Apparatus for microporation of biological membranes using thin film tissue interface devices, and method therefor

• US 6,692,456 B1
• Filed: 06/08/2000
• Issued: 02/17/2004
• Est. Priority Date: 06/08/1999
• Status: Expired due to Term

• Current Assignee: MidCap Funding III, LLC, ​Passport Technologies, Inc.
• Original Assignee: Altea Therapeutics Corporation (Nitto Denko Corporation)
• Inventors: Hatch, Michael R., Papp, Joseph, Eppstein, Jonathan A.
• Primary Examiner(s): Mendez, Manuel
• Assistant Examiner(s): Han, Mark K.
• Application Number:
  US09/590,787
• Time in Patent Office: 1,349 Days
• Field of Search: 604/19, 604/20, 604/21, 604/22, 604/27, 604/28, 604/46, 604/48, 604/289, 604/290, 600/309, 600/310, 600/316, 600/345, 600/365, 600/372, 600/373, 600/377, 600/378, 600/381, 600/573, 600/583, 606/9, 606/32, 606/41, 606/42, 606/43, 606/44, 606/45, 606/48, 606/131, 607/2, 607/96, 607/98, 607/99, 607/100, 607/103, 607/104, 607/108
• US Class Current: 604/22
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 2017/00761 Removing layer of skin tissue, e.g. wrinkles, scars or cancerous tissue
• CPC Class Codes: A61K 41/0047 Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
• CPC Class Codes: A61M 2005/3022 Worn on the body, e.g. as patches pressure infusion of the skin patch type A61M5/14248
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0038 having a channel at the side surface
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0452 Specially adapted for transcutaneous muscle stimulation [TMS]
• CPC Class Codes: A61N 1/0456 Specially adapted for transcutaneous electrical nerve stimulation [TENS]
• CPC Class Codes: A61N 1/0476 Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

The invention provides for improved devices and methods for forming openings in a biological membrane for delivering substances into an animal through the biological membrane for treatment applications, or extracting substances from the animal through the biological membrane for monitoring or other diagnosis applications and for increased transmembrane flux.

Claims

1. A microporation device, comprising:

at least one reservoir and

a tissue interface comprising probe elements and a substrate,

wherein the probe elements located on or within the substrate and

further comprising diodes for isolating the electrical circuits used for activating the probe elements.

2. The device of claim 1, wherein the substrate is selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

3. The device of claim 2, wherein the substrate comprises perforations.

4. The device of claim 3, further comprising a plug material on the perforations.

5. The device of claim 4, wherein the plug material comprises a volatile material.

6. The device of claim 2, wherein the woven material comprises conductive fibers and non-conductive fibers.

7. The device of claim 1, wherein the probe element is selected from the group consisting of a preformed wire conductor, a deposited conductive material, a machined conductive material, a laser cut conductive material, an adhesive foil, an electroplated material, a screen-printed material and an etched conductive material.

8. The device of claim 1, wherein the probe element is destroyed while ablating the biological membrane.

9. The device of claim 1, wherein two or more of the probe elements are connected in a parallel circuit configuration or a series circuit configuration or a combination thereof.

10. The device of claim 1, further comprising a material near the microporator, wherein the material is capable of producing an exothermic or endothermic reaction.

11. The device of claim 1, further comprising a microactuator.

12. The device of claim 11, wherein the microacuator is selected from the group consisting of electro-static microactuators, thermal bimorph microactuators, piezoelectric microactuators, electromagnetic microactuators, magneto-restrictive microactuators and shape memory alloy microactuators.

13. The device of claim 1, further comprising an electronic circuitry and a power source.

14. The device of claim 1, wherein the probe element comprises a conductive wire and the substrate comprises a non-conductive fabric.

15. The device of claim 14, wherein the conductive wire is woven in the non-conductive fabric.

16. The device of claim 1, wherein the substrate is embossed.

17. The device of claim 1, further comprising an enhancer material for enhancing transmembrane transport of a fluid across the biological membrane.

18. The device of claim 1, further comprising a flux enhancement device, wherein the flux enhancement device enhances a flux rate of a substance into the biological membrane.

19. The device of claim 18, wherein the flux enhancement device enhances a flux rate of a substance into the biological membrane by a technique selected from the group consisting of iontophoresis, electroporation, electro-osmosis, sonophoresis, and pressurization.

20. The device of claim 1, further comprising a mixer located on or within the substrate, the mixer being capable of mixing a substance prior to transdermal delivery of a substance into the biological membrane.

