JPH1012182A - Ion source and mass spectrometer - Google Patents

Abstract

(57) Abstract: In a sonic spray ion source and a mass spectrometer, the density of droplets taken into the mass spectrometer is set to an appropriate value to reduce noise. SOLUTION: A solution sample in a sample solution introduction unit 1 is introduced into a capillary 2. Capillary 2 is ion source 6
Installed in The gas supplied from the gas supply unit 4 is introduced into the ion source 6 by the gas pipe 5 and is supplied to the capillary 2.
And flows out from the orifice 3 into the atmosphere. The gas flow strikes the diffusion member 7 and is diffused. The minute droplets or ions generated in the atmosphere are
And is taken into the mass spectrometer 11 through the pores 10 and subjected to mass analysis. The present invention can be used even when the flow rate of the sample solution is higher than that of the conventional sonic spray ion source and mass spectrometer. The auto tuning reduces the adjustment work of the user.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a mass spectrometer and an ion source used for the same, and more particularly, to an ion source suitable for ionizing a sample existing in a liquid and introducing the ionized sample into a mass spectrometer. It relates to the mass spectrometer used.

[0002]

2. Description of the Related Art Capillary electrophoresis (CE) or liquid chromatography (LC) can separate a sample present in a solution, but it is difficult to identify the type of the separated sample. On the other hand, a mass spectrometer (MS) can identify a sample with high sensitivity, but cannot separate a sample in a solution. Therefore, when separating and analyzing a plurality of substances dissolved in a solvent such as water, a capillary electrophoresis / mass spectrometer (CE / M) in which capillary electrophoresis is connected to a mass spectrometer.
S), or a liquid chromatograph / mass spectrometer (LC / MS) coupled with a liquid chromatograph.

In order to analyze a sample separated by capillary electrophoresis or liquid chromatography with a mass spectrometer, it is necessary to convert sample molecules in a solution into gaseous ions. Conventional techniques for obtaining such ions include ion spraying (Analytical Chemistry),
Vol. 59 (1987) Paragraphs 2642 to 2646
Section) and the like are known. In this ion spray method, gas flows along the outer periphery of the capillary, and a high voltage (3) is applied between a capillary into which a sample solution is introduced and a pore (sampling orifice) for taking ions into a mass spectrometer. -6 kV) is applied, and a strong electric field is generated at the tip of the capillary. Due to the electrostatic spray phenomenon generated under such a configuration, small charged droplets are generated, and the above-mentioned gas vaporizes the solution in the charged droplets, thereby generating gaseous ions. The ions thus generated are introduced into a mass spectrometer via a sampling orifice and subjected to mass analysis. The above gas not only promotes the vaporization of the charged droplets but also suppresses the occurrence of discharge at the tip of the capillary.

When the flow rate of the solution supplied to the capillary is 1
An electrospray method (Journal of Physical Chemistry (Joun), which is a method of ionizing gas at a flow rate of 0 μL (microliter) / min or less without flowing gas.
al of Physical Chemistry), 8th
8 (1984) pp. 4451-4459)
Is distinguished from the ion spray method, but the principle of ion generation is the same as the ion spray method. Atmospheric pressure chemical ionization (analytical chemistry (An)
(Analytical Chemistry), Vol. 54 (1982), pp. 143 to 146), a method is provided in which an electrode for discharging is provided near the tip of the capillary and droplets sprayed under atmospheric pressure are ionized by discharging. Has been taken. In these various conventional spray ionization methods, in order to obtain high ion generation efficiency, a diameter of about 1 mm is required.
It is considered necessary to generate fine charged droplets of 0 nm or less.

[0005] United States Patent 5,352,892 describes a method of installing a liquid shield in front of a mass spectrometer, which allows only a central portion of a spray having many droplets having a small particle diameter to be ionized more efficiently by an ion spray. ing. Also, in order to efficiently ionize by the atmospheric pressure chemical ionization method, a sheet with a hole at the center is installed in front of the mass spectrometer to suppress the spread of the spray, and only the spray with a small spread angle is introduced into the mass spectrometer The method for this is described in JP-A-61-194349. Similarly, Japanese Patent Application Laid-Open No. Hei 7-159377 discloses a method in which a means for mixing sprays is provided to promote desolvation in order to efficiently ionize by atmospheric pressure chemical ionization. further,
Japanese Patent Application Laid-Open No. H5-256837 describes a method of heating droplets generated by spraying to promote vaporization.

[0006] Recently, as an ionization method, a sonic spray method in which ions are efficiently generated only by spraying a sample solution with a sonic gas has been reported (Analytical Chemistry).
istry, vol.66, pp4457-4559 (1994) or Analytical
Chemistry, vol. 67, pp. 2878-2882 (1995) or JP-A-7-306193). In this method, it is considered that fine charged droplets are generated by the flow of a sonic gas, and the solvent molecules are peeled off to generate ions.

In the above-mentioned sonic spray method, a high-speed gas flows from a very short distance from a fine hole of a mass spectrometer. When the flow rate of the sample solution is increased, a large amount of charged droplets are generated and taken into the mass spectrometer through the pores, and the cooled charged droplets aggregate due to adiabatic expansion to become large droplets, so that noise is generated. There was a problem that it was very large. Therefore, it cannot be used when the flow rate of the sample solution is as high as about 1 ml / min.

In addition, an adjustment operation for adjusting the gas flow rate in accordance with the flow rate of the sample solution and the type of the solvent is required, and the burden on the user is large.

[0009]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an ion source which further improves the ionization efficiency of the above-described sonic spray method of the prior art and reduces noise. Also, when used at a high solution flow rate of about 1 ml / min, a large amount of droplets are taken into the mass spectrometer from the pores, and the charged droplets cooled by adiabatic expansion condense into large droplets. There is a problem that noise is increased or measurement cannot be performed at all. The present invention addresses the problems encountered with such high solution flow rates. Further, the present invention has been made in order to reduce the adjustment work that the user has to perform.

