JP2008022991A - Energy transfer capillary, energy transfer apparatus, and method of forming energy transfer capillary - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an energy transfer capillary which performs an energy transfer by charged particles in a three-dimensional manner more precisely. <P>SOLUTION: The energy transfer capillary 1 for transferring energy by charged particles to a target is equipped with a main body part 3 of the capillary which is surrounded by cylindrical side walls and has a hollow part where the charged particles pass through in the direction of the axis of the capillary and a lid body part 2 for closing an open end of the hollow part at an end part of the main body part of the capillary. The hollow part 4 formed as a closed space in the main body part 3 by the lid body part 2 is kept in a vacuum state, and the thickness of the lid body part 2 is determined in a manner to perform the energy transfer by charged particles to the target in a region to a position at a prescribed distance from the outer surface of the lid body part. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an energy application capillary for applying energy by charged particles to a target, an energy application apparatus using the capillary, and a method for manufacturing the same.

Conventionally, in radiotherapy for cancer, treatment of destroying cancer cells by applying linear energy transfer (LET) to cancer tumors by charged particles such as proton beams, α rays, and heavy particle beams. Has been done. In this treatment, since it is important to accurately give the line energy to the affected part in order to avoid unnecessary exposure, a technique related to the positioning of the subject using the X-ray absorbing member is disclosed (for example, (See Patent Document 1). As a specific example of cancer treatment, linear energy is applied so that the Bragg peak of carbon ions (heavy particle beam) is located in the affected area. In order to avoid unnecessary exposure to the patient, Neat charged particle irradiation is required.
JP 2005-304909 A

  The size of chloroplasts and Golgi bodies in the cells of living organisms is generally on the order of 1 μm, and each forms a three-dimensional network. Therefore, in order to give energy by charged particles in consideration of the spread of the Bragg peak for these intracellular organs, the relative positional relationship between the charged particles and the target can be controlled three-dimensionally on the order of 1 μm. Is preferred.

  However, conventionally, in consideration of vacuum holding of an accelerator for generating a charged particle beam, a charged particle beam line, and handling of a target cell, the distance between the charged particle exit port and the target is 10 mm. Some distance is necessary. In this case, charged particles emitted from the emission port are scattered by the air layer, and a region to which energy is applied (hereinafter also referred to as “energy application region”) is greatly expanded. For example, in the case of a 500 keV proton beam with an air range of 8 mm, the range of the range is about 300 μm at half value. This means that it is difficult to accurately apply energy to the specific target by charged particles, and damage is given to a target that does not require energy application.

  In addition, by reducing the energy of the charged particle beam, it is possible to shorten the distance between the exit port and the target and minimize the influence of the air layer, but it may still be scattered by the air layer. If the target is located in a deep position such as inside the human body, it is difficult to give energy to the target. On the other hand, when the energy of the charged particle beam increases, the charged particles may penetrate the target and damage not only the front of the target but also normal cells behind the target.

  In the present invention, in view of the above-described problems, an energy application capillary capable of more accurately performing three-dimensional energy application to charged targets, and an energy application apparatus using the capillary, and It aims at providing the manufacturing method.

In the present invention, in order to solve the above-described problem, in the capillary for energy application for applying energy by charged particles to the target, a portion that is in a vacuum state for passing charged particles passes to the target as much as possible. A structure that can reach close positions has been adopted. By doing this, it is possible to avoid the presence of an air layer between the target and the charged particle exit, and to suppress the scattering of the charged particles, thereby suppressing the spread of the energy application region. It becomes.

  More specifically, the present invention is an energy application capillary for applying energy by charged particles to a target, and is a capillary body having a hollow portion surrounded by a cylindrical side wall and through which charged particles pass in the capillary axis direction. And a lid portion that closes the open end of the hollow portion at the distal end portion of the capillary body portion, and the hollow portion that is formed as a closed space in the capillary body portion by the lid portion is in a vacuum state The thickness of the lid portion is determined so that energy is applied to the target by charged particles in a region from the outer surface of the lid portion to a position at a predetermined distance. .

  The present invention also provides a capillary for energy application for applying energy by charged particles to a target, the capillary main body having a hollow part surrounded by a cylindrical side wall and through which charged particles pass in the capillary axis direction. An energy applying capillary comprising: a lid portion that closes an open end of the hollow portion at a distal end portion of the capillary body and that can maintain the hollow portion in a vacuum state.

  In the energy applying capillary, the charged particles pass through the hollow portion of the capillary body. Here, since the open end, that is, the end opposite to the end that supplies charged particles in the hollow portion is closed by the lid portion, a closed space is formed in the hollow portion. Since the closed space is in a vacuum state, the charged particles can reach the lid without scattering. Then, the reached charged particles pass through the lid body and are emitted to the outside of the capillary where the target exists. That is, the outer surface of the lid portion functions as a charged particle emission port.

  Note that the diameter of the emission port is appropriately set according to the size of the target. That is, when used for a very small target such as a cell in its usage, the diameter of the exit port of the energy applying capillary is preferably about the same as the size of the target in order to direct charged particles toward the target.