21. A microporation device, comprising:

at least one reservoir comprising multiple chambers and

a tissue interface comprising at least one microporator and a substrate,

wherein the microporator is located on or within the substrate and

wherein the multiple chambers comprise at least first and second chambers, said first chamber comprises a first substance and said second chamber comprises a second substance.

22. The device of claim 21 wherein said first and second substances are first and second biologically active agents.

23. The device of claim 21, wherein said device is capable of transdermal delivery of a substance in the first chamber or withdrawal of an analyte transdermally into the second chamber.

24. The device of claim 21, wherein said device is capable of simultaneous transdermal delivery of a substance in the first chamber and withdrawal of an analyte transdermally into the second chamber.

25. The device of claim 24, further comprising an analyzer for detecting or quantitating said analyte.

26. The device of claim 25, further comprising a control module for controlling the delivery of the substance based on a quantitative value of the analyte detected by the analyzer.

27. The device of claim 25, wherein said substance is insulin and said analyte is glucose.

28. The device of claim 21, further comprising a divider or valve disposed between said first and second chambers that prevents mixture of said first and second substances until said divider is removed or said valve is opened.

29. The device of claim 28, wherein said divider is a membrane.

30. The device of claim 29, wherein said first substance is a pharmaceutically active agent, and said second substance is a pharmaceutically acceptable carrier.

31. The device of claim 30, wherein said first substance is a dry formulation pharmaceutically active agent, and said second substance is a diluent for reconstituting said dry formulation into a pharmaceutically acceptable liquid or gel formulation.

32. The device of claim 22, wherein said multiple chambers comprise different substances.

33. The device of claim 32, wherein one or more of the substances are selected from the group consisting of bioactive peptides or proteins, therapeutic drugs, vaccines, pain medications, permeation enhancers and pH stabilizers.

34. The device of claim 32, wherein the different substances are delivered by the device in modulated amounts.

35. The device of claim 34, wherein at least one of the different substances passively diffuses into the biological membrane.

36. The device of claim 34, wherein the substances are delivered simultaneously, sequentially, alternately, or any combination thereof.

37. The device of claim 32, wherein the different substances are delivered by the device into the organism in adjacent locations in the biological membrane such that said different substances could combine and mix once they are within the tissue matrix of the organism.

38. The device of claim 21, wherein at least one of the multiple chambers is disposed after a single use of the device.

39. A microporation device, comprising:

at least one reservoir and

a tissue interface comprising at least one microporator and a substrate, wherein the microporator is located on or within the substrate,

said microporation device further comprising a disposable component,

wherein the disposable component comprises stimuli-responsive polymer gel sections comprising a material that is released by a thermal, chemical or electrical stimulus.

40. The device of claim 39 wherein the disposable component is treated with reagents which react with a biological fluid withdrawn from the biological membrane to produce a signal or measurable change in properties which is predictably related to the quantity of an analyte within the biological fluid.

41. The device of claim 39, wherein the disposable component is treated with one or any combination thereof of surfactants, hydrophilic or hydrophobic compounds.

42. The device of claim 39, wherein the disposable component is treated with antimicrobial or anticoagulent or protease inhibitor compounds.

43. The device of claim 39, wherein the disposable component comprises a material that releases a compound when heated.

44. A method for forming openings in a biological membrane, comprising:

placing a microporation device in close proximity of the biological membrane and triggering the microporation device to form at least one opening in the biological membrane, the microporation device, comprising;

at least one reservoir and a tissue interface comprising at least one microporator and a substrate, wherein the microporator is located on or within the substrate, said method further comprising mixing a substance prior to delivery of a substance into the biological membrane.

45. The method of claim 44, wherein the triggering transfers heat to the biological membrane.

46. The method of claim 44, wherein the at least one opening has a diameter of 1-1,000 microns.

47. The method of claim 44, further comprising applying an enhancer to the opening.

48. The method of claim 44, further comprising applying a permeant to the opening.

49. The method of claim 44, further comprising collecting a fluid from the opening.

50. The method of claim 49, further comprising monitoring an analyte in the fluid.

51. The method of claim 44, further comprising delivering a substance into the biological membrane and collecting a fluid from the biological membrane.

52. The method of claim 44, wherein the microporator is selected from the group consisting of a probe element capable of conductively delivering thermal energy via direct contact to a biological membrane to cause the ablation of some portion of said membrane deep enough to form a micropore, electro-mechanical actuator, a microlancet, an array of micro-needles or lancets, a sonic energy ablator, a laser ablation system, and a high pressure fluid jet puncturer.

53. The method of claim 52, wherein said probe element is selected from the group consisting of an electrically heated resistive element capable of ablating a biological lo membrane, an optically heated topical dye absorber layer and optically heated topical dye layer.