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1. 发明授权

US07815803B2 Preparation of samples for LC-MS/MS using magnetic particles 有权
标题翻译：使用磁性颗粒制备LC-MS / MS样品
公开(公告)号：US07815803B2
公开(公告)日：2010-10-19
申请号：US12133545
申请日：2008-06-05
申请人： Uwe Kobold , Albert Geiger , Rupert Herrmann , Michael Vogeser
发明人： Uwe Kobold , Albert Geiger , Rupert Herrmann , Michael Vogeser
IPC分类号： B01D15/08 , B01D59/44 , H01J49/00
CPC分类号： G01N33/6848 , B01D15/325 , B01J20/28009 , B01J20/287 , B01J20/3246 , B01J20/3276 , G01N33/54326 , G01N33/6842
摘要： The present invention provides a novel procedure of preparing samples for analysis by way of mass spectrometry, preferably LC-MS/MS. Accordingly, functionalized magnetic particles with a hydrophobic surface were used for extracting low molecular weight compounds from complex liquid biological samples such as plasma, serum, whole blood or hemolyzed blood. The method of the invention includes (a) contacting the sample with an amount of functionalized magnetic particles with a hydrophobic surface, (b) incubating the sample and the particles, thereby adsorbing the compound to the hydrophobic surface, (c) separating the particles by applying a magnetic field and removing the liquid, (d) optionally washing the particles, (e) eluting the compound from the particles.
摘要翻译：本发明提供了通过质谱法，优选LC-MS / MS制备用于分析的样品的新方法。因此，使用具有疏水性表面的官能化磁性颗粒从复杂的液体生物样品如血浆，血清，全血或溶血中提取低分子量化合物。本发明的方法包括（a）使样品与一定量的具有疏水性表面的官能化磁性颗粒接触，（b）将样品和颗粒温育，从而将化合物吸附到疏水表面，（c）将颗粒分离施加磁场并除去液体，（d）任选地洗涤颗粒，（e）从颗粒中洗脱化合物。

2. 发明申请

US20090253210A1 DIFFERENTIAL HEMOLYSIS OF A WHOLE BLOOD SAMPLE 有权
标题翻译：全血样品的差异分析
公开(公告)号：US20090253210A1
公开(公告)日：2009-10-08
申请号：US12328890
申请日：2008-12-05
申请人： Uwe Kobold , Thomas Duelffer , Rupert Herrmann , Herbert von der Eltz
发明人： Uwe Kobold , Thomas Duelffer , Rupert Herrmann , Herbert von der Eltz
IPC分类号： G01N33/48 , H01J49/00
CPC分类号： G01N30/06 , G01N30/603 , G01N30/7233 , G01N33/5002 , G01N2030/027 , Y10T436/24 , Y10T436/25
摘要： The invention relates to a method for differentially hemolyzing whole blood. It discloses method for detecting an analyte in a liquid sample known or suspected to comprise red blood cells and suspected or known to comprise eukaryotic cells, the method comprising the steps of processing said liquid sample with a membrane solubilizing agent under conditions appropriate to lyse cell membranes of red blood cells and at the same time not to cause precipitation of sample constituents, subjecting the processed sample to a chromatographic separation, and detecting the analyte. The differential hemolysis of red blood cells is of advantage in a method of detecting an analyte in a liquid sample that may comprise both erythrocytes as well as nucleated cells. The differential solubilization of red blood cells can be easily combined with an online detection methodology, like LC-MS, and is advantageous in the detection of many analytes, e.g. in the detection of folate or of immunosuppressive drugs, like tacrolimus or sirolimus.
摘要翻译：本发明涉及一种使全血不同溶血的方法。它公开了用于检测已知或怀疑包含红细胞并且怀疑或已知包含真核细胞的液体样品中的分析物的方法，所述方法包括以下步骤：在适合于裂解细胞膜的条件下用膜增溶剂处理所述液体样品的红细胞，同时不会引起样品成分沉淀，对经处理的样品进行色谱分离，并检测分析物。在检测可能包含红细胞和有核细胞的液体样品中的分析物的方法中，红细胞的差异溶血是有利的。红细胞的差异溶解可以容易地与诸如LC-MS的在线检测方法组合，并且在许多分析物的检测中是有利的，例如，在检测叶酸或免疫抑制药物，如他克莫司或西罗莫司。

