Abstract: Immobilized nucleotide primers of this invention include a modified nucleotide tethered to a support substrate through a linking group. In particular, the modified nucleotide is constructed such that the C-5′ end of the nucleotide is tetherable to the linking group and the protected C-3′ end is available for further controlled modification, e.g., addition of other nucleotides in specific sequences to the immobilized nucleotide primer. Additionally, the linking group is of sufficient length to allow the immobilized nucleotide primer to be used to synthesize and screen arrays of oligonucleotides, e.g., enzymatic C-3′ primer extension.

Abstract: A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Abstract: Various embodiments of the present invention provide both apparatus and method for the patterning of cells onto non-adhesive substrates and the controlled regulation of cells through the use of photoactivated cellular morphogenic factors.

Abstract: A biochip deposition system and method. The system comprises a deposit mechanism for depositing organic material in spots on a substrate; and a viewing system for detecting the spots on the substrate during a deposit operation and before the spots have dried, for determining if the spots have been correctly deposited, and if not, for generating a suitable output signal. The viewing system includes an illumination device for illuminating deposited spots at a relatively low angle relative to the substrate.

Abstract: Methods for stably associating a polyelectrolyte coating or film to a substrate surface, as well as the coated substrates produced thereby, are disclosed herein. In the subject methods, substrate surfaces are coated with a polyelectrolyte, and the coated substrate surfaces are treated with a bifunctional molecule under conditions sufficient to stably associate the film to the array surface. The subject methods find use in a variety of different applications, including the production of mircoarrarys.

Abstract: The present invention is directed to a process for coupling an adhesive glycoprotein to a surface of a bulk material comprising the following steps:

Abstract: Methods, devices and apparatus are disclosed for carrying out multiple chemical reactions, such as in situ synthesis of polynucleotides, on a surface comprising an array of discrete sites. Molecules are deposited at a predetermined number of the discrete sites on the surface for reaction at the discrete sites. The surface is positioned relative to an outlet of a fluid ejection device, which is activated to dispense a small volume of a fluid through the outlet to the surface to provide uniform coating of a continuous region of the surface comprising a multiple of the discrete sites. The fluid is dispensed as uniform particles having a diameter such that the uniform particles form a sheet to coat the continuous region of the surface. In one embodiment of the present invention, liquid is dispensed as uniform particles through a fluid ejection device activated by means of ultrasonic energy. The invention has particular application to the in situ synthesis of polynucleotides in arrays on a surface.

Abstract: Immobilized nucleotide primers of this invention include a modified nucleotide tethered to a support substrate through a linking group. In particular, the modified nucleotide is constructed such that the C-5′ end of the nucleotide is tetherable to the linking group and the protected C-3′ end is available for further controlled modification, e.g., addition of other nucleotides in specific sequences to the immobilized nucleotide primer. Additionally, the linking group is of sufficient length to allow the immobilized nucleotide primer to be used to synthesize and screen arrays of oligonucleotides, e.g., enzymatic C-3′ primer extension.

Abstract: A body 300 having a cavity 310 for mounting a substrate 120 fabricated with probe sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, is provided. The cavity includes inlets 350 and 360 for introducing selected fluids into the cavity to contact the probes. Accordingly, a commercially feasible device for use in high throughput assay systems is provided.

Abstract: Apparatus and methods are disclosed for synthesizing a plurality of compounds on the surface of supports. Biopolymer features are attached to the surfaces of the supports. The synthesis generally comprises a plurality of steps. In the present invention at least two of the steps are performed by placing a support having a functionalized surface into a chamber of a flow cell and subjecting the surface to a step of the synthesis and placing the support into a chamber of another flow cell and subjecting the surface to another step of the synthesis. An apparatus generally comprises a plurality of flow cells and one or more fluid dispensing stations are mounted on the platform and are in fluid communication with one or more of the plurality of flow cells. A station for monomer addition to the surface of the support is mounted on the platform. The apparatus further comprises a mechanism for moving a support to and from the station for monomer addition and a flow cell and from one flow cell to another flow cell.

Abstract: Methods, compositions and articles of manufacture for binding histidine containing proteins to substrates are provided. A substrate having reactive groups is contacted with a substrate modifier comprising a silane, a linker, and an active site to form an activated substrate. The activated substrate is then reacted with a reagent that binds to the active site and comprises a ligand that can bind to a metal ion to form a chelator which is then chelated to a metal ion to form a metal-chelated substrate. A histidine-containing protein having an arrangement of histidine residues that can bind to two available cis valencies on the chelated metal ion is then incubated with the metal-chelated substrate to form a protein-substrate complex. The protein can be deposited in a pattern through any suitable technique. The protein is bound in an active form allowing it to perform native functions, including enzymatic functions.

