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1. 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。

2. 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。

3. 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。

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

US5885431A Microgels for use in medical diagnosis and methods of making and using same 失效
标题翻译：用于医学诊断的微凝胶及其制造和使用方法
公开(公告)号：US5885431A
公开(公告)日：1999-03-23
申请号：US836269
申请日：1997-05-01
申请人： John A. Renfrew , Paul Waterhouse , John K. Stevens , Henryk Zaleski
发明人： John A. Renfrew , Paul Waterhouse , John K. Stevens , Henryk Zaleski
IPC分类号： G01N27/447 , G01N27/26
CPC分类号： G01N27/44743 , G01N27/44704 , G01N27/44747
摘要： An electrophoresis microgel is formed in a gel holder. The gel holder comprises a top substrate, a bottom substrate and a spacer disposed between the top substrate and the bottom substrate. The spacer establishes a separation of from 25 to 250 microns between the top substrate and the bottom substrate. A gel compartment is formed by partially sealing the top substrate to the bottom substrate, while leaving an opening for the introduction of unpolymerized gel. The gel compartment is then filled with an unpolymerized gel, which is polymerized in the gel compartment. Electrodes may be printed on the substrates, may be contacts to an exposed edge of gel, or may be applied through windows cut into one of the substrates. One type of gel holder makes use of graded beads having a diameter of 25 to 250 microns slurried in an adhesive such as an acrylate adhesive as the spacer. The slurry is printed onto the surface of one or both substrates to form a spacer of the desired shape, and then hardened using heat or light. If desired, the spacer can establish lanes within the gel.
摘要翻译： PCT No.PCT / US95 / 14531 Sec。 371日期1997年5月1日 102（e）日期1997年5月1日PCT提交1995年10月31日PCT公布。出版物WO96 / 日期1996年5月9日在凝胶保持器中形成电泳微凝胶。凝胶保持器包括顶部基底，底部基底和设置在顶部基底和底部基底之间的间隔物。间隔物在顶部基底和底部基底之间建立了从25至250微米的间隔。通过将顶部基底部分地密封到底部基底而形成凝胶室，同时留下用于引入未聚合凝胶的开口。然后用凝胶隔室填充未聚合的凝胶，其在凝胶隔室中聚合。电极可以印刷在基底上，可以与凝胶的暴露边缘接触，或者可以通过切割成一个基底的窗口来施加。一种类型的凝胶保持器使用在诸如丙烯酸酯粘合剂的粘合剂中作为间隔物浆化的直径为25至250微米的分级珠粒。将浆料印刷到一个或两个基材的表面上以形成所需形状的间隔物，然后使用热或光硬化。如果需要，间隔物可以在凝胶内建立泳道。

