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1. 发明申请

WO2014019943A1 DETECTION OF MIXTURES IN MASS-SPECTROMETRIC MICROBE IDENTIFICATION 审中-公开
标题翻译：检测质谱微量元素鉴定中的混合物
公开(公告)号：WO2014019943A1
公开(公告)日：2014-02-06
申请号：PCT/EP2013/065764
申请日：2013-07-25
申请人： BRUKER DALTONIK GMBH
发明人： FRANZEN, Jochen , KLEPEL, Stefan , KOSTRZEWA, Markus , MAIER, Thomas
IPC分类号： G01N33/68
CPC分类号： C12Q1/04 , G01N33/6848 , G01N2560/00 , G06F19/18
摘要： The invention relates to the identification of microbes in a sample by calculating the similarities between a mass spectrum of the sample and all reference spectra in a spectral library; it particularly concerns the detection of microbe mixtures. Microbe mixtures are probably present if several microbe species which are not closely related to each other are among the score list containing the most similar reference spectra. Methods are proposed which (1) operate with a list of the relationships, (2) determine the similarity between the reference spectra of the different microbe species of the score list, or (3) always carry out a mixture analysis in accordance with document DE 10 2009 007 266 Al from the score list, with the generation of combination spectra, and only afterwards check the similarity of the combined spectra and thus the relationship between the microbe strains concerned.
摘要翻译：本发明涉及通过计算样品的质谱和光谱库中所有参考光谱之间的相似性来鉴定样品中的微生物; 它特别涉及微生物混合物的检测。如果几个彼此不紧密相关的微生物种类在包含最相似的参考光谱的评分列表中，则可能存在微生物混合物。提出了（1）用关系列表进行操作的方法，（2）确定得分列表的不同微生物种的参考光谱之间的相似性，或（3）总是按照DE文件进行混合分析 10 2009 007 266 A1从分数列表中，与生成组合谱，后来检查组合光谱的相似性，从而检查相关微生物菌株之间的关系。

2. 发明申请

WO2011045144A1 ION CYCLOTRON RESONANCE MEASURING CELLS WITH HARMONIC TRAPPING POTENTIAL 审中-公开
标题翻译：离子循环谐振测量细胞与谐波捕获潜力
公开(公告)号：WO2011045144A1
公开(公告)日：2011-04-21
申请号：PCT/EP2010/063698
申请日：2010-09-17
申请人： BRUKER DALTONIK GMBH , NIKOLAEV, Evgenij , BOLDIN, Ivan , FRANZEN, Jochen
发明人： NIKOLAEV, Evgenij , BOLDIN, Ivan , FRANZEN, Jochen
IPC分类号： H01J49/38
CPC分类号： H01J49/38
摘要： The invention relates to devices and methods for the acquisition of mass spectra with very high mass resolution in ion cyclotron resonance mass spectrometers and methods to produce the devices. The invention presents cylindrical ICR measuring cells with special electrode geometries to generate harmonic trapping potentials for orbiting ions up to the walls of the cell. Only a single DC trapping voltage has to be applied to create the harmonic trapping potential distribution. The sheath of the cylindrical cell is divided by longitudinal gaps into a multitude of sheath electrodes, which either have to carry layers with resistance profiles able to generate parabolic voltage profiles along the sheath electrodes, or which form sheath electrodes of varying width by parabolic gaps, able to create complicated potential distributions which are harmonic on average for orbiting ions. Orbiting ions of a given mass m/z can oscillate harmonically in axial direction with exactly the same oscillation frequency, independent of the radius of their orbit and of their axial osci llation amplitude. Ideally, the cylinders are closed by endcaps with rotationally hyperbolic form, divided into partial electrodes like in infinity cells. The ions can then be excited to their cyclotron motions by dipolar excitation fields also uniformly filling the ICR cell up to the endcaps. The ion clouds orbiting on their cyclotron trajectory are kept together for much longer periods than was possible hitherto, even if they orbit near the sheath electrodes. The image currents thus give rise to minute-long transients, from which mass spectra with ultrahigh mass resolution can be obtained.
摘要翻译：本发明涉及用于在离子回旋共振质谱仪中以非常高质量分辨率获取质谱的装置和方法以及用于生产该装置的方法。本发明提出了具有特殊电极几何形状的圆柱形ICR测量单元，以产生用于将离子旋转至电池壁的谐波陷阱电位。必须应用单个DC捕获电压来产生谐波捕获电位分布。圆柱形电池的护套由纵向缝隙分成多个护套电极，这些护套电极必须携带具有能够沿着护套电极产生抛物线电压分布的电阻分布的层，或者通过抛物线间隙形成不同宽度的护套电极，能够创建复杂的电位分布，它们是轨道离子的平均谐波。给定质量m / z的轨道离子可以以完全相同的振荡频率在轴向上谐振振荡，与轨道的半径及其轴向振幅无关。理想情况下，气瓶由具有旋转双曲形式的端盖封闭，分成如无限细胞中的部分电极。然后可以通过偶极激发场将离子激发到它们的回旋加速器运动，同时也将ICR单元均匀地填充到端盖。在其回旋加速器轨迹上运动的离子云保持在一段比迄今为止更长的时间段，即使它们在护套电极附近轨道运行。因此，图像电流产生微小的瞬变，可以获得具有超高质量分辨率的质谱。

