JP2005098909A - Ionizer and mass spectrometer using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an ionization device for conducting soft ionization of the minute region of a sample, and to provide a mass spectrometer which uses the ionization device. <P>SOLUTION: In the mass spectrometer, having an ionization section 11 and a mass analyzer section 12, the ionization section 11 comprises a probe 20 made of a conductive material; and a laser light source 40. A probe tip 21 is directed toward the measurement part of the sample, the laser light source 40 is mounted for generating a proximity field light at the measurement part by irradiating the probe tip 21 with laser beams, and a sample 31 at the measurement part is excited by the proximity field light for ionization, thus guiding the ions to the mass analyzer section 12. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

The present invention relates to an ionization apparatus that ionizes a sample, and more particularly, to an ionization apparatus that ionizes a sample by narrowing the range to a fine region that is equal to or less than the wavelength of light.
The present invention can be used as an ion source of an analyzer that extracts and measures ions, for example, a mass spectrometer.
The present invention also relates to an analyzer for mapping and displaying an analysis result for each fine region, mainly to a mass spectrometer.

  Imaging mass spectrometry, which performs mass analysis of the sample while scanning the measurement position along the sample surface and displays the two-dimensional distribution data of the mass analysis results, provides information on the distribution of small molecules, polymers, and metal elements. It is used in many fields such as biotechnology, microelectronics, material science, geology, and surface science.

As a typical imaging mass spectrometry conventionally performed, sputtering is performed on the surface of a material using high-energy ions of several tens of KeV, and secondary ions ejected from a sample are detected (secondary ions). Mass spectrometry).
In SIMS analysis, an image with a high spatial resolution can be obtained by using Ga ions as a primary ion beam to obtain a very thin beam diameter of about 20 nm.
A sample having a relatively large molecular weight such as an organic substance can be measured by TOF-SIMS measurement in which SIMS and TOF (time-of-flight mass spectrometer) are combined.

  In recent years, it has been required to perform the same imaging for a polymer sample having a higher molecular weight or a sample in the bio field. However, in such a sample, it is necessary to perform soft ionization so that the sample is not broken during the ionization process. is there. However, when the ion beam as described above is used, the polymer sample or the sample in the bio field is damaged, and necessary information cannot be obtained.

Therefore, when a polymer sample or a sample in the bio field is handled, a method is used in which after adding an additional reagent to the sample, laser pulse light is condensed on the sample surface, and the sample is scattered and ionized.
This additional reagent is used to digest or divide the sample, and conversely, to prevent damage during ionization. In this way, after pretreatment with an additional reagent, mass distribution imaging data is obtained by performing mass analysis at a large number of measurement points while scanning a stage on which a laser light source or a sample is placed.

When laser ionization is used, laser light can be irradiated in a pulsed manner, and the mass of a sample is large, so that it is generally combined with a TOF type mass spectrometer (see, for example, Patent Document 1).
The condensing size of the laser beam used for TOF is several hundred micrometers because of the amount of scattered ions necessary for analysis, and even if it is condensed, it is at most about 1 micron due to the diffraction limit of light. Although a micron-sized mass distribution in a sample can be obtained, micron-sized resolution is insufficient to directly measure the intracellular mass distribution as currently required.
JP 9-320515 A

  As described above, in the conventional mass spectrometer, there is no ionization method capable of soft ionization with a fine size of micron or less, and for example, it is difficult to directly observe the intracellular mass distribution. If you want to see the mass distribution of each microscopic area in the cell, sample it in advance using another method, transfer it to another substrate, and increase the sample area. Since it is necessary to perform the measurement, much time and labor are required for the measurement. In addition, contamination by contamination and damage caused by contamination in the sample transfer process, etc., making it difficult to perform accurate mass distribution imaging with high position resolution.

  Therefore, the present invention can softly ionize each micron or smaller size, and performs ionization at a micron or smaller size, even for samples that are susceptible to damage such as cells and polymer samples. It is an object of the present invention to provide a mass spectrometer capable of performing the above.

  It is another object of the present invention to provide a mass spectrometer capable of obtaining a mass distribution from a soft ionized sample having a fine size of micron or less.

The ionization apparatus of the present invention made to solve the above-described problem has a probe formed of a conductive material or coated with a conductive material and a laser light source, and the tip of the probe is close to the measurement site of the sample. The laser light source is attached so as to irradiate the tip of the probe with laser light to generate near-field light at the measurement site, and ionizes the sample by exciting the sample at the measurement site with near-field light. I am doing so.
In addition, the ionization apparatus is used as an ionization unit to perform mass spectrometry.

