead trapping, dynamic manipulation of trapped beads in a flow field, and the subtraction of stationary background signals insensitive to the magnetic field. The results show that trafficking micro-scale objects can be effectively trapped in a stream with a flow rate up to 12 ml/min and the background can be significantly (greater than 15 dB) suppressed. It makes the proposed method very promising for sensitive detection of rare circulating tumor cells within high flow vessels with a highly absorptive optical background.

  8. Characterization of Iron-Oxide Loaded Adult Stem Cells for Magnetic Particle Imaging in Targeted Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Lüdtke-Buzug, Kerstin; Rapoport, Daniel Hans; Schneider, Dagmar

    2010-12-01

    Recently, magnetic particle imaging (MPI) has been presented as a new method for the measurement of the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIONs). MPI is based on the nonlinear magnetization response of nanoparticles that are subjected to a sinusoidal magnetic field. Spatial resolution and signal to noise ratio of MPI depend on the particle quality. This is particularly important when stem cells shall be tracked with MPI. Stem cell-based treatment is an upcoming technology in targeted cancer-therapy. In this study, we analyzed the particle quality of newly developed dextran-coated SPIONs—with respect to their response in the imaging experiment—using magnetic particle spectrometry. The uptake of dextran-coated SPIONs into rat and human adult stem cells was monitored via transmission electron microscopy. Furthermore, adult stem cells were incubated with FITC-dextran-coated SPIONs and stained for confocal laser scanning microscopy. The dextran- and FITC-dextran coated SPIONs were localized in the cytoplasm of rat and human adult stem cells. MPI promises real-time imaging with high spatial resolution at high sensitivity. Our data support iron oxide loaded adult stem cells as a powerful tool for targeted cancer therapy.

  9. Folic acid conjugated magnetic iron oxide nanoparticles for nondestructive separation and detection of ovarian cancer cells from whole blood.

    PubMed

    Liu, Wenting; Nie, Liju; Li, Fulai; Aguilar, Zoraida P; Xu, Hong; Xiong, Yonghua; Fu, Fen; Xu, Hengyi

    2016-01-01

    Because of the lack of early screening strategies, ovarian cancer is the most deadly cause of gynecologic malignancies. This paper describes an effective method for the separation and detection of ovarian cancer cells from female whole blood, using folic acid (FA) conjugated magnetic iron oxide nanoparticles (IO-FA nanoparticles). The IO nanoparticles were synthesized by thermal decomposition and then covalently conjugated with FA. The IO-FA nanoparticles were stably attached to the surface of ovarian cancer cells by coupling to the over-expressed folate receptor (FR), thereby making the cells magnetic. These "magnetic cells" were separated from the complex blood matrix without destruction under a magnetic field. The separation efficiency was as high as 61.3% when the abundance of spiked ovarian cancer SKOV3 cells was as low as 5 × 10(-5)%. We also successfully detected five (5) out of ten (10) metastatic ovarian cancer patients' whole blood. This study suggested the feasibility of early detecting of metastatic ovarian cancer cells, which may potentially improve the ovarian cancers patients' overall survival rate for clinical applications. PMID:26478922

  10. Microgel iron oxide nanoparticles for tracking human fetal mesenchymal stem cells through magnetic resonance imaging.

    PubMed

    Lee, Eddy S M; Chan, Jerry; Shuter, Borys; Tan, Lay Geok; Chong, Mark S K; Ramachandra, Durrgah L; Dawe, Gavin S; Ding, Jun; Teoh, Swee Hin; Beuf, Olivier; Briguet, Andre; Tam, Kam Chiu; Choolani, Mahesh; Wang, Shih-Chang

    2009-08-01

    Stem cell transplantation for regenerative medicine has made significant progress in various injury models, with the development of modalities to track stem cell fate and migration post-transplantation being currently pursued rigorously. Magnetic resonance imaging (MRI) allows serial high-resolution in vivo detection of transplanted stem cells labeled with iron oxide particles, but has been hampered by low labeling efficiencies. Here, we describe the use of microgel iron oxide (MGIO) particles of diameters spanning 100-750 nm for labeling human fetal mesenchymal stem cells (hfMSCs) for MRI tracking. We found that MGIO particle uptake by hfMSCs was size dependent, with 600-nm MGIO (M600) particles demonstrating three- to sixfold higher iron loading than the clinical particle ferucarbotran (33-263 versus 9.6-42.0 pg iron/hfMSC; p < .001). Cell labeling with either M600 particles or ferucarbotran did not affect either cellular proliferation or tri-lineage differentiation into osteoblasts, adipocytes, and chondrocytes, despite differences in gene expression on a genome-wide microarray analysis. Cell tracking in a rat photothrombotic stroke model using a clinical 1.5-T MRI scanner demonstrated the migration of labeled hfMSCs from the contralateral cortex to the stroke injury, with M600 particles achieving a five- to sevenfold higher sensitivity for MRI detection than ferucarbotran (p < .05). However, model-related cellular necrosis and acute inflammation limited the survival of hfMSCs beyond 5-12 days. The use of M600 particles allowed high detection sensitivity with low cellular toxicity to be achieved through a simple incubation protocol, and may thus be useful for cellular tracking using standard clinical MRI scanners. PMID:19544438

  11. Transcranial Magnetic Stimulation of Human Adult Stem Cells in the Mammalian Brain

    PubMed Central

    Kremer, Karlea L.; Smith, Ashleigh E.; Sandeman, Lauren; Inglis, Joshua M.; Ridding, Michael C.; Koblar, Simon A.

    2016-01-01

    Introduction: The burden of stroke on the community is growing, and therefore, so is the need for a therapy to overcome the disability following stroke. Cellular-based therapies are being actively investigated at a pre-clinical and clinical level. Studies have reported the beneficial effects of exogenous stem cell implantation, however, these benefits are also associated with limited survival of implanted stem cells. This exploratory study investigated the use of transcranial magnetic stimulation (TMS) as a complementary therapy to increase stem cell survival following implantation of human dental pulp stem cells (DPSC) in the rodent cortex. Methods: Sprague-Dawley rats were anesthetized and injected with 6 × 105 DPSC or control media via an intracranial injection, and then received real TMS (TMS0.2 Hz) or sham TMS (TMSsham) every 2nd day beginning on day 3 post DPSC injection for 2 weeks. Brain sections were analyzed for the survival, migration and differentiation characteristics of the implanted cells. Results: In animals treated with DPSC and TMS0.2 Hz there were significantly less implanted DPSC and those that survived remained in the original cerebral hemisphere compared to animals that received TMSsham. The surviving implanted DPSC in TMS0.2 Hz were also found to express the apoptotic marker Caspase-3. Conclusions: We suggest that TMS at this intensity may cause an increase in glutamate levels, which promotes an unfavorable environment for stem cell implantation, proliferation and differentiation. It should be noted that only one paradigm of TMS was tested as this was conducted as a exploratory study, and further TMS paradigms should be investigated in the future. PMID:27013982