[0010]

When the flow rate of the sample solution is high, a large amount of charged droplets are generated in the spray sprayed from the ion source. When the spray is taken into the mass spectrometer, the pressure drops sharply, causing adiabatic expansion and rapid cooling. If the density of the droplets in the spray taken into the mass spectrometer is too high, the droplets are cooled and aggregate to form large droplets, which increases noise and makes measurement difficult. Therefore, by installing a member that diffuses the spray between the ion source and the pores, reducing the density of the droplet during spraying, and then incorporating it into the mass spectrometer, the aggregation of the droplets is prevented. Will be resolved. In the sonic spray method, the droplet density near the center of the spray is high, so the central part of the spray is diffused, a droplet passage opening is provided in the peripheral part of the spray, and taken in the mass spectrometer. Go up. Further, by providing a room between the diffusion member and the pores, and further providing an exhaust port for allowing the gas in the room to escape to the atmosphere, the droplet density near the entrance of the pores becomes substantially constant, and more stable measurement can be performed. It becomes possible.

Further, the gas flow rate is changed according to the high solution flow rate, and an amount of gas sufficient to vaporize the solution is supplied. Alternatively, the flow rate of the solution is changed according to the flow rate of the gas, and an amount of the solution that is sufficiently vaporized by the gas amount is supplied. Further, the gas flow rate is changed according to the type of the solvent.

Further, by automatically tuning the optimal gas flow rate and solution flow rate based on the detection signal, the work of the user can be reduced.

[0013]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail with reference to the drawings.

(Embodiment 1) FIG. 1 is a block diagram showing an apparatus configuration of the present invention. The solution sample supplied to the sample solution introduction unit 1 is introduced into the capillary 2. The capillary 2 is fixed to the ion source body 6, and the tip is inserted into the orifice 3. The tip of the capillary 2 protrudes from the opening of the orifice by about -0.25 to 1.0 mm. The gas supplied from the gas supply unit 4 is introduced into the ion source main body 6 by the gas pipe 5 and flows along the outer periphery of the capillary. The gas from the orifice 3 into which the tip of the capillary 2 is inserted is approximately 200 m into the atmosphere. Jets at an F / S of at least / s. Here, the flow rate in the standard state of gas (20 ° C., 1 atm) is defined as F, and the space between the capillary 2 and the orifice 3 is substantially minimum on a plane substantially orthogonal to the central axis near the capillary tip. Is defined as S. As the spray gas, for example, nitrogen, argon, oxygen, air, or the like is used. The sample solution introduced into the capillary 2 is sprayed by a gas ejected along the tip of the capillary 2 to generate gaseous pseudo-molecular ions of sample molecules in addition to the microdroplets (this method uses sonic spray ( SonicSpray) method). The droplets or ions are diffused on the diffusion member 7 and further diffused.
And is taken into the inside of the mass spectrometer 11 from the pore 10 and subjected to mass analysis. A finite space 9 exists between the diffusion member 7 and the pores 10. A finite room may be installed as the space 9.

Instead of the above-mentioned ion source, an ion source which applies a voltage to the ion source body 6 and applies an electric field or voltage to the sample solution may be used.

FIG. 2 is a front view of a diffusion member according to an embodiment of the present invention. 6 for the circular plate-shaped diffusion member 7
The holes 8 are arranged in a circle. The position of the pore 10 is
It is installed so as to overlap the portion surrounded by the six holes 8.
In addition, the ion source is installed such that the central axis of the capillary 2 and the central axis of the pores 10 also substantially coincide with each other.

The effect of installing the diffusion member will be described below.

The density of droplets generated in the spray by the sonic spray method is high near the center axis of the spray,
The lower the distance from the center. FIG. 3 shows the density distribution. Since the center axis of the spray is substantially coincident with the center axis of the capillary 2, if the center axis of the capillary 2 and the center axis of the pore 10 are substantially coincident with each other, a gas having a high droplet density will flow from the pore 10 into the mass spectrometer. It is taken in. Droplets taken into the vacuum inside the mass spectrometer are rapidly cooled by adiabatic expansion. When a gas having a high droplet density is cooled, the droplets aggregate and become large droplets, which causes noise.

When the diffusion member 7 is provided in front of the pore 10 and the spray is diffused before the droplet is taken in from the pore 10, the distribution of the droplet density is averaged as shown in FIG. Therefore, the density of the droplets of the gas taken in from the pores 10 becomes low, so that aggregation does not easily occur even when cooled by adiabatic expansion, and noise can be reduced.

FIG. 5 is a sectional view of the diffusion member and the pores of the mass spectrometer when the diffusion member of FIG. 2 is a plate-like member. The central axes of the six holes 8 of the diffusion member and the central axes of the pores 10 are parallel but do not lie on a straight line. A spacer 13 is provided between the diffusion member 7 and the mass spectrometer.
Are arranged, and a finite space 9 is formed between the diffusion member 7 and the pores 10. The pores 10 are heated by a heater 12. Capillary 2 and pore 1 of ion source 6
Since the center axes of 0 are arranged so as to substantially coincide with each other,
The gas flow sprayed from the ion source is not directly taken into the pores 10 but is diffused by the diffusion member 7. The diffused droplet is taken into the mass spectrometer from the pore 10 via the hole 8.

The diffusing member 7 may be arranged so as to be in contact with the pores as shown in FIG.

FIG. 6 is a cross-sectional view of the diffusion member and the pores of the mass spectrometer when the diffusion member of FIG. 2 is another plate-like member. The central axes of the six holes 8 of the diffusion member 7 and the central axes of the pores 10 are parallel but do not lie on a straight line. The surface of the diffusion member 7 on the mass spectrometer side has a depression, and a finite room 18 is formed between the diffusion member 7 and the pores 10. The pores 10 are heated by a heater 12. Since the capillary 2 of the ion source 6 and the central axis of the pore 10 are substantially aligned, the gas flow sprayed from the ion source is not directly taken into the pore 10 but is diffused by the diffusion member 7. The diffused droplet enters the room 18 via the hole 8 and is further taken into the mass spectrometer through the pore 10.

The diffusing member 7 may be disposed so as to be in contact with the pores as shown in FIG.

In the embodiments shown in FIGS. 4, 5 and 6, when the flow rate of the solution is relatively low, the central axis of the capillary 2 and the central axis of one of the holes 8 substantially coincide with each other. It may be installed as follows.

