公开(公告)号：US07087898B2

公开(公告)日：2006-08-08

申请号：US10862304

申请日：2004-06-07

申请人： Ross C. Willoughby ,  Edward W. Sheehan ,  Craig M. Whitehouse

发明人： Ross C. Willoughby ,  Edward W. Sheehan ,  Craig M. Whitehouse

IPC分类号： H01J49/04 ,  H01J49/10 ,  H01J49/40

CPC分类号： H01J49/164 ,  H01J49/06

摘要： Atmospheric pressure, intermediate pressure and vacuum laser desorption ionization methods and ion sources are configured to increase ionization efficiency and the efficiency of transmitting ions to a mass to charge analyzer or ion mobility analyzer. An electric field is applied in the region of a sample target to accumulate ions generated from a local ion source on a solid or liquid phase sample prior to applying a laser desorption pulse. The electric field is changed just prior to or during the desorption laser pulse to promote the desorption of charged species and improve the ionization efficiency of desorbed sample species. After a delay, the electric field may be further changed to optimize focusing and transmission of ions into a mass spectrometer or ion mobility analyzer. Charged species may also be added to the region of the laser desorbed sample plume to promote ion-molecule reactions between the added ions and desorbed neutral sample species, increasing desorbed sample ionization efficiency and/or creating desired product ion species. The cycling of electric field changes is repeated in a timed sequence with one or more desorption laser pulse occurring per electric field change cycle. Embodiments of the invention comprise atmospheric pressure, intermediate pressure and vacuum pressure laser desorption ionization source methods and devices for increasing the analytical flexibility and improving the sensitivity of mass spectrometric analysis.

摘要翻译： 大气压力，中压和真空激光解吸电离方法和离子源被配置为增加电离效率和将离子传输到质量计量分析器或离子迁移率分析仪的效率。 在样品靶的区域内施加电场，以在施加激光解吸脉冲之前，在固相或液相样品上积聚从局部离子源产生的离子。 电场在解吸激光脉冲之前或期间改变，以促进带电物质的解吸附并提高解吸样品的离子化效率。 延迟后，可以进一步改变电场以优化离子聚焦和传输到质谱仪或离子迁移率分析仪中。 带电物质也可以加入到激光解吸样品羽流的区域中，以促进添加的离子和解吸的中性样品物质之间的离子 - 分子反应，增加解吸的样品电离效率和/或产生所需的产物离子种类。 以定时序列重复电场变化的循环，每个电场变化周期发生一个或多个解吸激光脉冲。 本发明的实施例包括大气压力，中压和真空压力激光解吸电离源的方法和装置，用于增加分析灵活性并提高质谱分析的灵敏度。

公开(公告)号：US07375319B1

公开(公告)日：2008-05-20

申请号：US11500055

申请日：2006-08-07

申请人： Ross C. Willoughby ,  Edward W. Sheehan ,  Craig M. Whitehouse

发明人： Ross C. Willoughby ,  Edward W. Sheehan ,  Craig M. Whitehouse

IPC分类号： H01J49/04

CPC分类号： H01J49/0463 ,  H01J49/145

摘要： Atmospheric pressure, intermediate pressure and vacuum laser desorption ionization methods and ion sources are configured to increase ionization efficiency and the efficiency of transmitting ions to a mass to charge analyzer or ion mobility analyzer. An electric field is applied in the region of a sample target to accumulate ions generated from a local ion source on a solid or liquid phase sample prior to applying a laser desorption pulse. The electric field is changed just prior to or during the desorption laser pulse to promote the desorption of charged species and improve the ionization efficiency of desorbed sample species. After a delay, the electric field may be further changed to optimize focusing and transmission of ions into a mass spectrometer or ion mobility analyzer. Charged species may also be added to the region of the laser desorbed sample plume to promote ion-molecule reactions between the added ions and desorbed neutral sample species, increasing desorbed sample ionization efficiency and/or creating desired production species. The cycling of electric field changes is repeated in a timed sequence with one or more desorption laser pulse occurring per electric field change cycle. Embodiments of the invention comprise atmospheric pressure, intermediate pressure and vacuum pressure laser desorption ionization source methods and devices for increasing the analytical flexibility and improving the sensitivity of mass spectrometric analysis.

