JPH02295054A - Mass spectrometer - Google Patents

Abstract

PURPOSE:To make it possible to carry out mass-analysis of even sucrose and lipide having weak affinity with proton while drawing sufficient ions out of them by generating ions by heating the end part of a metallic capillary at >=300 deg.C. CONSTITUTION:A sample which is separated by a liquid chromatography 1 and eluted from a column is introduced into a metallic capillary 2 and the capillary 2 is heated under control by a heating power source and a pair of heaters 4 having a temperature controlling function. The sample pass through the heated capillary and sprayed from the tip of the capillary and vaporized by heating and some of the vaporized sample is discharged as ions. The ions are produced even water is used and ion current is obtained when the end part of the capillary is heated at >=300 deg.C. In this way, cations dissolved in a sample solution are attached to molecules of the sucrose or lipide and the sucrose or lipide is taken out to gas phase as molecular ion and mass-analyzed efficiently.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to a device that combines a liquid chromatograph and a mass spectrometer, which is particularly important for the separation and analysis of biologically related substances, that is, an ion analyzer in a liquid chromatograph/mass spectrometer. Regarding the improvement of sources. [Prior Art] Currently, in the field of analysis, the development of liquid chroma 1 graph/mass spectrometers is emphasized. For reference, FIG. 7 shows the overall configuration of liquid-free chroma 1 Clough/{a quantity analysis R1 using a double convergence mass spectrometer consisting of an electric field and a magnetic field. J volumes of the sample in a solution are discharged from the Liquid Chroma 1 Kugraph and introduced into the ion source 19 through a pipe 9. The ion source 19 is controlled by the ion source power supply] 4. Ions related to sample molecules generated in the ion source 19 are introduced into the vacuum through the pores. Furthermore, the electric field analysis section 1 2 a r w ;. Field analysis department 1.
2b is introduced into the mass spectrometer section 2 for mass spectrometry. Ions subjected to mass spectrometry are detected by an ion detector 20, and a detection signal is sent to a data processing device 15 via a signal line 10. At this time, the mass spectrometer 12 consisting of the electric field analyzer 12a and the magnetic field analyzer 12b is exhausted by a suitable exhaust system 13. Now, the principle of the liquid chroma 1-graph/mass spectrometer is simple, but the compatibility is that the liquid chroma 1-graph handles samples in a solution, whereas the mass spectrometer handles samples in a gas. The development of this device has been extremely difficult due to its poor performance. Several methods have been proposed to solve this difficult problem, the most representative of which is the thermospray method described in Analytical Chemistry, 1983, Vol. 55, p. 750. There is. As shown in FIG. 8, in this method, a sample solution containing an electrolyte such as ammonium acetate from a liquid chromatograph is sprayed into a vacuum of several Torr or less using a heated capillary 2. The ions generated when the droplets are vaporized are introduced into the sample analysis section through the pores 7'a of the pore-equipped electrode 7' located in a direction perpendicular to the direction of travel of the spray flow, and mass spectrometry is performed. This is the way to do it. In FIG. 8, 16 is a heater, and 4' is a temperature sensor such as a thermal lightning pair. In the conventional method described in Section 2, as shown in Figure 3 (a), when the mobile phase in the liquid chromatograph is water, no ionic current can be obtained, so as shown in Figure 3 (b), the mobile phase Add 11 ammonium acetate to the solution. At this time, a high ion current (peak at 250'C) is obtained when the capillary tip temperature is less than 300°C, but wiHM occurs in this region when the molecule contains pro1-n like ammonium ions. It is a pro1-added molecule. However, with this conventional method, a high ionic current can be obtained when the molecule to be observed has a strong proton affinity, but there is a problem in that the ionic current is low for substances with a weak proton affinity, such as sugars and lipids. 4L [Problem to be Solved by the Invention 1] As mentioned in Section 2, the conventional technology had a problem in that a high ionic current could not be obtained when measuring sugars, lipids, etc. that have weak pro-I/N affinity. Therefore, an object of the present invention is to provide a mass spectrometer that can extract a sufficient amount of ions from the gas phase and perform mass spectrometry even in the case of sugars, lipids, etc. that have weak affinity for molecules. . [Means for Solving the Problem 1] The above object is to provide a mass spectrometer using a spray ion source that ionizes the sample molecules by spraying a solution containing the sample molecules from the tip of a heatable capillary manufactured by Konrin. This is achieved by operating the ion source at a heating temperature of 300° C. or higher at the tip of the metal capillary. At this time, the pores for introducing the generated ions into the mass spectrometer are designed so that the ions generated at the center of the spray flow from the tip of the capillary can be efficiently introduced into the mass spectrometer. It is desirable to arrange the pore so that the central axis of the pore is located on an extension of the central axis of the capillary. [Function] As a result of the research conducted by the present inventors, the temperature at the tip of the capillary in the spray ion source was set at 300'C or higher,
