Patent Description:
A mass spectrometer can count ions constituting a substance by each mass-to-charge ratio to obtain ionic strength which is quantitative information on the substance. The mass spectrometer can perform more accurate analysis by obtaining ionic strength having a favorable signal-to-noise ratio. Therefore, an analysis target, which is an ionized or 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 port, electrically charged droplets are ejected from the tip, solvents evaporate to reduce the volume of the electrically charged droplets, and the droplets finally split apart to generate gas-phase ions. This method can form electrically charged droplets at a rate of ejecting <NUM> to <NUM>µL/min of solution, in which the ejetion rate is not sufficient for use in conjunction with a liquid chromatography method.

A gas spray assisted electrospray ionization method (see, for example, <CIT>) 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. <CIT> and <CIT> are other examples of electrospray devices.

Patent Document <NUM>: <CIT>, Specification.

However, the gas spray assisted electrospray ionization method as disclosed in <CIT> generates electrically charged droplets having a large particle size; therefore, there is a need to use techniques such as promoting vaporization of solvents by using a heated gas, atomizing electrically charged droplets by collision with a plate-shaped target, or making the ejection direction orthogonal to the direction of introducing the atomized and electrically charged droplets in order to remove excessively large electrically charged droplets; as a result, electrically charged droplets cannot be efficiently obtained, which has been a problem.

One object of the present invention is to solve the aforementioned problems and provide a spray ionization device which can obtain atomized and electrically charged droplets, and is capable of efficiently ionizing molecules, clusters, etc. contained in liquid.

One aspect of the present invention provides a spray ionization device including:
a first tube including a first channel through which a liquid can flow, the first tube including a first outlet for ejecting the liquid at one end; a second tube surrounding the first tube; and a third tube surrounding the second tube with a gap, and having a second channel through which gas can flow, the third tube having a second outlet at the one end, in which the second channel is defined by an outer circumferential surface of the second tube and an inner circumferential surface of the third tube, in which the second outlet of the third tube is disposed at the same position in an axial direction as the first outlet or more downstream than the first outlet, an opening diameter of the second outlet is formed to be smaller than a diameter of the outer circumferential surface of the second tube, and the third tube has at least a tip including a second outlet consisting of an electrically conductive material as an electrode, and capable of applying an electric field to droplets ejected from the first outlet by a power source connected to the electrode to eject electrically charged droplets from the second outlet.

The second outlet of the third tube having the second channel through which gas can flow is arranged at the same position in the axial direction as the first outlet of the first tube having the first channel through which liquid can flow, or more downstream than this, and the opening diameter of the above-mentioned second outlet is formed to be smaller than the diameter of the outer circumferential surface of the above-mentioned second tube. The inner circumferential surface of the third tube progressively decreases in diameter towards the second outlet, the second channel has a constriction portion formed by the inner circumferential surface of the third tube and the tip of the second tube, and a channel area of the second channel defined on a plane perpendicular to a central axis progressively decreases from the supply end to the constriction portion. Therefore, in the region between the first outlet and the second outlet, the liquid ejected from the first outlet is atomized by the gas flowing in along the inner circumferential surface of the third tube from upstream thereof, and further, the atomized droplets are electrically charged by the electric field from the tip of the third tube. Since the electrically charged droplets are atomized, desolvation by evaporation is easily conducted, and thus it is possible to provide a spray ionization device capable of efficiently ionizing molecules, clusters, etc. of components contained in the sample liquid Lf.

Note that elements that are common between a plurality of drawings are denoted by the same reference characters, and detailed descriptions of such elements will not be repeated.

<FIG> is a diagram schematically illustrating a configuration of a spray ionization device according to a first embodiment of the present invention. <FIG> are cross-sectional views of a nozzle of a sprayer, in which <FIG> is an enlarged cross-sectional view of the nozzle in <FIG>, and <FIG> is a cross-sectional view along arrows Y-Y in <FIG>.

