JP2017033659A - Ionization device, mass spectrometer with the same and image creation system - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ionizing device having a probe, which can easily change the natural frequency of a vibrating portion of the probe without removing the probe. SOLUTION: A holding table for holding a sample, a probe for determining an ionizing portion of the sample held on the holding table, and a fixing having one end of the probe as a free end and fixing the probe to an ionizing device. To vibrate the probe, the extraction electrode that draws out the ionized ions of the sample, the liquid supply means that supplies the liquid to a part of the sample region, the means that applies a voltage between the probe and the extraction electrode, and the probe. The vibrating means has the vibration means of the first probe that vibrates at the natural frequency of the probe, and the vibration means of the nth order (n is an integer of 2 or more) of the natural frequency. It is a means to generate at least two vibrations of the second probe vibration. [Selection diagram] Fig. 2

Description

  The present invention relates to an ionizer that ionizes a substance, a mass spectrometer having the ionizer, an image generation system, an image display system, an ionization method, and the like.

  In recent years, imaging mass spectrometry applying mass spectrometry has been developed as an analysis technique for visualizing the distribution of substances and components existing on the surface of a sample.

  In imaging mass spectrometry, a sample is ionized at an arbitrary measurement point (micro area) on the surface of the sample. Subsequently, mass analysis is performed on the generated ions to obtain a mass spectrum. This is performed at a plurality of measurement points, and a mass spectrum image is formed by associating the obtained mass spectrum with the position information of the measurement points.

  In this case, the spatial resolution of the mass spectrum image is determined by the size of the measurement point when ionizing the sample. Therefore, in order to improve the spatial resolution of the mass spectrum image, a technique for selectively ionizing a sample existing in a minute region is required.

  As such a technique, a method of selectively ionizing using a probe that vibrates a substance existing on a sample surface has been proposed (Patent Document 1 and Patent Document 2).

  In the technique described in Patent Document 1, one end of a probe is fixed to a cantilever, and the cantilever is vibrated to move the tip of the probe so as to reciprocate between the sample and the front of the ion intake portion of the mass spectrometer. . When the tip of the probe comes into contact with the sample, the substance present in the micro area on the sample surface adheres to the probe. Subsequently, the tip portion of the probe to which the substance is attached moves in front of the ion extraction electrode, and the tip portion of the probe is irradiated with voltage or laser light. Thereby, only the substance adhering to the tip of the probe can be selectively ionized.

  The technique described in Patent Document 2 uses a vibrating capillary probe. In Patent Document 2, a liquid bridge is formed between the tip of a probe and a sample surface by supplying a liquid to a partial region of the sample surface through a capillary. By this liquid cross-linking, only the substances existing in the portion in contact with the liquid cross-linking among the substances existing on the sample surface are dissolved in the liquid. Thereafter, the probe vibrates, and the tip of the probe approaches the ion extraction electrode while the liquid forming the liquid bridge is held at the tip of the probe. Then, an electrospray of a liquid is generated by a strong electric field applied between the probe and the ion extraction electrode, and a substance dissolved in the liquid is ionized.

  The technique described in Patent Document 2 is different from the technique described in Patent Document 1, and it is not necessary to irradiate the substance with laser when ionizing the substance, and softer ionization can be performed.

  Non-patent document 1 is generated by using a device having the same configuration as the device described in patent document 1, and stopping the probe with a substance attached to the tip in the vicinity of the ion intake unit and continuing ionization. It is described that ionic species change over time.

International Publication No. 2007/126141 Specification JP 2013-181840 A

M.M. K. Mandal. , Et. al. , J .; Am. Soc. Mass. Spectrom. , 2011, 22, 1493-1500.

  As described in Non-Patent Document 1, the generated ion species can be changed by changing the time for generating the electrospray. By changing the vibration frequency of the probe in Patent Document 1 or Patent Document 2, the time during which the tip of the probe is approaching the ion extraction electrode can be changed. This suggests that the generated ion species can be changed.

  In the technique described in Patent Document 2, the probe is vibrated at a natural frequency in order to increase the amplitude of the probe. Therefore, in order to change the probe frequency in Patent Document 2, it is necessary to change the natural frequency of the probe.

  However, in Patent Document 2, in order to change the natural frequency of the probe, it was necessary to replace the probe itself. When the probe is replaced, the position on the sample surface where the tip of the probe contacts or approaches changes before and after the probe replacement. Therefore, when the probe is replaced, there is a problem that it takes time and effort to manually change the position of the tip of the probe after replacing the probe.

