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1. 发明申请

US20100140506A1 METHOD OF DETERMINING A MEASUREMENT VALUE ON THE BASIS OF SINGLE MOLECULE EVENTS 审中-公开
标题翻译：基于单分子事件确定测量值的方法
公开(公告)号：US20100140506A1
公开(公告)日：2010-06-10
申请号：US12687969
申请日：2010-01-15
申请人： Christian EGGELING , Andreas SCHÖNLE , Stefan W. HELL , Michael HILBERT
发明人： Christian EGGELING , Andreas SCHÖNLE , Stefan W. HELL , Michael HILBERT
IPC分类号： G01N21/64
CPC分类号： G01N21/6428 , G01N21/6408 , G01N21/6458 , G01N2021/6419 , G01N2021/6439
摘要： A method of determining a measurement value on the basis of a plurality of single molecule events of marker molecules in a sample comprises the steps of selecting the marker molecules from a group of marker molecules which are transferable between a measurable state in which a measurement signal necessary for determining the at least one measurement value is obtainable from the marker molecules and a non-measurable state, of providing the marker molecules in the sample at such an absolute concentration that the at least one measurement value is not determinable, if all marker molecules are in their measurable state, and adjusting a measurement concentration of the marker molecules in the measurable state by means of applying the physical signal to the sample at such an intensity that the at least one measurement value is determinable within a defined measurement area of the sample.
摘要翻译：基于样品中标记分子的多个单分子事件确定测量值的方法包括以下步骤：从一组标记分子中选择标记分子，所述标记分子可在可测量状态之间转移，其中测量信号必需用于确定所述至少一个测量值可从所述标记分子和不可测量的状态获得，以如下绝对浓度提供所述标记分子，所述绝对浓度至少一个测量值不能确定，如果所有标记分子是在可测量的状态下，并且以可测量状态的标记分子的测量浓度通过将样品的物理信号以样品的限定测量区域内的至少一个测量值确定的强度来调节。

2. 发明授权

US07345759B2 Method and device for the measurement of chemical and/or biological samples 有权
标题翻译：用于测量化学和/或生物样品的方法和装置
公开(公告)号：US07345759B2
公开(公告)日：2008-03-18
申请号：US10380192
申请日：2001-08-22
申请人： Rolf Guenther , Leif Brand , Christian Eggeling , Karsten Gall , Claus Seidel
发明人： Rolf Guenther , Leif Brand , Christian Eggeling , Karsten Gall , Claus Seidel
IPC分类号： G01N21/64
CPC分类号： G01N21/6428 , G01N2021/6419 , G01N2021/6421 , G01N2021/6441
摘要： A device for the measurement of chemical and/or biological samples, in particular by means of luminescence spectroscopy, comprises an irradiation unit, a sample receiver, at least one optical unit and a detector unit. The color marker in the sample, which contains at least one color marker, is stimulated by irradiation into producing luminescence and gives off light. The light emitted by the color markers is detected by detectors in the detector unit. According to the invention, the measurement results may be improved by the irradiation unit generating pulsed irradiation. The irradiation unit is thus preferably controlled by a control unit in such a way that the irradiation pulses impinge on the sample in a temporal sequence.
摘要翻译：用于测量化学和/或生物样品，特别是通过发光光谱测量的装置包括照射单元，样品接收器，至少一个光学单元和检测器单元。包含至少一种颜色标记的样品中的颜色标记物被照射刺激以产生发光并发光。由颜色标记发出的光由检测器单元中的检测器检测。根据本发明，可以通过产生脉冲照射的照射单元改善测量结果。因此，照射单元优选地由控制单元控制，使得照射脉冲以时间顺序照射在样品上。

3. 发明申请

US20110160083A1 HIGH SPATIAL RESOLUTION IMAGING OF A STRUCTURE OF INTEREST IN A SPECIMEN 有权
标题翻译：一个样本中利益结构的高空间分辨率成像
公开(公告)号：US20110160083A1
公开(公告)日：2011-06-30
申请号：US13013359
申请日：2011-01-25
申请人： Stefan Hell , Christian Eggeling , Alexander Egner , Jonas Fölling , Andreas Schönle , Mariano Bossi
发明人： Stefan Hell , Christian Eggeling , Alexander Egner , Jonas Fölling , Andreas Schönle , Mariano Bossi
IPC分类号： C40B30/04 , C40B30/10
CPC分类号： G01N21/6458 , G01N21/6428 , G02B21/16 , G02B21/367 , G02B27/58
摘要： For imaging of a structure, the structure is marked with a substance which can be converted by a switching signal from a first into a second state, and which provides an optical measurement signal in one of its states, only. The switching signal is applied such that at least 10% of the molecules of the substance being in the measurement signal providing state are at a distance from their closest neighbors, which is greater than the spatial resolution limit of imaging the specimen onto a sensor array, which in turn is greater than an average distance between the molecules of the substance. From an intensity distribution of the measurement signal recorded with the sensor array, the position is only determined for those molecules of the substance which are at a distance from their closest neighboring molecules in the measurement signal providing state, which is greater than the spatial resolution limit.
摘要翻译：对于结构的成像，结构用可以通过开关信号从第一状态转换为第二状态并且仅在其状态之一提供光学测量信号的物质标记。施加开关信号，使得处于测量信号提供状态的物质的至少10％的分子距离它们最近的邻近物一个距离，其大于将样本成像到传感器阵列上的空间分辨率极限，其又大于物质分子之间的平均距离。根据记录有传感器阵列的测量信号的强度分布，该位置仅对于在测量信号提供状态中离它们最近的相邻分子一定距离的物质的那些分子确定，其大于空间分辨率极限。

