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1. 发明授权

US6423966B2 Method and apparatus for maldi analysis 有权
公开(公告)号：US6423966B2
公开(公告)日：2002-07-23
申请号：US48362900
申请日：2000-01-14
申请人： SEQUENOM INC
发明人： HILLENKAMP FRANZ , LOUGH DAVID M , HIGGINS G SCOTT , REUTER DIRK
IPC分类号： G01N27/62 , B01D59/44 , C40B60/14 , G01N27/64 , H01J49/00 , H01J49/04 , H01J49/10 , H01J49/16
CPC分类号： H01J49/164 , B01J2219/00387 , C40B60/14 , H01J49/0418
摘要： 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 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.

2. 发明专利

DE69738206D1 未知
公开(公告)号：DE69738206D1
公开(公告)日：2007-11-22
申请号：DE69738206
申请日：1997-11-06
申请人： SEQUENOM INC
发明人： KOESTER HUBERT , LITTLE DANIEL P , BRAUN ANDREAS , JURINKE CHRISTIAN , VAN DEN BOOM DIRK , XIANG GUOBING , LOUGH DAVID M , RUPPERT ANDREAS , HILLENKAMP FRANZ
IPC分类号： C12Q1/68 , B01J19/00 , B01L3/02 , C07B61/00 , C07F9/24 , C07H21/00 , C40B40/06 , C40B40/10 , C40B60/14 , G01N35/00 , G01N35/10
摘要： 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 processed 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. A method and apparatus for creating multiple branch wells from a parent well is disclosed. A multiple branching sub is provided for placement at a branching node of a well. Such sub includes a branching chamber and a plurality of branching outlet members. The outlet members during construction of the branching sub, have previously been distorted into oblong shapes so that all of the branching outlet members fit within an imaginary cylinder which is coaxial with and substantially the same radius as the branching chamber. After deployment of the branching sub via a parent casing in the well, a forming tool is lowered to the interior of the sub. The outlet members are extended outwardly by the forming tool and simultaneously formed into substantially round tubes. Next, each outlet member is plugged with cement, after which each branch well is drilled through a respective outlet member. If desired, each branch may be lined with casing and sealed to a branching outlet by means of a casing hanger. A manifold placed in the branching chamber controls the production of each branch well to the parent well.

3. 发明专利

AU3896799A Infrared matrix-assisted laser desorption/ionization mass spectrometric analysisof macromolecules 未知
公开(公告)号：AU3896799A
公开(公告)日：1999-11-23
申请号：AU3896799
申请日：1999-05-07
申请人： SEQUENOM INC , HILLENKAMP FRANZ
发明人： HILLENKAMP FRANZ , KOSTER HUBERT
IPC分类号： G01N27/62 , C12Q1/68 , C12Q1/6872 , G01N27/64 , H01J49/04 , H01J49/16
摘要： Mass spectrometry of large nucleic acids by infrared Matrix-Assisted Laser Desorption/Ionization (MALDI) using a liquid matrix is reported.

4. 发明专利

CA2237946C METHOD AND APPARATUS FOR MALDI ANALYSIS 未知
公开(公告)号：CA2237946C
公开(公告)日：2003-06-17
申请号：CA2237946
申请日：1997-09-19
申请人： SEQUENOM INC
发明人： LOUGH DAVID M , HIGGINS SCOTT , REUTER DIRK , HILLENKAMP FRANZ
IPC分类号： G01N27/62 , B01D59/44 , C40B60/14 , G01N27/64 , H01J49/00 , H01J49/04 , H01J49/10 , H01J49/16
摘要： 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 velocit y 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- a nd 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.

5. 发明专利

AU724884B2 Method and apparatus for maldi analysis 未知
公开(公告)号：AU724884B2
公开(公告)日：2000-10-05
申请号：AU4342397
申请日：1997-09-19
申请人： SEQUENOM INC
发明人： HILLENKAMP FRANZ , HIGGINS SCOTT , LOUGH DAVID M , REUTER DIRK
IPC分类号： G01N27/62 , B01D59/44 , C40B60/14 , G01N27/64 , H01J49/00 , H01J49/04 , H01J49/10 , H01J49/16
摘要： 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.

