MEMS device and method for delivery of therapeutic agents

• US 8,764,708 B2
• Filed: 06/11/2012
• Issued: 07/01/2014
• Est. Priority Date: 03/14/2006
• Status: Expired due to Fees

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Tai, Yu-Chong, Humayun, Mark, Shih, Jason
• Primary Examiner(s): FLICK, JASON E
• Application Number:
  US13/493,611
• Publication Number:
  US 20130000119A1
• Time in Patent Office: 750 Days
• Field of Search: 604/114
• US Class Current: 604/114
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• 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: A61M 2005/14204 with gas-producing electrochemical cell
• CPC Class Codes: A61M 2205/0244 Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
• CPC Class Codes: A61M 2205/3507 with implanted devices, e.g. external control
• CPC Class Codes: A61M 2207/00 Methods of manufacture, assembly or production
• CPC Class Codes: A61M 2210/0612 Eyes
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/14593 the diaphragm being actuated by fluid pressure
• CPC Class Codes: A61M 5/155 pressurised by gas introduced into the reservoir
• CPC Class Codes: A61M 5/16877 Adjusting flow; Devices for setting a flow rate
• CPC Class Codes: A61M 5/16881 Regulating valves on-off valves, e.g. clamps A61M39/28
• CPC Class Codes: B81B 2201/058 Microfluidics not provided for in B81B2201/051 - B81B2201/054
• CPC Class Codes: B81C 1/00119 Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
• CPC Class Codes: B81C 2201/019 Bonding or gluing multiple substrate layers
• CPC Class Codes: F04B 43/043 Micropumps
• CPC Class Codes: F16K 2099/008 Multi-layer fabrications
• CPC Class Codes: F16K 2099/0088 Implanted devices
• CPC Class Codes: F16K 99/0001 : Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/0005 : Lift valves
• CPC Class Codes: F16K 99/0034 : Operating means specially adapted for microvalves
• CPC Class Codes: F16K 99/0057 : the fluid being the circulating fluid itself, e.g. check valves
• CPC Class Codes: Y10T 29/49236 : Fluid pump or compressor making

Abstract

Embodiments of an implantable device for delivering a therapeutic agent to a patient include a reservoir configured to contain a liquid comprising the therapeutic agent, and a cannula in fluid communication with the reservoir. The cannula is shaped to facilitate insertion thereof into a patient'"'"'s eyeball.

Claims

1. A method of manufacturing an implantable pump, the method comprising:

providing an upper layer comprising a dome structure for housing a drug chamber and a cannula in fluid communication with the drug chamber;

providing a middle deflection layer adjacent the drug chamber;

providing a bottom layer comprising electrolysis electrodes; and

bonding the upper layer, middle deflection layer, and bottom layer along a common peripheral exterior edge of the upper and middle deflection layers to form the pump.

2. The method of claim 1, further comprising the step of forming the drug chamber between the upper layer and the middle deflection layer after thermal bonding.

3. The method of claim 1, further comprising the step of forming the electrolysis chamber between the middle deflection layer and the bottom layer after thermal bonding.

4. The method of claim 1, further comprising providing at least one fill port in fluid communication with at least one of the electrolysis chamber or the drug chamber.

5. The method of claim 1, wherein at least one of the upper layer, the middle layer, and the bottom layer is formed by a lithographic process.

6. The method of claim 5, wherein the lithographic process comprises the steps of:

sequentially layering layers of a construction material and a photoresist material;

etching at least one of the construction material and a photoresist material to provide a required shape, and

subjecting the layers to photoresist stripper, thereby removing the photoresist material and leaving the shaped construction material in place.

7. The method of claim 1, wherein at least one of the upper layer, the middle layer, and the bottom layer is formed by a molding process.

8. The method of claim 1, wherein at least one of the upper layer, the middle layer, and the bottom layer comprises or consists essentially of parylene.

9. The method of claim 1, wherein the dome structure is manufactured by the steps of:

providing a mold having a domed shape;

conformably coating a layer of material on the mold; and

after the material has set, peeling the resulting dome structure from the mold.

10. The method of claim 1, wherein the cannula is manufactured according to steps comprising:

coating a first photoresist layer onto a silicon substrate as a sacrificial layer;

depositing a first parylene layer onto the photoresist layer to form a bottom surface of the cannula;

creating a through hole in the first parylene layer;

coating a second photoresist layer over the first parylene layer;

depositing a second parylene layer on the second photoresist layer, the second parylene layer forming a top and a side of the cannula;

patterning the first and second parylene layers to form a cannula shape; and

removing the first and second photoresist layers, thereby leaving the formed cannula.

11. The method of claim 10, wherein the patterning step comprises reactive-ion etching with a photoresist material used as an etching mask.

12. The method of claim 10, wherein the patterning step comprises patterning the first parylene layer and second parylene layer in a RIE oxygen plasma using a photoresist mask.

13. The method of claim 10, wherein at least one of the coating steps comprises spin-coating.

14. The method of claim 1, further comprising integrating at least one of a check valve, a flow sensor, a pressure sensor, or a chemical sensor into the pump.

15. The method of claim 11, wherein the middle deflection layer comprises a corrugated diaphragm.

16. The method of claim 15, wherein the corrugated diaphragm is formed according to steps comprising:

coating a first photoresist layer onto a silicon substrate;

etching the silicon substrate using the first photoresist layer as a mask;

removing the first photoresist layer, thereby leaving a mold formed by the silicon substrate;

coating a parylene layer on the silicon substrate; and

after the parylene layer has set, releasing the parylene layer from the silicon substrate thereby forming the corrugated diaphragm.

17. The method of claim 1, wherein the middle deflection layer comprises a bellows structure.

18. The method of claim 17, wherein the bellows structure is formed according to steps comprising:

coating a first photoresist layer onto a silicon substrate as a sacrificial layer;

depositing a first parylene layer onto the first photoresist layer to form a first layer of the bellows structure;

coating a second photoresist layer over the first parylene layer;

opening a bonding area in the second photoresist layer by lithography;

depositing a second parylene layer onto the second photoresist layer to form a second layer of the bellows structure, wherein the second parylene layer bonds to the first parylene layer at the bonding area;

patterning the first and second parylene layers;

coating a third photoresist layer onto the second parylene layer;

depositing a third parylene layer onto the third photoresist layer to form a third layer of the bellows structure;

patterning the bellows structure by etching through the second and third parylene layers; and

removing the photoresist layers by subjection to photoresist stripper, thereby leaving the parylene bellows structure.

19. The method of claim 1, wherein the bottom layer is formed according to steps comprising:

coating a first photoresist layer onto a silicon substrate as a sacrificial layer;

depositing a first parylene layer onto the first photoresist layer to form a first layer of the bottom layer;

depositing a metal electrode layer on the first parylene layer;

depositing a second parylene layer over the metal electrode layer;

etching the second parylene layers to expose at least a portion of the electrode; and

removing the photoresist layers by subjection to photoresist stripper, thereby leaving the bottom layer.

20. The method of claim 19, wherein the metal electrode layer is deposited by E-beam evaporation and patterned by life-off process or etching process.

21. The method of claim 19, wherein the etching step comprises RIE oxygen plasma etching masked by a photoresist mask.

22. The method of claim 19, further comprising annealing the bottom layer to improve the adhesion between the parylene layers and metal electrode layer.

23. The method of claim 19, wherein the metal electrode layer comprises or consists essentially of platinum.

24. The method of claim 1, further comprising a substantially rigid spacer comprising a refill hole.