4. 发明申请

US20110081653A1 High Spatial Resolution Imaging of a Structure of Interest in a Specimen 有权
标题翻译：样本中兴趣结构的高空间分辨率成像
公开(公告)号：US20110081653A1
公开(公告)日：2011-04-07
申请号：US12949159
申请日：2010-11-18
申请人： Stefan W. HELL , Jonas FÖLLING , Christian EGGELING , Alexander EGNER , Andreas SCHÖNLE , Mariano BOSSI
发明人： Stefan W. HELL , Jonas FÖLLING , Christian EGGELING , Alexander EGNER , Andreas SCHÖNLE , Mariano BOSSI
IPC分类号： G01N21/64 , G21K5/00 , C12Q1/68
CPC分类号： G01N21/6458 , G01N21/6428 , G02B21/16 , G02B21/367 , G02B27/58
摘要： In high spatial resolution imaging, a structure in a specimen is marked with a substance which, in a first electronic state, is excited by light of one wavelength to emit fluorescent light, which is also converted from its first into a second electronic state by that light, and which returns from its second into its first electronic state. The specimen is imaged onto a sensor at a spatial resolution not resolving an average spacing between neighboring molecules of the substance, and exposed to the light at such an intensity that the molecules in the first state are alternately excited to emit fluorescent light and converted into their second state, and that at least 10% of the molecules presently in their first state lie at a distance from their closest neighboring molecules in their first state which is greater than the spatial resolution of the imaging onto the sensor.
摘要翻译：在高空间分辨率成像中，样本中的结构用物质标记，该物质在第一电子状态下被一个波长的光激发以发射荧光，其也从其第一个电子状态转换成第二电子状态光，从第二个回到第一个电子状态。将样本以不分辨物质的相邻分子之间的平均间隔的空间分辨率成像到传感器上，并以如此强度暴露于光，使得第一状态下的分子被交替地激发以发射荧光并转换成它们并且目前处于其第一状态的至少10％的分子处于与它们的第一状态中最接近的相邻分子相距一定距离，其大于成像在传感器上的空间分辨率。

5. 发明授权

US07719679B2 Method and device for optically measuring a sample 失效
标题翻译：用于光学测量样品的方法和装置
公开(公告)号：US07719679B2
公开(公告)日：2010-05-18
申请号：US11955793
申请日：2007-12-13
申请人： Stefan Hell , Christian Eggeling , Gerald Donnert
发明人： Stefan Hell , Christian Eggeling , Gerald Donnert
IPC分类号： G01N21/64
CPC分类号： G01N21/6458
摘要： The inventive method for optically measuring a sample consists in temporarily repeatedly transmitting an electromagnetic signal (2) to the sample in such a way that a substance contained in the sample is transferred from a first electronic state (1) into a second electronic state (3), wherein at least one part of said substance in the second state (3) emits photons which are used for carrying out the optical measurement of the sample, the signal (2) is transmitted to the same sample area at a certain repetition interval and said repetition interval of the signal (2) is adjusted with a lifetime of the second state (3) of the substance having an order of magnitude of 1 ns on a value of at least 0.1 μs which is optimized with respect to photon yield from the substance.
摘要翻译：用于光学测量样品的本发明的方法在于将样品中包含的物质从第一电子状态（1）转移到第二电子状态（3）的方式临时重复地将电磁信号（2）发送到样品），其中在第二状态（3）中的所述物质的至少一部分发射用于进行样品的光学测量的光子，所述信号（2）以一定的重复间隔传输到相同的样品区域，所述信号（2）的所述重复间隔在具有1ns量级的物质的第二状态（3）的寿命的至少0.1μs的值上被调整，所述寿命针对来自物质。

6. 发明授权

US09759659B2 Method for detecting the impacts of interfering effects on experimental data 有权
公开(公告)号：US09759659B2
公开(公告)日：2017-09-12
申请号：US13044787
申请日：2011-03-10
申请人： Christian Eggeling , Kaupo Palo , Nicolas Fay , Maciej Hoffman-Wecker , Pierre Ilouga
发明人： Christian Eggeling , Kaupo Palo , Nicolas Fay , Maciej Hoffman-Wecker , Pierre Ilouga
IPC分类号： G06F17/18 , G01N21/64
CPC分类号： G01N21/6445 , G01N2201/1215
摘要： A method for identifying the impact on data, such as experimental data, of interfering effects, such as unwanted auto-fluorescence, fluorescence quenching, and fluorescent-sample deterioration, whether or not the data fulfill certain criteria with respect to a threshold indicative of the interfering effects.

