公开(公告)号：US06734421B2

公开(公告)日：2004-05-11

申请号：US10092026

申请日：2002-03-06

Applicant: Armin Holle ,  Jochen Franzen

Inventor： Armin Holle ,  Jochen Franzen

IPC: H01J4910

CPC classification number: H01J49/164 ,  H01J49/40

Abstract: The invention concerns a time-of-flight mass spectrometer for the analysis of a large number of samples on a sample carrier using laser desorption and associated analytical procedures. The invention uses a special beam focusing system for the pulsed laser beam in a time-of-flight mass spectrometer to generate a firm pattern of focal points, inserts a pattern of samples on a sample carrier into the pattern of focal points, and focuses the ions generated in the laser focal points by an ion-optical imaging system onto one or more ion detectors in such a way that the samples in the focus pattern are measured simultaneously or quasi-simultaneously. The pattern of pulsed focal points can be created simultaneously through spatially splitting the beam, or by a temporal sequence of different deflections towards the firm locations of the pattern.

Abstract translation: 本发明涉及飞行时间质谱仪，用于使用激光解吸和相关分析程序分析样品载体上的大量样品。 本发明在飞行时间质谱仪中使用用于脉冲激光束的特殊光束聚焦系统来产生牢固的焦点图案，将样品载体上的样本图案插入焦点图案，并将焦点 在激光焦点中通过离子光学成像系统在一个或多个离子检测器上产生的离子，使得聚焦图案中的样品同时或准同时测量。 脉冲焦点的图案可以通过空间分割光束或通过不同偏转的时间序列朝着图案的固定位置同时产生。

公开(公告)号：US06703608B2

公开(公告)日：2004-03-09

申请号：US09900478

申请日：2001-07-06

Applicant: Armin Holle ,  Jochen Franzen

Inventor： Armin Holle ,  Jochen Franzen

IPC: B01D5944

CPC classification number: H01J49/40

Abstract: The invention relates to methods and instruments for measuring daughter-ion spectra (also known as fragment-ion spectra or MS/MS spectra) in time-of-flight mass spectrometers, especially of those with reflectors, with post acceleration of selected parent and daughter ions by raising the potential of a “potential lift” during the passage of the ions. The invention consists of a potential lift device which is equipped with a power supply for velocity spread focusing by delayed acceleration of the ions after lifting the potential, thus making it possible to produce a focus of the velocity spreads of ions at the detector. In addition, it is possible to facilitate the adjustment of the mass spectrometer by dynamically shaping the acceleration pulse of the lift device to focus the velocity spreads of all ion masses in the spectrum on the detector.

Abstract translation: 本发明涉及用于测量飞行时间质谱仪中的子离子谱（也称为碎片离子谱或MS / MS谱）的方法和仪器，特别是具有反射镜的那些，具有所选择的母体和女儿的后加速度 离子通过在离子通过期间提高“电位升高”的电位。 本发明包括一个潜在的提升装置，其在提升电位之后配备有用于通过离子的延迟加速进行速度扩散聚焦的电源，从而可以产生离子在检测器处的​​速度扩散的焦点。 另外，通过动态地形成提升装置的加速度脉冲来使质谱仪的调节方便，可以将光谱中的所有离子质量的速度扩散集中在检测器上。

公开(公告)号：US06700117B2

公开(公告)日：2004-03-02

申请号：US09798250

申请日：2001-03-02

Applicant: Jochen Franzen

Inventor： Jochen Franzen

IPC: H01J4940

CPC classification number: H01J49/062 ,  H01J49/40

Abstract: The invention relates to a method and a device which reduces the phase space volume of ions in an ion beam in such a way that their injection into a downstream time-of-flight mass spectrometer optimizes the performance of that spectrometer. The performance of the time-of-flight mass spectrometer, i.e. the sensitivity of the spectrometer, the temporal resolution for fast concentration changes of the examined substances, and particularly the mass resolving power, relates critically to the transmission of the ions. The invention consists of completely decelerating the ions by means of collisions with a damping gas in an RF ion guide system, guiding them to the end of the ion guide system by active forward thrust, extracting them by a drawing lens system, and forming an ion beam with a low phase space volume. In particular, the ion guide system can take the form of a pair of wires coiled in a double helix and be surrounded by an envelope which is filled with the damping gas.

