Title of Invention	A DEVICE ADAPTED TO DELIVER PARTICLES INTO A TARGET CELL OR TISSUE
Abstract	The present invention relates to a device for delivering particles into a target cell or tissue, said device comprising: a body having an elongate acceleration passage formed therein, said passage having an inlet and an outlet; and a rotational flow element arranged upstream from the inlet of the acceleration passage, wherein said rotational flow element imparts a rotary motion in a flow of gas passing therethrough prior to entry of said gas flow into the acceleration passage.

Title of Invention

A DEVICE ADAPTED TO DELIVER PARTICLES INTO A TARGET CELL OR TISSUE

Abstract

The present invention relates to a device for delivering particles into a target cell or tissue, said device comprising: a body having an elongate acceleration passage formed therein, said passage having an inlet and an outlet; and a rotational flow element arranged upstream from the inlet of the acceleration passage, wherein said rotational flow element imparts a rotary motion in a flow of gas passing therethrough prior to entry of said gas flow into the acceleration passage.

Full Text	The present invention relates to a device adapted to deliver particles into a target cell or tissue, more particularly to instruments for delivering material into cells using particle-mediated delivery techniques. Particle-mediated delivery of materials, particularly nucleic acid molecules, into living cells and tissue has emerged as an important tool of plant and animal biotechnology. Transient and long-term expression of genetic material delivered via particle-mediated techniques into target cells has been demonstrated in a wide variety of microorganisms, plants and animals. Successful integration of DNA into germ cells has also been demonstrated using these techniques, and particle-mediated gene delivery instruments have been used to deliver other materials into cells, including pharmaceuticals and biopharmaceuticals such as proteins, peptides and hormones. As the fundamentals of the technology of particle-mediated delivery have developed, attention has increasingly shifted toward the development of devices that offer the operator the ability to perform the particle-mediated gene delivery in a swift and convenient fashion. It is also desirable for the operation of the delivery device to be efficient and highly replicable. One particular device, which uses compressed gas to accelerate carrier particles carrying biological materials into target tissue, is described in commonly owned International publication No. WO 95/19799, the disclosure of which is incorpcrated herein by reference. The distribution or spread of carrier particles delivered from a particle-mediated delivery device, such as the device of WO 95/19799, can be critical in some applications, particularly when biological material is being delivered, for example genetic material. In applications where germline transformation events are desired, the need to control the delivery pattern of carrier particles is substantially more acute In yet a further embodiment, a particle delivery device is provided which comprises a body with an elongate acceleration passage formed therein. The device includes a source of particles that is arranged adjacent to an inlet for the acceleration passage. A turbulent flow element is arranged upstream from both the acceleration passage and the source of particles, whereby such an element is used to create turbulence in a flow of gas passing therethrough prior to its contact with the source of particles. In one particular aspect of the invention, the turbulent flow element comprises a gas conduit arranged above the source of particles, wherein the gas conduit has stepped portion of increased diameter. In another embodiment of the invention, a particle delivery device is provided which comprises a flow constriction element that restricts flow of compressed gas into the device. Accordingly, the present invention provides a device adapted to deliver particles into a target cell or tissue, said device comprising: a body having an elongate acceleration chamber formed therein, said chamber having an inlet and an outlet; a source of compressed gas coupled to the body for delivery of a gas flow into the inlet of the acceleration chamber; and means to isolate a charge of compressed gas in the instrument for each particle delivery operation, such that additional volume of compressed gas from said source of compressed gas is prevented from flowing through the instrument during particle delivery. These and other objects, features and advantages of the present invention will become apparent from the following specification, read in light of the accompanying drawings, Figure 1 is an illustration depicting the general operation of a gas-driven particle delivery device. Figures 2A-2C are schematic illustrations of the effect of variations in the geometry of the exit nozzle in the device of Figure 1. WE CLAIM: 1. A device (10) adapted to deliver particles into a target cell or tissue, said device comprising; a body (33) having an elongate acceleration chamber formed therein, said chamber having an inlet and an outlet; a source of compressed gas (12) coupled to the body for delivery of a gas flow into the inlet of the acceleration chamber; and means to isolate a charge of compressed gas in the instrument for each particle delivery operation, such that additional volume of compressed gas from said source of compressed gas (12) is prevented from flowing through the instrument during particle delivery. 2. The device as claimed in claim 1, wherein said means to isolate a charge of compressed gas allows gas from said source (12) to recharge the instrument after the delivery operation. 3. The device as claimed in claim 1 or 2, wherein said means to isolate a charge of compressed gas comprises a flow constriction element (60) that limits flow of gas from the source (12) into the body. 4. The device as claimed in claim 3, wherein the flow constriction element (60) comprises a plug having an orifice (62) passing therethrough. 5. The device as claimed in claim 1 or 25 wherein said means to isolate a charge of compressed gas comprises a combination of valves. 