DE102015121830A1 - Broadband MR-TOF mass spectrometer - Google Patents

Abstract

The invention relates to a modified for broadband mass spectrometry MR ToF mass spectrometer. The mass spectrometer according to the invention comprises: a first module with an ion source and a multi-reflection time-of-flight unit (MR-ToF unit); and - a second module following the first module, having a magnetic sector field and a downstream location and time resolution detector.

Description

The invention relates to a modified for broadband mass spectrometry MR ToF mass spectrometer.

Technological background

In mass spectroscopy, ions are separated and registered according to their mass / charge ratio (m / z). The registration of the separated ions can be carried out electrically as ion current and the devices used are referred to as a mass spectrometer. A mass spectrometer consists in principle of three parts: a device for generating ions (ion source), a separation device (analyzer) and finally the detector (for example a Faraday cup or a secondary electron multiplier) for registering the ions. In addition to the necessary electronics, the accessories include a data processing system and pumps for the required vacuum.

Mass-specific separation systems are based on different principles. Particularly important for the present invention are two separation systems, namely (i) time-of-flight MS (ToF-MS) and (ii) sector-field mass spectrometers.

In ToF mass spectrometers, the ions generated in an ion source are accelerated by a surge and distinguished only by their mass-dependent time of flight on the route between the ion source and the detector. The mass range accessible in this method is theoretically unlimited and only dependent on the length of the flight path and the resulting flight time. The devices are characterized by a high recording speed, so that they can serve, for example, for the investigation of fast-running reactions. Furthermore, detection sensitivity is usually high, and even single ions can be detected. The disadvantage, however, is the only moderate resolution of this type of device.

Multi-reflection time-of-flight mass spectrometers (MR-ToF) consist of two ion mirrors, between which the ions to be examined are reflected back and forth. Thus, the flight path becomes many times (up to hundreds or thousands) of the physical length, i. of the ion mirror distance, extended. This increases the achievable resolution and the mass accuracy by similar orders of magnitude. The method has for the broad analytical application the disadvantage that in each measurement only a small mass cut is clearly accessible. For larger mass ranges, the different ion species "fly around" so that time-of-flight signals can no longer be unambiguously assigned without the need for systematically varying the number of cycles of ions in the device, so these devices are currently unimportant for larger mass applications.

In sector field mass spectrographs, the ions are deflected in static magnetic fields and therefore arrive at different points of the detector. This used to consist of photographic plates that were developed after irradiation in mass spectrographs. Meanwhile, electronic detectors can be used. If a suitable electrostatic field is applied between the acceleration section and the magnetic field, a so-called double-focusing mass spectrometer is obtained in which both directional focusing and energy focusing of ions of the same m / z ratio occur at one point of the detector. Knowing the energy and the momentum then the mass-to-charge ratio of the ions can be determined. This device type has a large mass range, but only a low resolution. Over the decades, high-resolution sector magnet devices have also been developed. However, these developments, in which no location-sensitive detector is used, but the ions are guided on narrow limit set paths, limited to very small mass ranges, or it takes a long time until a larger mass range can be analyzed. In addition, these devices are relatively large (and thus practically not portable) and costly, so that they are now almost completely disappeared from practical use.

Further, ion trap mass spectrometers such as Fourier Transform Ion Cyclotron Mass Spectrometer (FT-ICR) or Orbitrap Mass Spectrometer are known.

An FT-ICR mass spectrometer uses the ion frequency of cyclotron motion in magnetic fields for mass analysis. It is characterized by extremely high resolution at low masses and requires an ultra-high vacuum. At higher masses, the resolution decreases and the sensitivity remains good. However, the FT-ICR method generally involves the use of superconducting magnets for heavy ions, which means a considerable outlay.

In the Orbitrap ion trap there is a central, spindle-shaped electrode. The ions are shot into the orbitrap radially to this electrode and move around the central electrode due to the electrostatic attraction on orbits. Because the ions are not injected in the middle of the chamber, but decentrally At the same time, they swing along the axis of the central electrode. This ion oscillation generates signals in detector plates, which are converted by Fourier transformation into the corresponding frequencies, from which the m / q ratios follow. The principle is therefore similar to the FT-ICR, but works with an electrostatic field instead of a magnetic field. One limitation of these devices is that individual ions can only be detected at high charge states.

Summary of the invention

• – ein erstes Modul mit einer Ionenquelle und einer Multireflektions-Flugzeit-Einheit (MR-ToF-Einheit); und
• – ein sich dem ersten Modul anschließendes zweites Modul mit einem magnetischen Sektorfeld und einem nachgeordnetem orts- und zeitauflösenden Detektor.

