1003 results about "Protein mass spectrometry" patented technology

Fast and highly accurate mass spectrometry-based processes for detecting a particular nucleic acid sequence in a biological sample are provided. Depending on the sequence to be detected, the processes can be used, for example, to diagnose a genetic disease or chromosomal abnormality; a predisposition to a disease or condition, infection by a pathogenic organism, or for determining identity or heredity.

The instant invention provides an economical flow-through method for determining amount of target proteins in a sample. An antibody preparation (whether polyclonal or monoclonal, or any equivalent specific binding agent) is used to capture and thus enrich a specific monitor peptide (a specific peptide fragment of a protein to be quantitated in a proteolytic digest of a complex protein sample) and an internal standard peptide (the same chemical structure but including stable isotope labels). Upon elution into a suitable mass spectrometer, the natural (sample derived) and internal standard (isotope labeled) peptides are quantitated, and their measured abundance ratio used to calculate the abundance of the monitor peptide, and its parent protein, in the initial sample

Methods to detect, screen, and quantitate biological samples after administration of antibody conjugates, antibody-drug conjugates of Formula I, antibodies, and fragments and metabolites thereof, by affinity separation, chromatography, and mass spectrometry are disclosed. Ab-(L-D)p   I wherein Ab is an antibody; D is a drug moiety; L is a linker covalently attached to Ab, and covalently attached to D; and p is 1, 2, 3, 4, 5, 6, 7, or 8;

The present invention is directed to a method for separating, characterizing and / or identifying microorganisms in a test sample. The method of the invention comprises an optional lysis step for lysing non-microorganism cells that may be present in a test sample, followed by a subsequent separation step. The method may be useful for the separation, characterization and / or identification of microorganisms from complex samples such as blood-containing culture media. The invention further provides for interrogation of the separated microorganism sample by mass spectrometry to produce a mass spectrum of the microorganism and characterizing and / or identifying the microorganism in the sample using the mass spectrum obtained.

Provided are methods of detecting the presence or amount of a dihydroxyvitamin in D metabolite in a sample using mass spectrometry. The methods generally comprise ionizing a dihydroxyvitamin D metabolite in a sample and detecting the amount of the ion to determine the presence or amount of the vitamin D metabolite in the sample. In certain preferred embodiments the methods include immunopurifying the dihydroxyvitamin D metabolites prior to mass spectrometry. Also provided are methods to detect the presence or amount of two or more dihydroxyvitamin D metabolites in a single assay.

The invention presents a method for examining genetic material (deoxyribonucleic acid, DNA) to detect the presence of pre-known mutations, especially single nucleotide polymorphisms (SNP), using mass spectrometry with ionization by matrix-assisted laser desorption (MALDI). The invention uses nucleoside triphosphates with modified sites for the method of primer extension in a duplicating, enzymatic reaction and at least partially removal of primers from the extension product, in combination with product neutralization by chemical treatment of the modified sites, so that the resulting DNA products can be, by using special matrix materials, preferredly ionized in an adduct-free form over other constituents in the reaction solution without any further cleaning. The method is particularly suitable for simultaneous identification of several mutations by multiplexing.

Methods, systems and kits for the simultaneous or sequential analysis of a multitude of steroid hormones by mass spectrometry are disclosed. The methods require minimal sample size and minimal preparation time. The methods include ionizing the hormones and analyzing the hormones by mass spectrometry. In addition, methods, systems and kits for the simultaneous or sequential analysis of steroid hormones are disclosed including ionization of the steroid hormones by photoionization.

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.

The invention provides devices, device configurations and methods for improved sensitivity, resolution and efficiency in mass spectrometry, particularly as applied to biological molecules, including biological polymers, such as proteins and nucleic acids. More particularly, the invention provides methods and devices for analyzing and detecting electrically charged particles, especially suitable for gas phase ions generated from high molecular weight compounds. In one aspect, the invention provides devices and methods for determining the velocity, charged state or both of electrically charged particles and packets of electrically charged particles. In another aspect, the invention provides methods and devices for the time-of-flight analysis of electrically charged particles comprising spatially collimated sources. In another aspect, the invention relates to multiple detection using inductive detectors, improved methods of signal averaging and charged particle detection in coincidence.

The invention relates to ions guided by gas flows in mass spectrometers, particularly in RF multipole systems, and to RF quadrupole mass filters and their operation with gas flows in tandem mass spectrometers. The invention provides a tandem mass spectrometer in which the RF quadrupole mass filter is operated at vacuum pressures in the medium vacuum pressure regime, utilizing a gas flow to drive the ions are through the mass filter. Vacuum pressures between 0.5 to 10 pascal are maintained in the mass filter. The mass filter may be enclosed by a narrow enclosure to guide the gas flow. The quadrupole mass filter may be followed by an RF multipole system, operated at the same vacuum pressure, serving as fragmentation cell to fragment the selected parent ions. The fragmentation cell may be enclosed by the same enclosure which already encloses the mass filter, so the ions may be driven by the same gas flow at the same vacuum pressure, greatly simplifying the required vacuum pumping system in tandem mass spectrometers. There are many other applications utilizing gas flows including supersonic gas jets in mass spectrometry.

