Abstract: The invention describes quality control devices for assays that measure analytes in cells and tissue samples, and methods of use thereof. In particular, the quality control device comprises a matrix affixed with synthetic controls in different concentrations, or different synthetic controls. The quality control device can be adhered to a microscope slide via an adhesive or chemically attached to a microscope slide and processed simultaneously with a tissue sample.

Abstract: The invention suggests a method of producing an array for the detection of components from a biological sample, wherein the detection molecules are immobilized on one or more supports, said support(s) is/are embedded and subjected to curing, the support is separated into sections, and the sections are applied on another support.

Abstract: Disclosed are devices for detecting the presence of a preselected analyte in a fluid sample. The devices comprise a substrate microfabricated to define a sample inlet port, and a mesoscale flow system that includes a sample flow channel extending from the inlet port. The mesoscale flow system further includes an analyte detection region in fluid communication with the flow channel comprised of a binding moiety for specifically binding the analyte. The detection region is constructed with a mesoscale dimension sufficiently small to enhance binding of the binding moiety and the analyte. The binding moiety may be immobilized in the detection region. The mesoscale detection systems of the invention may be used in a wide range of applications, including the detection of cells or macromolecules, or for monitoring reactions or cell culture growth.

Abstract: This invention provides a novel device and method for preparing cytology slides. The device comprises a book-like form including an absorbent material and filter attached to the inside surface of a front cover and a cytology slide removeably attached to an inside surface of a back cover. A sample is removed from the body of a patient, placed in a liquid-based solution, and then on the filter. When the book-like form is closed, the sample is effectively transferred to the slide. The device can be modified so that a plurality of slides are prepared at the same time.

Abstract: The present invention features novel compositions, linkers, derivatized solid supports, and methods for the efficient solid phase synthesis of oligonucleotides, including RNA, DNA, RNA-DNA chimeras, and analogs thereof.

Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semicylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method has patches of capture molecules, each specific for a different analyte disposed adjacently within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers, which in turn are coupled to the waveguide surface or to a nonspecific binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers, the selective irradiation involving a mask, a laser light source, or the like.

Abstract: New reactive dyes are described which can be used to fluorescently label bioorganic molecules such as amino acids, proteins, antibodies, nucleotides and also polymer particles. The color of the new dyes and conjugates thereof can be varied over a wide range. In contrast to known symmetric cyanine dyes, the dyes of the invention contain only one reactive group. Hence the labelling takes place without the interfering cross-linking that occurs with bireactive dyes. Their fluorescence quantum yields are very high (especially in the conjugated form). Conjugates thereof with proteins, oligonucleotides or particles can be used in fluorescence-based analytical methods of determination e.g. in immunoassays, in hybridization assays, in cytometry or for pharmaceutical screening.

Abstract: The present invention overcomes the problems and disadvantages associated with prior art arrays by providing an array comprising a plurality of biological membrane microspots associated with a surface of a substrate that can be produced, used and stored, not in an aqueous environment, but in an environment exposed to air under ambient or controlled humidities. Preferably, the biological membrane microspots comprise a membrane bound protein. Most preferably, the membrane bound protein is a G-protein coupled receptor, an ion channel or a receptor tyrosine kinase.

Abstract: There is provided an apparatus for screening pharmacological agents for agents which induce regression of cancer. The apparatus includes an evanescent sensing device, at least one sensor having affixed to its surface molecules of a first type, which have affinity for molecules of a biological receptor, the surface molecule and receptor molecule combination having the effect that, in vivo, the binding affects the rate of transcription of gene products, and a molecular tag wherein the molecular tag is bound to the sensor wherein the binding between molecules of the first type and molecules the biological receptor cause the tag to produce a alteration in signal recorded by the evanescent sensing device, the tag also being bound to molecules of a second type, the molecules of the second type having affinity for the receptor molecules.

Abstract: This invention provides materials and methods for the site specific attachment of virtually any moiety to a layered silicate surface. The methods involve covalently attaching the moiety to an arginine tag; and contacting the arginine tag with the layered silicate (e.g., mica) surface.

