JP5475344B2 - Ion source apparatus, ionization probe manufacturing method, and ion source apparatus driving method - Google Patents

Description

  The present invention relates to an ion source device that extracts and ionizes a solution containing a component to be analyzed. The present invention also relates to an ionization probe manufacturing method and an ion source device driving method suitable for use in an ion source device.

  Therapeutic drug monitoring (TDM) is a method for reducing the side effects of drugs and formulating optimal treatment plans for individual patients. When therapeutic drug monitoring is applied to mass spectrometry using an automated blood analyzer, a technique with high throughput, high robustness, and low cost is important. When a general liquid chromatograph / mass spectrometer (LC / MS) is used, the sample solution is directly introduced into the switching valve. For this reason, a large amount of solvent is required for cleaning the switching valve, and cleaning time is also required. There are also many parts that cause clogging of switching valves and separation columns. On the other hand, in the solid phase extraction method, only the solution containing the component to be analyzed is extracted, and the extracted solution can be directly introduced into the ion source device, whereby ionization and mass spectrometry can be performed simultaneously. Thus, when the solid-phase extraction method is used, the switching valve and the separation column can be excluded from the flow path to the ion source.

  The apparatus configuration described in Patent Document 1 does not require a flow path like LC / MS, and can directly introduce the sample solution into the ion source apparatus. This device is ionized by connecting the tip of the pipette tip to a silicon substrate with many holes of several μm in a state where the solution is sucked into a pipette tip for transporting the solution, and ejecting the solution from the hole of the silicon substrate. Is realized. The apparatus described in Patent Document 2 also does not require a flow path like LC / MS, and can directly introduce the sample solution to the ion source. In this apparatus, a needle portion of a syringe for transporting a solution is used as a capillary electrode for electrospray ionization (ESI).

US Pat. No. 6,245,227 US Pat. No. 7,364,913

  The apparatus described in Patent Document 1 makes a pipette tip and a silicon substrate disposable. For this reason, there is no need for cleaning, high throughput, little contamination to the next analysis, and high robustness. However, this apparatus needs to use a silicon substrate, which is a relatively expensive part that requires fine processing. Moreover, since this apparatus performs solid phase extraction separately from the ionization step, it is necessary to dispose the solid phase extraction column and the container for receiving the extract. For this reason, there is a problem that the cost of consumables is high.

  On the other hand, in the case of the apparatus described in Patent Document 2, since the sample solution can be directly ionized by the needle of the syringe, there is no disposable part in the liquid feeding part. However, in the case of this apparatus, since the syringe and the needle portion are not exchanged, cleaning with a solvent or the like is required. For this reason, it is difficult to improve throughput, and it is difficult to completely eliminate contamination. Also in the case of the method of Patent Document 2, as in the method of Patent Document 1, it is necessary to make the solid phase extraction column used for the solid phase extraction and the container for receiving the extract liquid disposable.

  Therefore, the present invention realizes both the elution of the solution by the ionization probe and the ionization of the eluted solution by forming the ionization probe by connecting the extraction unit and the liquid sending unit used for washing and discarding unnecessary components. Provide a method.

  According to the present invention, it is possible to simultaneously elute the analysis target component in the sample solution and ionize it, thereby improving the throughput. Moreover, since an extraction part and a liquid feeding part can be made disposable, contamination can be suppressed and robustness can be improved. Furthermore, since the container for temporarily storing the eluate to be transferred to the liquid feeding unit is not necessary, the cost of consumables can be reduced.

The figure explaining the structure and processing operation | movement of an ion source apparatus in Embodiment 1 of this invention. The figure explaining the structural example of the ionization probe which concerns on Embodiment 1 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 2 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 3 of this invention. The graph which shows the measurement result of the solution flow volume in Embodiment 3 of this invention. The figure explaining the liquid feeding part which comprises the ionization probe which concerns on Embodiment 4 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 4 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 5 of this invention. The figure explaining the structure of the liquid feeding part which concerns on Embodiment 7 of this invention. The figure explaining the structure of the liquid feeding part which concerns on Embodiment 8 of this invention. The figure explaining the structure of the liquid feeding part which concerns on Embodiment 9 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 10 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 11 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 12 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 13 of this invention. The figure explaining the processing process of the ion source apparatus in Embodiment 14 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 15 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 16 of this invention. The figure explaining the structure of the ion source apparatus in Embodiment 17 of this invention.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. In addition, the content of the apparatus configuration and processing operation to be described later is merely an example, and other embodiments can be realized by combining or replacing the embodiments with known techniques.

(A) Embodiment 1
(Outline configuration)
In this embodiment, an ionization probe formed by connecting an extraction unit and a liquid feeding unit used for adsorption and elution of components contained in a sample solution will be described. Also, an ion source device that moves the completed ionization probe to the vicinity of an ion intake unit such as a mass spectrometer and simultaneously performs elution and ionization of components to be analyzed will be described.

  FIG. 1 schematically shows the configuration and operation of an ion source apparatus employing this method. In FIG. 1, portions surrounded by broken lines indicate the processing processes S1 to S8, and arrows between the processing processes indicate the progress direction of the processing processes.

  The ion source apparatus includes an ionization probe 1 (extraction unit 2 and liquid feeding unit 3), a decompression container 4, a transport robot 27, an exhaust pipe 33, and a decompression pump 34 as main parts. On the other hand, the treatment process includes a washing step S1, an equilibration step S2, an adsorption step S3, a washing step 4, a connecting step S5, a moving step S6, an elution / ionization step S7, and a disposal step S8.

(Washing step S1)
This cleaning step S1 is a step of cleaning with the cleaning solution 16 before using the extraction unit 2. For the cleaning solution 16, for example, an organic solvent such as methanol is used. Incidentally, the extraction unit 2 includes a cylindrical portion 5 and a tapered portion 23. Among these, the frit 15 is disposed inside the cylindrical portion 5 so as to be sandwiched from both sides of the filler 14. The cylindrical portion 5 and the tapered portion 23 are made of, for example, glass, polypropylene, polyethylene, or the like.

  Note that an opening having a relatively large diameter is formed at the upper end portion of the cylindrical portion 5, and the lower end side of the cylindrical portion 5 is closed by a tapered portion 23. The tapered portion 23 has a shape such that a funnel is coupled to an opening portion of a flat plate formed in a ring shape. Incidentally, an opening having a smaller diameter than the inner diameter of the cylindrical portion 5 is formed on the upper surface side of the tapered portion 23, and an opening having a smaller diameter than the two openings described above is formed on the lower surface side.

  The opening on the upper end side of the cylindrical portion 5 serves as a liquid inflow port, and the opening on the lower end side of the tapered portion 23 is used as a liquid output port. Furthermore, this taper part 23 is used for the connection with the taper part 24 provided in the liquid feeding part 3 side so that it may mention later.

  For the filler 14, polystyrene, carbon or the like is used. The particle size of the filler 14 is generally about several tens of μm. Glass fiber, polypropylene, polyethylene or the like is used for the frit 15. The bore diameter of the frit 15 is generally about 20 μm or less.

(Equilibration step S2)
This equilibration step S2 is a step of injecting the equilibration solution 18 so that the sample component 17 is easily adsorbed to the filler 14. For example, water is used as the equilibration solution 18.

