Gene gun

Abstract

To provide, in a device for delivering a plurality of doped metal particles to cells, a technique capable of making a speed of the metal particles delivered to the cells higher than that in the prior art.SOLUTION: 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 deflagration-to-detonation transition material and a detonable material. An example of the deflagration-to-detonation transition material is copper (I) 5-nitrotetrazolate. Another example of the deflagration-to-detonation transition material is lead azide. An example of the detonable material is pentaerythritol tetranitrate (PETN).SELECTED DRAWING: Figure 8

Description

[Technical Field]

[0001] The present disclosure relates to devices and methods for gene therapy. More particularly, the present disclosure relates to devices and methods relating to biolistic particle delivery systems for delivering foreign DNA (transgenes) to cells. [Background technology]

[0002] A gene gun accelerates small doped metal particles to the highest possible velocity. The particles pass through tissue on their way to the target cell. The particles have such high velocity and density, and are so small, that they penetrate tissue without permanently damaging it. Damage caused by the particles is easily repaired by the tissue due to the small size of the penetration path. Once at the target cell, the doping (consisting of DNA) is inserted into the cell's nucleus.

[0003] Furthermore, Patent Document 1 discloses a gene gun that uses gas to accelerate a solution containing a biological material, without using metal particles, to deliver the biological material into cells. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2004-236657 Summary of the Invention [Problem to be solved by the invention]

[0005] Currently, the practical limit for particle acceleration is the speed of sound in the gas medium used. The fastest existing technology accelerates particles in a helium atmosphere, increasing the speed of sound and therefore the practical limit of particle velocity. This limits the effectiveness of existing gene guns by limiting the particle penetration depth (particle penetration depth is a function of particle velocity). The only other gas with a high speed of sound is hydrogen, leading to flammability concerns. [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 the detonation phenomenon to achieve a doped metal particle velocity that is faster than the speed of sound in any gas. In certain embodiments, the gene gun generates a detonation wave that passes through a wall or wall segment but does not destroy the wall. The detonation wave passes through the wall at the speed of sound of the wall material. For example, in certain embodiments, the wall is stainless steel. For stainless steel, the speed of sound is 5,790 m / s. On the other side of the wall are doped metal particles. In the above example, the doped metal particles are released at the initial speed of the detonation wave, i.e., 5,790 m / s. This is significantly higher than the speed of sound in helium, which is 1,007 m / s.

[0007] One aspect is an accelerator module coupled to an initiator module and configured to generate ultrasonic waves from subsonic waves generated by the initiator module. The ultrasonic waves are configured to deliver particles to cells within tissue. The accelerator module includes a body defining 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 an outer surface of the body, and a plurality of doped metal particles contacting the outer surface of the body and substantially aligned with the bottom surface along the propagation axis. The first material and the second material are The initiator module is configured to be triggered by a subsonic wave generated by the initiator module to generate a supersonic wave. The supersonic wave passes through the wall segment and then The doped metal particles are configured to accelerate the doped metal particles to a velocity.

[0008] In certain embodiments, the speed includes supersonic speed.

[0009] In certain embodiments, the velocity comprises a velocity sufficient to penetrate (permeate) the cells within the tissue.

[0010] Certain embodiments include wherein the first material is a deflagration-to-detonation material (DDT).

[0011] Certain embodiments include wherein the deflagration-to-detonation transition material comprises a dry explosive (dry gunpowder).

[0012] Certain embodiments include wherein the deflagration-to-detonation transition material comprises lead azide.

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

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

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

[0016] Certain embodiments include wherein the detonation output material comprises pentaerythritol tetranitrate (PETN).

[0017] Certain aspects include the wall segments comprising stainless steel.

[0018] Certain aspects include the body comprising a wall segment.

[0019] Certain aspects include the material of the wall segments being selected so that they do not rupture when a supersonic wave passes through them.

[0020] Certain aspects include the thickness of the wall segment being selected so 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 configured to secure to the base forming at least a portion of the container therebetween.

[0022] In one particular aspect, the container is further configured to receive at least a portion of the initiator module when the cap is not secured to the base, and the container is configured to secure the initiator module relative to the body when the cap is secured to the base.

[0023] One particular aspect includes the body including an opening to the container 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] A particular embodiment includes the part of the initiator module being at least one electrical pin.

[0025] In one particular embodiment, the body includes an injection tube disposed on an opposite side of the wall segment from the container, the injection tube being aligned with the propagation axis, and the plurality of doped metal particles being disposed within the injection tube.

[0026] A particular embodiment includes the shot tube being a straight cylinder and the cross section of the shot tube having a similar size to the cross section of the container.

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

[0028] A particular embodiment includes the first portion and the second portion being aligned (in line) along the propagation axis.

[0029] A particular aspect includes the bottom surface being perpendicular to the propagation axis.

[0030] A particular embodiment further includes an adhesive disposed on at least a portion of the exterior surface of the body, the plurality of doped metal particles being suspended in the adhesive.

[0031] One particular embodiment further includes a screen secured to the body in a position covering the plurality of doped metal particles, and an adhesive disposed on the screen to inhibit the plurality of doped metal particles from passing through the screen in the absence of ultrasonic waves.

[0032] In certain embodiments, the container further includes a seal configured to receive at least a portion of the initiator module, the seal disposed within the container to form a seal with the initiator module.

[0033] A particular embodiment includes the particles of the plurality of doped metal particles having a diameter of about 1 micron.

[0034] A particular embodiment includes wherein the plurality of doped metal particles comprises gold.

[0035] A particular aspect includes the plurality of doped metal particles comprising tungsten.

[0036] A particular aspect includes the plurality of doped metal particles comprising a chemical substance.

[0037] Certain embodiments include wherein the chemical is DNA.

[0038] In a particular embodiment, the initiator module is an electroexplosive device. This includes being a device (EED).

[0039] In a particular embodiment, the electro-explosive device (EED) comprises an electrical input and a pyrotechnic output. This includes being able to do so.

[0040] A particular embodiment includes the pyrotechnic output portion being a mixture of zirconium and potassium perchlorate.

[0041] In a particular embodiment, the electric detonator (EED) includes a casing, and the pyrotechnic output section is disposed within the casing.

[0042] Certain embodiments include wherein the casing is metal.

[0043] One aspect is an accelerator module defining a body having a propagation axis and a vessel having a bottom surface, the propagation axis passing through the bottom surface. The accelerator module further includes: a material disposed within the vessel and configured to at least partially generate a detonation wave traveling at supersonic speed; a wall segment at least partially defined between the bottom surface of the vessel and an exterior surface of the body, the wall segment having a size that allows the detonation wave to travel therethrough without rupturing the wall segment; and a plurality of doped metal particles disposed on an opposite side of the vessel from the wall segment and generally aligned with the propagation axis.

