JP7111333B2 - ionizer - Google Patents

Description

The present invention relates to ionization devices.

An electrospray ionization apparatus (hereinafter referred to as ESI) is known which has a capillary and sprays droplets containing at least two or more solvents from the tip of the capillary. This ESI is a device that sprays ionized droplets from the tip of a capillary by applying a voltage to the capillary. As an example of such a device, one that is used as a set with a mass spectrometer has been proposed (see, for example, Patent Document 1).

U.S. Pat. No. 8,203,117

In the apparatus described in Patent Document 1, an object to be measured is placed on a stage, and droplets (hereinafter referred to as primary droplets) are sprayed from a capillary onto the object to be measured. As a result, droplets containing fragments of the object to be measured (hereinafter referred to as secondary droplets) are scattered. As the secondary droplet enters the inlet of the mass spectrometer, the mass of molecules contained in the secondary droplet is analyzed by the mass spectrometer.
By the way, in a mass spectrometer, it is preferable that ESI has a structure more suitable for mass spectrometry in order to more accurately detect the mass of molecules contained in the secondary droplets.

An object of the present invention is to provide an ionization device having a structure more suitable for mass spectrometry.

The present invention is an ionization device capable of downsizing atomized droplets, the ionization device comprising: a capillary for atomizing the droplets; Regarding.

Moreover, it is preferable that the capillary sprays the primary liquid droplets toward the object to be measured, and the sound wave irradiator irradiates the secondary liquid droplets reflected by the object to be measured with sound waves of a predetermined cycle.

Further, it is preferable that the sound wave irradiation section is arranged in front of the reflection position of the secondary droplet in the direction along the reflection direction of the secondary droplet.

Moreover, it is preferable that the sound wave irradiation unit is arranged near the entrance of a mass spectrometer that is arranged ahead of the reflection direction of the secondary droplet.

Moreover, it is preferable that the capillary sprays the primary liquid droplets toward the object to be measured, and the sound wave irradiation section irradiates the primary liquid droplets with sound waves of a predetermined cycle.

Further, it is preferable that the capillary atomizes a secondary liquid droplet containing the object to be measured, and the sound wave irradiation section irradiates the secondary liquid droplet with a sound wave having a predetermined frequency.

Moreover, it is preferable that the sound wave irradiation unit irradiates ultrasonic waves.

According to the present invention, an ionization device having a structure more suitable for mass spectrometry can be provided.

1 shows a schematic diagram of an ionization device according to a first embodiment of the present invention; FIG. FIG. 4 shows a partially enlarged view of an axial cross-section of the capillary of the first embodiment; The top view of the outer peripheral surface of the inner cylinder of 1st Embodiment is shown. FIG. 4 is a schematic diagram showing changes in the state of secondary droplets in the first embodiment; Fig. 2 shows a schematic diagram of an ionization device according to a second embodiment of the present invention; Fig. 3 shows a schematic diagram of an ionization device according to a third embodiment of the present invention; FIG. 12 shows a block diagram of a control unit of an ionization device according to a seventh embodiment of the present invention; FIG. 14 is a schematic diagram showing the moving direction of the stage of the seventh embodiment; FIG. 14 is a graph showing changes in the mixing ratio of solvents that are changed by the supply unit of the seventh embodiment; FIG. It is a graph which shows typically the intensity|strength information of 7th Embodiment.

An ionization device 1 according to each embodiment of the present invention will be described below with reference to FIGS. 1 to 10. FIG.

[First embodiment]
First, an ionization device 1 and an analysis system according to a first embodiment of the present invention will be described with reference to FIGS. 1 to 4. FIG.
The analysis system (not shown) is a system that analyzes the molecular mass (ionic strength) contained in the object to be measured S (for example, tissue derived from a living body impregnated with other molecules such as drugs). The analysis system includes a mass spectrometer 100 (see FIG. 8) and an ionization device 1 .
The mass spectrometer 100 is a device capable of outputting the molecular mass (ion intensity) of ions contained in the fragment of the object S introduced to the inlet E. FIG.

The ionization device 1 is, as shown in FIG. 1, a device that sprays two or more kinds of solvents toward an object S to be measured as primary liquid droplets f. Further, the ionization device 1 is a device for obtaining secondary droplets g containing ionized fragments of the object S to be measured by spraying the primary droplets f toward the object S to be measured. The ionization device 1 is a device capable of downsizing sprayed droplets (especially, secondary droplets g). The ionization device 1 is arranged adjacent to an entrance E (inlet) of a mass spectrometer 100 that analyzes the mass of the object S to be measured. Specifically, the ionization device 1 includes a casing (not shown) having a pressure higher than that inside the mass spectrometer 100 . An inlet E of the mass spectrometer 100 is arranged inside the casing. This ionization device 1 includes a stage 10 , a capillary 20 , a supply section 30 , a power supply section 40 , a sound wave irradiation section 50 and a control section 60 . In addition, in the following embodiments, when simply described as "droplet", it indicates at least one of "primary droplet f" and "secondary droplet g".

