JPWO2005074003A1 - Laser analysis apparatus and method - Google Patents

Abstract

The irradiation means irradiates the sample surface with a femtosecond laser in a low fluence region according to the material of the sample surface, which causes non-thermal desorption ionization on the sample surface by irradiating the sample surface. . The analyzing means analyzes molecular ions desorbed from the sample surface in accordance with the irradiated femtosecond laser by, for example, time-of-flight mass spectrometry.

Description

  The present invention relates to a technical field of a desorption ionization type laser analysis apparatus and method which are preferably used for nondestructive analysis such as nondestructive ultra-trace analysis on a solid surface using a laser.

  MALDI (Matrix Assisted Laser Desorption / Ionization) is widely known as a desorption ionization (desorption ionization) laser analysis method using this type of laser (patent) References 1 and 2 and Non-Patent References 1 and 2).

  According to such a MALDI method, by adding a matrix agent to the sample surface, molecular ions are desorbed and ionized from the sample surface in response to the irradiation of the nanosecond laser from the sample surface mixed with the matrix agent. Then, by analyzing the molecular ions thus desorbed, it is said that ultra-trace analysis such as mass analysis of the sample surface becomes possible. For example, by performing molecular ion spectrum analysis, mass analysis of a sample having a sample surface is performed from a peak that appears on the relative peak intensity spectrum other than the peak of the matrix agent.

JP 09-320515 A JP 09-326243 A “MALDI Analysis Using Inorganic Matrix (Shimadzu Corporation)” Koichi Tanaka and Shinichiro Kawabata 1995 Mass Spectrometry Union Discussion 1-P-32 “Matrix Assisted Laser Desorption / Ionization Mass Spectrometry” Koichi Tanaka (Shimadzu Corporation) Bunkeki, NO. 4 p253-261 (1996)

  However, according to the MALDI method described above, it is necessary to add a matrix agent to the sample surface or use a special substrate such as a specially processed silicon substrate, and the analysis is not always easy or efficient. There are technical problems. Furthermore, various peaks and noise-like components caused by the matrix agent appearing on the relative peak intensity spectrum during sample analysis must be made larger or smaller as a factor that lowers the analysis accuracy of the sample. In addition, performing non-destructive ultra-trace analysis of the sample surface, or performing analysis without damaging the sample, particularly performing analysis so as not to cause external damage to the biological sample, etc. However, according to the MALDI method using a conventional matrix agent or the like, there is also a problem that it is very difficult in practice.

  The present invention has been made in view of the above-described problems. For example, a solid sample such as a biological sample, a semiconductor material, a metal material, a chemical sample, and a compound sample can be analyzed as it is or nondestructively. It is an object of the present invention to provide a desorption ionization type laser analysis apparatus and method that can be realized.

  In order to solve the above problems, the laser analyzer of the present invention causes non-thermal desorption / ionization on the sample surface by irradiating the sample surface, and in a low fluence region corresponding to the material of the sample surface. Irradiation means for irradiating the sample surface with a femtosecond laser; and analysis means for analyzing molecular ions desorbed from the sample surface in response to the irradiated femtosecond laser.

According to the laser analyzer of the present invention, the femtosecond in the low fluence region corresponding to the material of the sample surface relating to the solid sample such as a biological sample, a semiconductor material, a metal material, a chemical sample, and a compound sample is applied by the irradiation means. A laser is irradiated onto the sample surface. Here, the “femtosecond laser” refers to a femtosecond order laser or a laser pulse having a pulse width of 1 picosecond (ps) or less. More specifically, for a material of a solid sample forming a solid surface, It means a femtosecond order pulse laser having a pulse width shorter than the collision relaxation time. That is, the pulse width itself related to the femtosecond laser is variable according to the material such as a biological sample, a semiconductor material, a metal material, a chemical sample, and a compound sample forming the sample surface. For example, it is 1.12 ps (picosecond) for Al (aluminum), 17.49 ps for Cu (copper), and 0.83 ps for Ti (titanium). “Fluence” is the energy density (J / cm ² ) obtained by dividing the output energy per pulse of the laser by the irradiation cross section. In addition, “low fluence” generally means that the value of fluence is relatively small, but “low fluence” or “low fluence region” according to the present invention means that the surface of the material is irradiated with a laser. This means the fluence near the minimum value of energy density (ablation threshold) at which the phenomenon that the material surface evaporates occurs. In other words, the “low fluence region” according to the present invention means a region near the ablation threshold where nonthermal ionization occurs on the solid surface. More specifically, it typically means within the region between the first lowest ablation threshold fluence and the second lowest ablation threshold fluence. Although the low fluence region varies depending on the material of the solid surface, for example, a fluence region on the order of 15 mJ / cm ^{2 to} 150 mJ / cm ² is cited here.

  In the present invention, in particular, the femtosecond laser irradiated by the irradiation means in this manner is a laser that causes nonthermal desorption ionization on the sample surface. The femtosecond laser irradiated in the present invention is a “low fluence high intensity laser pulse” having a low fluence and a high light intensity. Here, the “high intensity” or “high light intensity” of the laser according to the present invention refers to the irradiation of a femtosecond laser onto a solid surface, so that molecular ions or multiple ions can be emitted from the solid surface without dissociating the material on the solid surface. This means the intensity or light intensity of the laser that can be emitted as valence molecular ions, and this value is specific to the material of the solid surface. A molecule is formed by bonding a plurality of atoms, and applying energy (heat, electric field, etc.) to the molecule from the outside to break the bond is called “dissociation”. However, in the present invention, the condition for the parameter “light intensity” does not have to be required independently, and if the conditions related to the ablation threshold fluence described above are determined, the relationship of laser intensity (light intensity) = fluence / pulse width. From the formula, it is determined depending on the fluence. Then, molecular ions that are desorbed from the sample surface in response to irradiation with such a femtosecond laser (that is, ions that maintain the molecular structure or multivalent ions) are analyzed by the analyzing means. The analysis means is, for example, an ion detection type analyzer.

  Therefore, (i) high fluence laser irradiation or (ii) laser irradiation with a pulse longer than the collision relaxation time rather than a femtosecond laser does not cause thermal ionization on the solid surface, or melting or destruction by heating. Separation or desorption ionization can be performed at the atomic / molecular level without incurring. That is, it becomes possible to desorb a very small amount of molecular ions from the sample surface. At this time, by using an extremely short pulse of a low fluence and a femtosecond laser, a non-thermal ion emission phenomenon (or desorption ionization phenomenon related to ion generation) occurs on the sample surface. Separation at the atomic and molecular level is possible without being heated. In the present invention, the “atomic / molecular level” indicates a range or unit of nano-order or sub-nano-order near the sample surface, for example, one atom, several atoms, or several dozen to several tens of atoms.