6. The device as claimed in claim 5, wherein said values comprise an inlet valve arranged to be closed during the operation of the instrument, and then opened when the instrument is not being operated in order to charge the instrument for the subsequent operation. 7. The device as claimed in anyone of claims 1 to 6, further comprising a rotational flow element (50) arranged upstream from the inlet of the acceleration chamber, wherein said rotational flow element imparts a rotary motion in a flow of gas passing therethrough prior to entry of said gas flow into the acceleration chamber. 8. A device (10) adapted to deliver particles into a target cell or tissue, said device comprising: a body (33) having an acceleration passage formed therein, said passage having an inlet and an outlet; and a rotational flow element (50) arranged within the acceleration passage, wherein said rotational flow element imparts a rotary motion in a flow of gas passing therethrough, whereby particles are delivered into said target cell or tissue. 9. A device (10) adapted to deliver particles into a target cell or tissue, said device comprising: a body (33) having an acceleration passage, said passage having an inlet and an outlet; a actuator (30) for admitting a gaseous flow through the inlet into the passage, the gaseous flow accelerating through the passage and carrying particles out of the outlet; and a rotary flow inducing element (50) located in the passage to impart a rotary motion to the gaseous flow, whereby particles are delivered into said target cell or tissue. 10. A device (10) adapted to deliver particles into a target cell or tissue, said device comprising: a body (33) having an elongate acceleration chamber formed therein, said chamber having an inlet and an outlet; and a rotational flow element (50) arranged upstream from the inlet of the acceleration chamber, wherein said rotational flow element imparts a rotary motion in a flow of gas passing therethrough prior to entry of said gas flow into the acceleration chamber, whereby particles are delivered into said target cell or tissue. 11. The device as claimed in claim 10, wherein said rotational flow element comprises a baffle (50) disposed within a gas chamber or conduit arranged upstream from the acceleration chamber, said baffle having an upstream face (52) and a downstream face (54). 12. The device as claimed in claim 11, wherein said baffle is comprised of a substantially cylindrical plug having an outer surface with a gas channel (56) formed therein, said gas channel allowing passage of a gas flow from the upstream face to the downstream face of the baffle. 13. The device as claimed in claim 12, wherein the gas channel (56) is arranged in angular relation with the major axis of the baffle. 14. The device as claimed in claim 12 further comprising a plurality of gas channels (56) arranged in a radial array about the outer surface of the baffle, wherein said gas channels are each arranged in angular relation with the major axis of the baffle and allow passage of a gas flow therethrough. 15. The device as claimed in claim 12, wherein said baffle (70) further comprises a substantially linear central bore (82) passing between the upstream (76) and downstream faces of the baffle, said central bore allowing passage of a gas flow therethrough. 16. The device as claimed in claim 15, wherein said baffle further comprises an annular seat (84) coaxially aligned with the central bore and disposed within the upstream face of the baffle. 17. The device as claimed in claim 16, wherein the annular seat (84) is configured to accept and retain a cylindrical cartridge containing particles to be delivered from the device. 18. A device (10) adapted to deliver particles into a target cell or tissue, said device comprising: a body (33) having an elongate acceleration chamber formed therein, said chamber having an inlet, and an outlet which terminates in an exit nozzle (46); a mixing chamber (35) having an inlet, and an outlet that communicates with the inlet of the acceleration chamber; an upstream gas chamber (37) having an outlet that communicates with the inlet of the mixing chamber, wherein a rotational flow element is arranged in the outlet of the upstream gas chamber (50) and imparts a rotary motion in a flow of gas passing from the upstream gas chamber into the mixing chamber, whereby particles are delivered into said target cell or tissue. 19. The device as claimed in claim 18, wherein said rotational flow element (50) comprises a substantially cylindrical baffle having an outer surface, an upstream face and a downstream face, said baffle further having a plurality of gas channels (56) formed in the outer surface thereof which allow passage of a gas flow from the upstream face to the downstream face of the baffle. 20. The device as claimed in claim 19, wherein flow of gas through the plurality of gas channels (56) in the baffle creates a vortex within the mixing chamber. 21. The device as claimed in claim 20, wherein the baffle further comprises a substantially linear central bore (82) passing between the upstream and downstream faces of the baffle, said central bore allowing a gas flow containing particles to pass therethrough. 22. A device (10) for delivering particles into a target cell or tissue, said device comprising: a body (33) having an elongate acceleration chamber formed therein, said chamber having an inlet and an outlet; a source of particles to be delivered from the device, wherein said source is adjacent to the inlet of the acceleration chamber; and a turbulent flow element (100) arranged upstream from the inlet of the acceleration chamber and the source of particles, whereby said turbulent flow element creates turbulence in a flow of gas passing therethrough prior to contact of said gas flow with the source of particles. 23. The device as claimed in claim 22, wherein the turbulent flow element (100) comprises a gas conduit having a stepped portion (104) of increased diameter. 24. A device adapted to deliver particles into a target cell or tissue substantially as herein described with reference to the accompanying drawings.