The stage 10 is a mounting table on which the object S to be measured is mounted. The stage 10 is formed in a plate shape, for example. The stage 10 is arranged near the entrance E of the mass spectrometer 100 .

The capillary 20 has a cylindrical shape and is configured to be able to spray the solvent supplied to the base end from the tip. Capillary 20 is formed of a conductive material. The capillary 20 is arranged with its tip directed toward the stage 10 (object to be measured S) and separated from the stage 10 by a predetermined distance. Also, the tip of the capillary 20 is arranged to face the inlet E of the mass spectrometer 100 . The axial direction of the capillary 20 is arranged so as to overlap the line connecting the inlet E of the mass spectrometer 100 and the object S to be measured. The capillary 20 is tilted with respect to the stage 10 by an angle at which the secondary droplet g can be incident toward the inlet E of the mass spectrometer 100 . In this embodiment, the capillary 20 has a double structure in the radial direction. That is, the capillary 20 has an inner cylinder 21 and an outer cylinder 22 . Capillary 20 also includes rifling 23 .

The inner cylinder 21 is arranged so that its tip faces the stage 10 . The inner cylinder 21 is capable of circulating the two kinds of mixed solvents therein.

The outer cylinder 22 has an inner diameter larger than that of the inner cylinder 21 . The outer cylinder 22 is arranged radially outward of the inner cylinder 21 . That is, the outer cylinder 22 is capable of circulating an auxiliary fluid (for example, N2, other solvent, etc.) between the inner peripheral surface and the outer peripheral surface of the inner cylinder 21 .

The rifling 23 is arranged on the inner peripheral surface along the axial direction of the inner cylinder 21, as shown in FIGS. The rifling 23 causes the solvent flowing through the inner cylinder 21 to swirl. The rifling 23 is arranged along the axial direction on at least one of the outer peripheral surface of the inner cylinder 21 and the inner peripheral surface of the outer cylinder 22 . In this embodiment, the rifling 23 is arranged on both the outer peripheral surface of the inner cylinder 21 and the inner peripheral surface of the outer cylinder 22 . The rifling 23 causes the auxiliary fluid flowing between the outer peripheral surface of the inner cylinder 21 and the outer peripheral surface of the outer cylinder 22 to perform a turning motion.

According to the capillary 20 described above, two kinds of mixed solvents are supplied from the proximal end of the inner cylinder 21 toward the distal end. As a result, the two types of solvents are sprayed as primary droplets f from the tip of the inner cylinder 21 toward the object S on the stage 10 . At this time, the two types of solvents are sprayed from the tip of the inner cylinder 21 while swirling by the rifling 23 .

Auxiliary fluid is supplied from the proximal end to the distal end between the inner cylinder 21 and the outer cylinder 22 . At this time, the auxiliary fluid is discharged from between the inner cylinder 21 and the outer cylinder 22 while making a swirling motion by the rifling 23 . The primary droplets f fragment the object S to be measured by being sprayed onto the object S to be measured. The fragmented object S to be measured is included in the primary droplet f reflected by the object S to be measured. As a result, the primary droplet f reflected by the object S becomes the secondary droplet g.

The supply section 30 is connected to the proximal end of the capillary 20 . Specifically, the supply portion 30 is connected to the proximal end portion of the inner cylinder 21 . Supply unit 30 is configured to be able to dynamically change the mixing ratio of at least two types of solvents. In this embodiment, the supply unit 30 is configured to be able to dynamically change the mixing ratio of the two types of solvents. The supply section 30 includes two pump sections 31 and a mixer 32 .

Each of the pump units 31 is, for example, a syringe pump, and is configured to be able to supply different solvents. Specifically, each of the pump units 31 is configured to be able to supply a different solvent at a set supply amount.

Mixer 32 is a device that mixes the solvents against the back pressure of the two solvents. The mixer 32 is connected to the two pump portions 31 and to the base end portion of the inner cylinder 21 . The mixer 32 mixes the solvent supplied from each of the two pump units 31 . The mixer 32 supplies the mixed solvent to the base end of the inner cylinder 21 .

