Injector and method for injecting a solution containing a biomolecule into a cell of an injection target using the injector

Abstract

To provide a suitable technology for measuring behavior of liquid ejected toward an object from an ejection device by capturing by means of an imaging device.SOLUTION: A measurement system for measuring intra-object behavior of liquid ejected toward an object from an ejection device comprises: a container part formed from a resin material; an imaging device which is disposed in such a manner as to be capable of capturing, from a back surface side of the object and across the object, an image of a leading-end surface of the container part that has disposed therein an ejection port and that is in contact with the object while the ejection port is kept in a prescribed state in which the ejection port is positioned from a front surface side of the object with respect to the object; and a first irradiation device which irradiates the leading-end surface with first near-infrared light. With this configuration, the behavior of ejection liquid that is being ejected onto an object from an ejection device can be measured by capturing by means of the imaging device.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a measurement system that measures the behavior of ejected fluid ejected from an ejection device toward a target object, and a measurement method thereof. [Background technology]

[0002] Conventionally, various methods have been used to directly observe the flow behavior of a fluid, such as the tuft method, in which the direction of flow is determined from the way many short threads (tufts) flutter, the oil film method, in which a mixture of oil and pigment is applied to the surface of an object and the state, direction, and speed of the flow are determined from the streaks that appear due to the flow, the tracer method, in which fine particles that move with the fluid are mixed into the fluid and their movement is tracked to observe the flow, and as optical methods, the Schlieren method, which uses changes in refractive index based on changes in density, as well as the holographic method and laser speckle method (see, for example, Patent Document 1). Furthermore, Patent Document 2 discloses a technique for easily analyzing the behavior of tracer particles in captured images when the tracer method is used.

[0003] Near-infrared light is also used when observing the flow behavior of a fluid. For example, Patent Document 3 discloses a technology that uses near-infrared light as a visualization device to facilitate intravenous injection, taking advantage of the property that near-infrared light has good biological permeability while being strongly absorbed by blood. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2001-194379 A [Patent Document 2] Japanese Patent Application Publication No. 10-221357 [Patent Document 3] JP 2017-64094 A [Patent Document 4] JP 2004-358234 A [Patent Document 5] US Patent Application Publication No. 2005 / 0010168 Summary of the Invention [Problem to be solved by the invention]

[0005] The liquid ejected from the ejection device is subjected to a relatively high pressure for ejection. Therefore, the speed of the ejected liquid immediately after ejection is relatively high, and it is not easy to measure its behavior. In particular, when the ejected liquid is ejected into an object, if an image capturing device is used to optically capture and measure the behavior of the ejected liquid, the measurement becomes more difficult because the ejected liquid itself is present inside the object.

[0006] In view of the above-mentioned problems, the present invention has an object to provide a suitable technique for capturing an image of and measuring the behavior of ejected liquid when the ejected liquid is ejected from an ejection device onto an object, using an imaging device. [Means for solving the problem]

[0007] In order to solve the above problems, the present invention provides a measurement system for measuring behavior within an object of an ejection liquid ejected from an ejection device into the object, the measurement system comprising: a container section formed of a resin material and including an internal storage space for storing the ejection liquid and a flow path communicating the storage space with an ejection port through which the ejection liquid is ejected to the outside; an imaging device arranged to be able to image, from the rear side of the object, an image of a tip surface of the container section in which the ejection port is located and which is positioned relative to the object in a predetermined state in which the ejection port is positioned relative to the object from its front side; and a first irradiation device which irradiates the tip surface with first near-infrared light. And, it is equipped with.

[0008] The measurement system measures the behavior of the ejection liquid contained in the accommodation space of the container part in the ejection device when the ejection liquid flows through a flow path and is ejected from the ejection port toward the target object. Here, the ejection device includes the container part and a drive part that applies energy for ejection to the ejection liquid contained in the accommodation space. The application of energy for ejection can adopt a form of energy application by a known pressurizing technique. An example of the applied energy may be chemically generated energy, for example, combustion energy generated by an oxidation reaction of gunpowder, explosives, etc. Alternatively, the energy for pressurization may be generated electrically, for example, energy resulting from a piezoelectric element or an electromagnetic actuator driven by input power. Alternatively, the energy for pressurization may be generated physically, for example, elastic energy by an elastic body or internal energy of a compressed object such as compressed gas. In other words, the energy for pressurization may be any energy that enables the ejection of the ejection liquid in the ejection device. The energy for pressurization may be a composite energy that is an appropriate combination of combustion energy, electrical energy, elastic energy, and other internal energies.

[0009] As the ejection liquid, an appropriate liquid can be adopted depending on the ejection purpose from the ejection device. The ejection liquid may be in a state where a specific substance is dissolved, or may be in a state where the specific substance is simply mixed without being dissolved in the liquid. For example, when the ejection device is a syringe, in consideration of the ejection purpose, i.e., the purpose of delivering a substance expected to exhibit a specific medical effect to a target site of a living body, the specific substance may be a vaccine for antibody enhancement, a protein for beauty, cultured cells for hair regeneration, etc., and the ejection liquid is formed by containing these in a liquid medium so that they can be ejected.

[0010] The container part is formed of a resin material, and as described above, any material can be used as long as it can reflect the first near-infrared light from the tip surface of the container part and can allow the second near-infrared light to enter the inside of the container part. For example, the resin material can be known nylon 6-12, polyarylate, polycarbonate, polybutylene terephthalate, polyphenylene sulfide, liquid crystal polymer, etc. In addition, these resin materials may contain fillers such as glass fiber and glass filler, and polybutylene terephthalate can contain 20 to 80 mass % glass fiber, polyphenylene sulfide can contain 20 to 80 mass % glass fiber, and liquid crystal polymer can contain 20 to 80 mass % mineral.

[0011] Here, in the injection system, the tip surface of the container part positioned relative to the object, particularly the tip surface including the injection port, is imaged by the imaging device, and the behavior of the injection liquid injected from the injection port by the operation of the injection device is measured. Regarding the positioning of the container part relative to the object, i.e., the predetermined state, the tip surface of the container part may be in a state of contact with the object, and when some intervening object is interposed between the tip surface and the object, the container part may be positioned so that the tip surface of the container part and the intervening object are in contact and the intervening object are in contact with each other. The imaging device may directly image the tip surface of the container part, or may image the tip surface via a predetermined optical device (such as a mirror). At this time, the tip surface of the container part is imaged by the imaging device from the back side of the object with the object in between, so that the thickness of the object is preferably set to a predetermined thickness so that the injection port can be grasped. Then, the tip surface of the container part is irradiated with the first near-infrared light from the first irradiation device. As a result, the imaging device can suitably capture the ejaculated liquid ejected onto the target object in the captured image, and the behavior of the ejected liquid can be suitably measured.

[0012] Here, as one embodiment of the first irradiation device, the first irradiation device may be a device that irradiates the first near-infrared light from the back side of the object to the tip surface, and the irradiation angle of the first near-infrared light with respect to the tip surface may be set so that the reflected light of the first near-infrared light at the tip surface is directed toward the imaging device. In this embodiment, the irradiation angle of the first near-infrared light is set so that the reflected light of the first near-infrared light at the tip surface is directed toward the imaging device, so that a situation is created in which the imaging device can easily image the tip surface of the container part. As a result, by utilizing the irradiation of the first near-infrared light by the above-mentioned first irradiation device, the imaging device can suitably capture the ejected liquid ejected into the object on the captured image, and the behavior measurement of the ejected liquid is suitably realized. In addition, since the first near-infrared light is irradiated to the tip surface of the container part positioned relative to the object, the behavior of the ejected liquid can be measured regardless of the shape of the container part, particularly the shape of the part near the flow path formed in the container part.

[0013] In the above embodiment, more preferably, a tip-side reflective layer that reflects a part of the first near-infrared light irradiated from the back side of the object may be formed between the tip surface of the container part placed in the predetermined state and the object. By disposing the tip-side reflective layer between the tip surface and the object in this manner, more of the first near-infrared light can be delivered to the imaging device, thereby realizing more suitable behavior measurement of the ejected liquid.

[0014] In the above-mentioned ejection system, the first irradiation device may be configured to irradiate the first near-infrared light as pulsed light that blinks for a predetermined exposure time per frame for imaging by the imaging device. By irradiating the first near-infrared light as pulsed light in this manner, the time during which electricity is applied to the light-emitting element of the first irradiation device can be shortened, and heat generation of the light-emitting element can be suppressed. In other words, by applying a voltage several times higher than normal to the light-emitting element of the first irradiation device and irradiating the pulsed light, the behavior of the ejection liquid can be measured at high luminance while maintaining the operation of the light-emitting element in a favorable manner.

[0015] In the above-described measurement system, when the first near-infrared light is irradiated from the back side of the object and the container part is surrounded by air, the area corresponding to the tip surface of the container part may appear darker in the image captured by the imaging device than the surrounding area (the area corresponding to the air surrounding the container part). In particular, when the refractive index difference between the object and the container part is smaller than the refractive index difference between the object and the air in the predetermined state, the reflectance of the first near-infrared light at the tip surface of the container part is relatively low, so that the area corresponding to the tip surface in the captured image is likely to appear darker. When the area corresponding to the tip surface becomes dark in this way, the contrast with the ejected liquid to be imaged is reduced, and it may become difficult to grasp the behavior of the ejected liquid ejected from the ejection port of the tip surface.