One or more of the problems of the prior art can be solved or at least mitigated by means of the mass spectrometer according to the invention. The mass spectrometer according to the invention comprises:

• A first module with an ion source and a multi-reflection time-of-flight unit (MR-ToF unit); and
• - A subsequent to the first module second module with a magnetic sector field and a downstream location and time-resolved detector.

The invention is based on the finding that an MR-ToF analyzer can be combined with a downstream magnetic sector field and the ions can be detected with a location-sensitive time-of-flight detector. By using the magnetic sector field and the position sensitive detector, a mass spectrum of low resolution is obtained. By additionally using the time-of-flight information, however, the high resolution known from multireflection time-of-flight mass spectrometry results at the same time. The combination mentioned achieves this high resolution over a large mass range.

Alternatively, the core of the invention can also be described as follows: In the method also referred to here as broadband MR-ToF mass spectrometry, the high-resolution time-of-flight spectrum, which initially exists only as a superimposition of the spectra of many different mass ranges, is unfolded by the magnetic sector field spatially fanning out the mass areas and directing them to the appropriate locations of the location-sensitive detector.

Accordingly, the invention extends a conventional MR-ToF mass spectrometer such that broadband mass spectrometry can thus be operated and the device thus becomes interesting for analytical questions as well. The broadband MR-ToF mass spectrometer of the present invention can provide high mass resolution, mass accuracy analytical information over a wide mass range. Potential users include research institutions in science and industry, for example in the biological, medical and pharmaceutical fields. In addition, such devices could be used, for example, in the monitoring of biomedical and pharmaceutical production processes, petroleum studies or environmental analysis.

In comparison to FT-ICR or Orbitrap devices, the expected operating and acquisition costs of the mass spectrometer according to the invention are substantially lower. In addition, the sensitivity should at least be improved compared to Orbitrap devices, since single singly charged ions can be detected, while in the Orbitrap succeed only at high charge states.

The ionization of the test material takes place in a high vacuum in the ion source. A variety of ionization techniques have been developed, which are generally also useful for the purposes of the invention. For ionization in the gas phase, for example, electron impact ionization (EI), chemical ionization (CI) or ionization by a plasma (ICP) can be used. With liquids one can use among other things electrospray ionization (ESI). For solids, desorption methods such as laser desorption (LD, MALDI), desorption by atomic primary ions or cluster ions (SIMS) and field desorption (FD) are suitable.

According to a preferred embodiment, in particular insofar as the ion source is not already pulsed by itself, the first module comprises an ion pulse (or Buncher), which is arranged between the ion source and the MR-ToF unit. With the ion pulse, for example, a section of the primary ion beam can be accelerated into the flight path at an angle to the previous beam direction. If a continuous ion source is used, the ion pulse is preferably an ion trap. Particularly preferred in this constellation, the ion trap is a radio frequency (RF) ion trap, in particular a linear radio frequency (RF) ion trap.

In an ion trap, ions are held in place by means of electric and / or magnetic fields. Depending on the type and strength of the applied fields you can selectively store ions of a certain mass range. Alternatively, one can keep all ions in the trap in stock and forward by changing the fields all ions or those of a certain mass. The storage of the ions takes place in vacuum and without contact to a surface. There are different versions of the ion trap, for example the Paul trap and the Penning trap. In the Paul trap, a time-varying electric field is used to hold ions. If this field has the shape of a quadrupole, the trap is also called a quadrupole trap. In the case of the Penning trap, a combination of time-constant electric field and time-constant magnetic field leads to storage of the ions. The Paul trap has an alternating voltage in the radio frequency range at the end cap and ring electrodes. With proper tension, the trajectories of the masses become unstable, and only the ions of exactly matching m / z ratio remain trapped so that ion selection can occur.

According to a further preferred embodiment, the first module comprises a potentiallift, which is arranged between the ion source and the MR ToF unit or, if an ion pulse is present, is located between the ion pulse and the MR ToF unit. The ion-pulser is usually designed as a tube, which is switched to an appropriate new potential during the ion passage, in order to adjust the ion energy for the subsequent MR-ToF unit.

The MR-ToF unit can be designed in a conventional way and comprises at least two ion mirrors, between which the ions to be examined are reflected back and forth. Preferably, the MR-ToF unit also includes an integrated potentiallift (in-trap potentiallift). Alternatively, it is also possible to work without the potentiallift between the ion mirrors. In that case, however, the potentials of the ion mirrors must be switched even during the input and output of the ions.

A further preferred embodiment provides that the MR-ToF unit is followed by a further ion mirror (reflectron) for additional time focusing of the ion pulses. The additional ion mirror is located between the MR-ToF unit and the second module. With the optional integrated potentiallift of the MR-ToF unit you can achieve the time focusing for a certain number of revolutions. This is usually sufficient for the operation of narrow mass ranges. For broadband operation, where the ions will have very different numbers of cycles depending on the mass, it may be advantageous to carry out the focusing separately, since this is achieved for all types of ions.

