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1. 发明授权

US06318157B1 High-throughput parallel liquid chromatography system 有权
标题翻译：高通量平行液相色谱系统
公开(公告)号：US06318157B1
公开(公告)日：2001-11-20
申请号：US09553389
申请日：2000-04-20
申请人： Thomas N. Corso , Colleen K. Van Pelt
发明人： Thomas N. Corso , Colleen K. Van Pelt
IPC分类号： G01N3108
CPC分类号： G01N30/466 , B01J2219/00452 , B01J2219/00585 , B01J2219/00587 , B01J2219/00702 , G01N30/16 , G01N30/24 , G01N30/34 , G01N30/468 , G01N2030/202 , G01N2030/628
摘要： A high-throughput liquid chromatography system capable of parallel separations for increased sample throughput is described. The system comprises valves allowing for the use of multiple liquid chromatography columns and a single injector and pumping system while also minimizing extraneous plumbing and hardware. The system is capable of injecting individual samples and directing them to one of a multiplicity of columns followed by selective output to a detector. The system described allows for up to 16 columns, but the number may vary according to the application. The system may be run in an isocratic or gradient mode. Whereas currently available multi-probe systems incorporate a separate injector for each column, the invention described here uses only one injector and is independent of column number. This removes injector variability along with reducing the amount of pluming and mechanical parts in the system allowing for better separations while providing a more robust system. This device may be interfaced to existing HPLC injector, pumping, and detector technology.
摘要翻译：描述了能够平行分离以提高样品通量的高通量液相色谱系统。该系统包括允许使用多个液相色谱柱和单个注射器和泵送系统的阀，同时还使外部管道和硬件最小化。该系统能够注入单个样本并将其引导到多个列之一，然后选择性地输出到检测器。所描述的系统允许最多16列，但数量可能会根据应用而有所不同。系统可以以等度或梯度模式运行。虽然目前可用的多探针系统包括用于每列的单独的注射器，但是这里描述的本发明仅使用一个注射器，并且与柱号无关。这样可以减少喷射器的变化性，同时减少系统中的排气量和机械部件，从而实现更好的分离，同时提供更坚固的系统。该装置可以与现有的HPLC注射器，泵送和检测器技术连接。

2. 发明授权

US09011801B2 Fluidic interface 有权
标题翻译：流体界面
公开(公告)号：US09011801B2
公开(公告)日：2015-04-21
申请号：US13490261
申请日：2012-06-06
申请人： Thomas N. Corso , Colleen K. Van Pelt
发明人： Thomas N. Corso , Colleen K. Van Pelt
IPC分类号： B01L99/00 , B23P19/02 , B01L3/00 , B01L9/00
CPC分类号： B01L3/502715 , B01L3/563 , B01L3/567 , B01L9/50 , B01L9/527 , B01L2200/0689 , B01L2200/10 , B01L2400/06 , B33Y80/00 , Y10T29/53987 , Y10T29/53996 , Y10T137/0402 , Y10T137/0447
摘要： The invention provides for fluidic connections to be established between tubes, ports, fluidic components and fluidic devices. The leak-tight connections are formed through controlled, compressive forces and can be used for both low and high pressure applications.
摘要翻译：本发明提供在管，端口，流体组件和流体装置之间建立的流体连接。密封连接通过受控的压缩力形成，可用于低压和高压应用。

