Background technology
The percutaneous dosing mode has many kinds, comprise the mode of utilizing physical principle, theory of mechanics or both combinations, for instance, comparatively common percutaneous dosing mode includes electroporation, microinjection ... etc. method, its purpose is directly medicine to be imported skin surface, but the stability of the administering mode of these physical properties and success rate are all on the low side at present, and operation easier is quite high, still can not use widely.In recent years, the research of particle gun has become the main trend that the physical property gene changes plantation technology, and reason is that particle gun can overcome in the past other method and can't effectively carry material to the predicament of cell, thereby makes gene change the use of clinicalization of plantation technology to step further forward.
In more detail, the particle gun method is to utilize to carry biological material (for example: carrier DNA) (for example: goldc grains), mode with shooting at a high speed enters biological cell, reach gene and change the purpose of growing, and said gene rifle technology has been widely used in the field of many research and development, wherein common field includes botanical system, mammiferous somatic cell, gene therapy, and even nearest DNA (deoxyribonucleic acid) (DNA) vaccine research system.
Illustrate with example, particle gun can place the carrier that carries DNA on one body (cartridge), and utilize the instantaneous pressure air-flow to produce seismic wave, so that accelerate in the body that moment stops until running into an obstacle, but because the DNA on the body can continue because of the effect of inertia force to advance at utmost speed, thereby enter in the organism.But, the shortcoming of the particle gun maximum of this type is that noise is too big, and the high speed and high pressure gas that seismic wave produces is easy to kill target cell, and must consume high helium and the carrier (normally goldc grains) of a large amount of prices.
In addition, also has a kind of particle gun administering mode that utilizes low-pressure gas to accelerate, its liquid (suspension liquid that contains nanoparticle) that will carry DNA directly or indirectly injects in the nozzle of contraction-expanding, again with moment low-pressure air current enter in the organism through nozzle tape hydrodynamic body.Though the particle gun of this type can overcome the bottleneck that known particle gun meets with, but, because known particle gun flowed in turbulent flow (turbulence) mode before sample enters to its nozzle, so sample is easily because be condensed on its surface with the tube wall collision, and again because the structure Design of nozzle own has the dead angle, therefore the kinetic energy that the while low-pressure gas provides is low can't take the sample that residues on the tube wall out of effectively, be for the particle gun that accelerates for known low-pressure gas, its maximum shortcoming is to cause in the easy residual nozzle tube wall of liquid and can't quantitatively reaches the seriality operation.
Accordingly, the invention provides a kind of transmitting device to solve the bottleneck that is met with in the prior art.
Summary of the invention
The purpose of this invention is to provide a kind of transmitting device, it is with the designed physical property drug delivery system of Hydrodynamics Theory, this transmission system utilizes plural fluid circuit (for example: nitrogen to make Compressed Gas (air) or noble gas, helium) under certain pressure with (for example: DNA contain biological material, RNA, virion, chemicals ... etc.) or the liquid state of biochemical material, solid particle is mixed into biphase fluid mutually, with the speed of moment greater than 343 meters of per seconds, make biological material can pass surface structure or the cell membrane of organism, enter in Cytoplasm or the nucleus, reach the special extraneous protein of performance of biological cell.
The purpose of this invention is to provide a kind of transmitting device, it transfers to a target with a material in the mode of physical property, and described transmitting device comprises: an input module, and its transmission one passes carrying object; One transport module, itself and input module link, and the transport module internal memory has described material, and transport module receives and passes carrying object and mix with the atomizing material and with material; And an output module, it has one first opening and one second opening, the caliber size of first opening is greater than the caliber size of second opening, and material with pass mixing via first opening of carrying object and enter output module and via second opening output output module.