3. 发明申请

US20090090855A1 PREPARATION OF SAMPLES FOR LC-MS/MS USING MAGNETIC PARTICLES 有权
标题翻译：使用磁性颗粒制备LC-MS / MS样品
公开(公告)号：US20090090855A1
公开(公告)日：2009-04-09
申请号：US12133545
申请日：2008-06-05
申请人： Uwe Kobold , Albert Geiger , Rupert Herrmann , Michael Vogeser
发明人： Uwe Kobold , Albert Geiger , Rupert Herrmann , Michael Vogeser
IPC分类号： H01J49/00 , B01D15/26
CPC分类号： G01N33/6848 , B01D15/325 , B01J20/28009 , B01J20/287 , B01J20/3246 , B01J20/3276 , G01N33/54326 , G01N33/6842
摘要： The present invention provides a novel procedure of preparing samples for analysis by way of mass spectrometry, preferably LC-MS/MS. Accordingly, functionalized magnetic particles with a hydrophobic surface were used for extracting low molecular weight compounds from complex liquid biological samples such as plasma, serum, whole blood or hemolyzed blood. The method of the invention includes (a) contacting the sample with an amount of functionalized magnetic particles with a hydrophobic surface, (b) incubating the sample and the particles, thereby adsorbing the compound to the hydrophobic surface, (c) separating the particles by applying a magnetic field and removing the liquid, (d) optionally washing the particles, (e) eluting the compound from the particles.
摘要翻译：本发明提供了通过质谱法，优选LC-MS / MS制备用于分析的样品的新方法。因此，使用具有疏水性表面的官能化磁性颗粒从复杂的液体生物样品如血浆，血清，全血或溶血中提取低分子量化合物。本发明的方法包括（a）使样品与一定量的具有疏水性表面的官能化磁性颗粒接触，（b）将样品和颗粒温育，从而将化合物吸附到疏水表面，（c）将颗粒分离施加磁场并除去液体，（d）任选地洗涤颗粒，（e）从颗粒中洗脱化合物。

4. 发明授权

US5631140A Method for the quantitative determination of glycated proteins 失效
标题翻译：糖化蛋白定量测定方法
公开(公告)号：US5631140A
公开(公告)日：1997-05-20
申请号：US503224
申请日：1995-07-17
申请人： Uwe Kobold , Doris Renauer , Andreas Finke , Johann Karl
发明人： Uwe Kobold , Doris Renauer , Andreas Finke , Johann Karl
IPC分类号： C12Q1/37 , G01N30/02 , G01N30/88 , G01N33/66 , G01N33/68 , G01N33/72 , C12Q1/34
CPC分类号： G01N33/6842 , C12Q1/37 , G01N33/68 , G01N33/723 , G01N2030/027
摘要： Method for the quantitative determination of glycated protein in particular haemoglobin and HbA1c, wherein the respective sample is firstly contacted with a proteolytic enzyme and subsequently a non-immunological chromatographic separation process is carried out.
摘要翻译：用于定量测定糖化蛋白质，特别是血红蛋白和HbA1c的方法，其中各样品首先与蛋白水解酶接触，随后进行非免疫色谱分离过程。

5. 发明授权

US08003400B2 Measurement of vitamin D 有权
标题翻译：维生素D的测定
公开(公告)号：US08003400B2
公开(公告)日：2011-08-23
申请号：US12326972
申请日：2008-12-03
申请人： Uwe Kobold , Thomas Duelffer , Michael Grol , Rupert Herrmann , Herbert Von der Eltz , Leopold Von Proff
发明人： Uwe Kobold , Thomas Duelffer , Michael Grol , Rupert Herrmann , Herbert Von der Eltz , Leopold Von Proff
IPC分类号： G01N33/00
CPC分类号： G01N33/82 , Y10T436/20 , Y10T436/203332
摘要： The present invention relates to a method of measuring a vitamin D metabolite in a sample, the method comprising the steps of (a) treating said sample with a vitamin D metabolite releasing reagent under conditions appropriate to release a vitamin D metabolite from vitamin D-binding protein and not to cause protein precipitation, (b) subjecting the treated sample obtained in step (a) to a chromatographic separation, and (c) measuring a vitamin D metabolite during or after said chromatographic separation. The present invention also relates to methods for determining the vitamin D status of a subject, for use in the diagnosis of disease, and to agents and kits for use in performing the methods of the invention.
摘要翻译：本发明涉及一种测量样品中维生素D代谢物的方法，所述方法包括以下步骤：（a）在适于从维生素D结合物释放维生素D代谢物的条件下用维生素D代谢物释放试剂处理所述样品蛋白质，不会引起蛋白质沉淀，（b）使步骤（a）中得到的处理样品进行色谱分离，和（c）在所述色谱分离期间或之后测量维生素D代谢物。本发明还涉及确定用于疾病诊断的受试者的维生素D状态的方法以及用于实施本发明的方法的试剂和试剂盒。

