公开(公告)号：US07193206B2

公开(公告)日：2007-03-20

申请号：US10806907

申请日：2004-03-22

申请人： Jian Bai ,  Steven M. Fischer ,  J. Michael Flanagan

发明人： Jian Bai ,  Steven M. Fischer ,  J. Michael Flanagan

IPC分类号： B01D59/44 ,  H01J49/00

CPC分类号： H01J49/164

摘要： A mass spectrometer having a matrix-assisted laser desorption ionization (MALDI) source which operates at ambient pressure is disclosed. The apparatus and method are disclosed to analyze at least one sample which contains at least one analyte using matrix-assisted laser desorption ionization (MALDI), which apparatus comprises: The present invention relates to an apparatus and a method for ionizing at least one analyte in a sample for delivery to a mass analysis device, comprising: (a) an ionization enclosure including a passageway configured for delivery of ions to the mass analysis device; (b) means to maintain said ionization enclosure at an ambient pressure of greater than 100 mTorr; (c) a holder configured for maintaining a matrix containing said sample in the ionization enclosure at said ambient pressure; (d) a source of laser energy including means associated with the ionization enclosure for directing the laser energy onto said matrix maintained by the holder at the ambient pressure to desorb and ionize at least a portion of the analyte in the sample, and (e) means for directing at least a portion of the at least one ionized analyte into the passageway. The ambient pressure (AP-MALDI) source is compatible with various mass analyzers, particularly with mass spectrometers and solves many problems associated with conventional MALDI sources operating under vacuum. Atmospheric pressure MALDI is described. The analysis of organic molecules or fragments thereof, particularly biomolecules, e.g., biopolymers and organisms, is described.

摘要翻译： 公开了具有在环境压力下操作的基质辅助激光解吸电离（MALDI）源的质谱仪。 公开了该装置和方法以使用矩阵辅助激光解吸电离（MALDI）分析至少一个含有至少一种分析物的样品，该装置包括：本发明涉及用于将至少一种分析物离子化的装置和方法 用于传送到质量分析装置的样品，包括：（a）电离外壳，其包括经配置以将离子输送到质量分析装置的通道; （b）将所述电离外壳保持在大于100mTorr的环境压力下的装置; （c）构造成用于在所述环境压力下将包含所述样品的基质保持在所述电离外壳中的保持器; （d）激光能量源，其包括与电离外壳相关联的装置，用于将激光能量引导到由保持器在环境压力下维持的所述基体上以解吸并离子化样品中的至少一部分分析物，以及（e） 用于将所述至少一种离子化分析物的至少一部分引导到所述通道中的装置。 环境压力（AP-MALDI）源与各种质量分析仪兼容，特别是与质谱仪兼容，解决了与在真空下运行的常规MALDI源有关的许多问题。 描述了大气压力MALDI。 描述了有机分子或其片段，特别是生物分子，例如生物聚合物和生物体的分析。

公开(公告)号：US07180059B2

公开(公告)日：2007-02-20

申请号：US11471954

申请日：2006-06-21

申请人： Steven M. Fischer ,  Darrell L. Gourley ,  Glen F. Ingle ,  Timothy Herbert Joyce

发明人： Steven M. Fischer ,  Darrell L. Gourley ,  Glen F. Ingle ,  Timothy Herbert Joyce

IPC分类号： H01J49/10

CPC分类号： H01J49/04 ,  H01J49/10 ,  H01J49/107 ,  H01J49/165

摘要： The present invention relates to an apparatus and method for use with a mass spectrometry system. The invention provides an ion source, infrared emitter and sensor with closed control feedback loop coupled to the infrared emitter. Methods of control and heating using the apparatus of the present invention are also disclosed.

摘要翻译： 本发明涉及一种与质谱系统一起使用的装置和方法。 本发明提供一种离子源，红外发射器和传感器，其具有耦合到红外发射器的闭合控制反馈环路。 还公开了使用本发明的设备进行控制和加热的方法。

