Thermally-activated microchip chemical delivery devices

• US 6,527,762 B1
• Filed: 08/11/2000
• Issued: 03/04/2003
• Est. Priority Date: 08/18/1999
• Status: Expired due to Term

• Current Assignee: Microchips Biotech, Inc. (Keratin Biosciences, Inc.)
• Original Assignee: MicroCHIPS Inc.
• Inventors: Uhland, Scott Albert, Cima, Michael J., Santini, John T. Jr.
• Primary Examiner(s): Tanner, Harry B.
• Application Number:
  US09/638,109
• Time in Patent Office: 935 Days
• Field of Search: 604/890.1, 604/891.1, 604/892.1, 604/19, 216/2, 216/39, 216/56
• US Class Current: 604/890.1
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0097 Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 3/50853 with covers or lids

Abstract

Microchip delivery devices are provided that control both the rate and time of release of molecules, wherein the device includes a substrate, at least one reservoir in the substrate containing the molecules, and a reservoir cap positioned on the reservoir over the molecules, wherein the molecules are released from the reservoir upon heating or cooling the device or a portion thereof sufficient to rupture the reservoir cap. In a preferred embodiment, the device includes a resistor integrated into the reservoir or mounted near the reservoir, which upon application of an electric current through the resistor, causes at least one of the contents of the reservoir to thermally expand, vaporize, phase change, or undergo a thermally driven reaction, such that the reservoir cap ruptures due to mechanical stress. In another preferred embodiment, application of an electric current to a resistor located on or near the reservoir cap causes the cap to expand, contract, or undergo a phase change that results in the rupture of the reservoir cap. The reservoirs can contain multiple drugs or other molecules in variable dosages. Each of the reservoirs of a single microchip can contain different molecules and/or different amounts and concentrations, which can be released independently.

Claims

1. A microchip device for the release of molecules comprising:

a substrate;

a plurality of reservoirs in the substrate containing a release system including the molecules for release; and

a reservoir cap positioned on or in each of the reservoirs over the release system and formed of a material that undergoes a phase change in response to a change in temperature,

wherein the molecules can be selectively released from each reservoir upon heating said reservoir cap to cause said reservoir cap to undergo a phase change and rupture.

2. The device of claim 1 wherein the reservoir cap is formed of a material having a yield or tensile strength beyond which the material fails by fracture.

3. The device of claim 2 wherein the material is selected from the group consisting of metals, glasses, ceramics, semiconductors, and polymers.

4. The device of claim 1, wherein the material comprises a metal film.

5. The device of claim 1 wherein the reservoir cap is formed of a meltable material so that rupture of the reservoir cap occurs by melting.

6. The device of claim 5 wherein the material comprises a polymer.

7. The device of claim 6 wherein the polymer comprises copolymer having a melting temperature between about 35 and 50°

C.

8. The device of claim 1 further comprising a resistor integrated into or mounted near the reservoir to heat the release system contained therein upon application of an electric current through the resistor.

9. The device of claim 1 further comprising a resistor integrated into or mounted near the reservoir cap to heat the reservoir cap upon application of an electric current through the resistor.

10. The device of claim 1 wherein the reservoir contains a quantity of the molecules effective to cause the reservoir cap to rupture by thermal expansion or vaporization of, or by a phase change in, the release system.

11. The device of claim 1 wherein the molecules are selected from the group consisting of drugs, diagnostic reagents, perfumes, fragrances, dyes, and coloring agents.

12. The device of claim 1 wherein the molecules are incorporated into a degradable release system.

13. The device of claim 1 wherein the substrate is a composite or laminate substrate.

14. A method for the delivery of molecules comprising:

(a) providing the device of claim 1 at a site where the molecules are to be delivered; and

(b) heating a selected reservoir cap in an amount effective to cause the selected reservoir cap to undergo a phase change and rupture the reservoir cap and release the molecules.

15. The method of claim 14 wherein the heating is achieved by resistive heating of a resistor incorporated into the device.

