Gene gun

Abstract

An accelerator module is connected to an initiator module and generates supersonic waves from subsonic waves generated by the initiator module. The supersonic waves deliver particles to cells in tissues. The accelerator module may include a knocking-detonation transition metal and a detonation material. An example of the knocking-detonation transition metal is copper (I) 5-nitrotetrazolate. Another example of the knocking-detonation transition metal is lead azide. An example of the detonation material is pentaerythritol tetranitrate (PETN).

Description

Technical Field

[0001] The present disclosure relates to devices and methods for gene therapy. More specifically, the present disclosure relates to devices and methods related to a particle delivery system of a biolistic method for delivering exogenous DNA (transgene) into cells.

Background Art

[0002] A gene gun accelerates small doped metal particles to the highest possible speed. The particles pass through tissue on the way to the target cells. The particles have such high speeds and densities and are very small that they penetrate the tissue without permanently damaging it. The damage caused by the particles is easily repaired by the tissue because the size of the penetration path is small. When the target cells are reached, the doping (consisting of DNA) is inserted into the nucleus of the cell.

[0003] Also, Patent Document 1 discloses a gene gun that accelerates a solution containing a biological material using a gas to deliver the biological material into cells without using metal particles.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] Currently, the practical limit for accelerating particles is the speed of sound in the gaseous medium used. Existing state-of-the-art technologies accelerate particles in a helium atmosphere to increase the speed of sound and thus raise the practical limit of particle velocity. This limits the effectiveness of existing gene guns by restricting the penetration depth of the particles (the particle penetration depth is a function of particle velocity). The only other gas with a higher speed of sound is hydrogen, but this raises concerns about flammability.

Means for Solving the Problem

[0006] In certain medical applications, it may be advantageous to utilize a biolistic particle delivery system. In certain embodiments, the gene gun relies on a detonation phenomenon to achieve a doped metal particle velocity that is faster than the speed of sound in any gas (gaseous medium). In certain embodiments, the gene gun generates a blast wave that passes through a wall or wall segment without destroying the wall. The blast wave passes through the wall at the speed of sound of the wall material. For example, in certain embodiments, the wall is made of stainless steel. In the case of stainless steel, the speed of sound is 5,790 m / s. On the opposite side of the wall are the doped metal particles. The doped metal particles are released at the initial velocity of the blast wave in the above example, i.e., 5,790 m / s. This is well above the speed of sound in helium, which is 1,007 m / s.

[0007] One aspect is an accelerator module that is coupled to an initiator module and configured to generate a supersonic wave from a subsonic wave generated by the initiator module. The supersonic wave is configured to deliver particles to cells within tissue. The accelerator module includes a body that defines a receptacle having a propagation axis and a bottom surface. The receptacle includes a first portion and a second portion disposed between the first portion and the bottom surface. The accelerator module further includes a first material disposed in the first portion, a second material disposed in the second portion, a wall segment at least partially defined between the bottom surface of the receptacle and the outer surface of the body, and a plurality of doped metal particles that contact the outer surface of the body and are substantially aligned with the bottom surface along the propagation axis. The first material and the second material are configured to be triggered by the subsonic wave generated by the initiator module to generate a supersonic wave. The supersonic wave is configured to pass through the wall segment and then accelerate the plurality of doped metal particles to a certain velocity.

[0008] In certain embodiments, the velocity is supersonic.

[0009] In certain embodiments, the velocity is sufficient to penetrate the cells within the tissue.

[0010] In certain embodiments, the first material is a deflagration-to-detonation material (DDT).

[0011] In certain embodiments, the deflagration-to-detonation material comprises dry explosive.

[0012] In certain embodiments, the deflagration-to-detonation material comprises lead azide.

[0013] Certain embodiments include the deflagration-detonation transition material comprising copper(I) 5-nitrotetrazolate (DBX-1).

[0014] Certain embodiments include the second material being a detonating output material.

[0015] Certain embodiments include the detonating output material being dry gunpowder (dry explosive).

[0016] Certain embodiments include the detonating output material comprising pentaerythritol tetranitrate (PETN).

[0017] Certain embodiments include the wall segment comprising stainless steel.

[0018] Certain embodiments include the body comprising wall segments.

[0019] Certain embodiments include the material of the wall segment being selected such that the wall segment does not rupture when a supersonic wave passes therethrough.

[0020] Certain embodiments include the thickness of the wall segment being selected such that the wall segment does not rupture when a supersonic wave passes therethrough.

[0021] Certain embodiments include the body comprising a base and a cap. The cap is configured to be fixed to the base that forms at least a part of the container therebetween.

[0022] In certain embodiments, the container is further configured to receive at least a portion of the initiator module with the cap not fixed to the base. The container is configured to fix the initiator module to the body when the cap is fixed to the base.

[0023] Certain embodiments include the body having an opening to the container. The opening is sized and shaped such that a portion of the initiator module passes through the opening when the initiator module is coupled to the accelerator module.

[0024] Certain embodiments include a portion of the initiator module being at least one electrical pin.

[0025] Certain embodiments include the body having an injection cylinder (discharge tube) disposed on the opposite side of the wall segment as viewed from the container. The injection cylinder is aligned with the propagation axis. The plurality of doped metal particles are disposed within the injection cylinder.

[0026] Certain embodiments include the injection cylinder being a straight cylinder and having a cross-section size similar to that of the container.

[0027] Certain embodiments include the accelerator module being a component of a gene gun.

[0028] Certain embodiments include the first portion and the second portion being aligned along the propagation axis.

[0029] Certain embodiments include the bottom surface being perpendicular to the propagation axis.

[0030] Certain embodiments further include an adhesive disposed on at least a portion of the outer surface of the body. The plurality of doped metal particles are suspended in the adhesive.

[0031] Certain embodiments further include a screen fixed to the body at a position covering the plurality of doped metal particles, and an adhesive disposed on the screen to suppress the plurality of doped metal particles from passing through the screen in the absence of supersonic waves.

[0032] Certain embodiments further include a seal. The container is further configured to receive at least a portion of the initiator module. The seal is disposed in the container to form a seal with the initiator module.

[0033] Certain embodiments include that the particles of the plurality of doped metal particles have a diameter of about 1 micron.

[0034] Certain embodiments include that the plurality of doped metal particles comprise gold.

[0035] Certain embodiments include that the plurality of doped metal particles comprise tungsten.

[0036] Certain embodiments include that the plurality of doped metal particles comprise a chemical substance.

[0037] Certain embodiments include that the chemical substance is DNA.

[0038] Certain embodiments include that the initiator module is an electro explosive device (EED).

[0039] Certain embodiments include that the electro explosive device (EED) comprises an electrical input portion and an explosive output portion.

[0040] Certain embodiments include the explosive output portion being a mixture of zirconium and potassium perchlorate.

[0041] Certain embodiments include the electro-explosive device (EED) including a casing, with the explosive output portion disposed within the casing.

[0042] Certain embodiments include the casing being metallic.

[0043] One embodiment is an accelerator module that defines a body having a propagation axis and a container having a bottom surface. The propagation axis passes through the bottom surface. The accelerator module further includes a material disposed within the container and configured to at least partially generate a detonation wave traveling at supersonic speed, and a wall segment at least partially defined between the bottom surface of the container and the outer surface of the body, the wall segment having a size that allows the detonation wave to pass therethrough without rupturing the wall segment, and a plurality of doped metal particles disposed on the opposite side of the wall segment as viewed from the container and substantially aligned with the propagation axis.

[0044] One embodiment is a method for delivering a plurality of doped metal particles to cells within a tissue using a portable device. The method includes igniting an explosive charge disposed within the portable device to generate a subsonic wave, propagating the subsonic wave along an axis towards a material disposed within the portable device, igniting the material with the subsonic wave to generate a supersonic wave, continuing to propagate the supersonic wave along the axis towards a wall segment of the portable device, propagating the supersonic wave through the wall segment without rupturing the wall segment, and colliding the supersonic wave with the plurality of doped metal particles after passing through the wall segment to accelerate the plurality of doped metal particles to a certain velocity.

[0045] Another aspect is a gene gun having a propagation axis extending between at least a propellant charge (gunpowder) and a plurality of doped metal particles. This gene gun includes a deflagration-to-detonation material (DDT) disposed substantially along the propagation axis, a detonating output material disposed on the opposite side of the deflagration-to-detonation material as viewed from the propellant charge and disposed substantially along the propagation axis, and a wall segment separating the detonating output material from the plurality of doped metal particles.