公开(公告)号：US07102128B2

公开(公告)日：2006-09-05

申请号：US10806808

申请日：2004-03-22

申请人： Jian Bai ,  Steven M. Fischer ,  J. Michael Flanagan

发明人： Jian Bai ,  Steven M. Fischer ,  J. Michael Flanagan

IPC分类号： B01D59/44 ,  H01J49/00

CPC分类号： H01J49/164

摘要： A mass spectrometer having a matrix-assisted laser desorption ionization (MALDI) source which operates at ambient pressure is disclosed. The apparatus and method are disclosed to analyze at least one sample which contains at least one analyte using matrix-assisted laser desorption ionization (MALDI), which apparatus comprises:The present invention relates to an apparatus and a method for ionizing at least one analyte in a sample for delivery to a mass analysis device, comprising: (a) an ionization enclosure including a passageway configured for delivery of ions to the mass analysis device; (b) means to maintain said ionization enclosure at an ambient pressure of greater than 100 mTorr; (c) a holder configured for maintaining a matrix containing said sample in the ionization enclosure at said ambient pressure; (d) a source of laser energy including means associated with the ionization enclosure for directing the laser energy onto said matrix maintained by the holder at the ambient pressure to desorb and ionize at least a portion of the analyte in the sample, and (e) means for directing at least a portion of the at least one ionized analyte into the passageway. The ambient pressure (AP-MALDI) source is compatible with various mass analyzers, particularly with mass spectrometers and solves many problems associated with conventional MALDI sources operating under vacuum. Atmospheric pressure MALDI is described. The analysis of organic molecules or fragments thereof, particularly biomolecules, e.g., biopolymers and organisms, is described.

公开(公告)号：US06812459B2

公开(公告)日：2004-11-02

申请号：US10640151

申请日：2003-08-13

申请人： Steven M. Fischer ,  Darrell L. Gourley ,  Patricia H. Cormia ,  James L. Bertsch

发明人： Steven M. Fischer ,  Darrell L. Gourley ,  Patricia H. Cormia ,  James L. Bertsch

IPC分类号： H01J4926

CPC分类号： G01N30/7253 ,  H01J27/24 ,  H01J49/0431 ,  H01J49/145 ,  H01J49/162

摘要： An atmospheric pressure ion source, e.g. for a mass spectrometer, that produces ions by atmospheric pressure photoionization (APPI). It includes a vaporizer, a photon source for photoionizing vapor molecules upon exit from the vaporizer, a passageway for transporting ions to, for example, a mass spectrometer system, and a means for directing the ions into the passageway. The center axis of the vaporizer and the center axis of the passageway form an angle that may be about 90 degrees. Included in the invention is a method for creating ions by atmospheric pressure photoionization along an axis and directing them into a passageway oriented at an angle to that axis.

公开(公告)号：US06646257B1

公开(公告)日：2003-11-11

申请号：US10245987

申请日：2002-09-18

申请人： Steven M. Fischer ,  Darrell L. Gourley ,  James L. Bertsch

发明人： Steven M. Fischer ,  Darrell L. Gourley ,  James L. Bertsch

IPC分类号： B01D5944

CPC分类号： H01J49/107 ,  H01J49/162 ,  H01J49/165 ,  H01J49/168

摘要： The present invention provides an apparatus and method for use with a mass spectrometer. The multimode ionization source of the present invention provides one or more atmospheric pressure ionization sources (i.e. electrospray, atmospheric pressure chemical ionization and/or atmospheric pressure photoionization) for ionizing molecules. A method of producing ions using the multimode ionization source is also disclosed. The apparatus and method provide the advantages of the combined ion sources without the inherent disadvantages of the individual sources.

摘要翻译： 本发明提供了一种与质谱仪一起使用的装置和方法。 本发明的多模电离源提供用于电离分子的一个或多个大气压电离源（即电喷雾，大气压化学电离和/或大气压光电离）。 还公开了使用多模电离源产生离子的方法。 该装置和方法提供了组合离子源的优点，而没有各个源的固有缺点。

公开(公告)号：US06613523B2

公开(公告)日：2003-09-02

申请号：US09896299

申请日：2001-06-29

申请人： Steven M. Fischer

发明人： Steven M. Fischer

IPC分类号： C12Q168

CPC分类号： C12Q1/6869 ,  C12Q2525/186 ,  C12Q2523/319

摘要： The present invention provides novel systems for sequencing nucleic acid molecules using dNTPs that are 3′ end labeled with cleavable tags that block further extension and uniquely identify the bases to which they are attached. Removal of the tags liberates the 3′ ends of the extension products for further extension. In related embodiments, oligonucleotides containing sequence-related cleavable tags are employed in a ligation reaction to determine the sequence of a particular DNA sample.

