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1. 发明授权

US06727497B2 Charge reduction in electrospray mass spectrometry 有权
标题翻译：电喷雾质谱法中的电荷减少
公开(公告)号：US06727497B2
公开(公告)日：2004-04-27
申请号：US09815929
申请日：2001-03-23
申请人： Mark A. Scalf , Lloyd M. Smith , Michael S. Westphall , Daniel D. Ebeling
发明人： Mark A. Scalf , Lloyd M. Smith , Michael S. Westphall , Daniel D. Ebeling
IPC分类号： H01J4900
CPC分类号： H01J49/165
摘要： The charge state of ions produced by electrospray ionization is reduced in a controlled manner to yield predominantly singly charged ions through reactions with bipolar ions generated using a 210Po alpha particle source or equivalent. The multiply charged ions generated by the electrospray undergo charge reduction in a charge reduction chamber. The charge-reduced ions are then detected using a commercial orthogonal electrospray TOF mass spectrometer, although the charge reduction chamber can be adapted to virtually any mass analyzer. The results obtained exhibit a signal intensity drop-off with increased oligonucleotide size similar to that observed with MALDI mass spectrometry, yet with the softness of ESI and without the off-line sample purification and pre-separation required by MALDI.
摘要翻译：通过电喷雾电离产生的离子的电荷状态以受控的方式降低，以通过与使用<210>Poα粒子源或等同物产生的双极离子反应而主要产生单电荷离子。由电喷雾产生的多重带电离子在电荷还原室中经历电荷还原。然后使用商业正交电喷雾TOF质谱仪检测电荷减少的离子，尽管电荷减少室可适用于几乎任何质量分析仪。获得的结果表现出信号强度下降，其增加的寡核苷酸大小与使用MALDI质谱法观察到的寡核苷酸大小相似，但是具有ESI的柔软性，并且不需要MALDI要求的离线样品纯化和预分离。

2. 发明授权

US06649907B2 Charge reduction electrospray ionization ion source 有权
公开(公告)号：US06649907B2
公开(公告)日：2003-11-18
申请号：US09802322
申请日：2001-03-08
申请人： Daniel D. Ebeling , Michael S. Westphall , Mark A. Scalf , Lloyd M. Smith
发明人： Daniel D. Ebeling , Michael S. Westphall , Mark A. Scalf , Lloyd M. Smith
IPC分类号： B01D5944
CPC分类号： H01J49/165 , H01J49/044 , Y10S977/786 , Y10S977/795
摘要： Methods and devices for use in mass spectral analysis of samples. In particular, methods and devices for generating ions from liquid samples containing chemical species with high molecular masses. These methods and devices provide a continuous or pulsed stream of gas phase analyte ions of either positive polarity, negative polarity or both possessing either a selected fixed charge-state distribution or one that may be selectively varied with time. More specifically, ion sources with adjustable control of the charge-state distribution of the gas phase analyte ions generated are provided in which charged droplets and/or gas phase analyte ions are exposed to electrons and/or gas phase reagent ions generated by a reagent ion source to provide desired control. A corona discharge exemplifies the reagent ion source employed in charge-state distribution control. In a specific preferred ion source, a corona discharge is provided within a shielded region to minimize the deflection of gas phase analyte ions, charged droplets. The methods and devices provided herein are particularly well-suited to the analysis of polymers and biological species.

