Abstract: The present invention relates to new CRP immunoassay compositions. The compositions include a low affinity anti-human CRP monoclonal antibody, and an antiidiotypic antibody raised against it. The invention further provides a method for obtaining antiidiotypic monoclonal antibody populations directed to an antibody that is specific for a high concentration, high molecular weight target antigen.

Abstract: The present invention concerns polymer particle vaccine delivery systems in which a water insoluble protein antigen, e.g. a lipidated HpaA protein, is incorporated with particles comprising a polymer matrix. The present invention also concerns a method for incorporating such a water insoluble protein antigen with a polymer matrix in order to produce a polymer particle vaccine delivery system. In addition, the invention also provides a vaccine composition comprising the polymer particle delivery system. The vaccine can be used to treat and/or reduce the risk of for example Helicobacter infection.

Abstract: The use of impedance measurements to detect the presence of pathogens attached to antibody-coated beads. In a fluidic device antibodies are immobilized on a surface of a patterned interdigitated electrode. Pathogens in a sample fluid streaming past the electrode attach to the immobilized antibodies, which produces a change in impedance between two adjacent electrodes, which impedance change is measured and used to detect the presence of a pathogen. To amplify the signal, beads coated with antibodies are introduced and the beads would stick to the pathogen causing a greater change in impedance between the two adjacent electrodes.

Abstract: A composition which contains stabilized conjugates composed of colloidal particles and biomolecules is obtained by adding a detergent to a solution containing biomolecules before or/and during treatment of colloidal particles with this solution.

Abstract: The present invention relates to a kit for determining feline blood type, wherein the kit includes a mixture comprised of a first monoclonal antibody and a second monoclonal antibody, wherein both antibodies recognize feline blood group specific A antigens. The present invention also relates to a method for determining feline blood type, wherein the method utilizes two distinct monoclonal antibodies, which recognize feline blood group specific A antigens.

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: Reagents and the use of the reagents in a microparticle light scattering agglutination assay are disclosed. The reagents comprise a mixture of particles having relatively stronger light scattering properties and particles having relatively weak light scattering properties with respect to one another. The particles having strong light scattering properties carry a binding partner of high reactivity with the analyte. The particles having weak light scattering properties carry a binding partner of low reactivity with the analyte.

Abstract: An immunoassay reagent is obtained whereby a microscale substance such as an antigen or antibody can be assayed at a high sensitivity, and whereby a need to separate a reacted substance, e.g., an immunoreacted substance, from an unreacted substance can be eliminated or such a separation can be simplified. An immunoassay reagent, for use in the quantitative determination of a target antigen or antibody present in a sample, containing an insoluble carrier which carries an enzyme and an antibody or antigen corresponding to the antigen or antibody, an enzyme inhibitor for inhibiting the activity of the enzyme and a substrate with which the enzyme reacts.

Abstract: The methods and compositions disclosed herein concern highly diverse, novel labels comprising carbon nanotubes of discrete lengths and/or diameters. In certain embodiments, the nanotube labels may be attached to oligonucleotide or similar probes for use in DNA sequencing. Upon excitation, for example by an electron beam or UV laser, the carbon nanotubes exhibit distinguishable emission spectra. The nanotube labels are not limited to DNA sequencing, but rather are of use in any application where large numbers of distinguishable labels are desirable. Novel methods for production of carbon nanotubes and apparatus for detection of nanotubes are also disclosed herein.

Abstract: A method for separating and purifying HA-positive progenitor toxin(s) (LL and/or L toxins) and HA-negative progenitor toxin (M toxin) from a Clostridium botulinum strain is provided. The method comprises applying a liquid containing both the HA-positive progenitor toxin(s) and the HA-negative progenitor toxin to a lactose column. Also provided is a method for separating and purifying neurotoxin (7S toxin) from HA-positive progenitor toxins, which comprises treating HA-positive progenitor toxins with an alkaline buffer and then applying the resulting liquid containing dissociated neurotoxin and non-toxic components to a lactose column. Activated pure HA-positive toxins (L and LL toxins) and neurotoxin are obtained by simple procedures.

Abstract: A gelatin-based substrate for fabricating protein arrays, the substrate comprising: gelatin having at least one surface; a polymer scaffold affixed to the gelatin surface; wherein the polymer in the scaffold is rich in reactive units capable of immobilizing proteins.

