JP2003223864A - Atmospheric pressure ionization mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an atmospheric pressure ionization mass spectrometer capable of reducing chemical noises and largely improving the efficiency of ion cleavage in MS/MS. <P>SOLUTION: By heating a space where adiabatic expansion takes place, i.e., an ion guiding space, the cooling of ions and gas is prevented. In addition, by heating the mass spectrometer itself, the excitation and cleavage of ions are helped. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention introduces a sample solution into an atmospheric pressure ion source such as an electrospray (ESI) to ionize it, and the ions generated by the ion source are passed through an ion guide arranged in a vacuum chamber. The present invention relates to an atmospheric pressure ionization mass spectrometer that conducts mass analysis by guiding it to a mass spectrometer. In particular, it relates to an atmospheric pressure ionization mass spectrometer capable of significantly reducing chemical noise and enhancing the efficiency of collision-induced dissociation (CID) in MS / MS.

[0002]

2. Description of the Related Art Recently, research in the field of biotechnology has been remarkable, and the research target is multi-limb. In particular, since proteins, peptides, DNA, etc. have extremely important functions in the living body, they have been the targets of research by many researchers. Generally, these organic compounds derived from living organisms are present only in trace amounts in a complex matrix. A liquid chromatograph directly coupled mass spectrometer (LC / MS device) has come to play an important role in analyzing an extremely small amount of a biological-related organic compound extracted from a living body. The LC / MS device is a device for separating a mixture by LC and performing qualitative and quantitative analysis with high sensitivity by MS. A typical ionization means used in LC / MS is electrospray ionization (ESI). ES
I is an ionization method under atmospheric pressure.
First disclosed in 96. Analysis of trace organic compounds by binding of ESI to a chromatograph such as capillary electrophoresis (CE) is disclosed by Smith et al. In USP 4842701. This ESI is known as a mild and highly sensitive ionization method, and is now widely used for the analysis of biological substances.

ESI operates as follows. Inner diameter 0.
A certain distance with a metal capillary of about 1 mm (about 10 mm)
A voltage of several kV is applied between the counter electrodes which are arranged at intervals. When the sample solution is introduced into the metal capillary and a high voltage is applied, charged fine droplets are discharged from the tip of the solution into the atmosphere. The generated charged droplets fly in the atmosphere toward the counter electrode according to the electric field, and repeatedly collide with atmospheric molecules. As a result, the charged droplets are mechanically crushed, the evaporation of the solvent from the surface of the droplets is promoted, and the charged droplets are rapidly atomized. Eventually, the ions in the charged droplets are released into the atmosphere. The ions fly toward the counter electrode in the atmosphere, pass through a thin tube or a fine hole provided in the counter electrode, and are guided to a high-vacuum mass spectrometer for mass analysis.

In order to achieve high sensitivity and stability in ESI, it is important to produce a large amount of charged droplets that are as uniform and fine as possible at the spraying stage. Therefore, as a technique for improving the ESI method, a method has been proposed in which a metal thin tube is inserted into a thin tube having a large inner diameter, a sample solution is caused to flow through the metal thin tube, and a spray gas is caused to flow between the two thin tubes. 1 ml / min due to promotion of vaporization from the droplet surface by heat exchange between the droplet and gas molecule and mechanical fragmentation due to friction between droplet and gas molecule
A stable solution can be sprayed. This technique was disclosed by Henion et al. In USP 4861988 and became known as Ion Spray. In ESI and Ion Spray,
Although atomization of fine droplets has been achieved by atomization into the atmosphere, sometimes huge droplets are formed in the atomized droplets. When these giant droplets are introduced into a mass spectrometer, random noise is generated in the mass spectrum, the S / N ratio is deteriorated, and the high sensitivity characteristic of MS is significantly impaired. Several techniques have been proposed to solve this problem. USP4935624 and USP5122670 disclose a technique for preventing the introduction of droplets by curtain gas. A curtain gas such as dry nitrogen gas is caused to flow around the pores and the thin tubes provided in the vacuum partition wall facing the ESI spray thin tube. The curtain gas flow attempts to prevent the introduction of large droplets into the vacuum. On the other hand, the ions can be taken into the vacuum by the electric field. Furthermore,
USP 5235186 showed a method of heating a curtain gas to vaporize and dry fine droplets. However, since the noise (chemical noise) derived from large droplets cannot be removed even by the curtain gas, another method was proposed in USP 4977320. It heats a capillary tube that takes ions into a vacuum and attempts to heat vaporize the droplets while passing through the capillary tube. This method is followed by a heating capillary (Heat
ed Capillary) and has come to be adopted in many LC / MS devices.