FIG. 7 is a cross-sectional view of the diffusion member and the pore portion of the mass spectrometer when the diffusion member of FIG. 2 is another plate-shaped member. The central axes of the six holes 8 of the diffusion member 7 and the central axes of the pores 10 are parallel but do not lie on a straight line. The surface of the diffusion member 7 on the mass spectrometer side has a depression, and a finite room 18 is formed between the diffusion member 7 and the pores 10. Further, the diffusion member 7 is provided with an exhaust port 14 that escapes from the room 18 to the atmosphere, thereby preventing the gas pressure or the droplet density in the room 18 from increasing. When the density of the droplets in the room 18 increases, the density of the droplets taken into the mass spectrometer 11 increases, which causes noise. Therefore, the exhaust port 14 is provided to keep the density of the droplets in the room 18 at an appropriate value. There is a need. The pores 10 are heated by a heater 12. Since the center axis of the capillary 2 of the ion source 6 and the center axis of the pore 10 are substantially aligned, the gas flow sprayed from the ion source is not directly taken into the pore 10,
The light is diffused by the diffusion member 7. The diffused droplets are
And enters the room 18 via the pores 10 and further into the mass spectrometer through the pores 10. Excess droplets are discharged from the exhaust port 14 into the atmosphere.

The diffusing member 7 may be arranged so as to be in contact with the pores as shown in FIG.

FIG. 8 is a front view of a diffusion member according to another embodiment of the present invention. 1 for circular diffusion member 7
The holes 8 are cut out diagonally. The position of the pore 10 is set so as to overlap one opening of the hole 8.

FIG. 9 is a sectional view of the diffusion member 7 shown in FIG. 8 and a pore portion of the mass spectrometer. The hole 8 is cut obliquely so that the central axis of the hole 8 of the diffusion member 7 and the central axis of the pore 10 intersect. The pores 10 are heated by a heater 12. The gas stream sprayed from the capillary 2 of the ion source 6 is diffused by hitting the edge of the hole 8 and then reaches the pore 10 through the hole 8 cut obliquely. Therefore,
As in the other embodiments described above, noise can be reduced.

The diffusion member 7 may be disposed at a position apart from the pores as shown in FIG. 9 in addition to being disposed so as to be in contact with the pores.

FIG. 10 is a block diagram showing the structure of the apparatus when the diffusion member 7 is provided with a heating means. The diffusion member 7 is provided with a heating block 15 and is heated separately from the pores 10.

FIG. 11 is a view of the actual diffusion member viewed from the ion source side. Six holes 8 are formed in the circular plate-shaped diffusion member 7.
Are arranged in a circle. Also, four screw holes 16 are arranged.

FIG. 12 is a view of the diffusion member of FIG. 11 as viewed from the opposite side. Six holes 8 are arranged in a circular shape in a circular plate-shaped diffusion member 7. Also, four screw holes 16 are arranged.

FIG. 13 is a cross-sectional view of the diffusion member and the pores of the mass spectrometer when the diffusion member shown in FIGS. 11 and 12 is attached to the mass spectrometer. The central axes of the six holes 8 of the diffusion member and the central axes of the pores 10 are parallel but do not lie on a straight line. The diffusion member 7 is installed such that the position of the pore 10 overlaps the portion surrounded by the six holes 8. In addition, the capillary 2 of the ion source
And the central axis of the pores 10 are also substantially aligned. A spacer 13 is arranged between the diffusion member 7 and the mass spectrometer, and is fixed to the mass spectrometer by a screw 17 attached to a screw hole 16. Thereby, a finite space 9 is formed between the diffusion member 7 and the pores 10. The pores 10 are heated by a heater 12. Since the capillary 2 of the ion source 6 and the central axis of the pore 10 are substantially aligned, the gas flow sprayed from the ion source is not directly taken into the pore 10 but is diffused by the diffusion member 7. The diffused droplet is taken into the mass spectrometer from the pore 10 via the hole 8.

FIG. 14 is a view of another embodiment of the actual diffusion member viewed from the ion source side. Circular plate-shaped diffusion member 7
, Six holes 8 are arranged in a circle. Also, four screw holes 16 are arranged.

FIG. 15 is a view of the diffusion member of FIG. 14 as viewed from the opposite side. Six holes 8 are arranged in a circular shape in a circular plate-shaped diffusion member 7. Also, four screw holes 16 are arranged. A portion including the hole 8 is cut away to form a room 18 with the mass spectrometer.

FIG. 16 is a cross-sectional view of the diffusion member and the pores of the mass spectrometer when the diffusion member shown in FIGS. 14 and 15 is attached to the mass spectrometer. The central axes of the six holes 8 of the diffusion member and the central axes of the pores 10 are parallel but do not lie on a straight line. The diffusion member 7 is installed such that the position of the pore 10 overlaps the portion surrounded by the six holes 8. In addition, the capillary 2 of the ion source
And the central axis of the pores 10 are also substantially aligned. The diffusion member 7 is fixed to the mass spectrometer by a screw 17 attached to a screw hole 16. Since the mass spectrometer side of the diffusion member 7 is cut away, a finite room 18 is formed between the diffusion member 7 and the pores 10. The pores 10 are heated by a heater 12. Since the center axis of the capillary 2 of the ion source 6 and the center axis of the pore 10 are substantially coincident with each other, the gas flow sprayed from the ion source is not directly taken into the pore 10 and the diffusion member 7
Is diffused. The diffused droplet is taken into the mass spectrometer from the pore 10 via the hole 8.

Further, as shown in FIG. 17, a spacer 13 may be disposed between the diffusion member 7 and the mass spectrometer so that excessive droplets in the room 18 may be released to the atmosphere.

FIG. 18 is a diagram showing another embodiment of the actual diffusion member viewed from the ion source side. Six holes 8 are arranged in a circular shape in a circular plate-shaped diffusion member 7. Also, four screw holes 16 are arranged.

FIG. 19 is a view of the diffusion member of FIG. 18 as viewed from the opposite side. Six holes 8 are arranged in a circular shape in a circular plate-shaped diffusion member 7. Also, four screw holes 16 are arranged. A portion including the hole 8 is cut away to form a room 18 with the mass spectrometer. Further, the diffusion member 7
Are dug into four grooves from the room 18 to the edge of the diffusion member, and form an exhaust port 14 between the chamber 18 and the mass spectrometer.

