Abstract: 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.

Abstract: A method for computer-assisted analysis of one or more tissue sections of the human or animal body for preparing a digital stain test is provided. During the digital stain test, tissue zones in a tested tissue section with a predetermined clinical picture are detected. Spatially resolved hyperspectral data, particularly mass spectrometry data, is processed for a plurality of measurement positions. Multiple base spectra are determined from the hyperspectral data by obtaining base vectors. The base spectra are correlated with the hyperspectral data such that a plurality of correlation values for the base spectra is obtained for each measurement position. Subsequently, a regression model is calculated using a regression method, the regression model describing a mask of the one or more tissue sections, in which mask diseased tissue zones are marked based on the calculated correlation values. The regression model and the base spectra can then be used to conduct the digital stain test.

Abstract: The invention relates to the detection of specified, flagellated bacteria, particularly Salmonella, in food and stool. A single culturing period of about 12 to 24 hours in a liquid nutrient medium without agitation is combined with a position-selective sampling of the flagellated microbes from the liquid of the culture, after which a mass spectrometric detection method is used which recognizes the target bacteria in mixtures. A second culture step is only necessary in exceptional cases. A species-selective or genus-selective culture medium is advantageous. Positional selection becomes possible because these bacteria use their flagella to counteract sedimentation by chemotaxis, and they collect near the surface.

Abstract: 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.

Abstract: An ion guide system includes an ion guide with pole rods, a device for laterally introducing an ion species, and a mass spectrometer for analyzing product ions of reactions between different ion species. The device is configured and positioned such that an RF field with at least two-fold rotational symmetry with respect to the axis is generated. The device includes shortened pole rods and/or further electrodes. The pole rods and the further electrodes have at least two-fold rotational symmetry. The symmetry of the RF field allows ions to travel straight ahead through the ion guide with no hindrance. Such arrangements are particularly suitable for bringing together largely loss-free positive and negative ion species for reacting them. The reactions may be used to fragment multiply charged biopolymer ions by electron transfer or to remove excess charges of multiply charged biopolymer ions.

Abstract: The invention provides a method for acquiring fragment ion spectra of substances in complex substance mixtures wherein a trapped ion mobility spectrometer (“TIMS”) is used as the ion mobility separator separation device. The fragment ion spectra may be used for the identification of high numbers of proteins in complex mixtures, or for a safe quantification of some substances, by their fragment ion mass spectra in a mass spectrometer with up-front substance separator. TIMS with parallel accumulation provides the unique possibility to prolong the ion accumulation duration to find more detectable ion species without decreasing the measuring capacity for fragment ion mass spectra. The high measurement capacity for fragment ion mass spectra permits the repeated measurement of low abundance ion species to improve the quality of the fragment ion spectra.

Abstract: An ion guide system includes an ion guide with pole rods, a device for laterally introducing an ion species, and a mass spectrometer for analyzing product ions of reactions between different ion species. The device is configured and positioned such that an RF field with at least two-fold rotational symmetry with respect to the axis is generated. The device includes shortened pole rods and/or further electrodes. The pole rods and the further electrodes have at least two-fold rotational symmetry. The symmetry of the RF field allows ions to travel straight ahead through the ion guide with no hindrance. Such arrangements are particularly suitable for bringing together largely loss-free positive and negative ion species for reacting them. The reactions may be used to fragment multiply charged biopolymer ions by electron transfer or to remove excess charges of multiply charged biopolymer ions.

Abstract: A method and apparatus of compensating a magnetic field inhomogeneity in a dynamically harmonized FT-ICR cell is presented, based on adding of extra electrodes into the cell, the extra electrodes being shaped in such a way that the averaged electric field created by these electrodes produces a counter force to the forces caused by the inhomogeneous magnetic field on the cycling ions.

Abstract: A method for determining the concentration ratio in a sample of a target peptide to a reference peptide that is chemically identical with the target peptide, but labeled by isotopes, acquires mass spectra of the target and reference peptides. One of a plurality of families of superimposed bell-shaped curves which is a best fit to ion current peak groups of the target and reference peptides in the mass spectra is determined by varying parameters of the families. In each family, each bell-shaped curve has a predetermined height, the curves have fixed distances from each other and the relative curve heights and curve distances in the families are individually calculated from an elemental composition of the peptides and an isotope abundance distribution of elements composing the peptides, taking into account purity of the isotopes. The concentration ratio is then determined from the parameters of the best fit.

Abstract: The invention relates to the use of substances for the production of anions suitable for charge transfer reactions in mass spectrometers, particularly for the fragmentation of multiply positively charged biopolymer ions by electron transfer or for charge reduction by proton transfer. Diketones, particularly ?-diketones, are proposed as a newly found class of substances which can be used both for the production of radical anions for electron transfer dissociations (ETD) with a high yield of fragment ions and also for the production of non-radical anions for the charge reduction of multiply charged analyte ions by proton transfer reactions (PTR). These substances have favorable properties in terms of their handling and the associated analytical methods: they are largely nontoxic, cover a favorable range of molecular masses, and their volatility means that they can be stored in unheated containers outside of the vacuum system, which facilitates the refilling of the containers.

