Bruker Daltonik Gmbh

Bruker-franzen Analytik Gmbh

Other

US Government As Represented by the Secretary of the Army

Brucker Daltonik Gmbh

Bruker Saxonia Analytik Gmbh

Bruker Dalton K Gmbh

Bruker Deltonik Gmbh

Brunker Daltonik Gmbh

Jochen Franzen

Michael Schubert

Evgenij Nikolaev

Armin Holle

Gerhard Weiss

Claus Koster

Reemt-Holger Gabling

Karsten Michelmann

Andreas Brekenfeld

Markus Kostrzewa

Gökhan Baykut

Gerhard Heinen

Claus Köster

Vadim Markovich Govorun

Melvin Andrew Park

Oliver Räther

Martin Schürenberg

Thomas Maier

Carsten Stoermer

Arne Kasten

Ralf Hartmer

Detlev Suckau

Yang Wang

Wolfgang Pusch

Urs Steiner

Andreas Haase

Frank H Laukien

Jens Höhndorf

John Christian Fjeldsted

Katrin Sparbier

Stefan Ingo Meier

Thorsten Benter

G&ouml;khan Baykut

Stefan Klepel

Christian Berg

Ivo Glynne Gut

Christoph Lange

Alfred Kraffert

Eckhard Belau

Christian Gebhardt

Thomas Wehkamp

Martin Sch&uuml;renberg

Claus K&ouml;ster

Jens Boβmeyer

Matthias Mann

Matthias Wilm

Klaus J Brockmann

Ian Sanders

Hans-Jakob Baum

Peter Hufnagel

Jens Rebettke

Kai Rückriem

Franz-Josef Mayer-Posner

Curt Brunnee

Ivan Boldin

Hendrik Kersten

Matthias Lorenz

A method of detecting specified target microbes in different types of sample uses only one to two cultivation steps for the enrichment of the target microbes from the sample, preferably in selective culture media, combined with a mass spectrometric detection method that identifies the target microbes in mixtures with other microbes even if the target microbes account for only a small proportion of the mixture. The sample may be a food sample, a sample from bodies of water used for bathing, a soil sample, a swabbed sample, a stool sample, an impactor sample with collected aerosol particles, amongst many others. The detection method is several days faster than standard methods and less expensive.

Mass spectrophotometric detection of microbes

The invention relates to turbo molecular pumps enabling high pumping speed. The disclosure suggests using one or more cage-like rotor stages to optimize pumping speed on vacuum systems with low gas flows and low ultimate pressures. This allows for a smaller motor as well as smaller overall form factor and makes it well suited, in particular, for compact mass spectrometers and desk-top mass spectrometers.

Turbo molecular pump for mass spectrometer

The invention relates to methods and instruments for the rapid detection and rapid mass spectrometric identification of microbial infective agents in blood or other body fluids. The invention recognizes that blood is not a good environment for the cultivation of microbes and provides a method which (a) largely destroys or dissolves the human particles in body fluids, such as erythrocytes and leukocytes in blood, without impairing the ability of the microbes to reproduce, (b) separates the microbial pathogens from the fluid, (c) cultivates them in a nutrient broth which contains none of the antimicrobial components of the body fluids, (d) separates them from the nutrient broth, and (e) identifies the microbes by a mass spectrum of the microbial proteins. The dissolution of the human particles also releases the microbes nesting in macrophages. The cultivation in an optically clear nutrient broth with optimum composition not only accelerates the propagation of the microbes compared to all other cultivation methods, but also makes it possible to continuously measure their quantitative growth starting from a low microbe density. This firstly allows the mass spectrometric identification to be carried out at the earliest possible time, secondly provides a positive detection of microbes far ahead of their identification, which can be lifesaving for the patient; and thirdly makes it possible to start the determination of resistances early.

Mass spectrometric diagnosis of sepsis without blood culture

The invention relates to a mass spectrometric method for determining microbial resistances to antibiotics. The invention provides specific methods comprising cultivation in synthetic media, in which several amino acids, preferably only a single amino acid, are isotopically labeled by incorporatingC,N,O orS. If several amino acids are isotopically labeled, they are labeled in such a way that they are each heavier than the corresponding unlabeled amino acids by the same integer mass difference &#x394;m. This ensures that the mass shifts of the peaks always amount to an integer multiple of the mass difference &#x394;m. The total mass difference can be kept relatively small by selecting suitable amino acids. A mass shift of the protein peaks in media with antibiotics indicates that the microbes are resistant. A second embodiment first produces isotopically labeled microbes, which are then tested for their resistance by cultivating them in normal media.

Mass spectrometric determination of microbial resistances

Microorganisms, particularly bacteria, are identified and characterized on the basis of a mass spectrometric measurement of their protein profiles with ionization by matrix-assisted laser desorption. In order to measure the microbial resistance to antibiotics, the protein profiles of microorganisms are measured after cultivation for a short time duration in nutrient media containing the antibiotics.

