Mass spectrometer

Abstract

The mass spectrometer (1) provides an ionization chamber (11) therein with: a probe (15) having a sample to be measured flow path (155) for spraying a sample to be measured; and a standard sample flow path (255) for spraying a standard sample used for the calibration of the mass-to-charge ratio of the mass spectrum into the ionization chamber. The standard sample is intermittently introduced into the ionization chamber via a pulse valve (216). Thus, mixing of the sample to be measured and the standard sample can be prevented, while the timing according to which the standard sample is introduced can be appropriately controlled. It also becomes possible to acquire an accurate mass spectrum for each sample to be measured even in the case where a number of types of samples to be measured are introduced into the ionization chamber one after another over a short period of time.

Claims

1. A mass spectrometer, comprising: an ionization chamber where a sample is ionized, and a mass spectrometry unit into which ions are introduced from the ionization chamber, wherein said ionization chamber has a housing that provides a space inside the housing, a probe having a sample to be measured flow path in order to spray a sample to be measured into the inside of said ionization chamber is attached to said housing, and an ion introducing tube is created in said housing so that the inside of said ionization chamber and the inside of the mass spectrometry unit communicate, a mass spectrum value that is gained by measuring a sample to be measured is calibrated using a mass spectrum value that is gained by measuring the standard sample, and the mass spectrometer further comprises a standard sample flow path that sprays the standard sample into the inside of said ionization chamber, and a pulse valve that is arranged in a standard sample flow path so as to introduce the standard sample intermittently, and said standard sample flow path has a nozzle arranged in such a manner that said standard sample is sprayed between the spraying nozzle of said sample to be measured flow path and said ion introducing tube with respect to a blowing direction of the sample to be measured that has been sprayed from the spraying nozzle.

2. The mass spectrometer according to claim 1, characterized in that said standard sample flow path is the same flow path as a dry gas flow path that sprays a dry gas.

3. A mass spectrometer, comprising: an ionization chamber where a sample is ionized, and a mass spectrometry unit into which ions are introduced from the ionization chamber, wherein said ionization chamber has a housing that provides a space inside the housing, a probe having a sample to be measured flow path in order to spray a sample to be measured into the inside of said ionization chamber is attached to said housing, and an ion introducing tube is created in said housing so that the inside of said ionization chamber and the inside of the mass spectrometry unit communicate, a mass spectrum value that is gained by measuring a sample to be measured is calibrated using a mass spectrum value that is gained by measuring a standard sample, and the mass spectrometer further comprising a standard sample flow path that is branched from a first branching point in a middle of said sample to be measured flow path and into which a standard sample is intermittently introduced via a first pulse valve; and a flow path that is branched from a second branching point in a rear stage father from a spraying location of the probe than the first branching point in the middle of said sample to be measured flow path and into which a gas mobile phase is injected intermittently via a second pulse valve, wherein a sample to be measured and a standard sample are introduced alternately with a gas mobile phase in between the sample to be measured and the standard sample so that the sample to be measured and the standard sample are not be mixed with each other.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a schematic diagram showing the structure of the liquid chromatograph mass spectrometer using an ESI method according to the first embodiment of the present invention;

(2) FIG. 2 is a schematic diagram showing the structure according to the second embodiment of the present invention;

(3) FIG. 3 is a schematic diagram showing the structure according to the third embodiment of the present invention;

(4) FIG. 4 is a schematic diagram showing the structure of an example of a liquid chromatograph mass spectrometer using an ESI method;

(5) FIG. 5A is a side diagram showing a probe;

(6) FIG. 5B is a cross-sectional diagram showing an enlargement of A in FIG. 5A;

(7) FIG. 6 is a graph showing the relationship between the time and the amount of standard sample that has been discharged into the inside of the ionization chamber; and

(8) FIG. 7 is a diagram illustrating an example of a flow path when mobile phases are injected.

DESCRIPTION OF EMBODIMENTS

(9) In the following, the embodiments of the present invention are described in reference to the drawings. The present invention is not limited to the below-described embodiments, and various modifications can, of course, be included as long as the gist of the invention is not deviated from.

(10) <First Embodiment>

(11) FIG. 1 is a schematic diagram showing the structure of the liquid chromatograph mass spectrometer using an ESI method according to the first embodiment. Here, the same symbols are attached to the same components as in the above-described conventional liquid chromatograph mass spectrometer 201.

(12) A liquid crystal chromatograph mass spectrometer 1 is provided with an LC unit 2, a probe (ion source for sample to be measured) 15, a probe (ion source for standard sample) 215, a pulse valve 216, an ionization chamber 11 having a chamber (housing) 110, a first middle chamber 12 that is adjacent to the ionization chamber 11, a second middle chamber 13 that is adjacent to the first middle chamber 12, a mass spectrometry chamber (MS unit) 14 that is adjacent to the second middle chamber 13, and a computer 40 that controls the entirety of the liquid chromatograph mass spectrometer 1.

