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1. 发明授权

US6054036A Electrophoresis gels and gel holders having fiber spacers and method of making same 失效
标题翻译：具有纤维间隔物的电泳凝胶和凝胶保持器及其制造方法
公开(公告)号：US6054036A
公开(公告)日：2000-04-25
申请号：US77304
申请日：1998-12-31
申请人： Alexandre M. Izmailov , Paul Waterhouse , Henryk Zaleski
发明人： Alexandre M. Izmailov , Paul Waterhouse , Henryk Zaleski
IPC分类号： G01N21/64 , G01N27/447 , G01N27/26
CPC分类号： G01N27/44721 , G01N27/44704
摘要： Gel holders for electrophoresis gels are made using clad fibers, particularly glass fibers as spacers between substrates. A plurality of fibers with a high-melting interior core and a low-melting external cladding are placed between a first planar substrate and a second planar substrate. The fibers are heated to a temperature sufficient to at least soften the exterior cladding of the fibers without softening the interior core of the fibers, and then cooled while they are in contact with the first and second substrates to solidify the exterior cladding. This adheres the fibers to the first and second substrates, and forms a gel chamber between said first and second substrates. The gel chamber has a thickness defined by interior core of the fibers. The fibers may be heated before or after the second substrate is placed over the top of the fibers. The gel holders thus formed may be filled immediately with a gel forming solution such as a polyacrylamide, or they may be stored indefinitely and used as needed.
摘要翻译： PCT No.PCT / CA96 / 00832 Sec。 371 1998年12月31日第 102（e）1998年12月31日PCT PCT 1996年12月12日PCT公布。 WO97 / 21995 PCT公开号日期1996年6月19日凝胶凝胶保持器使用包覆纤维制成，特别是作为衬底之间的间隔物的玻璃纤维。具有高熔点内芯和低熔点外包层的多根纤维被放置在第一平面基板和第二平面基板之间。纤维被加热到足以至少软化纤维的外包层的温度，而不软化纤维的内芯，然后在与第一和第二基底接触的同时冷却，以固化外包层。这将纤维粘附到第一和第二基底上，并在所述第一和第二基底之间形成凝胶室。凝胶室具有由纤维的内芯限定的厚度。纤维可以在将第二基底放置在纤维顶部之前或之后被加热。如此形成的凝胶保持器可立即用诸如聚丙烯酰胺的凝胶形成溶液填充，或者可以无限期地储存并根据需要使用。

2. 发明授权

US5897842A Method and apparatus for thermal cycling and for automated sample preparation with thermal cycling 失效
标题翻译：用于热循环的方法和设备以及用于热循环的自动化样品制备
公开(公告)号：US5897842A
公开(公告)日：1999-04-27
申请号：US703730
申请日：1996-08-27
申请人： James M. Dunn , James Leushner , John Renfrew , Paul Waterhouse , Alexandre M. Izmailov , Henryk Zaleski
发明人： James M. Dunn , James Leushner , John Renfrew , Paul Waterhouse , Alexandre M. Izmailov , Henryk Zaleski
IPC分类号： B01L7/00 , C12Q1/68 , C12Q1/70 , G01N35/00 , B01L9/00 , C12M3/02
CPC分类号： B01L7/52 , B01L7/525 , C12Q1/6841 , C12Q1/6881 , C12Q1/689 , C12Q1/703 , C12Q2600/156 , C12Q2600/16 , G01N2035/00237
摘要： An apparatus and method for thermally cycling a reaction mixture in a reaction vessel to expose the mixture to the varying temperatures necessary to, for example, achieve PCR amplification or the preparation of sequencing fragments using a cycle sequencing operation makes use of flow-through reaction vessels, such as capillary tubes, for the preparation and thermal cycling of reaction mixtures. In order to prevent loss of the reaction mixture from the vessels during heating, the thermal cycling apparatus of the invention provides means for sealing the proximal and distal end of each reaction vessel. The proximal ends can be sealed by coupling to a pump which permits movement of the samples within the reaction vessels. As to the distal ends, the reaction vessels can be sealed by pressing the distal end of each vessel against a sealing element with a conformable surface, or by immersing the distal end of each vessel in the reservoir of liquid, preferably of an oil, that is not miscible with the reaction mixture.
摘要翻译：在反应容器中热循环反应混合物以将混合物暴露于例如实现PCR扩增所需的变化温度或使用循环测序操作制备测序片段的装置和方法使用流通反应容器，如毛细管，用于反应混合物的制备和热循环。为了防止加热期间反应混合物从容器中的损失，本发明的热循环装置提供了用于密封每个反应容器的近端和远端的装置。近端可以通过联接到允许样品在反应容器内移动的泵来密封。对于远端，可以通过将每个容器的远端压靠具有适形表面的密封元件，或通过将每个容器的远端浸入液体储存器（优选油）中来密封反应容器，与反应混合物不混溶。