Abstract: A supramolecule has a first supramolecular component including a first effector molecule covalently joined to a first nucleic acid, and a second supramolecular component including a second effector molecule covalently joined to a second nucleic acid, wherein the second nucleic acid has a region of at least partial complementarity to the first nucleic acid, wherein the first nucleic acid is in a base pairing relationship with the second nucleic acid and the first or second effector molecules are proteins, polypeptides, lipids or sugars. The supramolecule may further have a third supramolecule component which includes a third effector molecule covalently joined to a third nucleic acid, wherein the third nucleic acid has a region of at least partial complementary to the first nucleic acid or the second nucleic acid and wherein the third nucleic acid is in a base pairing relationship with the second nucleic acid or the first nucleic acid.

Abstract: A solid phase with at least one test area is described which contains reagents for the detection of at least one analyte in a sample, wherein the solid phase additionally comprises at least one control area for the detection of interfering reactions.

Abstract: A homogeneous assay for determining the deoxynivalenol (DON) content in grains uses the technique of fluorescence polarization. A grain extract is prepared by shaking a crushed grain sample with water. A mixture is prepared by combining the grain extract with a tracer and with monoclonal antibodies specific to DON. The tracer is able to bind to the monoclonal antibodies to produce a detectable change in fluorescence polarization. The tracer is prepared by conjugating DON to a suitable fluorophore. The fluorescence polarization of the mixture is measured. The DON concentration of the mixture may be calculated using a standard curve obtained by measuring the fluorescence polarization of a series of DON solutions of known concentration.

Abstract: A method and apparatus for assaying a drug candidate with a biosensor having one or more sensing surface-bound biomolecules associated therewith are disclosed. The method comprises the steps of measuring the binding interaction between the drug candidate and the one or more sensing surface-bound biomolecules of the biosensor to obtain an estimate of at least one binding interaction parameter of the drug candidate, and then comparing the estimated binding interaction parameter against a mathematical expression correlated from binding interaction data associated with known drug compounds to determine an estimate of at least pharmacokinetic parameter of absorption, distribution, metabolism, or excretion (ADME) that is related to the drug candidate. The present invention allows for the simultaneous measurement of different pharmacokinetic parameters of the drug candidate, as well as an indication of the drug candidate's solubility, by use of a single analytical instrument.

Abstract: The invention is directed to synthetic receptor(s) which comprises a polyfunctional organic template covalently linked to two or more oligomers which may independently be the same or different and may independently be straight chain, cyclic or branched. The template may be linked to an identifier which uniquely defines the synthetic receptor. The identifier is a stable chemical molecule or a plurality of stable chemical molecules distinguishable and detectable to picomolar levels or may be an oligonucleotide. In a preferred embodiment, the template is covalently linked to a solid support which is linked to an identifier. In addition, the invention includes methods of preparing synthetic receptors and synthetic receptor libraries. The synthetic library may be linked with identifiers such that the library comprises a plurality of different synthetic receptor members.

Abstract: A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.

Abstract: The invention provides novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics. Specifically, the claimed multi-dimensional methods involve combining a solution of heterogeneous ligands with the target of interest to screen the ligands on the basis of one or more binding characteristics. Ligands having the first binding characteristic bind to the target of interest thereby to form a target/ligand complex. The complex then optionally is separated from the unbound components using any of a variety of separation techniques, e.g., size exclusion. At least one of the complex or unbound components then is introduced to a second “dimension”. The second dimension is capable of separating components based upon a second binding characteristic. One then elutes the ligand having the desired binding characteristics.

Abstract: Combinatorial libraries are disclosed which are represented by Formula I: (T′—L)q—Ŝ—C(O)—L′—II′  I wherein: Ŝ is a solid support; T′—L— is an identifier residue; and —L′—II′ is a ligand/linker residue. These libraries contain dihydrobenzopyrans of the formula: which interact (i.e., as agonists or antagonists) with &agr; adrenergic receptors, dopamine receptors, &dgr;-opiate receptors, and K+ channels and are inhibitors of carbonic anhydrase isozymes. They are useful in the treatement of ocular diseases such as glaucoma.

Abstract: Provided are affinity support materials having intermediate binding affinity for biological samples. Among the materials provided by the present invention are hydrophilic solid supports composed of hydrophilic ligands coupled to hydrophilic matrixes which are compatible with biological samples, for example, a cell line, a biological fluid such as blood, or a tissue cell lysate. The ligands may include affinity property groups and hydrophilic groups pendent from a backbone, and be configured to at least partially resolve components of a biological sample. Affinity supports in accordance with the present invention may be used in a variety of techniques and apparatuses to achieve improved separations of complex biological samples and thereby enhance the results of biological sample component fractionations, enrichments, purifications, expression product determinations and comparisons, and other biological sample processing techniques.