[0044] One aspect is a method for delivering a plurality of doped metal particles to cells in tissue using a handheld device, the method including igniting a pyrotechnic charge (explosive powder) disposed within the handheld device to generate a subsonic wave, propagating the subsonic wave along an axis toward a material disposed within the handheld device, igniting the material with the subsonic wave to generate a supersonic wave, continuing to propagate the supersonic wave along the axis toward a wall segment of the handheld device, propagating the supersonic wave through the wall segment without rupturing the wall segment, and causing the supersonic wave to impact the plurality of doped metal particles after passing through the wall segment, accelerating the plurality of doped metal particles to a velocity.

[0045] Another aspect is a gene gun having an axis of propagation extending between at least a pyrotechnic charge (explosive) and a plurality of doped metal particles, the gene gun including a deflagration-to-detonation transition material (DDT) disposed generally along the axis of propagation, a detonating output material disposed on an opposite side of the deflagration-to-detonation transition material from the pyrotechnic charge and disposed generally along the axis of propagation, and a wall segment separating the detonation output material from a plurality of the doped metal particles. [Effects of the Invention]

[0046] The technology disclosed herein provides a device and method for delivering multiple doped metal particles to cells that can deliver metal particles to cells at a rate greater than conventionally possible. [Brief explanation of the drawings]

[0047] [Figure 1] 1 is a perspective view of an embodiment of a gene gun including a handle and an accelerator module or cartridge, according to a preferred embodiment of the present invention. The accelerator module is attached to the handle and can be replaced after use. [Figure 2] FIG. 2 is a perspective view of the distal end of the accelerator module shown in FIG. 1, showing a shot tube containing a plurality of particles. [Figure 3] 3 is a perspective view of the proximal end of the accelerator module shown in FIG. 1, showing at least one pin of the initiator for electrically coupling the accelerator module to the handle. [Figure 4] 4 is a side view of the accelerator module shown in FIG. 2, showing the cap and base of the accelerator module secured together to form a vessel that receives at least a portion of the initiator and defines a chamber. [Figure 5] FIG. 5 is a plan view of the distal end of the accelerator module shown in FIG. 2, showing a plurality of particles disposed within the injection tube. [Figure 6] FIG. 6 is a plan view of the proximal end of the accelerator module shown in FIG. 2, showing at least one pin configured to connect to a connector on the handle. [Figure 7] FIG. 7 is an exploded perspective view of the accelerator module shown in FIG. 2, showing, for example, the initiator separated from the vessel. [Figure 8] 8 is a cross-sectional view through the accelerator module shown in FIG. 4 taken along section plane 8-8 of FIG. 4, showing both the initiator and chamber aligned axially with the shot tube. A wall segment separates the chamber from the shot tube. [Figure 9] FIG. 9 is a cross-sectional view similar to FIG. 8, except that at least one pin is connected to a connector on the handle and the distal end of the accelerator module is positioned against tissue. [Figure 10A] FIG. 10A is a partial cross-sectional view similar to FIG. 9, except showing a step in which the accelerator module is ignited, where a supersonic shock wave passes through the wall segment, accelerating a plurality of particles out of the injection tube and through tissue. [Figure 10B] FIG. 10B is a partial cross-sectional view similar to FIG. 9, except showing a step in which the accelerator module is ignited, where a supersonic shock wave passes through the wall segment, accelerating a plurality of particles out of the injection tube and through tissue. [Figure 10C] FIG. 10C is a partial cross-sectional view similar to FIG. 9, except showing a step in which the accelerator module is ignited, where a supersonic shock wave passes through the wall segment, accelerating a plurality of particles out of the injection tube and through tissue. [Figure 11] FIG. 11 shows another embodiment of a shot tube that includes an adhesive to inhibit particles from falling out of the shot tube prior to ignition of the accelerator module. [Figure 12] FIG. 12 is a view similar to FIG. 11, except that a screen is positioned across the distal end of the shot barrel. [Figure 13] FIG. 13 is a diagram illustrating the propagation of energy through the accelerator module. DETAILED DESCRIPTION OF THE INVENTION

[0048] Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. Note that the configurations and combinations thereof in each embodiment are merely examples, and additions, omissions, substitutions, and other modifications of the configurations are possible as appropriate within the scope of the present invention. The present disclosure is not limited by the embodiments, but is limited only by the claims.

[0049] In the present disclosure, the particle delivery target to which the doped metal particles are delivered (introduced) is, for example, a tissue, preferably a cell within the tissue. When the particle delivery target is a cell within a tissue, the particle delivery target may be the nucleus within the cell or an organelle within the cell.

[0050] Examples of the tissue include animal tissue and plant tissue. Examples of the animal include vertebrates, specifically mammals (mammals), birds, reptiles, amphibians, and fish. Examples of the plant include seed plants and spore-forming plants, such as angiosperms and gymnosperms, and spore-forming plants such as ferns, bryophytes, and algae. When the tissue to which the particles are delivered is an animal tissue, examples of the tissue include epithelial tissue, connective tissue, muscle tissue, and nervous tissue, as well as organs, epidermis (stratum corneum, intradermal), dermis, subcutaneous tissue, and muscle. When the tissue to which the particles are delivered is a plant tissue, examples of the tissue include meristematic tissue (such as apical meristem and cambium), permanent tissue (such as epidermal tissue, conductive tissue, mechanical tissue, and parenchyma), as well as roots, stems, and leaves.

[0051] The particle delivery target may be an in vitro system, an in vivo system, or an ex vivo system. That is, the particle delivery target may be present within an individual (living body), or may be extracted or separated from an individual (living body). The latter means that the particle delivery target is not present within an individual (living body). For example, when the particle delivery target is a cell (preferably, a cell in a tissue), the cell (preferably, a cell in a tissue) may be in a state other than a cell present within an individual (living body) (preferably, a cell in a tissue). The individual (living body) may be an animal or a plant, and the embodiments of animals and plants are as described above. When the individual (living body) is an animal, it is preferably a vertebrate, and more preferably a mammal. Mammals are not particularly limited, but include humans and mammals other than humans. Humans include healthy individuals and individuals (patients) suffering from diseases, etc. Mammals other than humans include mice, rats, guinea pigs, hamsters, cows, goats, sheep, pigs, monkeys, dogs, and cats.