The instant invention provides an economical flow-through method for determining amount of target proteins in a sample. An antibody preparation (whether polyclonal or monoclonal, or any equivalent specific binding agent) is used to capture and thus enrich a specific monitor peptide (a specific peptide fragment of a protein to be quantitated in a proteolytic digest of a complex protein sample) and an internal standard peptide (the same chemical structure but including stable isotope labels). Upon elution into a suitable mass spectrometer, the natural (sample derived) and internal standard (isotope labeled) peptides are quantitated, and their measured abundance ratio used to calculate the abundance of the monitor peptide, and its parent protein, in the initial sample.

Methods to detect, characterize, and quantitate biological samples after administration of antibody conjugates, antibody-drug conjugates of Formula I, antibodies, and fragments and metabolites thereof, by immunoaffinity bead separation, chromatography, and mass spectrometry are disclosed.Ab-(L-D)p  IwhereinAb is an antibody;D is a drug moiety;L is a linker covalently attached to Ab, and covalently attached to D; andp is 1, 2, 3, 4, 5, 6, 7, or 8;

A method, apparatus and algorithms are disclosed for operating an open electrostatic trap (E-trap) or a multi-pass TOF mass spectrometer with an extended flight path. A string of start pulses with non equal time intervals is employed for triggering ion packet injection into the analyzer, a long spectrum is acquired to accept ions from the entire string and a true spectrum is reconstructed by eliminating or accounting overlapping signals at the data analysis stage while using logical analysis of peak groups. The method is particularly useful for tandem mass spectrometry wherein spectra are sparse. The method improves the duty cycle, the dynamic range and the space charge throughput of the analyzer and of the detector, so as the response time of the E-trap analyzer. It allows flight extension without degrading E-trap sensitivity.

There is provided a method for obtaining at least one calibration filter for a Mass Spectrometry (MS) instrument system. Measured isotope peak cluster data in a mass spectral range is obtained for a given calibration standard. Relative isotope abundances and actual mass locations of isotopes corresponding thereto are calculated for the given calibration standard. Mass spectral target peak shape functions centered within respective mass spectral ranges are specified. Convolution operations are performed between the calculated relative isotope abundances and the mass spectral target peak shape functions to form calculated isotope peak cluster data. A deconvolution operation is performed between the measured isotope peak cluster data and the calculated isotope peak cluster data after the convolution operations to obtain the at least one calibration filter.

A method for fragmentation of analyte ions for mass spectroscopy and a system for mass spectroscopy. The method produces gas-phase analyte ions, produces gas-phase radical species separately from the analyte ions, and mixes the gas-phase analyte ions and the radical species at substantially atmospheric pressure conditions to produce fragment ions prior to introduction into a mass spectrometer. The system includes a gas-phase analyte ion source, a gas-phase radical species source separate from the gas-phase analyte ion source, a mixing region where the gas-phase analyte ions and the radical species are mixed at substantially atmospheric pressure to produce fragment ions of the analyte ions, a mass spectrometer having an entrance where at least a portion of the fragment ions are introduced into a vacuum of the mass spectrometer, and a detector in the mass spectrometer which determines a mass to charge ratio analysis of the fragment ions.

A water trap system based on a thermoelectric cooling device is employed to remove a major fraction of the water from air samples, prior to analysis of these samples for chemical composition, by a variety of analytical techniques where water vapor interferes with the measurement process. These analytical techniques include infrared spectroscopy, mass spectrometry, ion mobility spectrometry and gas chromatography. The thermoelectric system for trapping water present in air samples can substantially improve detection sensitivity in these analytical techniques when it is necessary to measure trace analytes with concentrations in the ppm (parts per million) or ppb (parts per billion) partial pressure range. The thermoelectric trap design is compact and amenable to use in a portable gas monitoring instrumentation.

A fluid permeation testing apparatus provides for filling a first cavity of a test cell with a test fluid and filling a second cavity of the test cell with a challenge fluid. The challenge fluid comprises at least one analyte useful for testing permeation of the challenge fluid through a test film that separates the first and second cavities. Samples of the test fluid in the first cavity are introduced to a mass spectrometer, such as in a pulsed manner, without substantially changing the total pressure in first cavity. Samples of the test fluid in the first cavity may be introduced to the mass spectrometer while maintaining substantially balanced total pressures in the first and second cavities.