The power supply unit 40 is connected to the capillary 20 (inner cylinder 21). The power supply unit 40 applies a high voltage to the inner cylinder 21 . Thereby, the power supply unit 40 ionizes the mixed solvent flowing inside the inner cylinder 21 .

The sound wave irradiator 50 irradiates the atomized droplets with sound waves of a predetermined frequency. In the present embodiment, the sound wave irradiator 50 irradiates the secondary droplet g reflected by the object S with sound waves of a predetermined cycle. The sound wave irradiation unit 50 irradiates ultrasonic waves, for example. The sound wave irradiation unit 50 is arranged in front of the reflection position of the secondary droplet g (between the capillary 20 and the reflection position) in the direction along the reflection direction of the secondary droplet g. In other words, the acoustic wave irradiation unit 50 is arranged at a position facing the entrance E of the mass spectrometer 100 through the reflection position in the direction along the reflection direction of the secondary droplet g. The sound wave irradiator 50 irradiates sound waves in the direction toward the entrance E of the mass spectrometer 100 along the reflection direction of the secondary droplet g.

A control unit 60 is connected to the two pump units 31 and the stage 10 . The control unit 60 is configured to be able to dynamically change the amount of operation of the two pump units 31 . That is, the control unit 60 is configured to be able to dynamically change the mixing ratio of the solvent by the two pump units 31 . In this specification, the term “dynamically changeable” is not limited to continuously (for example, linear or curved) changeable, but also includes spot-wise changeable. Further, the control unit 60 is configured to be able to instruct the operation of the stage 10 (for example, movement in the in-plane direction).

Next, operations of the ionization device 1 and the analysis system according to this embodiment will be described.
First, the control unit 60 determines the amount of operation of the two pump units 31 based on a preset mixing ratio. The control unit 60 operates the pump unit 31 with the determined operating amount. Thereby, the mixed solvent is supplied to the proximal end portion of the inner cylinder 21 . Auxiliary fluid is also supplied between the inner cylinder 21 and the outer cylinder 22 .

Next, the power supply unit 40 starts applying voltage to the inner cylinder 21 . Thereby, the solvent supplied to the proximal end portion of the inner cylinder 21 is ionized. The ionized solvent is sprayed toward the object S from the tip of the inner cylinder 21 as primary droplets f. At this time, the solvent is sprayed onto the object S to be measured while rotating due to the rifling 23 provided on the inner peripheral surface of the inner cylinder 21 . Further, the auxiliary fluid that has flowed between the inner cylinder 21 and the outer cylinder 22 rotates due to the rifling 23 provided on the outer peripheral surface of the inner cylinder 21 and the inner peripheral surface of the outer cylinder 22, while moving the object S to be measured. emitted towards.

The object S to be measured is partially fragmented by being sprayed with the ionized primary liquid droplets f. In addition, the primary droplet f hits the object S and rebounds to become a secondary droplet g. The secondary droplet g contains the fragmented object S to be measured and moves toward the inlet E of the mass spectrometer 100 .

The sound wave irradiator 50 irradiates the secondary droplet g with a sound wave of a predetermined frequency. As shown in FIG. 4, the secondary droplet g vibrates due to the irradiation of sound waves. The vibrated secondary droplet g splits into a plurality of droplets. The total surface area of secondary droplets g increases due to breakup. This makes it easier for the solvent contained in the secondary droplet g to evaporate. Therefore, the secondary droplet g is introduced into the inlet E of the mass spectrometer 100 with a reduced amount of solvent.

If the molecular mass analysis accuracy of the mass spectrometer 100 is poor, it is conceivable that the mass of the fragment of the object to be measured S contained in the secondary droplet g is small. Therefore, the controller 60 dynamically changes the mixing ratio of the solvent. The control unit 60 changes the operation amount of the pump unit 31 according to the changed mixing ratio. The control unit 60 changes the operation amount of the pump unit 31 until a mixing ratio that provides better analysis accuracy is obtained.

The ionization device 1 and the analysis system of the first embodiment described above have the following effects.

(1) The ionization device 1 includes a cylindrical capillary 20 which is capable of spraying a solvent supplied to the proximal end from the distal end, and a capillary 20 connected to the proximal end of the capillary 20 to provide at least two types of solvent. and a supply unit 30 capable of dynamically changing the mixing ratio of the solvent. As a result, the mixed amount of the solvent sprayed from the capillary 20 can be dynamically changed, so that a suitable mixed amount of the solvent can be easily generated. Therefore, the ionization device 1 can have a structure more suitable for mass spectrometry.