3. 发明授权

US6014213A High dynamic range apparatus for separation and detection of polynucleotide fragments 失效
标题翻译：用于分离和检测多核苷酸片段的高动态范围装置
公开(公告)号：US6014213A
公开(公告)日：2000-01-11
申请号：US819910
申请日：1997-03-18
申请人： Paul Waterhouse , Alexandre M. Izmailov , Henryk Zaleski , John A. Renfrew , James W. Cassidy
发明人： Paul Waterhouse , Alexandre M. Izmailov , Henryk Zaleski , John A. Renfrew , James W. Cassidy
IPC分类号： G01N27/447 , G01N30/86 , G01N21/00
CPC分类号： G01N30/8603 , G01N27/44721
摘要： A high dynamic range apparatus for separation and detection of polynucleotide fragments has a housing adapted to receive an electrophoresis gel holder containing an electrophoresis gel loaded with fluorophore-labeled samples; one or more laser diodes for providing radiation of a frequency suitable for excitation of the fluorophore which irradiates a an array of excitation/detection sites on the electrophoresis gel; an array of detectors aligned with the excitation/detection sites for collecting fluorescent emissions; and one or more components for increasing the dynamic range of the instrument by at least an order of magnitude. These components, which can be used individually or in combination include detectors that are connected to a signal processing system that modulates the period of signal integration employed so that large signals are totaled at short time intervals and smaller signals are totaled at longer time intervals; the use of a beam splitter to produces a high intensity beam of emitted light and a low intensity beam of emitted light from each excitation/detection site; and a device for modulating the intensity of the excitation beam can be used to improve the dynamic range of the instrument.
摘要翻译：用于分离和检测多核苷酸片段的高动态范围装置具有适于接收含有装载有荧光团标记的样品的电泳凝胶的电泳凝胶保持器的壳体; 用于提供适于激发荧光团的频率的辐射的一个或多个激光二极管，其照射电泳凝胶上的激发/检测位点阵列; 与用于收集荧光发射的激发/检测部位对准的检测器阵列; 以及用于将仪器的动态范围增加至少一个数量级的一个或多个组件。可以单独或组合使用的这些组件包括连接到信号处理系统的检测器，该信号处理系统调制所采用的信号积分的周期，以便以较短的时间间隔合计大信号，并以更长的时间间隔合计较小的信号; 使用分束器产生高强度发射光束和来自每个激发/检测部位的低强度发射光束; 并且可以使用用于调制激发光束的强度的装置来改善仪器的动态范围。

4. 发明授权

US5618398A Electrophoresis gels and gel holders having fiber spacers and method of making same 失效
标题翻译：具有纤维间隔物的电泳凝胶和凝胶保持器及其制造方法
公开(公告)号：US5618398A
公开(公告)日：1997-04-08
申请号：US571297
申请日：1995-12-12
申请人： Alexandre M. Izmailov , Paul Waterhouse , Henryk Zaleski
发明人： Alexandre M. Izmailov , Paul Waterhouse , Henryk Zaleski
IPC分类号： G01N21/64 , G01N27/447 , G01N27/26
CPC分类号： G01N27/44721 , G01N27/44704
摘要： Gel holders for electrophoresis gels are made using clad fibers, particularly glass fibers as spacers between substrates. A plurality of fibers with an high-melting interior core and a low-melting external cladding are placed between a first planar substrate and a second planar substrate. The fibers are heated to a temperature sufficient to at least soften the exterior cladding of the fibers without softening the interior core of the fibers, and then cooled while they are in contact with the first and second substrates to resolidify the exterior cladding. This adheres the fibers to the first and second substrates, and forms a gel chamber between said first and second substrates. The gel chamber has a thickness defined by interior core of the fibers. The fibers may be heated before or after the second substrate is placed over the top of the fibers. The gel holders thus formed may be filled immediately with a gel forming solution such as a polyacrylamide, or they may be stored indefinitely and used as needed.
摘要翻译：电泳凝胶的凝胶保持器使用包覆纤维制成，特别是作为衬底之间的间隔物的玻璃纤维。具有高熔点内芯和低熔点外包层的多根纤维被放置在第一平面基板和第二平面基板之间。将纤维加热到足以至少软化纤维的外包层的温度，而不软化纤维的内芯，然后在与第一和第二基底接触的同时冷却，以重新固化外包层。这将纤维粘附到第一和第二基底上，并在所述第一和第二基底之间形成凝胶室。凝胶室具有由纤维的内芯限定的厚度。纤维可以在将第二基底放置在纤维顶部之前或之后被加热。如此形成的凝胶保持器可立即用诸如聚丙烯酰胺的凝胶形成溶液填充，或者可以无限期地储存并根据需要使用。

