JPS6253903B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an improvement in a sample introduction device to a mass spectrometer (MS), and in particular, to extremely effectively atomize a liquid sample containing a thermally unstable chemical species; This invention relates to a device that can continuously introduce atomized material into an MS.

A mass spectrometer (MS) collects ions onto one or more fixed ion collecting electrodes and measures the ion current obtained by continuously adjusting the accelerating voltage and magnetic field strength to generate a mass spectrum. This device is designed to obtain mass spectra and is widely used for the qualitative and quantitative determination of gases, as well as liquid and solid molecules that can be gasified. In recent years, attempts have also been made to use such MS in conjunction with other separation and analysis instruments for effective analysis of mixtures.

For example, liquid chromatography (LC), particularly high-performance liquid chromatography (HLC), which has been attracting attention in recent years, is capable of separating fat-soluble and water-soluble substances into their respective components without modification by selecting the solvent and column. It has been recognized that this method is an excellent means for separating each component in a mixture and conducting its quantitative analysis. However, it takes
Although HLC is excellent in its ability to separate a mixture into its components, it has a problem in that it has a weak ability to fix the separated components. On the other hand, a mass spectrometer (MS) can identify a single component with extremely high sensitivity and high performance, but in the case of a mixture, the spectrum becomes complex, making identification difficult. Therefore, an LC-MS analysis system that combines LC and MS has been proposed in an attempt to effectively utilize the strengths of these two devices and compensate for their weaknesses.

On the other hand, analysis by MS is performed by ionizing a gaseous sample, which causes various problems when the sample is in a liquid or solution state with another solvent. In other words, in the case of a liquid sample in a liquid or solution state, it is necessary to vaporize it and guide it to the ionization section (ion source) of the MS. It is difficult to vaporize the sample and introduce it to the ionization part, and this is particularly difficult when the sample is a compound with high polarity or large molecular weight. In addition, the LC-MS analysis system described above has the same problem as above because the eluate from the LC separation column is a liquid (liquid sample), and it is continuously supplied. The practical application of this LC-MS analysis method is hampered by the fact that it is not easy to continuously remove the solvent (mobile phase) from the eluate, and therefore no effective means of concentrating the target components in the eluate has been found. This is a major hindrance.

Therefore, various studies have been conducted on methods of introducing such liquid samples into MS, and in particular, the so-called interface, the coupling mechanism between LC and MS in LC-MS analysis systems, has been a key point in development. Although extensive research is being carried out, the current situation is that nothing effective for practical use has yet been developed.

As a result of various studies in view of the above circumstances, the inventors of the present invention have decided to atomize the liquid sample to be analyzed using the so-called atomizing principle and introduce it into the MS. As a result, we discovered a method to effectively vaporize liquid samples and enable continuous and stable introduction into MS, and this method was first published in Japanese Patent Application No. 53-111130 (Japanese Patent Publication No. 58-3592). A patent application was filed as

However, subsequent studies by the present inventors revealed that even with the previously applied sample introduction method, which has such excellent features, there is still room for further improvement. That is, in order to atomize and further vaporize the liquid sample, the atomization region of the liquid sample is generally heated by an appropriate heating means, and this heating causes the inside of the capillary tube to reach its tip nozzle. Therefore, especially when the sample component in the liquid sample is a thermally unstable chemical species such as glucose, such heating action The chemical species may deteriorate in the capillary tube, making accurate measurement impossible, or the chemical species may not be introduced to the tip nozzle in a solution state, and may precipitate as a solid, making measurement difficult. There are inherent problems such as:

Therefore, the present inventors further investigated the previously developed sample introduction mechanism and found that it is effective and effective even for liquid samples containing thermally unstable chemical species such as glucose as sample components. MS
They discovered a mechanism that could be introduced into the system and completed the present invention.

That is, the present invention allows a liquid sample supplied through a capillary tube to be discharged from the tip of the capillary tube, and at the same time, a jet jet of atomizing gas is ejected from around the tip of the capillary tube. A sample introducing device is configured to atomize the discharged liquid sample and then guide the formed atomized liquid sample to the ionization section of the mass spectrometer, (a) an area where the liquid sample is atomized; (b) heating means for heating the
(c) a cooling means provided near the tip of the capillary tube so as to surround the circumference thereof, and preventing heating of the capillary tube by the heating means; (c) provided at the tip of the capillary tube; and a heat collecting means made of a material with excellent thermal conductivity, which concentrates the heat from the heating means on the tip of the capillary tube. The tip (nozzle part) of the capillary tube is cooled by a cooling means to prevent heating from reaching the liquid sample being moved within the tube, while the tip of the capillary tube is cooled by a heat collecting means. Therefore, by concentrating the heat from the heating means that heats the atomization area and effectively atomizing or gasifying the liquid sample sprayed at the tip, thermally Even liquid samples containing unstable chemical species can now be effectively and efficiently introduced into MS without altering their quality.