Chemical noise due to large droplets generated during spraying was greatly reduced by employing a curtain gas and a heating capillary. However, chemical noise still existed in the LC / MS instrument, which hindered the high sensitivity of the LC / MS measurement. The reason why this chemical noise cannot be eliminated is considered as follows. When gas is introduced into the vacuum from the atmosphere, the gas expands adiabatically and is rapidly cooled to near 0 degrees. The temperature of the gas is cooled to about -263 [deg.] C. (10 K) in a vacuum a few mm away from the outlet of the thin tube having an inner diameter of 0.2 mm. When a cooled ion collides with a polar molecule, such as water, which is also cooled, the ion and the molecule do not have internal energy enough to dissociate again, and thus the added ion forms a cluster ion. This in turn adds water molecules to the snowball, forming cluster ions. Since the cluster ions are distributed over a wide mass range and dissociate during mass analysis, random noise (chemical noise) is generated in the mass spectrum and an effective signal is suppressed.

In order to prevent the formation of these cluster ions,
USP4999493 and USP501 are technologies for heating the first vacuum chamber (intermediate pressure chamber) that samples gas and ions from atmospheric pressure.
Shown in 5845. However, since the bio-related substances targeted by ESI are easily decomposed by heat, heating at about 300 ° C. is the limit. With such a degree of heating, the cooling effect due to adiabatic expansion is superior, and the cooling temperature can be increased from 10K to about 20K. That is, the cooling of the gas cannot be eliminated. This reduced the chemical noise, but could not eliminate it. On the other hand, application to the field of biotechnology has led to the miniaturization of samples, and has come to demand higher sensitivity of LC / MS devices.

Techniques for heating mass spectrometers for other purposes than LC / MS have been shown in US patents.
In USP 5767513, Dressler disclosed a technique for heating an ion guide (octapole) located between an ion source and a mass spectrometer. This relates to the apparatus used to study the ionic molecule reaction of ions generated by electron ionization (EI), which is ionization under high vacuum, with Na and D ₂ . The ions generated by EI are guided to the octapole to which a high frequency is applied, and the ion molecule reaction is caused there.
Octapole acts as a reaction cell. The reaction cell and the octopole rod itself were heated to 1,000 K in order to prevent side reactions and contamination in the reaction cell. In this USP 5767513, ions and gas are introduced and generated in the housing kept in a high vacuum, so that adiabatic expansion and cooling do not occur at all. There is no description about introduction of ions generated by atmospheric pressure ionization into vacuum, adiabatic expansion, cooling, etc. There is no mention of improving MS / MS efficiency of biopolymers or removing chemical noise.

Heating the ion trap itself is USP5
Shown by Palermo in 796100. This is related to electron ionization (EI) in which a sample gas is introduced into an ion trap and electrons are bombarded and ionized. It is intended to reduce the amount of the introduced non-ionized neutral sample molecules adsorbed on the electrode surface in the ion trap and thermally decomposed. USP5994697 showed heating of an LC / MS ion trap by Kato. Here, in order to eliminate water molecules adsorbed inside the ion trap and on the electrode surface,
A method of heating the ion trap itself or a method of heating a buffer gas and sending it into the electrode is shown. This USP5796100
In USP5994697, there is no description about introduction of ions generated by atmospheric pressure ionization into vacuum, accompanying problems such as adiabatic expansion and cooling, and means for solving them.
There is no mention of improving MS / MS efficiency of biopolymers.