[0016] Therefore, the measurement system may further include a second irradiation device that irradiates second near-infrared light from the front side of the object, the second near-infrared light being incident on an outer circumferential surface of the container part that is not in contact with the object in the predetermined state, and the angle of incidence of the second near-infrared light with respect to the outer circumferential surface is set so that the second near-infrared light incident on the container part passes through the container part toward the tip surface. The irradiated second near-infrared light is relatively unlikely to be reflected by the outer circumferential surface of the container part, and the angle of incidence of the second near-infrared light with respect to the outer circumferential surface is set so that the second near-infrared light passes through the container part toward the tip surface, thereby increasing the amount of light in a region corresponding to the tip surface of the container part in an image captured by an imaging device. Therefore, by combining the irradiation of the first near-infrared light by the first irradiation device and the irradiation of the second near-infrared light by the second irradiation device, the contrast with the ejected liquid, which is the imaged object, can be further increased, and the image pickup device can suitably capture the ejected liquid irradiated onto the object on the image, and the behavior measurement of the ejected liquid is suitably realized. Note that, like the first irradiation device, this second irradiation device may be configured to irradiate the second near-infrared light as pulsed light that blinks for a predetermined exposure time per frame for image pickup by the image pickup device. In this case, either one of the first irradiation device and the second irradiation device may be a device configured to irradiate pulsed light, or both of them may be devices configured to irradiate pulsed light.

[0017] Here, in the above-mentioned measurement system, the container part may be provided with a reflecting member that reflects the second near-infrared light that has passed through the container part from the light-entering position to the end part on the tip face side, which is at least a part of the outer circumferential surface, into the container part. By providing the reflecting member in the predetermined area of ​​the outer circumferential surface of the container part in this way, the second near-infrared light traveling through the container part can be reflected and directed toward the tip face. This is extremely useful in cases where the container part is designed so that a part or all of the second near-infrared light cannot travel directly from the light-entering position through the container part to the tip face due to the convenience of the arrangement of the second irradiation device. In other words, the reflecting member can prevent a part or all of the second near-infrared light traveling through the container part from escaping to the atmosphere in the predetermined area from the container part, and thus a larger amount of light can be collected on the tip face of the container part, and a suitable image of the ejected liquid near the tip face can be obtained by increasing the contrast with the ejected liquid that is the subject of the image.

[0018] As another embodiment of the first irradiation device, the first irradiation device may be a device that irradiates the first near-infrared light incident on the outer peripheral surface of the container part that is not in contact with the object in the predetermined state from the front side of the object, and the angle of incidence of the first near-infrared light with respect to the outer peripheral surface may be set so that the first near-infrared light incident on the container part passes through the container part toward the tip surface and irradiates the tip surface. Furthermore, the container part may be provided with an outer peripheral side reflecting member that reflects the first near-infrared light that passes through the container part from the light incident position and reaches the predetermined area into the container part in a predetermined area that is at least a part of the outer peripheral surface from the light incident position where the first near-infrared light is incident to the end on the tip surface side. Even in such an embodiment, the first near-infrared light may be configured to be irradiated as pulsed light that blinks with a predetermined exposure time.

[0019] The present invention can also be understood from the aspect of a measurement method for measuring the behavior of an ejection liquid ejected from an ejection device into an object within the object. The method includes preparing the ejection device equipped with a container part formed of a resin material, the container part including an accommodation space for the ejection liquid and a flow path communicating the accommodation space with an ejection port through which the ejection liquid is ejected to the outside, disposing an image capture device so as to capture an image of a tip end surface of the container part in which the ejection port is disposed and which is positioned with respect to the object from the rear side of the object in a predetermined state in which the ejection port is positioned with respect to the object, sandwiching the object between the tip end surface and the image capture device, irradiating the tip end surface with a first near-infrared light from a first irradiation device, and imaging the ejection liquid ejected from the ejection device with the image capture device in a state in which the tip end surface is irradiated with the first near-infrared light by the first irradiation device. Preferably, the first irradiation device may be set such that an irradiation angle of the first near-infrared light from the back side of the object with respect to the tip surface is such that the reflected light from the tip surface is directed toward the imaging device.The measurement method may further include irradiating the second near-infrared light from a second irradiation device set such that an incident angle of the second near-infrared light from the front side of the object with respect to an outer circumferential surface of the container part not in contact with the object in the predetermined state is such that the second near-infrared light entering the container part passes through the container part and is directed toward the tip surface, and imaging the ejection liquid ejected from the ejection device by the imaging device in a state in which the first near-infrared light is irradiated by the first irradiation device and the second near-infrared light is irradiated by the second irradiation device.

[0020] Alternatively, the first irradiation device is a device that irradiates the first near-infrared light from the front side of the object, the first near-infrared light being incident on an outer circumferential surface of the container part that is not in contact with the object in the predetermined state, and the angle of incidence of the first near-infrared light with respect to the outer circumferential surface of the container part is set to be equal to or larger than the angle of incidence of the first near-infrared light with respect to the outer circumferential surface of the container part. The first near-infrared light entering the nozzle portion may be directed toward the tip surface through the container portion to irradiate the tip surface.

[0021] The technical ideas disclosed in relation to the above measurement system are also applicable to the invention relating to the above measurement method, so long as no technical inconsistencies arise. Effect of the Invention

[0022] The behavior of the ejected liquid when it is ejected from the ejection device toward the target object can be measured by capturing an image of the ejected liquid using the imaging device. [Brief description of the drawings]

[0023] [Figure 1] FIG. 1 is a first diagram showing a schematic configuration of a measurement system. [Diagram 2] 1A and 1B are diagrams showing a configuration of a container part attached to an injection device and a first form of irradiation of near-infrared light onto the container part. [Diagram 3] 13A and 13B are diagrams showing the configuration of a container part attached to an injection device and a second form of irradiation of near-infrared light onto the container part. [Figure 4] 4 is a diagram showing a state in which near-infrared light travels toward a tip end face side of a container part when the near-infrared light shown in FIG. 3 is irradiated. FIG. [Diagram 5] This is an image of the tip surface of a container section captured from the rear side by a high-speed camera, with the object sandwiched between them. [Figure 6] 6 is a graph obtained by analyzing luminance on a captured image along a diagonal line of the captured image shown in FIG. 5. [Figure 7] 1 is a flowchart showing the flow of a method for measuring the behavior of ejected fluid in a measurement system. [Figure 8] 13 shows images of the tip surface of the container and the liquid medicine spreading inside the target object captured in time series by a high-speed camera when the injection device is injecting the injection liquid. [Figure 9] FIG. 2 is a second diagram showing a schematic configuration of the measurement system. [Figure 10] 10 is an enlarged view of a region in the vicinity of the tip of a nozzle portion in the embodiment shown in FIG. [Figure 11]This is an image of the tip surface of the container section in the configuration shown in Figure 9, captured by a high-speed camera from the rear side with an object sandwiched between them. [Figure 12] 12 is a graph obtained by analyzing the luminance on the captured image along the diagonal line of the captured image shown in FIG. 11. [Figure 13] FIG. 3 is a third diagram showing a schematic configuration of the measurement system. [Figure 14] 1 is a diagram showing a schematic configuration of an injector according to an embodiment of the present invention; [Figure 15-1] 1 is a graph showing the relationship between the displacement x of the front of a solution containing a biomolecule in an injection target and the velocity u(x) of the front of the solution in accordance with one embodiment of the present invention. [Figure 15-2] 1 is a graph showing the relationship between the displacement x of the front of a solution containing a biomolecule in an injection target and the velocity u(x) of the front of the solution in accordance with one embodiment of the present invention. [Figure 15-3] 1 is a graph showing the relationship between the displacement x of the front of a solution containing a biomolecule in an injection target and the velocity u(x) of the front of the solution in accordance with one embodiment of the present invention. [Figure 16] 1 is a graph showing the relationship between the displacement x of the front of a solution containing a biomolecule in an injection target and the velocity u(x) of the front of the solution normalized by a velocity coefficient u0 in accordance with one embodiment of the present invention. [Figure 17-1] FIG. 2 is a diagram (photograph in lieu of drawing) showing the distribution of cell nuclei in a mammalian individual (living body) and DNA injected into the mammalian individual (living body) according to one embodiment of the present invention. [Figure 17-2] FIG. 2 is a diagram (photograph in lieu of drawing) showing the distribution of cell nuclei in a mammalian individual (living body) and DNA injected into the mammalian individual (living body) according to one embodiment of the present invention. [Figure 17-3] FIG. 2 is a diagram showing the distribution of cell nuclei in a mammalian individual (living organism) and DNA injected into the mammalian individual (living organism) according to a comparative example of the present invention (a photograph substituting a drawing). [Figure 17-4] FIG. 2 is a diagram (photograph in lieu of drawing) showing tissue damage caused by injection of a DNA solution in a mammalian individual (living body) according to one embodiment of the present invention. [Figure 17-5]FIG. 2 is a diagram (photograph in lieu of drawing) showing tissue damage caused by injection of a DNA solution in a mammalian individual (living body) according to one embodiment of the present invention. [Figure 17-6] FIG. 2 is a diagram (photograph in lieu of drawing) showing tissue damage caused by injection of a DNA solution in a mammalian individual (living body) according to one embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] First Embodiment Hereinafter, a measurement system and a measurement method for measuring the behavior of the injection liquid injected from an injection device according to this embodiment will be described with reference to the drawings. In this embodiment, a needleless syringe (hereinafter, simply referred to as a "syringe") 1 that injects an injection liquid (injection liquid) into a target object without using a syringe needle is adopted as the injection device. The syringe 1 injects the injection liquid into a target object by utilizing the combustion energy of explosives. In this embodiment, the terms "tip side" and "base side" are used to represent the relative positional relationship in the longitudinal direction of the syringe 1. The "tip side" represents a position closer to the tip of the syringe 1, i.e., closer to the injection port 31a, and the "base side" represents a direction opposite to the "tip side" in the longitudinal direction of the syringe 1, i.e., the direction toward the drive unit 7. In addition, the configurations of the following embodiments are examples, and the configuration of the measurement system is not limited to the configuration of this embodiment.