Referring to <FIG>, <FIG>, a spray ionization device <NUM> according to a first embodiment of the present invention includes: a sprayer <NUM>; a container <NUM> containing a sample liquid Lf to be supplied to the sprayer <NUM>; a cylinder <NUM> for containing a spraying gas Gf to be supplied to the sprayer <NUM>; and a high-voltage power source <NUM> for applying a high electric field to droplets of the ejected sample liquid Lf. In the spray ionization device <NUM>, a nozzle <NUM> for ejecting electrically charged droplets is formed at one end (hereinafter also referred to as an ejection end) of the sprayer <NUM>. The sample liquid Lf and the spraying gas Gf are supplied from further toward the opposite end than the nozzle <NUM> (hereinafter also referred to as a supply end). The sample liquid Lf may be continuously or intermittently supplied from the container <NUM> by way of a pump <NUM> or the like. The sample liquid Lf 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 compressed gas cylinder <NUM> through the valve <NUM> to the supply port <NUM>. Inert gas such as nitrogen gas or argon gas, or air can be used for the spraying gas Gf, for example. A heating unit <NUM> such as a heater or dryer for heating the spraying gas Gf may be provided between the compressed gas cylinder <NUM> or the valve <NUM> and the supply port <NUM>. The spraying gas Gf is heated, whereby vaporization of solvents in the ejected sample liquid Lf can be promoted, and electrically charged droplets can be obtained more efficiently.

The sprayer <NUM> includes a liquid supply tube <NUM>, a protective tube <NUM> surrounding the liquid supply tube <NUM>, and a gas supply tube <NUM> that surrounds the protective tube <NUM> with a gap. The liquid supply tube <NUM>, protective tube <NUM> and the gas supply tube <NUM> have a triple tube structure, in which the tubes are preferably coaxial (central axis X-X) with one another.

The liquid supply tube <NUM> extends from the supply end to the ejection end. The liquid supply tube <NUM> includes a first channel <NUM> being tubular and defined by an inner circumferential surface 21b of the liquid supply tube <NUM>, and includes an outlet 21a of the nozzle <NUM> at the ejection end. In the liquid supply tube <NUM>, the sample liquid Lf is supplied from the supply side, passes through the first channel <NUM> and is ejected from the outlet 21a.

A diameter (inner diameter) of the inner circumferential surface 21b of the liquid supply tube <NUM> is preferably <NUM> to <NUM>, and a diameter (outer diameter) of an outer circumferential surface 21c of the liquid supply tube <NUM> is preferably <NUM> to <NUM>. In terms of atomizing droplets, an opening diameter of the outlet 21a is preferably <NUM> to <NUM>. In terms of atomizing droplets, the thickness (wall thickness) of the liquid supply tube <NUM> is preferably <NUM> to <NUM>. The liquid supply tube <NUM> is preferably formed from an electrically conductive material such as stainless steel (for example, SUS316), or a dielectric material made of glass and plastic.

The protective tube <NUM> surrounds the liquid supply tube <NUM>, and extends from the supply end to the ejection end. A tip 22a on the ejection side is arranged more to the supply side than the outlet 21a of the liquid supply tube <NUM>.

The gas supply tube <NUM> includes a second channel <NUM> defined by an inner circumferential surface 23b, 23b<NUM> of the gas supply tube <NUM> and the outer circumferential surface 22c of the protective tube <NUM>, and includes an outlet 23a of the nozzle <NUM>. Although not limited in particular, a diameter (inner diameter) of the inner circumferential surface 23b of the gas supply tube <NUM> is, for example, <NUM> further toward the supply end than the nozzle <NUM>.

The spraying gas Gf is pressurized and supplied from the supply port <NUM> of the gas supply tube <NUM>, flows through the second channel <NUM>, and is ejected from the outlet 23a. A flow rate of the spraying gas Gf is appropriately set in accordance with the flow rate of the sample liquid Lf, and is set to <NUM>/min to <NUM>/min, for example.

At the outlet 23a, the gas supply tube <NUM> functions as an electrode <NUM> for applying a high electric field to droplets of the sample liquid Lf ejected from the outlet 21a of the liquid supply tube <NUM>. In the gas supply tube <NUM>, at least the tip including the outlet 23a is formed from a conductive material, e.g. metallic material. As the metallic material, it is possible to use stainless steel (e.g., SUS316), aluminum or the like, and it is preferably stainless steel in the point of the heat-insulating property during heating. It should be noted that the entirety of the gas supply tube <NUM> may be formed by a conductive material such as a metal tube. A high-voltage power source <NUM> is connected to the electrode <NUM>. The high-voltage power source <NUM> is a power source for generating high-voltage direct current voltage, and is connected to the electrode <NUM>. The high-voltage power source <NUM> applies voltage of e.g., <NUM> kV to the electrode <NUM>, and preferably applies voltage in a range of -<NUM> kV to +<NUM> kV in terms of ionization.

