# US 11,309,174 B2 · Ionization method, ionization device, imaging spectrometry method, and imaging spectrometer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,309,174 B2 - Document ID: US11309174B2 - Status: Granted - Kind: B2 - Application number: 16/348,935 - Filed: 2016-11-18 - Published: 2019-09-12 - Granted: 2022-04-19 - Earliest claimed: 2016-11-18 - Assignees: Shimadzu Corporation - Applicants: Shimadzu Corporation - Inventors: Kenichi Taniguchi; Takeshi Uchida; Hiroto Itoi - Web page: https://patentgrep.com/patent/US11309174B2 ## CPC - H01J 49/165: {Electrospray ionisation} - G01N 27/62: by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode - H01J 49/0004: {Imaging particle spectrometry} - H01J 49/145: {using chemical ionisation} - H01J 49/168: {field ionisation, e.g. corona discharge (atmospheric pressure corona discharge per se H01T19/00)} - H01J 49/26: Mass spectrometers or separator tubes - H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Provided is an ionization method for ionizing a sample 21 adhered to a tip of a probe 11 that is electrically conductive, by applying an ionization voltage to the probe 11 to electrically charge the sample 21. The ionization method includes: subjecting the probe 11 to treatment to make a surface of the probe 11 homogenous; causing adhesion of the sample 21 to the tip of the probe 11; and ionizing the sample 21 by applying the ionization voltage to the probe 11 to electrically charge the sample 21. The treatment for making the surface of the probe 11 homogenous can be implemented by, for example, causing corona discharge at the probe 11. ## Claims ### Claim 1 An ionization method for ionizing a sample adhered to a tip of a probe that is electrically conductive, by applying an ionization voltage to the probe, the ionization method comprising: making a surface of the probe homogenous, by applying a discharge voltage to the probe to cause corona discharge or glow discharge, without adhesion of the sample to the tip of the probe; causing adhesion of the sample to the tip of the probe; and ionizing the sample by applying the ionization voltage to the probe to electrically charge the sample, the ionization voltage being lower than the discharge voltage and a voltage causing corona discharge, wherein the causing step and the ionization step are repeated multiple times and the making step is performed before each of at least two times of the causing step. ### Claim 2 (depends on 1) The ionization method according to claim 1, wherein the voltage to be applied to the tip of the probe upon application of the discharge voltage has an absolute value of magnitude that is 1.8 keV or more. ### Claim 3 (depends on 1) The ionization method according to claim 1, wherein the discharge voltage is applied to the probe for 30 msec or longer. ### Claim 4 (depends on 1) The ionization method according to claim 1, wherein the sample is adhered to the tip of the probe by changing a relative position between the probe and the sample. ### Claim 5 (depends on 1) The ionization method according to claim 1, wherein the surface of the probe is made homogenous by active oxygen including at least one of hydroxyl radical, superoxide anion radical, hydroperoxyl radical, hydrogen peroxide, singlet oxygen, nitrogen monoxide, nitrogen dioxide, and ozone. ### Claim 6 (depends on 1) The ionization method according to claim 1, wherein the sample is irradiated with laser light in applying the voltage to the probe to electrically charge the sample. ### Claim 7 (depends on 1) The ionization method according to claim 1, wherein the making the surface of the probe homogenous comprises sequentially applying the discharge voltage to the probe to cause corona discharge or glow discharge, without adhesion of a plurality of samples to the tip of the probe; causing adhesion of each sample to the tip of the probe; and ionizing each sample by applying the ionization voltage to the probe to electrically charge the sample, wherein the discharge voltage is applied to the probe before adhering each of the plurality of samples to the probe. ### Claim 8 (depends on 1) An imaging spectrometry method comprising: generating ions at a plurality of points on a surface of a sample by the ionization method according to claim 1 and conducting spectrometry of the generated ions. ### Claim 9 (depends on 8) The imaging spectrometry method according to claim 8, wherein the spectrometry is mass spectrometry. ### Claim 10 An ionization method for ionizing a sample adhered to a tip of a probe that is electrically conductive, by applying an ionization voltage to the probe, the ionization method comprising: making a surface of the probe homogenous by irradiating the probe with ultraviolet light without adhesion of the sample to the tip of the probe; causing adhesion of the sample on the homogenized surface of the probe; and ionizing the sample by applying the ionization voltage to the probe to electrically charge the sample, wherein the causing step and the ionization step are repeated multiple times and the making step is performed before each of at least two times of the causing step. ### Claim 11 (depends on 10) The ionization method according to claim 10, wherein the sample is adhered to the tip of the probe by changing a relative position between the probe and the sample. ### Claim 12 (depends on 10) The ionization method according to claim 10, wherein the surface of the probe is made homogenous by active oxygen including at least one of hydroxyl radical, superoxide anion radical, hydroperoxyl radical, hydrogen peroxide, singlet oxygen, nitrogen