  Here, as described above, the capillary for energy application according to the present invention forms a closed space between the capillary body and the lid, and the closed space can be maintained in a vacuum state. By bringing the outer surface of the lid portion closer to the target, the charged particles emitted from the lid portion can be irradiated to the target with as little influence as possible from the air layer. Therefore, by controlling the position of the capillary for energy application according to the present invention with respect to the target according to the position and size of the target, it becomes possible to carry the charged particles to the vicinity of the target, and thus the energy application by the charged particles is performed. It becomes possible to carry out more accurately.

  In other words, since it is possible to bring the exit of the charged particle close to the target, the energy application region by the charged particle is located between the outer surface of the lid, which is the exit of the charged particle, to a position at a predetermined distance. To easily position the target within that region. As a result, energy can be imparted more accurately by charged particles. Further, since the influence of the air layer between the emission port and the target is eliminated as much as possible, energy can be imparted to the target even with charged particles having a relatively low energy. When the energy of the charged particles is lowered, the range is naturally shortened, but the spread of the energy application region is suppressed. Therefore, the capillary for energy application according to the present invention contributes to accurate energy application to the target by the low energy charged particles.

Here, in the hollow portion as a closed space that is in a vacuum state, attenuation of the charged particle energy does not occur, but when the charged particles pass through the lid portion, the material of the lid portion and the thickness of the lid portion The energy of the charged particles is attenuated by (thickness from the hollow portion side to the outer surface side). In consideration of this point, it is possible to control the energy of charged particles emitted from the outer surface of the lid body portion by adjusting the thickness of the lid body portion. This is because the appearance position of the Bragg peak of the charged particle can be controlled by the thickness of the lid part, and further, it is formed outside from the outer surface of the lid part as a charged particle exit port. This means that the energy application region can be controlled by the thickness of the lid portion. Therefore, in the energy application capillary according to the present invention, the thickness of the lid is such that energy is applied to the target by charged particles in a region from the outer surface of the lid to a position at a predetermined distance. It is determined. Thus, the energy provision with respect to a target can be performed more correctly by adjusting the thickness of a cover body part.

  In the energy applying capillary described above, the hollow portion may have a taper shape so that the cross-sectional area of the hollow portion decreases as it advances toward the tip end side in the capillary axis direction.

  That is, by forming the tapered shape so that the tip is thin, a part of the charged particles that pass through the hollow portion is incident on the side wall of the capillary body, so that the charged particles emitted from the outer surface of the lid body The amount of. Thereby, the amount of charged particles finally irradiated from the energy applying capillary can be finely controlled. In addition, since the charged particles incident on the side wall are incident on the side wall at a relatively shallow angle, it is suppressed from being attenuated in the side wall and leaking outside.

  As for the side wall, the cylindrical side wall may have a thickness that enables leakage of the charged particles from the side wall based on an incident angle of the charged particles to the side wall. That is, the thickness of the side wall of the capillary main body is such a thickness that prevents charged particles from leaking out from the side wall and applying energy to a target around the side wall (a target that is not the original target). It is preferable.

  In the energy application capillary described above, the capillary body and the lid may be made of the same material. By configuring the capillary body portion and the lid portion with the same material, the vacuum state in the hollow portion formed as a closed space by the lid portion can be maintained better.

  In the energy application capillary described above, the inner diameter of the hollow portion on the tip side of the capillary body may be 0.2 μm to 25 μm in diameter. That is, it defines the exit diameter of the charged particles of the energy applying capillary. Considering that the size of the cell organ is within the above range when the target is a cell organ in the cell, the charged particle emitted from the emission port can be more reliably obtained in this way. It is possible to irradiate the target.

  Further, when the inner diameter of the hollow portion on the distal end side of the capillary body is taken from another side, the inner diameter may be 0.08 μm to 1 μm in diameter. When the energy applying capillary according to the present invention is used for applying energy to cells of a living body, the above dimensions are preferable in order to suppress unnecessary damage to the cells.

Here, the present invention can also be grasped from the side of an energy application device that applies energy by charged particles to the target using the above-described capillary for energy application. That is, an energy application apparatus using the energy application capillary, the vacuum holding unit for holding the inside of the hollow part of the energy application capillary in a vacuum state, and the charged particle supply unit for supplying charged particles to the energy application capillary Z-axis direction position adjusting means for adjusting the relative position between the energy-applying capillary and the target in the Z-axis direction, which is the irradiation direction of charged particles from the energy-applying capillary, and perpendicular to the Z-axis direction XY plane position adjusting means for adjusting a relative position between the energy applying capillary and the target on the XY plane which is a smooth plane.

  That is, the energy application device according to the present invention enables three-dimensional control of the relative positional relationship between the energy application capillary and the target by the Z-axis direction position adjustment unit and the XY plane position adjustment unit.

  In other words, the Z-axis direction is the beam axis of the charged particle beam, but if the Z-axis and the capillary axis are deviated, it is difficult to apply energy to the target by the charged particles. That is, the deviation between the Z axis and the capillary axis may affect the relative position of the energy application region with respect to the target. Therefore, a Z-axis angle adjusting means for adjusting a relative angle between the Z-axis direction and the capillary axis direction may be further provided.

  Here, in the energy application device, when the target changes a relative position with respect to the energy application capillary with time, the energy application capillary is adjusted by the Z-axis direction position adjustment unit and / or the XY plane position adjustment unit. A follow-up means for following the movement of the target with respect to the target relative to the target may be further provided.

