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1. 发明授权

US10006076B2 Mass spectrometric diagnosis of sepsis without blood culture 有权
公开(公告)号：US10006076B2
公开(公告)日：2018-06-26
申请号：US14113354
申请日：2011-07-29
申请人： Jochen Franzen , Markus Kostrzewa , Thomas Maier , Karsten Michelmann , Wolfgang Pusch
发明人： Jochen Franzen , Markus Kostrzewa , Thomas Maier , Karsten Michelmann , Wolfgang Pusch
IPC分类号： C12Q1/04 , G01N33/68 , G01N21/77
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.

2. 发明申请

US20130095511A1 MASS SPECTROMETRIC MEASUREMENT OF B-LACTAMASE RESISTANCES 审中-公开
标题翻译： B-LACTAMASE RESISTANCES的质谱测量
公开(公告)号：US20130095511A1
公开(公告)日：2013-04-18
申请号：US13582372
申请日：2011-06-10
申请人： Markus Kostrzewa , Karsten Michelmann , Katrin Sparbier
发明人： Markus Kostrzewa , Karsten Michelmann , Katrin Sparbier
IPC分类号： C12Q1/18
CPC分类号： C12Q1/18 , C12Q1/34 , G01N33/6851 , G01N2333/986 , G01N2800/26 , G01N2800/44
摘要： The invention relates to the determination of resistances of microorganisms which produce β-lactamases, in particular “extended spectrum β-lactamases” (ESBL). The invention provides a method whereby the microbial resistance can be measured very simply and quickly by means of the catalytic effect of the microbially produced β-lactamases on β-lactam antibiotics, which consists in a hydrolytic cleavage of the β-lactam ring. The method determines the resistance of the bacteria a few hours after a suitable substrate, either a β-lactam antibiotic or a customized β-lactam derivative, has been added to a suspension of the microbes, by direct mass spectrometric measurement of the substrate breakdown caused by the β-lactamases.
摘要翻译：本发明涉及测定产生β-内酰胺酶的微生物的抗性，特别是“延长光谱β-内酰胺酶”（ESBL）。本发明提供了一种通过微生物产生的β-内酰胺酶对β-内酰胺抗生素的催化作用非常简单和快速地测量微生物抗性的方法，其中β-内酰胺抗生素包括β-内酰胺环的水解裂解。该方法通过直接质谱测量引起的底物破坏，在合适的底物（β-内酰胺抗生素或定制的β-内酰胺衍生物）已添加到微生物的悬浮液中后几小时确定细菌的抗性由β-内酰胺酶。

3. 发明授权

US08227748B2 Confining positive and negative ions in a linear RF ion trap 有权
标题翻译：将正离子和负离子限制在线性RF离子阱中
公开(公告)号：US08227748B2
公开(公告)日：2012-07-24
申请号：US12784473
申请日：2010-05-20
申请人： Christian Berg , Desmond Allen Kaplan , Karsten Michelmann
发明人： Christian Berg , Desmond Allen Kaplan , Karsten Michelmann
IPC分类号： H01J49/26 , B01D59/44
CPC分类号： H01J49/4295 , H01J49/0072 , H01J49/422
摘要： In a linear ion trap, ions with two polarities are confined radially via an RF potential between the rods comprising the trap. Axially, ions of at least one polarity are confined via DC potentials applied to the elements of the trap or electrodes at the ends of the trap whereas ions of the other polarity are axially confined by a combination of pseudopotentials and/or DC potentials.
摘要翻译：在线性离子阱中，具有两个极性的离子通过包含捕获阱的棒之间的RF电位在径向上被限制。轴向上，至少一个极性的离子通过施加到陷阱的元件上的DC电位而被限制，而另一极性的离子被赝势和/或DC电势的组合轴向限制。

