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1. 发明授权

US07534576B2 Method and a device for the evaluation of biopolymer fitness 失效
标题翻译：用于评估生物聚合物适应性的方法和装置
公开(公告)号：US07534576B2
公开(公告)日：2009-05-19
申请号：US11730931
申请日：2007-04-04
申请人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehman
发明人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehman
IPC分类号： G01N33/569
CPC分类号： G01N21/6452 , C12Q1/04 , C12Q1/6827 , G01N21/64 , G01N21/6402 , G01N21/6408 , G01N21/6428 , G01N21/6458 , G02B21/24 , Y10S435/808 , Y10S436/805 , Y10T436/11 , C12Q2565/107 , C12Q2561/113 , C12Q2535/131
摘要： A Method for identifying one or a small number of molecules, especially in a dilution of ≦1 μM, using laser excited FCS with measuring times ≦500 ms and short diffusion paths of the molecules to be analyzed, wherein the measurement is performed in small volume units of preferably ≦10−14 l, by determining material-specific parameters which are determined by luminescence measurements of molecules to be examined.The device which can be preferably used for performing the method according to the invention is a per se known system of microscope optics for laser focusing for fluorescence excitation in a small measuring compartment of a very diluted solution and for imaging the emitted light in the subsequent measurement through confocal imaging wherein at least one system of optics with high numerical aperture of preferably ≧1.2 N.A. is employed, the light quantity is limited by a confocally arranged pinhole aperture in the object plane behind the microscope objective, and the measuring compartment is positioned at a distance of between 0 and 1000 μm from the observation objective.
摘要翻译：使用测量时间<= 500ms的激光激发FCS和要分析的分子的短扩散路径来识别一个或少数分子，特别是稀释度为<=1μM的分子的方法，其中测量在通过确定由待分析的分子的发光测量确定的材料特异性参数，优选<=10-14μl的小体积单位。可以优选用于执行根据本发明的方法的装置是本身已知的用于在非常稀释的溶液的小测量室中进行荧光激发的激光聚焦的显微镜光学系统，并且用于在后续测量中对发射的光进行成像通过共焦成像，其中使用具有优选> = 1.2NA的高数值孔径的至少一个光学系统，光量受到在显微镜物镜后面的物平面中的共同排列的针孔的限制，并且测量室位于与观察目标之间的距离为0至1000μm。

2. 发明申请

US20070243525A1 Method and a device for the evaluation of biopolymer fitness 失效
公开(公告)号：US20070243525A1
公开(公告)日：2007-10-18
申请号：US11730931
申请日：2007-04-04
申请人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehmann
发明人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehmann
IPC分类号： C12Q1/02 , C12Q1/70 , G01J3/30
CPC分类号： G01N21/6452 , C12Q1/04 , C12Q1/6827 , G01N21/64 , G01N21/6402 , G01N21/6408 , G01N21/6428 , G01N21/6458 , G02B21/24 , Y10S435/808 , Y10S436/805 , Y10T436/11 , C12Q2565/107 , C12Q2561/113 , C12Q2535/131
摘要： A Method for identifying one or a small number of molecules, especially in a dilution of ≦1 μM, using laser excited FCS with measuring times ≦500 ms and short diffusion paths of the molecules to be analyzed, wherein the measurement is performed in small volume units of preferably ≦10−14 l, by determining material-specific parameters which are determined by luminescence measurements of molecules to be examined. The device which can be preferably used for performing the method according to the invention is a per se known system of microscope optics for laser focusing for fluorescence excitation in a small measuring compartment of a very diluted solution and for imaging the emitted light in the subsequent measurement through confocal imaging wherein at least one system of optics with high numerical aperture of preferably ≧1.2 N.A. is employed, the light quantity is limited by a confocally arranged pinhole aperture in the object plane behind the microscope objective, and the measuring compartment is positioned at a distance of between 0 and 1000 μm from the observation objective.

