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

Abstract

The present invention aims to provide a syringe that can minimize tissue damage near the injection port of the injected object. It provides an syringe that injects a solution containing biomolecules from the syringe body into the injected object without injecting through a given structure inserted into the injected object. The syringe includes a container for holding the solution containing biomolecules and a nozzle for ejecting the pressurized solution through and out of the injected object. When fitting the relationship between the displacement x of the front end of the solution containing biomolecules within the injected object and the velocity u(x) of the front end of the solution using a fitting function expressed by equation (1) and employing the least squares method, the damping coefficient k is 1.59 or higher, and u(x) = u0exp(-kx) + u e (1), where u0 represents the velocity coefficient (m / s), k represents the damping coefficient (1 / mm), u e This indicates the asymptotic velocity (m / s).

Description

[0001] This application is a divisional application of the application filed on July 25, 2019, with application number 201980049473.1 and entitled "Measurement system, measurement method, injector, and injection method for injecting a solution containing biomolecules into the cells of an injection target using the injector". Technical Field

[0002] The present invention relates to a measurement system and a method for measuring the behavior of an ejaculated liquid ejected from an ejection device toward an object. Background Technology

[0003] In the past, various methods have been used to directly observe the flow behavior of fluids, such as the filament bundle method, which determines the flow direction based on the oscillation of a large number of short filaments (filament bundles); the oil film method, which determines the state, direction, and velocity of the flow by applying a mixture of oil and pigment to the surface of an object and observing the stripe pattern formed by the flow; the tracer method, which observes the flow by mixing particles that move with the fluid into the fluid and tracking their movement; the schlieren method, which utilizes refractive index changes based on density changes; and holography and laser speckle methods, etc. (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 using the tracer method.

[0004] Furthermore, near-infrared light can be used to observe the flow behavior of fluids. For example, Patent Document 3 discloses a technique that utilizes the characteristic of near-infrared light—that it has good transmissibility in living organisms but is strongly absorbed by blood—to create a visualization device that facilitates intravenous injection.

[0005] Existing technical documents

[0006] Patent documents

[0007] Patent Document 1: Japanese Patent Application Publication No. 2001-194379

[0008] Patent Document 2: Japanese Patent Application Publication No. 10-221357

[0009] Patent Document 3: Japanese Patent Application Publication No. 2017-64094

[0010] Patent Document 4: Japanese Patent Application Publication No. 2004-358234

[0011] Patent Document 5: U.S. Patent Application Publication No. 2005 / 0010168 Summary of the Invention

[0012] The problem that the invention aims to solve

[0013] For liquids ejected from an ejection device, high pressure is applied to facilitate their ejection. Therefore, the velocity of the ejected liquid immediately after ejection is high, making it difficult to measure its behavior. This is especially true when the ejected liquid is to be ejected into an object; attempting to optically photograph and measure the behavior of the ejected liquid using an imaging device becomes even more challenging because the liquid itself is already inside the object.

[0014] Therefore, in view of the above problems, the object of the present invention is to provide a technique suitable for photographing and measuring the behavior of an ejaculate when it is ejected from an ejection device toward an object using a photographing device.

[0015] Methods for solving problems

[0016] To address the aforementioned issues, the present invention relates to a measurement system for measuring the behavior of an eluent ejected from an ejection device into an object within that object. The measurement system comprises: a container, an imaging device, and a first irradiation device. The container is formed of a resin material and includes an internal containment space and a flow path. The containment space contains the eluent, and the flow path connects the containment space to an ejection port from which the eluent is ejected to the outside. The imaging device is configured to, in a given state where the ejection port is positioned relative to the object from its front side, capture an image of the front end face of the container, which has the ejection port and is positioned relative to the object, from the back side of the object. The first irradiation device irradiates the front end face with first near-infrared light.

[0017] The aforementioned measurement system measures the behavior of the ejected liquid as it flows through the flow path from the ejection port to the target object, within the container space of the ejection device. Here, the ejection device includes the container space and a drive unit that imparts energy for ejection to the ejected liquid contained in the container space. The energy imparted for ejection can be applied using known pressurization techniques. One example of the imparted energy is chemically generated energy, such as combustion energy generated through the oxidation reaction of gunpowder / explosives. Alternatively, the energy for pressurization can be electrically generated, for example, by a piezoelectric element driven by applied electricity or an electromagnetic actuator. Another method is physically generated energy, for example, based on the elastic energy of an elastomer or the internal energy of a compressed object such as compressed gas. In short, any energy can be used to impart energy that is sufficient to eject the ejected liquid within the ejection device. In addition, the energy used for pressurization can also be a composite energy that appropriately combines the aforementioned combustion energy, electrical energy, elastic energy, and other internal energies.

[0018] Furthermore, the ejaculate can be an appropriate liquid depending on the purpose of the substance being ejaculated from the ejaculation device. It should be noted that the substance can be dissolved in the ejaculate, or it can be simply mixed without dissolving in the liquid. For example, when the ejaculation device is a syringe, considering its purpose—to deliver a substance expected to exert a given medical effect, etc., to a target site in a living organism—the given substance could include vaccines for enhancing antibodies, proteins for cosmetic purposes, cultured cells for hair regeneration, etc., and the ejaculate is formed by containing these substances in a liquid medium in a manner that allows them to be ejaculated.

[0019] Furthermore, the container section is formed of a resin material, but any material that, as described above, can reflect the first near-infrared light at the front end of the container section and direct the second near-infrared light into the interior of the container section can be appropriately used. For example, known resin materials such as nylon 6-12, polyarylate, polycarbonate, polybutylene terephthalate, polyphenylene sulfide, or liquid crystal polymers can be used. Additionally, these resin materials may contain fillers such as glass fibers or glass fillers. For example, polybutylene terephthalate may contain 20-80% by mass of glass fibers, polyphenylene sulfide may contain 20-80% by mass of glass fibers, and liquid crystal polymers may contain 20-80% by mass of minerals.

[0020] Here, in the ejection system, by using an imaging device to photograph the front face of the container section, which is positioned relative to the object, particularly the front face including the ejection port, the behavior of the ejected liquid ejected from the ejection port during operation of the ejection device can be measured. Regarding the positioning relative to the object, i.e., the given state, it can be a state where the front face of the container section is in contact with the object. In the case of any impurities intervening between the front face and the object, it can also be a state where the front face of the container section is in contact with the impurities, and the impurities are in contact with the object. It should be noted that the imaging device can directly photograph the front face of the container section, or it can take pictures using a given optical device (mirror, etc.). In this case, since the front face of the container section is photographed from the back side of the object with the object in between, the thickness of the object is preferably set to a given thickness such that it is thinned to the point where the ejection port can be grasped. Furthermore, the front face of the container section is irradiated with first near-infrared light from a first irradiation device. As a result, the imaging device can appropriately capture the ejected liquid ejected towards the object in its captured image, thereby appropriately achieving the measurement of the behavior of the ejected liquid.

[0021] Here, as one embodiment of the first irradiation device, the first irradiation device is a device that irradiates the first near-infrared light onto the front surface of the object from the back side. The irradiation angle of the first near-infrared light relative to the front surface can be set such that the reflected light from the front surface of the first near-infrared light is directed towards the imaging device. In this embodiment, since the irradiation angle of the first near-infrared light is set such that the reflected light from the front surface is directed towards the imaging device, the imaging device can easily capture the front surface of the container. As a result, by irradiating the first near-infrared light using the first irradiation device, the imaging device can appropriately capture the extruded liquid ejected towards the object in its captured image, thereby enabling appropriate measurement of the behavior of the extruded liquid. Furthermore, since the first near-infrared light is irradiated onto the front surface of the container that is positioned relative to the object, the behavior of the extruded liquid can be measured regardless of the shape of the container, especially the shape of the area near the flow path formed in the container.

[0022] In the above embodiment, it is further preferable to form a front-side reflective layer between the front end face of the container portion, which is set to the given state, and the object, the front-side reflective layer reflecting a portion of the first near-infrared light irradiated from the rear side of the object. Thus, by positioning the front-side reflective layer between the front end face and the object, more of the first near-infrared light can reach the imaging device, thereby enabling more appropriate measurement of the behavior of the eluent.

[0023] Furthermore, in the aforementioned ejection system, the first irradiation device can be configured such that, for each frame captured using the aforementioned imaging device, the first near-infrared light is irradiated in the form of pulsed light flashing for a given exposure time. In this way, by irradiating the first near-infrared light in the form of pulsed light, the energizing time of the light-emitting element of the first irradiation device can be shortened, thereby suppressing the heating of the light-emitting element. In other words, when pulsed light is irradiated by applying a voltage several times higher than normal to the light-emitting element of the first irradiation device, the behavior of the ejected liquid can be measured with high brightness while appropriately maintaining the operation of the light-emitting element.

[0024] Here, for the measurement system described above, considering the presence of atmosphere around the container when the first near-infrared light is irradiated from the back side of the object, the area corresponding to the front surface of the container may appear darker than its surrounding area (the area corresponding to the atmosphere surrounding the container) in the image obtained by the imaging device. In particular, under the given conditions, when the difference in refractive index between the object and the container is less than the difference in refractive index between the object and the atmosphere, the reflectivity of the first near-infrared light at the front surface of the container is relatively reduced. Therefore, the area corresponding to the front surface in the image tends to be darker. When the area corresponding to the front surface becomes darker, the contrast with the ejected liquid, which is the object of the image, decreases, making it difficult to grasp the behavior of the ejected liquid exiting from the ejection port at the front surface.

