Abstract:
Devices, systems and methods that comprise or utilize implantable electrode arrays for neural stimulation and/or sensing. In some embodiments, the electrode array is implanted or inserted into the auditory nerve and is used to deliver electrical impulses to/receive data from the auditory nerve in the treatment of hearing disorders.

Description:
RELATED APPLICATION 
     This patent application claims priority to U.S. Provisional Patent Application No. 60/688,982 filed Jun. 8, 2005, which is expressly incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION 
     This invention relates generally to the fields of electrical and biomedical engineering and more particularly to implantable electrode arrays useable for neural stimulation and/or sensing. 
     BACKGROUND 
     The future development of advanced neuroprosthetic systems is likely to significantly improve the quality of life for persons who suffer from a variety of disorders, including those who are deaf, blind, or paralyzed, etc. Additionally, the development of apparatus and techniques for discretely sensing localized nerve impulses within neural tissue promises to provide new avenues for research and treatment of neurological disorders. However, the development of such advanced neuroprosthetic systems and sensing apparatus will be dependent upon the availability of microelectrode arrays which may be implanted into nerves for the purpose of providing reproducible, localized stimulation or sensing at discrete locations. 
     One example of an area where advanced neuroprosthetic systems may be of great benefit is in the treatment of hearing disorders. At present, devices known as cochlear implants are being used to restore varying levels of functional hearing in persons who suffer from certain types of hearing loss. The cochlea of the ear is a spiral-shaped, fluid-filled structure that is lined with auditory sensory cells known as “hair cells” which move in response to sound, thereby stimulating the adjacent auditory nerve. The cochlear electrode array resides within a region of the cochlea known as the scala tympani and, thus, is referred to as an “intrascalar electrode.” Such intrascalar electrode delivers electrical impulses that bypass the hair cells and stimulate the adjacent portion of the auditory nerve. However, the typical intrascalar electrode is located relatively far from the auditory nerve and is separated from the nerve by the impedance of the modiolar wall. Thus, the spatial resolution of the stimulation currents that each the auditory nerve is relatively low. This lack of spatial resolution limits the number of independent information channels that can be used to transfer auditory information through the auditory nerve to the brain. Moreover, relatively high threshold currents are needed by the intrascalar electrodes, thus resulting in high power consumption which affects the batter life of cochlear implants. 
     An alternative to the use of intrascalar electrodes is direct stimulation of the auditory nerve by way of an intraneural electrode array that is actually positioned within the auditory nerve. The use of an intraneural electrode array can substantially increase the number of functional channels and by increasing the selectivity and dynamic range of each stimulating electrode. It is believed that, at least in some patients, more accurate tonotopic representations may be obtained if an electrode array is placed directly within the auditory nerve instead of in the scala tympani of the cochlea. Direct stimulation of the auditory nerve may also offer increased spectral resolution and lower power consumption when compared to cochlear implants. The possibility exists to significantly improve human auditory prostheses by Simmon performed the early intranerual electrode implantations, but the relatively large size of the platinum-iridium wire electrodes did neither permit atraumatic insertion, nor accurate placement of these electrodes. 
     Early attempts in developing intraneural electrodes were based on platinum-iridium wire electrodes, which led to insertion trauma and reduced placement accuracy. In recent years, the development of Microelectromechanical Systems (MEMS) technology (sometimes referred to as Micro Systems Technology or “MST”) has made it possible to replace bulky off-chip components with microfabricated counterparts. Using MEMS technology, a number of researchers have fabricated microelectrode arrays intended for implantation in the central and peripheral nervous systems. However, even with the use of MEMS fabrication techniques, certain issues relating to electrode size, the need for electrical wires to communicate and transfer power to the arrays, and the need for hand assembly have remained largely unsolved. 
     SUMMARY OF THE INVENTION 
     The present invention provides electrode arrays and intraneural auditory prosthesis having form-fitted implantable micro-electrode arrays and on-chip wireless circuitry. A process known as “flip chip bump bonding” may be used to manufacture these micro-arrays. In a process known as “flip chip bump bonding” a bumped chip is bonded directly to a printed wiring board (PWB). In such process, low-temperature solder is hot-injection-deposited through a mask and onto the PWB. 