Advantages of the Invention

[0046] According to the technology related to the present disclosure, in an apparatus and method for delivering a plurality of doped metal particles to cells, a technology capable of increasing the speed of the metal particles delivered to the cells more than before can be provided.

Brief Description of the Drawings

[0047]

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Best Mode for Carrying Out the Invention

[0048] Embodiments according to the present disclosure will be described below with reference to the drawings. Note that each configuration and combinations thereof in each embodiment are examples, and within the scope not departing from the gist of the present invention, addition, omission, substitution, and other changes of the configuration can be made as appropriate. The present disclosure is not limited by the embodiments, but is limited only by the claims.

[0049] Examples of the particle delivery target to which the doped metal particles in the present disclosure are delivered (introduced) include tissues, and preferably cells within the tissue. Further, when the particle delivery target is a cell within the tissue, the particle delivery target may be a nucleus within the cell or an organelle within the cell.

[0050] Examples of the tissue include animal tissues and plant tissues. Examples of the animal include vertebrates, specifically mammals, birds, reptiles, amphibians, fish, etc. Examples of the plant include seed plants and spore plants. Examples of the seed plants include angiosperms and gymnosperms, and examples of the spore plants include fern plants, moss plants, algae, etc. When the tissue as the particle delivery target is an animal tissue, in addition to epithelial tissue, connective tissue, muscle tissue, nerve tissue, etc., for example, organs, viscera, epidermis (stratum corneum, dermis), dermis, subcutaneous tissue, muscle, etc. can be included. When the tissue as the particle delivery target is a plant tissue, meristematic tissue (such as apical meristem, cambium, etc.) and permanent tissue (such as epidermal tissue, conducting tissue, mechanical tissue, parenchyma tissue, etc.) can be included. In addition, for example, roots, stems, leaves, etc. can be included.

[0051] The particle delivery target may be any of in vitro systems, in vivo systems, and ex vivo systems. That is, the particle delivery target may be in a state of existing within an individual (living body), or may be in a state of being removed or separated from the individual (living body). The latter is, in other words, a state where the particle delivery target does not exist within the individual (living body). As a specific example, when the particle delivery target is a cell (preferably a cell within a tissue), the cell (preferably a cell within a tissue) may be in a form excluding the cells (preferably cells within a tissue) in a state of existing within the individual (living body). The individual (living body) may be an animal individual (living body) or a plant individual (living body), and the forms of animals and plants are as described above. When the individual (living body) is an animal individual (living body), it is preferably a vertebrate individual (living body), and more preferably a mammalian individual (living body). The mammals are not particularly limited, and examples include humans and mammals other than humans. Examples of humans include healthy individuals and those suffering from diseases or the like (patients). Examples of mammals other than humans include mice, rats, guinea pigs, hamsters, cows, goats, sheep, pigs, monkeys, dogs, cats, and the like.

[0052] Furthermore, the accelerator module according to the present disclosure includes a container having a propagation axis, a material disposed within the container that is ignited by a subsonic wave generated by an initiator module to generate a supersonic wave, and a wall segment that passes through the propagation axis and separates the interior and exterior of the container. A plurality of doped metal particles can be arranged along the propagation axis on the outer surface of the wall segment. After the supersonic wave generated by the material that generates the supersonic wave propagates through the wall segment and collides with the plurality of doped metal particles, the plurality of doped metal particles are accelerated. The initiator module has, for example, an explosive charge (gunpowder), and operates by receiving supply of operating power, so that the explosive charge is ignited and burned to generate deflagration, which is a subsonic wave. The deflagration, which is a subsonic wave generated by the initiator module, propagates along the propagation axis toward the material that generates the supersonic wave and is contained within the container, and the material is ignited by the deflagration, which is a subsonic wave. When the material that generates the supersonic wave is ignited, a detonation (explosion) wave, which is a supersonic wave, is generated, and the detonation wave, which is a supersonic wave, travels along the propagation axis toward the wall segment. The detonation wave (supersonic wave) that reaches the wall segment propagates (passes through) the interior of the solid wall segment and reaches the outer surface of the wall segment, and collides with the plurality of doped metal particles disposed on the outer surface. As a result, the metal particles are imparted with acceleration energy from the detonation wave (supersonic wave), the metal particles are ejected at high speed, and are delivered to the particle delivery target.

[0053] The explosive charge of the initiator module may be, for example, zirconium or potassium perchlorate, or a mixture thereof. Of course, the explosive charge is not limited to these, and various explosives that can generate deflagration, which is a subsonic wave, by ignition and combustion can be used. For example, the explosive charge according to the present disclosure can be preferably applied to the explosive charge used in an initiator for inflating an airbag for an automobile.

[0054] Also, the material that generates a supersonic wave by being ignited by a subsonic wave is not particularly limited, but various dry explosives can be preferably employed. The material that generates a supersonic wave by being ignited by a subsonic wave can be regarded as a material for transitioning deflagration to detonation. The material that generates a supersonic wave by being ignited by a subsonic wave can preferably contain, for example, lead azide, copper(I) 5-nitrotetrazolate (DBX-1), pentaerythritol tetranitrate (PETN), etc., but of course, it is not limited to these and various explosives can be adopted. Further, the container of the accelerator module can contain a plurality of types of the above-mentioned materials that generate a supersonic wave. For example, the material that generates a supersonic wave by being ignited by a subsonic wave can contain a first material and a second material, and they may be arranged so as to be aligned along the propagation axis in the container. The first material and the second material may be different types of explosive materials or the same type of explosive materials.

[0055] The wall segment of the accelerator module solidly propagates the detonation wave as a supersonic wave generated in the container. Here, the speed of sound is the speed of sound propagating in a substance (medium), which varies depending on the medium, and the speed of sound can be significantly increased when the medium is a solid compared to when the medium is a gas. For example, the speed of sound in stainless steel can reach several times the speed of sound in helium gas. Of course, the material used for the wall segment is not limited to stainless steel. The wall segment may be formed of, for example, aluminum or other metals, or may be formed of a material other than metal. The wall segment thus formed can further accelerate, for example, the detonation wave as a supersonic wave entering along the propagation axis by solid propagation. Then, by colliding the supersonic wave (detonation wave) reaching the outer surface of the wall segment with metal particles, for example, the metal particles can be ejected at supersonic speed. In this way, the accelerator module according to the present disclosure and the gene gun equipped with the same provide a more practical accelerator module or gene gun by increasing the ejection speed of metal particles compared to the prior art.

[0056] FIG. 1 is a perspective view of an embodiment of a gene gun 10 including a handle 11 and an accelerator module or cartridge 12 according to a preferred embodiment of the present invention. The accelerator module 12 is assembled to the handle 11 and can be replaced after use. Certain embodiments of the gene gun 10 can be used in a laboratory or medical facility for transplanting DNA into cell nuclei. The cell nuclei can be of a plant or an animal. For example, the cell nuclei can be of a patient (human).

[0057] In certain embodiments, the accelerator module 12 includes a body 14 and an initiator 30. In certain embodiments, the initiator 30 is assembled to the body 14. For example, in certain embodiments, the body 14 defines a container (most clearly shown in FIG. 8) sized and shaped to receive at least a portion of the initiator 30. In certain embodiments, the body 14 and the initiator 30 are separately assembled to a frame. The frame is configured to fix the position of the body 14 relative to the position of the initiator 30.

[0058] In certain embodiments, at least a portion of the body 14 includes a material selected at least in part based on material strength. In certain embodiments, the material is selected such that the body 14 can contain the forces caused by an explosion occurring within the body 14. In this way, the material exhibits sufficient strength to contain the explosive force within the body 14. In certain embodiments, at least a portion of the body 14 includes metal. Of course, the body 14 need not include metal and instead can include a material other than metal, or a combination of materials other than metal. For example, in certain embodiments, the body 14 includes a plurality of materials.

[0059] FIG. 2 is a perspective view of the distal end of the body 14 of the accelerator module 12 of FIG. 1 showing an injection barrel (discharge tube) 58 containing a plurality of particles 60. In certain embodiments, the plurality of particles 60 are doped metal particles. In certain embodiments, the plurality of particles 60 are free to move into the tissue without being hindered.

[0060] In certain embodiments, the body 14 comprises a wall segment 44 (most clearly shown in FIG. 8). In certain embodiments, the wall segment 44 is part of the body 14 and separates the container 20 from the plurality of particles 60. In certain embodiments, the gene gun 10 generates a detonation wave (explosion wave) that travels through the wall segment 44 of the accelerator module 12 without rupturing the wall segment 44.