[0025] <Configuration of Syringe 1> Here, FIG. 1 is a diagram showing the overall measurement system together with a schematic configuration of a syringe 1. In FIG. 1, the syringe 1 is shown in a cross-sectional state along its longitudinal direction. When measuring the behavior of an injection liquid with a measurement system, the injected injection liquid does not necessarily have to be the injection liquid when the syringe 1 is actually used (for example, a liquid formed by containing a predetermined substance that exerts an expected efficacy or function in a target object in a liquid medium), but may be a liquid for imaging that is easy to image with a high-speed camera 30, which is an imaging device. In this embodiment, such a liquid for imaging is also treated as one form of an injection liquid.

[0026] The syringe 1 is configured by mounting the container part 3 on the tip side of the syringe main body 6 and mounting the drive part 7 on the base end side. Here, the container part 3 is formed along the central axis of the main body, and is formed of resin to include therein a storage space 34 that is a space capable of storing an injection liquid, and a flow path 31 that communicates with the storage space 34 and opens at the tip side. More specifically, a nozzle part 31b including the flow path 31 is formed on the tip side of the container part 3, and the end face on the tip side of the nozzle part 31b is the tip face 32 (see Figs. 2 and 3 described later). Therefore, the nozzle part 31b is a part of the container part 3 that does not include the storage space 34. And the opening of this flow path 31 becomes the injection port 31a. As the resin material for forming the container part 3 including the nozzle part 31b, for example, known nylon 6-12, polyarylate, polycarbonate, polybutylene terephthalate, polyphenylene sulfide, liquid crystal polymer, etc. can be used. Furthermore, these resin materials may contain fillers such as glass fiber and glass filler. Polybutylene terephthalate may contain 20 to 80% by mass of glass fiber, polyphenylene sulfide may contain 20 to 80% by mass of glass fiber, and liquid crystal polymer may contain 20 to 80% by mass of minerals.

[0027] In the storage space 34 of the container section 3, the plunger 4 is disposed so as to be slidable in the direction of the flow path 31 (towards the tip side), and a part or all of the storage space 34 formed between the plunger 4 and the main body of the container section 3 becomes the space in which the injection liquid is actually sealed. Here, as the plunger 4 slides in the storage space 34, the injection liquid stored in the storage space 34 is pressed and ejected from the ejection port 31a provided on the tip side of the flow path 31. For this reason, the plunger 4 is formed of a material that allows smooth sliding in the storage space 34 and prevents the injection liquid from leaking out from the plunger 4 side. Specific materials for the plunger 4 include: For example, butyl rubber or silicon rubber can be used. Further examples include styrene-based elastomers, hydrogenated styrene-based elastomers, and mixtures thereof with polyolefins such as polyethylene, polypropylene, polybutene, and α-olefin copolymers, oils such as liquid paraben, process oil, and powdered inorganic materials such as talc, cast, and mica. Furthermore, various rubber materials (especially vulcanized ones) such as polyvinyl chloride-based elastomers, olefin-based elastomers, polyester-based elastomers, polyamide-based elastomers, polyurethane-based elastomers, natural rubber, isoprene rubber, chloroprene rubber, nitrile-butadiene rubber, and styrene-butadiene rubber, and mixtures thereof can also be used as the material of the plunger 4. In order to ensure and adjust the sliding property between the plunger 4 and the container part 3, the surface of the plunger 4 and the surface of the storage space 34 of the container part 3 may be coated or surface-treated with various substances. Examples of the coating agent that can be used include PTFE (polytetrafluoroethylene), silicon oil, diamond-like carbon, and nanodiamond.

[0028] Here, the contour of the tip side of the plunger 4 is shaped to roughly match the contour of the inner wall surface of the connection portion between the storage space 34 and the flow path 31. As a result, when the plunger 4 slides during injection of the injection solution and reaches the innermost position in the storage space 34, the gap formed between the plunger 4 and the inner wall surface of the connection portion can be made as small as possible, and the injection solution remaining in the storage space 34 and being wasted can be suppressed.

[0029] Returning now to the description of the container part 3, the inner diameter of the flow path 31 of the container part 3 is formed to be smaller than the inner diameter of the storage space 34. With this configuration, the highly pressurized injection liquid is injected to the outside from the injection port 31a of the flow path 31. In addition, a threaded portion for connecting the syringe body 6 and the container part 3 is formed in a portion located on the base end side of the container part 3.

[0030] Furthermore, in the container part 3, a piston 5 is disposed at a position adjacent to the plunger 4. The piston 5 is configured to slide in the storage space 34 by being pressurized by the combustion product generated by the igniter 71 of the drive part 7. The piston 5 is made of metal, and an O-ring or the like may be disposed on a part of the piston 5 to enhance adhesion with the sliding surface on which the piston 5 slides. Alternatively, the piston 5 may be made of resin, and in that case, metal may be used in combination with the part that requires heat resistance or pressure resistance. The end face on the base end side of the piston 5 is exposed to the through hole side formed inside the syringe body 6. The through hole is a combustion chamber into which the combustion product generated by the igniter 71 of the drive part 7 is released, or into which the gas generating agent 80 to be burned by the combustion product is disposed. Therefore, the end face on the base end side of the piston 5 receives pressure from the combustion chamber, and the pressure is transmitted to the injection liquid contained in the storage space 34 via the plunger 4 to pressurize it.

[0031] Next, the driving unit 7 will be described. The driving unit 7 has a cylindrical body and includes an igniter 71, which is an electric igniter that burns an ignition charge to generate energy for ejection. The igniter 71 is disposed in the syringe body 6 so as to face the base end face of the piston 5 so that the combustion energy from the igniter 71 can be transmitted to the base end face. The body of the driving unit 7 may be formed by fixing an injection-molded resin to a metal collar. A known method can be used for the injection molding. The body of the driving unit 7 is formed of the same resin material as the container unit 3.

[0032] Here, the combustion energy of the ignition charge used in the igniter 71 becomes the energy for the syringe 1 to inject the injection liquid to the target object. The ignition charge is preferably a powder containing zirconium and potassium perchlorate (ZPP), a powder containing titanium hydride and potassium perchlorate (THPP), a powder containing titanium and potassium perchlorate (TiPP), a powder containing aluminum and potassium perchlorate (APP), a powder containing aluminum and bismuth oxide (APP), or a powder containing titanium and potassium perchlorate (APP). Examples of explosives include aluminum and molybdenum oxide (ABO), aluminum and copper oxide (AMO), aluminum and iron oxide (ACO), and aluminum and iron oxide (AFO), or a combination of these explosives. These explosives generate high-temperature, high-pressure plasma when burning immediately after ignition, but when the temperature returns to room temperature and the combustion products condense, the generated pressure drops rapidly because they do not contain gas components. Other explosives may be used as the ignition charge as long as they can eject the appropriate injection liquid.

[0033] In addition, in the syringe 1, in order to adjust the pressure transition applied to the injection liquid via the piston 5, in addition to the above-mentioned ignition charge, a gas generating agent 80 that burns with the combustion products generated by the pyrotechnic combustion in the igniter 71 to generate gas is disposed in the through hole of the syringe body 6. The location of the gas generating agent is a location that can be exposed to the combustion products from the igniter 71. Alternatively, the gas generating agent 80 may be disposed in the igniter 71, as disclosed in International Publication No. 01-031282 and Japanese Patent Application Laid-Open No. 2003-25950. An example of the gas generating agent is a single-base smokeless powder consisting of 98% by mass of nitrocellulose, 0.8% by mass of diphenylamine, and 1.2% by mass of potassium sulfate. It is also possible to use various gas generating agents used in gas generators for airbags and gas generators for seatbelt pretensioners. By adjusting the dimensions, size, shape, and particularly the surface shape, of the gas generating agent when placed in the through hole 64 of the syringe body 6, it is possible to change the time until combustion of the gas generating agent is completed, thereby adjusting the pressure transition applied to the injection liquid and making it possible to obtain the desired transition in the injection pressure.

[0034] When DC power is supplied from the power supply device 40 to the drive unit 7 of the syringe 1 configured in this manner, the igniter 71 is activated to release a combustion product, and the gas generating agent 80 is burned by the combustion product. As a result, the piston 5 is pressed and the injection liquid is pressurized via the plunger 4. The pressurized injection liquid is ejected from the ejection port 31a of the nozzle part 31b. Note that FIG. 1 shows a state in which the tip surface 32 of the nozzle part 31b, in which the ejection port 31a is formed, is in contact with and positioned to the object 51 into which the injection liquid is ejected, and when the drive part 7 is operated, the injection liquid is ready to be ejected into the object 51. Here, the object 51 is an object into which the injection liquid is ejected, whose behavior is measured by the measurement system of this embodiment. For example, the object 51 can be an excised skin of a rat. In this embodiment, the object 51 is formed relatively thin in order to measure the behavior of the injection liquid in the object 51. 1, the target object 51 is placed on a colorless and transparent acrylic plate 52, and the syringe 1 is placed on the target object 51 with the tip surface 32 of the nozzle portion 31b positioned thereon. When the target object 51 is used as a reference in this manner, the side on which the syringe 1 is placed is defined as the front side of the target object 51.