  12. Polyaniline shell cross-linked Fe3O4 magnetic nanoparticles for heat activated killing of cancer cells.

    PubMed

    Rana, Suman; Jadhav, Neena V; Barick, K C; Pandey, B N; Hassan, P A

    2014-08-28

    Superparamagnetic Fe3O4 nanoparticles are appealing materials for heat activated killing of cancer cells. Here, we report a novel method to enhance the heat activated killing of cancer cells under an AC magnetic field (AMF) by introducing a polyaniline impregnated shell onto the surface of Fe3O4 nanoparticles. These polyaniline shell cross-linked magnetic nanoparticles (PSMN) were prepared by in situ polymerization of aniline hydrochloride on the surface of carboxyl PEGylated Fe3O4 nanoparticles. XRD and TEM analyses revealed the formation of single phase inverse spinel Fe3O4 nanoparticles of a size of about 10 nm. The successful growth of the polyaniline shell on the surface of carboxyl PEGylated magnetic nanoparticles (CPMN) is evident from FTIR spectra, DLS, TGA, zeta-potential and magnetic measurements. Both CPMN and PSMN show good colloidal stability, superparamagnetic behavior at room temperature and excellent heating efficacy under AMF. It has been observed that the heating efficacy of PSMN under AMF was slightly reduced as compared to that of CPMN. The enhanced toxicity of PSMN to cancer cells under AMF suggests their strong potential for magnetic hyperthermia. Furthermore, PSMN shows high loading affinity for an anticancer drug (doxorubicin), its sustained release and substantial internalization in tumor cells. PMID:24948377

  13. Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells

    PubMed Central

    Chen, Daozhen; Tang, Qiusha; Li, Xiangdong; Zhou, Xiaojin; Zang, Jia; Xue, Wen-qun; Xiang, Jing-ying; Guo, Cai-qin

    2012-01-01

    Background The objective of this study was to evaluate the synthesis and biocompatibility of Fe3O4 nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells. Methods Magnetic Fe3O4 nanoparticles were prepared using a coprecipitation method. The appearance, structure, phase composition, functional groups, surface charge, magnetic susceptibility, and release in vitro were characterized by transmission electron microscopy, x-ray diffraction, scanning electron microscopy-energy dispersive x-ray spectroscopy, and a vibrating sample magnetometer. Blood toxicity, in vitro toxicity, and genotoxicity were investigated. Therapeutic effects were evaluated by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] and flow cytometry assays. Results Transmission electron microscopy revealed that the shapes of the Fe3O4 nanoparticles were approximately spherical, with diameters of about 26.1 ± 5.2 nm. Only the spinel phase was indicated in a comparison of the x-ray diffraction data with Joint Corporation of Powder Diffraction Standards (JCPDS) X-ray powder diffraction files. The O-to-Fe ratio of the Fe3O4 was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe3O4. The vibrating sample magnetometer hysteresis loop suggested that the Fe3O4 nanoparticles were superparamagnetic at room temperature. MTT experiments showed that the toxicity of the material in mouse fibroblast (L-929) cell lines was between Grade 0 to Grade 1, and that the material lacked hemolysis activity. The acute toxicity (LD50) was 8.39 g/kg. Micronucleus testing showed no genotoxic effects. Pathomorphology and blood biochemistry testing demonstrated that the Fe3O4 nanoparticles had no effect on the main organs and blood biochemistry in a rabbit model. MTT and flow cytometry assays revealed that Fe3O4 nano magnetofluid thermotherapy inhibited MCF-7

  14. Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media.

    PubMed

    Tengood, Jillian E; Alferiev, Ivan S; Zhang, Kehan; Fishbein, Ilia; Levy, Robert J; Chorny, Michael

    2014-03-18

    The fate of nanoparticle (NP) formulations in the multifaceted biological environment is a key determinant of their biocompatibility and therapeutic performance. An understanding of the degradation patterns of different types of clinically used and experimental NP formulations is currently incomplete, posing an unmet need for novel analytical tools providing unbiased quantitative measurements of NP disassembly directly in the medium of interest and in conditions relevant to specific therapeutic/diagnostic applications. In the present study, this challenge was addressed with an approach enabling real-time in situ monitoring of the integrity status of NPs in cells and biomimetic media using Förster resonance energy transfer (FRET). Disassembly of polylactide-based magnetic NPs (MNPs) was investigated in a range of model biomimetic media and in cultured vascular cells using an experimentally established quantitative correlation between particle integrity and FRET efficiency controlled through adjustments in the spectral overlap between two custom-synthesized polylactide-fluorophore (boron dipyrromethene) conjugates incorporated in MNPs. The results suggest particle disassembly governed by diffusion-reaction processes with kinetics strongly dependent on conditions promoting release of oligomeric fragments from the particle matrix. Thus, incubation in gels simulating the extracellular environment and in protein-rich serum resulted in notably lower and higher MNP decomposition rates, respectively, compared with nonviscous liquid buffers. The diffusion-reaction mechanism also is consistent with a significant cell growth-dependent acceleration of MNP processing in dividing vs. contact-inhibited vascular cells. The FRET-based analytical strategy and experimental results reported herein may facilitate the development and inform optimization of biodegradable nanocarriers for cell and drug delivery applications. PMID:24591603

  15. Functional investigations on human mesenchymal stem cells exposed to magnetic fields and labeled with clinically approved iron nanoparticles

    PubMed Central

    2010-01-01

    Background For clinical applications of mesenchymal stem cells (MSCs), labeling and tracking is crucial to evaluate cell distribution and homing. Magnetic resonance imaging (MRI) has been successfully established detecting MSCs labeled with superparamagnetic particles of iron oxide (SPIO). Despite initial reports that labeling of MSCs with SPIO is safe without affecting the MSC's biology, recent studies report on influences of SPIO-labeling on metabolism and function of MSCs. Exposition of cells and tissues to high magnetic fields is the functional principle of MRI. In this study we established innovative labeling protocols for human MSCs using clinically established SPIO in combination with magnetic fields and investigated on functional effects (migration assays, quantification of colony forming units, analyses of gene and protein expression and analyses on the proliferation capacity, the viability and the differentiation potential) of magnetic fields on unlabeled and labeled human MSCs. To evaluate the imaging properties, quantification of the total iron load per cell (TIL), electron microscopy, and MRI at 3.0 T were performed. Results Human MSCs labeled with SPIO permanently exposed to magnetic fields arranged and grew according to the magnetic flux lines. Exposure of MSCs to magnetic fields after labeling with SPIO significantly enhanced the TIL compared to SPIO labeled MSCs without exposure to magnetic fields resulting in optimized imaging properties (detection limit: 1,000 MSCs). Concerning the TIL and the imaging properties, immediate exposition to magnetic fields after labeling was superior to exposition after 24 h. On functional level, exposition to magnetic fields inhibited the ability of colony formation of labeled MSCs and led to an enhanced expression of lipoprotein lipase and peroxisome proliferator-activated receptor-γ in labeled MSCs under adipogenic differentiation, and to a reduced expression of alkaline phosphatase in unlabeled MSCs under

  16. Transient electrically detected magnetic resonance spectroscopy applied to organic solar cells

    SciTech Connect

    Kraffert, Felix; Steyrleuthner, Robert; Meier, Christoph; Bittl, Robert; Behrends, Jan

    2015-07-27

    The influence of light-induced paramagnetic states on the photocurrent generated by polymer:fullerene solar cells is studied using spin-sensitive techniques in combination with laser-flash excitation. For this purpose, we developed a setup that allows for simultaneous detection of transient electron paramagnetic resonance as well as transient electrically detected magnetic resonance (trEDMR) signals from fully processed and encapsulated solar cells. Combining both techniques provides a direct link between photoinduced triplet excitons, charge transfer states, and free charge carriers as well as their influence on the photocurrent generated by organic photovoltaic devices. Our results obtained from solar cells based on poly(3-hexylthiophene) as electron donor and a fullerene-based electron acceptor show that the resonant signals observed in low-temperature (T = 80 K) trEDMR spectra can be attributed to positive polarons in the polymer as well as negative polarons in the fullerene phase, indicating that both centers are involved in spin-dependent processes that directly influence the photocurrent.

