CA2248622A1 - Biolistic apparatus for delivering substances into cells and tissues - Google Patents

Abstract

A biolistic apparatus is provided with a housing having a carrier membrane disposed in a chamber for movement relative to an outlet plate having a plurality of apertures therein.
The carrier membrane has a plurality of micro-particles adhered thereto on the surface of the membrane adjacent the apertures for delivery into cells or tissue. A plurality of rupturable membranes are mounted in spaced relation to the carrier membrane. Initially, a vacuum is provided within the assembly including the outlet opening to purge the apparatus of any undesirable gasses. High pressure helium is then delivered to the rupturable membranes and upon reaching a predetermined pressure, will cause the membranes to rupture allowing a shock front of high pressure helium to strike the carrier membrane and impel the articles through the outlet openings.

Description

1 PATE ~ 7UPP~ICA~IO~

8TIC APP~UURT~ FOR DB~IV~ING 8~nT2~N~
I2rrO CE~L~ 7~nD TI8B~E8 RP~T.~Il'~n aPPT.TCP.TION
Applicant~ claim priority bQnefits of provisional S applicat~on 60/059771 filed September 23, 1997 under 35 USC
ll9(e) BACKGRO~NP OF T~ L~ ON
The present invention i~ directed to a biolistic device for accelerating mî~ro-projectiles into intact cellsi or tissue6. More specifîcally, the pre~ent invention is airected to a biolistic devîce having a ga~ shock gen~rator ~or applying a gas 6hoc~ to a ~ixed carrier mRmbrane to di~end the membrane and separate micro-projectile~ from the sur~ce of the membrane at high ~ipeeds into th~ target cell~ or tissue~: ~
For medical application~, a biolistic ~evice muGt hAve ~everal characteristics including sa~ety, r~producibility, ease of use, n~n-trauma for the pat~ent and -;ni ~1 injury to the bombarded tissue. At the same time, maximum partiale dispersion, maximum particle velocity ~nd ~ 1 skin pene~ration are nee~ed. Existing bioli~ic devices need 1s lmprovement in ter~ of aelivery~ Rfficacy, reproducibility, gentleness and ease o~ u~e. Many o~ the prior art de~ice~
make a loud nois~ which can be frightening and impact ~he s~n ; ' ' , . ~ ,,.' . . . _ ~; . : i!'-,"

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2 P~TENT ~ P~ICATIO~

With a violerlt ~;hock wave o~ helium ga~;. Prior art configuration~; utilizinS~ a "flying disk" has ~:hot to ~;hot variation and ~ubj ect~ the ~kin to a viol~nt ghock wave and ~oes not achieve as much dispersal or penetration as might be de~ired.
~UMM~RY OF T~E T~V~N~ION
The present inv~ntion provid~s a new and impr~ed biolistic ~pparatus for injecting particles into cell~ and ti~sue~ whi~h i~ extrQmely ~afe, ea~y to use, highly reproducible, makes es~entially no noise, i~ painle~ and cause~ minimal trauma to the bombarded ~kin~
~he device according to the present i~vention ha6 ~een shown to re~ult in better particle di~pe~al, deeper ~kin penetration and h~gher sub~equent biolog~cal activitie~.
The pre~ent invention provide~ a new and improved bioli~tic device which effectively but gently accelerates micro-pro~ectiles into intact cell~ or ti~ues ~uch a~ ~kin compris~ng a gas shock generator, a fixed malleable membrane between the gas shock and the targ~t, a ~hap~d ~topping BUrface dispo~ed betw~3en thQ fix~3d m-3mbran~ and the target for controlled decslQrzltion of the di~tending membrane ana aper~ures in the ~topping ~urface which allow the tran~port of high 6peed micro-pro~ectile~ from the surface of the fi~ed membrane into the target.
The presen~ in~ention provides a new and improvea bioli~tic device ~or acceleratlng micro-projectiles into 3 PA~E ~ APP~I ~ TION