  By providing this follow-up means, the relative positional relationship between the energy applying capillary and the target can be maintained in a state suitable for energy application by charged particles. This is particularly useful when the target is fluid, i.e., changes relative to the energy application capillary over time.

  Here, in the energy application device, when energy is applied to the target by charged particles, the air layer is not interposed between the outer surface of the lid portion of the capillary for energy application and the target. It is preferable to apply energy to the target by charged particles. By doing in this way, scattering by an air layer can be avoided and energy can be more accurately applied to the target.

  Further, as a more specific form of energy application by the energy application device, when the target is a living cell, by the position adjustment by the Z-axis direction position adjustment means and / or the XY plane position adjustment means, In a state where the outer surface of the lid portion of the capillary for energy application is in contact with the outer surface portion of the cell, or in a state where the outer surface of the lid portion is inserted into the cell, that is, the target cell Energy may be imparted by charged particles to a predetermined site in the cell in a state where no air layer is interposed between the outer surface and the outer surface.

  Here, the present invention can also be grasped from the aspect of the method for producing the capillary for energy application. Specifically, a method for producing an energy application capillary for applying energy by charged particles to a target, the first step of creating a provisional capillary by stretching a tubular body while heating, and the first step Cutting the provisional capillary created by the second step to form an opening having a predetermined inner diameter, and heating and melting the opening side of the provisional capillary cut by the second step, thereby opening the opening. And a third step of closing.

In the first step, a temporary capillary whose inner diameter portion corresponds to the hollow portion is created by stretching the tubular body. Accordingly, the provisional capillary is the basis of the capillary body. And the said capillary main-body part is formed by performing a 2nd step with respect to a temporary capillary. Here, the predetermined inner diameter is the diameter of the emission port through which charged particles are finally emitted from the capillary, and the size is appropriately set according to the size of the target and the like.

  Thereafter, in the third step, the opening is closed by heating in the vicinity of the opening, so that the inner diameter portion in the temporary capillary becomes a closed space and can be maintained in a vacuum state. Therefore, the above-described manufacturing method can manufacture the above-described energy applying capillary according to the present invention.

  Furthermore, in the manufacturing method of the capillary for energy application, the fitting step further includes a fitting step of fitting a lid that closes the opening into the opening formed in the second step, and the third step is the fitting step. The opening in which the lid is fitted may be heated and melted, and the opening may be closed by integrating the lid with the temporary capillary. In this fitting step, the opening is closed with a lid, and in the third step, the lid and the temporary capillary are integrated, whereby the lid is formed. By this integration, the inner diameter portion in the temporary capillary becomes a closed space, which can be maintained in a vacuum state.

  Here, in the manufacturing method, the opening that is blocked in the third step is cut, and the thickness of the blocked opening is determined with respect to the target in a region from the outer surface to a position at a predetermined distance. You may make it further provide the 4th step made into the thickness by which the energy provision by a charged particle is made. The predetermined distance here is synonymous with the above-mentioned predetermined distance. That is, by adjusting the thickness of the lid in the fourth step, it becomes possible to adjust the energy application region by charged particles, which makes it possible to produce a capillary that enables more accurate energy application to the target. Will contribute.

  Here, when the tubular body and the lid are formed of a material having visible light permeability, the fourth step attaches a reference mark as a reference to the closed opening or the temporary capillary. And determining a position to cut the blocked opening based on the position of the reference mark and the inner surface of the blocked opening by an optical microscope, and a part of the blocked opening. May be cut off. Since the tubular body and the lid have visible light permeability, it is possible to adjust the thickness of the lid while confirming the position with an optical microscope. The inner surface of the lid is one of the elements that determine the thickness of the lid, and the outer surface of the lid, which is another element, is based on the reference mark and the inner surface of the lid. In order to set the thickness of the lid to a predetermined thickness, the position is determined by the fourth step, and the lid is cut.

  It is possible to provide a capillary for energy application capable of performing energy application by charged particles to a target more accurately in three dimensions, an energy application device using the same, and a method for manufacturing the same. Become.

  Embodiments of an energy applying capillary, an energy applying device using the same, and a method for manufacturing the same according to the present invention will be described with reference to the drawings.

  FIG. 1 is a diagram showing a schematic structure of an energy applying capillary (hereinafter simply referred to as “capillary”) 1 according to the present invention. The capillary 1 is made of glass made of borosilicate. A method for manufacturing the capillary 1 will be described later.

The capillary 1 has a tubular capillary body 3 having a side wall having a thickness Ts. A hollow portion 4 is formed at the center of the capillary body 3. A lid body portion 2 is provided on the distal end side of the hollow portion 4 so as to close the open end of the hollow portion 2. The capillary body 3 and the lid 2 are finally in an integrated state, but in this embodiment, in the manufacturing process, each is initially constituted by a separate member and later integrated. Go through. Therefore, the hollow portion 4 is formed in a closed space by the side wall of the capillary body portion 3 and the lid portion 2. The base end side of the capillary body 3 (the opposite end where the lid 2 is provided) is connected to a vacuum pump 15 that evacuates the capillary 1 and an accelerator 14 that supplies alpha rays to the capillary 1. Are connected (see FIG. 4).