[0052] The accelerator module according to the present disclosure includes a container having a propagation axis, a material disposed within the container that generates a supersonic wave when ignited by a subsonic wave generated by an initiator module, and a wall segment that separates the interior and exterior of the container along the propagation axis. A plurality of doped metal particles can be arranged on the outer surface of the wall segment so as to be aligned along the propagation axis. The supersonic wave generated by the supersonic wave-generating material propagates through the wall segment and collides with the plurality of doped metal particles, accelerating the plurality of doped metal particles. The initiator module includes, for example, a pyrotechnic charge (gunpowder), and is activated by receiving a supply of operating power to ignite and burn the pyrotechnic charge, thereby generating a subsonic wave deflagration. The subsonic wave deflagration generated by the initiator module propagates along the propagation axis toward the material contained within the container that generates the supersonic wave, and the material is ignited by the subsonic wave deflagration. When the ultrasonic wave-generating material is ignited, a detonation wave, which is a supersonic wave, is generated and the detonation wave travels along the propagation axis to the wall segment. After reaching the wall segment, the detonation wave (supersonic wave) propagates through the solid wall segment, reaching the outer surface of the wall segment and colliding with multiple doped metal particles arranged on the outer surface. As a result, the detonation wave (supersonic wave) imparts acceleration energy to the metal particles, causing them to be ejected at high speed and delivered to the target particle delivery target.

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

[0054] Furthermore, the material that generates a supersonic wave when ignited by a subsonic wave is not particularly limited, and various dry explosives can be suitably used. The material that generates a supersonic wave when ignited by a subsonic wave can be understood as a material that transitions a deflagration to a detonation. Examples of materials that generate a supersonic wave when ignited by a subsonic wave include lead azide, copper (I) 5-nitrotetrazolate (DBX-1), pentaerythritol tetranitrate, and the like. The explosive may preferably include PETN or the like, but is not limited thereto and various other explosives may be used. The accelerator module container may also include multiple types of materials that generate the supersonic waves. For example, the material that generates the supersonic waves when ignited by the subsonic waves may include a first material and a second material, which are arranged in the container so as to be aligned along the propagation axis. The first material and the second material may be different types of explosive materials or the same type of explosive material.

[0055] The wall segments of the accelerator module propagate the detonation wave, a supersonic wave generated within the vessel, through a solid. The sonic velocity, as used herein, refers to the speed of sound traveling through a substance (medium) and varies depending on the medium. The sonic velocity can be significantly higher when a solid medium is used than when a gas medium is used. For example, the sonic velocity in stainless steel is several times higher than that in helium gas. Of course, the material used for the wall segments is not limited to stainless steel. The wall segments may be formed of, for example, aluminum or other metals, or may be formed of materials other than metals. Wall segments formed in this manner can further accelerate the detonation wave, a supersonic wave traveling along the propagation axis, through solid propagation. Then, by colliding the supersonic wave (detonation wave) that reaches the outer surface of the wall segment with metal particles, the metal particles can be ejected at supersonic speeds, for example. In this way, the accelerator module and gene gun equipped with the accelerator module according to the present disclosure provide a more practical accelerator module or gene gun by increasing the injection velocity of metal particles compared to conventional methods.

[0056] 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 laboratories or medical facilities to transfer DNA into cell nuclei. The cell nuclei can be plant or animal. For example, the cell nuclei can be from a patient (human).

[0057] In certain embodiments, the accelerator module 12 comprises 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 (shown most clearly 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 body 14 comprises a material selected at least in part based on material strength. In certain embodiments, the material is selected to enable body 14 to contain forces caused by an explosion occurring within body 14. In this manner, the material exhibits sufficient strength to contain the explosive force within body 14. In certain embodiments, at least a portion of body 14 comprises a metal. Of course, body 14 need not comprise a metal, but instead could comprise a non-metallic material or a combination of non-metallic materials. For example, in certain embodiments, body 14 comprises multiple materials.

[0059] 2 is a perspective view of the distal end of the body 14 of the accelerator module 12 of FIG. 1 , showing the ejection 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 travel freely and unimpeded to the tissue.

[0060] In certain embodiments, the body 14 includes a wall segment 44 (shown most clearly 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 that travels through the wall segment 44 of the accelerator module 12 but does not rupture the wall segment 44.

[0061] In one particular embodiment, the wall segment 44 is configured to break when a blast wave passes through it. It does not crack, thus maintaining a barrier between the detonation material and the tissue. In certain embodiments, the wall segment 44 of the body 14 ruptures as the particles 60 are ejected from the ejection tube 58, but the size and shape of the rupture sufficiently attenuates the loss of pressure from the gene gun 10. As a result, the particles 60 still have an initial velocity greater than the speed of sound before entering the tissue.

[0062] The detonation wave travels through the wall segment 44 at the speed of sound in the wall material before exiting the wall segment 44. The outgoing detonation wave collides with particles 60, accelerating the particles 60 to an initial velocity that is approximately similar to the velocity of the detonation wave as it passes through the wall segment 44. As opposed to passing through a gas, the velocity of the detonation wave increases as the detonation wave passes through the wall segment 44 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 of the accelerator module 12 includes a material having a high speed of sound. In certain embodiments, the higher the speed of sound passing through the material, the greater the initial velocity of the particles 60 ejected from the ejection tube 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 thickness values. In certain embodiments, the material of the wall segment 44 is selected at least in part based on the speed of sound through the wall segment 44. In certain embodiments, the material of the wall segment 44 is selected so that the body 14 can accelerate the particles 60 to an initial velocity sufficient to penetrate (penetrate) the tissue to a desired depth. In this manner, the material of the wall segment 44 exhibits a speed of sound sufficient to allow the particles 60 to reach a desired depth within the tissue. In certain embodiments, a first portion of the body 14 comprises a material having sufficient strength to contain the explosive force, while a second portion of the body 14 comprises a material having a speed of sound sufficient to accelerate the particles 60 to a speed of sound sufficient to allow the particles 60 to reach a desired depth within the tissue.

[0065] 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) 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 the firing pulse at the desired time.

[0066] 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 fabricated 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 include complementary engagement structures 22. The engagement structures 22 are configured to secure the base 16 and the cap 18 together. In certain embodiments, the engagement structures 22 include one or more of a weld, an adhesive, a fastener, a mechanical lock, a screw, or any other structure capable of securing the base 16 to the cap 18. In other embodiments, the engagement structures 22 may be configured to secure the base 16 to the cap 18 without directly securing the base 16 to the cap 18. A frame is used to secure the base 16 to the cap 18 .

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

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

[0071] In certain embodiments, the plurality of particles 60 are metal particles. In certain embodiments, the plurality of particles 60 comprises 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 thereto and may be other sizes.

[0072] In certain embodiments, particles of the plurality of particles 60 have a spherical shape. In other embodiments, particles of the plurality of particles 60 have a conical shape. In other embodiments, particles of the plurality of particles 60 have a cylindrical shape. In other embodiments, particles of the plurality of particles 60 have a cubic shape. In other embodiments, 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 particles of the plurality of particles 60 differ in size and shape from some other particles.