Abstract: This invention relates to a particulate material comprising an inorganic low density, radiation tolerant core coated with a radionuclide, processes for its production and a method of radiation therapy utilising the particulate material.

Abstract: A method and apparatus for quick, easy mass production of biological polymer chips having uniform quality and involving deposition of very small quantities of biological polymers, wherein samples of the biological polymer are deposited on a substrate using a capillary array comprising a plurality of capillaries arranged at the same spacing interval as that of sites on the substrate, and applying an electric field or pneumatic pressure to the array of capillaries containing the biological polymer samples.

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: A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Abstract: A thermoplastic film for LCM tissue transfer is thermally coupled to a broadband energy-absorbing material. The broadband energy-absorbing material may either be introduced into the film composition as a dopant or may be in thermal contact with the film.

Abstract: A liquid discharging device includes a plurality of liquid discharge sections. Each liquid discharge section includes a reservoir, a nozzle that discharges a solution supplied from the reservoir, and discharge energy generating means that generates energy to discharge the solution from the nozzle. The number of the liquid discharge sections corresponds to the number of probe types to be formed. The nozzles are two-dimensionally arranged. Using this liquid discharging device, probe liquids are discharged from the corresponding reservoirs onto a solid-phase substrate to form a predetermined two-dimensional probe array of high-purity probes on the substrate. This process exhibits high reproducibility and processability, and the resulting probe array has high array density.

Abstract: The present invention relates to a method of preparing a substrate surface supporting a lipid film membrane structure, which method comprises the steps of contacting a substrate surface with an aqueous liquid containing detergent/lipid mixed micelles to adhere detergent/lipid mixed micelles to the substrate surface, and then contacting the substrate surface having detergent/lipid mixed micelles adhered thereto with an aqueous liquid substantially free from detergent to elute the detergent molecules from the adhered mixed micelles and make the remaining lipid molecules assemble into a lipid film membrane structure on the substrate surface. The invention also relates to a substrate supporting a lipid film membrane structure as prepared by the method, the use of a substrate supporting a lipid film membrane structure as prepared by the method for molecular interaction studies, and a substrate surface for use in the method.

Abstract: The invention relates to a method of adhering a biomolecule to a substrate, comprising treating the substrate with a surfactant compound and a biomolecule. More particularly, the invention relates to a method of adhering a biomolecule to a substrate wherein the surfactant compound is not covalently linked to the substrate. The invention also relates to a device for adhering a biomolecule in a predetermined position comprising: a substrate having thereon a plurality of cytophilic regions that can adhere a biomolecule on the substrate by cytophobic regions to which the biomolecules do not adhere contiguous with the cytophilic regions, wherein the cytophobic regions comprise one or more surfactant compounds.

Abstract: Methods for fabricating functionalized substrate surfaces for use in preparing biomolecular microarrays, such that the substrate surfaces feature a uniform distribution of attachment functionality, functionalized substrates having such uniform distribution of attachment functionality, and microarrays prepared from such functionalized substrates. A plurality of linker groups are coupled to a substrate surface. A plurality of spacer groups including attachment sites for biological receptors are coupled to the linker groups. The linker groups can be coupled to the surface using a gas phase reaction. Spacers can include polyfunctional linear, branched or dendritic structures, such as polyethylene glycols and Starburst™ dendrimers. Attachment sites can be activated for the attachment of biological receptors.

Abstract: A system and method for applying one or more chemicals to a tissue sample is provided. The system preferably includes a cassette for housing a slide device, a film, and an injection system. The slide device preferably includes a specimen slide for containing the tissue sample and a cover plate connected to the specimen slide. The film is preferably moveable through the cassette along guide rollers and preferably contains a plurality of containers containing one or more chemicals. The injection system may include a piston for displacing the chemicals from the containers through an injection port to the tissue sample. The cassette may be placed on a cassette driver that contains a motor-driven shaft for driving the piston and moving the film.

Abstract: The present invention provides cellular screening substrata which can be formed in simple processing steps. The cellular screening substrata can be formed which are characterized in that plural cellular screening substances are positioned and immobilized at predetermined positions on a base by micro-droplet discharging means, and plural areas having different cellular screening functions are formed thereon.