  According to the research of the present invention, such a phenomenon of non-thermal desorption ionization is performed when a femtosecond laser is irradiated in a low fluence region with almost no material dissociation phenomenon occurring on the sample surface. In this case, it is considered that, for example, the three-photon absorption process as a multivalent ionization phenomenon is remarkably or completely dominant as a factor of desorption ionization on the sample surface. The Originally, when a substance is excited (ionization / desorption) with a laser having a longer pulse width (irradiation time) than a femtosecond laser, thermal relaxation of the sample is indispensable, so a matrix agent such as the MALDI method is used. If is not present, a thermal reaction is induced and the sample molecules are broken. That is, non-destructive mass spectrometry is difficult or almost impossible. On the other hand, when the femtosecond laser is focused and irradiated, even if the sample is irradiated with light in a wavelength region where there is no absorption, if the light intensity is above a certain level, the sample is not dissociated. The sample can be desorbed and ionized.

  More specifically, (1) when the sample is a metal sample, desorption ionization is caused by irradiating with the light intensity controlled in the “low fluence high intensity femtosecond laser” according to the present invention as described above. Multivalent ions are produced fairly selectively. Correlation with the ablation threshold value is also possible. That is, in the case of a metal sample, a multivalent ion release phenomenon is observed. However, in addition to the metal sample, for example, in the case of a compound sample, a multivalent ion release phenomenon is observed. (2) When the sample is a chemical sample, molecular ions (monovalent ions) are efficiently generated by controlling the light intensity in the “low-fluence high-intensity femtosecond laser” according to the present invention as described above. Is done. Molecularly multiply charged ions are also observed. There is very little molecular dissociation. (3) When the sample is a biological sample, molecular ions are observed by irradiating while controlling the light intensity in the “low fluence high intensity femtosecond laser” according to the present invention as described above. can not see.

  Therefore, in the laser analyzer of the present invention, the laser intensity, wavelength and pulse width of the low fluence high intensity femtosecond laser are set according to the material of the sample surface (that is, metal sample, chemical sample, biological sample, etc.). By controlling, desorption ionization is achieved. Thereby, the dissociation reaction accompanying ionization can be suppressed by placing the fluence in the low fluence region and controlling the laser intensity in the vicinity of the ablation threshold.

  In addition, not only laser ionization but also ionization in many mass spectrometers may actively utilize molecular fragmentation. In the present invention, for example, it is possible to observe not only molecular ions but also fragment ions by intentionally increasing the laser intensity beyond the vicinity of the ablation threshold. By observing the mass of the fragment ion, it is possible to obtain information on the structure of a molecule having a relatively large molecular weight (in this case, a molecular weight of 1000 or more).

  As described above, according to the laser analyzer of the present invention, the laser irradiation for causing non-thermal desorption ionization is relatively easy and non-detached from the sample surface by peeling at the atomic / molecular level. Since trace amounts of molecular ions can be destructively desorbed, ultra-trace analysis such as mass spectrometry becomes possible. In particular, as in the MALDI method described above, almost no sample such as a biological sample, a semiconductor material, a metal material, a chemical sample, or a compound sample is required without adding a matrix agent or mixing, or without using a special substrate. In a practical sense, it can be analyzed as it is without any damage, which is very advantageous in practice. That is, extremely rapid and efficient ultra-trace analysis is possible. In addition, a biological sample having excellent resilience can be analyzed by desorption of a very small amount of molecular ions that can be instantaneously restored biologically, which is further advantageous.

  In addition, the analysis is based on the desorption of a very small amount of molecular ions in a non-destructive manner. In particular, since no matrix agent is used compared to the MALDI method, the distribution of the sample composition can be observed statically / dynamically. Is advantageous. That is, the present invention is also excellent in that the local composition distribution of the sample can be observed with a resolution of about the laser irradiation region. It is extremely advantageous when analyzing a dynamic distribution process in a biological sample. Furthermore, the position resolution related to the analysis can be easily obtained as much as the wavelength of the laser.

  According to the laser analysis apparatus of the present invention, a sample can be analyzed as it is in a non-destructive manner, so that it can be widely applied in various technical fields such as medicine, drug discovery, gene therapy-related fields, and the semiconductor industry.

  In one aspect of the laser analyzer of the present invention, the analyzing means includes a mass analyzing means for analyzing the mass of the desorbed molecular ions.

  According to this aspect, the molecular ions desorbed from the sample surface in response to the irradiation with the femtosecond laser are analyzed by the mass analyzing means. That is, nondestructive mass spectrometry can be performed as it is on samples of various shapes and forms, which is very advantageous in practice.

  In this aspect, the mass spectrometry means may include a concentration detection means for detecting the concentration of the desorbed molecular ions.

  If comprised in this way, it will also become possible to construct | assemble the laser analyzer of this invention comparatively cheaply by employ | adopting concentration detection means, such as the existing ion concentration detection apparatus.

  In another aspect of the laser analyzer of the present invention, the irradiation means irradiates the femtosecond laser onto the sample surface in a state where the matrix agent is not mixed.

  According to this aspect, molecular ions desorbed from the sample surface can be analyzed while eliminating the need for a matrix agent at all, which is extremely advantageous in terms of labor of analysis as compared with the conventional MALDI method.

  In another aspect of the laser analysis apparatus of the present invention, the light intensity of the femtosecond laser is determined from the surface of the sample by a tunnel ionization process by a laser electric field and a nonresonant multiphoton absorption process caused by the femtosecond laser. Is set to a value to desorb.

  According to this aspect, since the light intensity of the femtosecond laser is set to a value that causes the tunnel ionization process and the nonresonant multiphoton absorption process, molecules from the surface of the sample can be extremely efficiently and non-destructively generated. Ions can be desorbed. Therefore, sample analysis can be performed very efficiently. As described above, the condition for the parameter “light intensity” does not need to be independently requested. If the condition relating to the ablation threshold fluence described above is determined, it is determined depending on this.

  In another aspect of the laser analysis apparatus of the present invention, the sample surface is a surface of a biological sample or a solid sample, and the irradiation unit desorbs the molecular ions from the sample surface in a nondestructive manner.

  According to this aspect, since a biological sample or a solid sample can be analyzed nondestructively, a laser analyzer that is very useful in practice in various application technical fields can be realized.

  In another aspect of the laser analysis apparatus of the present invention, the sample surface comprises a surface of a biological sample, and the analysis means includes detection means for detecting a dynamic distribution process of the molecular ions on the sample surface.

  According to this aspect, since it is possible to analyze the dynamic distribution process in the biological sample, it is possible to realize a laser analyzer that is very useful in practice in various applied technical fields. For example, it is possible to analyze the dynamic distribution process related to one end and the other end of the cell, or the front side and the back side.

  In another aspect of the laser analysis apparatus of the present invention, an ion accelerator that accommodates a sample having the sample surface so that the irradiation means can irradiate the femtosecond laser and accelerates the desorbed molecular ions. And a vacuum vessel for guiding the accelerated molecular ions to the analyzing means.

