Abstract: Targeted molecular bar codes and methods for using the same are provided. The subject targeted molecular bar codes include a molecular bar code and a member of a specific binding pair, where the specific binding pair member is generally bonded to the bar code through a linking group. The subject molecular bar code may be read during translocation through a single nano-meter scale pore. The subject targeted molecular bar codes find use in a variety of different applications involving analyte detection, such as screening and diagnostic applications.

Abstract: The present invention is to prepare a novel polymerizable biotin derivative represented by formula (I) shown below and make it possible to synthesize or design a polyfunctional or multifunctional polymer using the derivative. In formula (I), R2 represents a hydrogen atom or an alkyl group, R3 and R4 each independently represents a hydrogen atom, an alkyl group or an aryl group, T represents an oxygen atom or ?NH, W represents a single bond, a carbonyl group, a thiocarbonyl group or a C1-5 alkylene group, U represents a single bond or —NH—, X represents a single bond, a C1-8 hydrocarbon bond, an oxygen atom or —NH—, Y represents a single bond, a carbonyl group, a thiocarbonyl group, —NH—, a 1,2-dioxyethylene group or a 1,2-diaminoethylene group, Z represents a single bond, a carbonyl group, a thiocarbonyl group, a C1-5 alkylene group, an oxygen atom or —NH—, and V represents a single bond or a C1-5 alkylene group.

Abstract: The present invention herein provides the design, synthesis and characterization of compositions comprising asymmetric bolaamphiphilic lipids that form extended polymeric ribbons and wide sheets. These compositions may be doped, or interspersed, with various compounds to fine-tune the fluidity and rigidity of the bolaamphiphilic lipid composition, and promote other morphologies of the composition, including fluid vesicles and truncated flat sheets. Upon an increase in pH these compositions undergo a calorimetric and morphological transformation.

Abstract: Molecular chemical and/or biological sensors that exhibit a very high density of sensing functionality and which are applicable to a wide variety of different analytes, and enable rapid, convenient and economical detection of analytes are prepared by reacting a dendritic polymer with a diacetylene reagent wherein the diacetylene functional groups are subsequently intramolecularly polymerized to form segments having alternating conjugated double and triple bonds. Sensory groups that can bind with an analyte are bonded to the acetylene monomer units to form molecular sensors that produce observable and measurable color changes when an analyte binds with the sensory groups.

Abstract: To provide fine particle films including fine particles which are arranged at a high density in a highly accurate and regular manner is enabled. The fine particle film is a fine particle film including a substrate and plural number of protein fine particles which are arranged on the surface of the substrate in a plane direction parallel to the surface of the substrate, wherein each of the protein fine particles has plural number of first binding sites and one or more second binding sites respectively including a condensed amino acid, and each of the first binding sites binds to other first binding site carried by an adjacent fine particle while the second binding site binds to the substrate, wherein at least a part of the condensed amino acids constituting the second binding site are substituted.

Abstract: The present invention relates to the use of fluorogenic or chromogenic dyes as reporter molecules for detecting cell entry by a specific molecule.

Abstract: Devices and methods are disclosed for containing and processing samples on the surface of supports. Biopolymer features are attached to the surfaces of the supports. A device in accordance with the invention comprises a housing and a support confined by the housing. The housing comprises a well having walls and at least one wall extending from the edge of the well. The height of the walls of the well is at least great enough, and the design of the at least one wall is such, that liquid contained in the well is not drawn out of the well to any substantial degree by surface tension or small movements or small mechanical vibrations. In one embodiment, the at least one wall is designed such that corners thereof are curved or are distant from the edge of the well to substantially eliminate wicking of liquid from the well. Also disclosed are methods for mixing materials on the surface of a support. A sample is incubated with the surface of the support of the aforementioned device.

Abstract: The invention concerns an analytical test element for the determination of an analyte in a liquid containing an inert carrier, a detection element and a channel capable of capillary liquid transport which has a sample application opening at one end and a vent opening at the other end of the channel capable of capillary liquid transport, wherein the channel capable of capillary liquid transport is formed at least partially by the carrier and the detection element and extends in the direction of capillary transport from the sample application opening at least to the edge of the detection test element that is nearest to the vent opening and wherein a notch is located in one of the surfaces forming the channel capable of capillary liquid transport at the edge of the test element forming the sample application opening so that one side of the edge of the test element forming the sample application opening is at least partially discontinuous and the surface opposite to the notch is exposed.

