Time-of-flight spectrometer with orthogonal pulsed ion detection

This invention provides an apparatus and method for efficient detection of ions in a time-of-flight mass spectrometer. The apparatus of the invention provides for orthogonal deflection of ions in the flight tube of a time of flight mass spectrometer to a detector or detectors positioned along or in the wall of the flight tube of the mass spectrometer. A method of detecting ions utilizing the apparatus is also provided.

TECHNICAL FIELD

The invention relates generally to ion analysis and more particularly to ion analysis in time-of-flight mass spectrometry.

BACKGROUND OF THE INVENTION

Time-of-flight mass spectrometers are based on the fundamental principal that ions which have the same initial kinetic energy but different masses will separate when allowed to drift down a field free region, e.g., the length of the flight tube in a conventional time-of-flight mass spectrometer. The ions acquire different velocities according to the mass-to-charge ratio of the ions. Accordingly, lower mass ions will arrive at a detector positioned at the end of the flight tube prior to ions of higher mass. The detector detects the ions collecting the data that yields the mass spectrum for the sample. Traditionally, the detection system is located at the end of the flight tube of a linear time-of-flight mass spectrometer opposite the end of the flight tube where the ions are generated.

Because the ions of different mass-to-charge ratios arrive at the detector at different times continual emission of ions from the ion source into the flight tube is problematic as ions with lower masses may over take slower moving higher mass ions emitted earlier. Accordingly, in the conventional time-of-flight mass spectrometer, it is necessary to allow all ions emitted at a given time to reach the detector before emitting more ions for analysis.

Conventionally the sample that passes into the flight tube is not a continual beam of ions. Usually the ion beam is divided into packets of ions at the ion source. The packets of ions are launched from the ion source at one end of the flight tube into the flight tube using a pulse and wait approach. When using the traditional pulse and wait approach, the release of an ion packet from the source is timed to ensure that the lower mass faster ions of a trailing packet do not pass the higher mass and slower ions of a preceding packet and that the ions of the preceding packet reach the detector before any overlap can occur. Accordingly, the period between release of packets is relatively long as compared to the amount of time for the release. This creates a low duty cycle. As ion sources typically generate ions from a sample continuously in the ion source, only a small portion of the ions generated in the ion source are emitted from the source as ion packets and undergo detection. Thus a significant amount of sample material is wasted and typically sensitivity is reduced. Further in the conventional time-of-flight mass spectrometer the ions of a given packet impinge on the detector in a sequential manner. Recovery of the detector between impacts may require at least a small amount of time. Impact of ions on the detector before recovery leads to degraded isotope resolution.

U.S. Pat. No. 5,396,065 describes a method of addressing the low duty cycle problem by generating an encoded sequence for launching packets of ions before sending them to the field-free region. Upon arrival at the detector, the ion signals are decoded and spectra are reconstructed. This method requires fairly complicated hardware and software algorithms.

U.S. Pat. No. 6,521,887 describes using a position sensitive detector at the end of the flight tube in combination with a system to raster the ion beam to enhance efficiency of detection of ions.

However, the need remains for an improved apparatus and method for time-of-flight mass spectrometry.

SUMMARY OF THE INVENTION

The present invention includes an apparatus for analyzing ions comprising a flight tube having a longitudinal main axis (e.g. a main axis of the flight tube), a means for generating ions with a trajectory along the main axis of the flight tube, a means for electrostatic deflection and at least one ion detector. The means for electrostatic deflection is positioned parallel to the main axis of the flight tube. Additionally, means for electrostatic deflection is controllable and has at least one first state of non-deflection and at least one second state of deflection. In the at least one second state of deflection at least a portion of the ions are deflected in a trajectory substantially orthogonal to the main axis of the flight tube. The at least one ion detector is positioned in the flight tube substantially parallel to the main axis such that at least a portion of the ions that are deflected in a trajectory substantially orthogonal to the main axis impinge the detector.

The means for electrostatic detection may comprise an ion detection pulser electrode placed in the flight tube in a position substantially parallel to the longitudinal axis of the flight tube. In some embodiments, the ion detection pulser electrode is paired with a second grid electrode placed in the flight tube such that ions passing along the main axis of the flight tube pass substantially between the two electrodes.

