Abstract: The present invention relates to nanoparticles with tumor necrosis factor (TNF) or cytokine immobilized thereon, where TNF or the cytokine is preferably immobilized in the form of a trimer in directed fashion and with retention of its biological activity on the carrier, to methods for the directed immobilization of TNF or cytokine on nanoparticles, to the use of the nanoparticles having immobilized TNF or cytokine for the identification and/or isolation of cytokine- or TNF-binding partners and for the identification and/or isolation of inhibitors of the interaction between TNF or cytokine and its binding partners, to the use of such nanoparticles for preparing a pharmaceutical composition, in particular for the therapy of tumors, and to pharmaceutical and diagnostic compositions which comprise such nanoparticles.

Abstract: A method for separating biological materials and other substances is disclosed, wherein a mixture containing desired and undesired components are exposed to magnetic particles having ligands capable of binding to the desired and/or the undesired components to form a magnetic mixture, placing the magnetic mixture onto a substrate material; exposing the substrate coated with the magnetic mixture to a magnetic field of sufficient strength to cause the magnetic components to migrate across the substrate; and repeatedly increasing and decreasing the magnetic field in a pulsing manner with a frequency sufficient to cause the desired magnetic components to separate spatially from the undesired magnetic components. A device for separating biological materials capable of being operated to increase and decrease magnetic field in a pulse fashion is also disclosed.

Abstract: A method of single parameter and multiparameter characterizing of cells, particularly immunophenotyping of cells, is provided. The method preferably uses antibody-coated microspheres which are adapted to bind to specific types of cells. One or more sets of coated microspheres are contacted simultaneously or sequentially with a suspension of cells and bind the cells they are adapted to bind to form bead-cell complexes. Cells may bind to one or more microspheres. The bead-cell complexes are then separated from the suspension The complexes are preferably stained and then examined to characterize the cells, preferably the cells bound to the microspheres. A method of quantitating a specific cell type is provided. A kit and apparatus for performing the method are also provided.

Abstract: Superparamagnetic (“SPM”) subunits of 1–30 nm average mean diameter (e.g. ferro fluid) subparticles are treated with a magnetically noninterfering substance capable of coating and covering them (e.g, BSA) and they spontaneously form agglomerates of about 100 nm to about 450 nm or higher average mean diameter and are then used to form complexes with target biological ligands such as viruses, contained in large volumes of liquid. The complexes are subjected to the gradient intensity of a strong magnetic field, and excess liquid is removed, where upon an immunochromatographic assay is conducted to determine the identity and/or amount of target ligand present, in which operation SPM particles that bonded to the ligand function as tags for ligand detection.

Abstract: The sensitivity of surface enhanced Raman spectroscopy to silver nano-particle/peptide aggregates is increased by prior treatment of the peptides. According to a first type of embodiment, an enzyme such as Glu-C is used for protein(s) digestion based on the enzyme's ability to cleave proteins at a selected location having a negative charge, such as at aspartic acid and glutamic acid. This type of digestion is used to derive a higher proportion of positively charged component peptides sequences as compared to the component peptides sequences obtained by standard tryptic digestion of protein(s). According to a second type of embodiment, methyl-esterification of peptides suppresses the negative charge contributions of portions of the peptides such as aspartic acid, glutamic acid, and the C-terminus. Both types of embodiments result in increased binding affinity of the resulting component sequence peptides with negatively charged nano-particles such as silver nano-particles.

Abstract: The present invention concerns a novel means by which specific chosen reactions can be accelerated through the use of a new type of artificial enzyme. The invention allows specific reactions to occur at an accelerated rate, even in the presence of other non-chosen molecules, which may be very similar in structure to the chosen reactant. The reactions may be stoichiometric or catalytic.