(2) The supply unit 30 includes a plurality of pump units 31 each supplying a different solvent. Accordingly, the mixing ratio can be easily changed by changing the amount of operation of the plurality of pump units 31 .

(3) The ionization device 1 includes a capillary 20 that sprays droplets, and a sound wave irradiation unit 50 that irradiates the sprayed droplets with sound waves of a predetermined cycle. As a result, by splitting the droplets and increasing the total surface area of the droplets, the amount of evaporation of the solvent contained in the droplets can be increased. Therefore, the amount of solvent contained in the secondary droplet g entering the inlet E of the mass spectrometer 100 can be reduced, and the structure of the ionization device 1 can be made more suitable for mass spectrometry.

(4) The capillary 20 sprays the primary droplets f toward the object S to be measured, and the sound wave irradiation unit 50 irradiates the secondary droplets g reflected by the object S to be measured with sound waves of a predetermined cycle. Thereby, the secondary droplet g can be split and the total surface area of the secondary droplet g can be increased. The secondary droplets g can increase the amount of solvent evaporated due to the increased total surface area. Therefore, the amount of solvent contained in the secondary droplet g entering the inlet E of the mass spectrometer 100 can be reduced, and the structure of the ionization device 1 can be made more suitable for mass spectrometry.

(5) The sound wave irradiation unit 50 is arranged in front of the reflection position of the secondary droplet g in the direction along the reflection direction of the secondary droplet g. As a result, the sound wave irradiating unit 50 can irradiate the sound wave along the movement direction of the secondary droplet g, thereby improving the splitting efficiency of the secondary droplet g. Therefore, the amount of solvent contained in the secondary droplet g entering the inlet E of the mass spectrometer 100 can be reduced, and the structure of the ionization device 1 can be made more suitable for mass spectrometry.

(6) The sound wave emitting unit 50 emits ultrasonic waves. As a result, the secondary droplets g are irradiated with sound waves of a relatively high frequency, so that the splitting efficiency of the secondary droplets g is improved. Therefore, the amount of solvent contained in the secondary droplet g entering the inlet E of the mass spectrometer 100 can be reduced, and the structure of the ionization device 1 can be made more suitable for mass spectrometry.

(7) The ionization device 1 includes a cylindrical capillary 20 for spraying the solvent supplied to the base end from the tip, wherein the capillary 20 has an inner peripheral surface along the axial direction, which is swirled by the solvent. It has rifling 23 that gives motion. Giving a swirling motion to the solvent increases the straightness of the primary droplet f. As a result, the amount of the primary liquid droplets f reflected by the object S to be measured increases. Therefore, more objects S to be measured can be included in the secondary droplet g. In addition, due to the swirling motion, the paths of the primary droplet f and the secondary droplet g to the entrance E of the mass spectrometer 100 become longer than when they simply move straight. As a result, the discharge of the primary droplets f and the secondary droplets g is reduced, and the solvent can be evaporated more efficiently. As described above, the structure of the ionization device 1 can be made more suitable for mass spectrometry.

(8) The capillary 20 has a cylindrical shape and includes an inner cylinder 21 through which a solvent can flow, and an outer cylinder 22 arranged radially outward of the inner cylinder 21. and an outer cylinder 22 through which an auxiliary fluid can flow between the inner cylinder 21 and the outer circumferential surface of the inner cylinder 21 . It is further arranged along the axial direction on at least one of the outer peripheral surface of the outer cylinder 22 and the inner peripheral surface of the outer cylinder 22 . As a result, the auxiliary fluid can also be given a swirling motion, and the straightness can be increased. Since the auxiliary fluid exists so as to cover the primary fluid in the circumferential direction, the diffusion of the primary fluid can be suppressed. Therefore, the structure of the ionization device 1 can be made more suitable for mass spectrometry.

[Second embodiment]
Next, an ionization device 1 and an analysis device according to a second embodiment of the invention will be described with reference to FIG. In the description of the second embodiment, the same components are denoted by the same reference numerals, and the description thereof will be omitted or simplified.
The ionization device 1 and analysis system according to the second embodiment differ from those of the first embodiment in that a plurality of capillaries 20 are provided. In addition, in the ionization apparatus 1 according to the second embodiment, the supply unit 30 supplies different solvents to the respective capillaries 20, and the supply amount of the solvent supplied to the respective capillaries 20 can be dynamically changed. This is different from the first embodiment.

