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WO2003010794A2 - Dispositif de spectrometrie de masse - Google Patents

Dispositif de spectrometrie de masse Download PDF

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Publication number
WO2003010794A2
WO2003010794A2 PCT/EP2002/007993 EP0207993W WO03010794A2 WO 2003010794 A2 WO2003010794 A2 WO 2003010794A2 EP 0207993 W EP0207993 W EP 0207993W WO 03010794 A2 WO03010794 A2 WO 03010794A2
Authority
WO
WIPO (PCT)
Prior art keywords
mass spectrometry
ions
ion
analysis
deflection elements
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2002/007993
Other languages
German (de)
English (en)
Other versions
WO2003010794A3 (fr
Inventor
Wolf-Georg Forssmann
Harald John
Michael Walden
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
IPF Pharmaceuticals GmbH
Original Assignee
IPF Pharmaceuticals GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by IPF Pharmaceuticals GmbH filed Critical IPF Pharmaceuticals GmbH
Priority to AU2002321234A priority Critical patent/AU2002321234A1/en
Publication of WO2003010794A2 publication Critical patent/WO2003010794A2/fr
Publication of WO2003010794A3 publication Critical patent/WO2003010794A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/06—Electron- or ion-optical arrangements
    • H01J49/062—Ion guides
    • H01J49/065—Ion guides having stacked electrodes, e.g. ring stack, plate stack
    • H01J49/066—Ion funnels
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/161—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission using photoionisation, e.g. by laser
    • H01J49/164—Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI]