A kind of transmitting device disclosed in this invention, it transfers to a target with a solid matter in the mode of physical property, and described transmitting device comprises: an input module, its transmission one passes carrying object; One mixed cell, itself and input module link, and the mixed cell internal memory has described solid matter, and mixed cell reception transport gas, and solid matter is mixed with transport gas; An and output module, it has one first opening and one second opening, the caliber size of first opening is greater than the caliber size of second opening, and solid matter entered output module and exports output module via second opening with mixing via first opening of biography carrying object.
A kind of transmitting device disclosed in this invention, it transfers to a target with a non-solid matter in the mode of physical property, and described transmitting device comprises: an input module, its transmission one passes carrying object; One atomization unit, it is linked to input module, and atomization unit passes carrying object with the non-solid matter that atomizes in order to store described non-solid matter and to utilize; One mixed cell, it is linked to input module, atomization unit and output unit, and the mixed cell utilization passes carrying object to mix the non-solid matter that has atomized and to pass carrying object; One output module, it has one first opening and one second opening, the caliber size of first opening is greater than the caliber size of second opening, and non-solid matter entered output module and exports output module via second opening with mixing via first opening of biography carrying object.
In sum as can be known, transmitting device disclosed in this invention can by atomizing with change fluid (comprise: liquid, gas, colloid ... etc.) particle diameter, and pass through mixed cell simultaneously, so that the material of atomizing or 500 microns with the internal solid particle can with pass carrying object and mix, after biphase different material is evenly mixed or causing suspended state, with the design of nozzle and the change of mode of operation, can utilize certain air pressure (for example: 10kg/cm again
2) condition produce the moment hypervelocity fluid and moment zubzero temperature, make biphase mixing sample be accelerated to high speed and moment phase variation (liquid phase is to the variation of solid phase, wherein solid phase system includes ice crystal, ice needle ... etc. form), pass the top layer of biology or cell to enter in the cell, reach the purpose of transmission.Compare with known techniques, the present invention except make contain biological material (as DNA, RNA, protein, virion, chemicals ... etc.) sample can adopt liquid solution or 500 microns with interior solid particles to improve outside the ease of use, also can be reduced in the difficulty for preparing in the application of conventional carriers (goldc grains), minimizing to the destruction of biological material and target (for example: injury target cell), and improve security row and the reliability of its use.
The specific embodiment
Be the ease of use that improves biological material sample and the degree of control of output dose, the difficulty for preparing for the reduction conventional carriers, minimizing are to the destruction of biological material and the injury that may cause target simultaneously, and improving safety and the reliability of its use, the present invention discloses a kind of transmitting device.Below, provide detailed explanatory note and accompanying drawing simultaneously, with aid illustration technical characterictic of the present invention.
At first, please refer to shown in Figure 1ly, it is the embodiment of a kind of transmitting device disclosed in this invention, wherein, described transmitting device 1 transfers to a target with a material in the mode of physical property, and described transmitting device 1 comprises an input module 12, a transport module 14 and an output module 16.Described input module 12 transmission one pass carrying object; Transport module 14 links with input module 12, and transport module 14 internal memories have described material, and transport module 14 receives and passes carrying objects and mix with the atomizing material and with material; Described output module 16 has one first opening 161 and one second opening 162, the caliber size of first opening 161 is greater than the caliber size of second opening 162, and material entered output module 16 and exports output modules 16 via second opening 162 with mixing via first opening 161 of biography carrying object.Wherein, the particle diameter of material after via atomizing is smaller or equal to 500 microns, and above-mentioned target comprises cell and tissue.
In addition, described transmitting device 1 also comprises a control module (figure does not show), itself and input module 12, transport module 14 and output module 16 link, in more detail, described control module is electrically connected with all module, so control module control passes carrying object and transfer rate and the time of material in input module 12, transport module 14 and output module 16.Be example with the present embodiment, control module can be logic circuit, and it controls transfer rate and the time of this transport gas in input module 12, transport module 14 and output module 16.