5. 发明授权

US5599434A Electrophoresis gels and gel holders having adhesive affixed fiber spacers and method of making same 失效
标题翻译：具有粘合剂的纤维间隔物的电泳凝胶和凝胶保持器及其制造方法
公开(公告)号：US5599434A
公开(公告)日：1997-02-04
申请号：US571132
申请日：1995-12-12
申请人： Alexandre M. Izmailov , Henryk Zaleski
发明人： Alexandre M. Izmailov , Henryk Zaleski
IPC分类号： G01N27/447 , G01N27/26
CPC分类号： G01N27/44704
摘要： Gel holders for electrophoresis gels are made using fibers, particularly glass fibers, which are affixed to the substrates forming the gel holder using an adhesive. These gel holders can be made by placing a plurality of adhesive-coated fibers between a first planar substrate and a second planar substrate; and applying pressure to the outside of the substrates to adhere the fibers to the first and second substrates. This forms a gel chamber between the first and second substrates which has a thickness defined by diameter of the fibers. Alternatively, uncoated fibers may be laid down in pairs, with a line of adhesive disposed between each fiber of the pair. When the adhesive is cured, it binds the fibers in position as spacers. At the same time, the fibers isolate the adhesive from the gel compartment. In this way, interference of components of the adhesive with the polymerization of the a gel in the gel chamber can be avoided. Gel holders formed using either of these methods may be filled immediately with a gel forming solution such as a polyacrylamide, or they may be stored indefinitely and used as needed.
摘要翻译：用于电泳凝胶的凝胶保持器使用纤维，特别是玻璃纤维制成，其使用粘合剂固定到形成凝胶保持器的基材上。这些凝胶保持器可以通过在第一平面基板和第二平面基板之间放置多个粘合剂涂覆的纤维来制造; 并向衬底外部施加压力以将纤维粘附到第一和第二衬底上。这在第一和第二基底之间形成凝胶室，其具有由纤维的直径限定的厚度。或者，未涂覆的纤维可以成对铺设，一对粘合剂布置在该对的每个纤维之间。当粘合剂固化时，其将纤维作为间隔物结合在适当位置。同时，纤维将胶粘剂与凝胶隔离隔离。以这种方式，可以避免粘合剂的组分与凝胶室中凝胶聚合的干扰。使用这些方法之一形成的凝胶容器可以立即用诸如聚丙烯酰胺的凝胶形成溶液填充，或者可以无限期地储存并根据需要使用。

6. 发明授权

US06110339A Nanofabricated separation matrix for analysis of biopolymers and methods of making and using same 失效
标题翻译：用于生物聚合物分析的纳米分离基质及其制备和使用方法
公开(公告)号：US06110339A
公开(公告)日：2000-08-29
申请号：US973932
申请日：1997-12-16
申请人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno Maruzzo , John K. Stevens , Marina T. Larson
发明人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno Maruzzo , John K. Stevens , Marina T. Larson
IPC分类号： G01N27/447
CPC分类号： G01N27/44704 , G01N27/44773 , G01N27/44791 , Y10T436/143333
摘要： Separation matrices useful in the formation of solid-state mm- to cm-scale devices for the rapid, high-resolution separation of single-stranded DNA ladder bands generated by the Sanger dideoxy- or Maxam/Gilbert chemical DNA sequencing procedures are formed from a solid support (1) having a plurality of posts (4) disposed on a first major surface thereof to form an obstacle course of posts (4) and pores (5). The posts are arranged in a regular X, Y array and are separated one from another by a distance of 100 nm or less, preferably 10 to 30 nm, and are optionally separated into lanes 2. The separation matrix can be manufactured by first forming a mold, preferably a reusable mold using lithography techniques. The mold is the reverse of the desired pattern of posts and pores of the obstacle course, and is used for casting the obstacle course. The cast obstacle course is then fused to a solid support and separated from the mold. Alternatively, the separation matrix can be formed from a polymer which undergoes specific and quantifiable swelling in the presence of a selected chemical compound. In this case, the matrix is cast on a mold in a conventional manner with a spacing between posts greater than the desired final spacing of 100 nm or less. For use, a buffer solution saturated with the specific chemical agent that controls swelling is added, causing the posts to swell to a defined amount to achieve the desired separation.
摘要翻译： PCT No.PCT / US96 / 09999 Sec。 371日期：1997年12月16日 102（e）日期1997年12月16日PCT提交1996年6月7日PCT公布。出版物WO96 / 42012 PCT 日期1996年12月27日用于形成固态mm至cm尺度装置的分离基质用于快速，高分辨率分离由Sanger双脱氧或Maxam / Gilbert化学DNA测序产生的单链DNA梯形带步骤由具有设置在其第一主表面上的多个柱（4）的固体支撑件（1）形成，以形成柱（4）和孔（5）的障碍物路线。柱以规则的X，Y阵列布置，并且彼此分离一个距离为100nm或更小，优选为10至30nm，并且任选地分离成通道2.分离基体可以通过首先形成模具，优选使用光刻技术的可重复使用的模具。模具与障碍物路线的柱和孔的期望图案相反，并且用于铸造障碍物路线。然后将铸造的障碍物道路融合到固体支撑物并与模具分离。或者，分离基质可以由在所选择的化合物存在下经历特异性和可定量溶胀的聚合物形成。在这种情况下，基体以常规方式在模具上铸造，柱之间的间距大于期望的最终间距为100nm或更小。为了使用，加入饱和了特定化学试剂的缓冲溶液以控制溶胀，导致柱膨胀至规定的量以达到所需的分离。