3. 发明授权

US06582903B1 Method and a device for the evaluation of biopolymer fitness 失效
标题翻译：用于评估生物聚合物适应性的方法和装置
公开(公告)号：US06582903B1
公开(公告)日：2003-06-24
申请号：US09021410
申请日：1998-02-10
申请人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehmann
发明人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehmann
IPC分类号： G01N33543
CPC分类号： G01N21/6402 , G01N21/6428 , G01N21/6458 , G01N2021/6417 , Y10S435/808 , Y10S436/805 , Y10T436/11
摘要： A method for identifying one or a small number of molecules, especially in a dilution of ≦1 &mgr;M, using laser excited FCS with measuring times ≦500 ms and short diffusion paths of the molecules to be analyzed, wherein the measurement is performed in small volume units of preferably ≦10−14 l, by determining material-specific parameters which are determined by luminescence measurements of molecules to be examined.
摘要翻译：使用测量时间<= 500ms的激光激发FCS和要分析的分子的短扩散路径来识别一个或少数分子，特别是稀释度为<=1μM的分子的方法，其中测量在通过确定由待分析的分子的发光测量确定的材料特异性参数，优选<=10-14μl的小体积单位。

4. 发明申请

US20090194706A1 Method and device for the selective withdrawal of compontents from complex mixtures 审中-公开
标题翻译：从复杂混合物中选择性取出组分的方法和装置
公开(公告)号：US20090194706A1
公开(公告)日：2009-08-06
申请号：US12385440
申请日：2009-04-08
申请人： Manfred Eigen , Rudolf Rigler , Karsten Henco
发明人： Manfred Eigen , Rudolf Rigler , Karsten Henco
IPC分类号： G01N21/64 , B67D5/52
CPC分类号： B01L3/0268 , C12M33/07 , G01N15/10 , Y10T436/2575
摘要： The method according to the invention permits a selected withdrawal of one or a few molecularly disperse or cellular components of a system, such as molecules, molecular complexes, vesicles, micelles, cells, optionally together with an associated volume element V having a size of 10−9 l≧V≧10−18 l from a larger sample volume. The selected transfer of the sought component to another environment is effected by defining the space and time of withdrawal by means of a signal correlating with the small component to be withdrawn. The method is particularly useful for the withdrawal of non-abundant components the existence of which can be detected in a preceding step by a scanning process. The method is also useful for the withdrawal of per se unidentified components.
摘要翻译：根据本发明的方法允许选择性地撤出系统的一种或几种分子分散或细胞组分，例如分子，分子复合物，囊泡，胶束，细胞，任选地与尺寸为10的相关体积元素V一起 -9 l> = V> = 10-18 l。所寻求的组件选择的转移到另一环境是通过借助与要撤回的小组件相关联的信号定义撤回的空间和时间来实现的。该方法对于通过扫描过程在前一步骤中可以检测到其存在的非丰富成分是特别有用的。该方法对于本身不确定的组分的撤回也是有用的。

5. 发明申请

US20050250157A1 Method and device for the selective withdrawal of components from complex mixtures 审中-公开
标题翻译：从复杂混合物中选择性取出组分的方法和装置
公开(公告)号：US20050250157A1
公开(公告)日：2005-11-10
申请号：US11015179
申请日：2004-12-20
申请人： Manfred Eigen , Rudolf Rigler , Karsten Henco
发明人： Manfred Eigen , Rudolf Rigler , Karsten Henco
IPC分类号： B01L3/02 , B67D7/70 , C12M1/26 , G01N15/10 , G01N33/53
CPC分类号： B01L3/0268 , C12M33/07 , G01N15/10 , Y10T436/2575
摘要： The method according to the invention permits a selected withdrawal of one or a few molecularly disperse or cellular components of a system, such as molecules, molecular complexes, vesicles, micelles, cells, optionally together with an associated volume element V having a size of 10−9 l≧V≧10−18 l from a larger sample volume. The selected transfer of the sought component to another environment is effected by defining the space and time of withdrawal by means of a signal correlating with the small component to be withdrawn. The method is particularly useful for the withdrawal of non-abundant components the existence of which can be detected in a preceding step by a scanning process. The method is also useful for the withdrawal of per se unidentified components.
摘要翻译：根据本发明的方法允许选择性地撤出系统的一种或几种分子分散或细胞组分，例如分子，分子复合物，囊泡，胶束，细胞，任选地与尺寸为10的相关体积元素V一起从较大的样品体积可以得到。所寻求的组件选择的转移到另一环境是通过借助与要撤回的小组件相关联的信号定义撤回的空间和时间来实现的。该方法对于通过扫描过程在前一步骤中可以检测到其存在的非丰富成分是特别有用的。该方法对于本身不确定的组分的撤回也是有用的。