  According to this aspect, if the sample surface of the sample accommodated in the ion accelerator is irradiated with a femtosecond laser, the molecular ions desorbed by the irradiation can be immediately accelerated by the ion accelerator. Further, by guiding the molecular ions thus accelerated to an analysis means such as a mass spectrometer using a vacuum vessel, it is possible to perform comparatively high-precision analysis based on an extremely small amount of molecular ions. In particular, if an ion accelerator is used, light molecular ions are easily accelerated by an electric field, whereas heavy molecular ions are difficult to accelerate. Mass spectrometry and the like can be performed based on properties such as being hardly accelerated.

  In order to solve the above problems, the laser analysis method of the present invention causes non-thermal desorption / ionization on the sample surface by irradiating the sample surface, and in the low fluence region according to the material of the sample surface. An irradiation step of irradiating the sample surface with a femtosecond laser; and an analysis step of analyzing molecular ions desorbed from the sample surface in response to the irradiated femtosecond laser.

  According to the laser analysis method of the present invention, the femtosecond laser irradiated in the irradiation step is a laser that causes non-thermal desorption ionization on the sample surface, and the sample surface in accordance with the irradiation of the femtosecond laser The molecular ions desorbed from are analyzed by an analysis process. Accordingly, as in the case of the laser analyzer of the present invention described above, the surface of the sample can be made relatively easy by laser irradiation for causing nonthermal desorption ionization, and peeled off at the atomic / molecular level. Since trace amounts of molecular ions can be desorbed nondestructively, ultra-trace analysis such as mass spectrometry becomes possible. In particular, as in the MALDI method described above, almost no sample such as a biological sample, a semiconductor material, a metal material, a chemical sample, or a compound sample is required without adding a matrix agent or mixing, or without using a special substrate. In a practical sense, it can be analyzed as it is without any damage, which is very advantageous in practice.

  In the laser analysis method of the present invention, the same aspects as the various aspects of the laser analysis apparatus of the present invention described above can be adopted as appropriate.

  In one aspect of the laser analyzer of the present invention, the irradiation step further includes a setting step of setting an irradiation fluence value related to the femtosecond laser in the low fluence region according to the material of the sample surface. Irradiates the femtosecond laser with the set irradiation fluence value on the sample surface.

According to this aspect, in the setting step, the value of the irradiation fluence related to the femtosecond laser that irradiates the sample surface is set according to the material of the sample surface. For example, in terms of the ablation rate, 0.01 nm / shot (nanometer / shot, where “shot” means one irradiation of a laser pulse), ie, at the atomic / molecular level, If a shallow peeling depth is preferable in terms of the properties of the sample, the value of the irradiation fluence is set to 0.1 J / cm ² , for example. In the irradiation process, the solid surface is irradiated with the femtosecond laser at the irradiation fluence value set in the setting process. Therefore, peeling or ablation can be performed at the atomic / molecular level without causing thermal ionization on the sample surface or causing melting or destruction by heating.

  Depending on the material of the sample surface, other parameters such as the light intensity and wavelength of the femtosecond laser can be adjusted and controlled. For example, the entire surface of the sample surface may be irradiated with a fluence that is low enough to prevent burning while relatively increasing the light intensity at the local surface of the sample surface.

  Such an operation and other advantages of the present invention will become apparent from the embodiments described below.

It is an external appearance perspective view which shows concretely the composition near a sample and a detection part among laser analyzers concerning an embodiment of the present invention. 1 is a block diagram schematically showing the overall configuration of a laser analyzer according to an embodiment of the present invention. It is a characteristic view which shows the waveform characteristic of the ultra-short pulse laser (namely, femtosecond laser) which concerns on embodiment of this invention. It is a table | surface which shows an example of the conditions which concern on various parameters, various equipment, etc. in the laser analyzer which concerns on embodiment. It is a block diagram which shows optical arrangement | positionings, such as a laser light source device and a CCD camera for verification, in the laser analyzer according to the embodiment. It is a characteristic view which shows the relationship between the irradiation fluence obtained by the laser analyzer which concerns on embodiment, and an ablation rate. It is a characteristic view which shows the relationship between the laser pulse width obtained by the laser analyzer which concerns on embodiment, and an ablation threshold value. It is a characteristic view (the 1) which shows the ion signal intensity detected with the laser analyzer concerning an embodiment to a time axis (horizontal axis). It is a characteristic view (the 2) which shows the ion signal strength detected with the laser analyzer concerning an embodiment to a time axis (horizontal axis). It is a characteristic view (the 3) which shows the ion signal strength detected by the laser analyzer concerning an embodiment to a time axis (horizontal axis). It is a characteristic view which shows the relationship between the temperature and distribution density about Cu (copper). It is a characteristic view which shows the relationship between the incident laser energy and ion signal intensity | strength about Cu obtained by the laser analyzer which concerns on embodiment. It is a conceptual diagram of the desorption ionization of the sample surface by the laser analyzer which concerns on embodiment. It is a conceptual diagram of the desorption ionization of the sample surface by the laser analyzer which concerns on a comparative example. It is a characteristic view which shows the time change of the ion signal intensity detected when the phosphatidylcholine molecule is used as a sample by the laser analyzer according to the embodiment. It is a characteristic view (the 1) which shows the time change of the ion signal strength detected when a coronene molecule is made into the sample by the laser analyzer which concerns on embodiment. It is a characteristic view (the 2) which shows the time change of the ion signal strength detected when a coronene molecule is made into the sample by the laser analyzer which concerns on embodiment. It is a characteristic view (the 3) which shows the time change of the ion signal strength detected when a coronene molecule is made into the sample by the laser analyzer which concerns on embodiment. It is a characteristic view (the 4) which shows the time change of the ion signal strength detected when a coronene molecule is made into the sample by the laser analyzer which concerns on embodiment. It is a characteristic view (the 1) which shows the time change of the ion signal strength detected when a fullerene molecule is made into the sample by the laser analyzer which concerns on embodiment. It is a characteristic view (the 2) which shows the time change of the ion signal strength detected when a fullerene molecule is made into the sample by the laser analyzer which concerns on embodiment. It is a characteristic view (the 3) which shows the time change of the ion signal intensity detected when the fullerene molecule is made into the sample by the laser analyzer which concerns on embodiment. It is a characteristic view (the 4) which shows the time change of the ion signal strength detected when a fullerene molecule is made into the sample by the laser analyzer which concerns on embodiment.

Explanation of symbols

2 ... Laser analyzer 10 ... Controller 11 ... Laser light source device 12 ... Condensing lens 13 ... Target (sample)
16 ... Detection device 101 ... Ion accelerator 102 ... Vacuum container

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  First, the configuration of the laser analyzer will be described with reference to FIGS. 1 and 2. FIG. 1 specifically shows the configuration in the vicinity of the sample and the detection unit in the laser analyzer according to the present embodiment, and FIG. 2 schematically shows the overall configuration of the laser analyzer according to the present embodiment. Show.

  In FIG. 1, the laser analyzer 2 includes a condenser lens 12, an ion accelerator 101, a vacuum container 102, and a detection device 16.