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

Abstract: A method to determine the presence or absence of Streptococcus Group A antigen in a sample, comprising the following steps: extracting the antigen from the sample in an assay chamber with two or less extraction reagents, wherein the two reagents may be added to the assay chamber in no particular sequence; introducing a lateral flow immunochromatographic assay device into the extraction reagents containing the extracted antigen without further addition of reagents or manipulation of the sample; forming an antigen-indicator labeling reagent complex; and determining the presence or absence of the antigen in the sample by the presence or absence of a signal formed by the binding of the antigen-indicator labeling reagent complex to an indicator capture reagent specific for said antigen-indicator labeling reagent complex.

Abstract: The present invention describes carbamic acid ester-derived and valeric acid ester-derived polyfunctional cross-linker molecules, and methods for their synthesis and use. The inclusion of polymeric moieties such as poly(alkylene oxide) in the cross-linkers of the present invention can provide advantageous solubility properties in aqueous environments. Such cross-linkers may be used to form conjugates for use in a variety of assay formats.

Abstract: The invention provides a hapten comprising a 6-[D-?-aminoacetamido] penicillin derivative crosslinked at the ?-amino group with a substituted or unsubstituted phenyldicarbaldehyde. In addition, the invention provides an immunogen comprising the aforementioned hapten coupled to an antigenicity-conferring carrier material, a conjugate comprising the aforementioned hapten coupled to a labelling agent, as well as, antibodies raised against the aforementioned immunogen and capable of binding with at least one structural epitope of an intact ?-lactam ring.

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 reagents for rapid purification and/or identification of particles in a liquid sample are described. The technique uses centrifugation to concentrate particles against a slanted surface having an agent specifically binding to the particles. This method is applicable for the rapid identification of viruses and other difficult or impossible to culture microorganisms without replication or amplification of the microorganism.

Abstract: The present invention relates to an interactive system comprising at least one active surface of plastic from monomers containing at least one structural element derived from a carbon dioxide (A), and at least one substance associated to a linker with at least one structural element (B) capable of establishing a hydrogen bond, and involving an interaction between the structural elements (A) and (B). That interactive system is suitable for presenting and eliminating substances in liquids.

Abstract: A liquid composition comprising a colloidal suspension of a biomolecule-binding matrix material (preferably nitrocellulose) dispersed in a liquid, with particles of the matrix material being of a defined particle size, and replicate copies of a biomolecule, e.g., protein or nucleic acid probes, which are distributed, preferably uniformly, throughout the colloidal suspension and are bound to the matrix material particles, is disclosed. The liquid composition of the invention can be used directly for sample analysis or preparation of biomolecules, or aliquots of the composition can be spotted onto a support to form a microporous matrix system or microarray for analysis or preparation of biomolecules. Compositions and microarrays according to the invention are useful in any type of analytical or preparative procedure relating to biomolecules. They are particularly useful, e.g.

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: 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 a method for detecting specific target-cells in a simple and time saving way, using paramagnetic particles, antibodies recognizing the Fc portions of target-cell associating antibodies and target-cell associating antibodies directed to specific antigen determinants in the target-cell membranes. Incubation of the cell suspension with a mild detergent and/or second set of antibodies or antibody fragments, prelabeled or not with fluorescent agents, metallocolloids, radioisotopes, biotincomplexes or certain enzymes allowing visualization, with dramatically increase the specificity of the method. The method can further be used for isolation of the target-cells by magnetic field application and kit for performing the method according to the invention is described.

Abstract: A bead dispensing system is provided for delivering small amounts of substances onto substrates. The system can include, for example, a movable support structure having an array of spaced-apart projections depending from its lower side. An attraction source, such as a vacuum, magnetic, and/or electrostatic force, is operable at each projection end region to attract and retain one bead. The projection array can be aligned with an array of bead-receiving regions of a substrate, e.g., an array of spaced-apart wells of a micro-plate or card. In one embodiment, a plurality of reagent-carrying beads are picked up, retained at respective projection end regions, and moved to a location over a multi-well plate. The beads are then released in a fashion permitting each bead to land in a respective well. The system of the invention is particularly useful for fabricating arrays of reagents.