4. 发明授权

US08013290B2 Method and apparatus for avoiding undesirable mass dispersion of ions in flight 有权
标题翻译：用于避免飞行中离子不期望质量分散的方法和装置
公开(公告)号：US08013290B2
公开(公告)日：2011-09-06
申请号：US11779452
申请日：2007-07-18
申请人： Oliver Räther , Karsten Michelmann , Jochen Franzen
发明人： Oliver Räther , Karsten Michelmann , Jochen Franzen
IPC分类号： H01J49/00 , B01D59/44
CPC分类号： H01J49/4265 , H01J49/004 , H01J49/062
摘要： In a mass spectrometer a target volume is filled with ions of different mass but substantially the same energy from a distant storage device by forming a plurality of spatially-limited ion swarms consisting of ions having the same mass. The ion swarms are ordered either by a mass-sequential extraction from the storage device or by rearranging the order of flight as the ions are in flight, so that swarms of different mass ions simultaneously enter the target volume despite having different flight velocities. A mass-sequential extraction in the order of decreasing mass can be achieved in one embodiment by decreasing a pseudopotential barrier at the storage device which causes the heavy ions to emerge first. In another embodiment, the ions can be rearranged in flight by applying a bunching potential. A second reverse bunching potential then restores the energy of the ions to their original values.
摘要翻译：在质谱仪中，通过形成由具有相同质量的离子组成的多个空间有限的离子群，在目标体积中填充来自遥远存储装置的质量不同但基本相同的能量的离子。离子群可以通过从存储装置进行质量顺序提取或通过在离子飞行中重新排列飞行顺序来排序，这样即使具有不同的飞行速度，不同质量离子的群也同时进入目标体积。在一个实施例中，可以通过减少存储装置处的伪电位势垒，使重离子首先出现，以质量递减的顺序提取质量。在另一个实施方案中，通过施加聚束电位，可以在飞行中重新排列离子。第二个反向聚束电位然后将离子的能量恢复到其原始值。

5. 发明申请

US20080156980A1 METHOD AND APPARATUS FOR AVOIDING UNDESIRABLE MASS DISPERSION OF IONS IN FLIGHT 有权
标题翻译：避免飞行中不可分离的大量离子的方法和装置
公开(公告)号：US20080156980A1
公开(公告)日：2008-07-03
申请号：US11779452
申请日：2007-07-18
申请人： Oliver Rather , Karsten Michelmann , Jochen Franzen
发明人： Oliver Rather , Karsten Michelmann , Jochen Franzen
IPC分类号： H01J49/00
CPC分类号： H01J49/4265 , H01J49/004 , H01J49/062
摘要： In a mass spectrometer a target volume is filled with ions of different mass but substantially the same energy from a distant storage device by forming a plurality of spatially-limited ion swarms consisting of ions having the same mass. The ion swarms are ordered either by a mass-sequential extraction from the storage device or by rearranging the order of flight as the ions are in flight, so that swarms of different mass ions simultaneously enter the target volume despite having different flight velocities. A mass-sequential extraction in the order of decreasing mass can be achieved in one embodiment by decreasing a pseudopotential barrier at the storage device which causes the heavy ions to emerge first. In another embodiment, the ions can be rearranged in flight by applying a bunching potential. A second reverse bunching potential then restores the energy of the ions to their original values.
摘要翻译：在质谱仪中，通过形成由具有相同质量的离子组成的多个空间有限的离子群，在目标体积中填充来自遥远存储装置的质量不同但基本相同的能量的离子。离子群可以通过从存储装置进行质量顺序提取或通过在离子飞行中重新排列飞行顺序来排序，这样即使具有不同的飞行速度，不同质量离子的群也同时进入目标体积。在一个实施例中，可以通过减少存储装置处的伪电位势垒，使重离子首先出现，以质量递减的顺序提取质量。在另一个实施方案中，通过施加聚束电位，可以在飞行中重新排列离子。第二个反向聚束电位然后将离子的能量恢复到其原始值。