  In addition, as will be described later, the cap body part 3 and the cap body part 2 may be formed of the same member in addition to the cap body part 3 and the cap body part 2, as will be described later. Even in such a case, the hollow portion 4 is finally closed space, the portion on the distal end side of the closed space becomes the lid portion 2, and the proximal end side thereof is connected to the accelerator 14.

  Further, details of the capillary 1 will be described. The hollow portion 4 has a tapered shape such that the cross-sectional area thereof becomes smaller as it advances toward the tip end in the axial direction of the capillary 1. This is due to the manufacturing process of the capillary 1. As described above, since the hollow portion 4 has a tapered shape, the α rays finally supplied to the capillary 1 pass through the lid portion 2 and irradiate the target Tg located outside the capillary 1. Will be.

  Here, the dimensions of the capillary 1 according to the present embodiment will be described. The inner diameter of the inside of the lid portion 2 (the hollow portion 4 side) is 1.5 μm in diameter, and the thickness of the lid portion 2 (inner side and outer side). The distance between them and Tm is 8 μm. Furthermore, the side wall thickness Ts of the capillary body 3 is 5 to 6 μm. These dimensions are merely examples, and the capillaries according to the present invention are not limited to those shown in these dimensions.

  The α rays supplied from the accelerator 14 travel through the hollow portion 4 maintained in a vacuum state. In this process, some α rays are incident on the side wall of the capillary body 3 without reaching the lid 2 (in this embodiment, the α rays incident at the incident angle θ are illustrated in FIG. The remainder is incident on the lid portion 2 (in the present embodiment, an example is shown in which the incident angle is incident on the inner side of the lid portion substantially perpendicularly). Here, when the α rays incident on the lid body part 2 are subjected to energy attenuation by a member (a glass member in the present embodiment) constituting the lid body part 2 and reach the outer surface of the lid body part 2. The α ray is reduced by the amount corresponding to the energy decay. Thereafter, the α rays emitted from the outer surface of the lid body 2 are irradiated to the target Tg.

  On the other hand, the α ray incident on the side wall of the capillary main body 3 is also subjected to energy attenuation by the member (glass member) constituting the side wall in the same manner as the α ray incident on the lid portion 2. Here, in the present embodiment, the thickness Ts of the side wall is slightly thinner than the thickness Tm of the lid portion 2. However, since α rays are incident on the side walls at an irradiation angle θ, the substantial thickness of the side walls in the direction of the α ray path is the thickness obtained by dividing Ts by sin θ. Since the tapered shape of the hollow portion 4 is a taper that is almost parallel to the capillary axis, the thickness obtained by dividing Ts by sin θ reaches several hundred times the thickness Tm. For this reason, a part of the α rays incident on the side wall returns to the hollow portion 4 and the rest is attenuated almost completely inside the side wall, and is not emitted outside the capillary 1 in contact with the side wall. Therefore, energy application by α rays is not performed on an object located near the side wall (an object that is not an original target), which is very important for enhancing the safety of energy application by the capillary 1. Is important to.

In summary, when the capillary 1 according to the present invention is used, the α-ray supplied to the capillary 1 applies energy to the target Tg only from the outer surface of the lid 2 by the α-ray. . That is, as one of the features of energy application using the capillary 1,
That is, the target is irradiated with α rays only from the outer surface of the lid 2. In other words, α rays supplied from the accelerator 14 to the capillary 1 are irradiated to the target from the lid portion 2 having an inner diameter of 1.5 μm through the hollow portion 4 maintained in a vacuum state. That is, the capillary 1 reliably guides α rays from the supply source to the target through the hollow portion 4 maintained in a vacuum state. As a result, it becomes possible to more reliably irradiate the target Tg with α rays.

  Next, energy application by α rays that are incident on the lid 2 from the hollow portion 4 and are then irradiated on the target Tg will be described. The α rays incident on the lid portion 2 are subjected to energy attenuation therein, and then travel within the target Tg by a distance corresponding to the energy of the α rays. In this process, a Bragg peak in the application of α-ray linear energy appears, and in the region (energy application region) indicated by a predetermined distance Le in FIG. 1 from the outer surface of the lid 2 to the position where the α-ray stops. Then, energy is applied by α rays. The appearance position of the Bragg peak occurs in the lid body 2 or the target Tg depending on the thickness of the lid body 2 or the like. Therefore, by providing the target Tg in the energy application region represented by the predetermined distance Le, energy application to the specific target Tg is performed reliably. Furthermore, when it is desired to apply energy at the Bragg peak to the specific part Tgp in the target Tg, the specific part Tgp is located at a position away from the outer surface of the lid 2 by the distance at which the Bragg peak appears. do it.

  From this, the energy application region represented by the predetermined distance Le is adjusted by adjusting the thickness Tm of the lid body portion 2 by utilizing the energy attenuation of α rays due to the thickness of the lid body portion 2. Also good. For example, when the energy given to the α ray from the accelerator 14 is 5 MeV, the range of the α ray in the glass made of borosilicate is 20 μm. Therefore, when the thickness of the lid portion 2 is set to be thinner than 20 μm, α rays that have received energy attenuation corresponding to the thickness are emitted from the outer surface of the lid portion 2. Accordingly, the thickness of the lid portion 2 may be adjusted so that the energy of the emitted α-rays forms a desired energy application region.

