JPH09145704A - Liquid chromatography mass analysis device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a liquid chromatography mass analysis device with a desolvation means which is less affected by a noise due to a charged liquid drop and can increase ion signal intensity. SOLUTION: A pipe 33 consisting of a heat-conductive and electrical- conductive material, a pipe 34 consisting of a heat-insulating and electrically- insulated material, and a pipe 35 consisting of a heat-conductive and electrically- conductive material are connected to the later stage of an ionization part 31 of an interface part 30 located between a liquid chromatography part 10 and a mass analysis part 20, temperature is independently set so that the pipe 33 and the pipe 35 are set to make the side of the pipe 35 lower by heaters 36 and 37, and potential gradient is generated within the pipe by a voltage source 39, thus leading generated ions to the side of a detector without breaking the ions, increasing an ion signal intensity, and reducing noise.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid chromatograph mass spectrometer (hereinafter referred to as LC / MS), and more particularly to an interface between a liquid chromatograph section of LC / MS and a mass spectrometric section.

[0002]

2. Description of the Related Art In LC / MS, a method of ionizing a component separated in a liquid chromatograph under atmospheric pressure and introducing it into a mass spectrometer may be used. In this case, an interface for ionizing the components separated by the column of the liquid chromatograph unit is required. There are several types of interfaces commonly used for LC / MS, such as an electrospray interface (ESI) and an atmospheric pressure chemical ionization interface (APCI).

In the ESI method, a liquid sample is sent to the tip of a thin nozzle and a high voltage is applied to the tip of the nozzle. As a result, a strong unequal electric field is formed at the tip of the nozzle, the liquid sample is sprayed as charged droplets by this strong electric field, and further, the Coulomb repulsive force of the ions in the droplets causes the droplets to split and ionize. Is done.

On the other hand, in the APCI method, a liquid sample is forcibly sprayed by a gas flow in a nebulizer (atomizer), and the liquid sample is desolvated by heating the liquid sample. Then, buffer ions generated by corona discharge are used. The sample is ionized (chemical ionization). Figure 3 shows the conventional LC /
It is a figure showing the general composition of MS. Reference numeral 10 denotes a liquid chromatograph unit, and reference numeral 20 denotes a mass spectrometric unit. Reference numeral 30 denotes an interface unit. In the figure, an electrospray ionization unit 31 using the ESI method is used. Further, a pipe 32 provided after the electrospray ionization section.
A heater mechanism (not shown) is attached to this, and this one functions as a desolvation means for promoting desolvation of the charged droplets generated in the electrospray ionization section 31. The electrospray probe 31a has a thin tube through which the sample liquid sent from the liquid chromatograph section 10 passes, and the tip on the side facing the pipe 32 has a needle shape, and the liquid passing through the thin tube has a needle tip nozzle. It is supposed to be ejected from the part. Then, a high voltage of about several KV is applied to the electrospray probe 31a from a high voltage generating circuit (not shown). With such a structure, the liquid sample sent from the liquid chromatograph unit 10 is drawn out in a spray form due to the strong electric field formed near the nozzle at the tip of the needle. Or charged droplets enter the pipe 32.

The charged droplets are heated by a heater in the pipe 32 to evaporate the solvent, and when the charged droplets collide with other particles, they are further miniaturized to promote ionization, and the generated ions are generated. And is sent to the mass spectrometric unit 20.

In this way, desolvation and ionization are promoted when passing through the pipe 32, and then ions are introduced into the mass spectrometric section.

On the other hand, when performing ionization by the APCI method, an atmospheric pressure chemical ionization section 54 as shown in FIG. 4 is attached instead of the electrospray ionization section 31 of FIG. That is, a probe 5 having a thin tube through which a sample liquid passes and having a needle-shaped tip.
4a, an atomizing chamber 54b provided so as to surround the needle portion of the probe 54a, and an atmospheric pressure chemical ionization section 5 including a discharge electrode 54c attached to the front surface of the opening of the atomizing chamber.
4 is attached. The atomization chamber 54b is heated by a heater (not shown), and a voltage of several KV is applied to the discharge electrode 54c. In this manner, the liquid sample sent from the liquid chromatograph unit 10 is separated from the nozzle at the needle tip of the probe 54a by the atomizing gas from the gas line separately connected to the probe.
And is deionized by a heater and then ionized by contact with buffer ions generated at a discharge electrode. The generated ions and charged droplets are sent to the mass spectrometry unit 20 via the heated pipe 32 while desolvation and ionization are promoted in the same manner as in the above-described ESI method.

