Metara, Inc.

Duquesne University of the Holy Ghost

Definitek, Inc.

Other

Berthold Gmbh & Co. Kg

Applied Isotope Technologies, Inc.

Howard M Kingston

Mehmet Pamukcu

Michael John Ahern

Marc R Anderson

Larry N Stewart

Michael J West

Mizanur Rahman

G&uuml;nter Knapp

David Lineman

A method of measuring and calculating (preferably by a computer with output to a user) tGSH (total glutathione very particularly defined) with sample preparation and assay methods that have been confirmed to provide accurate and reliable tGSH and related diagnostic assays in blood or tissue from a patient.

Accurate measurement of glutathione for disease diagnosis and drug metabolite screening

The present invention centers upon a novel 'molecular amplification spike,' which is an admixture of two components, namely, an aliquot of a quantity of a molecule, composition, compound or element of interest (an 'analyte') in its natural isotopic state and an aliquot of an isotopically enriched form of the same molecule, composition, compound or element. The molecular amplification spike contains 20% natural-abundance isotope, balance enriched isotope. The molecular amplification spike may optionally contain more than 20% natural-abundance isotope, with concomitantly reduced balance of enriched isotope. Such an admixed spike, when added to a sample prior to mass spectrometric analysis of that sample, creates new and significantly improved percentage of errors and quantification or confirmation of the absence of the molecule, composition, compound or element of interest in the sample.

Quantification of previously undetectable quantities

A method for the equilibration of enriched isotope species and natural isotope species prior to mass spectrometric analysis using solid phase and/or microwave isotope ratio equilibration and measurement.

Solid phase and catalyzed enabled automated isotope dilution and speciated isotope dilution mass spectrometry

A method of directed automated analysis of a plurality of analytes of a process solution includes providing a sample of the process solution containing a plurality of the analytes, admixing an enriched isotope spike for each of the plurality of analytes to be analyzed with the process solution sample thereby effecting admixture of the enriched ratio of isotopes with the naturally occurring ratio of each analyte to be analyzed, creating ions from the spikes, introducing the ions into a mass spectrometer for determination of the identity and quantity of each analyte and delivering the information to a microprocessor. If desired, the process solution sample may be diluted and/or subjected to the addition of reagents or standards prior to initiation of the analysis. The ions may be created by an atmospheric pressure ionization interface. The information obtained is processed in a computer which serves to control other portions of the practice of the method. Such controls may include delivery of analytes to the process solution based on the information obtained, control of the sample extraction, sample handling, ionizer, and mass spectrometer. The information may also be employed to control delivery of analytes in the process solution. In another embodiment, enriched isotopic ions are introduced into the process solution. Corresponding apparatus is provided.

Method and apparatus for automated analysis and characterization of chemical constituents of process solutions

A combination electrospray/microwave induced plasma (MIP) ionization source is used as the ionization source for a mass spectrometer. The electrospray can be operated in positive mode, negative mode, or it can be switched off. The microwave-induced plasma can also be switched on or off. This allows the instrument to be operated in multiple modes. With the electrospray off and the MIP on, the instrument will normally have its maximum elemental sensitivity. Mixed mode operation potentially allows the determination of additional information about the chemical constituents present in the analyte. In pure electrospray mode, it is possible to obtain molecular information and to analyze organic compounds.

Nebulizer with plasma source

An analytical apparatus to monitor fluid systems has at least one extraction module having a raw-sample reservoir connected by input fluid conduit to individual ones of said fluid systems, to extract raw samples for analysis from said fluid systems, one or more modification modules comprising additive materials to modify the extracted raw samples prior to analysis, an analytical device to receive at least a portion of said raw samples in an ordered sequence, and to determine concentration of at least one constituent of said sample portion, fluid-handling apparatus for transferring fluid through the analytical apparatus, and a computerized control and management system to manage operations of component modules and devices, and to report analytical results. The apparatus is characterized in that the control and management system coordinates extraction of raw samples, modification as needed, introduction of fluids to the analytical device, and reporting of analytical results on a continuous basis over plural cycles.

Method and instrument for automated analysis of fluid-based processing systems

A method and associated apparatus for in-process automated analysis employing a mass spectrometry ratio measurements is disclosed. It involves elemental and speciation threshold measurement that is optimized for quality assurance at and is capable of functioning at and near quantitative instrumental detection limits. The system is automated and may be employed in an unattended operation for identification and quantification of elemental or specie contaminants. In a preferred aspect of the method, a sample is subjected to equilibration with at least one spike after which it is subjected to ionization in an atmospheric ion generator and processed by a mass spectrometer with the output of the mass spectrometer being processed by a microprocessor which through a controller coordinates operation of sample and spike delivery and equilibration as well as the operation of the atmospheric ion generator and mass spectrometer. The method may in the alternative be employed qualitatively.

