Abstract: The present invention provides a protocol and apparatus for enriching circulating tumor cells and other rare cells from blood, including debris and other components, from samples with high precision and at high throughput rates. This invention discloses an improved processing system from previously described semi-automated sample processing. The system further reduces operator intervention and hands-on time from prior systems. While this system has general utility in processing diverse materials, the system is configured for sample processing of biological specimens to provide an enriched fraction suitable for detection, enumeration and identification of target cells by appropriate analytical methodologies.

Abstract: The invention concerns a device and a method for the manipulation of a liquid sample material in which magnetic microparticles are suspended whereby the microparticles have a functionalized surface and an analyte is bound to the surface. The sample material is introduced into a device with a liquid system through an injection device (50) and in a first mobile phase the sample material is carried to an extractor (90). In a first section (97a) of the extractor (90) the microparticles are immobilized by means of a magnetic field of a controllable device (96) and separated from the remaining sample material. By switching over of a switching unit (110) a second mobile phase (75) is carried to the extractor (90) and the second mobile phase (75) detaches the adsorbed analyte from the surface of the microparticles.

Abstract: A magnetic sensor for identifying small magnetic particles bound to a substrate includes a regular, planar orthogonal array of MTJ cells formed within or beneath that substrate. Each MTJ cell has a high aspect ratio and positions of stable magnetic equilibrium along an easy magnetic axis and positions of unstable magnetic equilibrium along a hard magnetic axis. By initializing the magnetizations of each MTJ cell in its unstable hard-axis position, the presence of even a small magnetic particle can exert a sufficient perturbative strayfield to tip the magnetization to its stable position. The magnetization change in an MTJ cell can be measured after each of two successive opposite polarity magnetizations of a bound particle and the presence of the particle thereby detected.

Abstract: Device for the separation of magnetic particles from a liquid, comprising a first vessel (10), a second vessel (20), a connecting surface (11, 21, 30; 200) that runs from the interior of the first vessel (10) to the interior of the second vessel (20), at least one magnet (40) for the provision of a magnetic field, and a guide element (50) by means of which the magnetic field can be guided along one side of the connecting surface (11, 21, 30; 200).

Abstract: The present invention relates to methods and systems for labeling, isolating, detecting, and/or enumerating a statistically significant number of biological cells, or other biological analytes of interest, present in a complex matrix sample. The isolation of a biological target of interest from a sample mixture is done by immunomagnetic separation. Upon introduction of the sample within an imaging chamber, the capture complex (biological target-magnetic capture agent) will be attracted by the magnetic field and will lay on the surface of the chamber in the focal plane of the imaging system.

Abstract: The present invention includes a container and a method of separating one or more components of interest bound to magnetic particles using centrifugal forces.

Abstract: A method and kit for assaying a cell sample for the presence of at least a threshold number of cells of a given type are disclosed. The kit includes an assay device having a sample chamber for receiving the cell sample and an elongate collection chamber containing a selected-density and/or viscosity medium and having along its length, a plurality of cell-collection regions, and particles which are capable of specific attachment to cells of the selected cell type, and which are effective, when attached to the cells, to increase the density or magnetic susceptibility of the cells. In operation, particle-bound cells and particles in the cell sample are drawn through the elongate collection chamber under the influence of a gravitational or selected centrifugal or magnetic-field force until the particle-bound cells and particles completely fill successive cell-collection regions in the collection chamber.

Abstract: The present invention provides materials and methods that can serve as a prosthetic and/or, for tissue engineer applications, as a supporting matrix in the stabilization of the myocardium.

Abstract: In a method for measurement of very small local magnetic fields, in particular of local magnetic stray fields produced by magnetic beads, at least one magnetoresistive element is used. The element includes a hard-magnetic reference layer and a soft-magnetic sensor layer, whose magnetization can be rotated to a parallel position or an antiparallel position with respect to the reference layer magnetization, and whose output signal which can be tapped off is dependent on the position of the sensor layer magnetization with respect to the reference layer magnetization.