6. 发明授权

US07241569B2 Method and a device for the evaluation of biopolymer fitness 有权
标题翻译：用于评估生物聚合物适应性的方法和装置
公开(公告)号：US07241569B2
公开(公告)日：2007-07-10
申请号：US10435674
申请日：2003-05-12
申请人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehman
发明人： Rudolf Rigler , Manfred Eigen , Karsten Henco , Ulo Mets , Jerker Widengren , Michael Stuke , Michael Brinkmeyer , Wolfgang Simm , Olaf Lehman
IPC分类号： G01N33/543
CPC分类号： G01N21/6452 , C12Q1/04 , C12Q1/6827 , G01N21/64 , G01N21/6402 , G01N21/6408 , G01N21/6428 , G01N21/6458 , G02B21/24 , Y10S435/808 , Y10S436/805 , Y10T436/11 , C12Q2565/107 , C12Q2561/113 , C12Q2535/131
摘要： A Method for identifying one or a small number of molecules, especially in a dilution of ≦1 μM, using laser excited FCS with measuring times ≦500 ms and short diffusion paths of the molecules to be analyzed, wherein the measurement is performed in small volume units of preferably ≦10−14 l, by determining material-specific parameters which are determined by luminescence measurements of molecules to be examined.The device which can be preferably used for performing the method according to the invention is a per se known system of microscope optics for laser focusing for fluorescence excitation in a small measuring compartment of a very diluted solution and for imaging the emitted light in the subsequent measurement through confocal imaging wherein at least one system of optics with high numerical aperture of preferably ≧1.2 N.A. is employed, the light quantity is limited by a confocally arranged pinhole aperture in the object plane behind the microscope objective, and the measuring compartment is positioned at a distance of between 0 and 1000 μm from the observation objective.
摘要翻译：使用测量时间<= 500ms的激光激发FCS和要分析的分子的短扩散路径来识别一个或少数分子，特别是稀释度为<=1μM的分子的方法，其中测量在通过确定通过待检测分子的发光测量确定的材料特异性参数，优选<= 10 -14 / 1的小体积单位。可以优选用于执行根据本发明的方法的装置是本身已知的用于在非常稀释的溶液的小测量室中进行荧光激发的激光聚焦的显微镜光学系统，并且用于在后续测量中对发射的光进行成像通过共焦成像，其中使用具有优选> = 1.2NA的高数值孔径的至少一个光学系统，光量受到在显微镜物镜后面的物平面中的共同排列的针孔的限制，并且测量室位于与观察目标之间的距离为0至1000μm。

7. 发明授权

US06849461B2 Method and device for the selective withdrawal of components from complex mixtures 失效
标题翻译：从复杂混合物中选择性取出组分的方法和装置
公开(公告)号：US06849461B2
公开(公告)日：2005-02-01
申请号：US08750715
申请日：1995-06-16
申请人： Manfred Eigen , Rudolf Rigler , Karsten Henco
发明人： Manfred Eigen , Rudolf Rigler , Karsten Henco
IPC分类号： B01L3/02 , B67D7/70 , C12M1/26 , G01N15/10 , G01N21/84 , G01N1/14 , G01N21/64 , G01N21/75 , G01N33/15
CPC分类号： B01L3/0268 , C12M33/07 , G01N15/10 , Y10T436/2575
摘要： The method according to the invention permits a selected withdrawal of one or a few molecularly disperse or cellular components of a system, such as molecules, molecular complexes, vesicles, micelles, cells, optionally together with an associated volume element V having a size of 10−9 l≧V≧10−18 l from a larger sample volume. The selected transfer of the sought component to another environment is effected by defining the space and time of withdrawal by means of a signal correlating with the small component to be withdrawn. The method is particularly useful for the withdrawal of non-abundant components the existence of which can be detected in a preceding step by a scanning process. The method is also useful for the withdrawal of per se unidentified components.
摘要翻译：根据本发明的方法允许选择性地撤出系统的一种或几种分子分散或细胞组分，例如分子，分子复合物，囊泡，胶束，细胞，任选地与尺寸为10的相关体积元素V一起 <9> l> = V> = 10 l。所寻求的组件选择的转移到另一环境是通过借助与要撤回的小组件相关联的信号定义撤回的空间和时间来实现的。该方法对于通过扫描过程在前一步骤中可以检测到其存在的非丰富成分是特别有用的。该方法对于本身不确定的组分的撤回也是有用的。

