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1. 发明授权

US09670540B2 Methods and devices for DNA sequencing and molecular diagnostics 有权
公开(公告)号：US09670540B2
公开(公告)日：2017-06-06
申请号：US14234011
申请日：2012-07-23
申请人： Francis A. Barany , Steven A. Soper , George Grills , Yu-wei Cheng , Jianmin Huang , Hong Wang , Malgorzata A. Witek , Daniel Sang-won Park , Michael C. Murphy , Robin Lindsey McCarley , Mateusz L. Hupert
发明人： Francis A. Barany , Steven A. Soper , George Grills , Yu-wei Cheng , Jianmin Huang , Hong Wang , Malgorzata A. Witek , Daniel Sang-won Park , Michael C. Murphy , Robin Lindsey McCarley , Mateusz L. Hupert
IPC分类号： C12Q1/68 , G01N33/58 , C07H21/04
CPC分类号： C12Q1/6874 , C12Q1/6806 , G01N33/585 , C12Q2525/197 , C12Q2525/313 , C12Q2535/122 , C12Q2563/131 , C12Q2565/543
摘要： The present invention is directed to methods for capturing, amplifying and identifying one or more of a plurality of target nucleotide sequences in a sample. The present invention is further directed to a device comprising a solid support having a plurality of wells or pillars and a plurality of oligonucleotides attached to the wells or pillars. Other aspects of the invention are directed to methods of making such devices.

2. 发明申请

US20150099642A1 METHODS AND DEVICES FOR DNA SEQUENCING AND MOLECULAR DIAGNOSTICS 有权
标题翻译：用于DNA测序和分子诊断的方法和设备
公开(公告)号：US20150099642A1
公开(公告)日：2015-04-09
申请号：US14234011
申请日：2012-07-23
申请人： Francis A. Barany , Steven A. Soper , George Grills , Yu-wei Cheng , Jianmin Huang , Malgorzata A. Witek , Daniel San-won Park , Michael C. Murphy , Robin Lindsey McCarley , Mateusz L. Hupert
发明人： Francis A. Barany , Steven A. Soper , George Grills , Yu-wei Cheng , Jianmin Huang , Malgorzata A. Witek , Daniel San-won Park , Michael C. Murphy , Robin Lindsey McCarley , Mateusz L. Hupert
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12Q1/6806 , G01N33/585 , C12Q2525/197 , C12Q2525/313 , C12Q2535/122 , C12Q2563/131 , C12Q2565/543
摘要： The present invention is directed to methods for capturing, amplifying and identifying one or more of a plurality of target nucleotide sequences in a sample. The present invention is further directed to a device comprising a solid support having a plurality of wells or pillars and a plurality of oligonucleotides attached to the wells or pillars. Other aspects of the invention are directed to methods of making such devices.
摘要翻译：本发明涉及用于捕获，扩增和鉴定样品中多个靶核苷酸序列中的一个或多个的方法。本发明进一步涉及包括具有多个孔或柱的固体支持物和连接到孔或支柱上的多个寡核苷酸的装置。本发明的其它方面涉及制造这种装置的方法。