Abstract: The present invention includes a magnetically susceptible polymer component, a method of making the same, and apparatuses and systems for mixing, separating or localizing a magnetically susceptible polymer compound in a reaction. The magnetically susceptible polymer component includes a polymer and a magnetically susceptible particle of a predetermined size, which yields a component having a much-improved magnetic reactivity due to the increase in magnetic material by mass percentage. The apparatuses and systems of the present invention employ controllable magnetic fields distributable in perpendicular directions in order to precisely control the orientation, position and relative motion of any magnetically susceptible components within a reaction vessel.

Abstract: A sensor device for detecting magnetic particles in a sensitive region of a sample chamber includes a dump region. Magnetic particles can be moved by magnetic forces from the sensitive region into the dump region which is arranged such that the magnetic particles cannot return to the sensitive region by pure sedimentation. The separation between the sensitive and the dump region can optionally be enforced by a barrier.

Abstract: A detection device and a detecting method using the detection device are provided in which a magnetic particle is used as a marker particle, and the ratio of a region with reversed magnetization to the whole area of a free layer of a magnetoresistive effect film is increased by a stray magnetic field generated through a biochemical reaction from the magnetic particle remaining on a surface of the magnetoresistive effect film, so that a large detection signal is obtained and obtained detection data can be stored with stability.

Abstract: A microfluidic separation system, which comprises a magnetic separator, which itself comprises a magnetic energy source; first and second magnetically conductive members leading from the magnetic energy source and having respective terminal ends that are separated by a gap over which a magnetic field is applied due to the magnetic energy source. The separation system further comprises a microfluidic chip for insertion into the gap, which comprises a body defining channels on respective faces of the body; and an exterior lining that seals the plurality of channels to allow separate test sample volumes to circulate in at least two of the channels. Upon insertion of the chip into the gap, a first test sample volume is confined to circulating closer to the terminal end of the first member and a second test sample volume is confined to circulating closer to the terminal end of the second member.

Abstract: Methods and devices for detecting an analyte are provided. An analyte binding molecule is fixed to a nanoparticle to form a nanoparticle complex. The analyte binding molecule is capable of binding an analyte. The nanoparticle complex is introduced into one of a circulatory system of an animal or biological fluid of the animal. The analyte is allowed to bind to the nanoparticle complex. The analyte bound nanoparticle complex can be extracted and the presence of the analyte can be detected.

Abstract: According to an aspect of the invention, there is provided a method for detecting a target compound including: injecting a test liquid containing a target compound into a colloid solution of magnetic nano-particles having an average particle diameter of 50 nm or less to allow the target compound to bind to the magnetic nano-particles, thereby forming bound magnetic nano-particles having a diameter of 100 nm or more; and bringing a dispersion liquid containing the bound magnetic nano-particles in proximity to a magnetic sensor including at least a magnetoresistive (MR) element and a permanent magnet while measuring the change in magnetic resistance to selectively detect the bound magnetic nano-particles, thereby indirectly detecting the target compound.

Abstract: An embodiment of the invention relates to a device for detecting an analyte in a sample. The device comprises a fluidic network and an integrated circuitry component. The fluidic network comprises a sample zone, a cleaning zone and a detection zone. The fluidic network contains a magnetic particle and/or a signal particle. A sample containing an analyte is introduced, and the analyte interacts with the magnetic particle and/or the signal particle through affinity agents. A microcoil array or a mechanically movable permanent magnet is functionally coupled to the fluidic network, which are activatable to generate a magnetic field within a portion of the fluidic network, and move the magnetic particle from the sample zone to the detection zone. A detection element is present which detects optical or electrical signals from the signal particle, thus indicating the presence of the analyte.

Abstract: The present invention relates generally to the field of magnetic resonance imaging and, more particularly, to devices and methods used in the observation of the diffusion of molecules across a permeable membrane using magnetic resonance techniques. A typical embodiment of the invention is a method of observing the diffusion of a molecule in a container having a permeable membrane that is disposed between a first solution and a second solution in the container, by using magnetic resonance imaging to obtain an image of the diffusion of the molecule in the first solution across the membrane in to the second solution.