In the nozzle <NUM>, the outlet 23a of the gas supply tube <NUM> is arranged at the same position in the X-axis direction as the outlet 21a of the liquid supply tube <NUM>, or further downstream therefrom. The gas supply tube <NUM> is formed such that a portion 23b<NUM> of the inner circumferential surface of the gas supply tube <NUM> has a diameter that progressively decreases from upstream toward downstream, whereby the channel area of the second channel <NUM> progressively decreases towards downstream. Here, the channel area refers to an area occupied by the second channel <NUM> on a plane perpendicular to the central axis X, in which the area is surrounded by the inner circumferential surface 23b<NUM> of the gas supply tube <NUM> and the outer circumferential surface 21c of the liquid supply tube <NUM> as illustrated in <FIG>. The distance (D3) in the X-axis direction between the outlet 21a of the liquid supply tube <NUM> and the outlet 23a of the gas supply tube <NUM> is preferably set to the range of <NUM> to <NUM>, in terms of the electrification of droplets.

An opening diameter D2 of the outlet 23a of the gas supply tube <NUM> is formed so as to become smaller than the diameter D1 of the outer circumferential surface of the protective tube <NUM>. The flow velocity of the spraying gas Gf flowing through the gas supply tube <NUM> increases, whereby it is possible to promote atomization of droplets of the sample liquid Lf ejected from the outlet 21a of the liquid supply tube <NUM>, and the atomized droplets can be electrically charged by the high electric field applied at the outlet 21a.

The gas supply tube <NUM> is preferably formed such that the diameter D2 of the inner circumferential surface of the outlet 23a of the gas supply tube <NUM> is equal to or larger than the opening diameter of the outlet 21a of the surface liquid supply tube <NUM>. With such a configuration, droplets of the sample liquid Lf are ejected from the outlet 21a of the liquid supply tube <NUM>, enveloped in the spraying gas Gf flowing through the second channel <NUM>, and flow downstream (page right side) while focusing along the X-axis in the central direction. As a result, droplets of the sample liquid Lf are suppressed from contacting the inner circumferential surface 22b<NUM> of the gas supply tube <NUM> in the vicinity of the outlet 21a of the liquid supply tube <NUM>, whereby the nozzle <NUM> can be prevented from clogging. In addition, the flow of the ejected sample liquid Lf focuses by the spraying gas Gf, whereby droplets are atomized.

In the nozzle <NUM>, the constriction portion <NUM> of the second channel <NUM> is formed by the tip 22a of the protective tube <NUM> and the portion 23b<NUM> of the inner circumferential surface of the gas supply tube <NUM>. As a result, the second channel <NUM> is formed such that the channel area of the second channel <NUM> progressively decreases from the supply end to the constriction portion <NUM>. The spraying gas Gf passes through the constriction portion <NUM> to gain the flow velocity, and the flow of droplets of the sample liquid Lf ejected from the outlet 21a of the liquid supply tube <NUM> further focuses, promoting atomization of droplets. Droplets ejected from the outlet 21a of the liquid supply tube <NUM> can be further suppressed from flowing backward and entering the constriction portion <NUM>. As a result, clogging of the constriction portion <NUM> due to precipitation of components such as salts contained in droplets can be suppressed, whereby stable ejection can be achieved. This constriction portion <NUM> achieves a flow-focusing effect, in which droplets ejected from the outlet 21a can be ejected at a narrower angle (i.e., in a smaller lateral spreading range with respect to the ejection direction) than the case without the constriction portion <NUM>. As a result, efficiency of generating gas phase ions in the ejected and electrically charged droplets can be enhanced.

The outer circumferential face 21c of the liquid supply tube <NUM>, has an outer diameter formed to be constant towards the outlet 21a, whereby the flow of spraying gas Gf converges the ejected sample liquid Lf at the outlet 21a of the liquid supply tube <NUM>, and it is possible to suppress splashing of the sample liquid Lf and effectively form droplets. It should be noted that the end face of the outlet 21a may be formed so as to progressively decrease in diameter from the upstream side towards the outlet 21a.

According to the first embodiment, the outlet 23a of the gas supply tube <NUM> is arranged at the same position in the X-axis direction as the outlet 21a of the liquid supply tube <NUM> or more downstream thereto, and the opening diameter D2 of the outlet 23a of the gas supply tube <NUM> is formed to be smaller than the diameter D1 of the outer circumferential surface of the protective tube <NUM>; therefore, in a region between the outlet 21a of the liquid supply tube <NUM> and the outlet 23a of the gas supply tube <NUM>, the sample liquid Lf ejected from the outlet 21a of the liquid supply tube <NUM> is atomized by the spraying gas Gf flowing in from the upstream along the inner circumferential surface 23b<NUM> of the gas supply tube <NUM>, and further, the atomized droplets electrically charge by the electric field from the tip of the gas supply tube <NUM>. Since the electrically charged droplets are atomized, desolvation by evaporation is easily conducted, and thus it is possible to provide a spray ionization device capable of efficiently ionizing molecules, clusters, etc. of components contained in the sample liquid Lf.