(Adsorption process S3)
The adsorption step S3 is a step in which the sample solution 20 including the analysis target component 19 is injected into the extraction unit 2 and the sample component 17 is adsorbed on the filler 14. Incidentally, as the sample solution 20, a solution whose concentration is adjusted by dissolving with water or the like may be used.

(Washing step S4)
The cleaning step S4 is a step of discarding the other contaminant components 21 together with the cleaning solution 22 so that only the analysis target component 19 remains adsorbed on the filler 14. For the cleaning solution 22, for example, methanol, acetonitrile or other organic solvent, water, a mixed solution thereof or the like is used.

(Summary of S1 to S4)
The type of solution used in each of the cleaning process S1, the equilibration process S2, the adsorption process S3, and the cleaning process S4 described above needs to be changed according to the material of the filler 14 and the like. Further, each solution injected into the extraction unit 2 is very difficult to flow because the filler 14 is densely packed. However, the solution can be made smoother by adopting a technique that creates a pressure difference between the upstream side and the downstream side of the filler 14 by pressurizing the upstream part of the extraction unit 2 or reducing the downstream part. Can pass through. There is also a method of forcibly passing a solution by a centrifugal separation method or the like.

(Connection step S5)
The connection step S5 is a step of assembling the ionization probe 1 by connecting the extraction unit 2 after discarding the contaminant component 21 in the washing step S4 and the liquid feeding unit 3. The liquid feeding part 3 has a funnel shape. Incidentally, the liquid feeding unit 3 includes a tapered portion 24 and a capillary 35. The tip outer diameter of the capillary 35 is set to 0.1 to 0.5 mm. In this embodiment, the tip outer diameter is 0.3 mm. However, the dimension of the outer diameter of the tip is a value determined on the assumption that the assumed flow rate of the capillary 35 is 500 nL / min to 20 μL / min.

  Here, the opening of the tapered portion 24 and the inclination of the inner wall surface are formed so that an airtight state is generated between the tapered portion 23 and the outer wall surface when the tapered portion 23 of the extracting portion 2 is pushed in. Yes. In FIG. 2, the detailed connection method of the extraction part 2 and the liquid feeding part 3 is shown.

  As described above, the connection of the two members is performed between the tapered portion 23 of the extraction unit 2 and the tapered portion 24 of the liquid feeding unit 3. At the time of connection, the tip portion (circumferential portion) of the tapered portion 23 is pushed along the inner wall surface of the tapered portion 24, and the connection is completed at a position where the gap is eliminated. The position where the gap is eliminated is the airtight portion 25. As shown in FIG. 2, a connecting robot 26 is used to connect the two members. The connecting robot 26 operates to push the two members together. Thus, if the extraction part 2 and the liquid feeding part 3 which have the shape which concerns on embodiment are used, airtightness can be ensured between two members by simple operation | movement. In the case of this embodiment, although the case where both the extraction part 2 and the liquid feeding part 3 have a taper shape is demonstrated, even when it does not have a taper shape about either one, it is an airtight state Can be formed.

(Move step S6)
The moving step S6 is a step of moving the ionization probe 1 connecting the extraction unit 2 and the liquid feeding unit 3 to a predetermined position in the ion source device. A transport robot 27 is used to move the ionization probe 1. A holder (not shown) is mounted on the arm 28 of the transfer robot 27, and the ionization probe 1 gripped by the holder is moved from a position before movement (a position indicated by a dotted line in the figure) to a position after movement (in the figure, The ionization probe 1 is moved to a position indicated by a solid line. The tip of the capillary 35 of the ionization probe 1 that has moved to the post-movement position is positioned around the ion take-in unit 31 in the ion detection unit 38 (for example, a mass spectrometer).

  At this time, the decompression container 4 and the ionization probe 1 are structured so as to obtain an airtight state. The ion source is completed by connecting the decompression container 4 and the ionization probe in a confidential state. Note that the transfer robot 27 and the connecting robot 26 may be the same.

(Elution / ionization process S7)
The elution / ionization step S7 is a step of injecting the eluate 32 into the extraction unit 3 to elute the analysis target component 19 from the filler 14 and ionize the eluted analysis target component 19 at the same time.

  For the eluent 32, for example, methanol, acetonitrile or other organic solvents, water, or a mixed solution thereof is used. Also in the case of this elution / ionization step S7, as described above, by causing a pressure difference between the upstream side and the downstream side of the filler 14, the solution can flow smoothly. In the case of this embodiment, elution is promoted by reducing the pressure inside the vacuum container 4.

  Here, one end of the exhaust pipe 33 is connected to the decompression vessel 4, and the other end is connected to the decompression pump 34. Therefore, the internal pressure of the decompression container 4 can be made smaller than the external pressure by discharging the air in the decompression container 4 by the decompression pump 34. That is, a so-called negative pressure state can be created.

  By depressurizing the decompression container 4, the eluate 32 elutes the analysis target component 19 from the filler 14 and flows out from the lower end of the capillary 35 constituting the liquid feeding unit 3. At this time, when the voltage 36 is applied to the capillary 35, the component 19 to be analyzed is ionized (electrospray ionization method: hereinafter referred to as “ESI method”). Thus, the ion source device in this embodiment can simultaneously perform elution and ionization of the analysis target component 19. That is, an ion source device with high throughput can be realized.

  In addition, it is necessary to change the kind of solution used for elution according to the material of the filler 14, etc. Further, the internal pressure of the decompression vessel 4 depends on the type of the filler 14. However, the solution can be passed smoothly by reducing the pressure to about -100 kPa at the maximum with respect to the atmospheric pressure.

  Incidentally, the ion 37 produced | generated by ionization is detected in ion detection parts 38, such as a mass spectrometer.

(Disposal process S8)
The ionization probe 1 that has completed the elution / ionization step S7 can be reused by washing or the like. However, it is not preferable when a minute amount of contamination or the like causes a problem such as therapeutic drug monitoring (TDM).

  Therefore, in the case of the present embodiment, the ionization probe 1 is discharged from the decompression container 4 using the transfer robot 39. A holder (not shown) is attached to the arm 40 of the transfer robot 39, and the ionization probe gripped by the holder is moved from the position before movement (position indicated by the dotted line in the figure) to the position after movement (in the figure, ionization probe). To the position indicated by the solid line). That is, the ionization probe 1 is moved from the periphery of the ion intake unit 31 such as a mass spectrometer. Thereafter, the used ionization probe discharged from the decompression vessel 4 is discarded. That is, the ionization probe 1 is made disposable.

  As a result, it is possible to minimize the influence of contamination during the next analysis. The transfer robot 39 and the transfer robot 27 may be the same.

(Effect of embodiment)
As in the present embodiment, the linking step S5 is arranged after the washing step S4 is performed, and the extraction unit 2 and the liquid feeding unit 3 are connected to each other, so that the contaminant component 21 is eluted when the analysis target component 21 is eluted. Thus, the problem of clogging the capillary 35 can be suppressed. In addition, in the case of the present embodiment, unlike the conventional method, a container for transferring the eluate of the analysis target component 21 to the liquid feeding unit 3 becomes unnecessary, and the cost can be reduced correspondingly. Can do.

