CA2491198C - Ion storage time-of-flight mass spectrometer - Google Patents

Abstract

A method and an apparatus which combines a linear two dimensional ion guide or a two dimensional ion storage device in tandem with a time-of-flight mass analyzer to analyze ionic chemical species generated by an ion source. The method improves the duty cycle, and therefore, the overall instrument sensitivity with respect to the analyzed chemical species.

Description

Ion Storage Time-~~ FIiQ6t Mass Spectrometer Field of the Invention This invention relates in general to mass spectrometers and in particular to the use of time-of flight (TOFU mass spectrometers in combination with two dimensional ion traps that are also used as ion guides and ion transport lenses.
Background of the Invention In a time-of flight mass spectrometer, ions are accelerated by electric fields out of an extraction region into a field free flight tube which is terminated by an ion detector. By applying a pulsed electric field or by momentary ionization in constant electric fields, a group of ions or packet starts to move at the same instant in time, which is the start time for the measurement of the flight time distribution of the ions. The flight time through the apparatus is related to the mass to charge ratios of the ions. Therefore, the measurement of the flight time is equivalent to a determination of the ion's m/z value. (See, e.g., the Wiley and McLaren; and, the Laiko and Dodonov references cited below).
Only those ions present in the extraction zone of the ion accelerator, (also referred to as "the pulser"), in the instant when the starting pulse is applied are sent towards the detector and can be used for analysis. In fact, speaal care must be taken not to allow any ions to enter the drift section at any other time, as those ions would degrade the measurement of the initial ion package.
For this reason, the coupling of a continuously operating ion source to a time-of flight mass spectrometer suffers from the inefficient use of the ions created in the ion source for the actual analysis in the mass spectrometer.
High repetition rates of the flight time measurements and the extraction of ions from a large volume can improve the situation, but the effective duty cycles achieved varies as a function of mass and can be less then 10% at low mass.
If extremely high sensitivity of the mass analysis is required or if the number of ions created in the ion source is relatively small, there is need to make use of all the ions available. This requires some sort of ion storage in-between the analysis cycles. Time-of flight instruments that use de plate electrode configurations or quadrupole ion traps for ion storage have been built and operated successfully. (See e.g., the Grix, Boyle, Mordehai, and Chien references cited below). While the storage efficiency of do configurations is limited, with quadrupole ion traps a compromise between efficient collisional trapping and collision free ion extraction has to be found.
In the present invention, a multiple pumping stage linear two dimensional multipole ion guide is configured in combination with a time-of-flight mass ,:
r ~ _ spectarometer with any type of ionization source to increase duty cycle and thus sensitivity and provide the capability to do mass selection. Previous systems, such as the ion trap/time-of flight system of Lubman (cited below), have combined a storage system with time-of-flight, however, these systems' trapping time are long, on the order of a second, thus not taking full advantage of the speed at which spectra can be acquired and -thereby limiting the intensity of the incoming ion beam. In addition, the ion trap is strictly used as the acceleration region and storage region. Also, 100% duty cycle is not possible with the ion trap TOF system due to the fact that the ion trap can not be filled and empty at the same time; in addition, there are currently electronic limitations (See e.g., Mordehai, cited below), whereas in this embodiment it is one of the possible modes of operation.
The use of a two dimensional multipole ion guide to store ions prior to mass analysis has been implemented by Dolnikowski et al. on a triple quadrupole mass spectrometer. This combination, in fact, has become routine analysis technique for triple quadrupoles. A more recent combination was made by Douglas (U.S. Patent No. 5,179,278) who combined a two dimensional multipole ion guide with a quadrupole ion trap mass spectrometer. Both of these systems are quite different from the current embodiment. In both of the above systems, the residence times of the ions in the linear two dimensional quadrupole ion guide were over 1-3 seconds, whereas, in the current embodiment the ions can be stored and pulsed out of the linear two dimensional multipole ion guide at a rate of more than 10,000/sec, thus utilizing much faster repetition rates. Due to the inherent fast mass spectral analysis feature, of the time-of-flight mass analyzers, continuously generated incoming ions are analyzed at a much better overall transmission efficiency than the dispersive spectrometers such as quadrupoles, ion traps, sectors or Fourie~r Transform mass analyzers. When an ion storage device is ~.

