JP2011034900A - Mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To increase a generated/collected ion amount by irradiating a laser light from upward nearly perpendicular to a sample, improve utilization efficiency of ions by transporting the collected ions to a mass spectrometer without waste, and improve analytical sensitivity as a result. <P>SOLUTION: Along the center axis C orthogonal to a sample plate 3 surface, an ion transportation optical system such as ion lenses 5, 6, an ion trap 7, and a mass separation/detection part such as a detection part 9 are arranged, and an ion optical axis matches the center axis C. A laser irradiation part 10 including a laser light source 11, and lenses 12, 13, 14 is arranged on the center axis C at a position further away from the detection part 9 as the farthest site from the sample S, and a light axis of the laser light matches the center axis C. The laser light which is emitted from the long focus lens 14 and of which the light flux diameter is gradually narrowed passes through an emission port 75 and an incident port 74 or the like, and hits the sample S without interception. Moreover, the ions discharged from the sample S is introduced into the ion trap 7 and placed for mass analysis without flection. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a mass spectrometer, and more particularly to a mass spectrometer using an ion source that irradiates a sample with laser light to ionize the sample.

  Various ionization methods are known as ion sources for mass spectrometers. Laser desorption / ionization (LDI = Laser Desorption / Ionization) is a method in which a sample is irradiated with laser light, and ionization is performed by accelerating the movement of charges inside the substance that has absorbed the laser light. Matrix Assisted Laser Desorption / Ionization (MALDI) absorbs laser light to analyze samples that are difficult to absorb laser light and samples that are easily damaged by laser light, such as proteins. A material that is easy to ionize and is easily ionized is mixed in advance in the sample as a matrix, and the sample is ionized by irradiating the sample with laser light. In particular, a mass spectrometer using MALDI can analyze a polymer compound having a large molecular weight without much cleavage, and is also suitable for microanalysis. Has been used.

  For example, Non-Patent Document 1 discloses a schematic configuration of an ion trap time-of-flight mass spectrometer using a MALDI ion source. In this apparatus, an ultraviolet laser beam having a wavelength of 337 nm emitted from a laser light source is focused to a minute diameter and irradiated onto a sample. At that time, in order not to obstruct the path of the ions emitted from the sample, the laser is irradiated so that the laser beam strikes from an oblique direction with an angle of about several degrees from the direction orthogonal to the sample (normal direction). An irradiation optical system is configured. On the other hand, ions generated from the sample are extracted in the normal direction of the sample, converged by an ion transport optical system such as an ion lens, and then introduced into a three-dimensional quadrupole ion trap.

  However, when the laser beam is incident obliquely on the sample, the proportion of ions emitted from the sample in a direction different from the normal direction is relatively increased. Therefore, the efficiency of ions used for mass spectrometry is not necessarily the best, and this contributes to a decrease in analysis sensitivity.

  In order to increase the efficiency of ions used for mass spectrometry, it is preferable to irradiate laser light from the normal direction of the sample. In the mass spectrometer described in Patent Document 1, the laser beam is incident on the sample from the normal direction, while the method is performed from the sample in order to avoid interference between the laser irradiation optical system and the ion path. While collecting ions released in the linear direction, the ion path is bent by an electric field while being transported to the mass spectrometer. However, bending the progression of ions using an electric field or the like in this way is likely to cause loss of ions in the process, and eventually, the amount of ions used for mass spectrometry is reduced, increasing the analysis sensitivity. There is a problem that is difficult.

Special table 2007-514274 gazette

Koichi Tanaka and one other, "Trial of top-down proteomics analysis method using MALDI-QIT-TOF MSn", Shimazu review, Shimadzu editorial department, Vol. 61, No. 1, No. 2, October 30, 2004 Issue

  The present invention has been made in order to solve the above-mentioned problems, and its object is to irradiate a sample with laser light for ionization from its normal direction, and from the sample to its normal direction. It is an object of the present invention to provide a mass spectrometer capable of improving analysis sensitivity by collecting ions released mainly from the center and efficiently using them for mass spectrometry.

