1. Field of the Invention
The invention relates to measurement methods for time-of-flight mass spectrometers which operate with pulsed ionization of superficially adsorbed analyte substances and with an improvement in the mass resolution by means of a time-delayed start of the ion acceleration; in particular with ion-accelerating voltages which change over time after a delayed start in order to obtain a rather constant mass resolution over broad mass ranges.
2. Description of the Related Art
Time-of-flight mass spectrometers are often operated with pulsed ionization of superficially adsorbed analyte substances; methods for the ionization of samples by matrix-assisted laser desorption (MALDI) are known in particular. A plasma cloud, which expands and thus produces a distribution of the velocities of the plasma particles, is generated in the laser focus, said distribution being wider the further the plasma particles (ions and molecules) are from the surface. The velocity distribution means that the mass resolution can be improved by temporally delaying the start of the ion acceleration. Ions of a higher velocity then only pass through a portion of the accelerating field, and thus receive a lower additional acceleration, so the originally slower ions can catch up with them in a temporal focal point. Unfortunately, ions of different mass do not have exactly the same focal point. The focal points for ions of different mass can, however, be made to approach one another if ion-accelerating voltages are used which vary over time after a delayed start, particularly if they continuously increase or decrease (depending on polarity). In combination with a Mamyrin reflector, it is possible to obtain a high mass resolution which is approximately constant over large mass ranges (cf. documents DE 196 38 577 C1, GB 2 317 495 B or U.S. Pat. No. 5,969,348 A, J. Franzen, 1996).
The international patent application WO 2005/114699 A1 describes a standard ion lens system as a corrective ion optic element.
The invention is based on the finding that the accelerating field in the space in front of the sample support plate produces a lens effect in the typically round aperture of the accelerating electrode, and thus slightly defocuses the ion beam. Since fast ions with low masses leave this acceleration space quickly, the increasing accelerating field strength has a greater effect on the slow ions with large masses than on faster ions with low masses. This produces a broadening of the ion beam at right angles to the direction of flight, and the inventor has observed that this broadening increases with ion mass. The invention now proposes to compensate, to the desired extent, for the broadening of the ion beam with the aid of an additional ion-optical lens whose voltage is also varied over time. The lens can be an einzel lens, or more precisely an element of an einzel lens, or an acceleration lens, for instance.
For ions of a very broad mass range, it is quite possible to keep the ion beam at a diameter of approximately four millimeters (or less) by focusing with this additional lens while the ions pass through the first flight path, the reflector and the second flight path.
For some other operating modes, a diameter slightly above this minimum can be optimal. For example, at the point of reversal of the ions in the reflector, where the ions fly very slowly, the mass resolution may be reduced by the effect of the space charge if the ion beam is too narrow. Or the ion detector may be saturated by an ion density which is too high at some points. An optimum for the mass resolution and dynamic measuring range can thus be achieved by suitable variation of the function for the variable lens voltage. In any case, the beam diameter can be significantly reduced compared to an operating mode with static lens voltage.
In general, the reduction and homogenization of the beam diameter over a broad mass range produces better quantifiability of the ions because without these steps, the ion beam would broaden too much for it to be completely accepted or received by the geometry of the reflector and/or detector over a large mass range. The outer ions, especially at high charge-related masses m/z, would be lost to the measurement and thus also diminish its sensitivity.
While the invention has been shown and described with reference to a number of embodiments thereof, it will be recognized by those skilled in the art that various changes in form and detail may be made herein without departing from the scope of the invention as defined by the appended claims.
As has been set out before, since the varying accelerating voltage in the acceleration space produces a broadening of the ion beam at right angles to the direction of flight, and this broadening increases with the ion mass, the invention proposes to compensate, to the desired extent, for the broadening of the ion beam with the aid of an additional ion-optical lens whose voltage is also varied over time.