Abstract: Arrays of protein-capture agents useful for the simultaneous detection of a plurality of proteins which are the expression products, or fragments thereof, of a cell or population of cells in an organism are provided. A variety of antibody arrays, in particular, are described. Methods of both making and using the arrays of protein-capture agents are also disclosed. The invention arrays are particularly useful for various proteomics applications including assessing patterns of protein expression and modification in cells.

Abstract: Methods for detecting anti-lipidic particles antibodies and lipidic particles in cellular membranes for the diagnosis of diseases associated to the antiphospholipid syndrome are disclosed. Kits or sets to put these methods of diagnosis into practice are also disclosed. Methods for the therapeutically treatment of diseases associated to the antiphospholipid syndrome are disclosed as well. In addition, methods for the detection of the diverse physiologic states of cells, and those kits useful for this are also disclosed.

Abstract: An ultrasonic energy source is used to provide a variable force for measuring the binding forces between molecular entities and for sensing the presence of an analyte in a test sample. The device includes a surface that has a first binding member attached thereto and one or more particles that have a second binding member attached thereto. A reaction vessel is provided for exposing the surface to the particles whereby, if the first binding member has a binding affinity for the second binding member, a complex is formed between individual first binding members and individual second binding members and the particles thereby become immobilized with respect to the surface. The ultrasonic energy source is positioned for applying a variable ultrasonic force onto the surface, and the position of the particles is monitored as the intensity of the ultrasonic force is varied.

Abstract: A method of making a high efficiency magnetic sensor for determining the presence or amount of an analyte in a test sample. The method typically includes providing a sensing device with a magnetic sensing element, exposing the sensing device to a fluid test medium suspected of containing an analyte and monitoring the resistance of the magnetic sensing element to detect any change in the electrical resistance of the magnetic sensing element in response to the immobilization of a magnetizable particle. The magnetic sensing element comprises at least one planar layer of electrically conductive ferromagnetic material having an initial state in which the material has a circular magnetic moment within the plane of the layer, a means to immobilize a magnetizable particle at a point along an axis that is perpendicular to the plane of the layer and passes through the center of the circular magnetic moment, and a means for detecting the change in the electrical resistance of each magnetic sensing element.

Abstract: The present disclosure relates to a method for determining cholesterol in low density lipoprotein comprising the steps of (a) measuring total cholesterol level in a sample containing at least high density lipoprotein, low density lipoprotein, very low density lipoprotein and chylomicron, and (b) measuring cholesterol levels in the high density lipoprotein, very low density lipoprotein and chylomicron in the sample, wherein the cholesterol level in the low density lipoprotein is determined by subtracting a value obtained in the step (b) from a value obtained in the step (a). The present invention enables concurrent determination of cholesterol level in low density lipoprotein and total cholesterol level, facilitating acquisition of two types of biological information at a time.

Abstract: The present invention relates to an immunological detection method capable of performing detection of an analyte in a test sample, and a kit used therefor. There is provided an immunological detection method for detecting an analyte by using a water-absorbent substrate in which a capture region is positioned in a given region on a surface thereof, the capture region being immobilized with a first immunochemical component capable of specifically binding to the analyte, wherein the detection signal is amplified and a kit used therefor.

Abstract: A biologically active conjugate is disclosed comprising a biopolymer and a therapeutic agent joined by a disulfide bond. The conjugate, when formulated in a pharmaceutical composition with a suitable carrier, has improved in vivo stability and activity, and can be targeted to a variety of cells, tissues and organs.

Abstract: The invention concerns the use of an adsorptive size exclusion chromatography gel, said gel essentially consisting of a polysaccharide matrix whereon is grafted a polymer coupled with an affinity ligand and having a cleavage threshold ranging between 2 kDa and 60 kDa for eliminating a purifying biomolecules.

Abstract: Compounds and the synthesis of compounds containing multiple precursor groups and allowing the efficient synthesis of highly functionalized oligonucleotides and oligomers are provided. Also, a branching unit that helps to further increase the density of functional groups on synthetic oligonucleotides and oligomers is provided.

Abstract: A process for detecting an analyte which process comprises (a) contacting a sample suspected of containing said analyte with a containment means comprising a barrier which separates signal generating reagents from said sample, in the presence of an element which interacts specifically with said analyte, under conditions whereby interaction between the analyte and the said element results in activation of the signal generating reagents within the containment means on the side of the barrier opposite to the sample, and (b) detecting any signal generated and retained within the containment means from the sample side of the barrier. The process of the invention provides for sensitive detection of very small numbers of analyte materials using measurement techniques which include counting methods such as flow cytometry.

