WO2016006192A1

WO2016006192A1 - Ionization apparatus, mass spectroscope having the same, image generating system, image display system, and ionization method

Info

Publication number: WO2016006192A1
Application number: PCT/JP2015/003229
Authority: WO
Inventors: Jumpei Naito; Yoichi Otsuka; Masafumi Kyogaku
Original assignee: Canon Kabushiki Kaisha
Priority date: 2014-07-09
Filing date: 2015-06-26
Publication date: 2016-01-14
Also published as: JP2016028228A

Abstract

An ionization apparatus(100) that brings a probe tip near to or into contact with a specimen surface and ionizes the specimen(18), includes: a fixing unit(16) fixing the probe(1) to the ionization apparatus(100); a liquid supply device(9) applying liquid to the probe tip; an ion extraction electrode(17); an electric field generating unit(10) generating an electric field between liquid on the probe tip and the ion extraction electrode(17); a vibrating unit(2) applying vibrations to the probe(1), thereby cyclically repeating liquid on the probe tip forming a liquid bridge(4) with the specimen(18), and the probe tip approaching the ion extraction electrode(17) and the liquid flying toward the ion extraction electrode(17) due to the electric field; and an eigenfrequency changing unit(20) changing an eigenfrequency of a vibrating portion of the probe(1) with the probe(1) fixed to the fixing unit(16).

Description

IONIZATION APPARATUS, MASS SPECTROSCOPE HAVING THE SAME, IMAGE GENERATING SYSTEM, IMAGE DISPLAY SYSTEM, AND IONIZATION METHOD

The present invention relates to an ionization apparatus, a mass spectroscope having the same, an image generating system, an image display system, and an ionization method.

Imaging mass spectrometry that applies mass spectrometry technology has been developed as of recent, as an analysis technology to visualize distribution of matter and compositions present on the surface of a specimen.

Imaging mass spectrometry involves ionizing a specimen at any measurement point (minute region) on the surface of the specimen. Mass spectrometry is then performed on the generated ions, yielding a mass spectrum. This is repeated at multiple measurement points, and the obtained mass spectra and the position information of the measurement points are correlated, thereby forming a mass spectrometry image.

In this case, the spatial resolution of the mass spectrum image is determined by the size of the measurement points when ionizing the specimen. Accordingly, there is demand for a technology to selectively ionize fine regions, to improve the spatial resolution of the mass spectrum image. Methods which use probes to vibrate matter on the surface of the specimen have been proposed heretofore as technologies to selectively ionize.

A technology described in PTL 1 involves fixing one end of a probe to a cantilever, and vibrating the cantilever such that the tip of the probe reciprocally moves between the specimen and in front of the ion intake of the mass spectrometry apparatus. The tip of the probe comes into contact with the specimen, whereby matter present in the fine region on the surface of the specimen adheres to the probe. Next, the tip portion of the probe to which the matter has adhered moves to in front of an ion extraction electrode, where voltage and laser is applied to the tip portion of the probe. Accordingly, just the matter adhering to the top of the probe can be selectively ionized.

A technology described in PTL 2 uses a vibrating capillary type probe. A partial region of the surface of the specimen is supplied with a liquid via the capillary in PTL 2, thereby forming a liquid bridge between the tip of the probe and the surface of the specimen. This liquid bridge causes only the portion of the matter present on the surface of the specimen coming in contact with the liquid bridge to be dissolved into the liquid, thereafter the probe vibrates, and the tip of the probe comes near the ion extraction electrode with the liquid forming the liquid bridge held at the tip of the probe. An electro-spray of the liquid is formed by the intense electric field applied between the probe and the ion extraction electrode, and the matter dissolved in the liquid is ionized. The technology described in PTL 2 does not need to irradiate the matter with later at the time of ionizing the matter, unlike the technology described in PTL 1, so softer ionization can be performed.

Further, NPL 1 describes using an apparatus having the same configuration as the apparatus described in PTL 1, and stopping the probe with the matter adhering to the tip near the ion intake, thereby changing the ion species being generated over time.

As described in NPL 1, changing the time of generating the electro-spray enables the generated ion species to be changed. Changing the vibrations of the probe in PTL 1 and PTL 2 enables the time over which the probe tip is in proximity of the ion extraction electrode to be changed. It is suggested that this enables the generated ion species to be changed.

The technology according to PTL 2 vibrates the probe with an eigenfrequency of the probe, to increase the amplitude of the probe. Accordingly, in order to change the vibration frequency of the probe in PTL 2, the eigenfrequency of the probe has to be changed. However, changing the eigenfrequency of the probe in PTL 2 involves changing the probe itself. Changing the probe means that the position of the tip of the probe in contact with or near the surface of the specimen changes before and after changing the probe. Thus, not only is exchanging the probe itself troublesome, there has been the problem of manual adjustment of the position of the probe tip after exchanging the probe being troublesome.

Specification of International Publication No. 2007/126141 U.S. Patent Application Publication No. 2013/0341279

M.K. Mandal et al., J.Am. Soc. Mass. Spectrom, 2011, 22, 1493-1500 J. Mass. Spectrom. Soc. JPN., Vol. 58, 139-154, 2010

An ionization apparatus brings a tip of a probe near to or into contact with a specimen surface, and ionizes the specimen included in a region where the probe has been brought near to or into contact. The ionization apparatus includes: a fixing unit configured to fix the probe to the ionization apparatus; a liquid supply device configured to supply liquid to the tip of the probe; an ion extraction electrode; an electric field generating unit configured to generate an electric field between the liquid adhering to the tip of the probe and the ion extraction electrode; a vibrating unit configured to apply vibrations to the probe, so as to cyclically repeat a state where the liquid adhering to the tip of the probe comes into contact with the specimen and forms a liquid bridge, and a state where the tip of the probe approaches the ion extraction electrode and the liquid flies toward the ion extraction electrode due to the electric field; and an eigenfrequency changing unit configured to change an eigenfrequency of a vibrating portion of the probe vibrated by the vibrating unit in a state where the probe is fixed to the fixing unit.

Further features of the present invention will become apparent from the following description of exemplary embodiments with reference to the attached drawings.

Fig. 1 is a schematic diagram illustrating the configuration of a mass image display system including an ionization apparatus according to an embodiment. Fig. 2A is a block diagram illustrating a configuration of an eigenfrequency changing system according to an embodiment. Fig. 2B is a flowchart illustrating operations of the eigenfrequency changing system in Fig. 2A. Fig. 3 is a flowchart illustrating an ionization method according to an embodiment. Fig. 4A is a schematic diagram schematically illustrating of the configuration of an eigenfrequency changing system according to a first embodiment. Fig. 4B is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the first embodiment. Fig. 5A is a schematic diagram schematically illustrating of the configuration of an eigenfrequency changing system according to a second embodiment. Fig. 5B is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the second embodiment. Fig. 5C is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the second embodiment. Fig. 6 is a schematic diagram schematically illustrating of the configuration of an eigenfrequency changing system according to a third embodiment. Fig. 7A is a schematic diagram schematically illustrating of the configuration of an eigenfrequency changing system according to a fourth embodiment. Fig. 7B is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the fourth embodiment. Fig. 7C is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the fourth embodiment. Fig. 7D is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the fourth embodiment. Fig. 8A is a schematic diagram schematically illustrating of the configuration of an eigenfrequency changing system according to a fifth embodiment. Fig. 8B is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the fifth embodiment. Fig. 8C is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the fifth embodiment. Fig. 8D is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the fifth embodiment. Fig. 9 is a schematic diagram schematically illustrating of the configuration of an eigenfrequency changing system according to a sixth embodiment. Fig. 10 is a flowchart illustrating operations of a fluctuation reduction system to reduce the effects of eigenfrequency fluctuation in the present embodiment. Fig. 11A is a schematic diagram schematically illustrating of the configuration of an eigenfrequency changing system according to an eighth embodiment. Fig. 11B is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the eighth embodiment. Fig. 11C is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the eighth embodiment. Fig. 11D is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the eighth embodiment. Fig. 12A is a schematic diagram schematically illustrating of the configuration of an eigenfrequency changing system according to a ninth embodiment. Fig. 12B is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the ninth embodiment. Fig. 12C is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the ninth embodiment. Fig. 12D is a schematic diagram schematically illustrating of the configuration of the eigenfrequency changing system according to the ninth embodiment.

Preferred embodiments of the present invention will be described below with reference to the drawings. Note that while these embodiments are examples of preferred embodiments of the invention, the present invention is not retracted to the configurations described in these embodiments.

Configuration of Ionization Apparatus 100

First, the configuration of an ionization apparatus 100 (hereinafter "apparatus 100") used in common in each of the embodiments of the present invention will be described with reference to Fig. 1. Fig. 1 is a schematic diagram illustrating the configuration of a mass image display system including the apparatus 100 according to the embodiments (hereinafter also collectively referred to as "present embodiment").

The apparatus 100 according to the present embodiment includes a probe 1, a vibrating unit 2, a specimen stage 8, and a liquid supply device 9. The apparatus 100 according to the present embodiment also includes an electroconductive channel 11, an ion intake 7, an electric field generating unit, and an eigenfrequency changing unit 20 (hereinafter referred to as "changing unit 20"). The electric field generating unit includes a voltage applying unit 10 and a voltage applying unit 14.

The ion intake 7 includes an ion extraction electrode 17 connected to the voltage applying unit 14. The ion intake 7 is also connected to a mass spectrometry unit 15, and is configured so that ions extracted from the ion intake 7 can be conveyed to the mass spectrometry unit 15.

A specimen 18 is loaded and held on a substrate 3. The substrate 3 is loaded on the specimen stage 8 connected to a specimen stage control unit 13. The specimen stage control unit 13 controls driving of the specimen stage 8, so that the specimen 18 can be relatively moved in relation to the probe 1. Specifically, the specimen stage control unit 13 can move the specimen 18 in a direction parallel to the upper face of the specimen stage 8 (X-Y direction) and in a direction perpendicular to the upper face of the specimen stage 8 (Z direction).

The probe 1 has a channel (omitted from illustration) internally or externally. Liquid supplied from the liquid supply device 9 passes through the channel (omitted from illustration) of the probe 1, and is disposed on a partial region on the surface of the specimen 18 held on the substrate 3. The liquid disposed on the partial region on the surface of the specimen 18 forms a liquid bridge 4 between the specimen 18 and the tip of the probe 1. Note that the term "liquid bridge" means liquid supplied from the probe 1 in a state of being in physical contact with at least both the probe 1 and the specimen 18. That is to say, the liquid bridge 4 is formed by the liquid adhering to the tip of the probe 1 physically coming into contact with the specimen 18. Note that the liquid bridge 4 is formed by surface tension and the like.