Abstract: A method of single parameter and multiparameter characterizing of cells, particularly immunophenotyping of cells, is provided. The method preferably uses antibody coated microspheres which are adapted to bind to specific types of cells. One or more sets of coated microspheres are added simultaneously or sequentially to a suspension of cells and bind the cells they are adapted to bind. Cells may bind to one or more microspheres. The suspension is then filtered to trap bead-cell complexes. The complexes are preferably stained and then examined to characterize the cells, preferably the cells bound to the microspheres. A kit and apparatus for performing the method are also provided.

Abstract: Method and arrangement (10, 20) for preparing samples (15, 27) submergible in a liquid medium. The arrangement includes a carrier structure (11). The carrier includes a device (13, 23) for controllable generation of a magnetic field through influence of a control signal to attract at least part of the at least first and second type of samples (15, 27) towards specific locations on the carrier when connected to a first control signal and to repel at least one of the first or second type of samples when connected to a second control signal.

Abstract: A method for capturing a target substance in a sample, comprising the steps of preparing particles capable of capturing the target substance in a dispersed state in a fluid, aggregating the particles, and allowing the particles to capture the target substance in the sample by bringing the sample into contact with the particles aggregated.

Abstract: The present invention concerns a novel means by which chemical preparations can be made. Reactions can be accelerated on special chips using microwave energy. The chips contain materials that efficiently absorb microwave energy causing chemical reaction rate increases. The invention is important in many small scale chemical transformations including those used in protein chemistry and in combinatorial chemistry.

Abstract: The present invention concerns a method for producing microparticles loaded with proteins which is characterized in that the microparticles are loaded in suspension under strongly alkaline conditions. The invention also concerns microparticles which can be produced using this method and their use in a binding test e.g. in an immunoassay.

Abstract: A composition comprising colloidal Fe3O4 particles coated with streptavidin is disclosed. These particles can be used in a method for separating biotinylated compounds from a solution in which the biotinylated compounds bind to the streptavidin-coated particles which are attracted to a surface by a magnet. Also disclosed is a method for making said streptavidin-coated composition, said method comprising the steps of forming colloidal Fe3O4 particles by mixing aqueous FeCl2 with aqueous FeCl3, adding aliquots of the mixture to an alkaline solution and adding streptavidin.

Abstract: Disclosed are silica-coated nanoparticles and a process for producing silica-coated nanoparticles. Silica-coated nanoparticles are prepared by precipitating nano-sized cores from reagents dissolved in the aqueous compartment of a water-in-oil microemulsion. A reactive silicate is added to coat the cores with silica. Also disclosed are methods for functionalizing silica-coated nanoparticles for use in a variety of applications.

Abstract: A highly sensitive assay is disclosed which combines immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis to detect, enumerate and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood and has a greater sensitivity than conventional PCR or immunohistochemistry by 1-2 orders of magnitude. In addition, the assay facilitates the biological characterization and staging of carcinoma cells.

Abstract: The invention concerns a method for detecting and/or quantifying at least an analyte in a liquid medium, characterized in that it consists in using magnetic colloidal particles functionalized at the surface with at least a ligand specific of the analyte to be detected and/or assayed and in that it comprises: contacting said particles with said medium to be analyzed; applying a magnetic field to said medium, at an intensity sufficient to cause said magnetic particles to be structured in the form of chains; maintaining said magnetic field for a sufficient time interval to enable coupling or combination of the analyte concerned with at least two specific ligands present respectively on two neighbouring particles of a chain; cancelling the magnetic field, and determining the presence and/or absence of said analyte and, as the case may be, its concentration via the presence and/or the absence of said permanent chains of magnetic particles.

Abstract: An apparatus and method for performing successive chemical or biochemical operations in an automated or semi-automated format are disclosed. The apparatus includes (i) a substrate having two or more wells, where each well is separated from adjacent well(s) by an energy barrier, (ii), a magnetic bead having a surface on which at least one of said operations is performed, and (iii) electromagnets positioned adjacent said wells, for use in producing controlled-time electromagnetic fields in one or more selected wells. A control unit operatively coupled to the electromagnets functions to produce controlled-time electromagnetic forces on the bead that are effective to transfer the bead from one well to another across the energy barrier and optionally, to agitate the bead within a well.