7. 发明授权

US08735444B2 Fluorinated rhodamines as photostable fluorescent dyes for labelling and imaging techniques 有权
标题翻译：氟化罗丹明作为用于标记和成像技术的光稳定荧光染料
公开(公告)号：US08735444B2
公开(公告)日：2014-05-27
申请号：US13380148
申请日：2009-06-26
申请人： Stefan W. Hell , Vladimir N. Belov , Gyuzel Mitronova , Mariano Bossi , Gael Moneron , Christian A. Wurm , Stefan Jakobs , Christian Eggeling , Jakob Bierwagen , Lars Meyer
发明人： Stefan W. Hell , Vladimir N. Belov , Gyuzel Mitronova , Mariano Bossi , Gael Moneron , Christian A. Wurm , Stefan Jakobs , Christian Eggeling , Jakob Bierwagen , Lars Meyer
IPC分类号： A61K31/352 , C07D311/82
CPC分类号： C07D311/82 , A61K49/0041 , A61K49/0058 , C07K1/13 , C09B11/24 , G01N33/582
摘要： The present invention relates to novel fluorinated 3,6-diaminoxanthene compounds derived from the basic structural formula (I) and to their uses as photostable fluorescent dyes, e.g. for immunostainings and spectroscopic and microscopic applications, in particular in conventional microscopy, stimulated emission depletion (STED) reversible saturable optically linear fluorescent transitions (RESOLFT) microscopy, and fluorescence correlation spectroscopy. The claimed compounds are also useful as molecular probes in various spectroscopic applications.
摘要翻译：本发明涉及衍生自基本结构式（I）的新型氟化3,6-二氨基呫吨化合物及其作为光稳定荧光染料的用途。用于免疫染色和光谱和微观应用，特别是在常规显微镜，受激发射耗尽（STED）可逆饱和光学线性荧光转换（RESOLFT）显微镜和荧光相关光谱学中。所要求保护的化合物也可用作各种光谱应用中的分子探针。

8. 发明授权

US08580579B2 Hydrophilic and lipophilic rhodamines for labelling and imaging 有权
标题翻译：亲水和亲脂罗丹明用于标记和成像
公开(公告)号：US08580579B2
公开(公告)日：2013-11-12
申请号：US13266775
申请日：2010-04-26
申请人： Stefan Hell , Vladimir N. Belov , Kirill Kolmakov , Volker Westphal , Marcel Lauterbach , Stefan Jakobs , Christian Wurm , Christian Eggeling , Christian Ringemann
发明人： Stefan Hell , Vladimir N. Belov , Kirill Kolmakov , Volker Westphal , Marcel Lauterbach , Stefan Jakobs , Christian Wurm , Christian Eggeling , Christian Ringemann
IPC分类号： G01N33/533 , G01N33/532 , G01N21/76
CPC分类号： C07D491/22 , C09B11/24 , G01N33/582
摘要： The invention relates to novel and improved photostable rhodamine dyes of the general structural formulae I or II and their uses as fluorescent markers, e.g. for immunostainings and spectroscopic and microscopic applications, in particular in conventional and stimulated emission depletion (STED) microscopy and fluorescence correlation spectroscopy. The partially deuterated analogues are useful as molecular mass distribution tags in mass spectroscopic applications, wherein R1=an unsubstituted or substituted alkyl group, including a cycloalkyl group, or heterocycloalkyl group; R2=H, an unsubstituted or substituted alkyl group, including a cycloalkyl group, or heterocycloalkyl group, or an unsubstituted or substituted aryl group or heteroaryl group, or any combination of such groups; X=CH2, C═O, C═NORa, C═NNRaNRb, CH(ORa), O, S, SO, SO2, or any other derivatives of these groups, with Ra and Rb independently being H or an organic residue, in particular an unsubstituted or substituted (cyclo)alkyl group or heterocycloalkyl group, an unsubstituted or substituted aryl group or heteroaryl group; Z=a negatively charged group with 1, 2, 3, 4 or 5 charges per anion.
摘要翻译：本发明涉及通用结构式I或II的新型和改进的光稳定罗丹明染料及其作为荧光标记物的用途。用于免疫染色和光谱和微观应用，特别是在常规和受激发射耗尽（STED）显微镜和荧光相关光谱学中。部分氘代类似物可用作质谱应用中的分子量分布标签，其中R1 =未取代或取代的烷基，包括环烷基或杂环烷基; R 2 = H，未取代或取代的烷基，包括环烷基或杂环烷基，或未取代或取代的芳基或杂芳基，或这些基团的任何组合; X = CH2，C = O，C = NORa，C = NNRaNRb，CH（ORa），O，S，SO，SO2或这些基团的任何其他衍生物，其中Ra和Rb独立地为H或有机残基，特别是未取代或取代的（环）烷基或杂环烷基，未取代或取代的芳基或杂芳基; Z =带负电荷的基团，每个阴离子具有1,2,3,4或5个电荷。