The liquid supplied from the liquid supply device 9 preferably is a liquid capable of dissolving the matter included in the specimen 18. One the liquid bridge 4 is formed, the matter at the surface of the specimen 18 is dissolved into the liquid making up the liquid bridge 4. No liquid bridge 4 is formed in a case where the liquid supplied from the probe 1 is insufficient or in a case where liquid is adhered to the probe 1 at the opposite side from the substrate 3.

The liquid supplied from the liquid supply device 9 is introduced into the channel (omitted from illustration) within the probe 1 via the electroconductive channel 11. At this time, the voltage applying unit 10 applies voltage to the liquid via the electroconductive channel 11. The type of voltage applied to the liquid is not restricted in particular, and may be any of DC voltage, AC voltage, and pulsed voltage. Further, the voltage applied to the liquid at this time may be zero volts, i.e., no voltage applied to the liquid. In this case, voltage which is not zero volts is applied to the later-described ion extraction electrode 17.

In the present embodiment, a potential, which differs from the potential applied to the later-described ion extraction electrode 17, is applied to the liquid passing through the channel of the probe 1. That is to say, a potential difference is created between the ion extraction electrode 17 and the liquid that passes through the channel of the probe 1 and adheres to the tip of the probe 1. This forms an electric field between the probe 1 in contact with the liquid and the ion extraction electrode 17. Note that the voltage which the voltage applying unit 10 applies may be zero volts as long as this electric field can be formed.

A capillary capable of supplying a minute volume of liquid, for example, may be used as a tube for connecting the probe 1, electroconductive channel 11, and the liquid supply device 9. The material of this capillary may be any of an insulator, a conductor, and a semiconductor. A silica capillary or a metal capillary or the like may be used, for example. The material of the capillary may be a material which changes in hardness depending on heat, such as a thermally softening material or a thermally hardening material, for example.

The electroconductive channel 11 makes up at least part of the channel where the liquid supplied from the liquid supply device 9 passes through the inside or outside of the probe 1 and is introduced to the tip of the probe 1 at the side opposite from the liquid supply device 9. Accordingly, the electroconductive channel 11 may be disposed at any position on the channel. For example, part or all of the electroconductive channel 11 may be included within the channel inside the probe 1. Alternatively, the electroconductive channel 11 may be formed by inserting an electroconductive matter such as a stainless steel wire, tungsten wire, platinum wire, or the like, into the channel within the probe 1. In a case where the channel of the probe 1 is to be formed on the outer side of the probe 1, a capillary having flexibility may be laid along the other side of the probe 1 from the liquid supply device 9, so that the discharge orifice of this capillary is situated at the tip of the probe 1.

The vibrating unit 2 acts to provide the probe 1 with vibrations. At least one end of the probe 1 supplied with vibrations by the vibrating unit 2 vibrates. These vibrations cause the distance between the tip of the probe 1 and the specimen 18 to cyclically change.

The vibrating unit 2 is not restricted in particular as long as vibrations having a certain amplitude are exhibited with reproducibility when voltage is applied from a voltage applying unit 12. For example, a piezoelectric element, a vibrational motor, or the like, may be used as the vibrating unit 2. Piezoelectric elements and vibrational motors are suitable for use as the vibrating unit 2 according to the present embodiment, as they are capable of providing vibrations with a high vibration frequency and are durable.

The position where the vibrating unit 2 is disposed is not restricted in particular, as long as vibrations can be transmitted to the probe 1. Note that the vibrating unit 2 does not have to be in contact with the probe 1 in a state where the probe 1 is stationary. However, in this case, the vibrating unit 2 has to come into contact with the probe 1 at some point of each vibration cycle of the probe 1, to transmit vibrations. An arrangement may also be made where multiple vibrating units 2 are made to face each other across the probe 1. This enables vibrations to be applied to the probe 1 in a stable manner.

A configuration may be made where the vibrating unit 2 is attached to the probe 1. In a case of attaching the vibrating unit 2 to the probe 1, the vibrating unit 2 may be attached externally to the probe 1, or may be built in the probe 1. Externally disposing the vibrating unit 2 to the probe 1 enables a small and lightweight probe to be manufactured. The configuration where the vibrating unit 2 is attached to the probe 1 enables the efficiency of vibration transmission from the vibrating unit 2 to the probe 1 to be improved, so stable vibrations of the probe 1 can be realized. Further, the vibrating unit 2 may be fixed to a portion of the apparatus 100 other than the probe 1.

An arrangement is employed in the present embodiment where the vibrating unit 2 itself vibrates and causes the probe 1 to vibrate by transmitting these vibrations, as a method of the vibrating unit 2 applying vibrations to the probe 1. However, an arrangement may be made where the material of the probe 1 is formed of a piezoelectric device or the like, and voltage is applied to the probe 1 by the vibrating unit 2, thereby causing the probe 1 to vibrate. Alternatively, an arrangement may be made where at least part of the probe 1 is formed of a magnetic substance, and a magnetic field is applied to the probe 1 by the vibrating unit 2, thereby causing the probe 1 to vibrate.

When vibrations are transmitted by the vibrating unit 2 to the probe 1 where the liquid bridge 4 has been formed between the probe 1 and the specimen 18, the probe 1 vibrates with the liquid forming the liquid bridge 4 adhering to the tip of the probe 1. That is to say, the vibrations of the probe 1 enable a state where the probe 1 and the specimen 18 are connected via the liquid, and a state where the probe 1 and the specimen 18 are separated, to be generated separately.

In the state where the probe 1 is separated from the specimen 18 due to vibration, the liquid which had been forming the liquid bridge 4 comes into proximity of the ion intake 7 having the ion extraction electrode 17. At this time, a voltage is applied to the ion extraction electrode 17 which is different to the voltage applied to the probe 1 by the voltage applying unit 14. That is to say, an electric field is formed between the liquid adhering to the tip of the probe 1, to which voltage has been applied via the electroconductive channel 11, and the ion extraction electrode 17. In other words, the apparatus 100 forms an electric field between the liquid adhering to the tip of the probe 1 and the ion extraction electrode 17, by the electric field generating unit which has the voltage applying unit 10 and the voltage applying unit 14.

This electric field causes the liquid to relocate to the side face of the probe 1 toward the ion intake 7, and to form a Taylor cone 5. Fig. 1 illustrates a Taylor cone 5 being formed on a continuous face extending in the longitudinal direction of the probe 1. However, this position is affected by the electric field between itself and the ion extraction electrode 17, wettability of the probe 1 by the liquid, and so forth, so the Taylor cone 5 may be formed at a position including a face other than this.

When the liquid adhering to the tip of the probe 1 come into sufficient proximity with the ion extraction electrode 17, the electric field at the tip portion of the Taylor cone 5 increases. This generates and electro-spray from the liquid, creating fine charged droplets 6. The charged droplets 6 fly toward the ion extraction electrode 17 due to the electric field generated between the ion extraction electrode 17 and the liquid. Setting the strength of the electric field to a suitable level enables Rayleigh fission of the charged droplets 6 to occur, with ions of a particular matter within the specimen 18 being generated. The charged droplets 6 and the ions are guided to the ion intake 7 along the airflow and magnetic field. The vibration of the probe 1 preferably includes an action in the direction of drawing near to the ion intake 7 such that the electric field around the liquid forming the Taylor cone 5 changes along with the vibration of the probe 1.

Rayleigh fission is a phenomenon where the charged droplets 6 reach their Rayleigh limit, and excessive charge within the charged droplets 6 is discharged as secondary droplets. It is known that while the liquid forms the Taylor cone 5 and electro-spray including the charged droplets 6 is generated from the tip portion of the Taylor cone 5 and Rayleigh fission occurs, gaseous phase ions of the matter contained in the charged droplets 6 are generated. It is also known that the threshold voltage Vc at which electro-spray occurs is Vc = 0.863 (γd/ε₀)^0.5, where γ represents the surface tension of the liquid, d represents the distance between the liquid and the ion extraction electrode 17, and ε₀ represents the permittivity of vacuum (see NPL 2).

Vibrations are provided to the probe 1 by the vibrating unit 2, and as a result, the portion of the probe 1 from a fixed end to a free end vibrates. In a case where the vibrating unit 2 is constantly in contact with the probe 1 while the vibrating unit 2 is vibrating, the position where the vibrating unit 2 is in contact with the probe 1 is the fixed end of the probe 1. In a case where the vibrating unit 2 departs from the probe 1 while the vibrating unit 2 is vibrating, a position where a probe fixing unit 16 is disposed is the fixed end of the probe 1. The probe fixing unit 16 is a part which fixes at least part of the probe 1 to a probe apparatus.

A probe vibrating portion 19 (hereinafter referred to as "vibrating portion 19") in the present specification means the portion of the probe 1 that substantially vibrates. That is to say, the vibrating portion 19 is the portion from the fixed end of the probe 1 to the free end thereof, out of the entire probe 1. The vibrating unit 2 is not included in the vibrating portion 19. The vibrating unit 2 vibrates the probe 1 in the directions indicated by the arrows in Fig. 1. The vibrations of the probe 1 may have an amplitude of several tens of nm to several hundreds of μm for example, and vibration frequency of 10 Hz to 1 MHz, for example.

The magnitude of the amplitude of the probe 1 is set so that formation of the liquid bridge 4 and generation of the electro-spray occur alternately. If the type of the probe 1, the eigenfrequency of the vibrating portion 19, or the intensity of the electric field generated between the probe 1 and the ion extraction electrode 17 is changed, the amplitude of the probe 1 is also preferably changed as appropriate.

A feature of the apparatus 100 according to the present embodiment is that ionization of the matter present in the minute region on the surface of the specimen 18 can be performed at high speed. The probe 1 is preferably vibrated at high speed to perform high-speed ionization of the matter on the surface of the specimen 18.

Another feature of the apparatus 100 according to the present embodiment is that the timing of generating and stopping the electro-spray can be controlled. Accordingly, the timing at which the liquid bridge 4 is formed between the tip of the probe 1 and the specimen 18, and the timing at which the electro-spray is generated, are preferably clearly separated. Accordingly, electro-spray is not generated while the liquid bridge 4 is being formed, and during this period, charge is just supplied to the liquid forming the liquid bridge 4. At the time of the tip of the probe 1 coming close to the ion extraction electrode 17 and the electro-spray being generated, sufficient charge has been accumulated in the liquid, so the electro-spray can be efficiently generated. To this end, the amplitude of the probe 1 is preferably large.