When a peptide, protein, DNA or the like is ionized by ESI by ESI, these molecules give a multivalent ion having a plurality of charges to one ion. The CPU can determine the molecular weight of the sample from a plurality of multiply charged ions. However, these bio-related molecules cannot be identified only by molecular weight information. Identification of proteins and DNAs requires information on the sequences of amino acids and nucleic acids that compose these bio-related molecules. However, it is not necessary to know all the sequences of all DNAs and proteins, and it is sufficient to know the sequences of some structures. It is possible to identify a protein or DNA by searching a library from this partial sequence and information on the molecular weight. MS / MS is a mass spectrometric means for providing this structural information.

As the MS / MS, a tandem type MS in which a plurality of MSs are connected in series, an ion trap mass spectrometer and the like are used. The ions generated by ESI are led to the first MS, isolated into one precursor ion and excluded from the other. Next, the isolated precursor ions are guided to a collision cell installed between the first MS1 and the second MS2, and dissociation (CID) is caused by collision between the target gas and the ions. Guide the generated product ions to the second MS,
Mass spectrometry is performed to obtain a mass spectrum.

The ion trap mass spectrometer is a single MS.
It is a device that can achieve MS / MS. Ionization, introduction and accumulation of ions in the ion trap, MS / MS, and mass spectrum acquisition of product ions are performed in time division. MS / MS is composed of a plurality of steps, and isolation of precursor ions and resonance dissociation of precursor ions are also performed by time division.

[0012] MS / MS causes resonance excitation of ions, and many times the ions collide with buffer gas molecules having a pressure of about 0.1 Pa, so that kinetic energy is gradually converted into internal energy of the ions, and finally the ions. Is a method of cleaving the chemical bond of. If the ions and gas molecules are cooled to 10 K, long-time excitation is required to dissociate the ions. In addition, the internal energy of biopolymers such as DNA and proteins converted by one collision with low-mass molecules such as buffer gas is tens of thousands to hundreds of thousands of the energy of collision. , Not enough excitation. Therefore, collision-induced dissociation (CID) of these biopolymers has been considered difficult.

A method has been proposed to solve this difficulty.
Infrared rays (I
R) Irradiating a laser to heat the ions themselves, and at the same time, the ions are resonantly excited to dissociate the ions. This method is based on the Infrared Multiphoton Dissoci
ation IRMPD). Cooks et al. Compare photodissociation of small molecules with CID (Cooks, Int.
J. Mass Spectrom. IonProcesses, 75 (1987) 345−35
2).

McLafferty and others are ICR mass spectrometers (FT-
IRMPD was used for MS) and the multivalent ion of a protein with a molecular weight of 29 kDa was cleaved and reported (McLaffert
y, Anal. Chem., 66 (1994) 2809-2815).

Further, a method has been proposed in which ions trapped in an ion trap mass spectrometer or an ICR mass spectrometer are heated from the surroundings without using a laser and thermally decomposed, and this method is a black body infrared radiation dissociation ( Blackbody Infrared radiati
ve Dissociation BIRD). Will
iams et al. reported that BIRD can cleave polyvalent ions of a protein of 8.6 kDa to obtain structural information (Williams, Anal. Chem., 69 (1997) 1119-1126).

[0016]

When the ions generated by the atmospheric pressure ion source are introduced into the vacuum chamber for mass analysis, the ions are rapidly cooled by adiabatic expansion. Cluster ions are generated in the ion guide and the ion trap by this rapid cooling. In order to excite the ions that have been once cooled and turned into cluster ions, it is necessary to dissociate the added polar molecules. After this, the excited dissociation of the ions must be performed. Therefore, much energy must be injected into the cluster ions, and C in the ion trap must be injected.
The efficiency of I is significantly reduced. On the contrary, it may sometimes cause decomposition of ions due to excessive excitation.

Further, since there is temperature unevenness in the ions introduced into the ion trap mass spectrometer at the beginning of the period of ion introduction and accumulation and the ions introduced at the end of the accumulation period, the CID efficiency varies. . In view of the above point, the present invention aims to provide an atmospheric pressure ionization mass spectrometer capable of increasing the efficiency of CID while making the ion excitation shorter.