Definitions

  • the invention relates to a mass spectrometry device for mass spectrometry (MS) of ions.
  • mass spectrometry With the help of mass spectrometry it is possible to determine the m / z ratio, and thus the molar mass of element and molecular ions.
  • mass spectrometry methods for example for protein or peptide analysis, use inter alia the ionization techniques ESI (electrospray ' ionization) or MALDI (matrix-assisted laser desorption ionization).
  • a liquid that contains the analyte to be examined in ionized form is sprayed out of a capillary.
  • the ions are accelerated by an acceleration device, such as an electric field, in the direction of an analysis device, by means of which the m / z ratio or the analyte ions are determined.
  • the analysis can be carried out, for example, using a flight tube (time of flight “TOP”) or one or more quadrupoles in conjunction with a detector. Since the analysis device has a small inlet aperture and the spray mist has finely distributed, diverging droplets, only an extremely small part of the ions to be detected reaches the analysis device. In conventional analysis devices, only about 1% o of the ions present in the spray mist get into the analyzer. A quantitative mass spectrometry with in particular almost complete ion yield and detection is therefore not possible.
  • the analyte solution is mixed with a large excess of a matrix solution (e.g. ⁇ -cyanocinnamic acid) on a metal plate or the like. crystallized.
  • a matrix solution e.g. ⁇ -cyanocinnamic acid
  • the analysis device which is usually a flight tube, also has a small aperture, since there is a vacuum inside the analysis device. Since the movement or trajectory of the molecular ions released from the sample by the laser runs in the most varied of directions and thus large scattering of generated molecular ions occurs, only a small proportion of the generated molecular ions is fed to the analysis device in this method.
  • the object of the invention is to provide a mass spectrometry device in which the proportion of detectable analyte ions is increased.
  • Mass spectrometry of ions has an ion delivery device.
  • the ion delivery device is, for example, an ESI or a MALDI device.
  • the ion delivery device is one
  • Accelerator such as an electric field
  • the ions are accelerated by the acceleration device in the direction of an analysis device, such as a flight tube or one or more quadrupoles.
  • the analysis device is usually followed by a detection device for detecting the ions.
  • the Detection device can be connected to an evaluation device, which in particular comprises a PC.
  • an ion focusing device is connected upstream of the analysis device to increase the ion yield.
  • the ions are directed in the direction of the analysis device by the ion focusing device. This is preferably done by generating suitable electrical fields by means of which, for example at ESI, the analyte ions contained in the spray are focused or channeled in the direction of the analysis device.
  • a voltage is preferably present at the ion focusing device, so that the ion focusing device is electrically charged in such a way that the ions are directed in the direction of the analysis device. At least the ions of the ion focusing device, if this corresponds to the ions, repel the ions. Ions which, for example, do not move out of the spray in the direction of the analysis device or an aperture of the analysis device in the case of ESI are thus deflected in the direction of the analysis device.
  • the ion focusing device preferably has a circular electromagnetic field.
  • the ion focusing device is preferably designed such that it tapers in the direction of the analysis device.
  • the diameter or cross section of the circular electromagnetic field thus decreases from the ion delivery device in the direction of the analysis device. This results in an increasing focus or channeling of the analyte ions.
  • the direction and size of the electromagnetic field generated with the aid of the ion focusing device also make it possible, for example, to focus or deflect only ions of a certain mass or charge in such a way that they reach the analysis device. It is thus possible to achieve a sort of pre-sorting of the ions by adjusting the electromagnetic field.
  • the ion focusing device has a plurality of deflection elements. Different voltages can be applied to the deflection elements. This makes it possible to predetermine or influence the trajectory of the individual ions, so that the pre-sorting can be improved.
  • the deflection elements are preferably arranged essentially one behind the other in the direction of movement of the ions.
  • the deflection elements are thus arranged one behind the other in the direction of the analysis device, starting from the ion delivery device. It is particularly preferred here to provide self-contained deflection elements, the cross-section of which preferably decreases in the direction of the analysis device. In the case of annular deflection elements, which are particularly preferred, this means that the diameter of deflection elements arranged one behind the other or successive in the direction of movement of the ions is reduced.
  • the deflection elements are preferably connected to a control device by means of which the voltage applied to the individual deflection elements can be controlled individually or in groups. As a result, the strength and direction of the generated electromagnetic field or the generated electromagnetic fields can be varied in particular.
  • analyte ions such as organic compounds, proteins and peptides from body fluids, tissue extracts etc.
  • the device according to the invention the To evaluate the state of body or organ functions, the state of development and / or the state of human, animal or plant diseases or the function of organisms differentially and / or globally (proteomics and peptidomics).
  • a particularly reliable analysis can be carried out, for example, to analyze the state of the bodily functions of persons, to evaluate the differential state of normal development and / or to analyze disease-specific markers in order to make a reliable diagnosis in the course of To receive diseases or as part of an integrated health care (ICH integrated health care) to optimize therapeutic interventions in medicine.
  • ICH integrated health care integrated health care
  • the use of the device according to the invention also improves the implementation of new binding assays for special proteins, peptides or other organic substances which are present in defined analyte concentrations on MALDI targets and / or in solutions to be used for the ESI-MS.
  • the binding of covalently target-bound capture molecules on chips, such as specific antibodies, is quantitatively defined at MALDI, like the concentration of analytes in injectable solutions at ESI.
  • the analyte concentration can be evaluated in defined standardized dilution series.
  • Binding substances are preferably proteins which are covalently bound to the target, in particular monoclonal antibodies, which interact specifically with the analyte.