(13) The ionization chamber 11 is provided with a chamber 110 in a rectangular parallelepiped form of 13 cm13 cm12 cm, and the chamber 110 has an upper wall, a partition (rear wall), a front wall, a right side wall, a left side wall and a lower wall. Thus, the space inside the ionization chamber 11 is surrounded by the upper wall, the partition, the front wall, the right side wall, the left side wall and the lower wall.

(14) A circular opening that runs in the forward and backward directions (X direction) is created in the front wall so that the probe 15 is attached in this opening.

(15) A circular opening that runs in the upward and downward directions (Z direction) is created in the lower wall, and the probe 215 is attached in this opening.

(16) The probe 215 has the same shape as the probe 15 in FIG. 5A and has a double tube structure so that the standard sample that is supplied through the standard sample flow path 255 is jetted from the inside of the circular tube. Meanwhile, the nitrogen gas that is supplied from the nebulizing gas flow path 256 is jetted between the circular tube and the nozzle in a circular tube form. As a result, the jetted standard sample is converted to an atomized state through the collision with the nebulizing gas that is jetted around the circular tube, and thus is sprayed.

(17) In addition, a high voltage of several kV is applied to the tip of the nozzle from the wires connected to the voltage supply so that ionization can be carried out.

(18) A standard sample where the peaks of fragment ions regularly appear is useful, and a standard sample having a low molecular amount such as PFTBA (perfluorotributylamine) is used in a region of a low mass-to-charge ratio (m/z), for example. Meanwhile, a standard sample having a high molecular amount such as triazine (tris-(perfluoroheptyl)-s-triazine) and PFK (perfluorokerosene) are used in a region of a high mass-to-charge ratio (m/z) where the mass-to-charge ratio (m/z) is approximately 700 or greater.

(19) The partition is arranged so as to partition the inside of the ionization chamber 11 from the inside of the first middle chamber 12. A solvent releasing tube (ion introducing tube) 19 in a circular tube form (having an outer diameter of 1.6 mm and an inner diameter of 0.5 mm) is formed in the partition, and a dry gas flow path 50 is formed so as to cover the surrounding of the solvent releasing tube 19. As a result, the inside of the ionization chamber 11 and the inside of the first middle chamber 12 communicate via the solvent releasing tube 19. In addition, the solvent releasing tube 19 functions to accelerate solvent releasing and ionization through the application of heat and through the collision when ions and microscopic droplets of the sample that have been sprayed from the probe 15 or the probe 215 pass through the inside of the solvent releasing tube 19. Furthermore, the solvent releasing tube 19 is dried by a dry gas when wet with a sample to be measured or a standard sample.

(20) The nozzle of the probe 15 is directed toward the front (X direction) so as to face the entrance of the solvent releasing tube 19 at a predetermined distance (2 cm, for example) in between. In addition, the nozzle of the probe 215 is directed upward (Z direction) so as to spray a standard sample between the nozzle of the probe 15 and the entrance of the solvent releasing tube 19 at a predetermined flow rate (0.1 ml/min, for example). As a result, the standard sample blows away the sample to be measured that is directed toward the solvent releasing tube 19 when the standard sample is sprayed so that only the standard sample is introduced into the solvent releasing tube 19.

(21) A drain 30 is created in the lower wall so that unnecessary samples can be discharged to the outside through the drain 30.

(22) An example of the pulse valve 216 arranged in the standard sample flow path 255 is one that is made by Musashi Engineering Co., LTD. Thus, the pulse valve 216 is switched by a control signal from the computer 40 so as to be either in an open state where a standard sample is introduced into the standard sample flow path 255 or in a closed state where a standard sample is not introduced.

(23) The computer 40 is provided with a CPU 41, a display device 42, an input device 43 and a memory 44. In addition, the processes in the CPU 41 can be described as function blocks that include an analysis control unit 41a that controls quadrupoles 16 and 17 through the input operation by a user, a detector control unit 41b that acquires an intensity signal from the detector 18, a generation unit 41c that generates a mass spectrum, which is then stored in the memory 44, and a pulse valve control unit 41d that controls the pulse vale 216 through the input operation by a user.

