Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Abstract: Method for detecting an analyte of interest, comprising the steps of providing a detection device comprising a light reflective or transmissive substrate supporting one or more layers comprising an adhering attachment layer to which is affixed a receptive material which specifically interacts with the analyte of interest; reacting the device with a sample potentially comprising the analyte under conditions in which the analyte binds to the receptive material; and reacting bound analyte with a reagent which creates a mass change on the surface of the device.

Abstract: The present invention relates to analytical devices for determining the presence or amount of an analyte in a test sample. The analytical devices comprise an inlet port, a vent, a channel, and an array of structures. The structures have immobilized reagent covalently or non-covalently attached to the surface of the structures. The immobilized reagent captures analyte in the test sample where it is detected by a detection system. The present invention also provides methods and reagents for performing assays utilizing the analytical devices of the present invention. The present invention also provides methods of manufacturing the analytical devices of the present invention.

Abstract: Improved affinity purification media are provided by the use of small specific binding agents, especially Fv antibody fragments or single domain antibody fragments, immobilised on porous carriers having pore sizes in the range 30-1000 angstroms, preferably 30-300 angstroms. Silica is a preferred carrier. The small fragments are able to penetrate the pores and maximise the effective surface area of the carrier, and the microporous silica is sufficiently robust to be used at high pressure, so enabling the speed and/or throughput of a purification procedure to be increased.

Abstract: Combinatorial chemical libraries of the Formula ?S!-C(O)-L'-Z containing biaryl amino acids are disclosed, in which ?S! represents a solid support and -L'-Z is a linker/compound residue. In these libraries, Z is --NR.sup.1 R.sup.2. R.sup.1 is chosen from H, C.sub.1 to C.sub.20 hydrocarbon, heteroaralkyl, heterocycloalkyl, substituted arylalkyl, alkoxyalkyl or alkyl-SO.sub.2 NH-alkyl and R.sup.4 is an acyl or sulfonyl residue. R.sup.2 is chosen from ##STR1## The combinatorial libraries are optionally encoded with tags. The use of these libraries in assays to discover biologically active compounds is also disclosed.

Abstract: The present invention relates to a sample processing method for rendering cellular components such as nucleic acids in a sample accessible. The method involves subjecting a sample of disrupted cells to sufficient agitation in the presence of particles to separate nucleic acids from other cellular components. A heat lysis process without other lysogenic agents or conditions is the preferred method of disrupting cells for the sample. Once accessed, the nucleic acids may be used in various molecular biology procedures.

Abstract: A method and device for detecting the presence, absence or amount of an analyte in a whole blood sample is disclosed. The device comprises four zones, a sample receiving zone, a labeling zone, a capture zone and an absorbent zone. The sample receiving zone contains an irreversibly immobilized reagent that allows for removal of substantially all red blood cells from the whole blood sample. Flow through the device is via capillary migration and all of the dissolved or dispersed components in the sample flow at substantially equal rates and with relatively unimpaired flow through the device. The method involves the use of the device for detection of analyte in a whole blood sample.

Abstract: A homogeneous method of measuring chemical binding relies on resonant, or "amplified," optical extinction (light scattering plus absorption) from a defined, specific class of colloidal particles wherein the real term n of the complex refractive index n-ik approaches zero while the imaginary term k approaches .sqroot.2. Chemical binding partners are coated onto the particles, which either aggregate or disperse during the binding reaction, causing an optical extinction change at one wavelength that is quantitatively related to the number of single colloidal particles and another at a second wavelength that is quantitatively related to the number of doublet colloidal particles.

Abstract: In accordance with a first aspect, a binding assay comprises a machine-readable storage medium which supports a molecular receptor (22). In accordance with a second aspect, a support member (50) supports first (22) and second (24) molecular receptors and first (26) and second (28) data identifying the molecular receptors (22,24). In accordance with a third aspect, a support member has a first annular portion (106) to support molecular receptors and a second annular portion (108) to support machine-readable data identifying the plurality of molecular receptors.

Abstract: The method of base sequence determination according to the present invention ensures an effective determination of a long DNA base sequence, by providing simultaneous determination of base sequences of two or more positions of the long DNA or base sequences of two or more DNAs, using the DNA probe chip which classifies and retains the DNA oligomers having various sequences, and using fluorophorelabeled primers which have the same sequencies as the oligomers in the chip and are labeled by various fluorophores, then followed by the extension of the determined base length by re-selection of the primers complementary to the sequence thus determined.