According to the ionization apparatus of the present invention, near-field light is generated in the vicinity of the probe tip by irradiating the conductive probe tip with laser light. The near-field light can greatly increase the energy intensity compared to the excitation by the irradiation laser due to the surface enhancement effect by the plasmon excitation. In addition, this effect causes the electric field to rapidly decrease as the distance increases, and a high electric field is generated in a local region smaller than the light wavelength size.
The local high electric field generated by the near-field light can excite and ionize the sample in the high electric field, so by ionizing the sample using the high electric field generated by the near-field light, it is much more than the laser wavelength. Only molecules within a very small size region can be softly excited and ionized.
And according to the mass spectrometer which used this ionization apparatus as the ionization part, the mass analysis data of the micro area | region which is not until now can be obtained by guide | induced the produced | generated ion to a mass analysis part.
Thereby, even a polymer sample or a sample in the bio field can be subjected to mass spectrometry with nano-order resolution.

In addition, the probe tip has a pore, and the inside of the probe is hollow so that excited ions or neutral molecules can pass through the probe and exit to the base side of the probe. You may be made to do.
According to the present invention, ions or neutral molecules excited by near-field light and ejected from the sample pass through the hollow space in the probe from the pore at the tip of the probe and exit from the base side of the probe. As a result, ions etc. can be sent directly to the mass analyzer from directly above the sample, which is the direction in which most of the ions etc. generated by the near-field light formed at the tip of the probe jump out. It can be performed.
Usually, such a probe is used along the surface of the sample to obtain sample information on the surface, but such a hollow probe can be inserted into the sample to obtain sample information on a specific area inside the sample. . The near-field light generated at the tip of the probe can generate a local near-field even inside the sample by devising the wavelength and the probe shape.

In addition, the stage surface of the probe further includes an XY direction control unit that relatively changes the probe position along the XY direction, an XY direction position sensor that detects the position of the probe in the XY direction, and a display unit. The direction position and the mass spectrometry result may be associated with each other and displayed on the display unit.
According to the present invention, the probe position is scanned relative to the sample in the XY direction by the XY direction control unit, and the probe position is monitored by the position sensor. Can be accurately obtained together with the position information, and the mass spectrometry data can be displayed together with the position information.

The probe outputs information depending on the distance between the probe tip and the sample, and outputs image data as a scanning probe microscope (SPM) based on the information depending on the distance between the probe tip and the sample. An image processing unit may be provided.
According to the present invention, since the probe also functions as an SPM probe, the SPM image and the mass distribution can be obtained in association with each other.

Also, a Z direction control unit that relatively changes the probe position along the Z direction, and a Z direction that detects the position of the probe in the depth direction in the sample when the tip of the probe is inserted into the sample. A position sensor and a display unit may be further provided, and the position in the depth direction of the probe and the mass analysis result may be associated with each other and displayed on the display unit.
According to the present invention, by changing the depth position of the probe tip relative to the sample, not only the sample surface but also the probe can be inserted into the sample to generate near-field light. The mass distribution data of the fine region can be measured, and the mass distribution data can be displayed together with the position information in the depth direction.

  The best mode for carrying out the present invention will be described below with reference to the drawings. The embodiment described below is merely an example, and modifications can be made without departing from the scope of the present invention.

FIG. 1 is a diagram showing an overall configuration of an ionization apparatus according to an embodiment of the present invention and a mass spectrometer connected thereto, and FIG. 2 is an enlarged view of a probe portion of the ionization section.
The mass spectrometer 10 mainly comprises an ionization unit 11, a TOF type mass analysis unit 12, and a computer 13 for controlling the entire apparatus and processing data. A display unit (not shown) (for example, a CRT or a liquid crystal panel) is connected to the computer 13, and various inputs / outputs are performed while viewing the screen of the display unit, or a surface observation image of the sample is displayed on the display unit screen as will be described later. Can be displayed.