[0074] In certain embodiments, the plurality of particles 60 are made from 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 relative to particles with a lower density when accelerated to the same velocity.

[0075] In certain embodiments, the plurality of particles 60 are doped. In certain embodiments, the particles have a chemical attached thereto. In certain embodiments, the plurality of particles 60 are coated with a chemical. In certain embodiments, the chemical comprises 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 doped plurality of particles 60 are coated with DNA and are subcellular in size. In certain embodiments, the DNA is chromosomal DNA.

[0076] In one particular embodiment, the ejection tube 58 outputs a plurality of particles 60 in a predetermined direction. For example, the shot tube 58 can output a plurality of particles 60 along an axis 28. In certain embodiments, the axis 28 is the axis of propagation. In some embodiments, the shot tube 58 can direct the plurality of particles 60 to a predetermined location on the tissue.

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

[0078] In certain embodiments, the shot tube 58 can have one or more deflector vanes formed on the inner wall of the bore of the shot tube 58. In certain embodiments, the one or more deflector vanes are sized and shaped to straighten the particles 60 as they are ejected from the gene gun 10. The vanes can reduce turbulence in the particles 60 as they are ejected from the shot tube 58.

[0079] In certain embodiments, the gene gun 10 fires the doped particles 60 into tissues, cells, and / or organelles. In certain embodiments, the firing of the doped particles 60 occurs in vitro. In certain other embodiments, the firing of the doped particles 60 occurs in vivo. In certain embodiments, the gene gun 10 fires the doped particles 60 into cell nuclei.

[0080] As the particles 60 are ejected, they desirably penetrate the tissue. In certain embodiments, the 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 predetermined. In certain embodiments, the desired depth is determined, at least in part, based on the composition of the particles 60. For example, the desired depth may be different for different accelerator modules 12.

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

[0082] In certain embodiments, the initiator 30 is ignited by an electrical input. In certain embodiments, at least one pin 38 receives the electrical input in the form of an electrical ignition 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 for activating the initiator 30. In certain embodiments, the one or more electronic components include a controller. In certain embodiments, the gene gun 10 includes an interface for a user to activate the one or more electronic components to activate 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 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 provides 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 initiator 30 via connector 40. In certain embodiments, the magnitude and duration of the electrical ignition pulse applied to initiator 30 are 1.2 amps and 2 ms. In certain embodiments, the magnitude and duration of the electrical ignition pulse applied to initiator 30 are 1.75 amps 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 initiator 30 are selected based at least in part on the operating characteristics of initiator 30.

[0086] 7 is an exploded perspective view of the accelerator module 12 shown in FIG. 2, showing, for example, the initiator 30 separated from the vessel 20. In certain embodiments, the initiator 30 can be any electro-explosive device (EED). In one embodiment, initiator 30 includes a pyrotechnic charge 34 (pyrotechnic output). Pyrotechnic charge 34 is configured to generate a flame when ignited. In one particular embodiment, initiator 30 includes a casing 32. In one particular embodiment, casing 32 includes pyrotechnic charge 34. In one particular embodiment, 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 the base 16 and the cap 18. In certain embodiments, the base 16 comprises at least a portion of the container 20. In certain embodiments, the cap 18 comprises 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 secured together to form the container. In certain embodiments, the initiator 30 is disposed within the container 20, and then the base 16 and the cap 18 are secured together.

[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 secured to the base 16. In this manner, the initiator 30 can be locked within the container 20 when at least the base 16 and the cap 18 are secured together.

[0089] 8 is a cross-sectional view through the accelerator module 12 shown in FIG. 4 taken along section plane 8-8 of FIG. 4, showing both the initiator 30, the chamber 45 aligned along axis 28, and the shot tube 58. In one particular embodiment, the chamber 45 is part of the vessel 20 and is disposed between the initiator 30 and the bottom surface 54 of the vessel 20. The wall segment 44 separates the chamber 45 from the shot tube 58.

[0090] In certain embodiments, the connector 40 is structurally secured 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 secure the connector 40 to the body 14. In an embodiment, the user can separate or remove the connector 40 from the body 14. For example, after using the accelerator module 12, the connector 40 can be detached from the body 14, allowing the used accelerator module 12 to 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 a surface of the initiator 30 and a 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 secured to the base 16 to form the complete container 20.

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

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

[0094] In certain embodiments, flame escaping casing 32 ignites material within chamber 45. When pyrotechnic charge 34 is ignited, pressure released by pyrotechnic charge 34 within casing 32 ruptures casing 32, causing a deflagration to propagate at subsonic speeds along axis 28, igniting 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 prevents flames escaping the casing 32 from leaking through the opening 26 toward the connector 40 when the initiator 30 is ignited. In certain embodiments, the seal 24 prevents materials exploded within the chamber 45 from leaking through the opening 26 toward the connector 40 when ignited by flames escaping the casing 32 through a rupture.

[0096] In certain embodiments, the material within chamber 45 generates a detonating wave when the material is ignited by a flame caused by ignition of pyrotechnic charge 34. In certain embodiments, the detonation (explosion) wave is selected to generate a sonic wave. proceeds at a speed greater than

[0097] In one particular embodiment, to achieve the desired detonation (explosion) wave from chamber 45, the overall pyrotechnic reaction is initially a subsonic deflagration caused by ignition of pyrotechnic charge 34. The velocity is increased to greater than the speed of sound by the detonation of material within chamber 45. In certain embodiments, one or more materials are placed within chamber 45 to generate the desired detonation (explosion) wave.

[0098] For example, in certain embodiments, the materials include 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 chamber 45. In certain embodiments, the materials include lead azide, copper(I) 5-diazide, and the like. The preferred materials are one or more of diisopropyl ether, ...

[0099] In certain embodiments, the materials include 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 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 location of the interface facilitates the propagation of a detonation wave along the axis 28 toward 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 can be smooth. In certain embodiments, the interface can be bumpy. It is also possible.

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

[0102] In one particular embodiment, the ratio of first material 48 to second material 52 is 50 / 50. Of course, other ratios are within the scope of the present disclosure. For example, in one particular embodiment, the ratio of first material 48 to second material 52 is 40 / 60. For example, in one particular embodiment, , 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 some embodiments, the first material 48 is a dry explosive. In one particular embodiment, the first material 48 is a lead azide material. In one particular embodiment, the first material 48 is copper(I) 5- Nitrotetrazolate (DBX-1) material.

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

[0105] In certain embodiments, the detonation wave continues through the wall segment 44, imparting velocity to a plurality of particles 60 disposed against the exterior surface 56 of the body 14. The detonation wave then ejects 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 an initial velocity that is the same as the velocity of the detonation wave passing through the wall segment 44.