FIG. 20 is a sectional view of the diffusion member and the pores of the mass spectrometer in a state where the diffusion member shown in FIGS. 18 and 19 is attached to the mass spectrometer. The central axes of the six holes 8 of the diffusion member and the central axes of the pores 10 are parallel but do not lie on a straight line. The diffusion member 7 is installed such that the position of the pore 10 overlaps the portion surrounded by the six holes 8. In addition, the capillary 2 of the ion source
And the central axis of the pores 10 are also substantially aligned. The diffusion member 7 is fixed to the mass spectrometer by a screw 17 attached to a screw hole 16. Since the mass spectrometer side of the diffusion member 7 is cut away, a finite room 18 is formed between the diffusion member 7 and the pores 10. Since the diffusion member 7 is dug in a groove shape from the portion of the room 18 to the edge, four exhaust ports 1 are provided between the diffusion member 7 and the mass spectrometer.
4 are formed and connect the room 18 to the atmosphere. The pores 10 are heated by a heater 12. Ion source 6
Are arranged so that the central axes of the capillary 2 and the pores 10 substantially coincide with each other. Therefore, the gas flow sprayed from the ion source is not directly taken into the pores 10 but is diffused by the diffusion member 7. The diffused droplets pass through pores 10 through holes 8.
From the mass spectrometer. Excess droplets in the room 18 are discharged from the exhaust port 14 to the atmosphere.

FIG. 21 is a diagram showing another embodiment of the diffusion member as viewed from the mass spectrometer side. Six holes 8 are arranged in a circular shape in a circular plate-shaped diffusion member 7. A portion including the hole 8 is cut away to form a room 18 with the mass spectrometer. Further, two diffusion members 7 are dug in a groove shape from the room 18 to the edge of the diffusion member, and form an exhaust port 14 between the diffusion member 7 and the mass spectrometer. The size of each part is shown in FIG.
As shown in FIG.

FIG. 22 shows an embodiment in which the ion source and the mass spectrometer according to the present invention are directly connected to a liquid chromatograph. The solution sample separated by the liquid chromatograph 22 is introduced into the ion source body 6 through the capillary 2. The flow rate of the gas supplied from the gas cylinder 19 is controlled by the regulator 20 and the gas flow controller 21, and the gas is introduced into the ion source body 6 by the gas pipe 5. Further, it is caused to flow along the outer peripheral portion of the capillary 2. The sample solution introduced into the capillary 2 is sprayed by a gas flowing along the outer peripheral portion of the capillary 2 to generate gaseous pseudo-molecular ions of sample molecules in addition to the microdroplets. The droplets or ions are diffused on the diffusion member 7, further pass through the holes 8 of the diffusion member 7,
From 0, it is taken into the mass spectrometer 11 and mass analyzed. The analysis data is sent to the personal computer 25, where it is stored and calculated. The inside of the mass spectrometer is kept in a vacuum by a vacuum pump in a vacuum section 24. A finite space 9 exists between the diffusion member 7 and the pores 10. A finite room may be installed as the space 9. Further, the ion source body 6 is X
It is installed on the YZ stage 23 and its position can be adjusted.

FIG. 23 shows the distances D and D between the diagonally arranged holes 8 of the circularly arranged holes 8 of the diffusion member 7.
That is, the relationship between the diameter D of the circle on which the hole 8 is disposed and the ionic strength of the monovalent protonated ion of lysine is shown. The sample solution is a 1 μmol / l lysine aqueous methanol solution. At this time, the distance between the surface of the diffusion member 7 and the ion source body 6 is 3 mm. The squares in the figure indicate that the solution flow rate is 1 ml / min, and the circles indicate that the solution flow rate is 0.2 ml / m.
In the case of “in”, the triangle indicates the case where the solution flow rate is 0.03 ml / min. When D = 4 mm, the ionic strength is high.

FIG. 24 shows the distances D and D between the diagonally arranged holes 8 of the circularly arranged holes 8 of the diffusion member 7.
That is, the relationship between the diameter D of the circle on which the hole 8 is disposed and the ion intensity of the divalent protonated ion of gramicidin S is shown. The vertical axis represents ion intensity (relative intensity), and the horizontal axis represents hole interval D. The sample solution is a 1 μmol / l aqueous solution of gramicidin S in methanol. At this time, the diffusion member 7
Of the ion source body 6 is 3 mm. The square in the figure indicates the case where the solution flow rate is 1 ml / min, the circle indicates the case where the solution flow rate is 0.2 ml / min, and the triangle indicates the solution flow rate.
This is the case of 0.03 ml / min. When D = 3 or 4 mm, the ionic strength is high.

FIGS. 23 and 24 show that when the distance between the surface of the diffusion member 7 and the ion source body 6 is 3 mm, the interval D between the holes 8 is optimally 3 mm or more and 4 mm or less. By analogy with this, the apex angle of an isosceles triangle with the distance D between the holes 8 as the base and the distance between the surface of the ion source body 6 and the surface of the diffusion member 7 as height is in the range of 53 to 64 degrees. The distance D between the holes 8 and the ion source body 6
It is advisable to adjust the distance between and the diffusion member 7.

FIG. 25 is a mass spectrum obtained from a 1 μmol / l lysine solution when the diffusion member of the embodiment of the present invention is installed and the solution flow rate is 1 ml / min. Since the density of droplets taken into the mass spectrometer is appropriate,
A clean spectrum is obtained, and the S / N is 27.

FIG. 26 is a spectrum obtained in the same manner as in FIG. 25 without disposing the diffusion member of the present invention. Since the liquid droplets are excessively taken into the mass spectrometer, cluster ions in which several solvent molecules are aggregated appear. Also, the S / N is as low as 7.

FIG. 27 is a mass spectrum obtained from a 1 μmol / l cytochrome C solution when the diffusion member of the embodiment of the present invention is installed and the solution flow rate is 1 ml / min. A series of multiply charged ions of cytochrome C has been observed. In this case, a voltage is applied to the ion source body 6, and an ion source that applies an electric field or voltage to the sample solution is used. Conventionally, multivalent ions of protein could not be measured at this solution flow rate, but the solution flow rate of 1 ml /
The measurement of multiply-charged ions became possible even in min.

