Abstract: The invention relates to devices and methods for desorption scanning of analyte material deposited on a sample support, which can comprise the following mode of operation: (a) setting a position of the support to approach an impingement region onto which a beam is directed for local desorption of analyte material; (b) determining an actual position of the support after setting the position; (c) comparing the determined actual position with a target position of the support to determine any deviation; (d) adjusting a beam orientation, if a deviation is detected, so that the beam is directed onto the impingement region on the support that results when there is no deviation; (e) applying the beam to the impingement region to locally desorb analyte material and deliver it to an analyzer; and (f) checking whether a predetermined end condition is satisfied and, if not, repeating steps (a)-(e) for a subsequent non-congruent impingement region.

Abstract: The disclosure relates to a method of operating a secondary-electron multiplier in the ion detector of a mass spectrometer so as to prolong the service life, wherein the secondary-electron multiplier is supplied with an operating voltage in such a way that an amplification of less than 106 secondary electrons per impinging ion results, while the output current of the secondary-electron multiplier is amplified using an electronic preamplifier mounted close to the secondary-electron multiplier with such a low noise level that the current pulses of individual ions impinging on the ion detector are detected above the noise at the input of a digitizing unit. Further disclosed are the use of the methods for imaging mass spectrometric analysis of a thin tissue section or mass spectrometric high-throughput analysis/massive-parallel analysis, and a time-of-flight mass spectrometer whose control unit is programmed to execute such methods.

Abstract: An apparatus to generate ions from sample material deposited on a substrate which is at least partially transparent to electromagnetic waves, comprises: —a support device having a holder for the substrate, —a desorption/ionization unit including a desorption device and an ionization device, said desorption device being configured to desorb deposited sample material from a desorption site on the substrate using at least one energy burst, and said ionization device being configured to irradiate the desorbed sample material above the substrate with electromagnetic waves after the at least one energy burst, wherein the electromagnetic waves pass through the substrate before encountering the desorbed sample material at a location which corresponds to the desorption site, and —an extraction device which is arranged and designed to extract ions from the desorbed sample material and transfer them into an analyzer. The invention also relates to a correspondingly arranged method.

Abstract: The disclosure relates to a method of operating a secondary-electron multiplier in the ion detector of a mass spectrometer so as to prolong the service life, wherein the secondary-electron multiplier is supplied with an operating voltage in such a way that an amplification of less than 106 secondary electrons per impinging ion results, while the output current of the secondary-electron multiplier is amplified using an electronic preamplifier mounted close to the secondary-electron multiplier with such a low noise level that the current pulses of individual ions impinging on the ion detector are detected above the noise at the input of a digitizing unit. Further disclosed are the use of the methods for imaging mass spectrometric analysis of a thin tissue section or mass spectrometric high-throughput analysis/massive-parallel analysis, and a time-of-flight mass spectrometer whose control unit is programmed to execute such methods.

Abstract: The invention relates to imaging mass spectrometry on thin sample sections, in particular using MALDI, where a high lateral image resolution means that a plethora of mass spectra has to be acquired and the image acquisition runs over many hours. The quality of the mass spectra deteriorates considerably over time in such cases. The invention is based on the finding that the decrease in spectral quality of continuous measurement series over many hours is only partially caused by a decrease in detector gain, and that another significant cause is a decrease in the number of usable ions per ion generating pulse, which is attributable to several phenomena that are difficult to regulate. The invention now proposes to instead regulate only the detector gain, and such that not only the decrease in the detector gain is compensated, but also the decrease in the number of usable ions per ion generating pulse.

Abstract: The disclosure relates to a method of operating a secondary-electron multiplier in the ion detector of a mass spectrometer so as to prolong the service life, wherein the secondary-electron multiplier is supplied with an operating voltage in such a way that an amplification of less than 106 secondary electrons per impinging ion results, while the output current of the secondary-electron multiplier is amplified using an electronic preamplifier mounted close to the secondary-electron multiplier with such a low noise level that the current pulses of individual ions impinging on the ion detector are detected above the noise at the input of a digitizing unit. Further disclosed are the use of the methods for imaging mass spectrometric analysis of a thin tissue section or mass spectrometric high-throughput analysis/massive-parallel analysis, and a time-of-flight mass spectrometer whose control unit is programmed to execute such methods.

Abstract: The invention relates to imaging mass spectrometry on thin sample sections, in particular using MALDI, where a high lateral image resolution means that a plethora of mass spectra has to be acquired and the image acquisition runs over many hours. The quality of the mass spectra deteriorates considerably over time in such cases. The invention is based on the finding that the decrease in spectral quality of continuous measurement series over many hours is only partially caused by a decrease in detector gain, and that another significant cause is a decrease in the number of usable ions per ion generating pulse, which is attributable to several phenomena that are difficult to regulate. The invention now proposes to instead regulate only the detector gain, and such that not only the decrease in the detector gain is compensated, but also the decrease in the number of usable ions per ion generating pulse.