<FIG> are cross-sectional views illustrating a variation of the nozzle of the sprayer of the first embodiment according to the present invention. Referring to <FIG>, the nozzle <NUM> of the first variation includes a blocking member <NUM> along a circumferential direction in a gap between the outer circumferential surface 21c of the liquid supply tube <NUM> and the inner circumferential surface 22b of the protective tube <NUM>, at the tip 22a toward the ejection end of the protective tube <NUM>. The blocking member <NUM> blocks this gap. Except that the closing member <NUM> is provided, the nozzle <NUM> has the same configuration as the nozzle <NUM> of the sprayer illustrated in <FIG>. With this configuration, the blocking member <NUM> prevents the spraying gas Gf having passed through the gas between the tip 22a of the protective tube <NUM> and the inner circumferential surface 23b<NUM> of the gas supply tube <NUM> (or constriction portion <NUM>) from entering the gap between the outer circumferential surface 21c of the liquid supply tube <NUM> and the inner circumferential surface 22b of the protective tube <NUM>. As a result, turbulence of the spraying gas Gf by entering to the gap is suppressed from occurring, the flow of droplets of the sample liquid Lf focuses, and atomization and electrical charging of droplets are promoted.

Referring to <FIG>, in the nozzle <NUM> of the second variation, a blocking member <NUM> is provided entirely along the circumferential direction and X-axis direction (longitudinal direction) of the gap between the outer circumferential surface 21a of the liquid supply tube <NUM> and the inner circumferential surface 22b of the protective tube <NUM>. In other words, the blocking member <NUM> is formed so that the protective tube <NUM> makes contact along the circumferential direction and longitudinal direction with the liquid supply tube <NUM>. It is thereby possible to fix the liquid supply tube <NUM>, and suppress the occurrence of turbulence from entry of spraying gas Gf to the gap. It should be noted that, by appropriately selecting the inside diameter of the protective tube <NUM> or outside diameter of the liquid supply tube <NUM>, it may be formed so that the inner circumferential surface 22b of the protective tube <NUM> directly contacts the outer circumferential surface 21c of the liquid supply tube <NUM>.

<FIG> is a diagram schematically illustrating a configuration of a spray ionization device according to a second embodiment of the present invention, and <FIG> is a cross-sectional view of a nozzle of a sprayer of this spray ionization device. Referring to <FIG> and <FIG>, the spray ionization device <NUM> has a sprayer <NUM> with a quadruple-tube structure having a liquid supply tube <NUM>, a protective tube <NUM> surrounding the liquid supply tube <NUM>, a gas supply tube <NUM> surrounding the protective tube <NUM> with a gap, and a second gas supply tube <NUM> surrounding the gas supply tube <NUM>. The structures of the liquid supply tube <NUM>, protective tube <NUM> and gas supply tube <NUM> are similar to the sprayer <NUM> of the first embodiment.

In the sprayer <NUM>, the sheath gas Gf<NUM> is supplied to the supply opening <NUM> via the valve <NUM> from a compressed gas cylinder <NUM> in the second gas supply tube <NUM>. The second gas supply tube <NUM> has a third channel <NUM> defined by an outer circumferential surface 23c of the gas supply tube <NUM> and an inner circumferential surface 128b of the second gas supply tube <NUM>, and extending in the X-axis direction. The inner circumferential surface 128b of the second gas supply tube <NUM> is formed so as to have a constant diameter from the supply side toward downstream until the position 128d. The position 128d is a position opposing the position at which the outer circumferential surface 23c of the gas supply tube <NUM> starts to decrease in diameter towards the outlet 23a. Furthermore, in the second gas supply tube <NUM>, the inner circumferential surface 128b<NUM> progressively expands in diameter from the position 128d towards the outlet 128a. The sheath gas Gf<NUM> thereby flows through the third channel <NUM>, ejects at the position 128d, flows in the direction of the outlet 23a along the outer circumferential surface 23c of the gas supply tube <NUM>, and flows so as to focus the electrically charged and atomized droplets ejected from the outlet 21a of the liquid supply tube 21a. Further downstream therefrom, since the inner circumferential surface 128b<NUM> of the second gas supply tube <NUM> progressively expands in diameter, the sheath gas Gf<NUM> flows so as to spread in the lateral direction to downstream. It is thereby possible to focus the flow of electrically charged and atomized droplets, and promote desolvation.