In order to solve the above problems, the present invention includes a laser irradiation unit that irradiates a sample placed on a sample plate with a laser beam, and ions derived from the sample generated by the irradiation of the laser beam. In a mass spectrometer comprising: a mass separation / detection unit for mass spectrometry; and an ion transport optical system that transports ions from the sample to the mass separation / detection unit,
The ion transport optical system and the mass separation / detection unit include an ion optical axis when ions travel from the sample plate surface to the mass separation / detection unit along a central axis perpendicular to the surface of the sample plate. Arranged so that the central axis coincides and a part of the components does not block the central axis,
The laser irradiator further includes a portion farthest from the sample in the ion transport optical system and the mass separation / detector so that the optical axis of the laser light emitted from the irradiator coincides with the central axis. It is characterized by being arranged at a distant position.

  As a sample plate for placing a sample, a conductive substrate having a substantially flat surface, a conductive substrate having a microwell formed at a sample placement position on a substantially flat surface, or the like is used.

  In addition, for example, an ion transport optical system is called an ion lens, an ion guide, etc., and by the action of an electric field, ions are converged, ions are accelerated / decelerated, or ions are temporarily captured / To hold or to hold. The mass separation / detection unit separates and detects ions according to the mass to charge ratio m / z.For example, a combination of an ion trap and a detector, a combination of a time-of-flight mass separator and a detector, A combination of a quadrupole mass filter and a detector is conceivable.

  The mass spectrometer according to the present invention can be applied to an apparatus that performs ionization by laser desorption ionization (LDI), and more practically, an apparatus that performs ionization by matrix-assisted laser desorption / ionization (MALDI). .

  The laser irradiation unit includes at least a laser light source and a long-focus laser optical system for narrowing a laser beam having a predetermined beam diameter to a minute beam diameter that can be regarded as one point or one point on the sample surface. Can do. In general, ion transport optics are configured so that ions generated from the sample are transported to the mass separation / detection unit with the highest efficiency, but the ion transport optical system has an ion passage opening until it reaches the sample. The laser irradiation unit may be configured so that a light beam whose diameter is gradually reduced is not blocked.

  According to this, components for mass analysis of ions such as an ion transport optical system and a mass separation / detection unit are arranged between the laser irradiation unit and the sample, but the laser emitted from the laser irradiation unit The light strikes the sample without being blocked by the components as described above. Since the optical axis of this laser beam coincides with the central axis perpendicular to the surface of the sample plate, the sample placed on the sample plate is exposed to the laser beam from substantially vertically above, and from the sample, The largest amount of ions is released in a substantially vertically upward direction. The ions thus released are efficiently collected by the ion transport optical system and reach the mass separation / detection unit. The ion optical axis is also coincident with the central axis perpendicular to the sample plate surface, and the direction of ion travel is not bent until it is subjected to mass analysis, so there is less loss of ions during transport and a larger amount of ions. Can be subjected to mass spectrometry.

  In the mass spectrometer according to the present invention, when a three-dimensional quadrupole ion trap is included as an ion transport optical system or a mass separation / detection unit, an ion incident port and an ion provided in an end cap electrode of the ion trap The ion trap may be arranged so that the center of the exit port coincides with the central axis. That is, in this configuration, the laser beam emitted from the laser irradiation unit enters the inside of the three-dimensional quadrupole ion trap from the ion emission port, passes through the ion emission port, and exits from the ion incident port toward the sample. Therefore, if the beam diameter of the laser beam when passing through the ion emission port is made smaller than the opening diameter of the ion emission port, the laser beam is irradiated onto the sample without being blocked by the ion trap.

  According to the mass spectrometer of the present invention, the laser beam can be irradiated so as to be substantially orthogonal to the sample, so that more ions derived from the sample are emitted in the direction orthogonal to the surface. Further, since the irradiation intensity of the laser beam is almost uniform on the sample surface, an increase in the amount of ions generated can be expected. In addition, ions emitted from the sample can be efficiently collected, transported while suppressing loss, and subjected to mass spectrometry. Thereby, the amount of ions finally subjected to mass spectrometry increases as compared with the conventional case, so that the analysis sensitivity can be improved.

The whole MALDI-IT-MS block diagram by one Example of this invention. The conceptual diagram for demonstrating the design method of a laser irradiation optical system. The conceptual diagram for demonstrating the design method of a laser irradiation optical system. The whole MALDI-IT-TOFMS block diagram by the other Example of this invention.

  MALDI-IT-MS, which is an embodiment of the present invention, will be described with reference to the accompanying drawings. FIG. 1 is a schematic configuration diagram of a MALDI-DIT-MS according to the present embodiment.

