Method and apparatus for enhancing flux rates of a fluid in a microporated biological tissue

• US 6,173,202 B1
• Filed: 03/06/1998
• Issued: 01/09/2001
• Est. Priority Date: 03/06/1998
• Status: Expired due to Term

• Current Assignee: MidCap Funding III, LLC, Nitto Denko Corporation
• Original Assignee: Altia Technology (Altia Group), Spectro Incorporated (Spectro Scientific, Inc.)
• Inventors: Eppstein, Jonathan A.
• Primary Examiner(s): Bockelman, Mark
• Application Number:
  US09/036,053
• Time in Patent Office: 1,040 Days
• Field of Search: 604/20-22, 604/27-28, 604/520, 604/501, 604/502, 604/506, 600/573, 435/285.2, 435/173.6, 514/947
• US Class Current: 604/20
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 18/20 using laser
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 2017/00765 Decreasing the barrier function of skin tissue by radiated energy, e.g. using ultrasound, using laser for skin perforation
• CPC Class Codes: A61K 41/0047 Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

A method and apparatus for enhancing the flux rate of a fluid through a biological membrane. The method includes the steps of porating a section of the tissue to form one or more micropores in the tissue, and applying a flux enhancer to the tissue through the one or more micropores. The resulting enhancement of fluid flux in the tissue enables more effective harvesting from the body of fluids, as well as more effective delivery of a drug.

Claims

1. A method for enhancing the flux rate of a substance through a porated tissue, comprising the step of delivering an effective amount of a flux enhancer into the tissue through at least one micropore made into an outer layer of the tissue so that the flux enhancer acts on tissue structures in or beneath the outer layer thereby increasing the flux rate of a substance through the tissue, wherein the step of delivering the flux enhancer comprises step of positioning a quantity of flux enhancer adjacent the porated tissue and applying sufficient energy to the quantity of flux enhancer to vaporize at least a portion of the quantity of flux enhancer, thereby releasing at least a portion of the quantity of flux enhancer into the tissue through the at least one micropore.

2. The method of claim 1, wherein the step of delivering the flux enhancer comprises inserting a probe carrying the effective amount of flux enhancer into the tissue.

3. The method of claim 1, wherein the step of applying sufficient energy to the quantity of flux enhancer comprises introducing a heated element into the quantity of flux enhancer.

4. The method of claim 1, wherein the step of positioning a quantity of the flux enhancer at the site comprises placing a carrier device having a reservoir containing the quantity of flux enhancer adjacent the porated tissue, and wherein the step of applying sufficient energy comprises applying energy to the carrier device to vaporize at least a portion of the quantity of flux enhancer.

5. The method of claim 4, and further comprising delivering a drug contained in the reservoir through the at least one micropore.

6. The method of claim 1, and further comprising delivering a quantity of a drug through the at least one micropore.

7. The method of claim 1, and further comprising collecting a sample of an analyte through the at least one micropore.

8. A method for enhancing the flux rate of a substance through a porated tissue, comprising the step of delivering an effective amount of a flux enhancer into the tissue through at least one micropore made into an outer layer of the tissue so that the flux enhancer acts on tissue structures in or beneath the outer layer thereby increasing the flux rate of a substance through the tissue, wherein the flux enhancer contains ammonia.

9. The method of claim 8, wherein the step of delivering the flux enhancer comprises inserting a probe carrying the effective amount of flux enhancer into the tissue.

10. The method of claim 8, wherein the step of delivering the flux enhancer comprises positioning a quantity of flux enhancer adjacent the porated tissue and releasing at least a portion of the quantity of flux enhancer into the tissue through the at least on micropore.

11. The method of claim 10, and further comprising the step of applying sufficient energy to the quantity of flux enhancer to vaporize at least a portion of the quantity of flux enhancer.

12. The method of claim 10, wherein the step of applying energy to the quantity of flux enhancer comprises introducing a heated element into the quantity of flux enhancer.

13. The method of claim 10, wherein the step of positioning a quantity of the flux enhancer at the site comprises placing a carrier device having a reservoir containing the quantity of flux enhancer adjacent the porated tissue, and wherein the step of releasing at least a portion of the quantity of flux enhancer into the tissue through the at least one micropore comprises applying energy onto the carrier device to vaporize at least a portion of the quantity of flux enhancer.

14. The method of claim 13, and further comprising the step of delivering a drug contained in the reservoir through the at least one micropore.