One of the plurality of capillaries 20 is arranged in the same manner as the capillaries 20 in the first embodiment. The other of the plurality of capillaries 20 is arranged with its tip toward the stage 10 (object to be measured S). In this embodiment, the other capillary 20 is arranged above the object S to be measured.

According to the ionization device 1 and the analysis device of the second embodiment described above, in addition to the above (1) to (8), the following effects are obtained.
(9) A plurality of capillaries 20 are provided. The supply unit 30 supplies different solvents to the respective capillaries 20 and can dynamically change the supply amount of the solvent supplied to the respective capillaries 20 . As a result, the solvent can be mixed above the object S to be measured, and the mixing amount can be dynamically changed. Since the supply amount of the solvent supplied to each capillary 20 can be changed independently, both the mixing ratio and the supply amount can be changed. Therefore, flexibility in mixing solvents can be improved.

[Third embodiment]
Next, an ionization device 1 and an analysis system according to a third embodiment of the invention will be described with reference to FIG. In the explanation of the third embodiment, the same components are denoted by the same reference numerals, and the explanation thereof is omitted or simplified.
In the ionization apparatus 1 and the analysis system according to the third embodiment, as shown in FIG. 6, the sound wave irradiation unit 50 is placed near the entrance E of the mass spectrometer 100 arranged ahead of the reflection direction of the secondary droplet g. It differs from the first and second embodiments in terms of arrangement.

According to the ionization device 1 and the analysis system of the third embodiment described above, in addition to the above (1) to (9), the following effects are obtained.
(10) The sound wave irradiation unit 50 is arranged near the inlet E of the mass spectrometer 100 arranged ahead of the reflection direction of the secondary droplet g. Even with such a configuration, the splitting efficiency of the secondary droplet g can be improved. Therefore, the amount of solvent contained in the secondary droplet g entering the inlet E of the mass spectrometer 100 can be reduced, and the structure of the ionization device 1 can be made more suitable for mass spectrometry.

[Fourth embodiment]
Next, an ionization device 1 and an analysis system according to a fourth embodiment of the invention will be described. In describing the fourth embodiment, the same reference numerals are given to the same components, and the description thereof will be omitted or simplified.
The ionization apparatus 1 and the analysis system according to the fourth embodiment differ from those of the first to third embodiments in that the acoustic wave irradiation unit 50 irradiates the primary droplet f with a predetermined period of sound waves.

According to the ionization device 1 and analysis system of the fourth embodiment described above, in addition to the above (1) to (10), the following effects are obtained.
(11) The capillary 20 sprays the primary droplets f toward the object S to be measured, and the sound wave irradiation unit 50 irradiates the primary droplets f with sound waves of a predetermined cycle. As a result, the size of the primary droplet f can be reduced. By miniaturizing the primary droplet f, it is considered that the amount of the object S to be measured contained in the secondary droplet g can be increased.

[Fifth embodiment]
Next, an ionization device 1 and an analysis system according to a fifth embodiment of the present invention will be described. In the description of the fifth embodiment, the same reference numerals are given to the same constituent elements, and the description thereof will be omitted or simplified.
The ionization apparatus 1 and analysis system according to the fifth embodiment differ from the first to fourth embodiments in that the capillary 20 sprays the secondary liquid droplets g containing the object S to be measured. Further, the ionization apparatus 1 according to the fifth embodiment differs from the first to fourth embodiments in that the sound wave irradiation unit 50 irradiates the secondary droplet g with sound waves of a predetermined frequency.

According to the ionization device 1 and analysis system according to the fifth embodiment described above, in addition to the above (1) to (11), the following effects are obtained.

(12) The capillary 20 sprays secondary liquid droplets g containing the object S to be measured, and the sound wave irradiation unit 50 irradiates the secondary liquid droplets g with sound waves of a predetermined frequency. This improves the splitting efficiency of the secondary droplets g sprayed by the capillary 20 . Therefore, the amount of solvent contained in the secondary droplet g entering the inlet E of the mass spectrometer 100 can be reduced, and the structure of the ionization device 1 can be made more suitable for mass spectrometry.

[Sixth embodiment]
Next, an ionization device 1 and an analysis system according to a sixth embodiment of the present invention will be described. In describing the sixth embodiment, the same reference numerals are given to the same components, and the description thereof will be omitted or simplified.
In the ionization device 1 and the analysis system according to the sixth embodiment, the pitch of the rifling 23 increases from the proximal end of the inner cylinder 21 or the outer cylinder 22 toward the distal end. Different from the embodiment.

According to the ionization device 1 and analysis system according to the sixth embodiment described above, in addition to the above (1) to (12), the following effects are obtained.

