Implantable Stimulator with Electrode Array and Conformal Substrate

Abstract

The use of nerve stimulation leads in the craniofacial region is associated with skin erosion and lead migration. The cylindrical shape and associated thickness of prior art leads result in lead erosion of the skin or lead displacement such that the electrodes no longer cover the target nerve. Provided are implantable stimulators 100, 1110 having substrates 300, 1400 and a pulse generator 500, the substrates 300, 1400 including a conformable portion having an electrode array. A plurality of electrical interconnects 250, 1210 are positioned between the surfaces of the substrate. The thickness of the conformable portion is equal to or less than 0.5 millimeters. Optionally, one or more encapsulation layers 1300 may be provided. Optionally, one or more adhesion layers 1500 including a ceramic material may also be provided. By providing a substrate that is more easily patterned, more complex electrode array configurations may be supported, allowing a higher degree of flexibility to address lateral and / or longitudinal misalignment. By providing a relatively thin implantable electrode array, user comfort may be increased. One or more adhesion layers improve the performance of the encapsulation.

Description

[0001] Copyright Notice

[0002] A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever. Technical Field

[0003] The present disclosure relates to an implantable stimulator for delivering electrical stimulation to human or animal tissue, having an electrode array positioned along a conformable portion of a substrate. Specifically, the present disclosure relates to an implantable stimulator having an encapsulation layer that at least partially covers a portion of the substrate. The present disclosure also relates to a method of manufacturing an implantable stimulator.

[0004] Background

[0005] Implantable electrical stimulation systems can be used to deliver electrical stimulation therapy to a patient to treat various symptoms or disorders, such as headache, lower back pain, and incontinence.

[0006] In many electrical stimulation applications, a stimulator, typically including a therapy lead (the lead including electrodes and electrical connections), desires to deliver electrical stimulation to one or more precise locations within the body. In many cases, due to the curvature of the tissue and anatomy, it can be difficult to precisely align the stimulation electrodes during implantation. A curvature mismatch of the electrode portion of the lead can create unexpected and / or unpredictable resistance between one or more electrodes and the underlying tissue. Additionally, repeated movement of the relevant area of the body can even exacerbate the mismatch. A particular problem with subcutaneous implants is that even minor differences in flexibility between the implant and the surrounding tissue can affect patient comfort and can lead to irritation of the overlying skin. This is a particular problem with subcutaneous implants.

[0007] In particular, the use of nerve stimulation leads in the craniofacial region is associated with skin erosion and lead migration. The cylindrical shape and associated thickness of prior art leads cause the lead to erode the skin or cause the lead to shift such that the electrodes no longer cover the target nerve.

[0008] Recently, plastics and polymers have been used which have inherent flexibility or can be formed into curved shapes, for example, as described in U.S. Application US 2016 / 0166828. Although such leads can be formed into curved shapes or deformed during implantation by manual manipulation, this is inconvenient. The high anatomical variability found in humans and animals means that manufacturers must provide a wide range or pre-curved leads, or allow for the leads to be sized. In cases where they are deformable during implantation, this further complicates the implantation process.

[0009] Implantable active devices require a protection method to protect the implanted electronics from the influence of body fluids present in humans or animals. Body fluids usually contain ions that can cause electrochemical reactions, such as corrosion, in the presence of an electric current. Therefore, encapsulation is a key component of medical device design, acting as a barrier between these ionic fluids and critical electronic / electrical interfaces to reduce and / or prevent the degradation of implanted electronics.

[0010] Polyimide is widely used as a substrate material for the microfabrication of electronic devices, and attempts have been made to encapsulate polyimide with silicone rubber encapsulants such as polydimethylsiloxane rubber (PDMS). As described by Hoang, Chung, and Elias in "Irreversible bonding of polyimide and polydimethylsiloxane (PDMS) based on a thiol-epoxy click reaction" published in Journal of Micromechanics and Microengineering, 10.1088 / 0960-1317 / 26 / 10 / 105019, bonding these two flexible materials remains a key challenge, and delamination of the encapsulant from the substrate to some extent reduces the resistance to fluid ingress. By functionalizing the surfaces of the PDMS and polyimide substrates with mercapto silane and epoxy silane respectively to form thiolepoxy bonds in the click reaction, the degree of bonding is improved. In addition, the degree of bonding is also improved by functionalizing one or both surfaces with mercapto silane and introducing an epoxy adhesion layer between the two surfaces.

[0011] Although PDMS can be substantially biocompatible, causing minimal tissue reaction while having relatively long-term biostability, it still has a relatively high moisture permeability, which may lead to the degradation of implanted electronics. Many other encapsulants with lower moisture permeability may have a lower degree of biocompatibility. In recent years, LCP (liquid crystal polymer) has been considered as a substrate for electronic devices, and at the same time, the bonding technology between LCP and encapsulants needs to be improved.

[0012] Overview

[0013] It should be understood that both the following overview and the detailed description are exemplary and illustrative, and are intended to provide further explanation of the present invention as claimed. Neither the following overview nor the subsequent description is intended to limit or restrict the scope of the present invention to the specific features mentioned in the overview or description. Instead, the scope of the present invention is defined by the appended claims.

[0014] In some embodiments, the disclosed embodiments may include one or more features described herein.

[0015] An implantable stimulator is provided, comprising: a substrate including a first surface and a second surface, wherein the thickness of the substrate is defined by the first surface and the second surface; a pulse generator configured to generate at least one stimulation pulse; and an electrode array including at least two electrodes positioned along a conformable portion of the substrate; the implantable stimulator further comprising: a plurality of electrical interconnects that electrically couple the pulse generator to at least two electrodes of the electrode array; wherein the plurality of electrical interconnects are located between the first surface and the second surface of the substrate; wherein the thickness of the substrate along the conformable portion is equal to or less than 0.5 millimeters.

[0016] The products and methods described herein provide a high degree of conformability and a high degree of configurability. A higher degree of conformability can increase user comfort. Optionally, the thickness of the conformable portion is equal to or less than 0.3 millimeters, or equal to or less than 0.2 millimeters, or equal to or less than 0.1 millimeters.

[0017] Optionally, wherein the substrate includes another portion along which the pulse generator is positioned, the implantable stimulator further includes an encapsulation layer at least partially covering the another portion of the substrate. Additionally or optionally, the another portion of the substrate and the pulse generator are at least partially embedded in one or more flexible biocompatible encapsulation layers.

[0018] Encapsulation can improve the reliability and / or lifespan of the implantable substrate.

[0019] Additionally or optionally, the implantable stimulator further includes an adhesion layer adjacent to at least a portion of the substrate. Optionally, the substrate includes more than one adjacent substrate layer, and the adhesion layer is located between the substrate layers.

[0020] One or more adhesion layers can improve the performance of the encapsulation. This can also improve the reliability and / or lifespan of the implantable substrate. By providing multiple layers, thinner wires can be used, increasing flexibility and thus improving conformability.

[0021] Optionally, the adhesion layer includes a ceramic material. The ceramic material can advantageously be included in the adhesion layer between the substrate material and the encapsulation material.

[0022] Optionally, the ceramic material is selected from the group consisting of: HfO2, Al2O3, Ta2O3, SiC, Si3N4, TiO2, and any combination thereof.