Full Text

The present invention relates to a device adapted to deliver particles into a target cell or tissue, more particularly to instruments for delivering material into cells using particle-mediated delivery techniques.
Particle-mediated delivery of materials, particularly nucleic acid molecules, into living cells and tissue has emerged as an important tool of plant and animal biotechnology. Transient and long-term expression of genetic material delivered via particle-mediated techniques into target cells has been demonstrated in a wide variety of microorganisms, plants and animals. Successful integration of DNA into germ cells has also been demonstrated using these techniques, and particle-mediated gene delivery instruments have been used to deliver other materials into cells, including pharmaceuticals and biopharmaceuticals such as proteins, peptides and hormones.
As the fundamentals of the technology of particle-mediated delivery have developed, attention has increasingly shifted toward the development of devices that offer the operator the ability to perform the particle-mediated gene delivery in a swift and convenient fashion. It is also desirable for the operation of the delivery device to be efficient and highly replicable.
One particular device, which uses compressed gas to accelerate carrier particles carrying biological materials into target tissue, is described in commonly owned International publication No. WO 95/19799, the disclosure of which is incorpcrated herein by reference.
The distribution or spread of carrier particles delivered from a particle-mediated delivery device, such as the device of WO 95/19799, can be critical in some applications, particularly when biological material is being delivered, for example genetic material. In applications where germline transformation events are desired, the need to control the delivery pattern of carrier particles is substantially more acute

In yet a further embodiment, a particle delivery device is provided which comprises a body with an elongate acceleration passage formed therein. The device includes a source of particles that is arranged adjacent to an inlet for the acceleration passage. A turbulent flow element is arranged upstream from both the acceleration passage and the source of particles, whereby such an element is used to create turbulence in a flow of gas passing therethrough prior to its contact with the source of particles. In one particular aspect of the invention, the turbulent flow element comprises a gas conduit arranged above the source of particles, wherein the gas conduit has stepped portion of increased diameter.
In another embodiment of the invention, a particle delivery device is provided which comprises a flow constriction element that restricts flow of compressed gas into the device.
Accordingly, the present invention provides a device adapted to deliver particles into a target cell or tissue, said device comprising: a body having an elongate acceleration chamber formed therein, said chamber having an inlet and an outlet; a source of compressed gas coupled to the body for delivery of a gas flow into the inlet of the acceleration chamber; and means to isolate a charge of compressed gas in the instrument for each particle delivery operation, such that additional volume of compressed gas from said source of compressed gas is prevented from flowing through the instrument during particle delivery.
These and other objects, features and advantages of the present invention will become apparent from the following specification, read in light of the accompanying drawings,
Figure 1 is an illustration depicting the general operation of a gas-driven particle delivery device.
Figures 2A-2C are schematic illustrations of the effect of variations in the geometry of the exit nozzle in the device of Figure 1.