Abstract: The optical sensor contains an optical waveguide (1) with a substrate (104), waveguiding material (105), a cover medium (106) and a waveguide grating structure (101-103). By means of a light source (2), light can be emitted to the waveguide grating structure (101-103) from the substrate side and/or from the cover medium side. (101-103). With means of detection (11), at least two differing light proportions (7-10) radiated from the waveguide (1) can be detected. For carrying out a measurement, the waveguide can be immovably fixed relative to the light source (2) and the means of detection (11). The waveguide grating structure (101-103) itself consists of one or several waveguide grating structure units (101-103), which if so required can be equipped with (bio-)chemo-sensitive layers. The sensor permits the generation of absolute measuring signals.

Abstract: Methods and compositions are provided for detecting biomolecular interactions. The use of labels is not required and the methods can be performed in a high-throughput manner. The invention also provides optical devices useful as narrow band filters.

Abstract: Immunoassay methods and apparatus are provided which utilize flow cytometry, coated latex microspheres, and fluorochrome labeled antibodies, to simultaneously detect the presence and amount of one or more analytes in a sample. Beads of several different sizes, colors or shapes, each bead are coated with a different analyte, for the simultaneous detection of one or more analytes and of cell components. The invention is also directed to platelet Ig positive control reagents and assays which provide for the setting of the fluorescence positive region for each patient. The platelet control is sized to fit between the platelets and red cells and thus making it ideal as a true biological control.

Abstract: An optical sensor device for determining the presence or concentration of an analyte, contains a waveguide disposed over a light source and a light detector mounted on a surface of a substrate and separated by an internal baffle, wherein the waveguide has a thickness corresponding to a far field emission point of the light source as determined by a light shielding baffle between the light source and light detector. An analyte indicator matrix is disposed on the outer surface of the waveguide. The sensor device geometry takes advantage of only direct illumination of the indicator matrix, and direct collection of indicator matrix illumination, without any significant reflection by said waveguide. Undesirable light noise generated by the light source passes directly out of the device through the waveguide.

Abstract: The invention includes a composition of matter and method that utilizes energy transfer between one or more donor and acceptor molecules. The composition of matter includes an encapsulation vesicle having a matrix, a surface coating of an organo-metallic complex and a transparent protection layer. The transparent protection layer is capable of modification by addition of biomolecules to the surface in order to bind other molecules. The proximity of the bound biomolecules to the protective layer allows for energy transfer from a donor molecule internal to the protection layer to an acceptor molecule outside the protection layer. The protection layer acts to diminish the effects of collisional quenching on the donor molecules caused by ubiquitous small molecules such as molecular oxygen. The application also teaches a method of making and applying the complexes to immunoassays.

Abstract: Immunoassay methods and apparatus are provided which utilize flow cytometry, coated latex microspheres, and fluorochrome labeled antibodies, to simultaneously detect the presence and amount of one or more analytes in a sample. By combining FALS and fluorescence, it is practical to use beads of several different sizes, colors or shapes, each bead coated with a different analyte, for the simultaneous detection of one or more analytes and of cell components such as platelets in a sample.

Abstract: A semiconductor nanocrystal compound is described capable of linking to an affinity molecule. The compound comprises (1) a semiconductor nanocrystal capable of emitting electromagnetic radiation and/or absorbing energy, and/or scattering or diffracting electromagnetic radiation—when excited by an electromagnetic radiation source or a particle beam; and (2) at least one linking agent, having a first portion linked to the semiconductor nanocrystal and a second portion capable of linking to an affinity molecule. The compound is linked to an affinity molecule to form a semiconductor nanocrystal probe capable of bonding with a detectable substance. Subsequent exposure to excitation energy will excite the semiconductor nanocrystal in the probe causing the emission of electromagnetic radiation.