  In FIG. 2, the laser analyzer 12 includes a control device 10 and a laser light source device 11 in addition to the components shown in FIG. 1.

  As shown in FIGS. 1 and 2, a low fluence femtosecond laser LB emitted from the laser light source device 11 is incident on the condenser lens 12 via another optical component, a lens, or the like. The condensing lens 12 is configured to condense the light toward a target 13 as an example of a sample having a “sample surface” according to the present invention.

  The laser light source device 11 receives drive control by the control device 10 and irradiates the femtosecond laser LB toward the target 13 through the condenser lens 12. The laser light source device 11 is desorbed and ionized non-thermally (that is, non-thermal desorbed) by the control device 10 according to the material of the target 13 at the surface of the target 13 at the atomic / molecular level or in a very small amount. The femtosecond laser LB is generated with an irradiation fluence value set to ionize the ionization. In addition to the irradiation fluence value related to the femtosecond laser LB, or in place of the value of the light intensity related to the femtosecond laser LB, the control device 10 causes the surface of the target 13 It may be set so as to be dethermally ionized non-thermally at the molecular level.

  The parameter setting related to the femtosecond laser LB by the control device 10 will be described in detail later.

  The target 13 is disposed in an ion accelerator 101 having a window for entering the femtosecond laser LB. However, it does not necessarily have to be arranged in the ion accelerator 101 in this way. The target 13 is arranged to be inclined by a predetermined angle θ, for example, 45 degrees with respect to the incident axis of the femtosecond laser LB (see FIG. 2), thereby desorbed and ionized molecules from the surface of the target 13. Ions are discharged into the ion accelerator 101 satisfactorily.

The ion accelerator 101 includes a plurality of electrodes. By generating an electric field using these electrodes, molecular ions M ⁺ desorbed and ionized from the sample surface of the target 13 in accordance with the irradiation of the femtosecond laser LB are vacuum containers. It is configured to accelerate toward 102 (that is, toward the left side in FIG. 1).

The vacuum vessel 102 internally defines a vacuum space extending in the flight direction of the molecular ions M ⁺ so as to increase the flight time of the molecular ions, that is, in FIG. 1, so that the ion track LP is sufficiently long. ing. And the detection apparatus 16 is arrange | positioned at the side which faces the ion accelerator 101 in the vacuum vessel 102. FIG. In FIG. 1, molecular ions M ⁺ are detected by changing the flight direction to the opposite direction in the vacuum vessel 102 after first flying toward the left side by acceleration by the ion accelerator 101 as indicated by the ion track LP. It will fly towards the device 16.

The detection device 16 includes, for example, a time-of-flight mass spectrometer that analyzes the mass of the molecular ion M ⁺ by detecting the concentration of the molecular ion M ⁺ that flew in the vacuum vessel 102 with respect to time. Detection information related to the analysis result of the molecular ion mass is input from the detection device 16 to the control device 10 including a CPU (Central Processing Unit) or a system controller, and the detection information is recorded here.

  As described above, in this embodiment, the laser light source device 11 and the condenser lens 12 constitute an example of the “irradiation means” according to the present invention, and the ion accelerator 101, the vacuum vessel 102, and the detection device 16 are It constitutes an example of “analyzing means” according to the invention.

  In FIGS. 1 and 2, for the sake of simplification of explanation, the condensing lens 12 is disposed in the optical path of the femtosecond laser LB as an optical system, but other lenses, prisms, mirrors, shutters, and the like are included in the optical system. The laser light source device 11 may be appropriately disposed in the optical path, and various laser devices such as a semiconductor laser device and optical components such as various lenses, shutters, polarizing plates, and retardation plates may be appropriately incorporated in the laser light source device 11. Good.

  Next, with reference to FIGS. 3 to 12, setting of the value of the irradiation fluence relating to the femtosecond laser LB in the laser analyzer 2 having the above-described configuration will be described. Here, the relationship between the value of the irradiation fluence and the ablation rate (corresponding to the peeling depth) on the surface of the target 13 is verified, and further, the ablation rate on the surface of the target 13 is a femtosecond laser LB in the low fluence region. It is verified that it can be adjusted and controlled by the irradiation fluence value or the light intensity value. Based on these verifications, in the laser analyzer 2 shown in FIGS. 1 and 2, the irradiation fluence value and the like are set so that only a very small amount of nonthermal desorption ionization is performed.

  First, the characteristics of the femtosecond laser having an extremely low fluence and high intensity used in the present embodiment will be described with reference to FIG. FIG. 3 shows the waveform characteristics of the ultrashort pulse laser (ie, femtosecond laser) according to this embodiment.

  As shown in FIG. 3, the ultrashort pulse laser (ie, femtosecond laser) irradiated by the laser light source device 11 is non-thermal without dissociating the material depending on the material of the target 13, for example. A “low fluence high intensity laser pulse” that is low fluence and high light intensity that causes ionized emission. Here, the “low fluence” according to the present embodiment is a fluence between the first smallest ablation threshold fluence F3, th and the second smallest ablation threshold fluence F2, th, as will be described in detail later. Means. The “high intensity” or “high light intensity” of the laser according to the present embodiment means a laser intensity (light intensity) exceeding the “ablation threshold laser intensity” as illustrated in FIG. In other words, “high intensity” or “high light intensity” means that a solid ion (here, the surface of the target 13) is irradiated with a femtosecond laser without dissociating the material on the solid surface. This means the intensity or light intensity of the laser that can be emitted as multivalent molecular ions, and this value is specific to the material of the solid surface (here, the surface of the target 13).

In general, the unit of “fluence” is J / cm ² , and the unit of “laser intensity” or “light intensity” is W / cm ² (that is, J / s · cm ² ). Accordingly, the fluence of the laser is obtained by dividing the energy of the laser by the irradiation area, and the laser intensity (light intensity) is obtained by dividing the fluence by the pulse width (time) of the laser. In other words, the laser intensity (light intensity) is obtained by dividing the laser energy by (irradiation area × laser pulse width). Therefore, in this embodiment, the laser intensity or the light intensity is adjusted by adjusting the laser energy, the laser irradiation area, and the laser pulse width. However, in the present embodiment, conditioning for the parameter “light intensity” is not required independently, and depends on this if the conditions relating to the ablation threshold fluences F3, th to F2, th as described later are satisfied. (Ie, from the relational expression laser intensity (light intensity) = fluence / pulse width).

FIG. 3 shows a “low-fluence high-intensity laser pulse” which is a laser having an energy of 300 μJ and a pulse width of 100 fs, and whose irradiation diameter is reduced to 20 μm on the surface of the target 13 by the condenser lens 12 or the like. ing. The definition of “pulse width (laser pulse width)” according to this embodiment is obtained by experimentally examining the time waveform of the laser intensity and measuring the time that is half of the maximum laser intensity. In the case of the laser pulse illustrated in FIG. 3, the fluence is as low as 95 J / cm ² (that is, low fluence), but the laser intensity is extremely high as 10 ¹⁵ W / cm ² (that is, high intensity). ). Incidentally, this laser has a power well exceeding 64.3 million kW (= 6 × 10 ¹⁰ W) at the peak of TEPCO's 2001 power consumption. This is one of the characteristics of an ultrashort pulse laser called a femtosecond laser.