摘要翻译： 大气压力，中压和真空激光解吸电离方法和离子源被配置为增加电离效率和将离子传输到质量计量分析器或离子迁移率分析仪的效率。 在样品靶的区域内施加电场，以在施加激光解吸脉冲之前，在固相或液相样品上积聚从局部离子源产生的离子。 电场在解吸激光脉冲之前或期间改变，以促进带电物质的解吸附并提高解吸样品的离子化效率。 延迟后，可以进一步改变电场以优化离子聚焦和传输到质谱仪或离子迁移率分析仪中。 带电物质也可以添加到激光解吸的样品羽毛的区域中，以促进添加的离子和解吸的中性样品物质之间的离子 - 分子反应，增加解吸的样品离子化效率和/或产生所需的生产物质。 以定时序列重复电场变化的循环，每个电场变化周期发生一个或多个解吸激光脉冲。 本发明的实施例包括大气压力，中压和真空压力激光解吸电离源的方法和装置，用于增加分析灵活性并提高质谱分析的灵敏度。

公开(公告)号：US06784424B1

公开(公告)日：2004-08-31

申请号：US10155151

申请日：2002-05-25

申请人： Ross C Willoughby ,  Edward W Sheehan

发明人： Ross C Willoughby ,  Edward W Sheehan

IPC分类号： H01J4926

CPC分类号： H01J49/4215

摘要： The present invention relates to an apparatus and method for focusing, separating, and detecting gas-phase ions using the principles of quadrupole fields, substantially at or near atmospheric pressure. Ions are entrained in a concentric flow of gas and travel through a high-transmission element into a RF/DC quadrupole, through a second high-transmission element, and then impact on an ion detector, such as a faraday plate; or through an aperture with subsequent identification by a mass spectrometer. Ions with stable trajectories pass through the RF/DC quadrupole while ions with unstable trajectories drift off-axis collide with the rods and are lost. Embodiments of this invention are devices and methods for focusing, separating and detecting gas-phase ions without the need for a vacuum chamber when coupled to atmospheric ionization sources.

摘要翻译： 本发明涉及一种基本上在大气压或接近大气压的四极场的原理聚焦，分离和检测气相离子的装置和方法。 离子被夹带在同心圆的气体中，并通过第二高传导元件穿过高传输元件进入RF / DC四极杆，然后冲击到诸如法拉第板的离子检测器; 或通过孔径随后通过质谱仪进行识别。 具有稳定轨迹的离子通过RF / DC四极杆，而具有不稳定轨迹的离子偏离轴与棒碰撞并丢失。 本发明的实施例是用于在与大气电离源耦合时不需要真空室的情况下聚焦，分离和检测气相离子的装置和方法。

公开(公告)号：US5285064A

公开(公告)日：1994-02-08

申请号：US40073

申请日：1993-03-30

申请人： Ross C. Willoughby

发明人： Ross C. Willoughby

IPC分类号： G01N1/00 ,  G01N30/02 ,  G01N30/30 ,  G01N30/72 ,  H01J49/04

CPC分类号： H01J49/049 ,  H01J49/045 ,  G01N1/22 ,  G01N2030/027 ,  G01N2030/3038 ,  G01N2030/3061 ,  G01N30/7253

摘要： Methods and apparatus for liquid sample introduction into chemical detectors that require the sample to be transformed from a flowing stream into either gaseous or particulate states. The effluent from either a process stream or a liquid chromatograph is nebulized by combined thermal and pneumatic processes within an inner fused silicon capillary tube heated by conduction from a surrounding electrical resistance heated outer capillary tube composed of a pure metal having a comparatively high linear relationship between temperature and electrical resistance to provide a uniform conduction of heat energy to the inner tube to form a well-collimated, partially or completely desolvated aerosol, with the less volatile solute components of the sample stream remaining in the particulate state. The gaseous components of the aerosol are separated from the solvent-depleted solute particles using either cryotrapping or momentum separation. The enriched solute particles are vaporized, ionized, and/or detected by suitable gas-phase or particle detectors. The device is primarily an interface between the liquid chromatograph or process streams and the mass spectrometer.

摘要翻译： 将液体样品引入化学检测器的方法和设备，其需要将样品从流动物流转变为气态或微粒状态。 来自工艺流或液相色谱仪的流出物通过内部熔融硅毛细管内的组合热和气动工艺进行喷雾，所述内部熔融硅毛细管由来自周围的电阻加热的外部毛细管的传导加热，所述外部毛细管由纯金属组成，所述纯金属具有相对较高的线性关系 温度和电阻，以向内管提供均匀的热能传导，以形成准直的，部分或完全脱溶的气溶胶，其中样品流的挥发性较低的溶质组分保持颗粒状态。 气溶胶的气态组分使用低温震荡或动量分离与溶剂不足的溶质颗粒分离。 富集的溶质颗粒被合适的气相或颗粒检测器蒸发，离子化和/或检测。 该装置主要是液相色谱仪或过程流与质谱仪之间的界面。