A greatly simplified schematic diagram of a MALDI time-of-flight mass spectrometer (MALDI-TOF) and a more detailed view of a corresponding ion source are shown in
The location (14) for the temporal focus of the ions can be selected at will via the time delay and amplitude of the accelerating voltage. It is usual to select a location which, as shown in
Unfortunately, the location (14) for the first temporal focusing of the ions is not at exactly the same position for ions of different mass. In fact, the focal length depends slightly on the mass of the ions. In order to make the location of the temporal focus approximately the same for ions of all masses, there is an operating mode in which the accelerating voltage is continuously varied after the delayed start of acceleration of the ions. The temporal variation of the accelerating voltage between sample support plate (1) and accelerating electrode (2) is depicted in the diagram of
As has already been mentioned, the typically round aperture of the accelerating electrode (2) acts like a lens because the field strengths on either side of the accelerating electrode (2) are different. This causes the ion beam (7) to become slightly defocused. Since fast ions with low masses leave this acceleration space quickly, the increasing accelerating field strength has a greater effect on the slow ions with large masses than on faster ions with low masses. This produces a broadening of the ion beam at right angles to the direction of flight, and this broadening increases with ion mass; as depicted by the curve (20) in the diagram of
The invention now proposes to compensate, to the desired extent, for the mass-dependent broadening of the ion beam by temporally varying the voltage of the middle element (5) of the einzel lens (4,5,6), which is used here by way of example. The lens voltage is varied during the spectral acquisition as a function of the time of flight and hence of the mass. As illustrated in
Different functions can be selected for the variation of the lens voltage. An exponential variation is simple to generate electrically, for example
where the lens voltage UL at time tL starts with the base voltage V1 and approaches the limit value (V1+W1) with the time constant t1. As has already been mentioned, the time tL can be identical to the time delay tv. A curve of this type is shown in the time diagram in
The time-of-flight mass spectrometer used, which is provided with ionization of the ions by matrix-assisted laser desorption, having a power supply for a delayed start and a varying accelerating voltage for the ions, and having a lens for spatial focusing of the ion beam, must therefore have a power supply for the lens which can supply a variable voltage on a short timescale, in the order of microseconds, during the spectral acquisition.
It should be noted here that a varying lens voltage requires a new mass calibration of the mass spectrometer, since a changed lens voltage has the effect of changing the dwell time of the ions in the lens. Such an adjustment is considered to be easily within the routine skill of a practitioner in this field, so no further explanation is required here.
The diagram in
For some operating modes, an ion beam diameter that is (slightly) larger than this minimum may be optimal. If, for example, high ion currents exist at the point of reversal of the ions in the reflector, where the ions fly very slowly, the effect of the space charge may cause the ions to mutually interfere, which leads to a reduction in the mass resolution. On the other hand, an ion detector, for example a multichannel plate, may be overloaded by too high an ion density at a particular point. In such cases, an optimum mass resolution, dynamic measuring range and/or sensitivity can be achieved by varying the temporal characteristic of the variable lens voltage. In any event, this achieves a significant improvement compared to the beam diameter as shown as curve (20) in
In some commercial time-of-flight mass spectrometers, it is possible to reflect a slightly divergent ion beam in the reflector onto the ion detector by solid angle focusing (cf. documents U.S. Pat. No. 6,740,872 B1 or GB 2 386 750 B; A. Holle, 2001). To this end, the equipotential surfaces in the reflector, near the ions' point of reversal, are slightly curved. The focusing is ideal only for ion beams of a limited diameter, however. Setting of the lens voltage variation according to the invention can be used here to illuminate the reflector in an ideal way. An optimum setting can be found by measuring the mass resolution and the sensitivity under varied conditions.
A time-of-flight mass spectrometer can also be operated without a reflector (or with the reflector switched off) in linear mode. In
Many time-of-flight mass spectrometers with reflectors are also equipped for measuring daughter ions of selected parent ions. The parent ions are selected by a “parent-ion selector” (not shown) at the location of the first temporal focus (14). It is a fast deflector which deflects ions of all masses and removes them from the ion path, the only exception being the selected parent ions. Here too, a lens voltage varying according to the invention can improve mass resolution and sensitivity.
The invention has been shown and described with reference to a number of different embodiments thereof. It will be understood, however, that various aspects or details of the invention may be changed, or various aspects or details of different embodiments may be arbitrarily combined, if practicable, without departing from the scope of the invention. Generally, the foregoing description is for the purpose of illustration only, and not for the purpose of limiting the invention which is defined solely by the appended claims.
Number | Date | Country | Kind |
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10 2014 115 034.1 | Oct 2014 | DE | national |