Abstract: A method for counting leukocytes which comprises liberating elastase from granulocytes contained in a specimen, adding an anti-granulocyte elastase antibody to the thus liberated elastase, measuring the antibody bonded to the elastase to thereby determine the concentration of the elastase, and then calculating therefrom the number of leukocytes contained in the specimen with the use of the ratio of the leukocyte count to the elastase concentration. This method makes it possible to conveniently and less expensively count leukocytes at a high accuracy comparable to the one established by using a conventional automatic blood cell counter, as the figure shows.

Abstract: The invention relates to a method for determining an analyte by means of binding reactions, which method comprises: i) applying the sample to an application zone for sample (ASZ) on a flow matrix in which transport of components present in the sample can take place (transport flow), the flow matrix further exhibiting: a) optionally an application zone (AR*Z) for a binding reactant (Reactant*=R*) which is analytically detectable; b) a detection zone (DZ), which is located downstream of ASZ and exhibits an additional binding reactant (Capturer) firmly anchored to the matrix, and in which a complex (signal complex) containing the Capturer and the analyte and/or Reactant* is formed during the reaction, and ii) detecting the signal complex in the detection zone, the measured signal being used for determining the analyte.

Abstract: A class of asymmetric monobenzoxanthene compounds useful as fluorescent dyes are disclosed having structure (I) wherein Y1 and Y2 are individually hydroxyl, amino, imminium, or oxygen, R1-R8 are hydrogen, fluorine, chlorine, alkyl, alkene, alkyne, sulfonate, amino, amido, nitrile, alkoxy, linking group, and combinatios thereof, and R9 is acetylene, alkane, alkene, cyano, substituted phenyl, and combinations thereof. The invention further includes novel intermediate compounds useful for the synthesis of asymmetric benzoxanthene compounds having general structure (II) where substituents R3-R7 correspond to like-referenced substituents in the structure of described above, and Y2 is hydroxyl or amine. In another aspect, the invention includes methods for synthesizing the above dye compounds and intermediates. In yet another aspect, the present invention includes reagents labeled with the asymmetric benzoxanthene dye compounds, including deoxynucleotides, dideoxynucleotides, phosphoramidites, and polynucleotides.

Abstract: The invention relates to a new dipstick assay for detecting and quantifying the content of an target analyte in a sample. The assay is particularly useful for example in the diagnosis and monitoring of alcoholism by the detection of asialo transferrin or carbohydrate free transferrin (CFT). Thus, provided is a dipstick for determining the content of a target analyte variant in a mixture of analyte variants in a sample, comprising: a) a sample application zone, b) a screening zone having an immobilised binding ligand having a binding affinity for a non-target analyte variant or varinats, c) a conjugate zone comprising a detector reagent, d) a reading zone for detection of said analyte.

Abstract: A predictive test for rheumatoid arthritis comprises the detection of antibodies to collagen in a biological sample from a patient by contacting the biological sample with an antigen comprising the CB10 peptide of mammalian type II collagen, or an antibody-binding fragment or variant thereof, for a time and under conditions for an antibody-antigen complex to form, and detecting the antibody-antigen complex, for example by immunoassay. A diagnostic test kit is also disclosed.

Abstract: Methods, compositions and kits are disclosed. The compositions are light emitting and comprise a polymeric matrix having dissolved therein a photoactive compound. The composition has the characteristic that, after activation of the photoactive compound, the rate of decrease in the intensity of light emission at any time during a 20-fold decrease in the intensity is proportional to the intensity of the light emission. In one embodiment the polymeric matrix is comprised of particles of about 20 nm to about 100 &mgr;m in diameter to which is bound a specific binding pair member. The particles generally comprise a polymeric matrix having dissolved therein about 1 to about 20% by weight of a dopant. The compositions may be used in methods for determining an analyte. A combination is provided comprising (1) a medium suspected of containing the analyte, (2) and the aforementioned composition.

Abstract: The present invention relates to the substantial elimination of errors attributable to carryover microspheres, doublets, or misclassification of microsphere subsets. The present invention is based upon passing a sufficient minimum number microspheres through the flow analyzer during an assay run.

Abstract: Mesoporous materials and a method for making such materials is disclosed in which the mesoporous materials are made by forming an aqueous solution having an organometallic compound; adding a solution comprising a pore forming material selected from the group consisting of monomeric polyols, polyacids, polyamines, carbohydrates, oligopeptides, oligonucleic acids, carbonyl functional organic compounds, and mixtures and derivatives of these materials to form a sol get matrix by polycondensation; drying the sot gel matrix; and removing the pore forming material from the dried sot-gel matrix to thereby form a mesoporous material. The mesoporous materials have pore diameters of from about 20 Å to about 100 Å and may be used with a biologically active agent immobilized within the pores of the mesoporous material and introduced into a biological system.