To vibrate the probe 1 at high speed and with a large amplitude as described above, the eigenfrequency of the vibrating portion 19 and the vibration frequency of the vibration provided by the vibrating unit 2 are preferably matched. That is to say, the vibrating unit 2 preferably provides vibrations according to the eigenfrequency of the vibrating portion 19 to the probe 1, to cause sympathetic resonance in the vibrating portion 19.

While ionization under atmospheric pressure will be described in the present embodiment, the method of changing the eigenfrequency of the vibrating portion 19 of the probe 1 according to the present embodiment may be applied to ionization under reduced pressure as well. While the type of liquid used in the present embodiment is not restricted in particular, a liquid which does not affect parts making up the channel is preferable. The matter to be ionized by the apparatus 100 according to the present embodiment is not particularly restricted, either. The apparatus 100 according to the present embodiment is suitable for ionization of biological specimens including high molecules such as fats, sugars, proteins, and so forth, since minute regions can be softly ionized under atmospheric pressure.

Eigenfrequency of Vibrating Portion 19

Next, the eigenfrequency of the vibrating portion 19 of the probe 1 according to the present embodiment will be described. Generally, the eigenfrequency of a cantilever-type probe which has a length L and has a weight of a mass m attached to the tip can be approximated by the following Expression (1), assuming that the mass of the probe itself is negligible.

In Expression (1), I represents the second moment of area of the probe, and E represents the Young's modulus. The length L of the probe is the length from the center of gravity of the entire probe to the fixed end of to the probe. The length L in this case is the length from the position where the weight having the mass m is attached to the fixed end. Further, in a case where the probe has a hollow cylindrical shape, such as a pipe for example, the second moment of area I is expressed as in the following Expression (2).

In Expression (2), D represents the outer diameter of the probe, and d represents the inner diameter of the probe. Accordingly, the eigenfrequency of the probe can be changed by changing at least one of the length L, mass m, Young's modulus E, and second moment of area I, of the probe. The changing unit 20 of the apparatus 100 according to the present embodiment can change the eigenfrequency of the vibrating portion 19 by changing at least one of these four parameters.

The position of the region where the liquid bridge 4 is formed on the surface of the specimen 18 is preferably not changed before and after changing the eigenfrequency of the vibrating portion 19. Accordingly, the changing unit 20 preferably changes the eigenfrequency of the vibrating portion 19 without changing the length from a reference point of the apparatus 100 to the tip of the probe 1. The reference point here is not particularly restricted as long as an immovable point on the apparatus 100. For example, a point serving as a reference for the specimen stage control unit 13 to move or scan the specimen stage 8 may serve as the reference point.

Now, even if the length from the reference point to the tip of the probe 1 changes when changing the eigenfrequency, the position of the region where the liquid bridge 4 is formed on the specimen 18 can be made to be unchanging, by controlling the specimen stage 8 based on the amount of change thereof. For example, the amount of change in position of the liquid bridge 4 before and after changing the eigenfrequency can be measured by a later-described computer 22. Driving the specimen stage 8 by an amount equal to the obtained amount of change in position of the liquid bridge 4 but on the opposite direction to this change enables the eigenfrequency of the vibrating portion 19 to be changed without changing the position of the region where the liquid bridge 4 is formed on the specimen 18. Alternatively, the coordinates of the position of the liquid bridge 4 may be corrected by the computer 22 based on the obtained amount of change in position of the liquid bridge 4.

The length of the probe 1 is not restricted in particular, as long as the liquid bridge 4 is formed between the specimen 18 on the substrate 3 and the probe 1 in a stable manner, and the electro-spray is generated when nearing the ion extraction electrode 17. Note however, if the length of the probe 1 is insufficient, the amplitude of the vibration of the probe 1 is small, and it becomes difficult to generate the liquid bridge 4 in a stable manner. On the other hand, if the probe 1 is too long, unintended vibrations in directions other than the direction of the vibrating unit 2 vibrating the probe 1 readily occur. Accordingly, consecutively measuring a certain position on the specimen 18 on the substrate 3 becomes difficult. From the above, the length of the probe 1 preferably is around several hundred μm to several cm or so.

The color and texture of the probe 1 is not restricted in particular. Scale marks may be inscribed in the longitudinal direction of the probe 1. Correlating the length from the free end of the probe 1 or the probe fixing unit 16 with scale marks enables the attaching position of the weight or the like attached to the probe 1 to be clearly comprehended. In a case where multiple types of scale marks are to be inscribed on the probe 1, different colors may be assigned to the different types of scale marks.

Next, an eigenfrequency changing system for the vibrating portion 19 according to the present embodiment will be described with reference to Figs. 2A and 2B. Fig. 2A is a block diagram illustrating a system for changing the eigenfrequency of the vibrating portion 19 according to the present embodiment. The system for changing the eigenfrequency of the vibrating portion 19 according to the present embodiment includes the apparatus 100, a mass spectrometry unit 15, a vibration detector 24, the computer 22, and an input unit 21 for the computer 22.

The vibration detector 24 is a part that detects vibrations of the probe 1, and measures the vibration frequency and amplitude of the vibrations of the probe 1. That is to say, the vibration detector 24 is a vibration frequency measuring unit, and also an amplitude measuring unit. It should be noted that the vibration frequency of the vibrations provided by the vibrating unit 2 and the vibration frequency of the vibrations of the probe do not necessarily agree. The vibration detector 24 detects vibrations of the probe 1 when the vibration frequency of the vibrating unit 2 is gradually changed, and obtains the vibration frequency at the point that the amplitude of the probe 1 is greatest as the eigenfrequency of the vibrating portion 19.

A high-speed camera may be used as the vibration detector 24. In this case, the vibration frequency and amplitude of the vibrations of the probe 1 can be obtained by imaging the vibrating probe 1 using the high-speed camera, and performing image analysis of the obtained image. Alternatively, a part of the probe 1 may be provided with a face capable of reflecting light, upon which a laser beam is cast, and the vibration frequency and amplitude of the probe 1 by be measured by an optical lever detector serving as the vibration detector 24, or a non-contact laser vibration detector may be used as the vibration detector 24. In this case, the vibration frequency and amplitude of the vibrations of the probe 1 can be obtained by measuring and analyzing the time it takes for the probe 1 to cross the laser beam.

The computer 22 is connected to the voltage applying unit 12 that applies voltage to the vibrating unit 2, the changing unit 20, the input unit 21, the vibration detector 24, and the mass spectrometry unit 15. The computer 22 can perform calculation and data analysis based on the data obtained at the mass spectrometry unit 15 and vibration detector 24. The computer 22 can also control the apparatus 100 and the mass spectrometry unit 15 based on the data input by the user via the input unit 21 and data sent from the vibration detector 24, mass spectrometry unit 15, voltage applying unit 12, and so forth.

The input unit 21 is a unit for the user to input data and instructions to the computer 22. A keyboard, mouse, touch panel, and so forth, can be used as the input unit 21.

Next, the operations of the system for changing the eigenfrequency of the vibrating portion 19 according to the present embodiment will be described with reference to Figs. 2A and 2B. Fig. 2B is a flowchart illustrating the operations of the changing system.

First, the computer 22 sets a vibration frequency f0 (S201).

Operations of Changing Eigenfrequency of Vibrating Portion 19

Next, the vibration detector 24 detects the vibrations of the probe 1, and measures the vibration frequency f of the vibrations of the probe 1 (S203).

The vibration detector 24 then transmits the detected vibration frequency f of the vibrations of the probe 1 to the computer 22. The computer 22 compares the vibration frequency f of the vibrations of the probe 1 received from the vibration detector 24 with the vibration frequency f0 set by the computer 22 in step S202 (S204).

In a case where the vibration frequency f of the vibrations of the probe 1 do not match the vibration frequency f0 set by the computer 22 in S202, the computer 22 drives the changing unit 20 (S205). Thus, the eigenfrequency of the vibrating portion 19 is changed. The computer 22 may control the driving amount of the changing unit 20 based on Expressions (1) and (2) at this time, so that the vibration frequency f of the vibrations of the probe 1 draw nearer to the vibration frequency f0 set by the computer 22 in S202.

Upon the vibration frequency f of the vibrations of the probe 1 matching the vibration frequency f0 set in S202, the computer 22 stops driving of the changing unit 20 (S206). Thus, changing of the eigenfrequency of the vibrating portion 19 ends (S207).

At the time of setting the vibration frequency f0 in S201, the user may input any vibration frequency f0 using the input unit 21. Alternatively, a vibration frequency obtained by increasing or decreasing the eigenfrequency of the vibrating portion 19 by a predetermined amount may be set as the vibration frequency f0.

The vibration frequency f0 may also be decided by the computer 22 based on the signal intensity of a certain signal obtained at the mass spectrometry unit 15. At this time, mass spectrometry may be performed while changing the vibration frequency of the vibrations of the probe 1, and set the vibration frequency of the vibrations of the probe 1 where the intensity of the signal with the intended component is greatest as the vibration frequency f0.

Thus, the eigenfrequency of the vibrating portion 19 is changed in the present embodiment by driving the changing unit 20.

Operations of Reducing Wavering in Eigenfrequency of Vibrating Portion 19

Next, the operations of a reduction system that reduces wavering in the eigenfrequency of the probe 1 will be described with reference to Fig. 10. Fig. 10 is a flowchart illustrating operations of the reduction system. Note that the amplitude of the vibrating portion 19 of the probe 1 here is an average value of amplitudes measured several times to several thousand times, or an average value of amplitudes measured within a predetermined amount of time.

The term "wavering of eigenfrequency" in the present specification refers to a phenomenon where the eigenfrequency of the vibrating portion 19 changes slightly. There are cases where the eigenfrequency of the vibrating portion 19 is changed so that vibrations are applied to the probe 1 at a certain vibration frequency f, but the eigenfrequency slightly fluctuates, and sympathetic resonance of the vibrating portion 19 cannot be continued. One conceivable factor of this is the contact state between the vibrating unit 2 and probe 1 causes the probe 1 to vibrate in an unintended direction. When wavering in eigenfrequency occurs at the vibrating portion 19, the sympathetic resonance of the vibrating portion 19 cannot be continued, and there may be variance in ionization conditions of the specimen 18 by the apparatus 100 among the measurement points. As a result, the reproducibility of measurement by the mass image display system according to the present embodiment may deteriorate. Accordingly, the wavering in eigenfrequency of the vibrating portion 19 is reduced in the present embodiment, by the reduction system described below.

First, the vibrating unit 2 applies vibrations to the probe 1 at the eigenfrequency f0 of the vibrating portion 19 (S209). Next, in a case where wavering of eigenfrequency of the vibrating portion 19 is to be reduced (yes in S210), the amplitude of the probe 1 is measured by the vibration detector 24, and the amplitude value is transmitted to the computer 22 (S211).

