Device and method for enhancing transdermal flux of agents being sampled

• US 6,537,264 B1
• Filed: 12/16/1999
• Issued: 03/25/2003
• Est. Priority Date: 06/18/1996
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Cormier, Michel J. N., Theeuwes, Felix
• Primary Examiner(s): KENNEDY, SHARON E
• Application Number:
  US09/466,819
• Time in Patent Office: 1,195 Days
• Field of Search: 604/21, 604/20, 604/264, 604/272, 604/890.1, 604/175, 604/239, 604/73, 604/506, 607/120, 607/126-128, 607/130, 607/131, 607/152, 600/575
• US Class Current: 604/506
• 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 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150099 by negative pressure, other than vacuum extraction into a syringe by pulling on the piston rod or into pre-evacuated tubes
• CPC Class Codes: A61B 5/150282 for piercing elements, e.g. blade, lancet, canula, needle
• CPC Class Codes: A61B 5/150427 Specific tip design, e.g. for improved penetration characteristics
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/15105 Purely manual piercing, i.e. the user pierces the skin without the assistance of any driving means or driving devices
• CPC Class Codes: A61B 5/15113 Manually triggered, i.e. the triggering requires a deliberate action by the user such as pressing a drive button
• CPC Class Codes: A61B 5/15142 Devices intended for single use, i.e. disposable
• 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 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• 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 1/303 Constructional details electrodes for external use A61N1/0428

Abstract

A minimally invasive transdermal agent sampling device (2, 10) comprises a sheet (6) having a plurality of openings (8) and a plurality of microblades (4) for piercing the skin (20). A suction device (10) applies a negative pressure through the openings (8) to the microslits in the skin (20) for enhanced efflux of interstitial fluid. The device (2, 10) can be used for transdermal sampling of body analytes such as glucose for measuring/estimating blood glucose concentration.

Claims

1. A device for piercing the stratum corneum of a body surface to form pathways through which a substance can be withdrawn for sampling, comprising:

a sheet having a plurality of openings therethrough and a plurality of microblades extending downward therefrom; and

a negative pressure sampling device which applies negative pressure to the pathways through the openings.

2. The device of claim 1, wherein the sampled substance is selected from the group consisting of body electrolytes, illicit drugs and glucose.

3. The device of claim 1, wherein the microblades have a length sufficient to pierce the stratum corneum of the body surface to a depth of at least about 25 μ

m.

4. The device of claim 1, wherein the sheet has at least about 10 microblades/cm².

5. The device of claim 1, wherein the sheet has at least about 10 openings/cm².

6. The device of claim 1, wherein the microblades are oriented approximately perpendicular to the sheet.

7. The device of claim 1, wherein the sheet and the plurality of microblades are composed of a material selected from the group consisting of metals, metal alloys, glasses, ceramics and rigid polymers.

8. The device of claim 1, wherein the sheet and the plurality of microblades are substantially impermeable to the passage of the agent.

9. The device of claim 1, wherein at least a portion of the plurality of microblades are located along a periphery of an opening through the sheet.

10. The device of claim 1, wherein at least a portion of the plurality of microblades are located along a periphery of a plurality of openings through the sheet.

11. The device of claim 1, wherein at least a portion of the plurality of microblades have a thickness in the range of about 7 μ

m to about 100 μ

m.

12. The device of claim 1, wherein at least a portion of the plurality of microblades have a thickness in the range of about 25 μ

m to about 50 μ

m.

13. The device of claim 1, including an anchor anchoring the sheet to the body surface.

14. The device of claim 13, wherein the anchor is selected from the group consisting:

(i) a projection extending out from the at least one microblade;

(ii) a barb;

(iii) at least one opening extending through the at least one microblade;

(iv) an adhesive on a body contacting surface of the sheet and on at least one surface of at least one of the plurality of microblades;

(v) each of the microblades having an axis, the microblades being oriented so that the microblade axes are substantially parallel and the axes form an angle of about 1°

to about 89°

relative to the sheet;

(vi) each one of the plurality of microblades defines essentially a plane and wherein the anchor comprises a portion of the plurality of microblades being oriented at an angle of about 90°

with respect to a remaining portion of the plurality of microblades; and

(vii) each one of the plurality of microblades defines essentially a plane and wherein the anchor comprises a portion of the plurality of microblades being oriented at an angle within a range of about 1°

to about 89°

with respect to a remaining portion of the plurality of microblades.

15. A method of transdermally sampling an agent, comprising:

a. placing a device on a body surface through which the agent is to be withdrawn, the device including a sheet having a plurality of openings therethrough and a plurality of microblades extending downward therefrom, whereby agent transmitting pathways are formed through the stratum corneum at the body surface;

b. applying a negative pressure to the pathways through the openings in the sheet, thereby withdrawing the agent through the pathways and said openings; and

c. collecting the agent in a reservoir.

16. The method of claim 15, wherein the sampled agent is selected from the group consisting of body analytes, electrolytes, blood gases, illicit drugs, licit drugs and glucose.

17. The method of claim 15, further comprising:

connecting a negative pressure driven sampling device to a side opposite of a side of the sheet having the microblades extending downward therefrom, the sampling device in negative pressure applying communication with the openings in the sheet.