  17. Extremely Low Frequency Magnetic Fields Induce Spermatogenic Germ Cell Apoptosis: Possible Mechanism

    PubMed Central

    Lee, Sang-Kon; Park, Sungman; Gimm, Yoon-Myoung; Kim, Yoon-Won

    2014-01-01

    The energy generated by an extremely low frequency electromagnetic field (ELF-EMF) is too weak to directly induce genotoxicity. However, it is reported that an extremely low frequency magnetic field (ELF-MF) is related to DNA strand breakage and apoptosis. The testes that conduct spermatogenesis through a dynamic cellular process involving meiosis and mitosis seem vulnerable to external stress such as heat, MF exposure, and chemical or physical agents. Nevertheless the results regarding adverse effects of ELF-EMF on human or animal reproductive functions are inconclusive. According to the guideline of the International Commission on Non-Ionizing Radiation Protection (ICNIRP; 2010) for limiting exposure to time-varying MF (1 Hz to 100 kHz), overall conclusion of epidemiologic studies has not consistently shown an association between human adverse reproductive outcomes and maternal or paternal exposure to low frequency fields. In animal studies there is no compelling evidence of causal relationship between prenatal development and ELF-MF exposure. However there is increasing evidence that EL-EMF exposure is involved with germ cell apoptosis in testes. Biophysical mechanism by which ELF-MF induces germ cell apoptosis has not been established. This review proposes the possible mechanism of germ cell apoptosis in testes induced by ELF-MF. PMID:25025060

  18. DNA recovery from a single bacterial cell using charge-reversible magnetic nanoparticles.

    PubMed

    Maeda, Yoshiaki; Toyoda, Takahiro; Mogi, Takeyuki; Taguchi, Tomoyuki; Tanaami, Takeo; Yoshino, Tomoko; Matsunaga, Tadashi; Tanaka, Tsuyoshi

    2016-03-01

    Highly efficient DNA recovery from a single bacterial cell was performed by means of imidazole-modified magnetic nanoparticles (Imi-MNPs). The modification by imidazole was confirmed by Fourier transform infrared spectroscopy. The Imi-MNPs were highly efficient at DNA extraction owing to the charge-reversible properties of Imi-MNPs, whereby DNA is attached to the particles at low pH and eluted at high pH because of electrostatic interactions. The DNA recovery ratio was determined by real-time PCR, and it revealed that complete recovery was guaranteed at ≥10(3) genome copies of Bacillus subtilis. Extraction of DNA from single bacterial cells was followed by PCR amplification of 16S rDNA and capillary electrophoresis. We achieved detection of single bacterial cells with a detection rate of 80%. We believe that our DNA recovery strategy may serve as a powerful tool for efficient DNA extraction and should be useful for quality control of cosmetics, foods, and pharmaceutical products. PMID:26704992

  19. SpyLigase peptide–peptide ligation polymerizes affibodies to enhance magnetic cancer cell capture

    PubMed Central

    Fierer, Jacob O.; Veggiani, Gianluca; Howarth, Mark

    2014-01-01

    Individual proteins can now often be modified with atomic precision, but there are still major obstacles to connecting proteins into larger assemblies. To direct protein assembly, ideally, peptide tags would be used, providing the minimal perturbation to protein function. However, binding to peptides is generally weak, so assemblies are unstable over time and disassemble with force or harsh conditions. We have recently developed an irreversible protein–peptide interaction (SpyTag/SpyCatcher), based on a protein domain from Streptococcus pyogenes, that locks itself together via spontaneous isopeptide bond formation. Here we develop irreversible peptide–peptide interaction, through redesign of this domain and genetic dissection into three parts: a protein domain termed SpyLigase, which now ligates two peptide tags to each other. All components expressed efficiently in Escherichia coli and peptide tags were reactive at the N terminus, at the C terminus, or at internal sites. Peptide–peptide ligation enabled covalent and site-specific polymerization of affibodies or antibodies against the tumor markers epidermal growth factor receptor (EGFR) and HER2. Magnetic capture of circulating tumor cells (CTCs) is one of the most promising approaches to improve cancer prognosis and management, but CTC capture is limited by inefficient recovery of cells expressing low levels of tumor antigen. SpyLigase-assembled protein polymers made possible the isolation of cancerous cells expressing lower levels of tumor antigen and should have general application in enhancing molecular capture. PMID:24639550

  20. Estimation of cell membrane permeability of the rat brain using diffusion magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Imae, T.; Shinohara, H.; Sekino, M.; Ueno, S.; Ohsaki, H.; Mima, K.; Ootomo, K.

    2008-04-01

    We propose a method to noninvasively evaluate the permeability of the cell membrane in the rat brain using diffusion magnetic resonance imaging (MRI). Diffusion MRI reflects the intra- and extracellular diffusion coefficients of water and cell membrane permeability. The images were acquired using a 4.7T MRI system with applications to motion-probing gradients in six directions. Numerical simulations based on the finite-difference method were carried out for estimating diffusion MRI signals with various combinations of membrane permeability and intracellular diffusion coefficient values. We defined an evaluative function as the difference between the signals estimated by simulation and experimentally obtained signals. We found that the combination of membrane permeability and intracellular diffusion coefficient in the simulation corresponding to the minimum value of the evaluative function leads to an estimation of these properties of the rat brain. The estimated intracellular diffusion coefficient and membrane permeability were (1.3±0.1)×10-3mm2/s and 74±23μm/s, respectively. Our method is useful for noninvasively estimating the cell membrane permeability of biological tissues, and is easily applicable to human tissues.

  1. Particle-in-Cell Modeling of Magnetized Argon Plasma Flow Through Small Mechanical Apertures

    SciTech Connect

    Adam B. Sefkow and Samuel A. Cohen

    2009-04-09

    Motivated by observations of supersonic argon-ion flow generated by linear helicon-heated plasma devices, a three-dimensional particle-in-cell (PIC) code is used to study whether stationary electrostatic layers form near mechanical apertures intersecting the flow of magnetized plasma. By self-consistently evaluating the temporal evolution of the plasma in the vicinity of the aperture, the PIC simulations characterize the roles of the imposed aperture and applied magnetic field on ion acceleration. The PIC model includes ionization of a background neutral-argon population by thermal and superthermal electrons, the latter found upstream of the aperture. Near the aperture, a transition from a collisional to a collisionless regime occurs. Perturbations of density and potential, with mm wavelengths and consistent with ion acoustic waves, propagate axially. An ion acceleration region of length ~ 200-300 λD,e forms at the location of the aperture and is found to be an electrostatic double layer, with axially-separated regions of net positive and negative charge. Reducing the aperture diameter or increasing its length increases the double layer strength.