3. 发明申请

US20090074637A1 Optimized Modular Microfluidic Devices 审中-公开
标题翻译：优化的模块化微流体装置
公开(公告)号：US20090074637A1
公开(公告)日：2009-03-19
申请号：US12164356
申请日：2008-06-30
申请人： Michael C. Murphy , Dimitris E. Nikitopoulos , Steven A. Soper , Pin-Chuan Chen , Daniel S.-W. Park , Mateusz L. Hupert
发明人： Michael C. Murphy , Dimitris E. Nikitopoulos , Steven A. Soper , Pin-Chuan Chen , Daniel S.-W. Park , Mateusz L. Hupert
IPC分类号： B01J19/00
CPC分类号： B01L3/502707 , B01L3/502715 , B01L3/50851 , B01L7/525 , B01L7/54 , B01L2200/025 , B01L2200/028 , B01L2300/0829 , B01L2300/0887
摘要： Passively aligned modular microfluidic devices, and a method for fabricating such passively aligned polymeric modular microfluidic devices have been reported. The modular units fabricated are plurality of integrated microdevices. Also reported are microfluidic devices wherein isolated temperature zones exist so that the temperature within each zone may be distinctly and accurately controlled, and a method for fabricating such microfluidic devices wherein there are isolated temperature zones so that the temperature within each zone may be distinctly and accurately controlled. Such devices allow one to define constant temperature zones along a microfluidic channel where different reactions or stages of reactions occur.
摘要翻译：已经报道了被动对准的模块化微流体装置，以及用于制造这种被动排列的聚合物模块化微流体装置的方法。所制造的模块化单元是多个集成的微型装置。还报道了微流体装置，其中存在隔离的温度区域，使得可以明确和精确地控制每个区域内的温度，以及制造这种微流体装置的方法，其中存在隔离的温度区域，使得每个区域内的温度可以明显且准确受控。这样的装置允许沿着微流体通道定义恒定温度区，其中发生不同的反应或反应阶段。

4. 发明授权

US10429376B2 Microfluidic isolation of tumor cells or other rare cells from whole blood or other liquids 有权
公开(公告)号：US10429376B2
公开(公告)日：2019-10-01
申请号：US12992225
申请日：2009-05-13
申请人： Steven A. Soper , Michael C. Murphy , June Feng , Robin L. McCarley , André A. Adams
发明人： Steven A. Soper , Michael C. Murphy , June Feng , Robin L. McCarley , André A. Adams
IPC分类号： B01L3/00 , G01N33/49 , G01N15/14 , G01N15/10
摘要： Microdevices are disclosed to efficiently, accurately, and rapidly isolate and enumerate rare cells, such as circulating tumor cells, from liquids such as whole blood. The system employs multiple parallel meandering channels having a width on the order of 1-2 cell diameters. The microdevices can be produced at low-cost, may readily be automated, and in many instances may be used without pre-processing of the sample. They may be used to isolate and enumerate rare cells, including for example the detection and diagnosis of cancers, cancer staging, or evaluating the effectiveness of a therapeutic intervention, or detecting pathogenic bacteria. The device may optionally be used to nondestructively capture and later to release target cells.

5. 发明申请

US20120100521A1 Microfluidic Isolation of Tumor Cells or Other Rare Cells from Whole Blood or Other Liquids 审中-公开
标题翻译：来自全血或其他液体的肿瘤细胞或其他罕见细胞的微流控分离
公开(公告)号：US20120100521A1
公开(公告)日：2012-04-26
申请号：US12992225
申请日：2009-05-13
申请人： Steven A. Soper , Michael C. Murphy , June Feng , Robin L. McCarley , André A. Adams
发明人： Steven A. Soper , Michael C. Murphy , June Feng , Robin L. McCarley , André A. Adams
IPC分类号： C12N5/078 , B01L99/00 , C12Q1/06 , C12M1/34 , C12N5/09
CPC分类号： G01N33/49 , B01L3/5027 , B01L2300/0645 , B01L2300/0816 , B01L2300/0864 , B01L2300/0883 , G01N15/1459 , G01N15/1484 , G01N33/4915 , G01N2015/1006
摘要： Microdevices are disclosed to efficiently, accurately, and rapidly isolate and enumerate rare cells, such as circulating tumor cells, from liquids such as whole blood. The system employs multiple parallel meandering channels having a width on the order of 1-2 cell diameters. The microdevices can be produced at low-cost, may readily be automated, and in many instances may be used without pre-processing of the sample. They may be used to isolate and enumerate rare cells, including for example the detection and diagnosis of cancers, cancer staging, or evaluating the effectiveness of a therapeutic intervention, or detecting pathogenic bacteria. The device may optionally be used to nondestructively capture and later to release target cells.
摘要翻译：公开了微装置，以从诸如全血的液体中有效地，准确地并快速地分离和枚举诸如循环肿瘤细胞的稀有细胞。该系统采用多个平行的曲折通道，其宽度为1-2个单元直径。微型器件可以以低成本生产，可以容易地自动化，并且在许多情况下可以使用，而不需要对样品进行预处理。它们可用于分离和枚举稀有细胞，包括例如癌症的检测和诊断，癌症分期或评估治疗干预的有效性或检测病原菌。该装置可以可选地用于非破坏性地捕获和稍后释放靶细胞。