3. 发明授权

US06956207B2 Separation media, multiple electrospray nozzle system and method 有权
标题翻译：分离介质，多重电喷雾喷嘴系统及方法
公开(公告)号：US06956207B2
公开(公告)日：2005-10-18
申请号：US10405689
申请日：2003-04-01
申请人： Thomas N. Corso , Gary A. Schultz , Simon J. Prosser , Xian Huang
发明人： Thomas N. Corso , Gary A. Schultz , Simon J. Prosser , Xian Huang
IPC分类号： G01N27/62 , B01D15/08 , B01D57/02 , B01D59/44 , B01J20/281 , B01J20/283 , B01J20/285 , B03C5/00 , B05B5/043 , G01N1/10 , G01N21/33 , G01N21/53 , G01N21/64 , G01N27/447 , G01N30/28 , G01N30/46 , G01N30/52 , G01N30/60 , G01N30/72 , G01N30/74 , G01N30/88 , G01N37/00 , H01J49/00 , H01J49/04 , H01J49/10
CPC分类号： G01N30/466 , B01J20/261 , B01J20/267 , B01J20/281 , B01J20/285 , B01J2220/54 , B01J2220/82 , G01N27/44717 , G01N30/463 , G01N30/467 , G01N30/48 , G01N30/6095 , G01N30/7266 , G01N2030/285 , G01N2030/528 , H01J49/0018 , H01J49/167
摘要： A microfabricated silicon chip with a separation material, such as in situ prepared porous polymer monoliths in its microchannels is disclosed. The polymer monoliths are liquid-permeable and serve as microcolumns for liquid chromatography, which are prepared by in situ radical polymerization of a mixture containing vinyl monomers and solvents (porogen) in the microchannels. A method and system are disclosed to generate one or more electrospray plumes from one or more nozzles that provide an ion intensity as measured by a mass spectrometer that is approximately proportional to the number of electrospray plumes formed for analyses contained within the fluid. A plurality of electrospray devices can be used in the form of an array of miniaturized separate electrospray devices for the purpose of generating multiple electrospray plumes from multiple nozzles for the same fluid for analysis. This invention dramatically increases the sensitivity of microchip electrospray devices compared to prior disclosed systems and methods. The silicon chip having the packed microchannels disclosed herein finds application in coupling with mass spectrometry for sample analysis. Also disclosed is a separation block having multiple through-substrate channels filled with a separation material such as polymer monolith which can be stacked in multiple blocks for sequential two-dimensional chromatographic separation and integrated with the electrospray device.
摘要翻译：公开了一种具有分离材料的微细硅芯片，例如在其微通道中原位制备的多孔聚合物整料。聚合物整料是液体可渗透的，用作液相色谱的微柱，其通过在微通道中含有乙烯基单体和溶剂（致孔剂）的混合物的原位自由基聚合制备。公开了一种方法和系统，以从一个或多个喷嘴产生一个或多个电喷雾羽流，其提供与质量分析仪测量的离子强度，其大小与为流体中包含的分析形成的电喷雾羽流的数量成比例。多个电喷雾装置可以以小型化的独立电喷雾装置阵列的形式使用，用于从用于分析的相同流体的多个喷嘴产生多个电喷雾羽流。与先前公开的系统和方法相比，本发明显着提高了微芯片电喷雾装置的灵敏度。具有本文公开的包装微通道的硅芯片可以与质谱联用进行样品分析。还公开了一种分离块，其具有填充有诸如聚合物整料的分离材料的多个通过基底通道，其可以堆叠在多个块中用于顺序的二维色谱分离并与电喷雾装置集成。

4. 发明授权

US06596988B2 Separation media, multiple electrospray nozzle system and method 有权
公开(公告)号：US06596988B2
公开(公告)日：2003-07-22
申请号：US09764698
申请日：2001-01-18
申请人： Thomas N. Corso , Gary A. Schultz , Simon J. Prosser , Xian Huang
发明人： Thomas N. Corso , Gary A. Schultz , Simon J. Prosser , Xian Huang
IPC分类号： H01J4904
CPC分类号： G01N30/466 , B01J20/261 , B01J20/267 , B01J20/281 , B01J20/285 , B01J2220/54 , B01J2220/82 , G01N27/44717 , G01N30/463 , G01N30/467 , G01N30/48 , G01N30/6095 , G01N30/7266 , G01N2030/285 , G01N2030/528 , H01J49/0018 , H01J49/167
摘要： A microfabricated silicon chip with a separation material, such as in situ prepared porous polymer monoliths in its microchannels is disclosed. The polymer monoliths are liquid-permeable and serve as microcolumns for liquid chromatography, which are prepared by in situ radical polymerization of a mixture containing vinyl monomers and solvents (porogen) in the microchannels. A method and system are disclosed to generate one or more electrospray plumes from one or more nozzles that provide an ion intensity as measured by a mass spectrometer that is approximately proportional to the number of electrospray plumes formed for analyses contained within the fluid. A plurality of electrospray devices can be used in the form of an array of miniaturized separate electrospray devices for the purpose of generating multiple electrospray plumes from multiple nozzles for the same fluid for analysis. This invention dramatically increases the sensitivity of microchip electrospray devices compared to prior disclosed systems and methods. The silicon chip having the packed microchannels disclosed herein finds application in coupling with mass spectrometry for sample analysis. Also disclosed is a separation block having multiple through-substrate channels filled with a separation material such as polymer monolith which can be stacked in multiple blocks for sequential two-dimensional chromatographic separation and integrated with the electrospray device.

