WO2004011083A1

WO2004011083A1 - Reinforcement elements in a silicone electrode array

Info

Publication number: WO2004011083A1
Application number: PCT/US2003/023500
Authority: WO
Inventors: Mariam Maghribi; Peter A. Krulevitch; Julie K. Hamilton; Mark S. Humayun; Dilek Guven
Original assignee: The Regents Of The University Of California
Priority date: 2002-07-25
Filing date: 2003-07-24
Publication date: 2004-02-05
Also published as: AU2003268030A1

Abstract

An electronic device for connection to tissue comprises a substrate composed of silicone that has the ability to conform to various shapes of tissue. Electrodes are embedded in the substrate for contacting the tissue. Reinforcement structural elements are formed in the substrate.

Description

REINFORCEMENT ELEMENTS IN A SILICONE ELECTRODE ARRAY [0001] The United States Government has rights in this invention pursuant to Contract No. W-7405-ENG-48 between the United States Department of Energy and the University of California for the operation of Lawrence Livermore National Laboratory.

CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of U.S. Provisional Application No. 60/398634 filed 07/25/2002 and titled "Stretchable Electrode Array with Reinforced Ribs." U.S. Provisional Application No. 60/398634 filed 07/25/2002 and titled "Stretchable Electrode Array with Reinforced Ribs" is incorporated herein in its entirety by this reference.

BACKGROUND OF THE INVENTION

Field of Endeavor [0003] The present invention relates to molding silicone devices and more particularly molding reinforcement elements for a silicone electrode array.

State of Technology [0004] U. S. Patent No. 4,573,481 for an implantable electrode array by Leo A. Bullara, patented March 4, 1986 provides the following background information, "It has been known for almost 200 years that muscle contraction can be controlled by applying an electrical stimulus to the associated nerves. Practical long-term application of this knowledge, however, was not possible until the relatively recent development of totally implantable miniature electronic circuits which avoid the risk of infection at the sites of percutaneous connecting wires. A well-known example of this modern technology is the artificial cardiac pacemaker which has been successfully implanted in many patients. Modern circuitry enables wireless control of implanted devices by wireless telemetry communication between external and internal circuits." [0005] U. S. Patent No. 6,052,624 for a directional programming for implantable electrode arrays by Carla M. Mann, patented April 18, 2000 provides the following background information, "Within the past several years, rapid advances have been made in medical devices and apparatus for controlling chronic intractable pain. One such apparatus involves the implantation of an electrode array within the body to electrically stimulate the area of the spinal cord that conducts electrochemical signals to and from the pain site."

[0006] U. S. Patent No. 6,230,057 for a multi-phasic microphotodiode retinal implant and adaptive imaging retinal stimulation system by Vincent

Chow and Alan Chow, patented May 8, 2001 and assigned to Optobionics

Corporation provides the following background information, "A variety of retinal diseases cause vision loss or blindness by destruction of the vascular layers of the eye including the choroid, choriocapillaris, and the outer retinal layers including Bruch's membrane and retinal pigment epithelium. Loss of these layers is followed by degeneration of the outer portion of the inner retina beginning with the photoreceptor layer. Variable sparing of the remaining inner retina composed of the outer nuclear, outer plexiform, inner nuclear, inner plexiform, ganglion cell and nerve fiber layers, may occur. The sparing of the inner retina allows electrical stimulation of this structure to produce sensations of light One such device was reportedly constructed and implanted into a patient's eye resulting in light perception but not formed imagery. A photovoltaic device artificial retina was also disclosed in U.S. Pat.

No. 5,024,223. That device was inserted into the potential space within the retina itself. That space, called the subretinal space, is located between the outer and inner layers of the retina. The device was comprised of a plurality of so-called Surface Electrode Microphotodiodes ("SEMCPs") deposited on a single silicon crystal substrate. SEMCPs transduced light into small electric currents that stimulated overlying and surrounding inner retinal cells."