FIG. 28 shows that the solution flow rate was 1 ml / min and 0.2 ml / mi.
It is a relation between ionic strength and gas flow rate when n and 0.03 ml / min. The vertical axis is gas flow, the horizontal axis is ion intensity (relative intensity)
It is. The squares in the figure indicate a solution flow rate of 1 ml / min, the circles indicate a solution flow rate of 0.2 ml / min, and the triangles indicate a solution flow rate of 0.03 ml / min.
This is the case for min. The on-strength of each flow rate is 3 ~
It is high at 4 l / min, and the difference due to the flow rate is relatively small. Therefore, if the flow rate slightly changes, it is not necessary to adjust the gas flow rate. By providing the diffusion member 7, the adjustment of the gas flow rate is simplified.

(Embodiment 2) When a diffusion member is not used as in the first embodiment, the gas flow rate is changed according to the solution flow rate, and an amount of gas sufficient to vaporize the solution is supplied. An apparatus will be described in which the flow rate of the solution is changed according to the flow rate, the solution is supplied in an amount sufficient to evaporate with the amount of the gas, and the gas flow rate is appropriately adjusted according to the type of the solvent. In this case, the usable solution flow rate is a relatively low value. The apparatus also performs automatic tuning of the optimal gas flow rate and solution flow rate based on the detection signal.

FIG. 29 is a block diagram showing an apparatus configuration according to the present invention. This will be described in detail below.

The solution sample supplied to the sample solution introducing section 1 is introduced into the capillary 2 by the pump 26. The pump 26 is controlled by the control unit 30 and changes the flow rate of the solution to be sent. A signal between the pump 26 and the control unit 30 is transmitted through a signal line 31. The control unit 30 performs automatic control, and also allows a user to input conditions and change operating conditions. The capillary 2 is fixed by being passed through a metal capillary 27 so as not to bend.
The metal capillary 27 is fixed to the ion source body 6. A part of the capillary 2 protrudes from the metal capillary 27, and its tip is inserted into the orifice 3. The tip of the capillary 2 protrudes from the opening of the orifice 3 by about -0.25 to 1.0 mm. The gas supplied from the gas supply unit 4 includes a gas pipe 5 and a solenoid valve 2.
8 and is introduced into the ion source body 6. Solenoid valve 28
Is controlled by the control unit 30 to change the gas flow rate. The signal between the solenoid valve 28 and the control unit 30 is
Conveyed through. The control unit 30 performs automatic control, and also allows a user to input conditions and change operating conditions. The gas introduced into the ion source body 6 is:
The gas flows along the outer periphery of the capillary 2 and is ejected into the atmosphere from the orifice 3 into which the tip of the capillary 2 is inserted. As the spray gas, for example, nitrogen, argon, oxygen, air, or the like is used. The sample solution introduced into the capillary is
It is sprayed by the gas ejected along the tip of the capillary, and gaseous pseudo-molecular ions of sample molecules are generated in addition to the microdroplets. The generated ions pass through the hole of the cover 34, are taken into the inside of the mass spectrometer 11 from the pore 10, are subjected to mass analysis, and the detector 29 detects the ion intensity.
The pores 10 are heated by a heater 12.
The detector 29 is connected to the control unit 30 by a signal line 33, and sends a signal to the control unit 30.

Further, instead of the above-mentioned ion source, an ion source which applies a voltage to the ion source body 6 and applies an electric field or voltage to the sample solution may be used.

Hereinafter, the control unit 30 will be described in more detail. The control unit 30 is connected to the pump 26, the solenoid valve 28, and the detector 29 by signal lines 31, 32, and 33, and obtains information on the solution flow rate, the gas flow rate, and the detected ionic strength. Further, the control unit 30 has a table of a necessary gas flow rate according to the type of the solvent and the flow rate of the solution, and automatically adjusts the solution flow rate or the gas flow rate based on the obtained information, the type of the solvent input by the user, and the like. Control. Further, the control unit 30 monitors the detected ionic strength obtained by the detector 29 and automatically controls the solution flow rate and the gas flow rate so that the detected ionic strength becomes higher. This allows
The user can perform the measurement without adjusting the gas flow rate or the solution flow rate. Further, the control unit 30 can also perform manual setting, the user can freely set each flow rate, and can fix the control amount regardless of the detection signal. Even if the user manually sets the initial value of each flow rate, the control unit 1
It is also possible that 8 monitors the detected ion intensity and automatically controls each flow rate (auto tuning).

FIGS. 30 and 31 are graphs showing the relationship between the ion intensity and the gas flow rate, showing that the gas flow rate required for ionizing the sample differs depending on the solution flow rate.

FIG. 30 shows the relationship between ionic strength and gas flow rate when the solution flow rate is 200 μl / min. The vertical axis is the gas flow rate,
The horizontal axis is the ion intensity (relative intensity). The ionic strength is
It is maximum when the gas flow rate is 6 l / min.
It can be seen that when the gas flow rate is 200 μl / min, the gas flow rate should be 6 l / min.

FIG. 31 shows the relationship between ionic strength and gas flow rate when the solution flow rate is 30 μl / min. The vertical axis is the gas flow rate,
The horizontal axis is the ion intensity (relative intensity). The ionic strength is
It is maximum when the gas flow rate is 3 l / min.
It can be seen that when the gas flow rate is 30 μl / min, the gas flow rate should be 3 l / min.

The controller 30 in FIG. 29 stores the above relationship in a table and controls each flow rate based on the table.

FIG. 32 is a mass spectrum obtained by the second embodiment of the present invention. The sample solution was prepared by dissolving 10 μmol / l thiuram in a 50% aqueous methanol solution. Proton (H) adduct ion of thiuram and sodium (N
a) Adduct ions have been detected.

The control unit 30 shown in FIG. 29 monitors the ionic strength of a specific mass (for example, 241 of proton-added thiuram ion or 263 of sodium-added thiuram ion) or the ionic strength of the entire spectrum, and controls the solution flow rate. Or control the gas flow rate.