[0025] Therefore, the aforementioned measurement system can further include a second irradiation device that irradiates second near-infrared light from the front side of the object. This second near-infrared light is directed towards the outer peripheral surface of the container portion, which is not in contact with the object in the given state. The angle of incidence of the second near-infrared light relative to the outer peripheral surface is set such that the light passes through the container portion and then faces the front end face. The irradiated second near-infrared light is less likely to be reflected by the outer peripheral surface of the container portion, and the angle of incidence of the second near-infrared light towards the outer peripheral surface is set such that the light passes through the container portion and then faces the front end face. Therefore, in the image obtained using the imaging device, the amount of light in the area corresponding to the front end face of the container portion can be increased. Therefore, by combining irradiation with the first near-infrared light from the first irradiation device and irradiation with the second near-infrared light from the second irradiation device, the contrast with the ejected liquid, which is the object to be photographed, can be further increased. The imaging device can then appropriately capture the ejected liquid directed towards the object in its captured image, thereby enabling appropriate measurement of the ejected liquid's behavior. It should be noted that the second irradiation device can be configured in the same manner as the first irradiation device, irradiating the second near-infrared light in the form of pulsed light flashing for a given exposure time for each frame captured by the imaging device. Furthermore, in this case, either the first or second irradiation device can be configured to irradiate pulsed light, or both can be configured to irradiate pulsed light.

[0026] Here, in the aforementioned measurement system, a reflective member can be provided in the container section. This reflective member reflects the second near-infrared light, which travels through the container section and reaches this given area within a given region from the injection position of the second near-infrared light to the end of the front end face. This given region is at least a portion of the outer peripheral surface. By providing the reflective member in this way within a given region of the outer peripheral surface of the container section, the second near-infrared light traveling within the container section can be reflected and directed towards its front end face. This configuration is extremely useful in situations where, due to the design of the container section or the configuration of the second irradiation device, it is impossible to directly direct part or all of the second near-infrared light from the injection position into the container section towards the front end face. That is, the reflective member prevents part or all of the second near-infrared light traveling within the container section from escaping into the atmosphere from the container section within a given region. Therefore, more light can be concentrated on the front end face of the container section, thereby increasing the contrast with the ejected liquid as the object of imaging and obtaining a suitable image of the ejected liquid near the front end face.

[0027] In another embodiment of the first irradiation device, 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 is incident on the outer peripheral surface of the container portion, which is not in contact with the object in the given state. The angle of incidence of the first near-infrared light relative to the outer peripheral surface is set such that the first near-infrared light entering the container portion passes through the container portion and irradiates the front end face. Further, an outer peripheral reflective member can be provided in the container portion. This outer peripheral reflective member reflects the first near-infrared light from the incident position to the end of the front end face within a given area, where the given area is at least a portion of the outer peripheral surface. In such an embodiment, the first near-infrared light can also be irradiated in the form of pulsed light that flashes for a given exposure time.

[0028] Additionally, the present invention can be understood from the aspect of the measurement method, which measures the behavior of an eluent ejected from an ejection device into an object within the object. The method includes: preparing the ejection device having a container portion formed of resin material and containing an internal receiving space and a flow path, the receiving space containing the eluent, and the flow path connecting the receiving space to an ejection port from which the eluent is ejected to the outside; configuring an imaging device such that, in a given state where the ejection port is positioned relative to the object from its front side, an image is taken of the front end face of the container portion, which has the ejection port and is positioned relative to the object, from the back side of the object, with the object in between; irradiating the front end face with first near-infrared light from a first irradiation device; and, while irradiated with the first near-infrared light using the first irradiation device, taking an image of the eluent ejected from the ejection device using the imaging device. Preferably, the irradiation angle of the first irradiation device irradiating the front face of the object with the first near-infrared light from the back side is set such that the reflected light of the first near-infrared light from the front face faces the imaging device. Furthermore, this measurement method may further include: irradiating the outer peripheral surface of the container with the second irradiation device, wherein the incident angle of the second irradiation device irradiating the second near-infrared light from the front side of the object relative to the outer peripheral surface that is not in contact with the object in the given state is set such that the second near-infrared light incident into the container faces the front face after passing through the container; and, after irradiating the first near-infrared light with the first irradiation device and the second near-infrared light with the second irradiation device, photographing the eluent ejected from the ejection device using the imaging device.

[0029] Alternatively, as another method, 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 is directed toward the outer peripheral surface of the container portion, which is not in contact with the object in the given state. The angle of incidence of the first near-infrared light relative to the outer peripheral surface is set such that the first near-infrared light directed toward the container portion passes through the container portion and then irradiates the front end surface.

[0030] It should be noted that, as long as there is no technical contradiction, the technical ideas disclosed in relation to the above-mentioned measurement system can also be applied to inventions involving the above-mentioned measurement methods.

[0031] The effects of the invention

[0032] The behavior of the ejected liquid when it is ejected from the ejection device to the object can be photographed and measured using an imaging device. Attached Figure Description

[0033] Figure 1 Figure 1 shows a schematic diagram of the measurement system.

[0034] Figure 2 This is a diagram showing the structure of the container section installed in the ejection device, and a first embodiment showing the irradiation of the container section with near-infrared light.

[0035] Figure 3 This is a diagram showing the structure of the container section installed in the ejection device, and a second embodiment showing the irradiation of the container section with near-infrared light.

[0036] Figure 4 It is shown that in the process Figure 3 The diagram shows the propagation of near-infrared light toward the front end face of the container when irradiated with near-infrared light.

[0037] Figure 5 It is an image of the front face of a container taken from the back side using a high-speed camera clamp, with the object in between.

[0038] Figure 6 It is along Figure 5 The image shown is a coordinate graph with the diagonal line used to analyze the brightness of the captured image.

[0039] Figure 7 This is a flowchart illustrating a method for measuring the behavior of an eluent in a measurement system.

[0040] Figure 8 These are images taken in time sequence by a high-speed camera during the ejection of liquid using an ejection device, showing the liquid spreading to the front face of the container and inside the object.

[0041] Figure 9 Figure 2 shows a schematic diagram of the measurement system.

[0042] Figure 10 yes Figure 9 An enlarged view of the area near the nozzle tip in the illustrated embodiment.

[0043] Figure 11 Is Figure 9 The embodiment shown uses a high-speed camera to capture an image of the front face of the container from the back side, with the object in between.

[0044] Figure 12 It is along Figure 11 The image shown is a coordinate graph with the diagonal line used to analyze the brightness of the captured image.

[0045] Figure 13 Figure 3 shows a schematic diagram of the measurement system.

[0046] Figure 14 This is a diagram illustrating the schematic structure of an injector according to one embodiment of the present invention.

[0047] Figure 15-1 This is a coordinate graph showing the relationship between the displacement x of the tip of the solution containing biomolecules injected into the object and the velocity u(x) of the tip of the solution in one embodiment of the present invention.

[0048] Figure 15-2 This is a coordinate graph showing the relationship between the displacement x of the tip of the solution containing biomolecules injected into the object and the velocity u(x) of the tip of the solution in one embodiment of the present invention.

[0049] Figure 15-3 This is a coordinate graph illustrating the relationship between the displacement x of the tip of a solution containing biomolecules injected into the object and the velocity u(x) of the tip of the solution, in one embodiment of the present invention.

[0050] Figure 16 This is a graph showing the relationship between the displacement x of the tip of the solution containing biomolecules injected into the object and the velocity obtained by normalizing the velocity u(x) of the tip of the solution using the velocity coefficient u0, in one embodiment of the present invention.

[0051] Figure 17-1 This is a diagram (alternate photograph) illustrating the distribution of cell nuclei and DNA injected into a mammalian individual (organism) in one embodiment of the present invention.

[0052] Figure 17-2 This is a diagram (alternate photograph) illustrating the distribution of cell nuclei and DNA injected into a mammalian individual (organism) in one embodiment of the present invention.

[0053] Figure 17-3 This is a diagram (alternate photograph) showing the distribution of cell nuclei and DNA injected into a mammalian individual (organism) in a comparative example of the present invention.

[0054] Figure 17-4 This is a diagram (alternate photograph) illustrating tissue damage in a mammalian individual (organism) caused by the injection of a DNA solution, according to one embodiment of the present invention.

[0055] Figure 17-5 This is a diagram (alternate photograph) illustrating tissue damage in a mammalian individual (organism) caused by the injection of a DNA solution, according to one embodiment of the present invention.

[0056] Figure 17-6This is a diagram (alternate photograph) illustrating tissue damage in a mammalian individual (organism) caused by the injection of a DNA solution, according to one embodiment of the present invention.

[0057] Symbol Explanation

[0058] 1: Syringe

[0059] 3: Container Section

[0060] 20: Control device

[0061] 21: First Irradiation Device

[0062] 22: Second Irradiation Device

[0063] 30: High-speed camera

[0064] 31: Flow path

[0065] 31a: Injection port

[0066] 31b: Nozzle section

[0067] 32: Front end

[0068] 33a: First outer peripheral surface

[0069] 33b: Second outer perimeter

[0070] 33c: Third outer peripheral surface

[0071] 34: Capacity

[0072] 35: Reflective component

[0073] 38: Reflective layer

[0074] 40: Power supply device

[0075] 51: Object

[0076] 101: Syringe

[0077] 102: Outer shell

[0078] 103: Syringe section

[0079] 104: Plunger

[0080] 105: Piston

[0081] 106: Syringe body

[0082] 107: Drive Unit

[0083] 108: Button

[0084] 109: Battery

[0085] 110: Syringe Assembly

[0086] 131: Nozzle section

[0087] 131a: Injection port

[0088] 132: Filling Chamber

[0089] 171: Igniter Detailed Implementation

[0090] <First Embodiment>

[0091] Hereinafter, with reference to the accompanying drawings, a measurement system and method for measuring the behavior of the ejaculated liquid ejected from the injection device in this embodiment will be described. It should be noted that in this embodiment, the injection device is a needleless syringe (hereinafter referred to as "syringe") 1 that ejects the injection liquid (ejaculated liquid) to the target object without using an injection needle. This syringe 1 utilizes the combustion energy of gunpowder to eject the injection liquid to the target object. It should be noted that in this embodiment, the terms "front end side" and "base end side" are used to indicate the relative positional relationship of the syringe 1 along its length. The "front end side" refers to the position near the front end of the syringe 1, i.e., near the injection port 31a, and the "base end side" refers to the direction along the length of the syringe 1 opposite to the "front end side," i.e., the direction towards the drive section 7. Furthermore, the configuration of the following embodiment is an example, and the configuration of the measurement system is not limited to the configuration of this embodiment.