公开(公告)号：US07816646B1

公开(公告)日：2010-10-19

申请号：US12123669

申请日：2008-05-20

申请人： Ross C. Willoughby ,  Edward W. Sheehan ,  Craig M. Whitehouse

发明人： Ross C. Willoughby ,  Edward W. Sheehan ,  Craig M. Whitehouse

IPC分类号： H01J49/04

CPC分类号： H01J49/0463 ,  H01J49/145

摘要： Atmospheric pressure, intermediate pressure and vacuum laser desorption ionization methods and ion sources are configured to increase ionization efficiency and the efficiency of transmitting ions to a mass to charge analyzer or ion mobility analyzer. An electric field is applied in the region of a sample target to accumulate ions generated from a local ion source on a solid or liquid phase sample prior to applying a laser desorption pulse. The electric field is changed just prior to or during the desorption laser pulse to promote the desorption of charged species and improve the ionization efficiency of desorbed sample species. After a delay, the electric field may be further changed to optimize focusing and transmission of ions into a mass spectrometer or ion mobility analyzer. Charged species may also be added to the region of the laser desorbed sample plume to promote ion-molecule reactions between the added ions and desorbed neutral sample species, increasing desorbed sample ionization efficiency and/or creating desired product ion species. The cycling of electric field changes is repeated in a timed sequence with one or more desorption laser pulse occurring per electric field change cycle. Embodiments of the invention comprise atmospheric pressure, intermediate pressure and vacuum pressure laser desorption ionization source methods and devices for increasing the analytical flexibility and improving the sensitivity of mass spectrometric analysis.

摘要翻译： 大气压力，中压和真空激光解吸电离方法和离子源被配置为增加电离效率和将离子传输到质量计量分析器或离子迁移率分析仪的效率。 在样品靶的区域内施加电场，以在施加激光解吸脉冲之前，在固相或液相样品上积聚从局部离子源产生的离子。 电场在解吸激光脉冲之前或期间改变，以促进带电物质的解吸附并提高解吸样品的离子化效率。 延迟后，可以进一步改变电场以优化离子聚焦和传输到质谱仪或离子迁移率分析仪中。 带电物质也可以加入到激光解吸样品羽流的区域中，以促进添加的离子和解吸的中性样品物质之间的离子 - 分子反应，增加脱附的样品电离效率和/或产生所需的产物离子种类。 以定时序列重复电场变化的循环，每个电场变化周期发生一个或多个解吸激光脉冲。 本发明的实施例包括大气压力，中压和真空压力激光解吸电离源的方法和装置，用于增加分析灵活性并提高质谱分析的灵敏度。

公开(公告)号：US06888132B1

公开(公告)日：2005-05-03

申请号：US10449344

申请日：2003-05-30

申请人： Edward W Sheehan ,  Ross C Willoughby

发明人： Edward W Sheehan ,  Ross C Willoughby

IPC分类号： H01J49/00

CPC分类号： H01J49/145

摘要： An improved ion source for collecting and focusing dispersed gas-phase ions from a reagent source at atmospheric or intermediate pressure, having a remote source of reagent ions separated from a low-field sample ionization region by a stratified array of elements, each element populated with a plurality of openings, wherein DC potentials are applied to each element necessary for transferring reagent ions from the remote source into the low-field sample ionization region where the reagent ions react with neutral and/or ionic sample forming ionic species. The resulting ionic species are then introduced into the vacuum system of a mass spectrometer or ion mobility spectrometer. Embodiments of this invention are methods and devices for improving sensitivity of mass spectrometry when gas and liquid chromatographic separation techniques are coupled to atmospheric and intermediate pressure photo-ionization, chemical ionization, and thermospray ionization sources.

