Gas driven gene delivery instrument

• US 5,584,807 A
• Filed: 01/20/1995
• Issued: 12/17/1996
• Est. Priority Date: 01/21/1994
• Status: Expired due to Term

• Current Assignee: PowderJect Vaccines, Inc. (Novartis Ag)
• Original Assignee: Agracetus Incorporated (Bayer AG)
• Inventors: McCabe, Dennis E.
• Primary Examiner(s): Green, Randall L.
• Assistant Examiner(s): VANOVER, PERRY
• Application Number:
  US08/376,319
• Time in Patent Office: 697 Days
• Field of Search: 604/68-72, 604/140-143, 604/146, 604/62, 604/23, 604/24
• US Class Current: 604/71
• CPC Class Codes: A61M 2005/005 Magazines with multiple ampoules directly inserted into an injection or infusion device, e.g. revolver-like magazines containing ampoules with or without needles
• CPC Class Codes: A61M 5/2053 Media being expelled from injector by pressurised fluid or vacuum for infusion A61M5/145, A61M5/155
• CPC Class Codes: A61M 5/3015 for injecting a dose of particles in form of powdered drug, e.g. mounted on a rupturable membrane and accelerated by a gaseous shock wave or supersonic gas flow cell injection devices C12M3/006
• CPC Class Codes: C12M 35/00 Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion machines for extracting juice from animal or plant tissue by electroplasmolysis A23N1/006, processes employing electric or wave energy B01J19/08; treatment of microorganisms or enzymes with electrical or wave energy C12N13/00; methods for cell fusion C12N15/02; introduction of foreign genetic material C12N15/87

Abstract

A gas driven apparatus for accelerating particles coated with a genetic material into a target comprises a reservoir for releasably retaining a gas at a sufficiently high pressure to detach the particles from the surface of a sample cartridge and to carry the particles through the apparatus toward the target. When leaving the apparatus, the particles entrained in the gas stream pass through a substantially conical exit nozzle which causes the pattern of distribution of the particles to greatly expand. Methods for using the apparatus and for preparing the sample cartridges are also described.

Claims

1. A gene delivery instrument adapted to be connected to a source of compressed gas, the instrument comprising

a body having a particle acceleration passage formed therein and opening at one end thereof;

a valve adapted to be connected to the source of compressed gas and connected to selectively admit compressed gas into the particle acceleration passage to make an accelerating gas stream;

a cartridge chamber of a shape adapted to receive therein a particle cartridge having carrier particles coated with genetic material deposited thereon, the chamber positioned in the body and in the particle acceleration passage so that the gas stream expanding down the particle acceleration passage will pass adjacent the particle cartridge and pick up and accelerate the carrier particles from the cartridge; and

a substantially conical exit nozzle at the opening of the particle acceleration passage from the body, the conical shape of the conical exit nozzle being such that the cone of the exit nozzle is significantly longer in the direction of gas flow than it is wide in the direction perpendicular to the gas flow at any point, the conical shape causing the gas stream exiting from the body to expand outward so as to distribute the carrier particles over a wider area than would be the case if the exit nozzle were not conical.

2. An instrument as claimed in claim 1 wherein there is a cartridge holder having multiple cartridge chambers formed in it, the cartridge holder movably attached to the body so that any one of the cartridge chambers can be positioned in the particle acceleration passage.

3. An instrument as claimed in claim 2 wherein the cartridge holder is a cylinder which rotates relative to the body to position different cartridge chambers in the particle acceleration passage.

4. An instrument as claimed in claim 3 wherein there is a registration mechanism to fix the cartridge holder in to position at each of the positions in which a one of the cartridge chambers is rotated into the particle acceleration passage.

5. An instrument as claimed in claim 1 wherein there is an orifice in the particle acceleration passage after the cartridge chamber, the orifice being narrower than the interior concave dimension of the particle cartridge to facilitate the gas stream accelerating the carrier particles after it picks the particles up off of the particle cartridge.

7. An instrument as claimed in claim 1 wherein the compressed gas is helium.

9. An instrument as claimed in claim 1 wherein the acceleration passage is polished until smooth.

6. A gene delivery instrument adapted to be connected to a source of compressed gas, the instrument comprising

a body having a particle acceleration passage formed therein and opening at one end thereof;

a valve adapted to be connected to the source of compressed gas and connected to selectively admit compressed gas into the particle acceleration passage to make an accelerating gas stream;

a cartridge chamber of a shape adapted to receive therein a particle cartridge having carrier particles coated with genetic material deposited thereon, the chamber positioned in the body and in the particle acceleration passage so that the gas stream expanding down the particle acceleration passage will pass adjacent the particle cartridge and pick up and accelerate the carrier particles from the cartridge;

a substantially conical exit nozzle at the opening of the particle acceleration passage from the body, the conical shape of the conical exit nozzle being such that the cone of the exit nozzle is longer in the direction of gas flow than it is wide in the direction perpendicular to the gas flow, the conical shape causing the gas stream exiting from the body to expand outward so as to distribute the carrier particles over a wider area than would be the case if the exit nozzle were not conical; and

a spacer attached to instrument at the end of the exit nozzle to space the instrument a predetermined distance from a tissue or living organism to be treated.

8. A gene delivery instrument adapted to be connected to a source of compressed gas, the instrument comprising

a body having a particle acceleration passage formed therein and opening at one end thereof;

a valve adapted to be connected to the source of compressed gas and connected to selectively admit compressed gas into the particle acceleration passage to make an accelerating gas stream;

a cartridge chamber of cylindrical shape adapted to receive therein a tubular particle cartridge having carrier particles coated with genetic material deposited on the interior of the cartridge, the chamber positioned in the body and in the particle acceleration passage so that the gas stream expanding down the particle acceleration passage will pass adjacent the particle cartridge and pick up and accelerate the carrier particles from the cartridge; and

a substantially conical exit nozzle at the opening of the particle acceleration passage from the body, the conical shape of the conical exit nozzle being such that the cone of the exit nozzle is longer in the direction of gas flow than it is wide in the direction perpendicular to the gas flow, the conical shape causing the gas stream exiting from the body to expand outward so as to distribute the carrier particles over a wider area than would be the case if the exit nozzle were not conical.