[0023] Additionally or optionally, the adhesion layer includes at least a first layer containing HfO2 and at least a second layer adjacent to the at least a first layer and containing Al2O3. Additionally or optionally, the adhesion layer includes at least a first layer containing Ta2O3 and at least a second layer adjacent to the at least a first layer and containing Al2O3. Additionally or optionally, the adhesion layer includes at least a first layer containing TiO2 and at least a second layer adjacent to the at least a first layer and containing Al2O3.

[0024] Optionally, the ceramic portion of the adhesion layer has an average thickness in the range of 25 nm to 200 nm. Optionally, the adhesion layer includes a ceramic portion applied using atomic layer deposition (ALD).

[0025] Additionally or optionally, the thickness of the stimulator along another portion is equal to or less than 5 mm, or equal to or less than 4 mm, or equal to or less than 3 mm.

[0026] This can further improve the conformability of another portion of the substrate.

[0027] Additionally or optionally, a plurality of electrical interconnects are positioned between the first surface and the second surface of the substrate using metallization. Additionally or optionally, the plurality of electrical interconnects are included in one or more conductive interconnect layers, and the one or more conductive interconnect layers are included between two adjacent polymer substrate layers.

[0028] By providing a substrate that is easier to pattern, more complex electrode array configurations can be supported, allowing a higher degree of flexibility to address lateral and / or longitudinal misalignment.

[0029] A method of manufacturing an implantable stimulator is provided, including: providing a substrate including a first surface and a second surface, wherein the thickness of the substrate is defined by the first surface and the second surface; providing a pulse generator configured to generate at least one stimulation pulse; positioning an electrode array including at least two electrodes along a conformable portion of the substrate; and depositing or electroplating a plurality of electrical interconnects on the substrate; electrically coupling the pulse generator to at least two electrodes of the electrode array; wherein the thickness of the substrate along the conformable portion is equal to or less than 0.5 mm.

[0030] Optionally, the pulse generator is disposed along another portion of the substrate, and the method further includes at least partially covering the another portion of the substrate with an encapsulation layer.

[0031] Additionally or optionally, the stimulator further includes: an encapsulation layer at least partially covering the substrate; and an adhesion layer at at least one location between the encapsulation layer and the substrate.

[0032] Additionally or optionally, an encapsulation layer covers at least a portion of the conformable portion of the substrate, and an adhesion layer is located between at least a portion of the conformable portion of the substrate and the encapsulation layer.

[0033] The products and associated methods described herein provide improved bonding to increase the resistance of fluid ingress into implantable devices including flexible substrates. The encapsulant / adhesion layer can be optimized to protect the surfaces of many types of substrates. If the substrate is configured and arranged to be substantially flexible, the substrate can have a high degree of conformability. The high adhesion of the encapsulant / adhesion layer allows the flexible encapsulant layer to provide a high degree of ingress protection for one or more surfaces of the flexible substrate.

[0034] One or more regions of the substrate surface can be protected by the encapsulant / adhesion layer. Each encapsulant / adhesion layer can be optimized to a predetermined degree, either individually or together.

[0035] Optionally, the conformable portion of the substrate includes liquid crystal polymer (LCP).

[0036] Additionally or optionally, where the substrate includes another portion along which a pulse generator is positioned, the encapsulation layer at least partially covers the other portion of the substrate.

[0037] Optionally, the encapsulation layer includes a polymer and / or polydimethylsiloxane (PDMS).

[0038] By providing a bilayer having an encapsulant containing PDMS and a conformable adhesion layer containing a ceramic material, the adhesion layer exhibits significantly higher stability in an ionic medium, thereby providing relatively longer protection in the event of any delamination or water penetration through the encapsulant. Due to flow between any defects and gaps in the adhesion layer, PDMS can further contribute to more durable adhesion and defect reduction. In particular, PDMS with a relatively low viscosity can provide an even higher degree of defect reduction.

[0039] Ceramic materials such as HfO2, Al2O3, Ta2O3, SiC, Si3N4, TiO2, and any combination thereof can be advantageously used as the adhesion layer for the PDMS encapsulant layer.

[0040] A method of manufacturing an implantable stimulator is provided, including: providing a substrate including a first surface and a second surface, wherein the thickness of the substrate is defined by the first surface and the second surface; providing a pulse generator configured to generate at least one stimulation pulse; positioning at least two electrodes along a conformable portion of the substrate; depositing or plating a plurality of electrical interconnects on the substrate, the plurality of electrical interconnects electrically coupling the pulse generator to the at least two electrodes; applying an adhesion layer at least partially covering the substrate; and applying an encapsulation layer on the adhesion layer; wherein the thickness of the substrate along the conformable portion is equal to or less than 0.5 millimeters.

[0041] Optionally, the adhesion layer is applied using atomic layer deposition (ALD). Additionally or alternatively, the pulse generator is disposed along another portion of the substrate, wherein the adhesion layer and the encapsulation layer are applied to at least partially cover the another portion of the substrate. Brief Description of the Drawings

[0043] Certain illustrative embodiments of the organization and method of operation and the purpose and advantages thereof may be best understood by reference to the following detailed description taken in conjunction with the accompanying drawings, which need not be drawn to scale.

[0044] The accompanying drawings, which are incorporated herein and form a part of the specification, illustrate exemplary embodiments and, together with the description, further serve to enable a person skilled in the art to make and use these embodiments and other embodiments that are apparent to those skilled in the art:

[0045] Figure 1A is a side view of a first embodiment of an implantable stimulator consistent with certain embodiments of the present invention.

[0046] Figure 1B is a top view of a first embodiment of an implantable stimulator consistent with certain embodiments of the present invention.

[0047] Figure 1C is a bottom view of a first embodiment of an implantable stimulator consistent with certain embodiments of the present invention.

[0048] Figure 2A is a side view of a second embodiment of an implantable stimulator consistent with certain embodiments of the present invention.

[0049] Figure 2B is a top view of a second embodiment of an implantable stimulator consistent with certain embodiments of the present invention.

[0050] Figure 2C is a bottom view of a second embodiment of an implantable stimulator consistent with certain embodiments of the present invention.

[0051] Figure 3AIs a lateral view of a third embodiment of an implantable stimulator consistent with certain embodiments of the present invention.

[0052] Figure 3B Is a top view of a third embodiment of an implantable stimulator consistent with certain embodiments of the present invention.

[0053] Figure 3C Is a bottom view of a third embodiment of an implantable stimulator consistent with certain embodiments of the present invention.

[0054] Figure 4A Is a first view of an alternative electrode configuration of an implantable stimulator consistent with certain embodiments of the present invention.

[0055] Figure 4B Is a second view of an alternative electrode configuration of an implantable stimulator consistent with certain embodiments of the present invention.

[0056] Figure 4C Is a third view of an alternative electrode configuration of an implantable stimulator consistent with certain embodiments of the present invention.

[0057] Figure 5 Shows the positions of nerves in the front part of the human head that can be treated by the operation of an implantable stimulator consistent with certain embodiments of the present invention.

[0058] Figure 6 Shows the positions of nerves in the back part of the human body that can be treated by the operation of an implantable stimulator consistent with certain embodiments of the present invention.

[0059] Figure 7 Shows the positions of nerves in the human body that can be treated by the operation of an implantable stimulator consistent with certain embodiments of the present invention.