FIG. 33 shows an example in which the present invention is applied to an ion spray method. The solution sample supplied to the sample solution introduction unit 1 is introduced into the metal capillary 35. The metal capillary 35 is a pipe-shaped ion spray ion source 3
6 is inserted. A voltage is applied between the metal capillary 35 and the mass spectrometer by the power supply 17 to spray the solution electrostatically. The gas supplied from the gas supply unit 4 is
Flow rate 1 ml / min to 3 ml / min by gas pipe 5
Is introduced into the ion spray ion source 35, and flows along the outer periphery of the capillary to help remove the solvent from the droplets generated by the electrostatic spraying. Also in this ion spray method, the droplet density near the central axis of the spray is high. Therefore, as in the case of the sonic spray method described above, when the flow rate of the solution is increased, a large amount of droplets are taken into the mass spectrometer, cooled by adiabatic expansion and aggregated, causing a problem of causing noise. Therefore, by using the diffusion member of the present invention to diffuse a gas containing high-density droplets near the center axis of the spray, and keeping the droplet density of the gas taken into the mass spectrometer at an appropriate value, It is self-evident that the problem will be solved.

[0062]

By using the ion source and the mass spectrometer having the diffusion member of the present invention, a large amount of droplets are taken into the mass spectrometer, and the droplets are aggregated due to adiabatic expansion, and large droplets are formed. The S / N can be prevented from becoming a cause of noise, so that the S / N becomes higher and the noise is reduced as compared with the conventional sonic spray method ion source and mass spectrometer. Further, it can be used even when the sample solution is as high as about 1 μl / min.

By supplying an appropriate gas flow rate according to the solution flow rate or the solvent type, efficient ion detection becomes possible. Further, the solution flow rate can be adjusted according to the type of the solvent or the gas flow rate. Furthermore, the solution flow rate or gas flow rate is automatically tuned so that the detected ionic strength is increased, and the user's adjustment work of the apparatus is reduced,
Easy handling for beginners.

[Brief description of the drawings]

FIG. 1 is a block diagram showing a configuration of an apparatus according to a first embodiment of the present invention.

FIG. 2 is a front view of a diffusion member according to the first embodiment of the present invention.

FIG. 3 shows the distribution of the droplet density when the diffusion member of the first embodiment of the present invention is not used.

FIG. 4 shows a distribution of droplet density when the diffusion member according to the first embodiment of the present invention is used.

FIG. 5 is a cross-sectional view of a diffusion member and pores according to the first embodiment of the present invention.

FIG. 6 is a cross-sectional view of another diffusion member and a pore portion according to the first embodiment of the present invention.

FIG. 7 is a cross-sectional view of still another diffusion member and a pore portion according to the first embodiment of the present invention.

FIG. 8 is a front view of the diffusion member according to the first embodiment of the present invention.

FIG. 9 is a cross-sectional view of a diffusion member and a pore portion according to the first embodiment of the present invention.

FIG. 10 is a cross-sectional view of a diffusion member having heating means and a pore portion according to the first embodiment of the present invention.

FIG. 11 is a view of the diffusion member according to the first embodiment of the present invention as viewed from the ion source side.

FIG. 12 is a view of the diffusion member according to the first embodiment of the present invention as viewed from the mass spectrometer side.

FIG. 13 is a cross-sectional view of the diffusion member and the pores of FIGS.

FIG. 14 is a view of another diffusion member according to the first embodiment of the present invention as viewed from the ion source side.

FIG. 15 is a view of another diffusion member according to the first embodiment of the present invention as viewed from the mass spectrometer side.

FIG. 16 is a cross-sectional view of the diffusion member and the pores of FIGS.

FIG. 17 is a cross-sectional view of the diffusion member and the pores of FIGS.

FIG. 18 is a diagram of another diffusion member according to the first embodiment of the present invention as viewed from the ion source side.

FIG. 19 is a view of a further diffusion member of the first embodiment of the present invention as viewed from the mass spectrometer side.

FIG. 20 is a cross-sectional view of the diffusion member and the pores of FIGS.

FIG. 21 is a diagram of another diffusion member according to the first embodiment of the present invention as viewed from the mass spectrometer side.

FIG. 22 is a configuration diagram of the first embodiment of the present invention when directly connected to a liquid chromatograph.

FIG. 23 is a diagram showing the interval D between diagonal holes among the circular holes 8 of the diffusion member 7 and the monovalent protonated ion of lysine according to the first embodiment of the present invention. Ionic strength relationship.

FIG. 24 is a diagram showing the interval D between diagonally arranged holes 8 of the circular holes 8 of the diffusion member 7 and the addition of divalent protons of gramicidin S in the first embodiment of the present invention. The relationship between the ionic strength of the ions.

FIG. 25 is a mass spectrum of lysine having a solution flow rate of 1 ml / min obtained when the diffusion member 7 is arranged according to the first embodiment of the present invention.

FIG. 26 is a mass spectrum of lysine having a solution flow rate of 1 ml / min, obtained when the diffusion member 7 is not provided.

FIG. 27 is a mass spectrum of cytochrome C having a solution flow rate of 1 ml / min obtained when the diffusion member 7 is arranged according to the first embodiment of the present invention.

FIG. 28 is a diagram illustrating a flow rate of a solution according to a first embodiment of the present invention.
FIG. 3 is a diagram showing the relationship between ionic strength and gas flow rate at 1, 0.2, and 0.03 ml / min.

FIG. 29 is a block diagram showing a configuration of an apparatus according to a second embodiment of the present invention.

FIG. 30 shows a second embodiment of the present invention.
FIG. 4 is a graph showing the relationship between ionic strength and gas flow rate showing the optimum gas flow rate at 200 μl / min.

FIG. 31 shows a second embodiment of the present invention.
FIG. 4 is a graph showing the relationship between ionic strength and gas flow rate showing the optimum gas flow rate at 30 μl / min.

FIG. 32 is a mass spectrum obtained by the apparatus according to the second embodiment of the present invention.

