公开(公告)号：US07816079B2

公开(公告)日：2010-10-19

申请号：US10611409

申请日：2003-06-30

申请人： Steven M. Fischer

发明人： Steven M. Fischer

IPC分类号： C12Q1/68 ,  C12P19/34 ,  C07H21/04

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：US07635573B2

公开(公告)日：2009-12-22

申请号：US11317993

申请日：2005-12-22

申请人： Steven M. Fischer

发明人： Steven M. Fischer

IPC分类号： C12Q1/37 ,  C07K1/00 ,  C07K17/06 ,  C07K17/08

CPC分类号： G01N33/6803 ,  C07K1/36 ,  C12Q1/37 ,  G01N33/6848 ,  Y10S530/815 ,  Y10S530/816

摘要： The present invention provides a new and improved method for quantitative determination and/or identification of proteins in a sample. In one aspect, the invention provides a mass spectroscopic method for comparing protein levels in two or more samples by differentially isotopically labeling each sample's proteins' N- or C-termini. In another aspect, the invention provides a mass-spectroscopic method for identifying a sample as source for a protein from a mixture of two or more samples by differentially isotopically labeling each sample's proteins' N- or C-termini.

摘要翻译： 本发明提供了用于样品中蛋白质的定量测定和/或鉴定的新的和改进的方法。 一方面，本发明提供了通过差异同位素标记每个样品的蛋白质的N-或C-末端来比较两个或更多个样品中的蛋白质水平的质谱分析方法。 另一方面，本发明提供了通过差异同位素标记每个样品的蛋白质的N-或C-末端，从两个或多个样品的混合物中鉴定样品作为蛋白质来源的质谱分析方法。

公开(公告)号：US07423261B2

公开(公告)日：2008-09-09

申请号：US11398163

申请日：2006-04-05

申请人： Jean-Luc Truche ,  Paul C. Goodley ,  Steven M. Fischer ,  Jian Bal

发明人： Jean-Luc Truche ,  Paul C. Goodley ,  Steven M. Fischer ,  Jian Bal

IPC分类号： B01D59/44 ,  H01J49/00

CPC分类号： H01J49/062

摘要： An ion sampling apparatus for use in a mass spectrometry system. The ion sampling apparatus includes a target support for receiving a sample, an irradiation source for emitting energetic radiation or particles toward the target support, and a conduit having a curved end and a longitudinal axis, the curved end having an inlet with a central axis, the conduit being adjacent to the target support. The longitudinal axis of the conduit and the central axis of the inlet intersect to define an angle that is between about 20 degrees and about 210 degrees.

摘要翻译： 用于质谱系统的离子取样装置。 离子采样设备包括用于接收样品的目标支撑体，用于向目标支撑体发射能量辐射或颗粒的辐射源，以及具有弯曲端部和纵向轴线的导管，该弯曲端部具有带有中心轴线的入口， 导管与目标支撑件相邻。 导管的纵向轴线和入口的中心轴线相交以限定约20度至约210度之间的角度。

公开(公告)号：US07332715B2

公开(公告)日：2008-02-19

申请号：US11505089

申请日：2006-08-16

申请人： Charles W. Russ, IV ,  Steven M. Fischer ,  Robert K. Crawford

发明人： Charles W. Russ, IV ,  Steven M. Fischer ,  Robert K. Crawford

IPC分类号： B01D59/44

CPC分类号： H01J49/061 ,  H01J49/04 ,  H01J49/10

摘要： For generation and delivery of ions from an ionization chamber through an ion entrance orifice to a mass analyzer operating at high vacuum, high pass ion filtration is effected within the ionization chamber by application of electrical potentials to an electrode associated with the ion entrance orifice and to an electrode between the ionization region and the ion entrance orifice to create a retarding electric field upstream from the ion entrance orifice. The retarding electric field hinders the movement to the ion entrance orifice of ions having drift velocities below a lower limit, and as the retarding voltage gradient is made steeper, the lower limit increases.

摘要翻译： 为了将离子从离子入口通过离子入口孔传送到在高真空下操作的质量分析器，通过将电位施加到与离子入口孔相关联的电极，在离子化室内进行高通离子过滤，并且 电离区域和离子入口孔之间的电极，以产生离子入口孔上游的延迟电场。 延迟电场阻碍了离子入口孔的移动，其离子入射孔的漂移速度低于下限，随着延迟电压梯度变得更陡峭，下限增加。

公开(公告)号：US06989530B2

公开(公告)日：2006-01-24

申请号：US10806685

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：US06952012B2

公开(公告)日：2005-10-04

申请号：US10806908

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： H01J49/04 ,  H01J49/16 ,  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：US06797947B2

公开(公告)日：2004-09-28

申请号：US10664512

申请日：2003-09-16

申请人： Charles W. Russ, IV ,  Steven M. Fischer

发明人： Charles W. Russ, IV ,  Steven M. Fischer

IPC分类号： H01J4910

CPC分类号： H01J49/0009 ,  H01J49/004

摘要： An apparatus and method for calibrating a mass spectrometer by internally introducing calibration masses at a post-source stage of the mass spectrometer is provided. A source of lock mass ions adjacent the ion optics creates lock mass ions within the ion optics. Lock mass ions mix with the analyte ions in the ion optics prior to mass analysis. The source of lock mass ions may include various means for ionizing lock mass molecules including but not limited to photoionization, field desorption-ionization, electron ionization, and thermal ionization means. An apparatus and method of mass calibrating a tandem mass spectrometer is also provided. The mass calibration apparatus includes a collision cell for fragmenting analyte ions and a source of lock mass ions adjacent said collision cell for creating lock mass ions in the collision cell.