[0092] <Structure of Syringe 1>

[0093] here, Figure 1 This is a schematic diagram showing the overall structure of syringe 1 and the measuring system. Figure 1 In the diagram, syringe 1 is shown in cross-section along its length. It should be noted that when measuring the behavior of the injection fluid using a measurement system, the injected fluid does not necessarily have to be the same fluid used in actual use of syringe 1 (e.g., a liquid formed by containing a given substance in a liquid medium that can exert the desired efficacy or function in the object). It can be a photographic fluid that is easily photographed using a high-speed camera 30, which serves as the photographing device. In this embodiment, such a photographic fluid is also considered a form of injection fluid.

[0094] The syringe 1 is configured such that a container portion 3 is mounted on the front end side of the syringe body 6, and a drive portion 7 is mounted on the base end side. Here, the container portion 3 is formed of resin and internally includes a receiving space 34 formed along the central axis of its body, serving as a space for containing the injection liquid, and a flow path 31 communicating with the receiving space 34 and opening at the front end side. More specifically, a nozzle portion 31b including the flow path 31 is formed at the front end side of the container portion 3, and the end face of the front end side of the nozzle portion 31b is designated as a front end face 32 (see below). Figure 2 , Figure 3 Therefore, the nozzle portion 31b is part of the container portion 3 that does not include the receiving space 34. Furthermore, the opening of this flow path 31 becomes the injection port 31a. As the resin material for forming the container portion 3 including the nozzle portion 31b, known materials such as nylon 6-12, polyarylate, polycarbonate, polybutylene terephthalate, polyphenylene sulfide, or liquid crystal polymers can be used. Additionally, these resin materials may also contain fillers such as glass fibers or glass fillers. For example, polybutylene terephthalate may contain 20-80% by mass of glass fibers, polyphenylene sulfide may contain 20-80% by mass of glass fibers, and liquid crystal polymers may contain 20-80% by mass of minerals.

[0095] Furthermore, in the receiving space 34 of the container section 3, the plunger 4 is arranged in a manner that allows it to slide along the direction of the flow path 31 (the front end side direction). Part or all of the receiving space 34 formed between the plunger 4 and the main body of the container section 3 becomes the space where the injection liquid is actually sealed. Here, by sliding the plunger 4 within the receiving space 34, the injection liquid contained in the receiving space 34 is pressed and ejected from the injection port 31a provided on the front end side of the flow path 31. Therefore, the plunger 4 is made of a material that allows smooth sliding within the receiving space 34 and prevents the injection liquid from leaking out from the plunger 4 side. As a specific material for the plunger 4, butyl rubber or silicone rubber can be used, for example. Further examples include: styrene-based elastomers, hydrogenated styrene-based elastomers, or materials in which polyolefins such as polyethylene, polypropylene, polybutene, and α-olefin copolymers, liquid paraffin, processing oils, talc, castings, and powdered inorganic materials such as mica are mixed. Alternatively, various rubber materials such as polyvinyl chloride elastomers, olefin elastomers, polyester elastomers, polyamide elastomers, polyurethane elastomers, natural rubber, isoprene rubber, chloroprene rubber, nitrile rubber, and styrene-butadiene rubber (especially vulcanized materials), or mixtures thereof, can be used as the material for the plunger 4. Furthermore, to ensure / adjust the sliding properties between the plunger 4 and the container section 3, various substances can be used to coat / surface-process the surface of the plunger 4 and the surface of the accommodating space 34 of the container section 3. As such coating agents, PTFE (polytetrafluoroethylene), silicone oil, diamond-like carbon, and nanodiamonds can be used.

[0096] Here, the profile of the front end of the plunger 4 is formed to be substantially consistent with the profile of the inner wall of the connection between the receiving space 34 and the flow path 31. As a result, when the injection fluid is ejected, as the plunger 4 slides to the deepest position located in the deepest part of the receiving space 34, the gap formed between the plunger 4 and the inner wall of the connection can be minimized, thereby preventing the injection fluid from remaining in the receiving space 34 and causing waste.

[0097] Here, we return to the description of the container section 3. The inner diameter of the flow path 31 of the container section 3 is made smaller than the inner diameter of the receiving space 34. With this structure, the injection liquid pressurized to high pressure is ejected from the injection port 31a of the flow path 31 to the outside. In addition, a threaded portion for connecting the syringe body 6 and the container section 3 is formed on the base end side of the container section 3.

[0098] Additionally, a piston 5 is disposed adjacent to the plunger 4 within the container section 3. The piston 5 is configured to slide within the receiving space 34 under pressure from the combustion products generated by the igniter 71 of the drive section 7. The piston 5 is made of metal, and to improve the seal between the piston 5 and its sliding surface, an O-ring or similar material may be provided on a portion thereof. Alternatively, the piston 5 may be made of resin; in this case, metal may be used in combination for parts requiring heat resistance and pressure resistance. The end face of the piston 5 at its base is exposed at a through-hole formed inside the syringe body 6. This through-hole allows the combustion products generated by the igniter 71 of the drive section 7 to be released, or it may contain a combustion chamber through which a gas generator 80 combusts. Therefore, the end face of the piston 5 at its base is subjected to pressure from this combustion chamber, and this pressure is transmitted via the plunger 4 to the injection liquid contained in the receiving space 34, thus pressurizing the piston.

[0099] Next, the drive unit 7 will be described. The main body of the drive unit 7 is cylindrical, and an igniter 71 is located inside it. The igniter 71 is an electric igniter that generates energy for ejection by igniting a propellant. The base end face of the piston 5 is disposed opposite to the igniter 71 on the syringe body 6 in such a way that the combustion energy generated by the igniter 71 can be transferred to the base end face of the piston 5. The main body of the drive unit 7 can be formed by fixing injection-molded resin to a metal sleeve. Known methods can be used for this injection molding. The resin material of the main body of the drive unit 7 is the same resin material as that of the container part 3.

[0100] Here, the combustion energy of the ignition propellant used in igniter 71 serves as the energy for syringe 1 to eject the injection liquid towards the target. It should be noted that the following are preferred examples of this ignition propellant: propellant containing zirconium and potassium perchlorate (ZPP), propellant containing titanium hydride and potassium perchlorate (THPP), propellant containing titanium and potassium perchlorate (TiPP), propellant containing aluminum and potassium perchlorate (APP), propellant containing aluminum and bismuth oxide (ABO), propellant containing aluminum and molybdenum oxide (AMO), propellant containing aluminum and copper oxide (ACO), propellant containing aluminum and iron oxide (AFO), or propellant composed of multiple combinations of these propellants. These propellants generate high-temperature, high-pressure plasma during combustion immediately after ignition, and exhibit a rapid pressure drop when the combustion products condense at room temperature due to the absence of gaseous components. Other propellants may also be used as ignition propellants, provided that the injection liquid can be ejected appropriately.

[0101] In addition, in order to adjust the pressure change of the injection fluid applied via the piston 5, a gas generating agent 80 is disposed in the through hole of the syringe body 6, in addition to the aforementioned ignition agent. This gas generating agent 80 is combusted by the combustion products generated by the combustion of the gunpowder in the igniter 71 and generates gas. Its placement location is a portion that can be exposed to the combustion products from the igniter 71. Alternatively, as disclosed in other methods, such as International Publication No. 01-031282 and Japanese Patent Application Publication No. 2003-25950, the gas generating agent 80 may also be disposed within the igniter 71. As an example of a gas generating agent, a single-base smokeless gunpowder comprising 98% by mass of nitrocellulose, 0.8% by mass of diphenylamine, and 1.2% by mass of potassium sulfate can be cited. Furthermore, various gas generating agents used in airbag gas generators and seatbelt pretensioner gas generators can also be used. By adjusting the size, shape, and especially the surface shape of the gas generator disposed within the through hole 64 of the syringe body 6, the combustion end time of the gas generator can be changed, thereby adjusting the pressure applied to the injection liquid to achieve the desired change in injection pressure.

[0102] When direct current is supplied to the drive unit 7 of the syringe 1 configured as such from the power supply unit 40, the igniter 71 operates to release combustion products, and the gas generator 80 is combusted by these combustion products. As a result, the piston 5 is pressed, pressurizing the injection liquid via the plunger 4. The pressurized injection liquid is ejected from the injection port 31a of the nozzle 31b. It should be noted that... Figure 1The nozzle portion 31b, with its injection outlet 31a, has its front end face 32 in contact with and positioned against the object 51 to be injected with the injection solution, thus enabling it to be injected into the object 51 when the drive unit 7 is operational. Here, the object 51 is the object to which the injection solution is to be injected, whose behavior is measured by the measurement system of this embodiment. For example, the object 51 could be a piece of skin removed from a rat. In this embodiment, the object 51 is formed relatively thinly in order to measure the behavior of the injection solution within it. Furthermore, in... Figure 1 In the shown configuration, object 51 is positioned on a colorless, transparent acrylic sheet 52, with syringe 1 positioned above the front end face 32 of nozzle portion 31b. Thus, with object 51 as a reference, the side with syringe 1 is considered the front side of object 51.

