Time-of-flight mass spectrometer for conducting high resolution mass analysis

Abstract

A first mass analysis is executed in a condition that gas is not introduced into a loop-flight chamber (4), and a time-of-flight spectrum obtained in a data processor (12) is stored in a storage unit (13). Next, a second mass analysis is executed on the same sample as the one used in the first mass analysis in a condition that a valve (8) is opened and helium gas (He) is introduced into the loop-flight chamber (4), and the time-of-flight spectrum is obtained in the data processor (12). If different kinds of ions having the same m/z value exit, these ions form a single peak in the first time-of-flight spectrum, while these ions appear as separate peaks in the second time-of-flight spectrum even though they have the same m/z value. This is because, in the second mass analysis, the ions collide with the gas and have different times of flight depending on their difference in size. A spectrum comparator (14) judges a change in the position or shape of the peak by comparing the two spectra, and outputs information relating to the difference in the size of the ions (the molecular structure, charge state, or molecular class of the ions), and the like. Accordingly, a wider variety of information than ever before can be provided.

Claims

1. A time-of-flight mass spectrometer conducting a mass analysis by providing a predetermined amount of kinetic energy to an ion to make the ion fly in a flight space, comprising: a flight chamber having the flight space in which an ion having a smaller mass-to-charge ratio flies at a higher speed than an ion having a larger mass-to-charge ratio, and a flight time required for an ion to fly through the flight space is measured and a mass-to-charge ratio of the ion is determined based on the flight time; a gas introduction member for introducing predetermined gas into at least a part of the flight space where ions are separated according to their flight time both in a condition that the gas is not introduced and in a condition that the gas is introduced; a control member for executing a mass analysis on a same sample both in a condition that the gas is not introduced and in a condition that the gas is introduced by the gas introduction member, respectively, and obtaining respective time-of-flight spectra from each mass analysis executed in the two conditions; and an ion identification member for identifying each ion among various kinds of ions having a same m/z value by making a comparison on at least one of a position, shape, or strength of peaks appearing in two time-of-flight spectra obtained under the control of the control member.

2. The time-of-flight mass spectrometer according to claim 1, wherein a multi-turn time-of-flight configuration for making ions to repeatedly fly in a same flight path is adopted.

3. The time-of-flight mass spectrometer according to claim 1, wherein the predetermined gas is helium gas.

4. The time-of-flight mass spectrometer according to claim 2, wherein the predetermined gas is helium gas.

5. A time-of-flight mass spectrometer conducting a mass analysis by providing a predetermined amount of kinetic energy to an ion to make the ion fly in a flight space, comprising: an ion source; a flight chamber coupled to the ion source, wherein the flight chamber has the flight space such that an ion having a smaller mass-to-charge ratio flies at a higher speed than an ion having a larger mass-to-charge ratio, and a flight time required for an ion to fly through the flight space is measured and a mass-to-charge ratio of the ion is determined based on the flight time; a gas introduction member for introducing predetermined gas into at least a part of the flight space where ions are separated according to their flight time both in a condition that the gas is not introduced and in a condition that the gas is introduced; a control member for executing a mass analysis on a same sample both in a condition that the gas is not introduced by the gas introduction means and in a condition that the gas is introduced, respectively, and obtaining respective time-of-flight spectra from each mass analysis executed in the two conditions; and an ion identification member for identifying each ion among various kinds of ions having a same m/z value by making a comparison on at least one of a position, shape, or strength of peaks appearing in two time-of-flight spectra obtained under the control of the analysis execution control means.

6. The time-of-flight mass spectrometer according to claim 5, wherein the flight chamber includes a multi-turn time-of-flight configuration for making ions fly repeatedly in a same flight path.

7. The time-of-flight mass spectrometer according to claim 5, wherein the predetermined gas is helium gas.

8. The time-of-flight mass spectrometer according to claim 6, wherein the predetermined gas is helium gas.

9. A time-of-flight mass spectrometer conducting a mass analysis by providing a predetermined amount of kinetic energy to an ion to make the ion fly in a flight space, comprising: a loop-flight chamber; a gas introduction member for introducing predetermined gas into at least a part of the loop-flight chamber where ions are separated according to their flight speeds both in a condition that the gas is not introduced and in a condition that the gas is introduced; a control member for executing a mass analysis on a same sample both in a condition that the gas is not introduced by the gas introduction means and in a condition that the gas is introduced, respectively, and obtaining respective time-of-flight spectra from each mass analysis executed in the two conditions; and an ion identification member for identifying each ion among various kinds of ions having a same m/z value by making a comparison on at least one of a position, shape, or strength of peaks appearing in two time-of-flight spectra obtained under the control of the analysis execution control means.

