Radiant energy – Ionic separation or analysis – Ion beam pulsing means with detector synchronizing means
Reexamination Certificate
2001-07-06
2004-03-09
Meier, Stephen D. (Department: 2853)
Radiant energy
Ionic separation or analysis
Ion beam pulsing means with detector synchronizing means
C250S282000
Reexamination Certificate
active
06703608
ABSTRACT:
FIELD OF THE INVENTION
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 those with reflectors, with post-acceleration of selected parent and daughter ions by raising the potential of a “potential lift cell” during the passage of the ions.
BACKGROUND OF THE INVENTION
In a time-of-flight mass spectrometer, the mass-to-charge ratio m/z of ions can be determined from their time of flight. Although it is always the mass-to-charge ratio m/z which is measured in mass spectrometry, with m being the mass and z being the number of elemental charges carried by the ion, in the following, for the sake of simplicity, only the mass m and its determination will be referred to. Since many types of ionization, such as MALDI, predominantly supply only single-charged ions (z=1), the difference ceases to exist in practice for these types of ionization.
In a time-of-flight mass spectrometer which is equipped with an ion selector and a velocity-focusing reflector, it is possible to measure the daughter-ion or fragment-ion spectra of parent ions which are selected by the ion selector on the basis of their time of flight. The decay of parent ions into daughter or fragment ions can be induced by introducing excess energy during ionization (so-called PSD “Post Source Decay” spectra) or by applying other methods such as collisionally induced fragmentation (so-called CID “Collisionally Induced Decomposition” spectra).
The two-stage ion reflector according to Mamyrin has achieved considerable popularity as a velocity-focusing reflector. The ions are strongly decelerated during the initial brake stage of the reflector but only weakly decelerated in the second deceleration stage. The faster ions penetrate further than the slower ions into the linear, relatively weak deceleration field of the second deceleration stage of the reflector and therefore travel for a greater distance. With proper adjustment of the two deceleration fields, this difference in distances can be used to compensate for the faster time-of-flight velocity of the ions from a primary focus so that they arrive at the secondary focus at precisely the same time. The focal length of the velocity-focusing device is slightly energy dependent.
The parent ions and the daughter ions resulting from their decay enter the reflector simultaneously with the same average velocity but with different mass-proportional energies, such that they will be dispersed according to their mass within the reflector by their different energies. However, this method of detecting daughter or fragment ions by using these types of reflectors has serious disadvantages. With reasonably good focusing, only ions within a relatively small energy range can be detected—in the commercially available instruments of standard design, this represents approximately 25-30% of the energy range. The reason for this is that the ions always have to pass through the first deceleration field in order to achieve velocity-focused reflection. However, the first deceleration field consumes a good ⅔ of the original acceleration energy. This means that, from parent ions with an initial mass of 3200 atomic mass units, only those fragments between about 2400 and 3200 atomic mass units can be scanned in an initial fragment-ion segment spectrum; only those between 1800 and 2400 mass units can be scanned in a second segment spectrum with reduced reflector voltage, and only those between 1350 and 1800 can be scanned in a third segment spectrum etc. Thus, for an average sized peptide, approximately 10 to 15 segment spectra have to be scanned in order to measure the whole fragment-ion spectrum. Then, a complicated mass-calibration procedure has to be applied to get all the masses from the segment spectra. Only after all these segment spectra have been pasted together, can the daughter ion spectrum be evaluated in the data system as an artificially generated single composite spectrum.
According to the patent application GB 2 344 454 (German patent DE 198 56 014), methods have now been put forward for recording daughter-ion spectra in a single scan using either a linear time-of-flight mass spectrometer, or a time-of-flight mass spectrometer equipped with a two-stage ion reflector. The patent application also describes PSD, CID, MALDI (Matrix Assisted Laser Desorption and Ionization) and velocity focusing by delayed acceleration in the ion source.
One of the proposed methods consists of subjecting the ions to relatively mild acceleration in the ion source (using an acceleration of the ions which is slightly delayed with respect to the ion-producing laser flash), allowing them to decay in an initial drift path, very rapidly lifting their ambient potential to a second acceleration potential during their flight through a small potential cell (a potential lift) and accelerating them in a second acceleration region into a second drift region. The second drift region can be at the same potential as the first drift region and both drift regions are preferably operated at the ground or chassis potential. In the second drift region, very light ions then possess the minimum energy provided by the second acceleration potential and the parent ions which have not decayed have the maximum energy corresponding to the sum of the first and second accelerations.
Such a mass spectrometer already can be used to analyze daughter ions in a linear mode (without using an ion reflector). However, it is more favorable to increase the performance of the instrument by an ion reflector.
If a reflector is able to reflect particles with energy deviations corresponding to about 30% of the maximum energy and the second acceleration potential provides about 70% of the total energy, then the reflector will be able to reflect all the daughter ions in a single voltage adjustment and the entire daughter-ion spectrum can be acquired in a single spectrum acquisition step.
The potential lift itself can be also used to select the parent ions for the daughter ion spectrum. However, it is more favorable to use an additional selector which can produce a better time resolution for the parent ions, i.e. for separating the selected parent ions from other potential ions of similar masses.
However, this very simple arrangement still has disadvantages. In the first place, the mass resolution produced by the velocity focusing function of the delayed acceleration in the ion source can only be adjusted relatively well at for one mass in the spectrum, and adjustment for all other masses is very poor. Secondly, the daughter-ion spectrum as a whole does not show particularly good mass resolution, which means that the signal-to-noise ratio is not very good either.
SUMMARY OF THE INVENTION
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. This is particularly useful for daughter-ion spectrum acquisition, providing improved mass resolution, signal-to-noise ratio and detection sensitivity for all masses in the spectrum.
The basic idea of the invention is to generate a spatial distribution of ions of the same mass which is correlated with different velocities inside the potential lift cell, and to use space-velocity correlation focussing for the ions to get better resolved daughter ion spectra. The expression “lift cell” is used here not only for a completely closed cell, it is also used for the space between two adjacent, parallel grids, forming an essentially open cell. The focusing can be performed, for example, by lifting the two grids limiting the lift cell to two slightly
Franzen Jochen
Holle Armin
Bruker Daltonik GmbH
Meier Stephen D.
Nguyen Lam
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