Abstract: Disclosed is a test cell and a method for detection of a preselected ligand in a liquid sample such as a body fluid. The test cell includes an elongate outer casing which houses an interior permeable material capable of transporting an aqueous solution and defining a sample inlet, a test volume, and a reservoir volume. The reservoir volume is disposed in a section of the test cell spaced apart from the inlet and is filled with sorbent material. The reservoir acts to receive liquid transported along a flow path defined by the permeable material and extending from the inlet and through the test volume. In the test volume is a test site which includes a first protein having a binding site specific to a first epitope of the ligand immobilized in fluid communication with the flow path. The test site can be observed through a window of the casing.

Abstract: The present invention includes a method and apparatus for the detection of a target material. The method and apparatus includes providing a substrate with a surface and forming a domains of deposited materials thereon. The deposited material can be placed on the surface and bound directly and non-specifically to the surface, or it may be specifically or non-specifically bound to the surface. The deposited material has an affinity for a specific target material. The domains thus created are termed affinity domains or deposition domains. Multiple affinity domains of deposited materials can be deposited on a single surface, creating a plurality of specific binding affinity domains for a plurality of target materials. Target materials may include, for example, pathogens or pathogenic markers such as viruses, bacteria, bacterial spores, parasites, prions, fungi, mold or pollen spores.

Abstract: An insertable analyte needle sensor, comprising a set of fine wires positioned together and a dielectric material covering a substantial portion of the fine wires but defining an opening filled with at least one partially permeable membrane. The wires may be treated with a gas plasma to facilitate membrane adherence. One membrane layer may comprise sulphonated polyethersulphone coated with silane.

Abstract: An array of chemical compounds can be produced by the electrostatic deposition of its components onto a substrate. The subunit building blocks are coupled to the chemical groups on the substrate to synthesize a complex compound. By localizing the electrostatic deposition, different building blocks can be coupled at different positions on the substrate. Thus, a diverse and addressable set of chemical compounds is produced on the substrate to form an array of chemical compounds, e.g., of biological polymers. One application of this concept is the production of an oligonucleotide array. Other concepts provided here can be used in combination with the electrostatic deposition method or with other chemical synthetic methods. The invention provides, in part, methods of dispensing the nucleic acid subunits as a dry composition (e.g., a particulate composition) for the in-situ synthesis of nucleic acid polymers.

Abstract: A method of manufacturing items in parallel. Selected samples of items to be manufactured are subjected to additional steps in a manufacturing process. If such sample items meet the requisite quality control standard, remaining items are subjected to further manufacturing steps. If the sample items which have been further processed do not meet the requisite quality control standard, the lot from which the samples do not undergo the additional manufacturing step. Invention provides an improved method of manufacturing in that it prevents unnecessary manufacturing steps.

Abstract: The application relates to a process for binding nucleic acids to a carrier, wherein the nucleic acids are dissolved in a solution containing at least one compound selected from the group consisting of betaines, said solution being applied to a carrier and the nucleic acids being bound to the carrier.

Abstract: The present invention provides surface imprint compositions useful for capturing, isolating, detecting, analyzing and/or quantifying molecules in a sample. The surface imprint compositions comprise a matrix material having imprint cavities of a template molecule or molecules imprinted thereon wherein a substantial number of the imprint cavities are located at or near the surface of the matrix material.

Abstract: A method of fabricating an array of multiple features of different chemical moieties on a substrate surface, and a method of using arrays so fabricated. The fabrication method includes determining an identity of a first direction across the substrate surface (such as a drawn direction) along which the substrate surface has a higher height uniformity than along a second direction across the substrate. Chemical moieties are placed on the substrate so as to provide features thereon along rows more closely aligned with the first direction than the second direction.

Abstract: A method of conducting accurate identification of biological species with a biochip, and a method of effectuating identification of biological species at a level higher than species are provided. Selection of specific probes for multiple biological species is also facilitated. A plurality of partial sequences A, A′; B, B′; and so on, which are specific to respective targets, are selected as probes in a manner that the partial sequences do not overlap one another. In addition, DNA regions I, J, K and L, which are common to some targets, respectively, are also selected as probes. Alternatively, if there is a common base sequence at leaves below a certain node based on a dendrogram of targets, such a base sequence is designed as a probe unique to the node.

