WO2003010794A2 - Mass spectrometry device - Google Patents

Mass spectrometry device

Info

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
Grant status
Application
Patent type
Prior art keywords
mass spectrometry
device
characterized
ions
ionenfokussiereinrichtung
Prior art date
Application number
PCT/EP2002/007993
Other languages
German (de)
French (fr)
Other versions
WO2003010794A3 (en )
Inventor
Wolf-Georg Forssmann
Harald John
Michael Walden
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

Links

Classifications

    • HELECTRICITY
    • H01BASIC ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/02Details
    • H01J49/04Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • HELECTRICITY
    • H01BASIC ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/02Details
    • H01J49/06Electron- or ion-optical arrangements
    • H01J49/062Ion guides
    • H01J49/065Ion guides having stacked electrodes, e.g. ring stack, plate stack
    • H01J49/066Ion funnels
    • HELECTRICITY
    • H01BASIC ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/02Details
    • H01J49/10Ion sources; Ion guns
    • H01J49/16Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/161Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission using photoionisation, e.g. by laser
    • H01J49/164Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI]

Abstract

The invention relates to a mass spectrometry device for the mass spectrometry of ions. The device comprises an ion emitting device (14; 36, 38). An accelerator device (20) is arranged after the ion emitting device to accelerate the ions in the direction of an analytical unit. According to the invention, the ion yield may be increased by the arrangement of an ion-focussing device (22) between the accelerating device (20) and the analytical device, which deflects the ions in the direction of the analytical unit and in particular in the direction of a diaphragm opening (24).

Description

Mass spectrometry device

The invention relates to a mass spectrometry apparatus for mass spectrometry (MS) of ions.

With the help of mass spectrometry is a determination of the m / z ratio, and thus the molecular weight of elemental and molecular ions possible. In known mass spectrometry method, for example, for protein or peptide analysis, including the ionization ESI (electro spray 'ionization) or MALDI be used (matrix-assisted laser desorption ionization).

In the ESI-technology is a liquid which contains the analyte to be tested in an ionized form, is sprayed from a capillary. The ions are by an acceleration device, such as an electric field, accelerated in the direction of an analysis device by which the determination of m / z ratio or the analyte. The analysis can be done for example by means of an air tube (Time of Flight "TOP) or one or more quadrupoles in conjunction with a detector. Since the analysis device has a small entrance aperture and the spray finely divided, comprises apart diverging droplets, enters only an extremely small part of the ions to be detected in the analysis means. In conventional analysis means only about 1% reaches the o present in the spray ions into the analyzer. A quantitative mass spectrometry with particular almost complete ion yield and detection is not possible.

In MALDI technology, the analyte solution with a large excess of a matrix solution (eg, α-cyanocinnamic acid) or the like is on a metal plate. crystallized. Using a pulsed laser beam usually individual molecules of the sample are desorbed and ionized by the matrix ions. These molecular ions are again accelerated by an electric field towards an analysis device. The analysis device, which is usually is a flight tube, also has a small aperture, as in the analysis means there is a vacuum. Since the movement or flight path of the out of the sample dissolved by the laser molecular ions extending in different directions, and thus a large scattering molecule ions produced occurs, only a small proportion of the molecular ions produced by the analyzing means is also supplied with this method.

The object of the invention is to provide a mass spectrometry device in which the proportion of the detectable analyte ions is increased.

The object is achieved according to the invention by the features of claim 1.

The mass spectrometry apparatus of the invention for

Mass spectrometry of ions has an ion dispenser. In the ion discharge means is, for example, be an ESI or MALDI facility. The ion discharge device is a

Acceleration means such as an electric field downstream. By the acceleration device, the ions towards an analysis device will, as a flight tube or one or more quadrupoles accelerated. The analysis means includes usually to a detection device for detection of the ions. The detection device may be connected to an evaluation device which includes in particular a PC. To increase the ion yield accordance with the invention of the analyzer a Ionenfokussiereinrichtung precedes. By Ionenfokussiereinrichtung the ions are directed toward the analyzing means. This is preferably done by generating appropriate electric fields through which, for example, at ESI • the analyte contained in the spray to be focused in the direction of the analysis device or channeled. In particular, in analyzers that have an aperture, which points in the direction of the Ionenfokussiereinrichtung, thus occurs steering of the individual ions in the direction of the aperture. This makes it possible to increase the number of detectable ions significantly. With the inventive device it is thus possible to carry out not only qualitative assessments, but also quantitative ratings high, nearly complete ion yield.