  Next, with reference to FIGS. 4 and 5 in addition to FIG. 2, the experiment will be further described in order to verify the relationship between the value of irradiation fluence and the ablation rate. Here, FIG. 4 shows an example of conditions relating to various parameters and various equipment related to the laser irradiation / analysis apparatus shown in FIG. 2, and FIG. 5 shows the conditions in the laser irradiation / analysis apparatus shown in FIG. An optical arrangement of a laser light source device and a CCD (Charged Coupled Device) camera for verification is shown. In FIG. 5, the same components as those in FIG. 1 are denoted by the same reference numerals, and description thereof will be omitted as appropriate.

  Next, referring to FIGS. 4 and 5 in addition to FIG. 2, an experiment for verifying the relationship between the value of irradiation fluence and the ablation rate will be described. FIG. 4 shows an example of conditions relating to various parameters and various equipments related to the laser irradiation / analysis apparatus, and FIG. 5 shows a laser light source apparatus and a verification CCD (Charged) in the laser irradiation / analysis apparatus. Coupled Device) Indicates the optical arrangement of a camera or the like. In FIG. 5, the same components as those in FIG. 1 are denoted by the same reference numerals, and description thereof will be omitted as appropriate.

As illustrated in the list of FIG. 4, in the laser analyzer 2, various parameters, various equipment, and various conditions relating to the target 13 are set. That is, as the target 13, a metal sample Cu, Al, Fe,... Is selected, and its size is set to 5 × 5 cm. The femtosecond laser LB has a wavelength of 800 nm (nanometer) or the like. In particular, the light intensity (energy) is variable between 0.21 and 600 μJ, and accordingly, the irradiation fluence is variable between 10 mJ / cm ^{2 and} 28 J / cm ² .

  As shown in FIG. 5, in addition to the laser light source device 11, a CCD camera 31 and the like, which are not shown in FIG. 2, are incorporated in the optical system in order to take an image of the surface of the target 13. ing. In FIG. 5, other components such as the detection device 16 and the control device 10 shown in FIG. 2 are omitted.

  In FIG. 5, a laser light source device 11 generates a femtosecond laser light source device (fs laser) 11a that generates a femtosecond laser Lfs for causing non-thermal ablation, and a laser La for optical alignment. Helium-neon gas laser light source (He-Ne laser) 11b. The femtosecond laser Lfs passes through the mirror 21, the laser La passes through the optical plate 25 for controlling the polarization state and the mirror 26, and is then synthesized at the half mirror (dichroic mirror) 22 to be combined with the laser LB on the same optical path. Is done. Further, the laser LB reaches a half mirror (dichroic mirror) 34. Of the lasers LB, the femtosecond laser Lfs is reflected by the half mirror 34 and irradiated onto the surface of the metal sample as the target 13 via the condenser lens 12. On the other hand, the alignment laser La among the lasers LB passes through the half mirror 34 and is used for alignment. The state of the surface of the metal sample that is ablated by the femtosecond laser Lfs is reflected by the reflected light Lr that reaches the CCD camera 31 through the condenser lens 12, the half mirror 34, the lens 33, and the mirror 32. 31 is used to capture an image.

  Next, referring to FIG. 6 to FIG. 12, the relationship between the irradiation fluence and the ablation rate obtained by the laser analyzer 2 as described above, in particular, three ablation threshold fluences identified on the characteristic curve indicating this relationship. , And the low fluence region showing the new ablation physics defined by these thresholds. 6 shows the relationship between the irradiation fluence obtained by the laser analyzer 2 and the ablation rate, and FIG. 7 shows the relationship between the laser pulse width obtained by the laser analyzer 2 and the ablation threshold (ablation threshold fluence). Indicates. 8 to 10 show the ion signal intensity detected by the laser analyzer 2 with respect to the time axis (horizontal axis), respectively. FIG. 11 shows the relationship between temperature and distribution density for Cu (copper), and FIG. 12 shows the relationship between incident laser energy and ion signal intensity for Cu obtained by the laser analyzer 2.

When the laser analyzer 2 described with reference to FIGS. 2 to 5 is used, the relationship between the irradiation fluence (laser irradiation fluence (J / cm ² )) and the ablation rate (nm / shot) as illustrated in FIG. can get. Here, the target 13 is Cu (copper), the wavelength of the femtosecond laser Ffs is 800 nm, the pulse width is 70 fs (femtosecond), and other conditions are as illustrated in FIG. .

As shown in FIG. 6, according to the discrete experimental data indicated by black circles, the characteristic curve indicating the relationship between irradiation fluence and ablation rate has three ablation threshold fluences in ascending order of ablation. It is confirmed that threshold fluences F3, th (= 0.018 J / cm ² ), F2, th (= 0.18 J / cm ² ) and F1, th (= 0.25 J / cm ² ) exist. .

  Here, “ablation rate” means the depth (peeling depth) of the crater formed on the surface of the target 13 per laser pulse, and is expressed by the following equation (1).

L = α ⁻¹ ln (F / Fth) (1)
However,
α ^-1 : light penetration length (cm),
F: Irradiation fluence (J / cm ² )
Therefore, from the equation (1), the three ablation threshold fluences Fth (F3, th, F2, th, F1, th) described above are evaluated from the irradiation fluence F where L = 0.

  More generally, when the laser spatial profile is expressed by a Gaussian function, the crater diameter Γ is expressed by the following equation (2).

Γ = a {ln (F / Fth)} ^0.5 (2)
However, a: Diameter of the incident laser beam Therefore, in this case, from the equation (2), the above-mentioned three ablation threshold fluences Fth (F3, th, F2, th, F1, th) are respectively Γ Evaluation is made from an irradiation fluence F of = 0.

  As described above, as shown in the equations (1) and (2), the ablation threshold fluence can be evaluated by two methods.

  6 is a characteristic curve on a log-log graph, the existence of these three ablation threshold fluences F3, th, F2, th and F1, th is somewhat difficult to see. Is plotted on a graph with only the horizontal axis (laser irradiation fluence axis) as a logarithm, as is clear from the above equations (1) and (2), these three ablation threshold fluences F3, th, F2, The presence of th and F1, th can be easily and clearly confirmed visually.

