Abstract: A sample separation apparatus including a porous, or rough, capillary column. The porous capillary column includes a matrix which defines pores, and may be formed from a material such as porous silicon. Alternatively, the capillary column may have a rough surface of hemispherical grain silicon. The capillary column is defined in a surface of a substrate, such as silicon. The sample separation apparatus may include a stationary phase or a capture substrate disposed on the surfaces thereof. The sample separation apparatus may also include a detector positioned proximate the capillary column. A variation of the sample separation apparatus includes an electrode proximate each end of the capillary column. The sample separation apparatus may be employed to effect various types of chromatographic separation, electrophoretic separation, and analyte identification.

Abstract: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.

Abstract: A method, apparatus, and computer program, for fabricating multiple arrays arranged successively in a first direction on a substrate and each having multiple feature sets arranged successively in the first direction within the array. The method uses a head system having multiple successive sets of dispensers. In the method, the head system is advanced in the first direction over the substrate while dispensing drop sets for each array from dispenser sets so as to form the arrays. In one aspect, drop sets are dispensed in an order the reverse of that from which the dispenser sets pass over a given location on the substrate as the head system advances in the first direction. In this case, each dispenser set deposits a drop set at a distance ahead of a drop set deposited by a preceding dispenser set which is less than the distance to the successive drop dispenser set which deposits the next drop set.

Abstract: The present invention contemplates a system for rapidly isolating nucleic acids. The system comprises an insoluble silica matrix and a buffered aqueous salt solution containing salt at a concentration of at least 3 molar and a buffering agent at a concentration sufficient to provide a buffering capacity corresponding to that which either tris(hydroxymethyl)aminomethane or phosphate ion at a concentration of 0.1 to 1 molar would provide in the solution. Methods of using the system are also contemplated.

Abstract: Method for Absorbing substances wherein adsorbent particles comprising superparamagnetic and/or low Curie Temperature transition metal-containing cores surrounded by a hydrous siliceous oxide coating can be formed by an aqueous process wherein the core is precipitated from an aqueous solution and a siliceous oxide coating is deposited thereon while complete drying of the core is avoided until after the siliceous oxide is deposited. The resulting siliceous adsorbents exhibit strong superparamagnetic and/or low Curie temperature magnetic properties with low transition metal leachability.

Abstract: The present invention relates to improved methods for conducting multiplexed assays of multiple target analytes in a manner that permits each target analyte to be assayed within a dynamic assay range. The invention further relates to reagents capable of implementing such methods.

Abstract: The invention provides biological molecules entrapped within a sol-gel matrix and incorporated into a microanalytical device for high throughput screening of samples. The pore sizes of the matrix may be chosen to match the size of the entrapped biological molecule or to correspond in size with the sample molecules to be analyzed. The sol-gel may be formed into structures that can be incorporated into or onto the microanalytical devices as microcolumns, microchannels, and microarrays. The sol-gel may incorporate substituted silanes and thereby provide a hydrophobic or hydrophilic surface, thereby providing the potential for use in microchromatography, microelectrophoresis or combinations thereof on the microanalytical device. A preferred detection method of samples is mass spectrometry.

Abstract: In a method for immobilizing biomolecules and affinity ligands water insoluble matrices, having amino groups and selected from test tubes, microtiter plates, microscope slides, beads, membranes, resins, and filters, are reacted with a cyclobutene carboxylic acid derivative, such as cyclobutene carboxylic acid diester, cyclobutene carboxylic acid halide, cyclobutene carboxylic acid ester halide, cyclobutene carboxylic acid dialkoxyester, and cyclobutene carboxylic acid imidazole, as an activating compound in methanol and triethylamine to form active matrices with active groups. A protein containing at least one primary or secondary amino group, is dissolved and added to the matrices. The activated matrices and the dissolved protein are incubated at pH of 7-10 and a temperature of +4° C. to +60° C. in an aqueous buffer system, free of primary and secondary amines, to thereby immobilize the protein on the matrices.

Abstract: A method of making a molecularly imprinted porous structure makes use of a surfactant analog of the molecule to be imprinted that has the imprint molecule portion serving as the surfactant headgroup. The surfactant analog is allowed to self-assemble in a mixture to create at least one supramolecular structure having exposed imprint groups. The imprinted porous structure is formed by adding reactive monomers to the mixture and allowing the monomers to polymerize, with the supramolecular structure serving as a template. The resulting solid structure has a shape that is complementary to the shape of the supramolecular structure and has cavities that are the mirror image of the imprint group. Similarly, molecularly imprinted particles may be made by using the surfactant to create a water-in-oil microemulsion wherein the imprint groups are exposed to the water phase.

