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1. 发明申请

WO2007016432A3 APPARATUS AND METHOD FOR COUPLING MICROFLUIDIC SYSTEMS WITH A MASS SPECTROMETER UTILIZING RAPID VOLTAGE SWITCHING 审中-公开
标题翻译：使用快速电压开关的质谱仪耦合微流体系统的装置和方法
公开(公告)号：WO2007016432A3
公开(公告)日：2007-11-22
申请号：PCT/US2006029600
申请日：2006-07-28
申请人： UNIV WEST VIRGINIA , TIMPERMAN AARON T , LENKE JAMES , RAZUNGUZWA TRUST
发明人： TIMPERMAN AARON T , LENKE JAMES , RAZUNGUZWA TRUST
IPC分类号： B01D59/44 , H01J49/00
CPC分类号： H01J49/165 , B01L3/5027 , C07K1/26 , H01J27/04 , H01J49/0018
摘要： The invention relates to an apparatus for coupling microfluidic systems with electrospray ionization mass spectrometry utilizing a hydrodynamic flow. The invention also relates to a method of preventing a sample in a main channel (25) of a microfluidic device (11) from migrating down either a first side channel (31) or a second side channel (33) by rapidly alternating a voltage being applied to the first side channel (31) and the second side channel (33).
摘要翻译：本发明涉及一种利用流体动力学流动的电喷雾质谱联用微流体系统的装置。本发明还涉及一种防止微流体装置（11）的主通道（25）中的样品沿着第一侧通道（31）或第二侧通道（33）向下移动的方法，通过快速交替地将电压施加到第一侧通道（31）和第二侧通道（33）。

2. 发明申请

WO2007002141A2 APPARATUS AND METHOD FOR COUPLING MICROFLUIDIC SYSTEMS WITH ELECTROSPRAY IONIZATION MASS SPECTROMETRY UTILIZING A HYDRODYNAMIC FLOW RESTRICTOR 审中-公开
标题翻译：用电化学离子化微流体系统耦合微流体系统的装置和方法利用水动力流量限制器
公开(公告)号：WO2007002141A2
公开(公告)日：2007-01-04
申请号：PCT/US2006024065
申请日：2006-06-20
申请人： UNIV WEST VIRGINIA , TIMPERMAN AARON T
发明人： TIMPERMAN AARON T
IPC分类号： B01L3/00
CPC分类号： B01L3/502746 , B01L3/0268 , B01L2300/0816 , B01L2400/0418 , B01L2400/0487 , B01L2400/086 , H01J49/0018 , H01J49/165
摘要： A microfluidic device is disclosed wherein a hydrodynamic flow restrictor is positioned in a main channel; a make-up flow channel engages the main channel at a position between the hydrodynamic flow restrictor and an output channel. The hydrodynamic flow restrictor substantially negates a hydrodynamic backpressure in the main channel to the extent that low electroosmotic flow may be utilized in the main channel. Further, a method is disclosed wherein a sample is delivered to the main channel and low EOF drives the sample through the main channel. The method comprises positioning a hydrodynamic flow restrictor in the main channel and delivering a make-up solution via hydrodynamic flow to the main channel at a position between a hydrodynamic flow restrictor and the output channel. The hydrodynamic flow restrictor substantially negates a hydrodynamic backpressure in the main channel to the extent that low electroosmotic flow may be utilized in the main channel.
摘要翻译：公开了一种微流体装置，其中流体动力学流量限制器位于主通道中; 补充流动通道在流体动力学流量限制器和输出通道之间的位置处接合主通道。流体动力学流量限制器基本上消除了主通道中的流体动力背压，达到在主通道中可以使用低电渗流量的程度。此外，公开了一种方法，其中将样品输送到主通道并且低EOF通过主通道驱动样品。该方法包括将流体动力流量限制器定位在主通道中，并且通过流体动力流将补充溶液在流体动力学流量限制器和输出通道之间的位置处输送到主通道。流体动力学流量限制器基本上消除了主通道中的流体动力背压，达到在主通道中可以使用低电渗流量的程度。