  Therefore, the present invention can easily change the vibration frequency of the probe vibration while ensuring a sufficiently large amplitude of the probe vibration without changing the probe to change the natural frequency of the vibration portion of the probe. An object of the present invention is to provide an ionization apparatus that can perform the above.

The present invention has been made to solve the above problems, and the ionization apparatus of the present invention provides:
A holding table for holding the sample;
A probe for determining an ionized portion of the sample held on the holding table;
One end of the probe as a free end, and a fixing part for fixing the probe to the ionization device;
An extraction electrode for extracting ionized ions of the sample;
Liquid supply means for supplying a liquid to a partial region of the sample;
Means for applying a voltage between the probe and the extraction electrode;
Vibration means for vibrating the probe,
The vibration means includes a first probe vibration that vibrates at a natural frequency of the probe, and a second probe vibration that vibrates at a harmonic frequency of an nth order (n is an integer of 2 or more) of the natural frequency. The ionization apparatus is characterized in that it is a means for generating at least two vibrations.

  According to the present invention, ionization at a plurality of frequencies can be realized with a simple configuration by utilizing harmonic vibration in addition to the natural vibration of the probe.

1 is a schematic diagram showing an image creation system having an ionization apparatus according to an embodiment of the present invention. The schematic diagram which shows the vibration of the probe of the ionization apparatus which concerns on embodiment of this invention. (A) The schematic diagram showing the vibration part of a probe. (B) The schematic diagram which shows the harmonic vibration of a probe. The schematic diagram which shows the displacement detection part of the ionization apparatus which concerns on embodiment of this invention.

  Hereinafter, the present invention will be described in detail using embodiments.

  FIG. 1 is a schematic diagram showing an ionization apparatus 100 according to an embodiment of the present invention and an image forming system having the ionization apparatus 100.

  The apparatus 100 according to the present embodiment includes a probe 1, a vibrating unit 2, a sample stage 8, a liquid supply unit 9, and a conductive pipe 11 that guides the liquid supplied from the liquid supply unit 9 to the probe 1. . One end of the probe 1 is a free end, and the other end is fixed to the main body of the ionization apparatus 100 by a fixing portion 16. A vibration means 2 for applying vibration to the probe 1 is disposed in the vicinity of the probe.

  The ionization apparatus 100 further includes a first voltage application unit 10 connected to the probe 1 or the pipe 11 and an ion take-in unit 7. The ion take-in unit 7 has an ion extraction electrode 17 connected to the second voltage application unit 14. When the first voltage is applied by the first voltage application unit 10 or the second voltage is applied by the second voltage application unit 14, an electric field is generated between the probe 1 and the extraction electrode 17.

  The extraction electrode 17 is a plate-like or cylindrical structure having an opening formed of a conductive member, and has a structure that allows ions to pass through the opening to the ion intake portion 7. A pump (not shown) is connected to the ion take-in unit 7 and has a negative pressure with respect to the external environment. For this reason, the ions move along the electric field, and are attracted to the extraction electrode 17 in the airflow surrounding the ions and pass through the opening of the extraction electrode 17.

  The sample 18 is placed and held on the substrate 3. Further, the substrate 3 is placed on the sample stage 8. The substrate is appropriately selected from conductive or insulating materials according to the conductivity of the sample. When the sample is conductive, it is preferable to select an insulating substrate, but it is not always necessary to be insulating.

  The probe 1 has a beam shape and the end thereof is in contact with the sample 18 or is disposed at a very close position. The probe 1 is a beam-like elastic body extending in the longitudinal direction, and it is preferable that one or more nodes and antinodes are formed in the longitudinal direction to obtain a harmonic vibration state. The probe 1 is preferably in the form of a thin cylinder having a channel inside thereof, such as a capillary. The solvent is continuously supplied from the liquid supply means 9 to the probe via the pipe 11. There is an opening at the end of the probe 1, and the solvent is supplied onto the surface of the sample 18 by continuously flowing the solvent from the opening.

  The solvent is a liquid that can dissolve the substance contained in the sample as a solute, and the solvent in which the solute is dissolved is hereinafter referred to as a “solution”. The solvent may be a mixture of water and an organic solvent, and may be further mixed with at least one of an acid and a base, but may be water or an organic solvent alone. When the mixture that is a solvent touches the sample, a substance that is easily dissolved in the solvent contained in the sample is easily dissolved, and the liquid that is the solvent changes into a solution.