It still is example with the present embodiment, described input module 12 (for example: gas pressure accumulation groove) includes a pressure accumulation unit 123, it passes carrying object in order to store, and logic circuit is then in order to control transfer rate and the time of transport gas in input module 12, transport module 14 and output module 16.In more detail, the basic design of input module 12 is except having the pressure accumulation unit 123 more than a group, for filtering the impurity that passes in the carrying object, described input module 12 also includes two groups of above filters 121,122 (degree of filtration is below 0.5 micron), and control module then comprises mechanical type or the by-pass valve control of electronic type and the combination of high voltage bearing pipeline of many groups.The start that its purpose is to utilize accurate logic electronics loop to control each parts and gas flow loop order, wherein the power gas source of Tui Donging is arrange in pairs or groups general air compressor, gas maker or compensation type high pressure gas steel cylinder.
In addition, also link a guide unit 18 between output module 16 disclosed in this invention and the transport module 14, wherein the design of output module 16 mainly is in order to mix and the transmission purpose so that biphase material reaches simultaneously for the treatment of the material of biphase (two-phase).In more detail, shown in present embodiment, wherein be example explanation output module 16 with the nozzle, and described output module 16 (that is, nozzle) have first opening 161, second opening 162 and is positioned between the two throat 163.
And as shown in Figure 2, it is the structural representation of guide unit and output module in the transmitting device of the present invention.Described guide unit 18 is linked to first opening 161 of output module 16.On structure Design, the opening bore D of guide unit 18 is 3 times of throat's bore d in the output module 16, and the length L 3 of guide unit 18 is more than or equal to the spacing L1 between second opening 162 and the throat 163 in the output module 16, and the junction of guide unit 18 and output module 16 has the design of a lead angle, and the taper angles A 1 of lead angle is approximately 9 to 45 times of taper angles A 2 of second opening 162 in the output module 16, for instance, when the taper angles A 2 of second opening 162 is that 1/2 times the bore d of throat (1/2d) is during to 1/3 times the bore d of throat (1/3d), then 1 of the taper angles A of lead angle can design the bore d of throat (15d) to 15 times between 3 times the bore d of throat (3d), and such design can help to allow the power gas source (just passing carrying object) of promotion and the material (comprising non-solid-state particle or the solid particles of suspension) after the atomizing can stablize reciprocal action on the one hand in guide unit 18, its reason is because the mass density that passes between carrying object and the material differs very big, therefore, under same barometric gradient, acceleration (or deceleration) effect that passes carrying object is come significantly more than material, then help the design by lead angle on the other hand, make biphase (the passing carrying object and material) of stablizing after the reciprocal action can flow into first opening 161 of output module 16 along lead angle, and can not produce residual at the tube wall of guide unit 18 because of turbulent flow.
In more detail, the spacing L2 between described first opening 161 and the throat 163 is more than or equal to the spacing L1 between second opening 162 and the throat 163, and the spacing L1 between second opening 162 and the throat 163 is between 3 times to 10 times the bore d of throat.Application with reality, said nozzle can Laval nozzle (Laval Nozzle) be the basis, it utilizes split-hair geometry to design contraction-expansion (converging-diverging) pipeline, obtain ultrasonic speed so that pass the speed of carrying object moment at second opening, 162 places, and utilize the speed that passes carrying object so that its potential energy is converted into kinetic energy, make and pass carrying object obtains rapid decline in the moment at second opening, 162 places temperature, and output module 16 temperature inside gradient curves system as shown in Figure 3, wherein X-axis is represented the position that output module 16 (nozzle) is inner, Y-axis is represented temperature, therefore, mixed atomizing material can form ice crystal or ice needle by the humidity of environment and the temperature of rapid decline with the biography carrying object, to reach the purpose of transmission.
In addition, in the contraction section of nozzle (just first opening 161 is between the throat 163), barometric gradient is forward (that is, identical with flow direction), and the acceleration ratio material that passes carrying object is bigger, therefore, the movement velocity that passes carrying object will be higher than material, on the contrary, and in the expansion segment of nozzle (just between throat's 163 to second openings 162), the direction of barometric gradient is opposite with flow direction, and the retarding efffect that passes carrying object will make the movement velocity that passes carrying object less than material speed.Especially when seismic wave occurring in the expansion segment in throat 163 downstreams, this deceleration phenomenon is more remarkable.
