Sterile aspiration/reinjection systems

• US 6,796,957 B2
• Filed: 10/23/2001
• Issued: 09/28/2004
• Est. Priority Date: 07/10/2001
• Status: Active Grant

• Current Assignee: Biomet Manufacturing, LLC (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Myocardial Therapeutics Incorporated
• Inventors: Li, Hong, Carpenter, Kenneth W., Sasamine, Kazuo, Malphus, E. Thomas, Fourmont, Michelle
• Primary Examiner(s): MENDEZ, MANUEL A
• Application Number:
  US10/004,525
• Publication Number:
  US 20030069543A1
• Time in Patent Office: 1,071 Days
• Field of Search: 604/65-67, 604/156, 604/30-36, 604/82, 604/131, 604/93.01, 604/154, 604/155, 604/157, 604/315, 128/DIG.1, 128/DIG.12, 128/DIG.13
• US Class Current: 604/93.01
• CPC Class Codes: A61B 2090/062 penetration depth
• CPC Class Codes: A61M 2025/0089 Single injection needle protruding axially, i.e. along the longitudinal axis of the catheter, from the distal tip
• CPC Class Codes: A61M 2202/0021 removed from and reintroduced into the body, e.g. after treatment
• CPC Class Codes: A61M 2202/0413 Blood
• CPC Class Codes: A61M 2205/75 with filters
• CPC Class Codes: A61M 25/0084 being one or more injection needles
• CPC Class Codes: Y10S 977/916 Gene therapy

Abstract

The invention provides systems containing a sterile container for aspiration, filtering, treating and reinjection into a subject of a bodily fluid in a sterile environment. The systems are particularly designed to facilitate transfection of cells within the sterile container by gene therapy molecules and reinjection of the transfected cells into the donor at controlled depth in precisely controlled volumes such as is useful for revascularization of ischemic cardiac tissue. For injection, a pressure actuator, preferably hand-held, applies force to liquids held within the sterile container in precisely controlled increments, thereby expressing liquids through a hollow needle or injection catheter in precisely controlled microvolumes. The invention systems include a hand-held injection device with audible cues that correspond to an operator-selected injection volume and/or audible cues that correspond to needle penetration depth selected by the operator.

Claims

1. An aspiration/injection system for a bodily liquid containing undesired components, said system comprising the following components:

a) a sterile container comprising in liquid-tight arrangement;

i) a liquid-tight cylindrical housing with an opening;

wherein the interior of the housing is maintained in a sterile condition and has a maximum internal volume in the range of about 3 ml to about 70 ml;

ii) a self-sealing puncturable sterile barrier covering the opening for receiving a hollow needle cannula, and

iii) a plunger in liquid-tight co-axial connection with the interior of the housing,

b) a pressure actuator co-axially coupleable to the plunger of the sterile container so that the pressure actuator exerts a positive pressure on the plunger to expel the liquid from the sterile container in a controlled volume by distal movement of the plunger one or more precisely controlled longitudinal distances;

c) a flow-through filter assembly, said filter assembly comprising;

i) one or more filters with pores sized to filter out undesired components from the liquid and;

ii) a filter receptacle having at least a distal part and a proximal part, which parts engage to cooperatively form a liquid-tight enclosure for the one or more filters;

iii) a hollow needle cannula attached to the exterior of the proximal part of the filter receptacle; and

iv) a liquid-tight liquid connector attached to the exterior of the distal side of the filter receptacle;

e) an aspiration needle with hub for attachment to the fluid connector; and

f) a two way diverter;

wherein components of the system can be operationally coupled in various fluid-tight combinations.

2. The aspiration/injection system of claim 1, wherein the precisely controlled volume is from about 10 ml to about 36 ml.

3. The-aspiration/injection system of claim 1, wherein the sterile container is sufficiently air-tight that the pressure actuator can establish a partial vacuum within the sterile container for aspiration of liquids therein.

4. The aspiration/injection system of claim 1, wherein the pressure actuator comprises a plunger and a seal between the plunger and the housing sufficient to establish a partial vacuum within the housing by withdrawal of the plunger.