By locating a wire hole on the central axis of the capillary for introducing ions into the mass spectrometer, cations dissolved in the solution are added to molecules such as sugars and lipids, and the cations are added to the gas phase as molecular ions. It was confirmed that the sample could be taken out and that it could be efficiently introduced into the mass spectrometer. [Example] Hereinafter, an example of the present invention will be described using FIG. 1. Note that although the case where a double convergence mass spectrometer set consisting of an electric field analysis section and a magnetic field analysis section is used will be explained here as an example, other types of mass spectrometers such as a quadrupole mass spectrometer may also be used. Needless to say. FIGS. 1(a) and 1(b) show the configuration of an ion source portion which is an example of the present invention. The difference between FIGS. 1(a) and 1(b) is whether the capillary 2 to be heated is placed under atmospheric pressure as shown in FIG. 1(a), or whether it is placed under atmospheric pressure as shown in FIG.
As shown in the figure, pump the air using a rotary pump etc.
The only difference is whether it is placed under a reduced pressure of about rr. Advantages of positioning capillary 2 under atmospheric pressure 1~
On the other hand, if the capillary 2 is located under reduced pressure, the vacuum in the mass spectrometer section will deteriorate even if the tip of the capillary 2 is located very close to the first electrode 6 with a pore. This is effective in increasing sensitivity. However, the results obtained using either mode are the same. The sample in the solution separated by the liquid chroma 1/graph 1 and eluted from the column is introduced into the metal capillary ~2. This capillary 2 can be heated and temperature controlled. The capillary 2 may be indirectly heated by welding a metal block containing a cartridge heater thereto, or the capillary 2
It may also be heated directly by applying electricity to itself. FIG. 1 shows the latter case of direct current heating. The capillary 2 is heated and controlled by a heating electric current rA5 with a temperature control function and a thermocouple 4. 3 indicates a current-carrying terminal. A sample solution that passes through the heated capillary 2 and is sprayed from its tip is heated and vaporized, but some of it is released as ions. What is important at this time is the temperature at the tip of the capillary 2. FIG. 2 clearly shows this difference. In the conventional thermospray method, when using a solution such as an aqueous ammonium acetate solution, ions are not generated and at the same time the solution is flowed.ffk ]. m Q / m j.
When used at n, an ion current can be obtained only when the temperature at the tip of the capillary is lower than 300'C, whereas in the present invention, ions are generated even when using simple water, The ion current is measured when the temperature at the tip of the cavity 2 is above 300°C (the peak is at 450°C).
C). As can be seen from this figure, the temperature at the tip of the cavity 2 is preferably 300°C or higher, preferably 4. It is preferable to use the temperature within the range of OO to 500°C. Note that the optimum temperature is 450°C. The generated ions are introduced into the high-vacuum mass spectrometry section through the pore 6a of the first electrode 6 and the pore 78 of the second electrode 7, which are located on the central axis of the capillary 2. As shown in Figure 4, in the conventional thermoblue spray method, the cavity 2
1 and the axis of the pore 7'a for introducing ions into a high vacuum are perpendicular to each other, and the ion extraction direction 17 and the direction 11 of the spray flow are perpendicular to each other. However, in the present invention, the direction of the spray flow emitted from the tip of the cavity 2]1 is the pore 6a of the first electrode 6.
and are arranged so as to coincide with the axis of the pore 7a of the second electrode 7. That is, the pore 6a is provided on an extension of the central axis of the capillary 2, and the ion extraction direction 18 coincides with the spray flow direction 11. With this arrangement, even if the temperature at the tip of the capillary 2 is increased,
) As shown in (d), it is possible to obtain a sufficient ionic current even when the mobile phase is water or ammonium acetate. On the other hand, the first electrode 6 and the second electrode 7 are electrically insulated by an insulator 8 such as a ceramic plate, so that a voltage can be applied between the two electrodes. Further, the space between both electrodes 6 and 7 is designed to be evacuated. The voltage applied between both electrodes 6 and 7 is such that ions are
When introduced through the pores 6a, the cluster ions generated from the seeds undergo adiabatic expansion, collide with neutral molecules, and cleave cluster ions that are inconvenient for analysis. As described above, the ions that have passed through the first electrode pore 6a and the second electrode pore 7a are subjected to mass analysis using double convergence mass spectrometry consisting of an electric field analysis section and a magnetic field analysis section, and are then detected by an ion detector. It will be detected. By the way, when looking at the mass spectra obtained by the conventional method and the present invention, the difference becomes even clearer (see FIG. 5). In the conventional thermospray method, the background ions observed at 250°C are mainly ammonium ions and their cluster ions, but in the present invention, the ions observed at 450°C are hydronium ions (H 301 ) and cations (Na", K"). In this way, if the temperature of the heated part of the capillary is raised to apply sufficient heat to the liquid inside the capillary to promote vaporization, even ions with high solvation energy such as cations (Na+, K+) can be observed sufficiently. I know what I can do. In addition, as shown in Figure 6, when measuring sucrose (a type of sugar), which has a weak affinity for pro-1 hene but a strong affinity for cations, it was found that the conventional method of adding protons to the molecule Addition molecule (M
Although +H)+ can be observed, its strength is not so strong, whereas the method of adding cations according to the present invention yields a cation-added molecule (M+Na)+ having a strong strength. You can see the superiority of [Effects of the Invention] According to the present invention, sugars, which are difficult to ionize using conventional liquid chroma graph/mass spectrometry ionization methods,
Even in the case of substances such as lipids, Na is added to these substances.
”, it became possible to add a K+ cation and extract it into the gas phase as a cation-added molecule for mass spectrometry.
Substances such as sugars and lipids can be detected with high sensitivity.