[0061] In certain embodiments, the wall segment 44 does not rupture when the explosion wave passes through it, thus maintaining a barrier between the detonation (explosion) material and the tissue. In certain embodiments, the wall segment 44 of the body 14 ruptures when the plurality of particles 60 are ejected (released) from the ejection cylinder 58, but, for example, due to the size and shape of the rupture, sufficiently attenuates the pressure loss from the gene gun 10. As a result, the plurality of particles 60 still have an initial velocity greater than the speed of sound before entering the tissue.

[0062] The detonation wave (explosion wave) travels through the wall segment 44 at the speed of sound in the wall material before exiting (emitting from) the wall segment 44. The exiting detonation wave (explosion wave) collides with the plurality of particles 60 and accelerates the plurality of particles 60 to an initial velocity approximately the same as the velocity of the detonation wave (explosion wave) when the detonation wave (explosion wave) passes through the wall segment 44. In contrast to passing through a gas, when the detonation wave (explosion wave) passes through the wall segment 44, the velocity of the detonation wave (explosion wave) increases to a value greater than the speed of sound when passing through a gas.

[0063] In certain embodiments, at least a portion of the body 14 in the accelerator module 12 comprises a material having a high speed of sound (a material with a high speed of sound). In certain embodiments, the higher the speed of sound when passing through the material, the greater the initial velocity of the plurality of particles 60 ejected from the ejection cylinder 58.

[0064] In certain embodiments, the wall segment 44 has a thickness of 1 mm. In certain embodiments, the wall segment 44 has a thickness of 0.5 mm. In certain embodiments, the wall segment 44 has a thickness of 2 mm. In certain embodiments, the wall segment 44 has a varying or non-uniform wall thickness. The present disclosure is not limited to the recited values and includes any other values for the thickness. In certain embodiments, the material of the wall segment 44 is selected based at least in part on the speed of sound through the wall segment 44. In certain embodiments, the material of the wall segment 44 is selected such that the body 14 can accelerate the plurality of particles 60 to an initial velocity sufficient to penetrate (permeate) the tissue to a desired depth with the plurality of particles 60. In this way, the material of the wall segment 44 exhibits a speed of sound sufficient for the plurality of particles 60 to reach a desired depth within the tissue. In certain embodiments, the first portion of the body 14 includes a material having sufficient strength to contain the explosive force. On the other hand, the second portion of the body 14 also includes a material having a speed of sound sufficient to accelerate the plurality of particles 60 to a speed of sound sufficient for the plurality of particles 60 to reach a desired depth within the tissue.

[0065] FIG. 3 is a perspective view of the proximal end of the accelerator module 12 shown in FIG. 1, showing at least one pin 38 (electrical input portion) of the initiator 30 for electrically coupling the accelerator module 12 to the handle 11. In certain embodiments, the accelerator module 12 is incorporated into the gene gun 10 by any desired means. As described below, in certain embodiments, an electrical firing mechanism such as the initiator 30 is used to provide a firing pulse at a desired time.

[0066] FIG. 4 is a side view of the accelerator module 12 shown in FIG. 2. In the illustrated embodiment, the body 14 of the accelerator module 12 includes a base 16 and a cap 18. In other embodiments, the body 14 is manufactured as a single monolithic structure. In other embodiments, the body 14 of the accelerator module 12 is assembled from three or more structures.

[0067] In certain embodiments, the base 16 and the cap 18 comprise complementary engagement structures 22. The engagement structures 22 are configured to integrally fix the base 16 and the cap 18. In certain embodiments, the engagement structures 22 include one or more of welding, adhesives, fasteners, mechanical locks, screws, or any other structure capable of fixing the base 16 to the cap 18. In other embodiments, a frame is used to fix the base 16 to the cap 18 without directly fixing the base 16 and the cap 18 to each other.

[0068] FIG. 5 is a plan view of the distal end of the accelerator module 12 shown in FIG. 2, showing a plurality of particles 60 disposed relative to the outer surface 56 (most clearly shown in FIG. 8) of the body 14. In certain embodiments, the outer surface 56 is part of a concave shape in the body 14. In certain embodiments, the concave shape has the form of an injection cylinder (discharge tube) 58. In certain embodiments, the plurality of particles 60 are supported by at least the outer surface 56 of the injection cylinder 58. In certain embodiments, at least a portion of the bore forming the cylindrical (tubular) wall of the injection cylinder 58 supports the plurality of particles 60.

[0069] In certain embodiments, the outer surface 56 is not part of a concave shape, but instead is part of a convex shape on which the plurality of particles 60 are disposed. In certain embodiments, the outer surface 56 on which the plurality of particles 60 are disposed has a planar shape.

[0070] In certain embodiments, the plurality of particles 60 are attached to at least the outer surface 56. In certain embodiments, the plurality of particles 60 are disposed on the outer surface 56. In certain embodiments, the plurality of particles 60 are deposited (laminated) on the outer surface 56. In certain embodiments, the plurality of particles 60 are randomly disposed on the outer surface 56.

[0071] In certain embodiments, the plurality of particles 60 are metal particles. In certain embodiments, the plurality of particles 60 include small metal particles. In certain embodiments, each particle in the plurality of particles 60 is on the order of 1 micron in size. In certain embodiments, each particle in the plurality of particles 60 is on the order of 2 microns in size. Of course, the size of the particles in the plurality of particles 60 is not limited to this, and other sizes may be used.

[0072] In certain embodiments, the particles of the plurality of particles 60 are spherical. In other embodiments, the particles of the plurality of particles 60 have a conical shape. In other embodiments, the particles of the plurality of particles 60 have a cylindrical shape. In other embodiments, the particles of the plurality of particles 60 have a cubic shape. In other embodiments, the particles of the plurality of particles 60 have a mixture of two or more shapes.

[0073] In certain embodiments, the particles of the plurality of particles 60 are homogeneous. In certain embodiments, at least some of the plurality of particles 60 have a different size and shape from some of the other particles.

[0074] In certain embodiments, the plurality of particles 60 are made of a high-density material. For example, in certain embodiments, the high-density material is gold, tungsten, or other known high-density materials. In certain embodiments, it may be desirable for the plurality of particles 60 to include a high density that increases the kinetic energy of the plurality of particles 60 more than particles of lower density when accelerated at the same speed.

[0075] In certain embodiments, a plurality of particles 60 are doped. In certain embodiments, a chemical substance is attached to the particles. In certain embodiments, the plurality of particles 60 are coated with a chemical substance. In certain embodiments, the chemical substance includes DNA. In certain embodiments, the DNA is plasmid DNA. In certain embodiments, the DNA is a circular double-stranded DNA molecule. In certain embodiments, the plurality of doped particles 60 are particles coated with DNA and smaller in size than cells. In certain embodiments, the DNA is chromosomal DNA.

[0076] In certain embodiments, the injection barrel 58 can output a plurality of particles 60 in a predetermined direction. For example, the injection barrel 58 can output a plurality of particles 60 along the axis 28. In certain embodiments, the axis 28 is the propagation axis. In some embodiments, the injection barrel 58 can direct a plurality of particles 60 to a predetermined position on the tissue.

[0077] In certain embodiments, the injection barrel 58 has a constant inner diameter. In certain embodiments, the injection barrel 58 has an inner diameter that converges in the injection direction (ejection direction). In certain embodiments, the injection barrel 58 has an inner diameter that diverges in the injection direction. In certain embodiments, the injection barrel 58 has an inner diameter that converges in the injection direction and then diverges in the injection direction.

[0078] In certain embodiments, the injection barrel 58 can have one or more deflection plates (vanes) formed on the inner wall of the bore of the injection barrel 58. In certain embodiments, the one or more deflection plates are sized and shaped to straighten the plurality of particles 60 ejected from the gene gun 10. The vanes can reduce the turbulent flow in the plurality of particles 60 when the plurality of particles 60 are ejected from the injection barrel 58.

[0079] In certain embodiments, the gene gun 10 injects a plurality of doped particles 60 into tissues, cells, and / or organelles. In certain embodiments, the injection of the plurality of doped particles 60 is performed in vitro (outside the body). In certain other embodiments, the injection of the plurality of doped particles 60 is performed in vivo (inside the body). In certain embodiments, the gene gun 10 injects a plurality of doped particles 60 into the cell nucleus.

[0080] When the plurality of particles 60 are injected, preferably the plurality of particles 60 penetrate the tissue. In certain embodiments, the plurality of particles 60 ejected by the gene gun 10 penetrate the tissue to a desired depth within the tissue. In certain embodiments, the desired depth is predefined. In certain embodiments, the desired depth is determined at least in part based on the composition of the plurality of particles 60. For example, the desired depth may vary for each different accelerator module 12.