  2. Anvil cell gasket design for high pressure nuclear magnetic resonance experiments beyond 30 GPa

    SciTech Connect

    Meier, Thomas; Haase, Jürgen

    2015-12-15

    Nuclear magnetic resonance (NMR) experiments are reported at up to 30.5 GPa of pressure using radiofrequency (RF) micro-coils with anvil cell designs. These are the highest pressures ever reported with NMR, and are made possible through an improved gasket design based on nano-crystalline powders embedded in epoxy resin. Cubic boron-nitride (c-BN), corundum (α-Al{sub 2}O{sub 3}), or diamond based composites have been tested, also in NMR experiments. These composite gaskets lose about 1/2 of their initial height up to 30.5 GPa, allowing for larger sample quantities and preventing damages to the RF micro-coils compared to precipitation hardened CuBe gaskets. It is shown that NMR shift and resolution are less affected by the composite gaskets as compared to the more magnetic CuBe. The sensitivity can be as high as at normal pressure. The new, inexpensive, and simple to engineer gaskets are thus superior for NMR experiments at high pressures.

  3. Anvil cell gasket design for high pressure nuclear magnetic resonance experiments beyond 30 GPa.

    PubMed

    Meier, Thomas; Haase, Jürgen

    2015-12-01

    Nuclear magnetic resonance (NMR) experiments are reported at up to 30.5 GPa of pressure using radiofrequency (RF) micro-coils with anvil cell designs. These are the highest pressures ever reported with NMR, and are made possible through an improved gasket design based on nano-crystalline powders embedded in epoxy resin. Cubic boron-nitride (c-BN), corundum (α-Al2O3), or diamond based composites have been tested, also in NMR experiments. These composite gaskets lose about 1/2 of their initial height up to 30.5 GPa, allowing for larger sample quantities and preventing damages to the RF micro-coils compared to precipitation hardened CuBe gaskets. It is shown that NMR shift and resolution are less affected by the composite gaskets as compared to the more magnetic CuBe. The sensitivity can be as high as at normal pressure. The new, inexpensive, and simple to engineer gaskets are thus superior for NMR experiments at high pressures. PMID:26724046

  4. Anvil cell gasket design for high pressure nuclear magnetic resonance experiments beyond 30 GPa

    NASA Astrophysics Data System (ADS)

    Meier, Thomas; Haase, Jürgen

    2015-12-01

    Nuclear magnetic resonance (NMR) experiments are reported at up to 30.5 GPa of pressure using radiofrequency (RF) micro-coils with anvil cell designs. These are the highest pressures ever reported with NMR, and are made possible through an improved gasket design based on nano-crystalline powders embedded in epoxy resin. Cubic boron-nitride (c-BN), corundum (α-Al2O3), or diamond based composites have been tested, also in NMR experiments. These composite gaskets lose about 1/2 of their initial height up to 30.5 GPa, allowing for larger sample quantities and preventing damages to the RF micro-coils compared to precipitation hardened CuBe gaskets. It is shown that NMR shift and resolution are less affected by the composite gaskets as compared to the more magnetic CuBe. The sensitivity can be as high as at normal pressure. The new, inexpensive, and simple to engineer gaskets are thus superior for NMR experiments at high pressures.

  5. Two-dimensional particle-in-cell simulations of transport in a magnetized electronegative plasma

    SciTech Connect

    Kawamura, E.; Lichtenberg, A. J.; Lieberman, M. A.

    2010-11-15

    Particle transport in a uniformly magnetized electronegative plasma is studied in two-dimensional (2D) geometry with insulating (dielectric) boundaries. A 2D particle-in-cell (PIC) code is employed, with the results compared to analytic one-dimensional models that approximate the end losses as volume losses. A modified oxygen reaction set is used to scale to the low densities used in PIC codes and also to approximately model other gases. The principal study is the limiting of the transverse electron flow due to strong electron magnetization. The plasma in the PIC calculation is maintained by axial currents that vary across the transverse dimension. For a cosine current profile nearly uniform electron temperature is obtained, which at the B-fields studied (600-1200 G) give a small but significant fraction (0.25 or less) of electron to negative ion transverse loss. For a more transverse-confined current, and approximating the higher mass and attachment reaction rate of iodine, the fraction of electron to negative ion transverse loss can be made very small. The models which have been constructed reasonably approximate the PIC results and indicate that the cross-field transport is nearly classical.

  6. Lactoferrin conjugated iron oxide nanoparticles for targeting brain glioma cells in magnetic particle imaging

    NASA Astrophysics Data System (ADS)

    Tomitaka, Asahi; Arami, Hamed; Gandhi, Sonu; Krishnan, Kannan M.

    2015-10-01

    Magnetic Particle Imaging (MPI) is a new real-time imaging modality, which promises high tracer mass sensitivity and spatial resolution directly generated from iron oxide nanoparticles. In this study, monodisperse iron oxide nanoparticles with median core diameters ranging from 14 to 26 nm were synthesized and their surface was conjugated with lactoferrin to convert them into brain glioma targeting agents. The conjugation was confirmed with the increase of the hydrodynamic diameters, change of zeta potential, and Bradford assay. Magnetic particle spectrometry (MPS), performed to evaluate the MPI performance of these nanoparticles, showed no change in signal after lactoferrin conjugation to nanoparticles for all core diameters, suggesting that the MPI signal is dominated by Néel relaxation and thus independent of hydrodynamic size difference or presence of coating molecules before and after conjugations. For this range of core sizes (14-26 nm), both MPS signal intensity and spatial resolution improved with increasing core diameter of nanoparticles. The lactoferrin conjugated iron oxide nanoparticles (Lf-IONPs) showed specific cellular internalization into C6 cells with a 5-fold increase in MPS signal compared to IONPs without lactoferrin, both after 24 h incubation. These results suggest that Lf-IONPs can be used as tracers for targeted brain glioma imaging using MPI.

  7. Explicit time-reversible orbit integration in Particle In Cell codes with static homogeneous magnetic field

    NASA Astrophysics Data System (ADS)

    Patacchini, L.; Hutchinson, I. H.

    2009-04-01

    A new explicit time-reversible orbit integrator for the equations of motion in a static homogeneous magnetic field - called Cyclotronic integrator - is presented. Like Spreiter and Walter's Taylor expansion algorithm, for sufficiently weak electric field gradients this second order method does not require a fine resolution of the Larmor motion; it has however the essential advantage of being symplectic, hence time-reversible. The Cyclotronic integrator is only subject to a linear stability constraint ( ΩΔ t < π, Ω being the Larmor angular frequency), and is therefore particularly suitable to electrostatic Particle In Cell codes with uniform magnetic field where Ω is larger than any other characteristic frequency, yet a resolution of the particles' gyromotion is required. Application examples and a detailed comparison with the well-known (time-reversible) Boris algorithm are presented; it is in particular shown that implementation of the Cyclotronic integrator in the kinetic codes SCEPTIC and Democritus can reduce the cost of orbit integration by up to a factor of ten.