[0018]

The present invention solves such a problem by heating the ion guide space where cooling due to adiabatic expansion takes place, thereby heating the ions. It also heats the ion trap space.

To this end, an atmospheric pressure ion source for introducing a sample solution into a fine capillary to generate ions under atmospheric pressure is provided, and the ions generated by the ion source are placed in a vacuum chamber and a high frequency is applied. In the atmospheric pressure ionization mass spectrometer which gives the mass spectrum through the ion guide, the ion guide and the mass spectrometer are heated at the same time.

Further, the sample solution is introduced into a fine thin tube to provide an atmospheric pressure ion source for generating ions under the atmospheric pressure, and the ions generated by the ion source are supplied to a thin tube or a fine hole provided in a vacuum partition. Introduced into the vacuum chamber, led to the mass spectrometer through the ion guide to which a high frequency is applied, in the atmospheric pressure ionization mass spectrometer that gives a mass spectrum, the ions between the mass spectrometer from the capillary tube or the pores Try to heat the space to be moved or trapped.

[0021]

FIG. 1 shows an apparatus according to an embodiment of the present invention. The sample component solution separated by the liquid chromatograph LC1 is sent to the ESI probe 3 of the ESI ion source 4 through the capillary tube 2. The ESI probe 3 is arranged on the XYZ triaxial positioning device 9. LC
The sample solution sent from No. 1 is sent to the nozzle of the ESI probe 3 and is sprayed from the nozzle tip into the atmosphere as a spray ion flow (charged droplet) 6. Ions are released from the charged droplets into the atmosphere, are provided in the vacuum partition wall 11, and are taken into the vacuum chamber 12 from the thin tube 8 (including the pores) heated by the heater 40. The mass spectrometer is composed of several chambers 12, 15, 19 having different pressures, and each chamber is evacuated by an independent vacuum pump 20, 21, 22. The ions are introduced into the mass spectrometer 17 through the high frequency ion guide 16 and subjected to mass analysis. When the high frequency voltage supplied from the mass sweep power supply 23 is swept, the ions are separated for each mass, and the detector 18 detects the ion current. The signal of the ion current corresponding to each mass is sent to the control data processing device 24 and collected as a mass spectrum.

A plurality of high frequency ion guides 16 (4, 6,
(8, ...) Cylindrical electrodes are arranged in parallel on the same circumference as heating means. Every other electrode is wired in common,
A high frequency is applied between the two electrode groups. A cylindrical shield tube 43 covers the high-frequency ion guide 16 for shielding the high-frequency ion guide. Shield tube 43
Together with the high frequency shield plays a role of keeping the gas 44 introduced into the shield at a constant pressure (about 0.1 Pa). An inert gas such as argon (Ar) or nitrogen gas (N ₂ ) gas is introduced into this shield.
A heater 41 is arranged as a heating means around the shield tube 43, and the shield tube and the high-frequency ion guide 16 are provided.
It can be heated. Also, the introduced gas itself may be heated by the heater 45. The electrodes of the ion trap mass spectrometer 17 are heated by a heater 25 which is a heating means. The number of heaters 25 may be increased to heat the entire electrode. Electric current is sent from the power supplies 42 and 26 controlled by the control data processing device 24 to the heaters 41 and 25. As a result, the high-frequency ion guide 16 arranged in the space inside the shield cylinder 43 and the introduced gas are kept at 20
Heated from 0 ° C to 300 ° C. Ions and gas molecules that have passed through the pores at the tip of the skimmer 13 and cooled to several tens of K in the vacuum chamber 12 are introduced into the high-frequency ion guide 16 from the opening of the shield cylinder 43. The introduced ions vibrate by the high-frequency electric field in the high-frequency ion guide and gradually move toward the mass spectrometer while converging on the central axis. Ions that move while vibrating in the high frequency ion guide 16 frequently collide with heated and hot gas molecules. As a result, heat exchange is performed between the gas molecules and the ions, and the ions are rapidly heated. The ions heated in the high-frequency ion guide 16 are sent to the high vacuum chamber 19 in which the ion trap mass spectrometer is placed and introduced into the ion trap mass spectrometer 17. The ion trap mass spectrometer 17 is heated to 200 to 300 ° C. by a heater 25 which is a heating means. That is, the space in which the ions are trapped is heated. Therefore, the introduced ions are introduced and accumulated in the ion trap mass spectrometer 17 while maintaining the temperature. This allows the ions to undergo MS / MS operation while being kept at a high temperature. The hot ions are excited by resonance excitation and collision with hot buffer gas molecules in the ion trap electrode,
The internal energy rises quickly. When the internal energy of the ions rises above the binding energy, the ions split and produce product ions. Next, the control data processing device 24 controls the power supply 23 to sweep the high frequency voltage applied to the ring electrode of the ion trap to acquire the mass spectrum of the generated product ions.