9. 发明申请

US20110218767A1 Method for Detecting The Impacts of Interfering Effects on Experimental Data 有权
标题翻译：检测干扰效应对实验数据影响的方法
公开(公告)号：US20110218767A1
公开(公告)日：2011-09-08
申请号：US13044787
申请日：2011-03-10
申请人： Christian Eggeling , Kaupo Palo , Nicolas Fay , Maciej Hoffman-Wecker , Pierre Ilouga
发明人： Christian Eggeling , Kaupo Palo , Nicolas Fay , Maciej Hoffman-Wecker , Pierre Ilouga
IPC分类号： G06F17/18
CPC分类号： G01N21/6445 , G01N2201/1215
摘要： The invention provides a method for identifying the impacts of interfering effects on experimental data. In particular, a method is described for identifying the impacts of unwanted auto-fluorescence, fluorescence quenching, and deterioration of a fluorescent sample under study on the collected experimental data. The data are analyzed whether or not said data fulfill certain criteria with respect to a threshold which is indicative for said interfering effect.
摘要翻译：本发明提供了一种识别干扰效应对实验数据的影响的方法。特别地，描述了一种用于识别不期望的自动荧光，荧光猝灭和正在研究的荧光样品的劣化对所收集的实验数据的影响的方法。分析数据是否所述数据是否符合指示所述干扰效应的阈值的某些标准。

10. 发明授权

US07880150B2 High spatial resolution imaging of a structure of interest in a specimen 有权
标题翻译：样本中感兴趣结构的高空间分辨率成像
公开(公告)号：US07880150B2
公开(公告)日：2011-02-01
申请号：US12128948
申请日：2008-05-29
申请人： Stefan Hell , Christian Eggeling , Alexander Egner , Jonas Fölling , Andreas Schönle , Mariano Bossi
发明人： Stefan Hell , Christian Eggeling , Alexander Egner , Jonas Fölling , Andreas Schönle , Mariano Bossi
IPC分类号： G01N21/64
CPC分类号： G01N21/6458 , G01N21/6428 , G02B21/16 , G02B21/367 , G02B27/58
摘要： For the high spatial resolution imaging of a structure of interest in a specimen, a substance is selected from a group of substances which have a fluorescent first state and a nonfluorescent second state; which can be converted fractionally from their first state into their second state by light which excites them into fluorescence, and which return from their second state into their first state; the specimen's structure of interest is imaged onto a sensor array, a spatial resolution limit of the imaging being greater (i.e. worse) than an average spacing between closest neighboring molecules of the substance in the specimen; the specimen is exposed to light in a region which has dimensions larger than the spatial resolution limit, fractions of the substance alternately being excited by the light to emit fluorescent light and converted into their second state, and at least 10% of the molecules of the substance that are respectively in the first state lying at a distance from their closest neighboring molecules in the first state which is greater than the spatial resolution limit; and the fluorescent light, which is spontaneously emitted by the substance from the region, is registered in a plurality of images recorded by the sensor array during continued exposure of the specimen to the light.
摘要翻译：对于样本中感兴趣的结构的高空间分辨率成像，物质选自具有荧光第一状态和非荧光第二状态的物质组; 其可以通过将它们激发成荧光的光从其第一状态分数转换成第二状态，并且从它们的第二状态返回到其第一状态; 将感兴趣的标本的结构成像到传感器阵列上，成像的空间分辨率极限比样品中物质的最接近的相邻分子之间的平均间距更大（即更差）试样在具有大于空间分辨率极限的尺寸的区域中暴露于光，该物质的部分交替地被光激发以发射荧光并转换成其第二状态，并且至少10％的分别处于第一状态的物质，其处于与第一状态相比最大相邻分子一定距离，该距离大于空间分辨率极限; 并且由该区域内的物质自发地发出的荧光被记录在传感器阵列记录的多个图像中，该样本在样品持续暴露于光下。

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