Abstract: A system and method for detecting specific binding reactions using magnetic labels.

Abstract: A system for the separation of magnetically attractable microparticles which are suspended in a liquid, which includes a magnet arrangement having at least two magnets in ring form, the magnet axis of which is oriented perpendicular to the ring plane, and the magnets are arranged above one another in the same direction or in opposite directions, and the ring inner spaces form a space for receiving a vessel. The invention also relates to methods for the separation of microparticles and to a system for the separation and suspension of microparticles in vessels including a magnet arrangement as described above and a vessel holder and a movement device for moving a vessel in the vessel holder in order to obtain a suspension of separated microparticles.

Abstract: An assay test strip and cassette. The test strip is positioned in a housing shaped and configured to allow a detector to access the test strip from the side, rather than from the lengthwise axis of the test strip. The housing may contain one or more test strips which may also be disposed on one or more surfaces of the housing. Preferably, the housing is generally C-shaped with the test strip spanning the space between the two arms of the C-shape. The housing is sealed to protect both the operator and instrument from possible contamination. The test strip is preferably embedded with paramagnetic particles and process chemistry specific for a particular application. Quantitative analysis may be accomplished using a magnetic reader device. In additional embodiments, detection is accomplished by visual means.

Abstract: The present invention provides methods, compositions, and kits for rapid detection of analytes in a sample. Surprisingly, it has been found that bulking materials having non-sugar sweeteners effectively enhance chromatographic detection methods by providing component stability and controlled release. Thus, the novel components and methods disclosed herein provide a completely new modality of chromatographic analyte detection.

Abstract: The present invention is related to a method for separating a first population of cells from a second population of cells in a sample by discontinuous density gradient separation using dense particles to target the first population of cells and a density separation medium (DSM) that is at least about 0.001 g/cm3 higher than the density of the second population of cells.

Abstract: A fluidics-based assay device for detecting the presence or quantity of an analyte residing in a test sample is provided. The device utilizes a self-calibrated magnetic binding assay format (e.g., sandwich, competitive, etc.) that includes detection probes capable of generating a detection signal (e.g., fluorescent non-magnetic particles) and calibration probes capable of generating a calibration signal (e.g., fluorescent magnetic particles). The amount of the analyte within the test sample is proportional (e.g., directly or inversely) to the intensity of the detection signal calibrated by the intensity of the calibration signal. It has been discovered that the fluidics-based device of the present invention provides an accurate, inexpensive, and readily controllable method of determining the presence of an analyte in a test sample.

Abstract: A device for transporting magnetic or magnetizable microbeads (25) in a capillary chamber (14) comprises a permanent magnet (10) or an electromagnet (11) for subjecting the capillary chamber to a substantially uniform magnetic field, to apply a permanent magnetic moment to the microbeads (25). At least one planar coil (22) and preferably an array of overlapping coils are located adjacent to the capillary chamber (14) for applying a complementary magnetic field on the microbeads parallel or antiparallel to said substantially uniform magnetic field, to drive the microbeads. An arrangement is provided for switching the current applied to the coil(s) (22) to invert the field produced thereby, to selectively apply an attractive or repulsive driving force on the microbeads (25). The device is usable to transport microbeads for performing chemical and biochemical reactions or assay, as is done for instance in clinical chemistry assays for medical diagnostic purposes.

Abstract: A system for detecting an analyte in a sample includes a resonant sensor that has a sensor surface coated with the capture agent. A plurality of magnetic particles, each of which is coated with a capture agent having an affinity for the analyte, is combined with the sample to form a plurality of analyte-particle complexes. The system also includes a transport arrangement for transporting the sample to the sensor surface, and a magnetic field inducing structure constructed and arranged to establish a magnetic field at and adjacent to the sensor surface. The resonant sensor produces a signal corresponding to an amount of analyte-particle complexes that are bound to the sensor surface.