Therefore, output module 16 is considered the reciprocal action between two-phase fluid when design, make the pressure and the speed that pass carrying object reach minimum and maximum respectively in throat 163.When passing in the flow field that carrying object accelerates gradually and when reaching critical state, throat 163 can produce choked flow (choking) phenomenons; The speed of pressure and biphase (comprise and pass carrying object and material) is all fixing before throat 163 no longer to be changed, when passing carrying object simultaneously and entering expansion segment by throat 163, not anti-reflection of speed increases, and reaches maximum at the downstream part slightly of throat 163, reaches the supersonic speed state.
And described transport module 14 is different and different according to the material phase of importing, and described material is selected from solid matter, non-solid matter and combination thereof, and therefore following will be that example is described in detail with solid matter and two kinds of embodiments of non-solid matter.
Be example with the solid matter at first, please also refer to Fig. 4 and shown in Figure 5, wherein Fig. 4 is a kind of embodiment that transmitting device of the present invention is applied to solid matter, and Fig. 5 then is the sketch map of the internal structure of mixed cell.The transmitting device 1a of present embodiment transfers to a target with a solid matter in the mode of physical property, and described transmitting device 1a comprises an input module 12, a mixed cell 141 and an output module 16.Wherein, input module 12 transmission one pass carrying object; Mixed cell 141 links with input module 12, and mixed cell 141 internal memories have described solid matter, and mixed cell 141 reception transport gas, and solid matter is mixed with transport gas; Output module 16 has one first opening 161 and one second opening 162, the caliber size of first opening 161 is greater than the caliber size of second opening 162, and solid matter entered output module 16 and exports output modules 16 via second opening 162 with mixing via first opening 161 of biography carrying object.Significantly, in order to the transmitting device 1a that transmits solid matter, because solid matter does not need extra atomizing, so solid matter can directly be stored in the mixed cell 141.Wherein, above-mentioned target comprises cell and tissue.
But it should be noted that, but mixed cell 141 described herein is except hybrid solid-state material and biography carrying object, it also makes the solid matter of mix homogeneously and biography carrying object present suspended state, so can make solid matter and pass carrying object before output, can be suspended in the mixed cell 141 and be unlikely to be deposited in the bottom of mixed cell 141, and the internal structure of described mixed cell 141 can be as shown in Figure 5; In addition, can be that the power gas source of by-pass valve control and the promotion of mechanical type or electronic type mixes and from mixed cell 141 derivation with mutual in order to the solid matter of exporting mix homogeneously and the mode that passes carrying object.
Moreover when described material was non-solid matter, the embodiment of transmitting device disclosed in this invention as shown in Figure 6.Described transmitting device 1b includes an input module 12, a transport module 14b (including an atomization unit 142 and a mixed cell 141) and an output module 16; Input module 12 transmission one pass carrying object; Atomization unit 142 is linked to input module 12, and atomization unit 142 passes carrying object with the non-solid matter that atomizes in order to store described non-solid matter and to utilize; Mixed cell 141 is linked to input module 12, atomization unit 142 and output unit 16, and mixed cell 141 utilizes and passes carrying object to mix the non-solid matter that has atomized and to pass carrying object; Output module 16 has one first opening 161 and one second opening 162, the caliber size of first opening 161 is greater than the caliber size of second opening 162, and non-solid matter entered output module 16 and exports output modules 16 via second opening 162 with mixing via first opening 161 of biography carrying object.Wherein, the particle diameter after material atomizes via atomization unit is smaller or equal to 500 microns, and above-mentioned target comprises cell and tissue.Different from the embodiment described above is, material in the present embodiment is non-solid matter, wherein include liquid, gaseous material and colloidal materials, for being able to physical property ground, the particle size that makes above-mentioned non-solid matter dwindles, with pass carrying object and mix before, process atomization unit 142 is to atomize non-solid matter earlier, and described atomization unit 142 can be electronics concussion formula nebulizer, two fluid-type nebulizers or fluid pressure type nebulizer, wherein the internal structure sketch map of electronics concussion formula nebulizer and two fluid-type nebulizers shows in Fig. 7 and Fig. 8 respectively.
