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1. 发明公开

EP2455759A1 Mass spectrometry imaging with substance identification 有权转让
标题翻译： Massenspektromie-Bildgebung mit Substanzidentifizierung
公开(公告)号：EP2455759A1
公开(公告)日：2012-05-23
申请号：EP11188385.6
申请日：2011-11-09
申请人： Bruker Daltonik GmbH
发明人： Suckau, Detlev , Schürenberg, Martin , Paape, Rainer , Lübbert, Christine
IPC分类号： G01N33/68 , H01J49/00
CPC分类号： G01N33/6848 , G01N2400/00
摘要： The invention relates to the mass spectrometry imaging of histologic thin tissue sections, where a mass spectrum is acquired for every image point. The invention provides a method for the identification and localization of proteins or other biomolecules of a histologic thin tissue section, comprising the following steps: a) the biomolecules of two similar thin tissue sections are enzymatically digested, substantially preserving the biomolecule positions in the tissue; b) a mass spectrometric image of the digest products in the first thin tissue section is acquired; c) the digest products of the second tissue section are extracted and separated with the aid of a separation method, and then introduced into a tandem mass spectrometer, which acquires mass spectra and daughter ion spectra of all the digest products present; d) a list of all identifiable biomolecules of the tissue is created by comparison of the mass spectra and daughter ion spectra of the digest products with spectra derived from biomolecule structure databases or correspondent spectral libraries; and e) the biomolecules in the list are assigned, on the basis of the masses of their digest products, to the digest products of the same mass in the mass spectra of the mass spectrometric image of the thin tissue section, after intelligent filtering, where necessary. With the aid of correlations of the mass-selective images, digest products can be identified as being wrongly assigned. The summation of well-correlating mass-selective images of the digest products of the biomolecules produces biomolecule-selective images, i.e. images of the distribution of the individual biomolecules in the thin tissue section.
摘要翻译：本发明涉及组织学薄组织切片的质谱成像，其中为每个图像点获取质谱。本发明提供了用于鉴定和定位组织学薄组织切片的蛋白质或其他生物分子的方法，包括以下步骤：a）将两个类似的薄组织切片的生物分子酶消化，基本上保留组织中的生物分子位置; b）获取第一薄组织切片中的消化产物的质谱图像; c）第二组织切片的消化产物借助于分离方法提取和分离，然后引入串联质谱仪，其获得存在的所有消化产物的质谱和子离子光谱; d）通过将消化产物的质谱和子离子谱与衍生自生物分子结构数据库或记录谱库的光谱进行比较来产生组织中所有可识别生物分子的列表; 和e）列表中的生物分子根据其消化产物的质量分配给薄组织切片的质谱图的质谱中相同质量的消化产物，在智能过滤之后，其中必要。借助于质量选择性图像的相关性，可以将消化产物识别为错误分配。生物分子的消化产物的良好相关的质量选择图像的总和产生生物分子选择性图像，即薄组织切片中各个生物分子分布的图像。

2. 发明授权

EP2455759B1 Mass spectrometry imaging with substance identification 有权转让
标题翻译： Massenspektromie成像物质识别
公开(公告)号：EP2455759B1
公开(公告)日：2015-01-07
申请号：EP11188385.6
申请日：2011-11-09
申请人： Bruker Daltonik GmbH
发明人： Suckau, Detlev , Schürenberg, Martin , Paape, Rainer , Lübbert, Christine
IPC分类号： G01N33/68 , H01J49/00
CPC分类号： G01N33/6848 , G01N2400/00

3. 发明授权

EP2848306B1 Dispenser system for mass spectrometric sample preparations 有权转让
标题翻译：用于质谱样品制剂分配系统
公开(公告)号：EP2848306B1
公开(公告)日：2016-04-06
申请号：EP13004465.4
申请日：2013-09-13
申请人： Bruker Daltonik GmbH
发明人： Schürenberg, Martin , Vossgröne, Alexander
IPC分类号： H01J49/04 , H01J49/26 , B01L3/02 , G01N35/10
CPC分类号： H01J49/0431 , B01L3/021 , B01L3/0241 , B01L2200/0615 , B01L2300/0654 , G01N35/1004 , H01J49/0418 , H01J49/26