3. 发明申请

WO2005043112A2 APPARATUS AND METHOD FOR EDMAN DEGRADATION ON A MICROFLUIDIC DEVICE UTILIZING AN ELECTROOSMOTIC FLOW PUMP 审中-公开
标题翻译：用于使用电动流量泵的微流体装置上的EDMAN降解的装置和方法
公开(公告)号：WO2005043112A2
公开(公告)日：2005-05-12
申请号：PCT/US2004032145
申请日：2004-09-30
申请人： UNIV WEST VIRGINIA , TIMPERMAN AARON T
发明人： TIMPERMAN AARON T
IPC分类号： G01N20060101 , G01N27/447 , G01N27/453 , G01N
CPC分类号： G01N27/44752
摘要： The present invention comprises an electroosmotic flow pump with both anion (43) and cation (41) exchange beads packed in separate channels (5, 9) that pump towards an intersection (8). Combining the two flow streams results in higher flowrates for the pump and allows operation of the pump over a wide pH range. The pump can be used to deliver solutions ranging from a pH of about 2 to about 12. In a preferred embodiment, the electroosmotic pump of the present invention is fabricated on a microfluidic device (55) capable of Edman degradation. In a preferred embodiment of the present invention, the beads (41, 43) are immobilized in the channels (5, 9) using weirs (7) and membranes, eliminating the need for frits. The pump may be comprised of capillaries (27, 29, 31). Additionally, the electroosmotic flow pump of the present invention may be integrated into an Integrated Microfluidic Proteome Analysis System.
摘要翻译：本发明包括具有阴离子（43）和阳离子（41）交换珠的电渗流量泵，所述交换珠填充在朝向交叉点（8）泵送的分离通道（5,9）中。结合两个流动流导致泵的较高流量，并允许泵在宽的pH范围内运行。该泵可用于输送约2至约12的pH范围内的溶液。在优选实施方案中，本发明的电渗泵在能够进行Edman降解的微流体装置（55）上制造。在本发明的优选实施方案中，使用堰（7）和膜将珠子（41,43）固定在通道（5,9）中，从而不再需要玻璃料。泵可以由毛细管（27,29,31）组成。另外，本发明的电渗流量泵可以集成到集成微流体蛋白质组分析系统中。

4. 发明申请

WO2004076497A9 APPARATUS AND METHOD OF USING BI-DIRECTIONAL CAPILLARY ELECTROPHORESIS 审中-公开
标题翻译：设备和方法使用双向毛细管电泳
公开(公告)号：WO2004076497A9
公开(公告)日：2005-03-10
申请号：PCT/US2004005451
申请日：2004-02-23
申请人： UNIV WEST VIRGINIA , TIMPERMAN AARON T
发明人： TIMPERMAN AARON T
IPC分类号： G01N27/447 , B01D57/02 , B01D59/42 , B01D59/50 , B01D61/42 , B01D61/58 , C02F1/40 , C02F11/00 , C12Q1/00 , G01N1/30
CPC分类号： G01N27/44756
摘要： The present invention provides an apparatus and method of utilizing bi-directional capillary electrophoresis ("CE") device 9. In one embodiment, cations are drawn into a first uncharged channel 23 towards a negative electrode 27 and anions are drawn into a second uncharged channel 24 towards a positive electrode 25. The uncharged channels 23,24 allows for minimal interaction between the sample and the walls of the channel 23,24 which allows for minimal sample loss. The present invention also provides a method of separating anions from cations. The method comprises delivering the mixture to a bi-directional CE device 9. Following delivery, cations are drawn into a first uncharged channel 23 towards a negative electrode 27 and anions are drawn into a second uncharged channel 24 towards a positive electrode 25. In one aspect of the present invention, the bi-directional CE device 9 engages a microfluidic proteome analysis system 31.
摘要翻译：本发明提供了一种利用双向毛细管电泳（“CE”）装置9的设备和方法。在一个实施例中，阳离子被抽入第一不带电的通道23中朝向负电极27，阴离子被吸入第二不带电的通道 24流向正电极25.不带电通道23,24允许样品与通道23,24的壁之间的最小相互作用，这允许最小的样品损失。本发明还提供了一种从阳离子中分离阴离子的方法。该方法包括将混合物输送到双向CE装置9.输送之后，阳离子被拉入到负电极27的第一不带电通道23中，并且阴离子被拉入到正电极25的第二不带电通道24中。在一个本发明的一个方面，双向CE装置9接合微流体蛋白质组分析系统31。