5. 发明授权

US06855251B2 Microfabricated electrospray device 有权
标题翻译：微型电喷雾装置
公开(公告)号：US06855251B2
公开(公告)日：2005-02-15
申请号：US10771553
申请日：2004-02-04
申请人： James E. Moon , Timothy J. Davis , Gregory J. Galvin , Gary A. Schultz , Thomas N. Corso , Stephen Lowes
发明人： James E. Moon , Timothy J. Davis , Gregory J. Galvin , Gary A. Schultz , Thomas N. Corso , Stephen Lowes
IPC分类号： G01N27/62 , B01D15/08 , G01N30/60 , G01N30/72 , G01N37/00 , H01J49/04 , H01J49/10
CPC分类号： G01N30/6095 , G01N30/7266 , G01N2030/6013 , H01J49/0018 , H01J49/167 , Y10T436/24 , Y10T436/2575
摘要： An electrospray device is disclosed. The electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate an electrospray; and, optionally, additional electrode(s) to further modify the electrospray.
摘要翻译：公开了一种电喷雾装置。电喷雾装置包括：基材，其限定在喷射表面上的入口孔与喷射表面上的出口孔之间的通道;由从出射孔周围的喷射表面凹陷的部分限定的喷嘴;以及用于施加电对基板进行优化和产生电喷雾的潜力; 和可选的附加电极以进一步改变电喷雾。

6. 发明授权

US06814870B2 Microchip electrospray device and column with affinity adsorbents and use of the same 有权
标题翻译： Microchip电喷雾装置和具有亲和吸附剂的柱和使用它们
公开(公告)号：US06814870B2
公开(公告)日：2004-11-09
申请号：US10658008
申请日：2003-09-09
申请人： Sheng Zhang , Xian Huang , Thomas N. Corso , Gary A. Schultz , Simon J. Prosser
发明人： Sheng Zhang , Xian Huang , Thomas N. Corso , Gary A. Schultz , Simon J. Prosser
IPC分类号： B01D1508
CPC分类号： G01N30/6095 , B01D15/3804 , B01J20/28042 , B01J20/285 , B01J20/286 , B01J20/321 , B01J20/3212 , B01J20/3219 , B01J20/3244 , B01J20/3251 , B01J20/3274 , B01J45/00 , B01J2220/52 , B01J2220/54 , B01J2220/58 , B01J2220/82 , G01N30/463 , G01N30/466 , G01N30/482 , G01N30/7266 , G01N2030/528 , H01J49/0018 , H01J49/167
摘要： A microchip-based electrospray ionization device and column with affinity adsorbents is disclosed. The invention includes a microchip array and a capillary tube or alone or attached in combination. At least a portion of the device or column has immobilized affinity adsorbents. Methods for using the device are provided as well for affinity capture of biomolecules to meet the needs for the modem life sciences such as proteomics and drug discover.
摘要翻译：公开了一种基于微芯片的电喷雾离子化装置和具有亲和吸附剂的柱。本发明包括微芯片阵列和毛细管，或单独或组合连接。装置或柱的至少一部分具有固定的亲和吸附剂。还提供了使用该装置的方法用于亲和捕获生物分子以满足现代生命科学如蛋白质组学和药物发现的需要。