4. 发明公开

EP2848306A1 Dispenser system for mass spectrometric sample preparations 有权转让
标题翻译： Proponubereitungen的Spendersystemfürmassenspektrometrische
公开(公告)号：EP2848306A1
公开(公告)日：2015-03-18
申请号：EP13004465.4
申请日：2013-09-13
申请人： Bruker Daltonik GmbH
发明人： Schürenberg, Martin , Vossgröne, Alexander
IPC分类号： B01L3/02 , G01N35/10
CPC分类号： H01J49/0431 , B01L3/021 , B01L3/0241 , B01L2200/0615 , B01L2300/0654 , G01N35/1004 , H01J49/0418 , H01J49/26
摘要： The invention relates to the preparation of samples on mass spectrometric sample supports with dispensing of liquids, and particularly to devices and methods to clean the dispenser. During dispensing of hundreds of samples, solved material may crystallize over time as deposit at the capillary tip of the dispenser, which impedes the vertical detachment of the drop in the medium and long run. Therefore, frequently cleaning the capillary tip is essential for a robust operation of the preparation device. The invention proposes to automatically clean the dispenser tip by creating a drop of washing fluid, such as pure solvent, fully enclosing the dispenser tip. The washing fluid is fed through a channel outside the central dispenser capillary to a location slightly above the capillary tip. The size of the hanging drop of washing fluid is photometrically regulated and monitored to prevent it from falling off prematurely.
摘要翻译：本发明涉及在分配液体的质谱样品支架上制备样品，特别涉及清洁分配器的装置和方法。在分配数百个样品期间，溶解的材料随着时间的推移可能随着分配器的毛细管尖端沉积而结晶，这阻碍了介质中的液滴的垂直分离并长期运行。因此，经常清洁毛细管尖端对于制备装置的鲁棒操作是必需的。本发明提出通过产生完全包围分配器尖端的一滴洗涤液（例如纯溶剂）来自动清洁分配器尖端。洗涤液通过中央分配器毛细管外部的通道进入到毛细管尖端稍微上方的位置。清洗液悬挂液滴的尺寸被光度调节和监测，以防过早脱落。

5. 发明公开

EP1053784A2 Processing samples in solutions having defined small contact area with support 审中-公开
标题翻译：在罗森堡的Verarbeitung von Proben mit einer definierten kleinenTrägerkontaktfläche
公开(公告)号：EP1053784A2
公开(公告)日：2000-11-22
申请号：EP00110123.7
申请日：2000-05-10
申请人： Bruker Daltonik GmbH
发明人： Nordhoff, Eckhard , Eickhoff, Holger , Schürenberg, Martin , Franzen, Jochen
IPC分类号： B01J19/00 , B01L3/00
CPC分类号： B01L3/0262 , B01J19/0046 , B01J2219/00315 , B01J2219/00479 , B01J2219/00533 , B01J2219/00585 , B01J2219/0065 , B01J2219/00659 , B01J2219/00704 , B01J2219/0072 , B01L3/5085 , B01L3/5088
摘要： The invention relates to the processing of very small quantities of sample, that is, the performing of chemical or enzymatic reactions, purifications, or analytic investigations, in very small quantities of liquid in the order of one microliter and less, particularly for very large numbers of samples in simultaneous processes.
The invention consists of reducing the vessel wall contact areas, which increase disproportionately with very small quantities of liquid, and have largely detrimental influences, by using standing (or suspended) droplets as microreactors for processing, whereby the droplets are supported by wetting-friendly (lyophilic) anchors in surfaces which would otherwise be hostile to wetting (lyophobic) and therefore possess a well-defined wall contact area. The anchors can be passivated in a required manner or also be made surface-active, the latter in order to support certain processing steps. It is also possible to integrate electrical, optical, fluidic, or other microstructured elements into the support in order to assist processing. The invention relates to the basic method of processing in the supported droplet and correspondingly designed supports.
摘要翻译：本发明涉及非常少量的样品的处理，即在非常少量的液体中进行化学或酶反应，纯化或分析研究，其量为1微升以下，特别是对于非常大的数量的同时进行的样品。本发明包括通过使用立式（或悬浮）液滴作为微反应器进行加工，减少与非常少量液体不成比例地增加的容器壁接触面积并且具有很大的不利影响，由此液滴被润湿友好地支撑亲液性）锚定在表面，否则这些表面将不利于润湿（疏液），因此具有良好限定的壁接触面积。锚可以以所需的方式被钝化或者也可以被制成表面活性的，后者是为了支持某些加工步骤。还可以将电气，光学，流体或其他微结构元件集成到支撑件中，以便于处理。本发明涉及在支撑液滴和相应设计的支撑件中的基本处理方法。