[0103] Furthermore, in the measurement system, a high-speed camera 30, serving as an imaging device, is positioned at a location that allows the front end face 32 of the nozzle portion 31b to be photographed from the back side of the object 51 (i.e., the side opposite to the front side where the syringe 1 is located). The high-speed camera 30 is capable of capturing phenomena occurring in a very short time at a high speed of approximately several thousand to ten thousand frames per second. For example, it is preferable to capture images at a speed of 1000 frames per second or more, preferably 5000 frames per second or more, and even more preferably 10000 frames per second or more. Since the injection liquid ejected from the syringe 1 diffuses within the object 51 in a very short time, such a high-speed camera 30 is useful. It should be noted that the high-speed camera 30 can directly photograph the front end face 32, or it can also... Figure 1 As shown, the front end 32 is photographed via an optical device such as a mirror 23. Furthermore, a control unit 20, which functions as a computer, is included in the measurement system. The control unit 20 controls the power supply unit 40 and the high-speed camera 30, while simultaneously collecting image data captured by the high-speed camera 30. By executing a given control program and performing image processing on the collected image data, the behavior of the injection solution is measured.

[0104] Here, in the measurement system, in order to supply the amount of light required for imaging to the front end face 32 of the nozzle section 31b in the field of view facing the high-speed camera 30, a back-side irradiation device 21 for irradiating near-infrared light of a given wavelength (in this case, equivalent to the first irradiation device of this application) is arranged on the back side of the object 51. The back-side irradiation device 21 is, for example, a laser irradiation device capable of irradiating 850nm near-infrared light. Furthermore, for the back-side irradiation device 21, the irradiation angle from the back-side irradiation device 21 to the front end face 32 is set such that the near-infrared light irradiates the front end face 32 and the reflected light at the front end face 32 is directed toward the high-speed camera 30 via the mirror 23. It should be noted that the irradiation angle refers to the angle between the normal direction of the front end face 32 and the irradiation direction of the near-infrared light. Therefore, by irradiating near-infrared light from the rear-side irradiation device 21, and with the high-speed camera 30 sandwiched between the object 51 and the front end 32, the behavior of the injection fluid inside the object 51 when the syringe 1 is working (e.g., how the injection fluid diffuses inside the object 51) can be captured.

[0105] However, in Figure 1 In the configuration of the syringe 1 shown, the front end face 32 of the nozzle portion 31b is in contact with the object 51, but the atmosphere exists on the side of the nozzle portion 31b. Therefore, in the field of view from the high-speed camera 30, the area corresponding to the front end face 32 tends to be relatively darker compared to the area corresponding to the surrounding atmosphere. This is because the refractive index of the object 51 is relatively close to the refractive index of the container portion 3 containing the nozzle portion 31b compared to the refractive index of the atmosphere. Therefore, the difference in refractive index between the object 51 and the container portion 3 is smaller than the difference in refractive index between the object 51 and the atmosphere surrounding the container portion 3. As a result, even when near-infrared light is irradiated using the back-side irradiation device 21, it cannot be sufficiently reflected at the front end face 32, and the amount of near-infrared light escaping from the object 51 through the front end face 32 into the container portion 3 increases. Therefore, in order to photograph the injection liquid at high speed, it is difficult to obtain a sufficient amount of reflected light.

[0106] Therefore, in the measurement system of this embodiment, in addition to the back-side irradiation device 21, a front-side irradiation device 22 is also provided (in this case, equivalent to the second irradiation device of this application). The front-side irradiation device 22 is also a laser irradiation device capable of irradiating near-infrared light of a given wavelength (e.g., 850 nm). Unlike the back-side irradiation device 21, the front-side irradiation device 22 is disposed on the front side of the object 51, and its near-infrared light irradiates the outer peripheral surface of the container portion 3. Here, in conjunction with... Figure 2 The first irradiation method of the near-infrared light generated by the frontal side irradiation device 22 will be described. It should be noted that, in Figure 2 The description of the plunger 4, piston 5, and injection solution in the container section 3 shown is omitted.

[0107] like Figure 2 As shown, regarding the container section 3, the nozzle section 31b is located at its front end, and a front end surface 32 is formed on this front end side, in which an injection port 31a is disposed. Furthermore, a flow path 31 is formed from the injection port 31a along the central axis of the nozzle section 31b, and it is connected to the receiving space 34. Here, in the outer peripheral surface of the container section 3, the outer peripheral surface other than the front end surface 32 that contacts the object 51 is the outer peripheral surface of the side surface of the container section 3, such as... Figure 2 As shown, from the front end side, the outer peripheral surfaces are: first outer peripheral surface 33a, second outer peripheral surface 33b, and third outer peripheral surface 33c. The first outer peripheral surface 33a is adjacent to the front end surface 32 and is located closest to the front end surface 32 of the container portion 3. On the other hand, the third outer peripheral surface 33c is located furthest from the front end surface 32 of the container portion 3 and is adjacent to the syringe body 6. Furthermore, the diameter D3 of the container portion 3 corresponding to the third outer peripheral surface 33c is larger than the diameter D1 of the container portion 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... Figure 2 The cross-section shown is inclined relative to the central axis of container section 3.

[0108] Here, near-infrared light from the front-side irradiation device 22 is directed toward point P1 on the third outer peripheral surface 33c. Point P1 on the third outer peripheral surface 33c is axially separated from the container portion 3 by a distance L1 with reference to the front end surface 32. Figure 2 As shown, the incident angle θ1 of the near-infrared light from the front-side irradiation device 22 is set such that the near-infrared light incident at point P1 travels within the container section 3 after being refracted at a refraction angle θ2, and directly reaches the front end face 32 of the nozzle section 31b. That is, considering the geometric conditions of the container section 3, such as the diameter D1 of the container section 3 corresponding to the first outer peripheral surface 33a (the diameter of the front end face 32), the diameter D3 of the container section 3 corresponding to the third outer peripheral surface 33c, and the distance L1 from the incident point P1 to the front end face, as well as the refraction of the near-infrared light incident from the atmosphere into the container section 3, the incident angle θ1 is set in such a way that the near-infrared light reaches the front end face 32. It should be noted that although a flow path 31 is formed in the nozzle section 31b of the container section 3, its flow path diameter is extremely small, so it does not hinder the travel of the near-infrared light within the container section 3.

[0109] By configuring the front-side illumination device 22 in this way, the near-infrared light irradiated from the front-side illumination device 22 is refracted at the incident point P1 and travels within the component of the container section 3. Here, in the container section 3, a large wall thickness is ensured between the inner wall surface of the receiving space 34 and the first outer peripheral surface 33a to the third outer peripheral surface 33c. Therefore, the near-infrared light can travel within the component with this wall thickness and directly reach the front end surface 32. As a result, in the field of view from the high-speed camera 30, an optimal amount of light can be supplied to the area corresponding to the front end surface 32 for shooting with the high-speed camera 30, and the area corresponding to the front end surface 32 tends to be relatively darker than the area corresponding to the atmosphere. By combining the illumination with the near-infrared light from the rear-side irradiation device 21, the high-speed camera 30 can appropriately capture images of the behavior of the injected liquid within the object 51 (e.g., how the injected liquid diffuses within the object 51) while facing the front end 32 with the object 51 sandwiched between it.

[0110] Next, combined Figure 3 The second irradiation mode of near-infrared light generated by the frontal side irradiation device 22 will be described. Figure 3 The container portion 3 shown has a reflective member 35 provided on its first outer peripheral surface 33a. Specifically, the reflective member 35 is an aluminum foil, which is provided on its surface in a way that tightly covers the first outer peripheral surface 33a. In addition, in the second irradiation mode, when the near-infrared light emitted from the front side irradiation device 22 enters the container portion 3 at part P1 and is refracted (refracted at a refraction angle θ2' relative to the incident angle θ1'), it does not directly reach the front end surface 32, but reaches the first outer peripheral surface 33a. However, since the reflective member 35 is provided on the first outer peripheral surface 33a, the near-infrared light reaching the first outer peripheral surface 33a is not leaked to the outside of the container portion 3 and is reflected by the reflective member 35, so that it can reach the front end surface 32. The incident angle θ1' of the near-infrared light from the front side irradiation device 22 following such an optical path can also be called the "incident angle set so that the near-infrared light emitted into the container portion 3 passes through the container portion 3 and then faces the front end surface 32".

[0111] Here, the syringe 1 is fixed in front of the front end face 32 without the object 51 being placed there, and as shown... Figure 3 When the container part 3 is irradiated with near-infrared light by the front side irradiation device 22 as shown, the state in which the reflective member 35 is installed (i.e., Figure 3 The front end face 32 is shown in the states shown below and in the state where the reflective member 35 has been removed. Figure 4 Specifically, Figure 4 The upper part (a) shows, as Figure 3The front end face 32 is shown in the state where the reflective member 35 is installed and irradiated with near-infrared light from the front side irradiation device 22. The lower part (b) shows the front end face 32 in the state where the reflective member 35 is removed and irradiated with near-infrared light from the front side irradiation device 22.

[0112] As can be understood from the upper part (a), the result of reflecting near-infrared light using the reflective member 35 is that the front region 321 of the front end face 32 becomes brighter. On the other hand, when the reflective member 35 is removed, as shown in the lower part (b), the brightness of the front region 321 of the front end face 32 becomes darker than in the upper part (a). Furthermore, it can be seen that a brighter area 322 appears at a position away from the front region 321. This exhibits the following state: that is, in the position shown in the upper part (b), the brightness of the front region 321 becomes darker than in the upper part (a). Figure 3 When the near-infrared light, which is refracted when it is incident on the container section 3, reaches the first outer peripheral surface 33a, it is directly emitted to the outside of the container section 3 without being reflected by the reflective member 35. It can be understood that by providing the reflective member 35 in this way, the front region 321 of the front end surface 32 of the nozzle section 31b can be effectively brightened.