Abstract translation: 本发明涉及一种减少离子束中离子的相空间体积的方法和装置，使得它们注入下游飞行时间质谱仪的方式优化了该光谱仪的性能。 飞行时间质谱仪的性能，即光谱仪的灵敏度，检测物质的快速浓度变化的时间分辨率，特别是质量分辨能力，与离子的透射有关。发明包括 通过与RF离子导向系统中的阻尼气体的碰撞来完全减速离子，通过主动向前推力将它们引导到离子导向系统的端部，通过拉伸透镜系统将其提取，并形成离子束 低相位空间体积。 特别地，离子导向系统可以采用双螺旋线缠绕的一对线的形式，并被填充有阻尼气体的外壳包围。

公开(公告)号：US06696302B1

公开(公告)日：2004-02-24

申请号：US09711023

申请日：2000-11-09

Applicant: Jochen Franzen

Inventor： Jochen Franzen

IPC: G01N110

CPC classification number: B01L3/50853 ,  Y10T436/2575

Abstract: The invention relates to devices and methods for the contamination-free transfer of biological specimens, for example from supply containers, into the microtiter plates or comparable processing devices used to process the specimens. Such contamination-free transfer systems for DNA samples are known for microtiter plates with 96 cavities; they are based on covers for the cavities which can be removed by pipetting robots. The invention consists in covering the processing volumes of the microtiter plates together by a slidable blind which has one or more openings that can be slid over the processing volumes and through which the specimens can be pipetted. The space under the foil is swept by clean gas which emerges from the openings in order to prevent contamination by aerosols.

Abstract translation: 本发明涉及用于将生物样品例如从供应容器无菌转移到用于处理样品的微量滴定板或类似处理装置中的装置和方法。 用于DNA样品的这种无污染的转移系统对于具有96个空腔的微量滴定板是已知的; 它们基于可以通过移液机器人去除的空腔的盖。本发明包括通过可滑动的盲板覆盖微量滴定板的加工体积，该盲板具有可以在处理体积上滑动的一个或多个开口， 标本可以被吸取。 箔下面的空间被从开口出来的清洁气体扫过，以防止气溶胶污染。

公开(公告)号：US06428987B2

公开(公告)日：2002-08-06

申请号：US09735372

申请日：2000-12-12

Applicant: Jochen Franzen

Inventor： Jochen Franzen

IPC: B01J1000

CPC classification number: B01L3/502707 ,  B01L7/52 ,  B01L7/525 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0864 ,  B01L2300/0883 ,  B01L2300/1822 ,  B01L2300/1827 ,  B01L2300/1844 ,  B01L2400/0487 ,  B01L2400/084 ,  C12Q1/686 ,  Y10S977/775 ,  Y10S977/783 ,  Y10S977/788 ,  Y10S977/80 ,  Y10S977/924 ,  C12Q2565/629 ,  C12Q2527/125 ,  C12Q2527/113

Abstract: The invention concerns instruments for fast, selective replication of deoxyribonucleic acid (DNA) from biomaterial through polymerase chain reaction (PCR), working in individual duplication thermocycles. The invention consists of extremely brief cycle times of only a few seconds for the PCR reactions, generated, on the one hand, by reaction chambers for the reception of the reaction solution constructed of a pattern of fine capillaries in close proximity to heating and cooling elements in order to optimally accelerate the temperature setting in the reaction solution for the three temperature phases of the PCR duplication cycles and, on the other hand, by keeping the flow rates in the capillaries to a minimum during the amplification phase so that the polymerase reaction is not disturbed. The capillary pattern can be simply produced by means of microsystem technology.