15. The method of claim 8, and further comprising delivering a drug into the tissue through the at least one micropore.

16. The method of claim 8, and further comprising collecting a sample of an analyte through the at least one micropore.

17. A method of enhancing the flux rate of a substance through a biological membrane, comprising steps of:

(a) porating the biological membrane to form at least one micropore in the biological membrane; and

(b) delivering an effective amount of a flux enhancer to through the micropore in the biological membrane, wherein the flux enhancer contains ammonia.

18. The method of claim 17, and further comprising the step of introducing a drug through the at least one micropore.

19. The method of claim 17, wherein the steps of porating and delivering comprise applying a sufficient amount of electromagnetic energy onto an energy absorbing layer placed adjacent the surface of the biological membrane, wherein the energy absorbing layer is treated with said effective amount of flux enhancer such that said reservoir is incorporated in said energy absorbing layer.

20. The method of claim 17, wherein the micropore extends to a selected depth into or through the biological membrane.

21. The method of claim 17, wherein the steps of porating and delivering comprise inserting a probe carrying a quantity of flux enhancer into the biological membrane.

22. The method of claim 21, wherein the step of inserting a probe comprises inserting a heated probe into the biological membrane.

23. The method of claim 17, wherein the step of delivering an effective amount of a flux enhancer comprises the steps of positioning a reservoir containing a quantity of flux enhancer adjacent the surface of the biological membrane, and releasing at least a portion of the quantity of flux enhancer from the reservoir into the at least one micropore.

24. The method of claim 23, and further comprising the step of applying sufficient energy to the reservoir of flux enhancer to vaporize at least a portion of the quantity of flux enhancer.

25. The method of claim 24, wherein the steps of porating the biological membrane and releasing at least a portion of the flux enhancer comprise the step of applying a sufficient amount of eletromagnetic energy onto an energy absorbing portion adjacent the reservoir to heat the energy absorbing portion to a temperature sufficient to form the at least one micropore and to vaporize at least a portion of the reservoir of flux enhancer.

26. The method of claim 25, wherein the step of measuring an impedance comprises measuring a complex impedance between the electrically heated probe and the electrode.

27. The method of claim 24, wherein the steps of porating the membrane and releasing at least a portion of the flux enhancer comprise the step of introducing a heated element through the reservoir and into the membrane.

28. The method of claim 23, and further comprising delivering a drug contained in the reservoir through the at least one micropore.

29. The method of claim 17, and further comprising the step of applying ultrasonic energy to the tissue to draw an interstitial fluid containing the analyte outwardly through the at least one micropore.

30. The method of claim 17, and further comprising the step of applying suction to the tissue to draw interstitial fluid comprising the analyte outwardly through the at least one micropore.

31. The method of claim 17, wherein the step of porating comprises measuring an impedance between an electrically heated probe that creates the micropore and an electrode spaced therefrom to control a depth of the micropore based on the impedance.

32. The method of claim 17, and further comprising collecting a sample of an analyte through the at least one micropore.

33. A method of enhancing the flux rate of a substance through a biological membrane, comprising steps of:

(a) porating the biological membrane to form at least one micropore in the biological membrane;

(b) delivering an effective amount of a flux enhancer to through the micropore in the biological membrane, wherein the step of delivering an effective amount of a flux enhancer comprises steps of positioning a reservoir containing a quantity of flux enhancer adjacent the surface of the biological membrane, and applying sufficient energy to the reservoir of flux enhancer to vaporize at least a portion of the quantity of flux enhancer thereby releasing at least a portion of the quantity of flux enhancer from the reservoir into the at least one micropore;

wherein the steps of porating the membrane and applying sufficient energy comprise the step of introducing a heated element through the reservoir and into the biological membrane.

34. The method of claim 33, wherein the micropore extends to a selected depth into or through the biological membrane.

35. The method of claim 33, and further comprising the step of applying ultrasonic energy to the tissue to draw an interstitial fluid containing the analyte outwardly through the at least one micropore.

36. The method of claim 33, and further comprising the step of applying suction to the tissue to draw interstitial fluid comprising the analyte outwardly through the at least one micropore.

37. The method of claim 33, wherein the step of porating comprises measuring an impedance between an electrically heated probe that creates the micropore and an electrode spaced therefrom to control a depth of the micropore based on the impedance.

38. The method of claim 37, wherein the step of measuring an impedance comprises measuring a complex impedance between the electrically heated probe and the electrode.

39. The method of claim 33, and further comprising the step of introducing a drug through the at least one micropore.

40. The method of claim 33, and further comprising collecting a sample of an analyte through the at least one micropore.