[0007] U. S. Patent No. 6,324,429 for a chronically implantable retinal prosthesis by Doug Shire, Joseph Rizzo, and John Wyatt, of the Massachusetts

Eye and Ear Infirmary Massachusetts Institute of Technology issued

November 27, 2001 provides the following information, "In the human eye, the ganglion cell layer of the retina becomes a monolayer at a distance of 2.5-

2.75 mm from the foveola center. Since the cells are no longer stacked in this outer region, this is the preferred location for stimulation with an epiretinal electrode array. The feasibility of a visual prosthesis operating on such a principle has been demonstrated by Humayun, et al. in an experiment in which the retinas of patients with retinitis pigmentosa, age-related macular degeneration, or similar degenerative diseases of the eye were stimulated using bundles of insulated platinum wire."

SUMMARY OF THE INVENTION

[0008] Features and advantages of the present invention will become apparent from the following description. Applicants are providing this description, which includes drawings and examples of specific embodiments, to give a broad representation of the invention. Various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this description and by practice of the invention. The scope of the invention is not intended to be limited to the particular forms disclosed and the invention covers all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the claims.

[0009] The present invention provides a system that includes molded features in silicone body. In one embodiment reinforcement elements are molded into a silicone electronic device for connection to tissue. The reinf or cement elements are of various sizes and shapes. Their function includes facilitating handling and implantation, to suit specific applications

(such as molded channels for drug delivery), and to tailor the stresses in membrane to conform uniformly to needed area (such as the curved surface of the retina). The silicone electronic device comprises a substrate composed of silicone that has the ability to conform to various shapes of the tissue.

Electrodes are embedded in the substrate for contacting the tissue and structural elements are formed in the substrate. The electronic device is produced by forming a silicone substrate in a mold. The mold includes forms for structural elements. Additional processing includes patterning conducting lines on the silicone substrate, producing electrodes operatively connected to the substrate, and removing the substrate from the mold. The reinforcement structural elements in this embodiment offer structural support of the implant device to facilitate handling and allow for modification of the mechanical properties of the thin silicone membrane.

[0010] The invention is susceptible to modifications and alternative forms.

Specific embodiments are shown by way of example. It is to be understood that the invention is not limited to the particular forms disclosed. The invention covers all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The accompanying drawings, which are incorporated into and constitute a part of the specification, illustrate specific embodiments of the invention and, together with the general description of the invention given above, and the detailed description of the specific embodiments, serve to explain the principles of the invention.

FIG. 1 illustrates a method of producing an electronic device with reinforcement structural elements. FIG. 2 shows a mold for producing reinforcement structural elements.

FIG. 3 A illustrates an embodiment of an electronic device with reinforcement structural elements.

FIG. 3B is an enlargement of a portion of FIG. 3A.

DETAILED DESCRIPTION OF THE INVENTION [0012] Referring now to the drawings, to the following detailed information, and to incorporated materials; a detailed description of the invention, including specific embodiments, is presented. The detailed description serves to explain the principles of the invention. The invention is susceptible to modifications and alternative forms. The invention is not limited to the particular forms disclosed. The invention covers all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the claims.

[0013] The present invention provides a system that includes molded features in silicone body. In one embodiment reinforcement structural elements are molded into an electronic device for connection to tissue. The device comprises a substrate composed of a silicone that has the ability to conform to various shapes of the tissue. Electrodes are embedded in the substrate for contacting the tissue and structural elements are formed in the substrate. The reinforcement elements are of various sizes and shapes. Their function includes facilitating, handling and implantation, to suite specific applications (such as molded channels for drug delivery), and to tailor the stresses in membrane to conform uniformly to needed area (such as the curved surface of the retina). The electronic device is produced by forming a mold in a silicone substrate. The mold includes forms for structural elements. Additional processing includes patterning conducting lines on the substrate, producing electrodes operatively connected to the substrate, and removing the substrate from the mold. The reinforcement structural elements in this embodiment offer structural support of the implant device to facilitate handling. In other embodiments features are molded or patterned that serve as electrodes, emission sources, and channels for drug delivery.

