Patent Publication Number: US-2011054579-A1

Title: Flexible penetrating electrodes for neuronal stimulation and recording and method of manufacturing same

Description:
FIELD OF THE INVENTION 
     The invention relates to penetrating electrodes and a method of producing flexible penetrating multi-electrode arrays for neuronal applications. 
     BACKGROUND OF THE INVENTION 
     Micro scale electrodes are known in the art and may be capable of stimulating and recording neural tissue. However known electrodes are generally 2D or surface electrodes and are manufactured by having a substrate layer usually an insulating polymer and consisting of a plurality of conductive electrodes fabricated on top of this. After coating another insulating polymer on these conducting electrodes, the conducting surface is exposed. 2D surface electrodes are limited in their ability to access various target surfaces and provide only limited access to different surfaces. It would however be desirable to realize 3-D penetrating electrodes as they could provide large charge transfer capability due to low electrode-electrolyte impedance and access various portions of a desired target. 
     Prior art penetrating electrodes currently are mostly made of silicon. Some of the drawbacks of the above silicon based penetrating stimulation electrodes is that they are complex in micro-fabrication and also their integration with electronics may require another flexible cable to be bonded and electrically connected using cumbersome methods like soldering etc. Another major disadvantage is that silicon has not been proved biocompatible. Additionally, silicon may trigger undesirable bodily reactions such the persistence of macrophages surrounding chronically or long term implanted neuroprosthetic devices and deleterious effects on adjacent nerve cell bodies and their processes. 
     Another problem with prior art penetrating movement of the penetrating rigid electrode array inside the soft tissue causing significant damage. There is therefore a need in the art for an improved array that is flexible to conform to various shaped targets and biocompatible. There is also a need in the art for an array that is easily mated with a microelectronic device. 
     SUMMARY OF THE INVENTION 
     In one aspect there is disclosed a method of forming a flexible penetrating array for neuronal applications including the steps of: providing a substrate; forming at least one opening in the substrate; applying at least one insulating layer overlying the opening and the substrate; applying at least one patterned conductive layer overlying the insulating layer; applying a first polymer layer overlying the conductive layer filling the opening and overlying the substrate; patterning at least one via on the first polymer layer accessing the conductive layer; applying at least one patterned metallization layer overlying the first polymer layer and in electrical contact with the conductive layer; applying at least one secondary polymer material overlying the first polymer layer sandwiching the metallization layer; patterning the substrate forming a second opening and etching the insulating layer; applying at least one secondary metallization layer overlying the conductive layer; and applying a third polymer layer overlying the entire array with at least one via opening to access the secondary metallization layer. 
     In another aspect there is disclosed a flexible penetrating array for neuronal applications that includes an insulating layer. A conductive layer is formed on the insulating layer. A flexible polymer substrate is formed on the conductive layer; the polymer substrate includes defined penetrating electrodes. A first metallization layer is formed on the polymer substrate. A second flexible polymer layer is formed on the first metallization layer. A second metallization layer is formed on the second flexible polymer layer. A third flexible polymer layer is formed on the second metallization layer. The third flexible polymer layer is patterned to expose the second metallization layer that is integrated with the out of plane conductive layer and first metallization layer. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1   a - 1   b  is a cross-sectional view showing the process flow for forming a flexible penetrating electrode array by etching trenches in the substrate and applying a conductor and insulator conforming to the trench; 
         FIG. 2   a - 2   b  is a cross-sectional view showing the process flow for forming a flexible penetrating electrode array by filling the trench with parylene and opening up the via to the underlying conductor to couple the metallization layer;. 