6. 发明授权

EP2669011B1 Bildprojektionsverfahren und -vorrichtung zur Unterstützung der händischen MALDI-Probenpräparation 有权转让
标题翻译：用于支持手动MALDI样品制备的图像投影方法和设备
公开(公告)号：EP2669011B1
公开(公告)日：2018-05-16
申请号：EP12170042.1
申请日：2012-05-30
申请人： Bruker Daltonik GmbH
发明人： Schmid, Christian , Schürenberg, Martin
IPC分类号： B01L99/00 , H01J49/04
CPC分类号： B01L9/50 , B01L9/523 , B01L99/00 , B01L2200/0621 , B01L2300/02 , B01L2300/0627 , B01L2300/0829 , H01J49/0418

7. 发明公开

EP2669011A1 Bildprojektionsverfahren und -vorrichtung zur Unterstützung der händischen MALDI-Probenpräparation 有权转让
标题翻译： Bildprojektionsverfahren und -vorrichtung zurUnterstützungderhändischenMALDI-Probenpräparation
公开(公告)号：EP2669011A1
公开(公告)日：2013-12-04
申请号：EP12170042.1
申请日：2012-05-30
申请人： Bruker Daltonik GmbH
发明人： Schmid, Christian , Schürenberg, Martin
IPC分类号： B01L99/00 , H01J49/04
CPC分类号： B01L9/50 , B01L9/523 , B01L99/00 , B01L2200/0621 , B01L2300/02 , B01L2300/0627 , B01L2300/0829 , H01J49/0418
摘要： Eine verbesserte Belegungshilfe für die händische Probenpräparation, insbesondere auf ebenen MALDI-Probenträgern, umfasst eine Aufnahme für einen Probenträger mit mehreren Probenorten, die an standardisierte Probenträger für die Ionisierung mit matrix-unterstützter Laserdesorption angepasst ist, eine Vorrichtung, die ein zwei-dimensionales optisches Bild, oder eine entsprechende Bildfolge, auf die die Probenorte aufweisende Vorderseite des Probenträgers wirft, wobei das Bild, oder die Bildfolge, so ausgelegt ist, dass ein ausgewählter Probenort, oder eine Gruppe von ausgewählten Probenorten, zumindest gegenüber dazu benachbarten nicht-ausgewählten Probenorten in für einen Menschen visuell wahrnehmbarer Weise hervorgehoben wird, eine Schnittstelle zur Bestätigung der Belegung von Hand und/oder eine Einrichtung zur automatisierten Erfassung eines händischen Belegungsvorgangs, und ein Leitsystem, das einen Probenort, oder eine Gruppe von Probenorten, auswählt und die Vorrichtung entsprechend ansteuert. Offenbart ist ebenfalls ein Verfahren zur Unterstützung einer händischen Belegung von Probenorten.
摘要翻译：沉积助剂（2）具有用于样品载体（8）的保持器（6），其具有多个样品位置，以及选择样品位置的引导系统。投影仪将构建的二维光学图像投影到样本位置的一部分上，使得所选择的样本位置相对于人眼感知的相邻未选择的样本位置被突出显示。控制系统（10）启动用于自动检测手动沉积过程的装置。包括用于辅助手动制备样品的方法的独立权利要求。

8. 发明公开

EP1053784A3 Processing samples in solutions having defined small contact area with support 审中-公开
标题翻译：样本在具有限定的小载体接触面的解决方案的处理
公开(公告)号：EP1053784A3
公开(公告)日：2001-05-23
申请号：EP00110123.7
申请日：2000-05-10
申请人： Bruker Daltonik GmbH
发明人： Nordhoff, Eckhard , Eickhoff, Holger , Schürenberg, Martin , Franzen, Jochen
IPC分类号： B01J19/00 , B01L3/00
CPC分类号： B01L3/0262 , B01J19/0046 , B01J2219/00315 , B01J2219/00479 , B01J2219/00533 , B01J2219/00585 , B01J2219/0065 , B01J2219/00659 , B01J2219/00704 , B01J2219/0072 , B01L3/5085 , B01L3/5088
摘要： The invention relates to the processing of very small quantities of sample, that is, the performing of chemical or enzymatic reactions, purifications, or analytic investigations, in very small quantities of liquid in the order of one microliter and less, particularly for very large numbers of samples in simultaneous processes. The invention consists of reducing the vessel wall contact areas, which increase disproportionately with very small quantities of liquid, and have largely detrimental influences, by using standing (or suspended) droplets as microreactors for processing, whereby the droplets are supported by wetting-friendly (lyophilic) anchors in surfaces which would otherwise be hostile to wetting (lyophobic) and therefore possess a well-defined wall contact area. The anchors can be passivated in a required manner or also be made surface-active, the latter in order to support certain processing steps. It is also possible to integrate electrical, optical, fluidic, or other microstructured elements into the support in order to assist processing. The invention relates to the basic method of processing in the supported droplet and correspondingly designed supports.

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