Abstract: Mass spectrometry of large nucleic acids by infrared Matrix-Assisted Laser Desorption/Ionization (MALDI) using a liquid matrix is reported.

Abstract: An improved biologic electrode array and methods for manufacturing and using the same. In one aspect, a matrix of electrodes each coupled to a respective sample-and-hold circuit is provided. The electrodes and sample-and-hold circuits are integral and form an array within a single semiconductor chip, such that each sample-and-hold circuit may be loaded with a predefined voltage provided by a single, time-shared digital-to-analog converter (DAC). Further, all of the sample-and-hold circuits may be accessed through a multiplexer which may be scanned through some or all of the electrode locations. Each sample-and-hold circuit may comprise a capacitor and one or more transistor switches, the switch(es), when closed, providing electrical communication between the capacitor and a source line formed in the matrix.

Abstract: The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.

Abstract: A 1,2-dioxetane derivative represented by the general formula: wherein R1, R2, R3, R4, R5, R6 and R7 each independently represents hydrogen atom, an alkyl group, or an aryl group, or one or more than one pair of R2 and R3, R4 and R5, and R6 and R7 can together form a cyclic alkyl group. The compound is easily handled because the compound itself is very stable, and it is capable of emitting light with a very high efficiency.

Abstract: The invention deals with the use of a reactive compound in immunological analyses. The compound is ouabain or its analog to which another compound, labeled by radioiodine or by a fluorogen, is coupled. The invention covers also the method to measure ouabain or its analog in plasma to diagnose cardiovascular and endocrine diseases and other harmful conditions.

Abstract: A reagent, kit and method for the quantative determination of ascorbic acid in a sample uses ascorbate oxidase which catalyzes the reaction of reduced ascorbic acid to oxidized ascorbic acid and hydrogen peroxide. Ascorbic acid in the sample is reacted with oxygen in the presence of the ascorbate oxidase, chromogen and peroxidase. Absorbance is determined and compared with a known calibration curve.

Abstract: The present invention is directed to an improved analyte systems which are able to compensate for interfering signals and to provide accurate detection and/or quantification of analytes in a sample. In particular, the invention describes new methods, systems, and devices for indirectly determining the presence of one or more analytes in a multi-component medium.

Abstract: Sensors (20, 50, 70) for use in detecting the presence of sugars and other analytes (target molecules). The sensor is composed of a metal complex that binds to the target molecule and releases a proton or includes an exchangable ligand which is exchanged for the target molecule during the binding interaction between the metal complex and the target molecule. The result of the binding interaction is the release of a proton, hydroxide ion or ligand species generated during the ligand exchange. Measurement of the release of proton, hydroxide ion or other ligand species from the sensor (20, 50, 70) provides an indirect indication of target molecule concentration. The metal complexes may be attached to support structures (10, 12) to provide both anchoring and positioning of the metal ions to increase selectivity of sugar/metal complex interactions. Detection systems in which pH is used as an indication of proton or hydroxide release are disclosed, as are detection systems in which Cl.sup.- release is used.

Abstract: A method for the determination of an individual's alcohol consumption, characterized in comprising the steps: i) determining the level of sialic acid in a body fluid sample from the individual; ii) comparing the level found in step (i) with the level for the normal population, an increased level being an indication of an increased alcohol consumption relative to the consumption (per individual) of the normal population.

Abstract: A method of determining intracellular levels of water-soluble and fat-soluble antioxidants. Peripheral blood mononuclear cell lysates are prepared from an individual and analyzed by HPLC, either directly or after extraction with organic solvents to extract fat-soluble antioxidants. The levels of antioxidants are compared to normal levels as an indication of the overall oxidative health of the individual.

Abstract: For the purpose of improving the accuracy and reproducibility of the measurement of .beta.-glucan by flow injection method using calcofluor, the present invention provides a method in which a gel filtration column having the volume of the interstice outside of the gel particles which is not larger than the column effluent volume within a certain period of time and the column content volume which is 10 times or more as large as the sample injection volume is placed between the sample injection port and the detector in said system.