[0060] Figure 8A and Figure 8B Depicts the electrochemical impedance spectra (EIS) of three samples, Figure 8A Is the result of a Bode plot of impedance magnitude, Figure 8B Is the result of a Bode plot of phase angle.

[0061] Figure 8C and Figure 8D Depicts the EIS results of four samples at 10 -2 Hz, soaked for 450 days, Figure 8C Is the impedance magnitude, Figure 8D Is the phase angle.

[0062] Figure 9 Presents the measurement results comparing the average tensile forces of LCP coated with PDMS using different processes after drying and soaking.

[0063] Figure 10 depicts a cross-section through a test sample.

[0064] Figure 11A and Figure 11B and Figure 11C depicts a cross-section through an improved implantable electronic device.

[0065] Figure 12A and Figure 12B depicts a cross-section through an improved implantable medical device that includes the improved implantable electronic device and one or more electrodes.

[0066] Detailed description

[0067] While the present invention may be embodied in many different forms of embodiments, specific embodiments are shown in the drawings and will be described in detail herein. It is understood that the present disclosure of these embodiments will be regarded as examples of the principles and not as intended to limit the present invention to the specific embodiments shown and described. The described embodiments and their detailed structures and elements are provided only to assist in a complete understanding of the present invention. The scope of the present invention is best defined by the appended claims. In the following description, the same reference numerals are used to describe the same, similar, or corresponding parts in multiple views of the drawings or even in different drawings.

[0068] Thus, it is apparent that the present invention can be implemented in many ways and does not require any specific features described herein. In addition, well-known functions or structures are not described in detail because they would obscure the present invention with unnecessary detail. Unless otherwise specifically stated, any signal arrows in the figures / drawings should be considered merely exemplary and not restrictive.

[0069] It will be understood that although the terms "first", "second", etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, without departing from the scope of the exemplary embodiments, the first element may be referred to as the second element, and similarly, the second element may be referred to as the first element. As used herein, the term "and / or" includes any combination and all combinations of one or more of the associated listed items. As used herein, "at least one of A, B, and C" means A or B or C or any combination thereof. As used herein, the singular form of a word includes the plural form, and the plural form of a word includes the singular form, unless the context clearly dictates otherwise.

[0070] As used herein, the term "a" or "an" is defined as one or more than one. As used herein, the term "plurality" is defined as two or more than two. As used herein, the term "another" is defined as at least a second or more. As used herein, the terms "including" and / or "having" are defined as comprising (i.e., open language). As used herein, the term "coupled" is defined as connected, although not necessarily directly, and not necessarily mechanically.

[0071] It should also be noted that in some alternative implementations, the functions / actions recited may not occur in the order noted in the figures. For example, two figures shown in succession may in fact be executed substantially concurrently, or may sometimes be executed in the reverse order, depending upon the functionality / action involved.

[0072] As used herein, ranges are used in a shorthand manner to avoid having to list and describe every value within the range. Where appropriate, any appropriate value within the range may be selected as the upper limit value, lower limit value, or endpoint of the range.

[0073] The words "comprise", "comprises" and "comprising" should be interpreted inclusively rather than exclusively. Similarly, the terms "include", "including" and "or" should all be interpreted inclusively, unless the context clearly prohibits such construction. The term "comprising" or "including" is intended to include embodiments covered by the terms "consisting essentially of" and "consisting of". Similarly, the term "consisting essentially of" is intended to include embodiments covered by the term "consisting of". Although having different meanings, the terms "include", "have", "contain" and "consist of" may be substituted for each other throughout the description of the present invention.

[0074] "About" means that the referenced numerical indication is plus or minus 10% of the referenced numerical indication. For example, the term "about 4" will include a range of 3.6 to 4.4. All numbers used in the specification to express the number of elements, reaction conditions, etc. should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise indicated, the numerical parameters set forth herein are approximations that can vary depending on the desired properties sought to be obtained. At least, rather than attempting to limit the application of the doctrine of equivalents to the scope of any claim, each numerical parameter should be interpreted according to the number of significant digits and ordinary rounding methods.

[0075] Wherever the phrases "for example," "such as," "including," etc. are used herein, they will be understood to be followed by the phrase "without limitation," unless expressly stated otherwise.

[0076] "Generally" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that such description includes instances where said event or circumstance occurs and instances where it does not occur.

[0077] Throughout this document, references to "one embodiment," "certain embodiments," "an embodiment," or similar terms mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of such phrases in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, in one or more embodiments, the particular features, structures, or characteristics may be combined in any suitable manner by those skilled in the art without limitation.

[0078] In the following detailed description, numerous non-limiting specific details are given to assist in understanding the present disclosure.

[0079] Figure 1A , Figure 1B and Figure 1C Depicted is a longitudinal section through a first embodiment 100 of an implantable stimulator comprising:

[0080] - a pulse generator 500 for generating at least one electrical therapy stimulation pulse (only in Figure 1B and Figure 1C ); and

[0081] A conformable portion of the foil-like substrate 300 having a longitudinal axis 600 extending from the pulse generator 500 to the distal end of the substrate 300. The substrate 300 comprises one or more adjacent polymer substrate layers and has a first planar (outer) surface 310 and a second planar (outer) surface 320.

[0082] The implantable stimulator 100 further includes:

[0083] - Electrode arrays 200, 400, which are near the distal end, having at least one first type of electrode 200a, 200b and at least one second type of electrode 400a, 400b. The electrodes 200, 400 are included in the first surface 310 or the second surface 320, and each can be configured to transfer treatment energy to human or animal tissue (as a stimulation electrode) and / or transfer treatment energy from human or animal tissue (as a return electrode) during use. In this context, the array can be considered as a systematic arrangement of two or more electrodes 200a, 200b, 400a, 400b. 1D, 2D or 3D arrays can be provided. Optionally, they can be arranged in rows and / or columns.

[0084] The implantable stimulator 100 further includes:

[0085] - One or more electrical interconnects 250 between the pulse generator 500 and the first electrodes 200a, 200b and the second electrodes 400a, 400b, for transferring electrical energy as one or more electrical treatment stimulation pulses to the coupled first electrodes 200a, 200b and / or second electrodes 400a, 400b. One or more electrical interconnects 250 are included (or located) between the first surface 310 and the second surface 320. A plurality of electrical interconnects 250 are considered as two or more than two electrical interconnects 250.

[0086] In the present disclosure, the conformability of the electrode arrays 200, 400 is determined to a relatively high degree by one or more of the following:

[0087] - The conformability of the portion of the substrate 300 near the electrodes 200, 300;

[0088] - The arrangement and position of the electrodes 200, 400;

[0089] - The materials included in the electrodes 200, 400 and the size (or range) of the materials;

[0090] - The arrangement and position of one or more interconnects 250 near the electrodes 200, 400; and

[0091] - The materials included in the interconnects 200, 400 and the size (or range) of the materials.

[0092] Through appropriate configuration, arrangement and optimization, foil-like (or film-like) and highly conformable implantable electrode arrays 200, 400 can be provided.

[0093] As depicted, the conformable portion of the foil-like substrate 300 preferably extends along the longitudinal axis 600 and has a strip shape, allowing the pulse generator 500 to be set (or positioned) at a location away from the electrodes 200, 400.