[0035] In addition, in the measurement system, a high-speed camera 30, which is an imaging device, is disposed at a position where it can image the tip surface 32 of the nozzle part 31b across the object 51 from the back side of the object 51 (i.e., the side opposite to the front side where the syringe 1 is disposed). The high-speed camera 30 is a camera that can image an event that occurs in an extremely short time at a high speed of about several thousand to 10,000 frames per second. For example, it is preferable that it can image at a speed of 1000 frames per second or more, preferably 5000 frames per second or more, and more preferably 10000 frames per second or more. Such a high-speed camera 30 is useful because the injection liquid ejected from the syringe 1 diffuses in the object 51 in an extremely short time. The high-speed camera 30 may directly image the tip surface 32, or may be disposed so as to image the tip surface 32 via an optical device such as a mirror 23 as shown in FIG. 1. Furthermore, the measurement system is equipped with a control device 20, which is a computer. The control device 20 controls the power supply 40 and the high-speed camera 30, collects image data captured by the high-speed camera 30, and executes a predetermined control program to measure the behavior of the injection liquid through image processing of the collected image data.

[0036] Here, in the measurement system, the tip of the nozzle portion 31b is in the field of view of the high-speed camera 30. In order to supply the end face 32 with the amount of light required for imaging, a backside irradiation device 21 (corresponding to the first irradiation device of the present application in this case) that irradiates near-infrared light of a predetermined wavelength is disposed on the back side of the object 51. The backside irradiation device 21 is, for example, a laser irradiation device that can irradiate near-infrared light of 850 nm. The backside irradiation device 21 irradiates the end face 32 with the near-infrared light, and an irradiation angle from the backside irradiation device 21 to the end face 32 is set so that the reflected light from the end face 32 is directed toward the high-speed camera 30 via the mirror 23. The irradiation angle is the angle between the normal direction of the end face 32 and the irradiation direction of the near-infrared light. By irradiating near-infrared light from the backside irradiation device 21 in this manner, it becomes possible to image the behavior of the injection liquid in the object 51 (for example, how the injection liquid diffuses in the object 51, etc.) when the syringe 1 is operated with the high-speed camera 30 facing the end face 32 across the object 51.

[0037] However, in the arrangement state of the syringe 1 shown in FIG. 1, the tip surface 32 of the nozzle portion 31b is in contact with the object 51, but the atmosphere is present on the side of the nozzle portion 31b. Therefore, in the field of view of the high-speed camera 30, the area corresponding to the tip surface 32 tends to appear darker than the area corresponding to the surrounding atmosphere. This is because the refractive index of the object 51 is relatively closer to the refractive index of the container portion 3 including the nozzle portion 31b than the refractive index of the atmosphere, and the refractive index difference between the object 51 and the container portion 3 is smaller than the refractive index difference between the object 51 and the atmosphere surrounding the container portion 3. As a result, even if near-infrared light is irradiated by the back side irradiation device 21, the amount of near-infrared light that is not sufficiently reflected by the tip surface 32 and passes from the object 51 into the container portion 3 through the tip surface 32 increases, making it difficult to obtain a sufficient amount of reflected light to capture the behavior of the injection liquid at high speed.

[0038] Therefore, in the measurement system of this embodiment, in addition to the backside irradiation device 21, a frontside irradiation device 22 (corresponding to the second irradiation device of the present application in this case) is arranged. The frontside irradiation device 22 is also a laser irradiation device capable of irradiating near-infrared light of a predetermined wavelength (for example, 850 nm). However, unlike the backside irradiation device 21, the frontside irradiation device 22 is arranged on the front side of the object 51, and the near-infrared light is irradiated onto the outer circumferential surface of the container part 3. Here, based on FIG. 2, a first irradiation form of near-infrared light by the frontside irradiation device 22 will be described. Note that in the container part 3 shown in FIG. 2, the plunger 4, the piston 5, and the injection liquid are omitted.

[0039] As shown in FIG. 2, the container part 3 has a nozzle part 31b located at its tip side, a tip surface 32 formed at the tip side, and an ejection port 31a disposed there. A flow path 31 is formed from the ejection port 31a along the central axis of the nozzle part 31b, and a storage space 34 is further connected to the flow path 31. Here, the outer peripheral surface of the container part 3, except for the tip surface 32 that contacts the object 51, is the outer peripheral surface on the side of the container part 3, and as shown in FIG. 2, it is a first outer peripheral surface 33a, a second outer peripheral surface 33b, and a third outer peripheral surface 33c from the tip side. The first outer peripheral surface 33a is the outer peripheral surface adjacent to the tip surface 32 and is located closest to the tip surface 32 of the container part 3, while the third outer peripheral surface 33c is the outer peripheral surface located farthest from the tip surface 32 of the container part 3 and is adjacent to the syringe body 6. The diameter D3 of the container part 3 corresponding to the third outer peripheral surface 33c is larger than the diameter D1 of the container part 3 corresponding to the first outer peripheral surface 33a. Therefore, the second outer peripheral surface 33b connecting the first outer peripheral surface 33a and the third outer peripheral surface 33c is inclined with respect to the central axis of the container portion 3 in the cross section shown in FIG.

[0040] Here, the near-infrared light from the front side irradiation device 22 is incident on a point P1 on the third outer peripheral surface 33c, which is a distance L1 away in the axial direction of the container part 3 when the tip surface 32 is used as a reference. The incidence angle θ1 of the near-infrared light from the front side irradiation device 22 at this time is set so that the near-infrared light incident at point P1 is refracted at a refraction angle θ2, travels inside the container part 3, and reaches the tip surface 32 of the nozzle part 31b as it is, as shown in FIG. 2. Considering the geometric conditions of the container part 3, such as the diameter D1 of the container part 3 (the diameter of the tip face 32), the diameter D3 of the container part 3 corresponding to the third outer circumferential face 33c, and the distance L1 from the tip face to the light entrance point P1, as well as the refraction of the near-infrared light entering the container part 3 from the atmosphere, the incident angle θ1 is set so that the near-infrared light reaches the tip face 32. Note that, although a flow path 31 is formed in the nozzle part 31b of the container part 3, the flow path diameter is extremely small and does not impede the progression of the near-infrared light within the container part 3.

[0041] By setting the front side irradiation device 22 in this way, the near-infrared light irradiated from the front side irradiation device 22 is refracted at the light entrance point P1 and travels inside the member of the container part 3. Here, in the container part 3, a relatively large thickness is secured between the inner wall surface of the storage space 34 and the first outer peripheral surface 33a to the third outer peripheral surface 33c. Therefore, the near-infrared light travels inside the member having that thickness and can reach the tip surface 32 directly. As a result, a preferable amount of light for imaging by the high-speed camera 30 can be supplied to the area corresponding to the tip surface 32, which tends to appear relatively darker than the area corresponding to the atmosphere in the field of view of the high-speed camera 30. By combining with the irradiation of the near-infrared light from the back side irradiation device 21 described above, it becomes possible to preferably image the behavior of the injected injection liquid in the target 51 (for example, how the injection liquid diffuses in the target 51, etc.) in a state where the high-speed camera 30 faces the tip surface 32 with the target 51 sandwiched therebetween.

[0042] Next, a second irradiation form of the near-infrared light by the front side irradiation device 22 will be described with reference to FIG. 3. The container part 3 shown in FIG. 3 has a reflecting member 35 on its first outer peripheral surface 33a. Specifically, the reflecting member 35 is a so-called aluminum foil, and is provided on the surface of the first outer peripheral surface 33a so as to cover the first outer peripheral surface 33a in close contact. In the second irradiation form, the near-infrared light emitted from the front side irradiation device 22 enters the container part 3 at point P1 and is refracted there (refracted at a refraction angle θ2' with respect to the incident angle θ1'), and reaches the first outer peripheral surface 33a without directly reaching the tip surface 32. However, since the reflecting member 35 is arranged on the first outer peripheral surface 33a, the near-infrared light that reaches the first outer peripheral surface 33a does not leak out to the outside of the container part 3, but is reflected by the reflecting member 35, and as a result, can reach the tip surface 32. The incident angle θ1' when the near-infrared light from the front side irradiation device 22 follows such an optical path can also be said to be an incident angle that is "set so that the near-infrared light entering the container section 3 passes through the container section 3 toward the tip surface 32."

[0043] Here, in the case where the syringe 1 is fixed without placing the object 51 in front of the tip surface 32 and the container part 3 is irradiated with near-infrared light from the front side irradiation device 22 as shown in Fig. 3, Fig. 4 shows the state of the tip surface 32 in a state where the reflecting member 35 is attached (i.e., the state shown in Fig. 3) and in a state where the reflecting member 35 is removed. Specifically, the upper part (a) of Fig. 4 shows the state of the tip surface 32 when the front side irradiation device 22 irradiates near-infrared light with the reflecting member 35 attached as shown in Fig. 3, and the lower part (b) shows the state of the tip surface 32 when the front side irradiation device 22 irradiates near-infrared light with the reflecting member 35 removed.

[0044] As can be seen from the upper row (a), the forward region 321 of the tip surface 32 is brightened as a result of reflection of the near-infrared light by the reflecting member 35. On the other hand, when the reflecting member 35 is removed, the brightness of the forward region 321 of the tip surface 32 becomes darker than that of the upper row (a), as shown in the lower row (b). Furthermore, it can be seen that a relatively bright area 322 appears in a location outside the forward region 321. This represents a state in which the near-infrared light refracted when entering the container part 3 reaches the first outer peripheral surface 33a as shown in FIG. 3, but is not reflected by the reflecting member 35 and goes outside the container part 3 as it is. It can be seen that the reflecting member 35 can be provided in this way to effectively brighten the forward region 321 of the tip surface 32 of the nozzle part 31b.

