Abstract: An image alignment tool is described for adjusting the alignment of a grid with an image. An initial grid aligner determines an initial, approximately aligned, position of the grid. An intensity scorer determines, for each of a plurality of test grid elements of the plurality of grid elements, a set of intensity scores. Each member of the set is based, at least in part, on intensities of pixels of one or more image features within the test grid element in one of the initial or additional positions. A combined-rank-score generator combines, for each of the initial and additional grid positions, members of sets of rank scores corresponding to the grid position in order to generate a combined rank score for the grid position. A grid alignment adjuster adjusts the alignment of the grid based on a comparison among the combined rank scores.

Abstract: A data manager is described for providing a publish database for access by data mining tools and other data processing software applications. The data manager includes a results-for-publication identifier that identifies synthesized probe array results and spotted probe array results for publishing. This identification may be based, at least in part, on user selections. The data in the publish database is organized in accordance with an integrated database schema. The data manager may also include an experimental results registration processor that registers the synthesized probe array results and the spotted probe array results for publishing. This registration may be based, at least in part, on user selections. For example, a user may select certain probe array results from a graphical user interface displaying a tree of files containing probe array results from multiple experiments with synthesized and/or spotted probe arrays.

Abstract: Systems, methods, and computer program products are described for specifying a scanning area of a substrate. In accordance with one method, steps include receiving location data corresponding to a plurality of probe-feature locations on the substrate, storing the location data, accessing the location data, and scanning the substrate based on the accessed location data. A scanning system is described that includes a computer, a scanner, and a computer program product. The product, when executed on the computer, accesses location data corresponding to a plurality of probe-feature locations on a substrate, and controls the scanner's scanning of the substrate based on the accessed location data.

Abstract: Fluorescently marked targets bind to a substrate 230 synthesized with polymer sequences at known locations. The targets are detected by exposing selected regions of the substrate 230 to light from a light source 100 and detecting the photons from the light fluoresced therefrom, and repeating the steps of exposure and detection until the substrate 230 is completely examined. The resulting data can be used to determine binding affinity of the targets to specific polymer sequences.

Abstract: For depositing fluid dots in an array, e.g., for microscopic analysis, a deposit device, e.g. a pin, cooperating with a fluid source defines a precisely sized drop of fluid of small diameter on a drop carrying surface. Transport mechanism positions the device precisely over the receiving surface and drive mechanism moves the deposit device toward and away from the surface. By repeated action, minute drops of fluid can be deposited precisely in a dense array, preferably under computer control. The drop-carrying surface shown has a diameter less than 375, preferably less than 300, preferably between about 15 and 250 micron, and is bound by a sharp rim that defines the perimeter of the fluid drop. The deposit device is compliant in the direction of deposition motion, e.g. by overcoming resistance of a resilient member. When depositing, the deposit device is laterally constrained to a reference position, e.g.

Abstract: A schema-isolated system is disclosed for developing, modifying, or maintaining client applications that accesses target databases. The system includes a middleware-table inserter that inserts middleware tables into the target database. The middleware tables include a set of compatibility data relating one or more client-application data requests with one or more corresponding target-database data capabilities. The middleware tables also include a data communication component. This component receives a client-application data request from the client application, and, based on at least a first datum of the set of compatibility data, provides to the client application the one or more target-database data capabilities corresponding to the client-application data request. The first compatibility datum relates the one or more client-application data requests with the one or more corresponding target-database data capabilities based, at least in part, on an application-usage-independent criterion.

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: A high torque electromagnetic device such as a moving magnet galvanometer includes a composite electromagnetic coil. The composite electromagnetic coil includes two pancake-shaped coil parts made using a rectangular conductor having a width and a thickness, wherein the winding formed for each pancake-shaped coil part has the width oriented in a direction substantially normal to the initially flat face of the pancake-shaped coil part. Each pancake-shaped coil part is subsequently shaped to a shape different from the initially flat shape. The coil parts are superposed and electrically connected to form a single tightly packed unit.

Abstract: Systems and methods are described for processing an emission signal, such as a fluorescent signal, to compensate for noise in an excitation beam, such as a laser beam. As one example, a scanning system is described that includes an excitation signal generator that provides an excitation signal having one or more representative excitation values representative of an excitation beam; an excitation reference provider that provides at least one excitation reference value; a normalization factor generator that compares the excitation reference value to at least one representative excitation value, thereby generating a normalization factor; and a comparison processor that adjusts at least one emission value corresponding to the at least one representative excitation value based, at least in part, on the normalization factor.

Abstract: A calibration tool for fluorescent microscopy comprises a support on which is carried a solid surface layer comprised of effective fluorophores, and a thin mask of non-fluorescent material defining reference feature openings of limited dimensions exposes portions of the fluorophore-comprising surface layer.

Abstract: For depositing fluid dots in an array, e.g., for microscopic analysis, a deposit device, e.g. a pin, cooperating with a fluid source defines a precisely sized drop of fluid of small diameter on a drop carrying surface. Transport mechanism positions the device precisely over the receiving surface and drive mechanism moves the deposit device toward and away from the surface. By repeated action, minute drops of fluid can be deposited precisely in a dense array, preferably under computer control. A mobile-fluid storage device resupplies the deposit device along the array, e.g. in the immediate vicinity of the deposit locations. Mobile annular storage rings are lowered and raised to obtain a supply of fluid, or a mobile multiwell plate is used. Cleaning mechanism is shown, in particular a jet arrangement that directs a jet from a pin or tool axis portal to deeper into the confinement chamber, to scrub along a pin or pin-like structure while inducing an air flow from the working zone to prevent back contamination.