3. 发明授权

US07884324B2 Nanopillar arrays for electron emission 有权
标题翻译：用于电子发射的纳米柱阵列
公开(公告)号：US07884324B2
公开(公告)日：2011-02-08
申请号：US12130103
申请日：2008-05-30
申请人： Robert H. Blick , Michael S. Westphall , Hua Qin , Lloyd M. Smith
发明人： Robert H. Blick , Michael S. Westphall , Hua Qin , Lloyd M. Smith
IPC分类号： G01N23/00 , G01N13/10 , H01J49/08
CPC分类号： H01J1/32 , H01J29/023 , H01J43/246 , Y10S977/762
摘要： The present invention provides systems, devices, device components and structures for modulating the intensity and/or energies of electrons, including a beam of incident electrons. In some embodiments, for example, the present invention provides nano-structured semiconductor membrane structures capable of generating secondary electron emission. Nano-structured semiconductor membranes of this aspect of the present invention include membranes having an array of nanopillar structures capable of providing electron emission for amplification, filtering and/or detection of incident radiation, for example secondary electron emission and/or field emission. Nano-structured semiconductor membranes of the present invention are useful as converters wherein interaction of incident primary electrons and nanopillars of the nanopillar array generates secondary emission. Nano-structured semiconductor membranes of this aspect of the present invention are also useful as directed charge amplifiers wherein secondary emission from a nanopillar array provides gain functionality for increasing the intensity of radiation comprising incident electrons.
摘要翻译：本发明提供了用于调制包括入射电子束的电子的强度和/或能量的系统，装置，器件组件和结构。在一些实施例中，例如，本发明提供能够产生二次电子发射的纳米结构的半导体膜结构。本发明该方面的纳米结构半导体膜包括具有能够提供用于放射，滤波和/或检测入射辐射的电子发射的纳米柱结构阵列的膜，例如二次电子发射和/或场发射。本发明的纳米结构半导体膜可用作其中纳米柱阵列的入射一次电子和纳米柱的相互作用产生二次发射的转换器。本发明该方面的纳米结构半导体膜也可用作定向电荷放大器，其中来自纳米柱阵列的二次发射提供了用于增加包括入射电子的辐射强度的增益功能。

4. 发明授权

US07518108B2 Electrospray ionization ion source with tunable charge reduction 有权
标题翻译：具有可调电荷还原的电喷雾离子源
公开(公告)号：US07518108B2
公开(公告)日：2009-04-14
申请号：US11272450
申请日：2005-11-10
申请人： Brian L. Frey , Lloyd M. Smith , Michael S. Westphall
发明人： Brian L. Frey , Lloyd M. Smith , Michael S. Westphall
IPC分类号： B01D59/44 , H01J49/00
CPC分类号： H01J49/165 , H01J49/0045
摘要： This invention provides methods, devices and device components for preparing ions from liquid samples containing chemical species and methods and devices for analyzing chemical species in liquid samples. The present invention provides an ion source for generating analyte ions having a selected charge state distribution, such as a reduced charged state distribution, that may be effectively interfaced with a variety of charged particle analyzers, including virtually any type of mass spectrometer.
摘要翻译：本发明提供用于从含有化学物质的液体样品制备离子的方法，装置和装置组件以及用于分析液体样品中的化学物质的方法和装置。本发明提供了一种用于产生具有选定的电荷状态分布的分析离子的离子源，所述电荷状态分布例如降低的充电状态分布，其可以有效地与包括实际上任何类型的质谱仪在内的各种带电粒子分析仪接口。

5. 发明申请

US20080248585A1 Protein/Peptide Sequencing By Chemical Degradation in the Gas Phase 有权
标题翻译：通过化学降解在气相中的蛋白质/肽测序
公开(公告)号：US20080248585A1
公开(公告)日：2008-10-09
申请号：US11568536
申请日：2005-07-15
申请人： Xiaoyu Chen , Michael S. Westphall , Lloyd M. Smith , Brian L. Frey
发明人： Xiaoyu Chen , Michael S. Westphall , Lloyd M. Smith , Brian L. Frey
IPC分类号： G01N33/00 , H01J49/36
CPC分类号： G01N33/6824 , G01N33/6848
摘要： A fast and sensitive method and device for protein sequencing are disclosed. The method uses a combination of Edman degradation chemistry and mass spectrometry to sequence proteins and polypeptides. A peptide degradation reaction is performed on a polypeptide or protein ion reactant in the gas phase. The reaction yields a first ion product corresponding to a first amino acid residue of the polypeptide or protein reactant and a polypeptide or protein fragment ion. The mass-to-charge ratio for the first ion product, or the polypeptide or protein fragment ion, or both, is then determined. The first amino acid residue of the polypeptide or protein reactant is then identified from the mass-to-charge ratio so determined.
摘要翻译：公开了用于蛋白质测序的快速且灵敏的方法和装置。该方法使用Edman降解化学和质谱联用来对蛋白质和多肽进行序列分析。在气相中对多肽或蛋白质离子反应物进行肽降解反应。该反应产生对应于多肽或蛋白质反应物的第一个氨基酸残基的第一离子产物和多肽或蛋白质片段离子。然后确定第一离子产物或多肽或蛋白质片段离子或两者的质荷比。然后从如此确定的质荷比鉴定多肽或蛋白质反应物的第一个氨基酸残基。