  8. Static magnetic field of 6 mT induces apoptosis and alters cell cycle in p53 mutant Jurkat cells.

    PubMed

    Ahmadianpour, Mohammad Reza; Abdolmaleki, Parviz; Mowla, Seyed Javad; Hosseinkhani, Saman

    2013-03-01

    This study aimed to investigate the effect of 6 milliTesla (mT) static magnetic field (SMF) on apoptosis induction and cell cycle alteration in T-lymphoblastoid Jurkat E6.1 cells. Exposure of human p53 mutant Jurkat cells to 6 mT SMF resulted in apoptosis, which was detected by luminometric and flow cytometric analysis also, phosphorylated ATM and E2F1 proteins were detected by western blot analysis. Based on luminescence detection data, apoptosis initiated 36 h after exposure to 6 mT SMF. Apoptosis also reached its maximum rate 48 h after treatment. Flow cytometric analysis revealed a temporary G2 arrest after exposure to 6 mT SMF. Indeed, cellular population of S and G2 phases was increased. Based on reports of other investigations on the effect of magnetic fields on Ca2+flux changes in cell membranes and the effect of MFs on free radical formation, it can be suggested that the magnetic fields may induce the apoptosis and alter the cell population in different cell cycle phases of Jurkat cells via changing the Ca2+fluxes through cell membranes and playing a role in free radical formation. Western blot analysis showed that the amount of phosphorylated ATM and E2F1 proteins were increased in treated cells. The results of luminometric and flow cytometric detection did not show a significant difference in the apoptosis rate between 6 h-treated and 24 h-treated cells by 6 mT SMF. Thus, 6 mT SMF can induce apoptosis and alter cell cycle in Jurkat cells via a p53-independent pathway. PMID:23320430

  9. CpG oligodeoxynucleotide-loaded PAMAM dendrimer-coated magnetic nanoparticles promote apoptosis in breast cancer cells.

    PubMed

    Taghavi Pourianazar, Negar; Gunduz, Ufuk

    2016-03-01

    One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which can generate a signal cascade for cell death. In our study, we utilized three-layer magnetic nanoparticles composed of a Fe3O4 magnetic core, an aminosilane (APTS) interlayer and a cationic poly(amidoamine) (PAMAM) dendrimer. This will be a novel targeted delivery system to enhance the accumulation of CpG-ODN molecules in tumor cells. The validation of CpG-ODN binding to DcMNPs was performed using agarose gel electrophoresis, UV-spectrophotometer, XPS analyses. Cytotoxicity of conjugates was assessed in MDA-MB231 and SKBR3 cancer cells based on cell viability by XTT assay and flow cytometric analysis. Our results indicated that the synthesized DcMNPs having high positive charges on their surface could attach to CpG-ODN molecules via electrostatic means. These nanoparticles with the average sizes of 40±10nm bind to CpG-ODN molecules efficiently and induce cell death in MDA-MB231 and SKBR3 tumor cells and could be considered a suitable targeted delivery system for CpG-ODN in biomedical applications. The magnetic core of these nanoparticles represents a promising option for selective drug targeting as they can be concentrated and held in position by means of an external magnetic field. PMID:26898428

  10. Application of pulsed-magnetic field enhances non-viral gene delivery in primary cells from different origins

    NASA Astrophysics Data System (ADS)

    Kamau Chapman, Sarah W.; Hassa, Paul O.; Koch-Schneidemann, Sabine; von Rechenberg, Brigitte; Hofmann-Amtenbrink, Margarethe; Steitz, Benedikt; Petri-Fink, Alke; Hofmann, Heinrich; Hottiger, Michael O.

    Primary cell lines are more difficult to transfect when compared to immortalized/transformed cell lines, and hence new techniques are required to enhance the transfection efficiency in these cells. We isolated and established primary cultures of synoviocytes, chondrocytes, osteoblasts, melanocytes, macrophages, lung fibroblasts, and embryonic fibroblasts. These cells differed in several properties, and hence were a good representative sample of cells that would be targeted for expression and delivery of therapeutic genes in vivo. The efficiency of gene delivery in all these cells was enhanced using polyethylenimine-coated polyMAG magnetic nanoparticles, and the rates (17-84.2%) surpassed those previously achieved using other methods, especially in cells that are difficult to transfect. The application of permanent and pulsating magnetic fields significantly enhanced the transfection efficiencies in synoviocytes, chondrocytes, osteoblasts, melanocytes and lung fibroblasts, within 5 min of exposure to these magnetic fields. This is an added advantage for future in vivo applications, where rapid gene delivery is required before systemic clearance or filtration of the gene vectors occurs.

  11. Application of a weak magnetic field to improve microbial fuel cell performance.

    PubMed

    Tong, Zhong-Hua; Yu, Han-Qing; Li, Wen-Wei; Wang, Yun-Kun; Sun, Min; Liu, Xian-Wei; Sheng, Guo-Ping

    2015-12-01

    Microbial fuel cells (MFCs) have emerged as a promising technology for wastewater treatment with concomitant energy production but the performance is usually limited by low microbial activities. This has spurred intensive research interest for microbial enhancement. This study demonstrated an interesting stimulation effect of a static magnetic field (MF) on sludge-inoculated MFCs and explored into the mechanisms. The implementation of a 100-mT MF accelerated the reactor startup and led to increased electricity generation. Under the MF exposure, the activation loss of the MFC was decreased, but there was no increased secretion of redox mediators. Thus, the MF effect was mainly due to enhanced bioelectrochemical activities of anodic microorganisms, which are likely attributed to the oxidative stress and magnetohydrodynamic effects under an MF exposure. This work implies that weak MF may be applied as a simple and effective approach to stimulate microbial activities for various bioelectrochemical energy production and decontamination applications. PMID:26410373

  12. Effects of Magnetic Nanoparticles and External Magnetostatic Field on the Bulk Heterojunction Polymer Solar Cells

    SciTech Connect

    Wang, Kai; Yi, Chao; Liu, Chang; Hu, Xiaowen; Chuang, Steven; Gong, Xiong

    2015-03-18

    The price of energy to separate tightly bound electron-hole pair (or charge-transfer state) and extract freely movable charges from low-mobility materials represents fundamental losses for many low-cost photovoltaic devices. In bulk heterojunction (BHJ) polymer solar cells (PSCs), approximately 50% of the total efficiency lost among all energy loss pathways is due to the photogenerated charge carrier recombination within PSCs and low charge carrier mobility of disordered organic materials. To address these issues, we introduce magnetic nanoparticles (MNPs) and orientate these MNPS within BHJ composite by an external magnetostatic field. Over 50% enhanced efficiency was observed from BHJ PSCs incorporated with MNPs and an external magnetostatic field alignment when compared to the control BHJ PSCs. The optimization of BHJ thin film morphology, suppression of charge carrier recombination, and enhancement in charge carrier collection result in a greatly increased short-circuit current density and fill factor, as a result, enhanced power conversion efficiency.

  13. Effects of Magnetic Nanoparticles and External Magnetostatic Field on the Bulk Heterojunction Polymer Solar Cells

    NASA Astrophysics Data System (ADS)

    Wang, Kai; Yi, Chao; Liu, Chang; Hu, Xiaowen; Chuang, Steven; Gong, Xiong

    2015-03-01

    The price of energy to separate tightly bound electron-hole pair (or charge-transfer state) and extract freely movable charges from low-mobility materials represents fundamental losses for many low-cost photovoltaic devices. In bulk heterojunction (BHJ) polymer solar cells (PSCs), approximately 50% of the total efficiency lost among all energy loss pathways is due to the photogenerated charge carrier recombination within PSCs and low charge carrier mobility of disordered organic materials. To address these issues, we introduce magnetic nanoparticles (MNPs) and orientate these MNPS within BHJ composite by an external magnetostatic field. Over 50% enhanced efficiency was observed from BHJ PSCs incorporated with MNPs and an external magnetostatic field alignment when compared to the control BHJ PSCs. The optimization of BHJ thin film morphology, suppression of charge carrier recombination, and enhancement in charge carrier collection result in a greatly increased short-circuit current density and fill factor, as a result, enhanced power conversion efficiency.

