CA2393603A1 - Microchip devices for delivery of molecules and methods of fabrication thereof - Google Patents

Microchip devices for delivery of molecules and methods of fabrication thereof

Info

Publication number
CA2393603A1
CA2393603A1 CA002393603A CA2393603A CA2393603A1 CA 2393603 A1 CA2393603 A1 CA 2393603A1 CA 002393603 A CA002393603 A CA 002393603A CA 2393603 A CA2393603 A CA 2393603A CA 2393603 A1 CA2393603 A1 CA 2393603A1
Authority
CA
Canada
Prior art keywords
molecules
reservoirs
release system
substrate
release
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002393603A
Other languages
French (fr)
Other versions
CA2393603C (en
Inventor
Amy C. Richards
John T. Santini
Michael J. Cima
Robert S. Langer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Massachusetts Institute of Technology
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2393603A1 publication Critical patent/CA2393603A1/en
Application granted granted Critical
Publication of CA2393603C publication Critical patent/CA2393603C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0097—Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation

Abstract

Methods of manufacturing microchip devices are provided for controlled release of molecules, such as drugs. Methods include compression molding and casting, alone or in combination with microfabrication techniques. In preferred embodiments, devices are made by (1) filling a die with a polymer powder; (2) compressing the powder to form a polymer preform; (3) thermal compression molding the preform to form a substrate in a mold having a plurality of protrusions that form reservoirs in the substrate;
and (4) filling the reservoirs with a release system comprising the molecules to be released. Alternatively, ceramic devices are formed by casting the substrate from a ceramic powder or a slurry using a mold having protrusions that form reservoirs in the substrate. Control over the release rate and time of the molecules from the reservoirs of the microchip device is provided by incorporating release systems and/or reservoir caps.

Claims (25)

