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公开(公告)号：US20110012016A1
公开(公告)日：2011-01-20
申请号：US12834504
申请日：2010-07-12
申请人： Thomas Maier , Markus Kostrzewa
发明人： Thomas Maier , Markus Kostrzewa
IPC分类号： B01D59/44
CPC分类号： G01N33/6848 , C12Q1/04 , G01N2560/00 , G06F19/24
摘要： A dual-stage method is provided for identifying a microbe by, for example, its species or its subspecies. The method includes measuring a mass spectrum of the microbe using a mass spectrometer, calculating indicators for similarities between reference mass spectra in a library and the measured mass spectrum, selecting a group of reference mass spectra similar to the measured mass spectrum, determining a distinguishing weight for each mass signal of the reference mass spectra in the group, where the distinguishing weights emphasize differences between the reference mass spectra in the group, and calculating indicators for similarities between the reference mass spectra in the group and the measured mass spectrum as a function of the distinguishing weights.
摘要翻译： 提供了用于通过例如其物种或其亚种鉴定微生物的双阶段方法。 该方法包括使用质谱仪测量微生物的质谱，计算文库中参考质谱与测量质谱之间的相似性的指标，选择与测得的质谱相似的一组参考质谱，确定鉴别重量 对于组中参考质谱的每个质量信号，其中区分权重强调组中参考质谱之间的差异，并且计算组中参考质谱与测量质谱之间的相似性的指标，作为 区别权重。
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公开(公告)号：US10006076B2
公开(公告)日：2018-06-26
申请号：US14113354
申请日：2011-07-29
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.
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公开(公告)号：US20060095212A1
公开(公告)日：2006-05-04
申请号：US11249147
申请日：2005-10-12
申请人： Markus Kostrzewa , Stefan Klepel , Thomas Maier
发明人： Markus Kostrzewa , Stefan Klepel , Thomas Maier
IPC分类号： G06F19/00
CPC分类号： H01J49/0036 , Y10T436/143333
摘要： The invention generates mass scale comparability between mass spectra which are acquired in time-of-flight mass spectrometers, particularly with ionization by matrix-assisted laser desorption. Always slightly distorted mass scales of different mass spectra from the same type of sample can be aligned. The flight times of identical ions always differ slightly from one mass spectrum to the next due to non-reproducible processes in the ionization method. Thus the apparent mass values of ion signals of identical substances in different mass spectra do not match even if the flight times are converted into mass values with the identical calibration equation. After alignment of the mass scales, mass spectra can be reliably compared with respect to deviations in intensities of bio-makers, or be added together without deterioration in the mass resolution, and improved reference spectrum libraries can be created. Furthermore, the invention allows more reliable library searches to be carried out.
摘要翻译： 本发明在飞行时间质谱仪中获得的质谱之间产生质谱比较，特别是通过基质辅助激光解吸电离。 始终可以对齐来自相同类型样品的不同质谱的轻微变形质谱。 由于电离方法中不可重复的过程，相同离子的飞行时间总是与一个质谱图稍微不同。 因此，即使以相同的校准方程将飞行时间转换为质量值，不同质谱中相同物质的离子信号的表观质量也不匹配。 在对质量标尺进行比对后，质谱可以与生物制造者的强度偏差可靠地进行比较，或者加在一起，而不会降低质量分辨率，并且可以创建改进的参考光谱库。 此外，本发明允许执行更可靠的库搜索。
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公开(公告)号：US08237107B2
公开(公告)日：2012-08-07
申请号：US12834504
申请日：2010-07-12
申请人： Thomas Maier , Markus Kostrzewa
发明人： Thomas Maier , Markus Kostrzewa
CPC分类号： G01N33/6848 , C12Q1/04 , G01N2560/00 , G06F19/24
摘要： A dual-stage method is provided for identifying a microbe by, for example, its species or its subspecies. The method includes measuring a mass spectrum of the microbe using a mass spectrometer, calculating indicators for similarities between reference mass spectra in a library and the measured mass spectrum, selecting a group of reference mass spectra similar to the measured mass spectrum, determining a distinguishing weight for each mass signal of the reference mass spectra in the group, where the distinguishing weights emphasize differences between the reference mass spectra in the group, and calculating indicators for similarities between the reference mass spectra in the group and the measured mass spectrum as a function of the distinguishing weights.