3. 发明申请

WO2011061147A1 UTILIZING GAS FLOWS IN MASS SPECTROMETERS 审中-公开
标题翻译：在大量光谱仪中使用气体流量
公开(公告)号：WO2011061147A1
公开(公告)日：2011-05-26
申请号：PCT/EP2010/067481
申请日：2010-11-15
申请人： BRUKER DALTONIK GMBH , FRANZEN, Jochen
发明人： FRANZEN, Jochen
IPC分类号： H01J49/42
CPC分类号： H01J49/421 , H01J49/401
摘要： The invention relates to ions guided by gas flows in mass spectrometers, particularly in RF multipole systems, and to RF quadrupole mass filters and their operation with gas flows in tandem mass spectrometers. The invention provides a tandem mass spectrometer in which the RF quadrupole mass filter is operated at vacuum pressures in the medium vacuum pressure regime, utilizing a gas flow to drive the ions are through the mass filter. Vacuum pressures between 0.5 to 10 pascal are maintained in the mass filter. The mass filter may be enclosed by a narrow enclosure to guide the gas flow. The quadrupole mass filter may be followed by an RF multipole system, operated at the same vacuum pressure, serving as fragmentation cell to fragment the selected parent ions. The fragmentation cell may be enclosed by the same enclosure which already encloses the mass filter, so the ions may be driven by the same gas flow at the same vacuum pressure, greatly simplifying the required vacuum pumping system in tandem mass spectrometers. There are many other applications utilizing gas flows including supersonic gas jets in mass spectrometry.
摘要翻译：本发明涉及在质谱仪，特别是RF多极系统中的气流引导的离子，以及RF串联质谱仪和其在串联质谱仪中的气流的操作。本发明提供一种串联质谱仪，其中RF四极杆质量过滤器在中等真空压力状态下在真空压力下操作，利用气流驱动离子通过质量过滤器。在质量过滤器中保持0.5至10帕斯卡之间的真空压力。质量过滤器可以被狭窄的外壳包围以引导气流。四极质量过滤器之后可以是在相同的真空压力下操作的RF多极体系统，用作碎裂细胞以分离所选择的母体离子。分裂单元可以被已经包围质量过滤器的相同外壳封闭，因此离子可以在相同的真空压力下由相同的气流驱动，大大简化了串联质谱仪中所需的真空泵送系统。在质谱法中还有许多其他的应用，包括使用超声波气体射流的气流。

4. 发明申请

WO2012016929A1 MASS SPECTROMETRIC DIAGNOSIS OF SEPSIS WITHOUT BLOOD CULTURE 审中-公开
标题翻译：没有血液文化的食物的大量光谱诊断
公开(公告)号：WO2012016929A1
公开(公告)日：2012-02-09
申请号：PCT/EP2011/063120
申请日：2011-07-29
申请人： BRUKER DALTONIK GMBH , KOSTRZEWA, Markus , PUSCH, Wolfgang , MAIER, Thomas , MICHELMANN, Karsten , FRANZEN, Jochen
发明人： KOSTRZEWA, Markus , PUSCH, Wolfgang , MAIER, Thomas , MICHELMANN, Karsten , FRANZEN, Jochen
IPC分类号： C12Q1/04 , G01N33/68 , C12M1/34 , C12M3/00
CPC分类号： C12Q1/04 , G01N21/77 , G01N33/6851 , G01N2021/7786 , G01N2800/26
摘要： The invention relates to methods and instruments for the rapid detection and rapid mass spectrometric identification of microbial infective agents in blood or other body fluids. The invention recognizes that blood is not a good environment for the cultivation of microbes and provides a method which (a) largely destroys or dissolves the human particles in body fluids, such as erythrocytes and leukocytes in blood, without impairing the ability of the microbes to reproduce, (b) separates the microbial pathogens from the fluid, (c) cultivates them in a nutrient broth which contains none of the antimicrobial components of the body fluids, (d) separates them from the nutrient broth, and (e) identifies the microbes by a mass spectrum of the microbial proteins. The dissolution of the human particles also releases the microbes nesting in macrophages. The cultivation in an optically clear nutrient broth with optimum composition not only accelerates the propagation of the microbes compared to all other cultivation methods, but also makes it possible to continuously measure their quantitative growth starting from a low microbe density. This firstly allows the mass spectrometric identification to be carried out at the earliest possible time, secondly provides a positive detection of microbes far ahead of their identification, which can be lifesaving for the patient; and thirdly makes it possible to start the determination of resistances early.
摘要翻译：本发明涉及快速检测和快速质谱鉴定血液或其他体液中微生物感染因子的方法和仪器。本发明认识到，血液不是微生物培养的良好环境，并且提供了（a）大大地破坏或溶解体液中的人体颗粒如血液中的红细胞和白细胞的方法，而不会损害微生物的能力（b）将微生物病原体从流体中分离出来，（c）在不含体液的抗微生物成分的营养液中培养它们，（d）将其与营养肉汤分开，以及（e）微生物通过微生物蛋白的质谱。人类颗粒的溶解也释放出嵌入巨噬细胞的微生物。在具有最佳组成的光学透明营养肉汤中培养不仅加速微生物与所有其他培养方法相比的繁殖，而且可以从低微生物密度开始连续测量其定量生长。这首先允许在最早的时候进行质谱鉴定，其次提供远远超出其鉴定的微生物的阳性检测，这可以为患者提供救生。第三，可以提前开始确定电阻。