Abstract: A first reactant, which is provided with a reaction site for specific binding with an analyte, and a fluorescent label site, and a second reactant, which is provided with a reaction site for specific binding with the analyte, and a fluorescence recognition site for recognizing fluorescence produced by the fluorescent label site of the first reactant, are respectively fixed onto a support such that the first reactant and the second reactant have a positional relationship adapted for the binding with the analyte.

Abstract: A process for the preparation of coated polymer particles containing superparamagnetic crystals, said process comprising reacting surface-functionalized, superparamagnetic crystal-containing polymer particles of diameter less than 0.5 ?m with at least one polyisocyanate and at least one diol.

Abstract: Disclosed is a disk based system for separating at least two types of particulates contained in a sample fluid. The system includes a disk-like carrier board and a magnetic attraction unit. The disk-like carrier board forms at least one flow channel structure, which includes an inner reservoir, at least one separation chamber, and at least one outer reservoir arranged in sequence from a geometric center of the disk-like carrier board to an outer circumferential rim of the disk-like carrier board. A method of separation carried out with the system includes introducing the sample fluid into the inner reservoir and then rotating the disk-like carrier board to induce a centrifugal force. The sample fluid contains particulates that are labeled with immunomagnetic beads and the labeled particulates are attracted by the magnetic force generated by the magnetic attraction unit to retain in the inner reservoir or the separation chamber.

Abstract: Methods and apparatuses for performing assays involving binding material elements with a plurality of bonds over a substantial area of a surface of a resonant device establishing a normalized exposure. The methods and apparatuses also involve controlling an external influence applied to the material elements over a first period of time and measuring a signal during a second period of time that is indicative of the change in the amount of material elements bound to the surface relative to the normalized exposure. In some cases, the measured signals are integrated with respect to time to determine the time averaged amount of material elements bound to the surface.

Abstract: A laboratory automation system that is capable of carrying out clinical chemistry assays, immunoassays, amplification of nucleic acid assays, and any combination of the foregoing, said laboratory automation system employing at least one of micro-well plates and deep multi-well plates as reaction vessels. The use of micro-well plates as reaction vessels enables the laboratory automation system to assume a variety of arrangements, i.e., the laboratory automation system can comprise a variety of functional modules that can be arranged in various ways. In order to effectively carry out immunoassays by means of micro-well plates, a technique known as inverse magnetic particle processing can be used to transfer the product(s) of immunoassays from one micro-well of a micro-well plate to another.

Abstract: Methods of isolating weakly interacting molecules in a fluidic sample using an immiscible phase filtration technique are disclosed. A complex is formed between a solid phase substrate, a molecule immobilized on the solid phase substrate, and at least one target molecule present in the fluidic sample. The complex is transferred into an immiscible phase by applying an external force to the solid phase substrate. The methods eliminate the need for complex and time consuming washing steps.

Abstract: The invention provides a method of processing a biological and/or chemical sample. The method includes providing a fluid droplet, which includes an inner phase and an outer phase. The outer phase is immiscible with the inner phase, and the outer phase is surrounding the inner phase. The inner phase includes the biological and/or chemical sample. The fluid droplet furthermore comprises magnetically attractable matter. The method also includes providing at least one surface, which is of such a texture and such a wettability for the fluid of the inner phase of the fluid droplet, that the fluid droplet remains intact upon being contacted therewith. The method further includes disposing the fluid droplet onto the at least one surface. The method also includes performing a process on the biological and/or chemical sample in the fluid droplet.

Abstract: A method and system for measuring agglutination in a target-induced agglutination assay with one or more magnetic particles is performed in a reaction chamber. After the magnetic particles, which are capable of binding to a target are provided in the assay, an agglutination process is performed resulting in agglutinated particles. Further an alternating current magnetic field (HAC) is applied to the assay. The method further includes measuring an effect of the HAC on the one or more magnetic particles unattached to any surface. The measured effect is indicative of one or more agglutination parameters.