[0081] FIG. 6 is a plan view of the proximal end of the accelerator module 12 shown in FIG. 2, showing at least one pin 38 of the initiator 30 configured to connect to the connector 40 of the handle 11. In certain embodiments, the at least one pin 38 includes two conductive pins. In certain embodiments, the two conductive pins are gold-plated. In certain embodiments, at least one pin 38 of the initiator 30 is electrically connected to the connector 40.

[0082] In certain embodiments, the initiator 30 is fired by an electrical input. In certain embodiments, the at least one pin 38 receives an electrical input in the form of an electrical firing pulse. In certain embodiments, the gene gun 10 includes one or more electronic components for operating the initiator 30. In certain embodiments, the one or more electronic components are supported by the gene gun 10.

[0083] In certain embodiments, the one or more electronic components are configured to generate a current to operate the initiator 30. In certain embodiments, the one or more electronic components include a controller. In certain embodiments, the gene gun 10 comprises an interface for activating the one or more electronic components for a user to operate the initiator 30. In certain embodiments, the interface is a pull trigger.

[0084] In certain embodiments, the gene gun 10 includes an energy source for the one or more electronic components. In certain embodiments, the energy source is supported by the handle 11. In certain embodiments, the energy source may be a battery. In certain embodiments, the battery supplies power to the one or more electronic components to ignite the initiator 30.

[0085] In certain embodiments, a battery or other electrical energy source provides an electrical ignition pulse to the initiator 30 via the connector 40. In certain embodiments, the magnitude and duration of the electrical ignition pulse applied to the initiator 30 are 1.2 amperes and 2 ms. In certain embodiments, the magnitude and duration of the electrical ignition pulse applied to the initiator 30 are 1.75 amperes and 0.5 ms. The present disclosure is not limited to the recited values and includes any other values for the magnitude and duration. In certain embodiments, the magnitude and duration of the electrical ignition pulse applied to the initiator 30 are selected based at least in part on the operating characteristics of the initiator 30.

[0086] Figure 7 is an exploded perspective view of the accelerator module 12 shown in Figure 2, and shows, for example, the initiator 30 separated from the container 20. In certain embodiments, the initiator 30 can be any electrical initiator device (EED). In certain embodiments, the initiator 30 includes an explosive charge 34 (explosive output section). The explosive charge 34 is configured to generate a flame when ignited. In certain embodiments, the initiator 30 includes a casing 32. In certain embodiments, the casing 32 includes the explosive charge 34. In certain embodiments, the initiator 30 is an automotive initiator. Examples of automotive initiators include initiators used in automotive airbags.

[0087] In certain embodiments, the container 20 is formed by a base 16 and a cap 18. In certain embodiments, the base 16 includes at least a portion of the container 20. In certain embodiments, the cap 18 includes at least a portion of the container 20. In certain embodiments, at least a portion of the initiator 30 is disposed within the container 20. In certain embodiments, the base 16 and the cap 18 are integrally fixed to form the container. In certain embodiments, after the initiator 30 is disposed within the container 20, the base 16 and the cap 18 are integrally fixed.

[0088] In certain embodiments, the container 20 is sized and shaped relative to the size and shape of the initiator 30 to prevent movement of the initiator 30 relative to the container 20 when the cap 18 is fixed to the base 16. In this way, the initiator 30 can be locked (fixed) within the container 20 when at least the base 16 and the cap 18 are integrally fixed.

[0089] FIG. 8 is a cross-sectional view through the accelerator module 12 shown in FIG. 4 as viewed along the cutting plane 8-8 of FIG. 4, showing both the initiator 30 and the chambers 45 aligned (lined up) along the axis 28 and the injection barrel 58. In certain embodiments, the chamber 45 is part of the container 20 and is disposed between the initiator 30 and the bottom surface 54 of the container 20. The wall segment 44 separates the chamber 45 from the injection barrel 58.

[0090] In certain embodiments, the connector 40 is structurally fixed to the body 14. In certain embodiments, the body 14 includes a lip 42 configured to capture a portion of the connector 40 and structurally fix the connector 40 to the body 14. In certain embodiments, the user can separate or remove the connector 40 from the body 14. For example, after use of the accelerator module 12, the connector 40 can be removed from the body 14, and the used accelerator module 12 can be removed and replaced with a new accelerator module 12.

[0091] In certain embodiments, the container 20 includes an opening 26. In certain embodiments, the opening 26 is disposed in the base 16. In certain embodiments, the opening 26 is disposed between the surface of the initiator 30 and the surface of the base 16. In certain embodiments, at least a portion of the initiator 30 passes through the opening 26 in the base 16 before the cap 18 is fixed to the base 16 to form the complete container 20.

[0092] In certain embodiments, initiator 30 includes a resistive element 36. In certain embodiments, resistive element 36 is disposed relative to casing 32. In certain embodiments, the electrical ignition pulse applied to initiator 30 heats the resistive element 36 within initiator 30. In some embodiments, resistive element 36 is heated sufficiently by the electrical ignition pulse to ignite the pyrotechnic charge (propellant) 34 within casing 32. In certain embodiments, pyrotechnic charge 34 is a mixture of zirconium and potassium perchlorate. In certain embodiments, pyrotechnic charge 34 is a single material or a mixture with other materials.

[0093] In certain embodiments, casing 32 is made of metal. In certain embodiments, the metal is stainless steel. Of course, casing 32 can be made of any other metal in addition to stainless steel. In certain embodiments, the metal is aluminum. In certain embodiments, casing 32 is made from a polymer. In certain embodiments, the material and thickness of casing 32 are selected such that the material ruptures in response to the pyrotechnic charge 34 being ignited. The rupture of casing 32 allows the flame to escape from casing 32 and travel or propagate subsonically along axis 28 towards chamber 45.

[0094] In certain embodiments, the flame escaping from casing 32 ignites the material within chamber 45. When pyrotechnic charge 34 is ignited, the pressure released by pyrotechnic charge 34 within casing 32 ruptures casing 32, and deflagration propagates subsonically along axis 28 to ignite the material within chamber 45.

[0095] In certain embodiments, the accelerator module 12 includes a seal 24. In certain embodiments, the seal 24 is a gasket, an O-ring, or other suitable structure. In certain embodiments, the seal 24 is disposed between one or more surfaces of the body 14 and one or more surfaces of the initiator 30. In certain embodiments, the seal 24 is disposed within the opening 26. In certain embodiments, the seal 24 inhibits flames escaping from the casing 32 from leaking through the opening 26 towards the connector 40 when the initiator 30 is ignited. In certain embodiments, the seal 24 inhibits materials that have exploded within the chamber 45 from leaking through the opening 26 towards the connector 40 when the seal 24 is ignited by flames that have escaped from the casing 32 through rupture.

[0096] In certain embodiments, the material within the chamber 45 is selected to generate a detonating wave when the material is ignited by a flame caused by the ignition of the pyrotechnic charge 34. In certain embodiments, the detonating wave travels at a speed greater than the speed of sound.

[0097] In certain embodiments, to achieve a desired detonating wave from the chamber 45, the overall speed of the pyrotechnic reaction, which is initially a subsonic deflagration caused by the ignition of the pyrotechnic charge 34, is increased by the explosion of the material within the chamber 45 to be greater than the speed of sound. In certain embodiments, one or more materials are disposed within the chamber 45 to generate a desired detonating wave.

[0098] For example, in certain embodiments, the material includes a deflagration to detonation transition (DDT) material and a detonating output material. In certain embodiments, each of the materials is disposed in at least a portion of the chamber 45. In certain embodiments, the material is one or more of lead azide, copper(I) 5-nitrotetrazolate (DBX-1), and pentaerythritol tetranitrate (PETN). Of course, the present disclosure is not limited to the listed materials or combinations of materials, and other materials or combinations of materials that produce a desired detonation (explosion) wave can be used.

[0099] In certain embodiments, the material includes at least a first material 48 and a second material 52. The first material 48 and the second material 52 may be disposed in a first portion 46 and a second portion 50 of the chamber 45, respectively. In certain embodiments, the first material 48 is separated from the second material 52 within the chamber 45. In certain embodiments, the first material 48 contacts the second material 52 at an interface. In certain embodiments, the first material 48 is separated from the second material 52 by a barrier. In certain embodiments, the barrier is a temporary barrier between the first material 48 and the second material 52. For example, when the first material 48 is ignited, the barrier ruptures. In certain embodiments, the first material 48 is disposed around the outer periphery of the second material 52. In certain embodiments, the first material 48 and the second material 52 form a mixture within the chamber 45.