Abstract: A particle-enhanced assay for determining an analyte in a test sample in which an additive for reducing non-specific particle aggregation is added in an amount to substantially reduce non-specific aggregation. The additive is selected form the group consisting of triethanolamine, trimethanolamine, N-butyldiethanolamine, 3-dimethylamino-2-methylpropyl chloride, N,N-dimethylglycine, N,N-dimethylguanidine, N,N-dimethylglycine ethyl ester, 3-dimethylaminopropionitrile, and N,N-dietylacetamide.

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: Single-mode and multi-mode fibers to achieve modal splitting and greater sensitivity in an optical fiber coupler for evanescent-wave biosensor applications. A source of light having multiple modes is coupled to the input to one of the multi-mode fibers, with the geometry of necked-down section being such that a limited number of modes may be carried by the multi-mode fiber as the light emerges from the coupler. At least one of the single-mode fibers is supported adjacent the multi-mode fiber to receive and carry one of the limited modes. A biomolecule enveloped by the evanescent field, exhibits a direct or indirect affinity to a binding partner, such that attachment of the binding partner is at least partially responsible for the limited number of modes carried by the multi-mode fiber as the light emerges from the coupler.

Abstract: The present invention relates to a linker system for activating surfaces for bioconjugation, and particularly to a linker system having a novel hydrophilic spacer group. The inventive linker system may be used for the construction of sensor chips or biochips for the detection of sample biomolecules.

Abstract: The present invention provides an apparatus for analyzing the sequences of polynucleotides. The apparatus comprises (a) flow cell which has at least one microfabricated multilayer elastomeric synthesis channel; and (b) an inlet port and an outlet port. The inlet port and outlet ports are in fluid communication with the flow cell for flowing fluids into and through the flow cell.

Abstract: A step-gradient composite waveguide for evanescent sensing in fluorescent binding assays comprises a thick substrate layer having one or more thin film waveguide channels deposited thereon. In one embodiment, the substrate is silicon dioxide and the thin film is silicon oxynitride. Specific binding molecules having the property of binding with specificity to an analyte are immobilized on the surface of the thin film channels. In preferred embodiments, the composite waveguide further includes light input coupling means integrally adapted to the thin film channels. Such light coupling means can be a grating etched into the substrate prior to deposition of the thin film, or a waveguide coupler affixed to the upper surface of the thin film. The waveguide coupler has a thick input waveguide of high refractive index which receives the laser light through one end and propagates it by total internal reflection.

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: The invention relates to devices, devices for arraying biomolecules, including cells, methods for arraying biomolecules, assays for monitoring cellular movement, and systems for monitoring cellular movement.

Abstract: An improved microfabricated apparatus for conducting a multiplicity of individual and simultaneous binding reactions is described. The apparatus comprises a substrate on which are located discrete and isolated sites for binding reactions. The apparatus is characterized by discrete and isolated regions that extend through said substrate and terminate on a second surface thereof such that when a test sample is applied to the substrate, it is capable of penetrating through each such region during the course of said binding reaction. The apparatus is especially useful for sequencing by hybridization of DNA molecules.

Abstract: A method of treating particles to be used in immunoassays reduces interference in particle agglutination assays. For particles having covalently bound antibodies and residual NHS-ester or sNHS-ester groups on the surface, the reactive esters are treated with an aqueous mixture containing an amine compound of formula (I): H2N—R—X??(I). The moiety —X is —NH2, —OH, or —CO2CH2CH3; and R is an alkyl group or an alkyl ether group. When —X is —NH2 or —CO2CH2CH3, R contains from 1 to 20 carbon atoms; and when —X is —OH, R contains from 4 to 20 carbon atoms.

Abstract: This invention provides a novel device and method for preparing cytology slides. The device comprises a book-like form including an absorbent material and filter attached to the inside surface of a front cover and a cytology slide removeably attached to an inside surface of a back cover. A sample is removed from the body of a patient, placed in a liquid-based solution, and then on the filter. When the book-like form is closed, the sample is effectively transferred to the slide.

Abstract: The microarrays of the present invention are prepared by using a separate fiber for each compound being used in the microarray. The fibers are bundled and sectioned to form a thin microarray that is glued to a backing.