WE CLAIM:
1. A device (10) adapted to deliver particles into a target cell or tissue, said device comprising; a body (33) having an elongate acceleration chamber formed therein, said chamber having an inlet and an outlet; a source of compressed gas (12) coupled to the body for delivery of a gas flow into the inlet of the acceleration chamber; and means to isolate a charge of compressed gas in the instrument for each particle delivery operation, such that additional volume of compressed gas from said source of compressed gas (12) is prevented from flowing through the instrument during particle delivery.
2. The device as claimed in claim 1, wherein said means to isolate a charge of compressed gas allows gas from said source (12) to recharge the instrument after the delivery operation.
3. The device as claimed in claim 1 or 2, wherein said means to isolate a charge of compressed gas comprises a flow constriction element (60) that limits flow of gas from the source (12) into the body.
4. The device as claimed in claim 3, wherein the flow constriction element (60) comprises a plug having an orifice (62) passing therethrough.
5. The device as claimed in claim 1 or 25 wherein said means to isolate a charge of compressed gas comprises a combination of valves.
6. The device as claimed in claim 5, wherein said values comprise an inlet valve arranged to be closed during the operation of the instrument, and then opened when the instrument is not being operated in order to charge the instrument for the subsequent operation.

7. The device as claimed in anyone of claims 1 to 6, further comprising a rotational flow element (50) arranged upstream from the inlet of the acceleration chamber, wherein said rotational flow element imparts a rotary motion in a flow of gas passing therethrough prior to entry of said gas flow into the acceleration chamber.
8. A device (10) adapted to deliver particles into a target cell or tissue, said device comprising: a body (33) having an acceleration passage formed therein, said passage having an inlet and an outlet; and a rotational flow element (50) arranged within the acceleration passage, wherein said rotational flow element imparts a rotary motion in a flow of gas passing therethrough, whereby particles are delivered into said target cell or tissue.
9. A device (10) adapted to deliver particles into a target cell or tissue, said device comprising: a body (33) having an acceleration passage, said passage having an inlet and an outlet; a actuator (30) for admitting a gaseous flow through the inlet into the passage, the gaseous flow accelerating through the passage and carrying particles out of the outlet; and a rotary flow inducing element (50) located in the passage to impart a rotary motion to the gaseous flow, whereby particles are delivered into said target cell or tissue.
10. A device (10) adapted to deliver particles into a target cell or tissue, said device
comprising: a body (33) having an elongate acceleration chamber formed therein, said
chamber having an inlet and an outlet; and a rotational flow element (50) arranged
upstream from the inlet of the acceleration chamber, wherein said rotational flow
element imparts a rotary motion in a flow of gas passing therethrough prior to entry of
said gas flow into the acceleration chamber, whereby particles are delivered into said
target cell or tissue.

11. The device as claimed in claim 10, wherein said rotational flow element comprises
a baffle (50) disposed within a gas chamber or conduit arranged upstream from the
acceleration chamber, said baffle having an upstream face (52) and a downstream face
(54).
12. The device as claimed in claim 11, wherein said baffle is comprised of a substantially cylindrical plug having an outer surface with a gas channel (56) formed therein, said gas channel allowing passage of a gas flow from the upstream face to the downstream face of the baffle.
13. The device as claimed in claim 12, wherein the gas channel (56) is arranged in angular relation with the major axis of the baffle.
14. The device as claimed in claim 12 further comprising a plurality of gas channels (56) arranged in a radial array about the outer surface of the baffle, wherein said gas channels are each arranged in angular relation with the major axis of the baffle and allow passage of a gas flow therethrough.
15. The device as claimed in claim 12, wherein said baffle (70) further comprises a substantially linear central bore (82) passing between the upstream (76) and downstream faces of the baffle, said central bore allowing passage of a gas flow therethrough.
16. The device as claimed in claim 15, wherein said baffle further comprises an annular seat (84) coaxially aligned with the central bore and disposed within the upstream face of the baffle.