intact cell8 or ti~ue~ wh~ch utilize~ a gas shock generator comprised o~ a plurality of bur~t membrane~ which are clampea together upon ini~ial ~pplication of p~es~ure and w$11 ~ubstantially, simultan~o~sly burst when the pre66ure appl~ed thereto reach~s a predetermined value ~hereby relea6ing the ga~ under pressure ~ub~antially instantaneously to create a ~hock wavQ for contacting a carrier membrane and impaling the mic~o-particles thereon into a target~
The pre~ent invention pro~ides ~ new ana improved bioli~tic device for accelerating micro-pro~ectiles into i~tact cells or ti~sue~ compri~ing a ga~ ~hock generator including a ~agnetically controlled valve which i6 held ~:hut by magnetic force until pres~ure being applied thereto i~
~uf~icient to ~reak the magnetic ~eal at which point the magnetic seal suddenly collapse~ and the ~alve open~ whereby a ~hock wave is projected again~t a de~ormable carrier membrane to impel th~ micro-par~icle~ thereon into the cell~
or ti6~ue~.
The above and other object~, ~eatur~s and advantages of the pre~ent invention will be more apparent and more readily appreclated ~rom the following detailed de~cription o~
pre~erred ex~mplary embodiment o~ th~ pre~ent invention, taken in connection with t~e accompanying drawingG.
~IEF DE8CRIPTTON ~F ~B DRAUING~

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~ PA~ ~ A~PLIC~TIO~

Fig. 1 is a 3ide el~3vation view of a bioliE;tic devic~3, partly in section and partly brokQn away, for accelerating m~cro-projectiles into intact cells or tis~ues.
Fig. 2 i~ a sectional vlew of thQ houqing of the device S 6hown in ~ig. 1.
Fig. 3 i~ a sectiona~ vie.w of the piston assembly which exterld~: through said housing in concentric relation thereto.
Fig. 4 is a sectional vi~w o~ the nozzle body as s~own in Fig~ 1.
Fig~ 5 is a sectional vi~w of the coupler ~hown in Fig.
1 between the bursti~le membranes and the carrier membrane with ga~ flow pa~ages shown in phantom llne~.
Fig. 6 i~; a rear end view of the coupler ~hown in Fig. 5.
Fig. 7 i~ a front end vlew of the coupler shown in Fig.
5.
Fig. 8 is a sectional ViQW of a supporting ring ~or the coupler a~ ~hown in Pig. 1.
Fig. 9 i~ a front end view of the support ring as ~ho~m in Fig. 8.
Fig. 10 is an ena view o~ a ~upport ring for ~upporting the forward end of the piston as~embly.
Fig. ~1 is a side elevation vi~w of the 6upport ring shown in Fig. 10.
Fig. 12 i~ a 6ectional view o~ the nozzle outlet plate as shown in Fig. 1.
Fig. 13 i~ a rear elevational view the~eof.

!'., . : . , -PATEN~ APPLICATION

E'~g. 14 i8 a :~ront elsvational view thereof~. --Fig. 15 i~ a sectional view of the retaining ring ~ecursd in the opposite end o~ the hou~ing ~rom the nozzle body Fig. 16 is a rear elevational view thereof.
Fig. 17 i~ a ~ront elevational view ther~of.
~ig. 18 is a sec~ional view of the pres~ure ch. ~r securea to the retainer rlng at the rear end of the housing.
Fig. 19 ~ a rear elQvational view ther~of.
Fig. 20 is a front elevational view th~reof.
Fig~ 21 is a s~ctional view of the end cap ~ecured to the pres~ure cham~er member.
~ig. 22 iG a rear elevational view ther~of.
~ig. 23 i~ a front ele~ational ~iew th~r~of.
Fig. 24 i~ a ~ectional view of a magn~tica;ly con~olled ga~ pre~sure valvQ according to a ~econd embodiment of the invention.
DET~TT.~D D~CR~PTIQN OF TEE l~v~lON
The app~ratus of the pre~ent invention i~ shown in a~6embled form in Figure 1 and i~; compriged o~ a hollow, cylindr~cal housing 20 having internal threads 22 and 24 at opposite ends thereof. An ~longated plE:ton as~embly Z6 is mounted ln ~he hollow, cylindrical housing 20 concentrically thereo~. The piston assembly 26 i8 ~upport~d at it~ forw~rd end ~ mean~ o~ an annular member 28 (Fig. 10~ di~po~d 1n threaded engagement ~ith the thread~ 24 of the hou6ing. The annular ~e~ber ~8 is provided with a plurality o~ radially, 6 PA~E ~ ~ ~lCA~ION