[0113] <Shooting Results>

[0114] Here, combined with Figure 5 and Figure 6 The results of the images captured using the high-speed camera 30 will be explained. Figure 5 (a) to (c) are images taken using a high-speed camera 30 under conditions 1 to 3 as shown below, without injecting the liquid using syringe 1.

[0115] Condition 1: Near-infrared light irradiation using only the back-side irradiation device 21

[0116] Condition 2: Near-infrared light irradiation using only the frontal side irradiation device 22

[0117] Condition 3: Near-infrared light irradiation using both the back-side irradiation device 21 and the front-side irradiation device 22.

[0118] in addition, Figure 6 It shows in Figure 5 The brightness of the image pixels in the same area (the area on the same diagonal of the white area in the image) in each captured image. Figure 6 Line L1 in the middle and Figure 5 Corresponding to (a), line L2 and Figure 5 Corresponding to (b), line L3 and Figure 5 (c) corresponds to.

[0119] In addition, the behavior measurement of the injection liquid using a high-speed camera 30 was conducted according to... Figure 7 The measurement method shown is implemented through a specific flow. First, in S101, settings are made such that the syringe 1, which serves as the ejection device, reaches... Figure 1 The state shown. At this time, it is preferable to carefully fix the syringe 1 in a way that makes the front end face 32 of the nozzle portion 31b of the syringe 1 contact the object 51, and that the syringe 1 will not be displaced due to impacts generated during operation. Next, in S102, the high-speed camera 30 is positioned such that the front end face 32 of the nozzle portion 31b is included in its field of view, as shown. Figure 1 The high-speed camera 30 is positioned on the rear side of the object 51 as shown. At this time, an optical device such as a mirror 23 can be arranged between the high-speed camera 30 and the front face 32, or the optical device can be removed.

[0120] Then, in S103, the back-side irradiation device 21 is arranged on the back side of the object 51 as described above, and near-infrared light is irradiated from there onto the front-side surface 32. Further, in S104, as... Figure 2 , Figure 3 The front-side irradiation device 22 is positioned on the front side of the object 51 to irradiate it with near-infrared light, causing the near-infrared light to enter the container section 3 and travel inside the container section 3 until it reaches the front end surface 32. After irradiation with near-infrared light using the back-side irradiation device 21 and the front-side irradiation device 22, process S105 is performed. In S105, firstly, the control device 20 issues a waiting-to-shoot instruction to the high-speed camera 30. Upon receiving this instruction, the high-speed camera 30 enters a standby state, enabling it to immediately take a picture when a trigger signal arrives from an external source. Then, in this 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 to take a picture is sent from the power supply device 40 to the high-speed camera 30. Upon receiving the trigger signal, the high-speed camera 30 begins to take a picture, and the result is displayed on the monitor of the control device 20. Furthermore, the picture obtained using the high-speed camera 30 is recorded in the recording device within the control device 20. It should be noted that the order of the processes in S102 to S104 can be changed, and they can also be performed simultaneously.

[0121] The images obtained through this measurement method are those captured under condition 3 described above. It should be noted that, when taking images under conditions 1 and 2, except for using a different irradiation device than that used in condition 3 for near-infrared light irradiation, the images are... Figure 7 The procedure for the determination method shown is the same.

[0122] Here, in Figure 5In particular, in (a) and (c), the clearly distinguishable circular outline corresponds to the outer outline of the front end face 32 of the nozzle portion 31b. Under condition 1, as... Figure 5 As shown in (a), the area corresponding to the front face 32 becomes very dark. From Figure 6 Line L1 can also be understood in this way. This is because, when near-infrared light is irradiated using only the back-side irradiation device 21 as described above, the difference in refractive index between the object 51 and the nozzle portion 31b (container portion 3) is relatively small, making it difficult to generate sufficient reflected near-infrared light. However, this does not mean that the shooting method based on condition 1 is excluded from the scope of the present invention, which will be explained in the second embodiment described later.

[0123] On the other hand, under condition 3, such as Figure 5 As shown in (c), the region corresponding to the front face 32 is brighter than in condition 1. Figure 6 Line L3 can also be understood in this way. This is because, by irradiating near-infrared light not only from the back-side irradiation device 21 but also from the front-side irradiation device 22 as described above, the near-infrared light can reach the front end face 32 from the inside of the container section 3. Therefore, if the injection liquid is ejected from the injection port 31a, the contrast with the injection liquid can be made larger, thus the presence of the injection liquid can be reliably confirmed. It should be noted that in condition 2, near-infrared light was irradiated only from the front-side irradiation device 22, but the observation... Figure 6 When using line L2, a brightness variation centered around a position of approximately 180° can be identified. However, because the brightness changes relatively slowly, it is difficult to identify the outer contour (outermost position) of the injected liquid. Nevertheless, since a brightness variation near the center, as shown by line L2, can be observed even with the imaging method based on condition 2, this method is also included within the scope of the present invention. It should be noted that the imaging method based on condition 2 will be described in the third embodiment described later.

[0124] Next, when the behavior of the injection solution was measured according to condition 3 above, the changes in diffusion of the injection solution were sequentially photographed using a high-speed camera 30, and the resulting images are shown below. Figure 8 . Figure 8The figures show the elapsed time from the start of operation of the syringe 1. Specifically, they are images captured using the high-speed camera 30 at elapsed times of 0 milliseconds, 1 millisecond, 1.2 milliseconds, 3 milliseconds, 4.9 milliseconds, and 10 milliseconds. In each figure, the outer contour line of the front end face 32 of the nozzle portion 31b is represented by a solid white line. In addition, in the figures other than those with an elapsed time of 0 milliseconds, the outer contour line of the injected liquid that diffuses within the object 51 after being ejected is represented by a dashed white line. In this way, according to the measurement system of this embodiment, the behavior of the injected liquid that occurs within a very short time can be appropriately measured. It can be understood that, in particular, the presence of the injected liquid can be appropriately detected even shortly after the syringe 1 has been operated.

[0125] <Second Implementation>

[0126] Next, combined Figure 9 The second embodiment of the measurement system will be described. Figure 9 The measurement system shown does not include, as an irradiation device, the following: Figure 1 The front-side irradiation device 22 in the illustrated measurement system configuration includes only the back-side irradiation device 21, and the other configurations are basically the same. In this case, the back-side irradiation device 21 is equivalent to the first irradiation device of this application. Since such a configuration can sufficiently obtain the reflected light from the front end face 32 of the nozzle portion 31b, the behavior of the injection liquid ejected from the injection port 31a can be sufficiently captured using the high-speed camera 30. For example, by appropriately selecting the material forming the container portion 3, which includes the nozzle portion 31b, to maximize the difference in refractive index between the container portion 3 and the object, the amount of reflected light from the front end face 32 can be increased.

[0127] Furthermore, with this type of measurement system, as long as reflected light from the front end 32 can be obtained, the behavior of the injected liquid can be captured. Therefore, regardless of the shape of the nozzle 31b or the container 3, the behavior of the injected liquid can be accurately measured. This is the same as the measurement system shown in the first embodiment described above.

[0128] Furthermore, as a variation of this embodiment, such as Figure 10As shown, a reflective layer 38 can also be formed between the front end face 32 of the nozzle portion 31b and the object 51, the reflective layer 38 reflecting a portion of the near-infrared light from the rear-side irradiation device 21. Specifically, this reflective layer 38 is formed by applying a white paint (acrylic pigment) of a given thickness to the front end face 32. In this configuration, the front end face 32 of the nozzle portion 31b is positioned relative to the object 51 with the reflective layer 38 sandwiched between it. Alternatively, the reflective layer 38 can be formed by applying white paint to the surface of the object 51 (the surface in contact with the front end face 32). That is, the reflective layer 38 can be configured to be sandwiched between the front end face 32 of the nozzle portion 31b and the surface of the object 51.

[0129] <Shooting Results>

[0130] In addition, combined Figure 11 and Figure 12 The results of the high-speed camera 30 in this embodiment will be explained. Figure 11 (a) and (b) are images taken using a high-speed camera 30 corresponding to conditions 11 to 12 shown below, in a state where the injection liquid is not being injected using syringe 1.

[0131] Condition 11: Near-infrared light irradiation is performed using only the back-side irradiation device 21, and a reflective layer 38 is formed.

[0132] Condition 12: Near-infrared light irradiation is performed using only the back-side irradiation device 21, and there is no reflective layer 38.

[0133] in addition, Figure 12 Indicates in Figure 11 The brightness of image pixels in the same area (the area on a straight line in the image) in each captured image. Figure 12 Line L11 in the middle and Figure 11 (a) Correspondingly, line L12 and Figure 11 (b) Correspondingly. It should be noted that the behavior measurement of the injection liquid using the high-speed camera 30 is performed according to the above... Figure 7 The measurement method shown in the figure is performed.

[0134] Under condition 11, such as Figure 11 As shown in (a), the region corresponding to the front face 32 is brighter than in condition 12, according to Figure 12 This can also be understood by comparing line L11 with line L12. This is because the near-infrared light from the back-side irradiation device 21 is reflected more by the reflective layer 38, which improves the contrast at the nozzle portion 31, resulting in the ability to reliably capture the presence of the injection fluid.

[0135] <Third Implementation>

[0136] Next, combined Figure 13 The third embodiment of the measurement system will be described. Figure 13 The measurement system shown does not include, as an irradiation device, the following: Figure 1 The back-side irradiation device 21 in the illustrated measurement system configuration includes only the front-side irradiation device 22, and the other configurations are basically the same. In this case, the front-side irradiation device 22 is equivalent to the first irradiation device of this application.