Hereinafter, the present invention will be explained in more detail based on embodiments shown in the drawings.

FIG. 1 is a cross-sectional view of a device (interface) according to an embodiment of the present invention, FIG. 2 is an enlarged cross-sectional view of the vicinity of the tip nozzle of a capillary tube in the device, and FIG. It is a further enlarged sectional view of the tube tip nozzle part.

In these figures, reference numeral 1 denotes an interface body with a double tube structure consisting of an inner tube 2 made of stainless steel and an outer tube 3 made of heat-resistant glass. It is screwed into and held by the holding member 4 and is airtightly attached to the rear end of the outer tube 3 via set screws 5 and 6 and threaded cylinders 7 and 8. Further, the rear portion of the cylindrical holding member 4 is provided with an axial capillary tube insertion portion 4a extending further rearward and an atomizing gas introduction portion 4b extending laterally from an intermediate portion of the insertion portion 4a.
A capillary tube 11 is provided passing through the plug 10 attached with a set screw 9 at the end of the introduction part 4a, and the rear end of the tube 11 is
It is connected to a flow path 13 for the eluate E flowing out from the column 12 of the HLC so that the eluate E from the column 12 is guided into the capillary tube 11, while the set screw of the introduction part 4b Atomizing gas (helium gas; He is used here) supplied from an atomizing gas source (not shown) is introduced into the cylindrical holding member 4 from the needle 16 that passes through the plug 15 attached at 14. It is adapted to be further guided into the inner tube 2.

Further, the front part of the interface main body 1 is attached to the body 17 of the MS with setscrews 18 and 19 so as to pass through it, as shown in FIG. front end)
It is connected to the ionization chamber 20 of a normal MS.

A bottomed heat insulating cylinder 21 made of a heat insulating material (Macor) is attached to the front end of the inner tube 3 coaxially held by the spacer 28 at its opening. Additionally, a copper heat collecting plate 2 is provided on the outside of the bottom of the heat insulating cylinder 21 as a heat collecting means.
2 is attached to the inside of the bottom of the heat insulating cylinder 21, consisting of an inner cylinder part 23a and an outer cylinder part 23b,
A cooling cylinder 23 having a double cylinder structure with both ends closed is housed and provided. Further, a guide tube 24 passing through the heat collecting plate 22 and the bottom of the heat insulating cylinder 21 is welded and fixed to the heat collecting plate 22, while a guide tube 24 is inserted into the inner cylinder part 23a of the cooling cylinder 23 for a predetermined length. It is extending. Further, a polyimide film 25 is wrapped around the outside of the cooling cylinder 23 (outer periphery of the outer cylinder part 23b) for heat insulation, and a supply for circulating a cooling medium (water in this case) inside the cooling cylinder 23. The pipe 26 penetrates and is installed to the innermost part of the cooling cylinder 23, and the discharge pipe 27 is inserted into the cooling cylinder 23.
It is provided at the inlet (rear end) of the The supply pipe 26 and the discharge pipe 27 pass through the inner pipe 2 and the cylindrical holding member 4, and extend from the rear of the cylindrical holding member 4 to the outside of the interface.

The capillary tube 11 that guides the eluate E from the column 12 extends into the heat insulating tube 21 through the space of the cylindrical holding member 4 and the space of the inner tube 2, and is shown in FIGS. 2 and 3. It is inserted into the guide tube 24 through the inner cylindrical part 23a of the cooling cylinder 23 as shown in FIG. There is. In addition, a piano wire (steel wire) 29 is further inserted as a core wire over the entire length into the capillary tube 11, and between the inner surface of the tube 11 and the outer surface of the piano wire 29. An eluate passage with an appropriate gap is formed in the tube 11 so that the eluate E can be continuously and stably ejected from the opening at the tip of the tube 11.