The solvent supplied from the probe 1 forms a liquid bridge 4 between the end of the probe 1 and the sample. The liquid bridge 4 is a liquid in a state where the probe 1 and the sample 18 are bridged by surface tension or the like under an atmospheric pressure environment. When the liquid bridge 4 is formed, the substance on the surface of the sample is dissolved in the liquid. The contact area of the liquid bridge 4 with the sample 18 is about 1 × 10 ⁻⁸ m ² , and the liquid bridge 4 is in contact with a very narrow partial region in the plane of the sample 18. The position where the probe 1 contacts via the liquid bridge 4 is the position where the sample 18 is ionized.

  The probe 1 is formed of a conductor or an insulating material. If the solvent has conductivity, an insulating probe may be used. However, when the probe 1 is a conductor, the first voltage applying means can be directly connected to the probe. The first voltage applied to the pipe 11 by the first voltage applying means 10 is also applied to the probe 1 and the solvent flowing out from the probe tip through the conductive solvent.

  When the probe 1 is vibrated by the vibrating means 2, the distance between the end of the probe 1 and the sample 18 changes periodically. The vibrating means 2 is not particularly limited as long as it vibrates with a constant amplitude. For example, as the vibration means 2, a piezoelectric element or a vibration motor that can provide vibration of an arbitrary frequency can be used.

  The position where the vibration means 2 is disposed is not particularly limited as long as it is a position where vibration can be transmitted to the probe 1. Further, the vibration means 2 may intermittently contact the probe when vibrating, and does not necessarily need to be in contact with the probe 1 while the probe is stationary.

  If the configuration in which the vibration means 2 is attached to the probe 1 is adopted, the shape of the probe 1 can be freely selected, the vibration can be efficiently transmitted to the probe 1, and the probe 1 can be vibrated stably. The vibration means 2 may be installed outside the probe 1 or may be built in the probe 1. The vibrating means 2 may be fixed to a part other than the probe 1 of the apparatus.

  Further, for example, the probe 1 may be made of a piezoelectric element or the like, and the probe 1 itself may also serve as the vibration means 2. Alternatively, at least a part of the probe 1 may be formed of a magnetic material, the vibration unit 2 may be configured of an electromagnet, and the probe 1 may be vibrated by applying an alternating magnetic field to the probe 1.

  When vibration is transmitted to the probe 1 in which the liquid bridge 4 is formed between the sample 18 and the sample 18 by the vibration means 2, the probe 1 vibrates while the liquid that has formed the liquid bridge 4 remains attached to the tip of the probe 1. That is, when the probe 1 vibrates, a state in which the probe 1 and the sample 18 are connected via the liquid bridge 4 and a state in which the probe 1 and the sample are separated can be alternately generated. When the probe 1 is separated from the sample 18 by the vibration of the probe 1, a part of the liquid forming the liquid bridge 4 remains at the tip of the probe 1.

  When the tip of the probe 1 further approaches the extraction electrode 17, the tip of the probe 1 has a high aspect ratio, so that the electric field strength increases due to electric field concentration. Due to this electric field, the liquid moves to the side surface of the probe 1 on the side of the ion take-in part 17 to form the Taylor cone 5. That is, the liquid forming the Taylor cone 5 includes a solution in which a substance contained in the sample is dissolved.

  When the liquid adhering to the end of the probe 1 is sufficiently close to the ion extraction electrode 17, the electric field is increased at the tip of the Taylor cone 5. As a result, electrospray is generated from the liquid, and minute charged droplets 6 are generated. The charged droplet 6 flies toward the ion extraction electrode 17 by an electric field generated between the ion extraction electrode 17 and the liquid. At this time, the charged droplet 6 undergoes Rayleigh splitting, and ions of a specific substance in the sample can be generated. The series of the formation of the Taylor cone 5, the spraying of the charged droplets 6 and the ionization will be collectively referred to as electrospray ionization hereinafter.

  The first voltage is set to a voltage that can generate a high electric field sufficient for the liquid to electrospray at the tip of the probe. The first voltage is usually a high voltage of 1 kV to 10 kV, more preferably 3 kV to 5 kV. However, the smaller the distance between the probe and the extraction electrode, the lower the voltage required to obtain the electric field strength for generating electrospray. In this case, the first voltage may be a voltage lower than 1 kV.