[0137] With this configuration, sufficient near-infrared light can be obtained from the front-side irradiation device 22, which passes through the container section 3 and reaches the front end surface 32 of the nozzle section 31b. Therefore, the high-speed camera 30 can adequately capture the behavior of the injection liquid ejected from the injection port 31a. Furthermore, preferably, as described above... Figure 3 As shown, by providing a reflective member 35 on the first outer peripheral surface 33a of the container section 3, the amount of near-infrared light reaching the front end surface 32 can be increased to a level suitable for measuring the behavior of the injection solution.

[0138] <Other Implementation Methods>

[0139] In the embodiments described above, the back-side illumination device 21 can be configured to illuminate near-infrared light in the form of pulsed light flashing for a given exposure time for each frame of the high-speed camera 30. For example, the given exposure time can be set to 10 microseconds when the high-speed camera 30's shooting speed is 10,000 fps (frames per second). In this way, by illuminating near-infrared light in the form of pulsed light with the back-side illumination device 21, the energizing time of the light-emitting element of the back-side illumination device 21 can be shortened, suppressing the heating of the light-emitting element. In other words, even if the energizing power to the light-emitting element of the back-side illumination device 21 is temporarily increased, increasing its luminous intensity during pulsed illumination, the light-emitting element can be maintained in a state where it can operate appropriately. As a result, the amount of reflected light from the front end face 32 can be effectively increased, thereby enabling the measurement of the behavior of the eluent liquid with higher brightness.

[0140] Next, this application also discloses an invention relating to the injector shown below and an injection method for injecting a solution containing biomolecules into the cells of the target using the injector.

[0141] As injectors for injecting drugs into living organisms, in addition to needle-based injectors that inject with a needle and needleless injectors that inject without a needle, there are also liquid delivery tubes that have a needle and a drive source to deliver the drug to the target.

[0142] Needle-free injectors sometimes employ a configuration that uses pressurized gas, a spring, or electromagnetic force to apply pressure to a chamber containing the injection solution, thereby ejecting the injection component. For example, one configuration has multiple nozzle holes formed inside the injector body, with pistons corresponding to each nozzle hole and driven during ejection. This configuration allows for simultaneous ejection of the injection solution from multiple nozzle holes, achieving uniform injection to the target. Furthermore, injecting plasmids containing the luciferase gene into rats has enabled highly efficient cell transduction.

[0143] In addition, pressurized gas can be used as a power source for the ejection of the injection fluid in a needle-free injector. For example, a pressurization method has been demonstrated in which a large pressure is applied momentarily at the initial stage of ejection, followed by a gradual reduction of the pressure over a period of 40 to 50 milliseconds.

[0144] On the other hand, when using existing injectors, tissue near the injection port can sometimes be damaged. Furthermore, there are no reports of using injectors to directly inject solutions containing biomolecules into large areas of the intracellular space of the target organism.

[0145] That is, there are no reports on the characteristics of the injector needed to minimize tissue damage near the injection port of the target. Furthermore, there are no reports on the characteristics of the injector required for the direct intracellular injection of solutions containing biomolecules over a large area of ​​the target.

[0146] Therefore, this application also discloses an invention that aims to provide a syringe that can minimize tissue damage near the injection port of the injected object, and preferably an invention that aims to provide a syringe that can directly inject a solution containing biomolecules into a large area of ​​the cells of the injected object.

[0147] Based on the above, the inventors conducted in-depth research and found that, for an injector containing a solution containing biomolecules, when fitting the relationship between the displacement x of the front end of the solution containing biomolecules within the injected object and the velocity u(x) of the front end of the solution using a fitting function expressed by the following equation (1) and employing the least squares method, if we focus on k, which is defined as a damping constant, and u, which is defined as an asymptotic velocity... e Then by making k or u e Given a numerical range, the above-mentioned problems can be solved, thus completing the present invention.

[0148] u(x)=u0exp(-kx)+u e ···(1)

[0149] In equation (1), u0 represents the velocity coefficient (m / s), k represents the damping coefficient (1 / mm), and u eThis indicates the asymptotic velocity (m / s).

[0150] The present invention is as follows.

[0151] [1] An injector that injects a solution containing biomolecules from an injector body into an injection object without injecting via the given structure into the injection object.

[0152] The injector has the following features:

[0153] A container for holding a solution containing biomolecules, and

[0154] It has a nozzle portion that allows the pressurized solution containing biomolecules to flow through and be ejected towards the injection target.

[0155] When fitting the relationship between the displacement x of the front end of the solution containing biomolecules within the injected object and the velocity u(x) of the front end of the solution using the least squares method with the fitting function expressed by the following equation (1), the damping coefficient k is 1.59 or higher.

[0156] u(x)=u0exp(-kx)+u e ···(1)

[0157] In equation (1), u0 represents the velocity coefficient (m / s), k represents the damping coefficient (1 / mm), and u e This indicates the asymptotic velocity (m / s).

[0158] [2] According to the injector described in [1], wherein the asymptotic velocity u e It is above 0.01.

[0159] [3] An injector that injects a solution containing biomolecules from an injector body into an injection object without injecting via the given structure into the injection object.

[0160] The injector has the following features:

[0161] A container for holding a solution containing biomolecules, and

[0162] It has a nozzle portion that allows the pressurized solution containing biomolecules to flow through and be ejected towards the injection target.

[0163] When fitting the relationship between the displacement x of the tip of the biomolecule-containing solution within the injected object and the velocity u(x) of the tip of the solution using a fitting function expressed by equation (1) and employing the least squares method, the asymptotic velocity u e It is above 0.01.

[0164] u(x)=u0exp(-kx)+u e ···(1)

[0165] In equation (1), u0 represents the velocity coefficient (m / s), k represents the damping coefficient (1 / mm), and u e This indicates the asymptotic velocity (m / s).

[0166] [4] A method of injecting a solution containing biomolecules into the cells of an injection target using any one of the injectors described in [1] to [3].

[0167] According to the present invention, a syringe capable of minimizing tissue damage near the injection port of the injected object can be provided. Preferably, a syringe capable of directly injecting a solution containing biomolecules into a large area of ​​the intracellular space of the injected object can be provided.

[0168] As described above, the present invention includes an injector and a method for injecting a solution containing biomolecules into the cells of an injection target using the injector, the details of which are described below.

[0169] <The Invention of the Injector>

[0170] One embodiment of the injector in this application relates to an injector that injects a solution containing biomolecules from an injector body into an injection object without injecting via the given structure into the injection object.

[0171] The injector has the following features:

[0172] A container for holding a solution containing biomolecules, and

[0173] It has a nozzle portion that allows the pressurized solution containing biomolecules to flow through and be ejected towards the injection target.

[0174] When fitting the relationship between the displacement x of the front end of the solution containing biomolecules within the injected object and the velocity u(x) of the front end of the solution using the least squares method with the fitting function expressed by the following equation (1), the damping coefficient k is 1.59 or higher.

[0175] u(x)=u0exp(-kx)+u e ···(1)

[0176] In equation (1), u0 represents the velocity coefficient (m / s), k represents the damping coefficient (1 / mm), and u e This indicates the asymptotic velocity (m / s).

[0177] For the injector of this application, when fitting the relationship between the displacement x of the front end of the solution containing biomolecules in the injected object and the velocity u(x) of the front end of the solution using the fitting function expressed by the above formula (1) and the least squares method, by making the damping coefficient k 1.59 or more, tissue damage near the injection port of the injected object can be minimized as much as possible.

[0178] The lower limit of the damping coefficient k is preferably 1.6 or higher, 1.8 or higher, and 2.0 or higher in that order. The upper limit of the damping coefficient k is not particularly limited and is usually below 10.0.

[0179] Specifically, it can be deduced that a damping coefficient k of 1.59 or higher is preferable, as a larger damping coefficient k reduces tissue damage near the injection port of the injected object. This can be considered as follows: A high velocity u(0) at the tip of the solution (in other words, the velocity of the tip of the solution immediately after injection) is necessary for the formation of pores in the biological tissue when the solution is injected. On the other hand, the solution is injected rapidly along the injection direction, further expanding axially around the injection direction, thereby expanding the surrounding intercellular matrix and causing damage to the biological tissue. Therefore, although a larger velocity u(0) at the tip of the solution is preferable, u0exp(-kx), the first term of equation (1) above, preferably decreases sharply with increasing x. That is, a larger damping coefficient k is preferred.

[0180] For the injector of this application, when fitting the relationship between the displacement x of the front end of the solution containing biomolecules within the injected object and the velocity u(x) of the front end of the solution using the fitting function expressed by the above equation (1) and the least squares method, if the asymptotic velocity u e Preferably, a concentration of 0.01 or higher allows for the direct injection of a solution containing biomolecules into a large area of ​​the cells within the target organism. Furthermore, in this specification, "intracellular" is preferably "intracellular" within the cell nucleus.

[0181] asymptotic velocity u e Preferably, the value is 0.01 or higher, more preferably 0.02 or higher, and on the other hand, preferably 0.04 or lower. Additionally, the asymptotic speed u... e There is no specific upper limit, and it is usually below 0.1. It should be noted that the velocity u(x) is subject to resistance within the injected tissue. Therefore, it becomes 0 within a finite time interval, and also becomes 0 within a finite displacement from the injection port.

[0182] Specifically, the asymptotic velocity u eWhen the value is above 0.01, due to the contribution of the damping coefficient k, the first term of the above equation (1) asymptotically approaches zero, and the solution will also expand around its periphery with the injection direction as the axis. It can directly inject a solution containing biomolecules into a large range of cells in the injection target. On the other hand, when the value is below 0.04, it can be inferred that the solution can be suppressed from being injected excessively into the weakly bound sites between cells and tissues, thereby increasing the injection rate into the cells.