Abstract: The present invention relates to a family of cyanine dyes possessing lipophilic alkyl chains and either one or more reactive functional groups, bromo or chloro, or phenyl, sulfophenyl or polysulfophenyl substituents or combinations thereof. The dyes of the invention are useful for staining membranes in cells or isolated from cells, and are well-retained therein. Additionally, the reactive dyes of the invention are useful for preparing dye-conjugates, thereby conferring the membrane staining ability of the subject dye onto the resulting dye-conjugate.

Abstract: An improved biologic electrode array and methods for manufacturing and using the same. In one aspect, a matrix of electrodes each coupled to a respective sample-and-hold circuit is provided. The electrodes and sample-and-hold circuits are integral and form an array within a single semiconductor chip, such that each sample-and-hold circuit may be loaded with a predefined voltage provided by a single, timeshared digital-to-analog converter (DAC). Further, all of the sample-and-hold circuits may be accessed through a multiplexer which may be scanned through some or all of the electrode locations. Each sample-and-hold circuit may comprise a capacitor and one or more transistor switches, the switch(es), when closed, providing electrical communication between the capacitor and a source line formed in the matrix.

Abstract: A process for the extraction and purification of TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin) from a sample matrix. The process of the present invention overcomes a problem of prior art processes for extracting TCDD, by providing for chemical destruction of potentially interfering components in a sample matrix making the steam distillation of TCDD possible. A typical sample matrix comprises blood serum.

Abstract: Chronic or long-term alcohol consumption is detected and diagnosed by determining the levels of an alcohol-specific ethanol glycoconjugate biomarker, identified as ethyl .beta.-glucuronide, in body fluids (e.g. urine) of subjects by calorimetric reaction using qualitative and quantitative assay methods. Ethyl glucuronide has been newly observed and detected as a direct indicator of chronic alcohol consumption, and can be isolated and purified. Economical and reproducible assay methods, such as a chromatographic spot assay, ascending or thin layer chromatography assay, and high pressure liquid chromatography assay provide reliable, objective, and sensitive methods for detecting and monitoring a chronic alcoholic condition. Both the presence of the alcohol-specific ethyl glucuronide and a substantial increase in its levels are diagnostic of chronic alcoholism.

Abstract: The present invention provides a method of using a reflectance-reading device to determine an initiation time point for measuring the chemical reaction of an analyte from a biological liquid sample on a test surface. The initiation time point is determined by using a device to read a reflectance of a test surface at a plurality of time points, and calculating the K/S ratio of the test surface at each time point according to the Kubelka-Munk equation. As the device continues to calculate a K/S ratio for each time point, the device monitors the rate of change of the K/S ratio with respect to time. The device then determines the initiation time point to be when the rate of change of the K/S ratio is maximal. The present invention also provides a method of measuring the concentration of an analyte on a test surface. The concentration is measured by determining an initiation time point according to the method described above and then measuring the concentration of the analyte at a variable end point.

Abstract: A microscale fluid handling system that permits the efficient transfer of nanoliter to picoliter quantities of a fluid sample from the spatially concentrated environment of a microfabricated chip to "off-chip" analytical or collection devices for further off-chip sample manipulation and analysis is disclosed. The fluid handling system is fabricated in the form of one or more channels, in any suitable format, provided in a microchip body or substrate of silica, polymer or other suitable non-conductive material, or of stainless steel, noble metal, silicon or other suitable conductive or semi-conductive material. The microchip fluid handling system includes one or more exit ports integral with the end of one or more of the channels for consecutive or simultaneous off-chip analysis or collection of the sample. The exit port or ports may be configured, for example, as an electrospray interface for transfer of a fluid sample to a mass spectrometer.