Abstract: The present invention relates to bioassay materials useful for the detection of toxic substances and, more particularly, to packaging materials for food and other products, along with methods for their manufacture and use. The invention provides a unique composite material capable of detecting and identifying multiple biological materials within a single package. The biological material identification system is designed for incorporation into existing types of flexible packaging material such as polyvinylchloride or polyolefin films, and its introduction into the existing packaging infrastructure will require little or no change to present systems or procedures.

Abstract: A method and test kit for an agglutination assay for antibodies in human or other mammal serum is described. The kit preferably contains latex particles and uses extracellular antigen(s) of Pythiosis insidiosum which bind to the particles and which in turn bind to the serum antibodies to produce the agglutination. The assay is particularly important for detecting early stages of Pythiosis.

Abstract: The invention relates to devices and methods for carrying out quantitative fluorescence immunoassays using evanescent field excitation. Light from at least one light source is directed onto the boundary between two media which have differing refractive indices. The light source emits practically monochromatic light with a wavelength suitable for exciting a marking substance. The light is directed onto a boundary surface disposed between an optically transparent base plate, the refractive index of which is greater than that of the material above the boundary surface, and a receiving region for the sample. The receiving region is covered with a covering plate on the side disposed opposite the base plate, there being arranged between the base plate and covering plate at least one functional layer. A detector for detecting the fluorescent light is disposed on the same side of the base plate as the light source.

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: The present invention refers to capsules encapsulating solid particles of signal-generating organic substances and carrying on the outer surface affinity molecules for specific recognition of and binding to target molecules in a sample. The invention is directed to the use of these capsules for signal production in the optical, electrochemical or chemical detection of target molecules. To obtain a signal the signal-generating organic substances are released and dissolved. A detection method and a kit are provided.

Abstract: This invention provides a process for effectively producing an immobilized protein that is immobilized only at the carboxy terminus.

Abstract: A method and device is disclosed for rapidly identifying a large number of proteins by placing a protein mixture in a sample chamber of an electrophoresis gel, and performing electrophoresis to separate the mixture by molecular weight, in a direction of separation, into a two-dimensional separation pattern in the gel. The separation pattern is transferred to a membrane, such as a sheet of nitrocellulose, and a plate with a set of separate, side-by-side slots is then applied to the membrane. A different antibody mixture is introduced into each of the slots by perfusing each antibody mixture under pressure through the slots. The antibody mixture that is perfused through each slot recognizes several different proteins of sufficiently different molecular weights that different protein bands can be resolved by the antibody mixture in each slot.

Abstract: Thrombotic or thromboembolic disease is detected or monitored by determining the presence or amount B in a urine sample.

Abstract: A test piece for use in biological analyses includes a plurality of different known specific binding substances disposed in predetermined positions on a substrate. The specific binding substances are disposed on a plurality of surfaces provided by the substrate and arranged in the direction of thickness of the substrate.

Abstract: A competitive binding assay is used to determine whether a non-nucleic acid molecule from a library of non-nucleic acid molecules binds to a target. The non-nucleic acid molecule competes with a nucleic acid ligand for binding to the target which may be immobilized. Detecting displacement of nucleic acid ligand from a complex of the nucleic acid ligand and the target determines binding of the non-nucleic acid molecule to the target. The nucleic acid ligand may be immobilized and contacted with a target to form a complex. Adding a non-nucleic acid molecule to the complex displaces target from the complex, and detecting displacement of the target determines binding of the non-nucleic acid molecule to the target. Labeled nucleic acid ligand or labeled target displaced from or remaining in the complex can be detected for detecting displacement. Nucleic acid ligands that bind to the target are identified by the SELEX method.

Abstract: Peptidomimetic azatides and combinatorial oligoazitide libraries are produced by means of a stepwise synthesis. Combinatorial library construction of this new biomimetic polymer provides a means to fabricate global peptidomimetic libraries.

Abstract: A chromatographic test strip comprising a solid support having at least a first portion and a second portion with said portions being in the same plane so as to permit capillary flow communication with each other. The sample is added to the first portion. The first portion also may comprise a tracer portion having a tracer movably supported therein. The tracer consists of a visible particulate marker. In the second portion, a binder is immobilized. The test strip is useful in a variety of immunoassays.