Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The invention relates to sample support plates with hydrophilic anchors in a strongly hydrophobic environment for mass spectroscopic analysis of biosubstances with ionization by matrix-assisted laser desorption and ionization (MALDI), procedures for manufacturing these sample supports, and connected procedures for loading these sample supports with biomolecular samples. The invention provides areas with affinity adsorbents adjacent to the hydrophilic anchors for purifying biosubstances and, if wanted, for performing an affinity selection of biosubstances, whereby the finally prepared matrix sample crystals with the biosubstances for the MALDI analysis are well localized on the hydrophilic anchors.

Abstract: The invention relates to the structure of sample support plates for the mass spectrometric analyses of samples with ionization by matrix-assisted laser desorption and ionization (MALDI). The invention consists in combining a very even substructure made from a mechanically stable material with a flush mounted cover made of plastic material of constant thickness to produce a composite sample support plate with a very even surface. The plastic cover is inexpensive to make, must only be used once and helps prevent the substance-memory problem. The surface and material of the plastic cover can be optimized for MALDI. The preferred embodiment of the composite plate has the overall dimensions of a microtiter plate.

Abstract: The invention refers to sample support plates for the mass spectrometric analysis of large molecules, preferrable biomolecules, methods for the manufacture of such sample support plates and methods for loading the sample support plates with samples of biomolecules from solutions together with matrix substance for the ionization of the biomolecules using matrix-assisted laser desorption (MALDI). The invention consists of making the surface of the sample support plate extremely hydrophobic, whereby a favorable structure of MALDI matrix crystals for effective ionization is generated when drying the sample droplets to sample spots. Using tiny, hydrophilic anchor areas for the sample droplets in this hydrophobic environment, the pipetting process is made much easier and the sample spots can be precisely located on the sample support plates.