     Devices of the present invention may include various development(s) or improvements over the prior art, including but not necessarily limited to one or more of the following:
         1. Custom-designed circuitry that may be fabricated by standard complementary metal-oxide semiconductor (CMOS) chip manufacturing processes,   2. Electrodes that may be fabricated with high-precision Deep Reactive-Ion Etching (DRIE),   3. Flip-chip and solder bump bonding to integrate electronics with the electrodes,   4. Individual electrodes that may be electrically isolated and held in place with a layer of dielectric at the base and shaped polymer layer around the base,   5. Etching, deposition, and molding techniques to create the form-fitted contour at the electrode base, and   6. Data transfer and power delivery to be provided with a wireless, inductive RF system.       

     Furthermore, this invention creates a three-dimensional, one-chip solution that allows the integration of high density electrodes while avoiding the interconnection problem via wireless, inductive RF telemetry in the CMOS chip. 
     The present invention provides for (1) accurate and secure placement of the implantable electrodes on the target auditory nerves with a form-fitted geometry, (2) improved reliability, functionality, and manufacturability by eliminating multiple long interconnects between electrodes and signal processing circuits, and (3) greatly enhanced usability and implant duration with wireless telemetry and power delivery to the neural implants. 
     In accordance with the invention, there are provided electrode arrays fabricated with MEMS for use as implants onto auditory nerve. Such, electrode arrays may be structured with wireless circuitry for both data transmission and power delivery. These electrode arrays may interface with the neurons inside the auditory nerve next to the cochlea and may be used to stimulate those neurons to elicit the sensation of sound, thereby restoring some amount of hearing to deaf patients who have total damage to the cochlea. The electrode arrays of the present invention may also act as neural recorders for research purposes, recording the electrical impulses generated from healthy cochlea in response to sounds. 
     The invention is intended for implanting onto human auditory nerves to restore hearing functions for profoundly deaf patients and to record electrical signals generated from sound in healthy subjects. The wireless telemetry and the electrode array design in this invention can also be applied to other neural prostheses including retinal and vestibular implants, as well as to serve as a general-purpose miniaturized device for chronically stimulating and recording the nervous system in electrophysiological and behavioral experiments involving conscious animals. 
     A flip chip assembly bonds the electrode array and the vendor fabricated electronic chip. The term “flip-chip” refers to the electronic component that is mounted directly onto another silicon substrate in a ‘face-down’ manner. Electrical connection is achieved through conductive bumps built on the surface of the chips, which is why the mounting process is ‘face-down’ in nature. During mounting, the chip is flipped on the substrate, with the bumps being precisely positioned on their target locations. Because flip chips do not require wire bonding, their size is much smaller than their conventional counterparts. Physically, the bump on a flip-chip is exactly just that—a bump formed on a bond pad of the die. Bumps serve various functions: 1) to provide an electrical connection between the die and the substrate; 2) to provide thermal conduction from the chip to the substrate, thereby helping dissipate heat from the flip chip; 3) to act as spacer for preventing electrical shorts between the die circuit and the substrate MEMS device; and 4) to provide mechanical support to the flip-chip. 