7. 发明授权

US06750076B2 Fabrication of a microchip-based electrospray device 有权
标题翻译：基于微芯片的电喷雾装置的制造
公开(公告)号：US06750076B2
公开(公告)日：2004-06-15
申请号：US10246011
申请日：2002-09-17
申请人： Thomas N. Corso
发明人： Thomas N. Corso
IPC分类号： H01L2100
CPC分类号： B81C1/00087 , B81B2201/058 , B81C2201/0142
摘要： A method for fabricating a nozzle of microchip-based electrospray device is disclosed. The method includes using a primary mask to accurately define the nozzle feature including the annulus and the through hole of the electrospray device. A secondary masking step is conducted to pattern the through channel (typical the photoresist would serve as the secondary mask), followed by the defining and etching of the primary mask containing the full nozzle feature. The secondary mask serves to selectively mask given areas of the primary mask for subsequent etching. The through hole feature of the secondary mask aligns over the already patterned primary mask through channel, except that the secondary mask contains a slightly larger through channel diameter. This serves to mask off the annulus, but allowing the silicon through channel to be exposed for etching.
摘要翻译：公开了一种用于制造基于微芯片的电喷雾装置的喷嘴的方法。该方法包括使用主掩模来精确地限定包括电喷雾装置的环形部分和通孔的喷嘴特征。进行二次掩模步骤以对穿通通道进行图案化（典型地，光致抗蚀剂将用作辅助掩模），然后限定和蚀刻含有全喷嘴特征的主掩模。辅助掩模用于选择性地掩蔽初级掩模的给定区域用于随后的蚀刻。辅助掩模的通孔特征通过通道对准已经图案化的初级掩模，不同之处在于次要掩模包含稍大的通道直径。这用于掩盖环形，但允许硅通过沟道暴露以进行蚀刻。

8. 发明授权

US06822231B2 Integrated monolithic microfabricated dispensing nozzle and liquid chromatography-electrospray system and method 有权
标题翻译：集成的单片微型配料喷嘴和液相色谱 - 电喷雾系统及方法
公开(公告)号：US06822231B2
公开(公告)日：2004-11-23
申请号：US10655246
申请日：2003-09-04
申请人： Gary A. Schultz , Thomas N. Corso
发明人： Gary A. Schultz , Thomas N. Corso
IPC分类号： H01J4904
CPC分类号： H01J49/167 , G01N30/6095 , G01N30/7266 , H01J49/0018
摘要： A droplet/electrospray device and a liquid chromatography-electrospray system are disclosed. The droplet/electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate droplets or an electrospray. A plurality of these electrospray devices can be used in the form of an array of miniaturized nozzles. The liquid chromatography-electrospray device comprises a separation substrate defining an introduction channel between an entrance orifice and a reservoir and a separation channel between the reservoir and an exit orifice, the separation channel being populated with separation posts perpendicular to the fluid flow. A cover substrate is bonded to the separation substrate to enclose the reservoir and the separation channel adjacent the cover substrate. The exit orifice of the liquid chromatography device is homogeneously interfaced with the entrance orifice of the electrospray device to form an integrated single system. Procedures for fabrication of the electrospray devices of the present invention are also disclosed.
摘要翻译：公开了液滴/电喷雾装置和液相色谱 - 电喷雾系统。液滴/电喷雾装置包括限定喷射表面上的入口和喷射表面上的出口之间的通道的基底，由从出射孔周围的喷射表面凹陷的部分限定的喷嘴，以及用于施加对基板的电位以优化和产生液滴或电喷雾。多个这样的电喷雾装置可以以小型化喷嘴阵列的形式使用。液相色谱 - 电喷雾装置包括分隔衬底，其限定了入口孔和储存器之间的引入通道以及储存器和出口孔之间的分离通道，分离通道具有垂直于流体流动的分离柱。覆盖基板被结合到分离基板以封闭储存器和邻近盖基板的分离通道。液相色谱装置的出口与电喷雾装置的入口孔均匀地接合，形成一个集成的单一系统。还公开了用于制造本发明的电喷雾装置的步骤。