inwardly directed projection~ 30 having ~nner end~ 32 di~po~ed on a circle having a diameter equal to the diameter of the p~e~ure chamber 34 at the forward end o~ the pi~ton a~embly.
A plurality of cut out portion~ 36 are located between each S pro;ection 30 to provide communication between the ahnular chamber 38 located between the pi~ton a~sembly 26 and thQ
hou~ing ~0 and the interior o~ the nozzle a~sembly 40.
The nozzle as~embly 40 (~ig~. 4-9 and 14) i~ comprised of a nozzle ~ody 42 having an externally threaded hub portion 44 di~po~ed in threaded engagement with the thread6 24 ~t the forward end o~ the housing 20. The oppo~te end of the nozzle body 42 is provided with a circular opening 46 which rec~ives a nozzls outlet plate 48. ~he nozzle outlet plate 48 i8 pro~ided with a larger diameter flange portion 50 adapted to engag~ the internal ~urface of an annular ~lang~ 52 formed on the nozzlQ body 4z. A smaller diameter central portion 54 having a plurality of through passages 56 is located within the opening 46 in the end of th~ nozzle body 42. An O ri~g 58 18 disposed in a groove on the internal fac~ of the flange ~2 to eeal the nozzle outle~ plate to the nozzle body 4Z. The internal ~:urface of the nozzle outle~ plate 48 i8 prov~ded with a recess 60 and the flange 50 i~ provided with four groo~e~ 62 equally ~paced apart.
An annular coupler 64 i~ mounted in the no~zle body ad~acent the nozzle o~let plate 48 by mean~ of an annular ring 66 c~f delrin material. The ~orward end of the ~;u~port , ~: , . ~ ' - , ' .. r ~ ' .

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7 ~T~ ~ ~iePLICATION

ring 66 is provid~d with ~our axially extending flange portion~ 68 ~guall~ spac~d about the circumference of the ring to de~ine gap~ 70 therebetween. The forward end of the coupler 64 is provided with a recQ~ 72 ha~ing a trape~oidal cros~ ~ection with the ~maller base ~f the trapezoid ha~ing a diameter equal to the diameter of the axially extending central passage 76 of the coupler 64. A plurality of axially ext~ndi~g bores 74 are equally ~paced about the central pasgage 76 to provide communication between the rece~s 72 and the rearward ~urface of the eoupler.
The rearward ~urface 78 of the coupler is provided wi~h an enlarged rec~3~3s 80 which i5 concentric with the axial bore 76 ~xtending through the coupler. The pres~ure chamber 34 of the plston assembly 26 i~ provided wi~h a forwardly ext~n~ng flange 82 with an annular crown 84 on the fo~ward end thereof.
The flange 82 is dimens~oned to clo~ely ~it within the reces~
80 in the coupler membe~. The pressure chamber portion 34 is provided with a ~ub~antially hemispherical pre sure chamber 86 which merge~ into a cyl~ndrical pasgage 88 extending through the flange 82 and having a diameter idQntical to the diameter of th~ bore 76 extending through the coupler 64. A
plurality o~ kapton membranes 90 having an ex~ernal diameter ~ub~tantially ~ual to the diameter o~ the recess 80 in the coupler, are disposed in the recess 80 for engagement by ~he Z5 crown 84 on thQ forward end o~ the flange S2 on the pre~sure ch~ ~cr member 34. ~he n~mber o~ membrane~ 90 may vary ~ ~aT~NT ~PPLICATIO~