  • 1 is a schematic side view of the device according to the invention using an ESI device, the spray direction of which points in the direction of the analysis device
  • 2 shows a schematic side view of the device according to the invention using an ESI device, the spray direction of which is oriented perpendicular to the analysis device
  • Fig. 3 is a schematic side view of the device according to the invention using a MALDI device.
  • an analyte 12 is pressed out of a capillary 14.
  • the generation of the spray can be supported by a gas stream (inert gas, for example N 2 ).
  • a gas stream inert gas, for example N 2
  • the capillary 14 is used, if appropriate in conjunction with a delivery device, such as a pump, to deliver the analyte 12 as an ion delivery device, the analyte being delivered through an outlet opening 18.
  • the analyte ions present in the solution are distributed in the spray and are positively charged in the exemplary embodiment shown.
  • the ions are accelerated in an accelerating device 20 in the direction of an ion focusing device 22 adjoining the accelerating device 20 and an adjoining analysis device, only one aperture 24 being shown by the analysis device, to which the analysis device is then attached, for example in the form of a flight tube or one or more quadrupoles.
  • the ions are accelerated in the acceleration device 20 by generating an electric field.
  • the capillary 14 is connected to the positive pole of a current source 26 and thus serves as an anode.
  • a ring-shaped element in the illustrated embodiment, which is electrically conductive, is also connected to the power source and serves as a cathode.
  • the element forming the aperture 24 is switched as a cathode.
  • the ion focusing device provided between the acceleration device 20 and the analysis device points in the illustrated
  • Embodiment several annular deflection elements 28.
  • the ring-shaped deflection elements 28 are each connected to a power source via a control device.
  • a potential is therefore present at the individual deflection elements 28. In the exemplary embodiment shown, this is positive, so that the ions located within the ion focusing device are repelled. This causes the ions in the spray 10 to be centered or channeled onto the aperture 24.
  • Insulators 30 are provided between the individual deflection elements 28.
  • the ion focusing device 22 is essentially funnel-shaped due to the plurality of deflection elements 28 provided, which have a different diameter in an annular configuration. This can be a funnel designed in a stepped manner through the individual deflection elements 28.
  • the individual deflection elements 28 can be controlled differently so that ions can be accelerated and deflected in a targeted manner, for example depending on their mass or their charge. Appropriate switching of the individual deflection elements enables increasing acceleration and focusing as well as channeling of certain preselected ions.
  • electromagnetic fields can be created that change in high-frequency and / or voltage-adapted modulation. Precisely predictable exclusion criteria are hereby possible, so that essentially only certain selected ions get into the analysis device. According to the invention, a large number of these selected ions reach the analysis device, so that in addition to a qualitative one, a quantitative determination with an almost complete one Ion yield is possible. Particles deflected too little or too strongly by the application of the electromagnetic fields hit the deflection elements 28 or insulators 30 outside the aperture 24.
  • the cathode 31 of the acceleration device 20 is likewise designed in a ring shape corresponding to the deflection elements 28.
  • the cathode 31 is separated from the first deflection element 28 by an insulator 30 and is in direct contact with the ion focusing device 22.
  • the ion yield with the aid of the device according to the invention is extremely high, depending on the application it can be over 80%, in particular over 90%, it is possible with the device according to the invention to carry out a quantitative, highly sensitive and highly selective analysis which relates in particular to proteomics and Peptodomics with ESI or MALDI technology can be used, but can also be used in all other mass spectrometry techniques known to the person skilled in the art.
  • Another advantage of the device according to the invention is that the concentration detection limit is considerably improved compared to known devices.
  • an ESI device is also provided, but is rotated through 90 ° compared to the embodiment shown in FIG. 1, so that the spray direction of the ESI device is 90 ° to the direction of movement of the ions to be selected, ie of the positively charged particles in the illustrated embodiment is rotated.
  • the same or similar components have the same reference numerals as in the embodiment shown in FIG. 1.
  • the embodiment shown in FIG. 2 has the additional advantage that neutral substances, such as, for example, solvent molecules or negatively charged ions 32 cannot get into the ion focusing device 22 or the analysis device. This avoids disruptive influences caused by such ions or neutral substances.
  • neutral substances such as, for example, solvent molecules or negatively charged ions 32 cannot get into the ion focusing device 22 or the analysis device. This avoids disruptive influences caused by such ions or neutral substances.
  • the ions are provided with the aid of the MALDI method.
  • the ion focusing device 22 and the type of acceleration device 25 correspond in principle to that based on FIGS. 1 and 2 described facilities. These are therefore identified by the same reference symbols.
  • a sample that has crystallized out, for example, with matrix 36 is immobilized on a metal plate 34.
  • particles are detached from sample 36 and the matrix molecules are ionized.
  • the analyte ions generated by charge transfer from matrix ions to analyte molecules are in the
  • Accelerating device 20 accelerates and then focused or channeled onto the aperture 24 in the ion focusing device.
  • the device according to the invention is in particular for the analysis of markers, for the analysis of peptidomes, for the specific analysis of proteomes, for the analysis of disease-specific markers, for DPD evaluation (differential peptide display), for the discovery of new substances which are particularly relevant as drug targets Identification of markers, particularly at IHC (integrated health care), is suitable for identifying new substances and markers from animal and plant organisms.
  • the device according to the invention can also be integrated into any other mass spectrometric concept known to the person skilled in the art.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Engineering & Computer Science (AREA)
  • Plasma & Fusion (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Electron Tubes For Measurement (AREA)

