Patent Application
20220250102
The present invention relates to a spray ionization device, an analysis device, and a surface coating device.
A mass spectrometer can count ions constituting a substance by each mass-to-charge ratio to obtain ion intensity which is quantitative information on the substance. The mass spectrometer can perform a more accurate analysis by obtaining an ion intensity having a good signal-to-noise ratio. Therefore, an analysis target, which is an ionized or a charged material, needs to be sufficiently introduced.
Examples of a method of ionizing a liquid sample include an electrospray ionization method. With the electrospray ionization method, high voltage of several kilovolts is applied to a sample solution in a narrow tube, a liquid cone (so-called Taylor cone) is formed at the tip of an outlet. Electrically charged droplets are ejected from the tip of the liquid cone, solvents evaporate to reduce the volume of the electrically charged droplets, and the electrically charged droplets finally split apart to generate gas-phase ions. This method can form electrically charged droplets at a rate of ejecting 1 to 10 μL/min of solution, in which the eject rate is not sufficient for use in conjunction with a liquid chromatography method.
A gas spray assisted electrospray ionization method (see, for example, U.S. Pat. No. 8,809,777) may be an example of a method for supporting generation of electrically charged droplets and vaporization of solvents by ejecting a gas from an outer tube surrounding a narrow tube of a sample solution, in order to promote vaporization of electrically charged droplets.
Patent Document 1: U.S. Pat. No. 8,809,777, Specification
However, with the gas spray assisted electrospray ionization method as disclosed in U.S. Pat. No. 8,809,777, it is difficult to stably form charged droplets in which a plurality of sample liquids are mixed, which has been a problem.
An object of the present invention is to solve the aforementioned problem and provide a spray ionization device capable of stably forming charged droplets in which a plurality of sample liquids are mixed, and an analysis device and a surface coating device including the same.
One aspect of the present invention provides a spray ionization device, including: a first tube including a first channel through which a first liquid can flow, the first tube including a first outlet for ejecting the first liquid at one end; a second tube including a second channel through which a second liquid can flow, the second tube including a second outlet for ejecting the second liquid at the one end; an outer tube including the first tube and the second tube, the outer tube surrounding an outer circumferential surface of at least one of the first tube and the second tube with a gap, the outer tube including a gas channel through which a gas can flow, the outer tube including an ejection port covered with a porous member at a distance downstream of the first outlet and the second outlet at the one end; and an electrode arranged between the first channel, the second channel and the first outlet, and the porous member, or between the first channel, the second channel and the second outlet, and the porous member, the electrode being capable of applying voltage to at least one of the first liquid and the second liquid by a power source connected to the electrode, in which charged droplets generated by mixing the first liquid and the second liquid together with the gas can be ejected from the ejection port.
According to the above aspect, voltage is applied to at least one of the first liquid and the second liquid, and the first liquid and the second liquid ejected from the first outlet and the second outlet, respectively, and the gas from the gas channel collide with the non-opening of the porous member to form a turbulent flow state. As a result, electrically charged droplets, in which the first liquid and the second liquid are mixed, are formed, and the charged droplets are introduced from the opening of the porous member and ejected from the ejection port. The first liquid and the second liquid, at least one of which is charged, are mixed immediately after being ejected and form electrically charged droplets, whereby the spray ionization device capable of stably ejecting charged droplets can be provided. In the case in which a chemical reaction takes place between the first liquid and the second liquid, the liquids can be introduced into the analysis device immediately after the chemical reaction takes place by mixing by ejection, whereby the spray ionization device capable of forming droplets allowing for accurately analyzing the reactant can be provided. In the case in which the first liquid is difficult to electrically charge as it is, the second liquid is electrically charged by applying voltage to the second liquid, whereby the spray ionization device capable of forming mixed droplets of the first liquid and the second liquid, which are electrically charged, can be provided.
One other aspect of the present invention provides an analysis device, including: the spray ionization device of the aspect described above; and an analysis unit that introduces and analyzes the electrically charged droplets sprayed from the spray ionization device.
According to the other aspect, the spray ionization device achieves various operational effects of the aspect, whereby the analysis device capable of performing analysis characterized by the operational effects can be provided.
