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。

公开(公告)号：US20040142386A1

公开(公告)日：2004-07-22

申请号：US10435674

申请日：2003-05-12

申请人： EVOTEC Biosystems GmbH

发明人： Rudolf Rigler ,  Manfrea Eigen ,  Karsten Henco ,  Ulo Mets ,  Jerker Widengren ,  Michael Stuke ,  Michael Brinkmeyer ,  Wolfgang Simm ,  Olaf Lehman

IPC分类号： G01N033/53 ,  G01N033/567

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 null1 nullM, using laser excited FCS with measuring times null500 ms and short diffusion paths of the molecules to be analyzed, wherein the measurement is performed in small volume units of preferably null10null14 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 null1.2 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 nullm 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>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。

公开(公告)号：US5871908A

公开(公告)日：1999-02-16

申请号：US157195

申请日：1993-12-08

申请人： Karsten Henco ,  Manfred Eigen ,  Detlev Riesner

发明人： Karsten Henco ,  Manfred Eigen ,  Detlev Riesner

IPC分类号： B01L7/00 ,  C12Q1/68 ,  C12P19/34

CPC分类号： B01L7/52 ,  C12Q1/6825 ,  C12Q1/686

摘要： A process for the qualitative and quantitative determination of at least one in vitro amplified nucleic acid in a sealed reaction chamber,wherein during or subsequent to the amplification of the nucleic acid at least one substance (probe) is present which interacts with the nucleic acid to be detected;wherein spectroscopically measurable parameters of said substance (probe) are subject to variation, creating a measurable signal;wherein the sample to be measured is exposed to the action of a gradient capable of at least partially denaturing nucleic acids;with detection of the measurable parameter undergoing variation through the action of the gradient; andthe entire amplification reaction, including qualitative and quantitative determination, may be carried out in a sealed reaction chamber (measuring compartment) without intermittent opening,permitting to automatically operate the diagnostic method of DNA and RNA amplification in qualitative and quantitative fashion on large series of samples.

摘要翻译： PCT No.PCT / EP93 / 00254 Sec。 371日期：1993年12月8日 102（e）日期1993年12月8日PCT提交1993年2月4日PCT公布。 公开号WO93 / 16194 日期1993年8月19日一种在密封反应室中定性和定量测定至少一种体外扩增的核酸的方法，其中在核酸扩增期间或之后存在至少一种物质（探针），其与 与待检测的核酸; 其中所述物质（探针）的光谱可测量参数经历变化，产生可测量的信号; 其中要测量的样品暴露于能够至少部分变性核酸的梯度的作用; 通过梯度的作用检测可测量的参数变化; 并且包括定性和定量测定的整个扩增反应可以在密封的反应室（测量室）中进行，而不间断地打开，允许以定性和定量的方式自动操作DNA和RNA扩增的诊断方法 样品。

公开(公告)号：US5849545A

公开(公告)日：1998-12-15

申请号：US834834

申请日：1997-04-10

申请人： Karsten Henco ,  Manfred Eigen

发明人： Karsten Henco ,  Manfred Eigen

IPC分类号： C12Q1/68 ,  C12P19/34

CPC分类号： C12Q1/6834

摘要： Described is a support material that can simultaneously bind both genotypic and phenotypic substances. The respective areas, which can have surface-modifying matter such as anionic exchangers and/or affinity ligands, simultaneously bind, for example, nucleic acids and proteins or peptides. The support materials described can be used in processes for evolutive optimization of biopolymers, wherein genotype and phenotype can be bound at the same time so as to furnish them for further analysis.

摘要翻译： 描述了可同时结合基因型和表型物质的支持材料。 可以具有表面改性物质如阴离子交换剂和/或亲和配体的各个区域同时结合例如核酸和蛋白质或肽。 所描述的载体材料可用于生物聚合物的进化优化的方法，其中基因型和表型可以同时结合，以便进一步分析。

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。

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。

公开(公告)号：US5933233A

公开(公告)日：1999-08-03

申请号：US836032

申请日：1997-04-28

申请人： Rolf Gunther

发明人： Rolf Gunther

IPC分类号： G01Q60/18 ,  G02B21/00 ,  G01N21/64

CPC分类号： G01Q60/22 ,  B82Y20/00 ,  B82Y35/00 ,  G01N21/645 ,  Y10S977/881 ,  Y10S977/95 ,  Y10S977/954

摘要： A method for the determination of material-specific parameters of one or a few molecules by means of correlation spectroscopy wherein the molecule or molecules in a sample in which the molecule(s) to be determined is (are) present in relatively high concentrations is (are) excited by electromagnetic radiation (excitation radiation) to emit electromagnetic radiation (emission radiation) wherein said excitation and/or emission radiation passes a means which is permeable to the corresponding wavelength of said electromagnetic radiation which means is disposed between an excitation or emission radiation source and an excitation or emission radiation detector, said means for transmitting electromagnetic waves having at least one region the largest dimension of which in at least one direction of space is smaller than the wavelength of said excitation and/or emission radiation of said molecule or molecules.

摘要翻译： PCT No.PCT / EP95 / 04213 371日期1997年04月28日 102（e）日期1997年4月28日PCT提交1995年10月26日PCT公布。 第WO96 / 13744号公报 日期1996年5月9日通过相关光谱法测定一个或几个分子的材料特异性参数的方法，其中待测分子的样品中的分子或分子存在于相对 通过电磁辐射（激发辐射）激发高浓度以发射电磁辐射（发射辐射），其中所述激发和/或发射辐射通过可透过所述电磁辐射的相应波长的装置，该装置被设置在 激发或发射辐射源和激发或发射辐射检测器，所述用于发射电磁波的装置具有至少一个区域，其中至少一个区域的最大尺寸在空间的至少一个方向上小于所述激发和/或发射辐射的波长 所述分子或分子。