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Bruker Daltonik Gmbh

Brucker Daltonik Gmbh

Andreas Haase

Jens Höhndorf

Armin Holle

Sebastian Böhm

Markus Kayser

Jens Hoehndorf

Jochen Franzen

Jens Bossmeyer

Marcel Niehaus

Jens BOßMEYER

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.

Desorption ion source with post-desorption ionization in transmission geometry

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.

Device for desorption scanning of analyte material on a sample support

Disclosed is a method for analytically measuring sample material deposited on a sample support surface, comprising: (a) defining a plurality of regions on the surface, several of which are in contact with sample material, (b1) sampling sections of sample on a region using a desorbing beam to generate desorbed molecules, which are ionized and transferred to an analyzer, (b2) in so doing, sweeping the region by changing an orientation setting of the beam relative to the surface along a non-rectilinear trajectory on the region selected from a plurality of predefined, non-rectilinear trajectories while keeping the support in one position, (c) transitioning from a swept region to a region to be swept next using spatial adjustment of the support, and (d) repeating steps (b1), (b2), and (c) until a predetermined termination condition is fulfilled. A system for analyzing ions, having an ion generation device and a control unit is also disclosed.

Method for the analytical measurement of sample material on a sample support

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 10secondary 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.

Method of operating a secondary-electron multiplier in the ion detector of a mass spectrometer

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.

Maintaining spectral quality over long measuring periods in imaging mass spectrometry

The invention relates to the operation of an energy-focusing and solid-angle-focusing reflector for time-of-flight mass spectrometers with pulsed ion acceleration into a flight tube, e.g. from an ion source with ionization by matrix-assisted laser desorption (MALDI). The objective of the invention is to generate high mass resolution in wide mass ranges up to high masses above eight kilodaltons by varying at least one operating voltage on one of the diaphragms of the reflector which can be varied according to a suitable time function during the spectrum acquisition. It may also be advantageous to adapt the operation of the accelerating voltages in the starting region of the ions accordingly. These measures make it possible to achieve a mass resolution much higher than R=100,000 in a wide mass range extending up to and above eight kilodaltons.

Wide-range high mass resolution in reflector time-of-flight mass spectrometers

The invention relates to a mass spectrometer with laser-desorption ion source, particularly for MALDI. A laser system with optical laser spot control is proposed in which the laser spot shift brought about by means of a temporally variable angular deflection at a mirror system is performed on the laser beam before or during the energy multiplication. The laser beam, which is deflected through a small angle by the mirror system, is converted by a suitable flat-field optical system into a parallel-shifted laser beam, which then passes through a multiplier crystal. After exiting the multiplier crystal system, the parallel-shifted beam is converted back into a slightly angled beam by a flat-field optical system, this latter beam then bringing about the spot shift on the sample. The multiplier crystal is conserved by the continuously temporally changed parallel shift of the laser beam in the multiplier crystal, thus prolonging its service life.

Mass spectrometer with a laser desorption ion source, and laser system with a long service life

The invention relates to mass spectrometers with optically pumped lasers, whose laser light can be used for ionization by laser desorption, for the fragmentation of ions by photodissociation (PD), for the initiation of ion reactions, and for other purposes. The invention provides a laser system for a mass spectrometer, with which at least two laser beams of different wavelengths can be generated for use at different points along an ion path from an ion source to an ion detector in the mass spectrometer.

Mass spectrometer with laser system for producing photons of different energies

The invention relates to optically pumped and pulsed solid-state lasers which are used in mass spectrometers in particular for ionization by matrix-assisted laser desorption (MALDI) and which operate at pulse frequencies of up to 10 kilohertz or even higher. The invention proposes that, instead of interrupting the clocked sequence of the laser operation, individual light pulses or groups of light pulses are blanked out so that subsequent light pulses do not have a higher energy density, in accordance with the requirements for LDI processes. Methods and devices for the blanking out of light pulses are provided which are, in particular, low cost and considerably less complex than other methods.

Blanking out of pulses in pulsed lasers for LDI mass spectrometers

The invention relates to mass spectrometers with an ion source, comprising a UV laser system for mass spectrometric analyses with ionization of analyte molecules in a sample by matrix-assisted laser desorption, which, with very low energy losses, can produce a spatially distributed spot pattern with several intensity peaks of equal height, thus making it possible to achieve an optimum degree of ionization of analyte ions for any task. Such a spot pattern can be generated from the UV beam with high transverse coherence, using a combination of a lens array and a lens, provided that the lens array satisfies a mathematical condition for separation of the micro-lenses from each other (pitch) and their focal length. For example, a lens array with square or round lenses produces a pattern of nine and five spots, respectively. The lens arrays are inexpensive and do not require any lateral adjustment in this arrangement.

Mass spectrometer with laser spot pattern for MALDI

Mass spectrometers ionize samples by matrix-assisted laser desorption (MALDI). The samples are located on a moveable support plate, and irradiated by a pulsed laser. A fast positional control of laser spots is provided via a system of rotatable mirrors to relieve strain on a support plate motion drive. If the spot position is finely adjusted by the mirror system and follows the movement of the sample support plate, the intermittent movement of the sample support can be replaced with a continuous uniform motion. The fast positional control allows more uniform ablation of a sample area. Galvo mirrors with low inertia may be used between the beam generation and a Kepler telescope in the housing of the laser. The positional control can also provide a fully automatic adjustment of MALDI time-of-flight mass spectrometers, at least if the ion-optical elements are equipped with movement devices.

Laser spot control in maldi mass spectrometers

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. This beam shaping not only produces a beam profile which illuminates the pattern generator homogeneously with low losses, but at the same time increases the efficiency of the frequency multiplication and the lifetime of the conversion crystals so that cost savings are achieved because less laser energy is required and the lifetime is increased.

Mass spectrometer with MALDI laser system

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.

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Bremen, Germany

Andreas Haase