coupled in front of a dispersive mass analyzer instrument, the overall transmission efficiency of an instrument, no doubt, increases; however, since the ion fill rate into the storage device is much faster than the full spectral mass analysis rate, the overall transmission efficiencies are limited by the mass spectral scan rates of the dispersive instruments which are at best on the order of seconds. Time-of flight mass analyzers, on the other hand, can take full use of the fast fill rates of the incoming continuous stream of ions since the mass spectral scan rates of 10,000 per second and more can well exceed these fill rates into a storage device.
Also unique to this embodiment is the fact that the ion packet pulse out of the linear two dimensional multipole ion guide forms a low resolution time of flight separation of the different m/z ions into the pulser where the timing is critical between when the pulse of ions are released from the linear two dimensional multipole ion guide and the time at which the pulser is activated.
This is to say that the linear two dimensional multipole ion guide pulse time and the delay time to raise the pulser can be controlled to achieve 100% duty cycle on any ion in the mass range or likewise a 0% duty cycle on any ion in the mass range or any duty cycle in between. Also, as pointed out by Douglas (U.S. Patent No. 5,179,278), an ion guide can hold many more ions than what the ion trap mass analyzer can use. This decreases the duty cycle of the system if all trapped ions are to be mass analyzed. In contrast, that is not an issue in the current embodiment.
As the linear two dimensional multipole ion guide trap is filled with more ions, the space charging effects or coulombie interactions between the ions increase resulting in two major consequences. First, the mass spectral characteristics may change due to overfilling of the storage device where more fragmentation will occur due to strong ionic interactions. Second, the internal energy of the ions will increase, making it. harder to control and stop the ions going into a mass analyzer device. The above problems can again be overcome using a time-of-flight mass analyzer at fast scan rates which will not allow excessive charge build up in the storage ion guide. Operating at very fast acquisition rates, time-of flight instrument does require intricate timing of the trapping and the pulsing components.
Brief Description of the Invention It is the principal object of this invention to provide means for increasing the deteedon limits of a continuous stream of ionic chemical species generated externally in a time-of flight mass spectrometer.
It is a further object of this invention to provide means for increasing the .
detection limits of said time-of flight instrument by increasing the duty cycle of the mass analysis.
In accordance with the above objects, a two dimensional ion guide device with accompanying ion optics and power supplies, switching circuitry, and tinung device for said switching circuitry is provided to increase the ion throughput into the time-of flight mass analyzer.
These and further objects, features, and advantages of the present invention will become apparent from the following description; along with the accompanying figures and drawings.
Brief Description of the Drawings FIG. 1 is a schematic representation of a simple linear time-of flight mass analyzer utilizing orthogonal acceleration with an atmospheric pressure ionization source.
FIG. 2 is a schematic representation of a simple reflectron time-of flight mass analyzer utilizing orthogonal acceleration with an atmospheric pressure ionization source.
FIG. 3 is a schematic drawing of the interface ion optics between the ion source and the mass analyzer.
FIG. 4 is a schematic drawing of the interface ion optics between the ion source and the mass analyzer using a two dimensional ion trap.
FIG. 5 is the detailed view of the ion guide and the surrounded ion optics (A), cross section of the -multipole ion guide with six rods (B), electrostatic voltage levels on the said ion optics when the ions are released (C) and trapped (D).
FIG. 6 is the relative timing diagram of the ion guide eidt lens and the time-of flight repeller lens voltages.
FIGS. 7A and 7B are the time-of flight mass spectral comparison between the continuous and ion storage mode of operations.
FIG. 8 is a schematic representation of a simple linear time-of flight mass analyzer utilizing axial acceleration with an atmospheric pressure ionization source.
Detailed Description of the Preferred Embodiments Among the many atmospheric pressure ionization time-of flight mass spectrometer configurations covered by prior art, FIG. 1 and FIG. 2 show the two basic time-of flight instruments used in this study demonstrating the present invention. FIG. 8 also shows an alternative but less frequent configuration used in our studies. The instruments contain an external atmospheric pressure ion source 10 and a means for transporting the ions from the atmospheric pressure ionization source to the mass analyzer all of which are encased by the vacuum housing walls 22. Both the ions and the background gas are introduced into the first stage pumping region 20 by means of a capillary interface 12 and are skimmed by a conical electrostatic lens 19 with a circular aperture 13. The ions are formed into a beam 21 by a multipole ion guide having round rods 11 and are collimated and transferred into the pulsing region 26 of the time-of flight mass analyzer by transfer ion optic lenses 15, 16, and 17. The mutipole ion guide can be a multipole ion guide extending through multiple vacuum pumping stages according to the preferred embodiment. Multipole ion guides extending through multiple vacuum pumping stages are described in U.S. Patent No. 5,652,427 dated July 29, 1997.
Alternatively, separate multipole ion guides in separate vacuum pumping stages can be used.
Electrically insulating materials such as spacers 18 are used to isolate the various ion optic lenses throughout the apparatus. Along the path of the transfer ion optics, the gas density is reduced going through four different pumping stages. The skimmer orifice separates the gas flow between the first and the second pumping stages 20 and 30, the ion guide support bracket 14 and the ion guide itself acts as a separator between the pumping stages 30 and 40. A hole 28 in the vacuum housing 22 separates the third pumping stage 40 from the fourth pumping stage 50 where the time-of flight mass analyzer components reside. The four vacuum stages are pumped conventionally with a combination of turbo and mechanical pumps.
The time-of flight mass analyzer shown in FIG. 1 and FIG. 2 are said to be operating in an orthogonal injection mode because ions generated outside of the spectrometers are injected perpendicularly to the direction of the accelerating fields 26 and 27 defined by the electrostatic lenses 23, 24, and (See e.g., the O'Halloran et al., Dodonov et al., USSR Patent SU 1681340 references cited below). The ion beam 21 enters the time-of flight analyzer through an aperture 28 and traverses the first accelerating or the extraction region 26. A Faraday cup 25 is used to monitor and optimize the ion current of the ion beam 21 into the region 26 when the electric field is off, i.e. the voltage on the repeller plate 23 is equal to the voltage on the draw-out plate 24. Typically that would be the ground voltage potential. By applying a pulsed electric field momentarily between the repeller lens 23 and the draw=
out lens 24, a group of ions 33 starts to move instantaneously in the direction ~55, through the second stage acceleration field set by the plates 24 and 35 and towards the field free drift region 60 surrounded by the flight tube 35. The pulsed electric field generated by the pulsing of the repeller lens 23 establishes the start time for the measurement of the flight time distribution of the ions arriving at the detector 36. The flight time through the apparatus is related to the mass to charge ratios of the ion. Therefore the measurement of the flight time is equivalent to a determination of the ion's m/z value. To offset or adjust the direction of the ion packet 33 to hit the detector 36, set of deflectors 32 may be used after the acceleration region 27 and inside the field free drift region 60. If the deflectors are not used with orthogonal injection, the detector has to be placed off axis at a position to account for the energy of the ions in the direction of the ion beam 21.