Abstract translation: 本发明涉及通过聚合酶链反应（PCR）从生物材料快速，选择性复制脱氧核糖核酸（DNA）的工具，在单独的复制热循环中工作。 本发明由PCR反应的极短的循环时间仅为几秒钟，一方面由反应室产生，用于接收由加热和冷却元件附近的精细毛细管图案构成的反应溶液 为了最佳地加速PCR复制循环的三个温度阶段的反应溶液中的温度设定，另一方面，通过在扩增阶段将毛细管中的流速保持在最小值，使得聚合酶反应为 不打扰 毛细管图案可以简单地通过微系统技术生产。

公开(公告)号：USRE36906E

公开(公告)日：2000-10-10

申请号：US975058

申请日：1997-11-20

Applicant: Jochen Franzen ,  Yang Wang

Inventor： Jochen Franzen ,  Yang Wang

IPC: H01J49/42

CPC classification number: H01J49/424

Abstract: An ion trap is provided in which higher multipole field fractions can be switched on and off and, in addition, can be electrically tuned. Specifically, the electrodes of an ideally shaped ion trap are divided into rotationally symmetrical component electrodes positioned facing the interior of the ion trap on a hyperboloidal surface with rotationally symmetry.

Abstract translation: 提供了一种离子阱，其中可以打开和关闭更高的多极场分数，并且另外可以电调谐离子阱。 具体地说，理想形状的离子阱的电极被分成旋转对称的分量电极，其位于面向离子阱内部的旋转对称的双曲面上。

公开(公告)号：US5859433A

公开(公告)日：1999-01-12

申请号：US671854

申请日：1996-06-28

Applicant: Jochen Franzen

Inventor： Jochen Franzen

IPC: H01J49/42 ,  G01D59/44 ,  H01J49/00

CPC classification number: H01J49/424 ,  H01J49/0404 ,  H01J49/24

Abstract: The invention relates to an RF quadrupole ion trap mass spectrometer with ionization of the substance molecules outside the vacuum system.The invention consists of using only a single high-vacuum pump for generating the vacuum without any differential pump stages and generating the necessary pressure stages for operating the mass spectrometer by means of a sequence of openings with adjusted conductances. The necessarily very small inlet opening to the vacuum system is only able to transport very small quantities of ions of the analyzed substances in the gas stream. However, these quantities are adequate for operating the mass spectrometer because the ion trap used as mass spectrometer is capable of collecting and storing ions over relatively long periods of time.

Abstract translation: 本发明涉及一种具有离子真空系统外的物质分子的RF四极离子阱质谱仪。 本发明包括仅使用单个高真空泵来产生没有任何差分泵级的真空，并且通过具有调节的电导的一系列开口产生用于操作质谱仪的必要的压力级。 到真空系统的必要非常小的入口仅能够在气流中输送非常少量的分析物质的离子。 然而，这些量足以操作质谱仪，因为用作质谱仪的离子阱能够在相当长的时间内收集和存储离子。

公开(公告)号：US5811800A

公开(公告)日：1998-09-22

申请号：US713812

申请日：1996-09-13

Applicant: Jochen Franzen ,  Michael Schubert

Inventor： Jochen Franzen ,  Michael Schubert

IPC: H01J49/42 ,  B01D59/44 ,  H01J49/00

CPC classification number: H01J49/062 ,  H01J49/422

Abstract: The invention relates to methods and devices for the temporary storage of ions which are to be subjected to mass spectrometric analysis. Such temporary storage of ions in an RF multipole rod system for their analysis in an RF quadrupole ion trap is known from U.S. Pat. No. 5,179,278. The invention uses this known temporary storage for such ions which are produced in an ion source from substance peaks from chromatographic or electrophoretich separation devices, or from other devices which feed substances in form of short-lasting peaks. The temporary store thereby accepts sufficient ions of a substance peak for several successive mass spectrometric analyses, so that a mass spectrometric characterization of the substances, which may also require varying measurement methods, is made possible to the desired degree. Particularly ions from electrophoretically or chromatographically separated substance peaks should be able to be temporarily stored long enough until the mass spectrometric analyses have been concluded to the desired extent. Several temporary stores can collect the ions from several rapidly successive substance peaks. However, short-lasting substance peaks from laser desorptive or pyrolitic processes can also be thoroughly analyzed by means of temporary storage.

