公开(公告)号：US20060110833A1

公开(公告)日：2006-05-25

申请号：US11223456

申请日：2005-09-09

Applicant: George Agnes ,  Michael Bogan

Inventor： George Agnes ,  Michael Bogan

IPC: G01N33/00 ,  B01D59/44 ,  H01J49/00

CPC classification number: B01L3/0268 ,  B01L2200/0626 ,  B01L2400/0415 ,  G01N30/7233 ,  G01N30/728 ,  H01J49/0431 ,  H01J49/164

Abstract: This application relates to a method and apparatus for coupling an analyte supply, such as a biomolecule separator, to an electrodynamic droplet processor. In one embodiment the biomolecule separator is a capillary liquid chromatography column and the droplet processor includes an droplet generator and an electrodynamic balance. The biomolecule separator and the droplet processor may be fluidly coupled to provide a continuous supply of analyte for analysis. The droplets may be controllably ejected from the electrodynamic balance and deposited on a target substrate for use in detecting the analyte by mass spectrometry, such as MALDI time of flight mass spectrometry. Prior to deposition, each of the droplets is levitated in the electrodynamic balance for a period sufficient to enable evaporation of volatile solvents present in the droplet solution, thereby increasing the analyte concentration in the droplet. The solution may include a MALDI liquid matrix and the target substrate may be a MALDI plate. In one embodiment, the method involves depositing a succession of discrete droplets on the target substrate to form one or more microspots having a high density of analytes. The microspots are then irradiated and the ions produced are analyzed by mass spectrometry. The invention improves the sensitivity of analyte detection while consuming a comparatively small volume of test solution.

Abstract translation: 本申请涉及用于将分析物供应（例如生物分子分离器）耦合到电动液滴处理器的方法和装置。 在一个实施方案中，生物分子分离器是毛细管液相色谱柱，液滴处理器包括液滴发生器和电动余量。 生物分子分离器和液滴处理器可以流体耦合以提供用于分析的分析物的连续供应。 液滴可以可控地从电动余量喷出并沉积在靶基质上，用于通过质谱法（如MALDI飞行时间质谱法）检测分析物。 在沉积之前，每个液滴在电动余量中悬浮一段足以能够蒸发存在于液滴溶液中的挥发性溶剂，从而增加液滴中的分析物浓度。 溶液可以包括MALDI液体基质，靶基质可以是MALDI板。 在一个实施方案中，该方法包括在目标基底上沉积一系列离散液滴以形成具有高密度分析物的一个或多个微点。 然后照射微孢子，通过质谱法分析产生的离子。 本发明在消耗相对小体积的测试溶液的同时提高了分析物检测的灵敏度。

公开(公告)号：US20060263899A1

公开(公告)日：2006-11-23

申请号：US10546799

申请日：2004-02-24

Applicant: George Agnes

Inventor： George Agnes

IPC: G01N1/10 ,  G01N24/00

CPC classification number: H01J49/164 ,  G01N35/1011 ,  G01N35/1074 ,  G01N2035/1034 ,  H01J49/0009 ,  H01J49/161 ,  Y10T436/24 ,  Y10T436/25

Abstract: This application relates to a process for controllably placing two or more microspots on a target substrate in close proximity to one another. The microspots may then be simultaneously irradiated and the resulting ions detected by mass spectrometry, such as time of flight mass spectrometry. In one embodiment the size and spacing of the microspots on the substrate may be controlled by using an electrodynamic balance during the deposition step. The deposition procedure ensures that at least some of the microspots are spaced-apart on the substrate a distance less than the focused output of a single laser. Simultaneous irradiation of the adjacent microspots may cause desorption plumes of the microspots to interact in a gas phase, such as by ion-molecule reactions. The microspots may be configured to improve the ionization yield of the sample material in the gas phase and/or to increase the frequency of ion-molecule collisions in the gas phase. This allows for desorption of particular classes of compounds to be optimized independently of ionization. Different microspots could include different amounts or types of matrix compounds to enable simultaneously detection of compounds of varied physical and chemical properties within the same sample. One or more of the microspots may include calibrants or other additives for improving detecting accuracy or quantitation. Organized array of closely packed microspots may be created for use as standard reference materials or analyte detectors.

Abstract translation: 本申请涉及一种用于将两个或更多个微孔子可控地放置在彼此靠近的目标基底上的方法。 然后可以同时照射微孢子，并通过质谱法检测所得到的离子，例如飞行时间质谱。 在一个实施例中，可以通过在沉积步骤期间使用电动平衡来控制衬底上的微孔的尺寸和间隔。 沉积程序确保至少一些微孔在衬底上间隔开距离小于单个激光器的聚焦输出。 相邻微孢子的同时照射可导致微孢子的解吸羽流在气相中相互作用，例如通过离子 - 分子反应。 微滴可以被配置为改善气相中样品材料的离子化收率和/或增加气相中离子 - 分子碰撞的频率。 这允许特定类别的化合物的解吸，以独立于电离而被优化。 不同的微孔可以包括不同量的或类型的基质化合物，以便同时检测同一样品中不同物理和化学性质的化合物。 一个或多个微点可以包括用于提高检测精度或定量的校准剂或其它添加剂。 可以创建紧密堆积的微孔的组织阵列用作标准参考材料或分析物检测器。

公开(公告)号：US07785897B2

公开(公告)日：2010-08-31

申请号：US10399823

申请日：2001-10-23

Applicant: George Agnes ,  Xiao Feng ,  Michael Bogan

Inventor： George Agnes ,  Xiao Feng ,  Michael Bogan

IPC: G01N24/00

CPC classification number: H01J49/04 ,  H05H3/04 ,  Y10T436/24

Abstract: A method and apparatus for producing a discrete particle for subsequent analysis (such as mass spectrometry) or manipulation is disclosed. A discrete particle is generated by a particle generator. A net charge is induced onto the particle by an induction electrode. The particle is delivered to a levitation device where it is then electrodynamically levitated. If the particle is a droplet, desolvation will occur, leading to Coloumbic fissioning of the droplet into smaller droplets. The movement of the levitated droplet(s) can be manipulated by an electrode assembly. The droplet(s), and the charge thereon, can be delivered to a mass spectrometer in one aspect of the invention, providing an ion source for mass spectrometry without the detrimental space charge effects of electrospray ionization techniques. In another aspect of the invention, the levitated particle(s) may be controllably and precisely deposited onto a plate for subsequent analysis by matrix assisted laser desorption and ionization mass spectrometry.

Abstract translation: 公开了用于生产用于后续分析（例如质谱）或操纵的离散粒子的方法和装置。 离散粒子由粒子发生器产生。 通过感应电极在微粒上引起净电荷。 将颗粒输送到悬浮装置，然后电动悬浮。 如果颗粒是液滴，则会发生去溶剂化，导致液滴向水滴的翘起裂开。 悬浮液滴的运动可由电极组件操纵。 在本发明的一个方面，液滴和其上的电荷可被输送到质谱仪，提供用于质谱的离子源，而没有电喷雾电离技术的有害的空间电荷效应。 在本发明的另一方面，悬浮颗粒可以可控地和精确地沉积在板上，用于通过基质辅助激光解吸和电离质谱法进行后续分析。