Abstract: The invention provides improved immunoassay techniques for detecting the presence of analytes in a liquid sample. The present immunoassay methods utilize anti-allotypic monoclonal antibodies as capture reagents for primary binding proteins specific for the analytes of interest. The monoclonal antibodies are highly specific for the allotypic determinants present on the primary binding protein. The use of anti-allotypic monoclonal antibodies as capture reagents provides improved levels of specificity and accuracy of the immunoassay, in part because interference from endogenous immunoglobulins in the sample is significantly reduced. The invention further provides anti-allotypic monoclonal antibodies.

Abstract: The present invention relates to methods for fabricating solid supports. More specifically, the present invention features methods for fabricating solid supports for in situ synthesis and for carrying out large numbers of reactions. The present invention also features solid supports with in situ synthesized long polynucleotides.

Abstract: A method for producing a derivatized aldehydic support matrix material includes activating surface hydroxyl groups on the support matrix material and reacting the activated hydroxyl groups with an aldehydic alkoxy silane. The derivatized aldehydic support matrix material produced is useful for immobilizing bio-molecules in biological applications.

Abstract: Method for specific detection of one or more analytes in a sample. The method includes specifically associating any one or more analytes in the sample with a scattered-light detectable particle, illuminating any particle associated with the analytes with light under conditions which produce scattered light from the particle and in which light scattered from one or more particles can be detected by a human eye with less than 500 times magnification and without electronic amplification. The method also includes detecting the light scattered by any such particles under those conditions as a measure of the presence of the analytes.

Abstract: Methods for the parallel, in vitro screening of biomolecular activity using miniaturized microfabricated devices are provided. The biomolecules that can be immobilized on the surface of the devices of the present invention include proteins, polypeptides, nucleic acids, polysaccharides, phospholipids, and related unnatural plyomers of biological relevance. These devices are useful in high-throughput drug screening and clinical diagnostics and are preferably used for the parallel screening of families of related proteins.

Abstract: A method of making a molecularly imprinted porous structure makes use of a surfactant analog of the molecule to be imprinted that has the imprint molecule portion serving as the surfactant headgroup. The surfactant analog is allowed to self-assemble in a mixture to create at least one supramolecular structure having exposed imprint groups. The imprinted porous structure is formed by adding reactive monomers to the mixture and allowing the monomers to polymerize, with the supramolecular structure serving as a template. The resulting solid structure has a shape that is complementary to the shape of the supramolecular structure and has cavities that are the mirror image of the imprint group. Similarly, molecularly imprinted particles may be made by using the surfactant to create a water-in-oil microemulsion wherein the imprint groups are exposed to the water phase.

Abstract: The invention provides methods and reagents for the enhancement of surface plasmon resonance (SPR)-based detection assays. The methods and reagents can be used in any molecular recognition assay that uses a solid support. The invention also provides an SPR instrument that operates in imaging mode.

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 biosensor involves a specially designed surface which can be optically coupled to a Surface Plasmon Resonance spectrometer. The key components of the biosensor are a bimetallic layer, a self assembled monolayer of chemicals and a layer of biomolecules such as special antibodies. The innovative bimetallic layer combines the sensitivity of silver metal and durability of gold and thus make it an ideal biosensor layer not only for a low volatility gas phase detection but also for a liquid phase detection. The successful application of the biosensor in high explosive substance detection proves that the biosensor is a sensitive and highly specific device for security and anti-terrorism applications, when it is combined with a Surface Plasmon Resonance Spectroscope.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Abstract: An optical fiber is tapered, preferably adiabatically, and has a material coated on it for chemical bonding with fluorophores. When the fluorophores couple with the material, evanescent radiation generated fibers causes the fluorophores to fluoresce, and the fluorescence is coupled back into the fiber.

Abstract: A chromatographic assay or test device for detection and/or determination of an analyte in a test sample, comprises a base member, and a chromatographic medium located in or on said base member, the base member being provided with a receptacle to receive an applicator having the sample applied thereto, and the applicator being movable when located in said receptacle between a first position in which the applicator is out of fluid contact with the chromatographic medium, and a second position in which the applicator is in fluid contact with the chromatographic medium so as to apply a sample on the applicator to the chromatographic medium. In an alternative aspect, the test device comprises a base member, and a second member, at least one of the base member and the second member including a chromatographic medium, and the second member being slidably movable with respect to the base member from a first position to a second position.