Abstract: Microscopes, including viewing and other microscopic systems, employ a hinged, tiltable plate to adjust focus on a flat object such as a microscope slide or biochip by motion, achieved by tilting, which is substantially normal to the focus point on the plane of the object. By employing two such tiltable arrangements, relatively long scan lines of e.g., flying objective, single pixel on-axis scanning can be accommodated. The tilting support plate is specifically constructed to provide tailored locations for different objects in series along the Y axis of the plate. The plate can accommodate heaters and cooled plates and/or the flat object being examined. In a fluorescence scanning microscope, locations are specifically adapted to receive microscope slides and biochip cartridges such as Affymetrix's “Gene Chip®”. A scanning microscope under computer control, employing such a focusing action, enables unattended scanning of biochips with a simple and economical instrument.

Abstract: A method of detecting locations on a nucleic acid probe array at which hybridization occurs between targets in a fluid sample and nucleic acid probes disposed on a surface of the nucleic acid probe array, comprising: measuring the temperature at a plurality of locations on the surface of the nucleic acid probe array; applying an oscillating level of energy to the surface of the nucleic acid probe array, thereby causing the temperature at the surface of the nucleic acid probe array to oscillate; and detecting a decreased range of temperature oscillation at least one of the plurality of locations on the nucleic acid probe array, thereby indicating an increased heat capacity caused by latent heat of hybridization between at least one target in the fluid sample and at least one nucleic acid probe disposed on a surface of the nucleic acid probe array.

Abstract: A package for hybridization includes a substrate and a housing. The substrate has a first surface that includes an array of probes having biological polymers immobilized thereon. The housing includes a fluid cavity constructed and arranged for hybridization of a target to a probe of the probe array located inside the fluid cavity. The housing also includes a bar code.

Abstract: Described is a novel relational database architecture that is adapted to storing information regarding the terms of one or more contracts, and the actions required to be performed under it. The database resides on a computer-readable storage medium as part of a multi-user computer network. By using simple subroutines readily apparent to one skilled in the computer arts, one can automatically generate alerts whenever an action needs to be performed. These alerts are then transmitted to users along the multi-computer network, appearing in an e-mail message that specifies the action, the individuals performing it, and the duties of each of these individuals. In this manner, one can ensure timely execution of the actions required under a contract.

Abstract: Limited rotation, micro-lens scanning of DNA arrays, microscope slides, biological materials, etc., is performed by arcuate and translational motion. A scanning system includes an objective lens located on a low moment of inertia oscillating arm, which provides optical coupling to a light source or a light detector arranged for transmission, reflection, or fluorescence microscopy.

Abstract: The present invention provides a miniaturized integrated nucleic acid diagnostic device and system. The device of the invention is generally capable of performing one or more sample acquisition and preparation operations, in combination with one or more sample analysis operations. For example, the device can integrate several or all of the operations involved in sample acquisition and storage, sample preparation and sample analysis, within a single integrated unit. The device is useful in a variety of applications, and most notably, nucleic acid based diagnostic applications and de novo sequencing applications.

Abstract: The present invention generally relates to miniaturized devices for carrying out and controlling chemical reactions and analyses. In particular, the present invention provides devices which have miniature temperature controlled reaction chambers for carrying out a variety of synthetic and diagnostic applications, such as PCR amplification, nucleic acid hybridization, chemical labeling, nucleic acid fragmentation and the like.

Abstract: A fluid deposit assembly mounted on a carrier for depositing minute drops of fluid at selected locations upon a substrate, comprising a deposit element having an exposed tip of diameter of 0.3 mm or less constructed and arranged to carry and deposit drops of fluid upon the substrate, stable lateral reference surfaces or surface portions exposed for engagement by the deposit element, the surfaces or surface portions being constructed and arranged to prevent X, Y displacement of the deposit element relative to the carrier when the deposit element is urged thereagainst and design for urging the deposit element against the reference surfaces or surface portions at least at the time that the deposit element approaches a substrate to deposit a fluid drop. The reference surfaces or surface portions and the design for urging are cooperating to precisely position the deposit tip in a precisely desired position as it contacts the substrate. The deposit element is shown as the tip of an axially moveable pin.

Abstract: Microscopes, including viewing and other microscopic systems, employ a hinged, tiltable plane to adjust focus on an object such as a microscope slide. A scanning microscope under computer control, employing such a focusing action, enables unattended scanning of biochips with a simple and economical instrument. Also shown are flexure-mounting of a support plate to define the hinge axis, techniques for automatically determining position and focus, and a rotatably oscillating flying micro-objective scanner combined with the tilting plane focus system. Construction and control techniques are shown that realize simple and accurate focusing. Methods of examination of biological materials are disclosed. Simple and efficient focused scanning with a flying micro-objective of ordered arrays of nucleotides and nucleic acid fragments carried upon a microscope slide or other substrate is discovered.