Abstract: A system for separating a solid magnetic substrate from liquid contents of a reaction vessel, the system comprising at least one micro-well plate having a plurality of rows and a plurality of magnets arranged in at least two rows. In one embodiment, the at least two rows of the plurality of magnets are controlled so as to cause the magnets in the at least two rows of magnets to move in unison. In another embodiment, one row of the at least two rows of the plurality of magnets is controlled so as to cause the magnets in said one row to move at a first velocity in the vertical direction and another row of the at least two rows of the plurality of magnets is controlled so as to cause the magnets in that other row to move at a second velocity in the vertical direction.

Abstract: A detection device and a detecting method using the detection device are provided in which a magnetic particle is used as a marker particle, and the ratio of a region with reversed magnetization to the whole area of a free layer of a magnetoresistive effect film is increased by a stray magnetic field generated through a biochemical reaction from the magnetic particle remaining on a surface of the magnetoresistive effect film, so that a large detection signal is obtained and obtained detection data can be stored with stability.

Abstract: Methods for in-line purification of surfactant from a first fluid, such as a microemulsion are disclosed. Magnetic particles coated with surfactant molecules may be used to bind surfactants from a fluid. A magnetic field may be used to separate the bound materials from the fluid.

Abstract: Accurate measurement cannot be performed due to magnetic signals from magnetic impurities included in a specimen container. By finding a difference between two measurement signals obtained by applying an external magnetic field for orientation to respective normal and reverse directions, the magnetic signals from the magnetic impurities included in the specimen container which are not dependent on the external magnetic field for orientation can be cancelled. The influence of the magnetic impurities included in the specimen container is reduced, and the signal of the intended bound magnetic marker can be measured with high sensitivity.

Abstract: The present invention is related to devices for manipulating magnetic particles that are suspended in a fluid, possibly containing a biological entity of interest, the magnetic particles being able to bind the entity of interest, the fluid being contained in a reaction vessel constituted by a large upper compartment with a funnel shape, an elongate lower compartment with a substantially constant cross-section and a closed base. The devices are especially useful in methods for the extraction of nucleic acid to enable them for further processing.

Abstract: A system for analyzing a sample including providing a microchannel flow channel; associating the sample with magnetic nanoparticles or magnetic polystyrene-coated beads; moving the sample with said magnetic nanoparticles or magnetic polystyrene-coated beads in the microchannel flow channel; holding the sample with the magnetic nanoparticles or magnetic polystyrene-coated beads in a magnetic trap in the microchannel flow channel; and analyzing the sample obtaining an enhanced analysis signal. An apparatus for analysis of a sample includes magnetic particles connected to the sample, a microchip, a flow channel in the microchip, a source of carrier fluid connected to the flow channel for moving the sample in the flow channel, an electromagnet trap connected to the flow line for selectively magnetically trapping the sample and the magnetic particles, and an analyzer for analyzing the sample.

Abstract: A process for the quantitative optical analysis of fluorescently labeled biological cells involves contacting a cell layer on a transparent support at the bottom of a reaction vessel with a solution containing the fluorescent dye. This process can also be used for improving the sensitivity in the quantitative optical analysis of a luminescent biological cell layer. Analogously, these process principles can also be used in receptor studies for the masking of the interfering background radiation in the quantitative optical analysis of fluorescently or luminescently labelled reaction components. In this case, a receptor layer at the bottom of a reaction vessel is in contact with a solution in which a fluorescent or luminescent ligand is dissolved.

Abstract: This invention features systems and methods for the detection of analytes, and their use in the treatment and diagnosis of disease.

Abstract: To provide a magnetic particle parallel processing apparatus permitting repeated use of a container, and a method of magnetic particle parallel processing permitting repeated use of a container, with which the rate of repeated use of a container is enhanced to thereby achieve a saving in the working space and a saving in the working time. The apparatus comprises: at least one reaction container; a liquid disposal tank; a reagent etc.

Abstract: An embodiment of the invention relates to a device for detecting an analyte in a sample. The device comprises a fluidic network and an integrated circuitry component. The fluidic network comprises a sample zone, a cleaning zone and a detection zone. The fluidic network contains a magnetic particle and/or a signal particle. A sample containing an analyte is introduced, and the analyte interacts with the magnetic particle and/or the signal particle through affinity agents. A microcoil array or a mechanically movable permanent magnet is functionally coupled to the fluidic network, which are activatable to generate a magnetic field within a portion of the fluidic network, and move the magnetic particle from the sample zone to the detection zone. A detection element is present which detects optical or electrical signals from the signal particle, thus indicating the presence of the analyte.