The heating temperature of the high frequency ion guide 16 and the heating temperature of the ion trap mass spectrometer 17 can be set independently by the control data processing device 24. The temperature of the high-frequency ion guide, which is cooled by adiabatic expansion and has a short residence time (several tens of microseconds), is set higher than the temperature of the ion trap mass spectrometer where the residence time of ions is several hundred milliseconds. To do. In the analysis of peptides, good results were obtained with a high-frequency ion guide temperature of 300 ° C and an ion trap mass spectrometer temperature of 200 ° C.

FIG. 3 shows an LC / LC in which a high-frequency ion guide having no heating means and an ion trap mass spectrometer are combined.
An example of a mass spectrum obtained by the MS device is shown. a,
b and c are mass peaks derived from the sample and impurities. On the other hand, the mass peaks appearing over the entire mass region are unknown in attribution and must be excluded from the information as chemical noise.
This chemical noise becomes remarkable when the sensitivity of the apparatus is increased when the amount of the sample is small. As shown in (2) of FIG. 3, c ions corresponding to the pseudo-molecular ions of the sample are isolated and MS / MS is performed. Exciting c ions, collision-induced dissociation (CID) is performed in the ion trap. However, when the ions have a mass of more than 1000 and the ions are cooled, the CID is not performed efficiently, the product ions have a small peak, and it is difficult to distinguish them from noise. As shown in (3) of FIG. 3, the excited quasi-molecular ion remains in the mass spectrum without changing its intensity.

With this sample, when a high frequency ion guide and an ion trap mass spectrometer are heated as in this method, a mass spectrum with less chemical noise can be obtained as shown in (1) of FIG. By improving the S / N ratio, the ions of the signals d and e buried in the chemical noise can be clearly distinguished. In the MS / MS measurement, the precursor ion c is first isolated. The precursor ions are sufficiently heated by heating the high frequency ion guide and the ion trap mass spectrum. By exciting the heated precursor ions, it is possible to cleave molecules having a mass of more than 1000, as shown in FIG.
The product ion mass spectrum as shown in (3) can be given. Due to the cleavage of the precursor ion c, the amount of ions is greatly reduced. On the other hand, product ions p1 to p
4 clearly appears.

The ion trap mass spectrometer temporarily stores ions in the ion trap and then performs MS / MS measurement and mass sweep. In order to avoid the influence of space charge in the ion trap during the accumulation process, the accumulation time is shortened when the amount of ions is large, and conversely, the accumulation time is lengthened when the ion current is small. That is, the iontophoretic storage time constantly changes. According to this method, since the temperature of the ions does not change even if the ion introduction and accumulation time changes, product ions by MS / MS can be acquired with good reproducibility.

Although ESI was mainly described here, the present invention is not limited to atmospheric pressure chemical ionization (APCI) and ESI.
Improved technology of ion spray (Ion Spray), sonic spray (Sonic Spray), nano spray (Nano Sp
It is applicable to the combination with ionization technology such as ray).

By this method, it is possible to prevent the cooling of ions and gases from the ion source to the ion trap mass spectrometer. As a result, generation of cluster ions can be prevented, and chemical noise can be further reduced.