Abstract: This invention is related to methods for the immobilization of labeled ligands on solid surfaces using soft metal-soft base bonding. The ligand-binding solid surface comprises a soft metal solid support and a heterobifunctional spacer chemi- or physisorbed to said soft metal solid support via soft metal-soft base bonding.

Abstract: A nucleic acid coating composition including a polyanion bound, directly or through one or more intermediates, to a medical device surface, with a condensate comprising a polycation and nucleic acid bound to the polyanion, devices incorporating such coating compositions, and methods for making. In one embodiment, a silyl-heparin complex is provided, bound to a medical device surface by hydrophobic interaction with the silyl moiety, with a polycation and nucleic acid condensate bound to the heparin by electrostatic interaction.

Abstract: Multilayered porous materials are formed by coating a porous substrate with a metal and adsorbing an organic layer comprising a recognition moiety onto the metal film. The recognition moiety interacts with an analyte of interest allowing for its detection, purification, etc. Suitable recognition moieties can be selected from a range of species including, small molecules, polymers and biomolecules and the like. The novel porous materials of the invention can be utilized in an array of methods including, ion-exchange, ion-selective ion-exchange, assays, affinity dialysis, size exclusion dialysis and the like.

Abstract: Echogenic devices, and methods of making and using such devices, are disclosed. In one aspect, the devices include a porous polymeric material that is preparable by extracting a phase separated composition. In another aspect, the echogenic devices include a polymeric composition having porous particles therein. Preferably the devices are medical devices.

Abstract: Heparin-polyoxyalkylenepolyamine adducts, and methods of making and using such adducts are disclosed. Compositions including a quaternary ammonium heparin complex, a moisture curable polysiloxane, and an organic solvent are also disclosed, along with methods of making and using such compositions.

Abstract: A flat plate-shaped probe carrier for carrying probes such as single stranded DNAs, proteins, etc. which are reactive specifically with target substances comprises a plurality of ring bodies arranged substantially in parallel and the external space among the ring bodies is filled with a filler such that the openings of the ring bodies are oriented to the surface of the probe carrier. Each ring body has a region for fixing a probe adapted to be bonded specifically to a target substance on its inner wall. The probe carrier is produced by bundling a plurality of hollow tubular members in parallel, then filling the external space among the bundled hollow members with a filler, and cutting the bundle along a plane intersecting the axial direction of the tubular members. Probes are fixed to the fixing region before or after filling the external space.

Abstract: The invention relates to a method for producing hydrophilic monomers which are particularly useful for electrophoresis and to electrophoresis compositions and coating compositions. The electrophoresis gel compositions and electrophoresis polymer compositions are hydrolytically stable and have high resolution. The method uses the steps of reacting a (meth)acryloyl with an aminoalcohol in the presence of a base in a polar solvent, optionally filtering an aqueous solution of the reaction product, deionizing an aqueous solution of the reaction product, and removing the solvent.

Abstract: A method for forming arrays of metal, alloy, semiconductor or magnetic clusters is described. The method comprises placing a scaffold on a substrate, the scaffold comprising molecules selected from the group consisting of polynucleotides, polypeptides, and perhaps combinations thereof. Polypeptides capable of forming &agr; helices are currently preferred for forming scaffolds. Arrays are then formed by contacting the scaffold with plural, monodispersed ligand-stabilized clusters. Each cluster, prior to contacting the scaffold, includes plural exchangeable ligands bonded thereto. If the clusters are metal clusters, then the metal preferably is selected from the group consisting of Ag, Au, Pt, Pd and mixtures thereof. A currently preferred metal is gold, and a currently preferred metal cluster is Au55 having a radius of from about 0.7 to about 1 nm. Compositions also are described, one use for which is in the formation of cluster arrays.

Abstract: Method of manufacture of probe carriers in which plural kinds of probes are arranged on substrates by ejecting plural kinds of probe solutions containing probe materials specifically associable to target substances from a liquid ejecting device onto the substrates, wherein the probe solutions are ejected from the liquid ejecting device onto the substrates while a substrate holding part whereupon the substrates are placed is moved relative to the liquid ejecting device and a manufacturing apparatus exclusively used for the method. The present invention enables stable manufacture of probe carriers without overflow of the probe solutions from reservoirs in which probe substances are held.