5. The aspiration/injection system of claim 1, wherein the pressure actuator applies mechanical pressure to the liquid within the sterile container so as to express the controlled volume of the liquid from the container.

6. The aspiration/injection system of claim 5, wherein the precisely controlled volume is in the range from about 0.1 ml to about 3.0 ml.

7. The aspiration/injection system of claim 1, wherein the sterile container is preloaded to contain one or more agents useful in processing of bone marrow aspirate liquids to enhance the yield of one or more autologous growth factors therefrom.

8. The aspiration/injection system of claim 7, wherein the growth factor is selected from the group consisting of human vascular endothelial growth factor (VEGF), VEGF-2, HIF-1, and basic fibroblast growth factor (bFGF).

9. The aspiration/injection system of claim 1, further comprising a hollow needle for releasable attachment to the liquid connector of the filter assembly.

10. The aspiration/injection system of claim 1, wherein the fluid connector is a male luer connection for releasably attaching the flow-through filter assembly to the hub of a hollow needle.

11. The aspiration/injection system of claim 1, wherein the distal part and the proximal part of the filter receptacle releasably engage by means selected from the group consisting of friction fitting, mating screw threads provided thereon, and luer lock.

12. The aspiration/injection system of claim 1, wherein the distal-most filter has a larger average pore size than the proximal-most filter.

13. The aspiration/injection system of claim 12 wherein the filters are spaced apart to prevent plugging and have average pore openings in the range from about 50 microns to about 300 microns.

14. The aspiration/injection system of claim 1, wherein the diameter of the filters is 3 to 10-fold larger than the interior diameter of the hub.

15. The aspiration/injection system of claim 1, wherein the sterile container-comprises in co-axial arrangement:

a housing having a cylindrical portion and a distal portion of reduced diameter;

a distal opening;

a puncturable, self-sealing sterile barrier covering the distal opening;

one or more piston ring-like stops fixedly mounted circumferentially around an interior wall of the cylindrical portion of the housing;

a piston-like plunger having a domed head portion shaped to conform to the interior of the distal end of the housing;

wherein the plunger is liquid-tightly and moveably mounted within the cylindrical portion of the housing so that the stroke of the plunger is defined by abutment of the head portion against the distal opening and against a stop; and

a proximally extending plunger handle for moving the plunger within the cylindrical portion of the housing;

wherein the sterile barrier, the cylindrical portion of the housing, and the exterior of the domed head portion of the plunger form the sterile chamber and the sterile chamber is expandable and compressible.

16. The aspiration/injection system of claim 15, wherein withdrawal of the plunger head from the distal portion of the housing by the pressure actuator generates a negative pressure within the sterile chamber for aspiration of fluids thereinto and movement of the plunger head from the stop towards the distal end creates a positive pressure on a liquid within the sterile chamber for expelling of the fluids therefrom.

17. The aspiration/injection system of claim 15, wherein the opening at the distal end of the container is surrounded by a protruding lip that is threaded or provides a male luer fitting for attachment to a hollow needle.

18. The aspiration/injection system of claim 15, wherein the stop is provided with a liquid-tight seal between the cylindrical portion of the plunger and the face of each of the one or more piston ring-like stops.

19. The aspiration/injection system of claim 18, wherein the liquid-tight seal is seated in a groove on the face of the one or more stops.

20. The aspiration/injection system of claim 15 wherein the head portion of the plunger has one or more seals circumferentially attached thereto, wherein the seals provide a liquid-tight seal between the interior wall of the housing and the head portion of the plunger.

21. The aspiration/injection system of claim 15 wherein the maximum interior volume of the sterile chamber is in the range from about 12 ml to 36 ml.

22. The aspiration/injection system of claim 15 wherein the sterile container is preloaded with one or more agents for treating or modifying the bodily liquid.

23. The aspiration/injection system of claim 15, wherein the sterile container is preloaded with one or more agents useful in processing of bone marrow aspirate liquids to enhance the yield of one or more autologous growth factors therefrom.