10. A gene delivery instrument adapted to be connected to a source of compressed gas, the instrument comprising

a body having a particle acceleration passage formed therein and opening at one end thereof;

a valve adapted to be connected to the source of compressed gas and connected to selectively admit compressed gas into the particle acceleration passage to make an accelerating gas stream;

a cartridge chamber of a shape adapted to receive therein a particle cartridge having carrier particles coated with genetic material deposited thereon, the chamber positioned in the body and in the particle acceleration passage so that the gas stream expanding down the particle acceleration passage will pass adjacent the particle cartridge and pick up and accelerate the carrier particles from the cartridge; and

a substantially conical exit nozzle at the opening of the particle acceleration passage from the body, the conical shape of the conical exit nozzle being such that the cone of the exit nozzle is longer in the direction of gas flow than it is wide in the direction perpendicular to the gas flow, the conical shape causing the gas stream exiting from the body to expand outward so as to distribute the carrier particles over a wider area than would be the case if the exit nozzle were not conical; and

a helium bleed tube provided extending across the valve to introduce residual helium in the exit nozzle prior to operation of the instrument.

11. As an article of manufacture, a cartridge for use in a compressed gas-driven gene delivery instrument, the cartridge comprising a concave rigid body with an arcuate linear passage formed on the interior thereof and a deposit of carrier particles coated with genetic material deposited in the passage in the cartridge so that the particles can be dislodged by an expanding gas stream passing through the passage, the cartridge being manually manipulable by a user without the user having to touch the carrier particles deposited on the cartridge.

12. A cartridge as claimed in claim 11 wherein the cartridge is a tubular shape with a cylindrical passage formed extending through the center thereof.

13. A cartridge as claimed in claim 11 wherein the carrier particles are gold particles.

14. A cartridge as claimed in claim 11 wherein the carrier particles are deposited in the passage in a linear pattern aligned with the axis of the passage.

15. As an article of manufacture, a cartridge for use in a compressed gas-driven gene delivery instrument, the cartridge comprising a cylindrical rigid tubular body with a cylindrical passage formed through the interior thereof and a deposit of carrier particles coated with genetic material deposited in the passage in the cartridge so that the particles can be dislodged by an expanding gas stream passing through the passage, the cartridge being manually manipulable by a user without the user having to touch the carrier particles deposited on the cartridge.

16. A method for delivery of genetic material into a target organism, the method comprising the steps of:

connecting a gene delivery instrument having formed in it a particle acceleration passage to a source of compressed gas through a controllable valve;

placing a particle cartridge of suitable shape into a suitably formed cartridge chamber in the particle acceleration passage of the gene delivery instrument, the particle cartridge having been previously loaded onto its interior concave surface with biologically inert carrier particles small in relation to the size of the cells of the organism onto which have been coated copies of the genetic material,

placing the gene delivery instrument adjacent to the target organism with the particle acceleration passage directed toward the target organism;

operating the valve to permit flow of compressed gas into and through the particle acceleration passage of the gene delivery instrument to create a gas stream in the particle acceleration passage under conditions such that the gas stream picks up the carrier particles from the particle cartridge and carries the carrier particles toward the target organism; and

expanding the gas stream as it passes out of the instrument by means of a conically tapered exit nozzle on the gene delivery instrument which acts on the gas stream to expand the gas stream generally perpendicularly to its direction of flow so that the particles are spread out when they impact the target organism.

17. A method as claimed in claim 16 wherein carrier particles are placed on the interior concave surface of the cartridge by suspending the carrier particles in liquid, placing the liquid suspension into the cartridge, and evaporating the liquid from the suspension.

18. A method as claimed in claim 17 wherein there is further added to the liquid suspension a mild adhesive agent to slightly adhere the carrier particles to the interior surface of the cartridge.

19. A method as claimed in claim 16 the placing step is performed by placing a spacer on the instrument against the target organism.

20. A method as claimed in claim 16 wherein the compressed gas is helium.

21. A method as claimed in claim 16 wherein the step of placing the particle cartridge into the cartridge chamber is performed by placing a plurality of particle cartridges into a cartridge holder having multiple cartridge chambers formed in it and then placing the cartridge holder into the instrument so that multiple operations of the instrument can be performed.

22. A method for delivery of genetic material into a target organism, the method comprising the steps of:

connecting a gene delivery instrument having formed in it a particle acceleration passage to a source of compressed gas through a controllable valve;

placing a particle cartridge in the particle acceleration passage of the gene delivery instrument, the particle cartridge having been previously loaded onto its interior concave surface with biologically inert carrier particles small in relation to the size of the cells of the organism onto which have been coated copies of the genetic material,

placing the gene delivery instrument adjacent to the target organism with the particle acceleration passage directed toward the target organism;

operating the valve to permit flow of compressed gas into and through the particle acceleration passage of the gene delivery instrument to create a gas stream in the particle acceleration passage under conditions such that the gas stream picks up the carrier particles from the particle cartridge and carries the carrier particles toward the target organism; and

expanding the gas stream as it passes out of the instrument by means of a conically tapered exit nozzle on the gene delivery instrument which acts on the gas stream to expand the gas stream generally perpendicularly to its direction of flow so that the particles are spread out when they impact the target organism.