  Inside the vacuum chamber 1 to be evacuated, a flat plate-like conductive sample plate 3 on which the sample S to be analyzed is placed is disposed, and a central axis (center in the present invention) orthogonal to the sample plate 3 is disposed. Aperture 4, first ion lens 5, mirror 8, second ion lens 6, ion trap 7, and detector 9 are arranged in this order along axis C), and do not obstruct center axis C and are coaxial. Are arranged as follows.

  The mirror 8 reflects the surface image of the sample S on the sample plate 3, and this image is taken out of the vacuum chamber 1 and photographed by the CCD camera 16. This captured image is displayed on a monitor or the like (not shown), whereby the user can observe the surface of the sample S.

  The ion trap 7 is a three-dimensional quadrupole ion trap, and has an annular ring electrode 71 having an inner circumferential surface having a rotating single-leaf hyperboloid shape, and an inner circumference arranged to face the annular ring electrode 71. The surface includes a pair of end cap electrodes 72 and 73 having a rotating two-leaf hyperboloid shape. An ion incident port 74 is formed at approximately the center of the entrance end cap electrode 72 and an ion exit port 75 is formed at approximately the center of the exit end cap electrode 73. The centers of the ion incident port 74 and the ion exit port 75 are provided. Is inserted through the central axis C. The detection unit 9 includes an aperture 91 that limits the passage range of ions, a conversion dynode 92 that converts ions into electrons, and a secondary electron multiplier 93 that multiplies and detects the converted electrons. The conversion dynode 92 and the secondary electron multiplier 93 are disposed to face each other with the central axis C interposed therebetween.

  A transmission window 2 made of quartz glass or the like is formed on the central axis C in the vacuum chamber 1, and through the transmission window 2, the inside of the vacuum chamber 1 that is in a vacuum state and the outside of the vacuum chamber 1 that is at substantially atmospheric pressure. Optically connected. A laser irradiation unit 10 for irradiating the sample S with laser light includes a laser light source 11, a first lens 12, a second lens 13 arranged outside the vacuum chamber 1, and a third arranged inside the vacuum chamber 1. And a lens 14, all of which are arranged on the central axis C.

  An analysis operation of the MALDI-IT-MS of this embodiment will be schematically described. Laser light emitted from the laser light source 11 is converted into parallel light having a predetermined light beam diameter by the first lens 12 and the second lens 13, passes through the transmission window 2, and is introduced into the vacuum chamber 1. Then, the light beam is narrowed by the third lens 14 so that the vicinity of the surface of the sample S becomes a focal point. The optical axis of the laser light reaching from the laser light source 11 to the sample S coincides with the central axis C.

  As described above, a large number of components for performing mass spectrometry are arranged between the third lens 14 and the sample S. However, on the central axis C, that is, on the optical axis of the laser light, There are no components. Further, as will be described later, the beam diameter of the laser beam is smaller than the diameter of the opening formed around the central axis C in these components. Therefore, the laser beam focused by the third lens 14 strikes the sample S with a very small diameter without being interrupted while the beam diameter is gradually reduced. That is, since the sample plate 3 is irradiated with laser light from the normal direction (that is, from vertically above), if the surface of the sample S can be regarded as being substantially parallel to the surface of the sample plate 3 at the laser light irradiation position. The laser beam is also irradiated substantially perpendicularly to the surface of the sample S.

  Ions are emitted from the sample S in a packet form by irradiating pulsed laser light for a very short time. In practice, ions are emitted in various directions. When the laser beam is irradiated from the normal direction as described above, the amount of ions emitted in the normal direction is usually the largest. Here, ions emitted in the range of a predetermined solid angle around the normal direction are converged by the ion lenses 5 and 6 through the aperture 4 and enter the space inside the ion trap 7 through the ion entrance 74. be introduced. The introduced ions are captured by the high frequency electric field formed by the high frequency voltage applied to the ring electrode 71 and confined in the ion trap 7. At this time, the ions are oscillating in the ion trap 7, but the orbit center of the oscillation is on the ion optical axis, that is, the central axis C.