depending upon thQ d~sired strength sinc~ the plurality of mem}~ran~s ar~ ad~pted to bur~;t ~rhen the desired pre~;sure i6 rsachea in the pres6ure chamber 86. A sinyle ~tronger carrier membrane 92 having a diamet~r e~ual to the diam~t~r of the nozzle outlet plate flange S0 is disposed between the ~lange ~ 50 and the coupler with ~ufficient play ~o allow co~munication between the through pas~agQs ~6~ ths rece-~sed portion 60, the rRcessea portion 7~ and the annular chamber 38 in the ab~ence of pre~surQ being applie~ to the membrane 92 in the forward direct1on.
Th~ piston assembly ~6 ha~ an axially extending bore 96 e~tending the ~ull length of the piston as~embly i~
communication with the pres~;ure ~h~ h~t~ 86 and a cylindrical reces~ 98 at ~he oppo~ite end thereof. ~he piston assembly 26 i~ provided with a cylindrical hub portion 100 ha~ing ~ larger diameter than the elongated body 102 o~ the pis~on assQmbly.
At the end of the pi~ton assembly, an enlarged flange l04 i~
provided adjac~nt the hub portion 100.
Adjacent the rRarward end of the housing 20, a retaining ring 106 having es~ternal thread6 108 thereon, i8 threaded into - Qngagement w~ th the int~rnal thread~ 22 of the housing 20.
The retaining ring 106 is provided with an axially extending rece~;E: 110 at thl3 forwar~ ena thereof having a plurallty c~f rad~ally directed passages 112 extending ou~war~ly to the threads }08. The retaining ring 106 is al30 pro~ided with a reduced diametPr bore 114 in which the hub portion 100 of the : !
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9 PATE ~ ~ PLICATION

piston as3embly 26 i~ ~lidably mounted. A pre~ure chamber memb~r 120 is provided with a forwardly ex~n~ing recess 122 having an int:-3rnally threaded portion 124 which i6 threaded onto the external thread~ o~ the retaining ring 106. The enlarged diame~er end portion 104 of the pi~ton asse~bly 26 i~
disposed in a reces~ 123 in the rearward portion of th~
retaining ring 1-6 and is ~xposed to pr~urQ in the reces~
122 o~ the pressure chamb~r m~mber. Th~ preggure chamber m~mber 120 is al~o provided with a plurality o~ ~hrough bor~
126 disposed adjacent the periphery o~ the pres~re member lZ0. A central ~ore 128 is prov~de~ for ln~r~duclng pres~ure into the pre~ure chamber and a plurality of threaded pa~ages 130 are provided about the central bore ~28 for the reception of connecting member~.
An end cap 140 is ~cur~d to the rQarward end of ~he pres~ure chamber member 120 by mean~ o~ cap scrQws (not shown) extending through three bore~ 142 wh~ch are in alignment with the threade~ pa~gages 130 in the prsssure chamber member. The rear end of the end cap i~ pro~ided with an ~xt~rnally threaaed nozzle 144 which is adapted to be connected to a ~uitable vacuum gource and a high prQ~Ure helium ~ource (not shown) The end cap i~ provid~d with a rece~s 146 ~n the forward end thereof ha~ing ~ tr~pezoidal cro~ section with the rece~ in ~v lnication with the inlet passage 148 ext~n~ng through the nozzle 144.