7. 发明授权

US06176990B1 Micro-electrophoresis chip for moving and separating nucleic acids and other charged molecules 失效
标题翻译：用于移动和分离核酸和其他带电分子的微电泳芯片
公开(公告)号：US06176990B1
公开(公告)日：2001-01-23
申请号：US08973933
申请日：1997-12-16
申请人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno C. Maruzzo , John K. Stevens , Marina T. Larson
发明人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno C. Maruzzo , John K. Stevens , Marina T. Larson
IPC分类号： G01N27453
CPC分类号： G01N27/44773 , G01N27/44704 , G01N27/44791
摘要： A microelectrophoresis chip comprises a substrate in which there are formed one or more channels, one channel for each sample to be evaluated. The channels extend for the length of the chip, a distance of generally around 1 cm, and are about 1 to 10 &mgr;m wide and 1 to 10 &mgr;m in depth. The channels are filled with a homogeneous separation matrix which acts as an obstacle to the electrophoretic migration of the charged molecules. Microelectrodes disposed in the channels are used to induce an electric field within the homogeneous separation medium. When a voltage is applied across two or more of the microelectrodes, the charged molecules are induced to move and separate according to the electric field density, the type of solvent film, and the charge, shape and size of the charged molecule. The chip may further comprise detectors, such as light polarization detectors, fluorescence emission detectors, biosensors, electrochemical sensors or other microcomponents which may include sites for enzymatic or chemical manipulation of the moved or separated charged molecules.
摘要翻译：微电泳芯片包括其中形成一个或多个通道的基底，每个待评估样品的通道一个通道。通道延长芯片的长度，通常约1厘米的距离，宽度约为1至10微米，深度为1至10毫米。通道充满均匀的分离基质，其作为电荷分子的电泳迁移的障碍。设置在通道中的微电极用于在均匀分离介质内诱发电场。当电压施加到两个或更多个微电极上时，根据电场密度，溶剂膜的类型和带电分子的电荷，形状和尺寸，诱导带电分子移动和分离。芯片还可以包括诸如光偏振检测器，荧光发射检测器，生物传感器，电化学传感器或其它微元件的检测器，其可以包括用于酶或分离带电分子的酶或化学操作的位点。