6. 发明申请

US20070196813A1 EXTRACTION OF SUBSTANCES OF INTEREST FROM BLOOD FOR MASS SPECTROMETRIC ANALYSIS 审中-公开
标题翻译：从血液中提取物质用于质谱分析
公开(公告)号：US20070196813A1
公开(公告)日：2007-08-23
申请号：US11626518
申请日：2007-01-24
申请人： Jochen Franzen , Hans-Jakob Baum , Karsten Michelmann
发明人： Jochen Franzen , Hans-Jakob Baum , Karsten Michelmann
IPC分类号： C12Q1/00 , G01N33/567 , C12M3/00 , A61M1/06
CPC分类号： A61B5/150793 , A61B5/150022 , A61B5/150343 , A61B5/150351 , A61B5/150755 , A61B5/150786 , B01L2200/185 , B01L2300/069 , G01N1/405 , G01N33/6848
摘要： In a method for preparing a blood sample for subsequent processing in a mass spectrometry laboratory, substances of interest are extracted from whole blood, blood plasma or blood serum immediately after the blood sample has been taken from a subject. The extraction is carried out by means of reversible immobilization on a surface, for example, the surface of a blood extraction vessel. Only the extracted substances of interest are sent in the immobilized state to the mass spectrometry laboratory.
摘要翻译：在用于制备用于随后在质谱实验室中处理的血液样品的方法中，在从受试者取出血液样本后，立即从全血，血浆或血清中提取目的物质。通过可逆地固定在表面上，例如血液提取容器的表面进行提取。将所提取的目的物质以固定状态送入质谱实验室。

7. 发明申请

US20160251694A1 MASS SPECTROMETRIC DIAGNOSIS OF SEPSIS WITHOUT BLOOD CULTURE 有权
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：US20160251694A1
公开(公告)日：2016-09-01
申请号：US14113354
申请日：2011-07-29
申请人： Jochen Franzen , Mark Kostrzewa , Thomas Maier , Karsten Michelmann , Wolfgang Pusch
发明人： Jochen Franzen , Mark Kostrzewa , Thomas Maier , Karsten Michelmann , Wolfgang Pusch
IPC分类号： C12Q1/04 , G01N21/77
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，血液不是培养微生物的良好环境，并且提供了（a）在体内流体中大量地破坏或溶解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）将微生物病原体与流体分离，（c）将其培养在不含体液抗微生物成分的营养肉汤中，（d）将其与营养液分离，以及（e）微生物通过微生物蛋白质的质谱。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。这首先允许在早期进行质谱鉴定，其次提供远远超过其鉴定的微生物的阳性检测，这可以为患者挽救; 第三，可以提前开始确定电阻。

8. 发明申请

US20110284741A1 MIXED RADIO FREQUENCY MULTIPOLE ROD SYSTEM AS ION REACTOR 有权
标题翻译：混合无线电频率多径系统作为离子反应器
公开(公告)号：US20110284741A1
公开(公告)日：2011-11-24
申请号：US13112593
申请日：2011-05-20
申请人： Carsten Stoermer , Karsten Michelmann , Michael Schubert
发明人： Carsten Stoermer , Karsten Michelmann , Michael Schubert
IPC分类号： H01J49/02
CPC分类号： H01J49/0072 , H01J49/063
摘要： The invention relates to a linear multipole ion storage device which is suitable for reactions between positive and negative ions, and for fragmentation reactions by electron transfer dissociation (ETD) in particular. The invention uses a linear RF ion trap with at least three pairs of rods with a new type of electronic power supply. The two phases of a first RF voltage are applied to the pole rods alternately around the circumference and confine positive as well as negative ions in the radial direction. A second RF voltage is either applied single-phase to some of the pole rods, but not to all of them, or two-phase to unequal numbers of pole rods so that the axis potential oscillates with the frequency of this second RF voltage and generates a pseudopotential barrier which acts axially on ions of both polarities at the ends of the ion storage device. In the interior, the second RF produces a complex superposition field resulting in an increased fragmentation yield for ETD.
摘要翻译：本发明涉及一种线性多极离子存储装置，其适用于正离子和负离子之间的反应，特别涉及电子转移离解（ETD）的断裂反应。本发明使用具有新型电子电源的至少三对杆的线性RF离子阱。第一RF电压的两相交替地围绕圆周施加到极棒，并且在径向方向上限制正极以及负离子。第二RF电压或者单相施加到一些极棒，但不是施加到一些极棒，而是施加到所有的极点，或者两相到不相等的极棒，使得轴电位以该第二RF电压的频率振荡并产生在离子存储装置的端部轴向地作用于两个极性的离子的赝势垒。在内部，第二RF产生复杂的叠加场，导致ETD的碎裂产率增加。

