Abstract: 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.

Abstract: The invention relates to devices and methods in mass spectrometers for the generation of ions of heavy molecules, especially biomolecules, by bombarding them with uncharged clusters of molecules. The analyte ions which are generated or released by cluster bombardment of analyte substances on the surface of sample support plates show a broad distribution of their kinetic energies, which prevents good ion-optical focusing. In the invention, the kinetic energies are homogenized in a higher-density collision gas. The collision gas is preferably located in an RF ion guide, more preferably an RF ion funnel, which can transfer the ions to the mass analyzer. The collision gas may be introduced with temporal pulsing, coordinated or synchronized with the pulsed supersonic gas jet. The collision gas may be pumped off again before the next supersonic gas pulse. In an advantageous embodiment, the collision gas can originate from the supersonic gas jet itself.

Abstract: The invention mainly relates to the mass spectrometric identification of pathogens in blood cultures from blood-stream infections (septicemia). The invention provides a method with which microbial pathogens can be separated in purified form from blood after a relatively brief cultivation in a blood culture flask, without any interfering human proteins or any residual fractions of blood particles such as erythrocytes and leukocytes, and can be directly identified by mass spectrometric measurement of their protein profiles. The method is based on the use of relatively strong tensides to destroy the blood particles by dissolving the weak cell membranes and most of the internal structures of the blood particles; in spite of the fact that tensides are regarded as strong ionization inhibitors in MALDI and other ionization processes required for mass spectrometric measurements.

Abstract: A Mixture of substances is provided for precise calibration of the mass scale of mass spectrometers equipped with ion sources that operate at atmospheric pressure (AP) with ionization of the analyte molecules, for example by APCI (chemical ionization), or by APPI (photoionization), often at high temperatures of up to 470° C. Out of physical reasons, the mass scale of any time-of-flight mass spectrometer deviates in the lower mass range from the theoretical relation between charge-related mass m/z and flight time t. A closely spaced arrangement of low mass calibration reference points is necessary if high mass accuracy is to be achieved for substances of low molecular weight. APCI and APPI sources are increasingly used in time-of-flight mass spectrometers with orthogonal ion injection (OTOF MS) for the detection of non-polar and weakly polar compounds, in particular, for analyte molecules with relatively low molecular weights.

Abstract: 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.

Abstract: The amplification of secondary-electron multipliers in mass spectrometers is automatically adjusted by generating mass spectra with single ion signals, determining the average value of the peak heights of these single ion signals, and setting the amplification so that the average peak height assumes a desired nominal value. The amplification may be set via the supply voltage of the secondary-electron multiplier and can be increased or decreased by a desired factor using the known characteristic of the secondary-electron multiplier.

Abstract: Charged droplets are guided along a defined path from a droplet source to a droplet sink. A focusing pseudopotential distribution generated by audio frequencies on electrodes of a guiding device guide the charged droplets from the droplet source to the droplet sink with low loss. The droplets can be driven along the droplet guide by a gas flow, an axial electric field or a combination of both. For example, charged droplets from a spray capillary of an electrospray ion source at atmospheric pressure may be introduced into the inlet capillary leading to the vacuum system of ion analyzers, a procedure similar to that used up to now in nanoelectrospraying, but with substantially higher flow rates. In the guiding device, the droplets can be manipulated in different ways, for example evaporated down to a desired size.

Abstract: The invention relates to a method by which the operator of a mass spectrometer with a MALDI ion source, particularly one which operates with delayed extraction of the ions, is provided with a technique for determining the degree of contamination, in particular to determine when the ion source must be cleaned. The method comprises the acquisition of at least one mass spectrum of ions which are generated in the ion source, the recording of at least one characteristic value for each of at least two mass signals in the mass spectrum, and the determination of an indicator number, derived from the characteristic values of at least two mass signals, which shows how urgently the ion source must be cleaned. The invention also relates to a mass spectrometer with a MALDI ion source which can be characterized accordingly.

Abstract: Identification of infectious pathogens, particularly viruses, bacteria and other microorganisms is effected with a method whereby pathogens of acute infections can be identified, without first culturing them in external nutrient media, by mass spectrometric measurement of their protein profiles obtained from pathogens directly precipitated from body fluid into pellets by centrifuging. With this method, pathogens which cause acute infections can be identified in less than one hour.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The pressure of a carrier gas entering a gas chromatography (GC) column is controlled by increasing or decreasing the gas pressure over a pressure change cycle by which a desired gas pressure is obtained while avoiding pressure pulses in the column. The pressure change cycle may follow a function that dictates the rate of pressure change. A gas flow controller that controls the gas pressure at the inlet or head of the column may be operated to implement the pressure change cycle. The gas flow controller may be controlled by an electronic controller.

Abstract: 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.

Abstract: 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.

Abstract: Identification of infectious pathogens, particularly viruses, bacteria and other microorganisms is effected with a method whereby pathogens of acute infections can be identified, without first culturing them in external nutrient media, by mass spectrometric measurement of their protein profiles obtained from pathogens directly precipitated from body fluid into pellets by centrifuging. With this method, pathogens which cause acute infections can be identified in less than one hour.

Abstract: The invention relates to measuring cells and measuring methods in oscillation mass spectrometers in which clouds of the same species of ion oscillate harmonically in a potential well in a longitudinal direction, decoupled from their motion transverse to this direction. A frequency analysis of the longitudinal oscillations of these ion clouds, which is carried out by a Fourier analysis of the induced image currents between two detection electrodes, leads to frequency spectra of the ions and hence to mass spectra. The position of the ion trajectories relative to the detection electrodes and the design of the measuring cells in the oscillation mass spectrometers is used to generate large proportions of harmonics in the image currents, and evaluate the frequency signals of the harmonics.

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: 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.

Abstract: The invention relates to a mass spectrometer comprising a laser system for mass-spectrometric analysis with ionization of analyte molecules in a sample by matrix-assisted laser desorption. A mass spectrometer with a pulsed UV laser system produces a spatially distributed spot pattern with peaks of uniform energy density on the sample, increasing thereby the degree of ionization for analyte ions as compared to conventional spot patterns. The spot pattern with peaks of uniform energy density can be produced by homogeneous illumination of a pattern generator, for example a lens array. The homogeneous illumination can be generated by a low-cost beam-shaping element, which does not act on the UV beam but on the original infrared beam, in conjunction with changes to the beam cross-section and beam profile brought about by the nonlinear conversion crystals.