JPH0314137B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an improved system for introducing a sample into an analytical instrument, particularly a mass spectrometer (MS), and more particularly relates to an improved system for introducing a sample into an analytical instrument, particularly a mass spectrometer (MS). A liquid sample containing seeds etc. can be atomized extremely effectively and stably, and the atomized product can be
This relates to a simple device that can be continuously introduced into an analyzer such as an MS.

Analyzers, such as mass spectrometers (MS), collect ions onto one or more fixed ion-collecting electrodes and measure the ion current by continuously adjusting the accelerating voltage and magnetic field strength. This device is designed to obtain a mass spectrum using the obtained mass spectrum, and is widely used for the qualitative and quantitative determination of gases, as well as liquids and solid molecules that can be converted into gases.

In recent years, such MS,
Attempts have also been made to use it in combination with other separation and analysis instruments for effective analysis of mixtures. For example, one example is an LC-MS analysis system that combines liquid chromatography (LC), particularly high performance liquid chromatography (HLC), which has been attracting attention in recent years.

Incidentally, analysis by MS is performed by ionizing a sample in a gaseous state, and therefore various problems arise when the sample is in a liquid state or a 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 problem with this LC is that it is not easy to continuously remove the solvent (mobile phase) from the eluate, and therefore no effective means have been found to concentrate the target components in the eluate.
-This is a major cause of hindering the practical application of MS analysis techniques.

Therefore, various studies have been conducted on methods for 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, is 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 present inventors decided to atomize the liquid sample to be analyzed and introduce it into the MS using the so-called atomizing principle. Therefore, we have developed various methods that enable effective vaporization of liquid samples and continuous and effective introduction into MS, and we have previously published these methods in Japanese Patent Application No. 111130/1983. 55-37778), etc. especially,
In Japanese Patent Application No. 55-176925 (Japanese Unexamined Patent Publication No. 57-101328) filed by the present applicant, even if the sample is a liquid sample containing thermally unstable chemical species such as glucose, He proposed a mechanism that can be introduced continuously into analysis equipment such as MS.

However, subsequent studies by the present inventors have 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 area where the liquid sample is atomized is generally heated by an appropriate heating means, and this heating causes the inside of the capillary tube to open at its tip. Therefore, the liquid sample that oozes out to the tip nozzle is desolvated by such heating, and the solute components are removed at the nozzle tip. It became clear that there were problems with long-term stability, such as causing precipitation and clogging. Furthermore, the production of the nozzle itself requires a fairly sophisticated technique, and it is extremely difficult to make the inner diameter of the capillary tube infinitely small in relation to the stainless steel wire inserted therein. In particular, when the sample components in the liquid sample are thermally unstable chemical species such as glucose or non-volatile chemical species, they are susceptible to alteration and precipitation effects due to desolvation, heating, etc. Problems such as decreased spray-vaporization stability and poor reproducibility were likely to occur.

Therefore, as a result of further studies on the previously developed sample introduction mechanism, the present inventors found that it is effective even for liquid samples containing thermally unstable chemical species such as glucose or non-volatile chemical species. They discovered a simple mechanism that can be stably and reproducibly introduced into analyzers such as MS, and have completed the present invention.

That is, the present invention allows a liquid sample to be supplied through a capillary tube into which a metal wire is inserted.
A liquid sample is formed after the discharged liquid sample is atomized by a jet jet of working gas discharged from the tip of the capillary tube and jetted from around the tip of the capillary tube. In a sample introduction device configured to guide an atomized liquid sample to a predetermined analysis device, (a) the metal wire inserted into and fixed in the tip opening of the capillary tube, and inserted into the capillary tube; and the capillary tube, the liquid sample is continuously introduced through the space between the
a capillary nozzle that allows self-injection through an inner hole smaller than the capillary tube;
(b) a heating means for heating the area where the liquid sample is atomized; and (c) a heating means provided near the tip of the capillary tube so as to surround it, and configured to prevent the capillary tube from being heated by the heating means. a cooling means for cooling the capillary tube; and (d) a material made of a material with excellent thermal conductivity, located at the tip of the capillary tube and concentrating the heat from the heating means on the tip of the capillary tube. A sample introduction device including a heat collecting means, which ejects the liquid sample under its own pressure to make it fly out in the form of fine particles a predetermined distance forward from the tip opening of the capillary tube, and By further making the fine particles of the liquid sample even finer and atomizing them by the jet jet of working gas, the liquid sample can be atomized or gasified very effectively. Furthermore, since the liquid sample does not ooze out at the nozzle tip, desolvation from the liquid sample and precipitation of solute components at the nozzle tip can be effectively prevented. As a result, the stability of atomization and vaporization has been significantly improved, and its reproducibility has also been improved further.