摘要翻译： 本发明提供了使用具有3'末端标记的可切割标签的dNTP来测序核酸分子的新型系统，其可以阻断进一步的扩增并且唯一地鉴定它们所连接的碱基。 移除标签可以扩展扩展产品的3'端，进一步扩展。 在相关实施方案中，在连接反应中使用含有序列相关可切割标签的寡核苷酸以确定特定DNA样品的序列。

公开(公告)号：US06406633B1

公开(公告)日：2002-06-18

申请号：US09611148

申请日：2000-07-06

申请人： Steven M. Fischer ,  Glen F. Ingle

发明人： Steven M. Fischer ,  Glen F. Ingle

IPC分类号： B01D1508

CPC分类号： G01N30/82 ,  G01N30/7233 ,  G01N30/62 ,  G01N30/84 ,  G01N30/10

摘要： A fraction collection system for liquid chromatography includes a conduit, which directs a sample eluent from an LC column through a flow splitter to a destructive analytical detector such as a mass spectrometer to analyze sample components, and to a fraction collector. A nondestructive detector such as a photodetector is positioned near the fraction collector to detect arrival of sample components. Optionally, a nondestructive detector such as a photodetector is situated upstream from the splitter, to detect passing sample components. Time intervals between detection of a calibrant or a sample component at any two of the detectors provide for automatable identification of selected sample components at the sample collector.

公开(公告)号：US6032876A

公开(公告)日：2000-03-07

申请号：US203907

申请日：1998-12-01

申请人： James L. Bertsch ,  Steven M. Fischer ,  Darrell L. Gourley ,  Harvey D. Loucks, Jr. ,  Hans-Peter Zimmerman

发明人： James L. Bertsch ,  Steven M. Fischer ,  Darrell L. Gourley ,  Harvey D. Loucks, Jr. ,  Hans-Peter Zimmerman

IPC分类号： G01N27/62 ,  G01N21/31 ,  G01N21/73 ,  G01N30/72 ,  G01N30/84 ,  H01J49/04 ,  F23D11/10

CPC分类号： H01J49/0431 ,  B05B15/06 ,  B05B5/0255 ,  B05B7/066 ,  B05B7/068 ,  G01N30/7246 ,  H01J49/167 ,  B05B13/0278 ,  B05B7/0876 ,  G01N2030/847

摘要： The invention relates to an apparatus for forming liquid droplets, such as a micro nebulizer, useful for preparing samples for subsequent analysis via MS, AA, ICP, CE/MS, and similar analytical systems. The apparatus has a mechanically stabilized inner microtube or needle, thereby ensuring controllably uniform droplet size. The mechanical stabilization is provided by securing the inner microtube or needle, such as by narrowing the inner diameter of the outer microtube or otherwise narrowing the annular intermediate space between the inner and outer microtubes for a predetermined length. Thus, the inner microtube is secured in a centered or otherwise predetermined fixed radial position, with minimum perturbation of the fluid flow. Further, a tip, when coupled with the exit end of the outer microtube, provides a region in which the sheath fluid flow in the outer microtube stabilizes prior to both exiting the tip and colliding with the liquid analyte exiting the inner microtube.

摘要翻译： 本发明涉及用于形成液滴的装置，例如微型喷雾器，可用于制备样品用于随后通过MS，AA，ICP，CE / MS和类似分析系统的分析。 该装置具有机械稳定的内微管或针，从而确保可控制地均匀的液滴尺寸。 通过固定内部微管或针来提供机械稳定性，例如通过使外部微管的内径变窄或以其它方式使内部和外部微管之间的环形中间空间变窄预定长度。 因此，内部微管被固定在中心或另外预定的固定的径向位置，同时具有最小的流体流扰动。 此外，当与外部微管的出口端耦合时，尖端提供了一个区域，其中外部微管中的鞘液流动在两个离开尖端之前稳定，并且与离开内微管的液体分析物碰撞。

公开(公告)号：US5872356A

公开(公告)日：1999-02-16

申请号：US956850

申请日：1997-10-23

申请人： Steven M. Fischer ,  Curt A. Flory ,  Kent D. Henry

发明人： Steven M. Fischer ,  Curt A. Flory ,  Kent D. Henry

IPC分类号： H01J49/40 ,  H01J49/48

CPC分类号： H01J49/40

摘要： A mass spectrometer is disclosed which yields fast, full-scan spectra over a wide mass-to-charge ratio range. The instrument contains an ion source which generates nearly monoenergetically-pulsed ion packets which spatially focus at a predetermined distance along the drift path of the ions, a mass filter/analyzer which linearly disperses or deflects the ions in the ion-packets by mass-to-charge ratio by applying a traverse, quadratically time-varying and increasing electric field over the entire length of the deflection region of the mass filter/analyzer, and a spatial mass detector. A method of analyzing the mass-to-charge ratio of ions is also disclosed.

摘要翻译： 公开了质谱仪，其在宽的质荷比范围内产生快速全扫描光谱。 该仪器包含一个离子源，其产生几乎单个脉冲的离子包，其沿离子的漂移路径以预定的距离空间聚焦;质量过滤器/分析器，其将离子包中的离子线性分散或偏转， 通过在质量过滤器/分析器的偏转区域的整个长度上施加横向，二次时变和增加的电场，以及空间质量检测器。 还公开了分析离子质荷比的方法。