5. 发明申请

WO2007098859A1 MASS SPECTROMETRIC DETERMINATION OF BLOOD ENZYME ACTIVITY 审中-公开
标题翻译：血清酶活性的质谱测定
公开(公告)号：WO2007098859A1
公开(公告)日：2007-09-07
申请号：PCT/EP2007/001299
申请日：2007-02-15
申请人： BRUKER DALTONIK GMBH , FRANZEN, Jochen , MICHELMANN, Karsten , KOSTRZEWA, Markus
发明人： FRANZEN, Jochen , MICHELMANN, Karsten , KOSTRZEWA, Markus
IPC分类号： G01N33/68 , C12Q1/37 , C12Q1/56
CPC分类号： G01N33/6848 , C12Q1/37 , C12Q1/56 , G01N2333/75 , G01N2333/976
摘要： The invention relates to the determination of the nature and strength of enzymatic activity in blood using mass spectrometric measurement of a profile of the reaction products. The determination of the enzymatic activity can be used for medical diagnostics, for example, and also to check the effectiveness of medication. The invention provides a method whereby adding probe substances usually not present in blood offers standardized substrates for measuring the enzymatic activity. The probe substances may be added to whole blood, plasma, or serum. The mass spectrometric measurement of the reaction products, after their reversible immobilization on actively binding surfaces of solids, for example, can deliver biomarker patterns of the reaction products which may be indicators for metabolic anomalies or diseases, since these are often accompanied by the formation or activation of characteristic enzymes.
摘要翻译：本发明涉及使用反应产物分布的质谱测量来测定血液中酶活性的性质和强度。酶活性的测定可以用于医学诊断，例如，以及检查药物的有效性。本发明提供了一种添加通常不存在于血液中的探针物质提供用于测量酶活性的标准化底物的方法。探针物质可以添加到全血，血浆或血清中。反应产物在其可固定地固定在固体的活性结合表面上之后的质谱测量可以提供反应产物的生物标志物模式，其可以是代谢异常或疾病的指标，因为它们通常伴随着形成或特征酶的活化。

6. 发明授权

EP2601304B1 MASS SPECTROMETRIC DIAGNOSIS OF SEPSIS WITHOUT BLOOD CULTURE 有权转让
公开(公告)号：EP2601304B1
公开(公告)日：2020-11-04
申请号：EP11749128.2
申请日：2011-07-29
申请人： Bruker Daltonik GmbH
发明人： KOSTRZEWA, Markus , PUSCH, Wolfgang , MAIER, Thomas , MICHELMANN, Karsten , FRANZEN, Jochen
IPC分类号： C12Q1/04 , G01N33/68 , C12M1/34 , C12M3/00

7. 发明授权

EP2489061B1 ION CYCLOTRON RESONANCE MEASURING CELLS WITH HARMONIC TRAPPING POTENTIAL 有权转让
公开(公告)号：EP2489061B1
公开(公告)日：2019-02-27
申请号：EP10757756.1
申请日：2010-09-17
申请人： Bruker Daltonik GmbH
发明人： NIKOLAEV, Evgenij , BOLDIN, Ivan , FRANZEN, Jochen
IPC分类号： H01J49/38