As shown in FIG. 7, on the characteristic curve showing the relationship between the laser pulse width (s) and the ablation threshold fluence (J / cm ² ), these three ablation threshold fluences F3, th, F2, th and F1, th Have properties that change depending on the pulse width of the femtosecond laser Lfs. Here, since the femtosecond laser Lfs has a pulse width shorter than the collision relaxation time in the target 13, the pulse width related to the femtosecond laser Lfs is variable according to the material of the surface of the target 13. For example, in the case of Cu, for example, 17.49 ps. (In this example, as in the case of FIG. 6, the target 13 is Cu (copper) and the wavelength of the femtosecond laser Ffs is 800 nm.) Thus, the three ablation threshold fluences F3, th, F2, Since th and F1, th change with the pulse width, respectively, it can be said that the laser intensity is also an important parameter depending on the pulse width (see FIG. 3). By changing the condensing optical system, the laser irradiation area on the surface of the target 13 changes, so that the laser intensity can be changed. That is, it is possible to adjust the time interval contributing to ablation to be longer or shorter. However, in the present embodiment, conditioning for the parameter “light intensity” is not required independently, and depends on this if the conditions relating to the ablation threshold fluences F3, th to F2, th as described above are satisfied. To be determined.

As can be seen from FIGS. 6 and 7, the “low fluence region” according to the present embodiment is a region between the first smallest ablation threshold fluence F3, th and the second smallest ablation threshold fluence F2, th. means. Therefore, the low fluence region varies depending on the material of the target 13, but in the example shown in FIG. 6 (that is, the example where the target is Cu), 0.018 J / cm ^{2 to} 0.18 J / cm ^2. The fluence region is a low fluence region. In other words, the fluence region of 0.018 J / cm ^{2 to} 0.18 J / cm ² means a region in the vicinity of the ablation threshold where nonthermal ionization occurs on the surface of the target 13 made of Cu.

In FIG. 6, a characteristic curve L ₃ (ξ ₃ ) simulated or modeled based on the three-photon absorption process is shown by a solid line. This characteristic curve L ₃ (ξ ₃ ) is consistent with the experimental data indicated by the black circles in the region between the ablation threshold fluence F3, th and the ablation threshold fluence F2, th, that is, in the low fluence region. It is confirmed.

Here, when m-th order multiphoton absorption occurs, if the absorption coefficient ζ _m (cm ^m / W ^m−1 ) is known, the ablation rate L _m (cm / shot) can be explained analytically, It is represented by the following formula (3).

L _m = 1 / {(m−1) ζ _m }
× {(E _th / τ _p ζ _m ) ^{((1-m) / m)} − (F / τ _p ) ^1-m } (3)
However,
m ≧ 2
τ _p (s): width of laser pulse,
E _TH (J / cm ³ ): Energy required to melt a unit volume of solid with heat of fusion And the condition for L _m = 0 is the ablation threshold fluence F _th and is expressed by the following equation (4): The

F _th = (E _th / ζ _m ) ^{1 / m} τ _p ^{((1-m) / m)} = β _m τ _p ^{((1-m) / m)} (4)
As can be seen from the above equation (3) and (4), the ablation threshold fluence F3, th is dependent on the pulse width, by three-photon absorption process shown by the characteristic curve L ₃ in FIG. 6 _{(xi] 3)} It is explained as a thing.

In FIG. 6, a characteristic curve ^{Lσ that} is simulated or modeled based on the two-photon absorption process is indicated by a broken line. This characteristic curve L ^sigma, the region between the ablation threshold fluence F2, th the ablation threshold fluence F1, and th, i.e., in the high fluence region adjacent to the low fluence region, and is consistent with the experimental data shown by black circles Is confirmed. In this high fluence region, the two-photon absorption process becomes dominant in the ablation phenomenon, and a thermal ionization emission phenomenon occurs.

Further, in FIG. 6, a characteristic curve L ^{1 that} is simulated or modeled based on the one-dimensional two-temperature thermal diffusion process is indicated by a one-dot chain line. The characteristic curve L ¹ is the ablation threshold fluence F1, at high high fluence region than th, it can be confirmed that that is consistent with the experimental data shown by black circles.

  As described above, when the femtosecond laser Ffs is used, the “three-photon absorption process” becomes notably or completely dominant as a factor of the ablation phenomenon in the low fluence region. In the case of the femtosecond laser Lfs, for example, when the wavelength is 800 nm, the photon has a particle property of 1.5 eV. Therefore, non-thermal ionization emission (non-thermal desorption ionization) is performed on the surface of the target 13 in accordance with the three-photon absorption process. On the contrary, in the high fluence region deviating from the low fluence region according to this embodiment, little or no non-thermal ionization emission phenomenon as in this embodiment has been confirmed, and the thermal ionization emission phenomenon is remarkable. It is confirmed.

Next, with reference to FIGS. 8 to 10, the characteristic curve L ₃ (ξ ₃ ) based on the two-photon absorption process in the low fluence region showing the novel ablation physics will be further verified. More specifically, an ionization emission process and a laser multiphoton absorption process (or a three-photon absorption process) based on molecular ions emitted from the surface of the target 13 measured by the detection device 16 in the laser analyzer 2. Consider the relevance of. Here, the pulse width of the femtosecond laser Lfs having a wavelength of 800 nm is fixed to 130 fs, and a lens with f (focal length) = 250 mm is used as the condenser lens 12. The surface of the Cu metal sample as the target 13 is irradiated with the femtosecond laser Lfs while changing the irradiation fluence in the range of 15 to 700 mJ / cm ² . Then, molecular ions emitted from the surface of the target 13 are measured by a time-of-flight mass analyzer (TOF) as an example of the detection device 16. The measurement results obtained in this way are shown in FIGS. 8 to 10 show the irradiation energy of the femtosecond laser Lfs in this order as 27 μJ (relatively high energy), 17 μJ (relatively medium energy), and 8.7 μJ (relatively low energy). Is.

As shown in FIG. 8 to FIG. 10, under these measurement conditions, in any case, peaks corresponding to Cu ³⁺ and Cu ²⁺ are measured, that is, polyvalent copper ions are remarkably released. It is confirmed. 8 to 10, the peak in the vicinity of 3 μs is due to hydrogen ions caused by the measurement environment, and is not particularly related to the verification related to the new ablation physics.

FIG. 11 shows the valence of copper ions (Cu ⁺ , Cu ²⁺ , Cu ³⁺ ) and copper (Cu) with respect to the temperature (k) when the ablation related to the measurement as described above is calculated by a thermal process. Distribution is shown. In contrast, FIG. 12 shows the valence distribution of copper ions (Cu ⁺ , Cu ²⁺ , Cu ³⁺ ) and copper (Cu) with respect to the incident laser energy (μJ) obtained by the measurement of the present embodiment as described above. Is shown. In FIG. 12, the peak seen when the incident laser energy is around 9 μJ indicates the ion signal intensity when no signal is obtained, and is not particularly relevant to the verification related to the new ablation physics. .

  From FIG. 11 and FIG. 12, it is presumed that the ablation or ionization emission phenomenon in the low fluence region shown in FIG. 6 occurs not in the thermal process but in the non-thermal process. As described above, in the low fluence region, the multiphoton absorption process or the three-photon absorption process becomes dominant or completely dominant as a factor of the ablation phenomenon, and multivalent ions are generated as molecular ions. The result supports the discussion.