A heating unit <NUM> may be provided downstream of the valve <NUM> so as to supply the sheath gas Gf<NUM> as heated gas; or a heating unit such as a ring heater (not illustrated) may be provided downstream of the outlet 23a of the gas supply tube <NUM> so as to surround a second gas supply tube <NUM>. As a result, desolvation of ejected droplets can be supported.

It should be noted that, in the second gas supply tube <NUM>, the inner circumferential surface 128b<NUM> may have a constant diameter from the position 128d toward the outlet 128a.

As a variation of the spray ionization device according to the second embodiment, the portion of the nozzle <NUM> consisting of the liquid supply tube <NUM>, protective tube <NUM> and gas supply tube <NUM> may be replaced with the nozzle <NUM> shown in <FIG>, or the nozzle <NUM> shown in <FIG>.

According to the second embodiment, the sheath gas Gf<NUM> passing through the third channel <NUM> of the second gas supply tube <NUM> flows so as to focus the electrically charged and atomized droplets ejected from the outlet 21a of the liquid supply tube <NUM>, and further downstream therefrom, since the inner circumferential surface 128b<NUM> of the second gas supply tube <NUM> progressively expands in diameter, the sheath gas Gf<NUM> flows so as to spread in the lateral direction to downstream. It is thereby possible to focus the flow of electrically charged and atomized droplets, and promote desolvation.

Hereinafter, measurement examples prepared using examples of the spray ionization devices according to embodiments of the present invention will be shown. Example <NUM> used a configuration having the sprayer <NUM> in the spray ionization device <NUM> of the first embodiment shown in <FIG>, <FIG>. The gas supply tube <NUM> was formed from SUS316, the high-voltage power source of a mass spectrometer main body was connected to the gas supply tube <NUM>, and the gas supply tube <NUM> was used as the electrode. The inside diameter of the liquid supply tube <NUM> is <NUM>, and the opening diameter (D2) of the gas supply tube <NUM> is <NUM>. The outside diameter (D1) of the protective tube <NUM> is <NUM>. The distance (D3) between the outlet 21a of the liquid supply tube <NUM> and the outlet 23a of the gas supply tube <NUM> was set as <NUM>.

Example <NUM> used a configuration having the sprayer <NUM> in the spray ionization device <NUM> of the second embodiment shown in <FIG> and <FIG>.

The spray ionization device of Comparative Example <NUM> was an ESI ion source applying the gas spray assist electrospray ionization (ESI) method, and used a sprayer (ESI probe (ion source)) belonging to a mass spectrometer model LCMS-<NUM> manufactured by Shimadzu Corp. The spray ionization device of Comparative Example <NUM> was an ESI ion source adopting the same ESI method, and used a sprayer belonging to a mass spectrometer model LCMS-<NUM> manufactured by Shimadzu Corp.

<FIG> is a schematic cross-sectional view of the nozzle of the sprayer according to Comparative Example <NUM>. Referring to <FIG>, the nozzle <NUM> of the sprayer of Comparative Example <NUM> has a double-tube structure, and has the liquid supply tube <NUM> through which the sample liquid Lf flows, and the gas supply tube <NUM> surrounding the liquid supply tube <NUM> and through which the spraying gas Gf flows. The outlet 221a of the liquid supply tube <NUM> is provided further downstream from the outlet 223a of the gas supply tube <NUM>. The liquid supply tube <NUM> and gas supply tube <NUM> are formed from a metallic material (SUS316). Using the gas supply tube <NUM> as the electrode <NUM>, the high-voltage power source <NUM> was connected thereto, and a high electric field was applied from the outlet 223a of the gas supply tube <NUM> to electrically charge droplets of the sample liquid Lf ejected from the outlet 221a of the gas supply tube <NUM>.

<FIG> is a schematic cross-sectional view of the nozzle of the sprayer according to Comparative Example <NUM>. Referring to <FIG>, the nozzle <NUM> of the sprayer of Comparative Example <NUM> has a triple-tube structure, and includes the liquid supply tube <NUM> through which the sample liquid Lf flows, the gas supply tube <NUM> surrounding the liquid supply tube <NUM> and through which the spraying gas Gf flows, and the second gas supply tube <NUM> surrounding the gas supply tube <NUM> and through which heated sheath gas Gf<NUM> flows. The liquid supply tube <NUM> and gas supply tube <NUM> are formed similarly to Comparative Example <NUM>. The second gas supply tube <NUM> is formed from a metallic material (SUS316). Using the gas supply tube <NUM> as the electrode, the high-voltage power source <NUM> was connected to this, and a high electric field was applied from the outlet 223a of the gas supply tube <NUM> to electrically charge droplets of the sample liquid Lf ejected from the outlet 221a of the gas supply tube <NUM>. The tip 328a of the second gas supply tube <NUM> is arranged close to the position at which the outer circumferential surface 23c of the gas supply tube <NUM> starts to decrease in diameter towards the outlet 23a.