[0183] The biomolecules injected into the cells of the target cell in this application are not particularly limited as long as they function within the target cell, preferably within the cell nucleus, upon injection. Furthermore, the biomolecules can be natural or synthetically produced. Examples include: nucleic acids or their derivatives; nucleosides, nucleotides, or their derivatives; amino acids, peptides, proteins, or their derivatives; lipids or their derivatives; metal ions; low-molecular-weight compounds or their derivatives; antibiotics; vitamins or their derivatives, etc. If nucleic acids are used, they can be DNA or RNA, and they can also contain genes. In the embodiments described later, free Cy3-labeled plasmid DNA was used as the biomolecule.

[0184] For biomolecules injected into the cells of the target, as long as the biomolecules exist stably and do not cause damage or other adverse effects to the target or the cells of the target, they can be in a free form or in a form fixed to a carrier such as nanoparticles, and can be modified, including solvents. There are no particular limitations on the implementation method.

[0185] When DNA contains genes, examples include designing expression cassettes or expression vectors containing the gene in a specific form. Alternatively, genes can be configured under the control of promoters appropriate to the type of DNA to be injected and the injection site. In other words, known genetic engineering methods can be used in any manner.

[0186] In the injector of this application, "front end side" refers to the side with an outlet for ejecting a solution containing biomolecules from the injector, and "base end side" refers to the side of the injector opposite to the front end side. These expressions do not limit the specific location or position.

[0187] The injector of this application is an injector that injects a solution containing biomolecules into the injection object from the injector body without inserting a given structure into the injection object. For the injector of the first invention, for example, in cases where the distance from the injector body to the injection object is large, a structure may be included to guide the solution containing biomolecules from the injector body to the injection object; for example, a given structure such as a liquid guide tube may be included. Therefore, the injector of the first invention may optionally include or not include such a given structure, but when the given structure is included, the injector does not inject the solution containing biomolecules into the injection object with the given structure inserted into the injection object.

[0188] In the injector of this application, there are no particular limitations on the drive unit used to pressurize the solution containing biomolecules. Pressurization can be achieved, for example, by the pressure generated when the pressure of compressed gas is released, or by the pressure generated by the combustion of gunpowder ignited by an ignition device. Alternatively, pressurization can be performed using electromagnetic force, for example, by using a linear electromagnetic actuator. Preferably, at least the pressure generated by the combustion of gunpowder ignited by an ignition device is used; furthermore, it can be used in combination with any one or both of the other two pressurization methods described above.

[0189] When pressurization is achieved by using pressure generated by the combustion of gunpowder ignited by an ignition device, the gunpowder can be, for example, any one of the following: zirconium and potassium perchlorate (ZPP), titanium hydride and potassium perchlorate (THPP), titanium and potassium perchlorate (TiPP), aluminum and potassium perchlorate (APP), aluminum and bismuth oxide (ABO), aluminum and molybdenum oxide (AMO), aluminum and copper oxide (ACO), aluminum and iron oxide (AFO), or a combination of several of these. A characteristic of these gunpowders is that their combustion products are gaseous even at high temperatures, but do not contain gaseous components at room temperature; therefore, the combustion products condense immediately after ignition.

[0190] In addition, when the energy generated by the gas generator is used as the ejection energy, various gas generators used in single-base smokeless gunpowder, gas generators for airbags, and gas generators for seat belt pretensioners can also be used as gas generators.

[0191] In the injector of this application, the filling chamber does not initially contain a solution containing biomolecules, but rather is contained by drawing the solution into the filling chamber through a nozzle having an injection outlet. Thus, by employing a configuration that requires filling the filling chamber, any desired solution containing biomolecules can be injected into the recipient. Therefore, in the injector of the first invention, the syringe portion is configured to be detachable.

[0192] Hereinafter, an example of an injector according to one embodiment of the first invention will be described with reference to the accompanying drawings. It should be noted that the configuration of the following embodiment is merely an example, and the invention is not limited to this configuration. It should be noted that the terms "front end side" and "base end side" are used to indicate the relative positional relationship in the longitudinal direction of the syringe 101. The "front end side" refers to the position near the front end of the syringe 101, i.e., near the ejection port 131a, while the "base end side" refers to the direction opposite to the "front end side" in the longitudinal direction of the syringe 1, i.e., the direction towards the drive section 107 side. Furthermore, this example uses the combustion energy of gunpowder ignited by an ignition device as the ejection energy and a DNA solution as the solution containing biomolecules, but the invention is not limited to this.

[0193] (Structure of syringe 101)

[0194] Figure 14 This is a schematic diagram showing the structure of syringe 101, and also a cross-sectional view of syringe 101 along its length. Syringe 101 is constructed by mounting syringe assembly 110 to housing (syringe housing) 102. Syringe assembly 110 is obtained by assembling a sub-assembly consisting of a syringe barrel 103 and a plunger 104, and a sub-assembly consisting of a syringe body 106, a piston 105, and a drive unit 107 into one unit.

[0195] As described above, the syringe assembly 110 is configured to be freely attachable and detachable from the housing 102. The filling chamber 132 formed between the syringe barrel 103 and the plunger 104 within the syringe assembly 110 is filled with DNA solution, and the syringe assembly 110 is a disposable unit that is discarded after each injection of the DNA solution. On the other hand, a battery 109 is included on the housing 102 side, which supplies power to the igniter 171 included in the drive unit 107 of the syringe assembly 110. Power is supplied from the battery 109 by the user pressing a button 108 provided on the housing 102, via wiring between electrodes on the housing 102 side and electrodes on the drive unit 107 side of the syringe assembly 110. It should be noted that the shape and position of the two electrodes are designed so that the electrodes on the housing 102 side and the electrodes on the drive unit 107 side of the syringe assembly 110 automatically contact each other when the syringe assembly 110 is installed on the housing 102. Furthermore, the housing 102 is a reusable unit as long as the battery 109 retains enough power to supply the drive unit 107. It should also be noted that if the battery 109 is depleted, the housing 102 can be used again simply by replacing the battery 109.

[0196] in addition, Figure 14 Although no additional gunpowder components are specifically configured inside the syringe body 106 shown, a gas generating agent that generates gas by combustion of the combustion products produced by the combustion of gunpowder in the igniter 171 can be configured inside the igniter 171 and the through hole of the syringe body 106 in order to adjust the pressure change applied to the DNA solution through the piston 105. The structure of configuring a gas generating agent inside the igniter 171 is known technology, as disclosed in International Publication No. 01-031282 and Japanese Patent Application Publication No. 2003-25950. Furthermore, as an example of a gas generating agent, a single-base smokeless gunpowder comprising 98% by mass of nitrocellulose, 0.8% by mass of diphenylamine, and 1.2% by mass of potassium sulfate can be cited. Additionally, various gas generating agents used in airbag gas generators and seatbelt pretensioner gas generators can also be used. By adjusting the size, shape, and especially the surface shape of the gas generator disposed within the through-hole, the combustion end time of the gas generator can be changed, thereby allowing for a desired change in the pressure applied to the DNA solution, i.e., a change that enables the DNA solution to be appropriately injected into the target. In this invention, the gas generator or the like used as needed is also included in the drive unit 107.

[0197] (Injection object)

[0198] The injection target of this application can be any object selected from cells, cells within cell sheets, cells within tissues, cells within organs, cells within organ systems, cells within an individual (organism), etc., without limitation. Preferred injection targets include those derived from mammals. More preferably, cells within a mammalian individual (organism) are used; further preferably, cells within the skin are used; and even more preferably, cells selected from one or more tissues chosen from intradermal, subcutaneous, and dermo-muscular sources are used. In this case, a method can be employed whereby a solution containing biomolecules is ejected from an injector onto the skin surface of the mammalian individual (organism) and injected from that skin surface into cells selected from one or more tissues chosen from intradermal, subcutaneous, and dermo-muscular sources within the skin.

[0199] Furthermore, the system that injects a solution containing biomolecules from an injector into the target body can be any system, primarily an in vitro system, an in vivo system, or an ex vivo system.

[0200] Furthermore, there are no specific restrictions on whether a mammal can be included; examples include: humans, mice, rats, guinea pigs, hamsters, cows, goats, sheep, pigs, monkeys, dogs, and cats. Additionally, depending on the recipient, other mammalian methods besides humans can also be cited.

[0201] (A method that confirms that a solution containing biomolecules has been directly injected into the cell nucleus of the recipient)

[0202] There are no particular limitations on the method used to confirm that a solution containing biomolecules has been directly injected into the cell nucleus of the recipient; well-known biological methods can be used. Examples include pre-labeling the biomolecules with fluorescence and then performing fluorescence microscopy after injection into the cell nucleus. In the embodiments described later, Cy3-labeled plasmid V7905 (manufactured by Mirus) was used as the DNA injected directly into the cell nucleus of a mammalian individual (organism), and DAPI was used as the nuclear staining pigment. Samples can be prepared, for example, by obtaining tissue and sectioning immediately after DNA injection. DAPI staining can then be performed simultaneously. Since red fluorescence is emitted at the site where Cy3-labeled plasmid V7905 was injected, and blue fluorescence is emitted at the cell nucleus due to DAPI, fluorescence microscopy can identify the location of the blue-violet fluorescence as the site of Cy3-labeled plasmid V7905 directly injected into the cell nucleus.

[0203] Other embodiments of the injector in this application relate to an injector that injects a solution containing biomolecules from an injector body into an injection object without injecting via the given structure into the injection object.