6. 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。

7. 发明授权

US6007689A Apparatus for preparing gels for use in electrophoretic separations and similar applications 失效
标题翻译：用于制备用于电泳分离和类似应用的凝胶的装置
公开(公告)号：US6007689A
公开(公告)日：1999-12-28
申请号：US836268
申请日：1997-05-01
申请人： John A. Renfrew , Eric Steinbach , John K. Stevens , Henryk Zaleski
发明人： John A. Renfrew , Eric Steinbach , John K. Stevens , Henryk Zaleski
IPC分类号： G01N27/447 , G01N27/26
CPC分类号： G01N27/44704
摘要： An apparatus for the rapid preparation of electrophoresis gels comprises: (a) a housing; (b) a support fixture removably disposed within the housing and adapted to receive a gel holder having an internal gel compartment, the support fixture being optionally adapted to permit filling of the gel holder within the housing; (c) an optional injection system, which is connectible to a reservoir for holding a polymerizable solution; (d) an optional solution injection connector adapted to couple the injection system to a gel holder placed within the filling fixture, (e) an optional controller for the injection system, which causes the injection system to inject polymerizable solution from the reservoir into the gel compartment; and (f) a radiation source disposed within the housing in a location effective to irradiate polymierizable solution within the gel compartment of a gel holder in the support fixture. The support fixture may be mounted on a drawer which is slidable between a position inside the housing, and a position outside the housing to permit easy placement of a gel holder into the support fixture.
摘要翻译： PCT No.PCT / US95 / 13955 Sec。 371日期1997年5月1日 102（e）日期1997年5月1日PCT提交1995年10月31日PCT公布。出版物WO96 / 日期：1996年5月9日。一种用于快速制备电泳凝胶的设备包括：（a）壳体; （b）可移除地设置在所述壳体内并适于接收具有内部凝胶隔室的凝胶保持器的支撑固定件，所述支撑固定件可选地适于允许在所述壳体内填充所述凝胶保持器; （c）可选的注射系统，其可连接到储存器以保持可聚合溶液; （d）可选的溶液注入连接器，其适于将注射系统耦合到置于填充夹具内的凝胶保持器，（e）用于注射系统的可选控制器，其使注射系统将可聚合溶液从储存器注入凝胶隔间以及（f）辐射源，其设置在所述壳体内的有效照射所述支撑夹具中的凝胶保持器的凝胶室内的可聚合溶液的位置。支撑固定件可以安装在可在壳体内的位置和壳体外部的位置之间滑动的抽屉上，以允许将凝胶保持器容易地放置到支撑夹具中。

8. 发明申请

US20130284914A1 FAST-SWITCHING DUAL-POLARITY ION MOBILITY SPECTROMETRY 有权
标题翻译：快速切换双极性离子移动光谱
公开(公告)号：US20130284914A1
公开(公告)日：2013-10-31
申请号：US13881821
申请日：2011-10-27
申请人： Henryk Zaleski , Mark Piniarski , Simon Feldberg , Jeff Anderson , Oleg Samarin
发明人： Henryk Zaleski , Mark Piniarski , Simon Feldberg , Jeff Anderson , Oleg Samarin
IPC分类号： H01J49/06 , H01J49/02
CPC分类号： G01N27/622 , G01N23/00 , G06K9/0053 , H01J49/0031 , H01J49/025 , H01J49/04 , H01J49/06 , H01J49/061
摘要： Systems and methods disclosed provide for methods of managing polarity switching in an ion mobility spectrometer, and provide for management of the repelling grid voltage, the gating grid voltage, and the fixed grid voltage during polarity switching. Systems and methods also provide for the management of the effect of dielectric relaxation in an insulator proximal to the collector, and provide for a preamplifier coupled to the collector including a switch, and a method of managing the collector output including the switch. Systems and methods consistent with the current disclosure further provide for a method of normalizing ion mobility data by determining fitting coefficients associated with a plurality of measurement data sets, and subtracting the curves determined by the fitting coefficients from the data acquired by the ion mobility spectrometer.
摘要翻译：所公开的系统和方法提供了在离子迁移谱仪中管理极性切换的方法，并且在极性切换期间提供排斥电网电压，门控电网电压和固定电网电压的管理。系统和方法还提供了在靠近集电极的绝缘体中对介电弛豫的影响的管理，并且提供耦合到集电器的前置放大器，包括开关，以及管理包括开关的集电极输出的方法。与本公开一致的系统和方法进一步提供了通过确定与多个测量数据集相关联的拟合系数来归一化离子迁移率数据的方法，以及从由离子迁移谱仪获取的数据中减去由拟合系数确定的曲线。

