Gridless time-of-flight mass spectrometer for orthogonal ion...

Radiant energy – Ionic separation or analysis – Ion beam pulsing means with detector synchronizing means

Reexamination Certificate

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C250S286000, C250S281000, C250S282000, C250S283000, C250S288000, C250S290000, C250S292000

Reexamination Certificate

active

06717132

ABSTRACT:

The invention relates to a time-of-flight mass spectrometer for injection of the ions orthogonally to the time-resolving axis-of-flight component, with a pulser for acceleration of the ions of the beam in the axis-of-flight direction, preferredly with a velocity-focusing reflector for reflecting the ion beam and with a flat detector at the end of the flight section.
The invention consists of using, both for acceleration in the pulser and for reflection in the reflectors, a gridless optical system made up of slit diaphragms which can spatially focus the ions onto the detector in the direction vertical to the directions of injection and flight axis, but which does not have any focusing or deflecting effect on the other directions. For some reflector geometries it is essential to use an additional cylindrical lens for focusing, and for other reflector geometries the use of such a lens may be advantageous.
PRIOR ART
Time-of-flight mass spectrometers, which have been known for over 50 years now, have seen a dramatic comeback over roughly the last ten years. On the one hand, these devices can be used advantageously for new types of ionization with which large biomolecules can be ionized, and on the other hand the development of fast electronics for digitizing the temporally fast-changing ion beam in the detector has made it possible to construct high-resolution apparatuses. Nowadays analog/digital converters with a dynamic range of 8 bits and a data conversion rate of up to 4 gigahertz are available, and for measuring individual ions there are time/digital converters available with temporal resolutions in the picosecond range.
Time-of-flight mass spectrometers are frequently abbreviated to TOF or TOF-MS (“Time-Of-Flight Mass Spectrometer”).
Two different types of time-of-flight mass spectrometer have been developed. The first type comprises time-of-flight mass spectrometers for measuring ions generated as ion cloud pulses in flight direction. An example for this is the generation of ions by matrix-assisted laser de-sorption, abbreviated to MALDI, a method of ionization suitable for ionizing large molecules. The second type consists of mass spectrometers for continuous injection of an ion beam, from which a section is then outpulsed in a “pulser” at right angles to the direction of injection and is caused to fly through the mass spectrometer in the form of a band-shaped ion beam consisting of linear ion beam segments. This second type is abbreviated to “Orthogonal Time-Of-Flight Mass Spectrometer” (OTOF); it is chiefly used in conjunction with continuous ion generation, for example electrospray (ESI). Due to the very high number of pulsed processes per unit of time (up to 50,000 pulses per second) a high number of spectra, each with a low number of ions, is generated in order to exploit the ions of the continuous beam as efficiently as possible. Electrospray is also suitable for the ionization of large molecules.
For measurement of the mass of large molecules by mass spectrometry, as particularly occurs in biochemistry, there is no spectrometer which is better than a time-of-flight mass spectrometer because of the limited mass ranges of other mass spectrometers.
Pulsed ion beams with ion cloud pulses originating from small sample spots, on the one hand, and band-shaped ion beams on the other, call for different ion optical systems for further focusing and guidance through the time-of-flight mass spectrometer: this is the reason for developing different types of mass spectrometer for these different types of ion injection.
In the simplest case of a TOF mass spectrometer, the ions are not focused at all. Acceleration of the ions generated by MALDI or ESI is performed by one or two grids, and the slight divergence of the ion beam caused by the initial velocities of the ions perpendicular to the direction of acceleration is accepted as being tolerable. The reflector also contains grids, one or even two grids depending on the type of reflector. In addition to beam divergence due to the spread of initial velocities there is a beam divergence caused by the small-angle scatter at the openings of the grid. If the electric field strength Is different on both sides of the grid, each opening in the grid will act as a weak ion lens. Divergence due to the spread of initial velocities can be reduced by selecting a high acceleration voltage but the small-angle scatter at the openings in the grid cannot be reduced. This small-angle scatter can only be reduced by making nets of finer mesh, albeit at the expense of grid transparency. Beam divergence creates a larger beam cross-section at the location of the detector, which necessitates a large-area detector. This large-area detector has disadvantages: a high level of noise and the necessity of very good two-dimensional directional adjustment in order to keep the flight path differences well below one micrometer.
For an optical system with two acceleration grids and one two-stage reflector with two grids, which each have to be transversed twice, there are already six grid passages. Even if the grids have a high level of transparency at 90%, which can only be achieved if the thickness of the grid wires is only about 5% of mesh size, total transparency is still only 48%. In addition there will be a non-negligible number of ions which are reflected by the grids and can be scattered back to the detector where they create background noise, which worsens signal-to-noise ratio.
The use of grids has therefore generally led to the use of single-stage reflectors. These must be much longer, about ⅓ of the total length of the spectrometer. The advantages of having only one grid (only two ion passages instead of four) and having to generate only one adjustable voltage are offset by considerable drawbacks: The mechanical design calls for many more diaphragms for homogenization of the reflection field; the long stay of the ions in the reflection field, however, leads to an increase in metastable decompositions in the reflector and therefore to diffused background noise in the spectrum because the decomposing ions turn back somewhere in the reflector due to changed energies so they cannot be temporally focused.
For the case of point-shaped ion origins (MALDI for example) gridless optical systems were therefore developed and introduced for acceleration of the ions (U.S. Pat. No. 5,742,049), particularly for their reflection in a two-stage reflector (EP 0 208 894). The gridless optical system consists of circular apertures which in principle represent spherical lenses. The ions from the point-shaped ion origin are therefore also imaged on a small-area detector (almost) in the shape of a point.
All the mass spectrometers known for orthogonal injection, however, have the very disadvantageous grids (due to the band-shaped ion beam which does not permit spherical lenses), both in the pulser and in the reflector.
OBJECTIVE OF THE INVENTION
It is the objective of the invention to find an accelerating and reflecting optical system for a time-of-flight mass spectrometer with orthogonal injection which operates without disadvantageous grids and focuses the ions on a small-area detector.
SUMMARY OF THE INVENTION
Throughout this text, we shall use the following nomenclature:
1) the original flight direction of the orthogonally injected ions defines the x-direction,
2) the direction in which the ions are pulsed by the pulser defines the y-direction,
3) the z-direction is defined to be perpendicular to the x- and y-direction. The three directions are orthogonal to each other; the y-direction is not completely identical with the flight path of the ions after being pulsed by the pulser.
The invention consists of using grid-free optical slit devices with long slits in the x-direction for the acceleration or deceleration of the in x-direction extended ion beam segments, both in the pulser and in the reflector (or in the reflectors if more than one is used), the optical slit devices being able to focus the band-shaped ion beam segments in the z-direction on a detector, which is na

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