Abstract: The disclosure relates to a method of operating a secondary-electron multiplier in the ion detector of a mass spectrometer so as to prolong the service life, wherein the secondary-electron multiplier is supplied with an operating voltage in such a way that an amplification of less than 106 secondary electrons per impinging ion results, while the output current of the secondary-electron multiplier is amplified using an electronic preamplifier mounted close to the secondary-electron multiplier with such a low noise level that the current pulses of individual ions impinging on the ion detector are detected above the noise at the input of a digitizing unit. Further disclosed are the use of the methods for imaging mass spectrometric analysis of a thin tissue section or mass spectrometric high-throughput analysis/massive-parallel analysis, and a time-of-flight mass spectrometer whose control unit is programmed to execute such methods.

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: 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: Mass spectrometry with lasers generates ions from analyte molecules by matrix assisted laser desorption for a variety of different mass spectrometric analysis procedures. The mass spectrometers with laser systems supply laser light pulses having at least two different pulse durations, and mass spectrometric measuring techniques use the laser light pulses of different durations. The duration of the laser light pulses allows the characteristics of the ionization of the analyte molecules, particularly the occurrence of the ISD (in-source decay) and PSD (post-source decay) types of fragmentation, whose fragment ion spectra supply different kinds of information, to be adapted to the analytic procedure.

Abstract: 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.

Abstract: In a time-of-flight mass spectrometer having an ion source with a first accelerating electrode, a distance between the surface of a sample and the first accelerating electrode is maintained at a predetermined distance which is critical for determining the mass and quantity of ions generated by the ion source. A digital image of the sample surface is obtained with a digital camera and a predetermined characteristic of the digital image is determined. The predetermined characteristic is then used to compute an adjustment amount by which the sample surface is moved to maintain the predetermined distance. Determining the predetermined characteristic can be simplified by projecting a light pattern onto the sample surface at an angle and determining the predetermined characteristic from the digital image of the pattern.

Abstract: Mass spectrometry with lasers generates ions from analyte molecules by matrix assisted laser desorption for a variety of different mass spectrometric analysis procedures. The mass spectrometers with laser systems supply laser light pulses having at least two different pulse durations, and mass spectrometric measuring techniques use the laser light pulses of different durations. The duration of the laser light pulses allows the characteristics of the ionization of the analyte molecules, particularly the occurrence of the ISD (in-source decay) and PSD (post-source decay) types of fragmentation, whose fragment ion spectra supply different kinds of information, to be adapted to the analytic procedure.

Abstract: 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.

Abstract: In a time-of-flight mass spectrometer having an ion source with a first accelerating electrode, a distance between the surface of a sample and the first accelerating electrode is maintained at a predetermined distance which is critical for determining the mass and quantity of ions generated by the ion source. A digital image of the sample surface is obtained with a digital camera and a predetermined characteristic of the digital image is determined. The predetermined characteristic is then used to compute an adjustment amount by which the sample surface is moved to maintain the predetermined distance. Determining the predetermined characteristic can be simplified by projecting a light pattern onto the sample surface at an angle and determining the predetermined characteristic from the digital image of the pattern.

Abstract: An ion source generating ions by matrix-assisted laser desorption/ionization (MALDI) comprising a MALDI sample support and a solid-state the laser system generating a pulsed laser beam, which has a wavelength in the range between 332 and 342 nanometers and is spatially shaped in the solid-state laser system such that the spatial intensity distribution of the laser beam on the MALDI sample support exhibits more than one intensity peak.

Abstract: The invention relates to a laser system for the ionization of a sample by matrix-assisted laser desorption in mass spectrometric analysis. The invention consists in providing an adjustable laser system which, in one setting, generates a single intensity peak on the sample and, in another setting, a multiplicity of intensity peaks, with the half-width, intensity, spatial arrangement and/or degree of spatial modulation of the single intensity peak and/or the intensity peaks being adjustable.

Abstract: The invention relates to a laser system for the ionization of a sample by matrix-assisted laser desorption in mass spectrometric analysis. The invention consists in providing a laser system which generates a spatially modulated intensity distribution with intensity spots on the sample, which significantly improves the quality and the robustness of the mass spectrometric analysis compared with a spatially homogeneous intensity distribution and, in particular, improves the ionization efficiency and, for a time-of-flight mass spectrometer with axial injection, the mass resolution and the signal-to-noise ratio.

Abstract: The invention relates to a laser system for the ionization of a sample by matrix-assisted laser desorption in mass spectrometric analysis. The invention consists in providing an adjustable laser system which, in one setting, generates a single intensity peak on the sample and, in another setting, a multiplicity of intensity peaks, with the half-width, intensity, spatial arrangement and/or degree of spatial modulation of the single intensity peak and/or the intensity peaks being adjustable.