Other

Bruker Daltonik Gmbh

Brucker Daltonik Gmbh

Spicer Gelenkwellenbau Gmbh

Bruker Daltonics Gmbh & Co. Kg

Martin Schürenberg

Sören-Oliver Deininger

Alexander Vossgröne

Jochen Franzen

Detlev Suckau

Nikolaus Martin Erlmann

Christian Schmid

Alice Ly

Eckhard Nordhoff

Eckhard Belau

Helmut E Meyer

Christine Lübbert

Rainer Paape

Kai Rückriem

Christoph Nordmann

Mirko Klinski

Dashmir Hajrula

The invention proposes preparing biological samples for spectrometry which contain cell structures and/or whole cells of human or animal origin (e.g. thin human and animal tissue sections) or prokaryotes (e.g. microorganisms), and which require constant relative humidity, in a temperature-controlled gas volume whose humidity is determined by a saturated substance solution, for example a suitable salt solution. The invention exploits a physico-chemical phenomenon called 'deliquescence', which manifests itself by keeping the relative humidity above the saturated substance solution constant with a high degree of precision when a specified temperature is maintained. Pure succinic acid exhibits deliquescence at approx. 99% relative humidity, for example. Since an enormous variety of deliquescent salts and other suitable substances are available, it is possible to find the suitable substance for almost any desired relative humidity, with adjustment of the temperature, where necessary.

Humidity stabilization during the preparation of biological samples for spectrometry

The invention relates to methods for drawing-off liquid from individual droplets which are in a predefined arrangement on a flat substrate and have sedimented material enclosed in them. A mask of an absorbent material comprising a pattern of indentations or holes which corresponds at least partially to the regular arrangement of the individual droplets, or a stiff, rigid plate of an absorbent material is positioned above the flat substrate in such a way that the droplets come into contact with the absorbent material peripherally so that liquid is drawn off there-into. The invention also relates to a mask of an absorbent material with a substantially rectangular shape which has a predefined pattern of indentations or holes for the purpose of separating liquid and sedimented material enclosed therein.

Separation of liquid in droplets and sedimented material enclosed therein

The invention relates to the identification and visualization of the spatial distribution of particular tissue states in histological tissue sections from mass spectrometric signals acquired with spatial resolution. The invention proposes a method by means of which regions of the tissue with similar mass spectra are found automatically, and it is further proposed that mass spectra of these regions are summed in order to improve the spectral quality to such an extent that known markers for tissue degenerations can be identified with increased certainty. Regions of similar mass spectra can be interconnected on a large scale, but can also be isolated from each other on a small scale.

Mass spectrometric determination of particular tissue states

The invention relates to the preparation of samples on mass spectrometric sample supports with dispensing of liquids, and particularly to devices and methods to clean the dispenser. During dispensing of hundreds of samples, solved material may crystallize over time as deposit at the capillary tip of the dispenser, which impedes the vertical detachment of the drop in the medium and long run. Therefore, frequently cleaning the capillary tip is essential for a robust operation of the preparation device. The invention proposes to automatically clean the dispenser tip by creating a drop of washing fluid, such as pure solvent, fully enclosing the dispenser tip. The washing fluid is fed through a channel outside the central dispenser capillary to a location slightly above the capillary tip. The size of the hanging drop of washing fluid is photometrically regulated and monitored to prevent it from falling off prematurely.

Dispenser system for mass spectrometric sample preparations

An improved deposition aid for manual sample preparation, particularly on flat MALDI sample supports, comprises a holder for a sample support with several sample sites, which is adapted to standardized sample supports for ionization with matrix-assisted laser desorption and a device which projects a two-dimensional optical image, or a suitable sequence of images, onto the sample sites. The image, or sequence of images, is constructed such that a selected sample site or group of selected sample sites is highlighted in a way which can be perceived by the human eye, at least with respect to neighboring, not-selected sample sites. The deposition aid also includes an interface for confirming the manual deposition and/or a device for the automatic detection of a manual deposition process; and a guidance system which selects a sample site or group of sample sites, and controls the device accordingly.

Image projection method and apparatus for supporting manual MALDI sample preparation

A method for the identification and localization of proteins or other biomolecules of a histologic tissue section comprises enzymatically digesting the biomolecules of two similar tissue sections while substantially preserving the biomolecule positions in the tissue sections. Next, a mass spectrometric image of the digest products in one of the tissue sections is acquired. Then, the digest products of the other tissue section are extracted and separated and the mass spectra and daughter ion spectra of all the digest products are acquired. A list of all identifiable biomolecules of the tissue section is created by comparing the mass spectra and daughter ion spectra with spectra in biomolecule structure databases or spectral libraries. Finally, the biomolecules in the list are assigned to digest products of the same mass in the mass spectra used to create the mass spectrometric image of the thin tissue section.

Mass spectrometry imaging with substance identification

The invention relates to the preparation of thin tissue sections for mass spectrometric (MALDI) imaging, and proposes a method wherein a microcrystalline layer of the matrix material is produced on the surface of the thin tissue sections, and soluble analyte molecules are transported orthogonally through the thin tissue section to the matrix layer, without substantial lateral diffusion, by means of a solvent flow with alternating or constant direction, and are then deposited in the matrix layer and, if possible, embedded in the matrix crystals. A solvent flow which alternates in direction can be produced by successive, alternating phases of swelling and drying, brought about by periodic changes to the thin tissue section temperature and/or the partial pressures of the solvents. A continuous solvent flow can be generated by applying the thin tissue section onto a porous support which supplies solvent to the rear surface of the thin tissue section.

Preparation of thin tissue sections for imaging mass spectrometry

The invention relates to preparing a matrix layer on a sample support for mass spectrometric analysis. An aspect of the invention includes detecting a light signal that is attenuated, reflected or scattered by the matrix layer, and using the light signal to examine the matrix layer or to regulate the preparation of the matrix layer.

Preparation of a matrix layer for spectrometry

The invention relates to the determination and visualization of the spatial distribution of tissue states in histologic tissue sections on the basis of mass spectrometric signals acquired so as to be spatially resolved. The invention provides a method which determines the tissue state for the tissue spots as a state characteristic, which is calculated as a mathematical or logical expression from at least two mass signals of this tissue spot, and which indicates the tissue state as a gray-level or false-color image in one or two dimensions.

Mass spectrometric differentiation of tissue states

A method for applying MALDI matrix substances to a surface, especially a histologic thin tissue section, for spatially-resolved mass spectrometric measurements of substance distributions in or on the surface uses vibration to nebulize a solution of the matrix substance without the assistance of a gas and deposits the nebulized droplets, preferably cyclically, on the surface.

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Tarmstedt, Germany

Martin Schürenberg