Next, the computer 22 drives the changing unit 20 so as to change the eigenfrequency from f0 to f0 + Δf, and measures the amplitude of the probe 1 (S212). The computer 22 then drives the changing unit 20 to change the eigenfrequency from f0 + Δf to f0 to f0 - Δf, and measures the amplitude of the probe 1 (S213). The series of operations of S211 through S213 enables the values to be obtained for the original eigenfrequency f0, and vibration frequencies where f0 has been increased and decreased by Δf.

Next, the computer 22 compares the amplitude measured in each step in S211 through S213 (S214). At this time, the variance in amplitude and significant difference E are calculated by the computer 22 when the vibration frequency is f0 + Δf and f0 - Δf. In a case where there is no significant difference in the amplitudes (no in S215), the computer 22 drives the changing unit 20 and changes the vibration frequency to f0 (S217).

In a case where there is significant difference in the amplitudes (yes in S215), the computer 22 drives the changing unit 20 and newly sets the eigenfrequency where the amplitude is the greatest to f0 (S216). Thereafter, the computer 22 drives the changing unit 20 and changes the vibration frequency to f0 (S217).

Repeating S208 through S217 every increment time t seconds enables the wavering in eigenfrequency of the vibrating portion 19 of the probe 1 to be reduced. Note that the values of Δf, t, and E are not restricted in particular, and the user can set these values optionally. Note that ease of use for the user can be improved by setting these parameters according to the configuration of the apparatus 100 and the type of the probe 1 beforehand, an enabling the user to select the type of probe 1 and configuration of the apparatus 100, so that the parameters are automatically input.

In a case of moving the specimen stage 8 by a large amount, such as in a case of moving the measurement region, the above-described operation may be stopped, and the operation of S208 through S218 restarted upon movement of the specimen stage 8 having ended. The above operations may be started as soon as the vibrations of the probe 1 are started, or the above operations may be started when change in amplitude of the probe 1 is detected. Further, an arrangement may be made where the above operations are stopped in a case where no change in amplitude of the probe 1 is detected for a predetermined amount of time, and the above operations are resumed when change in amplitude is detected again. Alternatively, an arrangement may be made where the above operations are started when the amplitude of the probe 1 falls to or below a stipulated level, and above operations are stopped when the amplitude of the probe 1 exceeds the stipulated level.

In a case where the vibrations of the probe 1 are to be modulated, or the specimen stage 8 is to be moved in the Z direction, the amplitude of the probe 1 cyclically fluctuates. In a case where the vibrations of the probe 1 are to be modulated, the largest amplitude in one vibration frequency may be measured and the above operations applied. Alternatively, the amount of time for obtaining the average amplitude of the probe 1 may be set so as to be sufficiently longer than the modulation cycle of the amplitude of the probe 1 or the frequency of amplitude of the specimen stage 8 in the Z direction.

While the eigenfrequency has been described as being charged in the order of f0, f0 + Δf, and f0 - Δf, the order for changing the eigenfrequency is optional, and may be changed in the order of f0, f0 - Δf, and f0 + Δf. Also, changing of the eigenfrequency is not restricted to the above three, and the types of eigenfrequency used in the changing may be increased, such as f0, f0 + Δf, f0 + 2Δf, f0 - Δf, and f0 - 2Δf, and so on. This enables the wavering of eigenfrequency of the vibrating portion 19 to be measured more accurately, and reduced more effectively. This, the eigenfrequency wavering of the vibrating portion 19 of the probe 1 can be reduced according to the present embodiment.

Ionization Method

Next, an ionization method according to the present embodiment will be described with reference to Fig. 3. Fig. 3 is a flowchart illustrating the ionization method according to the present embodiment.

First, the user sets conditions for performing ionization at the apparatus 100 (S301). The conditions set at this time include the vibration frequency of the probe 1 when performing ionization, the number of times of ionization per vibration frequency, the number of measurement points, position information of measurement regions, and so forth. At least two values are preferably set as eigenfrequencies for the probe 1 in the present embodiment, with ionization of the specimen 18 being performed at two different eigenfrequencies.

When the setting of conditions in S301 is completed, the apparatus 100 drives the vibrating unit 2 so as to vibrate the probe 1 (S302).

As described earlier, the liquid supply device 9 disposes the liquid at the end of the probe 1, and the apparatus 100 brings the end of the probe 1 where the liquid has been disposed near or into contact with the specimen 18. This forms the liquid bridge 4 between a partial region of the specimen 18 and the tip of the probe 1 (S303). The matter included in the specimen 18 is dissolved into the liquid making up the liquid bridge 4 at this time.

Next, the end of the probe 1 is brought near the ion extraction electrode 17 by vibrating the probe 1. The probe 1 is vibrated in a state of the liquid forming the liquid bridge 4 remaining adhered to the tip of the probe 1. As the tip of the probe 1 approaches the ion extraction electrode 17, an electro-spray of the liquid is generated by the electric field generated by the electric field generating unit between the ion extraction electrode 17 and the liquid at the tip of the probe 1 (S304).

Just the specimen 18 at the partial region where the liquid at the tip of the probe 1 has come into contact and formed the liquid bridge 4 can be ionized by this first step (S303) and second step (S304). The first step (S303) and second step (S304) are repeated, since the probe 1 is vibrating. The ionization is repeated until a predetermined number of times set in S301 (S305).

Although the number of times of repetition of S303 and S304 is stipulated here by stipulating the number of times of ionization, this is not restrictive. For example, time for performing ionization may be set as a condition set in S301, so that the repetition of S303 and S304 ends when a predetermined amount of time elapses.

Next, the computer 22 determines whether or not to change the vibration frequency of the probe 1 (S306). In a case where the vibration frequency is not to be changed, i.e., in a case where a next vibration frequency is not set in the conditions set in S301, vibration of the probe 1 is stopped (S308).

In a case of changing the vibration frequency of the probe 1, the eigenfrequency of the vibrating portion 19 is changed by the above-described eigenfrequency changing system, thereby changing the vibration frequency of the probe 1 (S305).

This changing of the eigenfrequency of the vibrating portion 19 of the probe 1 and performing the first step (S303) and second step (S304) at different eigenfrequencies is preferably performed at least twice in the present embodiment. Note that the same region is ionized at the different eigenfrequencies here, but this is not restrictive. That is to say, a method where the specimen 18 is ionized by ionizing a certain region at a first vibration frequency and ionizing a different region at a second vibration frequency is also included in the ionization method according to the present embodiment. The ionization apparatus according to the present embodiment may be an ionization apparatus where the eigenfrequency of the vibrating portion 19 of the probe 1 is changed, and ionization is performed at least twice at different eigenfrequencies.

The following is a description of configurations of the changing unit 20 that changes the eigenfrequency of the vibrating portion 19, that are applicable to the present invention.

First Embodiment

The eigenfrequency changing unit according to a first embodiment will be described with reference to Figs. 4A and 4B. Figs. 4A and 4B are schematic diagrams, schematically illustrating the eigenfrequency changing unit according to the first embodiment.

The changing unit 20 according to the present embodiment changes the eigenfrequency of the vibrating portion 19 by changing the length of the vibrating portion 19. That is to say, the changing unit 20 changes the L in Expression (1) to change the eigenfrequency. The changing unit 20 according to the present embodiment includes a fixing unit 31, a screw thread 32, a gear 33, a rotating mechanism 34, and a bearing 35, as illustrated in Fig. 4.

The fixing unit 31 is a portion that fixes the probe 1. That is to say, when the vibrating unit 2 provides vibrations to the probe 1 with the vibrating unit 2 disposed so as to be in contact with the probe 1 being situated closer to the free end of the probe 1 than the position where the fixing unit 31 is situated, the probe 1 vibrates with the fixing unit 31 as the fixed end. In other words, the portion of the probe 1 from the free end to the fixing unit 31 is the vibrating portion 19.

In a case where the vibrating unit 2 is constantly in contact with the probe 1 while the vibrating unit 2 is vibrating, the position at which the vibrating unit 2 is in contact with is the fixed end of the probe 1. In the other hand, in a case where the vibrating unit 2 is not in contact with the probe 1 while the vibrating unit 2 is vibrating, the position at which the fixing unit 31 is disposed is the fixed end of the probe 1. Accordingly, the vibrating unit 2 is disposed so as to be intermittently in contact with the probe 1 while the vibrating unit 2 is vibrating.

The fixing unit 31 has a screw thread of a shape corresponding to the screw thread 32, such that the screw thread of the fixing unit 31 meshes with the screw thread 32. The screw thread 32 is fixed to the probe, so rotating the probe 1 or the fixing unit 31 enables the position of the fixing unit 31 to be moved.

Fig. 4A illustrates the changing unit 20 according to the present embodiment where the position of the fixing unit 31 is moved by rotating the probe 1. The probe 1 is provided with the gear 33 in Fig. 4A, and the probe 1 is rotated by rotating the gear 33 using the rotating mechanism 34. Accordingly, the fixing unit 31 disposed meshing with the screw thread 32 fixed to the probe 1 moves. The fixing unit 31 is the fixed end of the vibrating portion 19, so the length of the vibrating portion 19 changes.

Fig. 4B illustrates the changing unit 20 according to the present embodiment where the position of the fixing unit 31 is moved by rotating the fixing unit 31. The fixing unit 31 is provided with the gear 33 in Fig. 4B, and the fixing unit 31 is rotated by rotating the gear 33 using the rotating mechanism 34. Accordingly, the fixing unit 31 disposed meshing with the screw thread 32 fixed to the probe 1 moves. The fixing unit 31 is the fixed end of the vibrating portion 19, so the length of the vibrating portion 19 changes.

Although the fixing unit 31 can be moved by manually rotating the probe 1 or the fixing unit 31, an arrangement where the fixing unit 31 is rotated by an electric rotating mechanism is preferably, since a certain amount of rotation can be performed quickly and accurately. A stepping motor or the like may be used for the rotating mechanism 34, for example. In this case, the eigenfrequency of the probe 1 can be changed precisely by controlling the number of driving pulses of the stepping motor by the computer 22, based on the relationship between the length L of the probe 1 in Expression (1) and the eigenfrequency.

The screw thread 32 in the present embodiment may be formed integrally with the probe 1 or may be created separately and attached to the probe 1. A material with a high Young's modulus, such as metal for example, may be used as the material for the screw thread 32. However, using a material with too high a rigidity as the material for the screw thread 32 may result in the fixed end of the probe 1 being fixed at the junction point between the probe 1 and the free end side of the screw thread 32. Accordingly, the material of the screw thread 32 used in the present embodiment is preferably a material with low rigidity.