After the MR-ToF unit, the ion beam is directed into the second module with a magnetic sector field and a downstream location and time resolution detector. In this case, the second module preferably comprises an electric sector field, which is arranged between the MR-ToF unit and the magnetic sector field. The second module is therefore constructed like a double-focusing mass spectrometer. In this case, the electrical sector field and the magnetic sector field are preferably arranged in Mattauch-Herzog geometry.

The location-sensitive detector is used to detect the previously separated ions. As a detector, for example, microchannel plates (MCP), in which the signal recording takes place with a corresponding anode arrangement ("delay-line") are used.

Further preferred embodiments of the invention will become apparent from the dependent claims and the description below.

Brief description of the figures

The invention will be explained in more detail with reference to an embodiment and an accompanying drawing. The only figure shows:

1 a schematic diagram illustrating the construction of an embodiment of the broadband MR-ToF mass spectrometer according to the invention.

Detailed description of the invention

Of the 1 is a schematic diagram illustrating the construction of an embodiment of the broadband MR-ToF mass spectrometer according to the invention 10 refer to. The mass spectrometer 10 is in two modules 20 . 50 divided. The first module 20 This corresponds largely to the construction of a conventional MR-ToF mass spectrometer and the second module directly connected thereto 50 in principle a mass spectrometer with magnetic sector field.

With an ion source 22 will be in the first module 20 first an ion beam 24 generated. The ion source 22 may be designed to generate a pulsed or continuous ion beam. According to the present embodiment, the ionization is carried out continuously, wherein the respective ionization method can be adapted to the examination material.

Subsequently, the ion beam passes through 24 an ionic pulser 26 , its entrance electrode 28 , Exit electrode 30 and multipole rods 32 are shown. The ionic pulser 26 is designed here as a linear high-frequency ion trap.

The ion pulser 26 downstream is a potentiallift 34 , which includes a tube, which is switched to an appropriate new potential during the ion passage, so as the ion energy for the then following MR ToF unit 36 adapt.

The MR ToF unit 36 includes a source-side ion mirror 38 , a detector-side ion mirror 40 and according to the present example, an additional in-trap potentiallift 42 ,

Overall, the first module delivers 20 Accordingly, a high-resolution time-of-flight spectrum is present, however, initially only as a superposition of the spectra of many different mass ranges. For the unfolding serves the directly subsequent second module 50 ,

Optionally, between the MR-ToF unit 36 and the second module 50 a further ion mirror (reflectron) may be arranged for additional time focusing of the ion pulses (not shown in the drawing).

The ion beam 24 first enters via an entrance gap 52 in the second module 50 and is in an electrostatic sector field 54 and a subsequent magnetic sector field 56 , which are arranged in Mattauch-Herzog geometry, double-focusing a space- and time-resolved detector 58 fed.

Claims (10)

Mass spectrometry ( 10 ), comprising: - a first module ( 20 ) with an ion source ( 22 ) and a multi-reflection time-of-flight unit ( 36 ); and - the first module ( 20 ) subsequent second module ( 50 ) with a magnetic sector field ( 56 ) and a downstream location and time resolution detector ( 58 ). A mass spectrometer according to claim 1, wherein the first module comprises an ion pulse ( 26 ) located between the ion source ( 22 ) and the multi-reflection time-of-flight unit ( 36 ) is arranged. Mass spectrometer according to claim 2, wherein the ion source ( 22 ) is a continuous ion source and the ion pulse ( 26 ) is an ion trap. Mass spectrometer according to claim 3, wherein the ion trap ( 26 ) is a radio frequency (RF) ion trap. The mass spectrometer of claim 4, wherein the radio frequency (RF) ion trap is a linear radio frequency (RF) ion trap. Mass spectrometer according to one of the preceding claims, in which the first module ( 20 ) a potentiallift ( 34 ) located between the ion source ( 22 ) and the multi-reflection time-of-flight unit ( 36 ) or, if an ionic pulser ( 26 ) is present between the ionic pulser ( 26 ) and the multi-reflection time-of-flight unit ( 36 ) is arranged. A mass spectrometer according to claim 1, wherein the multi-reflection time-of-flight unit ( 36 ) an integrated potentiallift ( 42 ). A mass spectrometer according to claim 1, wherein between the multi-reflection time-of-flight unit ( 36 ) and the second module ( 50 ) An ion mirror is arranged. A mass spectrometer according to claim 1, wherein the second module ( 50 ) an electric sector field ( 54 ) between the multi-reflection time-of-flight unit ( 36 ) and the magnetic sector field ( 56 ) is arranged. Mass spectrometer according to claim 8, wherein the electric sector field ( 54 ) and the magnetic sector field ( 56 ) are arranged in Mattauch-Herzog geometry.

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