Abstract: The present invention is directed to methods for immobilizing natural or synthetic biomolecules to surfaces comprising covalently linking the natural or synthetic biomolecule to a mono- or bi-functional polymer and covalently and/or electrostatically immobilizing the biomolecule/polymer conjugate to an unmodified or modified surface wherein the biomolecule is an oligonucleotide, a polynucleotide, a protein, a glycoprotein, a peptide or a carbohydrate that has been modified to incorporate a single or plurality of nucleophilic groups comprising an aliphatic or aromatic amino, thiol, hydrazine, thiosemicarbazide, hydrazide, thiocarbazide, carbazide, aminooxy, a derivative of 2-hydrazinopyridine or aminoxyacetic acid or a single or plurality of electrophilic groups comprising an aliphatic or aromatic aldehyde, ketone, epoxide, isocyanate, isothiocyanate, succinimidyl ester or cyanuric chloride or a linkable aromatic aldehyde or ketone and the surface has been modified to possess either neutral, cationic or anioni

Abstract: Provided is a method of spotting a probe densely and efficiently on a surface of a solid support. A liquid containing a probe is attached to a solid support as droplets to form spots containing the probe on the solid support by an ink jet method.

Abstract: Ambient humidity for a plurality of nozzles of a liquid ejection device for ejecting droplets of solutions containing probes to the surface of a carrier is controlled to 50% or more, preferably 60% or more. Part of solution supply passages to the plurality of nozzles are constructed from gas permeable membranes permitting gas-liquid separation under reduced pressure. These gas permeable membrane portions are gathered and altogether placed under reduced pressure to remove air bubbles from the respective solutions supplied to the plural nozzles and decrease the amount of a dissolved gas causing air bubble generation.

Abstract: A method apparatus, and computer program products for generating and using an addressable array of chemical moieties on a substrate. In a processing unit may retrieve array related data from a memory. Such array related data may comprise any of data on a characteristic of the fabricated array, an instruction for reading an array, or an instruction on processing data from a read array. The processing unit may automatically access a program routine for reading the array or processing data from the read array based on the retrieved data.

Abstract: A method for transferring molecules from a matrix to a laminate comprising a shrinkable polymeric film and a surface coating is disclosed.

Abstract: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Abstract: In an image information reader 100 that includes an excitation light source 45, a photoelectric reading mechanism, and an external light shield for reading a sample distributing specific organism-originated material labeled with a fluorescent dye, a sample tray 10 is provided having the qualities of easy rinsing and enduring of repeated use. The sample tray includes a base material, e.g. an aluminum plate 10d, that is coated with a fluororesin, e.g. an hybrid resin 10c of PTFE and PFA having a black color as a base. The tray can also include depressed or projected markings 10a on the surface on which the sample is placed which represent a readable range of the photoelectric reading mechanism. A method of making the sample tray for the reader is also described.

Abstract: A method for preserving cytological specimens for histological or histopathological use. A cytological sample from a biological tissue such as a tumor or a tumor cell line is dehydrated, disbursed and evenly distributed throughout a volume of molten material. The molten material is then drawn into a tubular member such as a pipette and allowed to solidify. Upon solidification, the cylindrical specimen is partially or completely extruded from the tube for further processing, including fixation, dehydration and molten paraffin infiltration and embedding as required for presentation to a sectioning device such as a microtome. Thin circular slices of the cylindrical specimen are removed from the cylindrical specimen and transferred to a slide, fixed and stained as desired. The device and method enable the production of a slide bearing a spatially homogeneous distribution of cytological material for microscopic examination.

Abstract: The invention relates to the fabrication and use of biosensors comprising a plurality of optical fibers each fiber having attached to its “sensor end” biological “binding partners” (molecules that specifically bind other molecules to form a binding complex such as antibody-antigen, lectin-carbohydrate, nucleic acid-nucleic acid, biotin-avidin, etc.). The biosensor preferably bears two or more different species of biological binding partner. The sensor is fabricated by providing a plurality of groups of optical fibers. Each group is treated as a batch to attach a different species of biological binding partner to the sensor ends of the fibers comprising that bundle. Each fiber, or group of fibers within a bundle, may be uniquely identified so that the fibers, or group of fibers, when later combined in an array of different fibers, can be discretely addressed. Fibers or groups of fibers are then selected and discretely separated from different bundles.

Abstract: A nucleotide compound is activated by an aerosol of a liquid composition that includes, dissolved therein, an activator compound that triggers the covalent coupling of the nucleotide compound to the support. The nucleotide compound can be deposited on the substrate, for example, as a thin film or a particulate composition.