Second Embodiment

The eigenfrequency changing unit according to a second embodiment will be described with reference to Figs. 5A through 5C. Figs. 5A through 5C are schematic diagrams, schematically illustrating the eigenfrequency changing unit according to the second embodiment.

The probe 1 has a weight 41 in the present embodiment. the weight 41 vibrates integrally with the probe 1. That is to say, the vibrating portion 19 according to the present embodiment includes the weight 41. The weight 41 is movable in the longitudinal direction of the probe 1. The eigenfrequency of the vibrating portion 19 is changed by moving the weight 41 in the longitudinal direction of the probe 1 in the changing unit 20 according to the present embodiment. Fig. 5A illustrates a changing unit 20 according to the present embodiment where the weight 41 mounted to the probe 1 can be moved in the longitudinal direction of the probe 1.

The mass of the probe 1 according to the present embodiment is sufficiently light as compared to the mass of the weight 41. Accordingly, the percentage of the mass of the probe 1 as compared to the total mass of the weight 41 and probe 1 is sufficiently small to where it is negligible. Thus, the movement of the weight 41 according to the present embodiment is equivalent to the change of the length L in Expression (1).

That is to say, moving the movable weight 41 mounted to the probe 1 toward the free end increases L, and the eigenfrequency of the probe 1 is lower. At this time, scale marks may be applied in the longitudinal direction of the probe 1, with the eigenfrequency of the vibrating portion 19 when the weight 41 is at each scale mark being correlated with the scale marks. Thus, the eigenfrequency of the vibrating portion 19 can be generally comprehended even without actually measuring the vibration of the probe 1.

The shape of the weight 41 is not restricted in particular. For example, corresponding screw threads may be formed on both the probe 1 and the weight 41 as illustrated in Fig. 5B, for example. This enables the position of the weight 41 on the probe 1 to be controlled precisely. In this case, the weight 41 can be moved in the longitudinal direction of the probe 1 by rotating at least one of the probe 1 and the weight 41.

Now, an arrangement where a screw hole is bored through the weight 41 and a screw thread 46 is formed therein, and the probe 1 is screwed therethrough, is preferable. In a case of moving the weight 41 in the longitudinal direction by rotating the probe 1, a guide rod 44 is preferably provided to control rotation of the weight 41. Multiple guide rods 44 with different hardnesses may be provided, with the guide 44 being replaced according to the eigenfrequency of the probe 1.

The guide rod 44 is disposed so as to be able to suppress rotation of the weight 41. The guide rod 44 may be inserted into the weight 41. Alternatively, the guide rod 44 may be pressed against the weight 41, or the guide rod 44 may be fit into a groove formed in the weight 41. The guide rod 44 does not always have to be in contact with the weight 41, and may be configured to be separated from the weight 41 while the probe 1 is vibrating.

Also, a configuration may be made where the weight 41 is moved in the longitudinal direction of the probe 1 by rotating the guide rod 44, as illustrated in Fig. 5C. In this case, a screw thread 47 is provided to the guide rod 44 and a screw thread corresponding to the screw thread 47 is provided to the weight 41 as well. The probe 1 and the guide rod 44 may be of a configuration so as to be rotated by a mechanism such as that in the first embodiment.

The weight 41 can be moved from the probe fixing unit 16 of the probe 1 to the free end thereof according to the present embodiment. However, there is the possibility that mounting the weight 41 at the free end of the probe 1 may impede generation of the liquid bridge 4 between the probe 1 and the substrate 3, or impede generation of the electro-spray. Accordingly, the movable range of the weight 41 at the free end is preferably up to a position at a certain distance from the free end. Also, providing two or more types of weights 41 and exchanging the weights 41 according to the intended eigenfrequency enables the mass m of the weight in Expression (1) to be changed as well. Accordingly, the range of variation of the eigenfrequency of the vibrating portion 19 can be expanded.

The material of the weight 41 is not restricted in particular. Examples of materials which can be used for the weight 41 include metals, rubbers, wood, or the like, but a metal weight 41 is preferable from the perspective of durability. Also, weights 41 formed of combinations of multiple materials may be used. For example, the portion of the weight 41 which comes into contact with the probe 1 may be formed using a material with a great friction factor, such as rubber for example. This can suppress the weight 41 from moving while the probe 1 is vibrating.

Third Embodiment

The eigenfrequency changing unit according to a third embodiment will be described with reference to Fig. 6. Fig. 6 is a schematic diagram, schematically illustrating the eigenfrequency changing unit according to the third embodiment.

The changing unit 20 according to the present embodiment changes the eigenfrequency of the vibrating portion 19 by attaching a detachable weight 51 to the probe 1. The mounted weight 51 vibrates integrally with the probe 1. That is to say, the vibrating portion 19 according to the present embodiment includes the weight 51. The eigenfrequency of the vibrating portion 19 is changed in the present embodiment by detaching the weight 51, exchanging the weight 51 with one of a different mass, and so forth. That is to say, the eigenfrequency of the vibrating portion 19 is changed in the present embodiment by changing the mass m in Expression (1).

Making the weight 51 that is mounted to the probe 1 heavier causes the m in Expression (1) to become larger, so the eigenfrequency is the vibrating portion 19 is lower. On the other hand, making the weight 51 that is mounted to the probe 1 lighter causes the m in Expression (1) to become smaller, so the eigenfrequency is the vibrating portion 19 is higher. Multiple types of weights 51 with different masses may be prepared as fixed weights 51, with the weight 51 being exchanged according to the intended eigenfrequency.

The weight 51 according to the present embodiment is exchanged each time in accordance with the intended eigenfrequency, so mounting to and detaching from the probe 1 is preferably easy. Accordingly, a weight mounting unit 52 for mounting the weight 51 to the probe 1 is provided in the present embodiment.

The weight mounting unit 52 is provided on at least one position on the probe 1. Multiple weights 51 may be mounted to a single weight mounting unit 52. The location where the weight 51 and weight mounting unit 52 are mounted may be any position on the probe 1. However, mounting at the free end of the probe 1 may impede formation of the liquid bridge 4 between the probe 1 and the substrate 3, or impede generation of the electro-spray, in the same way as with the second embodiment. Accordingly, the weight 51 and weight mounting unit 52 preferably are mounted to portions other than near the free end, so as to avoid impeding formation of the liquid bridge 4 and impeding generation of the electro-spray at the free end.

Mounting the weight 51 in a direction perpendicular to the vibrating direction of the probe 1 may cause the probe 1 to twist, by force in a direction other than the direction of vibration being applied to the probe 1 when vibrating. If the probe 1 twists, controlling the position of the liquid bridge 4 formed between the probe 1 and the substrate 3 to the correct position may be difficult. Accordingly, the center of gravity of the weight 51 and weight mounting unit 52 preferably are mounted so as to be situated on a plane on which the probe 1 vibrates.

The weight mounting unit 52 preferably fixes the weight 51 so that the weight 51 mounted to the weight mounting unit 52 does not move while the probe 1 is vibrating. Examples of methods to mount the weight 51 to the weight mounting unit 52 include screwing, magnets, adhesion, and so forth. The material of the weight mounting unit 52 preferably is metal, from the perspective of durability.

The shape and material of the weight 51 is not restricted in particular. A hollow weight 51 may be used. In this case, the mass of the weight 51 may be changed by changing the amount of fluid, such as a liquid, placed inside the hollow of the weight 51. Further, a weight having multiple hollows may be used, with the mass of the weight being changed by injecting a fluid such as a liquid into an optional number of hollows. In a case of using a weight 51 having a hollow therein, the weight 51 may be fixed to the probe 1.

While the fluid being injected is not restricted in particular, using a fluid with low viscosity may result in the eigenfrequency of the vibrating portion 19 not being constant, since the fluid injected into the weight 51 moves within the hollow when the probe 1 vibrates. Accordingly, the fluid to be injected preferably has a high viscosity. Using combinations of multiple fluids with different specific gravities can extend the range of variation of the mass of the weight 51. Consequently, the range of variation of the eigenfrequency of the vibrating portion 19 can be expanded.

Alternatively, a hollow may be provided in the probe 1 separately from the channel to supply the liquid from the liquid supply device 9. The eigenfrequency of the vibrating portion 19 can be changed by injecting a fluid into this hollow as described above, as well.

Fourth Embodiment

The eigenfrequency changing unit according to a fourth embodiment will be described with reference to Figs. 7A through 7D. Figs. 7A through 7D are schematic diagrams, schematically illustrating the eigenfrequency changing unit according to the fourth embodiment.

A tube-in-a-tube arrangement, where at least two tubes concentrically arrayed, is used as the probe 1 in the present embodiment. The changing unit 20 according to the present embodiment changes the eigenfrequency of the vibrating portion 19 by at least one of the tubes making up the tube-in-a-tube arrangement being moved relative to another tube.

Figs. 7A through 7D are enlarged illustrations of a case where the probe 1 is a tube-in-a-tube arrangement where two tubes are concentrically arrayed, illustrating the free tip side of the probe 1. The probe 1 has a channel to supply liquid supplied from the liquid supply device 9 to the substrate 3 inside the probe 1. The liquid supplied from the liquid supply device 9 is discharged from the tip of the probe 1. Accordingly, of the two tubes making up the probe 1, the one of which the free end is farther away from the fixed side discharges the liquid from the tip thereof. Of the two tubes making up the probe 1, the tube of which the free end is farther from the fixed end of the probe 1 is not moved; just the tube of which the free end is closer to the fixed end of the probe 1 is moved. Accordingly, the eigenfrequency of the vibrating portion 19 can be changed without changing the position where the liquid is discharged from the probe 1, and with the position where the liquid bridge 4 is formed on the substrate 3 being maintained.

An arrangement may be made where, of the two tubes making up the probe 1, the tube of which the position of the free end is farther from the fixed end of the probe 1 is moved. In this case, the computer 22 is used to obtain the amount of change of the position where the liquid bridge 4 is formed, and the specimen stage 8 is controlled based on the amount of change thereof. Accordingly, the eigenfrequency of the vibrating portion 19 can be changed without changing the position on the specimen 18 where the liquid bridge 4 is formed. Alternatively, coordinate information of data may be corrected based on the obtained amount of change.

Fig. 7A illustrates moving, of the tube-in-a-tube arrangement making upon the probe 1, an inner tube 62 in the longitudinal direction of the probe 1, so as to change the eigenfrequency of the vibrating portion 19. Inserting the inner tube 62 having an inner diameter d₂ into an outer tube 61 having an inner diameter d₁ gives an inner diameter d₂ for the tube-in-a-tube arrangement after insertion. Since d₂ is smaller than d₁, the inner diameter d of the probe 1 can be made smaller by inserting the inner tube 62 into the outer tube 61. The smaller the inner diameter d is, the larger the second moment of area I in Expression (2) is, and accordingly, the larger then eigenfrequency of the vibrating portion 19 becomes, according to Expression (1).