Abstract: An assay plate for detecting the presence of a mobile reactant that binds to a immobilized reactant and the methods of making and using the same. An assay plate according to the present invention includes a substrate and at least one dried aliquot of the immobilized reactant, the immobilized reactant being bound to the surface of the substrate. The immobilized reactant binds the mobile reactant when a solution containing the mobile reactant is brought into contact with the immobilized reactant. The mobile and immobilized reactants may be any pair of biological compounds that have a specific affinity for one another. For example the reactants may be nucleic acids or antibody-antigen pairs. The preferred embodiment of an assay plate according to the present invention includes a plurality of assay spots, each spot having a different immobilized reactant or concentration thereof.

Abstract: The invention provides a sensor for detecting an analyte comprising a support for a bioreceptor or biomimic and a detection means, wherein the support can retain a bioreceptor or biomimic and the support and the bioreceptor or biomimic and the detection means can be arranged such that when the sensor is placed in a medium containing a substrate, the substrate contacts the bioreceptor or biomimic and reacts to generate a response which is detectable by the detection means and which is relatable to the concentration of the analyte, and the support comprises a non-volatile organic liquid.

Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semi-cylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method have patches of capture molecules each specific for a different analyte disposed adjacent 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 non-specific-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: This invention relates to an improved method for detecting and quantifying the presence of a target molecule, such as an antigen, an antibody or a polynucleotide, in a sample which method uses alkaline phosphatase as the reporter enzyme and the reduction of a tetrazolium salt to a formazan as part of the detection/signaling system.

Abstract: A method for the repeated transfer of liquids from one of several storage containers into a transfer container wherein protective tips are placed onto a tip of a pipette in order to avoid contamination.

Abstract: A method for fractionating and sequencing DNA via affinity interaction is provided comprising contacting cleaved DNA to a first array of oligonucleotide molecules to facilitate hybridization between said cleaved DNA and the molecules; extracting the hybridized DNA from the molecules; contacting said extracted hybridized DNA with a second array of oligonucleotide molecules, wherein the oligonucleotide molecules in the second array have specified base sequences that are complementary to said extracted hybridized DNA; and attaching labeled DNA to the second array of oligonucleotide molecules, wherein the labeled re-hybridized DNA have sequences that are complementary to the oligomers.

Abstract: Methods are provided for conducting specific binding assays to determine the concentration or presence of at least one analyte in a sample. Dendrimer-reagent preparations with particular analyte specificities are mixed in solution with a sample to form dendrimer-reagent-sample complexes. The complexes are then immobilized on a solid phase. Immobilization is facilitated by coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.

Abstract: Novel sensor devices composed of a crystalline colloidal array (CCA) polymerized in a hydrogel are disclosed. The hydrogels are characterized as being capable of shrinking and swelling in response to specific stimuli applied thereto. As the hydrogels shrink or swell, the lattice structure of the CCA embedded therein changes, thereby changing the wavelength of light diffracted by the CCA. Thus by monitoring the change in diffracted wavelength, the concentration of a stimulus is determined. The gels can be modified to sense numerous different stimuli. The sensor devices are specific in that they are modified to react with only one species or family of species. These sensors have various applications in areas including, for example, environmental and chemical systems, chemomechanical systems, sensor devices and medical diagnostic tools. Various methods for making and using these devices are also disclosed.

Abstract: Simplicity, sensitivity and versatility of optical sensors based on competitive immunoassays using antibody-antigen reactions are achieved by solid-state, single-step reactions which permit accurate sensitive qualitative and quantitative information to be obtained without human participation. All of the chemistry-biochemistry is an inherent part of the sensor. A direct reaction occurs when the sample (antigen) is brought in contact with the sensor. The sensitivity of the competitive immunoassay optical sensor is controlled and increased by selecting a tag for the antigen or altering the attachment of a tag to an antigen so that the binding of tagged antigen to an antibody is decreased relative to the binding of untagged antigen to the antibody. The user can vary size, molecular weight and geometric configuration of the tagged antigen.