Abstract: The present invention relates to equine Fc epsilon receptor alpha chain nucleic acid molecules, proteins encoded by such nucleic acid molecules, antibodies raised against such proteins, and inhibitors of such proteins. The present invention also includes methods to detect IgE using such proteins and antibodies. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies and/or inhibitory compounds as well as the use of such therapeutic compositions to mediate Fc epsilon receptor-mediated biological responses.

Abstract: Radiation-activated catalysts (RACs), autocatalytic reactions, and protective groups are employed to achieve a highly sensitive, high resolution, radiation directed combinatorial synthesis of pattern arrays of diverse polymers. When irradiated, RACs produce catalysts that can react with enhancers, such as those involved in autocatalytic reactions. The autocatalytic reactions produce at least one product that removes protecting groups from synthesis intermediates. This invention has a wide variety of applications and is particularly useful for the solid phase combinatorial synthesis of polymers.

Abstract: The invention relates to a method for producing a detection system for detecting different analytes in a sample, characterised by the following steps: providing a planar or essentially planar substrate which has sensors for chemically, optically or electrically detecting the analytes; applying an already microstructured layer to the substrate or applying a continuous layer to the substrate and microstructuring said layer, the layer being applied in such a way in either case that the areas of the substrate that are separated from each other are not covered by the layer, the layer and substrate being sealingly interconnected at least around the uncovered areas; bringing at least some of the uncovered areas into contact with at least one liquid containing catcher molecules, in such a way that said catcher molecules are able to adhere or bond to the surface of the substrate and/or on the surface of the sensors; removing the non-adhering constituents of the liquid and removing the microstructured layer or parts th

Abstract: The present invention is directed to a variety of microfluidic devices with configurations including the use of biochannels or microchannels comprising arrays of capture binding ligands to capture target analytes in samples. The invention provides microfluidic cassettes or devices that can be used to effect a number of manipulations on a sample to ultimately result in target analyte detection or quantification.

Abstract: The present invention concerns methods and compositions relating to matrix arrays. In certain embodiments, the arrays are translucent. In other embodiments, the arrays are reconfigurable. In preferred embodiments, the arrays are translucent and reconfigurable. Reconfigurable arrays may be produced using small linker molecules, such as aptamers or affibodies, attached to the array substrate. Preferably, the small linker molecules bind to an IgG specific portion of antibodies. Such arrays may be used to detect any target that binds selectively or specifically to an IgG, allowing great flexibility of use. Translucent matrix arrays may utilize a translucent, colloidal form of nitrocellulose to coat the array substrate.

Abstract: The present invention provides a composition comprising fluorescent semiconductor nanocrystals associated to a compound, wherein the nanocrystals have a characteristic spectral emission, wherein said spectral emission is tunable to a desired wavelength by controlling the size of the nanocrystal, and wherein said emission provides information about a biological state or event.

Abstract: Microarrays are prepared by using a separate fiber for each compound being used in the microarray. The fibers are bundled and sectioned to form a thin microarray that is glued to a backing.

Abstract: The present invention is directed to a silicon substrate having a monolayer formed by an electrochemically-induced reaction between silicon hydride moieties on the silicon surface and optionally substituted alkynes covalently bound to the surface of the silicon substrate and to a method for electrochemically producing such a functionalized silicon substrate. The method of forming a covalently bound monolayer on a silicon surface comprises the steps of contacting the silicon surface with a C2-C24 alkyne and electrografting optionally substituted alkynes to the silicon surface.

Abstract: The invention relates to devices, devices for arraying biomolecules, including cells, methods for arraying biomolecules, assays for monitoring cellular movement, and systems for monitoring cellular movement.