1. A method of fabricating a microchip device for the release of molecules, the method comprising molding or casting a material in a mold to form a substrate for use in a microchip device, wherein a surface of the mold has a plurality of protrusions which form reservoirs in the substrate; and filling the reservoirs with a release system comprising the molecules to be released.
2. The method of claim 1 wherein the material is a metal or polymer preform and the molding is compression molding.
3. The method of claim 1 wherein the material is a ceramic powder which is cast in the mold.
4. The method of claim 3 further comprising firing the substrate to densify it.
5. The method of claim 1 further comprising exposing the ends of the reservoirs to the surface of the substrate by cutting the substrate, planarizing a surface of the substrate, or a combination thereof.
6. The method of claim 5 wherein the planarization is performed by a method selected from the group consisting of polishing, chemical etching, and plasma etching.
7. The method of claim 5 wherein the cutting is conducted using a laser, water jet, or saw.
8. The method of claim 1 further comprising capping the reservoirs with a reservoir cap material which is or can be rendered selectively permeable to the molecules, which disintegrates to release the molecules, or which is a combination thereof.
9. The method of claim 5 further comprising capping the reservoirs with a reservoir cap material to form reservoir caps at one end of the reservoirs and sealing the other end of the reservoirs.
10. A method of fabricating a microchip device for the release of molecules, the method comprising providing a substrate for use in a microchip device;
forming a plurality of reservoirs in the substrate;
depositing a thin film of conductive material on one or more surfaces of the substrate to form electrodes near, in, or partially covering the reservoirs; and filling the reservoirs with a release system comprising the molecules to be released.
11. The method of claim 10 wherein the release system, upon application of an electric potential or current across the electrodes, (a) disintegrates or becomes permeable to the molecules due to a local pH change, or (b) exchanges ions in solution with an ionically bound active substance, thereby releasing the molecules.
12. The method of claim 11 wherein the release system comprises a polymeric matrix.
13. The method of claim 10 further comprising forming reservoir caps which are positioned over the release systems in the reservoirs.
14. The method of claim 13 wherein the reservoir caps, upon application of an electric potential or current across the electrodes, (a) disintegrate or becomes permeable to the molecules due to a local pH change, or (b) exchange ions in solution with an ionically bound active substance, thereby releasing the molecules.
15. A microchip device for the release of molecules comprising:
a substrate having a plurality of reservoirs which contain a release system comprising the molecules for release; and one or more electrodes which are located (i) inside one or more of the reservoirs, (ii) on a surface of the substrate outside of the reservoirs but near enough to at least one of the reservoir to effect a change in the release system of said reservoir, or (iii) partially covering but not sealing one or more of the reservoirs, wherein said electrodes are operable to create a controlled, applied stimulus, wherein the release system releases the molecules in response to (a) direct stimulation of the release system by said stimulus, or (b) a change in the local environment of the device or reservoir, which change is induced by the stimulus.
16. The microchip device of claim 15 wherein the stimulus is an applied potential or current.
17. The microchip device of claim 16 wherein the release system, upon application of the potential or current across the electrodes, disintegrates dun to local pH changes induced by the potential or current.
18. The microchip device of claim 16 wherein the release system, upon application of an electric potential or current across the electrodes, exchanges ions in solution with an ionically bound active substance in the release system, thereby releasing the molecules.
19. The microchip device of claim 15 wherein the change in the local environment is the generation of an electric or magnetic field caused by the application of an electric potential or current to the electrodes.
20. The microchip device of claim 15 wherein the release system comprises a polymeric matrix.
21. The microchip device of claim 15 wherein the stimulus is selected from the group consisting of light and magnetic field.
22. A microchip device for the release of molecules comprising a substrate having a plurality of reservoirs which contain a release system comprising the molecules for release;
one or more electrodes which are located (i) inside one or more of the reservoirs, (ii) on a surface of the substrate outside of the reservoirs but near enough to at least one of the reservoir to effect a change in the release system of said reservoir, or (iii) partially covering but not sealing one or more of the reservoirs, wherein said electrodes are operable to create a controlled, applied stimulus, reservoir caps formed of a non-conducting material and positioned over the release system, wherein the reservoir caps respond to (a) direct stimulation by said stimulus, or (b) a change in the local environment of the device or reservoir, which change is induced by the stimulus, to enable the molecules to be released.
23. The microchip device of claim 22, wherein the reservoir caps are outer reservoir caps, and the device further comprises inner reservoir caps positioned in the reservoirs beneath the outer reservoir caps.
24. A method for the delivery of molecules comprising:
providing the microchip device of claim 16 at a site where the molecules are to be delivered; and applying an electric potential or current across the electrodes to cause the release system to disintegrate due to local pH changes or to cause the release system to exchange ions in solution with an ionically bound active substance in the release system, thereby releasing the molecules at the site.
25. A method for the delivery of molecules comprising:
providing the microchip device of claim 22 at a site where the molecules are to be delivered, wherein the stimulus is an applied electrical potential or current; and applying an electric potential or current across the electrodes to cause the reservoir caps to disintegrate due to local pH changes or to cause the release system to exchange ions in solution with an ionically bound active substance in the release system, thereby releasing the molecules at the site.
CA2393603A 1999-12-10 2000-12-01 Microchip devices for delivery of molecules and methods of fabrication thereof Expired - Fee Related CA2393603C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US17021899P 1999-12-10 1999-12-10
US60/170,218 1999-12-10
PCT/US2000/042478 WO2001041736A2 (en) 1999-12-10 2000-12-01 Microchip devices for delivery of molecules and methods of fabrication thereof

Publications (2)

Publication Number Publication Date
CA2393603A1 true CA2393603A1 (en) 2001-06-14
CA2393603C CA2393603C (en) 2010-09-21

Family

ID=22619035

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2393603A Expired - Fee Related CA2393603C (en) 1999-12-10 2000-12-01 Microchip devices for delivery of molecules and methods of fabrication thereof

Country Status (8)

Country Link
US (3) US6808522B2 (en)
EP (1) EP1235560B1 (en)
JP (1) JP2003516343A (en)
AT (1) ATE323470T1 (en)
AU (2) AU782639B2 (en)
CA (1) CA2393603C (en)
DE (1) DE60027458T2 (en)
WO (1) WO2001041736A2 (en)

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