  Thereafter, a predetermined voltage is applied to the end cap electrodes 72 and 73, and ions having a specific mass-to-charge ratio m / z are selectively ejected from the ion trap 7 through the ion emission port 75. When the discharged ions reach the detection unit 9, they are attracted by the electric field and collide with the conversion dynode 92, and the electrons emitted from the conversion dynode 92 reach the secondary electron multiplier 93 and are multiplied and detected. . In this configuration, the ion trap 7 itself corresponds to the mass separation unit, but the center of the ion path until the ions emitted from the sample S reach the ion trap 7, that is, the ion optical axis coincides with the central axis C. Yes. That is, in the MALDI-IT-MS of this embodiment, both the optical axis of the laser beam irradiated to the sample S and the ion optical axis from the sample S to the ion trap 7 are perpendicular to the sample S. Is coincident with the central axis C.

  Since the irradiation direction of the laser beam on the surface of the sample plate 3 is the normal direction, generally, the largest amount of ions is emitted from the sample S in the normal direction. In addition, since a relatively large amount of ions thus generated are collected and transported, and the ions are not bent or deflected by an electric field or the like before being introduced into the ion trap 7, Use efficiency of ions is high. Thereby, high analytical sensitivity can be achieved.

  In order to realize the laser irradiation optical system and the ion transport optical system as described above, in the MALDI-IT-MS of the present embodiment, a position further away from the detection unit 9 which is generally the most distant from the sample S. In addition, the laser irradiation unit 10 is installed on the central axis C. In order to prevent the laser light emitted from the laser irradiation unit 10 from being interrupted before reaching the sample S, the optical system of the laser irradiation unit 10 may be designed by the following procedure, for example.

  That is, between the sample S and the detection unit 9, a large number of components of the ion transport optical system and the mass separation / detection unit are arranged. In the case of the example of FIG. 1, the aperture 4, the ion lenses 5 and 6, the mirror 8, and the ion trap 7 correspond to this, but this differs depending on the configuration of the apparatus, and the shape of the constituent elements varies. It is. Among the above-described components, an opening that may interfere with the optical path of the laser beam is drawn according to the actual size as illustrated in FIG. Then, a lens L having an optical characteristic with a focal length f1 longer than the distance between the surface of the sample plate 3 and the detection unit 9 is selected, and is located on the central axis C at a position separated from the surface of the sample plate 3 by the focal length f1. Place the lens L. Next, among all the openings, when a line connecting the peripheral edge of the opening and the intersection of the surface of the sample plate 3 and the central axis C is drawn, the inside of the peripheral edge of all the other openings Find a line that looks like The opening through which this line is drawn is an opening that restricts the luminous flux of the laser light. In FIG. 2, what is indicated by the arrow a, that is, the ion emission port 75 of the ion trap 7 is an opening that restricts the light flux of the laser light.

  As shown in FIG. 2, when the line is extended to the position of the lens L, the maximum luminous flux size x ′ at which all the light can reach the sample S is obtained. If a parallel light beam having a light beam diameter smaller than x ′ is incident on the lens L, the laser beam in which the optical axis is in the normal direction with respect to the surface of the sample plate 3 and a part of the light beam is not blocked on the way is sample S. Can be irradiated. When the beam diameter of the laser light emitted as substantially parallel light from the laser light source 11 is less than x ′, the laser light emitted from the laser light source 11 may be incident on the lens L as it is.

  On the other hand, when the beam diameter of the laser beam emitted from the laser light source 11 exceeds x ′ as in the example shown in FIG. 1, the beam diameter is adjusted by a collimator. Specifically, as shown in FIG. 3, a collimator is constituted by a lens A having an appropriate focal length fa and a lens B having a focal length fb such that x '/ X> fb / fa. Here, X is a beam diameter of the laser beam emitted from the laser light source 11. Then, the lens A is placed at a position appropriately separated from the laser light source 11, and the lens B is placed at a position away from the lens A by fa + fb. As shown in FIG. 3, the laser beam incident on the lens A in parallel with the beam diameter X is once focused between the lens A and the lens B, then spread and incident on the lens B. Becomes a parallel laser beam with x ′ or less. In FIG. 1, the first lens 12 and the second lens 13 correspond to the lens A and the lens B. In FIG. 3, a spatial filter may be inserted at a position away from the lens A by fa.