6. 发明申请

US20090155894A1 Electrokinetic Thermal Cycler and Reactor 审中-公开
标题翻译：电动热循环器和反应器
公开(公告)号：US20090155894A1
公开(公告)日：2009-06-18
申请号：US12090396
申请日：2006-10-17
申请人： Steven A. Soper , Dimitris E. Nikitopoulos , Michael C. Murphy
发明人： Steven A. Soper , Dimitris E. Nikitopoulos , Michael C. Murphy
IPC分类号： C12M1/02 , B01J19/00 , G01N21/00
CPC分类号： B01L3/5027 , B01L7/525 , B01L2300/0816 , B01L2300/0861 , B01L2300/1827 , B01L2300/1883 , B01L2400/0418
摘要： Microfluidic devices are disclosed for carrying out cyclic or iterated reactions such as PCR, LDR, and other cyclic or iterated reactions. A microchannel forms a closed loop, through which a reaction mixture may be thermally cycled an arbitrary number of times. Flow is preferably mediated primarily by electrokinetics. Multiple temperature zones may be employed along the course of a single microchannel loop, for example for PCR. Embodiments may be compact, automated, fast, and operable in continuous-flow mode. Real-time reaction monitoring may optionally be used.
摘要翻译：公开了用于进行循环或重复反应的微流体装置，例如PCR，LDR和其它循环或重复反应。微通道形成闭环，通过该闭环，反应混合物可以热循环任意次数。流动优选主要由电动力介导。可以沿着单个微通道环路的过程使用多个温度区域，例如用于PCR。实施例可以是紧凑的，自动化的，快速的和可操作的连续流模式。可以可选地使用实时反应监测。

7. 发明申请

US20100108519A1 Polymeric Nanopillars and Nanotubes, Their Manufacture and Uses 有权
标题翻译：聚合物纳米管和纳米管，其制造和用途
公开(公告)号：US20100108519A1
公开(公告)日：2010-05-06
申请号：US12440546
申请日：2007-09-12
申请人： Steven A. Soper , Robin L. McCarley , Guofang Chen , Hamed Shadpour
发明人： Steven A. Soper , Robin L. McCarley , Guofang Chen , Hamed Shadpour
IPC分类号： G01N27/26 , B82B3/00 , B32B5/16
CPC分类号： B81C1/00111 , B81C2201/034 , G01N27/44773 , Y10T428/2982
摘要： A method is disclosed for fabricating free-standing polymeric nanopillars or nanotubes with remarkably high aspect ratios. The nanopillars and nanotubes may be used, for example, in integrated microfluidic systems for rapid, automated, high-capacity analysis or separation of complex protein mixtures or their enzyme digest products. One embodiment, preferably fabricated entirely from polymer substrates, comprises a cell lysis unit; a solid-phase extraction unit with free-standing, polymeric nanostructures; a multi-dimensional electrophoretic separation unit with high peak capacity; a solid-phase nanoreactor for the proteolytic digestion of isolated proteins; and a chromatographic unit for the separation of peptide fragments from the digestion of proteins. The nanopillars and nanotubes may also be used to increase surface area for reaction with a solid phase, for example, with immobilized enzymes or other catalysts within a microchannel, or as a solid support for capillary electrochromatography-based separations of proteins or peptides.
摘要翻译：公开了用于制造具有非常高的纵横比的独立聚合物纳米柱或纳米管的方法。纳米管和纳米管可用于例如用于快速，自动化，高容量分析或分离复杂蛋白质混合物或其酶消化产物的集成微流体系统。一个实施方案，优选完全由聚合物底物制造，包括细胞裂解单元; 具有独立的聚合物纳米结构的固相萃取装置; 具有高峰值容量的多维电泳分离单元; 用于分离蛋白质的蛋白水解消化的固相纳米反应器; 以及用于从蛋白质消化中分离肽片段的色谱单元。纳米柱和纳米管也可用于增加与固相反应的表面积，例如固定化酶或微通道内的其它催化剂，或作为固体支持物，用于基于毛细管电色谱法的蛋白质或肽分离。