         FIG. 3   a - 3   b  is a cross-sectional view showing the process flow for forming a flexible penetrating electrode array by applying another parylene layer overlying the metallization conductive layer, opening the backside of the substrate to access the conductive layer, penetrating portion and subsequently depositing another metallization layer; 
         FIG. 4   a - 4   b  is a cross-sectional view showing the process flow for forming a flexible penetrating electrode array releasing the device from the carrier substrate and subsequently applying another insulating parylene layer and opening the vias; 
         FIG. 5   a - 5   b  is a cross-sectional view showing the process flow for forming a flexible penetrating electrode array showing the bonding of the released device to a backing substrate layer; 
         FIG. 6  is a 3D view of the flexible penetrating array showing the matrix of penetrating electrodes. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Referring to the various figures, the present disclosure relates to flexible penetrating, multi-electrode arrays  10  for neural stimulation and recording and the method of manufacture for the same. The flexible nature of the arrays  10  includes the use of a polymer that is flexible and bio-compatible. In one aspect the polymer may include parylene. The term penetrating may also describe micro-needles and they are used interchangeably in this disclosure. Parylene is a United States Pharmacopoeia (USP) Class VI biocompatible material that has good barrier properties against, strong acids, inorganic and organic substances and water vapor. Parylene is a bio-stable and biocompatible material approved by the FDA for various applications. Manufacturing is also cost effective with various deposition techniques including CVD, or Chemical Vapor Deposition which takes place at low pressure and at room temperature. Parylene may also be etched in an Oxygen plasma environment using RIE (Reactive Ion etching). Various forms of parylene include: N, C, D, F, and HT. In one aspect, parylene C may be utilized. 
     The microfabrication for the penetrating flexible electrode array  10  starts by etching a trench  12  in a silicon substrate  14  as shown in  FIG. 1   a.  The trench  12  may be etched by DRIE or any other wet chemical etching to give the shape of the penetrating electrode  16 . The dimensions of the trench including the height “h” and width “w” define the dimensions and the shape of the penetrating electrode  16 . The height “h” may range from tens of microns to 1.5 mm and the width “w” may range from 5 microns to tens of microns. A person of ordinary skill in this art will be able to easily make further alterations and modifications after reading the present invention. It can easily be inferred that any particular embodiment illustrated with diagrams and explained cannot be considered limiting. Modifications to the current embodiment may include etching the trench  12  through the entire thickness of the substrate  14  or forming the trench  12  in such a way to have slanted walls or tips. 
     Again referring to  FIG. 1   a,  in this specific embodiment, next an insulating layer  18  such as silicon dioxide may be deposited to conform to the trench  12  and also to the silicon substrate  14 . In one aspect the silicon dioxide may be deposited by LPCVD. The insulating layer  18  may be utilized as a sacrificial layer to release the completed device from the silicon substrate  14 . The insulating layer  18  may have a thickness of from one micron to several microns. 
     Next, a conductive layer of polysilicon  20  may be deposited overlying the insulating layer  18  as shown in  FIG. 1   b.  In one aspect the polysilicon may be deposited by LPCVD. The polysilicon layer  20  formed on the silicon dioxide layer  18  may be patterned to have a defined pattern. The polysilicon layer  20  may be doped with boron or phosphorous to make it conductive and aid in defining an electrical layer on the penetrating electrode array  10  that will be used for neuronal stimulation or recording. A person of ordinary skill in this art will be able to easily make further alterations and modifications after reading the present invention. It can easily be inferred that any particular embodiment illustrated with diagrams and explained cannot be considered limiting. For example the sequence of forming the sacrificial and conductive layers can be added or subtracted or the sequence changed. 
     Next as shown in  FIG. 2   a , a polymer layer  22  may be applied over the polysilicon layer  20 . In one aspect the polymer layer  22  may be a layer of Parylene C that is formed to fill in the trench  12  and act as the mechanical penetrating electrode  16 . Since the deposition of parylene is conformal the polymer or parylene C layer is formed on the silicon substrate  14  as well and this will define the substrate for the final electrode array  10 . The deposition process forms a 3D profile to the electrode array  10 . 
     Next, the parylene C layer  22  formed overlying the conductive layer or polysilicon layer  20  may be patterned and etched in an oxygen plasma environment using Reactive Ion Etching (RIE) to define a via  24 . The via  24  allows access to the conductive layer  20 . 
     A metallization layer  26  may then be formed using a defined pattern on the parylene layer  22  that also connects to the polysilicon conductive layer  22  through the via  24 . The metallization layer  26  may be formed of materials including: metals such as, aluminum, copper, titanium, chrome, gold, silver, iridium or their combination that can be evaporated, sputtered or electroplated. The metallization layer  26  provides electrical contact to the conductive layer  20  on the penetrating electrode  16  and provides access for the array  10  to be interfaced with electronics. A person of ordinary skill in this art will be able to easily make further alterations and modifications after reading the present invention. It can easily be inferred that any particular embodiment illustrated with diagrams and explained cannot be considered limiting. For example the trench  12  may be filled by other materials including polymers such as polyimide and then be coated with parylene, the sequence of steps may be changed or modified and more than one metallization layer can be formed. 