摘要翻译： 提供了用于通过例如其物种或其亚种鉴定微生物的双阶段方法。 该方法包括使用质谱仪测量微生物的质谱，计算文库中参考质谱与测量质谱之间的相似性的指标，选择与测得的质谱相似的一组参考质谱，确定鉴别重量 对于组中参考质谱的每个质量信号，其中区分权重强调组中参考质谱之间的差异，并且计算组中参考质谱与测量质谱之间的相似性的指标，作为 区别权重。
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公开(公告)号：US20100248298A1
公开(公告)日：2010-09-30
申请号：US12695235
申请日：2010-01-28
申请人： Markus Kostrzewa , Thomas Maier , Stefan Klepel
发明人： Markus Kostrzewa , Thomas Maier , Stefan Klepel
IPC分类号： C12Q1/04
CPC分类号： G01N33/6848 , C12Q1/04 , G16B20/00 , Y02A50/58
摘要： Microorganisms are identified as present in a complex sample or mixed culture by acquiring a mass spectrum of the sample and comparing it to combination spectra, each of which is formed by combining at least two reference mass spectra of known microorganisms. Microorganisms corresponding to the reference spectra used to form the combination spectrum are identified as present in the sample if that combination spectrum exhibits a better match with the sample mass spectrum than any one of reference mass spectra used to form that combination spectrum. It is also possible to identify microorganisms by forming a difference spectrum by subtracting a reference mass spectrum from the sample mass spectrum and comparing the difference spectrum to the reference mass spectra.
摘要翻译： 通过获取样品的质谱并将其与组合光谱进行比较，将微生物鉴定为存在于复合物样品或混合培养物中，每个组合谱通过组合已知微生物的至少两个参考质谱而形成。 与用于形成组合光谱的参考光谱相对应的微生物被鉴定为存在于样品中，如果该组合光谱与样品质谱比与用于形成该组合光谱的参考质谱中的任何一个相比更好的匹配。 也可以通过从样品质谱中减去参考质谱并将差谱与参考质谱进行比较来形成差谱来鉴定微生物。
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公开(公告)号：US07391017B2
公开(公告)日：2008-06-24
申请号：US11249147
申请日：2005-10-12
申请人： Markus Kostrzewa , Stefan Klepel , Thomas Maier
发明人： Markus Kostrzewa , Stefan Klepel , Thomas Maier
CPC分类号： H01J49/0036 , Y10T436/143333
摘要： The invention generates mass scale comparability between mass spectra which are acquired in time-of-flight mass spectrometers, particularly with ionization by matrix-assisted laser desorption. Always slightly distorted mass scales of different mass spectra from the same type of sample can be aligned. The flight times of identical ions always differ slightly from one mass spectrum to the next due to non-reproducible processes in the ionization method. Thus the apparent mass values of ion signals of identical substances in different mass spectra do not match even if the flight times are converted into mass values with the identical calibration equation. After alignment of the mass scales, mass spectra can be reliably compared with respect to deviations in intensities of bio-makers, or be added together without deterioration in the mass resolution, and improved reference spectrum libraries can be created. Furthermore, the invention allows more reliable library searches to be carried out.
摘要翻译： 本发明在飞行时间质谱仪中获得的质谱之间产生质谱比较，特别是通过基质辅助激光解吸电离。 始终可以对齐来自相同类型样品的不同质谱的轻微变形质谱。 由于电离方法中不可重复的过程，相同离子的飞行时间总是与一个质谱图稍微不同。 因此，即使以相同的校准方程将飞行时间转换为质量值，不同质谱中相同物质的离子信号的表观质量也不匹配。 在对质量标尺进行比对后，质谱可以与生物制造者的强度偏差可靠地进行比较，或者加在一起，而不会降低质量分辨率，并且可以创建改进的参考光谱库。 此外，本发明允许执行更可靠的库搜索。
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公开(公告)号：US20160251694A1
公开(公告)日：2016-09-01
申请号：US14113354
申请日：2011-07-29
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。
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公开(公告)号：US08785659B2
公开(公告)日：2014-07-22
申请号：US12921928
申请日：2009-03-11
申请人： Matthias Müller , Bernd Müller , Thomas Maier
发明人： Matthias Müller , Bernd Müller , Thomas Maier
IPC分类号： C07D207/48
CPC分类号： C07D207/48 , C07D403/12
摘要： Process for the preparation of a compound of formula (I) wherein R1, R2, R3, R4, R5 and R6 have the meanings as defined in the specification, comprising the step of reacting an acrylic acid chloride compound of formula (II′): wherein R1, R2, R3, R4, R5 and R6 have the meanings as defined in the specification, with aqueous hydroxylamine and optionally converting the resulting compound into an acid addition salt thereof.
