The present invention provides a simplified method for identifying differences in nucleic acid abundances (e.g., expression levels) between two or more samples. The methods involve providing an array containing a large number (e.g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e.g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of hybridization is detected. Differences in the hybridization patterns between the samples indicates differences in expression of various genes between those samples. This invention also provides a method of end-labeling a nucleic acid. In one embodiment, the method involves providing a nucleic acid, providing a labeled oligonucleotide and then enzymatically ligating the oligonucleotide to the nucleic acid. Thus, for example, where the nucleic acid is an RNA, a labeled oligoribonucleotide can be ligated using an RNA ligase. In another embodiment, the end labeling can be accomplished by providing a nucleic acid, providing labeled nucleoside triphosphates, and attaching the nucleoside triphosphates to the nucleic acid using a terminal transferase.

Nucleic acid analysis techniques

An automated immunostaining apparatus having a reagent application zone and a reagent supply zone. The apparatus has a carousel slide support supporting a plurality of slide supports thereon, and drive means engaging the carousel slide support for consecutively positioning each of a plurality of slide supports in the reagent application zone. The apparatus also has a carousel reagent support having a plurality of reagent container supports thereon, and drive means engaging the carousel for rotating the carousel and positioning a preselected reagent container support in the reagent supply zone. The apparatus also has a reagent delivery actuator means positioned for engaging a reagent container positioned on a container support in the reagent delivery zone and initiating reagent delivery from the reagent container to a slide supported on a slide support in the reagent receiving zone.

Automated biological reaction apparatus

An apparatus is described that includes an optical disk, adapted to be read by an optical reader, comprising a first sector having substantially self-contained assay means for localizing an analyte suspected of being in a sample to at least one, predetermined location in the first sector and a second sector containing control means for conducting the assay and analyte location information, with respect to one or more analytes suspected of being in a sample, accessible to the reader, wherein the presence or absence of the analyte at said location is determinable by the reader using the control means and the location information. Depending on the nature of the assay, the disk will include fluid storage means, fluid transfer means, such as one or more capillary ducts, valves, batteries, dialyzers, columns, filters, sources of electric fields, wires or other electrical conductive means such as metallic surface deposits and the like.

Laboratory in a disk

An automated, continuous and random access analytical system (18), having apparatus and methodology capable of simultaneously performing multiple assays of liquid samples using different assay methodologies, and providing continuous and random access while performing a plurality of different assays on the same or different samples during the same time period, is disclosed. A method is also disclosed of operating an automated continuous and random access analytical system (18) capable of simultaneously effecting multiple assays of a plurality of liquid samples wherein scheduling of various assays of the plurality of liquid samples is followed by creating a unit dose disposable and separately transferring a first liquid sample (26) and reagents (30) to a reaction vessel (34) without initiation of an assay reaction sequence, followed by physical transfer of the unit dose disposable to a processing workstation (52), whereby a mixture of the unit dose disposable reagents and sample (34) are achieved during incubation. The system (18) is capable of performing more than one scheduled assay in any order, and assays where more than such scheduled assays are presented. The automated, continuous and random access analytical system (18) is also capable of analyzing the incubated reaction mixtures independently and individually by at least two assay procedures.

Automated continuous and random access analytical system

An improved automated immunoassay analyzer including a high throughput automated immunoassay system which can perform high volume testing on a broad range of analytes while selecting from among a diverse set of immunoassays for any given sample. The immunoanalyzer has the capacity to perform a wide range of different types of immunoassays by facile storage and automated combination aboard the instrument among a wide variety of different types of reagents and heterogenous immunoassay beads stored on-board the instrument. The automated design allows reduced user interface (e.g., tests are performed automatically from computer input) including the ability to order, perform and reassay tests reflexively based on test results without operator intervention. Further, the inventive analyzer is not sample tube specific; that is, an instrument that can accept sample tube sizes within a broad size range. The inventive automated immunoassay analyzer also provides a re-useable sample dilution well, and a high speed bead washing station that eliminates the need for assay tubes having integral, waste fluid collection chambers.