':" ' , ' ' ' . ~' ', ' . ' 10 PATENrr ~ PLIC~IO~

In the operation o~ the app~rat~ according to the present inv~ntion, th~i forward end o~ ~he nozzle body 40 i~
pres~ed again~t the ti~su~ to be inoculated with particleis 6uch as genetic material~ Since th~ foxward ~urface of ~he r~ozzle outlet plate 54 i8 recesssd rQl~tiv~ to thR nozzle body as be~t ~een in FigurQ 1, a thin chamber is formed in communication with the pa~age~ 56 through which th~ particles are ejected. A vacuum i~ applied to th~ ~ntir~ assQmbly by connecting t~e nozzle 144 to a ~uitabl~ vacuu~ ~ource through valve m~ans ~not ~hown). 'rhe vacuum i8 applied through the axial pa!3sagQ 148 of the nozzle 144, the rec~ 8 146 in the ~sind cap and the annular cbamber 38 by means o~ the connecting pa~sage~ 126. Th~ vacuum i~ al~o applied ~o the passag~s ~6 in the outlet pl~te 54 as well a~ the outèr surSac~ of the outlet plate 54 through the reces~ 60 in the outlet plate 4~, the pa~sage~ 74 ext~nding through the coupler 64 to the annular chamber 38 through the opsnings 36 in the annular support membQr 28, 5ince the carrier membranQ 92 is mounted ' ~th ~uf~icient play, it is po~ible for the vacuum to be applied around the periphery of the carrier membran~ through the grooves 62 in the flange of th~ ou~let plate. By applying the vacuum to the system, the atmospheric ~a~ses, as ~ell a~
any residual heli~m ~e~ ~rom a pr~vioug usage, a~e removed fxom the vacuum body a~ well as remo~ing any stray gas from the high ~res~ure chamber and the line~ ~upplying the accelerator. Thus, dur~ng a ~ubsequent Q~ ~ction opeiration, ''" '~1''' ' ~
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11 ~A~E ~ ~ PLIC~TIO~

only helium ga~ will be in the high pre~sure Gha~ber 86 rather than the u6ual mix of a~r and helium gas.
A~t~3r sufJ~icient vac~um ~ introduced, a vac~ ;en60r (not 6ho~n) will initiate the introduction o~ prQs~urized hellum ga~ through the nozzle 144~ The pre~surized heli~m ga~
will act on the enlarged end portion 104 of the pi~ton assembly 26 to ~hift the pi~ton a~embly 26 axially to brlng the crown 84 on the flange 82 of the pi~ton ~6emb1y 26 in~o clamping engagement with ~he bur~t membrane~ go by clamping the burst membranes 90 a~ain~t the bottom of the enlarged r~cess 80 in t~e rear ~ur$ace o~ the ~ouple~. The pressurized h~lium gas will also enter through the rece~6 98 in the rearward end of the pi6ton a6~e~bly ana the elongated through p~ssage 26 to the pre~6ure chamber 86. The pre~ure will ramp up in t~s high pressure chamber 86 un~11 it reache~ the yield pre~sure o~ the burst membrane~ 90. The membrane system can consist of ~ny d~ired number of membranes~ For example, the mem~rane ~ystem may con~ist of ~.0~2" (2 mil) kapton membran ~r di6k~. Each disk would have a bur~t pre~sure of approximately 400 psi. ~s the pre~ure reache~ the yield point of the kapton group, one of the membranes will bur~t, rapidly followed by the ~:econd, third and fourth. ~heln the ~ourth membrane y~eld~, t~e pressure against it i~ ~our times itQ burst point.
The ga~ chamb~r or high pre~u~e chamber 86 is designed l:o allow an energy ef~icient gas front to reach the captivated , ' ~ ;' ! , . ~; ' ,'i, !, !, . ~ , 12 ~ATE~r lLPP~IC~hTIO~