(B) Embodiment 2
(Outline configuration)
Also in the case of this embodiment, the extraction unit 2 after discarding unnecessary components and the liquid sending unit 3 are connected to complete the ionization probe 1, and this ionization probe 1 is connected to the ion intake unit 31 of a mass spectrometer or the like. A case of moving to the periphery will be described. In this respect, the present embodiment and the first embodiment are common. However, in this embodiment, a method of promoting elution of the analysis target component 21 by pressurizing the upstream of the extraction unit 2 will be described.

  FIG. 3 schematically shows the configuration and operation of an ion source apparatus employing this method. In FIG. 3, parts corresponding to those in FIG. The ion source device according to this embodiment includes an ionization probe 1 (extraction unit 2 and liquid feeding unit 3), a transfer robot 27, and a pressurizer 43 as main parts.

  In the case of the second embodiment, the decompression vessel 4, the exhaust pipe 33, and the decompression pump 34 that are required in the first embodiment are unnecessary. In this embodiment as well, the processing process is the same as in the first embodiment. That is, the washing step S1, the equilibration step S2, the adsorption step S3, the washing step S4, the connecting step S5, the moving step S6, the elution / ionization step S7, and the discarding step S8 are executed in order. Below, only transfer process S6, elution / ionization process S7, and disposal process S8 are explained.

(Move step S6)
In the moving step S6, the ionization probe 1 connecting the extraction unit 2 and the liquid feeding unit 3 is moved to a predetermined position in the ion source device. A transport robot 27 is used to move the ionization probe 1. A holder (not shown) is mounted on the arm 28 of the transfer robot 27, and the ionization probe 1 gripped by the holder is moved from a position before movement (a position indicated by a dotted line in the figure) to a position after movement (in the figure, The ionization probe 1 is moved to a position indicated by a solid line). Also in this case, the tip of the capillary 35 of the ionization probe 1 is positioned around the ion take-in unit 31 in the ion detection unit 38 (for example, a mass spectrometer).

  In this embodiment, since the decompression container 4 is unnecessary, the airtight treatment between the decompression container 4 and the ionization probe 1 is also unnecessary.

(Elution / ionization process S7)
The contents executed in the elution / ionization step S7 are basically the same as those in the first embodiment. First, the eluate 32 is injected from the upper opening side of the ionization probe 1. Thereafter, a pressurizer 43 is disposed in the upper opening of the ionization probe 1 and pressurizes the upstream side of the extraction unit 2 (the introduction side of the eluate 32). That is, a pressure difference is generated between the upstream side and the downstream side of the filler 14, and the droplet of the eluate 32 including the analysis target component 19 is discharged from the lower end side of the capillary 35 that constitutes the liquid feeding unit 3.

  Also in this embodiment, the eluent 32 uses, for example, methanol, acetonitrile or other organic solvents, water, or a mixed solution thereof. When the eluate 32 is injected, the gas 44 is introduced into the pressurizer 43, and pressurization of the extraction unit 2 is started. Incidentally, the pressurizer 43 may be, for example, a pressure pump or a piston. Further, the pressurizer 43 may be used exclusively for enhancing the airtightness with the extraction unit 2, and the pressurization itself may be realized by the pressurized gas 44.

  When the extraction unit 2 is pressurized, the eluate 32 elutes the analysis target component 19 from the filler 14 and flows out from the lower end of the capillary 35 constituting the liquid feeding unit 3. At this time, when the voltage 36 is applied to the capillary 35, the analysis target component 19 is ionized (ESI method).

  Needless to say, the connecting portion between the pressurizer 43 and the extraction unit 2 or the connecting portion between the pressurizer 43 and the liquid feeding unit 3 needs to be configured to obtain an airtight state. The gas 44 introduced into the pressurizer 43 is desirably an inert gas such as air or nitrogen. In addition, it is desirable to control a pressurization pressure according to the kind of solvent. By controlling the pressurization pressure according to the type of solvent, it is possible to send a stable solution.

  Thus, according to this Embodiment, the elution and ionization of the analysis object component 19 can be performed simultaneously. That is, an ion source with high throughput can be realized. In addition, it is necessary to change the kind of solution used for elution according to the material of the filler 14, etc.

  Thereafter, the ions 37 generated by ionization are detected by an ion detector 38 such as a mass spectrometer.

(Disposal process S8)
The ionization probe 1 that has completed the elution / ionization step S7 can be reused by washing or the like. However, it is not preferable when a minute amount of contamination or the like causes a problem such as therapeutic drug monitoring (TDM).

  Therefore, also in this embodiment, the ionization probe 1 after use is excluded from the vicinity of the ion intake unit 31 of the mass spectrometer or the like by using the transfer robot 39. Since the ionization probe 1 can be made disposable, it is possible to minimize the influence of contamination and the like during the next analysis. The transfer robot 39 and the transfer robot 27 may be the same.

(Effect of embodiment)
Also in the case of this embodiment, similarly to the case of the above-described first embodiment, the connecting step S5 is arranged after the execution of the cleaning step S4, and the extraction unit 2 and the liquid feeding unit 3 are connected to each other, The problem that the capillary 35 is clogged by the components of the filler 14 or the like can be suppressed. Of course, also in the case of the present embodiment, a container for transferring the eluate is not necessary, so that the cost can be reduced.

(C) Embodiment 3
(Outline configuration)
In the case of this embodiment, a method for improving ionization efficiency by flowing a gas along the outside of the capillary 35 constituting the liquid feeding unit 3 will be described. At the same time, in this embodiment, a method for heating the analysis target component discharged from the capillary 35 to improve the ionization efficiency will be described.

  FIG. 4 schematically shows the configuration and operation of an ion source apparatus employing this method. In FIG. 4, parts corresponding to those in FIG. The ion source apparatus according to this embodiment includes an ionization probe 1 (extraction unit 2 and liquid feeding unit 3), a decompression container 4, a transport robot 27, a gas spray tube 41, and a heater 42 as main parts. In the case of this embodiment, a gas spray tube 41 and a heater 42 are additionally arranged with respect to the ion source device described in the first embodiment.

  Here, the gas spray tube 41 is processed into a cylindrical shape so that the ionization probe 1 can be attached, and is attached to the decompression vessel 4 so as to maintain airtightness. Here, a cavity (holding portion 45) that is slightly larger than the ionization probe 1 is formed in the gas spray tube 41 so that the ionization probe 1 can be mounted so as to drop from the upper opening.

  A cavity (tapered portion 46) is formed at the bottom of the holding portion 45 so that the inner diameter is narrowed toward the lower end side so as to surround the periphery of the capillary 35. The bottom part of the holding part 45 is processed into a taper shape so as to maintain airtightness with the taper part 24 constituting the liquid feeding part 3. In addition, an introduction pipe 47 for introducing the gas 48 from the outside to the inside of the tapered portion 46 is formed inside the gas spray pipe 41.

  With these structures, the gas 48 introduced from the introduction pipe 47 is ejected to the outside from the tip of the tapered portion 46 as a flow along the capillary 35. Incidentally, the positional relationship is determined so that the tip of the capillary 35 slightly protrudes from the tip of the tapered portion 46. The tip outer diameter of the capillary 35 is set to 0.1 to 1 mm. In this embodiment, the tip outer diameter is 0.3 mm. However, the dimension of the outer diameter of the tip is determined assuming that the assumed flow rate of the capillary 35 is 10 μL / min to 5 mL / min.