On the other hand, Fig. 7B illustrates moving, of the tube-in-a-tube arrangement making upon the probe 1, the outer tube 61 in the longitudinal direction of the probe 1, so as to change the eigenfrequency of the vibrating portion 19. Fitting the outer tube 61 having an outer diameter D₁ onto the inner tube 62 having an outer diameter D₂ gives an outer diameter D₁ for the tube-in-a-tube arrangement after insertion. Since D₁ is larger than D₂, the outer diameter D of the probe 1 can be made larger by fitting the outer tube 61 over the inner tube 62. The larger the outer diameter D is, the larger the second moment of area I in Expression (2) is, and accordingly, the larger then eigenfrequency of the vibrating portion 19 becomes, according to Expression (1).

In this way, a tube-in-a-tube arrangement where at least two tubes concentrically arrayed is used as the probe 1 in the present embodiment to change the relative position of the tubes making up the probe 1. Accordingly, the outer diameter D or the inner diameter d of the probe 1 can be changed, thereby changing the eigenfrequency of the vibrating portion 19.

Note that the vibrating portion 19 according to the present embodiment may have a portion where the outer tube 61 and the inner tube 62 are overlapping, and a portion where these two tubes are not overlapping. That is to say, the vibrating portion 19 may have a single-tube portion, and a tube-in-a-tube portion. In this case, the second moment of area I of the entire vibrating portion 19 can be approximated as a weighted average where the length of each portion is weighted. That is to say, the eigenfrequency of the vibrating portion 19 can be adjusted by adjusting how deep the tubes are inserted. Further, of the tubes making up the probe 1, the wall of the tube that is moved may be tapered in thickness. This arrangement where wall of the tube that is moved is tapered in thickness enables adjustment of the eigenfrequency of the vibrating portion 19 to be adjusted more finely by adjusting the depth of insertion. Fitting another tube on the inside or outside of the tube-in-a-tube arrangement making up the probe 1 to have a tube-in-a-tube arrangement of three tubes or more enables the eigenfrequency of the vibrating portion 19 to be changed even more.

Note that the walls of the tubes that face each other of the at least two tubes or more making up the probe 1 may be provided with a screw thread 65, as illustrated in Fig. 7C. Thus, the depth of insertion of the tubes can be adjusted by rotating at least one tube. The tube to be rotated may be either of the inner tube 62 and the outer tube 61. Rotation of the tube may be performed in the same way as with the first embodiment. The tube which is not to be rotated may be fixed to a portion of the overall apparatus which is not to be moved, so that the tube which is not to be rotated does not rotate with the tube which is to be rotated. A seal material may be provided between the outer tube 61 and the inner tube 62. This, leakage of the liquid flowing through the probe 1 can be prevented from internally leaking.

The material of the tubes, such as the outer tube 61 and inner tube 62, used in the present embodiment, is not particularly restricted. Either an electroconductive material or an insulating material may be used. An arrangement where the tube to be inserted is replaceable, and multiple tubes having different hardnesses being exchanged and inserted, enables the eigenfrequency to be changed further. A rod or a plate not having an internal hollow may be used as the tube to be inserted, and does not have to be concentric with the probe 1, as long as the channel for the liquid is established inside or outside the probe 1.

The outer tube 61 and the inner tube 62 may be tubes where multiple materials are combined and joined. Joined multiple materials can be handled as an integral tube. Fig. 7D is a longitudinal-section drawing in a case of multiple tubes being combined and joined for the outer tube 61 and the inner tube 62. For example, an outer material 66 of the outer tube 61 may be formed using a metal material which is highly durable and which can be machined with precision. An inner material 67 of the outer tube 61 may be formed using a material such as Teflon (a registered trademark) which has a low friction factor and has excellent water repellence and chemical stability. This enables the inner tube 62 to be smoothly inserted into and removed from the outer tube 61, as well as realizing precise control of the eigenfrequency of the probe 1 at the same time.

In the same way as with the case of the outer tube 61, the inner tube 62 may also be a tube where multiple materials are combined. Using a material such as Teflon (a registered trademark) as the outer material 66 in the case of the inner tube 62 enables the inner tube 62 to be smoothly inserted into the outer tube 61. While there is no particular restriction regarding the inner material 67 of the inner tube 62, a resin material which is chemically stable, a metal material with a high Young's modulus, or the like, may be used.

Fifth Embodiment

The eigenfrequency changing unit according to a fifth embodiment will be described with reference to Figs. 8A through 8D. Figs. 8A through 8D are schematic diagrams, schematically illustrating the eigenfrequency changing unit according to the fifth embodiment.

The present embodiment is a structure where a spring 71 is disposed on the outer side or inner side of the probe 1, as illustrated in Fig. 8A or Fig. 8D. The changing unit 20 according to the present embodiment changes the eigenfrequency of the vibrating portion 19 by compressing and expanding the spring 71 using a spring compression mechanism 73.

The changing unit 20 according to the present embodiment includes the spring 71, a spring stopper 72, and the spring compression mechanism 73. Note that the spring 71 according to the present embodiment is disposed such that at least part of the spring 71 vibrates along with the probe 1. That is to say, the vibrating portion 19 according to the present embodiment includes at least part of the spring 71.

The spring compression mechanism 73 has a function to compress and expand the spring 71 in the natural state illustrated in Fig. 8A such as illustrated in Fig. 8B, or a function to twist the spring 71 as illustrated in Fig. 8C.

The spring compression mechanism 73 illustrated in Fig. 8B compresses and expands the spring 71 in the direction of the arrows in Fig. 8B. The changing unit 20 according to the present embodiment can harden the spring 71 by pressing and compressing the spring 71 by the spring compression mechanism 73. When the spring 71 is harder, the Young's modulus E of the vibrating portion 19 increases. On the other hand, the changing unit 20 according to the present embodiment can soften the spring 71 by stretching the spring 71 by the spring compression mechanism 73. When the spring 71 is softer, the Young's modulus E of the vibrating portion 19 decreases.

Thus, the changing unit 20 according to the present embodiment can change the Young's modulus E of the vibrating portion 19 by compressing and expanding the spring 71 using the spring compression mechanism 73. Thus, the eigenfrequency of the vibrating portion 19 can be changed according to Expression (1).

The spring compression mechanism 73 illustrated in Fig. 8C twists the spring 71 in the direction of the arrows in Fig. 8C. By twisting the spring 71 in the direction where the number of coils of the spring decreases, the changing unit 20 can increase the outer diameter of the spring 71. On the other hand, by twisting the spring 71 in the direction where the number of coils of the spring 71 increases, the changing unit 20 can reduce the outer diameter of the spring 71.

That is to say, the changing unit 20 according to the present embodiment can change the outer diameter of the spring 71 by twisting the spring 71. This changes the second moment of area of the spring 71. Note that the overall second moment of area of the vibrating portion 19 combining the spring 71 and the probe 1 is a value obtained by adding the second moment of area of the spring 71 and the second moment of area of the probe 1. Thus, the eigenfrequency of the vibrating portion 19 can be adjusted.

Now, the probe 1 according to the present embodiment needs to have the spring stopper 72 provided to the probe 1 so as to fix the free end of the spring 71 by the spring stopper 72. In a case of compressing and expanding the spring 71 by the spring compression mechanism 73 in Fig. 8B, the spring 71 may be fixed by the spring stopper 72 such that the spring 71 does not go past the spring stopper 72 when being compressed or expanded. On the other hand, in the case where the spring compression mechanism 73 twists the spring 71 such as illustrated in Fig. 8C, the free end of the spring 71 needs to be fixed to the probe 1 by the spring stopper 72 so that the one end of the spring 71 does not rotate. In this case as well, the fixed end of the spring 71 also has to be fixed at the spring compression mechanism 73 side so that the twisted spring 71 does not rotate.

Although the present embodiment has been described regarding an arrangement where the spring 71 is fit onto the outer side of the probe 1, an arrangement may be made where the spring 71 is disposed on the inner side of the probe 1, as illustrated in Fig. 8D.

Sixth Embodiment

The eigenfrequency changing unit according to a sixth embodiment will be described with reference to Fig. 9. Fig. 9 is a schematic diagram, schematically illustrating the eigenfrequency changing unit according to the sixth embodiment.

The changing unit 20 according to the present embodiment changes the eigenfrequency of the vibrating portion 19 by moving the vibrating unit 2 and changing the position where vibration is applied to the probe 1. Note that the changing unit 20 according to the present embodiment vibrates the probe 1 by the vibrating unit 2 vibrating the changing unit 20, and the vibrations thereof being transmitted to the probe 1. As illustrated in Fig. 9, the changing unit 20 according to the present embodiment includes a slide unit 81, a supporting unit 82, a fixing unit 83, and a sliding mechanism 84.

The supporting unit 82 is a portion which supports the vibrating unit 2. The vibrating unit 2 is fixed by the supporting unit 82. The supporting unit 82 is also fixed to the slide unit 81. The slide unit 81 is supported by the fixing unit 83. The sliding mechanism 84 is a portion which slides the slide unit 81, the supporting unit 82, and the vibrating unit 2, in the direction of the arrows in Fig. 9 (the longitudinal direction of the probe 1).

The vibrating unit 2 is disposed so as to constantly be in contact with the probe 1 while vibrating the probe 1 according to the present embodiment. Accordingly, the position where the vibrating unit 2 comes into contact is the fixed end of the probe 1. Thus, the portion of the probe 1 closer to the free end from the position where the vibrating unit 2 comes into contact is the vibrating portion 19. The changing unit 20 according to the present embodiment changes the length of the vibrating portion 19 by changing the position of the vibrating unit 2 using the sliding mechanism 84. Thus, the changing unit 20 according to the present embodiment changes the eigenfrequency of the vibrating portion 19 by changing L in Expression (1).

Seventh Embodiment

The eigenfrequency changing unit according to a seventh embodiment will be described with reference to Figs. 11A through 11D. Fig. 11A is a schematic diagrams, schematically illustrating the eigenfrequency changing unit according to the seventh embodiment.

The changing unit 20 according to the present embodiment includes a probe temperature control unit 101. The probe 1 according to the present embodiment also includes, in at least part of the material making up the probe 1, a thermally hardening material or a thermally softening material. A thermally softening material is a material which becomes softer under application of heat, meaning that the Young's modulus E drops. A thermally hardening material is a material which becomes harder under application of heat, meaning that the Young's modulus rises. Thermoplastic resin or thermally hardening resin can be used for the thermally softening material or thermally hardening material.