membr~ne. The gas chamber i~ de~igned with a l~ngth to width (aspect ratio) of approximately 1:1. The spherical rear ~hape of the high pre~ure chamber recover~ some of the energy lo~t when the membranes initially yield. The length o~ the chamber is optimized to create the most efficiQnt pressure front with the leas~ amount o~ exces~ ga~. ~hi~ allows a smaller vacuum body to be de~igned, a6 le~ total volume ~f helium gas has to be controlled. A~ the pre~ure front advance~, it accelerates th~ captive carrier membrane which i~ al~o made of kapton material. The carrisr membr~ne 1~ hal~ed abruptly as it ~tops again~t the flange o~ the outlet plate an~ clo~e~ tho grooves 62. The p~rticle~ adhered to th~ ~ur~ac~ o~ the carrier membranes, ~uch as generlc material, leave thQ carri~r membrane a~ it ~uddenly de~orms into the rece~ 60 and fly through the hole~ in the ~topping plate to enter the target t:i~8u~. ~he rece~;f3 60 in the nozzlQ outlet plate 48 allow~
the carrîer membrane to deform outwardly without ruptur~ng.
However, under c:~rtain circum~tances, it may be desirable to have the carrier membrane also rupture.
By contai~ing the carrier membranQ in tact, the ~orce of the ga~: bla~ will not reach the tis~3uQ, thQreby eliminati~g pre~3sure tr~uma to the t~su~. Force o~ the high pr~3s!3ure helium can be dissipated rearwardly through the pa~sages 74 in the coupler into the large annular chamber 38, which i~ ~till und~r vacuum.

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CA 02248622 l998-09-23 13 ~AT~ ~ APPLICA~IO~

T~e actual ~light di~tance of the carrier menibrane i~
reduced fro~n many centimeter~ in prior art ~;tructure~: to far lesG than one centinleter and the target i~: di~po~;ed in substantially inti~ate contact with the ~topping plate. The carrier m~mbrane so act~ a~ a one way valve ina~much a~
previou~ly allowed a vacuum to be introduc~d to the target but which is ~eale~ aga~n~t the outlet plate to prevent the gas front from getting ~n front of the carrier membrane and di~rupting the fligh~ characteri~tice of the genetic materia~.
Accor~ing to a second embodiment of the pre~ent invention, a magnetically controlled v~lve may ~e u~ili2ed ln lieu of the rupturablQ membrane~ of the f ir~ embodiment whereby repeatabi~ity can be enhanced without the need ~or replacing the ruptured me~brane~. The valve, as shown in Pig.
24, would ~till b~ used with the carrier membrane as ~hown in the previous embo~i ~nt.
A housing lS0 is provided with a rece~s having a valve body 152 secured therein by mea~s of a threaded connection 154. Th~ valve body 152 i~ provid~d with a valve opening 156 having an annular valve ~eat 158 extending outwardly from a valve chamber 160 def~ned between the housing and the valve bc ~ly . A neodymium magnet 162 is moun~ed in a rece~ in the hous~ng 150 with a ma~or ~urface th~reo~ expo~ed to the interior o~ the valve chamber 160. An iron or ~teel plunger 164 is mounted in ~he val~e chamber 160 and is provided with a E;tem 168 which extends through the valve opening lS6 and is 1~ PATE~rr ~ PLIC~ O~

provided with an enlarged head 166~ An O rlng 170 having a diamet~r equal to the diameter of the valve seat 158 is mounted in a groove 172 having a trapezoidal cro~6 section to as~i~t in ret~ining the 0 ring within the groove under E:tre~6~ul condition6.

In operation, the plunger i6 dratm int:o engagement:~rith the magnet, whereby the o ring will be moved into ~ealing engaqement with the valve ~eat. High pre~ure ga~ i~
introduced into the valve c~amber through a g~G line 17Z. The high pressure ga~ ~ill~ the valv~ chamber 160 in contact with opposite ~urface~ of the main body of the plunger and upon reaching a pred~termined pre~ure, wit~ cause ~e p~unqeL t~
separat~ from the magnet. Once the plunger leave~ contact with the magnet, the holding force will be substantially reduced and the plunger will move do~nwardly a~ viewed in Fig.
Z4 to relea~e the gas within th~ ch~ ~r with an explosive force creating a 8hock wave which will strike the carr~er membrane to inject the particles adherin~ to the opposite ~urface of the membrane into cell~ or ti~sue. once the pressure drops within the val~e chamber 160, the force of the magnet will retract the plunger into contact with the magnet and seal the valve opening by mean~ of the 0 ring 170.
Suitable bumper~ 176 are pro~ided on opposite sides of the ' ''' ''.''"'''~ , . .
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, 15 PAT~r ~iPPLICATION

