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BRUKER DALTONIK GMBH

BRUKER DALTONIK GMBH Patent applications
Patent application numberTitlePublished
20120129201MASS SPECTROMETRY IMAGING WITH SUBSTANCE IDENTIFICATION - A method for the identification and localization of proteins or other biomolecules of a histologic tissue section comprises enzymatically digesting the biomolecules of two similar tissue sections while substantially preserving the biomolecule positions in the tissue sections. Next, a mass spectrometric image of the digest products in one of the tissue sections is acquired. Then, the digest products of the other tissue section are extracted and separated and the mass spectra and daughter ion spectra of all the digest products are acquired. A list of all identifiable biomolecules of the tissue section is created by comparing the mass spectra and daughter ion spectra with spectra in biomolecule structure databases or spectral libraries. Finally, the biomolecules in the list are assigned to digest products of the same mass in the mass spectra used to create the mass spectrometric image of the thin tissue section.05-24-2012
20120074303CALIBRATION FUNCTION FOR TIME-OF-FLIGHT MASS SPECTROMETERS WITH EXTREME MASS ACCURACY - A calibration function for time-of-flight mass spectrometers that converts ion times of flight into mass to charge ratios, takes into account not only the time of flight of a specific ionic species, but also the ion signal intensity of that ionic species. Use of the conversion function reduces nonsystematic deviations of the calculated mass values from the true mass values previously experienced in time of flight mass spectrometers.03-29-2012
20120016598NORMALIZATION OF MASS SPECTRA ACQUIRED BY MASS SPECTROMETRIC IMAGING - Mass spectra acquired by imaging mass spectrometry (IMS), in particular MALDI imaging of tissue sections, are each normalized by one of: the p-norm of the mass spectrum transformed by applying an exclusion list, the p-norm of the mass spectrum transformed by square rooting the intensity values, the median of the mass spectrum, and the median absolute deviation of the noise level of the mass spectrum.01-19-2012
20110284738CONFINING POSITIVE AND NEGATIVE IONS IN A LINEAR RF ION TRAP - In a linear ion trap, ions with two polarities are confined radially via an RF potential between the rods comprising the trap. Axially, ions of at least one polarity are confined via DC potentials applied to the elements of the trap or electrodes at the ends of the trap whereas ions of the other polarity are axially confined by a combination of pseudopotentials and/or DC potentials.11-24-2011
20110280455Determination of Tissue States by Imaging Mass Spectrometry - Spatially resolved tissue states (status image) are determined from spectrally resolved mass spectra of a tissue section by (a) acquiring a plurality of spatially resolved mass spectra of the tissue section, (b) generating at least two mass images from the spatially resolved mass spectra, (c) smoothing the mass images using an edge-preserving smoothing algorithm and (d) calculating a status image from the smoothed mass images by means of a classification algorithm derived from mathematical statistics.11-17-2011
20110202282Multi-Stage Search for Microbe Mass Spectra in Reference Libraries - Microbes in a sample are identified by calculating similarities between a mass spectrum of the sample and reference mass spectra in a spectral library. The spectral library is divided into a hierarchy of sub-libraries where each sub-library contains reference mass spectra of microbes which are statistically the most prevalent in the samples, but are not included in other sub-libraries and all additional reference mass spectra in the library that have substantial similarity to the reference mass spectra of these microbes. Only if the search in a sub-library does not provide a hit with sufficient certainty of identification, is the search carried out in sub-libraries of higher stages.08-18-2011
20110139977MATRIX-ASSISTED LASER DESORPTION WITH HIGH IONIZATION YIELD - Analyte ions are generated in an ion source by matrix-assisted laser desorption (MALDI) in which laser light pulses have significantly less than one nanosecond duration, focal diameters of less than twenty micrometers and energy densities such that only about one picogram of sample is desorbed per pulse of laser light and per laser spot. An unexpectedly high degree of ionization of analyte molecules is produced for selected matrix substances. Many laser spots can be generated side-by-side from a single laser light pulse for use with MALDI time-of-flight mass spectrometers. Applying pulses with a repetition rate of around 50 kilohertz and moving the sample or guiding the laser light beam so each laser light pulse impinges on a cool sample spot allows the ion source to be used with spectrometers that require a constant ion current.06-16-2011