The mass resolution of a time-of flight mass spectrometer is defined as m/Am = tl2dt where m is the ion mass, Om is the width of the ion package arriving at the detector at full width half maximum (FWHM), t is the total flight time of this ion, and ~t is the arrival time distribution at the detector measured at FWHM. As a result, higher resolution can be achieved in one of two ways: increase the flight time of ions or decrease the arrival time distribution of the ions at the detector. Given a fixed field free drift length, the latter is achieved in the present mass spectrometer with a two stage accelerator of the type first used by Wiley and MeLaren. The electric fields in the two acceleration regions 26 and 27 are adjusted by the voltages applied to the lenses 23; 24, and 35 such that all ions of the same m/z start out as a package of ions 33 with a finite volume defined by the acceleration region 26 and end in a much narrower package 34 when they hit the detector. This is also called the time-space focusing of the ions which compensates for the different initial potential energy of the ions located in different positions in the electric field in region 26 during the pulse. The dme-space foccising of the ions does not however compensate for the different energy distribution of the ions along the direction of the acceleration field before the field is turned on.
The degree of the energy spread component of the ions in the acceleration axis determines the time distribution of the ions arriving at the detector.
The larger the spread of energy of the ions in this direction, the lower will be the mass resolving power of the instrument. The orthogonal injection of the ions does minimize, to some degree, the energy spread of the externally injected ions in the direction of acceleration resulting in a narrower package of ions hitting the detector. To further increase the resolution of the time of flight instrument caused by the energy spread of the ions, a reflectron of the type first used by Mamyrin (cited below) can be used. FIG. 2 shows such an instrument which is the same as in FIG. 1, except a reflectron 41 is added for operating the mass analyzer in a higher resolution and mass accuracy mode.