[0094] If the substrate 300 is substantially planar (in a non-limiting example, by allowing the substrate 300 to conform to a planar surface), the first surface 310 and the second surface 320 are disposed along substantially parallel transverse planes 600, 700. As Figure 1A depicted, the first surface 310 lies in a plane including the longitudinal axis 600 and a first transverse axis 700, which is substantially perpendicular to the longitudinal axis 600. As Figure 1A depicted, the plane of the first surface 310 is substantially perpendicular to the plane of the cross-sectional view (substantially perpendicular to the surface of the page).

[0095] The conforming portion of the foil-like substrate 300 has a maximum thickness of 0.5 millimeters or less near the first electrodes 200a, 200b and the second electrodes 400a, 400b, which is defined by the first surface 310 and the second surface 320 and can be determined by the vertical distance between corresponding points on the first planar surface 310 and the second planar surface 320. This is preferably determined when the substrate 300 conforms to a planar surface.

[0096] The foil-like substrate 300 has a thickness or extent along a second transverse axis 750, which is substantially perpendicular to the longitudinal axis 600 and the first transverse axis 700 and, as depicted, lies in the plane of the drawing (along the surface of the page). The first surface 310 is depicted as the upper surface and the second surface 320 is depicted as the lower surface.

[0097] Thus, the thickness can be determined by the vertical distance along the second transverse axis 750 between corresponding points on the first planar surface 310 and the second planar surface 320. The maximum thickness of the conforming portion of the foil-like substrate 300 near the first electrodes 200a, 200b and the second electrodes 400a, 400b is 0.5 mm or less, preferably 0.3 millimeters or less, even more preferably 0.2 millimeters or less, and still more preferably 0.1 millimeters or less.

[0098] Generally, the lower the maximum thickness (in other words, the thinner the substrate), the higher the degree of conformity. However, a higher maximum thickness may be preferred to increase mechanical strength.

[0099] To clarify the differences between the depicted different views, the nominal directions of the axes are given:

[0100] - The longitudinal axis 600 extends from the proximal end on the left side of the page (not depicted in Figure 1A but depicted in Figure 1B and Figure 1C to the distal end depicted on the right side of the page;

[0101] - The first transverse axis 700 extends into the page as depicted; and

[0102] - The second horizontal axis 750 extends from the bottom to the top as depicted.

[0103] The conformable portion of the foil substrate 300 can be configured and arranged as a multi-layer, which includes two or more adjacent polymer substrate layers fixed to each other, and has a first planar surface 310 and a second planar surface 320. One or more electrical interconnects 250 are also included (or positioned) between the first planar surface 310 and the second planar surface 320. However, it is not necessary for the two or more polymer layers and / or interconnects to have a similar extent along the first horizontal axis 700. In other words, in the context of the present disclosure, there can be regions where the interconnect 250 is sandwiched between regions of the polymer substrate (appearing as multi-layers in a longitudinal cross-section), adjacent to regions where the polymer substrate is substantially adjacent. Similarly, there can be regions where the interconnect 250 is sandwiched between two polymer substrate layers (appearing as multi-layers in a longitudinal cross-section), adjacent to regions of the substrate that include two adjacent substrate layers. Similarly, a substrate including two or more polymer substrate layers can be (physically and / or chemically) modified such that it appears as a single layer of polymer substrate.

[0104] These polymer substrate layers are selected to be conformable and include one or more electrical interconnects 250. Preferably, the polymer substrate material is also biocompatible and durable, such as materials selected from the group including: silicone rubber, siloxane polymer, polydimethylsiloxane, polyurethane, polyether polyurethane, polyether polyurethane urea, polyester polyurethane, polyamide, polycarbonate, polyester, polypropylene, polyethylene, polystyrene, polyvinyl chloride, polytetrafluoroethylene, polysulfone, cellulose acetate, polymethyl methacrylate, polyethylene, and polyvinyl acetate. Hassler, Boretius, Stieglitz in "Polymers for Neural Implants" in Journal of Polymer Science: Part B Polymer Physics, 2011, 49, 18 - 33 (DOI 10.1002 / polb.22169) describe suitable polymer materials (including LCP (liquid crystal polymer) films), and in particular, Table 1 is included herein by reference, which describes the properties of polyimide (UBE U-Varnish-S), parylene C (PCS Parylene C), PDMS (NuSil MED-1000), SU-8 (MicroChem SU-82000 and 3000 series), and LCP (Vectra MT1300).

[0105] The conformable foil substrate 300 is configured to very closely follow the contour of the underlying anatomical features through flexibility. The very thin foil substrate 300 has the additional advantage that they have increased flexibility.

[0106] Most preferably, the polymer substrate layer comprises LCP, parylene, and / or polyimide. LCP is a chemically and biologically stable thermoplastic polymer that allows the sealed sensor module to have a small size and low moisture permeability.

[0107] Advantageously, LCP can be thermoformed to allow for the provision of complex shapes. Very thin (and subsequently very conformal) and very flat (highly planar) layers of LCP can be provided. For fine-tuning of the shape, cutting can also be performed using a suitable laser.

[0108] In a non-limiting example, the conformal foil substrate 300 of LCP can have a thickness (extending along the second horizontal axis 750) in the range of 50 micrometers (μm) to 720 micrometers (μm), preferably 100 micrometers (μm) to 300 micrometers (μm). In an exemplary embodiment, values of 150 μm (micrometers), 100 μm, 50 μm, or 25 μm can be provided.

[0109] When conforming to a substantially planar surface, the foil surface 300 is substantially included in a plane whose lateral extent is substantially perpendicular to the longitudinal axis 600, where the planar width can be determined by the vertical distance between corresponding points along the lateral extent on the outer surface edges of the planar foil substrate 300. As depicted, this is along the first horizontal axis 700. In an embodiment, electrodes 200, 400 with a width of 2 mm to 20 mm can be provided using LCP.

[0110] At room temperature, the thin LCP film has mechanical properties similar to steel. This is important because the implantable substrate 300 should be strong enough to be implanted, strong enough to be removed (transplanted out), and strong enough to follow any movement of adjacent anatomical features and / or structures without degradation.

[0111] LCP belongs to polymer materials with the lowest permeability to gases and water. LCP can bond with itself, thus enabling a multi-layer structure with a homogeneous structure.

[0112] Compared with LCP, polyimide is a thermosetting polymer that requires an adhesive to construct a multi-layer part with an electrode array. Polyimide is a thermosetting polymer material with high temperature resistance and bend resistance.

[0113] In an embodiment, LCP can be used to provide the conformal substrate 300 as multi-layer, in other words, two or more adjacent polymer substrate layers. In a non-limiting example, these can be layers with a thickness of 25 μm (micrometers).

[0114] In an embodiment, one or more electrical interconnects 250 may be provided (or positioned) between the first surface 310 and the second surface 320 by metallization. These may be conductors embedded in the substrate 300, such as by having a single polymer layer and applying a conductive material using suitable deposition techniques known in the semiconductor industry.

[0115] In an embodiment, if two or more adjacent polymer substrate layers are provided, an interconnect layer may be provided using suitable techniques such as those from the semiconductor industry. The polymer substrate layers may also be considered adjacent when one of the multiple adhesion layers is used between the polymer substrate layers. Examples of suitable adhesion materials and adhesion layers are described below with reference to FIGS. 8 to 12.