17. The device as claimed in claim 16, wherein the annular seat (84) is configured to accept and retain a cylindrical cartridge containing particles to be delivered from the device.
18. A device (10) adapted to deliver particles into a target cell or tissue, said device comprising: a body (33) having an elongate acceleration chamber formed therein, said chamber having an inlet, and an outlet which terminates in an exit nozzle (46); a mixing chamber (35) having an inlet, and an outlet that communicates with the inlet of the acceleration chamber; an upstream gas chamber (37) having an outlet that communicates with the inlet of the mixing chamber, wherein a rotational flow element is arranged in the outlet of the upstream gas chamber (50) and imparts a rotary motion in a flow of gas passing from the upstream gas chamber into the mixing chamber, whereby particles are delivered into said target cell or tissue.
19. The device as claimed in claim 18, wherein said rotational flow element (50) comprises a substantially cylindrical baffle having an outer surface, an upstream face and a downstream face, said baffle further having a plurality of gas channels (56) formed in the outer surface thereof which allow passage of a gas flow from the upstream face to the downstream face of the baffle.
20. The device as claimed in claim 19, wherein flow of gas through the plurality of gas channels (56) in the baffle creates a vortex within the mixing chamber.
21. The device as claimed in claim 20, wherein the baffle further comprises a
substantially linear central bore (82) passing between the upstream and downstream
faces of the baffle, said central bore allowing a gas flow containing particles to pass
therethrough.

22. A device (10) for delivering particles into a target cell or tissue, said device
comprising: a body (33) having an elongate acceleration chamber formed therein, said
chamber having an inlet and an outlet; a source of particles to be delivered from the
device, wherein said source is adjacent to the inlet of the acceleration chamber; and a
turbulent flow element (100) arranged upstream from the inlet of the acceleration
chamber and the source of particles, whereby said turbulent flow element creates
turbulence in a flow of gas passing therethrough prior to contact of said gas flow with
the source of particles.
23. The device as claimed in claim 22, wherein the turbulent flow element (100)
comprises a gas conduit having a stepped portion (104) of increased diameter.
24. A device adapted to deliver particles into a target cell or tissue substantially as
herein described with reference to the accompanying drawings.

Documents:

2113-mas-1997- abstract.pdf

2113-mas-1997- assignment.pdf

2113-mas-1997- claims duplicate.pdf

2113-mas-1997- claims original.pdf

2113-mas-1997- correspondence others.pdf

2113-mas-1997- correspondence po.pdf

2113-mas-1997- descripiton complete duplicate.pdf

2113-mas-1997- descripiton complete original.pdf

2113-mas-1997- drawings.pdf

2113-mas-1997- form 1.pdf

2113-mas-1997- form 26.pdf

2113-mas-1997- form 3.pdf

2113-mas-1997- other documents.pdf

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Patent Number

204499

Indian Patent Application Number

2113/MAS/1997

PG Journal Number

26/2007

Publication Date

29-Jun-2007

Grant Date

22-Feb-2007

Date of Filing

25-Sep-1997

Name of Patentee

POWDERJET VACCINES INC.,

Applicant Address

585 SCIENCE DRIVE ,,SUITE C, MADISON,,WISCONSIN 53711

Inventors:

#	Inventor's Name	Inventor's Address
1	DENNIS E.McCABE.	8777 AIRPORT ROAD,MIDDLETON,WISCONSIN 53562
2	RICHARD J HEINZEN	8777 AIR5PORT R45OAD,MIDDLETON,WISCONSIN 53562

PCT International Classification Number

A61K048/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	08/719503	1996-09-25	U.S.A.