Abstract

L'invention concerne un dispositif de spectrométrie de masse destiné à la spectrométrie de masse des ions. Le dispositif présente des moyens d'émission d'ions (14 ; 36, 38) constitués par un dispositif d'accélération (20) servant à l'accélération des ions en direction d'un dispositif d'analyse monté en aval. En vue d'augmenter le rendement ionique, l'invention est caractérisée en ce qu'il est prévu entre le dispositif d'accélération (20) et le dispositif d'analyse, un dispositif de focalisation des ions (22) qui dévie les ions en direction du dispositif d'analyse, en particulier en direction d'une ouverture de diaphragme (24).
PCT/EP2002/007993 2001-07-20 2002-07-18 Dispositif de spectrometrie de masse Ceased WO2003010794A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002321234A AU2002321234A1 (en) 2001-07-20 2002-07-18 Mass spectrometry device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10134652.2 2001-07-20
DE10134652 2001-07-20

Publications (2)

Publication Number Publication Date
WO2003010794A2 true WO2003010794A2 (fr) 2003-02-06
WO2003010794A3 WO2003010794A3 (fr) 2003-09-18

Family

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PCT/EP2002/007993 Ceased WO2003010794A2 (fr) 2001-07-20 2002-07-18 Dispositif de spectrometrie de masse

Country Status (2)

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AU (1) AU2002321234A1 (fr)
WO (1) WO2003010794A2 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6818889B1 (en) 2002-06-01 2004-11-16 Edward W. Sheehan Laminated lens for focusing ions from atmospheric pressure
WO2004110583A2 (fr) 2003-06-07 2004-12-23 Sheehan Edward W Reseaux d'ouvertures d'enrichissement ionique
US6943347B1 (en) 2002-10-18 2005-09-13 Ross Clark Willoughby Laminated tube for the transport of charged particles contained in a gaseous medium
US6949740B1 (en) 2002-09-13 2005-09-27 Edward William Sheehan Laminated lens for introducing gas-phase ions into the vacuum systems of mass spectrometers
US7081621B1 (en) 2004-11-15 2006-07-25 Ross Clark Willoughby Laminated lens for focusing ions from atmospheric pressure
GB2457708A (en) * 2008-02-22 2009-08-26 Microsaic Systems Ltd Ion source interface for a mass spectrometer
US7816646B1 (en) 2003-06-07 2010-10-19 Chem-Space Associates, Inc. Laser desorption ion source
US7960711B1 (en) 2007-01-22 2011-06-14 Chem-Space Associates, Inc. Field-free electrospray nebulizer
US8178833B2 (en) 2007-06-02 2012-05-15 Chem-Space Associates, Inc High-flow tube for sampling ions from an atmospheric pressure ion source

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7095019B1 (en) 2003-05-30 2006-08-22 Chem-Space Associates, Inc. Remote reagent chemical ionization source
US7138626B1 (en) 2005-05-05 2006-11-21 Eai Corporation Method and device for non-contact sampling and detection
US7568401B1 (en) 2005-06-20 2009-08-04 Science Applications International Corporation Sample tube holder
US7576322B2 (en) 2005-11-08 2009-08-18 Science Applications International Corporation Non-contact detector system with plasma ion source

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8404683D0 (en) * 1984-02-22 1984-03-28 Vg Instr Group Mass spectrometers
GB9110960D0 (en) * 1991-05-21 1991-07-10 Logicflit Limited Mass spectrometer
US5663560A (en) * 1993-09-20 1997-09-02 Hitachi, Ltd. Method and apparatus for mass analysis of solution sample
DE19635645C2 (de) * 1996-09-03 2000-12-28 Bruker Daltonik Gmbh Verfahren für die hochauflösende Spektrenaufnahme von Analytionen in einem linearen Flugzeitmassenspektrometer

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6818889B1 (en) 2002-06-01 2004-11-16 Edward W. Sheehan Laminated lens for focusing ions from atmospheric pressure
US6949740B1 (en) 2002-09-13 2005-09-27 Edward William Sheehan Laminated lens for introducing gas-phase ions into the vacuum systems of mass spectrometers
US6943347B1 (en) 2002-10-18 2005-09-13 Ross Clark Willoughby Laminated tube for the transport of charged particles contained in a gaseous medium
WO2004110583A2 (fr) 2003-06-07 2004-12-23 Sheehan Edward W Reseaux d'ouvertures d'enrichissement ionique
US7816646B1 (en) 2003-06-07 2010-10-19 Chem-Space Associates, Inc. Laser desorption ion source
US7081621B1 (en) 2004-11-15 2006-07-25 Ross Clark Willoughby Laminated lens for focusing ions from atmospheric pressure
US7960711B1 (en) 2007-01-22 2011-06-14 Chem-Space Associates, Inc. Field-free electrospray nebulizer
US8178833B2 (en) 2007-06-02 2012-05-15 Chem-Space Associates, Inc High-flow tube for sampling ions from an atmospheric pressure ion source
GB2457708A (en) * 2008-02-22 2009-08-26 Microsaic Systems Ltd Ion source interface for a mass spectrometer
GB2457708B (en) * 2008-02-22 2010-04-14 Microsaic Systems Ltd Mass spectrometer system
US8269164B2 (en) 2008-02-22 2012-09-18 Microsaic Systems Plc Mass spectrometer system

Also Published As

Publication number Publication date
AU2002321234A1 (en) 2003-02-17
WO2003010794A3 (fr) 2003-09-18

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