Abstract: A method and apparatus for identifying molecular structures within a sample substance using an array having a plurality of test sites upon which the sample substance is applied. Each test site includes a probe formed therein to bond with an associated target molecular structure. An electrical signal is applied to the test site and the electrical properties of the test sites are detected to determine which probes have bonded to an associated target molecular structure.

Abstract: Disclosed are methods of purifying shiga-like toxins (SLTs) from Polymyxin B sulfate extracts of Verotoxin-producing Escherichia coli. The methods are facile, efficient and reproducible. In another aspect, the toxin is inactivated for use in a vaccine against SLT mediated disease conditions.

Abstract: This invention relates to a device comprising a hydrophobic solid support coated with a chemical that can capture bacterial lipopolysaccharides (LPS). This invention also relates to the use of such a device in an immunoassay for the detection of microorganisms. This invention also relates to the incorporation of such a device into a diagnostic kit.

Abstract: The present invention provides for the screening of candidate substances to identify active compounds that inhibit multidrug resistance (MDR). The expression of glucosylceramides has been determined to be a marker of MDR. By measuring glucosylceramide expression in cells exhibiting MDR, and the reduction in glucosylceramide levels in the presence of a candidate substance, the present invention provides for the identification of MDR inhibitory compounds.

Abstract: Method for the determination of chlamydial or gram negative bacterial antigen comprising contacting a sample potentially containing extracted antigen with an optically active surface comprising an attachment layer, and a layer of non-specific protein.

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: An optochemical fluorescence sensor with a biorecognitive layer for measuring the concentration of one or more analytes in a sample is provided with at least one island layer which is applied on a sensor substrate. The islands of the island layer are in the form of electrically-conductive material and have a diameter of less than 300 nm, the biorecognitive layer being directly applied on the island layer or bound via a spacer film. In addition, an analyte-specific fluorescent compound is provided which may be added to the sample or is provided in the sensor itself. The biorecognitive layer can bind the analyte to be measured directly or by means of analyte-binding molecules, the originally low quantum yield of the fluorescent compound increasing strongly in the vicinity of the island layer.

Abstract: A suspension of inert particles is prepared in an aqueous solution, to which an antibody or an antigen and a carrier-bound antigen or antibody, respectively, are needed in any desired order. After centrifuging, the positive, weakly positive, or negative reaction can easily be recognized on the basis of a simple pattern.

Abstract: Methods and compositions are provided for specific binding assays in which specific binding reagents are immobilized on a solid phase. Immobilization is facilitated by covalently coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.

Abstract: An exciting light 2 is introduced within a slab-type optical waveguide 1, an evanescent wave due to the exciting light 2 excites fluorescent light, and among the fluorescent light, a fluorescent light which is radiated in a direction which direction crosses the exciting light 2 by a predetermined angle, is detected by a fluorescent light detector 4. Consequently, the exciting light and the fluorescent light are spacially separated so as to reduce stray light, and an arrangement of an optical system is simplified.

Abstract: A patterned multiple antibody substrate for use in biosensors or immunosensors is produced by (1) coating an antibody-adsorbent substrate with a material that resists antibody adsorption, (2) using ion beam sputtering, laser ablation, or mechanical scribing to remove the coating at specific sites on the substrate, and then (3) adsorbing specific antibodies at the sites. The substrate is capable of detecting multiple chemical species simultaneously.

Abstract: A transducer for detecting biomolecules comprises a bottom and a top unit. The bottom unit has a set of parallel electrically conductive transmission lines thereon and probes attached to selected locations along each transmission line for binding with the target molecule. The top unit has thereon a second set of parallel transmission lines transverse to those on the bottom unit. By applying AC signals sequentially to the two sets of transmission lines, each of the probe locations at the intersection of the two transmission lines can be addressed and the response of the probe in an unfilled detector location or a complex formed by the probe and the target in a filled detector location can be measured. If the target has been labelled, than the label at each of the locations may also be detected. The device can also be used for measuring binding constants between the probe and the target and concentrations of target solutions.