Preferably, at the Ionenfokussiereinrichtung to a voltage such that the electrically charged Ionenfokussiereinrichtung is such that the ions are directed toward the analyzing means. At least a repulsion of the ions is performed by the charge of the Ionenfokussiereinrichtung, provided that corresponds to the charge of the ions. Ions that do not move, for example, at ESI from the spray in the direction of the analysis device or an aperture of the analyzer, are thus deflected in the direction of the analysis device. Here, preferably, the Ionenfokussiereinrichtung on a circular electromagnetic field.

Preferably, the Ionenfokussiereinrichtung is formed such that it tapers in the direction of the analyzing means. The diameter or the cross section of the circular electromagnetic field thus decreases from the ion discharge means in the direction of the analyzing means. This has an ever stronger focus and channeling the analyte result. By the direction and magnitude of the electromagnetic field generated by means of the Ionenfokussiereinrichtung it is also possible to focus, for example, only ions of certain mass or charge and deflect such that they reach to the analysis device. It is thus possible, by adjusting the electromagnetic field, to achieve a kind of pre-sorting of the ions.

In a particularly preferred embodiment, the Ionenfokussiereinrichtung has a plurality of deflecting elements. At the deflection different voltage can be applied. Thereby predetermining or affect the trajectory of each ion is possible, so that the sorting can be enhanced. The deflection elements are preferably arranged in the direction of movement of the ions in substantially a row. The deflection elements are thus, starting from the ion discharge means, arranged in the direction of the analysis device after the other. It is particularly preferred in this case to provide deflectors closed in itself, whose cross-section is preferably reduced toward the analyzing means. This means at annular baffles, which are especially preferred that the diameter of successively arranged or decreased in the direction of movement of the ions of consecutive deflecting members.

Preferably, the deflecting elements are connected to a control device, can be controlled in groups by the individually applied to each deflection voltage or. In this way, especially the strength and direction of the electromagnetic field generated or the generated electromagnetic fields can be varied.

With the inventive device is thus a quantitative analysis and quality of analyte, such as organic compounds, proteins and peptides from body fluids, tissue extracts, etc., are possible. In particular, it is possible with the inventive device, the state of body or organ functions, the development of state and / or the state of human, animal or plant diseases or the function of organisms differential and / or globally to evaluate (proteomics and peptidomics). By using the device of the invention a particularly reliable analysis can be performed to analyze for example the condition of the body functions of individuals to assess the differential state of normal development and / or to analyze disease-specific markers to a reliable diagnosis in the course of diseases or as part of an integrated health care (ICH integrated healthcare) to obtain for optimizing therapeutic intervention in medicine.

Surprisingly, it improves the use of the device according to the invention and the implementation of new binding assays for specific proteins, peptides or other organic substances that are present in defined analyte concentrations on MALDI-targets and / or in the ESI-MS to be used solutions. The binding of capture molecules covalently bound to target chips as specific antibodies in MALDI is quantitatively defined as the concentration of analyte in the injectable solutions in the ESI. The analyte concentration can be measured in defined standardized dilution series. Bondable substances are preferably proteins that are covalently bound to the target, in particular monoclonal antibodies, that specifically interact with the analyte.

The invention will be explained by means of preferred embodiments with reference to the accompanying drawings. Show it:

Fig. 1 is a schematic side view of the device of the invention using an ESI device whose spraying direction pointing in the direction of the analyzer, Fig. 2 is a schematic side view of the device of the invention using an ESI device whose spraying direction is oriented perpendicular to the analysis device, and

Fig. 3 is a schematic side view of the device of the invention using a MALDI device.

In order to produce a spray 10, an analyte is forced out of a capillary 14 12th At higher flow rates, the generation of the spray can be supported by a gas stream (inert gas, eg N 2). Here, when pushing of the analyte 12, first a so-called Taylor cone 16, which then expands into the spray 10 is formed. The capillary 14 is in the illustrated embodiment (Fig. 1), optionally in conjunction with a conveyor, such as a pump, for conveying the analyte 12 as the ion discharge means, wherein the analyte is delivered through an outlet port 18th Present in the solution analyte ions are distributed in the spray and are positively charged in the illustrated embodiment.