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

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 a capillary tube tip nozzle in the device, and FIGS. 3 and 4 is a further enlarged sectional view of the capillary tube tip nozzle portion.

In these figures, 1 is 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. Screwed onto and held by the member 4, set screws 5, 6 and threaded cylinder 7,
It is airtightly attached to the rear end of the outer tube 3 via the tube 8. Further, at the rear part of the cylindrical holding member 4, there is provided an axial capillary tube insertion part 4a extending further rearward and an atomizing gas (working gas) introduction part 4b extending laterally from the middle part of the insertion part 4a. It is being A capillary tube 11 is provided passing through the plug 10 attached with a set screw 9 at the end of the insertion portion 4a.
The rear end is connected to a flow path 13 for the eluate E flowing out from the HLC column 12 so that the eluate E from the column 12 is introduced into the capillary tube 11. Atomizing gas (helium gas; He is used here) as a working gas supplied from an atomizing gas source (not shown) is supplied from a needle 16 passing through a plug 15 attached with a set screw 14 of 4b. It is guided into the cylindrical holding member 4 and further 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 tube 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 almost the entire length into the capillary tube 11, and the inner surface of the tube 11 and the outer surface of the piano wire 29 are connected. An eluate passage with an appropriate gap is formed between the tubes so that the eluate E is continuously supplied to the distal end side of the tube 11. As shown in FIG. 4, a capillary nozzle 35 with a length of about 3 mm and a smaller inner diameter (here, 12 μm) is inserted into the tip opening of the tube 11, and an adhesive such as epoxy resin is inserted into the tip opening of the tube 11. It is fixed at 36. Therefore,
The eluate E introduced through the gap between the tube 11 and the wire 29 is self-injected through the small inner diameter hole of the capillary nozzle 35. The capillary nozzle 35 may be a fused silica capillary of a predetermined length (usually,
It is preferable to use a polyimide film layer 37 on its surface, which improves its handling properties.

In addition, the tip of the outer tube 3, which is located in the atomization area around the tip of the capillary tube 11 (nozzle 35) that penetrates the bottom of the heat insulating cylinder 21 and the heat collecting plate 22, and surrounds it, is shown in FIG. As shown, after being squeezed to gradually reduce its diameter, an introduction tube portion 30 is integrally formed at its tapering end. This introduction tube part 30 has a through hole in the center, and has a conical shape on the side of the capillary tube 11, and the tube 11 (nozzle 3
5) has an opening for introducing the atomized substance that opens opposite to the tip opening and at a predetermined distance therefrom, and has an opening that opens toward the ionization chamber 20 side of the MS. . And such outer tube 3
A heater 31 as a heating means is wound around the outside of the tip portion whose diameter gradually decreases to heat the area where the eluate E is atomized, and the atomized material formed by the atomization is heated. It is designed to supply heat of vaporization. and again,
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 self-injected through a smaller inner hole of a capillary nozzle 35 attached to the tip of the tube 11. Note that this eluate E
Self-spraying is made to eject forward at a predetermined distance, for example, a distance of several centimeters or more, by the feeding pressure of eluent E applied by an external pump action, and generally at least This can be effectively carried out at a linear flow rate of 3 m/sec or more, preferably several m/sec or more. Also,
The inner diameter of the capillary nozzle 35 that provides such self-injection is usually appropriately selected within the range of about 5 to 20 microns.

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 fine particles of the eluate E that are self-injected from the capillary nozzle 35 at the tip of the nozzle 35 are continuously atomized into a finer mist in the area in front of the nozzle 35. 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 using substances such as No. Also, during the transfer in the capillary tube 11, there was no longer any adverse effect due to the heating of the heater 31, and such cooling and insulation did not affect the capillary tube 11 (eluent E). Since the tip of the tube 11 is intensively heated by the heat from the heater 31 by the heat collecting plate 22, the eluate E guided there is more effectively heated. It is heated, thereby efficiently atomizing and vaporizing it.