Hereinafter, embodiments of the present invention will be described with reference to the drawings. Note that elements that are common between a plurality of drawings are denoted by the same reference characters, and detailed description of such elements will not be repeated.
Referring to
The sample liquids Lf1 and Lf2 and the spraying gas Gf are supplied from further toward the opposite end than the nozzle 18 (hereinafter also referred to as a supply end) of the sprayer 11. The sample liquids Lf1 and Lf2 are supplied from supply ports 22s and 23s from the containers 12 and 13, respectively, by way of a pump 19 and the like. The sample liquids Lf1 and Lf2 may be continuously or intermittently supplied. The sample liquids Lf1 and Lf2 may contain an analysis target in solvents, or may contain dissolved components, particulate matter, or the like, for example. The spraying gas Gf is supplied from the cylinder 14 through the valve 20 to the supply port 24s. Inert gas such as nitrogen gas or argon gas, or air can be used for the spraying gas Gf, for example. A heating unit 21 such as a heater or dryer for heating the spraying gas Gf may be provided between the cylinder 14 or the valve 20 and the supply port 24s. The spraying gas Gf is heated, whereby vaporization of solvents in the ejected sample liquids Lf1 and Lf2 can be promoted, and electrically charged droplets can be obtained more efficiently.
The sprayer 11 includes: a first liquid supply tube 22, a second liquid supply tube 23 surrounding the first liquid supply tube 22 with a gap; and a gas supply tube 24 surrounding the second liquid supply tube 23 with a gap. Sprayer 11 has a triple tube structure including the first liquid supply tube 22 on the inner side, the second liquid supply tube 23 on the outer side, and the gas supply tube 24. The first liquid supply tube 22, the second liquid supply tube 23, and gas supply tube 24 are preferably coaxial with each other.
A tubular first channel 25 is defined on an inner circumferential surface 22b of the first liquid supply tube 22. The first liquid supply tube 22 has an outlet 22a, in the nozzle 18. The sample liquid Lf1 is supplied from the supply port 22s of the first liquid supply tube 22, flows through the first channel 25, and is ejected from the outlet 22a. The first liquid supply tube 22 may be, for example, a straight tube. A diameter (inner diameter) of the inner circumferential surface 22b is preferably 10 μm to 250 μm, and a diameter (outer diameter) of the outer circumferential surface 22c is preferably 100 μm to 500 μm.
The inner circumferential surface 23b of the second liquid supply tube 23 and the outer circumferential surface 22c of the first liquid supply tube 22 define a second channel 26. The second liquid supply tube 23 has an outlet 23a, in the nozzle 18. The sample liquid Lf2 is supplied from the supply port 23s of the second liquid supply tube 23, flows through the second channel 26, and is ejected from the outlet 23a. The second liquid supply tube 23 may be, for example, a straight tube. A diameter (inner diameter) of the inner circumferential surface 23b is preferably 200 μm to 700 μm, and a diameter (outer diameter) of the outer circumferential surface 23c is preferably 300 μm to 800 μm.
The first liquid supply tube 22 and the second liquid supply tube 23 may be formed of a dielectric material made of glass and plastics. An electrode 15 as described later is provided to at least one of the first liquid supply tube 22 and the second liquid supply tube 23. As a variation of the electrode, part of at least one of the first liquid supply tube 22 and the second liquid supply tube 23 may be made of an electrical conductor material to form the electrode 15. Entirety of at least one of the first liquid supply tube 22 and the second liquid supply tube 23 may be made of an electrical conductor material, e.g., a metal tube such as stainless steel, to form the electrode 15.
The inner circumferential surface 24b of the gas supply tube 24 and the outer circumferential surface 23c of the second liquid supply tube 23 define the gas channel 28. The gas supply tube 24 includes an opening 24b2, in the nozzle 18. A diameter (inner diameter) of the inner circumferential surface 24b of the gas supply tube 24 is not limited in particular, and is, for example, 4 mm, further toward the supply end than the nozzle 18.
The gas supply tube 24 is preferably made of a dielectric material such as glass or plastics, and further preferably made of polyether ether ketone resin (PEEK resin).