The spray ionization device of Example <NUM> was applied to the LC (liquid chromatography)/MS (mass spectrometry)/MS device, a model LC-<NUM> series manufactured by Shimadzu Corp. was used as the LC device, and the model LCMS-<NUM> manufactured by Shimadzu Corp. was used as the MS device. The spraying gas Gf employed nitrogen gas at room temperature, and was supplied to the nozzle without heating.

The spray ionization device of Example <NUM> was applied to the LC device and MS/MS device, a model LC-<NUM> series manufactured by Shimadzu Corp. was used as the LC device, and the model LCMS-<NUM> manufactured by Shimadzu Corp. was used as the MS/MS device. The spraying gas Gf employed nitrogen gas at room temperature, the sheath gas Gf<NUM> employed nitrogen gas, and was supplied to the nozzle with heating.

In Examples <NUM> and <NUM>, for the interface between the LC device and MS device, it ejects towards the ion capture port of the MS device, and heating of the sprayed droplets was performed by heating the sheath gas.

The spray ionization device of Comparative Example <NUM> was adopted to the LC device/MS device, a model LC-<NUM> series manufactured by Shimadzu Corp. was used as the LC device, and the model LCMS-<NUM> manufactured by Shimadzu Corp. was used as the MS device/MS device. The spraying gas Gf used nitrogen gas at room temperature, and was supplied to the nozzle without heating.

The spray ionization device of Comparative Example <NUM> was applied to the LC device and MS/MS device, a model LC-<NUM> series manufactured by Shimadzu Corp. was used as the LC device, and the model LCMS-<NUM> manufactured by Shimadzu Corp. was used as the MS/MS device. The spraying gas Gf employed nitrogen gas at room temperature, the sheath gas Gf<NUM> employed nitrogen gas, and was supplied to the nozzle by heating. In Comparative Examples <NUM> and <NUM>, the interface of the LC device and MS device was performed following the specifications of Shimadzu Corp. Heating of the ejected droplets was not performed in Comparative Example <NUM>, and heating of droplets was performed by heating the sheath gas in Comparative Example <NUM>.

In Example <NUM>, Example <NUM>, Comparative Example <NUM> and Comparative Example <NUM>, the high-voltage power source (supply by mass spectrometer main body) was connected to the gas supply tubes <NUM>, <NUM>, <NUM>, and direct current voltage was applied to the sample liquid at the ion capture port of the MS device or MS/MS device.

A reserpine solution having a concentration of <NUM> ppb was introduced in an amount of <NUM>µL from the injector of the LC device, and a <NUM>% acetonitrile aqueous solution with mobile phase: acetonitrile = <NUM>:<NUM> was fed at <NUM>µL/min as eluent using the LC device. Selective ion monitoring (SIM) analysis was performed by the MS device by ejecting the fed eluent containing sample liquid by the spray ionization devices of Example <NUM> and Comparative Example <NUM>, and the total area of the peak of the ion signal in the positive ion mode with mass-to-charge ratio m/z = <NUM> was measured. Multiple-reaction monitoring (MRM) analysis was performed by the MS/MS device by ejecting the fed eluent containing sample liquid by the spray ionization devices of Example <NUM> and Comparative Example <NUM>, and the total area of the peak of the ion signal in the positive ion mode with mass-to-charge ratio m/z = <NUM> > <NUM> was measured, for a specific product ion produced by destroying precursor ion. Direct current voltage of +<NUM> kV was supplied to the gas supply tubes <NUM>, <NUM>, <NUM>.

The spraying gas Gf was set to a flowrate of <NUM>/min in Example <NUM> and Comparative Example <NUM>, and a flowrate of <NUM>/min in Example <NUM> and Comparative Example <NUM>. The sheath gas was heated to <NUM>, and the flowrate of <NUM>/min was set in Example <NUM> and Comparative Example <NUM>.

<FIG> are graphs illustrating a Measurement Example of reserpine, with <FIG> being a case of Example <NUM> and Comparative Example <NUM> not performing heating of the spraying gas, and <FIG> being a case of Example <NUM> and Comparative Example <NUM> performing heating of the sheath gas (<NUM>). The vertical axis is the peak area (count number), and by counting the peak area obtained per one measurement and measuring three times, the average value, standard deviation and relative standard device (RSD) (%) (=average value/standard deviation × <NUM>) were calculated, and the average value is shown by circles and the standard deviation is shown by error bars in <FIG>.