[0008]

In the conventional LC / MS, whether the electrospray ionization section, the atmospheric pressure chemical ionization section, or the other ionization section is provided, the ions generated in the ionization section, Charged droplets, etc. pass through a straight pipe-shaped pipe provided in the subsequent stage of the ionization section, and when passing through this pipe, they are sent to the next-stage mass analysis section while promoting desolvation and ionization. Was there. As the straight pipe, either a metal pipe or a glass pipe has been used.

However, even if a metal pipe is used,
Even when a glass pipe is used, it is difficult to accelerate desolvation while obtaining a large ion signal, and efficient desolvation and ionization cannot be performed for the following reasons.

That is, in the metal pipe, since the space inside the pipe has substantially the same potential, the ions inside cannot be accelerated by the potential gradient. Therefore, promotion of ionization by electrically accelerating in the pipe to give energy to the charged droplet cannot be expected. Instead, since the metal pipe has good thermal conductivity, heating the pipe to a temperature suitable for desolvation promotes evaporation of the solvent to miniaturize the droplets, and thermal energy is applied to cause ionization. I try to promote. However, in the case of promoting desolvation by heating, in terms of desolvation, higher heating temperature can promote solvation, but on the contrary, it also causes the generated ions to be broken by heating. It was On the other hand, when the heating temperature is kept low, the generated ions are not thermally broken, but desolvation is not promoted, and it is difficult to satisfy both desolvation and ionization.

In the case of a glass pipe, not only can it be heated as in the case of a metal pipe, but also ionization can be promoted by electrically accelerating in the pipe to give energy to the charged droplets. Further, the potential gradient facilitates the generated ions to be extracted to the detector side. However, even in this case, if the heating temperature is set high, the generated ions are broken, and if the heating temperature is set low, desolvation is not promoted.

Further, as a problem when the glass pipe is used, since the glass pipe has a poor thermal conductivity, it is difficult to uniformly heat the glass pipe even if it is heated, so that it is difficult to control the temperature and the temperature is locally changed. If there is a high point, it may cause ion fragmentation, and if there is a low temperature, it may cause droplet adhesion.

If analysis is performed in a state where desolvation is not sufficient, only noisy analysis can be performed. On the other hand, if the analysis is performed in a state where the ionization is not promoted, the ion signal intensity cannot be made large, so that the sensitive analysis cannot be performed.

The present invention solves the above problems and provides an interface capable of promoting both desolvation and ionization, whereby a liquid chromatograph mass capable of performing analysis with low noise and high sensitivity. An object is to provide an analyzer.

[0015]

A liquid chromatograph mass spectrometer (LC / MS) of the present invention made to solve the above problems is a liquid chromatograph between a liquid chromatograph section and a mass spectrometric section. Chromatographic mass spectrometer equipped with an interface section for ionizing the liquid sample sent from the ionization section by the ionization means and introducing the generated ions or charged droplets into the mass analysis section while desolvating by the desolvation means In the above, the desolvation means comprises a first pipe made of a heat conductive material and provided with a heating means, and a second heat insulating pipe made of a heat insulating material,
It is a structure in which a third pipe provided with a heating means made of a heat conductive material is connected, and the heating means is provided independently of the first pipe and the third pipe.