[0045] <Imaging results> Here, the results of imaging by the high-speed camera 30 will be described with reference to Figures 5 and 6. (a) to (c) in Figure 5 are images captured by the high-speed camera 30 corresponding to the following conditions 1 to 3 when no injection liquid is being ejected from the syringe 1. Condition 1: Irradiation of near-infrared light by only the rear side irradiation device 21 Condition 2: Near-infrared light irradiation by only the front side irradiation device 22 Condition 3: Irradiation of near-infrared light by both the backside irradiation device 21 and the frontside irradiation device 22 Moreover, Fig. 6 shows the luminance of image pixels at the same locations (locations on the same white diagonal line in the captured images) in each captured image in Fig. 5. Line L1 in Fig. 6 corresponds to (a) in Fig. 5, line L2 corresponds to (b) in Fig. 5, and line L3 corresponds to (c) in Fig. 5.

[0046] The behavior of the injection liquid is measured by the high-speed camera 30 according to the flow of the measurement method shown in FIG. 7. First, in S101, the syringe 1, which is the injection device, is set to the state shown in FIG. 1. At this time, it is preferable to fix the syringe 1 carefully so that the tip surface 32 of the nozzle portion 31b of the syringe 1 does not come into contact with the object 51 and the syringe 1 is not displaced due to impact or the like generated when the syringe 1 is operated. Next, in S102, the high-speed camera 30 is placed on the back side of the object 51 as shown in FIG. 1 so that the tip surface 32 of the nozzle portion 31b fits within the field of view of the high-speed camera 30. At this time, an optical device such as a mirror 23 may be placed between the high-speed camera 30 and the tip surface 32, or the optical device may be omitted.

[0047] Then, in S103, as described above, the backside irradiation device 21 is placed on the back side of the object 51, and near-infrared light is irradiated from there toward the tip surface 32. Furthermore, in S104, as shown in FIG. 2 and FIG. 3, the frontside irradiation device 22 is placed on the front side of the object 51 to irradiate near-infrared light, and the near-infrared light is made to enter the container part 3 and proceed inside the container part 3 to the tip surface 32. In such a state where the near-infrared light is being irradiated by the backside irradiation device 21 and the frontside irradiation device 22, the process of S105 is performed. In S105, first, the control device 20 issues an instruction to the high-speed camera 30 to wait for imaging. The high-speed camera 30 that has received the instruction is in a standby state so that it can immediately take an image when a trigger signal is received from the outside. Then, in that state, when the user operates the power supply device 40, driving power is supplied to the drive unit 7 of the syringe 1, and a trigger signal for taking an image is sent from the power supply device 40 to the high-speed camera 30. Upon receiving the trigger signal, the high-speed camera 30 starts capturing images, and the captured images are displayed on the monitor of the control device 20. The captured images by the high-speed camera 30 are recorded in a recording device within the control device 20. The processing of S102 to S104 may be interchanged in order, or may be performed simultaneously.

[0048] The captured image obtained by such a measurement method is an image captured according to the above condition 3. When capturing images according to the above conditions 1 and 2, the flow is the same as that of the measurement method shown in FIG. 7, except for the irradiation of near-infrared light by an irradiation device different from that in condition 3.

[0049] Here, the circular outline clearly seen in FIG. 5, especially in (a) and (c), corresponds to the outer contour of the tip surface 32 of the nozzle portion 31b. In the case of condition 1, as shown in (a) of FIG. 5, the area corresponding to the tip surface 32 is very dark. This can also be understood from the line L1 in FIG. 6. This is because, as described above, when near-infrared light is irradiated only by the backside irradiation device 21, the refractive index difference between the object 51 and the nozzle portion 31b (container portion 3) is relatively small, so that it is not easy to generate sufficient reflected light by the near-infrared light. However, this does not mean that the imaging form according to condition 1 is excluded from the scope of the present invention, and this point will be explained in the second embodiment described later.

[0050] On the other hand, in the case of condition 3, as shown in FIG. 5(c), the area corresponding to the tip surface 32 is 6. The image is brighter than that in the case of 1, and this can be understood from the line L3 in FIG. 6. This is because, as described above, by irradiating near-infrared light from the front-side irradiation device 22 in addition to the back-side irradiation device 21, the near-infrared light can reach the tip surface 32 from inside the container part 3. Therefore, if the injection liquid is ejected from the ejection port 31a, the contrast with the injection liquid can be relatively large, so that the presence of the injection liquid can be reliably captured. In addition, in the condition 2, the near-infrared light is irradiated only from the front-side irradiation device 22. However, when looking at the line L2 in FIG. 6, although the rise in the luminance transition can be recognized around the position near 180, the luminance transition is relatively gentle, so that the outer contour (the outermost position) of the ejected injection liquid is difficult to identify. However, even in the imaging form according to the condition 2, the rise in luminance can be found near the center as shown by the line L2, so that the form is also included in the scope of the present invention. The imaging form according to the condition 2 will be described in the third embodiment described later.

[0051] Next, the transition of the diffusion of the injection liquid when the behavior of the injection liquid is measured according to the above condition 3 is shown in FIG. 8, which is obtained by sequentially capturing images of the injection liquid by the high-speed camera 30. Each figure in FIG. 8 shows the elapsed time after the syringe 1 is actuated. Specifically, the images are captured by the high-speed camera 30 when the elapsed time is 0 msec, 1 msec, 1.2 msec, 3 msec, 4.9 msec, and 10 msec. In each figure, the white solid line shows the outline of the tip surface 32 of the nozzle part 31b. In each figure except for the figure where the elapsed time is 0 msec, the white dashed line shows the outline of the injection liquid that is injected and diffused in the target object 51. In this way, according to the measurement system of this embodiment, the behavior of the injected injection liquid that occurs in an extremely short time can be suitably measured. In particular, it can be seen that the presence of the injection liquid can be suitably captured even at a timing shortly after the syringe 1 is actuated.

[0052] <Second embodiment> Next, a second embodiment of the measurement system will be described based on FIG. 9. The measurement system shown in FIG. 9 does not include the front side irradiation device 22 of the configuration of the measurement system shown in FIG. 1 as an irradiation device, but only includes the back side irradiation device 21, and the other configurations are basically the same. In this case, the back side irradiation device 21 corresponds to the first irradiation device of the present application. Even with such a configuration, if a sufficient amount of reflected light from the tip surface 32 of the nozzle part 31b is obtained, it is possible to sufficiently capture the behavior of the injection liquid ejected from the ejection port 31a with the high-speed camera 30. For example, it is possible to increase the amount of reflected light from the tip surface 32 by appropriately selecting a material for forming the container part 3 so that the refractive index difference between the container part 3 including the nozzle part 31b and the object is relatively large.

[0053] In addition, in the measurement system configured as above, it is possible to capture an image of the behavior of the injected injection liquid if reflected light from the tip surface 32 is obtained. Therefore, it is possible to accurately grasp the behavior of the injection liquid regardless of the shapes of the nozzle part 31b and the container part 3. This point is also the same for the measurement system shown in the above-mentioned first embodiment.

[0054] As a further modification of this embodiment, as shown in FIG. 10, a reflective layer 38 that reflects a part of the near-infrared light from the backside irradiation device 21 may be formed between the tip surface 32 of the nozzle portion 31b and the object 51. Specifically, the reflective layer 38 is formed by applying a white paint (acrylic paint) to the tip surface 32 to a predetermined thickness. In this configuration, the tip surface 32 of the nozzle portion 31b is positioned relative to the object 51 with the reflective layer 38 sandwiched between them. Alternatively, the reflective layer 38 may be formed by applying a white paint onto the surface of the object 51 (the surface that the tip surface 32 contacts). That is, the reflective layer 38 may be disposed between the tip surface 32 of the nozzle portion 31b and the surface of the object 51.

[0055] <Imaging results> 11 and 12, the photograph taken by the high-speed camera 30 in this embodiment is 11(a) and 11(b) are images captured by the high-speed camera 30 under the following conditions 11 and 12 when the injection liquid was not being ejected from the syringe 1. Condition 11: Near-infrared light is irradiated only by the rear side irradiation device 21, and the reflective layer 38 is formed. Condition 12: Near-infrared light is irradiated only by the rear side irradiation device 21 and no reflective layer 38 is used Moreover, Fig. 12 shows the brightness of image pixels at the same location (location on a straight line in the captured image) in each captured image in Fig. 11. Line L11 in Fig. 12 corresponds to (a) in Fig. 11, and line L12 corresponds to (b) in Fig. 11. Note that the behavior measurement of the injection liquid by the high-speed camera 30 is performed according to the flow of the measurement method shown in Fig. 7 above.

[0056] In the case of condition 11, as shown in (a) of Fig. 11, the area corresponding to the tip surface 32 is brighter than in the case of condition 12, and this can also be understood from a comparison of lines L11 and L12 in Fig. 12. This is because more of the near-infrared light from the backside irradiation device 21 is reflected by the reflective layer 38, improving the contrast at the nozzle portion 31, and as a result, the presence of the injection liquid can be reliably captured.

[0057] <Third embodiment> Next, a third embodiment of the measurement system will be described with reference to Fig. 13. The measurement system shown in Fig. 13 does not include the rear side irradiation device 21 of the measurement system shown in Fig. 1 as an irradiation device, but only includes the front side irradiation device 22, and the other configurations are basically the same. In this case, the front side irradiation device 22 corresponds to the first irradiation device of the present application.

[0058] Even with this configuration, if a sufficient amount of near-infrared light is obtained that is irradiated from the front side irradiation device 22 and passes through the container part 3 to reach the tip surface 32 of the nozzle part 31b, it is possible to adequately capture the behavior of the injection liquid ejected from the ejection port 31a with the high-speed camera 30. Preferably, as shown in Fig. 3 above, a reflecting member 35 is provided on the first outer circumferential surface 33a of the container part 3, so that the amount of near-infrared light that reaches the tip surface 32 can be increased to a level suitable for measuring the behavior of the injection liquid.