(13) The pitch of the rifling 23 increases from the proximal end portion of the inner cylinder 21 or the outer cylinder 22 toward the distal end portion. As a result, the angular acceleration applied to the droplet at the base end is small, and the angular acceleration applied to the droplet at the tip end is increased. The flow velocity of the droplet increases due to the application of the voltage as it goes from the base end to the tip end. When the flow velocity is slow, the occurrence of turbulent flow at the base end can be suppressed by reducing the angular acceleration. On the other hand, by increasing the angular acceleration at the tip where the flow velocity is high, the turning motion can be made faster. Therefore, it is possible to efficiently give the primary droplet f a swirling motion.

[Seventh embodiment]
Next, an ionization device 1, an ionization method, a program, and an analysis system according to a seventh embodiment of the invention will be described with reference to FIGS. 7 to 10. FIG. In describing the sixth embodiment, the same reference numerals are given to the same components, and the description thereof will be omitted or simplified.

The ionization apparatus 1, the ionization method, the program, and the analysis system according to the seventh embodiment place a solution (hereinafter referred to as a standard solution P) in which the types and mixture ratio of molecules contained in advance are known on the stage 10. It is analyzed by the analyzer 100 . This analysis is a preliminary analysis performed in advance when the object S to be measured is analyzed. The ionization device 1, the ionization method, the program, and the analysis system according to the present embodiment include molecules equivalent to the molecules impregnated in the object S in the standard solution P, so that the object S can be analyzed. Optimize the best solvent mixture ratio. As shown in FIG. 7, the control unit 60 according to the seventh embodiment includes an operation instructing unit 61, a mixing ratio specifying unit 62, an intensity information acquiring unit 63, a timing detecting unit 64, and an optimum value determining unit 65. , provided.

The operation instruction section 61 transmits an operation signal to the supply section 30 and the stage 10 . Thereby, the operation instruction unit 61 causes the supply unit 30 to dynamically change the mixing ratio of at least two types of solvents (primary droplets f). The operation instruction unit 61 dynamically changes the mixing ratio of the two solvents by, for example, linearly changing the mixing ratio of one of the two solvents from 0% to 100%. In addition, the motion instructing section 61 moves the stage 10 . Specifically, the operation instruction unit 61 moves the stage 10 in one of the in-plane directions so that the solvent whose mixing ratio dynamically changes can be sprayed onto different positions of the object S to be measured. The operation instruction unit 61 moves the stage 10 from point C to point D in FIG. 8, for example. For example, as shown in FIG. 9, the operation instruction unit 61 dynamically adjusts the mixing ratio (the amount of one solvent to the total solvent) from 0% to 100% according to the moving speed from point C to point D. change. The operation instruction unit 61 causes the supply unit 30 to supply the solvent to the capillary 20 .

The mixture ratio specifying unit 62 specifies the mixture ratio of the solvent. For example, the mixing ratio specifying unit 62 acquires the operating speed of the pump unit 31 included in the operation signal transmitted to the supply unit 30 by the operation instructing unit 61, thereby mixing the solvents instructed by the operation instructing unit 61. Identify rates.

The intensity information acquisition unit 63 acquires the ion intensity obtained from the mass spectrometer 100 as intensity information. Specifically, the intensity information acquisition unit 63 acquires the ion intensity obtained by the mass spectrometer 100 as a result of being sprayed onto the object S to be measured as intensity information. For example, as shown in FIG. 10, the intensity information acquisition unit 63 acquires the ion intensity at each position after moving the stage 10 from point C to point D as intensity information.

The timing detection unit 64 refers to the intensity information acquired by the intensity information acquisition unit 63 . The timing detection unit 64 detects the timing (for example, time) when the ion intensity indicated by the intensity information becomes equal to or greater than a predetermined value. The timing detection unit 64 detects, for example, the timing when the ion intensity indicated by the intensity information reaches or exceeds a predetermined value. In this embodiment, the timing detection unit 64 detects the timing at which the ion intensity reaches the highest intensity as the timing at which the ion intensity reaches a predetermined value or more. The timing detector 64 outputs the detected timing.

The optimum value determination unit 65 determines the mixture ratio at the detected timing as the optimal value for ionization. Specifically, the optimum value determination unit 65 acquires the output timing, and acquires the mixture ratio of the solvent at the acquired timing from the mixture ratio identification unit 62 . The mixture ratio specifying unit 62 determines the obtained mixture ratio of the solvent to be an optimum value.