Abstract: A method and kit for monitoring autoantibodies to thyroid stimulating hormone (TSH) receptor in a sample of body fluid, which employs the steps of: (i) incubating TSH receptor with a sample of body fluid; (ii) reacting the incubated sample of body fluid with at least one binding agent which is capable of binding to the TSH receptor in competitive reaction with TSH receptor autoantibodies (TRAb), or in a case where TSH receptor is complexed to labelled antibody, reacting the sample of body fluid with at least one binding agent which can bind to TRAb in such a way as not substantially to interfere with binding of the TRAb to the TSH receptor; and (iii) detecting bound TRAb in the reacted incubated sample of body fluid.

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: An immunoassay for detecting an antigen in a sample, by: (a) sequentially contacting the sample with (i) a first antibody which is capable of specifically binding to a first binding site on the antigen, and then (ii) a second antibody which is capable of specifically binding to a second binding site on the antigen, thereby forming, when the antigen is present in the sample, an agglutinate comprising the first antibody, the antigen, and the second antibody; followed by (b) optically measuring the amount of the agglutinate.

Abstract: Sensors for determining the presence and concentration of bio-molecules in a biological sample are provided in the form of polymer brushes, which comprise a substrate having a surface that is modified with a water-dispersible or water-soluble polymer segment having functional groups that bind probes. The method of synthesis of such sensors preferably includes use of controlled free radical polymerization techniques, and in particular the use of an iniferter initiator, which allows for controlled architecture polymers to modify the surface of the substrate. In this manner functional groups in the polymer chain are removed from the surface, which allows for solution chemistry to be more realistically reproduced with the benefits of a solid bound probe.

Abstract: The invention relates to the use of carbopyronine compounds of general formula (I) as marker groups in methods for detecting analytes. The invention also relates to novel carbopyronine compounds and to a method for producing same.

Abstract: This invention relates to a method to characterize an array of polymeric materials comprising: depositing unsilanizable material onto a silanizable substrate in at least 10 regions, thereafter contacting the substrate with an organosilane agent thereby silanizing the substrate but not the unsilanizable material in said regions, optionally, partially or completely removing the unsilanizable material, depositing at least 10 polymeric materials onto said regions, and characterizing the materials. This invention also relates to method for forming an array of polymeric materials to be characterized onto a substrate comprising: (a) selecting ten or more polymers, (b) dissolving or suspending each polymer in a separate liquid, and (c) depositing a uniform amount of each of the ten or more polymer containing liquids onto a substrate in individual hydrophilic and/or hydrophobic regions.

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: Selective whole cell QCM biosensors are disclosed. Also disclosed are methods of making and using such whole cell QCM biosensors, e.g., to screen drugs and diagnose diseases.

Abstract: The present invention relates to methods for coupling labels to particular target moieties. The coupling reactions of the present invention use temporal spacing of the reactants through phase change (i.e. by rapid freezing) to control the initiation and termination of reaction. This process results in a simplified and improved method for linking labels to specific binding moieties using N-hydroxysuccinimide chemistry. The present invention further relates to kits comprising all necessary components to easily and rapidly make protein conjugates.

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: A multi-slide assembly includes various components that alone or in combination facilitate testing of test samples with minimal manipulation of assay components. Moreover, the various device components permit centrifugation, culturing and analysis of each test sample to be performed in the same assembly. A frame retains a plurality of reaction vessel assemblies between a pair of opposing channels that are configured to slidably receive the opposing ends of each reaction vessel assembly. A strip cap seals the openings in each reaction vessel using cap members having sealing rings circumscribing the external walls thereof to form compression seals with internal walls of the reaction vessels. Furthermore, in a method of making a multi-well slide assembly, an ultrasonic welding process removably bonds a plurality of wells to a slide plate to provide an adequate seal therebetween during centrifugation, yet still enable separation thereof by an operator.

Abstract: A device for detecting the presence of an antigen including (1) a cell having antibodies which are expressed on the surface of the cell and are specific for the antigen to be detected, where binding of the antigen to the antibodies results in an increase in calcium concentration in the cytosol of the cell, the cell further having a emitter molecule which, in response to the increased calcium concentration in the cytosol, emits a photon; (2) a liquid medium for receiving the antigen and in which the cell is immersed; and (3) an optical detector arranged for receiving the photon emitted from the cell.