     In at least some embodiments of the invention, electrode arrays of the present invention may be fabricated by initially bump bonding silicon wafer to CMOS chip. Columns approximately 750 mm in height are created by bulk micromachining this silicon wafer with deep reactive ion etching (DRIE). At this height the final electrodes can penetrate to the center of the auditory nerve, thereby stimulating and recording from the maximum number of neurons. In some embodiments, columns of varying height may be formed, such that the resultant electrodes will vary in length and will thereby stimulate nerve fibers at varying depth (or in various planes) within the acoustic nerve. Since the number of stimulated neurons correlates to the fidelity of the implant, the intraneural electrode arrays of the present invention may elicit better sound sensation than current cochlear implants. Also, DRIE etching uses a photo-definable masking layer that enables a substantially higher density of electrodes than the use of dicing saws. As a result, the present invention is able to achieve more than 100 electrodes in a 1.5 square millimeter area. Each electrode may have a diameter of about 80 microns and the space between two adjacent electrodes may be about 50 microns. The columns may be sharpened into a needle shape with a two-step isotropic etching, reactive ion etching (RIE) and HNA wet etching process. The passive array may be activated by deposition of iridium to form the electrode tips and conformal coating with a layer of biocompatible Parylene C. The tips may be exposed in the final step by selectively removing Parylene C from the tip area. The surface roughness on the electrodes can be reduced by refinement of the tip-shaping process. Also, the Parylene C coating may contribute to further reduction or elimination of surface roughness. 
     Further in accordance with the present invention, a CMOS chip may be flip-chip bump bonded to a silicon wafer before the electrode array fabrication. The CMOS chip will have both wireless communication and DSP functions for neural recording and stimulation. This on-chip circuitry will eliminate the need for an interconnection between the electronic chip and the MEMS electrode. The most significant advantages of using wireless link and on-chip DSP instead of transcutaneous electrical wires include ease of implant surgery, vastly improved mechanical robustness, and enabling chronic implantation with minimal complications. 
     Further aspects, elements and details of the present invention are described in and may be understood from the following detailed description and the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic diagram of an auditory neural prosthesis system of the present invention. 
         FIG. 2  is a side-view schematic diagram of one embodiment of an implantable device of the present invention having an array of intraneurally insertable electrodes attached to a chip having on-chip circuitry. 
         FIGS. 3A-3E  are diagrams showing steps in a method for fabricating the implantable device of  FIG. 2 . 
       FIGS.  3 A′- 3 E′ are diagrams showing steps in a method for fabricating an alternative embodiment of the implantable device of  FIG. 2  wherein the electrodes are of varied length. 
         FIG. 4  is a bottom-view schematic diagram of the workpiece shown in  FIG. 3A . 
         FIG. 5  is a block/flow diagram of one embodiment of on chip circuitry useable in this invention. 
         FIG. 6  is a schematic diagram of steps in a process for flip chip bonding of a circuit bearing chip to a silicon wafer substrate in accordance with the present invention. 
         FIG. 7  is a more detailed block/flow diagram of an auditory neural prosthesis system of the present invention. 
         FIG. 8  is a schematic diagram showing the use of an embossing tool in fabrication of a device of the present invention. 
         FIG. 9  is a schematic flow diagram showing steps in a process for blow molding a device of the present invention. 
     
    
    
     DETAILED DESCRIPTION 
     The following detailed description, the drawings and the above-set-forth Brief Description of the Drawings are intended to describe some, but not necessarily all, examples or embodiments of the invention. The contents of this detailed description, the accompanying drawings and the above-set-forth brief descriptions of the drawings do not limit the scope of the invention or the scope of the following claims, in any way. 
       FIG. 1  is a schematic diagram of a auditory neural prosthesis system  10  comprising an implantable device  12  and a signal processor  14 . The implantable device comprises an intraneural electrode array  16  with integrated on-chip circuitry  18  which can communicate in wireless fashion through the skin S with the signal processor  14 . The electrode array  16  with on-chip circuitry  18  is implanted such that the electrodes of the array  16  are inserted into the auditory nerve of a human or animal subject. A bi-directional RF telemetry link is used to transfer both data and power from the signal processor  14  to the implantable device  12 . The signal processor  14  may be battery powered and may be carried by the subject, subcutaneously implanted on the subject or otherwise maintained in sufficient proximity to the on chip circuitry  18  to allow data and power to be transmitted via the telemetry link. The processor  14  may deal with the data by using certain algorithms. The processor  14  may also be connected to a computer work station  15  by a Bluetooth or Wi-Fi link to advance data processing. 