The ions are in an acceleration device 20 in the direction of an adjoining the acceleration device 20 Ionenfokussiereinrichtung 22 and an accelerated thereto subsequent analysis means, being shown by the analysis device only an aperture 24, to which then the analysis device, for example in the form of a flight tube or one or more quadrupoles, is connected. The acceleration of the ions takes place in the accelerating device 20 by generating an electric field. To this end, the capillary 14 is connected to the positive pole of a current source 26 and thus serves as an anode. A toroidally-shaped in the illustrated embodiment element which is electrically conductive, is also connected to the power source and serving as a cathode. In the conventional mass spectrometry device that is connected in the aperture 24 forming member as a cathode. By the existing between anode and cathode potential difference to accelerate the ions in Fig. 1 is effected from left to right.

The provided between the acceleration device 20 and the analyzing means comprises in the illustrated Ionenfokussiereinrichtung

Embodiment, a plurality of annular baffle members 28. The ring-shaped deflectors 28 are each connected via a controller to a power source. Thus, a potential is in each case at the individual deflecting elements 28th In the illustrated embodiment this is positive, so that the ions located within the Ionenfokussiereinrichtung are repelled. This provides a centering or channeling of the ions takes place in the spray 10 to the aperture 24. Between the individual baffles 28 are insulators 30 are provided.

The Ionenfokussiereinrichtung 22 is substantially funnel-shaped due to the provided plurality of deflectors 28 which have an annular configuration with different diameters. This may be a step-shaped by the individual baffle members 28 funnel.

The individual deflecting elements 28 may be controlled differently, so that a targeted acceleration and deflection of ions, for example, depending on its composition or its charge, can take place. By an appropriate connection of the individual deflecting an increasing acceleration and focusing, as well as channeling certain preselected ions is possible. To this end, electromagnetic fields can be created that change in high-frequency and / or voltage adapted modulation. Thereby accurately predictable exclusion criteria are possible, so that essentially only certain selected ions enter the analyzer. passes from these selected ions According to the invention a large number in the analysis device, so that is possible in addition to a qualitative, quantitative determination with nearly complete ion yield. From the conditioning of electromagnetic fields too low or too strongly deflected particles strike outside of the aperture 24 on the deflector 28 and insulators 30th

The cathode 31 of the acceleration device 20 is formed the baffles 28 in the illustrated embodiment also annular accordingly. The cathode 31 is separated from the first deflection element 28 by an insulator 30 and lies directly on the Ionenfokussiereinrichtung 22nd

Since the ion yield is extremely high with the help of the device according to the invention, depending on the application over 80%, may be in particular over 90%, it is possible with the inventive apparatus to carry out a quantitative, highly sensitive and highly selective analysis, in particular to the proteomics and can be applied Peptodomik with ESI or MALDI technique, but can get known in all other mass spectrometry techniques to the expert used. Another advantage of the device according to the invention is that the concentration limit of detection over known devices is significantly improved.

In the illustrated in Fig. 2 embodiment, an ESI-device is also provided which is, however, rotated with respect to the embodiment shown in Fig. 1, by 90 ° so that the spray direction of the ESI means by 90 ° to the direction of movement of the to be selected ions, is rotated ie, the positively charged particles in the illustrated embodiment. In the illustrated in Fig. 2 embodiment, the same or similar components have the same reference numerals as that in embodiment of FIG.. 1

The embodiment shown in Fig. 2 has the additional advantage that neutral substances such as solvent molecules or negative ions 32 can not reach the Ionenfokussiereinrichtung 22 or the analysis device. In this way, caused by such ions or neutral substances disturbing influences are avoided.

In the illustrated in Fig. 3 embodiment, the provision of the ions using the MALDI method is carried out. The Ionenfokussiereinrichtung 22 and the type of accelerator 25 correspond in principle the reference to FIGS. 1 and 2 described devices. These are therefore denoted by the same reference numerals.

In the MALDI method, a sample with, for example, crystallized matrix is ​​immobilized on a metal plate 36 34th By a in Fig. 3 by the arrow 38 shown Laser particles are dissolved out from the sample 36 and ionizes the matrix molecules. The analyte ions generated by charge transfer from matrix ions to analyte molecules are in the

accelerated accelerator 20 and subsequently focused onto the aperture 24 in the Ionenfokussiereinrichtung or channeled.

The inventive apparatus is particularly for the analysis of markers for the analysis of peptide omen for the specific analysis of proteomes, for the analysis of disease-specific markers, for DPD rating (differential peptide display), to the discovery of new compounds which are particularly relevant as drug targets, for identification of markers, especially in the IHC (integrated healthcare), suitable for identifying new substances and markers from animal and plant organisms. The device can be integrated in principle and in any other, known in the art mass spectrometric approach.