[0204] The injector has the following features:

[0205] A container for holding a solution containing biomolecules, and

[0206] It has a nozzle portion that allows the pressurized solution containing biomolecules to flow through and be ejected towards the injection target.

[0207] When fitting the relationship between the displacement x of the tip of the biomolecule-containing solution within the injected object and the velocity u(x) of the tip of the solution using a fitting function expressed by equation (1) and employing the least squares method, the asymptotic velocity u e It is above 0.01.

[0208] u(x)=u0exp(-kx)+u e ···(1)

[0209] In equation (1), u0 represents the velocity coefficient (m / s), k represents the damping coefficient (1 / mm), and u e This indicates the asymptotic velocity (m / s).

[0210] The description of this embodiment references the disclosure of this application as described so far. That is, in order to measure the behavior (flow) of a solution containing biomolecules, a method based on... Figures 1 to 13 The description includes the measurement system and measurement method.

[0211] <Invention of a method for injecting a solution containing biomolecules into the cells of an injection target using an injector (hereinafter referred to as the "invention of the injection method")>

[0212] The present invention is a method for injecting a solution containing biomolecules into the cells of an injection target using the aforementioned injector.

[0213] For the injector, the injection target, and the solution containing biomolecules in the invention of the injection method, the description of the invention of the injector described above is cited.

[0214] Example

[0215] The present invention will be described in more detail below with reference to embodiments, but the present invention is not limited to the embodiments described below as long as it does not depart from its spirit.

[0216] (Evaluation of intradermal diffusion rate)

[0217] [Example 1-1]

[0218] Skin tissue harvested from rats was prepared. Figure 14The injector shown (nozzle diameter: 0.1 mm) is filled with 100 μL of ink, and the ink is injected into the skin tissue using the pressure generated by the combustion of the ignition propellant. The displacement x of the ink tip spreading within the skin tissue and the velocity u(x) of the ink tip were measured. In this measurement, combined with... Figures 1 to 13 The described measurement system and methods are useful. Additionally, 35 mg of zirconium-containing and potassium perchlorate-containing gunpowder (ZPP) was used as the gunpowder, and 40 mg of single-base smokeless gunpowder was used as the gas generator. A high-speed camera (Photoron, FASTCAM SA-Z) was used for the measurements.

[0219] [Examples 1-2]

[0220] Except that 55 mg of ZPP was used, the procedure was the same as in Example 1-1.

[0221] [Comparative Example 1-1]

[0222] As a needle-free injector, a Biojector 2000 (registered trademark, manufactured by Bioject Medical Technologies, nozzle diameter: 0.12 mm) was used, filled with 100 μL of ink, and the procedure was performed according to the instruction manual. The measurements were conducted in the same manner as in Examples 1-1.

[0223] Figure 15-1 Table 1-1 and Table 1-1 respectively show the relationship between the displacement x of the tip of the ink in the skin tissue and the velocity u(x) of the tip of the ink in Example 1-1.

[0224] It should be noted that in Table 1-1, the measured value (a) of the ink tip velocity at a certain moment is obtained by dividing the difference between the ink displacement at the preceding moment and the ink displacement at the following moment by that time. For example, in Table 1-1, the measured value in the 0.9 ms column is obtained by dividing the difference between the ink displacement at 0.8 ms and the ink displacement at 1.0 ms by the time 0.2 ms. It should also be noted that the calculated value (b) is the value used for fitting.

[0225] In addition, the time recorded in Table 1-1 starts from 0.8 milliseconds. This is only because the movement of ink in the injected object was observed after 0.8 milliseconds. 0.8 milliseconds itself has no special meaning.

[0226] [Table 1-1]

[0227]

[0228] Figure 15-2Tables 1 and 1-2 are respectively a graph and a table showing the relationship between the displacement x of the tip of the ink injected into the object and the velocity u(x) of the tip of the ink in Example 1-2. The values ​​in Table 1-2 are explained in the same way as those in Table 1-1.

[0229] [Table 1-2]

[0230]

[0231] Figure 15-3 Tables 1 and 1-3 are respectively a graph and a table showing the relationship between the displacement x of the tip of the ink injected into the object in Comparative Example 1-1 and the velocity u(x) of the tip of the ink. The values ​​in Table 1-3 are the same as those in Table 1-1.

[0232] [Table 1-3]

[0233]

[0234] The results obtained in Examples 1-1, 1-2, and Comparative Example 1-1 were normalized using the velocity coefficient u0, thereby obtaining... Figure 16 The coordinate graph.

[0235] The results can be summarized as follows:

[0236] In Example 1-1, u0 = 3.97, k = 2.89, u e =0.02.

[0237] In Examples 1-2, u0 = 5.11, k = 2.26, u e =0.04.

[0238] In Comparative Example 1-1, u0 = 7.54, k = 1.58, u e =0.00.

[0239] (An experiment involving the injection of a DNA solution into the nucleus of a cell within a mammalian organism)

[0240] [Example 2-1]

[0241] The injector used in Examples 1-1 above was filled with 35 mg of zirconium and potassium perchlorate-containing gunpowder (ZPP) as gunpowder, 40 mg of single-base smokeless gunpowder as 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 skin of the lower back of female SD rats (10 weeks old).

[0242] Skin was harvested immediately after injection and frozen using dry ice in an OCT compound (TissueTech OCTCompound, manufactured by Sakura Fine Tech Japan). The injected portion was sectioned into thin slices at a thickness of 6 μm using a cryostat (manufactured by Leica) and mounted with a mounting medium containing DAPI. Fluorescence observation of the prepared samples was performed using a multifunctional fluorescence microscope (Z-X700, manufactured by KEYENCE), obtaining red fluorescence images of Cy3 and blue fluorescence images of DAPI at thicknesses of 0.1–0.4 μm. Multiple fields of view images were obtained to obtain the injection distribution within the injection area. The results are presented below. Figure 17-1 It should be noted that the concentric circles marked with "1mm" or "2mm" and drawn with dashed lines are concentric circles centered on the injection port. The white arrow indicates the injection port.

[0243] The proportion of cells directly injected with DNA was calculated using the mixed cell counting function as described below. That is, for each analyzed region ( Figure 17-1 Within each region (enclosed by white dashed lines), cells with an area of ​​purple fluorescence (formed by the overlap of blue and red fluorescence) covering more than 50% of the cell's area are defined as cells directly injected with DNA, and their number is counted (referred to as cell number A). Conversely, the total number of cells within each analytical region is counted using the number of cell nuclei as an indicator (referred to as cell number B). Figure 17-1 The values ​​recorded in each analytical region represent the ratio of cell number A to cell number B. It should be noted that epidermis and hair follicles where Cy3 red fluorescence was substantially not observed were excluded from the analysis.

[0244] in addition, Figure 17-4 These are images of the area near the injection port, used to evaluate the extent of tissue damage caused by the injected DNA solution. The damaged area is the portion enclosed by a white line in each image.

[0245] [Example 2-2]

[0246] Except for the use of 55 mg of ZPP, the procedure was the same as in Example 2-1. The results are shown below. Figure 17-2 Additionally, an image of the area near the injection port is shown. Figure 17-5 .

[0247] [Comparative Example 2-1]

[0248] The Biojector 2000 used in Comparative Examples 1-1 above was replaced with a solution containing 70 μL of Cy3-labeled plasmid V7905, and the procedure was performed according to the instruction manual, except that it was performed in the same manner as in Example 2-1. The results are shown below. Figure 17-3 Additionally, an image of the area near the injection port is shown. Figure 17-6 .

[0249] according to Figure 17-1 , Figure 17-2 , Figure 17-3 Compared with Comparative Example 2-1, in Examples 2-1 and 2-2, the proportion of DNA in the cell nuclei of cells that were directly injected from the injection port over a large area was significantly increased.

[0250] In addition, according to Figure 17-4 , Figure 17-5 , Figure 17-6 Compared to Comparative Example 2-1, the damage to the tissue near the injection site was significantly reduced in Examples 2-1 and 2-2. Specifically, the area of ​​the damaged portion in Example 2-1 was 1.3 × 10⁻⁶. 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 is 2.7 × 10 4 μm 2 .

Claims

1. An injector that injects a solution containing biomolecules from an injector body into an injection target using a needle-free injector. The injector has the following features: A container for holding a solution containing biomolecules, and It has a nozzle portion that allows the pressurized solution containing biomolecules to flow through and be ejected towards the injection target. When fitting the relationship between the displacement x of the tip of the solution containing biomolecules within the injected object and the velocity u(x) of the tip of the solution using the least squares method with a fitting function expressed by equation (1) below, the damping coefficient k is 1.59 or higher. u(x)=u0exp(-kx)+u e ···(1) In equation (1), u0 represents the velocity coefficient (m / s), k represents the damping coefficient (1 / mm), and u e The asymptotic velocity (m / s) is represented by the displacement x in mm and the velocity u(x) in m / s.

2. The injector according to claim 1, wherein, asymptotic velocity u e It is above 0.01 (m / s).

3. An injector that injects a solution containing biomolecules from an injector body into an injection target using a needle-free injector. The injector has the following features: A container for holding a solution containing biomolecules, and It has a nozzle portion that allows the pressurized solution containing biomolecules to flow through and be ejected towards the injection target. When fitting the relationship between the displacement x of the tip of the biomolecule-containing solution within the injected object and the velocity u(x) of the tip of the solution using a fitting function expressed by equation (1) and employing the least squares method, the asymptotic velocity u e Above 0.01 u(x)=u0exp(-kx)+u e ···(1) In equation (1), u0 represents the velocity coefficient (m / s), k represents the damping coefficient (1 / mm), and u e The asymptotic velocity (m / s) is represented by the displacement x in mm and the velocity u(x) in m / s.

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