The ion detector may be a position sensitive detector. Additionally the ion detector may be a single detector or a plurality of detectors.

A method of analyzing ions using the apparatus of the invention is also provided.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides an apparatus and method that facilitates detection of ions for selected ions or a group of ions with a range of mass-to-charge ratios. The apparatus is a time-of-flight mass spectrometer which provides for reduced “waiting time” between the launching of packets of ions as compared to conventional time-of-flight mass spectrometry. This provides for increased speed of analysis and increased sensitivity due to more efficient use of the ions formed in the ion source. Further, unlike the conventional time of flight mass spectrometer which has sequential ion detection for a packet of ions, the time-of-flight mass spectrometer of the invention provides for simultaneous ion detection of a packet of ions which facilitates high accuracy for isotope distribution and improves exact mass measurement. Also a mass spectrum may be obtained using the mass spectrometer of the invention without complicated spectrum decoding.

In one embodiment, the detector placement is variable. Variable detection placement allows flexible configuration of the time-of-flight mass spectrometer to adjust resolution and speed parameters to optimize the balance between speed and resolution for a particular analysis in the time-of-flight mass spectrometer. These adjustments can be accomplished without significant hardware and software modification.

FIG. 1depicts a prior art conventional time-of-flight mass spectrometer10. An ion source20located at a first end23of flight tube26generates ions12,14,16. The ions12,14,16are sent into an acceleration field22. Typically the acceleration field22is constructed with planar electrodes and mesh grids. When an electrical pulse is applied to the acceleration field22a packet of ions containing all mass-to-charge ratios is formed and the packet is accelerated into a field-free region24of the flight tube26. The direction of acceleration of the ion packets is toward a second end28of the flight tube26in a path substantially parallel to flight tube main axis27. The flight tube26for a conventional time-of-flight mass spectrometer10is normally a conductive cylinder with a length substantially longer than its diameter.

In a conventional time-of-flight mass spectrometer an ion detector25is placed at the end of the field-free region at the second end28of the flight tube26. For the exemplary ions12,14,16accelerated by the same electrical pulse, those ions of low mass-to-charge ratios move through the field free region24faster than ions of higher mass to charge ratios at the same kinetic energy. As illustrated inFIG. 1, the ion16has a mass to charge ratio (e.g. m/z) less than ions12and14and ion14has an m/z ratio less than ion12. Ions12,14,16are detected sequentially when they impinge the ion detector25.

FIG. 2shows an exemplary embodiment of the time of flight mass spectrometer100. An ion source20generates ions which are sent into an acceleration field22. The acceleration field22may for example, be constructed of planer electrodes and mesh grids. An electrical pulse is applied to the acceleration field22and a packet of ions containing all mass to charge ratios generated from the sample is formed and the packet is accelerated into inner region124of the flight tube26. The inner region124is field free at the time that the ions enter the inner region124. The ions exiting the acceleration field22(exemplary ions12,14,16in this example) initially follow a trajectory substantially parallel to flight tube main axis27(e.g., initially they follow the same trajectory as in a conventional time-of-flight mass spectrometer). The ion source and acceleration field arrangement are exemplary of an apparatus and method for generating packets of ions. Other apparatus or methods known to those skilled in the art may be suitable for use in the practice of the invention.

In the exemplary embodiment shown inFIG. 2, the flight tube26is constructed with a set of electrodes30,32disposed along the flight tube26. The electrodes being positioned parallel to each other and substantially parallel to flight tube main axis27. The first electrode30is an ion detection pulser electrode. The second electrode32is a grid electrode. In one exemplary embodiment, the ion detection pulser electrode30is a planer electrode and the grid electrode32is constructed with mesh grid or grids. The electrodes are spaced such that ions traveling from the acceleration field22at the flight tube first end23in a trajectory substantially parallel to the flight tube main axis27toward the flight tube second end28pass between the ion detection pulser electrode30and the grid electrode32.