Abstract: This invention relates to binding protein assays. In particular, this invention relates to binding protein assays for B12 and folate in serum or plasma. More specifically, this invention provides a sequential assay that uses a combination of specific binding proteins, and anti-binding protein antibodies to measure B12 and folate in serum or plasma.

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: The present invention describes novel methods for making a substrate for selective cell patterning, and the substrates themselves, wherein the method comprises contacting reactive hydroxyl groups on the surface of a substrate with a hydroxyl-reactive bifunctional molecule to form a monolayer, and using stencils to deposit cell repulsive or cell adhesive moieties in controlled locations on the cell culture substrate. Methods comprising selective differentiation of stem cells to create tissue specific and organ-specific cell substrates, as well as the cell substrates themselves are also provided.

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: Disclosed are biochips having a high detecting sensitivity with readiness in fabrication of microarray, and a method for fabricating the same, in which a solid support wound with fibers is immersed in a solution containing biomolecules to immobilize the biomolecules onto the fiber, and the individual fibers with the biomolecules immobilized thereon are straightened and arranged. The arranged fibers are embedded with a defined material and cut in a direction perpendicular to the lengthwise arrangement direction of the fibers to obtain thin chips. The chips are placed on a substrate to remove the material used for embedding and thereby remain fibers with the immobilized biomolecules on the substrate. This biochip fabrication method immobilizes a great number of biomolecules onto the fibers having a large surface area to enhance the detection sensitivity and allows production of a great number of substrates with an array of biomolecules immobilized simultaneously.

Abstract: A selective adsorption material, especially suitable for adsorption of biological macromolecules, is described. The, adsorption material comprises a matrix with immobilised ligands, localised to selectively adsorb a predetermined molecule. A process for preparing a selective adsorption material, especially suitable for adsorption of biological macromolecules, is also described. The process is characterised in that a print molecule having at least two separate binding sites is bonded to the corresponding, at least two immobilisable ligands, the ligands are immobilised, and subsequently the print molecule is removed. The selective adsorption material can be used for purification or analysis, especially of biological macromolecules.

Abstract: Compositions and methods of use thereof for capture and detection of selected molecules are described. In one embodiment, a first composition includes a ligand component, such as an antibody coupled to a nucleic acid component. An a preferred embodiment, the nucleic acid is labeled with a fluorescent marker to facilitate detection. Another aspect of the invention is the ligand component bound to a solid support via a complementary nucleic acid component and a linker moiety. The method involves binding the target with the first composition in free solution, then binding the target to the solid support by means of both DNA hybridization and antibody-antigen affinity binding. Unbound molecules are washed away, and then the bound targets are detected by fluorescence detection. Vital stains can also be used to detect viable cells.

Abstract: Devices and methods for conducting binding reactions are described. The devices comprise first and second surfaces with channels extending between them. Specific binding reagents are immobilized in discrete groups of the channels. Sample passing through the channels reacts with the binding reagents. Binding of the sample component to the binding reagent in different groups of channels is detected providing information about sample composition. The devices provide increased surface area and accelerated reactions kinetics compared with flat surfaces.

Abstract: A method is provided for preparing an active slide, including introducing a monomer containing an aldehyde group, or a mixture of a monomer containing an aldehyde group and an acidic functional group provider into a plasma chamber; and depositing the aldehyde group and acidic functional group onto the surface of an organic or inorganic matrix using plasma deposition to form a slide comprising a layer of polymerized actively functional groups thereon. The aldehyde groups and negatively charged groups are deposited on the surface of the active slide, such that the bio-molecules bound thereto possess the properties of an inducible orientation and thus form a mono-layer.

Abstract: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.

Abstract: An array bundle is provided for creating multiple arrays for testing. The array bundle is adapted to be cut transversely to form a series of identical arrays of cells. In one embodiment, the array bundle is used in detecting predetermined components from sample mixtures.