8. 发明授权

US5795747A Process for manufacturing new biopolymers 失效
标题翻译：生产新生物聚合物的方法
公开(公告)号：US5795747A
公开(公告)日：1998-08-18
申请号：US507190
申请日：1995-06-26
申请人： Karsten Henco , Manfred Eigen
发明人： Karsten Henco , Manfred Eigen
IPC分类号： C12N15/10 , C12Q1/68 , C12P19/34
CPC分类号： C12N15/1079 , C12N15/1058 , C12Q1/6811
摘要： The process of generating new biopolymers with improved characteristics, assisted by polymerases, is characterized in that at least one cycle of the steps described below, will be performed in a series of parallel preparations which are to be compared. Sequences of nucleic acids or, a mixture of similar sequences of nucleic acids in the distribution of mutants of a quasi-species, are subjected, in the region of the error threshold, to limited mutagenesis. These mixtures are replicated under simultaneous conditions and/or in succession. The mixtures of the so product nucleic acids are compartmentalized by segregation, and thereafter selected by a selection system which reflects the characteristics of interest of the nucleic acid sequence itself or, indirectly, via its translation product.
摘要翻译：通过聚合酶辅助产生具有改进特征的新生物聚合物的方法的特征在于下述步骤的至少一个循环将在一系列待比较的平行制剂中进行。序列的核酸或类似核酸序列的混合物在拟种突变体的分布中，在误差阈值区域受到有限的诱变。这些混合物在同时条件下和/或连续复制。这样的产物核酸的混合物通过分离进行分隔，然后通过反映核酸序列本身的感兴趣特征的选择系统或通过其翻译产物间接选择。

9. 发明授权

US07015017B2 Process and agent for instabilizing viral quasi-species-distributions avoiding resistance phenomena 失效
公开(公告)号：US07015017B2
公开(公告)日：2006-03-21
申请号：US10032897
申请日：2001-10-25
申请人： Manfred Eigen , Andreas Schwienhorst , Christof Biebricher , Björn Lindemann , Esteban Domingo , John Holland , Karsten Henco
发明人： Manfred Eigen , Andreas Schwienhorst , Christof Biebricher , Björn Lindemann , Esteban Domingo , John Holland , Karsten Henco
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C12N15/11 , A61K48/00 , A61K2039/525 , C12N7/00 , C12N15/00 , C12N2740/16011 , C12N2795/18111 , Y10T436/143333
摘要： A process for instabilizing viral quasi-species-distributions under avoidance of resistance phenomena by replication of the nucleic acids of the viruses present in the quasi-species-distribution by of a defective replication system, a) whereby the defective replication system has a rate of misincorporation for nucleotides above the rate of misincorporation of the viral wild-type-replication system and, whereby the viruses are replicated by the replication system having the higher rate of misincorporation at least as effectively as it is done by the replication system of the wild-type virus, b) and/or negative influence of the replication of the consensus-sequence (nucleic acid sequence of the wild-type virus) in relation to other replicatable nucleic acids.

10. 发明授权

US06423516B1 Process and agent for instabilizing viral quasi-species-distributions avoiding resistance phenomena 失效
标题翻译：不稳定病毒准物种分布的过程和试剂，避免了阻力现象
公开(公告)号：US06423516B1
公开(公告)日：2002-07-23
申请号：US08362604
申请日：1996-03-22
申请人： Manfred Eigen , Andreas Schwienhorst , Christof Biebricher , Björn Lindemann , Esteban Domingo , John Holland , Karsten Henco
发明人： Manfred Eigen , Andreas Schwienhorst , Christof Biebricher , Björn Lindemann , Esteban Domingo , John Holland , Karsten Henco
IPC分类号： C12P1934
CPC分类号： C12N15/11 , A61K48/00 , A61K2039/525 , C12N7/00 , C12N15/00 , C12N2740/16011 , C12N2795/18111 , Y10T436/143333
摘要： A process for instabilizing viral quasi-species-distributions under avoidance of resistance phenomena by replication of the nucleic acids of the viruses present in the quasi-species-distribution by of a defective replication system, a) whereby the defective replication system has a rate of misincorporation for nucleotides above the rate of misincorporation of the viral wild-type-replication system and, whereby the viruses are replicated by the replication system having the higher rate of misincorporation at least as effectively as it is done by the replication system of the wild-type virus, b) and/or negative influence of the replication of the consensus-sequence (nucleic acid sequence of the wild-type virus) in relation to other replicatable nucleic acids.
摘要翻译：一种通过利用有缺陷的复制系统复制存在于准物种分布中的病毒的核酸来避免抗性现象来阻止病毒准物种分布的方法，其中缺陷复制系统的速率为对于高于病毒野生型复制系统错配的速率的核苷酸的错配，并且其中病毒由具有较高错配率的复制系统复制至少与野生型复制系统的复制系统一样有效地复制，类型病毒，b）和/或共有序列（野生型病毒的核酸序列）相对于其他可重复核酸的复制的负面影响。

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