[0106] Figure 9 is a cross-sectional view similar to Figure 8, except that at least one pin 38 is connected to connector 40 of handle 11 and the distal end of accelerator module 12 is positioned against tissue. Figures 10A-C are partial cross-sectional views similar to Figure 9, except that they show the step in which accelerator module 12 is ignited, where a supersonic shock wave passes through wall segment 44, accelerating a plurality of particles 60 out of injection tube 58 and through tissue.

[0107] FIG. 10A shows the initiator 30 being activated (ignited) by an electrical input. In one particular embodiment, at least one pin 38 receives the 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 when ignited. When the pyrotechnic charge 34 is ignited, the pressure released by the pyrotechnic charge 34 within the casing 32 ruptures the casing 32, allowing a 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 manner, the subsonic flame travels toward the chamber 45.

[0108] 10B shows an escaping deflagration igniting a first material 48 within chamber 45. In one particular embodiment, first material 48 is a deflagration-to-detonation transition (DDT) material. As the first material 48 transitions from a deflagration to a detonation (explosion), the subsonic flame eventually transitions to a detonation (explosion) as the first material 48 is ignited by the subsonic flame. In this manner, 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 that propagates toward the second material 52. As the flame (deflagration) transitions to a detonation (explosion), pressure increases. The detonation (explosion) creating a supersonic wave creates a powerful pressure wave traveling ahead of the propagating flame that raises the temperature of the first material 48 above its autoignition temperature.

[0109] 10C illustrates the detonation of second material 52 resulting from the detonation of first material 48. In certain embodiments, the detonation wave generated by second material 52 travels at a velocity greater than the speed of sound. The detonation wave generated by second material 52 generates a similar detonation wave within wall segment 44. The detonation wave continues through wall segment 44, imparting velocity to a plurality of particles 60 disposed against outer surface 56 of body 14. The detonation wave then ejects the plurality of particles 60 from body 14 at an initial velocity greater than the speed of sound.

[0110] The following describes a method for manufacturing the accelerator module 12. Of course, other methods involving more or fewer steps and / or a different order of steps may also be used within the scope of this disclosure. is within the range.

[0111] In one particular embodiment, a method for manufacturing an accelerator module 12 begins by providing a base 16. The base 16 includes a chamber 45 partially defined by a bottom surface 54. The bottom surface 54 is spaced from an outer surface 56 by wall segments 45. The distal end of the shot barrel 58 is configured to be placed against tissue. In certain embodiments, the shot barrel 58 is configured to support a plurality of particles 60.

[0112] A second material 52 is loaded into the 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 detonation-yielding material. In certain embodiments, the second material 52 is a dry explosive. In certain implementations, 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] First material 48 is loaded into first portion 46 of chamber 45 above second material 52. In certain embodiments, first material 48 is in contact with second material 52. In certain embodiments, first material 48 is a deflagration-to-detonation transition material. In certain embodiments, first material 48 is a dry explosive. In certain embodiments, first material 48 is lead azide. In certain embodiments, first material 48 is copper(I) 5-nitrotetrate. In one particular embodiment, first material 48 is compressed against second material 52 in chamber 45 with a pressure necessary to achieve the desired degree of compression. Of course, first material 48 and second material 52 can be compressed into chamber 45 simultaneously to achieve the desired degree of compression without being compressed separately.

[0114] The initiator 30 is then 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 of the vessel 20. In certain embodiments, the casing 32 is disposed adjacent to the first material 48.

[0115] In certain embodiments, the initiator 30 is attached to the opening 26 in the base 16 along with the seal 24. In certain embodiments, the seal 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 includes threads that are complementary to the threads on the base 16.

[0116] A plurality of particles 60 are placed within the shot barrel 58. When the gene gun 10 is used with the shot 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 shot barrel 58.

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

[0118] 11 illustrates another embodiment of the shot tube 58 that includes an adhesive 62 to inhibit the particles 60 from falling out of the shot tube 58 prior to ignition of the accelerator module 12. The adhesive 62 holds the particles 60 in place against the exterior surface 56. In certain embodiments, when the gene gun 10 is operated, the adhesive 62 crumbles and / or vaporizes, leaving the particles 60 able to continue traveling at the speed of a detonation wave. In this configuration, adhesive 62 is less dense than particles 60 and disperses or slows down more quickly. In this manner, adhesive 62 does not impede the movement of particles 60.

[0119] FIG. 12 is similar to FIG. 11, except that a screen (shroud) 64 is positioned across and secured to the distal end of the injection barrel 58. In the illustrated embodiment, adhesive 62 is held to the screen 64. In one particular embodiment, the screen 64 is made of a plurality of fine In certain embodiments, the pores are micropores. In certain embodiments, the screen 64 has a fine mesh that allows the particles 60 to pass through the pores of the screen 64 unimpeded.

[0120] FIG. 13 illustrates a method for propagating energy through an accelerator module 12. The method uses a handheld device, such as a gene gun 10, to deliver (introduce) a plurality of particles 60 to cells within tissue. The method begins in step 1302 by igniting a pyrotechnic charge 34 disposed within the handheld device to create a flame (deflagration) that travels as a subsonic wave. In certain embodiments, at least one pin 38 receives electrical input in the form of an electrical ignition pulse. The pyrotechnic charge 34 generates the 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, allowing the 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 manner, the subsonic flame propagates along the axis 28 toward the materials 48, 52 disposed within the chamber 45.

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

[0122] Next, in step 1306, the ultrasonic wave continues to propagate along axis 28 toward wall segment 45 of the handheld device. In step 1308, the method continues by propagating the ultrasonic wave through wall segment 45 without rupturing wall segment 45. The method continues in step 1310 by impinging the ultrasonic wave against the plurality of particles 60 after the ultrasonic wave passes through wall segment 45, accelerating the plurality of particles 60 to a velocity. In this manner, the detonation wave ejects the plurality of particles 60 from body 14 at an initial velocity that exceeds the speed of sound.

[0123] In certain embodiments, the method further includes penetrating the tissue with the plurality of particles 60. In certain embodiments, the method further includes penetrating the cells of the tissue with the plurality of particles 60. In certain embodiments, the velocity is supersonic. In certain embodiments, the supersonic velocity exceeds the speed of sound in hydrogen. In certain embodiments, the material 48, 52 is one or more of a deflagration-detonation transition (DDT) material and a detonation power material. In one particular embodiment, a plurality of particles 60 contacts the exterior surface 56 of the handheld device and is generally aligned (in a row) with the axis 28.