Abstract: The present invention provides a method of performing an immunological assay separately and in parallel for each of at least a first sample containing or prospectively containing a first binding moiety, which can be an antigen or an antibody, and a second sample containing or prospectively containing the first binding moiety, the method comprising: placing the first sample and the second sample into an array comprising a solid substrate, a plurality of wells and channels, wherein at least one channel is a crossover channel formed in the upper surface of the substrate and is situated above another channel formed in the lower surface of the substrate, thereby forming crossovers comprising crossing but non-intersecting channels; moving said first sample into a first well containing a second binding moiety, which can be an antigen or an antibody, that binds to the first binding moiety, wherein the second binding moiety is bound to the walls of the first well; moving said second sample into a second well containin

Abstract: Sensor devices for use in assaying for a ligand in a sample are described, the devices comprising: i) a discrete zone ("the measurement zone") on a region of which ("the measurement region") is immobilized directly or indirectly a first specific binding partner for the ligand under assay (or a reagent precomplexed with or capable of forming a complex with a specific binding partner for the ligand under assay), which zone additionally contains in releasable form, a first known amount of an optionally labelled second specific binding partner for the ligand under assay, the second specific binding partner being directed to an epitope of the ligand assay different to the epitope to which the first specific binding partner is directed; and ii) a second discrete zone ("the reference zone") on a region of which is immobilized directly or indirectly a first specific binding partner for the ligand under assay (or a reagent precomplexed with or capable of forming a complex with a specific binding partner for the ligand

Abstract: Methods are disclosed for measuring the accumulation of advanced glycosylation endproducts (AGEs), which are predicated on the discovery that such AGEs are present in tobacco and its byproducts. More particularly, the methods focus on the observation that individuals who smoke or otherwise use tobacco have increased levels of AGEs over non-smoking individuals. The present methods relate to the measurement of AGE levels in both individuals and in tobacco and its byproduct, smoke. Methods are also disclosed for the evaluation of the tobacco products to determine their storage status and organoleptic capacity and potential, as well as for the treatment of the ambient to lower AGE levels. For example, air or other samples may be taken and evaluated by a dosimeter or like device, to determine whether AGE levels exceed normal, after which measures could be implemented to remediate the ambient condition. All such methods and corresponding materials are contemplated and included.

Abstract: The present invention is an assay for determining glycoprotein IIb/IIIa receptor blockade in whole blood. Agglutinization of small polymeric beads coated with a glycoprotein IIb/IIIa ligand such as fibrinogen results when the beads are contacted with whole blood containing platelets with glycoprotein IIb/IIIa receptors that are not blocked. Failure to agglutinate indicates that blockade of the GPIIb/IIIa receptors has been achieved. In a preferred embodiment, the addition of a thrombin receptor activator results in an assay that is rapid and convenient enough to be performed at the bedside and that results in agglutination of the small polymeric beads within a convenient, known period of time if the glycoprotein IIb/IIIa receptors are not blocked.

Abstract: The invention concerns a binding matrix containing a carrier material with an oxidic surface and a solid phase reactant covalently bound thereto via anchor groups which is capable of binding to at least one free reaction partner, which is characterized in that the solid phase reactant forms a diluted and essentially laterally homogeneous binding layer on the surface of the carrier material and that the anchor groups are silane groups and are linked to the solid phase reactant via a spacer molecule.

Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide and optionally has multi-well features and improved evanescent field intensity. The preferred biosensor and assay method have the capture molecules immobilized to the waveguide surface by site-specific coupling chemistry. Additionally, the coatings used to immobilize the capture molecules provide reduced non-specific protein adsorption.

Abstract: A long range surface plasmon resonance sensor for use in biological, biochemical or chemical testing. The sensor includes a first dielectric medium and a second dielectric medium having an index of refraction approximately matching the first dielectric medium. A double-grating structure is located between the first dielectric medium and the second dielectric medium. A beam of electromagnetic radiation is introduced into the second dielectric medium in a manner which causes long range surface plasmon resonance to occur such that the beam of radiation suffers attenuated total reflection. The characteristics of the resonance dependent upon the reaction between the bonding layer and the targeted bonding molecule are then detected.

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 allowed 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: Methods for testing oligonucleotide arrays are disclosed including methods for testing the efficiency of nucleotide coupling; methods for testing amounts of deprotected oligonucleotides; methods for determining amounts of depurinated oligonucleotides; and methods of detecting the presence of cleavable structural features, such as double-stranded nucleic acids.