Abstract: The invention relates to an immunoassays, binding assays, solid phase substrates (12) and other devices with an antigen or antibody or ligand or receptor (11) embedded into a solid phase substrate (12). The antigen or antibody is mixed with a molten thermoplastic and formed into the solid phase substrate (12).

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

Abstract: A system for the detection of bacteria based on bacteria-antibody complexes. Bacteria attached to antibody are detected with resonance Raman spectroscopy. The bacteria are detected directly in a great numerical excess, e.g. 100 to 10,000 of antibody molecules. A sample to be tested is placed in a medium, the medium containing antibodies attached to a surface for binding to a specific bacteria to form an antigen to antibody complex. The medium is contacted with a beam of light energy. The bacteria, as a lower resonance enhanced Raman backscattered energy, is analyzed for the presence or absence of the bacteria.

Abstract: A system and method for removing contaminants from a surface. The system is designed to use very small particles having means thereon which are capable of selectively binding to a contaminant or contaminants of interest. The particles may contain a dye to render the particles visible in order for a user to observe the application and removal of the particles. The particles also have magnetic properties which may be provided by a high iron content. A carrier can be used to apply the particles to a surface whereupon the targeted contaminants bind to the particles. The particles may then be readily removed from the surface using magnets. When the particle is removed, the targeted contaminants are also removed. The invention is especially useful for the removal of contaminants from skin.

Abstract: The present invention provides a unique approach for the diagnosis and management of infections by Chlamydia species, particularly C. pneumoniae. The invention is based, in part, upon the discovery that a combination of agents directed toward the various stages of the chlamydial life cycle is effective in substantially reducing infection. Products comprising combination of antichlamydial agents, novel compositions and pharmaceutical packs are also described.

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

Abstract: 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: A high capacity assay platform capable of binding target molecules includes a substrate and a polymer matrix attached to the substrate. The polymer matrix comprises a plurality of polymer molecules where at least some of the polymer molecules are covalently attached directly to the substrate and at least some of which molecules are crosslinked to other polymer molecules. Some of the polymer molecules have at least one binding ligand covalently attached thereto, and the density of the polymer matrix on the substrate is at least 2 &mgr;g/cm2.

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

Abstract: The invention relates to porous polymeric materials, methods of making them, and applications in medical devices. A specific embodiment of the invention encompasses a material comprising a porous polyolefin substrate containing inclusions of a material to which chemical or biological moieties are attached directly or via a spacer.

Abstract: The invention provides methods of analzying a secreted protein from a cell encapsulated in a microdrop. The microdrop is formulated with biotinylated matrix molecules at a reduced ratio of biotin to matrix molecules compared with previous formulations. The reduced ratio is advantageous for improving the resolution of detection and allows simultaneous detection of multiple secreted proteins and/or multiple cell surface markers. The invention further provides inter alia methods of isolating IgG isotype antibodies that have switched from IgM isotype.

Abstract: Methods and compounds are provided for detecting target molecules in a sample using specific binding assays. In particular, methods are provided for detecting a nucleic acid target in a sample. In one embodiment, the presently claimed invention provides a method of labeling a hybridized target wherein the target comprises a binding ligand. In another embodiment, the presently claimed invention provides methods of signal amplification.

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

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

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

Abstract: Methods are disclosed for conjugating one moiety to another moiety. In the method the moieties are reacted with one another in a protic solvent. Reaction between the moieties and the protic solvent during the conjugating is negligible or reversible. A stable bond is formed between the moieties to produce a product that is not subject to &bgr;-elimination at elevated pH. Usually, one of the moieties comprises an unsaturation between two carbon atoms. One of the carbon atoms is or becomes an electrophile during the conjugating. The other of the moieties comprises a functionality reactive with the electrophile carbon atom to form a product that comprises the unsaturation. Compounds comprising both of the moieties as well as precursor molecules are also disclosed. Methods are also disclosed for determining an analyte in a sample employing compounds as described above.