20110139976Method for operating three-dimensional RF ion traps with high ion capture efficiency - In a three-dimensional Paul RF ion trap the ring electrode and end cap electrodes are formed from pairs of pole rods. This multipole rod system is then operated as a linear ion trap with a constant field distribution along the multipole rod system. While the system is operating as a linear ion trap, analyte ions are introduced and stored within the linear ion trap. After the ions have been stored, a single-phase RF voltage is supplied to all rods of a middle segment thus forming a three-dimensional ion trap, thereby collecting the ions in a spherical cloud within this middle segment. The collected analyte ions can then be reacted in the three-dimensional ion trap and the product ions resulting from the reactions can be ejected for mass analysis.06-16-2011
20110127424COLLISION-INDUCED DECOMPOSITION OF IONS IN RF ION TRAPS - In an RF ion trap, analyte ions are fragmented by applying a moderately high RF storage voltage to the trap. The ions are then excited via dipolar excitation, and after a short time, the ions are forced into a resting state, again using dipolar excitation. The RF storage voltage is then rapidly reduced to a low value thereby making it possible to store small fragment ions produced by ergodic decompositions that occur subsequent to the reduction of the RF storage voltage.06-02-2011
20110042562MASS SPECTROMETER WITH AN ELECTROSTATIC ION TRAP - In a mass spectrometer with an electrostatic ion trap, the electrostatic ion trap has an outer electrode with an ion-repelling electric potential applied to it and a plurality of inner electrodes with ion-attracting potentials applied to each inner electrode. The outer electrode and the inner electrodes are shaped and arranged in such a way that a harmonic electric potential is formed in one spatial direction and, perpendicular to this spatial direction, an electric potential is formed in which ions move in stable, radial trajectories.02-24-2011
20110039350HIGH YIELD ATMOSPHERIC PRESSURE ION SOURCE FOR ION SPECTROMETERS IN VACUUM - Gaseous analyte molecules are ionized at atmospheric pressure and provided to an inlet capillary of an ion spectrometer vacuum system by passing the ions through a reaction tube that ends in a conical intermediate piece for a gastight and smooth transition into the inlet capillary. The reaction tube is shaped so that the atmospheric pressure gas stream passing therethrough form the entrance of the tune to the intermediate piece is stably laminar. Analyte molecules from gas chromatographs, spray devices or vaporization devices can be introduced into the entrance of the reaction tube and ionized within the tube by single- or multi-photon ionization, by chemical ionization, by reactant ions or by physical ionization. For single- or multi-photon ionization, a beam from a laser can be passed axially down the reaction tube. Reactant ions can be produced by any means outside of the reaction tube and mixed with the analyte molecules within the tube.02-17-2011
20110036978INTRODUCTION OF IONS INTO MASS SPECTROMETERS THROUGH LAVAL NOZZLES - Ions entrained in a gas are transported into the vacuum system of an ion user, such as a mass spectrometer, from an ion source located outside the vacuum. The gas and ions pass through a nozzle that connects the ion source to the vacuum system and is shaped to form a supersonic gas jet in a first vacuum chamber of the vacuum system. In the first vacuum chamber, ions entrained in the supersonic gas jet are extracted electrically or magnetically and are collected, for example, by an RF ion funnel and transmitted to the ion user. The supersonic gas jet travels on and, after passing through the first vacuum chamber, the supersonic gas jet is directed into a separate pump chamber out of which the gas is pumped.02-17-2011
20100317044MASS SPECTROMETRIC ENDOPEPTIDASE ASSAY - The activity of a selected endopeptidase in a body fluid is determined by the mass spectrometric measurement of the reaction products of reporter substrate molecules added to the body fluid. Each reporter substrate molecule includes a peptide with the cleavage motif of the endopeptidase, an anchor group A1 on one side of the cleavage site and a different anchor group A2 on the other side of the cleavage site. One anchor is used to extract the reporter substrate molecules from the body fluid and the other anchor is used to extract digest fragments of the reporter molecules from the body fluid. Mass markers allow several reporter substrates to be used simultaneously in the same body fluid sample to measure the activity of different types of endopeptidase.12-16-2010
20100301204INTRODUCTION OF IONS INTO KINGDON ION TRAPS - In a Kingdon ion trap in which harmonic ion oscillation in a potential well in a longitudinal direction is completely decoupled from ion oscillation in a direction transverse to the longitudinal direction, ions enter the trap via an entrance tube extending through, but electrically insulated from, one of the Kingdon trap housing electrodes and located outside the minimum of the potential well in the longitudinal direction. The geometry of the Kingdon trap is arranged so that the oscillating ions introduced through the entrance tube cannot return to the entrance tube until they have performed several longitudinal oscillations during which time heavy ions can be introduced into the trap.12-02-2010