[0116] In an embodiment, lamination may also be used to provide the substrate 300 with desired physical and chemical properties, and / or to provide a convenient manufacturing method. In a non-limiting example, the substrate 300 may include three laminated polymer layers: two high-temperature thermoplastic layers with a low-temperature layer (bond-ply) therebetween, and the high-temperature layers facing the first surface 310 and the second surface 320.

[0117] In an alternative embodiment, two layers of siloxane may be provided as the polymer substrate layers: one layer of siloxane is provided, a metal pattern is formed on one of its outer surfaces, and a second layer of siloxane is added on the metal pattern by spraying, over-molding, or spin coating.

[0118] In an embodiment, the electrical interconnects 250 may include one or more conductive materials, such as metals, which are formed as needed in one or more conductive elements: wires, strands, foils, laminas, plates, and / or sheets. They may be substantially adjacent (one conductor). They may also include more than one conductor configured and arranged to be electrically connected to each other in use, in other words, one or more conductors are configured and arranged to be substantially electrically adjacent in use.

[0119] Alternatively, one or more electrical interconnects 250 may be included in one or more conductive interconnect layers 250, which are included (or positioned) between two adjacent polymer substrate layers. As Figure 1A depicted, multiple interconnects may be provided at different settings (or depths or positions) between the first surface 310 and the second surface 320.

[0120] In an embodiment, the interconnect 250 in the context of the present disclosure is configured or arranged to not come into contact with human or animal tissue during use. One or more interconnects 250 are embedded (or covered) in one or more layers of a low-conductivity or insulating polymer such as LCP. Additionally or alternatively, one or more encapsulation layers may be used.

[0121] One or more interconnect layers 250 may also be provided by metallization using techniques of the PCB (printed circuit board) industry, such as metallization with a biocompatible metal (such as gold or platinum). Electroplating may be used. Layers including LCP films are particularly suitable for metallization. These electrical interconnects 250 and / or interconnect layers 250 are configured to transfer electrical energy as one or more electrical therapy stimulation pulses from the pulse generator 500 to the coupled first electrodes 200a, 200b and / or second electrodes 400a, 400b.

[0122] Using a suitable polymer substrate material such as an LCP film allows for a conformal portion of the foil (or film) substrate 300 and the electrode array 200, 300 to have a high aspect ratio, providing a biocompatible electronic foil (or film), or a bioelectronic foil (or film).

[0123] In an embodiment, when the substrate 300 is conformal to a substantially planar surface, the ratio of the maximum planar width to the maximum thickness near the first electrodes 200a, 200b and the second electrodes 400a, 400b may be 7:1 or higher, preferably 10:1 or higher, more preferably 15:1 or higher, still more preferably 30:1 or higher, and even more preferably 50:1 or higher.

[0124] A ratio of 100:1 or higher is also advantageous and may be provided using one or more mechanically strong substrate layers of an LCP film having a width of approximately 20 mm and a thickness of approximately 0.2 mm. This provides a high degree of flexibility and thus also a high degree of conformability. Additional measures may also be taken to increase the conformability in the first lateral direction 700, such as changing the width of the substrate, adding one or more undulations and / or providing bending points.

[0125] In a non-limiting example, when using single-row electrodes 200, 400 and / or electrodes 200, 400 having a smaller width, the width may be 4 mm and the thickness is approximately 0.2 mm, which is a ratio of approximately 20:1.

[0126] In a non-limiting example, in a portion of the substrate near the pulse generator 500, a greater extension may be required, which further depends to a large extent on the size of the electronic components used, with a width of 20 mm and a thickness of 3 mm. This is a ratio of approximately 6.67:1.

[0127] As Figure 1AAs depicted, the distal end (or distal portion) of the conformable foil substrate 300 includes:

[0128] - Two electrodes 200a, 200b of a first type included in the first surface 310, and

[0129] - Two electrodes 400a, 400b of a second type also included in the first surface 310. The depicted order from proximal to distal is 200a, 400a, 200b, 400b, in other words, each electrode 200a, 200b of the first type is close to and included in the same surface 310 as the electrodes 400a, 400b of the second type.

[0130] The foil substrate 300 includes electrical interconnects 250 between each of the electrodes 200a, 400a, 200b, 400b and the pulse generator. In this embodiment, each electrical interconnect 250 is configured and arranged such that each of the electrodes 200a, 400a, 200b, 400b is electrically connected substantially independently, and thus, one of the operating modes obtainable by appropriately configuring the pulse generator 500 is substantially independent operation. One or more hardware, firmware, and / or software parameters can be used to configure the pulse generator 500.

[0131] Although depicted in Figure 1A as separate connectors 250 at different distances (or positions) between the first surface 310 and the second surface 320, those skilled in the art will also recognize that the same interconnects can be provided by appropriately configured interconnects 250 (or interconnect layers 250) at approximately the same distance (or position) between the first surface 310 and the second surface 320, similar to the embodiment depicted in Figure 3B and described hereinafter.

[0132] "Included in" the first surface 310 or the second surface 320 means that the electrodes 200a, 400a, 200b, 400b are relatively thin (e.g., when the substrate is arranged to conform to a substantially planar surface, its extension along the second transverse axis can be 20 micrometers to 50 micrometers or less. Even thinner electrodes can be used to further increase conformability, e.g., 1 micrometer or less), and are attached to (or at least partially embedded in) the surface.

[0133] The electrodes 200, 400 can include conductive materials such as gold, platinum, platinum black, TiN, IrO2, iridium, and / or platinum / iridium alloys and / or oxides. Conductive polymers such as Pedot can also be used. Preferably, biocompatible conductive materials are used. PCB / metallization techniques can be used to fabricate them on or in the first surface 310 and / or the second surface 330 of one or more polymer substrate layers.

[0134] For electrodes 200a, 200b, 400a, 400b, a thicker metal layer is generally preferred over a thinner metal layer because they can withstand body substances that can dissolve the metal. However, a thicker metal layer generally increases the rigidity (decreases conformability) near the thicker layer.

[0135] The stimulator 100 can be implanted by first creating a subcutaneous tunnel and / or using an implantation tool. However, a high degree of conformability may make implantation success more difficult. Even when using a suitable insertion tool, the electrode position may later be found to be incorrect due to misalignment, wire migration during implantation, or wire migration after implantation.

[0136] At least the distal ends of the electrode arrays 200, 400 are implanted. However, it may be advantageous to implant the stimulator 100.

[0137] Additionally, during implantation, it may be difficult to precisely identify the location required for stimulation. When implanted, the stimulator electrodes should be placed close enough to the nerve to be stimulated. However, the nerve pathway is not always clearly visible to the professional performing the implantation, and the distribution and path of the nerve pathway vary from person to person.

[0138] As shown in FIG. 1, there are no substantial hardware differences between the first type of electrodes 200a, 200b and the second type of electrodes 400a, 400b. In this implementation, any functional differences are mainly determined by the configuration (one or more hardware, firmware, and / or software parameters) of the pulse generator 500. Due to the arrangement and wiring of the interconnect 250, there may be a minor impact on the electrical properties.