(24) The pulse valve control unit 41d controls the pulse valve 216 on the basis of the input signal from the input device 43. In the case where the period of time between the measurement start time t.sub.1 and the measurement end time t.sub.2 is 31 minutes, and an input signal for the open state is inputted for one minute for every nine minutes, for example, a pulse signal (control signal) for introducing a standard sample of a predetermined amount is outputted to the pulse valve 216 from t.sub.1 to t.sub.1+1 minute, from t.sub.1+10 minutes to t.sub.1+11 minutes, from t.sub.1+20 minutes to t.sub.1+21 minutes, and from t.sub.1+30 minutes to t.sub.1+31 minutes, which is four times in total (see FIG. 6). Here, it is possible to change the contents of the conditions for the pulse signal through the input operation by a user, and thus, the operation time (introduction time) and the period of time of introduction (amount of introduction) can be set freely.

(25) The generation unit 41c controls the generation of a mass spectrum on the basis of the intensity signal acquired by the detector control unit 41b and allows the memory 44 to store the mass spectrum. This operation is in sync with the operation of the pulse valve 216 on the basis of the input signal inputted into the pulse valve control unit 41d so that the mass spectrum of a sample to be measured and the mass spectrum of a standard sample are separately stored in the memory 44. Thus, the values measured for each peak that are gained by measuring the sample to be measured (mass-to-charge ratio (m/z) and intensity value) are determined using the peaks that are gained by measuring the standard sample, and the mass spectrum of the standard sample of which the time is closest to the time when the mass spectrum of a sample to be measured is gained is selected as the mass spectrum of the standard sample. For example, the mass spectrum of the standard sample that is gained from t.sub.1 to t.sub.1+1 minute is used as the mass spectrum of a sample to be measured that is gained from t.sub.1+1 minute to t.sub.1+5 minutes, the mass spectrum of the standard sample that is gained from t.sub.1+10 minutes to t.sub.1+11 minutes is used as the mass spectrum of a sample to be measured that is gained from t.sub.1+5 minutes to t.sub.1+10 minutes and from t.sub.1+11 minutes to t.sub.1+15 minutes, the mass spectrum of the standard sample that is gained from t.sub.1+20 minutes to t.sub.1+21 minutes is used as the mass spectrum of a sample to be measured that is gained from t.sub.1+15 minutes to t.sub.1+20 minutes and from t.sub.1+21 minutes to t.sub.1+25 minutes, and the mass spectrum of the standard sample that is gained from t.sub.1+30 minutes to t.sub.1+31 minutes is used as the mass spectrum of a sample to be measured that is gained from t.sub.1+25 minutes to t.sub.1+30 minutes. As a result, it is possible to acquire a precise mass spectrum for each sample to be measured even in the case where a number of types of samples to be measured are introduced into the ionization chamber 11 one after another over a short period of time.

(26) As described above, in the liquid chromatograph mass spectrometer 1 according to the first embodiment, the time at which a standard sample is introduced can be controlled appropriately while preventing a sample to be measured and the standard sample from mixing.

(27) It is also possible to adjust the concentration of the standard sample that is introduced into the solvent releasing tube 19 by changing the amount of the standard sample that is introduced into the standard sample flow path 255 through the control of the pulse valve 216 at the time of the introduction of the standard sample.

(28) <Second Embodiment>

(29) FIG. 2 is a schematic diagram showing the configuration of the liquid chromatograph mass spectrometer using an ESI method according to the second embodiment. Here, the same symbols are attached to the same components as in the liquid chromatograph mass spectrometers 1 and 201.

(30) The liquid chromatograph mass spectrometer 301 is provided with an LC unit 2, a probe (ion source for sample to be measured) 15, a pulse valve 216, an ionization chamber 11 having a chamber (housing) 210, a first middle chamber 12 that is adjacent to the ionization chamber 11, a second middle chamber 13 that is adjacent to the first middle chamber 12, a mass spectrometry chamber (MS unit) 14 that is adjacent to the second middle chamber 13, and a computer 340 that controls the entirety of the liquid chromatograph mass spectrometer 301.

(31) The pulse valve 216 is arranged in a dry gas flow path (standard sample flow path) 51. As a result, the standard sample blows away the sample to be measured directed toward the solvent releasing tube 19 when the standard sample is sprayed, and thus, only the standard sample is introduced into the solvent releasing tube 19. In addition, the pulse valve 216 is switched when a control signal is inputted from the computer 340 so as to be either in an open state where a standard sample is introduced into the dry gas flow path 51 or in a closed state where a standard sample is not introduced.

(32) The computer 340 is provided with a CPU 341, a display device 42, an input device 43 and a memory 44. Furthermore, the processes in the CPU 341 can be described as function blocks that include an analysis control unit 41a that controls quadrupoles 16 and 17 through the input operation by a user, a detector control unit 41b that acquires an intensity signal from the detector 18, a generation unit 341c that generates a mass spectrum, which is then stored in the memory 44, and a pulse valve control unit 41d that controls the pulse vale 216 through the input operation by a user.

