公开(公告)号：WO02059563A3

公开(公告)日：2002-09-26

申请号：PCT/US0202467

申请日：2002-01-28

Applicant: ADVION BIOSCIENCES INC

Inventor： PROSSER SIMON J ,  RULE GEOFFREY S ,  SCHULTZ GARY A ,  CORSO THOMAS N

IPC: G01N27/62 ,  G01N1/00 ,  G01N35/00 ,  G01N35/04 ,  G01N35/10 ,  H01J49/04 ,  B01D59/44 ,  H01J49/00

CPC classification number: G01N35/10 ,  G01N35/0099 ,  G01N35/04 ,  G01N2035/00158 ,  G01N2035/0491 ,  G01N2035/1034 ,  H01J49/0413 ,  H01J49/165

Abstract: A robotic autosampler (1) provides for automated manipulation of microfluidic chips having multiple electrospray devices and/or sample inlets (113) for interface to a mass spectrometer (111) or other detection device. The autosampler also provides for connection of control voltages to the electrospray device to facilitate enablement, control and steering of charged droplets and ions. The autosampler further provides a method of fluid delivery that may be disposable or reusable. The delivery device may contain materials for component separation or sample purification. The delivery device may contain preloaded sample or the sample may be loaded by the autosampler. A method for automated manipulation of multiple electrosprays (115) in communication with a detector, includes: providing a robot autosampler having an electrospray chip (80); electrospraying at least one analyte from at least one electrospray device on the electrospray chip; and manipulating the electrospray chip in communication with a detector in a manner to detect analyte from the electrospray.

Abstract translation: 机器人自动进样器（1）提供具有多个电喷雾装置和/或样品入口（113）的微流体芯片的自动操作，用于与质谱仪（111）或其它检测装置的接口。 自动进样器还提供了将控制电压连接到电喷雾装置，以便于带电液滴和离子的启用，控制和转向。 自动进样器还提供可以是一次性的或可重复使用的流体输送方法。 输送装置可以含有用于组分分离或样品纯化的材料。 输送装置可以包含预加载的样品，或者样品可以由自动进样器装载。 一种用于与检测器通信的多个电喷雾（115）的自动操作的方法，包括：提供具有电喷雾芯片（80）的机器人自动进样器; 从电喷雾芯片上的至少一个电喷雾装置电喷雾至少一种分析物; 以及以检测来自电喷雾的分析物的方式操纵与检测器通信的电喷雾芯片。

公开(公告)号：CA2363414C

公开(公告)日：2008-02-05

申请号：CA2363414

申请日：2000-02-29

Applicant: ADVION BIOSCIENCES INC

Inventor： CORSO THOMAS N ,  SCHULTZ GARY A ,  GALVIN GREGORY J ,  DAVIS TIMOTHY J ,  MOON JAMES E

IPC: B05B5/025 ,  B81C1/00 ,  G01N27/26 ,  G01N27/447 ,  G01N30/60 ,  G01N30/72 ,  H01J49/04 ,  H01J49/10

Abstract: A droplet/electrospray device and a liquid chromatography-electrospray system are disclosed. The droplet/electrospray device (100) comprises a substrate (102) defining a channel (104) between an entrance orifice (106) on an injection surface (108) and an exit orifice on an ejection surface (112), a nozzle (110) defined by a portion recessed from the ejection surface (112) surrounding the exit orifice, and an electrode (122) for application of an electric potential to the substrate (102) to optimize and generate droplets or an electrospray (62). A plurality of these electrospray devices (100) can be used in the fonn of an array of miniaturized nozzles. The liquid chromatography-electrospray device (160) comprises a separation substrate (162) defining an introduction channel (164) between an entrance orifice and a reservoir (166) and a separation channel (168) between the reservoir (166) and an exit orifice (170), the separation channel (168) being populated with separation posts (174) perpendicular to the fluid flow.