Abstract: A competitive immunoassay, dye and method for rapidly detecting the presence of one or more target ligands within a fluid sample suspected of containing such ligand or ligands. The immunoassay comprises a protein-binding membrane, a first absorbent pad, a second absorbent pad, and a third absorbent pad. The protein-binding membrane has at least two regions of antibodies bound thereto for detecting dissimilar ligands. The second absorbent pad has formed therein a colloidal gold tracer having one, and preferably two or more ligand analog protein complexes adhering thereto. To utilize the system, the immunoassay strip is placed within a fluid sample. To the extent the target ligand is absent, a visual indicator will be provided signaling such absence. To the extent the target ligand is present at or above a threshold level, no such visual signal will be produced.

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: A sensor device is configured by using a sensor element including functions as a magnetic field sensor and capable of generating the magnetic field for collecting magnetic particles on a sensor surface by the application of the current. As a result, a sensor device can be provided in which the magnetic particles serving as a label can be effectively collected on the sensor, and at the same time, the influence given to the sensor by the magnetic field for collecting the magnetic particles can be reduced.

Abstract: The present invention provides a chemiluminescence enhancer treated to retain favorable dispersibility of fine solid carriers and stably exert a chemiluminescence enhancing action. The invention provides a chemiluminescence enhancer used for signal detection in a solid phase immunoassay using antigen or/and antibody immobilized onto fine solid carriers dispersible in a liquid medium, consisting of a water soluble macromolecular quaternary ammonium salt, a quaternary sulfonium salt or a quaternary phosphonium salt in order to enhance emission of light caused by an enzymatic reaction of a chemiluminescent substrate having dioxetane, wherein the chemiluminescence enhancer is given an aggregation inhibition treatment of the fine solid carriers by the treatment with an oxidizing agent or a reducing agent, and a chemiluminescence method and a kit using the chemiluminescence enhancer.

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: Immunological assays for several biological markers for thyroid disorders in a biological sample are performed in a single test with a combination of sandwich-type, sequential competitive, and serological assays by the use of particles classified into groups that are distinguishable by flow cytometry, one group for the assay of each marker. Each group of particles is coated with a different immunological binding member, and coating densities, co-coating materials, and special buffer solutions are used to adjust for differences in the sensitivities and dynamic ranges of each of the markers in the typical sample.

Abstract: This invention relates generally to the field of moiety or molecule isolation, detection and manipulation and library synthesis. In particular, the invention provides a microdevice, which microdevice comprises: a) a magnetizable substance; and b) a photorecognizable coding pattern, wherein said microdevice has a preferential axis of magnetization. Systems and methods for isolating, detecting and manipulating moieties and synthesizing libraries using the microdevices are also provided.

Abstract: A method of determining the number of magnetic particles within a sample using a tuned circuit having a capacitor and a coil. The method comprises: a. determining the difference in the resonant frequency of the tuned circuit when the sample is exposed to a magnetic field generated by the coil and when the sample is not exposed to the magnetic field generated by the coil; and b. using the difference in the resonant frequency to determine the number of magnetic particles within the sample.

Abstract: A ferromagnetic thin-film based magnetic field detection system used for detecting the presence of selected molecular species. A magnetic field sensor supported on a substrate has a binding molecule layer positioned on a side thereof capable of selectively binding to the selected molecular species. The magnetic field sensor can be substantially covered by an electrical insulating layer having a recess therein adjacent to the sensor in which the binding molecule layer is provided. An electrical interconnection conductor can be supported on the substrate at least in part between the sensor and the substrate, and is electrically connected to the sensor. The magnetic field sensor can be provided in a bridge circuit, and can be formed by a number of interconnected individual sensors.