     Referring back to  FIG. 3   a , another polymer layer  122  that may be formed of parylene C is then formed sandwiching the metallization layer  26 . The thickness of the polymer layer  122  may range from a couple of microns to several tens of microns. The backside of the silicon substrate  14  may then be patterned in a defined manner to access the penetrating electrode array by forming an opening  28  using DRIE. The formation of this opening  28  may aid in releasing the penetration part of the electrode  16  from the silicon substrate  14 . 
     Next, the insulating layer  18  may be etched in a wet etchant such as Buffered Hydrofluoric acid as shown in  FIG. 3   b . Another metallization layer  126  may then be deposited from the backside and be patterned onto the penetrating portion of the electrode  16 . The metallization layer  126  may be formed of metals such as, aluminum, copper, titanium, chrome, gold, silver, iridium or their combination that can be evaporated, sputtered or electroplated. A person of ordinary skill in this art will be able to easily make further alterations and modifications after reading the present invention. It can easily be inferred that any particular embodiment illustrated with diagrams and explained cannot be considered limiting. For example the sequence of forming the metallization layers onto the penetrating portion of the electrode  16  can be added or subtracted or the sequence changed. 
     Referring to  FIG. 4   a , the array  10  may be released from the silicon substrate  14 . A further polymer layer  222  such as parylene may be formed overlying the entire array  10 . The polymer layer  222  may then be patterned to form a via  30  to connect to outside electronics and also form an opening  31  to expose the tip  40  of the penetrating electrode  16  that includes the metallization layer  126 . 
     In an alternative embodiment shown in  FIG. 5   a,  after releasing the array  10  from the silicon substrate  14 , the flexible penetrating electrode array  10  may be mated to a carrier substrate  32 . The carrier substrate  32  may be formed of a flexible material such as, silicone or rigid materials such as metal alloys or semi conductive substrates. After mating the released array  10  to the carrier substrate  32  a new via  34  may be formed to access the metallization layer  126  as shown in  FIG. 5   b.    
     Referring to  FIG. 6 , there is shown a completed array  10  including the penetrating electrodes  16 . The array is shown mated to an electronic device  36  that may record signals or provide stimulation. As can be seen in the figure, the array  10  includes penetrating electrodes  16  that are formed of a flexible polymer allowing movement of the electrodes  16  to conform to various shapes. Additionally, the base  38  of the array  10  is also formed of a flexible material. The tips  40  of the electrodes  16  include a metallization layer  126  that may conduct signals or electro pulses to or from a substance that interfaces with the array  10 . 
     The array  10  overcomes problems in the prior art through the utilization of a flexible polymer material that is biocompatible. The penetrating electrode  16  is surrounded by a thin conductive layer of LPCVD polysilicon  20 . The flexible polymer forms the base layer of the array  10  providing flexibility to the entire device. The flexible polymer provides both the penetrating portion and the base because of the conformal coating of the deposition process. Since the penetrating part of the array is made of a flexible polymer such as parylene it eliminates the problem of the prior art with the ability to move along with the soft tissue leading to minimal or no tissue damage. The use of parylene provides flexibility and also mechanical strength with high tensile and yield strength. 
     Another difficulty with prior art 3D arrays or penetrating electrodes is the electrical interface. This invention further discloses a method to integrate out of plane or 3D conductors that are present on the penetrating electrode to the conductor present on the planar substrate in a very simple way. As described above, LPCVD polysilicon is first deposited to coat conforming to the shape of the penetrating array which is later insulated with parylene with the tip being exposed for neural interface. Parylene deposition which is conformal is then deposited to provide the mechanical rigidity to polysilicon and also the penetrating part of the electrode array. Parylene would also serve as the substrate or base layer. To access the LPCVD conductor present on the penetrating portion, a via is etched on the parylene and metal is deposited and patterned to make electrical contact. Parylene has also been proven to be compatible with Integrated circuits and this will simplify the integration of the array with various microelectronic devices. The flexible properties of the polymer layer such as parylene allows the penetrating array to easily conform to any non planar surface such as the cylindrical or spherical surface of nerves.