[0100] In certain embodiments, the interface between the first material 48 and the second material 52 is disposed perpendicular to the axis 28. In certain embodiments, the position of the interface facilitates the propagation of a detonation (explosion) wave along the axis 28 towards the wall segment 44. In certain embodiments, the interface is not disposed perpendicular to the axis 28. In certain embodiments, the size of the contact area between the first material 48 and the second material 52 is selected to facilitate the detonation of the second material 52 by the first material 48. In certain embodiments, the interface may be smooth. In certain embodiments, the interface may be bumpy.

[0101] In the illustrated embodiment, the first portion 46 is disposed closer to the initiator 30 than the second portion 50. In the illustrated embodiment, the second portion 50 is disposed between the first portion 46 and the wall segment 44.

[0102] In certain embodiments, the ratio of the first material 48 to the second material 52 is 50 / 50. Of course, other ratios are within the scope of the present disclosure. For example, in certain embodiments, the ratio of the first material 48 to the second material 52 is 40 / 60. For example, in certain embodiments, the ratio of the first material 48 to the second material 52 is 60 / 40.

[0103] In certain embodiments, the first material 48 is a deflagration-to-detonation transition (DDT) material. In certain embodiments, the first material 48 is a dry explosive. In certain embodiments, the first material 48 is a lead azide material. In certain embodiments, the first material 48 is a copper(I) 5-nitrotetrazolate (DBX-1) material.

[0104] In certain embodiments, the second material 52 is a detonating output material. In certain embodiments, the second material 52 is a dry explosive. In certain embodiments, the second material 52 is pentaerythritol tetranitrate (PETN). In certain embodiments, the detonation wave generated by PETN travels at a speed greater than the speed of sound. In certain embodiments, the detonation (explosion) wave generated by PETN generates a similar detonation (explosion) wave within the wall segment 44.

[0105] In certain embodiments, the detonation (explosion) wave continues through the wall segment 44 and imparts its velocity to a plurality of particles 60 disposed relative to the outer surface 56 in the body 14. The detonation (explosion) wave then ejects (releases) the plurality of particles 60 from the body 14 at an initial velocity that exceeds the speed of sound. In certain embodiments, the plurality of particles 60 are ejected at the same initial velocity as the velocity of the detonation (explosion) wave passing through the wall segment 44.

[0106] FIG. 9 is a cross-sectional view similar to FIG. 8 except that at least one pin 38 is connected to the connector 40 of the handle 11 and the distal end of the accelerator module 12 is disposed relative to the tissue. FIGS. 10A-C are partial cross-sectional views similar to FIG. 9 except that they show the steps in which the accelerator module 12 is fired such that a supersonic shock wave passes through the wall segment 44, accelerates the plurality of particles 60, and passes through the injection cylinder 58 and through the tissue.

[0107] FIG. 10A shows that the initiator 30 is actuated (fired) by an electrical input. In certain embodiments, at least one pin 38 receives an electrical input in the form of an electrical ignition pulse. The initiator 30 includes a pyrotechnic charge 34. The pyrotechnic charge 34 generates a flame upon ignition. When the pyrotechnic charge 34 is ignited, the pressure released by the pyrotechnic charge 34 within the casing 32 ruptures the casing 32 and allows deflagration to propagate subsonically along the axis 28 toward the first material 48 within the chamber 45. The deflagration caused by the pyrotechnic charge 34 generates a propagating subsonic flame. In this way, the subsonic flame moves toward the chamber 45.

[0108] Figure 10B shows a deflagration that ignites the first material 48 within the chamber 45. In certain embodiments, the first material 48 is a deflagration-detonation transition (DDT) material. When ignited, the first material 48 transitions from deflagration to detonation (explosion). While the first material 48 is ignited by a subsonic flame, the subsonic flame ultimately transitions to detonation (explosion). In this way, the subsonic flame entering the first material 48 exits the first material 48 as a supersonic flame. The flame front accelerates and becomes a supersonic flame propagating towards the second material 52. As the transition from flame (deflagration) to detonation (explosion) occurs, the pressure increases. The detonation (explosion) that causes a supersonic wave generates a powerful pressure wave that travels ahead of the propagating flame, raising the temperature of the first material above the autoignition temperature of the first material 48.

[0109] Figure 10C shows the detonation (explosion) of the second material 52 resulting from the detonation (explosion) of the first material 48. In certain embodiments, the detonation wave generated by the second material 52 travels at a speed greater than the speed of sound. The detonation wave generated by the second material 52 generates a similar detonation wave within the wall segment 44. The detonation wave continues through the wall segment 44 and imparts its velocity to a plurality of particles 60 disposed relative to the outer surface 56 of the body 14. The detonation wave then ejects (releases) the plurality of particles 60 from the body 14 at an initial velocity exceeding the speed of sound.

[0110] A method of manufacturing the accelerator module 12 will be described below. Of course, other methods including more or fewer steps and / or different orders of steps are also within the scope of the present disclosure.

[0111] In certain embodiments, a method for manufacturing the accelerator module 12 begins by providing a base 16. The base 16 includes a chamber 45 that is partially formed by a bottom surface 54. The bottom surface 54 is spaced from the outer surface 56 by a wall segment 45. The distal end of the injection cylinder 58 is configured to be disposed relative to tissue. In certain embodiments, the injection cylinder 58 is configured to support a plurality of particles 60.

[0112] A second material 52 is loaded into a second portion 50 of the chamber 45. In certain embodiments, the second material 52 is in contact with the bottom surface 54. In certain embodiments, the second material 52 is a detonating output material. In certain embodiments, the second material 52 is a dry explosive. In certain embodiments, the second material 52 is pentaerythritol tetranitrate (PETN). In certain embodiments, the second material 52 is pressed against the bottom surface 54 of the chamber 45 with a pressure necessary to achieve a desired degree of compression.

[0113] A first material 48 is loaded into a first portion 46 of the chamber 45, on top of the second material 52. In certain embodiments, the first material 48 is in contact with the second material 52. In certain embodiments, the first material 48 is a deflagration-to-detonation transition material. In certain embodiments, the first material 48 is a dry explosive. In certain embodiments, the first material 48 is lead azide. In certain embodiments, the first material 48 is copper(I) 5-nitrotetrazolate (DBX-1). In certain embodiments, the first material 48 is pressed against the second material 52 within the chamber 45 with a pressure necessary to achieve a desired degree of compression. Of course, the first material 48 and the second material 52 can be pushed into the chamber 45 simultaneously to achieve a desired degree of compression without being pressed separately.

[0114] Next, the initiator 30 is attached to the opening 26 of the base 16. In certain embodiments, at least a portion of the casing 32 is disposed within the chamber 45 in the container 20. In certain embodiments, the casing 32 is disposed in proximity to the first material 48.

[0115] In certain embodiments, the initiator 30 is attached to the opening 26 of the base 16 together with the sealant 24. In certain embodiments, the sealant 24 is a gasket or an O-ring. In certain embodiments, the initiator 30 is held in place by attaching the cap 18. In certain embodiments, the cap 18 comprises a thread complementary to the thread on the base 16.

[0116] The plurality of particles 60 are placed within the injection barrel 58. When the gene gun 10 is used with the injection barrel 58 facing upward, the plurality of particles 60 can be poured onto the exposed body 14 and held against the outer surface 56 of the body 14 by gravity. In certain embodiments, the plurality of particles 60 are poured onto the outer surface 56 of the body 14 within the injection barrel 58.

[0117] In certain embodiments, in order to use the gene gun 10 in any orientation, the plurality of particles 60 are held in a predetermined position relative to the outer surface 56 of the body 14. In this way, the detonation (explosion) wave exiting the wall segment 45 will be transmitted to the plurality of particles 60.

[0118] FIG. 11 shows another embodiment of the injection barrel 58 including an adhesive 62 for preventing the plurality of particles 60 from falling out of the injection barrel 58 before ignition of the accelerator module 12. The adhesive 62 holds the plurality of particles 60 in a predetermined position relative to the outer surface 56. In certain embodiments, when the gene gun 10 is operated, the adhesive 62 breaks away and / or evaporates leaving the plurality of particles 60 and can continue to travel at the speed of the detonation (explosion) wave. In certain embodiments, the adhesive 62 has a lower density than the plurality of particles 60 and disperses or decelerates rapidly. In this way, the adhesive 62 does not impede the movement of the plurality of particles 60.

[0119] Figure 12 is the same as Figure 11, except that the screen (cover) 64 is disposed across and fixed to the distal end of the injection barrel 58. In the illustrated embodiment, the adhesive 62 is held on the screen 64. In certain embodiments, the screen 64 has a plurality of pores. In certain embodiments, the plurality of pores are micropores. In certain embodiments, the screen 64 has a fine grid (mesh) that allows the plurality of particles 60 to pass through the pores of the screen 64 without being hindered.