       FIG. 2  shows one embodiment  12   a  of the implantable device  12 . In this embodiment  12   a , the electrode array  16   a  comprises a plurality of elongate electrodes  20  having sharpened distal ends  22 . The electrodes  20  are operatively inserted into the auditory nerve AN, as shown, while the on-chip circuitry  18   a  resides in juxtaposition to the auditory nerve AN. It has been reported that the auditory nerve AN in an adult human typically ranges in diameter from 1.06 to 1.5 mm. In this embodiment, the each electrode  20  is approximately 750 μm in length. This, when the electrodes  20  are advanced to their maximum extent into the auditory nerve AN, the distal tips  22  of the electrodes  20  will have traveled approximately half way through the nerve fiber, as shown in the diagram of  FIG. 2 . 
     In a process for manufacturing the implantable device  12 , as more fully described herebelow, customized circuitry is first fabricated on a chip by standard CMOS technique. The electrode array  16  is etched into or otherwise formed on the bottom of a silicon wafer. The circuitry-bearing chip is flip-chip bonded to the top of the silicon wafer and interconnections are made by solder between the two layers. Each individual electrode  20  is isolated by underfilling. This design proposes a 3D one-chip solution, which avoids the interconnection problem between the circuitry and the microelectrode array, and shows more potential for achieving higher density of electrode. The inductive RF telemetry transmits both data and power to the implantable device through tissue. 
     Manufacture of the Electrode Array 
       FIGS. 3A-3E  show a process for forming the electrode array  16   a  of the implantable device  12   a  shown in  FIG. 2  using CMOS technology. This process begins, a shown in  FIG. 3A , with a highly doped silicon wafer  21  having A CMOS chip  22  bonded thereon. Next, as shown in  FIG. 3B , a Bosch Deep Reactive Ion Etch (DRIE) is used to remove or cut away portions of the wafer  20  so as to form a number of substantially square silicon columns  24  on the underside of the wafer. In the example shown in the drawings, these columns  24  form an 8 electrode×8 electrode array that is less than 1 mm 2  in area, as shown in  FIG. 4 . Each column  24  is then wet etched by dipping in HNA acid to form a sharp needle tip  26  on each column  24  as shown in  FIG. 3C . Subsequently, the sharp needle tips  26  are coated with Iridium for charge transfer. As seen in  FIG. 3D , a photoresist material  30 , such as SU-8 (a near-UV photoresist used for MEMS fabrication), is then filled into the gaps among the columns  24  and molded with a PDMS mold (see  FIGS. 8 and 9 ) to form a concave curved surface  32  thereon. This curved surface  32  is generally of a shape that mates with the convex outer surface of the auditory nerve AN. In this manner, the curved surface  32  will make substantially abutting contact with the outer surface of the auditory nerve AN, thus providing additional stability and also limiting the extent to which the electrodes  20  may be advanced into the auditory nerve AN. As shown in  FIG. 3E , polyimide coating is then applied to each column  24  and a portion of such coating is then removed from a distal portion of each column  24 , thereby exposing the sharpened distal tips  26  and forming an array of individual electrodes  20   a.    
     It is to be appreciated that, in the example of  FIGS. 3A-3E , the electrodes  20   a  are of equal length. Thus, as shown in  FIG. 2 , when fully advanced into the auditory nerve AN, those electrodes  20   a  at the center of the array will advance to the center of the auditory nerve fiber while those electrodes  20   a  on the periphery of the array will remain in the periphery of the auditory nerve fiber. Also, the conductive distal portions of all of the electrodes  20   a  will thus be disposed in a horizontal plane within the auditory nerve AN and will connect only with nerve fiber(s) that run through that particular horizontal plane. The nerve fibers above and below this horizontal plane will not receive direct impulses from the electrodes  20   a . Also, many of these equal length electrodes  20   a  may redundantly deliver impulses directly to only certain fiber(s) that pass through the horizontal plane and not to other nerve fibers that pass through other portions of the auditory nerve AN. 