Mass spectrometric measurement of microbial resistances

The invention relates to the preparation of thin tissue sections for mass spectrometric (MALDI) imaging, and proposes a method wherein a microcrystalline layer of the matrix material is produced on the surface of the thin tissue sections, and soluble analyte molecules are transported orthogonally through the thin tissue section to the matrix layer, without substantial lateral diffusion, by means of a solvent flow with alternating or constant direction, and are then deposited in the matrix layer and, if possible, embedded in the matrix crystals. A solvent flow which alternates in direction can be produced by successive, alternating phases of swelling and drying, brought about by periodic changes to the thin tissue section temperature and/or the partial pressures of the solvents. A continuous solvent flow can be generated by applying the thin tissue section onto a porous support which supplies solvent to the rear surface of the thin tissue section.

Preparation of thin tissue sections for imaging mass spectrometry

The invention relates to the voltage supply of mass spectrometers, particularly electrostatic Kingdon ion analyzers, requiring extremely noise-free operating voltages. The invention proposes the use of passive charge storage devices, which operate without any feedback control and display no measurable noise or ripple if they are well shielded, instead of the usual actively operating high-voltage generators. Chemical charge storage devices or capacitors with good insulation can be used for this purpose. These may display slight voltage decreases due to continuous discharge, depending on their quality, but these decreases can be mathematically compensated.

Voltage supplies for mass spectrometers

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.

Introduction of ions into a magnetic field

The geometry of 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, 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 heavier ions can be introduced into the trap. In one embodiment, 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.

Introduction of ions into kingdon ion traps

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.

Utilizing gas flows in mass spectrometers

The invention relates to acquisition techniques for time-of-flight mass spectra with ionization of the analyte substances by matrix assisted laser desorption. Generally speaking, these acquisition techniques involve adding together a large number of individual time-of-flight spectra, each with restricted dynamic measuring range, to form a sum spectrum. The invention provides a method that improves, in particular, the reproducibility, the concentration accuracy and therefore the ability to quantify the mass spectra. Particular embodiments also increase the dynamic range of measurement. For this purpose, multiple series of mass spectra are acquired, whereby the energy density in the laser spot is increased in discrete steps. As a result, many ion signals saturate the detector and can therefore no longer be evaluated. However, it is possible to employ a technique in which the ion beam is increasingly defocused, or, secondly, to replace parts of the spectrum that are subject to saturation by intensity extrapolations from mass spectra acquired with lower energy density. In the first case, hundreds or thousands of individual mass spectra must be added together in order to increase the dynamic measuring range. In the second case, the finally acquired mass spectrum, with its replacements, forms a mass spectrum with a high dynamic measuring range, improved reproducibility and better concentration accuracy. The gradient of the increasing intensities of the ion signals, as a function of the energy density, supplies additional information about the proton affinity of the analyte ions. The concentration accuracy is enhanced because the increase in the number of proton donors in the ionization plasma leads to an increase in the ionization of those analyte substances that have a lower proton affinity.

Acquisition technique for MALDI time-of-flight mass spectra

The invention relates to the cell disruption of microbes and the preparation of the microbe proteins for mass spectrometric analysis. The cells of microbes from microcolonies are disrupted by physical or chemical means directly on the nutrient medium. The released proteins are then transferred to sample supports by direct contact with their contact surfaces; electrophoresis can be used for assistance. Once the proteins are firmly adsorbed on the contact surfaces, they can be washed with water in order to remove substances which interfere with the ionization process. For analysis by matrix-assisted laser desorption (MALDI), the proteins are prepared on the contact surfaces of the sample supports with matrix substances to form MALDI samples; the sample supports are then introduced into a MALDI mass spectrometer for the acquisition of mass spectra. The microbes are identified by similarity comparisons between the mass spectra of the microbe proteins and similarly obtained reference spectra.

Analysis of microbes from microcolonies by maldi mass spectrometry

Devices and methods for the acquisition of mass spectra with very high mass resolution in ion cyclotron resonance mass spectrometers include cylindrical ICR measuring cells with special electrode geometries to generate harmonic trapping potentials for orbiting ions. The sheath of the cylindrical cell is divided by longitudinal gaps into a multitude of sheath electrodes, which either have to carry layers with resistance profiles able to generate parabolic voltage profiles along the sheath electrodes, or which form sheath electrodes of varying width by parabolic gaps. Orbiting ions of a given mass m/z oscillate harmonically in an axial direction with the same frequency, independent of the radius of their orbit and their oscillation amplitude. Ideally, the cylinders are closed by endcaps with rotationally hyperbolic form, divided into partial electrodes. The ions are excited by dipolar excitation fields. The orbiting ion clouds are kept together for much longer periods than was possible hitherto.

Ion cyclotron resonance measuring cells with harmonic trapping potential

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Bremen, Germany

Jochen Franzen