Abstract: A mass spectrometry quantitation technique enables high-throughput quantitation of small molecules using a laser-desorption (e.g., MALDI) ion source coupled to a triple-quadrupole mass analyzer. The ions generated from the ion source are collisionally damped/cooled, and then quantitatively analyzed using the triple-quadrupole analyzer operated in the multiple-reaction-monitoring (MRM) mode. Significantly improved measurement throughput is obtained by applying the laser to each sample spot on the target for an irradiation duration significantly shorter than the time required to deplete the sample material in the sample spot. The irradiation duration may be set based on a determination of the MRM peak broadening caused by the ion optics.

Abstract: Sol-gel derived monolithic silica columns containing entrapped dihydrofolate reductase were used for frontal affinity chromatography of small molecule mixtures. The output from the column combined with a second stream containing the matrix molecule (HCCA) and was directly deposited onto a conventional MALDI plate that moved relative to the column via a computer controlled x-y stage, creating a semi-permanent record of the FAC run. The use of MALDI MS allowed for a decoupling of the FAC and MS methods allowing significantly higher ionic strength buffers to be used for FAC studies, which allowed for better retention of protein activity over multiple runs.

Abstract: The present invention relates to glycine transporter inhibiting compounds of formula (I): for treating disorders mediated by GlyT1, wherein R1—R9 are as in the description.

Abstract: A system and method of analyzing a sample is described. The system includes an ion source and a deflector for producing a plurality of ion beams each of which is detected in distinct detection regions. A detection system uses the information obtained from the detection region to analyze the sample.

Abstract: A process and apparatus are provided for simultaneously moving a first sample plate into an analytical apparatus and a second sample plate from the analytical apparatus. The first sample plate is moved on an entry path which is vertically spaced apart from an exit path for the second sample plate. The transfer mechanism is disclosed in operation with a MALDI-TOF mass spectrometer.

Abstract: An apparatus and method for performing mass spectroscopy uses an ion interface to provide the function of removing undesirable particulates from an ion stream from an atmospheric pressure ion source, such as an electrospray source or a MALDI source, before the ion stream enters a vacuum chamber containing the mass spectrometer. The ion interface includes an entrance cell with a bore that may be heated for desolvating charged droplets when the ion source is an electrospray source, and a particle discrimination cell with a bore disposed downstream of the bore of the entrance cell and before an aperture leading to the vacuum chamber. The particle discrimination cell creates gas dynamic and electric field conditions that enables separation of undesirable charged particulates from the ion stream.

Abstract: A sample container for minimizing evaporation of a contained volume of sample includes a container housing, a repuncturable self-sealing membrane, and a collapsible sample bag. The container housing includes an open end and a hollow interior region. The repuncturable self-sealing membrane configured to self-seal after repeated punctures is engaged in the open end of the container housing and includes an exterior surface exposed to the external environment and an interior surface oriented toward the hollow interior region of the container housing. The collapsible sample bag includes a proximate end that is permanently attached to the interior surface of the repuncturable self-sealing membrane.

Abstract: Methods for the detection and measurement of tagged (labeled) biologically active materials in a sample are described. The tagged biologically active materials are detected using an atomic mass or optical spectrometer having a source of atoms or atomic ions. Element-labeled biologically active materials, comprising antibodies, antibody Fab′ fragments, antigens, aptamers, protein complexes, growth factors, hormones, receptors and other biologically active materials attached to a stable elemental tag, can be used in specific binding assays and measured by elemental spectroscopic detection. Also described are methods for the determination of metals in samples of interest using specific antibodies to isolate the target metals and elemental spectroscopy for detection and quantitation. Kits are provided comprising reagents to detect and measure labeled biologically active materials or labeled competition analytes.

Abstract: A method and apparatus for the analysis of a narrow range of fragment ions by application of a notched broadband waveform during ion accumulation within a quadrupole collision cell operated as a linear ion trap. The fragment ions are formed via the axial acceleration and collision activated dissociation of mass resolved precursor ions. A narrow band of frequencies is purposefully omitted from the spectrum, so that the secular frequency of a particular fragment ion will fall within this notch of absent frequencies and as a result will not experience resonant excitation and are retained in the linear ion trap. Simultaneously, all other ions are lost either through neutralization when they strike electrodes or through (additional) collision activated dissociation. Accordingly, a particular mass or range of masses, whose secular frequencies fall within the notch of absent frequencies in the notched broadband waveform, may be selectively accumulated during the collision activated dissociation event.

Abstract: This invention comprises an apparatus and method for generating sample ions from sample molecules in which a mixture of a sample and a matrix are vaporized by a laser beam and subsequently ionized by reagent corona ions. The decoupling of the vaporization and ionization steps allows each process to be separately optimized. The vaporization and ionization steps can be done in a sub-atmospheric pressure region. Alternatively, the vaporization and ionization steps can be done in a higher pressure region. In addition, the reagent corona ions can be generated in a vacuum chamber or a chamber at atmospheric pressure. Alternatively, the reagent ions can be generated in a sub-atmospheric region while the laser desorption occurs in an atmospheric region.

Abstract: A method of setting a fill time for a mass spectrometer including a linear ion is provided. The mass spectrometer is operated first in a transmission mode and ions are supplied to the mass spectrometer. Ions are detected as they pass through at least part of the mass spectrometer in a preset time period, to determine the ion current. From a desired maximum charge density for the ion trap and the ion current, a fill time for the ion trap is determined. The mass spectrometer is operated in a trapping mode to trap ions in the ion trap, and the ion trap is filled for the fill time, as just determined. This utilizes the ion trap to its maximum, while avoiding problems due to overfilling the trap, causing space charge effects.

Abstract: A method of analyzing a protein, namely determining the amino acid sequence of a protein is described. Trypsin is added to a protein to form a liquid phase mixture of trypsin and the protein. The disulfide linkages of the protein may be reduced and the resulting sulfhydryl groups alkylated either before or after the addition of trypsin. The trypsin is allowed to digest the protein long enough to cleave protein into tryptic fragments. A portion of the digested mixture is ionized by ion evaporation to produce gas phase ions of the tryptic fragments, the gas phase ions being predominantly doubly charged with one charge at each end of the doubly charged ions. The gas phase ions of the tryptic fragments are analyzed by sequentially selecting therefrom ions of a desired mass to charge ratio in a first mass analyzer. The selected ions are fragmented by collision in a second mass analyzer to produce daughter ions, and the daughter ions are then analyzed in a third mass analyzer.

Abstract: Improved methods for the detection and quantitation of labeled biological materials in a sample using elemental spectroscopic detection are described. Element-labeled biologically active materials, comprising antibodies, antigens, growth factors, hormones, receptors and other biologically active materials covalently attached to a stable elemental tag, can be used in specific binding assays and measured by elemental spectroscopic detection. Also described are methods for the determination of metals in samples of interest using specific antibodies to isolate the target metals and elemental spectroscopy for detection and quantitation.