  As described above with reference to FIGS. 2 to 12, the surface of the target 13 can be ablated or ionized very softly at the atomic / molecular level, in other words, with a pulse related to one femtosecond laser. . At this time, a non-thermal ablation phenomenon in which only multivalent ions other than monovalent ions are remarkably released or a non-thermal ionization phenomenon has not been reported before the present invention.

  Further, in the present embodiment, the case where Cu is appropriately used as the metal is illustrated, but the same non-thermal ablation phenomenon or non-thermal ionization phenomenon is confirmed for all the metals illustrated in the table of FIG. . In summary, the fluence dependence of the ablation rate described with reference to FIG. 6 and the like is composed of three logarithmic components having different slopes even when all the metals are the target 13, and the ablation threshold fluence is There are three (F3, th, F2, th and F1, th), respectively. And about any metal, it is thought that the pulse dependence of ablation threshold fluence follows the multiphoton absorption process or the three-photon absorption process.

In view of the discussion with reference to FIGS. 4 to 12 described above, in the laser analyzer 2 according to the present embodiment shown in FIGS. 1 and 2, the irradiation fluence value in the setting process by the control device 10 or the like is the target. 13 in a low fluence region that causes non-thermal desorption ionization (i.e., non-thermal desorption ionization) (in the example of FIG. 6, 0.018 J / cm ^{2 to} 0.18 J / cm ² ). In the area). In the irradiation process by the laser light source device 11 or the like, the femtosecond laser LB is irradiated with this set value. Therefore, according to the laser analyzer 2, the atom / molecule can be obtained without causing thermal ionization on the surface of the target 13 by heating with a high fluence laser or by irradiating with a long pulse without causing melting or destruction by heating. Non-thermal desorption / ionization can be performed at the level, that is, by an extremely small amount. This will be described with reference to FIGS. 13 and 14. Here, FIG. 13 conceptually shows non-thermal desorption ionization caused on the surface of the target 13 by this embodiment, and FIG. 14 shows a comparative example of this embodiment by the MALDI method. The thermal desorption ionization caused by the sample mixed with the matrix agent on the special substrate 201 is conceptually shown.

  As illustrated in FIG. 13, according to the present embodiment, desorption / ionization at the atomic / molecular level can be caused on the surface of the target 13, for example, a minute amount compared to the case of physical contact such as touching with a hand. It is also possible to desorb the surface. Thereby, there is almost no difference between the surface state of the target 13 before the laser pulse irradiation shown on the left side in FIG. 13 and the surface state of the target 13 after the laser pulse irradiation shown on the right side in FIG. The trace of desorption can be confirmed slightly at a level enlarged with an electron microscope (see the lower right portion in FIG. 13).

  On the other hand, as shown in FIG. 14, according to the MALDI method, mass spectrometry can be performed in a state where sample molecules 202, impurities 203 and matrix agent (reagent molecules) 213 are mixed on a special substrate 201 made of silicon or the like. Done. Accordingly, the state of the surface of the target mixed with the sample molecules 202 before the laser pulse irradiation shown on the left side in FIG. 14 and the state of the surface of the target after the laser pulse irradiation shown on the right side in FIG. There is a significant difference by the amount of surface destruction. And the trace of desorption that is much larger than the atomic / molecular level can be clearly confirmed. That is, nondestructive mass spectrometry is difficult with the MALDI method. In addition, noise components are generated in the time-of-flight mass analysis due to the presence of the matrix agent 213 and the impurities 203. Therefore, in the MALDI method, the identification of the peak in the ion signal intensity becomes large and small, making it difficult. Here, in order to increase the analysis accuracy, it is necessary to appropriately change the type of the matrix agent 213 according to the type of the sample molecule 202.

  Subsequently, referring to FIG. 15 to FIG. 23, mass analysis is performed on various samples by the laser analyzer 2 according to this embodiment that performs analysis using the femtosecond laser LB in which the irradiation fluence is set as described above. The case will be described.

  First, referring to FIG. 15, a case where mass spectrometry is performed on a “biological sample” will be described.

  The ion signal intensity shown in FIG. 15 is obtained by performing mass spectrometry on a phosphatidylcholine molecule (PCM = 745 1 μmmol), which is well known as a cell membrane, as a typical example of a biological sample. Here, first, the biological sample is made into a dichloromethane solution, and 10 nmol is dried and coated on a glass substrate. Thereby, a very thin sample of 1 μmol is generated on the glass substrate. The glass substrate is irradiated with a femtosecond laser LB having a wavelength of 800 nm and a pulse width of 130 fs at a low fluence, as described above, to perform time-of-flight mass analysis. . The result is the ion signal intensity shown in FIG.

  In FIG. 15, the broad peak observed near 84.65 μs is identified as a phosphatidylcholine molecule. On the other hand, a strong peak observed at 25 μs or less is atomic ions generated by ablation from the glass substrate. Since no significant fragment ions are observed between 25 and 80 μs, desorption ionization in the low fluence region is considered to be soft ionization that selectively generates molecular ions. Further, as is apparent from FIG. 15, the analysis accuracy is not inferior or is far superior depending on the type of sample even when compared with a general MALDI method.

  Next, referring to FIG. 16 to FIG. 23, two “solid compound samples” are analyzed by the laser analyzer 2 according to this embodiment that performs analysis using the femtosecond laser LB in which the irradiation fluence is set as described above. A case where mass spectrometry is performed on an example will be described.

The ion signal intensities shown in FIGS. 16 to 19 are obtained by performing mass spectrometry on coronene molecules (C ₂₄ H ₁₂ : molecular weight 300.4) as an example of a solid compound sample. In particular, the ion signal intensities shown in FIGS. 16, 17, 18 and 19 are obtained by setting the laser light intensity to 5.5 μJ, 5.9 μJ, 6.5 μJ and 8.7 μJ in this order. is there. In the figure, “M ⁺ ” is a monovalent ion of a coronene molecule, and “M ₂ ⁺ ” is an ion of a dimer (two molecules are associated). By irradiating such a coronene molecule with a femtosecond laser LB having a wavelength of 800 nm and a pulse width of 130 fs at a low fluence, for example, as described above, a time-of-flight mass spectrometry is performed. Do. The result is the ion signal intensity shown in FIGS.

  As can be seen from FIG. 16 to FIG. 19, molecular ions are observed more markedly than in the case of the “biological sample” shown in FIG. Further, the amount of ions detected dramatically increases only by slightly increasing the laser intensity. At a laser intensity of 5.9 μJ or more, molecular dimer ions are also observed. Furthermore, fragment ions (fragmentation) are also observed with increasing laser intensity.