  This point will be described more specifically with reference to FIG. FIG. 2 shows the relationship between the thickness of the lid portion 2 of the capillary 1 and the energy application region represented by the distance Le. 2A shows a capillary with a lid 2 having a thickness of 8 μm, FIG. 2B shows a capillary with a lid 2 having a thickness of 5 μm, and FIG. 2C shows a thickness of the lid 2. Each corresponds to a capillary with a length of 1 μm. Here, when the α-ray of 3 MeV is incident on the lid part 2, in the case of FIG. 2A, as a result of energy attenuation corresponding to the thickness of 8 μm, energy is applied such that the distance Le is 3 μm. A region is formed in the target Tg. At this time, since the Bragg peak is greeted in the lid 2, no energy is imparted to the target Tg at the Bragg peak. In the case of FIG. 2B, as a result of energy attenuation corresponding to a thickness of 5 μm, an energy application region in which the distance Le is represented by 8 μm is formed in the target Tg. At this time, the Bragg peak is greeted at a position 5 μm away from the outer surface of the lid 2. Further, in the case of FIG. 2C, as a result of energy attenuation corresponding to the thickness of 1 μm, an energy application region where the distance Le is 16 μm is formed in the target Tg. At this time, the Bragg peak is greeted at a position 13 μm away from the outer surface of the lid 2.

  Thus, it becomes possible to adjust an energy provision area | region by changing the thickness of the cover body part 2, and the specific site | part Tgp etc. in the target Tg to which energy should be provided in this energy provision area | region are located. Thus, the desired energy application is performed.

Here, as described above, the capillary 1 according to the present invention can guide α-rays in a space in which a vacuum state is maintained up to the immediate vicinity of the target Tg. And the alpha ray is directly irradiated with respect to a target from the outer surface of the cover body part 2. FIG. As a result, the possibility of receiving α-ray scattering by the air layer becomes extremely low, and the energy application region represented by the distance Le can be controlled more accurately. Therefore, the adjustment of the thickness Tm of the lid portion 2 can greatly contribute to accurate energy application. In addition, by maintaining the vacuum state as close as possible to the target Tg in this way, it is also possible to use charged particles such as low-energy α rays that do not cause the Bragg peak to appear in the energy application process. As the charged particles become lower in energy, it becomes possible to suppress the spread of the energy application region, so that more accurate energy application by the charged particles becomes possible.

  Here, the dimensions of the capillary 1 according to the present embodiment are as described above, but dimensions other than those described above can also be applied to the capillary 1 when a living cell or an intracellular organ is assumed as the target Tg. According to the “Science Chronology”, the diameter of human egg cells is 140 μm, and the diameter of hepatocytes is 20 to 35 μm. Furthermore, the diameters and lengths of the nucleus, nucleolus, chloroplast, and Golgi apparatus, which are intracellular organs, are 5 to 25 μm, 1 to 4 μm, 4 to 8 μm, and 0.2 to 5.5 μm, respectively. The inner diameter on the distal end side of the hollow portion 4 that is the diameter of the α-ray emission port of the capillary 1 is preferably adapted to the size of the target Tg. This is because if the inner diameter on the distal end side of the hollow portion 4 is too large or too small with respect to the target, the α-rays may not be appropriately irradiated to the target. Therefore, when the intracellular organ is the target Tg, it is preferable that the inner diameter on the tip side of the hollow portion 4 is 0.2 μm to 25 μm depending on the size of the target.

  Further, as will be described later, the capillary 1 according to the present invention can be inserted into a living body cell to apply energy to the intracellular organ. At this time, in order to suppress extra damage to the cells, the inner diameter on the tip side of the capillary 1 is preferably in the range of 0.08 μm to 1 μm.

  Here, the result of the performance confirmation test of the capillary 1 according to the present invention is shown in FIG. FIG. 3A is a diagram showing a device configuration for the performance confirmation test. In the performance confirmation test, the liquid scintillator 20 was applied to the capillary 1 so as to cover the tip portion of the capillary 1 (the portion of the lid body portion 2 that is the α-ray emission port). In this state, the inside of the hollow portion 4 of the capillary 1 was evacuated, and α rays were supplied thereto from the accelerator 14. At this time, the α rays emitted from the outer surface of the lid body portion 2 travel through the liquid scintillator, and at that time, the region to which energy is given by the α rays appears as a light emission site EP (shaded portion in FIG. 3). . The length Le along the beam axis of the light emitting part EP reflects the range of the α rays in the liquid scintillator 20 and the spread in the beam axis direction, and the diameter De of the issuing part EP in the width direction is The inner diameter of the capillary 1 and the spread in the width direction are reflected.

  The result of the performance confirmation test shown in FIG. 3A is shown in FIG. When the beam energy of α rays is 4 MeV, the distance Le in the beam axis direction of α rays is 13 μm, the diameter De of the light emitting portion EP in the width direction is 5 μm, and when the beam energy of α rays is 3 MeV, Le is 6 μm, De is 4 μm. As described above, when the capillary 1 according to the present invention is used, energy can be imparted to the target by α rays with a relatively low extent.

  Here, the overall configuration of the energy application device that enables energy application to the target Tg using the capillary 1 will be described with reference to FIG. 4. The capillary 1 is supplied with α rays from the accelerator 14 in a state where the hollow portion 4 is evacuated by the vacuum pump 15. The α rays are irradiated to the target Tg. In this irradiation, the adjustment devices 11, 12, and 13 that adjust the relative positional relationship between the capillary 1 and the target Tg are included in the energy applying device according to the present invention. Is provided.