[0124] The following additional notes are provided regarding the above embodiment. (Appendix 1) an accelerator module coupled to the initiator module and configured to generate supersonic waves from the subsonic waves generated by the initiator module, the ultrasonic waves are configured to deliver particles to cells within the tissue; The accelerator module includes: a body having a propagation axis and defining a container having 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; and a wall segment at least partially defined between a bottom surface of the container and an outer surface of the body; and, a plurality of doped metal particles contacting the outer surface of the body and generally aligned with the bottom surface along the axis of propagation; Equipped with 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 being configured to pass through the wall segment and accelerate the plurality of doped metal particles to a velocity; Accelerator module. (Appendix 2) 2. The accelerator module of claim 1, wherein the speed is supersonic. (Appendix 3) 3. The accelerator module of claim 1 or 2, wherein the velocity is sufficient to penetrate the cells within the tissue. (Appendix 4) 4. The process of any of claims 1 to 3, wherein the first material is a deflagration-detonation transition (DDT) material. Speedometer module. (Appendix 5) 5. The accelerator module of claim 4, wherein the deflagration-to-detonation transition material comprises a dry explosive. (Appendix 6) 6. The accelerator module of claim 4 or 5, wherein the deflagration-to-detonation transition material comprises lead azide. (Appendix 7) Attachment 4 or Attachment 5, wherein the deflagration-detonation transition material comprises copper(I) 5-nitrotetrazolate (DBX-1). 7. An accelerator module according to any one of claims 1 to 6. (Appendix 8) 8. The accelerator module of any of claims 1 to 7, wherein the second material is a detonation power material. (Appendix 9) 9. The accelerator module of claim 8, wherein the detonation output material is a dry explosive. (Appendix 10) 10. The accelerator module of claim 8 or 9, wherein the detonation power material comprises pentaerythritol tetranitrate (PETN). (Appendix 11) 11. The accelerator module of any of claims 1 to 10, wherein the wall segments comprise stainless steel. (Appendix 12) 12. The accelerator module of any one of claims 1 to 11, wherein the body comprises the wall segments. (Appendix 13) 13. An accelerator module according to any one of claims 1 to 12, wherein the material of the wall segments is selected so that the wall segments do not rupture when the supersonic wave passes through them. (Appendix 14) 14. An accelerator module according to any one of claims 1 to 13, wherein the thickness of the wall segment is selected so that the wall segment does not burst when the supersonic wave passes through it. (Appendix 15) 15. An accelerator module according to any one of claims 1 to 14, wherein the main body comprises a base and a cap, the cap being fixed to the base so as to form at least a portion of the container between the base and the cap. (Appendix 16) 16. The accelerator module of claim 15, wherein the container is further configured to receive at least a portion of the initiator module when the cap is not secured to the base, and the container is configured to secure the initiator module to the body when the cap is secured to the base. (Appendix 17) 17. The accelerator module of any of claims 1 to 16, wherein the body includes an opening to the container, the opening being 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. (Appendix 18) 18. The accelerator module of claim 17, wherein the part of the initiator module is at least one electrical pin. (Appendix 19) 19. The accelerator module of any one of claims 1 to 18, wherein the body comprises an injection tube positioned on the opposite side of the wall segment from the vessel, the injection tube aligned with the propagation axis, and the plurality of doped metal particles positioned within the injection tube. (Appendix 20) 20. The accelerator module of claim 19, wherein the injection tube is a straight cylinder and the cross section of the injection tube has a size similar to the cross section of the vessel. (Appendix 21) 21. The accelerator module of any of claims 1 to 20, wherein the accelerator module is a component of a gene gun. (Appendix 22) 22. The accelerator module of any of claims 1 to 21, wherein the first portion and the second portion are aligned along the propagation axis. (Appendix 23) 23. The accelerator module of any of claims 1 to 22, wherein the bottom surface is perpendicular to the propagation axis. (Appendix 24) 24. The accelerator module of any of claims 1 to 23, further comprising an adhesive disposed on at least a portion of an outer surface of the body, the plurality of doped metal particles being suspended in the adhesive. (Appendix 25) a screen secured to the body in a position covering the plurality of doped metal particles; an adhesive disposed on the screen to inhibit the plurality of doped metal particles from passing through the screen in the absence of a supersonic wave; 25. The accelerator module of any of claims 1 to 24, further comprising: (Appendix 26) 26. The accelerator module of any of claims 1 to 25, further comprising a seal, the container further configured to receive at least a portion of the initiator module, the seal disposed within the container to form a seal with the initiator module. (Appendix 27) 27. The accelerator module of any of claims 1 to 26, wherein the particles of the plurality of doped metal particles have a diameter of about 1 micron. (Appendix 28) 28. The accelerator module of any one of claims 1 to 27, wherein the plurality of doped metal particles comprises gold. (Appendix 29) 29. The accelerator module of any of claims 1 to 28, wherein the plurality of doped metal particles comprises tungsten. (Appendix 30) 30. The accelerator module of any one of claims 1 to 29, wherein the plurality of doped metal particles comprises a chemical substance. (Appendix 31) 31. The accelerator module of claim 30, wherein the chemical is DNA. (Appendix 32) 32. Any of claims 1 to 31, wherein the initiator module is an electro-explosive device (EED). 10. The accelerator module according to claim 9. (Appendix 33)