l~
The coupling of continuously operating ion sources 10 to a time-of flight mass spectrometer suffers from the inefficient use of the ions created in the ion source for the actual analysis in the mass spectrometer. High repetition rates of the flight time measurements counted by the pulsing of the repeller lens 23 and the extraction of ions from an elongated volume 26 can improve the situation, but effective duty cycles achieved are still of the order of 1 to 50%.
To demonstrate the point, consider a continuous beam of ions 21 in FIG: 3 having a mixture of three ions 52, S3, and 54 with molecular weights 997 (Ml), 508 (Mz), and 118 (M3) entering the pulsing region 26 with electrostatic energy of 10 eV. With these parameters, the approximate velocity of the ions going through the acceleration region 26 at the absence of the field would be 4 mm/E,cs, 1.9 mm/~.s, and 1.4 mm/~s, respectively. If practical experimental parameters, for example, 10,000 repetition rate per second of the repeller lens 26 (a single scan lasting 100~s) and 20 mm of pulsing region length determined by the mesh size opening 38 on the lens 35, are used, for every one ion of mass M, 52, M2 53 and M3 54, going in the direction 55 of the time-of flight analyzer detector, seven, ten, and twenty ions will be lost going in the direction 21. The approximate calculated duty cycles for the ions M, 52, M2 53, and M3 54, will result in 14%, 10%, and S%, respectively.
In order to achieve higher extraction duty cycles with continuous ion beams several parameters can be adjusted. For example, repetition rates of 20,000 Hz or more can be used, the energy of the ions can be lowered, or the extraction region can be extended in the direction of the ion beam 21.
However, many of these changes will result in an increase of duty cycles by at best a factor of two before practical limitations can be exceeded. Difficult to build or expensive to buy mass analyzer components such as detectors with larger surface area, faster data acquisition systems etc., will be needed to achieve higher duty cycles.
To make use of the limited number of ions generated in the ion source 10, some sort of ion storage mechanism in-between the analysis cycles is required.
FIG. 3 shows a section of a time-of flight mass spectrometer that utilizes an existing RF-only multipole ion guide being used in the continuous ion mode of operation. FIG. 4, FIG. S, and FIG. 6 show the same multipole ion guide being used in the ion storage mode of operation with appropriate power supply and pulse d 'rne and delay generators.
In recent years, the commercial use of such RF-only multipole ion guides have been practiced widely in continuous mode, especially in mass spectrometers interfaced with atmospheric pressure ionization (APn sources.
The number of rods used in the multipole ion guide assemblies may vary; the examples in this imrention will show predominantly hexapole, meaning six round, equally spaced in a circle, and parallel, set of rods 11 as shown in FIG.
SB. The alternate rods 11 are connected together to an oscillating electrical potential. Such a device is known to confine the trajectories of charged particles in the plane perpendicular to the ion beam axis 2I, whereas motion in the axial beam direction is free giving rise to the term, "two dimensional ion trap". Depending on the frequency and amplitude of the oscillating electrical potential, stable confinement can be achieved for a broad range of values of the mass to charge ratio along the beam axis 2I. A static bias voltage potential 76 is applied to all the rods to define the mean electrical potential of the multipole with respect to the ion guide entry conical electrode 19 with voltage 75 and with respect to the ion guide exit electrode 15 with voltage value 77 or 78.