The adjusting device 11 adjusts the relative position between the capillary 1 and the target Tg in the Z-axis direction. The Z-axis direction is the beam axis direction of the α-ray, and the adjustment device 11 can adjust the position along the traveling direction of the α-ray. Further, the adjusting device 12 determines the relative position between the capillary 1 and the target Tg as X
Adjust in the Y-axis direction. The XY plane constituted by the X and Y axes is a plane orthogonal to the Z axis, and the adjustment device 12 can perform two-dimensional position adjustment in the XY plane. Further, the adjustment device 13 is provided on the adjustment device 11 and adjusts the relative angle between the Z-axis direction and the capillary 1 axial direction. As a result, the α-ray beam line can be aligned in a direction perpendicular to the outer surface of the lid portion 2 that is the exit of the capillary 1, and the energy is applied to the target by interlocking with the adjusting devices 11 and 12. Can be performed more accurately. In this embodiment, the adjusting devices 11 and 12 are provided on the capillary 1 side, but may be provided on the target Tg side instead.

  FIG. 5 shows a more specific example of α-ray irradiation to the target using the energy application device shown in FIG. 4. FIG. 5A shows the state of irradiation with α rays when the target is the cell itself. At this time, the adjustment device 11, 12, 13 causes the outer surface of the lid portion 2 of the capillary 1 to be in contact with the outer wall (cell wall) of the target cell, and then irradiates the target with α rays. Is done. As a result, energy is applied to the target by α rays. In this case, when the target cell has fluidity that changes its position over time, the position of the capillary 1 is adjusted by the adjusting devices 11, 12, and 13, so that the target cell is the capillary 1 and the target. It is possible to continuously apply energy to the cells while keeping the relative relationship with the cells constant. That is, the adjusting devices 11, 12, and 13 have a function of causing the capillary 1 to follow the target cell.

  FIG. 5B shows the state of irradiation with α rays when the target is an intracellular organ. In this case, the distal end portion of the capillary 1 (including the outer surface of the lid body portion 2 that is the α-ray emission port) is inserted into the target cell. Although the inside of the cell is generally filled with water, even if the tip of the capillary 1 is inserted into the cell as described above, the capillaries 2 cannot reach the vicinity of the target intracellular organ due to the presence of the lid 2. It becomes possible to make the hollow part 4 which is a vacuum state exist in 1. This means that it is possible to carry α-rays close to the target without scattering. Therefore, even in the case shown in FIG. 5B, it is possible to more accurately apply energy to the target by α rays.

<Capillary manufacturing process>
Next, the manufacturing process of the capillary 1 will be described based on FIG. 6 and FIGS. 7A to 7K. FIG. 6 is a flowchart showing the flow of the manufacturing process of the capillary 1, and FIGS. 7A to 7K are diagrams showing processes for manufacturing corresponding to the flowchart. First, as shown in S <b> 101, a capillary body that is a basic part of the capillary 1 is created. The diagrams corresponding to this step are FIGS. 7A and 7B. A general puller device is used to create a capillary tube serving as a capillary body. The device is a device that fixes a hollow tubular glass tube 30 and pulls the central portion of the glass tube 30 while heating the central portion with a heater. As shown in FIGS. 7A and 7B, the capillary tube is thinly pulled by this apparatus, and a capillary body is formed using a glass bulb 31 that can be controlled by a heater.

  The thinly stretched glass tube 30 is bonded to the glass bulb 31 while being heated by the glass bulb 31. Then, the glass tube 30a used as a capillary main-body part is created by applying stress to the glass tube 30. FIG. The remaining portion 30b of the glass tube 30 is not necessary for manufacturing the capillary 1. One end of the glass tube 30a is open. The inner diameter of the opening corresponds to the inner diameter of the hollow portion 4 on the tip side of the capillary 1 described above. Therefore, when it is necessary to set the inner diameter to a desired value (in the present embodiment, the inner diameter is 1.5 μm in diameter), the cut portion of the glass tube 30 must be appropriately selected.

Next, it progresses to S102 and the production | generation of the cover body part engage | inserted by the opening part of the said glass tube 30a is performed, The figure corresponding to this step is FIG. 7C and FIG. 7D. As shown in FIG. 7C, the tip of a new capillary 32 made of a new glass tube is heated by a glass bulb 31 so that there is no opening at the tip. Thereafter, as shown in FIG. 7D, the portion 32 b where the opening portion of the capillary 32 does not exist is pressed against the glass bulb 31 and separated from the main body side 32 a of the capillary 32. At this time, in the portion 32b remaining on the glass sphere 31, a portion having a thickness slightly smaller than the diameter of the opening of the glass tube 30a serving as the capillary body portion (a rectangular portion in FIG. 7D) is created. This square portion becomes the lid portion.