The present invention is not limited to the ion trap mass spectrometer, but it is a quadrupole mass spectrometer (QMS) or triple stage quadrupole mass spectrometer (TSQ) using an atmospheric pressure ion source and a high frequency ion guide. It can also be applied to an ICR mass spectrometer.

In the present invention, it is important to heat the ions and gas in a manner that compensates for the cooling due to adiabatic expansion. Therefore, it is necessary to maintain the heated state from the outlet of the thin tube 8 where adiabatic expansion occurs to the mass spectrometer 17. The heating means may be a heater as shown in FIG. 1 or may be an infrared lamp or a laser emitting infrared rays. In short, it is important that the ions are heated until they are detected by the detector 18.

[0031]

According to the present invention, peptides, proteins and DN
Even a biopolymer such as A can efficiently generate product ions. Further, it is possible to obtain a highly reproducible product ion current value, that is, a product ion mass spectrum, regardless of the ion introduction and accumulation time. Further, by suppressing the chemical ions, it has become possible to increase the sensitivity of the LC / MS device.

[Brief description of drawings]

FIG. 1 is a configuration diagram of an atmospheric pressure ionization mass spectrometer which is an embodiment of the present invention.

FIG. 2 is a mass spectrum diagram without chemical noise.

FIG. 3 is a product mass spectrum diagram.

[Explanation of symbols]

1 ... LC, 2 ... capillary tube, 3 ... ESI probe, 4 ... ESI ion source, 5 ... high voltage power supply, 6 ... spray ion flow, 7 ... ion source space, 8 ... capillary tube, 9 ... XYZ triaxial positioning mechanism, 11 , 14 ... Vacuum partition wall, 12, 15 ... Vacuum chamber, 13 ... Skimmer, 16 ... High-frequency ion guide, 1
7 ... Mass spectrometer, 18 ... Detector, 19 ... High vacuum chamber, 2
0, 21, 22, ... Vacuum pump, 23 ... Mass sweep power supply, 2
4 ... Control data processing device, 25, 40, 41, 45 ... Heater, 26, 42 ... Heater power supply, 43 ... Shield cylinder, 4
4 ... No gas.

[Procedure amendment]

[Submission date] February 8, 2002 (2002.2.8)

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0012

[Correction method] Change

[Correction content]

[0012] MS / MS causes resonance excitation of ions, and many times the ions collide with buffer gas molecules having a pressure of about 0.1 Pa, so that kinetic energy is gradually converted into internal energy of the ions, and finally the ions. Is a method of cleaving the chemical bond of. If the ions and gas molecules are cooled to 10 K, long-time excitation is required to dissociate the ions. Also, what biopolymers such as DNA and proteins, internal energy is converted by one collision with low mass molecules buffer gas such consists of several parts per million of the energy of the collision hundreds of thousands parts per , Not enough excitation. Therefore, collision-induced dissociation (CID) of these biopolymers has been considered difficult.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0016

[Correction method] Change

[Correction content]

[0016]

When the ions generated by the atmospheric pressure ion source are introduced into the vacuum chamber for mass analysis, the ions are rapidly cooled by adiabatic expansion. Cluster ions are generated in the ion guide and the ion trap by this rapid cooling. In order to excite the ions that have been once cooled and turned into cluster ions, it is necessary to dissociate the added polar molecules. After this, the excited dissociation of the ions must be performed. Therefore, much energy must be injected into the cluster ions, and C in the ion trap must be injected.
The efficiency of ID is significantly reduced. On the contrary, it may sometimes cause decomposition of ions due to excessive excitation.