Abstract: The present invention relates to methods of enriching for desired cell population from cell sources, such as body fluids, dispersed tissue specimens and cultured cells. In particular, the present invention relates to the use of a cell-trap centrifugation tube containing a specific density gradient solution adjusted to the specific density of a desired cell population to enrich for the desired cell from a cell source. The tube allows the desired cell population to be collected by decantation after centrifugation to minimize cell loss and maximize efficiency. In addition, the method can be further simplified by density-adjusted cell sorting which uses cell type-specific binding agents such as antibodies and lectins linked to carrier particles to impart a different density to the undesired populations in a more convenient manner. The rapid cell enrichment method described herein has a wide range of diagnostic and therapeutic applications.

Abstract: The present invention relates to a vehicle for delivery of particles to a sample of cells. The vehicle includes a barrier to retain the particles, which barrier is a dissolvable material. Once released into the sample, the particles are useful in methods to lyse or disrupt cells or in methods to separate cellular components from one another if the cells in the sample are already lysed or disrupted.

Abstract: Surfaced-enhanced, analytical procedures wherein a surfaced article includes a substrate surface, metal islands, a spacing/coupling agent layer, and binding partner molecules which bond with work piece molecules to be detected. A population of spaced apart metal islands are formed on the substrate and have at least some interconnections formed between them. A continuous layer coats the islands and all surfaces between the islands. The continuous layer includes a coupling agent which immobilizes first binding partner molecules. The first partner molecules bond to the coupling agent and the second binding partner molecules bind to the first binding partner molecules to allow detection of presence or concentration of the work piece binding partner molecules.

Abstract: Disclosed are novel compositions of morphogenic proteins constituting soluble forms of these proteins, antibodies that distinguish between soluble and mature forms, and method for producing these morphogenic proteins and antibodies.

Abstract: The invention relates to a biochemical sensor including a substrate on which yeast cells are deposited which are capable of capturing one type of molecules (M) and of producing a chemical entity (P) at the outcome of the capture; it also includes means for detecting the entity (P). The yeast cells employed are yeast cells obtained by genetic manipulation, in which the capture sites have been adapted to the type of molecules (M).

Abstract: Ligands that interact with a target can be more easily identified if false positive interactions (either specific or non-specific) from the detecting system are differentiated from the target-specific interaction. An improved method of identifying peptides which bind with a target protein is presented. The steps are: binding a random library of peptides to a support material, allowing detection reagents to contact the peptides and the support material then identifying these interactions, then allowing the target protein to selectively bind to the peptides, allowing detection reagents to contact the bound target protein, and characterizing the peptide bound to the identified support material. Interaction of a ligand or the support material with the detection reagents will cause a distinct color change which distinguishes those ligands which selectively bind to target protein. The characterized peptide can then be used in affinity purification of the target protein.

Abstract: An assembly for use in biological assays containing an integral ceramic core and, partially abutting the core, a sheath. The ceramic core has a mean pore size of from about 1 to about 400 microns, an apparent porosity of from, about 25 to about 60 percent, a hydrophilic surface, a length of from about 10 to about 200 millimeters, and a wicking rate of at least about 20 millimeters per minute; the sheath has a wicking rate of less than 5 millimeters per minute.

Abstract: A method of assaying for a ligand in a sample involves incubating the sample in contact with a specific binding partner for the ligand carried on one surface of an optical structure, irradiating the structure at a suitable angle or range of angles to the normal such that the resonance and/or total internal reflection of the radiation occurs within the optical structure and/or the layer of specific binding partner, and analyzing the radiation in order to determine whether, and if desired the extent to which and/or rate at which the generated radiation and/or optical characteristics of the optical structure are altered by complex formation.

Abstract: A chemical sensor includes a patterned layer having discrete sections, a -dimensional detector array, and a two-dimensional lens array that focuses an optical signal from the patterned layer onto the two dimensional detector array. Typically, the two-dimensional detector array is a charge-coupled device array and the lens array is a graded index of refraction lens array. The chemical sensor maintains good resolution throughout its field of view.

Abstract: A sol-gel glass doped with one or more reagent that provides chemical interactions with diffusible solutes or components in an adjacent liquid or gas phase. The reagent(s), the solutes or the components can be any organic or inorganic compounds or materials of biological origin, including enzymes. The doped sol-gel glass in various forms is useful as an analytical test, chromatographic medium, sensor, catalyst or biocatalyst, electrode or enzyme electrode, and other detection devices.