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1. 发明申请

WO2007106425A3 BIOMARKERS OF THE DYSPLASTIC STATE OF CELLS 审中-公开
标题翻译：细胞滋养状态的生物标志物
公开(公告)号：WO2007106425A3
公开(公告)日：2008-10-16
申请号：PCT/US2007006176
申请日：2007-03-12
申请人： UNIV NORTHEASTERN , CYTYC CORP , WU SHIAW-LIN , HANCOCK WILLIAM S , KARGER BARRY L , LINDER JAMES , HANLON DAVID W
发明人： WU SHIAW-LIN , HANCOCK WILLIAM S , KARGER BARRY L , LINDER JAMES , HANLON DAVID W
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： G01N33/57411
摘要： The invention relates to methods for detecting and identifying potential biomarkers of high-grade cervical dysplasia in an individual human subject. The invention also relates to newly discovered biomarkers, as set forth in Tables 1-4 herein, which are associated with the dysplastic state of cervical cells. It has been discovered that a differential level of expression of any of these markers or combination of these markers correlates with a dysplastic condition in a human subject, e.g., a patient.
摘要翻译：本发明涉及用于检测和鉴定个体人类受试者高级宫颈发育异常的潜在生物标志物的方法。本发明还涉及新发现的与本发明的表1-4所示的生物标志物，其与子宫颈细胞的发育不良状态相关。已经发现，这些标记物或这些标记物的组合的表达差异水平与人受试者例如患者中的发育异常状况相关。

2. 发明申请

WO2007149498A3 NARROW BORE POROUS LAYER OPEN TUBE CAPILLARY COLUMN AND USES THEREOF 审中-公开
公开(公告)号：WO2007149498A3
公开(公告)日：2007-12-27
申请号：PCT/US2007/014398
申请日：2007-06-20
申请人： NORTHEASTERN UNIVERSITY , KARGER, Barry, L. , ZHANG, Jian
发明人： KARGER, Barry, L. , ZHANG, Jian
IPC分类号： B01D15/08 , B01D15/00
摘要： A polymer-based PLOT column prepared by in situ copolymerization of a functional monomer, which usually contains the retentive chemistries, and a crosslinking monomer, which enhances the strength of the polymer matrix, is disclosed. Styrenic based monomers such as styrene and divinylbenzene or meth/acrylic based monomers such as butyl or stearyl methacrylate and ethylene glycol dimethacrylate, are preferred. Columns of the invention can be prepared in a robust fashion with a very narrow i.d., e.g. , 5-15 μm. Thus, they are suitable for commercial use in ultratrace LC/MS proteomic analysis. Columns according to the invention are characterized by high resolving power, high column- to-column reproducibility and relatively high loading capacity. When these columns are coupled on-line with, e.g. , ESI-MS detection, the resulting systems provide high sensitivity for analysis of complex proteomic samples, even down to the low attomole to sub-attomole level.