  14. Effects of Magnetic Nanoparticles and External Magnetostatic Field on the Bulk Heterojunction Polymer Solar Cells

    PubMed Central

    Wang, Kai; Yi, Chao; Liu, Chang; Hu, Xiaowen; Chuang, Steven; Gong, Xiong

    2015-01-01

    The price of energy to separate tightly bound electron-hole pair (or charge-transfer state) and extract freely movable charges from low-mobility materials represents fundamental losses for many low-cost photovoltaic devices. In bulk heterojunction (BHJ) polymer solar cells (PSCs), approximately 50% of the total efficiency lost among all energy loss pathways is due to the photogenerated charge carrier recombination within PSCs and low charge carrier mobility of disordered organic materials. To address these issues, we introduce magnetic nanoparticles (MNPs) and orientate these MNPS within BHJ composite by an external magnetostatic field. Over 50% enhanced efficiency was observed from BHJ PSCs incorporated with MNPs and an external magnetostatic field alignment when compared to the control BHJ PSCs. The optimization of BHJ thin film morphology, suppression of charge carrier recombination, and enhancement in charge carrier collection result in a greatly increased short-circuit current density and fill factor, as a result, enhanced power conversion efficiency. PMID:25783755

  15. Magnetic Tweezers-based 3D Microchannel Electroporation for High-Throughput Gene Transfection in Living Cells

    PubMed Central

    Liao, Wei-Ching; Chiang, Chi-Ling; Gallego-Perez, Daniel; Yang, Zhaogang; Lu, Wu; Byrd, John C.; Muthusamy, Natarajan; Lee, L. James.; Sooryakumar, Ratnasingham

    2015-01-01

    We report a novel, high throughput magnetic-tweezers based 3D microchannel electroporation system capable of transfecting 40,000 cells/cm2 on a single-chip for gene therapy, regenerative medicine and intracellular detection of target mRNA for screening cellular heterogeneity. A single cell or an ordered array of individual cells are remotely guided by programmable magnetic fields to poration sites with high (> 90%) cell alignment efficiency to enable various transfection reagents to be delivered simultaneously into the cells. The present technique, in contrast to the conventional vacuum based approach, is significantly gentler on the cellular membrane yielding > 90% cell viability and, moreover, allows transfected cells to be transported for further analysis. Illustrating the versatility of the system, the GATA2 molecular beacon was delivered into leukemia cells to detect the regulation level of the GATA2 gene that is associated with the initiation of leukemia. The uniform delivery and a sharp contrast of fluorescence intensity between GATA2 positive and negative cells demonstrate key aspects of the platform for gene transfer, screening and detection of targeted intracellular markers in living cells. PMID:25469659

  16. Novel Applications of Magnetic Cell Sorting to Analyze Cell-Type Specific Gene and Protein Expression in the Central Nervous System

    PubMed Central

    2016-01-01

    The isolation and study of cell-specific populations in the central nervous system (CNS) has gained significant interest in the neuroscience community. The ability to examine cell-specific gene and protein expression patterns in healthy and pathological tissue is critical for our understanding of CNS function. Several techniques currently exist to isolate cell-specific populations, each having their own inherent advantages and shortcomings. Isolation of distinct cell populations using magnetic sorting is a technique which has been available for nearly 3 decades, although rarely used in adult whole CNS tissue homogenate. In the current study we demonstrate that distinct cell populations can be isolated in rodents from early postnatal development through adulthood. We found this technique to be amendable to customization using commercially available membrane-targeted antibodies, allowing for cell-specific isolation across development and animal species. This technique yields RNA which can be utilized for downstream applications—including quantitative PCR and RNA sequencing—at relatively low cost and without the need for specialized equipment or fluorescently labeled cells. Adding to its utility, we demonstrate that cells can be isolated largely intact, retaining their processes, enabling analysis of extrasomatic proteins. We propose that magnetic cell sorting will prove to be a highly useful technique for the examination of cell specific CNS populations. PMID:26919701

  17. Electrostatically Stabilized Magnetic Nanoparticles – An Optimized Protocol to Label Murine T Cells for in vivo MRI

    PubMed Central

    Wuerfel, Eva; Smyth, Maureen; Millward, Jason M.; Schellenberger, Eyk; Glumm, Jana; Prozorovski, Timour; Aktas, Orhan; Schulze-Topphoff, Ulf; Schnorr, Jörg; Wagner, Susanne; Taupitz, Matthias; Infante-Duarte, Carmen; Wuerfel, Jens

    2011-01-01

    We present a novel highly efficient protocol to magnetically label T cells applying electrostatically stabilized very small superparamagnetic iron oxide particles (VSOP). Our long-term aim is to use magnetic resonance imaging (MRI) to investigate T cell dynamics in vivo during the course of neuroinflammatory disorders such as experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Encephalitogenic T cells were co-incubated with VSOP, or with protamine-complexed VSOP (VProt), respectively, at different conditions, optimizing concentrations and incubation times. Labeling efficacy was determined by atomic absorption spectrometry as well as histologically, and evaluated on a 7 T MR system. Furthermore, we investigated possible alterations of T cell physiology caused by the labeling procedure. T cell co-incubation with VSOP resulted in an efficient cellular iron uptake. T2 times of labeled cells dropped significantly, resulting in prominent hypointensity on T2*-weighted scans. Optimal labeling efficacy was achieved by VProt (1 mM Fe/ml, 8 h incubation; T2 time shortening of ∼80% compared to untreated cells). Although VSOP promoted T cell proliferation and altered the ratio of T cell subpopulations toward a CD4+ phenotype, no effects on CD4 T cell proliferation or phenotypic stability were observed by labeling in vitro differentiated Th17 cells with VProt. Yet, high concentrations of intracellular iron oxide might induce alterations in T cell function, which should be considered in cell tagging studies. Moreover, we demonstrated that labeling of encephalitogenic T cells did not affect pathogenicity; labeled T cells were still capable of inducing EAE in susceptible recipient mice. PMID:22203815

  18. Isolation of prostate cancer cell subpopulations of functional interest by use of an on-chip magnetic bead-based cell separator

    NASA Astrophysics Data System (ADS)

    Estes, Matthew D.; Ouyang, Bin; Ho, Shuk-mei; Ahn, Chong H.

    2009-09-01

    This work presents the design, fabrication and characterization of a modular magnetic bead-based cell separation device developed for the sequential sorting of a heterogeneous prostate cancer (CaP) cell population. The chief aim is cell sorting carried out on the basis of surface marker expression, serially selecting cellular subpopulations for capture by the use of antibody-coated magnetic beads. The markers of interest, prostate specific membrane antigen (PSMA) and CD10 were selected for their relevance to ongoing CaP development research. The separation device was fabricated out of plastic, by the use of cyclic olefin copolymer (COC) injection molding, nickel-iron electroplating and thermoplastic fusion bonding. Effective depletion and enrichment of cell subsets based on multiple surface markers was achieved. Various flow rates and incubation times were tested for optimizing the sorting procedure.