Furthermore, the liquid chromatograph mass spectrometer (LC / M) of the present invention made to solve the above problems.
S) is between the liquid chromatograph section and the mass spectrometric section,
A liquid chromatograph equipped with an interface section for ionizing a liquid sample sent from the liquid chromatograph section by an ionization means and introducing the generated ions or charged droplets into the mass spectrometric section while desolvating by the desolvation means. In the mass spectrometer, the desolvation means has a structure in which a first pipe made of a conductive material, a second pipe made of an electrically insulating material, and a third pipe made of a conductive material are connected to each other. And by the voltage applying means
It is characterized in that a potential difference is generated between the first pipe and the third pipe.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION In the LC / MS of the present invention, in the interface section, a first pipe made of a heat conductive material and provided with a heating means is provided at a subsequent stage of the ionization section, and a second pipe made of a heat insulating material. Since the heat insulating pipe and the third pipe provided with the heating means made of a heat conductive material are connected to each other, the first pipe and the third pipe are independently heated. Therefore, the number of generated ions is small and the heating temperature of the first pipe on the side of the ionization section where a large number of charged droplets having a large particle size exists is set high,
In addition to promoting desolvation, the heating temperature of the third pipe on the detector side is set to the heating temperature of the third pipe on the detector side where a large amount of generated ions and many charged droplets with small particle size are present. By setting the temperature lower than the temperature to prevent the generated ions from being broken, the ion signal intensity can be increased and the analysis can be performed with less noise.

Further, since the first pipe made of a conductive material, the second pipe made of an electrically insulating material, and the third pipe made of a conductive material are connected to the subsequent stage of the ionization section. , Between the first pipe and the third pipe,
The voltage applying means can generate a potential difference between the first pipe and the third pipe. Therefore, in the case of positive ions, the first pipe has a negative potential more than that of the third pipe, and in the case of negative ions, the first pipe has a more positive potential than that of the third pipe. By applying the voltage in advance, the ions can be accelerated even in the pipe, so that the amount of ions that can pass through the pipe can be increased and the ion signal intensity can be increased.

Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is a block diagram showing an LC / MS showing an embodiment of the present invention. 2 is the same as the conventional example.
The same reference numeral as 3 is used to omit the description.

As shown in the figure, the interface section 30 includes
The electrospray ionization unit 31 is fixed to the housing of the mass analysis unit 20. Then, the electrospray probe 31 of the electrospray ionization unit 31.
At a position near the rear stage of the nozzle portion at the needle tip of a, the pipe 33 and the heat insulating pipe 3 functioning as desolvation means.
4, the pipe 35 is connected. A good heat conductor material such as metal is used for the pipes 33 and 35, and a material having poor heat conductivity such as glass or ceramic resin is used for the heat insulating pipe 34. Pipe 3
3, the heat insulating pipe 34, and the pipe 35 are provided with through holes that communicate with each other. The pipe 33 side of this hole is directed to the outlet side of the preceding ionization unit, and the pipe 35 side of this hole is connected to the mass analysis unit 20. I am doing it. A heater 36 is attached to the pipe 33, and a heater 37 is attached to the pipe 35 separately. Since the heat insulating pipe 34 is interposed between the pipe 33 and the pipe 35, the temperature can be set independently. It is like this. The pipe 33 side is set to 250 degrees Celsius, the pipe 35 side is set to 150 degrees Celsius, and the pipe 33 side is set to a high temperature. The set temperature may be a temperature suitable for the solvent used, but normally the pipe 33 side is set to 200 to 300 degrees Celsius, and the pipe 35 side is set to a value lower than the set value on the pipe 33 side. To do.

In this LC / MS, the ions and charged liquid droplets atomized and generated by the electrospray ionization unit 31 enter the pipe 33. When entering the pipe 33, the number of produced ions is still small and the charged droplets have a large particle size, but since the pipe 33 is set to a high temperature so as to easily evaporate the solvent, desolvation is promoted. At the same time, thermal energy is given to the particles to cause collision with other particles and the like, whereby the particles are miniaturized and ionization is also promoted. In this way, the number of ions increases when passing through the pipe 33, and the charged liquid droplets are miniaturized and the insulating pipe 3
4, introduced into the pipe 35. On the other hand, since the pipe 35 is independently controlled so that the set temperature is lower than that of the pipe 33, the generated ions are not easily broken in the pipe 35. Therefore, although the ions sent from the pipe 33 are not broken and the temperature is set to a low temperature, the solvent can be evaporated, so that the desolvation is further promoted and the ions are sent to the detector side. Be done. Therefore, it is possible to increase the ion signal intensity and obtain a signal with less noise. FIG.
FIG. 6 is a configuration diagram showing an LC / MS showing another embodiment of the present invention. Regarding this, the same parts as those in FIG. 1 and the conventional example are denoted by the same reference numerals as those in FIGS.