Referring to <FIG>, Example <NUM> was <NUM>×<NUM><NUM> counts; whereas, the Comparative Example was <NUM>×<NUM><NUM> counts. In the Examples, <NUM> times the signal intensity was obtained in the case of no heat treatment relative to the Comparative Examples, whereby it was found that Example <NUM> much more efficiently ionized reserpine than Comparative Example <NUM>.

Referring to <FIG>, Example <NUM> was <NUM>×<NUM><NUM> counts; whereas, Comparative Example <NUM> was <NUM>×<NUM><NUM> counts. In Example <NUM>, <NUM> times the signal intensity was obtained in the case of heat treatment relative to Comparative Example <NUM>, whereby it was found that the Examples much more efficiently ionized reserpine than the Comparative Examples.

A chloramphenicol solution having a concentration of <NUM> ppb was introduced in an amount of <NUM>µL from the injector of the LC device, and a <NUM>% acetonitrile aqueous solution with mobile phase: acetonitrile = <NUM>:<NUM> was fed at <NUM>µL/min as eluent using the LC device. SIM analysis was performed by the MS device similarly to Measurement Example <NUM> by ejecting the fed eluent containing sample liquid by the spray ionization devices of Example <NUM> and Comparative Example <NUM>, and the total area of the peak of the ion signal in the negative ion mode with mass-to-charge ratio m/z = <NUM> was measured. MRM analysis was performed by the MS/MS device by ejecting the fed eluent containing sample liquid to the spray ionization devices of Example <NUM> and Comparative Example <NUM>, and the total area of the peak of the ion signal was measured in the negative ion mode of mass-to-charge ratio m/z=<NUM> > <NUM>. Direct current voltage of -<NUM> kV was supplied to the gas supply tubes <NUM>, <NUM>, <NUM>.

<FIG> are graphs illustrating a Measurement Example of chloramphenicol, with <FIG> being a case of Example <NUM> and Comparative Example <NUM> not performing heating of the spraying gas, and <FIG> being a case of Example <NUM> and Comparative Example <NUM> performing heating of the sheath gas (<NUM>). The vertical axis is the peak area (count number), and shows the average value, standard deviation and RSD, similarly to Measurement Example <NUM>.

Referring to <FIG>, Example <NUM> was <NUM>×<NUM><NUM> counts; whereas, Comparative Example <NUM> was <NUM>×<NUM><NUM> counts. In Example <NUM>, <NUM> times the signal intensity was obtained relative to Comparative Example <NUM>, whereby it was found that Example <NUM> much more efficiently ionized chloramphenicol than Comparative Example <NUM>.

Referring to <FIG>, Example <NUM> was <NUM>×<NUM><NUM> counts; whereas, Comparative Example <NUM> was <NUM>×<NUM><NUM> counts. In Example <NUM>, <NUM> times the signal intensity was obtained in the case of heat treatment relative to Comparative Example <NUM>, whereby it was found that Example <NUM> could much more efficiently ionize chloramphenicol than Comparative Example <NUM>.

A testosterone solution having a concentration of <NUM> ppb was introduced in an amount of <NUM>µL from the injector of the LC device, and a <NUM>% acetonitrile aqueous solution with mobile phase: acetonitrile = <NUM>:<NUM> was fed at <NUM>µL/min as eluent using the LC device. SIM analysis was performed by the MS device similarly to Measurement Example <NUM> by ejecting the fed eluent containing sample liquid by the spray ionization devices of Example <NUM> and Comparative Example <NUM>, and the total area of the peak of the ion signal in the positive ion mode with mass-to-charge ratio m/z = <NUM> was measured. MRM analysis was performed by the MS/MS device by ejecting the fed eluent containing sample liquid to the spray ionization devices of Example <NUM> and Comparative Example <NUM>, and the total area of the peak of the ion signal was measured in the positive ion mode of mass-to-charge ratio m/z=<NUM> > <NUM>. Direct current voltage of +<NUM> kV was supplied to the gas supply tubes <NUM>, <NUM>, <NUM>.

<FIG> are graphs illustrating a Measurement Example of testosterone, with <FIG> being a case of Example <NUM> and Comparative Example <NUM> not performing heating of the spraying gas, and <FIG> being a case of Example <NUM> and Comparative Example <NUM> performing heating of the sheath gas (<NUM>). The vertical axis is the peak area (count number), and shows the average value, standard deviation and RSD, similarly to Measurement Example <NUM>.