  19. Utility of Magnetic Cell Separation as a Molecular Sperm Preparation Technique

    PubMed Central

    Said, Tamer M.; Agarwal, Ashok; Zborowski, Maciej; Grunewald, Sonja; Glander, Hans-Juergen; Paasch, Uwe

    2009-01-01

    Assisted reproductive techniques (ART) have become the treatment of choice in many cases of infertility; however the current success rates of these procedures remain suboptimal. Programmed cell death (apoptosis) most likely contributes to failed ART and to the decrease in sperm quality after cryopreservation. There is likelihood that some sperm selected for ART will display features of apoptosis despite their normal appearance, which may be partially responsible for the low fertilization and implantation rates seen with ART. One of the features of apoptosis is the externalization of phosphatidylserine (PS) residues, which are normally present on the inner leaflet of the sperm plasma membrane. Colloidal super-paramagnetic microbeads (~50 nm in diameter) conjugated with annexin-V bind to PS are used to separate dead and apoptotic spermatozoa by magnetic cell sorting (MACS). Cells with externalized PS will bind to these microbeads, while non-apoptotic cells with intact membranes do not bind and could be used during ART. We have conducted a series of experiments to investigate if the MACS technology could be used to improve ART outcomes. Our results clearly indicate that integrating MACS as a part of sperm preparation techniques will improve semen quality and cryosurvival rates by eliminating apoptotic sperm. Non-apoptotic spermatozoa prepared by MACS display higher quality in terms of routine sperm parameters and apoptosis markers. The higher sperm quality is represented by an increased oocyte penetration potential and cryosurvival rates. Thus, the selection of non-apoptotic spermatozoa by MACS should be considered to enhance ART success rates. PMID:18077822

  20. MAGNETIC FIELD INFLUENCE ON NGF-STIMULATED NEURITE OUTGROWTH IN PC-12 CELLS: EFFECT OF PAINT FUMES

    EPA Science Inventory

    MAGNETIC FIELD INFLUENCE ON NGF-STIMULATED NEURITE OUTGROWTH IN PC-12 CELLS: EFFECT OF PAINT FUMES. C. F. Blackman1, D. E. House2*, S. G. Benane3*, A. Ubeda4, M.A. TrilIo4. 1 National Health and Environmental Effects Research Laboratory, EPA,
    Research Triangle Park, North Caro...

  1. 3D Electromagnetic Particle-in-Cell simulations of the solar wind interaction with lunar magnetic anomalies

    NASA Astrophysics Data System (ADS)

    Deca, J.; Lapenta, G.; Divin, A. V.; Lembege, B.; Markidis, S.

    2013-12-01

    Unlike the Earth and Mercury, our Moon has no global magnetic field and is therefore not shielded from the impinging solar wind by a magnetosphere. However, lunar magnetic field measurements made by the Apollo missions provided direct evidence that the Moon has regions of small-scale crustal magnetic fields, ranging up to a few 100km in scale size with surface magnetic field strengths up to hundreds of nanoTeslas. More recently, the Lunar Prospector spacecraft has provided high-resolution observations allowing to construct magnetic field maps of the entire Moon, confirming the earlier results from Apollo, but also showing that the lunar plasma environment is much richer than earlier believed. Typically the small-scale magnetic fields are non-dipolar and rather tiny compared to the lunar radius and mainly clustered on the far side of the moon. Using iPic3D we present the first 3D fully kinetic and electromagnetic Particle-in-Cell simulations of the solar wind interaction with lunar magnetic anomalies. We study the behaviour of a dipole model with variable surface magnetic field strength under changing solar wind conditions and confirm that lunar crustal magnetic fields may indeed be strong enough to stand off the solar wind and form a mini-magnetosphere, as suggested by MHD and hybrid simulations and spacecraft observations. 3D-PIC simulations reveal to be very helpful to analyze the diversion/braking of the particle flux and the characteristics of the resulting particles accumulation. The particle flux to the surface is significantly reduced at the magnetic anomaly, surrounded by a region of enhanced density due to the magnetic mirror effect. Second, the ability of iPic3D to resolve all plasma components (heavy ions, protons and electrons) allows to discuss in detail the electron physics leading to the highly non-adiabatic interactions expected as well as the implications for solar wind shielding of the lunar surface, depending on the scale size (solar wind protons

  2. Particle-in-cell simulation for different magnetic mirror effects on the plasma distribution in a cusped field thruster

    NASA Astrophysics Data System (ADS)

    Liu, Hui; Chen, Peng-Bo; Zhao, Yin-Jian; Yu, Da-Ren

    2015-08-01

    Magnetic mirror used as an efficient tool to confine plasma has been widely adopted in many different areas especially in recent cusped field thrusters. In order to check the influence of magnetic mirror effect on the plasma distribution in a cusped field thruster, three different radii of the discharge channel (6 mm, 4 mm, and 2 mm) in a cusped field thruster are investigated by using Particle-in-Cell Plus Monte Carlo (PIC-MCC) simulated method, under the condition of a fixed axial length of the discharge channel and the same operating parameters. It is found that magnetic cusps inside the small radius discharge channel cannot confine electrons very well. Thus, the electric field is hard to establish. With the reduction of the discharge channel’s diameter, more electrons will escape from cusps to the centerline area near the anode due to a lower magnetic mirror ratio. Meanwhile, the leak width of the cusped magnetic field will increase at the cusp. By increasing the magnetic field strength in a small radius model of a cusped field thruster, the negative effect caused by the weak magnetic mirror effect can be partially compensated. Therefore, according to engineering design, the increase of magnetic field strength can contribute to obtaining a good performance, when the radial distance between the magnets and the inner surface of the discharge channel is relatively big. Project supported by the National Natural Science Foundation of China (Grant No. 51006028) and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 51121004).

  3. Magnetic ferroferric oxide nanoparticles induce vascular endothelial cell dysfunction and inflammation by disturbing autophagy.

    PubMed

    Zhang, Lu; Wang, XueQin; Miao, YiMing; Chen, ZhiQiang; Qiang, PengFei; Cui, LiuQing; Jing, Hongjuan; Guo, YuQi

    2016-03-01

    Despite the considerable use of magnetic ferroferric oxide nanoparticles (Fe3O4NPs) worldwide, their safety is still an important topic of debate. In the present study, we detected the toxicity and biological behavior of bare-Fe3O4NPs (B-Fe3O4NPs) on human umbilical vascular endothelial cells (HUVECs). Our results showed that B-Fe3O4NPs did not induce cell death within 24h even at concentrations up to 400 μg/ml. The level of nitric oxide (NO) and the activity of endothelial NO synthase (eNOS) were decreased after exposure to B-Fe3O4NPs, whereas the levels of proinflammatory cytokines were elevated. Importantly, B-Fe3O4NPs increased the accumulation of autophagosomes and LC3-II in HUVECs through both autophagy induction and the blockade of autophagy flux. The levels of Beclin 1 and VPS34, but not phosphorylated mTOR, were increased in the B-Fe3O4NP-treated HUVECs. Suppression of autophagy induction or stimulation of autophagy flux, at least partially, attenuated the B-Fe3O4NP-induced HUVEC dysfunction. Additionally, enhanced autophagic activity might be linked to the B-Fe3O4NP-induced production of proinflammatory cytokines. Taken together, these results demonstrated that B-Fe3O4NPs disturb the process of autophagy in HUVECs, and eventually lead to endothelial dysfunction and inflammation. PMID:26551222