     To deliver impulses directly to more auditory nerve fibers and to minimize unnecessary redundancy in stimulation of the auditory nerve fiber(s), it may be desirable in some embodiments of the invention to vary the length of the individual electrodes  20   a . FIGS.  3 A′- 3 E′ show an example of an alternative manufacturing process for forming an implantable device  12   a  having an electrode  16   a  with electrodes  20   a  of varying length. In this example, a 10×10 electrode array is created in a 1 mm 2  area by way of a bulk-machining process. 
     As seen in FIG.  3 A′ this process begins with silicon wafer  21   a  bump bonded to a signal-processing and wireless-communication CMOS chip  22   a . The bump bonding process is known in the art and is described in more detail herebelow. A 10×10 array of individual columns  24   a  is then created in the silicon wafer  21   a  by micromachining this silicon wafer  21   a  with DRIE. The widths (i.e., diameters) of the columns  24   a  range from 70 μm in the center of the array to 80 μm at the edges of the array, increasing by increments of 2 μm per column. Each column  24   a  is then sharpened into a needle shape with an isotropic etchant solution of 20% Hydrofluoric, 70% Nitric, and 10% Acetic acid (HNA). Various concentrations of acid in this etchant solution can result in different column geometry. This etching process also shortens the columns  24   a  to different lengths due to the differences in column width (i.e., the wider columns have greater mass and therefore remain longer while the narrower columns have less mass and therefore become shorter). In this example, after completion of the etchant step, the columns  24   a  vary in length from 200 μm to 750 μm. A lift-off iridium coating is then applied to the columns  24   a . The columns  24   a  are then coated with a layer of biocompatible Parylene C and such Parylene C coating is then removed from the distal portions of the columns  24   a  by O 2  plasma, thereby forming the individual electrodes  20   b . As seen in FIG.  3 E′, when these electrodes  20   b  are inserted into the auditory nerve AN, the exposed tips of the electrodes  20   b  will reside within a number of different horizontal planes within the nerve AN, thereby delivering impulses to nerve fibers located in those various horizontal planes. 
     On-Chip Circuitry 
     In this example, the on-chip circuitry is fabricated by AMIS ABN 1.5 μm process.  FIG. 5  shows a block/flow diagram of one embodiment of the on chip circuitry  18  useable in this invention. This circuitry contains both neural recording and stimulation function. 
     To record the neural signals, Pre-amplifiers are first to use to amplify the neural signals, which usually are much weak. Time division multiplexers then are employed for each eight electrodes to save more external leads and discriminate signals from different record sites. Before the signals are sent to the signal processor, they are amplified and digitalized. The processor codes the signals into a train for advanced exploration. On the other hand, to stimulate the auditory nerve AN, the signal sequence is first decoded, and converted to analogy signals, which will trigger the current source to generate bi-phase current pulses to fire the nerve fibers. 
     In the 64-channel neural signal recording circuit shown in the example of  FIG. 5 , low-noise pre-amplifiers are necessary for the active microelectrodes because of the relatively weak signal. Time division multiplexers are employed for each group of eight electrodes to conserve external leads and discriminate signals from different recording sites. Before further processing, the signals are amplified with a second-stage operational amplifier, and then digitized with an 8-bit A/D converter. The chip  22  or  22   a  is fabricated with AMI 0.5 μm triple-metal and double-poly CMOS technology with a die size 1.5×1.5 mm 2 . Low-noise amplifier is employed in our design. The 8:1 multiplexer is implemented by full CMOS switches. The 8-bit charge redistribution successive approximation A/D converter is chosen in this design to take advantage of the minimal amount of analog hardware in order to meet our primary design goal of low-power consumption and small layout area. The successive converters apply a binary search algorithm to determine the closest digital word to match an input signal. The ADC sampling rate is 100 kS/sec in order to sample from 8 channels. The maximum magnitudes of Integral Nonlinearity (INL) and Differential Nonlinearity (DNL) are less then 0.8 LSB. The total power consumption of the chip is lees than 100 μW. 