FIG. 33 is a block diagram of an embodiment in which the present invention is applied to an ion spray method.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Sample solution introduction part, 2 ... Capillary, 3 ... Orifice, 4 ... Gas supply part, 5 ... Gas pipe, 6 ... Ion source body,
7 ... diffusion member, 8 ... hole of diffusion member 7, 9 ... space, 10 ...
Pores, 11: mass spectrometer, 12: heater, 13: spacer, 14: exhaust port, 15: heating block, 16:
Screw hole, 17 ... screw, 18 ... room, 19 ... gas cylinder,
20: Regulator, 21: Gas flow controller, 22: Liquid chromatograph, 23: XYZ stage, 24: Vacuum unit, 25: Computer, 26: Pump, 27: Metal capillary, 28: Solenoid valve, 29 ...
Detector, 30 ... control unit, 31, 32, 33 ... signal line, 3
4 ... cover, 35 ... metal capillary, 36 ... ion spray ion source, 37 ... power supply.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Minoru Sakairi, 1-280 Higashi Koikekubo, Kokubunji-shi, Tokyo Inside the Central Research Laboratory, Hitachi, Ltd. Central Research Laboratory

Claims (44)

[Claims] An ion source for spraying an introduced sample solution into the atmosphere with a high-speed gas to ionize a sample dissolved in the solution, a pore for taking in generated ions into a vacuum, and a mass spectrometer. An ion source and a mass spectrometer having a mass spectrometer having a diffusion member for diffusing a sprayed droplet between the ion source and the pore. 2. An ion source for spraying an introduced sample solution into the atmosphere with a high-speed gas to ionize a sample dissolved in the solution, a pore for taking in generated ions into a vacuum, and a mass spectrometer. A mass spectrometer having a diffusion member for diffusing the sprayed droplets between the ion source and the pores, and having a finite space between the pores and the diffusion member. Characterized ion source and mass spectrometer. 3. The diffusing member is a plate-like member having one or a plurality of holes, and each hole of the plate-like member and the central axis of the pore are not on a straight line. The ion source and the mass spectrometer according to claim 1 or 2, wherein 4. The diffusing member is a plate-like member having one or a plurality of holes, and a central axis of one or a plurality of holes of the plate-like member and a central axis of the pore intersect. The ion source and the mass spectrometer according to claim 1, 2 or 3, which are installed. 5. The diffusion member is a plate-like member having one or more holes, and a central axis of one or more holes of the plate-like member and a central axis of the pore are substantially parallel. The ion source and the mass spectrometer according to claim 1, 2 or 3, which are installed. 6. The ion source and mass according to claim 1, wherein the diffusion member is a plate-like member having a plurality of holes, and the plurality of holes are arranged substantially along a circle. Analysis equipment. 7. The method according to claim 6, wherein the diameter of the circle along which the plurality of holes are arranged is 3 mm or more and 4 mm or less.
2 or 3 ion sources and mass spectrometers. 8. A vertex angle of an isosceles triangle in which a diameter of the circle along which a plurality of holes are arranged is a base and a distance between the ion source and the diffusion member is a height, 4. The ion source and mass spectrometer according to claim 1, wherein the angle ranges from 53 degrees to 64 degrees. 9. An ion source for spraying an introduced sample solution into the atmosphere with a high-speed gas to ionize a sample dissolved in the solution, a pore for taking in generated ions into a vacuum, and a mass spectrometer. A mass spectrometer having a diffusion member for diffusing the sprayed droplets between the ion source and the pore, having a finite space between the pore and the diffusion member, Further, the diffusion member is a plate-like member having one or a plurality of holes, wherein the center axis of each hole of the plate-like member and the pore is not on a straight line, Mass spectrometer. 10. An ion source and a mass spectrometer according to claim 1, wherein a heating means is provided in said diffusion member. 11. An ion source and a mass spectrometer according to claim 1, wherein said diffusion member has no protrusion near a portion where the sprayed droplet is diffused. 12. An ion source and a mass spectrometer according to claim 1, further comprising means for separating a mixed solution before the ion source. 13. The ion source and mass spectrometer according to claim 12, wherein the means for separating the mixed solution is a liquid chromatograph. 14. The ion source and mass spectrometer according to claim 12, wherein the means for separating the mixed solution is a capillary electrophoresis apparatus. 15. An ion source for spraying an introduced sample solution into the atmosphere with a high-speed gas to ionize a sample dissolved in the solution, a pore for taking in generated ions into a vacuum, and a mass spectrometer. A mass spectrometer having a diffusion member for diffusing the sprayed droplets between the ion source and the pores, and having a finite room between the pores and the diffusion member. Characterized ion source and mass spectrometer. 16. The diffusion member is a plate-like member having one or a plurality of holes, a room between the pores and the diffusion member is connected to the atmosphere by the hole, and the plate-like member has 16. The ion source and mass spectrometer according to claim 1, wherein each of the holes and the central axis of the pore are not on a straight line. 17. The diffusing member is a plate-like member having one or a plurality of holes, a room between the pores and the diffusing member is connected to the atmosphere by the hole, and The central axis of one or more holes and the central axis of the pores are installed so as to intersect with each other.
6. The ion source and the mass spectrometer of 6. 18. The diffusing member is a plate-like member having one or a plurality of holes, a room between the pores and the diffusing member is connected to the atmosphere by the hole, and The central axis of one or a plurality of holes and the central axis of the pore are installed substantially in parallel.
Ion source and mass spectrometer. 19. The diffusing member is a plate-like member having a plurality of holes, a room between the pores and the diffusing member is connected to the atmosphere by the holes, and the plurality of holes substantially follow a circle. 17. The device according to claim 1, 15 or 1, wherein