Abstract: The present invention provides a method of detecting a biological agent including contacting a sample with a sensor including a polymer system capable of having an alterable measurable property from the group of luminescence, anisotropy, redox potential and uv/vis absorption, the polymer system including an ionic conjugated polymer and an electronically inert polyelectrolyte having a biological agent recognition element bound thereto, the electronically inert polyelectrolyte adapted for undergoing a conformational structural change upon exposure to a biological agent having affinity for binding to the recognition element bound to the electronically inert polyelectrolyte, and, detecting the detectable change in the alterable measurable property. A chemical moiety being the reaction product of (i) a polyelectrolyte monomer and (ii) a biological agent recognition element-substituted polyelectrolyte monomer is also provided.

Abstract: There is provided a probe for a scanning probe microscope, comprising: a proximal end; and a distal tip portion, wherein the distal tip portion has a tip surface which faces a fixed sample, and at least one monolayer is formed at least on the tip surface, and a molecule having a chemical sensor function or catalytic function is placed in or on an outermost monolayer above the tip surface. There is provided a probe for a scanning probe microscope, comprising: a cover layer containing an electrically conductive polymer; and a catalyst in the cover layer, the catalyst being selected from a group consisting of inorganic catalysts and organic catalysts. There are provided a scanning probe microscope equipped with the above probe, and a molecule processing method using such a scanning probe microscope.

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

Abstract: The present invention provides solid supports (e.g., glass) and polymer hydrogels (particularly polymer hydrogel arrays present on a solid support) comprising one or more reactive sites for the attachment of biomolecules, as well as biomolecules comprising one or more reactive sites for attachment to solid supports and polymer hydrogels. The invention further provides novel compositions and methods for the preparation of biomolecules, solid supports, and polymer hydrogels comprising reactive sites. The invention also provides for preparation of crosslinked solid supports, polymer hydrogels, and hydrogel arrays, wherein one or more biomolecules is attached by means of the reactive sites in a photocycloaddition reaction. Advantageously, according to the invention, crosslinking of the hydrogel and attachment of biomolecules can be done in a single step.

Abstract: In this disclosure, novel caanabinol-based tracers suitable for use in immunoassays that detect cannabinoids in a biological sample are disclosed. These cannabinol-based tracers are particularly useful in a continuous flow displacement immunoassay. The disclosure also describes the processes for synthesizing the novel tracers, and the application of these tracers in fluorescence immunoassays for detecting and quantifying cannabinoids in biological samples.

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

Abstract: The present invention is directed to a composition and method for regulating the adhesion of cells and biomolecules to hydrophobic surfaces and hydrophobic coated surfaces. The composition is a biomolecule conjugated end-group activated polymer (EGAP). The biomolecule conjugated EGAP can be put to numerous uses including cell adhesion, cell growth, cell sorting, and other biological assays.

Abstract: This invention relates to a method of assaying pyrrole-containing biological compounds and chemical compositions that can be used in the method. The method involves contacting a biological compound with one of: a) a bound or bindable derivatizing agent which forms a reaction product with the biological compound, followed by exposure to a detectable molecule which forms a complex with the reaction product; or b) a derivatizing agent which forms a reaction product with the biological compound, followed by exposure to a bound binding agent specific to the biological compound in the reaction product; or c) a binding agent specific to the biological compound, followed by exposure to a derivatizing agent which forms a reaction product with the biological compound, and determining the amount of bound biological compound. There is also provided a method of preparing an antigen.

Abstract: Solid phase methods for the identification of an analyte in a biological medium, such as a body fluid, using bioluminescence are provided. A chip designed for performing the method and detecting the bioluminescence is also provided. Methods employing biomineralization for depositing silicon on a matrix support are also provided. A synthetic synapse is also provided.

Abstract: Solid phase methods for the identification of an analyte in a biological medium, such as a body fluid, using bioluminescence are provided. A chip designed for performing the method and detecting the bioluminescence is also provided. Methods employing biomineralization for depositing silicon on a matrix support are also provided. A synthetic synapse is also provided.

Abstract: A waveguide probe for the detection of pathogens in a sample which comprises a laser, a first and a second tubes that converge at a point to form a proximal end. A magnet is positioned in the end to configure to focus paramagnetic microspheres attached to antigen/antibody/optically labeled antibody complexes in the field of view. The proximal end is polished to form an aperture.

Abstract: This invention provides novel methods for monitoring urine for type II collagen fragment using a combination of a capture antibody and a detection antibody, such that type II collagen is distinguished from other collagen fragments.