10. The time-of-flight mass spectrometer according to claim 9, wherein the loop-flight chamber includes a multi-turn time-of-flight configuration for making ions fly repeatedly in a same flight path.

11. The time-of-flight mass spectrometer according to claim 9, wherein the predetermined gas is helium gas.

12. The time-of-flight mass spectrometer according to claim 10, wherein the predetermined gas is helium gas.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a schematic configuration diagram showing a multi-turn time-of-flight mass spectrometer according to an embodiment of the present invention.

(2) FIG. 2 is an explanatory diagram showing an analysis operation in the multi-turn time-of-flight mass spectrometer according to the present embodiment.

(3) FIG. 3 is the explanatory diagram showing the analysis operation in the multi-turn time-of-flight mass spectrometer according to the present embodiment.

(4) FIG. 4 is a schematic explanatory diagram showing an energy attenuation due to a collision of ions with gas.

EXPLANATION OF NUMERALS

(5) 1 . . . Ion Source 2 . . . Loop Orbit 3 . . . Sector-Shaped Electrode Pair 4 . . . Loop-Flight Chamber 5 . . . Detector 6 . . . Vacuum Chamber 7 . . . Gas Source 8 . . . Valve 9 . . . Voltage Application Unit 10 . . . Controller 11 . . . A/D Converter 12 . . . Data Processor 13 . . . Spectrum Storage Unit 14 . . . Spectrum Comparator 15 . . . Output Unit

BEST MODE FOR CARRYING OUT THE INVENTION

(6) A multi-turn time-of-flight mass spectrometer according to an embodiment of the present invention is described with reference to the attached drawings. FIG. 1 is a schematic configuration diagram showing the multi-turn time-of-flight mass spectrometer according to the present embodiment.

(7) In a vacuum chamber 6 evacuated by a non-illustrated vacuum pump, an ion source 1, a loop-flight chamber 4, and a detector 5 are disposed. Inside the loop-flight chamber 4, a plurality of sector-shaped electrode pairs 3 which define a loop orbit 2 are arranged. Into the loop-flight chamber 4, predetermined gas is supplied at a predetermined pressure from a gas source 7 at a time when a valve 8 is opened. The valve 8, the sector-shaped electrode pairs 3 and a voltage application unit 9 for applying a predetermined voltage to the ion source 1 are controlled by a controller 10. A detection signal detected by the detector 5 is converted by an A/D converter 11 to digital data at a predetermined sampling time interval, and the obtained data is processed by a data processor 12. The data processor 12 includes a spectrum storage unit 13 and a spectrum comparator 14 as functional blocks which are characteristic of the present embodiment, and the result of the processing is output from an output unit 15. As the predetermined gas prepared in the gas source 7, light inert gas is preferable for reasons which will be described later. Helium gas is used in the present embodiment.

(8) In the ion source 1, a sample molecule is ionized. The generated various kinds of ions are provided with predetermined initial energy and begin flying. It should be noted that, like a three-dimensional quadrupole ion trap or similar device, the ion source 1 may temporarily retain various kinds of ions generated in an outside area and concurrently provide energy to these ions at a predetermined timing so as to make the ions begin flying.

(9) The ions which begin flying from the ion source 1 serving as a starting point enter the loop-flight chamber 4 and are placed on the loop orbit 2 created by the effect of a plurality of sector-shaped electric fields respectively formed between the electrodes of a plurality of sector-shaped electrode pairs 3. The shape of the loop orbit 2 is not limited to the one illustrated in FIG. 1, but various shapes including an approximately elliptical shape and a figure eight are realizable. The ions are made to leave the loop orbit 2 after flying through the loop orbit 2 once or a plurality of times. The ions exit from the loop-flight chamber 4, and arrive at and detected by the detector 5 disposed outside of the loop-flight chamber 4. The various kinds of ions are provided with the same amount of kinetic energy and begin flying. This means that an ion having a smaller m/z value flies at a higher speed. For this reason, the ion having the smaller m/z value arrives at the detector 5 earlier. The larger the m/z value of an ion is, the later the ion arrives at the detector 5.

(10) In a condition that the valve 8 is closed so as to prevent helium gas from being introduced into the loop-flight chamber 4, an analysis operation is executed in the same manner as in the case of a conventionally known multi-turn time-of-flight mass spectrometer. Specifically, a flight distance Lto1 from a point where a certain ion departs from the ion source 1 to a point where the ion arrives at the detector 5 is:
Lto1=n.Math.L+Lin+Lout
where n is the number of turn of the ion in the loop orbit 2, L is the circumferential length of the loop orbit, Lin is the length of an entrance path, and Lout is the length of an exit path, as shown in FIG. 1. As the flight distance becomes longer, in other words, as the number of turns n increases, the mass resolving power is further improved.