[0059] <Other embodiments> In each of the above-mentioned embodiments, the backside irradiation device 21 may be configured to irradiate near-infrared light as pulsed light that blinks at a predetermined exposure time per frame of the high-speed camera 30. The predetermined exposure time may be, for example, 10 μsec when the shooting speed of the high-speed camera 30 is 10000 fps (frames per second). By irradiating near-infrared light as pulsed light in this way, the time during which electricity is applied to the light-emitting element of the backside irradiation device 21 can be shortened and heat generation of the light-emitting element can be suppressed. In other words, even if the amount of electricity applied to the light-emitting element of the backside irradiation device 21 is temporarily increased to increase the amount of light emitted when the pulse is ON, the light-emitting element can be maintained in a state in which it can operate favorably. As a result, the amount of light reflected from the tip surface 32 can be effectively increased, and the behavior of the ejected liquid can be measured with higher brightness.

[0060] Next, the present application also discloses an invention relating to an injector and a method for injecting a solution containing a biomolecule into a cell of an injection target using the injector, as described below.

[0061] Injectors for injecting medicinal liquids into living organisms include needle-equipped syringes that inject via a needle, needleless syringes that inject without a needle, and catheters equipped with a needle and a drive source for transporting medicinal liquid to the injection target. Among these, needleless syringes may be configured to inject the injection components by applying pressure to a storage chamber containing the injection liquid using pressurized gas, a spring, or electromagnetic force. The device has multiple nozzle holes formed inside the device body, and a piston that is driven during injection is arranged corresponding to each nozzle hole. This configuration allows the injection liquid to be ejected simultaneously from multiple nozzle holes, achieving uniform injection into the subject. A plasmid containing the luciferase gene was then injected into rats, achieving highly efficient cell transfer. In addition, there is a type of needleless syringe that uses pressurized gas as a power source for injecting the injection liquid. For example, there is a pressurization type in which a large pressure is applied instantaneously at the beginning of injection, and then the pressure is gradually reduced over 40 to 50 msec.

[0062] On the other hand, when a conventional injector is used, the tissue near the injection port of the injection target may be damaged. Also, it has not been reported that a solution containing a biomolecule can be directly injected into a wide range of cells of an injection target using an injector. That is, there is no report on the characteristics of the injector necessary to minimize damage to tissues near the injection port of the injection target, nor on the characteristics of the injector necessary to directly inject a solution containing biomolecules into a wide range of cells of the injection target.

[0063] Therefore, the present application discloses an invention having the object of providing a syringe capable of minimizing damage to tissue near the injection port of the injection target, and preferably having the object of providing a syringe capable of directly injecting a solution containing a biomolecule into a wide range of cells in the injection target.

[0064] In light of the above, the present inventors have conducted extensive research and have found that, in an injector containing a solution containing a biomolecule, the relationship between the displacement x of the tip of the solution containing the biomolecule in an injection target and the velocity u(x) of the tip of the solution is fitted by the least squares method using a fitting function represented by the following formula (1), and k defined as the attenuation constant and u defined as the asymptotic velocity are e As a result of focusing on k or u e The present invention has been completed based on the discovery that the above problems can be solved by setting the value of the saturation angle .theta. u(x)=u0exp(-kx)+u e (1) (In equation (1), u0 is the velocity coefficient (m / s), k is the damping coefficient (1 / mm), and u e indicates the asymptotic velocity (m / s).

[0065] The present invention is as follows. [1] An injector that injects a solution containing a biomolecule into an injection target from an injector body without injecting the solution through a predetermined structure in a state in which the predetermined structure is inserted into the injection target, A storage section for storing a solution containing a biomolecule; a nozzle portion having an ejection port through which the pressurized solution containing the biomolecule flows and is ejected toward the injection target; Equipped with When the relationship between the displacement x of the tip of the solution containing the biomolecule in the injection target and the velocity u(x) of the tip of the solution is fitted using the least squares method with a fitting function represented by the following formula (1), the attenuation coefficient k is 1.59 or more. syringe. u(x)=u0exp(-kx)+u e (1) (In equation (1), u0 is the velocity coefficient (m / s), k is the damping coefficient (1 / mm), and u e indicates the asymptotic velocity (m / s). [2] Asymptotic velocity u e The injector according to [1], wherein is 0.01 or more. [3] An injector that injects a solution containing a biomolecule into an injection target from an injector body without injecting the solution through a predetermined structure in a state in which the predetermined structure is inserted into the injection target, A storage section for storing a solution containing a biomolecule; a nozzle portion having an ejection port through which the pressurized solution containing the biomolecule flows and is ejected toward the injection target; Equipped with When the relationship between the displacement x of the front of the solution containing the biomolecule in the injection target and the velocity u(x) of the front of the solution is fitted by the least squares method using a fitting function represented by the following formula (1), the asymptotic velocity u e is 0.01 or more, syringe. u(x)=u0exp(-kx)+u e (1) (In equation (1), u0 is the velocity coefficient (m / s), k is the damping coefficient (1 / mm), and u e indicates the asymptotic velocity (m / s). [4] A method for injecting a solution containing a biomolecule into a cell of an injection target using the injector according to any one of [1] to [3].

[0066] According to the present invention, it is possible to provide a syringe capable of minimizing damage to tissues around an injection port of an injection target, and preferably a syringe capable of directly injecting a solution containing a biomolecule into a wide range of cells of an injection target.

[0067] As described above, the present invention includes an invention of an injector and an invention of a method for injecting a solution containing a biomolecule into a cell of an injection target using the injector, and the details thereof are described below.

[0068] <Invention of the injector> One aspect of the injector of the present application is an injector that injects a solution containing a biomolecule into an injection target from an injector body without injecting the solution through a predetermined structure in a state in which the predetermined structure is inserted into the injection target, the injector comprising: A storage section for storing a solution containing a biomolecule; a nozzle portion having an ejection port through which the pressurized solution containing the biomolecule flows and is ejected toward the injection target; Equipped with When the displacement x of the tip of the solution containing the biomolecule in the injection target and the velocity u(x) of the tip of the solution are fitted using the least squares method with a fitting function represented by the following formula (1), the attenuation coefficient k is 1.59 or more. It is an injector. u(x)=u0exp(-kx)+u e (1) (In equation (1), u0 is the velocity coefficient (m / s), k is the damping coefficient (1 / mm), and u e indicates the asymptotic velocity (m / s).

[0069] In the injector of the present application, when the relationship between the displacement x of the tip of the solution containing the biomolecule in the injection target and the velocity u(x) of the tip of the solution is fitted by the least squares method with the fitting function expressed by the above formula (1), the attenuation coefficient k is 1.59 or more, so that damage to tissue in the vicinity of the injection port of the injection target can be minimized. The lower limit of the damping coefficient k is, in order of increasing preference, 1.6 or more, 1.8 or more, and 2.0 or more. The upper limit of the damping coefficient k is not particularly limited, but is usually 10.0 or less. In detail, it is presumed that the greater the attenuation coefficient k, the less damage can be caused to the tissue near the injection port of the injection target. This is believed to be due to the following. That is, a high velocity u(0) of the tip of the solution (in other words, the velocity of the tip of the solution immediately after injection) is necessary for forming holes in the biological tissue when the solution is injected into the biological tissue. On the other hand, when the solution is injected in the injection direction at a high velocity and further spreads to the surrounding area with the injection direction as its axis, the surrounding interstitial cells are also spread, causing damage to the biological tissue. For this reason, although a high velocity u(0) of the tip of the solution is preferable, It is preferable that u0exp(-kx), which is the first term in the above formula (1), decreases sharply as x increases. In other words, it is preferable that the damping coefficient k is large.

[0070] In the injector of the present application, when the relationship between the displacement x of the tip of the solution containing the biomolecule in the injection target and the velocity u(x) of the tip of the solution is fitted by the fitting function expressed by the above formula (1) using the least squares method, the asymptotic velocity u e is preferably 0.01 or more, a solution containing a biomolecule can be directly injected into a wide range of cells in an injection subject. In addition, in the present specification, "intracellular" preferably means intracellular. asymptotic velocity u e is preferably 0.01 or more, more preferably 0.02 or more, while being preferably 0.04 or less. Also, the asymptotic velocity u e The upper limit of is not particularly limited, but is usually 0.1 or less. The velocity u(x) is subjected to resistance within the tissue of the injection target. Therefore, it becomes 0 within a finite time and within a finite displacement from the injection port. In detail, the asymptotic velocity u eWhen k is 0.01 or more, the solution spreads around the injection direction even after the first term of the above equation (1) approaches zero due to the contribution of the attenuation coefficient k, making it possible to directly inject a solution containing biomolecules into a wide range of cells in the injection target. On the other hand, when k is 0.04 or less, excessive injection of the solution into areas with weak bonds between cells or tissues is suppressed, and it is presumed that the injection rate into cells can be increased.

[0071] In the present application, the biomolecule to be injected into the cells of the subject is not particularly limited as long as it functions in the cells, preferably in the cell nucleus, of the subject when injected into the cells of the subject. The biomolecule may be a natural product or may be artificially synthesized. For example, nucleic acid or a derivative thereof; nucleoside, nucleotide or a derivative thereof; amino acid, peptide, protein or a derivative thereof; lipid or a derivative thereof; metal ion; low molecular weight compound or a derivative thereof; antibiotic; vitamin or a derivative thereof, etc. may be mentioned. If it is a nucleic acid, it may be DNA or RNA, and may contain a gene. In the examples described later, free Cy3-labeled plasmid DNA is used as the biomolecule. The biomolecule to be injected into the cells of the subject may be in a free form, fixed to a carrier such as a nanoparticle, or modified, as long as the biomolecule exists stably and does not have any adverse effects such as destroying the subject or the cells of the subject, and the form, including the solvent, is not particularly limited. When the DNA contains a gene, the gene may be designed to be contained in an expression cassette or expression vector. Furthermore, for example, the gene may be placed under the control of a promoter suitable for the type of subject and the injection site into which the DNA is injected. That is, in any embodiment, known genetic engineering techniques can be used.