[0120] Figure 13 is a drawing illustrating a method for propagating energy through the accelerator module 12. This method uses a portable device such as the gene gun 10 to deliver (introduce) a plurality of particles 60 into cells within a tissue. This method begins in step 1302 by igniting the pyrotechnic charge 34 disposed within the portable device to create a flame (deflagration) that travels as a subsonic wave. In certain embodiments, at least one pin 38 receives an electrical input in the form of an electrical ignition pulse. The pyrotechnic charge 34 generates a flame upon ignition. When the pyrotechnic charge 34 is ignited, the pressure released by the pyrotechnic charge 34 within the casing 32 ruptures the casing 32 and allows the deflagration to propagate subsonically along the axis 28 towards the first material 48 within the chamber 45. The deflagration caused by the pyrotechnic charge 34 generates a propagating subsonic flame. In this manner, the subsonic flame propagates along the axis 28 towards the materials 48, 52 disposed within the chamber 45.

[0121] Next, in step 1304, the materials 48, 52 are ignited by the flame to generate a supersonic wave. In certain embodiments, the first material 48 is a deflagration - detonation transition (DDT) material. When ignited, the first material 48 transitions from deflagration to detonation (explosion). While the first material 48 is being ignited by the subsonic flame, the subsonic flame ultimately transitions to detonation (explosion). The flame front accelerates into a supersonic flame that propagates through the second material 52.

[0122] Next, at step 1306, the supersonic wave continues to propagate along axis 28 towards wall segment 45 of the portable device. At step 1308, the method continues by propagating the supersonic wave through wall segment 45 without rupturing wall segment 45. The method continues to step 1310 by causing the supersonic wave to impinge on a plurality of particles 60 after the supersonic wave has passed through wall segment 45, thereby accelerating the plurality of particles 60 to a certain velocity. In this way, the detonation (explosion) wave ejects the plurality of particles 60 from the body 14 at an initial velocity exceeding the speed of sound.

[0123] In certain embodiments, the method further includes penetrating a plurality of particles 60 into tissue. In certain embodiments, the method further includes penetrating cells of the tissue with the plurality of particles 60. In certain embodiments, the above velocity is supersonic. In one embodiment, the supersonic speed exceeds the speed of sound in hydrogen. In certain embodiments, materials 48, 52 are one or more of deflagration-detonation transition (DDT) materials and detonation output materials. In certain embodiments, the plurality of particles 60 are in contact with the outer surface 56 of the portable device and are substantially aligned (in a row) with axis 28.