     Wafer Bonding 
     In this example, the fabricated electronic chip  22  is bonded to the silicone wafer  21  by a “flip chip” process whereby the circuit bearing chip  22  is mounted on the silicone wafer  21  in a ‘face-down’ manner.  FIG. 6  shows a schematic diagram of the process flow for flip chip bonding. In accordance with the art of flip chip bonding, electrical connection is achieved through conductive bumps  40  that are built into the circuit formed on the surface of chip  22 , which is why the mounting process is ‘face-down’ in nature. During mounting, the chip  22  is flipped onto the wafer  21 , with the bumps  40  being precisely positioned on their target locations to correspond to the position of each individual electrode  24 . Because no wire bonding is required, the chip  22  may be smaller in size than a conventional chip having the same functional circuitry. Physically, each bump  40  on the flip-chip is exactly just that—a bump formed on a bond pad of the die. Bumps  40  serve various functions: 1) to provide an electrical connection between the die and the substrate; 2) to provide thermal conduction from the chip to the substrate, thereby helping dissipate heat from the flip chip; 3) to act as spacer for preventing electrical shorts between the die circuit and the substrate MEMS device; and 4) to provide mechanical support to the flip-chip. 
     The open spaces  42  between the flip chip surface and the substrate are filled with a non-conductive adhesive ‘underfill’ material. Various types of underfill adhesives may be used. One example of a suitable underfill adhesive that may be used for this purpose is a two part cold cured epoxy resin adhesive available as DELO-DUOPOX™ available from Delo Industrial Adhesives, Landsberg, Germany. Such underfill material may serve to protect the bumps  40  and the circuitry of the chip  22  from moisture, contaminants, and other environmental hazards. Also, this underfill material mechanically locks the flip chip  22  to the silicon wafer  21 , thereby reducing the differences between the expansion of the flip chip  22  and the wafer  21 . This prevents the bumps  40  from being damaged by shear stresses caused by differences between the thermal expansions of the chip and the wafer substrate  21 . Meanwhile, it provides the isolation at the root of the electrode. 
     Inductive RF Telemetry 
     As illustrated in the flow diagram of  FIG. 7 , in wireless embodiments of the present invention, inductive radio frequency (RF) telemetry may be used to provide communication between the signal processor  14  and the on chip circuitry  18  of the implantable device  12  or  12   a . Such wireless connection avoids the risk of infection associated with the use of wires to penetrate through biological tissue. Data and power signals can be transmitted by means of two inductively coupled coils  40 ,  42  on the both sides of the tissue (e.g., through the skin and adjacent tissues surrounding the ear). The forward coil  40  is driven by a class E power amplifier, which can achieve high transfer efficiency, to transmit power and data to the implantable device. A voltage regulator on the on chip circuit  18  stabilizes the received power and supplies other components on the chip  22  or  22   a . Stimulation data through the forward coil  40  are converted to bi-phase pulse trains, then sent to the electrode array  16  or  16   a  to fire the target nerve fibers. A transmitter included in the on chip circuitry  18  collects the pre-processed recording data, and sends such data outside the tissue by a backward coil  42 . The manufacturer and/or implanting professional may tune the transcutaneous link to optimize transmission and/or to account for variations in implant size and shape of the coils, location of the implant, misalignment and displacement tolerance, power and regulation requirements, efficiency, communication bandwidth, and power supply. 
     It is to be appreciated that the invention has been described hereabove with reference to certain examples or embodiments of the invention but that various additions, deletions, alterations and modifications may be made to those examples and embodiments without departing from the intended spirit and scope of the invention. For example, any element or attribute of one embodiment or example may be incorporated into or used with another embodiment or example, unless otherwise stated or unless doing so would render the embodiment or example unsuitable for its intended use. Also, where the steps of a method or process are stated in a particular order, the order of such steps may be changed or varied unless otherwise stated or unless doing so would render that method or process unsuitable for its intended use. All reasonable additions, deletions, modifications and alterations are to be considered equivalents of the described examples and embodiments and are to be included within the scope of the following claims.