5. 发明申请

WO2004077017A3 APPARATUS AND METHOD FOR ON-CHIP CONCENTRATION USING A MICROFLUIDIC DEVICE WITH AN INTEGRATED ULTRAFILTRATION MEMBRANE STRUCTURE 审中-公开
标题翻译：使用具有一体化超滤膜结构的微流体装置的芯片浓度的装置和方法
公开(公告)号：WO2004077017A3
公开(公告)日：2004-12-09
申请号：PCT/US2004005212
申请日：2004-02-23
申请人： UNIV WEST VIRGINIA , TIMPERMAN AARON T
发明人： TIMPERMAN AARON T
IPC分类号： B01D57/02 , B01D61/18 , B01D61/42 , B01L3/00 , C12M1/34 , C12Q1/00 , C12Q1/37 , C12Q1/42 , G01N1/40 , G01N27/447
CPC分类号： G01N27/44791 , B01D57/02 , B01D61/18 , B01D61/425 , B01L3/5027 , B01L3/502753 , B01L2200/0631 , B01L2300/0681 , B01L2300/0816 , B01L2300/0887 , B01L2400/0418 , B82Y30/00 , C12Q1/00 , C12Q1/37 , C12Q1/42 , G01N1/40 , G01N2001/4038
摘要： The present invention provides a microfluidic device (5) capable of reacting an enzyme or other agent with a substantially purified polypeptide. In one embodiment of the present invention, the microfluic device (5) comprises a plurality of reaction channels (8) wherein the substantially purified polypeptide is delivered to a reaction channel (8). Once confined within the reaction channel (8), the substantially purified polypeptide engages the enzyme or agent and produces a reaction product. In a preferred embodiment of the present invention, the reaction product is concentrated at a charged membrane (101,103) prior to being removed from the microfluidic device (5). Additionally, the present invention provides a method of concentrating a positive analyte at a positively charged membrane (103) and a negative analyte at a negatively charged membrane (101). Once concentrated, the analytes may be removed from the microfluidic device (5).
摘要翻译：本发明提供能够使酶或其它试剂与基本上纯化的多肽反应的微流体装置（5）。在本发明的一个实施方案中，微流体装置（5）包含多个反应通道（8），其中基本上纯化的多肽被递送至反应通道（8）。一旦限制在反应通道（8）内，基本纯化的多肽与酶或试剂接合并产生反应产物。在本发明的优选实施方案中，在从微流体装置（5）中取出之前，将反应产物在带电膜（101,103）处浓缩。此外，本发明提供了一种在带正电荷的膜（103）和带负电荷的膜（101）上的阴性分析物浓缩阳性分析物的方法。一旦浓缩，可以从微流体装置（5）中除去分析物。

6. 发明申请

WO03044221A9 MICROFLUIDIC SYSTEM FOR PROTEOME ANALYSIS 审中-公开
标题翻译：微生物分析系统
公开(公告)号：WO03044221A9
公开(公告)日：2004-05-13
申请号：PCT/US0233319
申请日：2002-10-18
申请人： UNIV WEST VIRGINIA , TIMPERMAN AARON T
发明人： TIMPERMAN AARON T
IPC分类号： G01N27/62 , B01L3/00 , C12M1/12 , G01N27/447 , G01N27/64 , G01N33/68 , G01N37/00 , C12Q1/37 , C12M1/40
CPC分类号： G01N27/44791 , B01L3/5027 , B01L3/502707 , B01L3/502753 , B01L2200/10 , B01L2400/0415 , G01N27/44717 , G01N27/44743 , G01N27/44773 , G01N33/6803
摘要： The invention provides a microfluidic system and method to rapidly analyze large number of compounds or complex mixtures of compounds, particularly, low abundance cellular proteins involved in cell signaling pathways. In one aspect, an integrated microfluidic system (1) comprises an upstream separation module (2) (preferably, a multi-dimensional separation device (2a)), a microfluidic device (5) for on-device protein digestion of substantially separated proteins received from the upstream separation module (2), a downstream separation module (14) for separating digestion products of said proteins, a peptide analysis module (17) and a processor (18) for determining the amino acid sequence of said proteins. Preferably, the integrated microfluidic system (1) comprises an interfacing microfluidic device (5i) between the downstream separation module (14) and the peptide analysis module (17).
摘要翻译：本发明提供了一种微流体系统和方法，用于快速分析大量化合物或化合物的复合混合物，特别是涉及细胞信号通路的低丰度细胞蛋白质。在一个方面，集成微流体系统（1）包括上游分离模块（2）（优选地，多维分离装置（2a）），用于装置上蛋白质消化基本上分离的蛋白质的微流体装置（5）来自上游分离模块（2）的用于分离所述蛋白质的消化产物的下游分离模块（14），用于测定所述蛋白质的氨基酸序列的肽分析模块（17）和处理器（18）。优选地，集成微流体系统（1）包括在下游分离模块（14）和肽分析模块（17）之间的界面微流体装置（5i）。