  As in the example shown in FIG. 1, the third lens 14 corresponding to the lens L in FIG. 2 is disposed in the vacuum chamber 1, and when it is difficult to adjust the position, it corresponds to the lens B. By moving the second lens 13 along the central axis C in the extending direction, the beam diameter of the laser light on the surface of the sample S can be adjusted. On the other hand, when the third lens 14 corresponding to the lens L is arranged outside the vacuum chamber 1, the lens 14 is moved along the central axis C in the extending direction so that the surface of the sample S The beam diameter of the laser beam at can be adjusted. However, when the optical system of the laser irradiation unit 10 is designed so that the laser beam can be condensed on the surface of the sample S as described above, the beam diameter of the laser beam on the surface of the sample S is increased. In some cases, a part of the luminous flux is blocked by some of the components of the ion transport optical system and the mass separation / detection unit.

  The constituent elements such as the ion transport optical system and the ion mass separation / detection unit are not limited to those described in the above embodiments. For example, FIG. 4 is a schematic configuration diagram of a MALDI-IT-TOFMS according to another embodiment of the present invention. This apparatus includes a reflection time-of-flight mass separator 100 having a reflectron 101 that turns ions back by an electrostatic field as a mass separator, and detects the ions separated according to the mass-to-charge ratio when flying back. 102 is provided as a detection unit. Here, the ion trap 7 functions as an ion emission unit that applies initial energy to ions and sends them to the reflection time-of-flight mass separator 100.

  Also in the configuration of this embodiment, similarly to the configuration of FIG. 1, the laser irradiation unit 10 is arranged at a position further away from the reflectron 101 that is the part farthest from the sample plate 3 in the mass separation / detection unit. ing. In addition, a component that blocks the light beam is not arranged on the central axis C, and the laser beam emitted from the laser irradiation unit 10 is irradiated to the sample S without being blocked at all. On the other hand, the ions emitted from the sample S in the normal direction of the surface of the sample plate 3 and around the sample plate 3 are subjected to mass spectrometry without the trajectory being bent by an electric field or the like on the way. Therefore, it is obvious that this configuration can achieve the same effect as the above embodiment.

  Further, the above-described embodiments are merely examples of the present invention, and it is a matter of course that modifications, additions, and modifications as appropriate within the scope of the present invention are included in the scope of the claims of the present application.

DESCRIPTION OF SYMBOLS 10 ... Laser irradiation part 11 ... Laser light source 12 ... 1st lens 13 ... 2nd lens 14 ... 3rd lens 2 ... Transmission window 3 ... Sample plate 4 ... Aperture 5, 6 ... Ion lens 7 ... Ion trap 71 ... Ring electrode 72 ... Inlet side end cap electrode 73 ... Outlet side end cap electrode 74 ... Ion entrance port 75 ... Ion exit port 8 ... Mirror 9 ... Detector 91 ... Aperture 92 ... Conversion dynode 93 ... Secondary electron multiplier 16 ... CCD camera 100 ... reflection time-of-flight mass separator 101 ... reflectron 102 ... detector S ... sample

Claims (4)

A laser irradiation unit for irradiating a sample placed on a sample plate with a laser beam; a mass separation / detection unit for mass-analyzing ions derived from the sample generated by the irradiation of the laser beam; and the sample An ion transport optical system that transports ions from the mass separation / detection unit to a mass spectrometer,
The ion transport optical system and the mass separation / detection unit include an ion optical axis when ions travel from the sample plate surface to the mass separation / detection unit along a central axis perpendicular to the sample plate surface, and the ion optical axis. Arranged so that the central axis coincides and a part of the central axis does not block the central axis,
The laser irradiator further includes a portion farthest from the sample in the ion transport optical system and the mass separation / detector so that the optical axis of the laser light emitted from the irradiator coincides with the central axis. A mass spectrometer characterized by being arranged at a distant position. The mass spectrometer according to claim 1,
The laser irradiation unit includes a laser light source and a long-focus laser optical system for narrowing a laser beam having a predetermined beam diameter to a minute beam diameter that can be regarded as one point or one point on the sample surface. Mass spectrometer. The mass spectrometer according to claim 2,
The laser irradiation unit is an ion passage opening provided in the transport optical system and the mass separation / detection unit so that a light beam whose diameter is gradually reduced is not blocked until reaching the sample. apparatus. The mass spectrometer according to any one of claims 1 to 3,
The ion transport optical system or the mass separation / detection unit includes a three-dimensional quadrupole ion trap, and the centers of the ion entrance and the ion exit provided in the end cap electrode of the ion trap coincide with the central axis A mass spectrometer characterized in that the ion trap is arranged as described above.

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