As seen in FIG. SC, in the continuous mode of operation, for a positively charged stream of ions Z1 to enter and be focused into the ion guide through a skimmer orifice 13, the voltage value 75 applied to the conical electrode 19 has to be higher than the bias voltage value 76 applied to the ion guide rods 11. By the same token, to push and focus the ions beyond the ion guide, a voltage value 77 even less than the bias voltage value 76 needs to be applied to the ion guide exit lens electrode 15. When the ion guide is operated in the storage mode as $een in FIG SD, the voltage value on the exit lens electrode 15 is raised from 77 to 78 which is higher than the ion guide bias voltage 76.
This higher voltage value 78 on the lens electrode 15 repels the ions in the exit region 72 of the ion guide back towards the entrance region 71 of the ion guide. As evident from FIG. SD, the voltage values set in this manner form a potential well in the longitudinal direction of the ion guide efficiently preventing the ions from leaving the ion guide.
A particularly useful feature of the ion guide in regards to this invention is the higher gas pressure in the ion entry region 71 and the region up to the .
second and third pumping stage partitioning wall 14 inside the ion guide.
Due to the expanding background gas jet, this region 30 is under viscous flow pressure regime with gas flowing and becoming less dense in the direction of the ion beam 21. This feature accomplishes two important functions in the time-of flight instrument. One, due to collisional cooling, it sets a well defined and narrow ion energy of the beam 21. Two, it allows high efficiency trapping of the ions along the ion guide enclosed by the rods 11, the conical lens 19 and the exit lens 15.
Both in the continuous mode of operation and in the storage mode, the final electrostatic energy of the ions entering the time-of flight analyzer pulsing region 26 is determined by the voltage difference set between the ion guide bias voltage 76 and the time-of flight repeller plate 23 when the field is off.
Due to collisions with the molecules of the dense gas jet in the region 71, the ions do not gain kinetic energy in the electric field but slide gradually down the electric potential well shown in FIG. SD. In this way, they attain a total energy close to the bias potential 76.
The ion guide rods 11 extend both through the second 30 and third 40 pumping stages without any interruptions; they allow ions to flow freely in the forward and backward directions in the ion guide with close to 1003'0 efficiency. As ions move backwards towards the conical lens 19, the higher gas density moving in the forward direction prevents the ions from hitting the walls of the conical lens. The ions are efficiently brought to thermal equilibrium by these multiple collisions with residual or bath gas molecules while ions front the ion source are constantly filled into the trap through the aperture 13. The higher pressure in the vacuum stage 30 also allows ions to go back and forth multiple times inside the ion guide. As a result, the ion guide exit lens voltage 78 can be adjusted freely not only higher than the bias voltage 76, but also higher than the conical lens voltage 75. If the higher pressure region 71 was absent in the ion guide, a voltage setting 78 higher than 75 would have crashed the ions into the conical lens 19 after a single pass. Without the higher pressure region 71, the voltage settings 75, 76 and would be more critical and difficult to set with respect to each other for efficient trapping of the ions in the ion guide.
As the voltage on the exit lens 15 is switched from level 78 to 77 for a short duration (of the, order of microseconds), high density ion bunches are extracted collision free from the low pressure storage region 72 and injected into the orthogonal time-of flight analyzer. The mechanism for the storage mode of operation can be seen in FIG. 4. The ions are subsequently accelerated by means of additional electrodes 16 and 17. These electrodes in the present system are held at constant potentials, but they can be switched synchronously to the switching of the lens 15. After being pulsed out of the region 72, all ions of the packet originally extracted will have in first order approximation the same final kinetic energy qUo, where Uo is the total accelerating potential difference between the ion guide bias voltage 76 and the time-of flight repeller lens voltage when the field is off in the pulsing region 26. Then, ions of a specific mass to charge ratio will have a final velocity which is proportional to the reciprocal square root of this ratio:
2xgx va=kIx m (1) Here, k, is a constant, q=ze is the charge of the ion, and m is its mass. Ions will travel a distance L to arrive at the same point in the pulsing region 26 after a certain time T shown by k2 is a constant that takes into account the ion acceleration process. Hence, ions with a different m/z ratio will pass a point in region 26.
i z kl ZS
Accordingly, the initial ion package is spread out in space along the region in the direction of the ion beam.
FiG. 6 shows the driving mechanism and the timing sequence between the ion guide exit lens 15 and the time-of flight repeller lens 23 for a single cycle, i.e. a single mass spectral scan. The trace 83 shows the ion guide exit lens voltage status switching between the two voltage levels 77 and 78 and the trace 82 shows the repeller lens voltage status switching between the two levels 79 and 80. The power supply 91 sets the desired upper and lower voltage levels to be delivered to the lenses at all times. The electrically isolated fast switching circuitry 92 synchronously controls the desired voltage levels of the len electrode iS and the repeller plate 23 to be switched back and forth during the designated time intenials controlled by the pulse and delay generating device 93, which is an accurate timing device, which in turn is controlled by the user interface.