(33) The generation unit 341c controls the generation of a mass spectrum on the basis of the intensity signal acquired by the detector control unit 41b and allows the memory 44 to store the mass spectrum. Thus, the mass-to-charge ratio (m/z) for each peak that is gained by measuring a sample to be measured is determined by using the peak that is gained by measuring a standard sample. The two mass spectra, one is before and the other is after the time when the mass spectrum for a sample to be measured is gained, that sandwich the time at which the mass spectrum of the sample to be measured is gained are used as the mass spectra of the standard sample.

(34) As described above, in the liquid chromatograph mass spectrometer 301 according to the second embodiment, the time at which a standard sample is introduced can be controlled appropriately by preventing a sample to be measured and the standard sample from mixing. It is also possible to adjust the concentration of the standard sample that is introduced into the solvent releasing tube 19 by changing the amount of the standard sample that is introduced into the dry gas flow path 51 through the control of the pulse valve 216 at the time of the introduction of the standard sample.

(35) <Third Embodiment>

(36) FIG. 3 is a schematic diagram showing the configuration of the liquid chromatograph mass spectrometer using an ESI method according to the third embodiment. Here, the same symbols are attached to the same components as in the liquid chromatograph mass spectrometer 1.

(37) The liquid chromatograph mass spectrometer 401 is provided with an LC unit 2, a probe (ion source for sample to be measured) 15, a pulse valve 216, a pulse valve 416, an ionization chamber 11 having a chamber (housing) 210, a first middle chamber 12 that is adjacent to the ionization chamber 11, a second middle chamber 13 that is adjacent to the first middle chamber 12, a mass spectrometry chamber (MS unit) 14 that is adjacent to the second middle chamber 13, and a computer 440 that controls the entirety of the liquid chromatograph mass spectrometer 401.

(38) The pulse valve 216 is arranged in the sample to be measured flow path (standard sample flow path) 155. Thus, the pulse valve 216 is switched when a control signal is inputted from the computer 440 so as to be either in an open state where a predetermined amount of standard sample is introduced into the sample to be measured flow path 155 or in a closed state where a standard sample is not introduced.

(39) In addition, the pulse valve 416 is arranged in the sample to be measured flow path 155 in a stage before the pulse valve 216 in the sample to be measured flow path 155. Thus, the pulse valve 416 is switched when a control signal is inputted from the computer 440 so as to be either in an open state where a predetermined amount of gas (mobile phase) is introduced into the sample to be measured flow path 155 or in a closed state where a gas (mobile phase) is not introduced.

(40) As a result, a gas (mobile phase) can be injected between a sample to be measured and a standard sample in the sample to be measured flow path 155 so that the sample to be measured and the standard sample do not mix in the sample to be measured flow path 155 (see FIG. 7).

(41) The computer 440 is provided with a CPU 441, a display device 42, an input device 43 and a memory 44. In addition, the processes in the CPU 441 can be described as function blocks that include an analysis control unit 41a that controls quadrupoles 16 and 17 through the input operation by a user, a detector control unit 41b that acquires an intensity signal from the detector 18, a generation unit 41c that generates a mass spectrum, which is then stored in the memory 44, and a pulse valve control unit 441d that controls the pulse vale 216 and the pulse valve 416 through the input operation by a user.

(42) As described above, in the liquid chromatograph mass spectrometer 401 according to the third embodiment, the time at which a standard sample is introduced can be controlled appropriately by preventing a sample to be measured and the standard sample from mixing. In addition, a gas (mobile phase) can be injected so that one sample to be measured and another sample to be measured do not mix in the sample to be measured flow path 155, and therefore, a number of LC units may be linked to the sample to be measured flow path 155.

(43) <Other Embodiments>

(44) (1) Though the liquid chromatograph mass spectrometer 301 has a configuration where the pulse valve 216 is arranged in the dry gas flow path 51 as described above, such a configuration is possible where the pulse valve 216 is arranged in the nebulizing gas flow path 156.

(45) (2) Though the configurations of liquid chromatograph mass spectrometers are described above, the configurations may be applied to gas chromatograph mass spectrometers.

INDUSTRIAL APPLICABILITY

(46) The present invention is applicable to a calibration method for a mass spectrometry unit in a chromatograph mass spectrometer, for example.

REFERENCE SIGNS LIST

(47) 1 liquid chromatograph mass spectrometer

(48) 11 ionization chamber

(49) 14 mass spectrometry chamber (mass spectrometry unit)

(50) 15 probe

(51) 19 solvent releasing tube (ion introducing tube)

(52) 110 chamber (housing)

(53) 155 sample to be measured flow path

(54) 216 pulse valve

(55) 255 standard sample flow path