20100248298MASS SPECTROMETRIC IDENTIFICATION OF MICROORGANISMS IN COMPLEX SAMPLES - Microorganisms are identified as present in a complex sample or mixed culture by acquiring a mass spectrum of the sample and comparing it to combination spectra, each of which is formed by combining at least two reference mass spectra of known microorganisms. Microorganisms corresponding to the reference spectra used to form the combination spectrum are identified as present in the sample if that combination spectrum exhibits a better match with the sample mass spectrum than any one of reference mass spectra used to form that combination spectrum. It is also possible to identify microorganisms by forming a difference spectrum by subtracting a reference mass spectrum from the sample mass spectrum and comparing the difference spectrum to the reference mass spectra.09-30-2010
20100237238PROTEIN SEQUENCING WITH MALDI MASS SPECTROMETRY - In a mass spectrometer, sample ions are produced by using matrix assisted laser desorption with a matrix substance that supports spontaneous, non-ergodic ISD fragmentation and a laser light source with nanosecond light pulses and a multiple spot beam profile. A plurality of individual time-of-flight spectra are recorded from the resulting ions in such a way that amplification of ion signals in the mass spectrometer detector is initially reduced so that only ions with masses near a mass range limit are initially recorded. During the repeated acquisitions of the individual time-of-flight spectra, both the detector amplification and the mass range limit are increased. By these methods, it is possible to evaluate c and z fragment ions in lower mass ranges and to directly read N-terminal sequences from near terminus up to 80 amino acids and beyond, and C-terminal sequences up to more than 60 amino acids.09-23-2010
20100207020HIGH MASS RESOLUTION WITH ICR MEASURING CELLS - The compensation potentials on the compensation electrodes of an ICR measuring cell are sequentially adjusted so that an ICR measurement with the longest possible usable image current transient is produced. Then, subsequent ICR measurements are made using the ICR cell with the optimally adjusted compensation potentials. Depending on the kind of ion mixture involved, measurements with image current transients from 10 to more than 20 seconds long can be performed, from which mass spectra with a maximum mass resolution without peak coalescence can be obtained.08-19-2010
20100176289EXCITATION OF IONS IN ICR MASS SPECTROMETERS - In an ion cyclotron resonance mass spectrometer ions are excited into cyclotron orbits by an alternating current excitation signal having a nonlinear function of the excitation frequency vs. time in a “chirp.” Such an excitation signal produces transients which have no pronounced beats, even if mixtures of many ion species, all having the same mass differences, are present. The dynamic measuring range for the image currents can thus be better utilized. In particular, sum spectra of specified quality can be generated from a significantly smaller number of individual transients, and thus in a significantly shorter measuring time.07-15-2010
20100140466RADICAL ANIONS FOR ELECTRON TRANSFER DISSOCIATION - Radical anions for use in the fragmentation of positively charged biopolymer ions by means of electron transfer are produced from substances previously unknown for use as ETD production substances. The inventive substances produce radical anions that lead to electron transfer dissociations with a high yield of fragment ions. The substances have high volatility that allows them to be kept in unheated containers outside the vacuum system and transported into the vacuum system to an in vacuum electron attachment ion source via unheated lines and low molecular weights that allow the measurement of even very light fragment ions. In one embodiment, a suitable substance is 1-3-5-7-cyclooctatetraene.06-10-2010
20100108880LINEAR ION TRAP AS ION REACTOR - In a linear ion trap ions of both positive and negative polarities are stored simultaneously for fragmentation reactions caused by electron transfer dissociation (ETD). The ion trap comprises a plurality of parallel pole rods or stacked rings and the ions are stored by applying two phases of a first RF voltage to the pole rods or stacked rings in alternation, thereby radially confining both positive and negative ions. A second, single-phase RF voltage is applied to all the pole rods or stacked rings in common and creates a pseudopotential barrier at the ends of the linear ion trap that acts axially on ions of both polarities in order to maintain the ions in the trap.05-06-2010
20100090102ION MOBILITY MEASUREMENT AT A POTENTIAL BARRIER - Ion mobilities are measured by entraining the ions in a gas and adiabatically expanding the ion-containing gas through a nozzle to form a gas jet. An electrical field barrier with variable height is located at the nozzle exit. The field barrier may be located adjacent to the nozzle exit or an ion guide may be located between the nozzle and the field barrier. If a continuous ion current is supplied, the height of the barrier is varied and the ion current of the ions passing over the barrier is measured, the ion current can be differentiated to generate a mobility spectrum. Alternatively, the ions can be temporarily stored in the ion guide so that measurement of the ion current of the ions passing over the barrier results in a direct measurement of the mobility spectrum.04-15-2010