(11) Next, the analysis operation characteristic of the multi-turn time-of-flight mass spectrometer according to the present embodiment is described with reference to FIGS. 2 and 3.

(12) As previously described, the controller 10 executes a first mass analysis on a sample in a condition that the valve 8 is closed, and a time-of-flight spectrum is obtained in the data processor 12. Here, for simplicity of the description, the case is considered where a single peak is obtained on the time-of-flight spectrum, which is shown in FIG. 2(a). Since the time-of-flight can be uniquely converted into the m/z value, when a mass spectrum is calculated from the time-of-flight spectrum shown in FIG. 2(a), one peak also appears on the mass spectrum. This is the peak due to a packet of ions having the m/z values that can be considered identical within a margin of error in the mass resolving power. In the conventional multi-turn time-of-flight mass spectrometer, the analysis is terminated at this point, after which the obtained mass spectrum is immediately analyzed and processed.

(13) On the other hand, in the multi-turn time-of-flight mass spectrometer according to the present embodiment, the time-of-flight spectrum obtained in the previously described first mass analysis is stored in the spectrum storage unit 13. Subsequently, the controller 10 opens the valve 8 to introduce helium gas into the loop-flight chamber 4 so that the inside of the loop-flight chamber 4 is kept at a predetermined gas pressure. Under this condition, a second mass analysis with respect to the sample identical to the one in the first mass analysis is implemented and the time-of-flight spectrum is again obtained in the data processor 12. The analysis conditions are made to be the same as those in the first mass analysis except for introducing helium gas in the loop-flight chamber 4 to keep the inside thereof at the predetermined gas pressure.

(14) For Example, though a nitrogen molecular dication (.sup.14N.sub.2.sup.2+) and a nitrogen atomic ion (.sup.14N.sup.+) are different kinds of ions from each other, they have the same m/z value. For this reason, they form the same single peak on the time-of-flight spectrum obtained in the previously described first analysis. It does not appear that the peak derives from plural kinds of ions. On the other hand, in the second mass analysis executed under the condition that helium gas is introduced into the loop-flight chamber 4 at an appropriate gas pressure, even such ions that have the same m/z value will have different times of flight if their sizes are different from each other.

(15) Now, consideration is given to the case where two kinds of ions having the same m/z value but different sizes are provided with the same kinetic energy and simultaneously introduced into a flight space, as shown in FIG. 3(a). When no gas exists in the flight space (i.e., when the space is in vacuum), the flight speed of the ions depends on the m/z value. Accordingly, no difference occurs in the time-of-flight (see FIG. 3(b)), and the two kinds of ions should arrive at the detector at the same time. In contrast, if helium gas exists in the flight space, the ions collide with the gas in the flight space and gradually lose kinetic energy. Accordingly, the flight speed of the ions slows down, i.e., the ions decelerate. The larger the size of an ion is, the larger the degree of deceleration is, since the larger ion has more opportunities to collide with gas. Therefore, as shown in FIG. 3(c), the difference occurs in the time-of-flight depending on the size of ions, and the ions respectively arrive at the detector at different points in time.

(16) The collision of ions with gas can be recognized as a collision between spherical objects, i.e., between an ion having a radius of R.sub.A and gas having a radius of R.sub.B, as shown in FIG. 4(a). This case can be considered using a further abstracted model as shown in FIG. 4(b). Specifically, this model regards an ion as a tiny point having an infinitely small radius, in which case the collision of the ion with the gas occurs when this tiny point passes through a circular region having a radius of R.sub.A+R.sub.B. The cross section of the circular region is called a collision cross section and given by (R.sub.A+R.sub.B).sup.2. When the point representing the ion passes through this region, the ion loses a portion of its kinetic energy due to an interaction with the gas (such as an attracting force or a repulsive force). On the other hand, when the ion bypasses the region, the ion does not undergo mutual interaction with the gas, and thus, the kinetic energy of the ion is maintained as it is. The collision cross section can be considered as an apparent size of the gas, viewed from the ion. The collision cross section for an ion practically depends on the molecular structure (shape) or charge state of the ion or the type of a functional group added on the ion, in addition to the size of the ion.

