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1.发明申请METHOD AND APPARATUS FOR AVOIDING UNDESIRABLE MASS DISPERSION OF IONS IN FLIGHT 有权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
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。
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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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3.发明授权Method and apparatus for avoiding undesirable mass dispersion of ions in flight 有权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
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。
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4.发明申请EXTRACTION OF SUBSTANCES OF INTEREST FROM BLOOD FOR MASS SPECTROMETRIC ANALYSIS 审中-公开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
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。
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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：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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公开(公告)号：US08142996B2
公开(公告)日：2012-03-27
申请号：US12224388
申请日：2007-02-15
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。 本发明提供了通过添加通常不存在于血液中的探针物质来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。
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公开(公告)号：US20090084949A1
公开(公告)日：2009-04-02
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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公开(公告)号：US07504640B2
公开(公告)日：2009-03-17
申请号：US11522112
申请日：2006-09-15
申请人： Jochen Franzen , Karsten Michelmann
发明人： Jochen Franzen , Karsten Michelmann
CPC分类号： G01N27/62 , H01J49/0463 , H01J49/0481 , H01J49/145
摘要： An ion source generates ions from analyte molecules which are desorbed from a sample on the surface of a sample support in a pressure range of approximately 30 to 300 pascal. Reactant ions are generated in a separate ion source and guided by ion guides to the point in front of the sample or to a reaction chamber in which the desorbed molecules are located. The reactant ions ionize the desorbed molecules to form analyte ions. The analyte molecules can be mixed in matrix material or adsorbed on the sample support surface without additives. The desorption can be continuous or pulsed, for example by light from lasers or diodes.
摘要翻译： 离子源从分析物分子产生离子，其在约30至300帕斯卡的压力范围内从样品载体表面上的样品解吸。 反应物离子在单独的离子源中产生并由离子导向器引导到样品前面的点或解吸的分子位于其中的反应室。 反应物离子离子解吸分子形成分析离子。 分析物分子可以在基质材料中混合或吸附在样品支持体表面上而无添加剂。 解吸可以是连续的或脉冲的，例如通过来自激光器或二极管的光。
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公开(公告)号：US20090305327A1
公开(公告)日：2009-12-10
申请号：US12224388
申请日：2007-02-15
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。 本发明提供了通过添加通常不存在于血液中的探针物质来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。
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