  The heater 42 is used for heating the analysis target component 19 ejected from the capillary 35. The heating method by the heater 42 includes a heated gas blowing method and a lamp heating method. In the case of the heated gas blowing method, the outlet of the heater is arranged so that the heat 49 is obliquely incident on the flow of the analysis target component 19 so as not to disturb the flow of the capillary 35.

  In this embodiment as well, the processing process is the same as in the first embodiment. That is, the washing step S1, the equilibration step S2, the adsorption step S3, the washing step S4, the connecting step S5, the moving step S6, the elution / ionization step S7, and the discarding step S8 are sequentially executed. Below, only transfer process S6, elution / ionization process S7, and disposal process S8 are explained.

(Move step S6)
In the moving step S6, the ionization probe 1 connecting the extraction unit 2 and the liquid feeding unit 3 is moved to a predetermined position in the ion source device. A transport robot 27 is used to move the ionization probe 1. A holder (not shown) is mounted on the arm 28 of the transfer robot 27, and the ionization probe 1 held by the holder is moved from the position before movement (in the figure, the position indicated by the dotted line in the figure) to the position after movement (in the figure). The ionization probe 1 is moved to a position indicated by a solid line). Also in this case, the tip of the capillary 35 of the ionization probe 1 is positioned around the ion take-in unit 31 in the ion detection unit 38 (for example, a mass spectrometer). During the movement, the ionization probe 1 is attached to the inside of the holding portion 45 and the taper portion 46 formed inside the gas spray tube 41 so as to maintain airtightness. Note that the transfer robot 27 and the connecting robot 26 may be the same.

(Elution / ionization process S7)
In the elution / ionization step S <b> 7, simultaneously with the application of the voltage 36, a gas 48 such as nitrogen or other inert gas or air is ejected from the capillary 35 and the tip opening of the gas spray tube 41. Vaporization of the solution flowing out from the lower end of the capillary 35 is promoted by the ejected gas 48, and the ionization efficiency of the analysis target component 19 can be improved. The promotion of vaporization is particularly effective when the flow rate of the solution flowing inside the capillary 35 is large. In parallel with this operation, heat 49 is ejected from the heater 42. The heat 49 superheats the solution flowing out of the capillary 35 and further promotes its vaporization.

(Disposal process S8)
The ionization probe 1 that has completed the elution / ionization step S7 can be reused by washing or the like. However, it is not preferable when a minute amount of contamination or the like causes a problem such as therapeutic drug monitoring (TDM).

  Therefore, in the case of the present embodiment, the ionization probe 1 is discharged from the decompression container 4 using the transfer robot 39. A holder (not shown) is mounted on the arm 40 of the transfer robot 37, and the ionization probe held by the holder is moved from the position before movement (position indicated by the dotted line in the figure) to the position after movement (in the figure, ionization probe). To the position indicated by the solid line). That is, the ionization probe is moved from the periphery of the ion intake unit 31 such as a mass spectrometer. Thereafter, the used ionization probe discharged from the decompression vessel 4 is discarded. Thereby, the ionization probe can be made disposable.

  As a result, it is possible to minimize the influence of contamination during the next analysis. The transfer robot 39 and the transfer robot 27 may be the same.

(Measurement result of flow rate)
Here, the result of measuring the flow rate of the solution flowing inside the capillary 35 will be described. FIG. 5 shows changes in the flow rate of the solution when the primary pressure of the decompression pump 34 is changed. The horizontal axis represents the primary pressure of the decompression pump 34, and the vertical axis represents the flow rate of the sample. Each plot corresponds to the case where the eluent 32 is methanol, pure water, or a mixture of water and methanol at a ratio of 1: 1. With reference to the measurement result of FIG. 5, stable solution feeding can be realized by adjusting the exhaust speed of the decompression pump 34 according to the type of solvent (by controlling the primary pressure of the decompression pump 34).

(Application examples)
In this embodiment, a method of generating a flow of gas 48 along the outer surface of the capillary 35 and a method of heating the downstream of the capillary 35 are combined with a method of reducing the pressure downstream of the filler 14 (FIG. 1). Explained the case. However, the method of generating the flow of the gas 48 along the outer surface of the capillary 35 and the method of heating the downstream of the capillary 35 can be combined with those of the second embodiment (FIG. 3). Alternatively, only one of a method for generating a flow of gas 48 along the outer surface of the capillary 35 and a method for heating the downstream of the capillary 35 can be used.

(Effect of embodiment)
Also in the case of this embodiment, similarly to the case of the above-described first embodiment, the connecting step S5 is arranged after the execution of the cleaning step S4, and the extraction unit 2 and the liquid feeding unit 3 are connected to each other, The problem that the capillary 35 is clogged by the components of the filler 14 or the like can be suppressed. Of course, also in the case of the present embodiment, a container for transferring the eluate is not necessary, so that the cost can be reduced.

(D) Embodiment 4
(Outline configuration)
In this embodiment, another configuration example of the capillary 35 constituting the liquid feeding unit 3 will be described. In FIG. 6, the structural example of the liquid feeding part 3 is shown. The liquid feeding unit 3 includes a capillary 35 and a tapered portion 24. In the case of this embodiment, the capillary 35 is made of metal, and the tapered portion 24 is made of resin. In this embodiment, a voltage is applied to the metal capillary 35 to ionize the solution. Below, each process of movement process S6 and elution / ionization process S7 is demonstrated according to FIG. FIG. 7 shows the premise of the device configuration of the third embodiment. That is, it is premised on an apparatus configuration in which the gas spray tube 41 is attached to the decompression vessel 4.

(Conveying step S6)
7 shows a state in which the liquid feeding unit 3 has already been moved around the ion intake unit 31 of the mass spectrometer or the like. In the case of this embodiment, the gas spray pipe 41 is formed with a hole reaching the tapered portion 46 from the outer wall, and a slide electrode 51 is attached so as to be freely slidable with respect to this hole. The slide electrode 51 is taken in and out by a drive unit (not shown). In addition, taking in and out of the slide electrode 51 is controlled by a control unit (not shown) (microprocessor or the like). At the end of the conveying step S6, the tip portion of the slide electrode 51 is stored in the inner wall of the gas spray tube 41 as shown in FIG.

(Elution / ionization process S7)
When starting the elution / ionization step S <b> 7, the slide electrode 51 is moved so as to protrude from the inner wall side of the gas spray tube 41 to the tapered portion 46 by a drive unit (not shown). At this time, the slide electrode 51 is slid until its tip contacts the surface of the capillary 35.

  At the same time, a pressure difference is generated between the upstream side and the downstream side of the filler 14, and the eluate 32 containing the analysis target component 19 flows out from the lower end of the capillary 35 of the liquid feeding unit 3. At the same time, a voltage 36 is applied to the capillary 35 through the slide electrode 51. By applying this voltage, the eluate 32 flowing out from the tip of the capillary 35 is ionized. At this time, the potential of the gas spray tube 41 may be controlled to the same potential as the capillary 35.