[0139] Through appropriate configuration of the pulse generator 500, one or more coupled electrodes 200a, 200b or 400a, 400b of the same type can operate substantially the same. In other words, the stimulation energy applied to the electrodes 200, 400 is substantially the same at substantially the same time instances (usually measured as voltage, current, power, charge, or any combination thereof). This can also be used to predict and / or correct misalignment and / or wire migration, which is advantageous because it allows at least partial use of software to perform the configuration.

[0140] Additionally or alternatively, one or more parameters of the pulse generator 500 can be used to configure and arrange two or more electrodes 200, 400 as stimulation electrodes or return electrodes. This can provide a higher degree of configurability because only the substrate 300 needs to be implanted such that at least two electrodes are near the desired stimulation location.

[0141] In this embodiment 100, the first type of electrodes 200a, 200b are nominally configured and arranged to operate as stimulation electrodes.

[0142] The second type of electrodes 400a, 400b are nominally configured to operate as return electrodes, each configured to provide an electrical return for one or more stimulating electrodes 200a, 200b in use. In other words, the electrical returns 400a, 400b close the circuit. It can also be similarly configured to provide an electrical ground for the corresponding electrical energy source.

[0143] Accordingly, three configurations are provided based on this nominal configuration:

[0144] - The stimulating / return electrode pair 200a / 400a is close to the first surface 310 at the stimulating / return location; or

[0145] - The stimulating / return electrode pair 200b / 400b is close to the first surface 310 at the stimulating / return location; or

[0146] - A combination thereof.

[0147] In an embodiment, one or more stimulating electrodes 200a, 200b may be provided in such a stimulator 100. The number, size, and / or spacing of the stimulating electrodes 200a, 200b may be selected and optimized according to the treatment. In an embodiment, if more than one stimulating electrode 200a, 200b is provided, each stimulating electrode 200a, 200b may provide:

[0148] - Different stimulating effects, similar stimulating effects, or the same stimulating effect.

[0149] To avoid misalignment, one or both of the electrodes 200a, 200b close to the tissue where the effect is to be produced may be selected.

[0150] If stimulation is required over a larger area and / or at a location between the active stimulating electrodes 200a, 200b, two or more stimulating electrodes 200a, 200b may be activated substantially simultaneously.

[0151] In an embodiment, the stimulating electrodes 200a, 200b may have a size of approximately 6 mm to 8 mm along the longitudinal axis 600 and a size of 3 mm to 5 mm along the first transverse axis 700, thus approximately 18 to 40 square millimeters (mm 2 )

[0152] In an embodiment, a foil substrate 300 suitable for an implantable stimulator may include up to 12 stimulating electrodes 200a, 200b and return electrodes 400a, 400b over a 15 cm length to allow for correction of misalignment or simply to allow an expert to select the most effective stimulating location.

[0153] In an embodiment, Figure 1B depicts Figure 1AView of the second surface 320 of the implantable distal end (or portion) of the foil substrate 300 depicted. In other words, the second surface 320 is depicted in the plane of the page, along the longitudinal axis 600 (depicted from bottom to top) and the first transverse axis 700 (depicted from left to right). The second transverse axis 750 extends into the page. The first surface 310 is not depicted in Figure 1B but is located at a higher position along the second transverse axis 750 (into the page) and is also substantially parallel to the plane of the drawing. The foil substrate 300 is arranged to conform to a substantially planar surface.

[0154] The pulse generator 500 can be set (or positioned) between the second surface 320 and the first surface 310. In Figure 1B and Figure 1C it is depicted with a dashed line. Alternatively, the pulse generator 500 can be at least partially set on the first surface 310 or the second surface 320. Alternatively, the pulse generator 500 can be at least partially embedded in the first surface 310 or the second surface 320.

[0155] The maximum thickness can be optimized according to the degree of embedding and one or more electrical components for the pulse generator 500. The components can be thinned to minimize the thickness. If the substrate 300 is configured and arranged to be conformable and / or foil-like, the maximum thickness of the implantable stimulator 100 in the portion of the substrate near the pulse generator 500 can be 5 millimeters or less, preferably 4 millimeters or less, and even more preferably 3 millimeters or less, which is determined by the vertical distance between corresponding points on the outer planar surface when the implantable stimulator 100 conforms to a substantially planar surface. Additionally optional electrical components (such as antennas, including coils or dipoles or fractal antennas) can also affect the thickness according to the degree to which they are embedded in the substrate.

[0156] The stimulator 100 and the foil substrate 300 extend along the first transverse axis 700 (considering the planar width of the stimulator 100 / foil substrate 300 when conforming to a substantially planar surface). As shown, the planar width in the portion of the substrate near the pulse generator 500 can be greater than the planar width in another portion of the electrodes 200a, 200b, 400a, 400b near the distal end (or portion) of the foil substrate 300. The planar width near the pulse generator 500 can depend on the hardware and components for the pulse generator 500. Generally, it is at least the width of the integrated circuit for the pulse generator 500. Additionally optional electrical components, such as antennas including coils or dipoles or fractal antennas, can also affect the planar width.

[0157] In an embodiment, the planar width near electrodes 200a, 200b, 400a, 400b may depend on the conductor used for electrodes 200a, 200b, 400a, 400b and one or more interconnects 250. In an embodiment, the planar width is at least the width of the first electrodes 200a, 200b or the second electrodes 400a, 400b.

[0158] In an embodiment, Figure 1C depicts a view of the first surface 310 of the implantable distal end (or portion) of the foil substrate 300 depicted in Figure 1A and Figure 1B . In other words, the first surface 310 is depicted in the plane of the page, along the longitudinal axis 600 (depicted from bottom to top) and the first transverse axis 700 (depicted from right to left). The second transverse axis 750 extends out of the page. This is a view facing the animal or human tissue to be stimulated (in use). The second surface 320 is not depicted in Figure 1C but is located at a lower position along the second transverse axis 750 (into the page) and is also substantially parallel to the plane of the drawing. The foil substrate 300 is arranged to conform to a substantially planar surface.

[0159] One or more interconnects 250 are provided (or positioned) between the first surface 310 and the second surface 320, as Figure 1A shown. In Figure 1C , they are depicted as dashed lines, indicating the interconnects 250 (or appropriately configured one or more interconnect layers 250) provided for each of the electrodes 200a, 200b, 400a, 400b in this embodiment. A single dashed line 250 is depicted between the pulse generator 500 and the electrodes 200, 400 to indicate that in embodiment 100 the interconnects 250 are in a substantially identical arrangement along the first transverse axis 700.

[0160] As Figure 1C shown, the electrodes 200a, 200b, 400a, 400b each have a longitudinal extent (length) along the longitudinal axis 600 and a transverse extent (width) along the first transverse axis 700.

[0161] Although described as similar, in fact, each of the electrodes 200a, 200b, 400a, 400b may vary in shape, transverse cross-section, orientation, and / or size (or extent) depending on the intended use and / or desired degree of configurability.

[0162] After implanting at least the distal end (or portion) of the stimulator 100 or including the electrode arrays 200, 400, the pulse generator 500 may be configured and arranged to provide electrical energy to one or more first - type coupling electrodes 200a, 200b relative to the electrical return applied to one or more second - type coupling electrodes 400a, 400b in use.