[Brief explanation of the drawing]

FIGS. 1(a) and (b) are block diagrams of the ion source portion of a liquid chroma 1 to graph/mass spectrometer, respectively, which are an embodiment of the present invention, and FIGS. 2(a) and (b) are FIGS. 3(a) to 3(d) are curve diagrams showing a comparison of the operating temperature ranges of the ion source according to the conventional method and the ion source according to the present invention. Fig. 4 is a curve diagram showing a comparison of the ion current generated by the conventional method, and Fig. 5(a) is a schematic diagram illustrating the difference in the configuration of the ion source according to the conventional method and the beak ion source according to the present invention. (b) is a diagram comparing the mass spectra obtained by the ion source according to the conventional method and the ion source according to the present invention, and FIG.
) and (b) are sucrose (a type of sugar) obtained using the ion source according to the conventional method a; and the ion source according to the present invention.
Figure 7 is a diagram showing the general configuration of a liquid chroma I graph/surface analyzer, and Figure 8 is a diagram showing the configuration of an ion source using a conventional method. be. 1...Liquid chroma I graph, 2 capillary 3
Current heating terminal, 4. Thermocouple, 5. Heating power source with temperature control function, 6. L electrode with pores, 6a. 1st electrode pore, 7. 2nd electrode with pore, 7a. 2nd electrode. Ultra-fine pores, 8
・・Insulator, 9・Piping, 10 Signal line, 12 Mass spectrometer, 13 Vacuum pump, 14・Ion source power supply,
15 data processing device, 9 ion source, 20-ion detector 3, O! Go to the board! ←Eighth vote! Special \1 ticket. -、＼Sakai○ V-hole＼・Seirin! ←＼・Ichihime Kamatagari Tohachihosho, i%. Sai; ni゜・τ11tope・2＼ψmoβ;8shise≦
Procedural amendment (method) 1990 [April 13

Claims (1)

[Scope of Claims] 1. A mass spectrometer consisting of a spray ion source made of a heatable metal capacitor and a mass spectrometer that introduces the generated ions into a high vacuum through a pore and performs mass analysis. A mass spectrometer characterized in that ions are generated by heating the tip of the metal capillary to a high temperature of 300° C. or higher. 2. The mass spectrometer according to claim 1, wherein the pore is provided on an extension of the central axis of the metal capillary.