Abstract: The invention relates to a measurement apparatus (1) for analysing fluids, comprising a container (3) in the form of a syringe, into which a fluid may be taken in via an intake device (14) through at least one opening (5), and further comprising a sensor (7) which is either integrated in the container wall (9) or is attached to said container wall (9), the sensor(s) (7) being so disposed that it/they can come into contact with the fluid which may be taken up into the cavity (10).

Abstract: Acid is added to a target sample such as urine, blood plasma or serum for converting mevalonic acid contained in the sample to lactone mevalonate, and the sample is irradiated with near infrared Raman excitation light, for determining mevalonic acid by measuring generated Raman scattered light. This method employs no mediatory reaction with simple pretreatment, requires no high-priced measuring apparatus, and can determine mevalonic acid in a short time.

Abstract: A method and an instrument for separating and analyzing a very small quantity of constituents to be inspected contained in an analyte such as a class of catecholamines by liquid chromatography after labeling. The entire processes of analytical operations include principally three processes, a preparing process, an impurity elimination process and a separation process. When one sample is perceived, the sample is processed in these three processes. In this case, while one sample is being processed in an impurity elimination process, a sample preceeding the one sample is processed in a separation process, and a succeeding sample is processed in a preparing process. In other words, these three processes are performed essentially in parallel. With this, it is possible to remarkably reduce analysis time as compared with individual single sample analysis.

Abstract: Chronic or long-term alcohol consumption is detected and monitored by determining the level of a newly-observed, alcohol-specific carbohydrate in body fluids (e.g. urine) of subjects by calorimetric reaction using qualitative and quantitative assay methods. The alcohol-specific carbohydrate have been identified as a novel ethyl glucuronide. Ethyl glucuronide is observed and detected in direct response to alcohol consumption in body fluids, and can be isolated and purified. Simple, economical, and reproducible assay methods, such as a spot assay and an ascending or thin layer chromatography assay, provide reliable, objective, and sensitive methods for detecting and monitoring a chronic alcoholic condition. Both the presence of the alcohol-specific ethyl glucuronide and a substantial increase in its levels are indicative of chronic alcoholism.

Abstract: The present invention is a method for the detection of hydrogen peroxide in biological fluids or an aqueous solution which involves contacting the solution with an oxidation-reduction indicator and a transition metal complex. The transition metal complex is either a creatinine coordinated with iron or a guanidine coordinated with iron.

Abstract: Water-treatment compositions are provided which contain a water-soluble, water-treatment polymer and, optionally, additional water-treatment chemicals. The polymers are prepared from water-treatment monomers and a photo-inert, latently-detectable moiety which is covalently bonded to the polymer backbone. When the residue of the photo-inert moiety is contacted with an amount of a photoactivator which is effective to cause the residue of the photo-inert moiety to absorb within a wavelength ranging from 300 to 800 nanometers, the residue of the photo-inert moiety is detectable at concentrations of less than 100 parts per million. Methods are also provided which allow for the determination of the concentration of low levels, i.e., less than 100 ppm, of the water-treatment polymer present in an aqueous system.

Abstract: This invention relates to power transformers. More particularly, this invention pertains to a method and apparatus for detecting the degree of degradation of paper insulation in a transformer by determining the concentration of furaldehyde in the transformer oil. A reagent for detecting the presence of furaldehyde in transformer oil comprising: (a) a primary amine selected from the group consisting of aniline, toluidine, anisidine, aminophenol or an amine; (b) a second component having about 3 mL of about 15 to 33 (weight to volume) percent of acetic acid alone, or in combination with citric acid; from about 67 to 85 (volume) percent of a halogenated hydrocarbon selected from the group consisting of dichloromethane, chloroform, carbontetrachloride, dichloroethane, trichloroethane, tetrachloroethane, trichloroethylene, tetrachloroethylene; about 4 (weight to volume) percent of salicylic acid; and about 1 (weight to volume) percent of an anti-oxidant; and (c) a third component having about 1.