摘要翻译： 一种改进的离子源，用于在大气压或中压下从试剂源收集和聚焦分散的气相离子，其具有通过分层的元素阵列与低场样品电离区域分离的试剂离子的远程源，每个元素填充有 多个开口，其中DC电位被施加到将试剂离子从远程源传输到低场样品电离区所需的每个元件，其中试剂离子与形成中性和/或离子样品的离子物质反应。 然后将所得的离子物质引入质谱仪或离子迁移谱仪的真空系统中。 本发明的实施例是当气体和液相色谱分离技术与大气和中压光电离，化学电离和热喷射电离源耦合时提高质谱灵敏度的方法和装置。

公开(公告)号：US4977785A

公开(公告)日：1990-12-18

申请号：US157626

申请日：1988-02-19

申请人： Ross C. Willoughby ,  James D. Buchner

发明人： Ross C. Willoughby ,  James D. Buchner

IPC分类号： G01N30/02 ,  G01N30/72 ,  H01J49/04

CPC分类号： H01J49/0468 ,  H01J49/0445 ,  G01N30/02 ,  G01N30/7246 ,  G01N30/7273 ,  G01N30/7293

摘要： Methods and apparatus for introduction of sample from a flowing stream into mass spectrometers or other analyzing apparatus for analytical and process stream analysis of the sample. The apparatus generates an aerosol during the decompression of a gas, liquid or supercritical fluid stream. The aerosol's properties are dependent upon mass flow, pressure, temperature, solubility of sample, and the physical dimensions of the aerosol generating device. Upon aerosol generation, a less volatile sample in the form of condensed particles is separated from the gaseous components by accelerating the aerosol through a nozzle restrictor and utilizing momentum differences between solute particles and carrier gas molecules to obtain high solute enrichments at various particles or gas-phase detectors. The device functions primarily as an interface between a supercritical fluid chromatograph and the mass spectrometer.

摘要翻译： 将样品从流动物引入质谱仪或其他分析装置中以用于样品的分析和工艺流分析的方法和装置。 该装置在减压气体，液体或超临界流体流期间产生气溶胶。 气溶胶的性质取决于质量流量，压力，温度，样品的溶解度和气溶胶发生装置的物理尺寸。 气溶胶产生时，通过喷嘴限制器加速气溶胶并利用溶质颗粒和载气分子之间的动量差异，在各种颗粒或气体分离器中获得高溶质富集，从而将冷凝颗粒形式的较不易挥发的样品与气体组分分离， 相位检测器。 该装置主要作为超临界流体色谱仪和质谱仪之间的界面。

公开(公告)号：US4968885A

公开(公告)日：1990-11-06

申请号：US393846

申请日：1989-08-14

申请人： Ross C. Willoughby

发明人： Ross C. Willoughby

IPC分类号： G01N1/00 ,  G01N30/02 ,  G01N30/30 ,  G01N30/72 ,  H01J49/04

CPC分类号： H01J49/049 ,  H01J49/045 ,  G01N1/22 ,  G01N2030/027 ,  G01N2030/3038 ,  G01N2030/3061 ,  G01N30/7253

摘要： Methods and apparatus for liquid sample introduction into chemical detectors that require the sample to be transformed from a flowing stream into either gaseous or particulate states. The effluent from either a process stream or a liquid chromatograph is nebulized by combined thermal and penumatic processes within an inner fused silicon capillary tube heated by conduction through a relatively conductive sheathing gas such as helium or hydrogen from a surrounding electrical resistance heated outer capillary tube composed of a pure metal having a comparatively high linear relationship between temperature and electrical resistance to provide a uniform conduction of heat energy to the inner tube to form a well-collimated, partially or completely desolvated aerosol, with the less volatile solute components of the sample stream remaining in the particulate state. An expansion chamber at atmospheric pressure or less pressure slows the sheathing gas which surrounds the solvent vapor and solute particles sufficiently to form a stream which carries the solute particles in a manner that they avoid impacting the walls of the expansion chamber. The gaseous components of the aerosol are then separated from the solvent-depleted solute particles using either cryotrapping or momentum separation. The enriched solute particles are vaporized, ionized, and/or detected by suitable gas-phase or particle detectors. The device is primarily an interface between the liquid chromatograph or process streams and the mass spectrometer.

摘要翻译： 将液体样品引入化学检测器的方法和设备，其需要将样品从流动物流转变为气态或微粒状态。 来自工艺流或液相色谱仪的流出物通过内部熔融硅毛细管中的组合的热和阴离子工艺雾化，所述内部熔融硅毛细管通过相对导电的护套气体例如氦气或氢气从由周围的电阻加热的外部毛细管组成的导热加热 具有在温度和电阻之间具有较高线性关系的纯金属，以向内管提供均匀的热能传导以形成准直的，部分或完全脱溶的气溶胶，其中样品流的挥发性较低的溶质成分 保持颗粒状态。 在大气压或更低压力下的膨胀室减慢包围溶剂蒸气的护套气体，并充分溶解颗粒以形成携带溶质颗粒的流，使其不会影响膨胀室的壁。 然后气溶胶的气态组分使用低温震动或动量分离与溶剂消耗的溶质颗粒分离。 富集的溶质颗粒被合适的气相或颗粒检测器蒸发，离子化和/或检测。 该装置主要是液相色谱仪或过程流与质谱仪之间的界面。