Referring to <FIG>, Example <NUM> was <NUM>×<NUM><NUM> counts; whereas, Comparative Example <NUM> was <NUM>×<NUM><NUM> counts. In Example <NUM>, <NUM> times the signal intensity was obtained relative to Comparative Example <NUM>, whereby it was found that Example <NUM> could much more efficiently ionize testosterone than Comparative Example <NUM>.

Referring to <FIG>, Example <NUM> was <NUM>×<NUM><NUM> counts; whereas, Comparative Example <NUM> was <NUM>×<NUM><NUM> counts. In Example <NUM>, <NUM> times the signal intensity was obtained in the case of heat treatment relative to Comparative Example <NUM>, whereby it was found that the Example <NUM> could much more efficiently ionize testosterone than Comparative Example <NUM>.

<FIG> is a diagram schematically illustrating a configuration of an analysis device according to an embodiment of the present invention. Referring to <FIG>, an analysis device <NUM> includes the spray ionization device <NUM> of the first embodiment or the spray ionization device <NUM> of the second embodiment; and an analysis unit <NUM> which performs mass spectrometry, etc. by introducing atomized electrically charged droplets from the spray ionization device <NUM>, <NUM>.

The spray ionization device <NUM>, <NUM> is selected from among the spray ionization devices <NUM> and <NUM> of the aforementioned first and second embodiments. The spray ionization device <NUM>, <NUM> sends to the analysis unit <NUM> the electrically charged droplets atomized by the sample liquid Lf being sprayed. The atomized electrically charged droplets are introduced to the analysis unit <NUM> in a state in which molecules, clusters, etc. of components contained in the sample liquid are electrically charged by evaporation of solvent.

The analysis unit <NUM>, in the case of being a mass spectrometer, has an ion lens, quadrupole mass filter and detector (none illustrated). Ions of the components of the sample liquid Lf generated in the spray ionization device <NUM>, <NUM> are focused by the ion lens, specific ions are separated based on mass-to-charge ratio by the quadrupole mass filter, detected for every mass number by the detector, and the signals thereof are outputted.

The spray ionization device <NUM>, <NUM> efficiently generates ions of the components of the sample liquid; therefore, it is possible to use as the ion source of trace amount components. The analysis device <NUM> is a liquid chromatography-mass spectrometer (LC/MS) including the spray ionization device <NUM> as the ion source.

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 each of the aforementioned embodiments 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.

The spray ionization devices <NUM> and <NUM> according to the aforementioned first and second embodiments, by applying to a surface coating apparatus, can form a coating film on the surface of an object by spraying electrically charged droplets of a coating liquid. In addition, the spray ionization devices <NUM> and <NUM> according to the aforementioned first and second embodiments, by applying to a granulation apparatus, can form particles of components contained in a suspension by spraying electrically charged droplets of the suspension.

Claim 1:
A spray ionization device (<NUM>, <NUM>), comprising:
a first tube (<NUM>) including a first channel (<NUM>) through which a liquid can flow, the first tube (<NUM>) including a first outlet (21a) for ejecting the liquid at one end;
a second tube (<NUM>) surrounding the first tube (<NUM>); and
a third tube (<NUM>) surrounding the second tube (<NUM>) with a gap, and having a second channel (<NUM>) through which gas can flow, the third tube (<NUM>) having a second outlet (23a) at the one end, in which the second channel (<NUM>) is defined by an outer circumferential surface of the second tube (<NUM>) and an inner circumferential surface of the third tube (<NUM>),
wherein a tip of the second tube (<NUM>) is formed more to an opposite end side than the first outlet (21a), and the second outlet (23a) is disposed at the same position in an axial direction as the first outlet (21a) or more downstream than the first outlet (21a),
wherein an opening diameter of the second outlet (23a) is formed to be smaller than a diameter of the outer circumferential surface of the second tube (<NUM>),
wherein the third tube (<NUM>) has at least a tip including the second outlet (23a) consisting of an electrically conductive material as an electrode (<NUM>), and capable of applying an electric field to droplets ejected from the first outlet (21a) by a power source (<NUM>) connected to the electrode (<NUM>) to eject electrically charged droplets from the second outlet (23a),
wherein the inner circumferential surface of the third tube (<NUM>) progressively decreases in diameter towards the second outlet (23a),
wherein the second channel (<NUM>) has a constriction portion (<NUM>) formed by the inner circumferential surface of the third tube (<NUM>) and the tip of the second tube (<NUM>), and
characterized in that
a channel area of the second channel (<NUM>) defined on a plane perpendicular to a central axis progressively decreases from the opposite end to the constriction portion (<NUM>).