8. 发明公开

EP2489061A1 ION CYCLOTRON RESONANCE MEASURING CELLS WITH HARMONIC TRAPPING POTENTIAL 有权转让
标题翻译： IONENZYKLOTRONRESONANZ-MESSZELLEN MIT HARMONISCHEM FANGPOTENZIAL
公开(公告)号：EP2489061A1
公开(公告)日：2012-08-22
申请号：EP10757756.1
申请日：2010-09-17
申请人： Bruker Daltonik GmbH
发明人： NIKOLAEV, Evgenij , BOLDIN, Ivan , FRANZEN, Jochen
IPC分类号： H01J49/38
CPC分类号： H01J49/38
摘要： The invention relates to devices and methods for the acquisition of mass spectra with very high mass resolution in ion cyclotron resonance mass spectrometers and methods to produce the devices. The invention presents cylindrical ICR measuring cells with special electrode geometries to generate harmonic trapping potentials for orbiting ions up to the walls of the cell. Only a single DC trapping voltage has to be applied to create the harmonic trapping potential distribution. The sheath of the cylindrical cell is divided by longitudinal gaps into a multitude of sheath electrodes, which either have to carry layers with resistance profiles able to generate parabolic voltage profiles along the sheath electrodes, or which form sheath electrodes of varying width by parabolic gaps, able to create complicated potential distributions which are harmonic on average for orbiting ions. Orbiting ions of a given mass m/z can oscillate harmonically in axial direction with exactly the same oscillation frequency, independent of the radius of their orbit and of their axial osci llation amplitude. Ideally, the cylinders are closed by endcaps with rotationally hyperbolic form, divided into partial electrodes like in infinity cells. The ions can then be excited to their cyclotron motions by dipolar excitation fields also uniformly filling the ICR cell up to the endcaps. The ion clouds orbiting on their cyclotron trajectory are kept together for much longer periods than was possible hitherto, even if they orbit near the sheath electrodes. The image currents thus give rise to minute-long transients, from which mass spectra with ultrahigh mass resolution can be obtained.

9. 发明授权

EP2880450B1 DETECTION OF MIXTURES IN MASS-SPECTROMETRIC MICROBE IDENTIFICATION 有权转让
标题翻译：质谱法检测混合物中微量元素的鉴定
公开(公告)号：EP2880450B1
公开(公告)日：2017-11-29
申请号：EP13742213.5
申请日：2013-07-25
申请人： Bruker Daltonik GmbH
发明人： FRANZEN, Jochen , KLEPEL, Stefan , KOSTRZEWA, Markus , MAIER, Thomas
IPC分类号： G01N33/68
CPC分类号： C12Q1/04 , G01N33/6848 , G01N2560/00 , G06F19/18

10. 发明公开

EP2880450A1 DETECTION OF MIXTURES IN MASS-SPECTROMETRIC MICROBE IDENTIFICATION 有权转让
标题翻译： DETEKTION VON MISCHUNGEN BEI DER MIKROBENDETEKTION DURCH MASSENSPEKTROMETRIE
公开(公告)号：EP2880450A1
公开(公告)日：2015-06-10
申请号：EP13742213.5
申请日：2013-07-25
申请人： Bruker Daltonik GmbH
发明人： FRANZEN, Jochen , KLEPEL, Stefan , KOSTRZEWA, Markus , MAIER, Thomas
IPC分类号： G01N33/68
CPC分类号： C12Q1/04 , G01N33/6848 , G01N2560/00 , G06F19/18
摘要： The invention relates to the identification of microbes in a sample by calculating the similarities between a mass spectrum of the sample and all reference spectra in a spectral library; it particularly concerns the detection of microbe mixtures. Microbe mixtures are probably present if several microbe species which are not closely related to each other are among the score list containing the most similar reference spectra. Methods are proposed which (1) operate with a list of the relationships, (2) determine the similarity between the reference spectra of the different microbe species of the score list, or (3) always carry out a mixture analysis in accordance with document DE 10 2009 007 266 Al from the score list, with the generation of combination spectra, and only afterwards check the similarity of the combined spectra and thus the relationship between the microbe strains concerned.
摘要翻译：本发明涉及通过计算样品的质谱和光谱库中所有参考光谱之间的相似性来鉴定样品中的微生物; 它特别涉及微生物混合物的检测。如果几个彼此不紧密相关的微生物种类在包含最相似的参考光谱的评分列表中，则可能存在微生物混合物。提出了（1）用关系列表进行操作的方法，（2）确定得分列表的不同微生物种的参考光谱之间的相似性，或（3）总是按照DE文件进行混合分析 10 2009 007 266 A1从得分列表中，产生组合谱，并且之后才检查组合谱的相似性，从而检查相关微生物菌株之间的关系。

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