公开(公告)号：US20140349328A1

公开(公告)日：2014-11-27

申请号：US13901569

申请日：2013-05-24

申请人： James D. Buchner ,  Ross C. Willoughby

发明人： James D. Buchner ,  Ross C. Willoughby

IPC分类号： G01N1/20

CPC分类号： G01N1/20 ,  G01N1/10 ,  G01N1/14 ,  G01N1/16 ,  G01N2001/1037

摘要： The current invention describes in vivo and vitro (cultured) sampling technologies that allow direct temporal and spatial sampling from living ecosystems such as those associated with marine ecology. The optional use of parallel sampling methods, observatory design, provides for the ability to measure the response of individual organisms to a variety of both biotic and abiotic stresses. Sampling in small volumes and close proximity to living organisms has allowed direct measurement of various invertebrate and other aquatic species in marine ecosystems. These sampling techniques are intended to apply to any liquid based ecosystem in an attempt to minimize sampling as a dependent variable in measuring the chemical and biological behavior of the ecosystem. If is intended that this sampling technology be used to directly measure the chemical behavior of a wide variety of organisms; including, plants, animals, and micro-organisms (e.g. algae, plankton). These probes facilitate the direct measurement of metabolism, decomposition, pollution, and stress or stimuli from the local environment. A variety of sampling tips and probes have been developed for discrete and continuous sampling. A variety of sampling probe geometries, sizes, and sampling capabilities are disclosed that enable both contact and non-contact sampling of the chemical environment. The liquid sampling has been optimized for chemical analysis with liquid chromatography mass spectrometry. Fatty acid and lipid profiling have been demonstrated on a number of species from a cultured aquatic using these techniques.

摘要翻译： 本发明描述了体内和体外（培养）采样技术，其允许从诸如与海洋生态相关联的生物生态系统进行时间和空间的采样。 平行采样方法，天文台设计的可选使用提供了测量各种生物对各种生物和非生物胁迫的反应的能力。 小规模取样和靠近生物体的样品允许直接测量海洋生态系统中各种无脊椎动物和其他水生物种。 这些采样技术旨在适用于任何基于液体的生态系统，以尽量减少采样作为测量生态系统的化学和生物行为的因变量。 如果使用这种采样技术来直接测量各种生物体的化学行为; 包括植物，动物和微生物（例如藻类，浮游生物）。 这些探针有助于直接测量当地环境中的新陈代谢，分解，污染和压力或刺激。 已经开发了用于离散和连续采样的各种采样尖端和探针。 公开了各种采样探针几何形状，尺寸和采样能力，其能够实现化学环境的接触和非接触取样。 液体取样已通过液相色谱质谱法进行化学分析。 使用这些技术已经从培养的水生植物的许多物种上证明了脂肪酸和脂质谱。

公开(公告)号：US08723110B2

公开(公告)日：2014-05-13

申请号：US13218800

申请日：2011-08-26

申请人： Craig M. Whitehouse ,  Thomas P. White ,  Ross C. Willoughby ,  Edward William Sheehan

发明人： Craig M. Whitehouse ,  Thomas P. White ,  Ross C. Willoughby ,  Edward William Sheehan

IPC分类号： H01J49/00

CPC分类号： H01J49/165 ,  H01J49/0431 ,  H01J49/107 ,  H01J49/168 ,  H01J49/26

摘要： An apparatus for generating ions includes an Electrospray ionization source configured to provide a spray of charged droplets from a sample solution during operation of the apparatus; an atmospheric pressure chemical ionization (APCI) source including a corona discharge needle configured to produce a corona discharge that further ionizes the spray during operation of the apparatus; and a gas delivery system configured to deliver a gas flow to the corona discharge needle during operation of the apparatus, wherein the gas flow comprises a reagent ion gas which facilitates ionization of the spray by the corona discharge.

摘要翻译： 一种用于产生离子的装置包括：电喷雾离子化源，其构造成在装置运行期间提供来自样品溶液的带电液滴的喷雾; 包括电晕放电针的大气压化学电离源（APCI），其被配置为产生电晕放电，所述电晕放电在所述装置的操作期间进一步电离所述喷雾; 以及气体输送系统，其构造成在所述装置的操作期间将气流输送到所述电晕放电针，其中所述气流包括试剂离子气体，所述试剂离子气体有助于所述电晕放电引起所述喷雾的离子化。