Abstract: Electrochemical devices, methods, and systems for detecting and quantifying analytes are disclosed. A chemical detection reagent is locally generated in a test solution by electrochemical reaction of a precursor compound caused to migrate into the test solution from a precursor solution separated from the test solution by a cell separator. This approach provides precise metering of the reagent, via the charge passed, and avoids the need to store a reagent solution that may be chemically unstable. In one embodiment, the starch concentration in a colloidal solution can be measured via spectroscopic detection of a blue complex formed by the interaction of starch with iodine produced, on demand, by electrochemical oxidation of iodide ion. The approach may also be used to characterize certain types of analytes. The invention is amenable to automation and is particularly useful for on-line monitoring of production processes, including the inclusion of feed back loop mechanisms for process control.

Abstract: A method and system for detecting magnetic nanoparticles include measuring a magneto-optical enhancement of the plasmon absorption in the optical response.

Abstract: An apparatus is disclosed for carrying out an analysis process, in which probe molecules which are immobilized on a substrate within an analysis area are brought into contact with an analyte solution, which contains target molecules as reaction partners, and reaction events are detected between target molecules and probe molecules with the aid of magnetic marker particles which are coupled to the target molecules or to the probe molecules. An inhomogeneous magnetic field is applied to the analysis area before and/or after detection. In the apparatus, magnetic-field devices are provided at least for the production of an inhomogeneous magnetic field acting in the analysis area, with these magnetic-field devices being part of sequence control for determination of the bonding forces of the reaction events.

Abstract: Bodily fluid is analyzed for the presence of drugs of a selected panel of drugs in a simultaneous assay in which sample of the fluid is incubated with additional amounts of all drugs of the panel, antibodies specific to each of the drugs of the panel, and microparticles, the microparticles being divided into subsets, one subset for each drug in the panel and each subset distinguishable from the others. The incubation is performed in a liquid medium in which competitive binding occurs, the drugs in the sample competing with those added to the assay medium for binding to the antibodies. In one procedure, the added drugs are pre-coupled to the microparticles while the antibodies are not, and the incubation is followed by further incubating the microparticles with labeled ligands that have affinity for the antibodies.

Abstract: The invention relates to a kit comprising MHC Class I and Class II HLA-coated beads containing specific antigenic peptides for binding to antigen-specific T cells and the appropriate negative control peptides. Also provided are methods for making the coated beads and methods for use. The application of these beads go to the stimulation of peripheral blood cell populations and in vitro-stimulated culture for the elicitation of functional activities such as cell activation and signaling, cytokine secretion, proliferation and cytotoxicity activity.

Abstract: A sensor array comprising a series connection of parallel GMR sensor stripes provides a sensitive mechanism for detecting the presence of magnetized particles bonded to biological molecules that are affixed to a substrate. The adverse effect of hysteresis on the maintenance of a stable bias point for the magnetic moment of the sensor free layer is eliminated by a combination of biasing the sensor along its longitudinal direction rather than the usual transverse direction and by using the overcoat stress and magnetostriction of magnetic layers to create a compensatory transverse magnetic anisotropy. By making the spaces between the stripes narrower than the dimension of the magnetized particle and by making the width of the stripes equal to the dimension of the particle, the sensitivity of the sensor array is enhanced.

Abstract: The enumeration of cells in fluids by flow cytometry is widely used across many disciplines such as assessment of leukocyte subsets in different bodily fluids or of bacterial contamination in environmental samples, food products and bodily fluids. For many applications the cost, size and complexity of the instruments prevents wider use, for example, CD4 analysis in HIV monitoring in resource-poor countries. The novel device, methods and algorithms disclosed herein largely overcome these limitations. Briefly, all cells in a biological sample are fluorescently labeled, but only the target cells are also magnetically labeled. The labeled sample, in a chamber or cuvet, is placed between two wedge-shaped magnets to selectively move the magnetically labeled cells to the observation surface of the cuvet. An LED illuminates the cells and a CCD camera captures the images of the fluorescent light emitted by the target cells.