  Next, the process proceeds to S103, and the lid part created in S102 is fitted into the opening of the capillary body part created in S101. The diagrams corresponding to this step are FIGS. 7E and 7F. As shown to FIG. 7E, the square part which is a part of the part 32 stuck on the glass bulb | ball 31 is engage | inserted in the opening part of the glass tube 30a. And stress is applied to this state, and as shown to FIG. 7F, a square-shaped part is cut | disconnected and it is set as the state engage | inserted in the glass tube 30a as the cover part 30c. At the time of cutting off the square portion, careful attention may be paid so that the glass tube 30a is not broken, and stress may be applied while heating with the glass bulb 31.

  Next, it progresses to S104 and integration with the cover part 30c and the glass tube 30a is performed. The diagram corresponding to this step is FIG. 7G. In this integration, the glass tube 30a and the lid portion 30c shown in FIG. As a result, a closed space 30 d corresponding to the hollow portion is formed in the glass tube 30.

  Next, it progresses to S105 and the reference mark 30e is stamped on the glass tube 30a in the state which the cover part 30c and the glass tube 30a integrated. The diagram corresponding to this step is FIG. 7H. This marking is performed by a FIB (Focused Ion Beam) apparatus so that the reference mark 30e has a size that allows its shape and position to be confirmed with an optical microscope. The position, number, and shape of the reference mark 30e may be arbitrary. In the present embodiment, as shown in FIG. 7H, the number of reference marks 30e is one.

  Next, in S106, a part of the lid part 30c integrated with the glass tube 30a is cut using the reference mark 30e as a reference to adjust the thickness of the lid part 30c. The diagrams corresponding to this step are FIGS. 7I, 7J, and 7K. First, as shown in FIG. 7I, the relationship between the reference mark 30e and the position of the end of the closed space 30d serving as a hollow portion is confirmed using an optical microscope. That is, the reference mark 30e is for confirming the thickness of the lid portion 30c finally remaining on the glass tube 30a. For example, in the case shown in FIG. 7I, when the lid 30c is cut at the left end of the reference mark 30e, the thickness of the lid is 10 μm, and when the lid 30c is cut at the right end of the reference mark 30e, the thickness of the lid is obtained. Is 3 μm. This is because in the FIB apparatus used when performing microfabrication of the capillary, the appearance of the capillary can be confirmed, but the position of the hollow portion (closed space 30d) existing therein cannot be confirmed. Therefore, using the fact that the glass member forming the glass tube 30a has visible light transmittance, as shown in FIG. 7I, after confirming the relative positional relationship between the reference mark 30e and the closed space 30d, the FIB The lid 30c is cut by the apparatus (see FIG. 7J).

  FIG. 7J shows a glass tube 30a in which a part of the lid 30c is cut by the FIB device. The left side view of FIG. 7J is a side view of the glass tube 30a after cutting, and the right side view is a view of the cut glass tube 30a as viewed from 45 degrees obliquely downward. In the present embodiment, a portion slightly on the right side of the left end portion of the reference mark 30e was cut by the FIB apparatus. It should be noted at this point that a hole is not made in the distal end portion of the glass tube 30a by cutting the lid portion 30c.

  Thereafter, as shown in FIG. 7K, using the optical microscope again, in the cut glass tube 30a, it is confirmed whether or not the thickness of the lid portion 30c is a desired thickness. In the present embodiment, the lid 30c is slightly thicker than the desired thickness of 5 μm, so that the lid 30c is cut again by the FIB apparatus. By repeating this, it is possible to manufacture the capillary according to the present invention having a lid portion having a desired thickness.

<Other capillary manufacturing processes>
Instead of the above-described capillary manufacturing method, available manufacturing methods are shown below. In this manufacturing method, instead of the processing of S102 to S104 shown in FIG. 6, the glass tube 30a that is the capillary body portion having the opening created in S101 is subjected to heat treatment via the glass bulb 31. As a result, the glass tube 30a is melted to close the opening of the glass tube 30a. In this case, since there is no object fitted in the opening in S103 described above, it is necessary to perform sufficient heating to close the opening of the glass tube 30a. In addition, the part which block | closes the opening part by fuse | melting the glass tube 30a exhibits a function equivalent to said cover part 30c, The thickness gives energy by performing the process of above-mentioned S105 and S106. It is adjusted to a thickness suitable for.

It is a figure which shows the structure of the capillary for energy provision which concerns on the Example of this invention. It is a figure which shows the relationship between the thickness of the cover body part of the capillary for energy provision which concerns on the Example of this invention, and the energy provision area | region represented by distance Le. It is a figure which shows the performance test result of the capillary for energy provision which concerns on the Example of this invention. It is a figure which shows schematic structure of the energy provision apparatus using the capillary for energy provision which concerns on the Example of this invention. It is a figure explaining adjustment of the position of the capillary for energy provision at the time of performing energy provision with respect to the cell which is a target using the energy provision apparatus which concerns on the Example of this invention. It is a flowchart which shows the flow of the process for manufacturing the capillary for energy provision which concerns on the Example of this invention. It is a 1st figure explaining the process of producing a capillary main-body part in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a 2nd figure explaining the process of producing a capillary main-body part in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a 1st figure explaining the process of creating a cover part in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a 2nd figure explaining the process of creating a cover part in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a 1st figure explaining the process of fitting a cover body part in the opening part of a capillary main-body part in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a 2nd figure explaining the process of fitting a cover body part in the opening part of a capillary main-body part in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a figure explaining the process of integrating the cover body part engage | inserted by the opening part of the capillary main-body part in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a figure explaining the process of marking a reference mark on a glass tube in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a 1st figure explaining the process of adjusting the thickness of the cover body part integrated with the glass tube in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a 2nd figure explaining the process of adjusting the thickness of the cover body part integrated with the glass tube in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention. It is a 3rd figure explaining the process of adjusting the thickness of the cover part integrated with the glass tube in the manufacturing process of the capillary for energy provision which concerns on the Example of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ...... Capillary for energy provision 2 .... Lid body part 3 .... Capillary main-body part 4 .... Hollow part 11, 12, 13 ... Adjusting device 14 ... Accelerator 15 .... Vacuum pump 30a ... Glass tube 30c ... Lid 30d ... Closed space 30e ... Reference mark