6. 发明专利

DE69718438D1 未知
公开(公告)号：DE69718438D1
公开(公告)日：2003-02-20
申请号：DE69718438
申请日：1997-09-19
申请人： SEQUENOM INC
发明人： HILLENKAMP FRANZ
IPC分类号： G01N27/62 , B01D59/44 , C40B60/14 , G01N27/64 , H01J49/00 , H01J49/04 , H01J49/10 , H01J49/16
摘要： 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.

7. 发明专利

NO20005539A 未知
公开(公告)号：NO20005539A
公开(公告)日：2001-01-05
申请号：NO20005539
申请日：2000-11-02
申请人： SEQUENOM INC
发明人： HILLENKAMP FRANZ , KOESTER HUBERT
IPC分类号： G01N27/62 , C12Q1/68 , G01N27/64 , H01J49/04 , H01J49/16 , G01N30/72
CPC分类号： H01J49/164 , B01J2219/00702 , C12Q1/6872 , Y10T436/11 , Y10T436/14 , Y10T436/142222 , Y10T436/143333 , Y10T436/24 , Y10T436/25 , Y10T436/25875

8. 发明专利

CA2328110A1 INFRARED MATRIX-ASSISTED LASER DESORPTION/IONIZATION MASS SPECTROMETRIC ANALYSIS OF MACROMOLECULES 未知
公开(公告)号：CA2328110A1
公开(公告)日：1999-11-11
申请号：CA2328110
申请日：1999-05-07
申请人： SEQUENOM INC
发明人： HILLENKAMP FRANZ , KOSTER HUBERT
IPC分类号： G01N27/62 , C12Q1/68 , C12Q1/6872 , G01N27/64 , H01J49/04 , H01J49/16
摘要： 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 (IRMALDI) 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.

9. 发明申请

WO9957318A3 INFRARED MATRIX-ASSISTED LASER DESORPTION/IONIZATION MASS SPECTROMETRIC ANALYSIS OF MACROMOLECULES 审中-公开
标题翻译：红外线矩阵辅助激光解吸/离子化大分子光谱分析
公开(公告)号：WO9957318A3
公开(公告)日：2000-03-23
申请号：PCT/US9910251
申请日：1999-05-07
申请人： SEQUENOM INC , HILLENKAMP FRANZ , KOESTER HUBERT
发明人： HILLENKAMP FRANZ , KOESTER HUBERT
IPC分类号： G01N27/62 , C12Q1/68 , G01N27/64 , H01J49/04 , H01J49/16
CPC分类号： H01J49/164 , B01J2219/00702 , C12Q1/6872 , Y10T436/11 , Y10T436/14 , Y10T436/142222 , Y10T436/143333 , Y10T436/24 , Y10T436/25 , Y10T436/25875
摘要： 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.
摘要翻译：提供了含有吸收红外（IR）辐射的生物大分子如核酸分子或多肽和液体基质的混合物。这些混合物可用于通过IR基质辅助激光解吸/电离（IR-MALDI）质谱分析生物大分子。还提供了使用IR-MALDI质谱法分析生物大分子的方法。例如，提供了用于检测样品中生物大分子的存在或身份或用于测序生物大分子的方法。

10. 发明专利

NO20005539L 未知
公开(公告)号：NO20005539L
公开(公告)日：2001-01-05
申请号：NO20005539
申请日：2000-11-02
申请人： SEQUENOM INC
发明人： HILLENKAMP FRANZ , KOESTER HUBERT
IPC分类号： G01N27/62 , C12Q1/68 , C12Q1/6872 , G01N27/64 , H01J49/04 , H01J49/16 , G01N30/72
摘要： Mass spectrometry of large nucleic acids by infrared Matrix-Assisted Laser Desorption/Ionization (MALDI) using a liquid matrix is reported.

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