Abstract: A method for determining the concentration ratio in a sample of a target peptide to a reference peptide that is chemically identical with the target peptide, but labeled by isotopes, acquires mass spectra of the target and reference peptides. One of a plurality of families of superimposed bell-shaped curves which is a best fit to ion current peak groups of the target and reference peptides in the mass spectra is determined by varying parameters of the families. In each family, each bell-shaped curve has a predetermined height, the curves have fixed distances from each other and the relative curve heights and curve distances in the families are individually calculated from an elemental composition of the peptides and an isotope abundance distribution of elements composing the peptides, taking into account purity of the isotopes. The concentration ratio is then determined from the parameters of the best fit.

Abstract: Aspects relate to methods for processing individual spectra acquired with a time-of-flight mass spectrometer to form a sum spectrum. The peak position of a peak and its total intensity are determined in an individual spectrum, and entries in an addition raster of the sum spectrum adjacent to the peak position are selected; then the total intensity is divided up into portions, wherein more of the total intensity is added to entries which are closer to the peak position than is added to entries which are further away from the peak position.

Abstract: The invention relates to time-of-flight mass spectrometers in which individual time-of-flight spectra are measured by detection systems with limited dynamic measurement range and are summed to sum spectra. The invention proposes a method to increase the dynamic range of measurement of the spectrum. To achieve this, those ion signals whose measured values display saturation of the analog-to-digital converter (ADC) are replaced by correction values, particularly if several successive measured values are in saturation. The correction values are obtained from the width of the signals, preferably simply from the number of measured values in saturation.

Abstract: A method and a device increases (e.g., uniformly) the internal energy of ions, in order to remove water shells or adducts, to decompose clusters or molecular agglomerations, to unfold large folded ions, or to prepare ions for fragmentation with high yield. The ions can be heated at a gas pressure of a few hectopascal viscously dragged through a tube comprising on-axis RF fields with strong axial field components. The ions are introduced, as usual together with entraining gas, into a vacuum system of a mass spectrometer through a small hole or capillary, and are driven by the gas flow through the tube with the RF fields. The RF fields decelerate and re-accelerate the ions, which travel through the tube, in rapid succession mainly in forward and backward direction, thus causing high numbers of collisions with the gas molecules and heating up the ions in a uniform manner.

Abstract: 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.

Abstract: An ion guide system includes an ion guide with pole rods, a device for laterally introducing an ion species, and a mass spectrometer for analyzing product ions of reactions between different ion species. The device is configured and positioned such that an RF field with at least two-fold rotational symmetry with respect to the axis is generated. The device includes shortened pole rods and/or further electrodes. The pole rods and the further electrodes have at least two-fold rotational symmetry. The symmetry of the RF field allows ions to travel straight ahead through the ion guide with no hindrance. Such arrangements are particularly suitable for bringing together largely loss-free positive and negative ion species for reacting them. The reactions may be used to fragment multiply charged biopolymer ions by electron transfer or to remove excess charges of multiply charged biopolymer ions.

Abstract: An ion source for chemical ionization of analytes at atmospheric pressure with a non-radioactive electron source in a vacuum chamber, includes, a reaction chamber at atmospheric pressure, and a window with an electron-permeable and essentially gas-impermeable membrane in between. The window may be a structured window membrane, i.e. a window membrane with a structured form comprising a multitude of structural elements, between the reaction chamber and the vacuum chamber.

Abstract: The invention concerns the reduction of the risk of an incorrect assignment of samples to sample sites during the manual deposition of samples for ionization by laser desorption (for example MALDI or LDCI). The invention offers a method wherein a sample support with several sample sites is provided, at least one sample site is selected, and the selected sample site is highlighted, at least in contrast to neighboring not selected sample sites, in a way which the human eye can perceive.

Abstract: A method for determining an expression of human epidermal growth factor receptor 2 (HER2) of a subject. The method includes providing a sample from the subject; measuring one of (i) amounts of two or more proteins in the sample, each protein having a molecular weight substantially equal to 4740, 8404, 8419, 8435, 8450, 8455, 8465, 8570, 8607 or 8626 atomic mass units, and (ii) amounts of at least one of human cystein-rich intestinal protein 1 (CRIP1), one or more variants of the human cystein-rich intestinal protein 1 (CRIP1 variants), and proteolytic digestion products thereof in the sample; and comparing the amounts of the proteins to control amounts, which control amounts are determinative of the expression of the human epidermal growth factor receptor 2.

Abstract: Fine structures of isotopic peak clusters of substances are determined using ultrahigh resolution mass spectrometry, e.g, FT-ICR mass spectrometry. Resolved individual peaks in the fine structure of the non-monoisotopic peak clusters of organic substances usually contain the additional elemental isotopes 13C, 15N, 17O, 18O, 2H, 33S, 34S, and combinations thereof. In each of a series of experiments, one of the non-monoisotopic peak clusters is isolated and the corresponding fine structure spectrum acquired. Abundances of the resolved fine structure peaks and their positions on the mass scale are recorded and, after measuring some or all of the isotopic peaks, the atomic composition of the measured substance is calculated. By excluding the monoisotopic peak and isolating only one isotopic peak cluster at a time, the number of ions in the FT-ICR cell is kept low, which avoids resolving power losses due to space charge effects and ion-ion interaction phenomena.