  In order to generate an electric field between the probe 1 and the extraction electrode 17, the second voltage is usually set to 100 V or less or a low voltage close to the ground potential of the ionizer.

(Mass spectrometer)
When mass analyzing an ionized substance by the ionization apparatus 100 described above, the mass analysis unit 15 is connected to the ionization apparatus 100 to configure the mass analysis apparatus. The ion take-in unit 7 is connected to the mass analysis unit 15 and configured to be able to transfer ions taken from the ion take-in unit 7 to the mass analysis unit 15. The substance contained in the droplet is introduced in an ionized state in the mass analyzer 15. The mass analyzer 15 measures the mass-to-charge ratio of ions. In addition, the extraction electrode 17 may be configured integrally with a housing that holds the ion capturing unit 7 or the mass analyzing unit 15 in a vacuum.

(Image creation system)
An image creation system according to an embodiment of the present invention includes the above-described mass spectrometer and an image forming apparatus. The image forming apparatus includes a sample stage control unit 13, an input unit 21, a computer 22, and an image display unit 23. The image display unit 23 is a monitor such as a display. The computer 22 controls the operation of the image forming system in an integrated manner. The input means 21 is a user interface for inputting information for controlling the system. The computer is also an image forming unit that forms image information based on mass spectrometry data.

  The stage control means 13 drives and controls the sample stage 8 and controls the sample 18 with respect to the probe 1 in a direction horizontal to the upper surface of the sample stage 8 (XY direction) and a direction perpendicular to the upper surface of the sample stage 8 (Z direction). Can be moved relatively. The computer 22 controls the sample stage by outputting the analysis position information to the stage control means 13. By scanning the surface of the sample 18 with the probe 1, the surface of the sample can be widely analyzed in a plane.

  The mass analysis result is obtained as mass information such as mass spectrum data by the mass analyzer 15. The computer 22 integrates mass spectrum data and position information to form image information. The image information output from the computer 22 is sent to the image display unit 23 and displayed.

  From the mass analysis result, the components of the solute dissolved in the liquid bridge can be known, so that the image constitutes a component distribution image or a mass distribution image. On the image, for example, the type of component and its amount are displayed. The difference between the type and amount is displayed, for example, by color or brightness. It is also possible to superimpose and display an optical microscope image of a sample acquired in advance and a mass distribution image.

(Probe vibration)
Next, the vibration of the probe will be described. FIG. 2 is a schematic diagram showing how the probe 1 vibrates, and FIG. 2A is a schematic diagram showing the vibration of the probe, taking the natural vibration of the probe as an example. The vibration means 2 is installed in the vicinity of the fixed end of the probe 1. When the vibration means 2 is activated, the probe vibration portion 19 vibrates. In this specification, the probe vibrating portion 19 (hereinafter referred to as “vibrating portion”) refers to a portion of the probe that vibrates substantially, that is, a portion from the fixed end to the free end of the probe. The vibration means 2 is not included in the vibration part 19. In the configuration in which the vibration means 2 is always in contact with the probe 1, the position where the vibration means 2 is in contact is the fixed end of the probe 1. On the other hand, in the configuration in which the vibrating means 2 and the probe 1 are intermittently in contact with the vibrating means 2, the place where the probe is in contact with the probe fixing portion 16 is the fixed end. The probe fixing part 16 is a part for fixing at least a part of the probe to the casing of the ionization apparatus.

  The vibration means 2 vibrates the probe 1 in a direction in which the free end of the probe 1 repeatedly approaches and separates from the sample or the extraction electrode 17. The vibration of the probe 1 has a frequency of, for example, about 10 Hz to 1 MHz, an amplitude of the free end of, for example, about several tens of μm to several mm, and the amplitude of the probe 1 is such that liquid bridge formation and electrospray are generated. Set to occur alternately. When the type of the probe 1, the frequency of the vibrating portion 19, and the strength of the electric field generated between the probe 1 and the extraction electrode 17 are changed, it is desirable to change the amplitude of the probe 1 as appropriate. .