6. The ion source and the mass spectrometer of 6. 20. The ion source according to claim 1, wherein the diameter of the circle along which the plurality of holes are arranged is 3 mm or more and 4 mm or less. And mass spectrometer. 21. The apex angle of an isosceles triangle in which the diameter of the circle along which a plurality of holes are arranged is defined as the base and the distance between the ion source and the diffusion member is the height. 17. The ion source and mass spectrometer according to claim 1, 15 or 16, wherein the angle is in a range of 53 degrees to 64 degrees. 22. An ion source for spraying the introduced sample solution into the atmosphere with a high-speed gas to ionize the sample dissolved in the solution, a pore for taking in the generated ions into a vacuum, and a mass spectrometer. A mass spectrometer having a diffusion member for diffusing the sprayed droplets between the ion source and the pores, having a finite room between the pores and the diffusion member, Further, the diffusion member is a plate-like member having one or a plurality of holes, a room between the pores and the diffusion member is connected to the atmosphere by the hole, and each hole of the plate-like member is An ion source and a mass spectrometer, wherein a center axis of the pore is not on a straight line. 23. An ion source and a mass spectrometer according to claim 15, wherein said diffusion member is provided with a heating means. 24. The ion source and mass spectrometer according to claim 15, wherein said diffusion member has no protrusion near a portion where the sprayed droplet is diffused. 25. The ion source and mass spectrometer according to claim 15, further comprising means for separating a mixed solution before the ion source. 26. The ion source and mass spectrometer according to claim 25, wherein the means for separating the mixed solution is a liquid chromatograph. 27. The ion source and mass spectrometer according to claim 25, wherein the means for separating the mixed solution is a capillary electrophoresis apparatus. 28. An ion source for spraying an introduced sample solution into the atmosphere with a high-speed gas to ionize a sample dissolved in the solution, a pore for taking in generated ions into a vacuum, and a mass spectrometer. A mass spectrometer having a diffusion member for diffusing a sprayed droplet between the ion source and the pore, a finite room between the pore and the diffusion member, and the room An ion source and a mass spectrometer having an exhaust port for discharging gas inside the air to the atmosphere. 29. The diffusing member is a plate-like member having one or a plurality of holes, and a room between the pores and the diffusing member is connected to the atmosphere by the hole. 29. The ion source and mass spectrometer according to claim 1 or 28, wherein each hole and the central axis of the pore are not on a straight line. 30. The diffusing member is a plate-like member having one or a plurality of holes, and a room between the pores and the diffusing member is connected to the atmosphere by the hole. 3. The device according to claim 1, wherein the central axis of one or more holes and the central axis of the pore intersect.
Nine ion sources and mass spectrometers. 31. The diffusing member is a plate-like member having one or a plurality of holes, and a room between the pores and the diffusing member is connected to the atmosphere by the hole. 30. The central axis of one or more holes and the central axis of the pore are set substantially parallel.
Ion source and mass spectrometer. 32. The diffusing member is a plate-like member having a plurality of holes, a room between the pores and the diffusing member is connected to the atmosphere by the holes, and the plurality of holes substantially follow a circle. 3. The device according to claim 1, wherein the device is arranged at a right angle.
Nine ion sources and mass spectrometers. 33. The ion source according to claim 1, 28 or 29, wherein the diameter of the circle along which the plurality of holes are arranged is 3 mm or more and 4 mm or less. And mass spectrometer. 34. The isosceles triangle according to claim 32, wherein a diameter of the circle along which a plurality of holes are arranged is a base, and a distance between the ion source and the diffusion member is a height, 30. The ion source and mass spectrometer of claim 1, 28 or 29, wherein the angle is in the range of 53 degrees to 64 degrees. 35. An ion source for spraying the introduced sample solution into the atmosphere with a high-speed gas to ionize the sample dissolved in the solution, a pore for taking in the generated ions into a vacuum, and a mass spectrometer. A mass spectrometer having a diffusion member for diffusing a sprayed droplet between the ion source and the pore, a finite room between the pore and the diffusion member, and the room An exhaust port for discharging gas in the atmosphere into the atmosphere, the diffusion member is a plate-like member having one or more holes, and a room between the pores and the diffusion member is An ion source and a mass spectrometer, wherein the hole is connected to the atmosphere, and the center axis of each hole of the plate member and the center of the pore are not on a straight line. 36. The ion source and mass spectrometer according to claim 28, wherein a heating means is provided on said diffusion member. 37. The ion source and mass spectrometer according to claim 28, wherein the diffusion member has no protrusion near a portion where the sprayed droplet is diffused. 38. The ion source and mass spectrometer according to claim 28, further comprising means for separating a mixed solution before the ion source. 39. The ion source and mass spectrometer according to claim 38, wherein the means for separating the mixed solution is a liquid chromatograph. 40. The ion source and mass spectrometer according to claim 38, wherein the means for separating the mixed solution is a capillary electrophoresis apparatus. 41. A sample solution supply section, a capillary through which the solution supplied from the sample supply section flows, a solution flow rate control means for controlling a flow rate of the solution flowing through the capillary, A gas supply unit for ionizing, a gas flow control unit for controlling the flow rate of the gas, an analysis unit for analyzing the ionized sample, and the solution flow control unit and the gas flow control unit for a predetermined solution flow rate. And a flow control means for instructing a control amount to the mass spectrometer. 42. A sample solution supply section, a capillary through which the solution supplied from the sample solution supply section flows, voltage applying means for applying an electric field to the solution via an insulator, Solution flow rate control means for controlling the flow rate, a gas supply unit for spraying the sample solution and ionizing the sample, a gas flow rate control means for controlling the flow rate of the gas, and an analysis unit for analyzing the ionized sample, A mass spectrometer comprising a flow rate control means for instructing the solution flow rate control means and the gas flow rate control means with a control amount for a predetermined solution flow rate. 43. A sample solution supply section, a capillary through which the solution supplied from the sample supply section flows, a solution flow rate control means for controlling a flow rate of the solution flowing through the capillary, A gas supply unit for ionizing the gas, a gas flow control unit for controlling the flow rate of the gas, an analysis unit for analyzing the ionized sample, and a detection unit for detecting an ion intensity signal of the ionized sample,
A mass spectrometer comprising a flow rate control means for instructing the solution flow rate control means and the gas flow rate control means to control a predetermined solution flow rate based on a signal from the detection means. 44. A sample solution supply section, a capillary through which the solution supplied from the sample solution supply section flows, voltage applying means for applying an electric field to the solution through an insulator, and a solution flowing through the capillary. Solution flow rate control means for controlling the flow rate, a gas supply unit for spraying the sample solution and ionizing the sample, a gas flow rate control means for controlling the flow rate of the gas, and an analysis unit for analyzing the ionized sample, Detecting means for detecting an ion intensity signal of the ionized sample; and a flow control for instructing the solution flow rate controlling means and the gas flow rate controlling means for a predetermined solution flow rate based on a signal from the detecting means. And a mass spectrometer.