monoxide, nitrogen dioxide, and ozone. ### Claim 13 (depends on 10) The ionization method according to claim 10, wherein the sample is irradiated with laser light in applying the voltage to the probe to electrically charge the sample. ### Claim 14 (depends on 10) An imaging spectrometry method comprising: generating ions at a plurality of points on a surface of a sample by the ionization method according to claim 10 and conducting spectrometry of the generated ions. ### Claim 15 (depends on 14) The imaging spectrometry method according to claim 14, wherein the spectrometry is mass spectrometry. ### Claim 16 An ionization device comprising: a probe that is electrically conductive; a voltage application unit configured to: apply a discharge voltage to the probe to cause corona discharge or glow discharge at the probe to make a surface of the probe homogenous without adhesion of the sample to the tip of the probe; and apply an ionization voltage to the probe to electrically charge and ionize a sample adhered to the probe, the ionization voltage being lower than the discharge voltage and a voltage causing corona discharge; a sample introduction unit configured to cause adhesion of the sample to a tip of the probe; and a control unit configured to cause the voltage application unit and the sample introduction unit to repeat the adhesion and ionization of the sample by applying the ionization voltage multiple times, and to make the surface of the probe homogeneous before each of at least two times of the adhesion. ### Claim 17 (depends on 16) The ionization device according to claim 16, wherein the sample introduction unit includes a moving mechanism configured to change a relative position between the probe and the sample to a first position at which the tip of the probe is separate from the sample, and to a second position at which the tip of the probe is in contact with the sample, and the control unit applies the discharge voltage to the probe at the first position, change the relative position to the second position, and applies the ionization voltage to the probe. ### Claim 18 (depends on 16) The ionization device according to claim 16, further comprising: a laser light source configured to irradiate the tip of the probe at a position at which the tip of the probe is separate from the sample with laser light, wherein the control unit causes the laser light source to irradiate the probe having the tip, to which the sample is adhered, with the laser light. ### Claim 19 (depends on 16) The ionization device according to claim 16, wherein the voltage application unit is configured to apply the discharge voltage to the probe to cause corona discharge or glow discharge at the probe to make a surface of the probe homogenous without adhesion of a plurality of samples to the a tip of the probe; the sample introduction unit is configured to cause adhesion of the plurality of samples to the tip of the probe; and the control unit is configured to cause the voltage application unit and the sample introduction unit to apply the discharge voltage to the probe, to cause the adhesion of the plurality of samples to the tip of the probe, and to apply the ionization voltage to the probe, where the irradiation of the ultraviolet light is performed before each of the plurality of samples is adhered to the probe for ionization. ### Claim 20 (depends on 16) An imaging spectrometer comprising: the ionization device according to claim 16, further including a sample stage, and a moving mechanism configured to move a relative position between the probe and the sample placed on the sample stage; and a spectrometry unit configured to conduct spectrometry of ions generated from a plurality of positions on the sample. ### Claim 21 (depends on 20) The imaging spectrometer according to claim 20, wherein the spectrometry is mass spectrometry. ### Claim 22 An ionization device comprising: a probe that is electrically conductive; a light source configured to irradiate the probe with ultraviolet light to make a surface of the probe homogenous without adhesion of the sample to the tip of the probe; a voltage application unit configured to apply an ionization voltage to the probe to electrically charge and ionize a sample adhered to the probe; a sample introduction unit configured to cause adhesion of the sample on the homogenized surface of the probe of the probe; and a control unit configured to cause the light source, the voltage application unit, and the sample introduction unit to repeat the adhesion and ionization of the sample by applying the ionization voltage multiple times, and to make the surface of the probe homogeneous before each of at least two times of the adhesion. ### Claim 23 (depends on 22) The ionization device according to claim 22, further comprising: a laser light source configured to irradiate the tip of the probe at a position at which the tip of the probe is separate from the sample with laser light, wherein the control unit causes the laser light source to irradiate the probe having the tip, to which the sample is adhered, with the laser light. ### Claim 24 (depends on 22) An imaging spectrometer comprising: the ionization device according to claim 22, further including a sample stage, and a moving mechanism configured to move a relative position between the probe and the sample placed on the sample stage; and a spectrometry unit configured to conduct spectrometry of ions generated from a plurality of positions on the sample. ### Claim 25 (depends on 24) The imaging spectrometer according to claim 24, wherein the spectrometry is mass spectrometry.