plung~r plate to cu~;h~on the impact of ~ e plunger plate ~gainst the housing and the valve boay.
The entire di6clo~ure o~ the provisional applicatlon upon which pr~ority is claimed, i~ hereby incorpor~ted into the present appl~ation by reference.
. While the invent~on ha~ been particularly ~hown and described with reference to preferred embodi.ments thereof, it will be und~rstood by those in ~he art that the foregoing ~nd other chang~s in form and aetails may be ma~e therein without departing from the ~pirit and scope of the invention~

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Claims (7)

1. An apparatus for delivering micro-projectiles into cells or tissue comprising:
a hollow cylindrical housing, a nozzle assembly secured to one end of said housing and including a plate having a plurality of through passages, an annular ring slidably mounted in said nozzle, a carrier membrane for carrying micro-projectiles disposed between said annular ring and said plate, a piston coaxially disposed in said housing in radial spaced relation thereto and having a central bore extending coaxially through said piston, one end of said piston having a pressure chamber therein and a flange disposed about said chamber, support means mounting said piston for axial sliding movement relative to said housing, a plurality of burst membranes disposed between said flange and said annular ring, an opposite end of said piston having a radially extending flange, pressure means for applying pressure to said flange for moving said piston to clamp said burst membranes against said ring and for applying pressure to said burst membranes whereby upon rupture of said burst membranes a surge of high pressure will engage said carrier membrane to impel said micro-projectiles outwardly of said nozzle assembly through said passage in said plate.

2. An apparatus as set forth in claim 1, wherein said carrier membrane is mounted for movement relative to said plate, said plate having a peripheral flange with a plurality of radially extending grooves whereby upon application of pressure to said carrier membrane said carrier membrane will be moved into engagement with said flange to close said grooves.

3. An apparatus as set forth in claim 2, further comprising a plurality of axially extending passages in said annular ring disposed in communication with said grooves in said plate in the absence of pressure being applied to said carrier membrane and disposed in communication with an annular space between said housing and said piston and means for connecting said annular space to a vacuum source to provide a vacuum in said passages of said plate when said nozzle assembly is disposed in contact with tissue.

4. An apparatus as set forth in claim 3, further comprising an end cap secured to an opposite end of said housing and having vacuum and pressure connecting means therein.

5. An apparatus as set forth in claim 1, wherein said pressure chamber in said one end of said piston has a length to width ratio of approximately 1:1 and is provided with a substantially hemispherical configuration.

6. A biolistic device which effectively but gently accelerates micro-projectiles into intact cells or tissues such as skin comprising:
a gas shock generator, a fixed, malleable membrane between the gas shock and the target, a shaped stopping surfaced for controlled de-acceleration of the distending membrane, immediately separating the fixed membrane and the target, and apertures in the stopping surface which allow transport of high speed micro-projectiles from the surface of the fixed membrane into the target.

7. A high pressure fast valve, which effectively contains high pressure until desired and which then opens essentially instantaneously or sufficiently rapidly as to crease an explosive gas shock, comprising:
either a permanent or electro-magnet with a smooth, flat, magnetically active surface and a smooth, flat, magnetically responsive surface which surfaces, when coupled, effectively seal a valve, a valve assembly which directs the force of the above stated magnetic coupling in direct opposition to either high pressure gas or liquid, and explosive release of the gas or liquid is achieved either when the pressure of the gas or liquid exceeds the strength of the magnetic closure force or when the magnetic filed is disrupted.