[0072] In the injector of the present application, the "tip side" refers to the side where the injection port through which a solution containing biomolecules is injected from the injector is located, and the "base side" refers to the side of the injector opposite the tip side, and these terms do not refer exclusively to a specific location or position.

[0073] The injector of the present application injects a solution containing a biomolecule from the injector body to the injection target without injecting the solution through a predetermined structure inserted into the injection target. The injector according to the first invention of the present invention may include a predetermined structure such as a catheter that guides the solution containing a biomolecule from the injector body to the injection target, for example, when the distance from the injector body to the injection target is large. Therefore, the injector according to the first invention of the present invention may or may not include such a predetermined structure, but if it includes a predetermined structure, the solution containing a biomolecule is not injected into the injection target with the predetermined structure inserted into the injection target.

[0074] In the injector of the present application, the driving unit for pressurizing the solution containing the biomolecule is not particularly limited. The pressurization may be, for example, the pressure generated when the pressure of the compressed gas is released, or the pressure generated by the combustion of the explosive ignited by the ignition device. It may also be pressurized using electromagnetic force, for example, pressurized by a linear electromagnetic actuator. Preferably, it is an embodiment that uses at least the pressure generated by the combustion of the explosive ignited by the ignition device, and further, it may be used in combination with either or both of the other two pressurization embodiments described above. In the case of adopting an embodiment in which the pressure generated by the combustion of explosives ignited by an ignition device is used as the pressurization, the explosives may be, for example, any one of explosives containing zirconium and potassium perchlorate (ZPP), explosives containing titanium hydride and potassium perchlorate (THPP), explosives containing titanium and potassium perchlorate (TiPP), explosives containing aluminum and potassium perchlorate (APP), explosives containing aluminum and bismuth oxide (ABO), explosives containing aluminum and molybdenum oxide (AMO), explosives containing aluminum and copper oxide (ACO), and explosives containing aluminum and iron oxide (AFO), or explosives consisting of a combination of a plurality of these. A feature of these explosives is that the combustion products are gaseous at high temperatures but do not contain gaseous components at room temperature, so that the combustion products immediately condense after ignition. In addition, when the generated energy of the gas generating agent is used as the ejection energy, it is also possible to use, as the gas generating agent, various gas generating agents used in single-base smokeless powder, gas generators for airbags, and gas generators for seatbelt pretensioners.

[0075] In the injector of the present application, the filling chamber is not initially filled with a solution containing biomolecules, but is filled by aspirating the solution containing biomolecules into the filling chamber through a nozzle having an injection port. In this way, by adopting a configuration that requires a filling operation into the filling chamber, it becomes possible to inject a solution containing any desired biomolecule into an injection target. Therefore, in the injector according to the first aspect of the present invention, the syringe part is configured to be detachable.

[0076] Hereinafter, a syringe 1 (needleless syringe) will be described as an example of an injector according to an embodiment of the first invention of the present invention with reference to the drawings. Note that the configuration of the following embodiment is an example, and the present invention is not limited to the configuration of this embodiment. Note that the terms "tip side" and "base side" are used to indicate the relative positional relationship in the longitudinal direction of the syringe 101. The "tip side" indicates a position closer to the tip of the syringe 101 described later, that is, closer to the ejection port 131a, and the "base side" indicates a direction opposite to the "tip side" in the longitudinal direction of the syringe 1, that is, a direction toward the drive unit 107. In addition, this example is an example in which the combustion energy of a gunpowder ignited by an ignition device is used as ejection energy, and a DNA solution is used as a solution containing biomolecules, but the invention of the present invention is not limited thereto.

[0077] (Configuration of syringe 101) 14 is a diagram showing a schematic configuration of syringe 101, and is also a cross-sectional view along the longitudinal direction of syringe 101. Syringe 101 is configured by attaching syringe assembly 110, in which a sub-assembly consisting of syringe portion 103 and plunger 104 and a sub-assembly consisting of syringe body 106, piston 105, and drive portion 107 are integrally assembled, to housing (syringe housing) 102.

[0078] As described above, the syringe assembly 110 is configured to be detachable from the housing 102. The filling chamber 132 formed between the syringe portion 103 and the plunger 104 included in the syringe assembly 110 is filled with DNA solution, and the syringe assembly 110 is a unit that is disposable every time the DNA solution is injected. On the other hand, the housing 102 includes a battery 109 that supplies power to an igniter 171 included in a drive unit 107 of the syringe assembly 110. The power supply from the battery 109 can be controlled by the user by adjusting the volume of the housing 102. By pressing the button 108 provided on the housing 102, a connection is made between an electrode on the housing 102 side and an electrode on the drive unit 107 side of the syringe assembly 110 via a wire. The shape and position of the electrode on the housing 102 side and the electrode on the drive unit 107 side of the syringe assembly 110 are designed so that they automatically come into contact when the syringe assembly 110 is attached to the housing 102. The housing 102 is a unit that can be used repeatedly as long as the battery 109 has power remaining to supply to the drive unit 107. When the battery 109 runs out of power, the housing 102 may continue to be used by replacing only the battery 109.

[0079] In addition, although no additional explosive components are particularly arranged in the syringe body 106 shown in FIG. 14, in order to adjust the pressure transition applied to the DNA solution via the piston 105, a gas generating agent that burns and generates gas by a combustion product generated by explosive combustion in the igniter 171 can be arranged in the igniter 171 or in the through hole of the syringe body 106. The configuration of arranging a gas generating agent in the igniter 171 is already a known technique as disclosed in International Publication No. 01-031282 and Japanese Patent Application Laid-Open No. 2003-25950. In addition, as an example of a gas generating agent, a single-base smokeless powder consisting of 98% by mass of nitrocellulose, 0.8% by mass of diphenylamine, and 1.2% by mass of potassium sulfate can be mentioned. In addition, various gas generating agents used in gas generators for airbags and gas generators for seatbelt pretensioners can also be used. By adjusting the dimensions, size, shape, and especially the surface shape, of the gas generating agent when placed in the through-hole, it is possible to change the time until the combustion of the gas generating agent is completed, and this makes it possible to make the pressure transition applied to the DNA solution a desired transition, i.e., a transition that allows the DNA solution to be appropriately injected into the injection target. In the present invention, the gas generating agent used as needed is also included in the driving unit 107.

[0080] (Injection target) The injection target in the present application may be, for example, any of cells, cells in a cell sheet, cells in a tissue, cells in an organ, cells in an organ system, cells in an individual (living body), etc., and is not limited thereto. Preferred injection targets include the above-mentioned injection targets derived from mammals. More preferably, the injection targets are cells in an individual mammal (living body), even more preferably cells in the skin, and even more preferably cells in one or more tissues selected from the group consisting of intradermal, subcutaneous, and panniculus carnosus. In this case, a method can be adopted in which a solution containing a biomolecule is ejected from an injector onto the skin surface of an individual mammal (living body), and then injected from the skin surface into cells in one or more tissues selected from the group consisting of intradermal, subcutaneous, and panniculus carnosus in the skin. Furthermore, the system in which a solution containing a biomolecule is injected from an injector into an injection target may be any system, including an in vitro system, an in vivo system, and an ex vivo system. Furthermore, the mammal is not particularly limited, and examples thereof include humans, mice, rats, guinea pigs, hamsters, cows, goats, sheep, pigs, monkeys, dogs, cats, etc. Depending on the subject of injection, the mammal may be any animal other than humans.

[0081] (A method to confirm that a solution containing biomolecules has been directly injected into the target cell nucleus) There is no particular limitation on the method for confirming that a solution containing a biomolecule has been directly injected into the cell nucleus of the injection target, and known biological techniques can be used. For example, a method in which a biomolecule is fluorescently labeled in advance and then injected into the cell nucleus of the injection target and then observed under a fluorescent microscope can be used. In the examples described below, Cy3-labeled plasmid V7905 (Mirus) is used as the DNA to be directly injected into the cell nucleus of a cell in a mammalian individual (living organism), and DAPI is used as the nuclear staining dye. The sample can be prepared, for example, by obtaining tissue immediately after injecting DNA and sectioning it. At this time, DAPI staining may be performed at the same time. Since red fluorescence is emitted at the position where the Cy3-labeled plasmid V7905 was injected and blue fluorescence is emitted by DAPI at the position of the cell nucleus, the position emitting blue-purple fluorescence can be observed under a fluorescent microscope. The position can be identified as the location of Cy3-labeled plasmid V7905 that was directly injected into the cell nucleus.

[0082] Another aspect of the injector of the present application is an injector that injects a solution containing a biomolecule into an injection target from an injector body without injecting the solution through a predetermined structure in a state in which the predetermined structure is inserted into the injection target, the injector comprising: A storage section for storing a solution containing a biomolecule; a nozzle portion having an ejection port through which the pressurized solution containing the biomolecule flows and is ejected toward the injection target; Equipped with When the relationship between the displacement x of the front of the solution containing the biomolecule in the injection target and the velocity u(x) of the front of the solution is fitted by the least squares method using a fitting function represented by the following formula (1), the asymptotic velocity u e is 0.01 or more, It is an injector. u(x)=u0exp(-kx)+u e (1) (In equation (1), u0 is the velocity coefficient (m / s), k is the damping coefficient (1 / mm), and u e indicates the asymptotic velocity (m / s).

[0083] The disclosure of the present application described above is incorporated herein by reference in the description of this embodiment. That is, the measurement system and method described with reference to Figs. 1 to 13 can be applied to measure the behavior (flow) of a solution containing biomolecules.