  When the ionization ends, the slide electrode 51 is accommodated in the inner wall of the gas spray tube 41 again so that the ionization probe 1 can be discarded. Thus, the slide electrode 51 is taken in and out in conjunction with the progress of the operation in order to avoid damage to the capillary 35. For example, when the slide electrode 51 protrudes from the inner wall of the gas spray tube 41 before the ionization probe 1 is mounted, the capillary 35 having a very thin diameter can be bent or broken by contacting or colliding with the slide electrode 51. There is sex.

(Application examples)
Also in this embodiment, the case of combining with the ion source device of the type in which the eluate 32 flows out of the ionization probe 1 by depressurization has been described, but the ion of the method of flowing out the eluate 32 from the ionization probe 1 by pressurization. It can also be applied to the source device. Moreover, in the case of embodiment mentioned above, although the ion source apparatus in which the gas spray tube 41 exists is illustrated, it can be applied also to the ion source apparatus which does not have the gas spray tube 41.

  In the case of the above-described embodiment, the case where the slide operation of the slide electrode 51 is started after the ionization probe 1 is mounted on the gas spray tube 41 has been described. However, you may use the drive part which puts in / out the slide electrode 51 according to the position accompanying attachment to the gas spray tube 41 of the ionization probe 1. FIG. For example, a drive unit that combines a spring mechanism and a link mechanism may be used. In this case, the link mechanism pushes the slide electrode 51 so as to protrude from the taper portion 46 in conjunction with the downward movement accompanying the mounting of the ionization probe 1, and when the removal of the ionization probe 1 is started, the slide is caused by the restoring force of the spring mechanism. The electrode 51 may be operated so as to be retracted from the tapered portion 46.

(Effect of embodiment)
Also in the case of this embodiment, similarly to the case of the above-described first embodiment, the connecting step S5 is arranged after the execution of the cleaning step S4, and the extraction unit 2 and the liquid feeding unit 3 are connected to each other, The problem that the capillary 35 is clogged by the components of the filler 14 or the like can be suppressed. Of course, also in the case of the present embodiment, a container for transferring the eluate is not necessary, so that the cost can be reduced.

(E) Embodiment 5
(Outline configuration)
In this embodiment, a method of applying a voltage to the capillary 35 without using the slide electrode 51 will be described. The basic structure of the liquid feeding section 3 used in this embodiment is almost the same as the structure shown in FIG. That is, the liquid feeding unit 3 includes a capillary 35 and a taper unit 24. However, both the capillary 35 and the tapered portion 24 are made of metal.

  FIG. 8 shows a configuration example of the ion source device according to the embodiment. FIG. 8 shows a state at the time when the moving step S6 in the ion source device is completed. As shown in the figure, this ion source device is constituted by a combination structure of a decompression system and a gas spray tube 41.

  In the case of the present embodiment, as described above, the tapered portion 24 is made of metal. The gas spray tube 41 is also made of metal. Therefore, when the ionization probe 1 is attached to the gas spray tube 41 and the taper portion 24 and the gas spray tube 41 are in an airtight state (contact state), the capillary 35 and the gas spray tube 45 have the same potential. For this reason, when the voltage 36 is applied to the gas spray tube 41, the voltage 36 can also be supplied to the capillary 35.

  When this structure is adopted, it is not necessary to bring the slide electrode 51 into contact with the capillary 35 as in the case of FIG. That is, the drive mechanism for the slide electrode 51 can be eliminated. Accordingly, in the case of this embodiment, the structure can be simplified as compared with the fourth embodiment. In addition, since the voltage 36 is applied through the tapered portion 24 of the liquid feeding section 3, the possibility of damaging the capillary 35 due to mechanical contact can be eliminated.

(Application examples)
Also in this embodiment, the case of combining with the ion source device of the type in which the eluate 32 flows out of the ionization probe 1 by depressurization has been described, but the ion of the method of flowing out the eluate 32 from the ionization probe 1 by pressurization. It can also be applied to the source device. Further, in the case of the above-described embodiment, the ion source device in which the gas spray tube 41 is present is illustrated. However, if the voltage 36 can be applied to the conductive member in contact with the tapered portion 24, the gas The present invention can also be applied to an ion source device that does not have the spray tube 41.

(Effect of embodiment)
Also in the case of this embodiment, similarly to the case of the above-described first embodiment, the connecting step S5 is arranged after the execution of the cleaning step S4, and the extraction unit 2 and the liquid feeding unit 3 are connected to each other, The problem that the capillary 35 is clogged by the components of the filler 14 or the like can be suppressed. Of course, also in the case of the present embodiment, a container for transferring the eluate is not necessary, so that the cost can be reduced.

(F) Embodiment 6
In this embodiment, a modification of the fifth embodiment will be described. That is, an embodiment in which the slide electrode 51 is not used will be described. In the case of the fifth embodiment, the case where both the capillary 35 and the tapered portion 24 are made of metal has been described. However, the same operation as in the fifth embodiment can be realized by making the tapered portion 24 made of a conductive resin.

(G) Embodiment 7
In this embodiment, an embodiment in which the slide electrode 51 is not used will be described. In FIG. 9, the structural example of the liquid feeding part 3 used by this embodiment is shown. In the case of this embodiment, both the capillary 35 and the taper part 24 constituting the liquid feeding part 3 are made of a conductive resin. Note that the capillary 35 and the tapered portion 24 may be integrated, or separate members may be combined. Also in this embodiment, the same effect as that of the fifth embodiment can be realized.

(H) Embodiment 8
In this embodiment, an embodiment in which the slide electrode 51 is not used will be described. In FIG. 10, the structural example of the liquid feeding part 3 used by this embodiment is shown. In this embodiment, the capillary 35 constituting the liquid feeding part 3 is made of metal, and the tapered part 24 is made of resin. However, the entire surface of the tapered portion 24 is covered with the conductive layer 52. It is assumed that at least a part of the conductive layer 52 is electrically coupled to the capillary 35. If an electrical path is formed between the gas spray tube 41 and the like holding the tapered portion 24, the conductive layer 52, and the capillary 35, the conductive layer 52 does not necessarily cover the entire surface of the tapered portion 24. It may not be formed. Also in this embodiment, the same effect as that of the fifth embodiment can be realized.

(I) Embodiment 9
In this embodiment, an embodiment in which the slide electrode 51 is not used will be described. In FIG. 11, the structural example of the liquid feeding part 3 used by this embodiment is shown. In the case of this embodiment, it is assumed that both the capillary 35 and the taper portion 24 constituting the liquid feeding section 3 are made of resin. However, the entire surface is covered with the conductive layer 52. Since the conductive layer 52 covers the entire surface of the substrate, the same effect as in the fifth embodiment can be obtained.

(J) Embodiment 10
(Outline configuration)
In this embodiment, a method of monitoring the pressure of the decompression container 4 and controlling the exhaust speed of the decompression pump 34 so that the eluate 32 can be sent stably will be described.

  FIG. 12 schematically shows the configuration and operation of an ion source apparatus employing this method. In FIG. 12, parts corresponding to those in FIG. The ion source device in this embodiment includes an ionization probe 1 (extraction unit 2 and liquid feeding unit 3), a decompression container 4, a transport robot 27 (not shown), an exhaust pipe 33, a decompression pump 34, and a pressure gauge 53 as main parts. To do.

