Bruker-franzen Analytik Gmbh

Bruker Daltonik Gmbh

Bruker Analytical Instruments, Inc.

Claus Koster

Jochen Franzen

Armin Holle

Melvin Andrew Park

Frank H Laukien

Jens Rebettge

Jurgen Grotemeyer

Johann Grundwurmer

The invention relates to ionization with low fragmentation and adduct formation, of high-molecular analyte molecules, particularly of large biopolymers, by matrix-assisted laser desorption (MALDI) from liquid matrices for mass-spectrometric analysis of the resulting ions, particularly for determination of their molecular weight. The invention uses liquids as matrix substances with very low vapor pressures from the group of minimally trihydroxylic alcohols with at least one ether bond (ether polyols or polyether polyols). These can be used advantageously for energy absorption and ionization by infrared lasers (IR-MALDI), however other lasers, such as conventional. UV lasers, can be used for other wavebands by the addition of light-absorbing compounds.

Ionization of high-molecular substances by laser desorption from liquid matrices

The invention relates to ion detectors for heavy ions with high mass resolution and high sensitivity usable in time-of-flight mass spectrometers. It relates to sensitive measuring methods for large masses in the range of about ten thousand to several hundred thousand atomic mass units. Specifically it relates to the conversion of large ions into smaller ions, which can then be detected with standard ion detectors for ions of smaller and average masses. The invention consists of a thin multichannel plate, such as is normally used for secondary-electron multiplication, used as a conversion device, in combination with a standard ion detector. However, in contrast to normal secondary-electron multiplier operation, it is operated at reversed polarity in order to produce large numbers of low-weight positive ions by a self-contained amplification process engaging secondary electrons accelerated in backward direction. This device and operating method leads to a reduction in signal width and offers high sensitivity for large ions.

High-mass detector with high mass-resolution for time-of-flight mass

A time-of-flight mass spectrometers, in which the ions are generated by ionization of analyte substances on a sample support, by matrix-assisted laser desorption (MALDI). The time-of-flight mass spectrometer consists of using space-adjusting actuators to set the spacing of the sample support from the nearest acceleration electrode so that the flight time of ions of a reference substance prescribed by the calibration can be precisely adjusted. Due to this adjustment of the spacing, a once only calibration of the relationship between the flight time and mass (i.e. the mass scale) may be constantly retained.

Adjustment of the sample support in time-of-flight mass spectrometers

The invention relates to the exact mass determination of analyte ions in time-of-flight mass spectrometers with ionization of analyte substances on sample supports by matrix-assisted laser desorption (MALDI), and with an improvement in mass resolution by delayed ion acceleration in the field between the sample support and an intermediate electrode. It particularly relates to methods for subsequent correction of the flight time values if, during the scan, an incorrect adjustment of the distance from the sample support to the nearest acceleration electrode has occurred. The invention obtains a correction parameter for the flight times of all ions in the spectrum from an internal reference substance and corrects all flight times using a quadratic correction equation, before using the calibrated mass scale for the calculation of the exact masses. The quadratic correction equation contains a control parameter which multiplicatively affects both the linear and quadratic correction term. If no better suitable reference ions are available, oligomeric ions from the matrix of the MALDI method may be used as reference ions. The method can be applied regardless of adjustment in the optimum focus range before measurement of the spectrum, if the adjustments were made in a particular manner.

Accurate mass determination with maldi time-of-flight mass spectrometers

A method relates to exact mass determination of analyte ions in time-of-flight mass spectrometers using an ionization of analyte substances on sample supports by matrix-assisted laser desorption (MALDI), and an improvement in mass resolution by time-delayed ion acceleration in the field between the sample support and an intermediate acceleration electrode. It particularly relates to methods for the stabilization of a once calibrated mass scale when there are unwanted changes in the distance of the sample support from the intermediate acceleration electrode.An unknown change of this distance can be compensated for by a coupled change of both total accelerating voltage and partial acceleration voltage between sample support and intermediate electrode in a simple manner by adjusting the time of flight of ions from a reference substance to the value given by the calibrated mass scale. Oligomeric ions from the matrix of the MALDI method serve very well as reference ions. Furthermore, if the range of optimum focus is shifted by a change in the time delay, the calibrated mass scale can be kept valid for all masses through a simultaneous change of the accelerating voltage.

Exact mass determination with maldi time-of-flight mass spectrometers

A system and a method for the introduction of sample supports, which hold large numbers of analysis samples, into the ion source region of a mass spectrometer. The sample supports are especially intended for the ionization method using matrix-assisted desorption through laser bombardment (MALDI). The system consists of using an evacuable, sealable and removable cassette which, instead of using a through-passage lock chamber with two lock valves, can be attached in a simple manner to the entrance opening for the ion source of the mass spectrometer. Only the entrance opening has a lock valve, and the expensive second lock valve in the lock chamber is no longer needed. The cassette can also be used for protected transport and for storage of the sample supports, and in particular for storage of the samples under protective gas or vacuum.