Abstract: The present invention is directed to processes of separating, analyzing and/or collecting selected species within a target sample by use of magnetic microspheres including magnetic particles, the magnetic microspheres adapted for attachment to a receptor agent that can subsequently bind to selected species within the target sample. The magnetic microspheres can be sorted into a number of distinct populations, each population with a specific range of magnetic moments and different receptor agents can be attached to each distinct population of magnetic microsphere.

Abstract: The present invention is related to a method for controlled transport of magnetic beads between a position X and different position Y, such that the magnetic beads are manipulated or transported by applying successively a series of N local magnetic fields which have magnetic field gradients different from 0 in the neighborhood of said magnetic beads. Each of these N local magnetic fields is generated by a single current carrying structure, in which the current density is not constant. The invention generally relates to application in the domain of biochips and micro-arrays, used in diagnostics, genetics and molecular studies.

Abstract: A container having a flexible wall receives a continuous flow of a biological fluid that includes a target antigen and emits a continuous flow of the biological fluid at least partially depleted from the target antigen. The container further comprises a compartment with magnetic beads coupled to an affinity marker that binds the target antigen, and the target antigen is separated from the biological fluid using a magnetic force and an automatic mechanical force, wherein at least one of the magnetic force and automatic mechanical force is transmitted through the flexible wall.

Abstract: Heterogeneous assays for different analytes in a single biological sample are performed simultaneously in a multiplexed assay that combines flow cytometry with the use of magnetic particles as the solid phase and yields an individual result for each analyte. The particles are distinguishable from each other by characteristics that permit them to be differentiated into groups, each group carrying an assay reagent bonded to the particle surface that is distinct from the assay reagents of particles in other groups. The magnetic particles facilitate separation of the solid and liquid phases, permitting the assays to be performed by automated equipment. Assays are also disclosed for the simultaneous detection of antibodies of different classes and a common antigen specificity or of a common class and different antigen specificities.

Abstract: Disclosed are methods and apparatuses for separating cells using magnets and droplet type cell suspension according to the present invention, which may effectively separate cells by forming droplet type cell suspension with cell suspension sample containing cells to which magnetic beads are coupled and applying magnetic force to the droplet type cell suspension.

Abstract: New derivatives of FK 506 are disclosed. These new derivatives and other derivatives that are useful for determining the levels of FK 506 in a sample are also provided as are assay procedures and kits for use in determining the levels of FK 506 or other macrophilin binding substances in blood, particularly un-extracted blood in the presence of specific binding proteins for FK 506.

Abstract: Method and apparatus for manipulating and monitoring analyte flowing in fluid streams. A giant magnetoresistive sensor has an array of sensing elements that produce electrical output signals which vary in dependence on changes in the magnetic field proximate the sensing elements. The analyte is included in a stream, such that the stream has a magnetic property which is dependent on the concentration and distribution on the analyte therein. The stream is flowed past the giant magnetoresistive sensor and in sufficiently close proximity to cause the magnetic properties of the stream to produce electrical output signals. The electrical output signals are monitored as an indicator of analyte concentration or distribution in the stream flowing past the GMR sensor. Changes in the magnetic field produced by the background stream are introduced by analyte molecules, whose presence in the flow past the GMR will effect the output reading.

Abstract: Methods and devices for electrochemical detection of a specific binding pair member utilizing a microsphere with an incorporated electroactive marker, wherein a member of the specific binding pair to be detected is bound, directly or through one or more intermediates, to the microsphere. Multiple specific binding pair members may be detected by use of electrochemically distinguishable electroactive markers. Microspheres with incorporated electroactive markers may include one or more functional groups for binding members of specific binding pairs, and are preferably insoluble in aqueous solvents but soluble in selected organic solvents.