3. 发明申请

WO2007140016A2 DEVICES, METHODS AND APPLICATIONS FOR EXTRACTION OF MOLECULES FROM POLYMERIC GEL ELECTROPHORETIC MEDIA 审中-公开
标题翻译：从聚合胶体电泳介质中提取分子的装置，方法和应用
公开(公告)号：WO2007140016A2
公开(公告)日：2007-12-06
申请号：PCT/US2007/012729
申请日：2007-05-29
申请人： NORTHEASTERN UNIVERSITY , LAZAREV, Alexander , REJTAR, Thomas , KARGER, Barry, L.
发明人： LAZAREV, Alexander , REJTAR, Thomas , KARGER, Barry, L.
IPC分类号： B02C18/28
CPC分类号： B01L3/502 , B01L2200/06 , B01L2300/0832 , B01L2400/0409 , G01N1/34 , G01N35/0099
摘要： A device and method to provide a simplified wash process and controlled disintegration of a soft substance, such as a gel, are disclosed. In use, a block of, e.g., gel matrix is placed in the device and washed with a series of appropriate solutions to remove interfering contaminants. The washing liquid is removed through a deformable narrow opening in the bottom of the device, and, subsequently, the gel block is extruded through the deformable narrow opening, by a physical force, such as centrifugal force, a vacuum or positive pressure from a gas or liquid, etc., resulting in fragmentation of the gel block into a series of particles of similar size. The fragmentation of the gel results from shear forces exerted onto the gel block traveling through the deformable narrow opening in the device. The rate of such fragmentation and resulting fragment size can be controlled by extruding the gel block using a predefined level of force as well as by controlling the dimensions and shape of the narrow opening (s) in the device.
摘要翻译：公开了一种提供简化的洗涤过程并控制软物质如凝胶的分解的装置和方法。在使用中，将一块例如凝胶基质置于装置中并用一系列适当的溶液洗涤以除去干扰的污染物。洗涤液体通过设备底部的可变形的窄开口被去除，随后，凝胶块通过物理力，例如离心力，来自气体的真空或正压挤压通过可变形的窄开口或液体等，导致凝胶块破碎成一系列类似尺寸的颗粒。凝胶的断裂是由施加在凝胶块上的剪切力所引起的，该凝胶块穿过装置中的可变形的窄开口。可以通过使用预定水平的力挤压凝胶块以及通过控制装置中的窄开口的尺寸和形状来控制这种碎裂和所得碎片尺寸的速率。

4. 发明申请

WO2006026569A2 COMPREHENSIVE CHARACTERIZATION OF COMPLEX PROTEINS AT TRACE LEVELS 审中-公开
标题翻译：复杂蛋白质的综合表征
公开(公告)号：WO2006026569A2
公开(公告)日：2006-03-09
申请号：PCT/US2005030713
申请日：2005-08-29
申请人： UNIV NORTHEASTERN , WU SHIAW-LIN , HANCOCK WILLIAM S , KARGER BARRY L
发明人： WU SHIAW-LIN , HANCOCK WILLIAM S , KARGER BARRY L
IPC分类号： G01N33/50
CPC分类号： G01N33/6848 , G01N33/6842
摘要： An LC-MS platform, Extended Range Proteomic Analysis, which is able to achieve very high sequence coverage and comprehensive characterization of posttranslational modifications in complex proteins at the trace level (e.g., low pmole to fmole), is described. The platform according to the invention provides advantages of both the top-down and bottom-up proteomic approaches by combining, In a preferred embodiment of the method, (i) digestion of the protein with an enzyme, such as Lys-C, that cuts less frequently than trypsin, or limited digestion with, e.g., trypsin, leading to, on average, a higher molecular weight peptide size with greater than 90% of the protein's peptide backbone sequence contained in fragments that are between 500 and 25,000 Da; (ii) high-performance LC separation of these resulting fragments; (iii) a new data acquisition strategy using on-line coupling of specific separated fragments to analysis in, e.g., the LTQ-FTMS, a hybrid mass spectrometer that couples a linear ion trap with a Fourier transform ion cyclotron resonance (FTICR) cell, for peptide analysis, preferably of the fragments in the range of 3000 to 10,000 Da; and (iv) new data analysis methods for assigning large peptide structures and determining the site of attachment of posttranslational modifications as well as structural features from the accurate precursor mass together with MS
摘要翻译：描述了能够在痕量水平（例如低pmole至fmole）的复杂蛋白质中实现非常高的序列覆盖率和翻译后修饰的全面表征的LC-MS平台，扩展范围蛋白质组学分析。根据本发明的平台通过组合来提供自顶向下和自下而上的蛋白质组学方法的优点。在该方法的优选实施方案中，（i）将蛋白质与诸如Lys-C的酶消化，平均来说，胰蛋白酶的平均消化速度比胰蛋白酶低，或者限制在500到25,000Da之间的片段中含有大于蛋白质肽主链序列的90％的分子量肽; （ii）这些得到的片段的高效液相色谱分离; （iii）使用特定分离片段的在线耦合来分析例如LTQ-FTMS，将线性离子阱与傅立叶变换离子回旋共振（FTICR）单元耦合的混合质谱仪的新数据采集策略，用于肽分析，优选在3000至10,000Da范围内的片段; 和（iv）用于分配大肽结构并确定翻译后修饰的附着位点的新数据分析方法以及来自准确前体质量的结构特征以及MS