Abstract: A fluorescent immunoassay employing the interior surface of a capillary tube is provided. Devices to permit immunoassays using one or more capillary tubes, an apparatus for use with the devices, and a process for screening for analyte in a sample using the devices and apparatus are also provided. Samples suspected of containing analyte are added to a disposable self-contained sample tray containing one or more sample wells, mixed with a reagent, drawn into one or more spaced-apart capillary tubes held within a disposable cartridge connected to an analytical apparatus, reacted with a binding member on the surface of the capillary tube, washed to stop the reaction, and dried by the apparatus. The capillary tube is then exposed to a signal generation device to create a fluorescence signal that is detected using a signal detector. The apparatus determines the presence of the analyte and optionally determines the amount of analyte present in the sample, and presents the results to the operator.

Abstract: The present invention relates to a method of diagnosing, classifying and grading of tumor growths and to determine whether the use of chimeric polioviruses is a proper course for the treatment of the tumors. More particularly, the method is directed to the use of antibodies to a poliovirus receptor (PVR), CD155, to detect the presence of CD155 on tumor cells in various organs, such as: breast, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain.

Abstract: A system for producing substantially identical specific binding ligand (e.g., nucleic acid) probe arrays, for instance, by preparing and replicating an original master array and/or by providing a reusable assay array that is capable of being regenerated. In one embodiment the system includes the preparation and use of a) a master array surface having address sequences immobilized in the form of a patterned, and optionally random, array, b) a multi-ligand conjugate having a binding domain complementary to an address sequence, a binding domain complementary to a target sequence, and a third ligand for use in forming (e.g., by binding or polymerization) the conjugates into or onto the surface of assay array, which can be used with or upon disassociation of the address and its complementary sequences.

Abstract: An improved electrochemical method for disassociating a biological binding partner from a corresponding second biological binding partner associated with a waveguide surface, the electrochemical method involving the application of an electrical potential to said waveguide surface (118), the improvement comprising: applying the electrical potential to the waveguide surface (118) as a square wave polarization function. Preferably, the waveguide surface is comprised of indium tin oxide. The biological binding partners are selected from the group consisting of antigen-antibody, avidin-biotin, enzyme-substrate, cell receptor-substrate/analog, antibody/anti-antibody, DNA, RNA, and fragments thereof. The antigen may be comprised of an epitope. The epitope is produced by a solid phase peptide synthesis performed on said waveguide surface (118).

Abstract: A combinatorial chemistry bead that includes an electromagnetic spectral emitter that radiates a distinct electromagnetic code for each bead that uniquely identifies each bead, a terminal apparatus for receiving the electromagnetic code from each bead, and a method for performing combinatorial synthesis using a bead that transmits a distinct electromagnetic code. The invention includes a large number of spectrally narrowed light emitting mechanisms for generating distinct optical codes.

Abstract: A novel magnetic carrier is provided which comprises particulate silica containing a magnetic material, having polyacrylamide on the surface thereof in an amount ranging from 0.3 to 5 mmol/g in terms of monomeric acrylamide. A process for producing the magnetic carrier is also provided in which the surface of particulate silica containing a magnetic material is treated with a coupling agent, and the treated particulate silica is reacted with acrylamide and/or polyacrylamide. The magnetic carrier is useful for extraction of nucleic acid. The magnetic carrier can be produced readily by controlling the shape, the particle diameter, and the pore diameter, and is excellent in strength and adsorption efficiency. The extraction of a nucleic acid can be automated by use of the magnetic carrier.

Abstract: A method for encapsulating organic molecules, and in particular, biomolecules using sol-gel chemistry. A silica sol is prepared from an aqueous alkali metal silicate solution, such as a mixture of silicon dioxide and sodium or potassium oxide in water. The pH is adjusted to a suitably low value to stabilize the sol by minimizing the rate of siloxane condensation, thereby allowing storage stability of the sol prior to gelation. The organic molecules, generally in solution, is then added with the organic molecules being encapsulated in the sol matrix. After aging, either a thin film can be prepared or a gel can be formed with the encapsulated molecules. Depending upon the acid used, pH, and other processing conditions, the gelation time can be from one minute up to several days. In the method of the present invention, no alcohols are generated as by-products during the sol-gel and encapsulation steps.

Abstract: A macro array comprises a film-shaped hard porous body and a plurality of spots, which contain test substances and are arrayed on the film-shaped hard porous body. The film-shaped hard porous body may be constituted of a surface layer region, which is provided with through-pores having a comparatively small mean pore diameter, and a base layer region, which is provided with through-pores having a comparatively large mean pore diameter. The surface of the film-shaped hard porous body, on which surface the spots are to be arrayed, may be coated with an auxiliary substance for promoting fixation of the test substances to the surface of the film-shaped hard porous body.