(17) As previously described, even if there are different kinds of ions having the same m/z value, these ions will have different times of flight if they differ from each other in size (or in any of the aforementioned factors that influence the collision cross section). Therefore, on the time-of-flight spectrum obtained by the second mass analysis, two peaks originating from the same m/z value separately appear as shown in FIG. 2(b). It can be assumed that component A, which appears earlier than component B, has, for example, a smaller size of ion than that of the component B which appears later. Accordingly, the spectrum comparator 14 compares a time-of-flight spectrum obtained in the first mass analysis with a time-of-flight spectrum obtained in the second mass analysis; specifically, the comparison is made in terms of the position, shape, strength or other properties of the peaks which appear on the respective time-of-flight spectra. In this example, since it is obvious that one peak is separated into two peaks, the judgment can be made that there are two kinds of ions that differ from each other in size, molecular structure, charge state, molecular class, and so on. The result of the judgment is outputted from the output unit 15.

(18) Furthermore, information relating to the quantities or molecular structures of a plurality of components can be obtained by analyzing the strength or temporal difference of the peaks separated in the spectrum comparator 14. It is possible to conduct the analysis for various materials contained in a sample more minutely and accurately by using the information and the mass spectrum obtained by the usual mass analysis (i.e., the first mass analysis).

(19) When a flying ion collides with gas, the ion may undergo collision induced dissociation under some conditions, to be divided into smaller fragments. If dissociation occurs, a discrimination of each ion among the different kinds of ions having the same m/z value becomes difficult. Therefore, it is preferable to perform the second mass analysis under a condition that makes the dissociation least likely to occur.

(20) With respect to the collision induced dissociation in which an ion having a kinetic energy collides with gas, it can be said that the heavier the gas is, the more likely it is to cause the collision induced dissociation. For this reason, helium gas, which is the lightest inert gas, is used to avoid collision induced dissociation in the previously described embodiment. Furthermore, if heavier gas, such as xenon, is introduced into the loop-flight chamber 4, the collision of an ion with gas can make a strong impact on the ion, causing the ion to significantly change its flight path, if not dissociated. It increases the possibility of the ion to run off the loop orbit 2. In contrast, the use of light gas prevents the collided ion from running off the loop orbit 2, advantageously reducing the loss of the ions during their flight.

(21) Another possible method for making the collision induced dissociation harder to occur is to reduce the amount of gas introduced into the loop-flight chamber 4. However, it requires a certain degree of amount of gas to be introduced into the loop-flight chamber 4 in order to cause the previously described difference in the time of flight to occur depending on the size of the ions. Accordingly, it is preferable to conduct a preliminary experiment to determine an appropriate gas pressure in the loop-flight chamber 4 at which the change in the positions or shapes of the peaks originating from the ions having different sizes can appear clearly and the problem of dissociation does not arise. The supplied amount of gas may be controlled in such a manner that the practical gas pressure in the loop-flight chamber 4 is maintained at the experimentally determined gas pressure.

(22) Still another method for making the collision induced dissociation harder to occur is to reduce the initial kinetic energy given to the ions released from the ion source 1. This will suppress the collision energy generated at a time when the ions collide with gas. However, if the initial kinetic energy is extremely reduced, the loss of ions during their flight increases. Furthermore, the time of flight is totally increased, elongating a time period required for the analysis. The increase in the number of turns could also cause some ions to lose their ability to fly on the way. Therefore, the present case also needs a preliminary experiment for determining the appropriate initial kinetic energy in advance.

(23) Although helium gas is introduced into the whole loop orbit 2 in the previous embodiment, it is possible, in principle, to introduce the gas into a limited part of the flight path of the ions. However, introducing the gas into the longest possible section of the flight path is advantageous in that the effect of the deceleration of the ions will be sufficiently obtained even if the amount of the introduced gas is small. This results in a noticeable change in the position or shape of the peak as shown in FIG. 2(b).

(24) Furthermore, the time-of-flight mass spectrometer according to the present invention can be applied not only to a multi-turn time-of-flight type mass spectrometer according to the previously described embodiment, but also to other types of time-of-flight mass spectrometers having various flight paths, including a linear-type flight path or a reflectron-type flight path. However, as it is clear in the previous description, it is preferable that the flight path into which gas is introduced is made to be as long as possible. In this point, the multi-turn time-of-flight type configuration is preferable. The term multi-turn time-of-flight type does not always mean that ions repeatedly fly in a closed orbit; it also includes a system that makes ions repeatedly reciprocate in a linear or curved orbit.

(25) Furthermore, it is clear that an appropriate change, modification, or addition within the range of the subject matter of the present invention is included in the scope of the claims of the present application.