In addition, the tip portion of the outer tube 3, which is located in the atomization area around the tip opening of the capillary tube 11 that penetrates the bottom of the heat insulating tube 21 and the heat collecting plate 22, and surrounds it, is as shown in FIG. After being squeezed to gradually reduce its diameter, an introduction tube portion 30 is integrally formed at its gradually decreasing end. This introduction tube part 30 has a through hole in the center,
The side of the capillary tube 11 has a conical shape, and has an opening for introducing atomized material, which opens opposite to the tip opening of the tube 11 and at a predetermined distance therefrom. It has an opening that opens to the ionization chamber 20 side.
A heater 31 as a heating means is wound around the outside of the tip portion of the outer tube 3 whose diameter gradually decreases to heat the atomization area of the eluate E, which is formed by spraying. The heat of vaporization is supplied to the atomized material. Further, the outer tube 3 is connected to a rotary pump 32 which is a vacuum pump so that the inside of the outer tube 3 including the atomization region is maintained at a predetermined degree of reduced pressure (degree of vacuum).

Therefore, in such a configuration, column 1 of the LC
The eluate E flowing out from the tube 13 is guided into the capillary tube 11 through the flow path 13, and passes through the passage (gap) between the inner surface of the tube 11 and the piano wire 29 to the cylindrical holding member 4 and the inside. The pipe 2 section leads to the heat insulating pipe 21 and further into the cooling pipe 23, where the capillary tube 11 connects to the heat insulating pipe 2.
1. Due to the heat insulation provided by the polyimide film 25 and the cooling provided by the cooling tube 23, the heating effect from the heater 31 is not substantially applied.
Furthermore, the eluate E transferred within the capillary tube 11 is not subjected to such heating action. The eluate E thus guided while avoiding the heating effect of the heater 31 as much as possible is intensively subjected to the heating effect from the heat collecting plate 22 provided at the tip of the capillary tube 11. At the same time, the liquid is discharged forward from the opening at the tip of the tube 11. Note that this eluate E is forcibly discharged by a pressure reduction action within the outer tube 3 and/or by an external pump action.

On the other hand, the atomized gas introduced into the space of the cylindrical holding member 4 through the needle 16;
The liquid is ejected from the space 3a, through the gap between the guide tube 24 and the capillary tube 11, and from the opening at the tip of the guide tube 24 at high speed.

Therefore, due to the jet jet of the spray gas He, the capillary tube 11
The eluate E discharged from the tip opening of the
A fine mist is continuously sprayed in the area in front of the tip opening. In addition, this spray area is not only affected by the high vacuum of the MS, but also maintained at a predetermined degree of depressurization by the rotary pump 32, and at the same time heated by the heater 31. Part of the atomized product (aerosol) of eluent E is desolvated by heat and vacuum to form a dry aerosol, and these are combined into a high vacuum action on the MS side through the orifice of the introduction tube section 30. Therefore, it is guided to the ionization chamber 20.

In this way, in the above embodiment, the eluent E guided inside the capillary tube 11 to the spraying section
However, in order to avoid the heating effect by the heater 31,
The cooling cylinder 23 is cooled by a suitable cooling medium such as water that is passed through the cooling cylinder 23, and the heat insulating cylinder 2
Heat insulation by 1, further polyimide film 2
The effect is further enhanced by blocking heat through the capillary tube 11, etc., and therefore even if the eluate (liquid sample) contains thermally unstable chemical species such as glucose, During transport within
There is no longer any adverse effect caused by the heating of the heater 31, and even if such cooling and insulation are applied to the capillary tube 11 (eluate E), the tip of the tube 11 Since the part is heated intensively by the heat collecting plate 22 with the heat from the heater 31, the eluate E led thereto is heated more effectively, and is thereby efficiently atomized. It ends up being vaporized.

In addition, in the spray region in front of the opening at the tip of the capillary tube 11, at least a portion of the low-boiling point solvent constituting the eluate E is vaporized, so the atomized product formed becomes even finer particles. As a result, the solvent becomes more easily vaporized, and the vaporized solvent is sucked into the rotary pump 32 and removed, so that the atomized material can be easily concentrated (improved solute component concentration). The concentrated atomized material is then transferred to the ionization chamber 2.
By being guided to 0, mass spectrometry of the eluate E can be effectively performed.