Automated immunoassay analyzer

Electrochemiluminescence (ECL) is a powerful transduction technique with a leading role in the biosensing field due to its high sensitivity and low background signal. Although the intrinsic analytical strength of ECL depends critically on the overall efficiency of the mechanisms of its generation, studies aimed at enhancing the ECL signal have mostly focused on the investigation of materials, either luminophores or coreactants, while fundamental mechanistic studies are relatively scarce. Here, we discover an unexpected but highly efficient mechanistic path for ECL generation close to the electrode surface (signal enhancement, 128%) using an innovative combination of ECL imaging techniques and electrochemical mapping of radical generation. Our findings, which are also supported by quantum chemical calculations and spin trapping methods, led to the identification of a family of alternative branched amine coreactants, which raises the analytical strength of ECL well beyond that of present state-of-the-art immunoassays, thus creating potential ECL applications in ultrasensitive bioanalysis. Electrochemiluminescence (ECL) is a leading technique in biosensing. Here the authors identify an ECL generation mechanism near the electrode surface, which they exploit in combination with the use of branched amine coreactants to improve the ECL signal beyond the state-of-the-art immunoassays.

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Insights into the mechanism of coreactant electrochemiluminescence facilitating enhanced bioanalytical performance

An automatic analyzing system has a sample table for supporting a plurality of sample vessels and a reagent table for supporting a plurality of reagent vessels. The sample table and the reagent table are fixed to a common drive shaft. The system further has a rotatable reaction table for supporting a plurality of reaction vessels. The reaction table is arranged in a side-by-side relation to the sample table and the reagent table. The system further has a single pipetting device disposed between the reaction table and the stack of the sample table and the reagent table for a swinging motion therebetween so as to suck samples and reagents from the sample vessels and the reagent vessels and to deliver the same to the reaction vessels. The pipetting device is operated in such a manner as to transfer all the samples to the reaction vessels followed by the supply of the reagents to these reaction vessels.

Automatic analyzing system

Sample sampling to an analysis apparatus 200 or 820 for analyzing a biochemical analysis item is performed by a pipetting device 202 or 840 which uses a repetitively used pipette nozzle, and sample sampling to an analysis apparatus 100 or 810 for analyzing an immune analysis item is performed by a pipetting device 102 or 830 which uses a disposable nozzle tip. A sample bottle containing a sample to be analyzed on both of a biochemical analysis item and an immune analysis item is sample-pipetted by the nozzle tip first, and then transported so as to be sample-pipetted by the pipette nozzle.

Handling method of body fluid sample and analysis apparatus using the same

An analyzer has a reaction disk for holding a plurality of reaction containers and a fluorophotometer for measuring fluorescence stemming from solutions in the containers. Most of the containers contain solid phases attached with antibodies but at least one container does not contain any solid phase. In normal operation of the analyzer, a test sample containing antigens and a latently fluorescent reagent such as an antibody labeled by an enzyme are added to a container containing a solid phase. In this container, a fluorescent substance is created through an enzyme reaction. Light is irradiated on the container and the fluorescence emitted from the fluorescent substance is measured. While measuring test samples, fluorescence stemming from a reference sample, such as quinine sulfate, is measured to produce values for the reference sample by which measured values for the test samples are corrected. Prior to measuring general test samples by the analyzer, fluorescence stemming from a reference sample in a container removed of any solid phase is measured and compared with a setting value. If the results of the comparison indicate that the normal operation will be difficult to continue, then the sampling operation by the pipetter is discontinued.

Method and apparatus for automatic measurement of fluorescence

Before analysis, the correspondence between the vessel positions and the reaction vessels held in the vessel positions respectively at the time of completion of all the operations of a turntable upon completion of the last analysis are stored in a computer in advance. When a start switch is turned on, a judgment is made as to whether the correspondences between the vessel positions and the reaction vessels coincide with those stored in the computer or not. In the case of coincidence, reaction vessels in vessel positions are regarded as having been already cleaned, so that these reaction vessels are subjected to blank measurement and sample addition in the case of optical measurement, whereas these reaction vessels are directly subjected to sample addition in the case of ISE measurement.

Kyoko Imai

Papers

Insights into the mechanism of coreactant electrochemiluminescence facilitating enhanced bioanalytical performance

Automatic analyzing system

Handling method of body fluid sample and analysis apparatus using the same

Method and apparatus for automatic measurement of fluorescence

Automatic analyzer having cuvette cleaning control device