Abstract: A device for detection of one or more analytes in a sample is disclosed. The device can simultaneously detect and quantitate multiple analytes in a sample. The device comprises an eletromagnetic radiation generator having one or more chemical sensors thereon. The chemical sensor interacts with or reacts with specific analytes in a sample. The presence of an analyte is detected by a comparison of the spectroscopic properties of the chemical sensor in the absence and presence of the analyte. A method is also disclosed for the detection and quantitation of analytes using the device of the present invention. In addition, a method of making the device of the present invention is also disclosed.

Abstract: Methods and apparatus for qualitatively or quantitatively determining one or more analytes in matrices such as foods, biological fluids, etc. An embodiment for determination of a single analyte comprises a sample receiving vessel, a first membrane and a reagent-containing well. The prepared sample passes through the first membrane whereby extraneous matter is removed, and a filtrate enters the reagent-containing well to provide a filtrate-reagent admixture from which the analyte may be determined. An embodiment for determination for multiple analytes includes one or more additional membranes in series with the first membrane, each such additional membrane being operative to capture one or more analytes. Each of the additional analytes may then be eluted from the membrane upon which it has been captured, into a separate reagent-containing well to provide eluant-reagent admixture from which each desired analyte may be determined. Formulations for preparation additives are also included.

Abstract: The present invention relates to methods and compositions for the direct detection of analytes using color changes that occur in immobilized biopolymeric material in response to selective binding of analytes to their surface. In particular, the present invention provides methods and compositions related to the encapsulation of biopolymeric material into metal oxide glass using the sol-gel method.

Abstract: The present invention is to provide calixcrown derivatives of formulae 1 to 3 requisite for the preparation of a self-assembled monolayer as well as a process for the preparation thereof. Further the present invention is to provide a self-assembled monolayer which is produced by immersing a gold substrate or related metal substrate in an organic solution containing said calixcrown derivatives of formulae 1 to 3. Still further the present invention provides a process for fixing a protein monolayer by fixing proteins having molecular weight of not less than 20,000D (20KD) on said self-assembled monolayer.

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 concerns a method for the immunological determination of an analyte in a sample using magnetic particles coated with the analyte to be determined or analyte-specific bonding partners and directly detectable non-magnetic particles coated with analyte-specific bonding partners or the analyte to be determined or using a non-magnetic substance which is indirectly detectable, and incubation of the reaction mixture. The method is characterized in that the magnetic particles are subsequently separated from the reaction mixture using a magnetic test strip and the analyte concentration is determined directly.

Abstract: The present invention provides low molecular weight fluorescent labeling complexes with large wavelength shifts between absorption of one dye in the complex and emission from another dye in the complex. These complexes can be used, for example, for multiparameter fluorescence cell analysis using a single excitation wavelength. The low molecular weight of the complex permits materials labeled with the complex to penetrate cell structures for use as probes. The labeling complexes are synthesized by covalently attaching through linkers at least one cyanine fluorochrome to another low molecular weight fluorochrome to form energy donor-acceptor complexes. Resonance energy transfer from an excited donor to fluorescent acceptor provides wavelength shifts up to 300 nm. The fluorescent labeling complexes preferably contain reactive groups for the labeling of functional groups on target compounds, such as derivatized oxy and deoxy polynucleic acids, antibodies, enzymes, proteins and other materials.

Abstract: The invention provides devices for preparing a reaction substrate for use as an assay device, and methods of using these devices. The devices prepare reaction substrates comprising arrays of biosites bound to reaction substrates. The devices have a plurality of bundled capillary tubes that convey capture probes from a storage area for eventual deposition onto a biosite on a reaction substrate.

Abstract: A method for the detection of point mutation and polymorphisms in nucleic acids or for sequencing of unknown nucleic acids by a simple procedure using arrays uses nucleic acid analoges as sequence discriminators. This procedure simplifies the working mode in complex problematic cases.

Abstract: Protein arrays for the parallel, in vitro screening of biomolecular activity are provided. Methods of using the protein arrays are also disclosed. On the arrays, a plurality of different proteins, such as different members of a single protein family, are immobilized on one or more organic thinfilms on the substrate surface. The protein arrays are particularly useful in drug development, proteomics, and clinical diagnostics.