Moreover, according to the present invention, the eluate E guided through the capillary tube 11 is transferred to the capillary nozzle 3 having an even smaller inner diameter of about 5 to 20 μm.
5, the droplets are ejected by self-pressure, so that the droplets do not stay at the tip opening of the nozzle 35, and therefore, the solute part is precipitated by desolvation at the tip of the nozzle 35. Degeneration etc.
Therefore, problems such as nozzle clogging can be completely prevented.Furthermore, the eluate E, which has been atomized by the self-spraying, is effectively made finer by the atomization effect of the jet jet. As a result, the stability of atomization and vaporization can be significantly improved.

Incidentally, using the above device, a methanol solution of aminopyrine (MW231) of 1μ (1μg/1μ)
FIG. 5 shows a mass chromatogram obtained by performing MS analysis on a sample under the following conditions.

Solvent: MeOH 30μ/min GIM: m/z=232 Working gas: He 50ml/min Ionization chamber temperature: 190℃ Heater 31 temperature: 205℃ CV: 3% As is clear from the mass chromatogram in Figure 5, repeated It has become clear that the shape of the peak for the sample introduced shows good stability of introduction, and that the reproducibility also shows a good value of CV=3%.

Further, according to the configuration in which the capillary nozzle 35 is provided at the tip of the capillary tube 11,
While the eluate E is guided through the narrow channel of the capillary tube 11 without being guided, the fine channel for self-spraying is simply a short portion of the capillary nozzle 35, so the eluate E is fed. Not only can this effectively solve the problem of high back pressure, but it is also extremely easy to manufacture the nozzle part because it is sufficient to simply attach the capillary nozzle 35, which is a fine thin tube, to the tip of the capillary tube 11. This is also a great advantage of the present invention.

In addition, in the spray region in front of the capillary nozzle 35 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 formed atomized material becomes even finer. The solvent becomes particles and becomes more easily vaporized, and the vaporized solvent is sucked into the rotary pump 32 and removed, thereby concentrating the atomized material (improving the solute component concentration).
can be easily carried out, and by introducing the concentrated atomized material into the ionization chamber 20,
MS measurement 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. Furthermore, in addition to using the eluate from LC as a liquid sample, it is also possible to use a solution or liquid prepared for MS analysis as a sample and introduce it into the MS according to the present invention. It will be introduced into the tube 11 by pressurization. Furthermore, as the atomizing gas (working gas), in addition to the above-mentioned helium gas (He), any gas can be used as long as it does not have an adverse effect on the mass spectrum measurement in MS, such as nitrogen, Examples include argon, methane, isobutane, and ammonia.

Furthermore, a heat collecting plate 22 as a heat collecting means provided at the tip of the capillary tube 11
is made of copper material in the above example, but it may be made of other materials with excellent thermal conductivity, such as aluminum. Furthermore, as the cooling medium that is allowed to flow through the cooling cylinder 23, various known cooling mediums may be used as appropriate, in addition to the water shown as an example.

Furthermore, although the above example describes MS, the sample introduction device according to the present invention can also be used as an efficient atomization sample introduction device for other inorganic solutions, such as an emission spectrometer or an atomic absorption spectrometer. It can be widely used as a sample introduction device for various analytical devices.

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.

[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. FIG. 4 is a further enlarged sectional view of only the tip of the capillary tube. FIG. 5 is an example of a mass chromatogram obtained using the apparatus of the present invention. 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, 35: capillary nozzle, 36: adhesive, 37: polyimide film layer.

Claims (1)

[Scope of Claims] 1. A liquid sample supplied through a capillary tube into which a metal wire is inserted is discharged from the tip of the capillary tube, and a working gas is ejected from around the tip of the capillary tube. In the sample introduction device, the discharged liquid sample is atomized by a jet jet, and then the atomized liquid sample that is formed is guided to a predetermined analysis device, wherein the tip opening of the capillary tube is The liquid sample is inserted and fixed into the capillary tube, and the liquid sample is continuously guided through the gap between the metal wire inserted into the capillary tube and the capillary tube. a capillary nozzle configured to self-inject through a hole; a heating means for heating an area where the liquid sample is atomized; and a heating means provided near the tip of the capillary tube so as to surround it; a cooling means for cooling the capillary tube so as not to be heated; and a cooling means located at the tip of the capillary tube,
An apparatus for introducing a sample into an analytical apparatus, comprising: a heat collection means made of a material with excellent thermal conductivity, which concentrates the heat from the heating means on 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. A mist comprising 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 as the analysis device. 2. The apparatus according to claim 1, further comprising a compound introducing means. 7. Claims 1 to 7, wherein the capillary tube is connected to a flow path for eluate flowing out from the liquid chromatography device, and a part or all of the eluate is supplied to the tube. The device according to any of Item 6.