The pressurized spraying gas Gf is supplied from the supply port 24s of the gas supply tube 24, flows through the gas channel 28, and is ejected from a gap between the outlet 23a of the second liquid supply tube 23 and the gas supply tube 24. A flow rate of the spraying gas Gf is appropriately set in accordance with the flow rate of the sample liquids Lf1 and Lf2, and is set to 0.5 L/min to 5.0 L/min, for example.
High-voltage power source 16 is a high-voltage DC or high-frequency alternating-current voltage capable power supply. The high-voltage power source 16 is connected to the electrode 15 arranged so as to be able to contact the sample liquid Lf1 flowing through the sprayer 11. The high-voltage power source 16 applies voltage of e.g., 4.0 kV to the electrode 15, and preferably applies voltage in a range of 0.5 kV to 10.0 kV in terms of ionization. In the case in which the high-voltage power source 16 generates high-frequency alternating-current voltage, the waveform of the alternating-current voltage is not limited in particular, and is a sine wave, a rectangular wave, or the like. In the case of ionization utilizing a chemical reaction, the frequency of the alternating-current voltage is preferably 100 Hz to 1000 kHz.
As illustrated in
As a variation of the electrode 15 illustrated in
In the case in which the electrode 15 is formed so as to be able to contact the sample liquid Lf2 flowing through the second channel 26 of the second liquid supply tube 23, the electrode 15 may be formed in substantially the same manner as the configuration illustrated in
An ejection port 30 is provided to the gas supply tube 24, in the nozzle 18.
The porous member 31 is arranged at a gap downstream of the outlet 22a of the first liquid supply tube 22 and the outlet 23a of the second liquid supply tube 23. In this gap (also referred to as the “mixing region 33”), the electrically charged sample liquid Lf1 ejected from outlet 22a of the first liquid supply tube 22, the sample liquid Lf2 ejected from the outlet 23a of the second liquid supply tube 23, and the spraying gas Gf collide with a non-opening of the porous member 31 to form a turbulent flow state. As a result, the sample liquid Lf1 and the sample liquid Lf2 are atomized into droplets, and the electrically charged droplets of the sample liquid Lf1 and the droplets of the sample liquid Lf2 are combined to form electrically charged mixed droplets in a mixed state. Chemical reactions take place in the electrically charged mixed droplets, depending on the components of sample liquids Lf1 and Lf2.
A distance between the porous member 31 and the outlet 23a of the second liquid supply tube 23 is preferably 5 μm or more and 1000 μm or less, from a perspective that the electrically charged droplets of the sample liquid Lf1 and the droplets of the sample liquid Lf2 are mixed in the mixing region 33, electrically charged mixed droplets are sufficiently formed, and the droplets are atomized.
The outlet 23a of the second liquid supply tube 23 is preferably arranged at the same position as, or protrudes further downstream than, the outlet 22a of the first liquid supply tube 22 in the ejection direction, from a perspective that droplets of the sample liquid Lf1 and droplets of the sample liquid Lf2 can be easily mixed in the mixing region 33. In this case, a distance between the outlet 23a and the outlet 22a in the ejection direction is particularly preferably set between 0 μm and 1000 μm.
The electrically charged and atomized mixed droplets flow through the opening of the porous member 31 by way of the spraying gas Gf, and are ejected from the ejection port 30. The retaining member 32 may be formed at an angle so as to have a diameter that progressively increases downstream from the ejection port 30.
As illustrated in
A distance between the portion 24b1 of the inner circumferential surface of gas supply tube 24 and the outer circumferential surface 23c of the second liquid supply tube 23 is preferably set to 20 μm to 400 μm, in the constriction portion 34.
The electrode 415 may be arranged through the gas channel 28 of the gas supply tube 24 to reach the mixing zone 33 upstream of the porous member 31. As a result, droplets or mixed droplets of the sample liquid Lf1 and Lf2 generated in the mixing region 33 can be electrically charged.
