Abstract: Apparatus and methods for optical detection with improved read speed and/or signal-to-noise ratio. These apparatus and methods may involve among others moving an sample substrate (108) while simulataneously detecting light transmitted from one or more sample sites (110) on the substrate (108) by sequentially tracking the sample sites (110) as they move. A stage (101), movable in a first direction, supports the substrate (108). A detector (118) detects light emanating from an examination region (102) delimited by a detection initiation position (106a) and a detection termination position (106b). An optical relay structure (122) transmit light from the examination region (102) to the detector (118). A scanning mechanism (120) simultaneously moves the optical relay structure (122) and the substrate in the first direction. The optical relay structure (122) tracks the substrate (108) between the detection initiation position (106a) and the detection termination position (106b).

Abstract: Apparatus and methods for optical detection with improved read speed and/or signal-to-noise ratio.

Abstract: Methods and apparatus for detecting polynucleotide hybridization in luminescence-based assays. The methods may include (1) contacting a sample polynucleotide with a reference polynucleotide at an assay site, where at least one of the polynucleotides is capable of emitting luminescence, (2) illuminating the assay site with light capable of stimulating such luminescence, (3) detecting light transmitted from the assay site, and (4) deriving information relating to the extent of hybridization between the sample and reference polynucleotides based on the detected light. The methods may further include (1) illuminating with and/or detecting polarized light, (2) deriving information relating to the sequence of the sample polynucleotide from the extent of hybridization, and (3) converting the light to a signal and distinguishing between a portion of the signal attributable to luminescence and a portion attributable to background.

Abstract: Methods and apparatus for detecting polynucleotide hybridization in luminescence-based assays. The methods may include (1) allele-specific hybridization, using luminescence detection, (2) allele-specific oligonucleotide ligation, using dye-labeled oligonucleotide ligation with luminescence resonance energy transfer (FRET) detection, and (3) allele-specific nucleotide incorporation, using primer extension with luminescence polarization (FP) detection. More specifically, the methods may include (1) locating a sample containing a nucleic acid material at an examination site, (2) illuminating the sample, (3) detecting light transmitted from the sample, and (4) determining the presence, absence, and/or identity of a nucleic acid target in the sample using the light transmitted from the sample.

Abstract: Devices for using optical filters in a filter holder that enable optical filters to be simply, conveniently, and flexibly interchanged.

Abstract: Apparatus and methods for determining temporal properties of photoluminescent samples using frequency-domain photoluminescence measurements, where the measurements may include photon counting and/or the separation of measured luminescence into potentially overlapping time bins.

Abstract: Apparatus and methods for identifying and correcting for quenching in luminescence assays using luminescence lifetimes and/or luminescence intensities. One aspect of the invention involves identifying quenching using combinations of luminescence lifetimes and/or intensities. Another aspect of the invention involves correcting for quenching by eliminating false positives or false negatives due to quenching in luminescence assays.

Abstract: Apparatus and methods for measuring light transmitted from a sample. The apparatus may include a stage, a light source, and a detector. The stage may be configured to hold a microplate having a plurality of sample wells. The apparatus may be configured to take measurements of one or more of absorbance, scattering, reflectance and luminescence. The apparatus may permit simultaneous measurements of two or more of these properties.

Abstract: Devices and methods for supporting a sample container. In one embodiment, the device includes a holder for supporting a sample container, and a releasable clamp mechanism that applies a force against a side of the sample container. In another embodiment, the device includes a holder for supporting a sample container, wherein the holder has a central opening that permits analysis of a sample to be carried out from below the holder, and an open end that permits a sample container transfer device to enter a portion of the holder. In yet another embodiment, the device includes a holder for supporting a sample container, and drive mechanisms that move the holder between a docking station outside an analyzer and an examination site inside the analyzer, so that the holder can function both as a sample delivery device in and out of the analyzer, and as a moveable stage for supporting the sample container at the examination site.

Abstract: Reference fiducials for sample holders. The reference fiducials may be configured to provide information that facilitates sample handling and/or analysis. The sample holders may include microplates and biochips.

Abstract: Devices and methods for containing and analyzing small sample volumes that are sandwiched between solid surfaces. The devices may include an automated drive mechanism that controls the relative positions of the surfaces and an environmental-control mechanism that controls the humidity, temperature, and/or other environmental conditions around the small sample volume. In some embodiments, at least one of the surfaces has a light-transmissive window for allowing optical analysis of a sample contained between the surfaces.

Abstract: Apparatus and methods for measuring light transmitted from a sample. The apparatus may include a stage, a light source, and a detector. The stage may be configured to hold a microplate having a plurality of sample wells. The apparatus may be configured to take frequency-domain time-resolved measurements of one or more of luminescence lifetimes and reorientational correlation times of a luminescent analyte in the sample.

Abstract: A device for detecting chemiluminescence from a sample. The device may include a stage for supporting a sample and one or more of the following elements: (1) an optics head, (2) an optical relay structure for transmitting chemiluminescence from the sample to a detector, (3) a drive mechanism, (4) a sensor for detecting proximity of the optical relay structure to the sample, (5) a mask structure for selecting an effective diameter of the optical relay structure, and (6) a baffle for blocking extraneous light from entering the optical relay structure.

Abstract: An optical sensor (40) that provides a monotonic level-dependent output signal that varies smoothly and at an easily detectable rate over the entire length of the sensor includes first and second spaced waveguides (45, 50) extending along an axis, with each extending between its respective first and second ends. The first waveguide does not have surfaces contacting the liquid along the first waveguide's length. The second waveguide has at least a longitudinally extending portion of an outer surface in optical contact with the liquid. One or more web portions (50a, 50b, 50c) extend along and between both waveguides so that some of the light traveling along the first waveguide is coupled through the web portion(s) into the second waveguide. Light is injected into an end of the first waveguide (52), allowed to travel along the first waveguide, with a portion leaking into the second waveguide. Light is detected (55), with the amount representing the level of liquid.

Abstract: Devices and methods for supporting a sample container. In one embodiment, the device includes a holder for supporting a sample container, and a releasable clamp mechanism that applies a force against a side of the sample container. In another embodiment, the device includes a holder for supporting a sample container, wherein the holder has a central opening that permits analysis of a sample to be carried out from below the holder, and an open end that permits a sample container transfer device to enter a portion of the holder. In yet another embodiment, the device includes a holder for supporting a sample container, and drive mechanisms that move the holder between a docking station outside an analyzer and an examination site inside the analyzer, so that the holder can function both as a sample delivery device in and out of the analyzer, and as a moveable stage for supporting the sample container at the examination site.

Abstract: A device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are delivered through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.

Abstract: An apparatus and method is provided for preparing and using a very large and diverse array of compounds on a substrate having rapidly accessible locations. The substrate contains cells in which the compounds of the array are located. Surrounding the cells is a non-wetable surface that prevents the solution in one cell from moving to adjacent cells. The compounds are delivered to the individual cells of the array by a micropipette attached to an X-Y translation stage.

Abstract: A high-throughput light detection instrument and method are described. In some embodiments, switch mechanisms and optical relay structures permit different light sources and/or detectors to be selected for different applications. In other embodiments, switch mechanisms and optical paths permit top/bottom illumination and/or top/bottom detection, or combinations thereof.

Abstract: A high-throughput light detection instrument and method are described. Confocal optics structure enables exclusive light detection from a sensed volume in a composition.

Abstract: An array is created by moving a dispenser toward a solid support until a tip of the dispenser touches the support, withdrawing the tip from the surface and releasing a drop of 5 nanoliters or less in an area smaller than 1 mm.sup.2 to create an array of at least 100 spots.