Bruker Daltonik Gmbh

Other

Bruker Daltonics Gmbh & Co. Kg

Karsten Michelmann

Jochen Franzen

Markus Kostrzewa

Oliver Räther

Thomas Maier

Wolfgang Pusch

Carsten Stoermer

Michael Schubert

Claus Köster

Desmond Allen Kaplan

Katrin Sparbier

Christian Berg

Disclosed is a method and device for the mass spectrometric quantification of two or more known target ion species, in which a mass spectrometric signal, composed of signal components of the two or more target ion species, which are not mass resolved in the mass spectrum, is weighted with quantification functions and summed, and a quantification parameter is determined for the two or more target ion species from the weighted sums.

Method and device for the quantification of target ion species

The invention relates to the determination of resistances of microorganisms which produce β-lactamases, in particular 'extended spectrum β-lactamases' (ESBL). The invention provides a method whereby the microbial resistance can be measured very simply and quickly by means of the catalytic effect of the microbially produced β-lactamases on β-lactam antibiotics, which consists in a hydrolytic cleavage of the β-lactam ring. The method determines the resistance of the bacteria a few hours after a suitable substrate, either a β-lactam antibiotic or a customized β-lactam derivative, has been added to a suspension of the microbes, by direct mass spectrometric measurement of the substrate breakdown caused by the β-lactamases.

Mass spectrometric measurement of β-lactamase resistances

The invention provides methods and devices for determining the reduced ion mobility Kof an ion species by trapped ion mobility spectrometry wherein the reduced ion mobility Kis determined from a measured arrival time tof the ion species and predetermined instrumental parameters by applying the inverse of a system function: K=SYS(t,p) or from multiple arrival times tof the ion species measured for multiple values of an instrumental parameter.

Determining the reduced ion mobility of ion species by trapped ion mobility spectrometry (TIMS)

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 linear multipole ion storage device which is suitable for reactions between positive and negative ions, and for fragmentation reactions by electron transfer dissociation (ETD) in particular. The invention uses a linear RF ion trap with at least three pairs of rods with a new type of electronic power supply. The two phases of a first RF voltage are applied to the pole rods alternately around the circumference and confine positive as well as negative ions in the radial direction. A second RF voltage is either applied single-phase to some of the pole rods, but not to all of them, or two-phase to unequal numbers of pole rods so that the axis potential oscillates with the frequency of this second RF voltage and generates a pseudopotential barrier which acts axially on ions of both polarities at the ends of the ion storage device. In the interior, the second RF produces a complex superposition field resulting in an increased fragmentation yield for ETD.

Mixed radio frequency multipole rod system as ion reactor

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.

Confining positive and negative ions in a linear RF ion trap

The invention relates to the determination of the nature and strength of enzymatic activity in blood using mass spectrometric measurement of a profile of the reaction products. The determination of the enzymatic activity can be used for medical diagnostics, for example, and also to check the effectiveness of medication. The invention provides a method whereby adding probe substances usually not present in blood offers standardized substrates for measuring the enzymatic activity. The probe substances may be added to whole blood, plasma, or serum. The mass spectrometric measurement of the reaction products, after their reversible immobilization on actively binding surfaces of solids, for example, can deliver biomarker patterns of the reaction products which may be indicators for metabolic anomalies or diseases, since these are often accompanied by the formation or activation of characteristic enzymes.

Mass spectrometric determination of blood enzyme activity

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.

Measuring the mobility of mass selected ions

In a mass spectrometer a target volume is filled with ions of different mass but substantially the same energy from a distant storage device by forming a plurality of spatially-limited ion swarms consisting of ions having the same mass. The ion swarms are ordered either by a mass-sequential extraction from the storage device or by rearranging the order of flight as the ions are in flight, so that swarms of different mass ions simultaneously enter the target volume despite having different flight velocities. A mass-sequential extraction in the order of decreasing mass can be achieved in one embodiment by decreasing a pseudopotential barrier at the storage device which causes the heavy ions to emerge first. In another embodiment, the ions can be rearranged in flight by applying a bunching potential. A second reverse bunching potential then restores the energy of the ions to their original values.

Method and apparatus for avoiding undesirable mass dispersion of ions in flight

The invention relates to the evaluation of mass spectra from mass spectrometers in which ions are excited to mass-specific oscillating or orbiting motions, and the ion motion is recorded as a time signal. The invention provides methods to detect parameter drift that occurs during the recording of a time signal in such a 'frequency mass spectrometer' by analyzing the instantaneous frequency or the phase spectrum of a frequency component, and provides a method to correct for influence of the frequency drift on the mass spectrum correspondingly. In one embodiment a Fourier transformation converts a measured time signal into a frequency spectrum and examines the phase spectrum of a frequency component to establish whether this phase spectrum deviates from the phase spectrum of a harmonic time signal. The phase spectrum of a harmonic time signal is either linear or constant. In another embodiment the time domain signal is processed using a Short Time Fourier Transformation function to determine an instantaneous frequency, which can be used to correct the parameter drift, yielding a corrected time signal. From the corrected time signal a mass spectrum with better mass resolution can be derived, as can be seen from corrected mass signal profile compared with uncorrected mass signal profile.

Evaluation of frequency mass spectra

The invention relates to mass spectrometers in which ion clouds are stored in two spatial directions by radial forces while oscillating largely harmonically at a mass-specific frequency in a third spatial direction perpendicular to the other two, in a potential minimum, the shape of which is as close to a parabola as possible. Analysis of the oscillation frequencies of these ion clouds, preferably by a Fourier analysis, leads via a frequency spectrum to a mass spectrum. The frequency spectrum is analyzed to identify false signals in the frequency spectrum as harmonics and eliminating them where necessary.

Evaluation of spectra in oscillation mass spectrometers

In a linear ion trap in which an essentially quadrupole RF electrical field is generated between at least four rod-shaped electrodes, ions may be mass-selectively ejected orthogonally to the axis. An aspect of the invention comprises compensating for field irregularities along the axis of a linear ion trap, which result, at different ejection locations, in the ejection of ions of the same masses at slightly different times, by of measuring the ions that are ejected at the different ejection locations using a number of separate detectors, and correcting, after a mass calibration of each of the mass spectra, the time shifts of the various location-dependent mass spectra during their addition to a combined spectrum.

Linear RF ion trap with high mass resolution

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.

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Bremen, Germany

Karsten Michelmann