Claims (16)

An energy applying capillary for applying energy by charged particles to a target,
A capillary body part surrounded by a cylindrical side wall and having a hollow part through which charged particles pass in the capillary axis direction;
A lid that closes the open end of the hollow portion at the tip of the capillary body,
The hollow part formed as a closed space in the capillary body part by the lid part can be maintained in a vacuum state,
The thickness of the lid portion is determined so that energy is applied to the target by charged particles in a region from the outer surface of the lid portion to a position at a predetermined distance. Capillary for application. An energy applying capillary for applying energy by charged particles to a target,
A capillary body part surrounded by a cylindrical side wall and having a hollow part through which charged particles pass in the capillary axis direction;
A lid portion that closes an open end of the hollow portion at a tip portion of the capillary body, and allows the hollow portion to be maintained in a vacuum state;
An energy applying capillary characterized by comprising:   The said hollow part has a taper shape so that the cross-sectional area of this hollow part may become small as it advances to the front-end | tip part side in the said capillary axial direction, The energy application of Claim 1 or Claim 2 characterized by the above-mentioned. Capillary.   The cylindrical side wall has a thickness that enables leakage of the charged particles from the side wall based on an incident angle of the charged particles to the side wall. The capillary for energy provision as described in any of the above.   The capillary for energy application according to any one of claims 1 to 4, wherein the material of the capillary body and the lid are the same material.   6. The energy applying capillary according to claim 1, wherein an inner diameter of the hollow portion on a distal end side of the capillary body is 0.2 μm to 25 μm in diameter.   6. The energy applying capillary according to claim 1, wherein an inner diameter of the hollow portion on a distal end side of the capillary body is 0.08 μm to 1 μm in diameter. An energy application device that applies energy by charged particles to the target using the capillary for energy application according to any one of claims 1 to 7,
Vacuum holding means for holding the inside of the hollow portion of the energy applying capillary in a vacuum state;
Charged particle supply means for supplying charged particles to the energy applying capillary;
Z-axis direction position adjusting means for adjusting the relative position between the energy-applying capillary and the target in the Z-axis direction, which is the irradiation direction of charged particles from the energy-applying capillary;
XY plane position adjusting means for adjusting a relative position between the capillary for energy application and the target on the XY plane that is a plane perpendicular to the Z-axis direction;
An energy applicator characterized by comprising:   The energy application device according to claim 8, further comprising Z-axis angle adjusting means for adjusting a relative angle between the Z-axis direction and the capillary axis direction.   When the relative position of the target with respect to the energy application capillary changes with time, the relative position of the energy application capillary with respect to the target is changed by the Z-axis direction position adjustment means and / or the XY plane position adjustment means. The energy applying apparatus according to claim 8, further comprising a follow-up unit that follows the movement of the target.   11. The energy application by charged particles is performed on the target in a state where no air layer is interposed between the outer surface of the lid portion of the capillary for energy application and the target. The energy applicator described. The target is a living cell,
In a state where the outer surface of the lid portion of the capillary for energy application is in contact with the outer surface portion of the cell by the position adjustment by the Z-axis direction position adjusting means and / or the XY plane position adjusting means, or the lid body portion The energy application device according to any one of claims 8 to 10, wherein energy is applied by a charged particle to a predetermined site in the cell in a state where the outer surface of the cell is inserted into the cell. . A method for producing an energy applying capillary for applying energy by charged particles to a target,
A first step of creating a temporary capillary by heating and stretching the tubular body;
Cutting the provisional capillary created by the first step to form an opening with a predetermined inner diameter; and
A third step of heating and melting the opening side of the temporary capillary cut by the second step to close the opening;
The manufacturing method of the capillary for energy provision characterized by including these. A fitting step of fitting a lid that closes the opening into the opening formed in the second step;
In the third step, the opening in which the lid is fitted in the fitting step is heated and melted, and the opening is closed by integrating the lid with the temporary capillary. The method for producing a capillary for energy application according to claim 13.   The opening blocked in the third step is cut, and the thickness of the blocked opening is given energy by the charged particles to the target in a region from the outer surface to a predetermined distance. The method for producing a capillary for energy application according to claim 13 or 14, further comprising a fourth step of setting the thickness to a predetermined thickness. The tubular body and the lid are formed of a material having visible light permeability,
In the fourth step, a reference mark serving as a reference is attached to the closed opening or the temporary capillary, and based on the position of the reference mark and the inner surface of the closed opening by an optical microscope. 16. The method for manufacturing an energy applying capillary according to claim 15, wherein a position for cutting the blocked opening is determined, and a part of the blocked opening is cut.

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