Next, the operation of the ionization device 1, ionization method, program, and analysis system according to this embodiment will be described.
First, the standard solution P is placed on the stage 10 as shown in FIG.

Next, the motion instructing section 61 moves the stage 10 from the point C position to the point D position. In addition, while the stage 10 is moving from the position of the point C to the position of the point D, the operation instruction unit 61 causes the supply unit 30 to dynamically change the mixing ratio of at least two kinds of solvents, and to is supplied to the capillary. As a result, the capillary sprays solvents at different mixing ratios at different positions from point C to point D, as shown in FIG. The sprayed solvent is taken into the inlet of the mass spectrometer 100 and subjected to mass analysis.

Here, the mixing ratio specifying unit 62 specifies the mixing ratio of the solvent indicated by the operation instructing unit 61 . The mixing ratio specifying unit 62 specifies the mixing ratio of the solvent, for example, based on the operating speed of the pump unit 31 instructed by the operation instructing unit 61 .

The intensity information acquisition unit 63 acquires the ion intensity obtained as a result of being taken in the inlet E of the mass spectrometer 100 as intensity information. The intensity information acquisition unit 63 acquires intensity information as shown in FIG. 9 from the mass spectrometer 100, for example. The intensity information acquisition section 63 sends the acquired intensity information to the timing detection section 64 .

The timing detector 64 detects the timing when the ion intensity contained in the intensity information becomes equal to or greater than a predetermined value. For example, as shown in FIG. 9, the timing detection unit 64 outputs time t to the optimum value determination unit 65 as the detected timing.

The optimum value determination unit 65 acquires the timing from the timing detection unit 64 and acquires the mixture ratio at time t from the mixture ratio identification unit 62 . Thereby, the optimum value determining unit 65 determines the optimum mixing ratio in the standard solution P.

According to the ionization device 1, the ionization method, the program, and the analysis system according to the seventh embodiment described above, in addition to the effects (1) to (13), the following effects are obtained.
(14) The ionization apparatus 1 further includes a control unit 60 that optimizes the mixing ratio of the solvent in the supply unit 30. The control unit 60 causes the supply unit 30 to dynamically change the mixture ratio of at least two solvents. an operation instruction unit 61 for supplying the solvent to the capillary, a mixture ratio specifying unit 62 for specifying the mixture ratio of the solvent, and an intensity information acquisition unit 63 for acquiring the ion intensity obtained from the mass spectrometer 100 as intensity information. , a timing detection unit 64 for detecting the timing at which the ion intensity indicated by the intensity information becomes equal to or greater than a predetermined value, and an optimum value determination unit 65 for determining the mixing ratio at the detected timing as the optimum value for ionization. . In the mass spectrometer 100, the mixing ratio can be optimized in advance for the standard solution P containing molecules to be analyzed. As a result, the mixing ratio can be optimized for the molecules that are considered to be contained in the object S to be actually analyzed, so that the accuracy of analysis of the object S can be improved. The same is true for ionization methods, programs, and analysis systems.

Although preferred embodiments of the ionization device, ionization method, program, and analysis system of the present invention have been described above, the present invention is not limited to the above-described embodiments and can be modified as appropriate.

For example, in the above embodiment, two types of solvents are mixed, but more solvents may be mixed. In this case, the number of pump units 31 may be increased in the first embodiment. In the second embodiment, the number of capillaries 20 and pump units 31 may be increased.

Also, in the above embodiment, the pump section 31 has two or more syringe pumps, but instead, the pump section 31 may have two or more plunger pumps.

Further, in the above embodiment, the capillary 20 may be single. In this case, the rifling 23 is arranged axially on its inner circumference. Thereby, a swirling motion can be imparted to the solvent.

Also, in the above-described second embodiment, the other capillary 20 is arranged above the object S to be measured, but the present invention is not limited to this. The other capillary 20 may be arranged in any way as long as the tip thereof faces the object S to be measured and the solvent can be sprayed onto the object S to be measured.

Also, in the above seventh embodiment, an example in which the standard solution P is analyzed has been shown. In addition to this, a homogenate of the object S to be measured to which the standard solution P is added may be analyzed. In other words, the liquefied object S to be measured and the standard solution P added thereto may be analyzed. Thereby, the mixing ratio may be further optimized based on a preliminary analysis in line with the actual analysis.

Further, in the above-described seventh embodiment, the mixture ratio identifying unit 62 identifies the mixture ratio based on the operating speed of the pump unit 31, but the present invention is not limited to this. The mixing ratio specifying unit 62 may specify the mixing ratio based on the pressure ratio of the pump unit 31, for example. Further, the mixing rate determining unit may specify the mixing rate based on the degree of opening of valves (not shown) provided in the mixer 32 and arranged in the flow paths of the respective pump sections 31, for example.