As an example to the ion storage mode of operation, let us again use the same mixture of ions Ml, M2, and M3 of ionic masses 997, 508 and 118 as used above in continuous mode of operation. As shown in FIG. a, and FIG. 6 the pulsed ion beam of duration tl from the region 72 is injected between the parallel plates 23 and 24 when the plates are initially held at the absence of an electric field, i.e. voltage level 79 on the repeller lens 23. According to the above equation (3), Lighter ions moving faster than the heavier ions, the three masses will start to separate from each other in the region 26. After a certain variable delay t2, the electric field in the region 26 is pulsed on for a short period of time t3 by the repeUer plate 23. The delay time t2 can be changed to allow different sections of the original ion beam i.e. different m/z packages, to acxelerate perpendicular to their original direction towards the flight tube 35 to be detected for mass analysis. In this example, a delay time t2 was chosen to pulse only a narrow range of ions centered around mass (M=) 53 which were accelerated in the direction 63 at the instant the field was turned on. At the same instant , both the masses M, 52 and M3 54 will hit the sides of the lenses moving in the approximate direction 62 and 64 and will not be detected by the mass analyzer.
The range of the detectable m/z window around a certain mass can be adjusted with several parameters. For a fixed exit lens pulse width tl and a delay time t2, the width of the mesh aperture 38 and the detector 36, for example, determines the m/z packet size along the direction 21 that is allowed to pass. The wider the aperture size on the mesh 38 and the detector 36, the larger will be the detected mass range. In addition, the pulse width tl of the lens 15 can be kept longer to sample a wider mass range of ions coming from the part of the ion guide that is further inside and away from the exit lens 15.
As the pulse width tl of the lens 15 is kept longer, multiple time-of flight ejection pulses are possible for one ion trap extraction cycle approaching the continuous mode of operation.
FIGS. 7A and 7B show the actual experimental results acquired using both the continuous and ion storage mode of operations for a sample using a mixture of ions used in the above examples. The actual sample was a mixture of three compounds Valise, tri-tyrosine, and hexa-tyrosine. Upon electrospray ionization of this mixture, the predominant molecular ions with nominal masses 118, 508, and 99'7 are generated in the ionization source 10. The bottom trace of FIG. 7A shows all three of these ions detected and registered as peaks 73, 71, and 74 when the mass spectrometer was in the continuous mode of operation. The top trace mass spectrum in FIG. 7A shows the results when the mass spectrometer was changed to the ion storage mode of operation. Both modes were acquired in similar experimental conditions. The acquisition rate i.e. the repetition rate counted by the repeller lens was per second. Each trace represents 4100 full averaged scans. As seen from the top spectral trace, there is only one predominant registered peak 72 in the spectrum. This peak corresponds to a molecular ion 508 enhanced in signal strength by about a factor of ten with respect to the peak 71 in continuous mode of operation. For the reasons explained in above examples, both of the molecular ions 118 and 997 are absent from the ion storage mode spectral trace as expected. The signal intensity increase comes from the fact that all of the ions that would otherwise be lost in the continuous ion mode were actually being stored in the ion guide for the next scan. According to the above example, fox the continuous mode of operation, the approximate duty cycle calculated for the 508 peak at 8,200 scans/s would be 9% i.e. one out of every twelve ions being detected. As the experimental results suggest in the ion storage mode of operation at 8,200 scans/s in FIG. 7A, most of the lost ions predicted in the continuous ion mode were recovered. FIG. 7B shows the same spectral traces, except the m/z region is expanded between 500 and 520 to show the isotopic peaks in more detail. The slight shift between the peaks 71 and 72 are due to the different tuning conditions of the ions by the lenses 16 and 17 that lands the ions in different position in the acceleration region 26. These differences resulted in the slight arrival time shifts of the ions on the detector resulting in different mass assignments.
Consequently, in summary and in conclusion, an improved apparatus for analyzing ionic species using a time-of flight mass analyzer is provided herein. In the preferred embodiment, the apparatus, has an atmospheric pressure ionization source which produces ions for transmission to a time-of-flight mass analyzer. The apparatus. has a two dimensional ion guide enhancing the efficiency of transmission of the ions, operating between the atomospheric pressure ion source and the time-of-flight mass analyzer, the ion guide having a set of equally spaced, parallel, multipole rods and operating in 1g the RF-only mode of operation, having an ion aWance section where the ions enter said ion guide and ion exit section where the ions exit the ion guide, and having an ion entrance lens placed at the ion entrance section and an ion eatit lens at the ion exit section. The ion guide is positioned such that the ion entrance section of the ion guide is placed in a region where background gas presstue is at viscous flow, and such that the presstus along the ion guide at the ion exit section drops to molecular flow pressure regimes without a break in the structure of the ion guide. The ion guide is operated in the ion storage mode using a fast vohage switching device to switch voltage levels of the ion guide exit lens. The apparatus further has a time of light acceleration region the ions are pulsed out momentarily to be mass analyzed, witty the ions being injected into the time-of flight acceleration region in a direction orthogonal to the diraxion of the acceleration field of the time-of flight acceleration region.
A detector is also provided where the ions are mass analyzed according to their arrival times, and an accurate timing device is provided that synchronizes the voltage swit,;h device, and which determines the respective voltage levels and the duration of the voltage levels of the ion guide exit lens and the time-of flight acceleration field to each other.
Ahhough the invention has been described in terms of specaflc preferred embodiments, it will be obvious and understood to one of ordinary skill in the art that various modif rations and substitutions are contemplated by the invention disclosed herein and that all such modifications and substitutions are included within the scope of the invention as defined in the appended claims.
References Cit~,~d:
The following references have been referred to above:

U.S. Patelrt Documents:
5,179,278 Jan. IZ,I993 D. J. Douglas 2,685,035 July 27, 1954 W. C. Wiley foreign Patent Documents:
SU 1681340 A1 Feb. 25, 1987 USSR Patent Dodonov et al.
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Conference, Amsterdam (1991).

G.G Dolnikowski, M.J. Kristo, C.G. Enke, and J.T. Dawson, Intl. Jour. of Mass Spec. Ion Proc., 82, p.l-1S, (1988), Ion Trapping Technique for Ion/Molecule Reaction Studies in the Center Quadrupole of a Triple Quadrupole Mass Spectrometer.
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93,323(1989).
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Claims (29)

1. An apparatus for analyzing chemical species comprising:
a time-of-flight mass analyzer with an ion pulsing region having a pulsing axis and a detector, an ion source configured external to said ion pulsing region of said time-of-flight mass analyzer for producing ions from said chemical species, a multipole ion guide, said ion guide having an axis and an entrance end where said ions enter said ion guide from said ion source and an exit end where said ions exit said ion guide, means to controllably trap ions in said ion guide and controllably release ions from said ion guide, means to transfer said released ions into said ion pulsing region, means for pulsing said ions transferred into said ion pulsing region into said time-of-flight mass analyzer for mass analysis, and means for detecting said mass analyzed ions with said detector.

2. An apparatus according to claim 1, wherein said mass analyzer contains a reflectron to compensate for energy distribution of ions in said ion pulsing region.

3. An apparatus according to claim 1, wherein said multipole ion guide is configured as a quadrupole.

4. An apparatus according to claim 1, wherein said multipole ion guide is configured as a hexapole.

5. An apparatus according to claim 1, wherein said multipole ion guide is configured with eight or more rods.

6. An apparatus according to claim 1, wherein said multipole ion guide is configured with at least two segments.

7. An apparatus according to claim 1, wherein said transferred ions are pulsed substantially in the orthogonal direction into said time-of-flight mass analyzer.

8. An apparatus according to claim 1, wherein the axis of said multipole ion guide is configured substantially perpendicular to the axis of said time-of-flight mass analyzer.

9. An apparatus according to claim 1, wherein the axis of said multipole ion guide is configured substantially parallel to said pulsing axis.

10. An apparatus according to claim 1, wherein said ions enter said ion guide during said ion trapping and ion release.

11. An apparatus according to claim 1, wherein only a portion of said ions trapped in said ion guide are released for each said time-of-flight pulse.

12. An apparatus according to claim 1, wherein said time-of-flight pulsing region is comprised of flat plate lens elements.