8. 发明授权

US06261430B1 Micro-electrophoresis chip for moving and separating nucleic acids and other charged molecules 失效
标题翻译：用于移动和分离核酸和其他带电分子的微电泳芯片
公开(公告)号：US06261430B1
公开(公告)日：2001-07-17
申请号：US09505659
申请日：2000-02-17
申请人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno C. Maruzzo , John K. Stevens , Marina T. Larson
发明人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno C. Maruzzo , John K. Stevens , Marina T. Larson
IPC分类号： G01N2726
CPC分类号： G01N27/44773 , G01N27/44704 , G01N27/44791
摘要： A microelectrophoresis chip comprises a substrate in which there are formed one or more channels, one channel for each sample to be evaluated. The channels extend for the length of the chip, a distance of generally around 1 cm, and are about 1 to 10 &mgr;m wide and 1 to 10 &mgr;m in depth. The channels are filled with a homogeneous separation matrix which acts as an obstacle to the electrophoretic migration of the charged molecules. Microelectrodes disposed in the channels are used to induce an electric filed within the homogeneous separation medium. When a voltage is applied across two or more of the microelectrodes, the charged molecules are induced to move and separate according to the electric field density, the type of solvent film, and the charge, shape and size of the charged molecule. The chip may further comprise detectors, such as light polarization detectors, fluorescence emission detectors, biosensors, electrochemical sensors or other microcomponents which may include sites for enzymatic or chemical manipulation of the moved or separated charged molecules.
摘要翻译：微电泳芯片包括其中形成一个或多个通道的基底，每个待评估样品的通道一个通道。通道延长芯片的长度，通常约1厘米的距离，宽度约为1至10微米，深度为1至10毫米。通道充满均匀的分离基质，其作为电荷分子的电泳迁移的障碍。设置在通道中的微电极用于诱导均匀分离介质内的电场。当电压施加到两个或更多个微电极上时，根据电场密度，溶剂膜的类型和带电分子的电荷，形状和尺寸，诱导带电分子移动和分离。芯片还可以包括诸如光偏振检测器，荧光发射检测器，生物传感器，电化学传感器或其它微元件的检测器，其可以包括用于酶或分离带电分子的酶或化学操作的位点。

9. 发明授权

US07222059B2 Electrophoretic trace simulator 失效
标题翻译：电泳痕迹模拟器
公开(公告)号：US07222059B2
公开(公告)日：2007-05-22
申请号：US10295964
申请日：2002-11-15
申请人： Alexandre M. Izmailov , Thomas Yager
发明人： Alexandre M. Izmailov , Thomas Yager
IPC分类号： G06F17/50 , C12Q1/68
CPC分类号： G01N27/44717 , G01N27/44721
摘要： A simulated electrophoretic trace is prepared by first obtaining an input file containing an input base sequence comprising a string of letters (A, C, G and/or T) in an order corresponding to the input base sequence, and then modifying the input file using one or more functions to take into account perturbations associated with (1) changes in peak intensity as a function of base number; (2) peak shape as a function of base number; (3) peak skew; (4) spacing between peaks; (5) background; (6) noise; (7) spectral cross-talk; (8) instrumental effects and/or (9) gel electrophoresis effects to produce a modified file representing a simulated electrophoretic trace. The method may be performed using a specially adapted apparatus.
摘要翻译：通过首先以与输入的基本序列相对应的顺序获得包含字母串（A，C，G和/或T）的输入基序列的输入文件，然后使用考虑与（1）峰值强度变化作为基数的函数相关的扰动的一个或多个功能; （2）峰值形状作为基数的函数; （3）峰偏; （4）峰之间的间距; （5）背景; （6）噪音; （7）频谱串扰; （8）仪器效应和/或（9）凝胶电泳效应以产生表示模拟电泳迹线的修改文件。该方法可以使用特别适配的装置来执行。

10. 发明申请

US20080306696A1 Methods for Resolving Convoluted Peaks in a Chromatogram 有权
标题翻译：解决色谱峰的方法
公开(公告)号：US20080306696A1
公开(公告)日：2008-12-11
申请号：US12159213
申请日：2007-02-06
申请人： Alexandre M. Izmailov , Murugathas Yuwaraj
发明人： Alexandre M. Izmailov , Murugathas Yuwaraj
IPC分类号： G06F19/00
CPC分类号： G01N30/8624 , G01N30/8631
摘要： The present invention relates to methods for resolving convoluted peaks in a chromatogram into one or more constituent peaks using peak resolution values. The peaks methods of the invention determine empirical peak resolution values of “well-defined” or “isolated” peaks in the data, then extrapolate these empirical resolution values to peaks in neighboring regions to predict the number of constituent peaks at a given peak position. Predicted peak resolution values are compared to observed peak resolution values of low-resolution or convoluted peaks to determine the number of constituent peaks in the convoluted peaks. These methods enable extension of the region of data that can used for identifying nucleotide sequences, and increase base-calling accuracy in the low-resolution region (end region) of data.
摘要翻译：本发明涉及使用峰值分辨率将色谱图中的卷曲峰分解成一个或多个组成峰的方法。本发明的峰方法确定数据中“明确”或“隔离”峰的经验峰分辨率值，然后将这些经验分辨率值推算到相邻区域中的峰值，以预测在给定峰位置处的构成峰的数量。将预测的峰值分辨率值与观察到的低分辨率或卷积峰值的峰值分辨率进行比较，以确定卷积峰值中的组成峰数。这些方法能够扩展可用于识别核苷酸序列的数据区域，并增加数据的低分辨率区域（结束区域）中的基本呼叫精度。

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