First, the structure of the ionization part 11 is demonstrated. The ionization unit 11 includes a probe 20, a stage 30 on which a sample 31 is placed, and a laser light source 40.
The probe 20 is made of a conductive material such as metal, and has a hollow cone-shaped portion with a sharp tip 21 and a root 22 extending. An opening 26 is formed at the tip 21, and a light scatterer 24 made of a fine metal sphere is attached so as to surround the opening 26. The light scatterer 24 promotes the generation of near-field light in the vicinity of the tip 21 by generating scattered light when this portion is irradiated with laser light.
The root side 22 becomes an arm portion 23, and the arm portion 23 is fixed to a support member 27. The support member 27 is provided with a Z-direction drive unit 28 for driving the probe 20 in the Z-axis direction (vertical direction). The Z-direction drive unit 28 is controlled by a Z-direction control unit 29 of the computer 13.

  The stage 30 is made of a translucent member such as glass (or light transmitted to the stage) so that the sample 31 can be irradiated with laser light from below the stage 30 (the laser light source and laser optical system will be described later). May be provided). The stage 30 is provided with an XY direction drive unit 32 for moving the sample in the XY direction (stage surface direction). The XY direction drive unit 32 is controlled by an XY direction control unit 33 of the computer 13.

  Further, an optical lever type position sensor 45 used for detecting the position of the probe 20 in the Z direction and the XY direction is attached to the arm portion 23. The position of the probe 20 is detected and the Z direction control unit is detected. 29, position information is sent to the XY direction control unit 33.

  The probe 20 also functions as a probe of a scanning probe microscope (SPM) such as a scanning tunneling microscope (STM) or a scanning atomic force microscope (AFM). When functioning as a microscope (STM), a tunnel current amplifying unit 46 detects a tunnel current flowing between the tip of the probe 20 and the sample 21, and sends detection data to the image processing unit 47 to obtain a surface observation image. It is supposed to be.

An objective lens 34 is attached below the stage 30. The objective lens 34 is provided with an objective lens driving unit 35 that drives the objective lens 34 in the Z direction (vertical direction). The objective lens driving unit 35 is controlled by the objective lens control unit 36.
This objective lens 34 is used for the following two purposes. First, the laser beam sent from the laser light source 40 to the objective lens 34 via the half mirror 41 is used to focus on the vicinity of the probe tip 21. When the laser beam is focused in the vicinity of the probe tip 21, near-field light is generated in the vicinity of the probe tip due to the interaction between the laser beam and the probe tip 21.
Second, the objective lens 34 is used to guide the image of the measurement site near the probe tip 21 to the optical detector 43 via the half mirrors 41 and 42 and observe the optical image of the measurement site. Alternatively, it is used to observe a confocal observation image by providing a detector at the confocal position of the objective lens 34.

  Therefore, the ionization unit 11 having the above-described configuration serves as a scanning probe microscope that displays the surface observation image of the sample using near-field light as well as the original function as an ion source that ionizes the sample using near-field light. It has a structure that combines functions.

Next, the configuration of the mass analyzer 12 will be described. The mass analyzer 12 performs mass analysis by an ion lens 51 that extracts ions that have passed through the hollow structure portion of the probe 20, an ion lens 52 that bends the traveling direction of ions extracted by the ion lens 51, and the TOF method. A flight space 53 provided with ion optical system parts such as a mirror for the purpose, and an ion detector 54 for detecting ions flying in the flight space 53.
Note that the mass spectrometer is not limited to the TOF as long as measurement is possible, and other types of mass analyzers (for example, an ion trap mass analyzer, a quadrupole mass analyzer, etc.) may be used.
The operation of the mass analysis unit 12 is controlled by the mass analysis control unit 55 of the computer 13.

  In the configuration of the mass spectrometer described above, at least the mass analyzer 12 is maintained in a high vacuum state in the vacuum vessel. The ionization unit 11 as a whole is also preferably used in a vacuum atmosphere in terms of suppressing noise, but if used in a vacuum atmosphere, the operation mechanism becomes complicated. Since ionization does not necessarily require a vacuum state, the sample 31 is ionized at atmospheric pressure by partitioning the ionization unit 11 and the mass analysis unit 12 with a partition wall having pores. Alternatively, ionization may be performed in a desired gas atmosphere so that only generated ions are guided from the pores to the mass analyzer 12.

Next, the operation when performing mass spectrometry using the above apparatus will be described.
A sample 31 is placed on the stage 30 and a surface observation image of the sample is acquired by a normal SPM measurement procedure. At this time, the positional information from the position sensor 45 is acquired at the same time, the positional relationship between the surface observation image and the probe 20 is obtained, and the positional relationship with the surface observation image is grasped when the probe 20 is scanned later. Keep it available.