(Natural frequency of vibration part)
Next, the natural frequency of the vibrating portion 19 of the probe 1 according to this embodiment will be described. The natural frequency in consideration of the mass m ′ of the beam-like probe is calculated by an expression representing the natural frequency of the beam-like probe in which a weight having an equivalent mass m is added to the tip. In general, the natural frequency of a beam-like probe 1 having a length L, in which the mass of the probe itself is ignored and a weight of mass m is added to the tip, can be approximated by the following equation (1).

  Here, I is the cross-sectional second moment of the probe, and E is the Young's modulus of the probe. The probe length L is the length from the center of gravity of the entire probe to the fixed end of the probe. In this case, the length L is the length from the position where the weight of mass m is added to the fixed end of the probe. The cross-sectional second moment is a quantity representing the difficulty of deformation of the object determined by the shape of the probe.

(Operation to change vibration frequency by harmonic generation)
FIG. 2B is a schematic diagram showing harmonic vibration of the probe. N is the harmonic order. The probe generates bending vibration in a plane perpendicular to the longitudinal direction. The ionization apparatus of the present invention is not limited to the first probe vibration that vibrates the probe 1 at the natural frequency, but also the second probe vibration at the n-th harmonic (n represents an integer of 2 or more) of the natural vibration. It is made to produce.

  If the probe is a beam-like elastic body that bends in a direction perpendicular to the longitudinal direction, one or more nodes and antinodes are formed in the longitudinal direction as shown in FIG. Can be easily obtained.

  The order of the n-th harmonic of the natural vibration is not particularly limited, but it is preferable that n is any order of 2 to 5, particularly the second order or the third order.

  Further, a third probe vibration that oscillates at a harmonic frequency of the mth order (m is an integer of 2 or more and n ≠ m) of the natural frequency may be generated.

  Furthermore, a configuration in which fourth, fifth,..., Probe vibrations having different orders may be generated.

  Increasing the length of the probe in the longitudinal direction tends to generate higher-order harmonic vibrations, but makes it difficult to handle as a probe. Also, vibrations of two components orthogonal to each other are likely to occur, and the contact point of the probe with the sample is likely to deviate from the target point.

  The shape of the probe may be set as appropriate according to the required harmonic order and the like. For example, the length may be 10 mm or more and 200 mm or less, and the cross-sectional diameter may be 0.1 mm or more and 2 mm or less. In particular, a glass capillary having a shape of 20 mm to 100 mm and a cross-sectional diameter of 0.2 mm to 1 mm can be given.

  The vibration control means 12 is driven by changing the vibration frequency of the vibration means 2. When the vibration frequency coincides with a harmonic frequency that is an integral multiple of the natural frequency of the probe 1, the probe vibrates in a resonant manner, and probe vibration in which the amplitude of the probe tip increases is generated. If this state is maintained, the probe 1 can contact the sample at the open end and cause electrospray ionization. The probe 1 can be used at a plurality of frequencies without changing the probe by changing the order n to generate harmonic vibration. By driving the probe at different frequencies to ionize the substance on the sample surface and changing the frequency, the molecular species to be detected efficiently can be changed.

  The frequency of the probe vibration can be changed freely. However, when forming the component distribution image or the mass distribution image as described above, the probe vibration is performed following the scanning of the probe by the stage control means 13. It is preferable to change.

Specifically, the following forms are mentioned.
(1) Ionization and mass analysis by the first probe vibration are performed at a certain position, and the ionization and mass analysis are performed at that position by changing to the second probe vibration. Thereafter, the sample stage 8 is moved to change the position of the probe on the sample. After the movement, the ionization and mass analysis by the first probe vibration are similarly performed, and then the ionization and the mass by the second probe vibration are performed. Analyze sequentially. By repeating this, a scanned image is acquired.
(2) Ionization and mass spectrometry by the first probe vibration are continuously performed without changing while scanning the probe. Thereby, a scanning image by the first probe vibration is first acquired, and similarly, ionization and mass spectrometry by the second probe vibration are continuously performed while scanning the probe to acquire a scanning image.

  Similarly, when scanning images with the third and fourth probe vibrations are acquired, the scanning images may be sequentially changed.

  In these cases, ionization and mass spectrometry at each frequency may be performed at the same position, or ionization may be performed at positions adjacent to each other with an offset.

(Probe vibration monitor)
Next, the displacement measuring means 200 for measuring the displacement of the probe 1 will be described. The displacement measuring unit 200 can employ a configuration using various methods, but is not limited to the method described below. FIG. 4 shows an image forming system provided with the displacement measuring means 200.