24. The aspiration/injection system of claim 23, wherein the agents are selected from the group consisting of heparin, vascular endothelial growth factor (VEGF), VEGF-2, HIF-1 and basic fibroblast growth factor (bFGF).

25. The aspiration/injection system of claim 23, wherein the one or more agents includes a growth factor that promotes angiogenesis.

26. The aspiration/injection system of claim 23, wherein the one or more agents includes a polynucleotide encoding a therapeutic protein.

27. The aspiration/injection system of claim 26, wherein the polynucleotide encodes a growth factor that promotes angiogenesis.

28. The aspiration/injection system of claim 26, wherein the polynucleotide is contained in a vector for transfection into cells in the liquid for expression of the polynucleotide.

29. The aspiration/injection system of claim 15, wherein the container further comprises a scanable chip on the exterior of the container that provides information regarding the contents of the container that can be read by a suitable scanner.

30. The aspiration/injection system of claim 29, wherein the scanable chip contains information regarding the contents of the sterile container that can be read by an optical scanner.

31. The aspiration/injection system of claim 30 wherein the scanable chip is an optically scanable bar code and the exterior of the pressure actuator further comprises an optical scanner positioned thereon such that operational coupling of the sterile container and the pressure actuator places the optical scanner in visual alignment with the scan chip.

32. The aspiration/injection system of claim 30, wherein information read by the scanner is transferred electronically to the motor in the pressure actuator so as to selectively control the precisely controlled distance the motor moves the container plunger.

33. The aspiration/injection system of claim 23, wherein the exterior of the container has an optical scan chip that provides information regarding the one or more agents preloaded into the container.

34. The aspiration/injection system of claim 33, wherein the scan chip contains visible barcode information concerning the modifying or treating of bodily liquids introduced into the container.

35. The aspiration/injection system of claim 1, wherein the system is configured as a hand-held device.

36. The aspiration/injection system of claim 1 wherein the pressure actuator further comprises a motor that repeatedly exerts the positive pressure on liquid in the sterile container by operational attachment to and movement of the the plunger a precisely controlled longitudinal distance.

37. The aspiration/injection system of claim 36, wherein the precisely controlled distance is calibrated to expel a fixed volume of liquid in the range from about 100 μ

L to about 2000 μ

L from the sterile chamber.

38. The aspiration/injection system of claim 36 wherein the motor is a precision motion control motor.

39. The aspiration/injection system of claim 38, wherein the precision motion control motor is operator-controlled.

40. The aspiration/injection system of claim 36 wherein the proximal end of the sterile container and the distal end of the actuator contain mating parts of an alignment mechanism to facilitate operational coupling of the plunger of the sterile container to the pressure actuator.

41. The aspiration/injection system of claim 40, wherein the pressure actuator comprises a piston co-axially housed within a cylindrical housing and the container plunger can be operationally coupled with the distal end of the piston such that the motor drives the piston the predetermined proximal distance within the pressure actuator housing.

42. The aspiration/injection system of claim 41, wherein one or more pins located on the exterior of the plunger handle and a J-shaped slot in the distal end of the pressure actuator piston cooperate to form an operational coupling mechanism for coupling a plunger handle and the piston.

43. The aspiration/injection system of claim 41, wherein the sterile container and the pressure actuator each further comprises an exterior interlocking alignment feature for operational coupling thereof.

44. The aspiration/injection system of claim 36, wherein the system further comprises:

a computer system for assembly in operational communication with the precision motion control motor for actuating the motor so as to expel the fixed volume of liquid from the sterile container.

45. The aspiration/injection system of claim 1 further comprising:

e) an aspiration syringe with moveable plunger, which can be operationally coupled with the hub of the aspiration needle; and

f) a three-way diverter;

wherein the needle cannula of the filter assembly can puncture the sterile septum of the sterile container and wherein the three way flow diverter can be operationally coupled to divert liquids aspirated through the aspiration needle into the syringe and to divert liquids ejected from the syringe into the sterile container through the flow-through filter assembly.