[0084] <An invention of a method for injecting a solution containing a biomolecule into a cell of an injection target using an injector (hereinafter, also simply referred to as an "injection method invention")> The present invention relates to a method for injecting a solution containing a biomolecule into a cell of an injection target using the above-mentioned injector. The above description of the injector of the invention relates to the injector, the injection subject, and the solution containing biomolecules in the invention of the injection method. EXAMPLES

[0085] The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to the following examples as long as it does not deviate from the gist of the present invention.

[0086] (Evaluation of intradermal diffusion rate) [Example 1-1] Skin tissue was prepared by excising from a rat. 100 μL of India ink was filled into an injector (nozzle diameter: 0.1 mm) shown in FIG. 14, and the India ink was injected into the skin tissue by the pressure generated by the combustion of an ignition charge. The displacement x of the tip of the India ink spreading in the skin tissue and the velocity u(x) of the tip of the India ink were measured. In this measurement, the measurement system and measurement method described based on FIG. 1 to FIG. 13 are useful. In addition, 35 mg of explosive (ZPP) containing zirconium and potassium perchlorate was used as the explosive, and 40 mg of single-base smokeless powder was used as the gas generating agent. A high-speed camera (Photoron, FASTCAM SA-Z) was used for the measurement. [Example 1-2] The same procedure as in Example 1-1 was carried out except that 55 mg of ZPP was used. [Comparative Example 1-1] A Biojector 2000 (registered trademark, manufactured by Bioject Medical Technologies, Inc., nozzle diameter: 0.12 mm) was used as a needleless syringe, and 100 μL of India ink was filled in the syringe, and the measurement was performed according to the instruction manual. The measurement was performed in the same manner as in Example 1-1.

[0087] FIG. 15-1 and Table 1-1 respectively show the ink in the skin tissue in Example 1-1. 1 is a graph and table showing the relationship between the tip displacement x and the ink tip velocity u(x). In Table 1-1, the measured value (a) of the ink tip velocity at a certain time is the value of the ink tip velocity at the time just before. It is the difference between the ink displacement at the listed time and the ink displacement at the next listed time divided by that time. For example, in Table 1-1, the measurement value in the 0.9 milliseconds time column is the difference between the ink displacement at 0.8 milliseconds time and the ink displacement at 1.0 milliseconds time divided by that time, 0.2 milliseconds. The calculated value (b) is the value used for fitting. be. In addition, although the times in Table 1-1 are listed from 0.8 milliseconds onwards, this simply means that the movement of ink within the injection subject was observed after 0.8 milliseconds; the time 0.8 milliseconds itself does not have any significance.

[0088] [Table 1-1]

[0089] Figure 15-2 and Table 1-2 are a graph and a table showing the relationship between the displacement x of the ink tip in the injection target and the velocity u(x) of the ink tip in Example 1-2. The numerical values ​​in Table 1-2 are the same as those in Table 1-1 already described.

[0090] [Table 1-2]

[0091] Figure 15-3 and Table 1-3 are a graph and a table showing the relationship between the displacement x of the ink tip in the injection target and the velocity u(x) of the ink tip in Comparative Example 1-1. The numerical values ​​in Table 1-3 are the same as those in Table 1-1 already described.

[0092] [Table 1-3]

[0093] The results obtained in Example 1-1, Example 1-2, and Comparative Example 1-1 were normalized by the velocity coefficient u0 to obtain the graph in FIG. When the results are compiled, In Example 1-1, u0=3.97, k=2.89, u e =0.02. In Example 1-2, u0=5.11, k=2.26, u e =0.04. In Comparative Example 1-1, u0=7.54, k=1.58, u e =0.00.

[0094] (Injection test of DNA solution into the cell nucleus of a mammalian individual (living organism)) [Example 2-1] The injector used in Example 1-1 above was filled with 35 mg of zirconium and potassium perchlorate-containing explosive (ZPP) as the explosive, 40 mg of single-base smokeless powder as the gas generator, and 30 μL of a solution containing Cy3-labeled plasmid V7905 (solvent: endotoxin-free TE buffer, final concentration: 0.1 mg / mL), and injected into the lumbar skin of a female SD rat (10 weeks old).

[0095] Immediately after injection, the skin was harvested and frozen in OCT compound (embedding medium for frozen tissue section preparation (Tissue-Tec OCT compound), Sakura Finetech Japan Co., Ltd.) on dry ice. The cross section of the injected area was sliced ​​at a thickness of 6 μm using a cryostat (Leica Co., Ltd.) and mounted with mounting medium containing DAPI. The prepared specimen was observed with an all-in-one fluorescence microscope (Z-X700, Keyence Co., Ltd.), and red fluorescent images of Cy3 and blue fluorescent images of DAPI were obtained at thicknesses of 0.1 to 0.4 μm. Images were taken in multiple fields of view to obtain the injection distribution in the injected area. The results are shown in Figure 17-1. The concentric circles drawn with dashed lines and labeled "1 mm" and "2 mm" are concentric circles centered on the injection port. The white arrow indicates the injection port. The ratio of the number of cells directly injected with DNA was calculated using the hybrid cell count function as follows. That is, for each cell in each analysis target area (each area surrounded by a white dashed line in Figure 17-1), a cell in which the area of ​​purple fluorescence, where blue fluorescence and red fluorescence overlap, is 50% or more of the cell area was defined as a cell directly injected with DNA, and the number of such cells was counted (this is called cell number A). Meanwhile, the total number of cells in each analysis target area was counted using the number of cell nuclei as an index (this is called cell number B). The numerical values ​​written in each analysis target area in Figure 17-1 are the ratio of cell number A to cell number B. The epidermis and hair follicles in which red fluorescence of Cy3 is hardly observed were excluded from the analysis.

[0096] Figure 17-4 shows images of the vicinity of the injection port, which are used to evaluate the degree of damage to the tissue near the injection port caused by the injection of the DNA solution. The damaged areas are the areas surrounded by white lines in each figure.

[0097] [Example 2-2] The procedure was the same as in Example 2-1, except that 55 mg of ZPP was used. The results are shown in Figure 17-2. An image of the vicinity of the injection port is shown in Figure 17-5.

[0098] [Comparative Example 2-1] The procedure was the same as in Example 2-1, except that the Biojector 2000 used in Comparative Example 1-1 was used, the solution containing Cy3-labeled plasmid V7905 was changed to 70 μL, and the procedure was carried out according to the instruction manual. The results are shown in Figure 17-3. An image of the vicinity of the injection port is shown in Figure 17-6.

[0099] 17-1, 17-2 and 17-3 show that the proportion of DNA directly injected from the injection port into the cell nuclei of cells over a wide range was significantly higher in Examples 2-1 and 2-2 than in Comparative Example 2-1. 17-4, 17-5, and 17-6, the damage to the tissue near the injection port was significantly smaller in Examples 2-1 and 2-2 than in Comparative Example 2-1. In detail, the area of ​​the damaged part was 1.3×10 4 μm 2 In Example 2-2, it is 5.2 × 10 3 μm 2 On the other hand, in Comparative Example 1-1, it was 2.7 × 10 4 μm 2 It was. [Explanation of symbols]

[0100] 1 :Syringe 3: Container section 20: Control device 21:First irradiation device 22:Second irradiation device 30: High-speed camera 31: Flow path 31a: Injection port 31b: Nozzle section 32:Tip surface 33a: First outer peripheral surface 33b: Second outer peripheral surface 33c: Third outer peripheral surface 34: Containment space 35: Reflective material 38: Reflective layer 40: Power supply 51: Object 101 :Syringe 102: Housing 103: Syringe part 104: Plunger 105: Piston 106:Syringe body 107: Drive unit 108: Button 109: Battery 110:Syringe assembly 131: Nozzle section 131a: Injection port 132: Filling chamber 171:Igniter

Claims

1. A needleless injector that injects a solution containing a biomolecule from an injector body into an injection target, A storage section for storing a solution containing a biomolecule; a nozzle portion having an ejection port through which the pressurized solution containing the biomolecule flows and is ejected toward the injection target; Equipped with When the relationship between the displacement x [mm] of the tip of the solution containing the biomolecule in the injection target and the velocity u (x) [m / s] of the tip of the solution is fitted using the least squares method with a fitting function represented by the following formula (1), the attenuation coefficient k is 1.59 or more. syringe. u(x)=u ０ exp(-kx)+u ｅ ・・・(1) (In formula (1), u ０ denotes the velocity coefficient (m / s), k denotes the damping coefficient (1 / mm), and u ｅ indicates the asymptotic velocity (m / s).

2. Asymptotic velocity u ｅ 2. The injector of claim 1, wherein the velocity is 0.01 m / s or greater.

3. A needleless injector that injects a solution containing a biomolecule from an injector body into an injection target, A storage section for storing a solution containing a biomolecule; a nozzle portion having an ejection port through which the pressurized solution containing the biomolecule flows and is ejected toward the injection target; Equipped with When the relationship between the displacement x [mm] of the tip of the solution containing the biomolecule in the injection target and the velocity u(x) [m / s] of the tip of the solution is fitted by the least squares method using a fitting function represented by the following formula (1), the asymptotic velocity u ｅ is 0.01 m / s or more, syringe. u(x)=u ０ exp(-kx)+u ｅ ・・・(1) (In formula (1), u ０ denotes the velocity coefficient (m / s), k denotes the damping coefficient (1 / mm), and u ｅ indicates the asymptotic velocity (m / s).

4. A method for injecting a solution containing a biomolecule into cells of an injection subject using the injector according to any one of claims 1 to 3 (excluding methods in which the injection subject is a human).

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