[0163] The configurable nature of the stimulator 100 allows for the determination and / or adjustment of the operation of one or more electrodes 200a, 200b, 400a, 400b before, during, and / or after the implantation of at least the distal end (or portion) of the electrode arrays 200, 400. The operation may also be reconfigured one or more times during the period of implanting the stimulator 100 to optimize and / or extend the treatment.

[0164] In an embodiment, the pulse generator 500 may initially be configured to nominally operate 200a and 400a as a stimulation / return electrode pair, respectively. After implanting at least the distal ends 200, 400, inadequate stimulation may be observed and / or measured. If it is assumed to be mainly due to longitudinal misalignment, the pulse generator 500 may optionally be configured using one or more parameters to nominally operate 200b and 400b as a stimulation / return electrode pair, respectively.

[0165] The stimulator 100 may further be configured and arranged to switch the pulse generator 500 between these configurations under predetermined and / or controlled conditions. These configurations may conveniently be further regarded as a first electrode mode and a second electrode mode, and allow the user to select one mode as a preference and / or switch modes. Alternatively, the pulse generator 500 may switch modes under predetermined and / or controlled conditions.

[0166] Additionally or alternatively, other modes for configuring the pulse generator 500 to operate in the following manner may also be provided:

[0167] - A first electrode mode, in which electrical stimulation energy is provided as one or more electrical therapeutic stimulation pulses to one or more first - type coupling electrodes 200a, 200b, and one or more second - type coupling electrodes 400a, 400b are configured to provide a corresponding electrical return for one or more first electrodes 200a, 200b in use; or

[0168] - A second electrode mode, in which energy is provided as one or more electrical therapeutic stimulation pulses to one or more second - type coupling electrodes 400a, 400b, and one or more first - type coupling electrodes 200a, 200b are configured to provide a corresponding electrical return for one or more second electrodes 400a, 400b in use.

[0169] Again, the stimulator 100 can be further configured and arranged to switch the pulse generator 500 between these configurations or modes under predetermined and / or controlled conditions. Additionally or alternatively, a user can be allowed to select a mode as a preference and / or switch modes.

[0170] Those skilled in the art will recognize that the electrodes 200a, 200b, 400a, 400b can be configured to operate in more complex configurations, such as:

[0171] - 400a and 200a can operate as a stimulation / return electrode pair, respectively (contrary to the original intended operation);

[0172] - 400b and 200b can operate as a stimulation / return electrode pair, respectively;

[0173] - If intermediate stimulation is preferred, two or more of the electrodes 200a, 200b, 400a, 400b can operate as one or more stimulation electrodes substantially simultaneously;

[0174] - One or more of the electrodes 200a, 200b, 400a, 400b can operate as one or more return electrodes;

[0175] - Electrode 400a operates as a stimulation electrode in combination with electrodes 200a and 200b as return electrodes;

[0176] - Electrodes 400a and 200b operate as stimulation electrodes in combination with electrodes 200a and 400b as return electrodes.

[0177] Alternatively or additionally, the shape, orientation, transverse cross-section, and / or size (or length) of one or more stimulation electrodes can be configured differently compared to one or more return electrodes.

[0178] When configuring and arranging a portion of the foil substrate 300 close to the electrode arrays 200, 400 for conformability, many parameters and characteristics can be considered, such as:

[0179] - The transverse extension 700 and / or longitudinal extension 600 of one or more of the electrodes 200a, 200b, 400a, 400b

[0180] - The thickness of the foil substrate 300, or the perpendicular distance between the first surface 310 and the second surface 320

[0181] - The material included in the foil substrate 300 and its physical properties

[0182] - The number and extension of the interconnects 250 and / or the interconnect layer 250 between the first surface 310 and the second surface 320.

[0183] Attempts have been made to make traditional wires (such as cylindrical wires) thinner by flattening them to allow subcutaneous implantation and / or increase comfort. However, the surface area of the flattened electrodes may become undesirably small.

[0184] In a non-limiting example, a traditional 0.2 mm circular wire with a 1 cm long electrode is estimated to produce an electrode with an electrode surface of approximately 6 mm 2 .

[0185] However, using the conformal electrode array described herein, a thin substrate 300 having dimensions of 0.2 mm thick and 4 mm wide can be configured and arranged to provide an electrode surface of approximately 35 mm over the same length. 2 It is estimated that this can reduce the impedance to about 6 / 35 of the original and reduce the power consumption to about 6 / 35 of the original.

[0186] In an embodiment, Figure 2A , Figure 2B and Figure 2C depicts a longitudinal cross-section through a second embodiment 101 of an implantable stimulator. It is similar to Figure 1A , Figure 1B and Figure 1C depicted in the first embodiment 100, except that:

[0187] - Instead of including four electrodes in the first surface 310, this embodiment includes two electrodes in the first surface 310, a nominally first type of electrode 200a and a nominally second type of electrode 400a. From proximal to distal, the depicted order is 200a, 400a, in other words, the first type of electrode 200a is adjacent to the second type of electrode 400a in the first surface 310.

[0188] - The distal end of the stimulator 101 also includes two electrodes in the second surface 320, another electrode 200b of the nominally first type and another electrode 400b of the nominally second type. From proximal to distal, the depicted order is 200b, 400b, in other words, the first type of electrode 200b is adjacent to the second type of electrode 400b in the second surface 320.

[0189] - In Figure 2B , a view of the second surface 320 depicts the two electrodes 200a, 400a included in that surface, and one or more interconnects 250 are depicted using dashed lines;

[0190] - In Figure 2C , a view of the second surface 320 depicts the two electrodes 200b, 400b included in that surface, and one or more interconnects 250 are depicted using dashed lines;

[0191] In this Example 101, the first type of electrodes 200a, 200b are nominally configured and arranged to operate as stimulation electrodes, and the second type of electrodes 400a, 400b are nominally configured to operate as return electrodes.

[0192] Thus, three main configurations are provided:

[0193] - The stimulation / return electrode pair 200a / 400a is close to the first surface 310; or

[0194] - The stimulation / return electrode pair 200b / 400b is close to the second surface 320; or

[0195] - A combination of both.

[0196] This can be advantageous if it is not certain whether the implantable distal end of the foil substrate 300 will be "above" or "below" the target tissue, such as a nerve. This can be determined after implantation by attempting stimulation in each nominal configuration and by observing and / or measuring the presence of nerve stimulation.

[0197] As described above, with respect to Figure 1A 、 Figure 1B and Figure 1C , each of the electrodes 200a, 200b, 400a, 400b can operate as one or more stimulation electrodes, or as one or more return electrodes.

[0198] In an embodiment, Figure 3A 、 Figure 3B and Figure 3C depicts a longitudinal cross-section of a third Example 102 of an implantable stimulator. It is similar to the second Example 101 depicted in Figure 2A 、 Figure 2B and Figure 2C , except that:

[0199] - The interconnects 250 are arranged in a substantially identical layout along the second transverse axis 750, as Figure 3A shown. The lines 250 are hatched to indicate that they are not depicted as being in the same longitudinal cross-section, and there are interconnects 250 arranged at substantially different positions along the first transverse axis 700;

[0200] - The interconnects 250 are arranged in a substantially different layout along the first transverse axis 700, as Figure 3B and Figure 3C shown as two adjacent dashed lines between the electrode arrays 200, 400 and the pulse generator 500;

[0201] - Instead of nominally including a first type of electrode 200 and a second type of electrode 400 in the first surface 310, the first surface 310 includes a first electrode 200a and a second electrode 200b of the nominally first type of electrode 200;

[0202] - Instead of nominally including a first type of electrode 200 and a second type of electrode 400 in the second surface 320, the second surface 320 includes a first electrode 400a and a second electrode 400b of the nominally second type of electrode 400;

[0203] In the present embodiment 102, the first type of electrodes 200a, 200b are nominally configured and arranged to operate as stimulation electrodes, and the second type of electrodes 400a, 400b are nominally configured to operate as return electrodes.