  The XY direction driving unit 32 and the objective lens driving unit 35 are controlled by the optical image of the optical detector 43 or while confirming the observation image by the SPM measurement, so that the objective lens 34 is focused on the measurement position of the sample. Then, the Z-direction drive unit 28 is controlled so that the tip 21 of the probe 20 is brought close to the measurement position so that near-field light is generated at the measurement position.

  The mass spectrometer 12 is set in a standby state to wait for ions to come. In this state, the pulsed laser is irradiated from the laser light source 40 to the tip 21 region of the probe 20 to start measurement. Thereby, near-field light is generated in the probe tip 21 region, the sample is excited, and ions are ejected. The ions that have jumped out are guided to the flight space 53 by the ion lenses 51 and 52 and eventually reach the detector 54. The time-of-flight data of the ion at this time is measured to determine the ion mass.

  When the measurement at the first measurement point is completed, the stage 30 is driven to adjust the focus of the objective lens 34 and the probe tip 21 to the next measurement point. When the mass spectrometer 12 enters the standby state, the second measurement is performed in the same procedure. Thereafter, the driving and measurement of the stage 30 are similarly repeated, and two-dimensional mass distribution data of the sample is acquired.

  Subsequently, data processing for associating the positional relationship between the obtained mass distribution data and the previously obtained surface observation image is performed. As a result, correlation data between the surface observation image by SPM and the mass distribution data can be obtained.

The above operation scans the stage 30 and acquires mass distribution data in the XY directions. The depth is obtained by scanning the probe 20 and the objective lens 34 in the Z direction and performing the same measurement as described above. It is also possible to acquire mass distribution data in the direction (Z direction).
That is, the scanning direction of the probe 20 in the Z direction by the Z direction driving unit 28 and the scanning of the objective lens 34 in the Z direction by the objective lens driving unit 35 are performed in conjunction with each other, whereby the generation position of the near-field light is determined. The mass distribution data in the Z direction is acquired by moving the ion generation position in the depth direction by changing in the Z direction.

  It is also possible to acquire the three-dimensional mass distribution data of the sample by sequentially measuring the mass distribution data in the XY direction and the quality distribution data in the Z direction.

  FIG. 3 is a diagram showing a configuration of an ionization unit of a mass spectrometer that is another embodiment of the present invention. In FIG. 3, the same components as those in FIG. In this embodiment, the laser light source 40 is provided above the stage 30 on which the sample is placed.

In the present embodiment, since the probe 20 exists just above the sample 31 placed on the stage 30, the objective lens 34 is installed obliquely upward so that the probe 20 and the objective lens 34 do not interfere with each other. . Laser light from the laser light source 40 is sent to the objective lens 34 via the half mirror 41, and an optical image of the sample is sent to the optical detector 43 via the objective lens 34 and the half mirror 41. The objective lens 34 is driven by an objective lens driving unit 35.
The probe 20 is brought close to the measurement site, and the objective lens 34 irradiates laser light toward the probe tip 21, thereby causing ions excited by the near-field light to jump out of the sample 31 as in FIG.

  Also in this embodiment, if the probe 20 having the same shape as that shown in FIG. 1 is used, it is possible to send ions that have passed through the hollow portion in the probe to the mass spectrometer. The ion lens 51 for extracting ions is provided obliquely above the sample 31 (see FIG. 3), and the ions are excited by a probe having another shape. .

  FIG. 4 is a diagram showing the configuration of the tip 21 of the probe 20 used in the mass spectrometer of FIG. The tip 61 sharpens the tip of the optical fiber 62, forms a metal coating surface 63 on the peripheral portion of the fiber excluding the tip, and further provides a minute scatterer 64 on the tip, The near-field light is blurred in the vicinity of the scatterer 64 by irradiating the scatterer 64 with the laser beam 65 from above.

  FIG. 5 is a diagram showing another configuration of the tip 21 of the probe 20 used in the mass spectrometer of FIG. The tip 66 sharpens the metal wire 67 and is provided with a minute scatterer 68 at the forefront. By irradiating the scatterer 68 with laser light 69 from the outside, near-field light is generated in the vicinity of the scatterer 68. It is to blur.