16. The method of claim 15 wherein resistive heating of a resistor heats the reservoir cap.

17. The method of claim 15 wherein resistive heating of a resistor heats the molecules in the reservoir.

18. The device of claim 1, wherein at least two of the reservoir caps are formed of different materials from one another, the different materials having different melting temperatures.

35. The device of claim 1, 23, 27, 31, or 33, wherein the molecules for release comprise drug molecules.

36. The device of claim 35, wherein the release system comprises a pharmaceutically acceptable carrier or excipient.

19. A method of fabricating a microchip device for release of molecules having reservoirs containing the molecules for release comprising:

providing a substrate;

forming a plurality of reservoirs in the substrate;

filling the reservoirs with a release system comprising the molecules; and

capping the reservoirs with a reservoir cap that undergoes a phase change to rupture upon a selected degree of heating or cooling.

20. The method of claim 19 further comprising forming a thin film resistor near the reservoir cap or inside the reservoirs.

21. The method of claim 19 wherein the reservoirs are forming by

depositing and patterning a material on the substrate for use as an etch mask; and

etching a plurality of reservoirs in the substrate.

22. The method of claim 19 wherein the reservoirs are formed using a micromolding or laser machining technique.

23. A microchip device for the release of molecules comprising:

at least one substrate;

a plurality of reservoirs in the substrate containing a release system including the molecules; and

a reservoir cap, comprising a membrane, positioned on or in each of the reservoirs over the release system, said membrane being substantially impermeable to the molecules when the membrane is at a temperature below a selected temperature and becomes permeable to the molecules at a temperature equal to or greater than the selected temperature,

wherein the molecules are released from the reservoir upon heating of the reservoir cap to the selected temperature.

24. The device of claim 23 wherein the reservoirs are covered with a membrane that is substantially impermeable to the molecules when the membrane is at a temperature below the selected temperature and becomes permeable to the molecules at a temperature equal to or greater than the selected temperature.

25. The device of claim 23 wherein the molecules remain substantially in the reservoirs when at a temperature below the selected temperature, but are released when the release system is at a temperature equal to or greater than the selected temperature.

26. The device of claim 23, further comprising a resistor within or near each of the reservoirs.

37. The device of claim 9, 26, 31, or 33, further comprising control circuitry to direct electric current to specific resistors.

38. The device of claim 37, further comprising an input source selected from the group consisting of a PROM, a remote control, and a biosensor.

27. A microchip device for the release of molecules comprising:

a substrate;

a plurality of reservoirs in the substrate containing a release system including the molecules for release;

a reservoir cap positioned on or in each of the reservoirs over the release system; and

a means for heating said release system to increase the pressure within the reservoir to cause the reservoir cap to rupture.

28. The device of claim 27, wherein the heating means comprises a resistor integrated into or mounted near the reservoir to heat the release system contained therein upon application of an electric current through the resistor.

29. The device of claim 27, wherein the heating causes the release system to expand.

30. The device of claim 27, wherein the heating causes molecules in the reservoir to vaporize or undergo a reaction which increases the pressure in the reservoir.

31. A microchip device for the release of molecules comprising:

a substrate;

a plurality of reservoirs in the substrate containing a release system including the molecules for release; and

a reservoir cap in the form of a metal film positioned on or in each of the reservoirs over the release system,

wherein the molecules can be selectively released from each reservoir upon by rupturing said reservoir cap by heating or cooling said reservoir cap, the reservoir release system, or both.

32. The device of claim 31, further comprising a resistor to heat said reservoir cap, the reservoir release system, or both upon application of an electric current through the resistor.

33. A microchip device for the release of molecules comprising:

a substrate;

a plurality of reservoirs in the substrate containing a release system including the molecules for release;

a reservoir cap positioned on or in each of the reservoirs over the release system and formed of a material that undergoes a temperature-dependent chemical degradation; and

a resistor integrated into or mounted near the reservoir cap to heat the reservoir cap upon application of an electric current through the resistor,

wherein the molecules can be selectively released from each reservoir upon heating said reservoir cap to cause said reservoir cap to chemically degrade and rupture.

34. The device of claim 33, wherein the material comprises a biodegradable polymer.