As shown in the figure, in this embodiment, a pipe 33, an insulating pipe 38, and a pipe 35 are connected as a desolvation means. The pipe 33 and the pipe 35 are made of a material having good electrical conductivity such as metal, and the insulating pipe 34 is made of an electrically insulating material such as glass or ceramic resin. Pipe 33, insulating pipe 3
4. The pipe 35 is provided with a through hole communicating with each other. The pipe 33 side of this hole is directed to the outlet side of the preceding ionization section, and the pipe 35 side of this hole is connected to the mass spectrometric section 20. A voltage source is connected to the pipe 33 and the pipe 35 so that the pipe 33 and the pipe 35 can be set to different potentials and a potential gradient can be generated between them. The potential gradient between the pipes 33 and 35 is such that the pipe 35 side becomes negative when the target ion is a positive ion, and the pipe 35 side becomes positive when the target ion is a negative ion. The applied voltage may be about ± several V to several 100 V.

In such LC / MS, the pipe 33,
Since the potentials between 35 are different, a potential gradient occurs in the pipe. Similar to the previous embodiment, when the ions enter the pipe 33, the number of produced ions is still small, and the charged droplets have a large particle size, but the applied voltage imparts electrical energy to the particles to accelerate them. By colliding with particles and the like, the particles are miniaturized to promote ionization. In this way, the number of ions increases when passing through the pipe 33, and charged droplets are introduced into the insulating pipe 34 and the pipe 35 while being miniaturized. Since the ions are accelerated by the potential gradient even in the pipe, the amount of ions extracted to the detector side increases and the ion signal intensity increases.

In the above embodiments, desolvation and ionization by heating and electrical desolvation and ionization were performed separately, but by performing both of these at the same time, more effective desolvation is achieved. It goes without saying that ionization and ionization can be performed. In this case, metal may be used for the first and third pipes and ceramic or glass may be used for the second pipe.

Further, as another embodiment of the present invention, FIG.
As shown in the figure, there is one in which the ion passage of the desolvation means is made into a bent path to generate a potential gradient in the bent portion. That is, similar to FIG. 2, the pipes 41 and 43 made of a conductive material such as metal and the insulating pipe 42 made of an electrically insulating material such as ceramic are interposed therebetween. A slanted shape creates a bent shape. And pipe 4
By applying a voltage between the 1 and the pipe 43 by the voltage source 44, a potential gradient is generated in the portion of the insulating pipe 42.

In this case, the hole of the pipe 41 and the hole of the pipe 43 are not linearly connected. Therefore, the particles incident on the pipe 41 collide with the wall in the vicinity of the pipe 42, which is the bent portion, and easily adhere to the wall at that time. As a result, it is advantageous in that particles that are noise sources can be reduced, but there is a possibility that the essential ion signal intensity is lowered. However, since there is a potential gradient between the pipe 41 and the pipe 43, the ions or charged droplets having a small mass are relatively easily bent due to the potential gradient and pass to the pipe 43 side. Therefore, the required ion signal strength can be maintained and unnecessary noise signals can be reduced, so that highly sensitive measurement can be performed.

In this case, if the heaters 45 and 46 are provided on the pipe 41 and the pipe 43, respectively, and the temperature of the pipe 41 is higher than that of the pipe 43 as shown in the first embodiment, the desolvation is more efficient. It can be ionized and ionized.

The embodiments will be summarized below.

(1) Between the liquid chromatograph section and the mass spectrometric section, the liquid sample sent from the liquid chromatograph section is ionized by the ionization means, and the generated ions or charged droplets are desolvated means. In a liquid chromatograph mass spectrometer equipped with an interface part which is introduced into the mass spectrometric part while being desolvated by means of the first aspect, the desolvation means comprises a conductive material and a heat conductive material.
Is connected to a second pipe made of an electrically and thermally insulating material, and a third pipe made of a conductive material and a heat conductive material.
Chromatographic mass spectrometry, characterized in that a potential difference is generated between the first pipe and the third pipe, and the first pipe and the third pipe are independently provided with heating means. apparatus.