Abstract translation: 本发明涉及临时储存待进行质谱分析的离子的方法和装置。 在RF多极杆系统中这样的临时存储离子在RF四极杆离子阱中进行分析是已知的。 第5,179,278号。 本发明使用这种已知的临时储存用于离子源中产生的这些离子，所述离子源来自色谱或电泳分离装置的物质峰，或者从其它以短持久峰形式供给物质的装置。 临时存储器由此接受足够的物质峰离子以进行几次连续的质谱分析，使得可能需要改变测量方法的物质的质谱表征成为可能达到期望的程度。 特别是来自电泳或色谱分离的物质峰的离子应该能够被暂时保存足够长的时间，直到质谱分析已经达到预期的程度。 几个临时商店可以从几个快速连续的物质峰中收集离子。 然而，也可以通过临时储存来彻底地分析来自激光解吸或热解过程的短暂物质峰。

公开(公告)号：US5770860A

公开(公告)日：1998-06-23

申请号：US891362

申请日：1997-07-10

Applicant: Jochen Franzen

Inventor： Jochen Franzen

IPC: B01L3/00 ,  C40B60/14 ,  G01N35/00 ,  G01N35/10 ,  H01J49/04 ,  H01J49/00

CPC classification number: H01J49/0418 ,  B01L3/5085 ,  B01L3/50853 ,  H01J49/0413 ,  B01J2219/00317 ,  B01J2219/00364 ,  B01J2219/00659 ,  B01J2219/00702 ,  B01L2300/0893 ,  C40B60/14 ,  G01N2035/00237 ,  G01N2035/1037 ,  G01N35/1065 ,  G01N35/1072 ,  G01N35/1074

Abstract: A method for rapid loading of large sample supports with a very large number of analyte samples for mass spectrometric analysis using the ionization method of matrix-assisted desorption by laser bombardment (MALDI). The method consists of using microtiter plates already introduced in biochemistry and molecular genetics for parallel processing of a large number of dissolved samples and a multiple pipette unit for simultaneous transfer of sample solution quantities from all reaction wells on a microtiter plate to the sample support, the sample support having at least the same size. By repeated loading with samples from other microtiter plates, spaced between the samples already applied, a very high density of samples can be achieved. Some of these samples can be reserved for a mass spectrometric determination of the sample positioning on the sample support, and the positions of the other samples can then be interpolated.

Abstract translation: 使用通过激光轰击（MALDI）的基质辅助解吸电离方法快速装载大量样品载体的方法，其用大量分析物样品进行质谱分析。 该方法包括使用已经在生物化学和分子遗传学中引入的微量滴定板平行处理大量溶解的样品，以及多个移液管单元，用于将样品溶液量从微量滴定板上的所有反应孔同时转移到样品载体上， 样品支架具有至少相同的尺寸。 通过重复加载来自其他微量滴定板的样品，在已经施加的样品之间间隔开，可以实现非常高密度的样品。 这些样品中的一些可以保留用于样品支架上样品定位的质谱测定，然后可以插入其他样品的位置。

公开(公告)号：US5719392A

公开(公告)日：1998-02-17

申请号：US637199

申请日：1996-04-24

Applicant: Jochen Franzen

Inventor： Jochen Franzen

IPC: G01N27/64 ,  H01J49/40

CPC classification number: G01N27/622

Abstract: A method for measuring the mobility spectra of ions with ion mobility spectrometers (IMS). The method consists of impressing upon the essentially continuous ion flow of an IMS ion source, which comprises various ion types with various mobitities, a temporal switching signature with an ion admission of approximately 50% by using a very fast ion flow switch, whereby the signatures for the various ion types are displaced toward each other in different manners during the operating time due to the different velocities. From the quasi-continuously received ion current signal at the end of the path of the ion mobility spectrometer the composition of the ion types can be recovered according to mobility and intensity by decoding the switching signature. At the same time an improvement in resolution can be achieved by deconvolution of the diffusion profile. The method has a high duty cycle for the substance admitted and for the ions of ion flow.

Abstract translation: 用离子迁移光谱仪（IMS）测量离子的迁移谱的方法。 该方法包括通过使用非常快的离子流量开关，使IMS离子源的基本上连续的离子流（其包括具有各种动力学的各种离子类型）具有大约50％的离子入口的时间切换特征，由此签名 由于不同的速度，各种离子类型在操作时间内以不同的方式彼此移位。 从离子迁移谱仪路径末端的准连续接收离子电流信号可以通过对切换特征进行解码，根据迁移率和强度恢复离子类型的组成。 同时可以通过扩散分布的去卷积来实现分辨率的改善。 该方法对于允许的物质和离子流的离子具有高占空比。