[0124] Regarding the above embodiments, the following appendices are further shown. (Appendix 1) An accelerator module coupled to an initiator module and configured to generate a supersonic wave from a subsonic wave generated by the initiator module, wherein the supersonic wave is configured to deliver particles to cells within tissue, wherein the accelerator module is a body that defines a container having a propagation axis and a bottom surface, the container comprising a first portion and a second portion disposed between the first portion and the bottom surface, a first material disposed in the first portion, a second material disposed in the second portion, A wall segment at least partially defined between the bottom surface of the container and the outer surface of the body, a plurality of doped metal particles in contact with the outer surface of the body and substantially aligned with the bottom surface along the propagation axis, comprising, the first material and the second material are configured to be ignited by the subsonic wave generated by the initiator module to generate a supersonic wave, the supersonic wave passes through the wall segment, and is configured to accelerate the plurality of doped metal particles to a certain speed, an accelerator module. (Appendix 2) The accelerator module according to Appendix 1, wherein the speed is supersonic. (Appendix 3) The accelerator module according to Appendix 1 or 2, wherein the speed is sufficient to penetrate the cells in the tissue. (Appendix 4) The accelerator module according to any one of Appendices 1 to 3, wherein the first material is a deflagration-detonation transition (DDT) material. (Appendix 5) The accelerator module according to Appendix 4, wherein the deflagration-detonation transition material contains dry explosive. (Appendix 6) The accelerator module according to Appendix 4 or 5, wherein the deflagration-detonation transition material contains lead azide. (Appendix 7) The accelerator module according to any one of Appendices 4 to 6, wherein the deflagration-detonation transition material contains copper(I) 5-nitrotetrazolate (DBX-1). (Appendix 8) The accelerator module according to any one of Appendices 1 to 7, wherein the second material is a detonation output material. (Appendix 9) The accelerator module according to Appendix 8, wherein the detonation output material is dry explosive. (Appendix 10) The accelerator module according to Appendix 8 or 9, wherein the detonation output material contains pentaerythritol tetranitrate (PETN). (Appendix 11) The accelerator module according to any one of Appendices 1 to 10, wherein the wall segment contains stainless steel. (Appendix 12) The accelerator module according to any one of Appendices 1 to 11, wherein the main body includes the wall segment. (Appendix 13) The accelerator module according to any one of Appendices 1 to 12, wherein the material of the wall segment is selected such that the wall segment does not rupture when the supersonic wave passes through. (Appendix 14) The accelerator module according to any one of Appendices 1 to 13, wherein the thickness of the wall segment is selected such that the wall segment does not rupture when the supersonic wave passes through. (Appendix 15) The accelerator module according to any one of Appendices 1 to 14, wherein the main body includes a base and a cap, and the cap is fixed to the base so as to form at least a part of the container therebetween. (Appendix 16) The accelerator module according to Appendix 15, wherein the container is further configured to receive at least a part of the initiator module when the cap is not fixed to the base, and the container is configured to fix the initiator module to the main body when the cap is fixed to the base. (Appendix 17) The accelerator module according to any one of Appendices 1 to 16, wherein the main body includes an opening to the container, and the opening has a size and shape such that a part of the initiator module passes through the opening when the initiator module is connected to the accelerator module. (Appendix 18) The accelerator module according to Appendix 17, wherein a part of the initiator module is at least one electrical pin. (Appendix 19) The main body includes an injection cylinder disposed on the opposite side of the wall segment as viewed from the container, the injection cylinder is aligned with the propagation axis, and the plurality of doped metal particles are disposed within the injection cylinder, the accelerator module according to any one of Appendices 1 to 18. (Appendix 20) The injection cylinder is a linear cylinder, and the cross section of the injection cylinder has a size similar to that of the container, the accelerator module according to Appendix 19. (Appendix 21) The accelerator module is a component of a gene gun, the accelerator module according to any one of Appendices 1 to 20. (Appendix 22) The first part and the second part are aligned along the propagation axis, the accelerator module according to any one of Appendices 1 to 21. (Appendix 23) The bottom surface is perpendicular to the propagation axis, the accelerator module according to any one of Appendices 1 to 22. (Appendix 24) The accelerator module according to any one of Appendices 1 to 23, further including an adhesive disposed on at least a part of the outer surface of the main body, and the plurality of doped metal particles are suspended in the adhesive. (Appendix 25) A screen fixed to the main body at a position covering the plurality of doped metal particles, An adhesive disposed on the screen to prevent the plurality of doped metal particles from passing through the screen in the absence of supersonic waves, The accelerator module according to any one of Appendices 1 to 24, further comprising the above. (Appendix 26) The accelerator module according to any one of Appendices 1 to 25, further comprising a sealing material, the container is further configured to receive at least a part of the initiator module, and the sealing material is disposed within the container to form a seal with the initiator module. (Appendix 27) The accelerator module according to any one of Appendices 1 to 26, wherein the particles of the plurality of doped metal particles have a diameter of about 1 micron. (Appendix 28) The accelerator module according to any one of Appendices 1 to 27, wherein the plurality of doped metal particles contain gold. (Appendix 29) The accelerator module according to any one of Appendices 1 to 28, wherein the plurality of doped metal particles contain tungsten. (Appendix 30) The accelerator module according to any one of Appendices 1 to 29, wherein the plurality of doped metal particles contain a chemical substance. (Appendix 31) The accelerator module according to Appendix 30, wherein the chemical substance is DNA. (Appendix 32) The accelerator module according to any one of Appendices 1 to 31, wherein the initiator module is an electric detonator (EED). (Appendix 33) The accelerator module according to Appendix 32, wherein the electric detonator (EED) includes an electric input part and an explosive output part. (Appendix 34) The accelerator module according to Appendix 33, wherein the explosive output part is a mixture of zirconium and potassium perchlorate. (Appendix 35) The accelerator module according to Appendix 33 or 34, wherein the electric explosion device (EED) is provided with a casing, and the explosive output part is arranged in the casing. (Appendix 36) The accelerator module according to Appendix 35, wherein the casing is made of metal. (Appendix 37) A main body that defines a container having a propagation axis and a bottom surface, wherein the propagation axis passes through the bottom surface, the main body, A material that is arranged in the container and is configured to at least partially generate a detonation wave that travels at supersonic speed, A wall segment at least partially defined between the bottom surface of the container and the outer surface of the body, the wall segment having a size that allows the detonation wave to pass through without breaking the wall segment. A plurality of doped metal particles disposed on the opposite side of the wall segment as viewed from the container and substantially aligned with the propagation axis. An accelerator module comprising the above. (Appendix 38) The accelerator module according to Appendix 37, wherein the plurality of doped metal particles are in contact with the outer surface of the body. (Appendix 39) The accelerator module according to Appendix 37 or 38, wherein the propagation axis is perpendicular to the bottom surface. (Appendix 40) The accelerator module according to any one of Appendices 37 to 39, wherein the material contains deflagration-to-detonation transition material (DDT). (Appendix 41) The accelerator module according to any one of Appendices 37 to 40, wherein the material contains detonation output material. (Appendix 42) The container includes a first part and a second part, the second part is disposed between the first part and the bottom surface, the material includes a first material and a second material, the first material is disposed in the first part, and the second material is disposed in the second part. The accelerator module according to any one of Appendices 37 to 41. (Appendix 43) The accelerator module according to any one of Appendices 37 to 42, wherein the accelerator module is configured to be connected to an initiator module, and the initiator module is configured to ignite the material with a subsonic wave. (Appendix 44) The accelerator module according to any one of Appendices 37 to 43, wherein the detonation wave accelerates the plurality of doped metal particles after passing through the wall segment. (Appendix 45) A method for delivering a plurality of doped metal particles to cells (preferably cells within a tissue. Also, embodiments excluding cells (preferably cells within a tissue) in a state of being present within a human individual (living body) are also preferred. Further, embodiments excluding cells (preferably cells within a tissue) in a state of being present within an animal individual (living body) are also preferred.) using a portable device, igniting a pyrotechnic charge disposed within the portable device to generate a subsonic wave and propagating the subsonic wave along an axis towards a material disposed within the portable device, igniting the material by the subsonic wave to generate a supersonic wave and continuing to propagate the supersonic wave along the axis towards a wall segment of the portable device, propagating the supersonic wave through the wall segment without rupturing the wall segment, and after passing through the wall segment, colliding the supersonic wave with the plurality of doped metal particles to accelerate the plurality of doped metal particles to a certain velocity, A method comprising: (Appendix 46) The method according to Appendix 45, further comprising penetrating a tissue with the plurality of doped metal particles. (Appendix 47) The method according to Appendix 46, further comprising penetrating the cells of the tissue with the plurality of doped metal particles. (Appendix 48) The method according to any one of Appendices 45 to 47, wherein the velocity is supersonic. (Appendix 49) The method according to Appendix 48, wherein the supersonic velocity exceeds the speed of sound in hydrogen. (Appendix 50) The method according to any one of Appendices 45 to 49, wherein the material is a deflagration-detonation transition material (DDT). (Appendix 51) The method according to any one of Appendices 45 to 50, wherein the material is a detonation output material. (Appendix 52) The method according to any one of Appendices 45 to 51, wherein the plurality of doped metal particles are in contact with the outer surface of the portable device and are substantially aligned with the axis. (Appendix 53) A gene gun having a propagation axis extending at least between a propellant charge and a plurality of doped metal particles, a deflagration-to-detonation transition material (DDT) disposed substantially along the propagation axis, a detonation output material disposed on the opposite side of the deflagration-to-detonation transition material (DDT) from the propellant charge and disposed substantially along the propagation axis, and a wall segment separating the detonation output material from the plurality of doped metal particles, The gene gun comprising the above. (Appendix 54) The gene gun according to Appendix 53, wherein the wall segment has a size that does not rupture in response to the explosion of the detonation output material. (Appendix 55) An accelerator module connected to an initiator module for delivering particles to cells in a tissue as a plurality of doped metal particles, a main body defining a container having a propagation axis and a bottom surface, a material disposed within the container that generates a supersonic wave by being ignited by the subsonic wave generated by the initiator module, a wall segment passing through the propagation axis and separating the interior and exterior of the container, comprising, on an outer surface of the wall segment, a plurality of doped metal particles can be arranged to be aligned along the propagation axis, the supersonic wave generated by the material generating the supersonic wave collides with the plurality of doped metal particles after propagating through the wall segment to accelerate the plurality of doped metal particles, The accelerator module. (Appendix 56) The accelerator module according to Appendix 55, wherein the material generating the supersonic wave generates a detonating wave that travels at supersonic speed by being ignited by the subsonic wave. (Appendix 57) The accelerator module according to Appendix 55 or 56, wherein the material generating the supersonic wave is an explosive powder. (Supplementary Note 58) The accelerator module according to any one of Supplementary Notes 55 to 57, wherein the bottom surface is perpendicular to the propagation axis. (Supplementary Note 59) The accelerator module according to any one of Supplementary Notes 55 to 58, wherein the wall segment is configured not to rupture when the supersonic wave passes through. (Supplementary Note 60) The accelerator module according to any one of Supplementary Notes 55 to 59, wherein the main body includes an injection cylinder disposed on the opposite side of the wall segment as viewed from the container, the injection cylinder is aligned with the propagation axis, and the plurality of doped metal particles are disposed in the injection cylinder. (Supplementary Note 61) The container includes a first portion and a second portion disposed between the first portion and the bottom surface. The material includes a first material disposed in the first portion and a second material disposed in the second portion. The accelerator module according to any one of Supplementary Notes 55 to 60. (Supplementary Note 62) The accelerator module according to Supplementary Note 61, wherein the first portion and the second portion are aligned along the propagation axis. (Supplementary Note 63) The accelerator module according to Supplementary Note 61 or 62, wherein the first material is a deflagration-detonation transition (DDT) material. (Supplementary Note 64) The accelerator module according to Supplementary Note 63, wherein the deflagration-detonation transition (DDT) material includes at least one of lead azide and copper(I) 5-nitrotetrazolate (DBX-1). (Supplementary Note 65) The accelerator module according to any one of Supplementary Notes 61 to 64, wherein the second material is a detonation output material. (Supplementary Note 66) The accelerator module according to Supplementary Note 65, wherein the detonation output material includes pentaerythritol tetranitrate (PETN). (Supplementary Note 67) The initiator module has an explosive charge, and the accelerator module according to any one of Appendices 55 to 66, which ignites the explosive charge to generate the subsonic wave. (Appendix 68) A gene gun comprising the accelerator module according to any one of Appendices 55 to 67. (Appendix 69) A method for delivering a plurality of doped metal particles to cells (preferably cells within a tissue. Also, embodiments excluding cells (preferably cells within a tissue) in a state existing within a human individual (living body) are also preferred. Also, embodiments excluding cells (preferably cells within a tissue) in a state existing within an animal individual (living body) are also preferred.) using a portable device, comprising: igniting an explosive charge disposed within the portable device to generate a subsonic wave and propagating the subsonic wave along an axis towards a material disposed within the portable device; igniting the material by the subsonic wave to generate a supersonic wave and continuing to propagate the supersonic wave along the axis towards a wall segment of the portable device; propagating the supersonic wave through the wall segment, and after passing through the wall segment, colliding the supersonic wave with the plurality of doped metal particles to accelerate the plurality of doped metal particles; A method including the above steps.

[0125] <Term> Although specific embodiments and examples are disclosed herein, the subject matter of the present invention extends beyond the examples in the specifically disclosed embodiments to other alternative embodiments and / or uses, and their modifications and equivalents. Accordingly, the scope of the claims appended hereto is not limited by any of the specific embodiments described above. For example, in any method or process disclosed herein, the operations or steps (operations) of the method or process may be performed in any suitable order and are not necessarily limited to the specific disclosed order. The various steps (operations) may be described sequentially as a plurality of separate steps (operations) in a manner that may be helpful in understanding the specific embodiments, but the order of the description should not be construed as implying that these steps (operations) are order-dependent. Further, the structures, systems, and / or devices described herein may be embodied as integrated components or as separate components. For purposes of comparing the various embodiments, specific aspects and advantages of these embodiments are described. Thus, for example, the various embodiments may be implemented in a manner that achieves or optimizes one aspect, advantage, or group of advantages as taught herein without necessarily achieving other aspects or advantages as may be taught or suggested herein.