(2) Between the liquid chromatograph section and the mass spectrometric section, the liquid sample sent from the liquid chromatograph section is ionized by the ionization means, and the generated ions or charged droplets are desolvated means. In a liquid chromatograph mass spectrometer equipped with an interface part which is introduced into the mass spectrometric part while being desolvated by means of the first aspect, the desolvation means comprises a conductive material and a heat conductive material.
And a second pipe made of an electrically and thermally insulating material and having a bent conduit, and a third pipe made of a conductive material and a thermally conductive material are connected to each other. The liquid chromatograph mass spectrometer according to claim 1, wherein a potential difference is generated between the first pipe and the third pipe.

[0031]

As described above, as described above, the LC / M according to the present invention is used.
In S, the interface section has a first pipe made of a heat conductive material, a second pipe made of a heat insulating material, and a third pipe made of a heat conductive material.
Since the first pipe is set to a temperature higher than that of the second pipe, the ions are efficiently generated on the first pipe side, and the generated ions are damaged on the third pipe side. Further, since ionization and desolvation can be further promoted, the ion signal intensity is high and the measurement with less noise can be performed.

Similarly, a first pipe made of a conductive material, a second pipe made of an electrically insulating material, and a third pipe made of a conductive material are connected to each other, and the first pipe and the third pipe are connected to each other. Since the potential gradient is generated in the pipe, the generated ions can be accelerated even in the pipe, the ions can be efficiently generated, and the generated ions can be extracted to the detector side.

In particular, the second pipe is bent and the first and third pipes are bent.
When a potential gradient is generated between the pipe and the pipe, the required ion signal strength can be maintained and the unnecessary noise signal can be reduced, so that the measurement can be performed with high sensitivity.

[Brief description of the drawings]

FIG. 1 is a configuration diagram of a liquid chromatograph mass spectrometer according to an embodiment of the present invention.

FIG. 2 is a configuration diagram of a liquid chromatograph mass spectrometer according to another embodiment of the present invention.

FIG. 3 is a block diagram of a conventional liquid chromatograph mass spectrometer (ESI method).

FIG. 4 is a block diagram of a conventional liquid chromatograph mass spectrometer (APCI method).

FIG. 5 is a configuration diagram of a main part of a liquid chromatograph mass spectrometer using a bent pipe which is another embodiment of the present invention.

[Explanation of symbols]

 10: Liquid chromatograph section 20: Mass analysis section 30: Interface section 31: Electrospray ionization section 33, 34: Pipe 35: Adiabatic pipe 36, 37: Heater 38: Insulation pipe 39: Voltage source 42: Bending pipe 54: Large Atmospheric pressure chemical ionization unit

Claims (2)

[Claims] 1. A liquid sample sent from the liquid chromatograph section is ionized by an ionization means between the liquid chromatograph section and the mass spectrometric section, and the generated ions or charged droplets are desolvated by the desolvation means. In a liquid chromatograph mass spectrometer equipped with an interface part that is introduced into a mass spectrometric part while desolventizing, the desolventizing part is made of a heat conductive material and is provided with a first pipe, and a heat insulating material. And a third pipe provided with a heating means made of a heat conductive material are connected to each other. The first pipe and the third pipe are independently heated. A liquid chromatograph mass spectrometer characterized by comprising: 2. The liquid sample sent from the liquid chromatograph section is ionized by the ionization means between the liquid chromatograph section and the mass spectrometric section, and the generated ions or charged droplets are desolvated by the desolvation means. In a liquid chromatograph mass spectrometer equipped with an interface part that is introduced into the mass spectrometric part while desolventizing, the desolventizing means comprises a first pipe made of a conductive material and a second pipe made of an electrically insulating material. A structure in which a pipe and a third pipe made of a conductive material are connected to each other, and a potential difference is generated between the first pipe and the third pipe by the voltage applying means. Characteristic liquid chromatograph mass spectrometer.