6. 发明授权

US07078679B2 Inductive detection for mass spectrometry 有权
标题翻译：电化学检测
公开(公告)号：US07078679B2
公开(公告)日：2006-07-18
申请号：US10723462
申请日：2003-11-26
申请人： Michael S. Westphall , Lloyd M. Smith
发明人： Michael S. Westphall , Lloyd M. Smith
IPC分类号： B01D59/44 , H01J49/00
CPC分类号： H01J49/06 , H01J49/027
摘要： The invention provides devices, device configurations and methods for improved sensitivity, resolution and efficiency in mass spectrometry, particularly as applied to biological molecules, including biological polymers, such as proteins and nucleic acids. More particularly, the invention provides methods and devices for analyzing and detecting electrically charged particles, especially suitable for gas phase ions generated from high molecular weight compounds. In one aspect, the invention provides devices and methods for determining the velocity, charged state or both of electrically charged particles and packets of electrically charged particles. In another aspect, the invention provides methods and devices for the time-of-flight analysis of electrically charged particles comprising spatially collimated sources. In another aspect, the invention relates to multiple detection using inductive detectors, improved methods of signal averaging and charged particle detection in coincidence.
摘要翻译：本发明提供了用于提高质谱法的灵敏度，分辨率和效率的装置，装置配置和方法，特别是适用于包括生物聚合物如蛋白质和核酸在内的生物分子。更具体地，本发明提供用于分析和检测带电粒子的方法和装置，特别适用于由高分子量化合物产生的气相离子。一方面，本发明提供用于确定带电粒子和带电粒子的包的速度，带电状态或两者的装置和方法。在另一方面，本发明提供了用于包括空间准直源的带电粒子的飞行时间分析的方法和装置。另一方面，本发明涉及使用感应检测器的多重检测，符合信号平均和带电粒子检测的改进方法。

7. 发明授权

US08628974B2 Protein/peptide sequencing by chemical degradation in the gas phase 有权
标题翻译：通过化学降解在气相中进行蛋白质/肽测序
公开(公告)号：US08628974B2
公开(公告)日：2014-01-14
申请号：US11568536
申请日：2005-07-15
申请人： Xiaoyu Chen , Michael S. Westphall , Lloyd M. Smith , Brian L. Frey
发明人： Xiaoyu Chen , Michael S. Westphall , Lloyd M. Smith , Brian L. Frey
IPC分类号： G01N33/00 , H01J49/36
CPC分类号： G01N33/6824 , G01N33/6848
摘要： A fast and sensitive method and device for protein sequencing are disclosed. The method uses a combination of Edman degradation chemistry and mass spectrometry to sequence proteins and polypeptides. A peptide degradation reaction is performed on a polypeptide or protein ion reactant in the gas phase. The reaction yields a first ion product corresponding to a first amino acid residue of the polypeptide or protein reactant and a polypeptide or protein fragment ion. The mass-to-charge ratio for the first ion product, or the polypeptide or protein fragment ion, or both, is then determined. The first amino acid residue of the polypeptide or protein reactant is then identified from the mass-to-charge ratio so determined.
摘要翻译：公开了用于蛋白质测序的快速且灵敏的方法和装置。该方法使用Edman降解化学和质谱联用来对蛋白质和多肽进行序列分析。在气相中对多肽或蛋白质离子反应物进行肽降解反应。该反应产生对应于多肽或蛋白质反应物的第一个氨基酸残基的第一离子产物和多肽或蛋白质片段离子。然后确定第一离子产物或多肽或蛋白质片段离子或两者的质荷比。然后从如此确定的质荷比鉴定多肽或蛋白质反应物的第一个氨基酸残基。

