Sequenom, Inc.

Finnigan Corporation

Finnigan Mat Gmbh

Covalx Ag

Franz Hillenkamp

Dirk Johannes Van Den Boom

Hubert Köster

Andreas Braun

Christian Jurinke

David M Lough

G Scott Higgins

Andreas Ruppert

Dirk Reuter

Michael Karas

Daniel P Little

Alexis Nazabal

Ryan Wenzel

Ulrich Giessmann

Ulrich Rohling

Ulrich-Peter Giessmann

Described here is a detector for measuring heavy mass ions with high sensitivity and low saturation for time-of-flight mass spectrometry and a detector housing for selecting between multiple detectors.

Detector device for high mass ion detection, a method for analyzing ions of high mass and a device for selection between ion detectors

Provided are methods for detecting a target nucleic acid in a biological sample using RNA amplification. In an embodiment, provided is a method that comprises (a) amplifying a target nucleic acid, or portion thereof, using a primer comprising a sequence that is complementary to a polynucleotide sequence in the target nucleic acid, or a complement thereof, and a sequence that encodes an RNA polymerase promoter; (b) synthesizing RNA using an RNA polymerase that recognizes the promoter; and (c) detecting the presence or absence of the resulting RNA using mass spectrometry thereby detecting the presence or absence of the target nucleic acid in the biological sample.

DNA diagnostics based on mass spectrometry

Fast and highly accurate mass spectrometry-based processes for detecting a particular nucleic acid sequence in a biological sample are provided. Depending on the sequence to be detected, the processes can be used, for example, to diagnose a genetic disease or chromosomal abnormality; a predisposition to a disease or condition, infection by a pathogenic organism, or for determining identity or heredity.

Matrix assisted laser desorption/ionization (MALDI) is performed in a manner that thermalizes large analyte ions in a plume of desorbed material for spectroscopic analysis. The thermalized ions have a low or zero mean velocity and are presented at a well-defined instant in time, reducing artifacts and sharpening the spectral peaks. In one embodiment the light is delivered to a matrix or sample holder having a cover, baffle or compartment. The baffle or compartment impedes or contains a plume of desorbed material and the analyte undergoes collisions to lower its mean velocity and directionality. Thus &ldquo;thermalized&rdquo; the analyte ions are passed to a mass analysis instrument.

Method and apparatus for MALDI analysis

Mass spectrometry of large nucleic acids by infrared Matrix-Assisted Laser Desorption/Ionization (MALDI) using a liquid matrix is reported.

IR MALDI mass spectrometry of nucleic acids using liquid matrices

IR-MALDI mass spectrometry of nucleic acids using liquid matrices

Mixtures containing a biological macromolecule, such as a nucleic acid molecule or a polypeptide, and a liquid matrix, which absorbs infrared (IR) radiation, are provided. These mixtures are useful for analysis of the biological macromolecule by IR matrix assisted laser desorption/ionization (IR-MALDI) mass spectrometry. Also provided are processes for analyzing a biological macromolecule using IR-MALDI mass spectrometry. For example, processes for detecting the presence or identity of a biological macromolecule in a sample, or for sequencing a biological macromolecule are provided.

Infrared matrix-assisted laser desorption/ionization mass spectrometric analysis of macromolecules

Matrix assisted laser desorption/ionization is performed,in a manner to thermalize large analyte ions in a plume of desorbed material for spectroscopic analysis. The thermalized ions have a low or zero mean velocity and are presented at a well-defined instant in time, reducing artifacts and sharpening the spectral peaks. In one embodiment the light is delivered to a matrix or sample holder having a cover, baffle or compartment. The baffle or compartment impedes or contains a plume of desorbed material and the analyte undergoes collisions to lower its mean velocity and directionality. Thus &ldquo;thermalized&rdquo; the analyte ions are passed to a mass analysis instrument. In a preferred embodiment an optical fiber butts up against a thin transparent plate on which the specimen resides, with the matrix side in a vacuum acceleration chamber. A mechanical stage moves the specimen in both the x- and y-directions to select a point on the specimen which is to receive the radiation. The use of a fiber optic illuminator allows the entire stage assembly to be subsumed essentially within the dimensions of a conventional stage. In other embodiments, a thermalizing compartment is provided in a capillary tube about the end of the illumination fiber and the sample matrix is deposited along the inner cylindrical wall of the tube, so the capillary forms a migration path to the outlet for thermalization of the desorbed analyte. In other embodiments microstructures having the shape of a small lean-to, overhang or perforated cover plate, or providing a high aspect surface texture, provide the necessary containment to promote thermalization of the released analyte. A thin layer or cover of fibrous or permeable material may also be used to thermalize the analyte before mass analysis, and in other embodiment this material may also act as the substrate. An automated instrument may include a fixed array of illumination fibers which are illuminated at different times to eject samples from a corresponding array of points on the specimen.

Method and apparatus for maldi analysis

Matrix assisted laser desorption/ionization is performed in a manner to thermalize large analyte ions in a plume of desorbed material for spectroscopic analysis. The thermalized ions have a low or zero mean velocity and are presented at a well-defined instant in time, reducing artifacts and sharpening the spectral peaks. In one embodiment the light is delivered to a matrix or sample holder having a cover, baffle or compartment. The baffle or compartment impedes or contains a plume of desorbed material and the analyte undergoes collisions to lower its mean velocity and directionality. Thus 'thermalized' the analyte ions are passed to a mass analysis instrument. In a preferred embodiment an optical fiber butts up against a thin transparent plate on which the specimen resides, with the matrix side in a vacuum acceleration chamber. A mechanical stage moves the specimen in both the x- and y-directions to select a point on the specimen which is to receive the radiation. The use of a fiber optic illuminator allows the entire stage assembly to be subsumed essentially within the dimensions of a conventional stage. In other embodiments, a thermalizing compartment is provided in a capillary tube about the end of the illumination fiber and the sample matrix is deposited along the inner cylindrical wall of the tube, so the capillary forms a migration path to the outlet for thermalization of the desorbed analyte. In other embodiments microstructures having the shape of a small lean-to, overhang or perforated cover plate, or providing a high aspect surface texture, provide the necessary containment to promote thermalization of the released analyte. A thin layer or cover of fibrous or permeable material may also be used to thermalize the analyte before mass analysis, and in another embodiment this material may also act as the substrate. An automated instrument may include a fixed array of illumination fibers which are illuminated at different times to eject samples from a corresponding array of points on the specimen.

Detector device for analyzing ions of high mass using a time-of-flight (TOF) analytical method, consisting of a mass spectrometer 1, accelerating electrodes 2 and a magnetic field and/or electric field, all of which serves to deflect secondary ions 5 emerging from a first conversion dynode 8, so that the secondary ions impinge according to polarity on a second 7 and third 7' conversion dynode.

Device and method for analyzing ions of high mass

The invention relates to a process for the laser desorption of analyte molecular ions, especially of biomolecules, from a specimen. The object of the invention is to improve a process of this type in such a way that intact desorption of biomolecules, preferably of large molecular mass, is also possible with a laser. This is achieved by using laser light of a wavelength of about 300 nm or greater than 300 nm and using a matrix which is able to absorb in the selected wavelength range.

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Munster, Germany

Franz Hillenkamp