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公开(公告)号：US10457972B2
公开(公告)日：2019-10-29
申请号：US14271508
申请日：2014-05-07
申请人： Bruker Daltonik GmbH
IPC分类号： C12Q1/04
摘要： The invention relates to a mass spectrometric method for determining microbial resistances to antibiotics. The invention provides specific methods comprising cultivation in synthetic media, in which several amino acids, preferably only a single amino acid, are isotopically labeled by incorporating 13C, 15N, 18O or 34S. If several amino acids are isotopically labeled, they are labeled in such a way that they are each heavier than the corresponding unlabeled amino acids by the same integer mass difference Δm. This ensures that the mass shifts of the peaks always amount to an integer multiple of the mass difference Δm. The total mass difference can be kept relatively small by selecting suitable amino acids. A mass shift of the protein peaks in media with antibiotics indicates that the microbes are resistant. A second embodiment first produces isotopically labeled microbes, which are then tested for their resistance by cultivating them in normal media.
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公开(公告)号：US09245727B2
公开(公告)日：2016-01-26
申请号：US13886641
申请日：2013-05-03
申请人： Bruker Daltonik GmbH
发明人： Jochen Franzen , Claus Köster
CPC分类号： H01J49/26 , H01J49/425
摘要： The invention relates to the voltage supply of mass spectrometers, particularly electrostatic Kingdon ion analyzers, requiring extremely noise-free operating voltages. The invention proposes the use of passive charge storage devices, which operate without any feedback control and display no measurable noise or ripple if they are well shielded, instead of the usual actively operating high-voltage generators. Chemical charge storage devices or capacitors with good insulation can be used for this purpose. These may display slight voltage decreases due to continuous discharge, depending on their quality, but these decreases can be mathematically compensated.
摘要翻译： 本发明涉及质谱仪，特别是静电Kingdon离子分析仪的电压供应，其需要极高的无噪声工作电压。 本发明提出使用无源电荷存储装置，其在没有任何反馈控制的情况下工作，并且如果它们被良好屏蔽而不是通常的主动操作的高压发生器，则不显示可测量的噪声或纹波。 可以使用具有良好绝缘性的化学电荷存储装置或电容器。 这些可能由于连续放电而显示出轻微的电压降低，这取决于其质量，但是这些减少可以在数学上得到补偿。
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公开(公告)号：US20150211042A1
公开(公告)日：2015-07-30
申请号：US14419010
申请日：2013-07-25
申请人： Bruker Daltonik GmbH
发明人： Jochen Franzen , Stefan Klepel , Markus Kostrzewa , Thomas Maier
IPC分类号： C12Q1/04
CPC分类号： C12Q1/04 , G01N33/6848 , G01N2560/00 , G16B20/00
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 A1 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）使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类的参考光谱之间的相似性，或（3）总是根据文献DE进行混合分析 10 2009 007 266 A1从得分列表中，产生组合谱，后来才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。
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公开(公告)号：US09051594B2
公开(公告)日：2015-06-09
申请号：US14050446
申请日：2013-10-10
申请人： Bruker Daltonik GmbH
CPC分类号： G01N33/6851 , C12Q1/18
摘要： Microorganisms, particularly bacteria, are identified and characterized on the basis of a mass spectrometric measurement of their protein profiles with ionization by matrix-assisted laser desorption. In order to measure the microbial resistance to antibiotics, the protein profiles of microorganisms are measured after cultivation for a short time duration in nutrient media containing the antibiotics.
摘要翻译： 基于通过基质辅助激光解吸电离的蛋白质谱的质谱测定，鉴定和表征微生物，特别是细菌。 为了测量微生物对抗生素的抗性，微生物的蛋白质分布在含有抗生素的营养培养基中培养短时间后测量。
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公开(公告)号：US10597692B2
公开(公告)日：2020-03-24
申请号：US15983324
申请日：2018-05-18
申请人： Bruker Daltonik GmbH
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：US20180265909A1
公开(公告)日：2018-09-20
申请号：US15983324
申请日：2018-05-18
申请人： Bruker Daltonik GmbH
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：US20140117220A1
公开(公告)日：2014-05-01
申请号：US13886641
申请日：2013-05-03
申请人： Bruker Daltonik GmbH
发明人： Jochen Franzen , Claus Köster
IPC分类号： H01J49/26
CPC分类号： H01J49/26 , H01J49/425
摘要： The invention relates to the voltage supply of mass spectrometers, particularly electrostatic Kingdon ion analyzers, requiring extremely noise-free operating voltages. The invention proposes the use of passive charge storage devices, which operate without any feedback control and display no measureable noise or ripple if they are well shielded, instead of the usual actively operating high-voltage generators. Chemical charge storage devices or capacitors with good insulation can be used for this purpose. These may display slight voltage decreases due to continuous discharge, depending on their quality, but these decreases can be mathematically compensated.