A system for the analysis of polyionic molecules by mass spectrometry is provided. The polyionic molecule is attached to a charged tag which neutralizes some of the charge on the polyionic analyte. The formed adduct with a reduced net charge is then analyzed by mass spectrometry, and the determined molecular weight of the adduct can be used to calculate the molecular weight of the analyte. Mass spectrometric analyses of polynucleotides and proteins are particularly amenable to this method.

A system and method for ample analysis including acquiring a tissue sample, preparing the tissue sample for mass spectrometry imaging, conducting a mass spectrometry procedure on the tissue sample to produce an image, analyzing the image to determine the presence or absence of a biomarker; and generating a report indicating a presence or absence of cancer.

The present invention provides a multiple part capillary for use in mass analysis instruments. Specifically, a multiple part capillary comprising at least two capillary sections joined with airtight seal by a union for use in mass spectrometry (particularly with ionization sources) to transport ions between pressure regions of a mass spectrometer for analysis is described herein. Preferably, the capillary is useful to transport ions from an elevated pressure ionization source to a first vacuum region of a mass analysis system.

Described is an affinity microcolumn comprising a high surface area material, which has high flow properties and a low dead volume, contained within a housing and having affinity reagents bound to the surface of the high surface area material that are either activated or activatable. The affinity reagents bound to the surface of the affinity microcolumn further comprise affinity receptors for the integration into high throughput analysis of biomolecules.

Multiple ionization ion sources and multiple mass analyzers are combined into one mass spectrometer instrument by a six-electrodes ion trap or an array of six-electrodes ion traps. The six-electrodes ion trap can be operated as an independent two-dimensional ion guide or linear ion tap in an arbitrarily selected direction among three orthogonal XYZ directions. The two-dimensional ion guide / linear ion trap can be alternated from one direction to another among the three orthogonal directions electrically. A six-electrodes ion trap generates six equivalent importing and exporting interfaces, each of the interfaces can be used to trap external ions and transfer the trapped ions to any of the other five interfaces. The six-electrodes ion trap provide a mass spectrometer with versatility, multiply functions, high duty-cycles and high sample throughput.

A multiple function atmospheric pressure ion source interfaced to a mass spectrometer comprises multiple liquid inlet probes configured such that the sprays from two or more probes intersect in a mixing region. Gas phase sample ions or neutral species generated in the spray of one probe can react with reagent gas ions generated from one or more other probes by such ionization methods as Electrospray, photoionization, corona discharge and glow discharge ionization. Reagent ions may be optimally selected to promote such processes as Atmospheric Pressure Chemical Ionization of neutral sample molecules, or charge reduction or electron transfer dissociation of multiply charged sample ions. Selected neutral reagent species can also be introduced into the mixing region to promote charge reduction of multiply charged sample ions through ion-neutral reactions. Different operating modes can be performed alternately or simultaneously, and can be rapidly turned on and off under manual or software control.

The invention provides a spectrum library generating method, comprising the following steps: selecting analyzed spectrograms of an experimental tandem mass spectrometry, in which information of female ionic peptide sequences, electronic charges, modified types and sites are included; removing redundant spectrograms from the analyzed spectrograms of the experimental tandem mass spectrometry to obtain representing spectrograms; dividing the female ionic peptide sequences corresponding to the representing spectrograms according to a theoretical fragmentation mode to obtain theoretical spectrograms corresponding to the representing spectrograms; combining the theoretical spectrograms and the representing spectrograms to obtain optimized spectrograms; and labeling spectral peaks for the optimized spectrograms, and utilizing the optimized spectrograms with labeled spectral peaks to generate a spectrogram database. The invention further provides a spectrogram identifying method of the tandemmass spectrometry. In the invention, in the process of matching candidate spectrograms and the spectrograms of the tandem mass spectrometry to be analyzed, mass-to-charge ratio offset of the spectralpeak possibly introduced by a potential modification is concerned so that ionic spectral peak containing modified fragments is matched, thereby achieving better modified spectrogram identifying effect.

Fluid permeation testing involves filling a first cavity of a test cell with a test fluid and filling a second cavity of the test cell with a challenge fluid. The challenge fluid comprises at least one analyte useful for testing permeation of the challenge fluid through a test film that separates the first and second cavities. Samples of the test fluid in the first cavity are introduced to a mass spectrometer, such as in a pulsed manner, without substantially changing the total pressure in first cavity. Samples of the test fluid in the first cavity may be introduced to the mass spectrometer while maintaining substantially balanced total pressures in the first and second cavities.

The present invention is directed in part to a method for detecting a target nucleic acid using detector oligonucleotides detectable by mass spectrometry. This method takes advantage of the 5′ to 3′ nuclease activity of a nucleic acid polymerase to cleave annealed oligonucleotide probes from hybridized duplexes and releases labels for detection by mass spectrometry. This process is easily incorporated into a polymerase chain reaction (PCR) amplification assay. The method also includes embodiments directed to quantitative analysis of target nucleic acids.