In more detail, when atomization unit 142 shakes formula nebulizer 142a for electronics (as shown in Figure 7), because the fluid atomizing mechanism of electronics concussion formula nebulizer 142a is to utilize electronics concussion principle, therefore use piezoelectric quartz body oscillator to produce altofrequency seismic wave (ultrasound), fluid atomizing is become minimum vaporific particle, and the pattern by water proof concussion, just fluid is placed in the container, with water be medium and utilize the electronics concussion to produce altofrequency seismic wave (ultrasound) both produce common shake mode, so that fluid becomes vaporific fog particles, what deserves to be mentioned is big or small about 0.5 to 6 micron of the atomizing particle size that constitutes by the way.But, utilizing the fluid of aforesaid way must be can conducting fluids.
When atomization unit 142 is two fluid-type nebulizer 142b (as shown in Figure 8), because the biography carrying object that the liquid state of two fluid-type nebulizer 142b atomizing mechanism is utilization to be compressed (for example: air) swiftly flowing principle and Bernoulli's theorem, (for example: nozzle) mixture with non-solid matter and biography carrying object is atomized into minimum vaporific particle, big or small about 10.0 microns of its atomizing particle size through output module 16 by using flow rate of fluid and pressure to make to pass carrying object and non-solid matter.
But because the liquid state of two fluid-type nebulizer 142b atomizing mechanism is divided into run-in index and rectilinear two kinds of patterns again on the container structure of non-solid matter.Wherein, the run-in index pattern is to utilize the biography carrying object of compression under swiftly flowing state, biography carrying object by compression is when output module 16 (with nozzle be example at this), owing to can moment produce vacuum when passing carrying object through output module 16, the biography carrying object of adding compression fills and hits so that non-solid matter produces flow-disturbing in container, and then non-solid matter guided, make biphase mixing form two fluids at last, therefore the non-solid matter of exporting via output module 16 can atomize and form minimum vaporific particle.In addition, rectilinear pattern is to utilize the little principle of the big part pressure of flow velocity in the Bernoulli's theorem, therefore, passes carrying object and causes the pressure of flow export little owing to flowing out rapidly, and then non-solid matter is attracted, and make non-solid matter atomizing form minimum vaporific particle via output module 16.
In addition, when atomization unit 142 is that the fluid pressure type nebulizer is not when (figure shows), because the fluid pressure type nebulizer utilizes external force so that non-solid matter is pressurizeed, can through output unit the time, directly be atomized by this non-solid matter of pressure official post that adds and form minimum vaporific particle.
From the above as can be known, transmitting device disclosed in this invention can by the atomizing change fluid (comprise: liquid, gas, colloid ... etc.) particle diameter, and pass through mixed cell simultaneously, make the material of atomizing or 500 microns with interior solid particles can with pass carrying object and mix, after biphase different material is evenly mixed or causing suspended state, again with the design of nozzle and the change of mode of operation, can be at certain air pressure (for example: 10kg/cm
2) condition under produce the moment hypervelocity fluid and moment zubzero temperature, make biphase mixing sample be accelerated to high speed and moment phase variation (liquid phase is to the variation of solid phase, wherein solid phase system includes ice crystal, ice needle ... etc. form), pass the top layer of biology or cell to enter in the cell, reach the purpose of transmission.
The above only is illustrative, but not is restrictive.Anyly do not break away from spirit of the present invention and category, and to its equivalent modifications of carrying out or change, all should be contained in the appended claim scope.