摘要翻译： 提供了通过在质谱仪的后源阶段内部引入校准质量来校准质谱仪的装置和方法。 与离子光学器件相邻的锁定质量离子源产生离子光学器件内的锁定质子离子。 在质量分析之前，将质子离子与离子光学中的分析物离子混合。 锁定质量离子的来源可以包括用于电离锁定质量分子的各种装置，包括但不限于光电离，场解吸电离，电子离子化和热电离装置。 还提供了质量校准串联质谱仪的装置和方法。 质量校准装置包括用于碎裂分析物离子的碰撞单元和邻近所述碰撞室的锁定质量离子源，用于在碰撞室中产生锁定质量离子。

公开(公告)号：US06583407B1

公开(公告)日：2003-06-24

申请号：US09645050

申请日：2000-08-23

申请人： Steven M. Fischer ,  Charles W. Russ, IV

发明人： Steven M. Fischer ,  Charles W. Russ, IV

IPC分类号： B01D5944

CPC分类号： H01J49/04

摘要： The present invention relates to a method for selectively delivering ions to a mass analyzer operating in a vacuum region. The method involves providing a dielectric conduit having an axial bore originating in an inlet opening that communicates with an ion source and terminating in an exit opening disposed within the vacuum region. A gas stream comprising an ion having a polarity and traveling at a drift velocity is flowed through the bore from the inlet opening toward the exit opening. A motion component is altered in a manner that does not substantially depend on the polarity of the ion to effect a change in the drift velocity of the ion. The invention also provides an apparatus to carry out the method.

摘要翻译： 本发明涉及一种用于选择性地将离子输送到在真空区域中操作的质量分析器的方法。 该方法包括提供具有源自入口开口的轴向孔的电介质导管，其与离子源连通并终止于设置在真空区域内的出口。 包含具有极性并以漂移速度行进的离子的气流从入口开口流向出口。 改变运动分量的方式基本上不取决于离子的极性来实现离子的漂移速度的变化。 本发明还提供一种执行该方法的装置。

公开(公告)号：US6153880A

公开(公告)日：2000-11-28

申请号：US410379

申请日：1999-09-30

申请人： Charles William Russ, IV ,  Jerry T. Dowell ,  Steven M. Fischer

发明人： Charles William Russ, IV ,  Jerry T. Dowell ,  Steven M. Fischer

IPC分类号： H01J49/42

CPC分类号： H01J49/4215 ,  H01J49/067

摘要： A mass spectrometer method and apparatus improve resolution and sensitivity. A voltage supply is coupled to a mass filter for applying a radio frequency voltage and for operating at at least one selected frequency. An ion optical element such as an entrance lens is driven by a voltage supply that is phase coherent with the voltage applied to the mass filter. The ion beam is tailored so that the phase space relationship of the ions is more closely matched to the acceptance of the mass filter. The ions in the incoming beam are dynamically matched to the acceptance of the mass filter over each cycle of the voltage applied to the mass filter. The ion optical element may be a single entrance lens to which is applied only a single phase coherent voltage.

摘要翻译： 质谱仪方法和设备提高分辨率和灵敏度。 电压源耦合到质量过滤器以施加射频电压并且以至少一个所选择的频率进行操作。 诸如入射透镜的离子光学元件由与施加到质量过滤器的电压相位相干的电压源驱动。 定制离子束，使得离子的相位空间关系与质量过滤器的接受度更接近。 入射束中的离子与施加到质量过滤器的电压的每个周期动态地匹配质量过滤器的接受。 离子光学元件可以是仅施加单相相干电压的单个入射透镜。

公开(公告)号：US20080042056A1

公开(公告)日：2008-02-21

申请号：US11506933

申请日：2006-08-18

申请人： Steven M. Fischer ,  Harry F. Prest ,  Robert Lee

发明人： Steven M. Fischer ,  Harry F. Prest ,  Robert Lee

IPC分类号： H01J49/10

CPC分类号： H01J49/0059 ,  G01N33/6848 ,  G01N33/6851 ,  H01J49/0068

摘要： The invention provides a system apparatus and methods for fragmenting various molecules. In particular, the invention may be employed for fragmenting biomolecules like peptides to determine sequence information. The invention provides a mass spectrometry system for photo-activated collision induced dissociation. The mass spectrometry system or device includes an ion source for producing ions, a photon source adjacent to the ion source for photo-activating ions produced by the ion source, an electrical element adjacent to the photon source for creating an electric field for accelerating ions produced by the ion source and photo-activated by the photon source; wherein ions are produced by the ion source, photo-activated by the photon source and accelerated into a surface to cause dissociation of the activated ions; and a detector downstream from the ion source for detecting the collision induced and dissociated ions.Methods for molecule and/or peptide fragmentation are also disclosed.

摘要翻译： 本发明提供了一种分散各种分子的系统装置和方法。 特别地，本发明可用于片段生物分子如肽以确定序列信息。 本发明提供了一种用于光激活碰撞诱导解离的质谱系统。 质谱系统或装置包括用于产生离子的离子源，邻近于离子源的光子源，用于由离子源产生的光激活离子;邻近光子源的电元件，用于产生用于加速产生的离子的电场 由离子源和光子源激活; 其中离子由离子源产生，由光子源光激活并加速到表面以引起活化离子的解离; 以及用于检测碰撞诱导和离解离子的离子源下游的检测器。 还公开了分子和/或肽断裂的方法。