Abstract: Microfluidic systems are disclosed, including microfluidic devices and methods, useful for simultaneously analyzing multiple analytes in each of a plurality of distinct nanoliter-volume samples.

Abstract: Detection of magnetic beads at temperature below room temperature can increase the signal level significantly as compared to the same detection when performed at room temperature. Additional improvement is obtained if the beads are below 30 nm in size and if deviations of bead size from the median are small. A preferred format for the beads is a suspension of super-paramagnetic particles in a non-magnetic medium.

Abstract: Methods and devices for rapid lateral flow immunoassays to detect specific antibodies within a liquid sample while also validating the adequacy of the liquid sample for the presence of immunoglobulin and the integrity and immunoreactivity of the test reagents that detect the antibodies of interest, without requiring instrumentation. The methods and devices provide for delivery of a diluted liquid sample to a single location that simultaneously directs the liquid flow along two or more separate flow paths, one that serves as a positive control to confirm that all critical reagents of the test are immunoreactive, and that the sample being tested is adequate, and the other to detect specific antibodies if present.

Abstract: An embodiment of the invention relates to a device comprising (1) an array of electromagnetic elements comprising coils, metal cores, and metal core heads, and (2) a controller that is adapted to control a current for one or more coils individually, to vary the current for said one or more coils individually, to reverse the current for one or more coils individually, and to generate a specific magnetic flux distribution and gradient across two or more coils; wherein the metal core head is at one end of the coil and the metal core head has a geometry to create a desired magnetic flux, intensity and gradient, in a region of interest between two adjacent coils; further wherein the device is functionally coupled to a fluidic device to concentrate and transport magnetic particles in a fluid without fluidic movement of the fluid.

Abstract: It is intended to provide a method capable of simply aggregating magnetic particles having a surface modified with a thermoresponsive polymer at a given temperature without heating or cooling an aqueous solution containing the magnetic particles, and a separation method and a detection method of a substance to be detected in a sample using the method. The method of separating a substance to be detected from a sample includes the steps of: mixing an adsorbent and the sample in an aqueous solution to adsorb the substance to be detected on the adsorbent, aggregating the adsorbent by changing a salt concentration in the aqueous solution; and collecting the adsorbent from the aqueous solution by a magnetic force, wherein said adsorbent comprises a magnetic particle of an average particle size of 50 to 1000 nm, a surface of which is modified with a thermoresponsive polymer and is immobilized with a substance having an affinity for the substance to be detected.

Abstract: The invention relates to a magnetic immunodiagnostic method for the demonstration of antibody-antigen complexes. One such method involves the research and/or identification of antibodies or antigens, preferably anti-antigen antibodies or antigens of a blood group, and comprises a suspension of magnetic particles coated with antigens that can be carried by cells such as erythrocytes. The invention also relates to a device and a kit for carrying out one such method.

Abstract: The present invention provides a magnetic sensor which detects a target substance indirectly by making a labeling substance larger than the target substance bond with the target substance contained in a sample in a detection area, and detecting the labeling substance, comprising a capture area which is relatively easy to capture the target substance, and a non-capture area which is relatively hard to capture the target substance, on a surface of a member which is comprised in a detection area, wherein the capture area is surrounded by the non-capture area. Thereby, the sensor enables to detect comparatively accurately the number and concentration of substances which cannot be directly detected, and enables to be used for detection of various target substances.

Abstract: Methods and reagents are disclosed for detecting a false result in an assay for determining a concentration of an analyte in a whole blood sample suspected of containing the analyte. The method comprises determining by means of the assay a concentration of the analyte utilizing a hemolyzed portion of the blood sample to obtain concentration value 1 and determining by means of the assay a concentration of the analyte utilizing a non-hemolyzed portion of the blood sample and multiplying the concentration times a hematocrit factor to obtain concentration value 2. A ratio of concentration value 1 divided by concentration value 2 is determined and is compared to a predetermined ratio of known reliability. If the ratio is less than the predetermined ratio, a false result is indicated.