5. 发明申请

WO2007140016A3 DEVICES, METHODS AND APPLICATIONS FOR EXTRACTION OF MOLECULES FROM POLYMERIC GEL ELECTROPHORETIC MEDIA 审中-公开
标题翻译：用于从聚合物凝胶电泳介质中提取分子的装置，方法和应用
公开(公告)号：WO2007140016A3
公开(公告)日：2008-08-14
申请号：PCT/US2007012729
申请日：2007-05-29
申请人： UNIV NORTHEASTERN , LAZAREV ALEXANDER , REJTAR THOMAS , KARGER BARRY L
发明人： LAZAREV ALEXANDER , REJTAR THOMAS , KARGER BARRY L
IPC分类号： B02C1/00 , B02C11/00 , B02C21/00 , B02C23/00
CPC分类号： B01L3/502 , B01L2200/06 , B01L2300/0832 , B01L2400/0409 , G01N1/34 , G01N35/0099
摘要： A device and method to provide a simplified wash process and controlled disintegration of a soft substance, such as a gel, are disclosed. In use, a block of, e.g., gel matrix is placed in the device and washed with a series of appropriate solutions to remove interfering contaminants. The washing liquid is removed through a deformable narrow opening in the bottom of the device, and, subsequently, the gel block is extruded through the deformable narrow opening, by a physical force, such as centrifugal force, a vacuum or positive pressure from a gas or liquid, etc., resulting in fragmentation of the gel block into a series of particles of similar size. The fragmentation of the gel results from shear forces exerted onto the gel block traveling through the deformable narrow opening in the device. The rate of such fragmentation and resulting fragment size can be controlled by extruding the gel block using a predefined level of force as well as by controlling the dimensions and shape of the narrow opening (s) in the device.
摘要翻译：公开了一种用于提供诸如凝胶的软质物质的简化洗涤过程和受控分解的装置和方法。在使用中，将一块例如凝胶基质放置在装置中并用一系列合适的溶液洗涤以去除干扰性污染物。洗涤液通过装置底部的可变形的窄开口被除去，随后凝胶块通过可变形的窄开口被物理力如离心力，真空或来自气体的真空压力挤出或液体等，导致凝胶块碎裂成一系列相似尺寸的颗粒。凝胶的碎裂是由施加到凝胶块上的剪切力通过装置中的可变形窄开口而产生的。通过使用预定的力度挤出凝胶块以及通过控制装置中的窄开口的尺寸和形状，可以控制这种碎裂和产生的碎片大小的速率。

6. 发明申请

WO0153794A8 PARALLEL SAMPLE LOADING AND INJECTION DEVICE FOR MULTICHANNEL MICROFLUIDIC DEVICES 审中-公开
标题翻译：多通道微流体装置并联样品装入和注入装置
公开(公告)号：WO0153794A8
公开(公告)日：2008-02-21
申请号：PCT/US0101705
申请日：2001-01-18
申请人： UNIV NORTHEASTERN , FORET FRANTISEK , REJTAR THOMAS , ZHANG BAILIN , KARGER BARRY L
发明人： FORET FRANTISEK , REJTAR THOMAS , ZHANG BAILIN , KARGER BARRY L
IPC分类号： B01L3/00 , G01N27/447 , G01N35/10
CPC分类号： B01L3/502715 , B01L3/5025 , B01L2200/027 , B01L2400/0415 , B01L2400/049 , G01N27/44743 , G01N27/44791 , G01N35/1065 , G01N2035/1037
摘要： A sample load and injection device (10) includes sample introduction capillaries (11) attached to a microfluidic device (12). Sample introduction capillaries (11) are connected to sample introduction channels (18). Sample introduction capillaries (18) are connected to separation channels (20) at connection points (21). At a defined distance along the separation channels (20), auxilliary channels (23) originate at connection points (24). The sample load and injection device includes cover plate (28) which has connecting channels (26, 32). Connecting channel (26) is associated with ends (24) of sample introduction channels (18). Connecting channel (32) is associated with ends (20).
摘要翻译：样品装载和注射装置（10）包括连接到微流体装置（12）的样品引入毛细管（11）。样品引入毛细管（11）连接到样品引入通道（18）。样品引入毛细管（18）在连接点（21）处连接到分离通道（20）。在沿着分离通道（20）的限定距离处，辅助通道（23）起始于连接点（24）。样品装载和注射装置包括具有连接通道（26,32）的盖板（28）。连接通道（26）与样品引入通道（18）的端部（24）相关联。连接通道（32）与端部（20）相关联。