公开(公告)号：HK1066863A1

公开(公告)日：2005-04-01

申请号：HK04109844

申请日：2004-12-13

Applicant: ADVION BIOSCIENCES INC ,  KIONIX INC

Inventor： MOON JAMES E ,  SCHULTZ GARY A ,  CORSO THOMAS N ,  DAVIS TIMOTHY J ,  GALVIN GREGORY J ,  LOWES STEPHEN

IPC: G01N20060101 ,  B01D20060101 ,  G01N27/62 ,  B01D15/08 ,  G01N30/60 ,  G01N30/72 ,  G01N37/00 ,  H01J20060101 ,  H01J49/04

Abstract: An electrospray device, a liquid chromatography device and an electrospray-liquid chromatography system are 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. The liquid chromatography 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 bonded to the separation substrate to enclose the reservoir and the separation channel adjacent the cover substrate; and, optionally, electrode(s) for application of a electric potential to the fluid. The exit orifice of the liquid chromatography device may be homogeneously interfaced with the entrance orifice of the electrospray device to form an integrated single system. An array of multiple systems may be fabricated in a single monolithic chip for rapid sequential fluid processing and generation of electrospray for subsequent analysis, such as by positioning the exit orifices of the electrospray devices near the sampling orifice of a mass spectrometer.

公开(公告)号：AU3506100A

公开(公告)日：2000-09-21

申请号：AU3506100

申请日：2000-02-29

Applicant: ADVION BIOSCIENCES INC

Inventor： SCHULTZ GARY A ,  CORSO THOMAS N

IPC: G01N30/60 ,  G01N30/72 ,  H01J49/04 ,  G01N27/26 ,  H01J49/10

Abstract: An electrospray device comprises a capillary tube (52) having a passage for conducting fluids through the capillary tube and connecting an entrance orifice and an exit orifice (56). First and the second electrodes are positioned to define an electric field surrounding the exit orifice (56). The first electrode (70) circumscribes the capillary tube proximate the exit orifice, and the second electrode imparts a second potential to the fluid. A mass spectrometry device may be provided to receive fluid droplets/sprays of fluid (60,62) from the exit orifice (56).

公开(公告)号：WO0234883A3

公开(公告)日：2002-11-07

申请号：PCT/US0150857

申请日：2001-10-27

Applicant: ADVION BIOSCIENCES INC

Inventor： ZHANG SHENG ,  VAN PELT COLLEEN K ,  SCHULTZ GARY A

IPC: C12Q1/68

CPC classification number: C12Q1/6827 ,  C12Q1/6858 ,  C12Q2535/125 ,  C12Q2531/113 ,  C12Q2521/525 ,  C12Q2565/501

Abstract: The present invention relates to a novel one-well assay which couples a conventional polymerase chain reaction (PCR) amplification step to a single nucleotide primer extension step for the the determination of nucleotide sequence variations in the genotyping of single nucleotide polymorphisms and other DNA variations detected by primer extension methods. A PCR amplification step, a phosphatase digestion step (or a molecular weight-selective filter step), and a primer extension step are consecutively performed in the same well plate followed by electrospray mass spectrometry detection of a single nucleotide polymorphism bases. Alternative one-well assays which utilize exonuclease I or lambda -exonuclease in addition to the phosphatase digestion step are also disclosed.

Abstract translation: 本发明涉及将常规聚合酶链式反应（PCR）扩增步骤偶联至单核苷酸引物延伸步骤以用于确定单核苷酸多态性和检测到的其他DNA变异的基因型分析中的核苷酸序列变异的新颖单孔试验 通过引物延伸方法。 在同一孔板中连续进行PCR扩增步骤，磷酸酶消化步骤（或分子量选择性过滤步骤）和引物延伸步骤，接着通过电喷雾质谱检测单核苷酸多态性碱基。 也公开了除了磷酸酶消化步骤之外还使用外切核酸酶I或λ-外切核酸酶的替代性单孔测定法。

公开(公告)号：WO0153819A9

公开(公告)日：2002-10-17

申请号：PCT/US0101785

申请日：2001-01-18

Applicant: ADVION BIOSCIENCES INC

Inventor： CORSO THOMAS N ,  SCHULTZ GARY A ,  PROSSER SIMON J ,  HUANG XIAN

IPC: 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 ,  G01N27/26 ,  B32B31/00 ,  H01J49/14 ,  G01N27/477

CPC classification number: 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

Abstract: A microfabricated silicon chip with a separation material, such as in situ prepared porous polymer monoliths (254) 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 (250) 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 (242) for the same fluid for analysis.