  In the case of this embodiment, a pressure gauge 53 is additionally arranged in the decompression vessel 4 of the ion source device described in the first embodiment.

  Also in this embodiment, as in the first embodiment, the washing step S1, the equilibration step S2, the adsorption step S3, the washing step S4, the connecting step S5, the moving step S6, the elution / ionization step S7, and the discarding step S8. Are executed in order. Only the elution / ionization step S7 will be described below.

(Elution / ionization process S7)
In the case of this embodiment, the pressure gauge 53 measures the pressure in the decompression vessel 4 and feeds back the measurement result to the decompression pump 34. That is, the exhaust speed of the decompression pump 34 is controlled according to the measured pressure fluctuation. Adjustment of the exhaust speed of the decompression pump 34 includes a method of controlling by a valve and a method of adjusting an output value of a voltage for driving the decompression pump 34. By this pressure adjustment, it is possible to send the eluate 32 stably.

  In the case of FIG. 12, an ion source device that does not use the gas spray tube 41 is illustrated. However, in the case of an ion source device that uses the gas spray tube 41, the same can be achieved by arranging the pressure gauge 53. The effect can be realized. In addition, the mechanism of this embodiment can be combined with the liquid feeding unit 3 described in the fourth to ninth embodiments.

(K) Embodiment 11
(Outline configuration)
In this embodiment, a method of monitoring the pressure of the pressurizer 43 and controlling the pressurization pressure so that the eluate 32 can be sent stably will be described.

  FIG. 13 schematically shows the configuration and operation of an ion source apparatus employing this method. In FIG. 13, parts corresponding to those in FIG. The ion source apparatus according to this embodiment includes an ionization probe 1 (extraction unit 2 and liquid feeding unit 3), a transfer robot 27, a pressurizer 43, and a pressure gauge 54 as main parts.

  Also in this embodiment, the washing step S1, the equilibration step S2, the adsorption step S3, the washing step S4, the connecting step S5, the moving step S6, the elution / ionization step S7, and the discarding step S8 are executed in order. Only the elution / ionization step S7 will be described below.

(Elution / ionization process S7)
In the case of this embodiment, the pressure gauge 54 measures the pressure of the pressurizer 43 and feeds back the measurement result to the introduction amount of the gas 44 or the adjustment of the pressure. That is, the amount or pressure of the gas 44 introduced into the pressurizer 43 is controlled according to the measured pressure fluctuation. The pressure can be realized by adjusting a pressure valve, for example. By this pressure adjustment, it is possible to send the eluate 32 stably.

  In the case of FIG. 13, an ion source device that does not use the gas spray tube 41 is illustrated, but the ion source device that uses the gas spray tube 41 also has the same effect by disposing the pressure gauge 53. The effect can be realized. In addition, the mechanism of this embodiment can be combined with the liquid feeding unit 3 described in the fourth to ninth embodiments.

(L) Embodiment 12
In this embodiment, a method of monitoring the liquid level of the solution 32 injected into the extraction unit 2 with a liquid level sensor and controlling the reduced pressure of the reduced pressure pump 34 so that the eluate 32 can be sent stably. To do.

  FIG. 14 schematically shows the configuration and operation of an ion source apparatus employing this method. In FIG. 14, parts corresponding to those in FIG. The ion source device according to this embodiment includes an ionization probe 1 (extraction unit 2 and liquid feeding unit 3), a transport robot 27, an exhaust pipe 33, a decompression pump 34, and a liquid level sensor 56 as main parts.

  Also in this embodiment, the washing step S1, the equilibration step S2, the adsorption step S3, the washing step S4, the connecting step S5, the moving step S6, the elution / ionization step S7, and the discarding step S8 are executed in order. Only the elution / ionization step S7 will be described below.

(Elution / ionization process S7)
In this embodiment, the liquid level sensor 56 monitors the lowering state of the liquid level 55 of the eluate 32 injected into the extraction unit 2 and controls the exhaust speed of the decompression pump 34 according to the fluctuation of the lowering speed. . That is, the exhaust speed of the decompression pump 34 is controlled so that the decreasing speed is constant. As a premise of this embodiment, it is necessary that the liquid level sensor 56 can measure the liquid level of the extraction unit 2 directly or indirectly. FIG. 14 shows an example in which the liquid level sensor 56 is arranged on the side surface of the extraction unit 2 and the position of the liquid level 55 is measured transparently. A liquid level sensor 56 that measures the height of the liquid level 55 from above the extraction unit 2 can also be used.

  By the pressure adjustment described above, it is possible to send the eluate 32 stably. In the case of FIG. 14, an ion source device that does not use the gas spray tube 41 is illustrated. However, in the case of an ion source device that uses the gas spray tube 41, the same can be achieved by arranging the pressure gauge 53. The effect can be realized. Moreover, the liquid feeding part 3 demonstrated in Embodiment 4-9 can also be combined.

(M) Embodiment 13
In this embodiment, a modification of the twelfth embodiment will be described. In the case of this embodiment, a method of monitoring the liquid level of the solution 32 injected into the extraction unit 2 with a liquid level sensor and controlling the pressurizing pressure of the pressurizer 43 will be described.

  FIG. 15 schematically shows the configuration and operation of an ion source apparatus employing this method. In FIG. 15, the same reference numerals are assigned to the corresponding parts to those in FIG. The ion source apparatus according to this embodiment includes an ionization probe 1 (extraction unit 2 and liquid feeding unit 3), a transfer robot 27, a pressurizer 43, and a liquid level sensor 56 as main parts.

  Also in this embodiment, the washing step S1, the equilibration step S2, the adsorption step S3, the washing step S4, the connecting step S5, the moving step S6, the elution / ionization step S7, and the discarding step S8 are executed in order. Only the elution / ionization step S7 will be described below.

(Elution / ionization process S7)
In the case of this embodiment, the state of the liquid level 55 of the eluate 32 injected into the extraction unit 2 is monitored by the liquid level sensor 56, and the gas 44 introduced into the pressurizer 43 according to the variation in the speed of decrease. Adjust the amount or pressure introduced. By this adjustment, it is possible to send the eluate 32 stably.

  In the case of FIG. 15, an ion source device that does not use the gas spray tube 41 is illustrated. However, in the case of an ion source device that uses the gas spray tube 41, the same can be achieved by arranging the pressure gauge 53. The effect can be realized. Moreover, the liquid feeding part 3 demonstrated in Embodiment 4-9 can also be combined.

(N) Embodiment 14
(Outline configuration)
In the case of this embodiment, a method of injecting the internal standard substance 61 when injecting the sample solution 20 into the extraction unit 2 in order to realize quantitative analysis will be described.

  FIG. 16 schematically shows the configuration and operation of an ion source apparatus employing this method. In FIG. 16, the same reference numerals are given to portions corresponding to those in FIG. 1. However, in order to simplify the description, only the extraction unit 2 and the liquid feeding unit 3 are shown in FIG.

  As in the case of the first embodiment, also in this embodiment, the washing step S1, the equilibration step S2, the adsorption step S3, the washing step S4, the connecting step S5, the moving step S6, the elution / ionization step S7, and the disposal step S8 is executed in order. Only the adsorption step S3, the cleaning step S4, and the elution / ionization step S7 will be described below.