7. 发明申请

WO2007140016A9 DEVICES, METHODS AND APPLICATIONS FOR EXTRACTION OF MOLECULES FROM POLYMERIC GEL ELECTROPHORETIC MEDIA 审中-公开
标题翻译：从聚合胶体电泳介质中提取分子的装置，方法和应用
公开(公告)号：WO2007140016A9
公开(公告)日：2008-01-24
申请号：PCT/US2007012729
申请日：2007-05-29
申请人： UNIV NORTHEASTERN , LAZAREV ALEXANDER , REJTAR THOMAS , KARGER BARRY L
发明人： LAZAREV ALEXANDER , REJTAR THOMAS , KARGER BARRY L
IPC分类号： B02C18/28
CPC分类号： B01L3/502 , B01L2200/06 , B01L2300/0832 , B01L2400/0409 , G01N1/34 , G01N35/0099
摘要： A device and method to provide a simplified wash process and controlled disintegration of a soft substance, such as a gel, are disclosed. In use, a block of, e.g., gel matrix is placed in the device and washed with a series of appropriate solutions to remove interfering contaminants. The washing liquid is removed through a deformable narrow opening in the bottom of the device, and, subsequently, the gel block is extruded through the deformable narrow opening, by a physical force, such as centrifugal force, a vacuum or positive pressure from a gas or liquid, etc., resulting in fragmentation of the gel block into a series of particles of similar size. The fragmentation of the gel results from shear forces exerted onto the gel block traveling through the deformable narrow opening in the device. The rate of such fragmentation and resulting fragment size can be controlled by extruding the gel block using a predefined level of force as well as by controlling the dimensions and shape of the narrow opening (s) in the device.
摘要翻译：公开了一种提供简化的洗涤过程并控制软物质如凝胶的分解的装置和方法。在使用中，将一块例如凝胶基质置于装置中并用一系列适当的溶液洗涤以除去干扰的污染物。洗涤液体通过设备底部的可变形的窄开口被去除，随后，凝胶块通过物理力，例如离心力，来自气体的真空或正压挤压通过可变形的窄开口或液体等，导致凝胶块破碎成一系列类似尺寸的颗粒。凝胶的断裂是由施加在凝胶块上的剪切力所引起的，该凝胶块穿过装置中的可变形的窄开口。可以通过使用预定水平的力挤压凝胶块以及通过控制装置中的窄开口的尺寸和形状来控制这种碎裂和所得碎片尺寸的速率。

8. 发明申请

WO2006026569A3 COMPREHENSIVE CHARACTERIZATION OF COMPLEX PROTEINS AT TRACE LEVELS 审中-公开
公开(公告)号：WO2006026569A3
公开(公告)日：2006-03-09
申请号：PCT/US2005/030713
申请日：2005-08-29
申请人： NORTHEASTERN UNIVERSITY , WU, Shiaw-Lin , HANCOCK, William, S. , KARGER, Barry, L.
发明人： WU, Shiaw-Lin , HANCOCK, William, S. , KARGER, Barry, L.
IPC分类号： G01N24/00 , G01N24/14
摘要： A combination of “bottom up” anf “top down” MS analysis of posstranslational modifications in complex proteins is described. The method comprises digestion of the protein with an enzyme that forms larger peptide fragments than trypsin (> 3000 D), performing HPLC with the fragments and applying a new data acquisition strategy using on-line coupling with e.g. LTQ-FTMS, a hybrid mass spectrometer that couples a linear ion trap with a Fourier transform ion cyclotron resonance (FTICR) cell. The method is applied to analysis of posstranslational modifications of protein isoforms.