13. An apparatus according to claim 1, wherein only DC voltage levels are applied to a flat lens elements in said time-of flight pulsing region.

14. An apparatus according to claim 1, wherein said means to transfer said released ions into said pulsing region comprises electrostatic lenses in the region of said exit end.

15. An apparatus according to claim 1, wherein said means to transfer said released ions into said pulsing region comprises a segmented ion guide section.

16. An apparatus according to claim 1, wherein said multipole ion guide extends continuously into more than one vacuum pumping stage.

17. An apparatus as claimed in claim 1, wherein said ion pulsing region is bounded by flat plate electrodes positioned substantially perpendicular to the pulsing axis.

18. An apparatus according to claim 17, wherein said transferred ions are pulsed into said ion pulsing region by creating an accelerating electric field between said flat plate electrodes.

19. An apparatus according to claim 17, wherein said means to controllably release said trapped ions in said ion guide can produce a short duration ion packet comprised of a portion of said ions initially trapped in said ion guide.

20. An apparatus according to claim 18 wherein said means for pulsing ions transferred into said ion pulsing region comprises a variable timing means which can delay the time period when said ions are released from said ion guide to when voltage is applied to said ion pulsing region flat plate electrodes to pulse said transferred ions into said time-of flight mass analyzer for mass analysis.

21. An apparatus according to claim 1, further comprising a bias voltage applied to said ion guide, and wherein said means to trap ions in said ion guide comprises means to change the ion guide bias voltage relative to the voltage applied to lens elements positioned in said ion guide exit region.

22. A method for analyzing chemical species comprising:
utilizing a time-of flight mass analyzer with an ion pulsing region having a pulsing axis and a detector, an ion source located external to said ion pulsing region, a multipole ion guide having an ion guide entrance and exit ends, lens elements positioned proximal to said ion guide entrance and exit ends, producing ions from a sample substance in said external ion source, directing said ions into said entrance end of said multipole ion guide, trapping said ions in said multipole ion guide, releasing said ions from said multipole ion guide, transferring said ions through said lens elements into said pulsing axis, pulsing said ions into said time-of flight mass analyzer for mass analysis, and detecting said mass analyzed ions with said detector.

23. A method according to claim 22, wherein said mass analyzer contains a reflectron.

24. The method according to claim 22, wherein a two dimensional ion guide axis is configured perpendicular to the pulsing axis.

25. The method according to claim 22, wherein a two dimensional ion guide axis is configured parallel to the pulsing axis.

26. A method for analyzing chemical species comprising:
utilizing a time-of flight mass analyzer with an ion pulsing region comprised of flat plate lens elements and a detector, an ion source located external to said ion pulsing region, a multipole ion guide having an entrance end and an exit end, lens elements positioned proximal to said ion guide entrance and exit ends, producing ions from a sample substance in said external ion source, directing said ions into said entrance end of said multipole ion guide, trapping said ions in said multipole ion guide, releasing said ions from said multipole ion guide, transferring said ions through said lens elements into said ion pulsing region, pulsing said ions into said time-of flight mass analyzer for mass analysis, and detecting said mass analyzed ions with said detector.

27. An apparatus for analyzing chemical species comprising:
a time-of flight mass analyzer with an ion pulsing region and a detector, an ion source for producing ions forming an ion beam from said chemical species, a two-dimensional multipole ion guide having an entrance end where ions enter said ion guide from said ion source and an exit end where ions exit said ion guide, said two-dimensional multipole ion guide functioning as a two-dimensional ion trap, wherein said two-dimensional multipole ion guide comprises a plurality of spaced apart rods parallel to each other and extending from said entrance end to said exit end, said ion beam having an axis thereof which is parallel to said spaced apart rods, means for transferring said ions from said multipole ion guide into said pulsing region;

means for pulsing said ions transferred into said pulsing region into said time-of flight mass analyzer for mass analysis, and means for detecting said mass analyzed ion.

28. An apparatus as set forth in claim 27 comprising means to control the timing of said means for pulsing said ions transferred into said pulsing region.

29. An apparatus as set forth in claim 27 wherein said ions in said multipole ion guide are scanned at a scan rate sufficiently rapid to prevent excessive charge buildup in said multipole ion guide.