In the case of a probe having the most advanced aperture as shown in FIG. 4, near-field light in a local area of about 100 nm is obtained, and in a scattering system as in FIG. 5, near-field light in a local area in the range of several tens of nm is obtained.
Since near-field light is greatly attenuated in the Z-axis direction, the affected area of near-field light can be further limited by changing the position of the tip of the probe with respect to the sample in the Z direction.

  FIG. 6 is a diagram showing the tip shape of a probe used in a mass spectrometer of another type. The tip 71 of the probe sharpens the tip of the optical fiber 72 in the same manner as in FIG. 4 to form a metal coating surface 73 on the peripheral portion of the tip excluding the leading edge, and a minute scatterer 74 on the leading edge. Is provided. However, the laser beam 75 causes near-field light to bleed in the vicinity of the scatterer 64 so as to travel in the fiber from the other end of the fiber. In this case, it is not necessary to irradiate the laser beam through the objective lens 34, and adjustment of the laser irradiation position by the objective lens becomes unnecessary.

  FIG. 7 shows a type in which laser light is irradiated from the other end side of the optical fiber in the same manner as FIG. 6. The tip 76 has a metal coating surface 78 formed around it, and the tip of the fiber 77 is cut out flat. A sharp metal probe 79 is provided on the flat surface. The tip 76 does not require adjustment of the laser irradiation position by the objective lens, and can also limit the area of near-field light.

  The tip 81 in FIG. 8 irradiates the metal probe 84 with the laser light 85 using lens optical systems 82 and 83 instead of the optical fiber. In FIGS. 7 and 8, optical components are arranged on the same axis, and the laser beam is guided to the tip of the probe.

  Although several probe tip shapes have been described above, the present invention can be applied to other probe tips as long as the sample can be ionized by diffusing near-field light at the probe tip. Can be realized.

  Since the present invention can extract softly ionized ions from a nano-order minute region in the ionization process of the mass spectrometer, it can be used as a mass spectrometer capable of obtaining high-precision mapping for polymers and biosamples. Useful.

The block diagram of the apparatus for mass spectrometry which is one Example of this invention. The enlarged view of the probe part of the mass spectrometer which is one Example of this invention. The block diagram of the ionization part of the mass spectrometer which is another Example of this invention. The figure which shows the shape of a probe tip. The figure which shows the shape of a probe tip. The figure which shows the shape of a probe tip. The figure which shows the shape of a probe tip. The figure which shows the shape of a probe tip.

Explanation of symbols

10: Mass spectrometer 11: Ionization unit 12: Mass analysis unit 20: Probe 21: Tip 24: Scattering body 26: Aperture 28: Z direction drive unit 29: Z direction control unit 30: Stage 31: Sample 32: XY direction Drive unit 33: XY direction control unit 34: objective lens 35: objective lens drive unit 36: objective lens control unit 40: laser light source 43: optical detector 45: position sensor 46: tunnel current amplification unit 47: image processing unit 51: Ion lens

Claims (6)

A probe formed of a conductive material or coated with a conductive material and a laser light source;
The tip of the probe is installed in the vicinity of the measurement site of the sample, and the laser light source is attached so as to irradiate the probe tip with laser light and generate near-field light at the measurement site.
An ionization apparatus characterized in that a sample at a measurement site is ionized by exciting the sample with near-field light. A mass spectrometer characterized in that the ionizer is an ionizer. The probe is formed in a hollow so that a pore is formed at the tip of the probe and excited ions or neutral molecules can pass through the probe from the pore and exit to the base side of the probe. The ionization apparatus according to claim 1. An XY direction controller that relatively changes the probe position along the XY direction, which is the surface direction of the stage on which the sample is placed;
An XY direction position sensor for detecting the position of the probe in the XY direction;
A display unit,
The mass spectrometer according to claim 2, wherein the position of the probe in the stage surface direction and the mass analysis result are displayed in association with each other on the display unit. The probe outputs information depending on the distance between the probe tip and the sample and outputs image data as a scanning probe microscope (SPM) based on the information depending on the distance between the probe tip and the sample. The mass spectrometer according to claim 4, further comprising an image processing unit. A Z direction control unit that relatively changes the probe position along the Z direction orthogonal to the XY direction;
A Z-direction position sensor for detecting the position of the probe in the depth direction in the sample when the tip of the probe is inserted into the sample by control in the Z direction;
A display unit,
The mass spectrometer according to claim 2, wherein a position in the depth direction of the probe and a mass analysis result are displayed in association with each other on the display unit.

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