Claims

1. Mass Spectrometry apparatus for mass spectrometry of ions with
an ion discharge means (14; 36,38) and
one of the ion emission means (14; 36,38) downstream of the acceleration means (20) for accelerating the ions towards an analysis device,
marked by
an upstream of the analysis means Ionenfokussiereinrichtung (22) that directs the ions toward the analyzing means.
2. mass spectrometry apparatus according to claim 1, characterized in that the Ionenfokussiereinrichtung (22) is designed such that the ions towards an aperture (24) of the analysis device directs.
3. Mass spectrometry apparatus according to claim 1 or 2, characterized in that the Ionenfokussiereinrichtung (22) between the acceleration device (20) and the analysis means is arranged.
4. mass spectrometry device of any one of claims 1-3, characterized in that the Ionenfokussiereinrichtung (22) generates an electromagnetic field through which the to be detected charged ions are directed toward the analyzing means.
5. mass spectrometry apparatus according to claim 4, characterized ■, in that the charge of the Ionenfokussiereinrichtung
Ion charge corresponds. ,
6. mass spectrometry device of any one of claims 1-5, characterized in that the Ionenfokussiereinrichtung (22) is tapered in the direction of the analyzing means.
7. mass spectrometry device of any one of claims 1-6, characterized in that the Ionenfokussiereinrichtung (22) is substantially funnel-shaped.
8. mass spectrometry device of any one of claims 1-7, characterized in that the Ionenfokussiereinrichtung (22) having a plurality of deflection elements (28) can be applied to the preferably different voltage.
9. mass spectrometry apparatus according to claim 8, characterized in that the deflection members (28) are arranged in the direction of movement of the ions in substantially a row.
10. mass spectrometry apparatus according to claim 8 or 9, characterized in that the deflection members (28) closed in themselves, are preferably annular.
11. mass spectrometry device of any one of claims 7-10, characterized in that the cross section of successive deflector elements (28) is reduced ϊn the direction of the analysis device.
12. mass spectrometry device of any one of claims 8-11, characterized in that between the deflection elements (28), insulators (30) are arranged.
13. mass spectrometry device of any one of claims 8-12, characterized in that the deflection members (28) are connected to a control means for controlling the applied voltage.
14. mass spectrometry device of any one of claims 1-13, characterized in that the acceleration device (20) comprises an acceleration element (31) which is opposite to the ions to be selected loaded.
15-mass spectrometry device according to claim 14, characterized in that the accelerator member (31) corresponding to a deflection member (28) is formed.
16-mass spectrometry apparatus of claim 14 or 15, characterized in that the accelerator member (31) immediately adjacent to the Ionenfokussiereinrichtung (22).
PCT/EP2002/007993 2001-07-20 2002-07-18 Mass spectrometry device WO2003010794A3 (en)

Priority Applications (2)

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

Publications (2)

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

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Family Applications (1)

Application Number Title Priority Date Filing Date
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Country Status (1)

Country Link
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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 (en) 2003-06-07 2004-12-23 Sheehan Edward W Ion enrichment aperture arrays
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

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4647772A (en) * 1984-02-22 1987-03-03 Vg Instruments Group Limited Mass spectrometers
US5426301A (en) * 1991-05-21 1995-06-20 Turner; Patrick Off-axis interface for a mass spectrometer
US5663560A (en) * 1993-09-20 1997-09-02 Hitachi, Ltd. Method and apparatus for mass analysis of solution sample
US5898173A (en) * 1996-09-03 1999-04-27 Bruker Daltonik Gmbh High resolution ion detection for linear time-of-flight mass spectrometers

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4647772A (en) * 1984-02-22 1987-03-03 Vg Instruments Group Limited Mass spectrometers
US5426301A (en) * 1991-05-21 1995-06-20 Turner; Patrick Off-axis interface for a mass spectrometer
US5663560A (en) * 1993-09-20 1997-09-02 Hitachi, Ltd. Method and apparatus for mass analysis of solution sample
US5898173A (en) * 1996-09-03 1999-04-27 Bruker Daltonik Gmbh High resolution ion detection for linear time-of-flight mass spectrometers

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 (en) 2003-06-07 2004-12-23 Sheehan Edward W Ion enrichment aperture arrays
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

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