Hereinafter, a variation of the sprayer according to the first embodiment of the present invention will be described. In the variation, configurations different from those of the nozzle 18 illustrated in
Referring to
The first liquid supply tube 122 has a configuration similar to that of the first liquid supply tube 122 illustrated in
The gas supply tube 24 has a configuration similar to that of the gas supply tube 24 illustrated in
The spraying gas Gf flows through the gas channel 128. As illustrated in
The outlet 122a of the first liquid supply tube 122 and the outlet 123a of the second liquid supply tube 123 are arranged at substantially the same position in the ejection direction. A mixing region 133 for the sample liquids Lf1 and Lf2 and the spraying gas Gf is formed between the outlets 122a and 123a and the porous member 31, in which atomized and electrically charged mixed droplets are generated in the same manner as in the mixing region 33 illustrated in
A liquid supply tube for supplying and mixing still another sample liquid may be added to the first liquid supply tube 122 and the second liquid supply tube 123. A third liquid supply tube may be provided in parallel with the second liquid supply tube 23 illustrated in
The second gas supply tube 330 includes a gas channel 331. The gas channel 331 is defined by the outer circumferential surface 24c of the gas supply tube 24 and an inner circumferential surface 330b of the second gas supply tube 330, and extends in the ejection direction. The inner circumferential surface 330b of the second gas supply tube 330 has a constant diameter toward the outlet 330a. The flow of the sheath gas Gf2 flowing through the gas channel 331 is restricted from spreading by the inner circumferential surface 330b of the second gas supply tube 330 toward the outlet 330a. The electrically charged mixed droplets ejected from the nozzle 318 are enveloped in the sheath gas Gf2. As a result, the electrically charged mixed droplets are ejected from the outlet 330a of the second gas supply tube 330 along the ejection direction. With such a configuration, the sprayer 311 can eject focused and electrically charged mixed droplets.
A heating unit 319 may be provided downstream of the valve 320 so as to supply the sheath gas Gf2 as heated gas. A heating unit such as a ring-heater (not illustrated) may be provided downstream of the retaining member 32 of the gas supply tube 24 so as to surround the second gas supply tube 330. As a result, desolvation of droplets can be supported.
The sprayer 311 can employ the sprayer 111 having the configuration illustrated in
The sheath gas Gf2 flowing through the gas channel 431 flows toward the outlet 430a such that the flow focuses while being restricted by the inner circumferential surface 430b of the second gas supply tube 430. The electrically charged mixed droplets ejected from the nozzle 318 are enveloped in the sheath gas Gf2 and focus onto the axial center along the ejection direction. As a result, the focused and electrically charged mixed droplets are ejected from the outlet 430a of the second gas supply tube 430. With this configuration, even if the nozzle 318 cannot eject electrically charged droplets with sufficient focusing thereof, the sprayer 411 can focus and eject droplets.
The spray ionization device 10 can be applied to the first and second variations of the first embodiment and the spray ionization device of the second and third embodiments. The spray ionization device 10 sends the electrically charged mixed droplets, which have been atomized by ejecting a plurality of sample liquids, to the analysis unit 501. The atomized and electrically charged mixed droplets are introduced into the analysis unit 501 in a state in which the molecules, clusters, and the like of components contained in the droplets are electrically charged by evaporation of solvents.
In the case in which the analysis unit 501 is a mass spectrometer, the analysis unit 501 includes, for example, an ion lens, a quadrupole mass filter, and a detection unit (all not illustrated). The ion les focuses ions of the components of the mixed droplets generated by the spray ionization device 10, and the quadrupole mass filter separates out specific ions based on a mass-to-charge ratio. The detection unit detects the specific ions for each mass number, and outputs detection signals.
The spray ionization device 10 efficiently generates ions of components of the droplets, in which sample liquids Lf1 and Lf2 are mixed, and can therefore be used as an ion source of trace components. The analysis device 500 is, for example, a liquid chromatography-mass spectrometry (LC/MS) device including the spray ionization device 10 as an ion source.
Hereinafter, Measurement Examples using Examples of the spray ionization devices according to the embodiments of the present invention will be described. As a Comparative Example, an ESI ion source using a gas spray assisted electrospray ionization (ESI) method was used.
Example 1 is the spray ionization device of the first embodiment illustrated in
Example 2 is the spray ionization device of the first embodiment illustrated in
A sprayer (ESI-probe (ion source)) attached to model API2000, a mass spectrometer manufactured by AB SCIEX, U.S.A. was used in the Comparative Example 1. The ESI-probe of Comparative Example 1 has a structure in which only a single sample liquid is supplied to a sprayer. The sample liquids Lf1 and Lf2 were mixed by a T-connector upstream of the sprayer, and a solution of the sample liquids was supplied into the single sprayer, electrically charged, and sprayed.