Abstract: Dicitrate cyclic diester (dicitrate) is a novel compound which is found in patients who do not exhibit symptoms or predisposition to idiopathic renal calculous disease. Kits are provided for the detection of dicitrate cyclic diester.

Abstract: A method of treating contact lenses comprising the use of an iodine-chromophore to indicate neutralization of oxidative disinfectants.

Abstract: Halo, azido, and amino cyclodextrin/epichlorohydrin copolymers, methods of preparing the copolymers, and the use of the copolymers for removing aflatoxins and phytoestrogens from a sample, for detecting the presence of aflatoxins and phytoestrogens, and for quantifying aflatoxin and phytoestrogen levels.

Abstract: The amount of lipid bound sialic acid in a blood plasma or serum sample may be determined by an improved method, which may be automated, involving the following steps to be performed simultaneously on the sample and a standard consisting of commercially available n-acetyl nueraminic acid (NANA); diluting with a buffer; mixing the diluted sample; adding a mixture of a chlorinated lower aklyl hydrocarbon and a lower alkyl alcohol; treating by mixing and centrifuging to yield a substantially clear upper phase; treating the upper phase with a color development reagent; mixing; boiling the admixture; cooling the admixture; and determining the amount of lipid bound sialic acid present in the sample by comparing the optical density of the sample to the optical density of the NANA.

Abstract: The present invention is directed to a method for determining the presence of an oxidant or reductant in a sample by contacting the sample with a thin film of polyaniline in the reduced state or oxidized state, respectively, and measuring the color change occurring with the oxidation or reduction, respectively, of the polyaniline film.

Abstract: A new enzymatic rate method is disclosed for the analysis of Vitamin C using ascorbate oxidase. Total Vitamin C can be measured in a single analysis, in a procedure amenable to automation. Any dehydroascorbic acid (DHAA) in the sample is reduced to ascorbic acid. Then a coupling agent such as o-phenylenediamine (OPDA) is added to the sample, and any nonspecific reactions with, or spectrometric interferences from, other components of the sample are measured, to be blanked out from the final measurement. Then ascorbate oxidase is added, oxidizing ascorbic acid to DHAA; the DHAA then reacts with the OPDA already present from the prior step, and the quinoxaline derivative product may be measured spectrometrically, e.g., by absorbance at 350 nm.

Abstract: Dicitrate cyclic diester (dicitrate) is a novel compound which is found in patients who do not exhibit symptoms or predisposition to idiopathic renal calculous disease. Dicitrate can be isolated and detected by novel chromatographic methods. Further, treating patients prophylactically and therapeutically with dicitrate cyclic diester can prevent or reduce the effects of calcification-related disease, including some types of kidney stones.

Abstract: Compounds containing .alpha.-discarbonyl groups are rendered capable of fluorescent emission by conjugation with carboxylic acid-terminated ortho-diaminoaryl reagents. The carboxylic acid groups serve as ionizable moieties which facilitate the conjugation reaction, and are retained in the conjugation product to enable, or enhance the ability of, the conjugated compounds to be separated in chromatographic and electromigration separation processes, notably electrophoresis. Ortho-dinitro derivatives of the reagents are also disclosed, these derivatives offering the advantage of stability as well as the ability to be used directly in the reaction in the presence of a reducing agent.

Abstract: The amount of lipid bound sialic acid in a blood plasma or serum sample may be determined by an improved method which may be automated involving the following steps to be performed simultaneously on the sample and a known standard prepared from human or animal blood or tissue; diluting with distilled water; mixing; adding a mixture of a chlorinated lower aklyl alcohol; mixing, diluting with water and then treating by mixing further and centrifuging to yield a substantially clear upper phase; recovering the upper phase and adding to it a protein precipitating agent, mixing the resulting admixture; recovering the resulting precipitate, suspending the precipitate in a hydrolysis agent and determining the amount of lipid bound sialic acid present by comparing the optical density of the sample to the optical density of the standard.