The ion detection pulser electrode30and mesh grid electrode32have a first state and at least one second state. In the first state both the ion detection pulser electrode30and grid electrode32are at the same potential as the flight tube26. In this first state, the region between the first and second electrodes30,32in the flight tube26is a field-free region. Ions of different mass-to-charge ratios (exemplary ions12,14,16in this example) travel along the flight tube and separate from each other in space according to their mass-to-charge ratio, as they would in a conventional time-of-flight mass spectrometer. At a time point t, exemplary ion12arrives at point A, and exemplary ions14and16arrive at point B and point C, respectively. At time t, an electrical pulse is applied to the ion detection pulser electrode30. This creates a second state in which the inner region124between the ion detection pulser electrode30and the grid electrode32is no longer field free, e.g., a transversal acceleration field is established between the ion detection pulser electrode30and grid electrode32. In the second state, as shown inFIG. 2, ions (e.g. exemplary ions12,14,16in this schematic) are accelerated toward the grid electrode32in a trajectory substantially orthogonal to the flight tube main axis27. A position-sensitive ion detector40substantially parallel to the main axis27is placed between the grid electrode32and the wall29of the flight tube26. The position sensitive detector40detects the deflected ions collecting the date that yields the mass spectrum. Alternatively, the detector40may be positioned at or in the wall29.

Typically, the application of the electric pulse to the ion detection pulser electrode30(e.g., the ion detection pulse) is synchronized with the application of the electric pulse to the accelerator field22(e.g., the ion acceleration pulse) and formation of the packet of ions. The ion detection pulser electrode30is shown as a single electrode. Multiple ion detection pulser electrodes may be used and/or the ion detection pulser electrode may be segmented such that ions may be deflected orthogonally at one or more specific points along the flight tube26. Similarly the grid electrode32may be, in some embodiments, multiple electrodes and/or segmented.

The mass-to-charge ratio of the ions impinging on the detector is determined by

mq=2⁢U⁡(tL)2
where U is the accelerating voltage applied to ion acceleration field, t is the delay time between the ion acceleration pulse and ion detection pulse, L is the position measured with the position-sensitive detector for the apparatus of the invention (for the conventional time-of-flight instrument in which the detector is positioned at the end of the flight tube opposite the end bearing the ion source, L is the length of the flight tube), m is mass and q is charge.

There is a small additional time delay between the ion detection pulse and ion arrival at the detector40, so the total delay time is uknown. The instrument is calibrated with a sample with known mass-to-charge ratio

(m0q0)
to determine a coefficient c

Thus for examples analyzed in the instrument, the mass-to-charge ratio of an unknown ion is determined by

The apparatus and method for ion detection described above can, in some embodiments, yield a higher speed detection e.g. higher speed analysis in comparison to a conventional time-of-flight mass spectrometer10. For example, in conventional time-of-flight mass spectrometers10the time needed for detecting all mass-to-charge ratios is determined by the maximum mass-to-charge ratio of interest. For example, for a conventional time-of flight mass spectrometer10with a flight tube of 1 meter, and an ion acceleration voltage of 1000 volts, the detection time in μs for an ion of mass-to-charge ratio 500 is about 49 μs as calculated below:

In contrast, the time needed for mass analysis in the time of flight mass spectrometer100is determined by the lowest mass-to-charge ratio of interest. For instance, if the lowest mass to charge ratio of interest is 5, the time needed for detecting ions of all mass-to-charge ratios is equal to about 4.9 μs as calculated below:

For this illustrative example, the mass to charge analysis is accomplished about 10 times faster in the apparatuses and method described than in a conventional instrument. Accordingly the duty cycle for the illustrative example is increased about 10 fold. This example is exemplary of how analysis time is calculated in conventional instruments10and instruments of the invention100and values will vary depending on such parameters as flight tube length and the dispositive mass to charge ratio as identified above, for example.

Commercially available position-sensitive detectors may be used in the apparatuses described. However, specially designed or configured detectors are also suitable for use. The mass resolution of the time-of-flight instrument of the invention is determined in a large part by the resolution of the position-sensitive detector. At the time of detection, the separation of a mass-to-charge ratio m and m+Δm is given by

Δ⁢⁢L=-12⁢Δ⁢⁢mm⁢L=-12⁢Δ⁢⁢mm⁢(0.014⁢Um⁢t)
with t in μs. For separation of mass-to-charge ratio of m=500 and m+Δm=501,

Thus, for this representative example, a position-sensitive detector with a resolution of 100 μm is required for detection of m=500 and m+Δm=501. Such a detector is commercially available for example, through Del Mar Ventures (4119 Twilight Dr., San Diego, Calif. 92103, USA).