[0014] The electronic device has many uses including implantable devices such as epiretinal, subretinal, and cortical artificial vision implants, cochlear implants, neurological implants, spinal cord implants and other neural interface implants; sensors and stimulators for interfacing with human body and inanimate objects; shaped acoustic sensors and transmitters; biological, chemical, temperature, radiation sensors; non-destructive evaluation sensors; flexible display monitors; and other devices. In one embodiment of the invention applicants describe a microelectrode array for stimulating retinal cells, that is flexible and will conform to the retina, that is robust and will sustain handling during fabrication and implantation, that is biocompatible interface with electronics.

[0015] Referring now to in FIG. 1, a method 100 of producing an electronic device is illustrated. U. S. Patent Application Serial No. 10/115676, filed April

3, 2002, titled "Flexible Electrode Array for Artificial Vision," incorporated herein by reference, describes electrode arrays for connection to tissue containing cells. The electronic device includes a substrate composed of a polymer. The polymer has the ability to conform to various shapes of the tissue. Electrodes are embedded in the substrate for contacting the tissue.

Conductive leads are connected to the electrodes. The electrodes are useful for stimulating the cells.

[0016] The electronic device can be produced by batch fabrication techniques of the PDMS metalization process, including creating reinforcement structural elements that make the device more robust and easier to handle. Applicants developed an appreciation for the benefit of reinforcement structural elements after observing implantation of a first generation electrode array into a dog's eye. The implantation procedure is extremely complex and the 1st generation device proved to be very difficult to handle during implantation due to the fact that the device has to be very thin

(-50 microns) to conform to the retina. Applicants implantation experiment was to test for the conformability of the PDMS membrane within the eye and the durability of the metal traces. The PDMS device was shown to conform to the retina, but there was evidence of damage to the outer electrode leads near the edge of the device, where forceps were used to grab it. The reinforcement structural elements facilitate handling of the device by providing structural support to the thin device and also provide a safety-zone along the edge of the device to ensure enough area to be able to use forceps without damaging the metal traces. In addition to facilitating handling the structural elements allow for custom tailoring of membrane curvature to perfectly suit the area it is designed to conform to. The dimensions and shapes of the molded structural elements can be altered to control the stresses in the membrane making it more conformable to the needed surface.

[0017] Applicants have developed a system of selective passivation metal traces with PDMS exposing the traces only in areas needed to make contact with the outside world. This includes improvements in the process of metalizing PDMS, selective passivation, using batch fabrication photolithographic techniques to fabricate PDMS, and producing stretchable metal traces that are capable of withstanding strains of 7% with S.D. 1. This also includes incorporating reinforcement structural elements into the PDMS.

[0018] Applicants approach is to use PDMS as the substrate material to batch produces a low-cost device that is ready for implantation without the need for additional packaging steps. Because PDMS has not previously been used in this type of micromachining application, Applicants developed new fabrication processes enabling PDMS patterning, metalization, and selective passivation. The metal features are embedded within a thin substrate fabricated using poly (dimethylsiloxane) (PDMS), an inert biocompatible elastomeric material that has simultaneously low water and high oxygen permeability. The conformable nature of PDMS is critical for ensuring uniform contact with the curved surface of the retina. PDMS is a form of silicone rubber, a material that is used in many implants and has been demonstrated to withstand the body's chemical and physical conditions without causing adverse side effects, suggesting that PDMS may be a favorable material to implant within the body. Robustness of the metalized

PDMS is another important design criterion that applicants consider, as stretching and bending occur during fabrication and implantation of the device. While the project Applicants are working on concerns retinal implants, this technology can be applied to a wide range of implant applications, including: neural interface implants (such as epiretinal implant, subretinal implant, cortical implant, cochlear implant, spinal cord impland, deep brains stimulation), also other biomedical applications such as drug delivery and non-biomedical applications.

[0019] Step 101 (Provide Mold for Subsequent Processing) The fabrication process starts with silicon handle wafer with a series of 50-micron deep

V-grooves etched using traditional photolithographic methods and silicon etching techniques. The V-grooves in the silicon act as a molds for the PDMS.

These grooves form reinforcement structural elements in the PDMS along the boundaries of the stretchable micro-electrode array devices. The reinforcement structural elements act as safety zone to facilitate the handling and implantation of these devices into the retina.