9. 发明授权

US06760668B1 Method for alignment of DNA sequences with enhanced accuracy and read length 失效
标题翻译： DNA序列比对准确性和读取长度的方法
公开(公告)号：US06760668B1
公开(公告)日：2004-07-06
申请号：US09536111
申请日：2000-03-24
申请人： Alexandre Izmailov , Henryk Zaleski , Stephen Darasch
发明人： Alexandre Izmailov , Henryk Zaleski , Stephen Darasch
IPC分类号： G06F1900
CPC分类号： G06F19/22
摘要： In order to align DNA sequence data traces, an experimental data trace representing the positions of a first species of base within a target polynucleotide and a reference data trace representing the positions of a second species of base (which may be the same as or different from the first species) within a reference polynucleotide are obtained by separating appropriate sequencing fragments generated from the target and reference polynucleotides on an electrophoresis gel. For each reference data trace, a plurality of peaks corresponding to fragments having a size in the range of 40 to 1200 bases are selected. A base number is assigned to each of the selected peaks in the reference data trace, and a numerical “peak file” is created with information about the peak number and migration time (or distance). This peak file is analyzed to determine a set of polynomial coefficients which will allow substantial linearization of a plot of peak number versus separation between adjacent peaks and alignment of the traces with respect to each other. These coefficients are used to create a corrected time scale identifying where peaks should be located on a given experimental gel. This corrected time scale is used to guide the sampling of the experimental data, and for assignment of peaks within the data.
摘要翻译：为了校准DNA序列数据迹线，表示靶多核苷酸中第一种碱基的位置的实验数据迹线和表示第二种碱基的位置的参考数据迹线（其可以相同或不同于通过在电泳凝胶上分离从靶标和参考多核苷酸产生的合适的测序片段获得参考多核苷酸内的第一种。对于每个参考数据迹线，选择对应于尺寸在40至1200个碱基范围内的片段的多个峰。基准号被分配给参考数据轨迹中的每个选定的峰，并且创建具有关于峰值和迁移时间（或距离）的信息的数值“峰值文件”。分析该峰值文件以确定一组多项式系数，其将允许峰值数量对相邻峰值之间的分离和迹线相对于彼此的对准的实质线性化。这些系数用于产生校正时间标度，以确定哪些峰应位于给定的实验凝胶上。该校正时间标度用于指导实验数据的采样，以及数据中峰的分配。

10. 发明授权

US09287102B2 Fast-switching dual-polarity ion mobility spectrometry 有权
标题翻译：快速开关双极性离子迁移谱
公开(公告)号：US09287102B2
公开(公告)日：2016-03-15
申请号：US13881821
申请日：2011-10-27
申请人： Henryk Zaleski , Mark Piniarski , Simon Feldberg , Jeff Anderson , Oleg Samarin
发明人： Henryk Zaleski , Mark Piniarski , Simon Feldberg , Jeff Anderson , Oleg Samarin
IPC分类号： G01N27/62 , H01J49/04 , G06K9/00 , H01J49/02 , H01J49/06 , G01N23/00
CPC分类号： G01N27/622 , G01N23/00 , G06K9/0053 , H01J49/0031 , H01J49/025 , H01J49/04 , H01J49/06 , H01J49/061
摘要： Systems and methods disclosed provide for methods of managing polarity switching in an ion mobility spectrometer, and provide for management of the repelling grid voltage, the gating grid voltage, and the fixed grid voltage during polarity switching. Systems and methods also provide for the management of the effect of dielectric relaxation in an insulator proximal to the collector, and provide for a preamplifier coupled to the collector including a switch, and a method of managing the collector output including the switch. Systems and methods consistent with the current disclosure further provide for a method of normalizing ion mobility data by determining fitting coefficients associated with a plurality of measurement data sets, and subtracting the curves determined by the fitting coefficients from the data acquired by the ion mobility spectrometer.
摘要翻译：所公开的系统和方法提供了在离子迁移谱仪中管理极性切换的方法，并且在极性切换期间提供排斥电网电压，门控电网电压和固定电网电压的管理。系统和方法还提供了在靠近集电极的绝缘体中对介电弛豫的影响的管理，并且提供耦合到集电器的前置放大器，包括开关，以及管理包括开关的集电极输出的方法。与本公开一致的系统和方法进一步提供了通过确定与多个测量数据集相关联的拟合系数来归一化离子迁移率数据的方法，以及从由离子迁移谱仪获取的数据中减去由拟合系数确定的曲线。

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