Abstract: The preferred embodiments of the present invention use MRAM technology to detect a shift in the magnetic switching field of a sensor. The shift in the magnetic switching field is caused by the presence of magnetic tagged beads. By measuring the magnitude of the shift in the magnetic field and correlating the magnitude of the shift to the presence of the target molecules, accurate measurements regarding the presence of the target molecules can be made.

Abstract: A method for measuring the responses of sets or subsets of lymphocytes to mitogens or antigens in a sample is disclosed comprising incubating a population of cells with a mitogen or antigen, separating the desired subset of cells by means of the interaction of a specific binding reagent that is attached to the solid phase with a cell surface determinant that is present on the cell subset of interest, lysing the separated cells, and measuring an intracellular component that is increased if the cells have responded to the stimulus. The method provides a convenient, simple, and reliable method for measuring immune function in a variety of conditions.

Abstract: An improved method for separating materials is provided, using colloidal, magnetizable aggregates, optionally silanized, and coated with a one or more layers of novel polysaccharide derivatives. Materials separated by the aggregates of the invention include inorganic and organic molecules, viruses, organelles, and cells. The invention also relates to a kit for separating such materials. The separated materials are useful in analytical and preparative or in diagnostic and therapeutic techniques.

Abstract: The present disclosure provides a high performance hybrid magnetic structure made from a combination of permanent magnets and ferromagnetic pole materials which are assembled in a predetermined array. The hybrid magnetic structure provides for separation and other biotechnology applications involving holding, manipulation, or separation of magnetic or magnetizable molecular structures and targets. Also disclosed are: a method of assembling the hybrid magnetic plates, a high throughput protocol featuring the hybrid magnetic structure, and other embodiments of the ferromagnetic pole shape, attachment and adapter interfaces for adapting the use of the hybrid magnetic structure for use with liquid handling and other robots for use in high throughput processes.

Abstract: A sandwich immunoassay is disclosed that provides simple to perform yet sensitive identification of analytes in samples. All assay constituents needed (except analyte to be detected) for one assay are dried. Upon reconstitution with sample, a 10 to 15 minute incubation gives a rapid and convenient detection assay capability. The method incorporates the capture of antigen to an immobilized capture antibody. A labeled reporter antibody with the molecule, binds to the antigen to form an immunocomplex capable of generating a detectable signal.

Abstract: The present invention is related to a method and corresponding devices for controlled transport of magnetic beads between a position X and different position Y, such that the magnetic beads are manipulated or transported by applying successively a series of N local magnetic fields which have magnetic field gradients different from 0 in the neighborhood of said magnetic beads. Each of these N local magnetic fields is generated by a single current carrying structure, in which the current density is not constant. The invention mainly points to application in the domain of biochips and microarrays, used in diagnostics, genetics and molecular studies.

Abstract: The present invention provides labeled synthetic libraries of random oligomers and methods and apparatus for generating labeled synthetic oligomer libraries. Each member of such a library is labeled with a unique identifier tag that specifies the structure or sequence of the oligomer. In a preferred embodiment of the present invention the identifier tag is a microchip that is pre-encoded or encodable with information that is related back to a detector when the identifier tag is pulsed with electromagnetic radiation.

Abstract: The present invention provides labeled synthetic libraries of random oligomers and methods and apparatus for generating labeled synthetic oligomer libraries. Each member of such a library is labeled with a unique identifier tag that specifies the structure or sequence of the oligomer. In a preferred embodiment of the present invention the identifier tag is a microchip that is pre-encoded or encodable with information that is related back to a detector when the identifier tag is pulsed with electromagnetic radiation.

Abstract: The present invention provides labeled synthetic libraries of random oligomers and methods and apparatus for generating labeled synthetic oligomer libraries. Each member of such a library is labeled with a unique identifier tag that specifies the structure or sequence of the oligomer. In a preferred embodiment of the present invention the identifier tag is a microchip that is pre-encoded or encodable with information that is related back to a detector when the identifier tag is pulsed with electromagnetic radiation.