6. 发明授权

US07951598B2 Differential hemolysis of a whole blood sample 有权
标题翻译：全血样品的差异溶血
公开(公告)号：US07951598B2
公开(公告)日：2011-05-31
申请号：US12328890
申请日：2008-12-05
申请人： Uwe Kobold , Thomas Duelffer , Rupert Herrmann , Herbert von der Eltz
发明人： Uwe Kobold , Thomas Duelffer , Rupert Herrmann , Herbert von der Eltz
IPC分类号： G01N33/48
CPC分类号： G01N30/06 , G01N30/603 , G01N30/7233 , G01N33/5002 , G01N2030/027 , Y10T436/24 , Y10T436/25
摘要： The invention relates to a method for differentially hemolyzing whole blood. It discloses methods for detecting an analyte in a liquid sample known or suspected to contain red blood cells and suspected or known to contain eukaryotic cells, the method including the steps of processing the liquid sample with a membrane solubilizing agent under conditions appropriate to lyse cell membranes of red blood cells and at the same time not to cause precipitation of sample constituents, subjecting the processed sample to a chromatographic separation, and detecting the analyte. The differential hemolysis of red blood cells is of advantage in a method of detecting an analyte in a liquid sample that may contain both erythrocytes and nucleated cells. The differential solubilization of red blood cells can be easily combined with an online detection methodology, like LC-MS, and is advantageous in the detection of many analytes, e.g. in the detection of folate or of immunosuppressive drugs, like tacrolimus or sirolimus.
摘要翻译：本发明涉及一种使全血不同溶血的方法。它公开了用于检测已知或怀疑含有红细胞并且怀疑或已知含有真核细胞的液体样品中的分析物的方法，该方法包括在适于裂解细胞膜的条件下用膜增溶剂处理液体样品的步骤的红细胞，同时不会引起样品成分沉淀，对经处理的样品进行色谱分离，并检测分析物。在检测可能含有红细胞和有核细胞的液体样品中的分析物的方法中，红细胞的差异溶血是有利的。红细胞的差异溶解可以容易地与诸如LC-MS的在线检测方法组合，并且在许多分析物的检测中是有利的，例如，在检测叶酸或免疫抑制药物，如他克莫司或西罗莫司。

7. 发明授权

US07890268B2 De-novo sequencing of nucleic acids 失效
标题翻译：核酸的重新测序
公开(公告)号：US07890268B2
公开(公告)日：2011-02-15
申请号：US11304448
申请日：2005-12-14
申请人： Thomas Koch , Roderic Fuerst , Uwe Kobold , Dieter Heindl , Herbert von der Eltz , David Gelfand , Ivo Gut , Christoph Steinbeck
发明人： Thomas Koch , Roderic Fuerst , Uwe Kobold , Dieter Heindl , Herbert von der Eltz , David Gelfand , Ivo Gut , Christoph Steinbeck
IPC分类号： G06F19/00 , G01R23/16
CPC分类号： G06F19/18 , C12Q1/6872
摘要： The present invention is directed to an improved analysis procedure for the comparative sequencing of nucleic acids using multistage mass spectrometry. More precisely, the invention is directed to a method enabling the de-novo sequencing of nucleic acid molecules using multistage mass spectrometry.
摘要翻译：本发明涉及使用多级质谱法进行核酸比较测序的改进的分析程序。更准确地说，本发明涉及一种能够使用多级质谱法进行核酸分子的即时测序的方法。