A mixed liquid (hereinafter, also referred to as “dAMP mixed liquid”) composed of an aqueous deoxyadenosine monophosphate (dAMP) solution (50 ppm concentration) separated by liquid chromatograph and ammonium formate (pH 3) having concentration of 10 mM as a solvent was supplied as a sample solution Lf2 to the second liquid supply tube 23 of Examples 1 and 2. The flow rate was 25 μL/min.
An aqueous ammoniacal solution for pH-adjustment (abbreviated as “NH3”) (pH 11) was supplied as a sample solution Lf1 to the first liquid supply tube 22 of Examples 1 and 2. The flow rate was 25 μL/min. In Measurement Example 1, in the case of separating dAMP by liquid chromatography, if other nucleotides were present in the sample, dAMP was separated in a low-pH solution and dissociated in the neutral region by a mass spectrometer to expect increase in dAMP sensitivity.
In the ESI-probe of Comparative Example 1, the sample solution Lf1 and Lf2 were mixed by the T-connector at the base of the sprayer. The flow rate of the sample solution Lf1 and Lf2 was 25 μL/min. Nitrogen gas at 25° C. was used for the spraying gas Gf in Examples 1 and 2 and Comparative Example 1. The gas flow rate was 2 L/min in Examples 1 and 2, and at a set value of 18 as a recommended value of the manufacturer of the mass spectrometer in Comparative Example 1.
In Examples 1 and 2, a high-voltage power source (manufactured by AB SCIEX, Model API2000 equipment) was connected to the electrode, in which DC voltage of 4.5 kV was applied to the sample solution Lf2 in Example 1, and applied to the sample solution Lf1 and Lf2 by the first liquid supply tube 22 made of stainless steel in Example 2. In Comparative Example 1, DC voltage of 4.5 kV was applied to a sample solution in which the sample solution Lf1 and Lf2 were mixed.
Model LC-10Avp manufactured by Shimadzu Corporation was used for the liquid chromatograph, and Model API 2000 manufactured by AB SCIEX (LC/MS/MS (method of detecting a specific m/z (mass-to-charge ratio) by coupling a mass spectrometer to a liquid chromatograph)) was used for the mass spectrometer, in which signal intensity of the mass chromatogram of m/z=329.604 was measured.
Referring to
Referring to
Example 3 mimics an aspect, in which the sprayer of Example 1 is applied to the sprayer having the second gas supply tube 330 illustrated in
The average value of the signal intensity in Example 4 was 2.3 times the average value of the signal intensity in Example 3, revealing that ionization can be performed extremely efficiently in Example 4 as in the case of Example 2.
In the foregoing, the preferred embodiments of the present invention have been described in detail; however, the present invention is not limited to the specific embodiments, and various modifications and changes can be made within the scope of the present invention described in the claims.
The shape of the cross-section and the channel of the liquid supply tube has been described as circular, but may be triangular, square, pentagonal, hexagonal or other polygonal shapes, or other shapes such as an elliptical shape. The shape of the outer circumferential surface and the inner circumferential surface of the gas supply tube and the second gas supply tube can be selected from these shapes, depending on the shape of the liquid supply tube.
The spray ionization device of the present invention can be used as an ion source of various devices; for example, in the field of trace sample analysis, the spray ionization device can be used for mass spectrometry such as mass spectrometry of molecules in a biological sample, elemental analysis, chemical morphology analysis, and charged particle analysis.
In the field of surface treatment and granulation, the spray ionization device of the present invention can be used for surface coating devices utilizing surface coating techniques of spraying electrically charged droplets, and particle forming devices utilizing particle forming techniques by spraying electrically charged droplets of suspension.
In the field of food production, healthcare, and agriculture, the spray ionization device of the present invention can be used for space processing devices utilizing sterilization, deodorization, dust collection, and chemical reactions, utilizing gas-phase or spatial chemical reactions by spraying electrically charged droplets.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2019-141193 | Jul 2019 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2020/027873 | 7/17/2020 | WO |