In addition, in the above seventh embodiment, the timing detection unit 64 detects the timing when the ion intensity contained in the intensity information becomes equal to or greater than a predetermined value, but the present invention is not limited to this. The timing detection unit 64 may set the time from when the solvent is supplied from the capillary 20 to when the mass spectrometry is performed in the mass spectrometer 100 as the delay time. In this case, the timing detector 64 may output the timing obtained by subtracting the delay time from the timing at which the ion intensity equal to or greater than the predetermined value is obtained. As a result, the time at which the solvent is sprayed from the tip of the capillary 20 and the time at which the solvent reaches the mass spectrometer 100 can be corrected to further optimize the mixing ratio.

In addition, in the above-described seventh embodiment, the intensity information acquiring unit 63 acquires intensity information indicating ion intensity with respect to time as shown in FIG. 10, but the present invention is not limited to this. The intensity information acquisition unit 63 may acquire instantaneous ion intensity as intensity information. In this case, the timing detector 64 may detect the timing after accumulating intensity information.

Further, in the seventh embodiment, an example was shown in which the operation instruction unit 61 causes the supply unit 30 to linearly change the mixing ratio, but the present invention is not limited to this. The operation instructing section 61 may cause the supply section 30 to change the mixing rate spotwise, or may change the mixing rate intermittently.

Also, in the seventh embodiment, the control unit 60 can be realized by hardware, software, or a combination thereof. Here, "implemented by software" means implemented by a computer reading and executing a program. When configured by hardware, part or all of the control unit 60 is integrated circuits such as LSI (Large Scale Integrated circuit), ASIC (Application Specific Integrated Circuit), gate array, FPGA (Field Programmable Gate Array), etc. ( IC).

When all or part of the functions provided by the control unit 60 included in the present invention are configured by software, a hard disk, ROM, or the like storing a program describing all or part of the operation of the control unit 60 included in the present invention In a computer consisting of a storage unit, a DRAM that stores data necessary for calculation, a CPU, and a bus that connects each unit, the information necessary for calculation is stored in the DRAM, and the program is operated by the CPU. can do.

Also, each function provided in the control unit 60 included in the present invention may be configured to be executed on one or a plurality of servers as appropriate. Also, each function provided in the control unit 60 included in the present invention may be implemented using a virtual server function or the like on the cloud.

The program can be stored and delivered to the computer using various types of computer readable medium. A computer readable medium includes various types of tangible storage medium. Examples of computer-readable media include magnetic recording media (eg, flexible discs, magnetic tapes, hard disk drives), magneto-optical recording media (eg, magneto-optical discs), CD-ROMs (Read Only Memory), CD-Rs, CD- R/W, semiconductor memory (eg, mask ROM, PROM (Programmable ROM), EPROM (Erasable PROM), flash ROM, RAM (random access memory)).

1 ionization device 10 stage 20 capillary 21 inner cylinder 22 outer cylinder 23 rifling 30 supply unit 31 pump unit 32 mixer 40 power supply unit 50 sound wave irradiation unit 60 control unit 61 operation instruction unit 62 mixing ratio identification unit 63 intensity information acquisition unit 64 Timing detection unit 65 Optimal value determination unit 100 Mass spectrometer E Inlet f Primary droplet g Secondary droplet S Object to be measured

Claims (4)

An ionization device capable of miniaturizing atomized droplets,
a capillary for spraying primary droplets toward the object to be measured ;
a sound wave irradiating unit that irradiates sound waves of a predetermined cycle toward the sprayed primary droplets;
An ionization device comprising: An ionization device capable of miniaturizing atomized droplets,
a capillary for spraying primary droplets toward the object to be measured;
A sound wave irradiating unit that irradiates the secondary droplet reflected by the object to be measured with a sound wave of a predetermined period, the position facing the entrance of the mass spectrometer through the reflection position in the direction along the reflection direction of the secondary droplet. a sound wave emitting unit arranged in the mass spectrometer for emitting sound waves in a direction toward the entrance of the mass spectrometer;
An ionization device comprising : 3. The ionization device according to claim 2, wherein the sound wave irradiation unit is arranged in front of a reflection position of the secondary droplet in a direction along the reflection direction of the secondary droplet. The ionization device according to any one of claims 1 to 3 , wherein the sound wave irradiation unit irradiates ultrasonic waves.

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