[0023] The electro-explosive device (EED) as described in claim 32, wherein the EED has an electrical input and a pyrotechnic output. accelerator module. (Appendix 34) 34. The accelerator module of claim 33, wherein the pyrotechnic output section is a mixture of zirconium and potassium perchlorate. (Appendix 35) The electro-explosive device (EED) comprises a casing, and the pyrotechnic output section is disposed within the casing. 35. The accelerator module of claim 33 or 34, wherein (Appendix 36) 36. The accelerator module of claim 35, wherein the casing is metal. (Appendix 37) a body defining a vessel having a base and having an axis of propagation, the axis of propagation passing through the base; a material disposed within the vessel and configured to at least partially generate a detonation wave traveling at supersonic speed; a wall segment at least partially defined between the bottom surface of the container and an outer surface of the body, the wall segment having a size that allows the detonation wave to travel therethrough without fracturing the wall segment; a plurality of doped metal particles disposed on an opposite side of the wall segment from the vessel and substantially aligned with the axis of propagation; An accelerator module comprising: (Appendix 38) 38. The accelerator module of claim 37, wherein the plurality of doped metal particles contact the outer surface of the body. (Appendix 39) 39. The accelerator module of claim 37 or 38, wherein the propagation axis is perpendicular to the bottom surface. (Appendix 40) 40. The acceleration method of any of claims 37 to 39, wherein the material comprises a deflagration-detonation transition material (DDT). Instrument module. (Appendix 41) 41. The accelerator module of any of claims 37 to 40, wherein the material comprises a detonation power material. (Appendix 42) 42. The accelerator module of any of claims 37 to 41, wherein the container includes a first portion and a second portion, the second portion being disposed between the first portion and the bottom surface, and the material includes a first material and a second material, the first material being disposed in the first portion and the second material being disposed in the second portion. (Appendix 43) 43. The accelerator module of any of claims 37 to 42, wherein the accelerator module is configured to be coupled to an initiator module, the initiator module being configured to ignite the material with subsonic waves. (Appendix 44) 44. The accelerator module of any of claims 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 in tissue, and also preferred embodiments excluding cells in a state in which they exist in a human individual (living body) (preferably cells in tissue), and also preferred embodiments excluding cells in a state in which they exist in an animal individual (living body) (preferably cells in tissue)) using a portable device, comprising: igniting a pyrotechnic charge disposed within the handheld device to generate a subsonic wave, and propagating the subsonic wave along an axis toward a material disposed within the handheld device; igniting the material with the subsonic wave to generate a supersonic wave, and continuing to propagate the supersonic wave along the axis toward a wall segment of the handheld device; propagating the ultrasonic wave through the wall segment without rupturing the wall segment, and causing the ultrasonic wave to impinge on the plurality of doped metal particles after passing through the wall segment, thereby accelerating the plurality of doped metal particles to a velocity; A method comprising: (Appendix 46) 46. ​​The method of claim 45, further comprising penetrating tissue with the plurality of doped metal particles. (Appendix 47) 47. The method of claim 46, further comprising penetrating cells of the tissue with the plurality of doped metal particles. (Appendix 48) 48. The method of any one of claims 45 to 47, wherein the velocity is supersonic. (Appendix 49) 49. The method of claim 48, wherein the supersonic speed exceeds the speed of sound in hydrogen. (Appendix 50) 50. The method of any of claims 45 to 49, wherein the material is a deflagration-detonation transition material (DDT). . (Appendix 51) 51. The method of any of claims 45 to 50, wherein the material is a detonation-powered material. (Appendix 52) 52. The method of any of claims 45 to 51, wherein the plurality of doped metal particles contact an exterior surface of the handheld device and are generally aligned with the axis. (Appendix 53) 1. A gene gun having a propagation axis extending between at least a pyrotechnic charge and a plurality of doped metal particles, a deflagration-to-detonation transition material (DDT) disposed generally along the propagation axis; a pyrotechnic charge disposed on the opposite side of the deflagration-detonation transition material (DDT), the propagation axis a detonation output material disposed substantially along the a wall segment separating the detonation power material from the plurality of doped metal particles; Including, gene gun. (Appendix 54) 54. The gene gun of claim 53, wherein the wall segments are sized so as not to rupture in response to detonation of the detonation output material. (Appendix 55) A plurality of doped metal particles are connected to an initiator module and deliver the particles to cells within the tissue. 1. An accelerator module for delivering progeny, comprising: a body having a propagation axis and defining a vessel having a bottom surface; a material disposed within the container that generates a supersonic wave when ignited by the subsonic wave generated by the initiator module; a wall segment passing through the propagation axis and separating an interior and an exterior of the container; Equipped with a plurality of doped metal particles may be disposed on an outer surface of the wall segment so as to be aligned along the propagation axis; the ultrasonic waves generated by the ultrasonic wave-generating material propagate through the wall segment and then collide with the plurality of doped metal particles, thereby accelerating the plurality of doped metal particles. Accelerator module. (Appendix 56) 56. The accelerator module of claim 55, wherein the supersonic wave-generating material is ignited by the subsonic wave to generate a detonation wave traveling at supersonic speed. (Appendix 57) 57. The accelerator module of claim 55 or 56, wherein the material that generates the supersonic waves is a dry explosive. (Appendix 58) 58. The accelerator module of any of claims 55 to 57, wherein the bottom surface is perpendicular to the propagation axis. (Appendix 59) 59. The accelerator module of any of claims 55 to 58, wherein the wall segments are configured not to burst when the supersonic waves pass through them. (Appendix 60) 60. The accelerator module of any of claims 55 to 59, wherein the body comprises an injection tube positioned on the opposite side of the wall segment from the vessel, the injection tube aligned with the propagation axis, and the plurality of doped metal particles positioned within the injection tube. (Appendix 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; 61. The accelerator module of any of clauses 55 to 60. (Appendix 62) 62. The accelerator module of claim 61, wherein the first portion and the second portion are aligned along the propagation axis. (Appendix 63) 63. The acceleration method of claim 61 or 62, wherein the first material is a deflagration-detonation transition (DDT) material. Instrument module. (Appendix 64) 64. The accelerator module of claim 63, wherein the deflagration-to-detonation transition (DDT) material comprises at least one of lead azide and copper(I) 5-nitrotetrazolate (DBX-1). (Appendix 65) 65. The accelerator module of any of claims 61 to 64, wherein the second material is a detonation power material. (Appendix 66) 66. The accelerator module of claim 65, wherein the detonation power material comprises pentaerythritol tetranitrate (PETN). (Appendix 67) 67. The accelerator module of any of claims 55 to 66, wherein the initiator module has a pyrotechnic charge and ignites the pyrotechnic charge to generate the subsonic wave. (Appendix 68) 68. A gene gun comprising an accelerator module according to any one of claims 55 to 67. (Appendix 69) A method for delivering a plurality of doped metal particles to cells (preferably cells in tissue, and also preferred embodiments excluding cells in a state in which they exist in a human individual (living body) (preferably cells in tissue), and also preferred embodiments excluding cells in a state in which they exist in an animal individual (living body) (preferably cells in tissue)) using a portable device, comprising: igniting a pyrotechnic charge disposed within the handheld device to generate a subsonic wave, and propagating the subsonic wave along an axis toward a material disposed within the handheld device; igniting the material with the subsonic wave to generate a supersonic wave, and continuing to propagate the supersonic wave along the axis toward a wall segment of the handheld device; propagating the ultrasonic wave through the wall segment and causing the ultrasonic wave to impinge on the plurality of doped metal particles after passing through the wall segment, thereby accelerating the plurality of doped metal particles; A method comprising:

[0125] <Terminology> While particular embodiments and examples are disclosed herein, the subject matter of the present invention extends beyond the implementation in the specifically disclosed embodiments to other alternative embodiments and / or uses, and modifications and equivalents thereof. 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 particular order disclosed. Although various steps (operations) may be described sequentially as multiple separate steps (operations) in a manner that may be helpful in understanding a particular embodiment, the order of description should not be construed to imply that these steps (operations) are order dependent. Furthermore, structures, systems, and / or devices described herein may be implemented as integrated components. The various embodiments may be implemented as a single unit or as separate components. For purposes of comparing various embodiments, certain aspects and advantages of those embodiments are described. Thus, for example, 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] It should be understood that features, materials, properties, or combinations thereof described in connection with a particular aspect, embodiment, or example may also be applied to any other aspect, embodiment, or example described in this section or elsewhere in this specification, to the extent compatible. All features disclosed herein (including the accompanying claims, abstract, and drawings), and / or all steps of any method or process so disclosed, are incorporated herein by reference. Unless at least some of the features and / or steps are mutually exclusive, such and may be combined in any combination. Not necessarily all such aspects or advantages will be achieved in accordance with any particular embodiment. For example, one or more features may be combined in any combination, including 1) a combination of DDT and PETN; 2) a pyrotechnic charge (explosive) and a gas turbine engine positioned downstream of the pyrotechnic charge; 3) a DDT that receives the initiator module and a PETN that is placed downstream of the DDT. and 4) separating the detonation power material from the doped metal particles. 5) a detonation that passes through a wall segment without destroying the wall segment. 6) doped metal particles achieving supersonic velocities; 7) doped metal particles positioned downstream of the detonation (explosion) wave and / or 8) detonation using deflagration. ) waves. Thus, protection is not limited to the details of the foregoing embodiments. Protection extends to any novel one or any novel combination of features disclosed in this specification (including the accompanying claims, abstract and drawings), or to any novel one or any novel combination of steps of any method or process so disclosed.

[0127] Furthermore, certain features that are described in this disclosure in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable subcombination. Furthermore, while features may be described above as acting in a particular combination, one or more features from a claimed combination can, in some cases, be carved out of the combination, and the combination may be claimed as a subcombination or a variation of the subcombination.

[0128] Additionally, while steps may be illustrated in the figures or described herein in a particular order, such steps need not all be performed in the particular order shown or sequential order to achieve desired results. Other steps not shown or described may be incorporated into the example methods and processes. For example, one or more additional steps may be performed before, after, simultaneously with, or between described steps. Furthermore, steps may be rearranged or reordered in other implementations. Those skilled in the art will appreciate that, in some embodiments, the actual steps taken in the illustrated and / or disclosed processes may be different from those described in the examples. It will be understood that the steps may differ from those shown in the figures. Depending on the embodiment, some of the above steps may be omitted, and other steps may be added. Furthermore, the features and characteristics of the specific embodiments disclosed above may be combined in different ways to form additional embodiments, all of which are within the scope of the present disclosure. Also, it should be understood that the separation of various system components in the above embodiments should not be understood as requiring such separation in all embodiments, and that the described components and systems may generally be integrated into a single product or packaged into multiple products.

[0129] For purposes of this disclosure, certain aspects, advantages, and novel features have been 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 carried out in a way that achieves one advantage or 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 described apparatus is used or the described method is performed, regardless of its orientation. The term "floor" is interchangeable with the term "ground." The term "vertical," as defined, refers to a direction perpendicular to the horizontal. Terms such as "above," "below," "bottom," "top," "side," "higher," "lower," "upper," "over," and "under" are defined relative to the horizontal plane.

[0131] In particular, conditional terms used herein, such as "can," "could," "might," "may," "eg," and the like, unless expressly stated otherwise or understood otherwise within the context of use, are generally intended to convey that certain embodiments include certain features, elements, and / or steps, while other embodiments do not. Thus, such conditional terms generally convey that the features, elements, and / or steps are somehow required by one or more embodiments. or that one or more embodiments may include, with or without other input or indication, these features, elements, and / or steps in any particular embodiment. The term "comprises," "includes," "has," and the like are synonymous and are used in an open-ended, inclusive manner and do not exclude additional elements, features, acts, operations, etc. Additionally, the term "or" is used in its inclusive (and not exclusive) sense; for example, when used to connect a list of elements, "or" may refer to one, some, or all of the elements in the list.

[0132] Conjunctions such as the phrase "at least one of X, Y, and Z," unless otherwise indicated, are understood apart from the context in which they are generally used to convey that an article, term, etc. can be either X, Y, or Z. Thus, such conjunctions do not generally 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, "degree of" language, such as the terms "approximately," "about," "generally," and "substantially," refers to a value, amount, or characteristic that is close to the stated value, amount, or characteristic while still performing a desired function or achieving a desired result. For example, the terms "approximately," "about," "generally," and "substantially" can refer to an amount that is within 10%, 5%, 1%, 0.1%, and 0.01% of the stated amount. As another example, in certain embodiments, the terms "generally parallel" and "substantially parallel" refer to a value, amount, or characteristic that deviates from strictly parallel by no more than 15 degrees, 10 degrees, 5 degrees, 3 degrees, 1 degree, 0.1 degrees, or other degrees.

[0134] Although the gene gun has been disclosed in the context of specific embodiments and examples, the gene gun may be used in other alternative embodiments and / or uses beyond the specifically disclosed embodiments. It will be understood by those skilled in the art that the present invention covers all modifications and equivalents thereof. Therefore, the scope of the gene gun disclosed herein should not be limited by the specific disclosed embodiments described above, but should be determined solely by a fair reading of the following claims.

[0135] Each feature disclosed herein may be combined with any other feature disclosed herein. [Explanation of symbols]

[0136] 10. Gene gun 11 Handle 12 Accelerator Module 14. Main unit 16...Base 20...container 30 Initiator 32 Casing 34. Pyrotechnic Charge 44 Wall Segment 45 Chamber 46...First part 48...First material 50...Second part 52...Second Material 54 Bottom 58...Injection tube 60...particles

Claims

1. an initiator module having a pyrotechnic charge and a casing containing the pyrotechnic charge, the initiator module igniting the pyrotechnic charge to generate a subsonic wave; an accelerator module coupled to the initiator module for delivering a plurality of doped metal particles to cells within the tissue; The accelerator module includes: a body having a propagation axis and defining a vessel having a bottom surface; a material disposed within the vessel that generates a supersonic wave when ignited by the subsonic wave generated by the initiator module; a wall segment passing through the axis of propagation and separating an interior from an exterior of the vessel; Equipped with a plurality of doped metal particles may be disposed on an outer surface of the wall segment so as to be aligned along the propagation axis; the ultrasonic waves generated by the ultrasonic wave-generating material propagate through the wall segment and then collide with the plurality of doped metal particles, thereby accelerating the plurality of doped metal particles; the container has a first portion; the ultrasonic wave-generating material includes a first material disposed in the first portion; a gap is formed between the casing and the first material; Gene gun.

2. the container further comprises a second portion disposed between the first portion and the bottom surface; the ultrasonic wave-generating material further comprises a second material disposed in the second portion; The gene gun of claim 1.

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