20090294656FRAGMENTATION OF IONS IN KINGDON ION TRAPS - Fragment ion spectra are acquired in Kingdon ion traps that have a potential well for harmonic oscillations of the ions in the longitudinal direction and in which the ions can oscillate radially in a plane between two or more inner electrodes. Metastable ions, preferably produced by laser desorption, are introduced into the Kingdon ion trap close to the minimum of the longitudinal potential well and stored there locally for a predetermined time period. Excess internal energy in the metastable ions causes most of the ions to decompose ergodically to fragment ions. Then the fragment ions and any remaining analyte ions are excited to execute harmonic oscillations in the longitudinal potential well. The harmonic oscillations are measured as image currents, from which a high-resolution mass spectrum of the fragment ions can be calculated.12-03-2009
20090294647MEASURING THE MOBILITY OF MASS SELECTED IONS - In an ion mobility spectrometer (IMS) coupled to a mass spectrometer (MS), the ion current from a suitable ion source is modulated with an analog modulation having a smooth modulation function, whose instantaneous frequency varies with time over a wide frequency range. The modulated ion current is continuously fed through a mobility drift region into the mass spectrometer, where the temporally varying ion current profile of at least one ion species is measured. The mobility spectrum of the ion species is then generated by correlating its ion current time profile with the modulation function.12-03-2009
200902836753D ION TRAP AS FRAGMENTATION CELL - In a tandem mass spectrometer with mass selector spatially separated from a mass analyzer, ions are fragmented in a three-dimensional RF by electron transfer dissociation. The fragment ions are then extracted from the 3D ion trap and introduced into the mass analyzer. The extraction is accomplished by providing, in one of the ion trap end cap electrodes, an aperture with a relatively large area covered by a conductive mesh or formed by closely spaced smaller apertures. The fragment ions are extracted from the RF ion trap by applying a DC voltage to one of the end cap electrodes.11-19-2009
20090283672FRAGMENTATION OF ANALYTE IONS BY COLLISIONS IN RF ION TRAPS - Analyte ions, particularly biopolymer ions, stored in an RF ion trap are ergodically fragmented by bombarding the analyte ions with collision ions, for example medium-mass, mono-atomic ions having a charge of opposite polarity to the charge of the analyte ions. Since the analyte ions are not fragmented by accelerating and/or exciting them to oscillations, as is the case with conventional collision-induced dissociation, the RF voltage of the ion trap can be set low enough that daughter ions with light charge-related masses that are produced by the fragmentation can also remain trapped in the ion trap.11-19-2009
20090249897TRANSFER OF SUBSTANCES ADHERING TO SURFACES INTO A DETECTION INSTRUMENT - A method for the transfer of target substances (drugs, pollutants, explosives and chemical warfare agents) from a surface to be investigated into a detection instrument, the target substances being present in the form of condensations of vapors on the surface itself or on particles adhering to it, or as particles sticking to the surface. The method comprises the steps of (a) moving a sampler, consisting of either a fiber bundle or a fastener strip with fiber loops, over the surface to be investigated, thus transferring substances to the fibers or the fiber loops or embedding particles into the gaps between the fibers or the fiber loops of the sampler, (b) transferring the sampler into a desorption device of the detection device, and (c) heating the sampler to evaporate the target substances. Various sampler designs can be incorporated into devices using the method.10-08-2009
20090200457AUTOMATIC CLEANING OF MALDI ION SOURCES - In an ion source that generates ions by matrix-assisted laser desorption (MALDI), ion acceleration diaphragms having apertures though which ions are accelerated and which have become contaminated by matrix material, are cleaned by temporarily heating the diaphragms. During the cleaning process, the sample support plate is moved aside but remains in the ion source housing, and the heating is preferably limited to regions surrounding the apertures in the diaphragms. In one embodiment, the diaphragms are heated by irradiation generated by infrared laser diodes.08-13-2009
20090095903CLEANED DAUGHTER ION SPECTRA FROM MALDI IONIZATION - In a mass spectrometer having an ion source in which analyte substances are ionized by matrix assisted laser desorption and form an ion beam that travels to a parent ion selector for selecting ions to form daughter ions, the ion beam is reflected in at least one reflector prior to the parent ion selector so that only ions that have both the mass of the parent ions and their kinetic energy are allowed to pass to the parent ion selector. By taking this measure, the mass resolution in the daughter ion spectra is also increased; the improved mass resolution and improved signal-to-noise ratio produce higher sensitivity, even though fewer ions are admitted for analysis in the daughter ion spectrum.04-16-2009