The changing unit 20 according to the present embodiment changes the Young's modulus E of the probe 1 by adjusting the temperature of the probe 1 by applying heat to the probe 1 using the probe temperature control unit 101. Accordingly, the eigenfrequency of the vibrating portion 19 can be changed from Expression (1).

A heating unit such as a heater, or a cooling unit such as a Peltier element may be used as the probe temperature control unit 101, and further a heating unit and cooling unit may be combined. A configuration further provided with a thermometer such as a theremocouple or the like can maintain the temperature and an optional temperature.

The probe 1 used in the present embodiment may be a probe fabricated by combining a metal material which has high thermal conductivity and heat resistance, and a thermally softening material. Accordingly, the strength and mechanical precision of the probe 1 can be maintained even if the Young's modulus E is changed by heating or cooling. Figs. 11B and 11C are longitudinal-section views of the probe 1 according to the present embodiment. The probe 1 may be a configuration where the outer side of a metal capillary 102 is covered with a thermally softening material 103 such as illustrated in Fig. 11B, or may be a structure where the thermally softening material 103 is disposed on the inner side of the metal capillary 102 as illustrated in Fig. 10C.

The probe temperature control unit 101 may transmit heat to the entire vibrating portion 19 of the probe 1, or may transmit heat to part of the vibrating portion 19 of the probe 1. The probe temperature control unit 101 preferably is in contact with the probe 1, but does not have to be in contact with the probe 1. An arrangement may be made where the probe temperature control unit 101 is disposed on the electroconductive channel 11 between the probe 1 and the liquid supply device 9, or on the liquid supply device 9, so as to transmit heat to the probe 1 via the liquid, as illustrated in Fig. 11D for example. Note that a fixing unit 104 is the fixed end of the vibrating portion 19 of the probe 1 in Fig. 11D.

Further, the probe temperature control unit 101 may be disposed near the probe 1. In this case, the temperature of gas around the probe 1 is adjusted by the probe temperature control unit 101, thereby adjusting the temperature of the probe 1 by the gas. Alternatively, the probe temperature control unit 101 may be a unit which transmits heat to the probe 1 by radiant infrared rays. Further, the probe temperature control unit 101 may be a unit which applies heat to the probe 1 by irradiation by laser, or irradiating a heat generating member mounted onto the probe by laser to heat the probe 1. Moreover, a configuration may be made where the specimen is heated, heat is transmitted to the probe 1 via the liquid bridge generated between the specimen and the probe 1.

As described above, the probe temperature control unit 101 according to the present embodiment can change the Young's modulus E of the vibrating portion 19 of the probe 1, and thus change the eigenfrequency. The present embodiment may further have the following advantages. That is to say, heating the probe 1 also heats the liquid adhering to the tip of the probe 1, and accordingly the Taylor cone 5 and liquid bridge 4 also are heated. Heating the Taylor cone 5 has an effect of promoting generation of electro-spray from the Taylor cone 5. Also, heating the liquid bridge 4 has an effect of promoting dissolving of the matter in the specimen 18 into the liquid bridge 4. According to the present embodiment, the efficiency of ionization can be improved by either of these effects, as compared to a case where the probe 1 is not heated.

Eighth Embodiment

The eigenfrequency changing unit according to an eighth embodiment will be described with reference to Figs. 12A through 12D. Fig. 12A is a schematic diagrams, schematically illustrating the eigenfrequency changing unit according to the eighth embodiment.

The changing unit 20 according to the present embodiment has a probe rotating unit 121 that rotates the probe 1 in the direction of the arrows in Fig. 12A. The probe rotating unit 121 can be realized by the screw thread 32, gear 33, rotating mechanism 34, bearing 35, and so forth in the first embodiment. The probe rotating unit 121 can rotate the probe 1 in the direction of the arrows in Fig. 12A by an optional angle θ.

The probe 1 according to the present embodiment is a probe where the eigenfrequency differs depending on the direction of vibration. A probe where the Young's modulus E differs depending on the direction of vibration may be used as the probe where the eigenfrequency differs depending on the direction of rotation, or a probe where the second moment of area I differs may be used. A probe where the Young's modulus E differs depending on the direction of vibration may be fabricated using a material of which minute structures differ depending on the direction, or an anisotropic material with different crystalline structures depending on the direction. The probe 1 may be formed using a single material, or may be fabricated by joining multiple materials by adhesion or a like method.

Fig. 12B is a cross-sectional view of the probe 1, applicable to the present embodiment, taken along a plane orthogonal to the longitudinal direction. The probe 1 here is a probe where the second moment of area I differs depending on the direction of vibration.

The arrow 124 in represent the direction of vibration which the vibrating unit 2 applies to the probe 1 (hereinafter "y direction"). The arrows 125 represent the direction of vibration of the probe 1 vibrating by vibrations being applied by the vibrating unit 2. The tilt angle θ indicates how much the direction in which the second moment of area I of the probe 1 (the direction of the dotted line in Fig. 12B) is tilted as to the direction orthogonal to the y direction (hereinafter "x direction"), as illustrated in Fig. 12B.

In the case illustrated in Fig. 12B, the eigenfrequency of the probe 1 in the y direction increases as the tilt angle θ increases, within a range where θ is 0° or greater but 90° or smaller. Controlling the tilt angle θ in the present embodiment enables the second moment of area I of the probe 1 in the y direction to be changed, thereby controlling eigenfrequency of the probe 1 the y direction.

Vibration in the x direction of the probe 1 is preferably suppressed in the apparatus 100 according to the present embodiment, in order to stabilize the position where the liquid bridge 4 is formed on the substrate 3. In the present embodiment, changing the tilt angle θ by tilting the probe 1 may change the position, angle, and/or contact area of the changing unit 20 and the probe 1. Accordingly, vibrations readily occur in the x direction of the probe 1. Accordingly, a guide 126 may be disposed as a vibration suppressing unit to suppress vibration of the probe 1 the x direction, as illustrated in Fig. 12C, thereby stabilizing the vibrations of the probe 1. Vibration of the probe 1 in the x direction can also be suppressed by restricting the range of changing the tilt angle θ to nearby 0° or nearby 90°. Vibrations of the probe 1 in the x direction can be suppressed if the tilt angle θ is 0° or 90°.

If using the guide 126, an arrangement where the spacing (indicated by arrows 128) of the guide 126 is adjustable to an optional distance enables the guide 126 to be used regardless of the width of the probe 1, as illustrated in Fig. 12D. A guide support portion 127 and a guide support rod 129 which support the guide 126 have screw threads formed thereupon in Fig. 12D. The spacing of the guide 126 can be adjusted by rotating the guide support rod 129 by a rotating mechanism using a motor or the like.

Although the guide 126 preferably is disposed at any position from the portion where the probe 1 comes into contact with the changing unit 20 to the tip (free end) of the probe 1, the guide 126 may be disposed between the fixed end of the probe 1 and the portion where the probe 1 comes into contact with the changing unit 20. A wider guide 126 in the longitudinal direction of the probe 1 is preferably, since vibration of the probe 1 in the x direction can be effectively suppressed.

Ninth Embodiment

A mass image display system according to a ninth embodiment will be described with reference to Fig. 1. The mass image display system according to the present embodiment has a mass spectrometry apparatus, the computer 22 which is a mass image generating unit, and a display unit 23. The mass spectrometry apparatus according to the present embodiment includes the apparatus 100 according to any one of the above-described Embodiments 1 through 8, and the mass spectrometry unit 15.

The apparatus 100 ionizes the matter included in the specimen 18 at the region where the liquid bridge 4 is being formed. The generated ions enter the ion intake 7, fly in a gaseous phase state, and reach the mass spectrometry unit 15.

The mass spectrometry unit 15 according to the present embodiment is a time-of-flight mass spectrometry unit. That is to say, the mass spectrometry unit 15 measures the time of ions flying through a vacuum in a flight tube, thereby calculating the mass-to-charge ratio of the ions, and thus performs mass spectrometry of the ionized matter. The mass spectrometry unit 15 may be other known mass spectrometry units besides a time-of-flight mass spectrometry unit, such as a quadrupole type, a magnetic deflection type, ion trap type, ion cyclotron type, or the like.

The computer 22 instructs the specimen stage control unit 13 of the position of the region on the surface of the specimen 18 where to form the liquid bridge 4. The specimen stage control unit 13 controls the position of the specimen stage 8 connected to the specimen stage control unit 13.

The computer 22 obtains the position information of the region where the liquid bridge 4 is formed from the specimen stage control unit 13, and obtains mass information (mass spectrum) of the specimen 18 at that position from the mass spectrometry unit 15. The mass image display system according to the present embodiment changes the position of the region where the liquid bridge 4 is formed by moving the specimen stage 8, performing mass spectrometry at multiple positions on the surface of the specimen 18. The computer 22 uses the multiple mass spectra and position information that have been obtained to form image data representing the distribution of matter contained in the specimen 18.

The eigenfrequency of the vibrating portion 19 may be changed as described above, performing ionization of the specimen 18 at different eigenfrequencies, thereby forming two or more sets of image data.

The computer 22 outputs the formed image data to an image display unit 23 such as a display connected to the computer 22 or the like, thereby displaying the image. Note that the image data may be two-dimensional data or three-dimensional data.

The amount of each matter may be displayed in addition to the position information of the matter, when displaying the image. The amount of matter may be displayed by changing the color or brightness of pixels corresponding to each position, for example. In a case where there are multiple types of matter present in the specimen 18 to be analyzed, each matter maybe displayed in a different color, with the amount of each matter being displayed by changing the brightness.

Also, an arrangement may be made where an optical microscope image of the specimen 18 is obtained beforehand, and a mass spectrometry microscope image obtained by the mass spectrometry apparatus according to the present embodiment are overlaid by the computer 22 and displayed.

Although an image display system has been described having the display unit 23, the display unit 23 is not indispensable. That is to say, an image generating system including the mass spectrometry apparatus and image generating apparatus is encompassed by the present invention.

Each piece of equipment in a system configured by combining multiple pieces of equipment to which the present invention is applied may be partly or entirely connected by a network including the Internet. For example, data obtained by the mass spectrometry apparatus may be transmitted to a server connected to the network, a mass image formed at the server, the results received from the servicer, and image display and the like performed.

Other Embodiments

Although preferred embodiments of the present invention have been described, the present invention is not restricted to these embodiments, and various modifications and alterations may be made within the scope of the essence of the present invention. Also, the above-described embodiments may be carried out in combination with each other.