8. 发明授权

US07303869B2 Solid-phase reactions 有权
标题翻译：固相反应
公开(公告)号：US07303869B2
公开(公告)日：2007-12-04
申请号：US10269222
申请日：2002-10-11
申请人： Priscilla Wilkins Stevens , David Kelso , Victor Lyamichev , Jeff Hall , Bruce P. Neri , Robert W. Kwiatkowski, Jr. , Lloyd M. Smith
发明人： Priscilla Wilkins Stevens , David Kelso , Victor Lyamichev , Jeff Hall , Bruce P. Neri , Robert W. Kwiatkowski, Jr. , Lloyd M. Smith
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/683 , C12Q2561/109 , C12Q2565/101
摘要： The present invention relates to systems, compositions, and methods for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. The present invention relates to methods for attaching nucleic acids to solid supports and modifying nucleic acids. For example, in some embodiments, the 5′ nuclease activity of a cleavage agent is used to cleave a cleavage structure formed on the solid support, the occurrence of the cleavage event indicating the presence of specific nucleic acid sequences.
摘要翻译：本发明涉及核酸序列的检测和表征以及核酸序列变异的系统，组合物和方法。本发明涉及将核酸连接到固体支持物和修饰核酸的方法。例如，在一些实施方案中，切割剂的5'核酸酶活性用于切割在固体支持物上形成的切割结构，裂解事件的发生表明存在特定的核酸序列。

9. 发明授权

US5228971A Horizontal gel electrophoresis apparatus 失效
标题翻译：水平凝胶电泳仪
公开(公告)号：US5228971A
公开(公告)日：1993-07-20
申请号：US878632
申请日：1992-05-04
申请人： Robert L. Brumley, Jr. , Lloyd M. Smith
发明人： Robert L. Brumley, Jr. , Lloyd M. Smith
IPC分类号： G01N27/447
CPC分类号： G01N27/44704 , G01N27/44756
摘要： A horizontal electrophoresis assembly is described which is designed to utilize very thin gels of polyacrylamide. The assembly allows for water cooling of the gel during electrophoresis so that higher voltages can be applied to the gel without polymer degradation. The gel mold is made from a set of glass plates which are clamped into place defining a gel mold between them. In one embodiment, the site of field introduction is separated from the site of sample introduction so that the electric field is generally linear at the region of sample introduction.
摘要翻译：描述了一种设计用于使用非常薄的聚丙烯酰胺凝胶的水平电泳组件。该组件允许在电泳期间水冷却凝胶，使得更高的电压可以施加到凝胶上而没有聚合物降解。凝胶模具由一组玻璃板制成，这些玻璃板被夹紧就位，在它们之间限定凝胶模具。在一个实施例中，场引入位置与样品引入位置分离，使得电场在样品引入区域通常是线性的。

10. 发明授权

US5171534A Automated DNA sequencing technique 失效
标题翻译：自动DNA测序技术
公开(公告)号：US5171534A
公开(公告)日：1992-12-15
申请号：US558312
申请日：1990-10-15
申请人： Lloyd M. Smith , Leroy E. Hood , Michael W. Hunkapiller , Tim J. Hunkapiller
发明人： Lloyd M. Smith , Leroy E. Hood , Michael W. Hunkapiller , Tim J. Hunkapiller
IPC分类号： C12Q1/68 , G01N27/447
CPC分类号： G01N27/44726 , C12Q1/6869 , G01N27/44721 , Y10T436/143333
摘要： A system for the electrophoretic analysis of DNA fragments produced in DNA sequencing operations comprising: a source of chromophore or fluorescent tagged DNA fragments; a zone for contacting an electrophoresis gel; means for introducing said tagged DNA fragments to said zone; and photometric means for monitoring said tagged DNA fragments as they move through said gel.
摘要翻译：用于在DNA测序操作中产生的DNA片段的电泳分析系统，包括：发色团或荧光标记的DNA片段; 用于接触电泳凝胶的区域; 用于将所述标记的DNA片段引入所述区域的方法; 以及用于在所述标记的DNA片段移动通过所述凝胶时监测所述标记的DNA片段的光度装置

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