[0126] Features, materials, characteristics, or combinations thereof described in connection with a particular aspect, embodiment, or example are to be understood as applicable to any other aspect, embodiment, or example described in this section or elsewhere in this specification, as long as they are compatible with the same. All features disclosed in this specification (including the appended claims, abstract, and drawings), and / or all steps of any method or process so disclosed, can be combined in any combination, unless at least some of such features and / or steps are mutually exclusive. It is not necessarily the case that all such aspects or advantages are achieved by a particular embodiment. For example, one or more features include: 1) a combination of DDT and PETN, 2) an explosive charge (gunpowder), DDT disposed downstream of the explosive charge, and PETN disposed downstream of DDT, 3) an accelerator module configured to receive an initiator module, 4) a wall segment separating the detonation output material from the doped metal particles, 5) a detonation (explosion) wave passing through the wall segment without destroying the wall segment, 6) doped metal particles achieving a speed exceeding the speed of sound, 7) doped metal particles disposed downstream of the detonation (explosion) wave, and / or 8) using deflagration to ignite the detonation (explosion) wave. Accordingly, the protection is not limited to the details of the foregoing embodiments. The protection extends to any novel one, or any novel combination, of the features disclosed in this specification (including the appended claims, abstract, and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

[0127] Furthermore, the specific features described in the context of separate embodiments may also be implemented in combination in a single embodiment. Conversely, the various features described in the context of a single embodiment may also be implemented separately in multiple embodiments, or in any suitable sub-combination. Further, although features may be described above as acting in a particular combination, one or more features from the claimed combination may, in some cases, be excised from the combination, and that combination may be claimed as a sub-combination or variation of the sub-combination.

[0128] Furthermore, the steps may be shown in the drawings or described herein in a particular order, but such steps need not be performed in the particular order shown or in a sequential order for all steps to achieve the desired result. Other steps not shown or described may be incorporated into the exemplary methods and processes. For example, one or more additional steps may be performed before, after, simultaneously with, or between the described steps. Further, the steps may be rearranged or reordered in other embodiments. One of ordinary skill in the art will understand that in some embodiments, the actual steps taken in the illustrated and / or disclosed process may differ from those shown in the drawings. Depending on the embodiment, some of the above steps may be omitted, and other steps may be added. Further, the features and characteristics of the specific embodiments disclosed above may be combined in different ways to form additional embodiments, and all of them are within the scope of the present disclosure. Also, the separation of the various system components in the above embodiments should not be understood as being required in all embodiments, and it should be understood that the components and systems described may generally be integrated into a single product or packaged into multiple products.

[0129] For purposes of the present disclosure, certain aspects, advantages, and novel features are described herein. Not necessarily all such advantages may be achieved in accordance with a particular embodiment. Thus, for example, one skilled in the art will recognize that the present disclosure may be embodied or practiced in a manner that achieves one advantage or a group of advantages taught herein without necessarily achieving other advantages that may be taught or suggested herein.

[0130] For purposes of explanation, the term "horizontal" as used herein is defined as a plane parallel to the plane or surface of the floor or ground of the area in which the device being described is used or the method being described is performed, regardless of its orientation. The term "floor" may be replaced with the term "ground". The term "vertical" refers to a direction perpendicular to horizontal, as defined. Terms such as "above", "below", "bottom", "top", "side", "higher", "lower", "upper", "over", and "under" are defined with respect to a horizontal plane.

[0131] In particular, conditional terms used in this specification such as "can", "could", "might, may", "e.g.", etc., unless otherwise specified or understood to have another meaning within the context in which they are used, generally intend to convey that a particular embodiment includes a particular feature, element, and / or step, while other embodiments do not. Thus, such conditional terms generally do not imply that a feature, element, and / or step is required in any way in one or more embodiments, or that, regardless of the presence or absence of other inputs or instructions, the logic for determining whether these features, elements, and / or steps are included in or should be performed in any particular embodiment. Terms such as "comprise", "include", "have", etc. are synonyms and are used in an open-ended and inclusive manner and do not exclude additional elements, features, actions, operations, etc. Also, the term "or" is used in its inclusive sense (not in an exclusive sense), so, for example, when used to connect a list of elements, the term "or" means one, some, or all of the elements in the list.

[0132] Conjunctions such as the phrase "at least one of X, Y, and Z" are understood separately from the context in which they are generally used to convey that an article, term, etc. can be any of X, Y, or Z, unless otherwise specified. Thus, such conjunctions generally do not imply that a particular embodiment requires the presence of at least one of X, at least one of Y, and at least one of Z.

[0133] As used herein, “about,” “approximately,” “generally,” and “substantially,” such “terms of degree” as used herein, represent values, amounts, or characteristics that are close to the recited values, amounts, or characteristics and still perform the desired function or achieve the desired result. For example, the terms “about,” “approximately,” “generally,” and “substantially” may refer to amounts within less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of the recited amount. As another example, in certain embodiments, the terms “generally parallel” and “substantially parallel” refer to values, amounts, or characteristics that deviate from exact parallelism by 15 degrees, 10 degrees, 5 degrees, 3 degrees, 1 degree, 0.1 degree, or otherwise less.

[0134] Although the gene gun has been disclosed in the context of specific embodiments and examples, it will be understood by those skilled in the art that the gene gun extends beyond the specifically disclosed embodiments to other alternative embodiments and / or uses of the embodiments, as well as modifications and equivalents thereof. Accordingly, the scope of the gene gun disclosed herein should not be limited by the specific disclosed embodiments described above, but should be determined only by a fair reading of the following claims.

[0135] Each aspect disclosed herein can be combined with any other feature disclosed herein.

Explanation of Reference Numerals

[0136] 10 ··· Gene gun 11 ··· Handle 12 ··· Accelerator module 14 ··· Body 16 ··· Base 20 ··· Container 30 ··· Initiator 32 ··· Casing 34 ··· Pyrotechnic charge 44 ··· Wall segment 45 ··· Chamber 46 ··· First part 48 ··· First material 50 ··· The second part 52 ··· The second material 54 ··· Bottom surface 58 ··· Injection barrel 60 ··· Particles

Claims

Claim 1. A gene gun comprising a pyrotechnic charge and a casing for housing the pyrotechnic charge, and an initiator module for igniting the pyrotechnic charge to generate a subsonic wave. An accelerator module connected to the initiator module for delivering a plurality of doped metal particles to cells in tissue. The accelerator module includes: A main body defining a container having a propagation axis and a bottom surface; A material disposed within the container that is ignited by the subsonic wave generated by the initiator module to generate a supersonic wave; A wall segment passing through the propagation axis and separating the interior and exterior of the container; And is provided with On the outer surface of the wall segment, a plurality of doped metal particles can be arranged to be aligned along the propagation axis. The supersonic wave generated by the material for generating the supersonic wave collides with the plurality of doped metal particles after propagating through and passing through the wall segment, thereby accelerating the plurality of doped metal particles. The plurality of doped metal particles are homogeneous. The container has a first portion. The material for generating the supersonic wave includes a first material disposed in the first portion. A gap is formed between the casing and the first material. A gene gun. Claim 2. The gene gun according to claim 1, wherein the material for generating the supersonic wave generates a detonation wave that travels at supersonic speed when ignited by the subsonic wave. Claim 3. The gene gun according to claim 1 or 2, wherein the material for generating the supersonic wave is an explosive powder. Claim 4. The gene gun according to any one of claims 1 to 3, wherein the bottom surface is perpendicular to the propagation axis. Claim 5. The wall segment is configured not to rupture when the supersonic wave passes through. The gene gun according to any one of claims 1 to 4. Claim 6. The main body includes an injection cylinder disposed on the opposite side of the wall segment as viewed from the container. The injection cylinder is aligned with the propagation axis, and the plurality of doped metal particles are disposed within the injection cylinder. The gene gun according to any one of claims 1 to 5. Claim 7. The container further includes a second portion disposed between the first portion and the bottom surface. The material further includes a second material disposed in the second portion. The gene gun according to any one of claims 1 to 6. Claim 8. The gene gun according to claim 7, wherein the first part and the second part are aligned along the propagation axis.

9. The gene gun according to claim 7 or 8, wherein the first material is a deflagration-to-detonation transition (DDT) material. gun.

10. The gene gun according to claim 9, wherein the deflagration-to-detonation transition (DDT) material contains at least one of lead azide and copper(I) 5-nitrotetrazolate (DBX-1).

11. The gene gun according to any one of claims 7 to 10, wherein the second material is a detonation output material.

12. The gene gun according to claim 11, wherein the detonation output material contains pentaerythritol tetranitrate (PETN).

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