Example

An example of the present invention will now be described. Mass spectrometry of a specimen was performed using a mass spectrometry apparatus such as illustrated in Fig. 1. A solution where water : MeOH : formic acid is 50:50:0.2 was discharged from the tip of the probe 1 at a rate of 1 nL/minute to perform ionization for mass spectrometry.

The probe 1 used here was that having a movable weight 41 mounted thereto, such as illustrated in Fig. 5A. A glass capillary was used for the probe 1. A rubber piece weighing 0.5 with a hole was used as the movable weight 41. The probe 1 was passed through the hole in the rubber piece, thus mounting the rubber piece to the probe 1. Note that the rubber piece (movable weight 41) was in tight contact with the probe 1, and did not move while the probe 1 was vibrating.

The probe 1 was disposed pressed against the vibrating unit 2. The probe 1 and the vibrating unit 2 were in constant contact while the vibrating unit 2 was vibrating. Accordingly, the vibrating portion 19 according to the present embodiment was the portion between the point of contact with the vibrating unit 2 which is the fixed end, and the tip of the probe 1 which is the free end. The distance from the fixed end to the free end was approximately 2 cm.

Next, the movable weight 41 was manually moved and set to a position 15 mm from the free end. The eigenfrequency of the vibrating portion 19 was measured by the same procedures described above. The eigenfrequency of the vibrating portion 19 with the movable weight 41 set at the position 15 mm from the free end was approximately 500 Hz.

Next, mass spectrometry was performed with a different eigenfrequency for the vibrating portion 19 of the probe 1. The specimen 18 used was a compound of bovine insulin and phosphatidylcholine, coated on a slide glass serving as the substrate 3, and dried. Five samples of the specimen 18 were prepared, each with different compound ratios of the two components. The samples were prepared such that the amount of phosphatidylcholine as to the bovine insulin was 0 eq (sample 1), 0.01 eq (sample 2), 0.1 eq (sample 3), 1 eq (sample 4), and 10 eq (sample 5).

Table 1 illustrates the measurement results of a case where the eigenfrequency of the vibrating portion 19 of the probe 1 was changed, driving the probe 1 at 300 Hz and at 500 Hz. Table 1 illustrates the ion counts of mass-to-charge ratio for each of pentavalent insulin and hexavalent insulin which are generated when ionizing bovine insulin.

In the sample 1 containing no phosphatidylcholine at all, the signals were stronger when the probe 1 was driven at 300 Hz (i.e., the eigenfrequency of the vibrating portion 19 was 300 Hz) for both pentavalent insulin and hexavalent insulin.

However, at the driving frequency of 300 Hz for the probe 1, increase in the amount of phosphatidylcholine in the compound rapidly led to decrease in the insulin signals (sample 2 and sample 3). Further, insulin signals could not be detected in the sample 4 and sample 5 with a large amount of phosphatidylcholine in the compound at the driving frequency of 300 Hz for the probe 1.

On the other hand, at the driving frequency of 500 Hz for the probe 1, the insulin signals were weaker for the sample 1 containing no phosphatidylcholine at all as compared to the driving frequency of 300 Hz for the probe 1.

Also, increase in the amount of phosphatidylcholine in the compound led to decrease in the insulin signals in the same way as with the case of the driving frequency of 300 Hz for the probe 1. However, while insulin signals could not be detected in the sample 4 and sample 5 at the driving frequency of 300 Hz for the probe 1, insulin signals could be detected in the sample 4 and sample 5 at in the case of 500 Hz. It was thus found that in a case where the amount of phosphatidylcholine in the compound is large, insulin signals are more readily detected when driving at 500 Hz as compared to driving at 300 Hz. Moreover, signals of ions originating from phosphatidylcholine were stronger for all samples when driving the probe 1 at 500 HZ than at 300 Hz.

Accordingly, ionization of bovine insulin was performed with the probe 1 being driven at a driving frequency of 300 Hz for the sample containing no phosphatidylcholine, and at 500 Hz for the samples containing no phosphatidylcholine. Ionization of phosphatidylcholine was also performed by driving at 300 Hz. Thus, ionization of an intended compound can be effectively performed by changing the frequency of the probe 1 according to the component to be ionized and the state of the sample.

The eigenfrequency of the vibrating portion 19 of the probe 1 was changed by moving the movable weight 41 in the longitudinal direction of the probe 1 in the present example. Thus, the eigenfrequency of the vibrating portion 19 of the probe 1 was changed without removing the probe 1.

Also, the position where the liquid bridge 4 was formed on the substrate 3 was unchanged before and after changing the eigenfrequency of the vibrating portion 19 of the probe 1. That is to say, the same measurement point was measured even after the eigenfrequency of the vibrating portion 19 of the probe 1 was changed in the mass spectrometry apparatus according to the present example. Accordingly, there was no need to perform calibration regarding the position of the tip of the probe 1 after the eigenfrequency of the vibrating portion 19 of the probe 1 was changed in the present example. Thus, using the mass spectrometry apparatus according to the present example enabled changing of the eigenfrequency of the vibrating portion 19 and mass spectrometry to be performed consecutively, thereby improving efficiency of analysis.

While the present invention has been described with reference to exemplary embodiments, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. The scope of the following claims is to be accorded the broadest interpretation so as to encompass all such modifications and equivalent structures and functions.

This application claims the benefit of Japanese Patent Application No. 2014-141803, filed July 9, 2014, which is hereby incorporated by reference herein in its entirety.

Claims

An ionization apparatus that brings a tip of a probe near to or into contact with a specimen surface, and ionizes the specimen included in a region where the probe has been brought near to or into contact, the ionization apparatus comprising:
a fixing unit configured to fix the probe to the ionization apparatus;
a liquid supply device configured to supply liquid to the tip of the probe;
an ion extraction electrode;
an electric field generating unit configured to generate an electric field between the liquid adhering to the tip of the probe and the ion extraction electrode;
a vibrating unit configured to apply vibrations to the probe, so as to cyclically repeat a state where the liquid adhering to the tip of the probe comes into contact with the specimen and forms a liquid bridge, and a state where the tip of the probe approaches the ion extraction electrode and the liquid flies toward the ion extraction electrode due to the electric field; and
an eigenfrequency changing unit configured to change an eigenfrequency of a vibrating portion of the probe vibrated by the vibrating unit in a state where the probe is fixed to the fixing unit.
The ionization apparatus according to Claim 1,
wherein the vibrating unit applies vibrations of the eigenfrequency to the probe.
The ionization apparatus according to either Claim 1 or 2,
wherein the eigenfrequency changing unit changes the eigenfrequency without changing the position of the region on the specimen where the liquid adhering to the tip of the probe forms the liquid bridge.
The ionization apparatus according to any one of Claims 1 through 3,
wherein the eigenfrequency changing unit changes at least one of length, mass, second moment of area, and Young's modulus, of the vibrating portion of the probe, to change the eigenfrequency.
The ionization apparatus according to any one of Claims 1 through 4,
wherein the probe further includes a weight movable in a longitudinal direction of the probe,
and wherein the eigenfrequency changing unit changes the eigenfrequency by moving the weight in the longitudinal direction of the probe.
The ionization apparatus according to any one of Claims 1 through 4,
wherein the vibrating unit is a unit configured to vibrate the prove by coming into contact with the probe,
and wherein the eigenfrequency changing unit changes the eigenfrequency by changing the position where the vibrating unit comes into contact with the probe.
The ionization apparatus according to any one of Claims 1 through 4,
wherein the probe further includes a weight mounting portion,
and wherein the eigenfrequency changing unit changes the eigenfrequency by mounting and detaching of the weight to the weight mounting portion.
The ionization apparatus according to any one of Claims 1 through 4,
wherein the probe has a hollow portion within the probe,
and wherein the eigenfrequency changing unit changes the eigenfrequency by injecting a liquid into the hollow portion.
The ionization apparatus according to any one of Claims 1 through 4,
wherein the probe is a tube-in-a-tube arrangement including at least two tubes arranged concentrically,
and wherein the eigenfrequency changing unit changes the eigenfrequency by moving at least one tube relative to another tube.
The ionization apparatus according to any one of Claims 1 through 4,
wherein the probe has a structure where a spring is disposed on an inside or an outside of a tube,
and wherein the eigenfrequency changing unit changes the eigenfrequency by compressing and expanding the spring, or twisting the spring.
The ionization apparatus according to any one of Claims 1 through 4,
wherein the probe includes, at least partially, a thermally hardening material or a thermally softening material,
and wherein the eigenfrequency changing unit changes the eigenfrequency by changing the temperature of the probe.
The ionization apparatus according to any one of Claims 1 through 4,
wherein the probe has different eigenfrequencies depending on the direction of vibration,
and wherein the eigenfrequency changing unit changes the eigenfrequency by rotating the probe to change the direction of vibration.
The ionization apparatus according to any one of Claims 1 through 12,
wherein ionization of the specimen is performed at least twice at different eigenfrequencies.
The ionization apparatus according to any one of Claims 1 through 13, further comprising:
a vibration suppressing unit configured to suppress vibration of the probe in directions other than the direction of vibration applied by the vibrating unit.
The ionization apparatus according to any one of Claims 1 through 14, further comprising:
an amplitude measurement unit configured to measure amplitude of vibration of the probe,
wherein the amplitude of vibration of the probe is changed and is measured by the amplitude measurement unit at different eigenfrequencies,
and wherein the eigenfrequency changing unit changes the eigenfrequency to where the amplitude is greatest.
A mass spectrometry apparatus comprising:
the ionization apparatus according to any one of Claims 1 through 15; and
a mass spectrometry unit configured to perform mass spectrometry of the ions generated by the ionization apparatus.
The mass spectrometry apparatus according to Claim 16,
wherein the mass spectrometry unit is a time-of-flight mass spectrometry unit.
An image generating system comprising:
the mass spectrometry apparatus according to either Claim 16 or 17; and
an image generating unit configured to generate an image representing distribution of components included in the specimen, based on mass information obtained by the mass spectrometry unit and position information of the region on the specimen surface.
An image display system comprising:
the image generating system according to Claim 18; and
a display device configured to display the image data as an image.
An ionization method comprising:
creating a first state where liquid adhering to a tip of a probe comes near to or into contact with a specimen and forms a liquid bridge as to the specimen, the liquid bridge containing matter included in the specimen; and
creating a second state where the tip of the probe approaches an ion extraction electrode of the probe by the probe being vibrated, and the liquid flies toward the ion extraction electrode due to an electric field generated between the ion extraction electrode and the tip of the probe,
wherein both of the creating of the first state and the creating of the second state is performed at different eigenfrequencies by changing the eigenfrequency of a vibrating portion of the probe without removing the probe from an apparatus proper to which the probe is affixed.