  4. Magnetic separation of encapsulated islet cells labeled with superparamagnetic iron oxide nano particles.

    PubMed

    Mettler, Esther; Trenkler, Anja; Feilen, Peter J; Wiegand, Frederik; Fottner, Christian; Ehrhart, Friederike; Zimmermann, Heiko; Hwang, Yong Hwa; Lee, Dong Yun; Fischer, Stefan; Schreiber, Laura M; Weber, Matthias M

    2013-01-01

    Islet cell transplantation is a promising option for the restoration of normal glucose homeostasis in patients with type 1 diabetes. Because graft volume is a crucial issue in islet transplantations for patients with diabetes, we evaluated a new method for increasing functional tissue yield in xenogeneic grafts of encapsulated islets. Islets were labeled with three different superparamagnetic iron oxide nano particles (SPIONs; dextran-coated SPION, siloxane-coated SPION, and heparin-coated SPION). Magnetic separation was performed to separate encapsulated islets from the empty capsules, and cell viability and function were tested. Islets labeled with 1000 μg Fe/ml dextran-coated SPIONs experienced a 69.9% reduction in graft volume, with a 33.2% loss of islet-containing capsules. Islets labeled with 100 μg Fe/ml heparin-coated SPIONs showed a 46.4% reduction in graft volume, with a 4.5% loss of capsules containing islets. No purification could be achieved using siloxane-coated SPIONs due to its toxicity to the primary islets. SPION labeling of islets is useful for transplant purification during islet separation as well as in vivo imaging after transplantation. Furthermore, purification of encapsulated islets can also reduce the volume of the encapsulated islets without impairing their function by removing empty capsules. PMID:23789985

  5. Characterization of proton exchange membrane materials for fuel cells by solid state nuclear magnetic resonance

    SciTech Connect

    Kong, Zueqian

    2010-01-01

    Solid-state nuclear magnetic resonance (NMR) has been used to explore the nanometer-scale structure of Nafion, the widely used fuel cell membrane, and its composites. We have shown that solid-state NMR can characterize chemical structure and composition, domain size and morphology, internuclear distances, molecular dynamics, etc. The newly-developed water channel model of Nafion has been confirmed, and important characteristic length-scales established. Nafion-based organic and inorganic composites with special properties have also been characterized and their structures elucidated. The morphology of Nafion varies with hydration level, and is reflected in the changes in surface-to-volume (S/V) ratio of the polymer obtained by small-angle X-ray scattering (SAXS). The S/V ratios of different Nafion models have been evaluated numerically. It has been found that only the water channel model gives the measured S/V ratios in the normal hydration range of a working fuel cell, while dispersed water molecules and polymer ribbons account for the structures at low and high hydration levels, respectively.

  6. Differentiation of Glioma and Radiation Injury in Rats Using In Vitro Produce Magnetically Labeled Cytotoxic T-Cells and MRI

    PubMed Central

    Arbab, Ali S.; Janic, Branislava; Jafari-Khouzani, Kourosh; Iskander, A. S. M.; Kumar, Sanath; Varma, Nadimpalli R. S.; Knight, Robert A.; Soltanian-Zadeh, Hamid; Brown, Stephen L.; Frank, Joseph A.

    2010-01-01

    Background A limitation with current imaging strategies of recurrent glioma undergoing radiotherapy is that tumor and radiation injury cannot be differentiated with post contrast CT or MRI, or with PET or other more complex parametric analyses of MRI data. We propose to address the imaging limitation building on emerging evidence indicating that effective therapy for recurrent glioma can be attained by sensitized T-cells following vaccination of primed dendritic cells (DCs). The purpose of this study was to determine whether cord blood T-cells can be sensitized against glioma cells (U-251) and if these sensitized cytotoxic T-cells (CTLs) can be used as cellular magnetic resonance imaging probes to identify and differentiate glioma from radiation necrosis in rodent models. Methodology/Principal Findings Cord blood T and CD14+ cells were collected. Isolated CD14+ cells were then converted to dendritic cells (DCs), primed with glioma cell lysate and used to sensitize T-cells. Phenotypical expression of the generated DCs were analyzed to determine the expression level of CD14, CD86, CD83 and HLA-DR. Cells positive for CD25, CD4, CD8 were determined in generated CTLs. Specificity of cytotoxicity of the generated CTLs was also determined by lactate dehydrogenase (LDH) release assay. Secondary proliferation capacity of magnetically labeled and unlabeled CTLs was also determined. Generated CTLs were magnetically labeled and intravenously injected into glioma bearing animals that underwent MRI on days 3 and 7 post- injection. CTLs were also administered to animals with focal radiation injury to determine whether these CTLs accumulated non-specifically to the injury sites. Multi-echo T2- and T2*-weighted images were acquired and R2 and R2* maps created. Our method produced functional, sensitized CTLs that specifically induced U251 cell death in vitro. Both labeled and unlabeled CTLs proliferated equally after the secondary stimulation. There were significantly higher CD25

  7. Feasibilty of a Multi-bit Cell Perpendicular Magnetic Tunnel Junction Device

    NASA Astrophysics Data System (ADS)

    Kim, Chang Soo

    The ultimate objective of this research project was to explore the feasibility of making a multi-bit cell perpendicular magnetic tunnel junction (PMTJ) device to increase the storage density of spin-transfer-torque random access memory (STT-RAM). As a first step toward demonstrating a multi-bit cell device, this dissertation contributed a systematic and detailed study of developing a single cell PMTJ device using L10 FePt films. In the beginning of this research, 13 up-and-coming non-volatile memory (NVM) technologies were investigated and evaluated to see whether one of them might outperform NAND flash memories and even HDDs on a cost-per-TB basis in 2020. This evaluation showed that STT-RAM appears to potentially offer superior power efficiency, among other advantages. It is predicted that STTRAM's density could make it a promising candidate for replacing NAND flash memories and possibly HDDs if STTRAM could be improved to store multiple bits per cell. Ta/Mg0 under-layers were used first in order to develop (001) L1 0 ordering of FePt at a low temperature of below 400 °C. It was found that the tradeoff between surface roughness and (001) L10 ordering of FePt makes it difficult to achieve low surface roughness and good perpendicular magnetic properties simultaneously when Ta/Mg0 under-layers are used. It was, therefore, decided to investigate MgO/CrRu under-layers to simultaneously achieve smooth films with good ordering below 400°C. A well ordered 4 nm L10 FePt film with RMS surface roughness close to 0.4 nm, perpendicular coercivity of about 5 kOe, and perpendicular squareness near 1 was obtained at a deposition temperature of 390 °C on a thermally oxidized Si substrate when MgO/CrRu under-layers are used. A PMTJ device was developed by depositing a thin MgO tunnel barrier layer and a top L10 FePt film and then being postannealed at 450 °C for 30 minutes. It was fo