8. 发明授权

US07863040B2 Ready-to-use whole blood collection vessel 有权
标题翻译：即用型全血采集器
公开(公告)号：US07863040B2
公开(公告)日：2011-01-04
申请号：US12327854
申请日：2008-12-04
申请人： Werner Naser , Thomas Duelffer , Rupert Herrmann , Uwe Kobold , Herbert von der Eltz
发明人： Werner Naser , Thomas Duelffer , Rupert Herrmann , Uwe Kobold , Herbert von der Eltz
IPC分类号： C12M1/33 , C12M3/08
CPC分类号： G01N33/5002
摘要： The present invention relates to a sampling tube for collecting and processing a whole blood sample. The sampling tube contains a reagent for differential hemolysis of whole blood, wherein said reagent for differential hemolysis comprises a chemical for differential hemolysis and an anti-coagulant, and wherein said sampling tube is a ready-to-use and single-use sampling tube. It also relates to the use of said sampling tube in the processing of a whole blood sample for liquid chromatography and also to the use of a blood sample processed in such sampling tube in a liquid chromatography-based analysis.
摘要翻译：本发明涉及一种用于收集和处理全血样本的取样管。采样管含有用于全血差异溶血的试剂，其中所述用于差异溶血的试剂包括用于差异溶血的化学药剂和抗凝血剂，并且其中所述采样管是即用型和一次性采样管。它还涉及在液相色谱法的全血样品的处理中使用所述采样管以及在基于液相色谱的分析中使用在这种采样管中处理的血液样品。

9. 发明申请

US20090246814A1 REAGENT FOR DIGESTION OF HEMOGLOBIN 有权
标题翻译：用于消除HEMOGLOBIN的试剂
公开(公告)号：US20090246814A1
公开(公告)日：2009-10-01
申请号：US12330725
申请日：2008-12-09
申请人： Uwe Kobold , Thomas Dueiffer , Rupert Hermann , Bernd Vogt , Herbert von der Eltz
发明人： Uwe Kobold , Thomas Dueiffer , Rupert Hermann , Bernd Vogt , Herbert von der Eltz
IPC分类号： C12Q1/37 , C12P21/04 , C12M1/00
CPC分类号： G01N33/723 , G01N2333/95
摘要： The present invention relates to a reagent for digestion of hemoglobin comprising a buffer, pepsin and a 1,3-dialkyl-imidazolium salt. It also discloses to the use of this reagent in a method for digesting hemoglobin, in a method for detecting HbA1c, and to a sampling tube for collection of a whole blood sample comprising said reagent for digesting hemoglobin.
摘要翻译：本发明涉及一种用于消化血红蛋白的试剂，其包含缓冲液，胃蛋白酶和1,3-二烷基 - 咪唑鎓盐。还公开了在用于消化血红蛋白的方法中使用该试剂，在检测HbA1c的方法中，以及用于收集包含用于消化血红蛋白的所述试剂的全血样品的采样管。

10. 发明授权

US06235476B1 Process for detecting nucleic acids by mass determination 有权
标题翻译：通过质量测定检测核酸的方法
公开(公告)号：US06235476B1
公开(公告)日：2001-05-22
申请号：US09242536
申请日：1999-03-17
申请人： Frank Bergmann , Rupert Herrmann , Uwe Kobold
发明人： Frank Bergmann , Rupert Herrmann , Uwe Kobold
IPC分类号： C12Q168
CPC分类号： C12Q1/6872 , C12Q1/6827 , Y10T436/143333
摘要： A method for detecting nucleic acids by binding a probe P to a partial sequence S contained in the nucleic acid to produce a binding product B1, degrading the nucleic acid to produce a binding product B2 containing a partial nucleic acid F of a defined length and detecting the binding product B2 or the partial nucleic acid F a part based on its mass is particularly suitable for the parallel detection of nucleic acid of different sequences.
摘要翻译：通过将探针P与核酸中所含的部分序列S结合以产生结合产物B1来检测核酸的方法，使核酸降解以产生含有限定长度的部分核酸F的结合产物B2并检测结合产物B2或部分核酸F基于其质量的部分特别适用于不同序列的核酸的平行检测。

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