8. 发明申请

US20090068596A1 Negative-tone,Ultraviolet Photoresists for Fabricating High Aspect Ratio Microstructures 审中-公开
标题翻译：负色调，紫外光刻胶，用于制造高纵横比微结构
公开(公告)号：US20090068596A1
公开(公告)日：2009-03-12
申请号：US12185455
申请日：2008-08-04
申请人： Ren Yang , Steven A. Soper , Wanjun Wang
发明人： Ren Yang , Steven A. Soper , Wanjun Wang
IPC分类号： G03F7/20 , C08F2/46 , B32B37/12
CPC分类号： C08F2/48 , C08K5/0025 , C09J5/00 , C09J2205/31 , G03F7/0385 , G03F7/40
摘要： UV photoresist materials are disclosed, based on EPON 154 or EPON 165. Preferred embodiments, based on a composite of EPON 154 and EPON 165, spread evenly into a flat, uniform layer, even without spin-coating. The preferred embodiments bond strongly to all substrates, and are resistant to cracking and debonding following exposure and development. The preferred embodiments have high UV transmittance, which promotes uniform photopolymerization throughout a thick layer. Structures may be produced by UV lithography that have a sidewall quality that has previously been attainable only by photolithography with a collimated x-ray source.
摘要翻译：公开了基于EPON 154或EPON 165的UV光致抗蚀剂材料。基于EPON 154和EPON 165的复合材料的优选实施方案均匀地均匀地扩散到平坦均匀的层中，甚至没有旋涂。优选的实施例强烈地粘合到所有的基材上，并且在曝光和显影之后耐开裂和剥离。优选的实施方案具有高的UV透射率，其促进整个厚层的均匀光聚合。结构可以通过UV光刻制造，其具有先前仅通过具有准直X射线源的光刻法才能获得的侧壁质量。

9. 发明授权

US08524891B2 Tetraazaporphyrin-based compounds and their uses 有权
标题翻译：基于四氮杂卟啉的化合物及其用途
公开(公告)号：US08524891B2
公开(公告)日：2013-09-03
申请号：US11995244
申请日：2006-07-14
申请人： Robert P. Hammer , Steven A. Soper , Serhii Pakhomov , Timothy J. Jensen , Michael W. Allen , Irina V. Nesterova , Maria da Graça Henriques Vicente
发明人： Robert P. Hammer , Steven A. Soper , Serhii Pakhomov , Timothy J. Jensen , Michael W. Allen , Irina V. Nesterova , Maria da Graça Henriques Vicente
IPC分类号： C07D487/22 , C07B47/00
CPC分类号： C07D487/22
摘要： Asymmetrically substituted metal-phthalocyanine compounds are disclosed. These compounds and other phthalocyanine-derivatives are used in bioimaging, bioanalysis, FRET and quenching techniques, photodynamic therapy, DNA analysis for cells, proteins, tissues and other biological entities, and other applications. Near-infrared fluorescence minimizes matrix effects typically seen in other methods of analyzing biochemical entities in cells, proteins, tissues and other biological entities.
摘要翻译：公开了不对称取代的金属酞菁化合物。这些化合物和其他酞菁衍生物用于生物成像，生物分析，FRET和淬灭技术，光动力学治疗，细胞，蛋白质，组织和其他生物实体的DNA分析以及其他应用。近红外荧光最小化通常在分析细胞，蛋白质，组织和其他生物实体中的生物化学实体的其他方法中看到的基质效应。