9. 发明申请

WO2005059512A3 METHOD FOR EFFICIENT TRANSPORT OF SMALL LIQUID VOLUMES TO, FROM OR WITHIN MICROFLUIDIC DEVICES 审中-公开
标题翻译：小液体运输到微流体装置中或从微流体装置运输的方法
公开(公告)号：WO2005059512A3
公开(公告)日：2005-09-09
申请号：PCT/US2004041923
申请日：2004-12-10
申请人： UNIV NORTHEASTERN , KAUTZ ROGER A , KARGER BARRY L
发明人： KAUTZ ROGER A , KARGER BARRY L
IPC分类号： B01L3/00 , B01L3/02 , C02F1/40 , C25D1/12 , G01N20060101 , G01N1/00 , G01N1/10 , G01R33/30
CPC分类号： G01R33/307 , B01L3/502784 , B01L2200/027 , B01L2200/0673 , B01L2300/0838 , B01L2300/165 , G01N35/1095 , G01R33/302 , Y10T436/117497 , Y10T436/208339 , Y10T436/24 , Y10T436/25 , Y10T436/2575
摘要： Methods are presented for realizing zero-dispersion segmented flow for transfer of small microfluidic samples onto or within microfluidic analysis or processing devices. Where fluidic systems are in whole or in part made of materials favorable to the zero-dispersion conditions for an indicated solvent/carrier fluid system, the system may be covalently coated to impart the necessary surface properties. This invention is demonstrated in an embodiment where 1 microliter samples (6) are robotically prepared and transferred through 3 meters of capillary tubing (4) to a microcoil NMR probe.
摘要翻译：提出了用于实现零分散分段流以将微流体样品转移到微流体分析或处理装置上或之内的方法。如果流体系统全部或部分地由对于指定的溶剂/载体流体系统的零分散条件有利的材料制成，则该系统可以共价涂覆以赋予必要的表面性质。本发明在其中1微升样品（6）被机器人制备并通过3米毛细管（4）转移到微线圈NMR探针上的实施例中得到证明。

10. 发明申请

WO2004064974A2 NARROW I.D. MONOLITHIC CAPILLARY COLUMNS FOR HIGH EFFICIENCY SEPARATION AND HIGH SENSITIVITY ANALYSIS OF BIOMOLECULES 审中-公开
标题翻译： NARROW I.D. 单分子毛细管柱高效分离和生物分子的高灵敏度分析
公开(公告)号：WO2004064974A2
公开(公告)日：2004-08-05
申请号：PCT/US2004/001569
申请日：2004-01-20
申请人： NORTHEASTERN UNIVERSITY , IVANOV, Alexander, R. , ZANG, Li , KARGER, Barry, L.
发明人： IVANOV, Alexander, R. , ZANG, Li , KARGER, Barry, L.
IPC分类号： B01D
CPC分类号： B01J20/28042 , B01J20/26 , B01J20/261 , B01J20/267 , B01J20/28014 , B01J20/285 , B01J2220/58 , B01J2220/82 , B01J2220/84 , G01N30/52 , G01N30/6095 , G01N2030/528
摘要： A method of preparing an ultra-nanoscale-LC monolithic separation medium for use in capillary columns, or channels in microfabricated devices (microchips), and capillaries prepared by the method are disclosed. The application of moderate positive pressure to both ends of the capillary during the monolith polymerization process permits the preparation of monolithic capillary columns having very low i.d., e.g., 25 μm and smaller, with enhances mass transfer properties and low back pressures, and excellent column-to-column reproducibility of retention times.
摘要翻译：公开了一种制备用于毛细管柱或微细加工装置（微芯片）中的通道的超纳米LC单片分离介质的方法和通过该方法制备的毛细管。在整料聚合过程中对毛细管两端施加适度的正压使得制备具有非常低的id（例如25μm和更小）的整体毛细管柱，具有增强的传质性能和低的背压，保留时间至柱重现性。

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