The ion signal intensity shown in FIGS. 20 to 23 is obtained by performing mass spectrometry on fullerene C ₆₀ molecules (C ₆₀ : molecular weight 720) as another example of the solid compound sample. In particular, the ion signal intensities shown in FIGS. 20, 21, 22 and 23 are obtained by setting the laser light intensity to 9.4 μJ, 11 μJ, 13 μJ and 17 μJ in this order. By irradiating such a fullerene C ₆₀ molecule with a femtosecond laser LB having a wavelength of 800 nm and a pulse width of 130 fs with a low fluence, for example, as described above, a time-of-flight mass is obtained. Perform analysis. The result is the ion signal intensity shown in FIGS.

  As can be seen from FIGS. 20 to 23, molecular ions are observed more markedly than in the case of the “biological sample” shown in FIG. Further, the amount of ions detected dramatically increases only by slightly increasing the laser intensity. Furthermore, molecular dimer ions are observed, and fragment ions (fragmentation) are also observed in a particularly strong region.

  As described above with reference to FIGS. 16 to 23, both the coronene molecules and the fullerene molecules have fewer fragments and molecular ions are remarkably observed than in the case of the biological sample (see FIG. 15). This is considered to be caused by (1) a very high concentration of sample molecules and (2) a relatively small molecular size.

As described above in detail, according to the laser analyzer 2 of the present embodiment, a low fluence and femtosecond laser with respect to various targets 13 such as a metal sample, a biological sample, a chemical sample, and a compound sample. By using an extremely short pulse of LB, a non-thermal molecular ion release phenomenon occurs on the surface of the target 13, and the surface can be peeled off at the atomic / molecular level without being heated. In particular, the light intensity of the femtosecond laser LB is set to a value at which the molecular ion M ⁺ is desorbed from the surface of the target 13 by the tunnel ionization process and the nonresonant multiphoton absorption process by the laser electric field caused by the femtosecond laser LB. By doing so, it becomes possible to desorb molecular ions M ⁺ from the surface of the target 13 extremely efficiently and non-destructively. Therefore, according to the laser analyzer 2, non-destructive mass spectrometry is possible, and it is not particularly necessary to add a matrix agent or the like as in the MALDI method described above, and a biological sample, a semiconductor material, a metal material, a chemical sample, Since various samples such as compound samples can be analyzed as they are with little or no damage in a practical sense, it is very advantageous in practice.

  Further, even if the target 13 is made of a material other than a metal sample or a biological sample, for example, a semiconductor material or an insulator, a femtosecond laser LB in a low fluence region corresponding to the material of the target 13 is used as the material of the target 13. By irradiating with the corresponding light intensity, non-destructive analysis is possible for any target 13. For example, by increasing the laser intensity, an insulator or the like can be mass analyzed as the target 13 with relatively no problem. Alternatively, since the laser is irradiated at a low fluence, a compound or biological sample that is easily destroyed can be subjected to mass spectrometry or the like as the target 13 with relatively no problem. This embodiment is useful for elucidating biological functions, for example, by detecting the dynamic distribution process of molecules in cells and biological organs because it can detect substances that affect cells in living cells. It can be a tool. In addition, the present embodiment can be an effective tool for elucidating the process of inducing and suppressing gene expression of post-genomic drugs, and can also be an innovative control technique in genome drug discovery.

  In this way, the present invention provides extremely important analytical techniques over a wide range of fields such as nanotechnology, information technology, environmental technology, biotechnology, and manufacturing technology, where miniaturization proceeds.

  Note that the three ablation threshold fluences F3, th, F2, th and F1, th as illustrated in FIG. 6 can be quantified or tabulated in advance depending on the material of the surface of the target 13. Therefore, once these values are obtained, the value of the irradiation fluence in the setting process by the control device 10 (see FIG. 2) is uniquely determined according to the material of the target 13 that is actually the target of laser irradiation. It becomes possible to decide. That is, when the analysis is actually performed on various types of samples, the setting of the irradiation fluence value by the control device 10 can be performed quickly and easily.

  In addition, in the above-described embodiment, under the drive control by the control device 10, the laser analysis device 2 can irradiate one laser pulse as a femtosecond laser LB in a time independent manner from the other laser pulses. May be configured. As a result, by irradiating one laser pulse in a time independent manner from other laser pulses, molecular ions are desorbed and ionized from the surface of the target 13 with an extremely fine amount of separation corresponding to one laser pulse. It becomes possible to make it. Alternatively, the laser analyzer 2 may be configured to irradiate a plurality of laser pulses collectively or continuously under drive control by the control device 10. Thereby, molecular ions can be released from the target 13 with a large amount of peeling, and the analysis speed and analysis accuracy in the analyzer 2 can be increased.

  The present invention is not limited to the above-described embodiments, and can be changed as appropriate without departing from the spirit or philosophy of the invention that can be read from the claims and the entire specification. And the method are also included in the technical scope of the present invention.

The laser analysis apparatus and method according to the present invention can be used for nondestructive analysis such as nondestructive ultratrace analysis on a solid surface using a laser.

Claims (10)

Irradiation means for irradiating the sample surface with a femtosecond laser in a low fluence region according to the material of the sample surface that causes non-thermal desorption ionization on the sample surface by irradiating the sample surface When,
And an analyzing means for analyzing molecular ions desorbed from the sample surface in response to the irradiated femtosecond laser. 2. The laser analyzer according to claim 1, wherein the analyzing means includes a mass analyzing means for analyzing a mass of the desorbed molecular ions. 3. The laser analyzer according to claim 2, wherein the mass analyzing means includes a concentration detecting means for detecting the concentration of the desorbed molecular ions. 2. The laser analyzer according to claim 1, wherein the irradiation unit irradiates the femtosecond laser onto the sample surface in a state where a matrix agent is not mixed. 3. The light intensity of the femtosecond laser is set to a value at which the molecular ions are desorbed from the sample surface by a tunnel ionization process and a non-resonant multiphoton absorption process by a laser electric field caused by the femtosecond laser. The laser analyzer according to claim 1. The sample surface comprises a surface of a biological sample or a solid sample,
2. The laser analyzer according to claim 1, wherein the irradiation means desorbs the molecular ions from the sample surface in a nondestructive manner. The sample surface consists of the surface of a biological sample,
The laser analyzing apparatus according to claim 1, wherein the analyzing means includes a detecting means for detecting a dynamic distribution process of the molecular ions on the sample surface. An ion accelerator for accelerating the desorbed molecular ions while accommodating the sample having the sample surface so that the irradiation means can irradiate the femtosecond laser;
The laser analysis apparatus according to claim 1, further comprising: a vacuum vessel for guiding the accelerated molecular ions to the analysis means. Irradiation step of irradiating the sample surface with a femtosecond laser in a low fluence region corresponding to the material of the sample surface that causes non-thermal desorption ionization on the sample surface by irradiating the sample surface When,
An analysis step of analyzing molecular ions desorbed from the sample surface in response to the irradiated femtosecond laser. According to the material of the sample surface, further comprising a setting step of setting an irradiation fluence value related to the femtosecond laser in the low fluence region,
The laser analysis method according to claim 9, wherein the irradiation step irradiates the femtosecond laser with the set irradiation fluence value on the sample surface.

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