  When the tip of the probe 1 comes close to and comes into contact with the surface of the sample, repulsive force and adhesion force due to liquid bridge are generated, so that the vibration is limited, and the amplitude and the frequency are slightly shifted. Furthermore, since the adhesion force and repulsive force due to the liquid bridge change according to the distance between the surface of the sample 18 and the tip of the probe 1, the amplitude and the shift amount of the frequency of the probe 1 change accordingly.

  As a method for detecting the deflection of the probe 1, an optical lever method, an optical interference method, or the like can be applied. The probe 1 may be formed of a piezoelectric material, and a voltage generated according to the displacement of the probe 1 may be detected.

  The displacement measuring means 200 applying the optical lever method will be described. The laser beam emitted from the light irradiator 201 is irradiated on the back surface of the probe 1, the reflected light is detected by the light detector 202, and the displacement amount of the probe 1 from the displacement of the light detection position in the light detector 202. Can be detected. In order to facilitate optical path adjustment, a reflecting mirror may be installed on the optical path.

  The vibration state of the probe 1 can be known from the time change of the displacement amount of the probe 1. The displacement signal from the photodetector is also an alternating signal that vibrates. The frequency of vibration can be detected by using a means such as a frequency counter or heterodyne detection for the displacement signal from the photodetector. The amplitude of vibration can be detected by converting the displacement signal from the photodetector into a DC component by means of a rectifier or by means such as lock-in detection.

  The natural frequency of the probe can be found as follows. That is, the vibration frequency of the vibrator is changed to measure the displacement of the probe tip, and the point where the amplitude becomes maximum is taken as the resonance point. Here, the frequency of the probe can be measured by an optical method of irradiating the probe tip with laser light.

  Moreover, if the vibration state is imaged with a camera, the order of vibration due to harmonics can be known. A vibrating probe is photographed with a camera, and the number and amplitude of harmonic vibration nodes can be obtained by image analysis. The harmonic order is obtained from the number of nodes. It is also possible to know the frequency of probe vibration by using a high-speed camera.

  Alternatively, the natural frequency of the probe can be measured by the impulse response of the probe. For this purpose, an impulse signal is applied to the vibrator to vibrate the probe, and the time change of the probe displacement is measured by the method using the laser beam described above. If the time change data of the probe displacement is analyzed by FFT (Fast Fourier Transform Analysis), the natural frequency and the harmonic frequency can be derived.

  A frequency table or the like may be prepared based on the measurement result of the harmonic frequency obtained in advance. With reference to the frequency table, the frequency for vibrating the probe is designated. Alternatively, instead of using a table, a basic primary natural frequency may be measured, and based on this, the frequency of the nth harmonic may be obtained by calculation.

  Further, as described above, the frequency at which ionization can be efficiently performed may vary depending on the molecular species. Therefore, it is preferable to sequentially perform ionization by switching the harmonic order and vibrating the probe. The generated ions are detected by a mass analyzer as will be described later. A table may be prepared in advance by preparing a sample containing a representative molecular species, generating and detecting ions by changing the order of harmonics, examining the frequency at which ionization can be performed most efficiently. Depending on the molecular species to be detected, the probe may be vibrated by appropriately selecting the drive frequency closest to the optimum frequency from the natural frequency of the probe or the harmonic frequency.

(Modification of ionizer)
The ionization apparatus according to the present embodiment has a configuration in which the probe has a flow path inside, and the solvent flows in the flow path. The solvent is supplied from the liquid supply means to the probe, and the solvent travels along the surface of the probe. It may be configured to move and form the liquid bridge 7 at the probe tip.

  The ionization apparatus according to the present embodiment is a mass spectrometer such as a time-of-flight mass spectrometer, a quadrupole mass spectrometer, a magnetic field deflection mass spectrometer, an ion trap mass spectrometer, or an ion cyclotron mass spectrometer. You may use as an ion generating part.

  The ionization apparatus according to the present embodiment forms a liquid bridge under an atmospheric pressure environment to ionize the substance, and the atmospheric pressure is in the range of 0.1 to 10 times the standard atmospheric pressure of 101325 Pa. The environment may be the same atmosphere as a normal room, or an inert gas atmosphere such as a nitrogen atmosphere or an argon atmosphere.