摘要翻译： 制备其中R 1，R 2，R 3，R 4，R 5和R 6具有如本说明书中所定义的含义的式（I）化合物的方法，包括使式（II'）的丙烯酰氯化合物： 其中R 1，R 2，R 3，R 4，R 5和R 6具有本说明书中定义的含义，与羟胺水解反应，并任选地将所得化合物转化为其酸加成盐。
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9.发明授权公开(公告)号：US08618755B2
公开(公告)日：2013-12-31
申请号：US13129434
申请日：2009-10-23
IPC分类号： H02P6/16
摘要： A control device is for a motor, especially a brushless DC motor. The control device contains a bridge circuit for generating a rotating field for the motor and a sensor system for detecting a position of a rotor of the motor, a control signal for the bridge circuit being derivable from the signal representing the rotor position. The sensor system includes an absolute value transmitter which detects the absolute position of the rotor and which is configured to derive at least one incremental signal from the absolute position and to make it directly available to a control component for controlling the bridge circuit for commuting the motor.
摘要翻译： 控制装置用于电动机，特别是无刷直流电动机。 控制装置包括用于产生用于电动机的旋转场的桥接电路和用于检测电动机的转子位置的传感器系统，桥接电路的控制信号可从表示转子位置的信号导出。 传感器系统包括绝对值发射器，其检测转子的绝对位置，其被配置为从绝对位置导出至少一个增量信号，并使其直接用于控制部件，用于控制用于使电动机通勤的桥接电路 。
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公开(公告)号：US20120115182A1
公开(公告)日：2012-05-10
申请号：US13322363
申请日：2010-07-14
申请人： Thomas Maier
发明人： Thomas Maier
IPC分类号： C12Q1/04
CPC分类号： C12Q1/24 , C12Q1/04 , G01N33/6851 , G01N2560/00 , G01N2570/00 , G01N2800/26
摘要： The invention mainly relates to the mass spectrometric identification of pathogens in blood cultures from blood-stream infections (septicemia). The invention provides a method with which microbial pathogens can be separated in purified form from blood after a relatively brief cultivation in a blood culture flask, without any interfering human proteins or any residual fractions of blood particles such as erythrocytes and leukocytes, and can be directly identified by mass spectrometric measurement of their protein profiles. The method is based on the use of relatively strong tensides to destroy the blood particles by dissolving the weak cell membranes and most of the internal structures of the blood particles; in spite of the fact that tensides are regarded as strong ionization inhibitors in MALDI and other ionization processes required for mass spectrometric measurements. This method allows unknown pathogens to be obtained in their pure form by centrifuging or filtration and to be identified on the taxonomic level of species or subspecies. Problems with DNA from high levels of leukocytes can be resolved by special measures. After sufficient cultivation, the identification in a mass spectrometric laboratory takes only half an hour.
摘要翻译： 本发明主要涉及血流感染（败血病）血液培养物中病原体的质谱鉴定。 本发明提供了一种在血培养瓶中比较短暂的培养后，将微生物病原体与血液分离的方法，其中没有任何干扰的人类蛋白质或血液颗粒如红细胞和白细胞的任何残留部分，并且可直接 通过其蛋白质谱的质谱测定来鉴定。 该方法基于使用相对较强的表面活性剂通过溶解弱细胞膜和血液颗粒的大部分内部结构来破坏血液颗粒; 尽管在MALDI和质谱测量所需的其他电离过程中，表面活性剂被认为是强电离抑制剂。 该方法允许通过离心或过滤以其纯形式获得未知的病原体，并根据物种或亚种的分类级别进行鉴定。 通过特殊措施可以解决高水平白细胞DNA的问题。 在充分培养后，质谱实验室的鉴定只需半小时。
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