9. 发明授权

US07964842B2 Evaluation of frequency mass spectra 有权
标题翻译：频率质谱评估
公开(公告)号：US07964842B2
公开(公告)日：2011-06-21
申请号：US12474953
申请日：2009-05-29
申请人： Claus Köster , Karsten Michelmann
发明人： Claus Köster , Karsten Michelmann
IPC分类号： B01J59/44
CPC分类号： H01J49/38
摘要： The invention relates to the evaluation of mass spectra from mass spectrometers in which ions are excited to mass-specific oscillating or orbiting motions, and the ion motion is recorded as a time signal. The invention provides methods to detect parameter drift that occurs during the recording of a time signal in such a “frequency mass spectrometer” by analyzing the instantaneous frequency or the phase spectrum of a frequency component, and provides a method to correct for influence of the frequency drift on the mass spectrum correspondingly. In one embodiment a Fourier transformation converts a measured time signal into a frequency spectrum and examines the phase spectrum of a frequency component to establish whether this phase spectrum deviates from the phase spectrum of a harmonic time signal. The phase spectrum of a harmonic time signal is either linear or constant. In another embodiment the time domain signal is processed using a Short Time Fourier Transformation function to determine an instantaneous frequency, which can be used to correct the parameter drift, yielding a corrected time signal. From the corrected time signal a mass spectrum with better mass resolution can be derived, as can be seen from corrected mass signal profile compared with uncorrected mass signal profile.
摘要翻译：本发明涉及对离子被激发到质量特定的振荡或轨道运动的质谱仪的质谱的评估，离子运动被记录为时间信号。本发明提供了通过分析频率分量的瞬时频率或相位频谱来检测在这种“频率质谱仪”记录时间信号期间发生的参数漂移的方法，并提供了一种校正频率影响的方法相应地在质谱上漂移。在一个实施例中，傅里叶变换将测量的时间信号转换成频谱，并检查频率分量的相位谱，以确定该相位谱是否偏离谐波时间信号的相位谱。谐波时间信号的相位频谱是线性或恒定的。在另一个实施例中，使用短时傅里叶变换函数来处理时域信号，以确定可用于校正参数漂移的瞬时频率，产生校正的时间信号。从校正的时间信号可以推导出质量分辨率更高的质谱，从校正的质量信号曲线可以看出，与未校正的质量信号曲线相比。

10. 发明授权

US07888633B2 Evaluation of spectra in oscillation mass spectrometers 有权
标题翻译：振动质谱仪中光谱的评估
公开(公告)号：US07888633B2
公开(公告)日：2011-02-15
申请号：US12037506
申请日：2008-02-26
申请人： Jochen Franzen , Karsten Michelmann
发明人： Jochen Franzen , Karsten Michelmann
IPC分类号： B01D59/44
CPC分类号： H01J49/42 , H01J49/0036 , H01J49/027
摘要： The invention relates to mass spectrometers in which ion clouds are stored in two spatial directions by radial forces while oscillating largely harmonically at a mass-specific frequency in a third spatial direction perpendicular to the other two, in a potential minimum, the shape of which is as close to a parabola as possible. Analysis of the oscillation frequencies of these ion clouds, preferably by a Fourier analysis, leads via a frequency spectrum to a mass spectrum. The frequency spectrum is analyzed to identify false signals in the frequency spectrum as harmonics and eliminating them where necessary.
摘要翻译：本发明涉及质谱仪，其中离子云通过径向力在两个空间方向上存储，同时以与另外两个垂直的第三空间方向上的质量特定频率大量谐波地振荡，其形状为尽可能接近抛物线。这些离子云的振荡频率的分析优选通过傅立叶分析，经由频谱到达质谱。分析频谱以将频谱中的伪信号作为谐波识别，并在必要时消除它们。

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