In one exemplary embodiment of the time of flight mass spectrometer of the invention100, a position-sensitive detector is not necessarily needed. As shown inFIG. 3, the detector42is segmented. The segmented detector42may include a plurality of short detector portions142,143,144of linear type disposed along the flight tube26at positions selected for detecting ions of certain mass-to-charge ratios of interest. Several positions-sensitive detectors or a single position sensitive detector physically divided into segments may form the detector portions142,143,144in some embodiments. Alternatively, small conventional detectors may be suitable in some applications to form detector portions142,143,144. Three detector portions142,143,144, as shown inFIG. 3, is exemplary. A segmented detection42will have at least two detector portions but may have more. The use of the term segmented detector herein should be taken to include a plurality of detector portions which may comprise a plurality of conventional detectors, a plurality of position sensitive detectors or a combination thereof. Further, the plurality of detector portions may be individual detectors or derived by physically dividing a single detector into sections. Use of either conventional or small position sensitive detectors may offer the advantage of reduced instrument cost. In embodiments with segmented a detector42, the detector portions142,143,144may have the same or different resolutions. For example, for detecting ions of low mass-to-charge ratio, a lower resolution detector may be used than for detecting higher mass ions.

FIG. 4shows another exemplary embodiment of the invention. In the embodiment ofFIG. 4, the position-sensitive detector44has a length substantially less then the length of the flight tube26. The position-sensitive detector44is movable in a direction that parallels the main axis27of the flight tube26. An exemplary use of this embodiment is for a sample containing few components or only few a components of interest. The detector can be moved to a particular position to detect a particular component. This facilitates analysis in which one particular ion is the focus of the analysis, for example.

FIG. 5andFIG. 6show cross sectional schematic diagrams of two exemplary embodiments of time of flight mass spectrometer100. InFIG. 5the ion detection pulser electrode30and the grid electrode32are positioned inside the flight tube26. As shown, the detector40may be positioned inside the flight tube wall29between the grid electrode32and the flight tube wall29. Alternatively, the detector40may be an integral part of the flight tube wall29.

FIG. 6shows a cross sectional diagram of an embodiment of the time of flight mass spectrometer100. In the embodiment shown inFIG. 6, the ion detection pulser electrode30and grid electrode32are integral parts of the flight tube wall29. In the embodiment shown inFIG. 6, the voltage applied to the ion detection pulser electrode30is the same as that of the flight tube26in the first state when the ions follow a trajectory substantially parallel to the main axis27of the flight tube26and a different voltage is applied to the ion detection pulser electrode30to create the second state and deflect the ions in a trajectory orthogonal to their trajectory in the first state. In the second state, the ions are deflected toward the grid electrode32and the detector40. Although the ion detection pulser electrode30is shown as a integral part of the flight tube wall structure in the embodiment depicted inFIG. 6, it should be noted that the ion detection pulser electrode30should be electrically isolated from the flight tube26.

In another embodiment of the invention not shown in the figures, there is no grid electrode. In this embodiment, an ion detection pulser electrode30as described for other embodiments may be used (e.g., an ion detector pulser electrode30is positioned substantially parallel to the main axis27of the flight tube26and electrically isolated from the flight tube wall.) The ion detection pulser30may be an integral part of the flight tube wall29or positioned between the flight tube wall29and the trajectory of the ions as they leave the ion acceleration field22. The at least one detector40is placed at a position near or in the flight tube wall29opposite the ion detection pulser electrode30such that the trajectory of the ions leaving the acceleration field22passes between the ion detection pulser electrode30and the detector40.

In the first state in which ions follow a trajectory in the flight tube26substantially parallel to the main axis27of the flight tube26, the voltage applied to the ion detection pulser electrode30is the same as that of the flight tube26. For detection, a different voltage is applied to the ion detection pulser electrode30to create a second state in which at least a portion of the ions are deflected in a trajectory substantially orthogonal to the main axis27. At least a portion of the deflected ions then impinge on the detector40positioned near or in the wall of the flight tube29.

The foregoing discussion discloses and describes many exemplary methods and embodiments of the present invention. As will be understood by those familiar with the art, the invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. Accordingly, the disclosure of the present invention is intended to be illustrative, but not limiting, of the scope of the invention, which is set forth in the following claims.