[0020] In step 102 (First Silicone Layer Applied to Mold), a first flexible polymer layer is applied to the matrix. The polymer used for the first flexible polymer layer and the second flexible polymer layer has characteristics that include at least one of being fluid, resinous, rubbery, stable in high temperatures, and hydrophobic. The flexible polymer used as polymer layers of the electronic apparatus is a silicone. The silicone is poly(dimethylsiloxane) known as PDMS. PDMS has very low water permeability and protects the electronic components from the environment. PDMS is flexible and will conform to curved surfaces. It is transparent, stretchable, resinous, rubbery, stable in high temperatures.

[0021] In step 103 (Pattern Circuit on First Silicone Layer), the process of forming the electrical circuit lines is initiated. A photoresist (AZ®1518,

Clariant) is spun onto the PDMS surface at 1000 rpm for 20 seconds and baked at 60°C for 45 minutes and then the temperature is brought down slowly (30 min to ram temperature down) to room temperature to avoid cracking in the Photoresist. Prior to photoresist application, the section is placed in an oxygen plasma to oxidize the surface. This allows the resist to wet the PDMS surface eliminating beading and ensuring the formation of a smooth and uniform coat of photoresist on the polymer surface. The substrate is placed in the oxygen plasma for 1 minute at an RF power of 100 Watts with oxygen owing at 300 seem. The photoresist features are then UV exposed at

279 mj and developed in AZ developer 1:1 for 70sec. Then the section is rinsed under slow stream of water gently and quickly and then dried using

N2. The section is placed for a second time in the oxygen plasma to activate the newly exposed PDMS surface, and promote adhesion of the metal.

[0022] In step 10 a metal layer is deposited in the patterned circuit in the first silicone layer. In step 105 a second silicone layer is applied over the components, circuits, and first silicone layer. The completed reinforcement elements are of various sizes and shapes. Their function includes facilitating handling and implantation, to suite specific applications (such as molded channels for drug delivery), and to tailor the stresses in membrane to conform uniformly to needed area (such as the curved surface of the retina).

[0023] Referring now to FIG. 2, a mold for producing reinforcement structural elements is shown. The mold is designated generally by the reference numeral 200. The fabrication process starts with silicon handle wafer 201 with a series of 50-micron deep V-grooves 202 etched using traditional photolithographic methods and silicon etching techniques. The

V-grooves 202 in the silicon 201 act as a molds for the PDMS. These grooves

202 form reinforcement structural elements. The reinforcement structural elements 202 are produced in the PDMS along the boundaries of the stretchable micro-electrode array section of the finished devices. The reinforcement elements are of various sizes and shapes. Their function includes facilitating handling and implantation, to suite specific applications

(such as molded channels for drug delivery), and to tailor the stresses in membrane to conform uniformly to needed area (such as the curved surface of the retina). The reinforcement structural elements 202 act as safety zone to facilitate the handling and to control stresses in the membrane implantation of these devices into the retina. The reinforcement structural elements 202 in this embodiment can be described as reinforcement ribs.

[0024] FIG. 3 A shows an electronic device with reinforcement structural elements produced by the method illustrated in FIGS. 1 and 2. The electronic device is designated generally by the reference numeral 300. The electronic device 300 is implantable. An implantable electrode device is shown and described in U. S. Patent No. 4,573,481 by Leo A. Bullara, patented March 4,

1986. The disclosure of this patent is incorporated herein in its entirety by reference. A directional programming for implantable electrode arrays is shown in U. S. Patent No. 6,052,624 for by Carla M. Mann, patented April 18,

2000. The disclosure of this patent is incorporated herein in its entirety by reference. A multi-phasic microphotodiode retinal implant and adaptive imaging retinal stimulation system, patented May 8, 2001, is shown in U. S.

Patent No. 6,230,057 by Vincent Chow and Alan Chow. The disclosure of this patent is incorporated herein in its entirety by reference. A photovoltaic artificial retina device is in U.S. Pat. No. 5,397,350. The disclosure of this patent is incorporated herein in its entirety by reference.