9. 发明授权

US06723985B2 Multiple electrospray device, systems and methods 有权
标题翻译：多种电喷装置，系统和方法
公开(公告)号：US06723985B2
公开(公告)日：2004-04-20
申请号：US10350542
申请日：2003-01-23
申请人： Gary A. Schultz , Thomas N. Corso , Simon J. Prosser
发明人： Gary A. Schultz , Thomas N. Corso , Simon J. Prosser
IPC分类号： H01J4904
CPC分类号： H01J49/167 , H01J49/0018 , H01J49/04
摘要： A microchip-based electrospray device, system, and method of fabrication thereof are disclosed. The electrospray device includes a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electric field generating source for application of an electric potential to the substrate to optimize and generate an electrospray. A method and system are disclosed to generate multiple electrospray plumes from a single fluid stream that provides an ion intensity as measured by a mass spectrometer that is approximately proportional to the number of electrospray plumes formed for analytes contained within the fluid. A plurality of electrospray nozzle devices can be used in the form of an array of miniaturized nozzles for the purpose of generating multiple electrospray plumes from multiple nozzles for the same fluid stream. This invention dramatically increases the sensitivity of microchip electrospray devices compared to prior disclosed systems and methods.
摘要翻译：公开了一种基于微芯片的电喷雾器件，系统及其制造方法。电喷雾装置包括限定喷射表面上的入口孔和喷射表面上的出口之间的通道的基底，由从出射孔周围的喷射表面凹陷的部分限定的喷嘴和用于应用的电场产生源对基板进行电位优化并产生电喷雾。公开了一种方法和系统，其从单个流体流产生多个电喷雾羽流，其提供通过质谱仪测量的离子强度，该离子强度与为流体中包含的分析物形成的电喷雾羽流的数量大致成比例。多个电喷雾喷嘴装置可以以小型喷嘴阵列的形式使用，用于从同一流体流的多个喷嘴产生多个电喷雾羽流。与先前公开的系统和方法相比，本发明显着提高了微芯片电喷雾装置的灵敏度。

10. 发明授权

US06858842B2 Electrospray nozzle and monolithic substrate 有权
标题翻译：电喷雾喷嘴和整体式基板
公开(公告)号：US06858842B2
公开(公告)日：2005-02-22
申请号：US10814207
申请日：2004-03-31
申请人： James E. Moon , Timothy J. Davis , Gregory J. Galvin , Gary A. Schultz , Thomas N. Corso , Stephen Lowes
发明人： James E. Moon , Timothy J. Davis , Gregory J. Galvin , Gary A. Schultz , Thomas N. Corso , Stephen Lowes
IPC分类号： G01N27/62 , B01D15/08 , G01N30/60 , G01N30/72 , G01N37/00 , H01J49/04 , B01D59/44 , H01J49/10
CPC分类号： G01N30/6095 , G01N30/7266 , G01N2030/6013 , H01J49/0018 , H01J49/167 , Y10T436/24 , Y10T436/2575
摘要： An electrospray nozzle system is disclosed. The electrospray portion of the device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate an electrospray; and, optionally, additional electrode(s) to further modify the electrospray. The nozzle system may be utilized alone or as part of a liquid chromatography system.
摘要翻译：公开了一种电喷雾喷嘴系统。该装置的电喷雾部分包括限定喷射表面上的入口孔和喷射表面上的出口之间的通道的基底，由从出射孔周围的喷射表面凹陷的部分限定的喷嘴和用于应用的电极对基板进行电势优化并产生电喷雾; 和可选的附加电极以进一步改变电喷雾。喷嘴系统可以单独使用或作为液相色谱系统的一部分使用。

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