(Adsorption process S3)
In the adsorption step S <b> 3, the internal standard substance 61 is also injected into the extraction unit 2 together with the sample solution 20. As the internal standard material 61, an element obtained by isotopic substitution of some elements (carbon and hydrogen) of the analysis target component 19 is used. The internal standard substance component 62 is adsorbed on the filler 14 together with the sample component 17 including the analysis target component 19 and the contaminant component 21 by the adsorption step S3.

(Washing step S4)
In the cleaning step S4, the contaminant component 21 is discarded by injecting the cleaning solution 22 into the extraction unit 2. Since the internal standard substance component 62 has a composition very similar to the analysis target component 19, it is adsorbed to the filler 14 together with the analysis target component 19 and is not discarded.

(Elution / ionization process S7)
In the elution / ionization step S7, the eluate 32 is injected into the extraction unit 2, and elution and ionization are performed simultaneously. At this time, the ions 37 of the analysis target component 19 and the ions 63 of the internal standard substance component 62 are simultaneously generated and detected.

  The analysis target component 19 contained in the sample solution 20 can be quantified by comparing the detected intensity of the ion 63 of the internal standard substance component 62 whose concentration is known in advance and the ion 37 of the analysis target component 19. It becomes possible.

(Application examples)
In the case of the above-described embodiment, the sample solution 20 and the internal standard substance 61 are separately injected into the extraction unit 2, but a solution obtained by mixing the sample solution 20 and the internal standard substance 61 in advance is injected into the extraction unit 2. You may do it. This embodiment can be combined with the first to thirteenth embodiments.

(O) Embodiment 15
(Outline configuration)
In this embodiment, in order to realize further high-throughput analysis, a plurality of ionization probes 1 (extraction unit 2 and liquid feeding unit 3) are arranged in the vicinity of an ion intake unit 31 such as a mass spectrometer. Will be described.

  FIG. 17 schematically shows the configuration and operation of an ion source device employing this method. In FIG. 17, only the portions of the extraction unit 2 and the liquid feeding unit 3 are shown in order to simplify the description. Of course, the cleaning step S1, the equilibration step S2, the adsorption step S3, the cleaning step S4, the connecting step S5, the moving step S6, the elution / ionization step S7, and the discarding step S8 are sequentially executed for each ionization probe 1.

  In the case of this embodiment, since two sets of ionization probes 1 can be attached to the ion source device, using the period during which the ionization probes 1 that have finished the moving step S6 and the elution / ionization step S7 are discarded, Ionization can be performed by the other ionization probe 1. In this case, time loss can be reduced. For this reason, high-throughput analysis can be realized.

  Of course, if three or more sets of ionization probes 1 can be attached to the ion source device, further throughput can be increased.

(Application examples)
In the case of FIG. 17, an example of a pressurization method in which the eluate 32 is eluted by introducing the gas 44 into the pressurizer 43 is illustrated. is there. However, in the case of the depressurization method, depressurization cannot be performed if at least one ionization probe 1 is not attached to the depressurization container 4 in the moving step S6 or the like. For this reason, a mechanism for closing the hole where the ionization probe 1 is attached is required during the moving step S6 and the like. Further, this embodiment can be combined with any of Embodiments 1 to 14 described above.

(P) Embodiment 16
(Outline configuration)
In this embodiment, a system in which a flexible pipe is connected to the opening of the extraction section and the ionization process proceeds while the pipe is connected will be described.

  FIG. 18 schematically shows the configuration and operation of an ion source apparatus employing this method. In FIG. 18, only the portions of the extraction unit 2, the liquid feeding unit 3, and the pipe 65 are shown in order to simplify the description. The pipe 57 is made of a flexible resin. The pipe 57 is a pipe that can move freely while the extraction unit 2 and the pipe 65 are coupled. The ion source device according to this embodiment can be combined with any of the above-described first to fifteenth embodiments. However, when a pressurization method is employed for elution of the eluate 32, the pipe 65 is resistant to pressure. It is desirable to be excellent.

  Of course, also in this embodiment, for each ionization probe 1, the cleaning step S1, the equilibration step S2, the adsorption step S3, the cleaning step S4, the coupling step S5, the transfer step S6, the elution / ionization step S7, and the disposal Step S8 is performed in order. Below, only adsorption process S3, washing process S4, connection process S5, and elution / ionization process S7 are explained.

(Adsorption process S3)
In the adsorption step S3, the sample solution 20 is introduced into the extraction unit 2 through the pipe 65. The pipe 65 and the extraction unit 2 are combined. In this adsorption step S 3, the sample component 17 including the analysis target component 19 and the contaminant component 21 is adsorbed by the filler 14.

(Washing step S4)
In the cleaning step S <b> 4, the solvent 66 is introduced into the extraction unit 2 through the pipe 65. The contaminant component 21 adsorbed on the filler 14 is discarded together with the solvent 66. Therefore, when the cleaning is completed, only the analysis target component 19 is adsorbed on the filler 14.

(Connection step S5)
In the coupling step S5, the extraction unit 2 and the liquid feeding unit 3 after the contaminant component 21 is discarded are coupled to complete the ionization probe 1. The extraction unit 2 and the liquid feeding unit 3 need to be connected so as to obtain an airtight state. The details of the connection method are as described in the first embodiment.

(Elution / ionization process S7)
When the ionization probe 1 is transported to a predetermined position, the elution / ionization step S7 is started. In the elution / ionization step S <b> 7, the solvent 67 is introduced into the ionization probe 1 (extraction unit 2, liquid feeding unit 3) via the pipe 65. The analysis target component 19 adsorbed by the extraction unit 2 is eluted by the introduced solvent 67 and flows out from the lower end of the capillary 35 constituting the liquid feeding unit 3. At this time, when the voltage 36 is applied to the capillary 35, the analysis target component 19 is ionized (ESI method). The ionized ions 37 are detected by an ion detector 38 such as a mass spectrometer.

(Q) Embodiment 17
In the case of the first to sixteenth embodiments described above, after the ionization probe 1 is assembled by connecting the extraction unit 2 and the liquid feeding unit 3, around the ion intake unit such as a mass spectrometer. The driving method for moving and performing elution and ionization of the analysis target component 19 has been described.

  In this embodiment, first, only the liquid feeding part 3 is moved and positioned around the ion intake part of the mass spectrometer or the like, and then the extraction part 2 on which only the analysis target component 19 is adsorbed is sent. A method of completing the ionization probe 1 by being connected to the liquid part 3 will be described.

  FIG. 19 schematically shows the configuration and operation of an ion source apparatus employing this method. The ion source device according to this embodiment has the same device configuration as that of the first embodiment. In this embodiment, the process proceeds in the order of the washing step S1, the equilibration step S2, the adsorption step S3, the washing step S4, the moving step S6, the connecting step S5, the elution / ionization step S7, and the disposal step S8. And That is, the order of the moving step S6 and the connecting step S5 is changed from the other embodiments. FIG. 19 shows only the moving step S6 and the connecting step S5 that are peculiar to this embodiment.