Further, in this embodiment, the capillary tube 11 is directly connected to the eluate flow path 13 from the column 12, so that all the eluate flowing out from the column 12 is guided into the tube 11. However, it goes without saying that a portion of the eluate can be guided into the capillary tube 11 by providing a suitable splitter. However, the feature of the present invention is that, unlike conventional interfaces, MS and LC (particularly HLC) can be directly connected as in this embodiment. In addition, in addition to using the eluate from LC as a liquid sample, it is also possible to introduce a solution or liquid prepared for mass spectrometry into the MS according to the present invention. It will be introduced into the tube 11 by pressurization. Furthermore, as the atomizing gas, in addition to the above-mentioned helium gas (He), any gas can be used as long as it does not adversely affect the mass spectrum measurement in MS, such as nitrogen, argon, methane, Examples include isobutane and ammonia.

Further, the heat collecting plate 22 as a heat collecting means provided at the opening at the tip of the capillary tube 11 is made of copper material in the above example, but may be made of other materials with excellent thermal conductivity such as aluminum. It doesn't make any difference even if it is given to someone. Also, as a cooling medium that can be circulated inside the cooling cylinder 23,
In addition to the exemplified water, various known materials may be used as appropriate.

Of course, the present invention is not limited to the above-mentioned specific examples, and various changes and improvements can be made based on the knowledge of those skilled in the art without departing from the spirit of the present invention. It goes without saying.

As described in detail above, the present invention effectively combines a cooling means and a heat collecting means to control the action of the heating means on a liquid sample guided inside a capillary tube and to efficiently heat the liquid sample. As a result, even if a liquid sample contains thermally unstable chemical species, it can be effectively atomized or vaporized while avoiding denaturation of such chemical species, and can be processed by MS. This makes it possible to measure the spectrum by guiding the ionizing part to the ionization part, and this is where the great industrial significance of the present invention lies.

[Brief explanation of the drawing]

FIG. 1 is a sectional view of a device (interface) according to an embodiment of the present invention, FIG. 2 is an enlarged sectional view of the vicinity of the tip of the capillary tube in the device of FIG. 1, and FIG. It is a further enlarged sectional view. 1: Interface body, 2: Inner tube, 3: Outer tube, 11: Capillary tube, 17: MS body, 20: Ionization chamber, 21: Heat insulation tube, 22: Heat collection plate, 23: Cooling tube, 24: Guide tube, 2
6: Supply pipe, 27: Discharge pipe, 29: Piano wire, 3
0: Introduction tube part, 31: Heater.

Claims (1)

[Claims] 1. A liquid sample supplied through a capillary tube is discharged from the tip of the capillary tube, and a jet jet of atomizing gas is ejected from around the tip of the capillary tube, After atomizing the discharged liquid sample, a sample introducing device is configured to guide the formed atomized liquid sample to the ionization section of the mass spectrometer, and the area where the liquid sample is atomized is heated. a cooling means provided near and surrounding the tip of the capillary tube and cooling the capillary tube so as not to be heated by the heating means; a tip of the capillary tube; established in
An apparatus for introducing a sample into a mass spectrometer, comprising: a heat collecting means made of a material with excellent thermal conductivity, which concentrates the heat from the heating means at the tip of the capillary tube. 2. A heat insulating means made of a heat insulating material is provided between the heat collecting means and the cooling means and extending in a direction away from the tip of the capillary tube so as to surround the cooling means. Device. 3. The cooling means is a double cylindrical body closed at both ends, consisting of an inner cylinder through which the capillary tube passes and an outer cylinder through which a cooling medium flows between the inner cylinder, 2. The apparatus according to claim 1, wherein said double cylindrical body is provided with a cooling medium supply pipe and a cooling medium discharge pipe, respectively. 4. Claim No. 4, wherein the heat collecting means is a plate-like body or a block made of copper, and the tip of the capillary tube is disposed through the plate-like body or block. The device according to item 1. 5. The apparatus according to claim 1, further comprising a decompression mechanism that maintains a region where the liquid sample is atomized under a predetermined reduced pressure. 6. An atomized substance introduction means consisting of an introduction tube part arranged such that one opening is located opposite the tip of the capillary tube and the other opening opens into the ionization part of the mass spectrometer, Apparatus according to claim 1 provided. 7 A metal wire is inserted into the capillary tube, and the liquid sample continuously and stably discharged from the gap between the tube and the metal wire at the tip of the tube is continuously and stably absorbed by the atomized gas. 2. The device according to claim 1, wherein the atomization is performed by a jet jet. 8. Claims 1 to 7, wherein the capillary tube is connected to a flow path for eluate flowing out from the liquid chromatograph, and part or all of the eluate is supplied to the tube. The device described in any of the above.