Automated in-process ratio mass spectrometry

A method of speciated isotope dilution mass spectrometry (SIDMS) which will permit determination of concentrations of one or more species from a sample even if the sample has been subjected to species conversion prior to species separation or degradation or incomplete separation exists. At least one predetermined stable isotope is spiked to convert the stable isotope to a speciated enriched isotope corresponding to the specie or species to be measured in the sample. The sample containing the species to be measured is spiked and the isotopic spiked specie and species to be measured are equilibrated. The species are separated from the sample and an isotope ratio determination for each specie to be measured is made. The species concentrations are then mathematically deconvoluted while correcting for species conversion and/or incomplete separation. The method may be employed to validate other methods. The method may also be employed in the preparation and analysis of speciated standard reference materials. The method may be employed in quantifying Cr(III) and Cr(VI).

Speciated isotope dilution mass spectrometry of reactive species and related methods

The present invention refers to an apparatus for carrying out wet chemical reactions under pressure comprising a pressure sure vessel in which a reaction liquid can be provided and which is adapted to be sealed in a pressure-tight manner by closure means. When the reaction liquid is heated, the pressure in the interior of the pressure vessel will increase; the stressability limit of the pressure vessel must, however, not be exceeded. The total pressure in the interior is composed of the partial pressures of the reaction liquid and of the reaction products. The reaction liquid must be maintained at so low a temperature that the sum of the partial pressures of the reaction liquid and of the gaseous reaction products does not exceed the maximum load value of the pressure vessel. For achieving a wet chemical reaction which is as fast and as efficient as possible, the highest possible temperature of the reaction liquid is, however, required. In accordance with the present invention these problems are solved by a rinsing device for rinsing the pressure vessel while removing gaseous reaction products from the pressurized pressure vessel and while maintaining a predetermined pressure therein. This has the effect that the gaseous reaction products are removed from the pressure vessel so that said gaseous reaction products will neither displace the reaction equilibrium nor influence the pressure conditions.

Apparatus for carrying out wet chemical reactions under pressure

A method of microwave assisted chemical reaction includes providing a microwavable reaction vessel which contains at least one material in a sample. The sample is heated by microwave energy to elevate the temperature of the reagent and at least partially volatilize the sample to establish a gas phase within the vessel followed by positive cooling of the gas phase to reduce the temperature and responsively reduce the pressure of the gas phase without effecting substantial cooling of the liquid phase. The method may involve employing cooling exteriorly of and adjacent to the gas phase containing portion of the vessel or cooling by means of a coolant flowing within coils disposed in the interior of the vessel or both. The process is preferably a continuous process. The apparatus may be a vessel transparent to microwave energy for receiving the sample. The vessel has space overlying the liquid phase containing portion for a gas phase. Structures for cooling means for positively cooling the gas phase to reduce the pressure of the gas phase without effecting substantial cooling of the reagent are provided. These structures for cooling may be contained within the vessel, exteriorly of the vessel or modification of the vessel configuration to facilitate gas phase cooling or combinations thereof.

Method and apparatus for microwave assisted chemical reactions

The method of determining the concentration of a specie in a sample includes providing at least one predetermined, enriched isotope in the same speciated form as the species to be measured, spiking the sample containing the species to be measured, equilibrating the spiked species with the species to be measured, separating the species from the sample and subsequently determining the concentration of the species to be measured by employing isotopic element specie ratios. In one embodiment, a single speciated isotope spike is employed and, in others, two or more such spikes may be employed. In a preferred embodiment, time resolution chromatography is used to effect separation of these species from the sample and mass spectrometer is employed in determining isotopic elemental ratios. It is also preferred that a method be employed to determine if there has been conversion from one species to another. In another embodiment, spiking of the several different isotopically enriched analogs of the same specie are added at various steps in the sampling procedure and the stability and integrity of the specie with respect to these processes is evaluated by mass spectrometric measurements of the various isotopic ratios. Chemical processes, extraction methods, dissolution procedures and storage procedures are evaluated. In another embodiment, speciated isotope dilution is used to determine the effect on species of various sample preparation methods and portions of sample preparation techniques. Extraction and separation procedures employ the technique to provide definitive evidence of accurate specie manipulation and provide for performance based measurement.

Growing community of inventors

Pittsburgh, PA, United States of America

Howard M Kingston