20090084948OVERCOMING SPACE CHARGE EFFECTS IN ION CYCLOTRON RESONANCE MASS SPECTROMETERS - In an ion cyclotron resonance mass spectrometer in which ions are trapped axially by applying electrical potentials to a pattern of electrode elements to produce an inhomogeneous alternating radio-frequency electric field with a repulsive effect, an additional electrostatic ion-attracting field is superimposed on the repulsive electric field. The voltage of the ion-attracting field is adjusted to compensate for a cyclotron frequency shift of the ions caused by the ion space charge. The voltage of the ion-attracting field can be adjusted so that the ion cyclotron frequency of all ions becomes independent of the number of ions inside the spectrometer.04-02-2009
20090039283IONIZATION OF DESORBED MOLECULES - An ion source generates ions from analyte molecules which are desorbed from a sample on the surface of a sample support in a pressure range of approximately 30 to 300 pascal. Reactant ions are generated in a separate ion source and guided by ion guides to the point in front of the sample or to a reaction chamber in which the desorbed molecules are located. The reactant ions ionize the desorbed molecules to form analyte ions. The analyte molecules can be mixed in matrix material or adsorbed on the sample support surface without additives. The desorption can be continuous or pulsed, for example by light from lasers or diodes.02-12-2009
20090039282MATRIX-ASSISTED LASER DESORPTION WITH HIGH IONIZATION YIELD - Analyte ions are generated in an ion source by matrix-assisted laser desorption (MALDI) in which laser light pulses have significantly less than one nanosecond duration, focal diameters of less than twenty micrometers and energy densities such that only about one picogram of sample is desorbed per pulse of laser light and per laser spot. An unexpectedly high degree of ionization of analyte molecules is produced for selected matrix substances. Many laser spots can be generated side-by-side from a single laser light pulse for use with MALDI time-of-flight mass spectrometers. Applying pulses with a repetition rate of around 50 kilohertz and moving the sample or guiding the laser light beam so each laser light pulse impinges on a cool sample spot allows the ion source to be used with spectrometers that require a constant ion current.02-12-2009
20090032700THREE-DIMENSIONAL RF ION TRAPS WITH HIGH ION CAPTURE EFFICIENCY - In a three-dimensional Paul RF ion trap at least one of the ring electrode and end cap electrodes is structured to produce a high capture efficiency for analyte ions introduced into the trap. The electrode structuring may be produced by an electrode surface profile having edges or protrusions, resulting in a scattering reflection of the introduced ions. Alternatively, at least one electrode may be formed by physically separate electrode components. In one embodiment, the trap can be switched between operating as a linear ion trap with good capture efficiency and operating as a three-dimensional ion trap with good ion reaction conditions.02-05-2009
20080296485Method and Device for Mass Spectrometry Examination of Analytes - The invention relates to a method for the mass spectrometry examination of at least one analyte, wherein an analyte to be examined is photoionized and the mass of the ions produced is determined in a mass spectrometer. The analyte to be examined is ionized at normal atmospheric ambient pressure by means of laser light using multiphoton ionization, especially resonant multiphoton ionization. The invention also relates to a device which comprises an ionization chamber in which an analyte to be examined is ionized at normal atmospheric ambient pressure using resonant multiphoton ionization and is transferred into a mass spectrometer. Said device can be used as an interface between a device for the chromatographic or electrophoretic separation of analytes and a mass spectrometer.12-04-2008
20080251715INTRODUCTION OF IONS INTO A MAGNETIC FIELD - In a mass spectrometer that uses a space-restricted magnetic field, such as an ion cyclotron resonance mass spectrometer, ions with a wide mass range generated in an ion supply located outside the magnetic field are transported in the direction of the magnetic field lines to an ion storage device located inside the magnetic field without losing ions by guiding the ions through the region in which the magnetic field strength increases with a special ion guide. This ion guide consists of an arrangement of coaxial ring diaphragms which are alternately supplied with the phases of an RF voltage. In an alternative embodiment, the ion guide uses two wires wound in a double helix where each wire is supplied with one phase of a two-phase RF voltage.10-16-2008
20080251712MEASUREMENT OF THE MOBILITY OF MASS-SELECTED IONS - The mobility of mass-selected ions in gases is measured at pressures of a few hectopascal by selecting the ions under investigation in a quadrupole filter according to their mass-to-charge ratio m/z, measuring their mobility in a drift region at a pressure of a few hundred Pascal under the influence of a DC electric field and then filtering the measured ions by means of a quadrupole field in order to eliminate, or detect changes in, the mass-to-charge ratio. Several embodiments for the drift region are disclosed, in which the ions are kept in the axis of the drift region by RF fields. As these drift regions can also be utilized for a collision-induced decomposition of the ions, the device can additionally be used as a so-called triple quadrupole mass spectrometer.10-16-2008

Patent applications by BRUKER DALTONIK GMBH