[Procedure 3]

[Document name to be amended] Statement

[Name of item to be corrected] 0022

[Correction method] Change

[Correction content]

A plurality of high frequency ion guides 16 (4, 6,
8, ... is cylindrical electrode of the present) are arranged parallel on the same circumference. Every other electrode is commonly wired and a high frequency is applied between the two electrode groups. A cylindrical shield tube 43 covers the high-frequency ion guide 16 for shielding the high-frequency ion guide. The shield tube 43 plays a role of keeping the gas 44 introduced into the shield at a constant pressure (about 0.1 Pa) together with the high frequency shield.
An inert gas such as argon (Ar) or nitrogen gas (N ₂ ) gas is introduced into this shield. A heater 41 is arranged as a heating means around the shield cylinder 43 so that the shield cylinder and the high-frequency ion guide 16 can be heated. Also, the introduced gas itself may be heated by the heater 45. The electrodes of the ion trap mass spectrometer 17 are heated by a heater 25 which is a heating means. The number of heaters 25 may be increased to heat the entire electrode. Electric current is sent from the power supplies 42 and 26 controlled by the control data processing device 24 to the heaters 41 and 25. As a result, the high-frequency ion guide 16 arranged in the space inside the shield tube 43 and the introduced gas are heated from 200 ° C to 300 ° C. Ions and gas molecules that have passed through the pores at the tip of the skimmer 13 and cooled to several tens of K in the vacuum chamber 12 are introduced into the high-frequency ion guide 16 from the opening of the shield cylinder 43. The introduced ions vibrate by the high-frequency electric field in the high-frequency ion guide and gradually move toward the mass spectrometer while converging on the central axis. Ions moving while oscillating a high-frequency ion guide 16 medium frequently collide with the heated hot gas molecules. This allows
The heat exchange between the gas molecules and the ions is performed, and the ions are rapidly heated. The ions heated in the high-frequency ion guide 16 are stored in the high vacuum chamber 1 in which the ion trap mass spectrometer is placed.
9 and introduced into the ion trap mass spectrometer 17. The ion trap mass spectrometer 17 is heated to 200 to 300 ° C. by a heater 25 which is a heating means.
That is, the space for trapping the ions is heated. Therefore, the introduced ions are introduced and accumulated in the ion trap mass spectrometer 17 while maintaining the temperature. This allows the ions to undergo MS / MS operation while being kept at a high temperature. The internal energy of the high-temperature ions rapidly rises due to resonance excitation in the ion trap electrode and collision with high-temperature buffer gas molecules. When the internal energy of the ions rises above the binding energy, the ions split and produce product ions. Next, the control data processing device 2
Reference numeral 4 controls the power supply 23 to sweep the high frequency voltage applied to the ring electrode of the ion trap to acquire the mass spectrum of the generated product ions.

Claims (8)

[Claims] 1. An atmospheric pressure ion source for generating ions at atmospheric pressure by introducing a sample solution into a fine capillary, and the ions generated by the ion source are placed in a vacuum chamber and a high frequency is applied. An atmospheric pressure ionization mass spectrometer, wherein the ion guide and the mass spectrometer are both provided with heating means in an atmospheric pressure ionization mass spectrometer which guides the mass spectrum through an ion guide and gives a mass spectrum. 2. The atmospheric pressure ionization mass spectrometer according to claim 1, wherein the ion guide and the mass spectrometer are independently heated and controlled. 3. The atmospheric pressure ionization mass spectrometer according to claim 1, wherein a heating temperature of the ion guide is set higher than a heating temperature of the mass spectrometer. 4. The atmospheric pressure ionization mass spectrometer according to any one of claims 1 to 3, wherein the ion source is an electrospray (ESI) ion source. 5. The atmospheric pressure ionization mass spectrometer according to any one of claims 1 to 3, wherein the ion source is an ion spray ion source. 6. The atmospheric pressure ionization mass spectrometer according to claim 1, wherein the ion source is a nanospray ion source. 7. An atmospheric pressure ionization mass spectrometer according to any one of claims 1 to 3, wherein the ion source is an atmospheric pressure chemical ionization (APCI) ion source. 8. An atmospheric pressure ion source for producing ions at atmospheric pressure by introducing a sample solution into a fine capillary, and the ions generated by the ion source are supplied to a vacuum partition to form a capillary or a pore. Introduced into the vacuum chamber, led to the mass spectrometer through the ion guide to which a high frequency is applied, in the atmospheric pressure ionization mass spectrometer that gives a mass spectrum, the ions between the mass spectrometer from the capillary tube or the pores An atmospheric pressure ionization mass spectrometer designed to heat the space to be moved and trapped.