(Feedback control)
A case will be described in which feedback control is performed with respect to the position of the probe with respect to the sample surface in order to precisely maintain the average distance between the probe and the sample surface and perform stable scanning. When the average distance between the tip of the probe and the surface of the sample changes, the movable range of the probe tip changes and the adhesion force due to liquid bridge changes, so the frequency or amplitude of the probe changes. The position of the sample surface is feedback controlled as follows so as to keep the frequency or amplitude of the probe constant.

  In addition to displacement in the direction parallel to the surface of the sample 2, the moving means is given a displacement function in the Z direction perpendicular to the surface of the sample. Upon receiving the signal from the displacement measuring means, the feedback circuit outputs a feedback control signal to the position specifying unit so that this signal becomes constant. The position designation unit controls the position in the Z direction with respect to the moving means. The feedback control signal is a signal that depends on the difference between the reference signal and the signal from the displacement measuring means. By this series of feedback control, the distance between the probe and the surface of the sample can be kept approximately constant, and the formation time or amount of the liquid bridge 7 can be stabilized. Moreover, since it is possible to avoid applying an excessive force to the sample, it is possible to stably scan the sample surface and ionize components on the sample surface.

DESCRIPTION OF SYMBOLS 1 Probe 2 Vibrating means 3 Substrate 7 Ion taking-in part 8 Sample stage 9 Liquid supply means 10 First voltage applying means 11 Fixing part 14 Second voltage applying means 17 Ion extraction electrode 18 Sample 100 Ionizer

Claims (11)

An ionizer,
A holding table for holding the sample;
A probe for determining an ionized portion of the sample held on the holding table;
One end of the probe as a free end, and a fixing part for fixing the probe to the ionization device;
An extraction electrode for extracting ionized ions of the sample;
Liquid supply means for supplying a liquid to a partial region of the sample;
Means for applying a voltage between the probe and the extraction electrode;
Vibration means for vibrating the probe,
The vibration means includes a first probe vibration that vibrates at a natural frequency of the probe, and a second probe vibration that vibrates at a harmonic frequency of an nth order (n is an integer of 2 or more) of the natural frequency. An ionizer characterized by being means for generating at least two vibrations.   The vibration means is means for generating a third probe vibration that vibrates at a harmonic frequency of the m-th order (m is an integer of 2 or more and n ≠ m) of the natural frequency. Item 4. The ionization apparatus according to Item 1.   The ionization apparatus according to claim 1, wherein the n is 2. 4.   4. The ionization apparatus according to claim 1, wherein the vibration unit is a unit that alternately generates the first probe vibration and the second probe vibration. 5.   The probe is a beam-like elastic body that bends in an in-plane direction perpendicular to the longitudinal direction, and forms one or more nodes and antinodes in the longitudinal direction to obtain a harmonic co-vibration state. The ionization apparatus as described in any one of Claim 1 to 4.   A mass spectrometer comprising: the ionization apparatus according to claim 1; and a mass analysis unit that analyzes a mass-to-charge ratio of ions. An image forming system comprising the mass spectrometer according to claim 6 and an image forming apparatus,
The image forming apparatus generates image information for displaying an image of a distribution of components of a substance contained in a sample from mass information analyzed by the mass spectrometer and position information of the region on the sample surface. An image forming apparatus, and an image display unit that outputs the image information to a display device,
An image forming system comprising: An ionization method comprising:
Determining a portion of the sample to be ionized by a probe having one end as a free end and the other end fixed to an ionizer;
Extracting ionized ions of the sample with an extraction electrode;
Supplying a liquid to a partial region of the sample;
Applying a voltage between the probe and the extraction electrode;
Oscillating the probe, and
The step of vibrating the probe includes a first probe vibration that vibrates at a natural frequency of the probe, and a second vibration that vibrates at a harmonic frequency of an n-th order (n is an integer of 2 or more) of the natural frequency. An ionization method characterized by generating at least two vibrations of the probe.   The step of oscillating is a step of generating a third probe vibration that oscillates at a harmonic frequency of the m-th order (m is an integer of 2 or more and n ≠ m) of the natural frequency. The ionization method according to claim 8.   A mass spectrometry method for analyzing a mass-to-charge ratio of ions generated by the ionization method according to claim 8.   An image forming method for forming a distribution of a substance component on a sample surface as image information by scanning an ionized portion of the sample and sequentially performing mass spectrometry according to claim 10.

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