(Move step S6)
In the moving step S6, only the liquid feeding unit 3 is moved to the periphery of the ion detection unit 38 such as a mass spectrometer by the arm 69 driven by the transfer robot 68. Next, the arm 69 returns to the original position, grabs the extraction unit 2 after the contaminant component 21 is discarded in the cleaning step S4, and moves to the vicinity of the liquid feeding unit 3 that has been moved previously. The transfer robot 68 and the arm 69 may be the same as the transfer robot 27 and the arm 28 described above.

(Connection step S5)
In the connecting step S5, the extracting unit 2 and the liquid feeding unit 3 are connected using the connecting robot 26 so as to obtain airtightness. In the case of this embodiment, the extraction unit 2 and the liquid feeding unit 3 are connected in the decompression vessel 4. The connecting robot 26 may be the same as the transfer robot 27 or 28.

(Application examples)
Also in the case of this embodiment, the extraction unit 2 and the liquid feeding unit 3 after the elution / ionization step S7 can be cleaned and reused. However, if a trace amount of contamination is a problem, such as therapeutic drug monitoring (TDM), it is desirable to evacuate without reuse. By making the ionization probe 1 disposable, it is possible to minimize the influence of contamination on the next analysis.

  Note that this assembling method can be easily applied to the methods described in the first to sixteenth embodiments.

(R) Other Embodiments In the above-described embodiment, the case where the pressure difference condition is controlled according to the type of solvent used for elution of the analysis target component is described. The pressure difference condition may be controlled on the basis of information (conductance) of the flow degree of the solution.

  In Embodiments 1 to 17 described above, the ion source device corresponding to the electrospray ionization method (ESI) has been described. However, the ionization probe 1 according to the present invention may be used as a sample solution supply unit used in various ionization methods such as atmospheric pressure chemical ionization (APCI) and DART ionization (Direct Analysis in Real Time).

DESCRIPTION OF SYMBOLS 1 ... Ionization probe, 2 ... Extraction part, 3 ... Liquid feeding part, 4 ... Depressurization container, 14 ... Filler, 15 ... Frit, 16 ... Cleaning solution, 17 ... Sample component, 18 ... Equilibration solution, 19 ... Analysis object Ingredients 20 ... Sample solution 21 ... Contaminant component 22 ... Cleaning solution 23 ... Tapered part 24 ... Tapered part 25 ... Airtight part 26 ... Linked robot 27 ... Transport robot 28 ... Arm 31 ... Ion Intake section, 32 ... eluate, 33 ... exhaust pipe, 34 ... decompression pump, 35 ... capillary, 36 ... voltage, 37 ... ion, 38 ... ion detector, 39 ... transport robot, 40 ... arm, 41 ... gas spray tube , 42 ... heater, 43 ... pressurizer, 44 ... gas, 45 ... holding part, 46 ... taper part, 47 ... introduction tube, 48 ... gas, 49 ... heat, 51 ... slide electrode, 52 ... conductive layer, 53 ... Pressure gauge, 54 Pressure gauge, 55 ... liquid level, 56 ... liquid level sensor, 61 ... internal standard substance, 62 ... internal standard substance component, 63 ... ion, 65 ... piping, 66 ... solvent, 67 ... solvent, 68 ... transport robot, 69 ... arm.

Claims (20)

An ionization probe in which an extraction unit having a filler for adsorbing a sample component in a cylinder and a liquid feeding unit having a capillary for ionization are connected;
A power source for applying a voltage to the capillary,
The extraction unit is connected to the liquid feeding unit after eluting and discarding the contaminant component adsorbed on the filler together with the analysis target component contained in the sample component,
An ion source for performing ionization by applying a voltage to the capillaries of the ionization probes connected to each other and eluting the component to be analyzed from the lower end of the cylinder while introducing an eluate from the upper end of the cylinder apparatus. The solution in the capillary which comprises the said ionization probe is sent to the area | region to ionize using the pressure difference of the downstream of the said ionization probe, and the pressure part of the upstream of the said ionization probe, The ionization probe of Claim 1 characterized by the above-mentioned. Ion source device. The ion source device according to claim 1, further comprising a transport mechanism that discards the used ionization probe every time ionization of the solution of the analysis target component is completed. The ion source device according to any one of claims 1 to 3, further comprising an assembly mechanism that connects the extraction unit and the liquid feeding unit so that an airtight state is obtained in the connection part. The one part or both of the said extraction part and the said liquid feeding part are the parts where the said extraction part and the said liquid feeding part are mutually connected are formed in the taper shape. The ion source device according to any one of the above. The ion source device according to claim 1, further comprising a tube that forms a gas flow along an outer surface of the capillary. The ion source device according to any one of claims 1 to 3, wherein the liquid feeding unit is configured by a metal, a resin, or a composite structure of a metal and a resin. The ion source device according to claim 7, wherein at least a part of the liquid feeding unit is made of a conductive resin. The ion source device according to claim 7, wherein a surface of a portion made of resin in the liquid feeding unit is covered with a conductive layer. The ion source apparatus according to claim 2, wherein the pressure difference condition is controlled according to a type of a solvent used for elution of the analysis target component. The ion source device according to claim 2, wherein the pressure difference condition is controlled according to the elution performance of the analysis target component acquired in advance for the extraction unit. The ion source device according to claim 1, further comprising a heating unit that heats a downstream portion of the capillary. A pressure gauge that measures a pressure downstream of the ionization probe or a pressure upstream of the ionization probe;
The ion source apparatus according to claim 2, wherein the pressure difference is controlled in accordance with a measured pressure fluctuation. A liquid level detection unit for detecting the height of the liquid level of the solution injected into the extraction unit;
The ion source device according to claim 2, wherein the pressure difference is controlled in accordance with a change in a liquid level lowering speed detected by the liquid level detection unit. When the component contained in the sample solution is adsorbed to the filler, the internal standard substance is also adsorbed to the extraction unit, and when the solution of the analysis target component is eluted from the filler and ionized, the sample The ion source device according to claim 1, wherein a component contained in the solution and the internal standard substance are eluted simultaneously. The ion source device according to claim 1, wherein a plurality of the ionization probes are arranged. The ion source device according to claim 1, further comprising a moving mechanism that moves the ionization probe to which the extraction unit and the liquid feeding unit are connected to a predetermined position for performing ionization. The ion source apparatus according to claim 17, further comprising: an ionization chamber including an ion detection unit, wherein the moving mechanism moves the connected ionization probe to the ionization chamber and then performs ionization. . A step of adsorbing a component to be analyzed and a contaminant component contained in a sample component to a filler provided in a cylindrical extraction unit;
Eluting and discarding the contaminant components from the filler;
The extractor after discarding eluting the contaminant components, linked to the liquid supply portion having a capillary ionization probe, characterized in that a step of assembling the ionization probe for ionizing the analyte Production method. A step of adsorbing a component to be analyzed and a contaminant component contained in a sample component to a filler provided in a cylindrical extraction unit;
Eluting and discarding the contaminant components from the filler;
The extractor after discarding eluting the contaminant components, a step of connecting to the liquid feeding unit having a capillary assembling the ionization probe,
Introducing an eluent from an upper end of the cylindrical extraction unit, and simultaneously ionizing the solution of the analysis target component from the filler in the ionization probe while eluting from the lower end of the extraction unit. A driving method of an ion source device characterized by the above.

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