摘要翻译： 本发明涉及质谱仪，特别是静电Kingdon离子分析仪的电压供应，其需要极高的无噪声工作电压。 本发明提出使用无源电荷存储装置，其在没有任何反馈控制的情况下工作，并且如果它们被良好屏蔽而不是通常的主动操作的高压发生器，则不显示可测量的噪声或纹波。 可以使用具有良好绝缘性的化学电荷存储装置或电容器。 这些可能由于连续放电而显示出轻微的电压降低，这取决于其质量，但是这些减少可以在数学上得到补偿。
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8.发明申请ANALYSIS OF MICROBES FROM MICROCOLONIES BY MALDI MASS SPECTROMETRY 有权通过MALDI MASS SPECTROMETRY分析MICROCOLONIES微生物公开(公告)号：US20130337502A1
公开(公告)日：2013-12-19
申请号：US13910279
申请日：2013-06-05
申请人： Bruker Daltonik GmbH
发明人： Jens Boßmeyer , Jochen Franzen
IPC分类号： G01N27/62
CPC分类号： G01N27/62 , C12Q1/04 , G01N33/5438 , G01N33/6848 , H01J49/0418
摘要： The invention relates to the cell disruption of microbes and the preparation of the microbe proteins for mass spectrometric analysis. The cells of microbes from microcolonies are disrupted by physical or chemical means directly on the nutrient medium. The released proteins are then transferred to sample supports by direct contact with their contact surfaces; electrophoresis can be used for assistance. Once the the proteins are firmly adsorbed on the contact surfaces, they can be washed with water in order to remove substances which interfere with the ionization process. For analysis by matrix-assisted laser desorption (MALDI), the proteins are prepared on the contact surfaces of the sample supports with matrix substances to form MALDI samples; the sample supports are then introduced into a MALDI mass spectrometer for the acquisition of the mass spectra. The microbes are identified by similarity comparisons between the mass spectra of the microbe proteins and similarly obtained reference spectra.
摘要翻译： 本发明涉及微生物的细胞破碎和用于质谱分析的微生物蛋白质的制备。 来自微小菌落的微生物的细胞通过物理或化学方式直接在营养培养基上破坏。 然后将释放的蛋白质通过与其接触表面直接接触而转移到样品支架中; 电泳可用于协助。 一旦蛋白质被牢固地吸附在接触表面上，它们可以用水洗涤，以去除干扰电离过程的物质。 为了通过基质辅助激光解吸（MALDI）分析，蛋白质在样品载体与基质物质的接触表面上制备形成MALDI样品; 然后将样品载体引入MALDI质谱仪中以获取质谱。 微生物通过微生物蛋白的质谱和类似获得的参考光谱之间的相似性比较来鉴定。
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公开(公告)号：US09897613B2
公开(公告)日：2018-02-20
申请号：US14697674
申请日：2015-04-28
申请人： Bruker Daltonik GmbH
CPC分类号： G01N33/6851 , C12Q1/18
摘要： Microorganisms, particularly bacteria, are identified and characterized on the basis of a mass spectrometric measurement of their protein profiles with ionization by matrix-assisted laser desorption. In order to measure the microbial resistance to antibiotics, the protein profiles of microorganisms are measured after cultivation for a short time duration in nutrient media containing the antibiotics.
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公开(公告)号：US09891146B2
公开(公告)日：2018-02-13
申请号：US14499388
申请日：2014-09-29
申请人： Bruker Daltonik GmbH
CPC分类号： G01N1/30 , G01N1/31 , G01N1/4055 , H01J49/0418
摘要： The invention relates to the preparation of thin tissue sections for mass spectrometric (MALDI) imaging, and proposes a method wherein a microcrystalline layer of the matrix material is produced on the surface of the thin tissue sections, and soluble analyte molecules are transported orthogonally through the thin tissue section to the matrix layer, without substantial lateral diffusion, by means of a solvent flow with alternating or constant direction, and are then deposited in the matrix layer and, if possible, embedded in the matrix crystals. A solvent flow which alternates in direction can be produced by successive, alternating phases of swelling and drying, brought about by periodic changes to the thin tissue section temperature and/or the partial pressures of the solvents. A continuous solvent flow can be generated by applying the thin tissue section onto a porous support which supplies solvent to the rear surface of the thin tissue section.
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