Abstract: The method of identification of the country of origin of CANNABIS (Marijuana). The method comprises gas chromatographic/mass spectrometric analysis of extracts of multiple samples of marijuana plant material from a country or geographical location, preparing a location profile from the chemical profiles made from analysis of the multiple samples from a specific country or location. The analyzed profile of a sample of unknown origin is compared with the location profiles of the various countries growing marijuana.

Abstract: Spectrophotometric methods, including the use of convention spectroscopic absorption or circular dichroism, for clinical chemistry detection methods. More specifically, with the use of such spectrophotometric methods in the measurement of cholesterol levels and direct measurement of cholesterol subfractions in clinical samples, and in the measurement of lipoprotein levels in a clinical test sample, as well as in the detection of anabolic steroids and other steroid products. The invention is also concerned with providing certain CD and conventional spectrophotometric apparatus useful in each of the aforesaid chemical methods.

Abstract: A method for quantifying in vivo ascorbate concentration in body fluids uses gas chromatography/mass spectrometry (GC/MS). Further provided is a method for measuring redox potentials of body fluid by determining the ratio of in vivo concentration of ascorbate to one or more of its metabolites.

Abstract: Methods for diagnosing pre-hypertension, hypertension, congestive cardiomyopathy, renal failure, salt-sensitivity and adenomas and endocrine cell hyperplasias are disclosed. Also disclosed are methods for monitoring hypertension therapy, congestive cardiomyopathy therapy, renal failure therapy and adenoma and endocrine call hyperplasia therapy. These methods involve using an antibody having binding specificity to ouabain to immunologically measure the level of human ouabain in body fluid or tissue of a subject. Additionally, methods for treating a hypertensive subject by inducing passive or active immunity to human ouabain in the subject are disclosed, along with an antibody having binding specificity for ouabain.

Abstract: An immunoassay for trichothecenes that have at least three hydroxyl groups at specified positions is disclosed. It relies on developing antibodies to close trichothecene variants that are missing at least one of the hydroxyl groups, and then using these antibodies to test specimens in which the trichothecene has been converted to the variant (usually to the OAC variant). For example, DON and T-2 tetraol can be assayed for using this invention.

Abstract: Catecholamines can be detected with high sensitivity in a shortened time period, by introducing a sample containing catecholamines into an adsorption column packed with an adsorbent to adsorb catecholamines to the column, then introducing a reagent for derivatization to effect pre-column labeling and then analyzing the pre-column labeled catecholamines by means of high performance liquid chromatography. Connection of the adsorption column and a separation column of high performance liquid chromatography via a fluid path changeover valve enables to automated analysis of catecholamines.

Abstract: The present invention provides a method for extracting lipid bound sialic acid from a sample of blood plasma or serum and determining the amount of sialic acid present in the sample which comprises:(a) adding to the sample a mixture of a lower alkyl alcohol and a chlorinated lower alkyl hydrocarbon so as to form a resulting admixture, the volume ratio of the lower alkyl alcohol to the chlorinated lower alkyl hydrocarbon being in the range from about 70:30 to about 85:15;(b) mixing the resulting admixture for a period of time sufficient to dissolve lipid bound sialic acid present in the sample;(c) treating the admixture so as to form a recoverable, substantially clear lipid bound sialic acid-containing upper phase;(d) separately recovering from the clear upper phase so formed a predetermined volume of the upper phase; and(e) determining the amount of lipid bound sialic acid present in the predetermined volume of the upper phase and thereby the amount of sialic acid present in the sample.

Abstract: A method for detecting the presence of drug metabolites in the meconium of newborn infants is described. The method involves separation of the drug metabolites from meconium in solution and then assaying the solution for the presence of the drug metabolites. The method is particularly useful for detection of cocaine, morphine and cannabinoids; however, any drug metabolite in the infant meconium can be tested. Conventional assay methods are used for the drug metabolites in the solutions derived from the meconium. The method provides for early detection of drug presence in infants which contribute to infant illness.