10. 发明授权

US5846727A Microsystem for rapid DNA sequencing 失效
标题翻译：用于快速DNA测序的微系统
公开(公告)号：US5846727A
公开(公告)日：1998-12-08
申请号：US865275
申请日：1997-05-29
申请人： Steven A. Soper , Jack D. Davies , Yuli Vladimirsky
发明人： Steven A. Soper , Jack D. Davies , Yuli Vladimirsky
IPC分类号： B01J19/00 , C07H21/00 , C12Q1/68 , C12M1/00 , C12M3/04 , C12N15/00
CPC分类号： B01L7/52 , B01J19/0093 , C07H21/00 , C12Q1/6869 , B01L2200/10 , B01L2300/0819 , B01L2400/0421 , B01L3/502753
摘要： A system is disclosed for the rapid and cost-effective sequencing of DNA. There are three principal components of the system: (1) a microreactor, which prepares DNA sequencing "ladders" using solid-phase techniques, preferably in capillary tubes whose volumes are on the order of 10-1000 nanoliters, preferably 10-200 nanoliters; (2) a microfabricated electrophoresis capillary separation unit; and (3) a fluorescence detector with single-mode optical fibers interfaced directly to the electrophoresis capillary. The system is suitable for a highly multiplexed, automated DNA sequencing device Typical. steps in sequencing are as follows: (1) PCR amplification of a DNA template in microtiter dishes using labelled primers, e.g., primers labelled with biotin; (2) immobilizing the labelled PCR products on the walls of one or more capillary tubes having volumes on the order of 10-200 nanoliters; (3) preparing nanoliter quantities of labelled Sanger extension products of the amplified DNA; (4) purifying the oligonucleotide sequencing ladders; (5) high speed electrophoretic separation of the sequencing ladders; and (6) near-infrared, laser-induced fluorescence detection of the oligonucleotides. Base-calling is preferably performed in a single lane format with a single fluorophore, in which the bases are distinguished by different fluorescence lifetimes of dyes that otherwise have similar absorption and fluorescence emission spectra at the wavelengths used. Typical read lengths are on the order of 400-500 bases. Fluorescence is performed on-chip with one single-mode optical fiber carrying the excitation light to the capillary channel, and a second single-mode optical fiber collecting the fluorescent photons. Only sub-microliter volumes of expensive sequencing reagents and dye-labeled ddNTPs are required in this system.
摘要翻译：公开了用于DNA的快速和成本有效的测序的系统。该系统有三个主要组成部分：（1）微反应器，其使用固相技术制备DNA测序“梯子”，优选在其体积在10-1000纳升级，优选10-200纳升级的毛细管中; （2）微细电泳毛细管分离单元; 和（3）具有直接连接到电泳毛细管的单模光纤的荧光检测器。该系统适用于高度多路复用的自动DNA测序装置。测序步骤如下：（1）使用标记的引物，例如用生物素标记的引物，在微量滴定板中PCR扩增DNA模板; （2）将标记的PCR产物固定在体积为10-200纳升的一个或多个毛细管的壁上; （3）制备经扩增的DNA的纳升量的标记的Sanger延伸产物; （4）纯化寡核苷酸测序梯; （5）测序梯的高速电泳分离; 和（6）寡核苷酸的近红外激光诱导荧光检测。碱基调用优选以单一道路格式与单个荧光团进行，其中碱基通过在所用波长处具有相似吸收和荧光发射光谱的染料的不同荧光寿命来区分。典型读取长度约为400-500个碱基。使用向毛细管通道携带激发光的一个单模光纤进行片上荧光，以及收集荧光光子的第二单模光纤。在该系统中仅需要亚微升体积的昂贵的测序试剂和染料标记的ddNTP。

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