[0025] The electronic device 300 comprises a flexible polymer body 301 with at least one electrode 303 in the flexible polymer body 301. The electrode

303 is shown in a cut away section because the electrode can not be seen on the back face 304 shown in FIG. 3A. The electrode 303 is exposed on the front face 305. Reinforcement structural elements 302 in the flexible polymer body

301 along the boundaries of the body act as a safety zone to facilitate the handling and implantation of the device.

[0026] FIG. 3B is an enlargement of a portion of FIG. 3A showing more details of the reinforcement structural elements 302. The reinforcement structural elements 302 are inverted "V" shaped structural elements that act as safety zone to facilitate the handling and implantation of the electronic device 300.

[0027] The electronic device 300 has use as an intraocular prosthesis. This provides a system that restores vision to people with certain types of eye disorders. An image is captured or otherwise converted into a signal representing the image. The signal is transmitted to the retina utilizing an implant. The electronic device 300 is made of a compliant material. Electrodes and conductive leads are embedded in the substrate. The electronic device 300 includes a substrate composed of a polymer. The polymer has the ability to conform to various shapes of the tissue. The fact that the electronic device is stretchable is advantageous because it will conform to various shapes and will resist damage during handling. The reinforcement structural elements act as safety zone to facilitate the handling and implantation of these devices.

[0028] While the invention may be susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and have been described in detail herein. However, it should be understood that the invention is not intended to be limited to the particular forms disclosed. Rather, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the following appended claims.

Claims

THE INVENTION CLAIMED IS

1. An electronic device for connection to tissue, comprising: a substrate composed of silicone that has the ability to conform to various shapes of said tissue, electrodes embedded in said substrate for contacting said tissue, and structural elements formed in said substrate.

2. The electronic device of claim 1 wherein said substrate comprises a flexible silicone body with structural elements formed in said silicone body.

3. The electronic device of claim 1 wherein said substrate comprises a poly(dimethylsiloxane) body.

4. The electronic device of claim 1 including conductive leads connected to said electrodes.

5. The electronic device of claim 1 wherein said substrate is poly(dimethylsiloxane) with structural elements formed in said poly (dimethylsiloxane) .

6. The electronic device of claim 1 wherein said structural elements formed in said substrate comprise rib support elements.

7. The electronic device of claim 1 wherein said structural elements formed in said substrate comprise structural elements for facilitating handling of said electronic device.

8. The electronic device of claim 1 wherein said structural elements formed in said substrate comprise structural elements for facilitating implantation of said electronic device.

9. The electronic device of claim 1 wherein said structural elements formed in said substrate comprise structural elements for drug delivery.

10. The electronic device of claim 1 wherein said structural elements formed in said substrate comprise structural elements for tailoring the stresses in said electronic device.

11. The electronic device of claim 1 wherein said structural elements formed in said substrate comprise structural elements for tailoring the stresses in said electronic device to conform uniformly to needed areas.

12. The electronic device of claim 1 wherein said structural elements formed in said substrate comprise structural elements for tailoring the stresses in said electronic device to conform uniformly to the curved surface of a retina.

13. The electronic device of claim 1 wherein said structural elements formed in said substrate comprise inverted "V" shaped structural elements.

14. A method of producing an electronic device, comprising the steps of: forming a polymer substrate in a mold that includes forms for structural elements, patterning conducting lines on said polymer substrate, producing electrodes operatively connected to said substrate, and removing said polymer substrate from said mold.

15. The method of producing an electronic device of claim 14 wherein said conductive lines are biocompatable.

16. The method of producing an electronic device of claim 14 wherein said conductive lines are comprised of gold, platinum, or iridium.

17. The method of producing an electronic device of claim 14 wherein said polymer is an elastomer.

18. The method of producing an electronic device of claim 14 wherein said polymer is an elastomer that is flexible.

19. The method of producing an electronic device of claim 14 wherein said polymer is an elastomer that is flexible and stretchable.

20. The method of producing an electronic device of claim 14 wherein said elastomer is silicone.

21. The method of producing an electronic device of claim 14 wherein said elastomer is poly(dimethylsiloxane).

22. The method of producing an electronic device of claim 14 wherein said mold is a "V" shaped mold.