Abstract: An improved method for determining the nucleotide base sequence of a DNA molecule. The method includes annealing the DNA molecule with a primer molecule able to hybridize to the DNA molecule; incubating the annealed mixture in a vessel containing four different deoxynucleoside triphosphates, a DNA polymerase, and one or more DNA synthesis terminating agents which terminate DNA synthesis at a specific nucleotide base, wherein each the agent terminates DNA synthesis at a different nucleotide base; and separating the DNA products of the incubating reaction according to size, whereby at least a part of the nucleotide base sequence of the DNA can be determined. The improvement is provision of a DNA-polymerase which is a .phi.29-type DNA polymerase.

Abstract: A method is provided for the detection of a disease associated with the metabolic abnormality of L-fucose in a subject. The concentration of free L-fucose in a specimen from the subject is determined and the determined concentration is compared with a normal concentration of free L-fucose.

Abstract: The interference of dehydroascorbic acid, an oxidation product of ascorbic acid, in analytical methods is reduced with the use of certain nitrogen-containing organic buffers. Dehydroascorbic acid tends to cause premature reduction of reducible compounds which are used to provide detectable species in the presence of an analyte. These organic buffers, as opposed to inorganic buffers, prevent premature reduction of the reducible compounds. An analytical method can be carried out in solution or in a dry analytical element.

Abstract: An immunoassay for trichothecenes that have at least three hydroxyl groups at specified positions is disclosed. It relies on developing antibodies to close trichothecene variants that are missing at least one of the hydroxyl groups, and then using these antibodies to test specimens in which the trichothecene has been converted to the variant (usually to the OAC variant). For example, DON and T-2 tetraol can be assayed for using this invention.

Abstract: Certain methanol soluble ortho-benzo or -naphthoquinones are useful electron transfer agents. They are particularly useful in the detection of cells in urine.

Abstract: A method of measuring lipid-bound sialic acid (LSA) which comprises, mixing a LSA separating agent comprising a polar solvent with a sample containing LSA and other sialic acid(s), separating the precipitate formed to obtain a supernatant, and measuring the sialic acid concentration of said supernatant by using an enzyme capable of acting on sialic acid in a lipid-bound state. When a sample is treated with the LSA separating agent comprising a polar solvent, various components in the sample such as protein-bound sialic acid and proteinous substances precipitate while the desired lipid-bound sialic acid remains in the supernatent. Accordingly, by measuring sialic acid concentration of the supernatent, LSA concentration of the sample is easily determined. The method of the invention is simple and superior in reproducibility. The method of the invention is suitable for treating a large number of samples, and it can easily by automated. This method is suitable as a screening test for cancer.

Abstract: Monitoring exposure to ethylene oxide using a dosimeter or monitoring device avoids using devices that collect a sample for future testing or devices that must be sent away for lab analysis. The device comprises a reactive coating including a layer of activated alumina particles coated with p-nitrobenzyl pyridine and ammonium chloride, and is adapted to instantly produce a color intensity change directly related to the dosage of the reactive coating to ethylene oxide upon the addition of a developer.

Abstract: A method for detecting cannabinoids in body fluids which comprises filtering body fluids through a cellulosic filtering means treated with a binding agent for cannabinoids and the filtering means. The binding agent is an arylcarboxylic acid. The cannabinoids are then treated with a subsequent reagent to produce a color reaction. A device for detecting cannabinoids is also disclosed which contains the filtering means treated with the binding agent so as to concentrate the cannabinoid prior to reaction with a suitable indicator.

Abstract: A method for detecting basic narcotics or drugs in body fluids which comprises filtering body fluids through a cellulosic filtering means treated with a binding agent for the narcotics or drugs and the filtering means. The binding agent is a polycarboxylic acid. The narcotics or drugs are then treated with a subsequent reagent to produce a color reaction. A device for detecting basic narcotics or drugs in also disclosed which contains the filtering means treated with the binding agent so as to concentrate the narcotic or drug prior to reaction with a suitable indicator.