Abstract translation: 公开了一种具有分离材料的微制造硅芯片，例如其微通道中原位制备的多孔聚合物整料（254）。 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。 多个电喷射装置（250）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（242）产生多个电喷雾羽流。

公开(公告)号：EP1383592A4

公开(公告)日：2007-02-21

申请号：EP02706034

申请日：2002-01-28

Applicant: ADVION BIOSCIENCES INC

Inventor： PROSSER SIMON J ,  RULE GEOFFREY S ,  SCHULTZ GARY A ,  CORSO THOMAS N

IPC: G01N27/62 ,  G01N1/00 ,  G01N35/00 ,  G01N35/04 ,  G01N35/10 ,  H01J49/04 ,  B01D59/44 ,  H01J49/00

CPC classification number: G01N35/10 ,  G01N35/0099 ,  G01N35/04 ,  G01N2035/00158 ,  G01N2035/0491 ,  G01N2035/1034 ,  H01J49/0413 ,  H01J49/165

Abstract: A robotic autosampler (1) provides for automated manipulation of microfluidic chips having multiple electrospray devices and/or sample inlets (113) for interface to a mass spectrometer (111) or other detection device. The autosampler also provides for connection of control voltages to the electrospray device to facilitate enablement, control and steering of charged droplets and ions. The autosampler further provides a method of fluid delivery that may be disposable or reusable. The delivery device may contain materials for component separation or sample purification. The delivery device may contain preloaded sample or the sample may be loaded by the autosampler. A method for automated manipulation of multiple electrosprays (115) in communication with a detector, includes: providing a robot autosampler having an electrospray chip (80); electrospraying at least one analyte from at least one electrospray device on the electrospray chip; and manipulating the electrospray chip in communication with a detector in a manner to detect analyte from the electrospray.

公开(公告)号：EP1442476A4

公开(公告)日：2008-03-12

申请号：EP02766293

申请日：2002-09-17

Applicant: ADVION BIOSCIENCES INC

Inventor： LI JIE ,  CORSO THOMAS N ,  SCHULTZ GARY A

IPC: G01N27/447 ,  H01L21/306 ,  B32B7/00 ,  B81B1/00 ,  G01N30/72 ,  G01N37/00 ,  G02B1/11 ,  H01B3/10 ,  H01B3/12 ,  H01B7/282 ,  H01B17/60 ,  H01J49/04 ,  H01L29/00 ,  H01L29/74 ,  H01L29/76 ,  H01L29/78

CPC classification number: H01B7/2825 ,  G01N27/44704 ,  G01N30/7266 ,  H01B3/10 ,  H01B3/12 ,  H01L21/3143 ,  H01L21/3145 ,  H01L21/3146

Abstract: A dielectric film is provided which includes a base layer and a capping layer, preferably silicon oxynitride, wherein the film is an effective moisture and ion barrier when disposed between a conductive substrate and a liquid having an electrical potential different than the electrical potential of the substrate.

公开(公告)号：EP1248949A4

公开(公告)日：2007-07-25

申请号：EP01942714

申请日：2001-01-18

Applicant: ADVION BIOSCIENCES INC

Inventor： CORSO THOMAS N ,  SCHULTZ GARY A ,  PROSSER SIMON J ,  HUANG XIAN

IPC: 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 classification number: 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

Abstract: A microfabricated silicon chip with a separation material, such as in situ prepared porous polymer monoliths (254) 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 (250) 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 (242) for the same fluid for analysis.

公开(公告)号：EP1163512A4

公开(公告)日：2007-08-08

申请号：EP00913655

申请日：2000-02-29

Applicant: ADVION BIOSCIENCES INC ,  KIONIX INC

Inventor： SCHULTZ GARY A ,  CORSO THOMAS N ,  MOON JAMES E ,  DAVIS TIMOTHY J ,  GALVIN GREGORY J

IPC: G01N30/60 ,  G01N30/72 ,  H01J49/04 ,  H01J49/10

CPC classification number: H01J49/167 ,  G01N30/6095 ,  G01N30/7266 ,  H01J49/0018

Abstract: A droplet/electrospray device and a liquid chromatography-electrospray system are disclosed. The droplet/electrospray device (100) comprises a substrate (102) defining a channel (104) between an entrance orifice (106) on an injection surface (108) and an exit orifice on an ejection surface (112), a nozzle (110) defined by a portion recessed from the ejection surface (112) surrounding the exit orifice, and an electrode (122) for application of an electric potential to the substrate (102) to optimize and generate droplets or an electrospray (62). A plurality of these electrospray devices (100) can be used in the form of an array of miniaturized nozzles. The liquid chromatography-electrospray device (160) comprises a separation substrate (162) defining an introduction channel (164) between an entrance orifice and a reservoir (166) and a separation channel (168) between the reservoir (166) and an exit orifice (170), the separation channel (168) being populated with separation posts (174) perpendicular to the fluid flow.