Device and method for introduction of sample supports into a mass

A method for matrix-assisted ionizing laser desorption of large analyte molecules (MALDI) in a vacuum for the generation of ions for mass spectrometric investigation of the analyte substance is provided. The matrix substance for matrix-assisted ionizing laser desorption is formed from at least two different components. One of the components is very adsorptive, as well as being decomposable thermolytically into small fractions. Additional matrix components are selected for protonation of the analyte molecules. In particular, a thin layer of nitrocellulose (also called cellulose nitrate) with a protonating substance embedded within it is particularly suitable. This layer, which is insoluble in water, adsorbs large analyte molecules from an aqueous solution at its surface.

Method for matrix-assisted laser desorption ionization

The invention relates to the use of a time-of-flight mass spectrometer to analyze substance molecules which are ionized by laser desorption, particularly by matrix-assisted laser desorption (MALDI). In detail it relates to the process for improving mass resolution by the known method of delayed acceleration (sometimes called delayed extraction) of the ions, and devices for the performance of this method. The invention consists of using an optical device with gridless apertures for the acceleration of the ions and refocusing the ion beam divergence due to the lens effect of the apertures, by means of a lens arrangement in the drift region of the time-of-flight spectrometer. For laser light pulses, illumination, and observation, there are further lateral holes in the electrodes of the optical device.

Method of improving mass resolution in time-of-flight mass spectrometry

In a time-of-flight mass spectrometer with an ion reflector located after the ion source and before the ion detector, to compensate for different starting energies of ions of equal masses, in the ion flight path inside or after the ion reflector at least one electrode is provided for, to which a pulsed high voltage is applied in such a way that within a predetermined narrow range of ion masses, time-of-flight errors for ions of equal masses due to different formation locations or times in the ion source are compensated for at the ion detector. In this way, apart from an energy compensation, also time-of-flight errors of the ions under investigation can simultaneously be compensated for.

Device and method for the improved mass resolution of time-of-flight

The invention relates to methods for the structural analysis of large substance molecules, preferably of chain molecules such as peptides for example, by scanning daughter or fragment ion mass spectra in time-of-flight mass spectrometers with reflectors. The invention consists in the differentiation between daughter ions from spontaneous fragmentations of ions by high-energy collisions and those from delayed fragmentations of metastable ions, by separately detecting the different kinds of ions using a special electrostatic energy filtration by a short Einzel lens directly behind the collision zone. Spontaneously decomposing ions leave the fragmentation zone with smaller kinetic energy due to the loss of mass. Daughter ions from spontaneous decompositions on the one hand, and from metastable decompositions on the other, display characteristic differences which can be used for the determination of structure. Spontaneously decomposing peptide ions preferably show, for example, simultaneously occurring fragmentations of the main and side chains on the then terminal links, while metastable decompositions display no fragmentations of the side chains. In this way, for example, it can be distinguished whether the terminal amino acid is leucine or isoleucine, even though both amino acids have the same mass.

Method for time-of-flight mass spectrometry of daughter ions

A method and apparatus to direct ions away from their otherwise intended or parallel course. Deflectors are used to establish electric fields in regions through which ions are to pass. With such electric fields, ions may be deflected to a desired trajectory. According to the present invention, a multideflector, in the form of a series of bipolar plates spaced evenly across the ion beam path, is used as an ion deflector.

Multideflector

The invention relates to a device and method for the ionization of non-vaporizable substance molecules at atmospheric pressure by chemical ionization (APCI=atmospheric pressure chemical ionization). The invention consists of desorbing the analyte substances which are mixed with decomposable substances (matrix substances) in solid form on a solid support, by laser irradiation at atmospheric pressure into a gas stream, and to add sufficient ions for proton transfer reactions to the gas stream. Explosives like cellulosis trinitrate or trinitro toluene (TNT) form a preferred class of decomposable matrix substances.

Method for the ionization of heavy molecules at atmospheric pressure

A method for the high resolution analysis of analyte ions in a time-of-flight mass spectrometer. The method consists of the generation of an intermediate time-focus plane for ions of a certain mass at a location between an ion source and an ion reflector, and then using the ion reflector to temporally focus the ions of equal mass and differing velocities which pass this plane at the same time onto a detector. For time-of-flight mass spectrometers with an ion selector, the ion selector is particularly favorable location for this intermediate plane with time focus; and with a collision cell for the collision fragmentation of the ions, the collision cell is a particularly favorable location.

Mass resolution in time-of-flight mass spectrometers with reflectors

The invention relates to the use of a time-of-flight mass spectrometer to analyze substance molecules which are ionized by laser desorption, particularly by matrix-assisted laser desorption (MALDI). In detail it relates to the process for improving mass resolution by the known method of delayed acceleration of the ions in the space in front of the sample support plate. The invention consists of switching the potential of an intermediate electrode which is located at a short distance in front of the sample support plate, instead of switching the potential of the sample support plate itself.

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Lilienthal, Germany

Claus Koster