7. 发明申请

WO2004076497A3 APPARATUS AND METHOD OF USING BI-DIRECTIONAL CAPILLARY ELECTROPHORESIS 审中-公开
标题翻译：装置和使用双向毛细管电泳的方法
公开(公告)号：WO2004076497A3
公开(公告)日：2005-01-20
申请号：PCT/US2004005451
申请日：2004-02-23
申请人： UNIV WEST VIRGINIA , TIMPERMAN AARON T
发明人： TIMPERMAN AARON T
IPC分类号： G01N27/447 , B01D57/02 , B01D59/42 , B01D59/50 , B01D61/42 , B01D61/58 , C02F1/40 , C02F11/00 , C12Q1/00 , G01N1/30
CPC分类号： G01N27/44756
摘要： The present invention provides an apparatus and method of utilizing bi-directional capillary electrophoresis ("CE") device 9. In one embodiment, cations are drawn into a first uncharged channel 23 towards a negative electrode 27 and anions are drawn into a second uncharged channel 24 towards a positive electrode 25. The uncharged channels 23,24 allows for minimal interaction between the sample and the walls of the channel 23,24 which allows for minimal sample loss. The present invention also provides a method of separating anions from cations. The method comprises delivering the mixture to a bi-directional CE device 9. Following delivery, cations are drawn into a first uncharged channel 23 towards a negative electrode 27 and anions are drawn into a second uncharged channel 24 towards a positive electrode 25. In one aspect of the present invention, the bi-directional CE device 9 engages a microfluidic proteome analysis system 31.
摘要翻译：本发明提供一种使用双向毛细管电泳（“CE”）装置9的装置和方法。在一个实施方案中，将阳离子吸入第一不带电通道23朝向负极27，阴离子被吸入第二不带电通道 24通过正电极25.不带电的通道23,24允许样品与通道23,24的壁之间的最小的相互作用，其允许最小的样品损失。本发明还提供了一种从阳离子中分离阴离子的方法。该方法包括将混合物输送到双向CE器件9.在传送之后，阳离子被吸入朝向负极27的第一不带电通道23中，阴离子被吸入朝向正电极25的第二不带电通道24中。在一个本发明的方面，双向CE器件9接合微流体蛋白质组分析系统31。

8. 发明申请

WO2004059283A2 APPARATUS AND METHOD FOR EDMAN DEGRADATION USING A MICROFLUIDIC SYSTEM 审中-公开
标题翻译：使用微流控系统进行EDMAN降解的装置和方法
公开(公告)号：WO2004059283A2
公开(公告)日：2004-07-15
申请号：PCT/US0340387
申请日：2003-12-18
申请人： UNIV WEST VIRGINIA
发明人： TIMPERMAN AARON T
IPC分类号： B01L3/00 , C07K1/12 , C12M1/34 , G01N20060101 , G01N33/543 , G01N33/553 , G01N33/68 , G01N35/00 , G01N
CPC分类号： G01N33/54326 , B01L3/502753 , B01L2300/0867 , B01L2400/0409 , B01L2400/0418 , B01L2400/0421 , B01L2400/0487 , C07K1/128 , G01N33/6818
摘要： An apparatus and method for Edman degradation using a microfluidic system to identify and characterize peptides is disclosed. A microfluidic device comprises an entrance channel through which a substantially purified polypeptide is accepted, a reaction channel engaging the entrance channel wherein the substantially purified polypeptide is digested, producing a digestion product, a reagent reservoir engaging the reaction channel, the reagent reservoir capable of delivering a reagent to the reaction channel, and an exit channel extending from the reaction channel, wherein the digestion product travels through the exit channel upon leaving the reaction channel. Protein digestion on the device comprises delivering a substantially purified polypeptide to a reaction channel, confining the polypeptide in the reaction channel, digesting the polypeptide in the reaction channel producing a digestion product, and removing the digestion product from the reaction channel, wherein the last two steps are repeated until the polypeptide is substantially digested.
摘要翻译：公开了使用微流体系统鉴定和表征肽的Edman降解的装置和方法。微流体装置包括入口通道，基本上纯化的多肽被接受，入口通道的反应通道，其中基本上纯化的多肽被消化，产生消化产物，与反应通道接合的试剂储存器，能够递送的试剂储存器反应通道的试剂和从反应通道延伸的出口通道，其中消除产物在离开反应通道时通过出口通道。在装置上的蛋白质消化包括将基本上纯化的多肽递送至反应通道，将多肽限制在反应通道中，消化产生消化产物的反应通道中的多肽，以及从反应通道中除去消化产物，其中最后两个重复步骤直到多肽被基本消化。

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