[0204] Thus, three main configurations are provided:

[0205] - A stimulation / return electrode pair 200a / 400a for performing stimulation between the first surface 310 and the second surface 320 at a location close to the electrode pair; or

[0206] - A stimulation / return electrode pair 200b / 400b for performing stimulation between the first surface 310 and the second surface 320 at a location close to the electrode pair; or

[0207] - A combination of both.

[0208] This may be beneficial for correcting longitudinal misalignment, or simply allow a healthcare professional to select the most effective stimulation location.

[0209] As described above, with respect to Figure 2A 、 Figure 2B and Figure 2C , each of the electrodes 200a, 200b, 400a, 400b can operate as one or more stimulation electrodes, or as one or more return electrodes.

[0210] Additionally or alternatively, one or more electrodes 200a, 200b or 400a, 400b of the same type can be electrically connected to each other by appropriately configuring one or more interconnects 250. Then, they will be operated substantially identically. This can be used to predict and / or correct misalignment and / or wire migration, since longitudinal positioning is less sensitive (providing stimulation over a greater longitudinal and / or lateral range).

[0211] Figure 4A 、 Figure 4B and Figure 4CDepicts alternative electrode array 200, 400 configurations suitable for inclusion in implantable stimulators 100, 101, 102 as described herein.

[0212] Figure 4A Depicts the implantable distal end of another embodiment 103 of a stimulator. Similar to Figure 1C the distal end depicted in

[0213] - Two electrodes 200a, 200b of a first type and two electrodes 400a, 400b of a second type. From proximal to distal, the depicted order is 200a, 400a, 200b, 400b. In other words, each electrode 200a, 200b of the first type is adjacent to an electrode 400a, 400b of the second type and is included in the same surface 310.

[0214] Figure 4A The depicted distal end is the same as Figure 1A that depicted in

[0215] - Electrodes 200, 400 extend at an angle to the longitudinal axis 600. This can reduce sensitivity to longitudinal misalignment as it increases the longitudinal positions at which tissue stimulation can be provided.

[0216] Additionally or alternatively, the second surface 320 may similarly include two electrodes 200a, 200b of a first type and two electrodes 400a, 400b of a second type.

[0217] As described above, each electrode 200a, 200b, 400a, 400b may operate as one or more stimulation electrodes or as one or more return electrodes.

[0218] Figure 4B Depicts the implantable distal end of another embodiment 104 of a stimulator. Similar to Figure 1C the distal end depicted in

[0219] - Four electrodes 200a, 200b, 200c, 200d of a first type and an electrode 400 of a second type. From proximal to distal, the depicted order is 200a, 200b, 200c, 200d. Lateral to the four electrodes 200 of the first type is the electrode 400 of the second type, which extends longitudinally to be adjacent to each electrode 200 of the first type.

[0220] Nominal, the electrodes 200 of the first type may operate as one or more stimulation electrodes. The electrode 400 of the second type may nominally operate as a return electrode for one or more stimulation electrodes.

[0221] This can reduce the sensitivity to longitudinal misalignment because four different longitudinal positions are provided that can be selected for stimulation, increasing the locations where tissue stimulation can be provided.

[0222] Additionally or alternatively, the second surface 320 can similarly include four electrodes 200a, 200b, 200c, 200d of a first type and one adjacent and longitudinally extending electrode 400 of a second type.

[0223] As described above, each of the electrodes 200a, 200b, 200c, 200d, 400 can operate as one or more stimulation electrodes or as one or more return electrodes.

[0224] Figure 4C Depicted is the implantable distal end of another embodiment 105 of a stimulator. Similar to Figure 4B the distal end depicted in, the first surface 310 includes four electrodes 200a, 200b, 200c, 200d of a first type. However, in this embodiment 105, the first surface 310 also includes four adjacent electrodes 400a, 400b, 400c, 400d of a second type. From proximal to distal, the depicted sequence is 200a / 400a, 200b / 400b, 200c / 400c, 200d / 400d. Adjacent to each of the four electrodes 200 of the first type is an electrode 400 of the second type along the longitudinal axis 600 in a substantially identical layout.

[0225] Nominal, the electrodes 200 of the first type can operate as one or more stimulation electrodes. The electrodes 400 of the second type can nominally operate as return electrodes for one or more stimulation electrodes. Nominally, adjacent electrodes can be considered a stimulation / return pair 200 / 400.

[0226] In other words, a 2×4 electrode array is provided - two along the transverse axis and four along the longitudinal axis.

[0227] This can reduce the sensitivity to longitudinal misalignment because four different stimulation / return pairs 200 / 400 are provided at substantially different longitudinal positions, and the four different stimulation / return pairs 200 / 400 can be selected for stimulation, increasing the locations where tissue stimulation can be provided.

[0228] Additionally or alternatively, the second surface 320 can similarly include four electrodes 200a, 200b, 200c, 200d of a first type and four adjacent electrodes 400a, 400b, 400c, 400d of a second type.

[0229] As described above, each of the electrodes 200a, 200b, 200c, 200d, 400a, 400b, 400c, 400d can operate as one or more stimulation electrodes or as one or more return electrodes. This can also reduce the sensitivity to lateral misalignment.

[0230] The stimulators 100, 101, 102, 103, 104, 105 may further include:

[0231] - An energy receiver configured and arranged to wirelessly receive energy from an associated energy transmitter when the associated energy transmitter is in proximity.

[0232] The pulse generator 500 is also configured and arranged to receive electrical energy from the energy receiver for its operation.

[0233] Figure 5 and Figure 6 depicts the configuration of nerves that can be stimulated using an implantable distal end of a suitably configured stimulator 100, 101, 102, 103, 104, 105 to provide nerve stimulation for treating conditions such as headache or primary headache.

[0234] Figure 5 depicts the left supraorbital nerve 910 and the right supraorbital nerve 920 that can be electrically stimulated using a suitably configured device. Figure 6 depicts the left greater occipital nerve 930 and the right greater occipital nerve 940 that can also be electrically stimulated using a suitably configured device.

[0235] Based on the size of the area to be stimulated and the dimensions of the portion of the device to be implanted, an appropriate location is determined to provide the electrical stimulation required for treatment. The approximate implant locations for the distal portions of the stimulation devices including the stimulation devices 100, 101, 102, 103, 104, 105 are depicted as regions:

[0236] - The location 810 for left supraorbital stimulation and the location 820 for right supraorbital stimulation for treating chronic headaches such as migraines and cluster headaches.

[0237] - The location 830a or 830b for left occipital stimulation and the location 840a or 840b for right occipital stimulation for treating chronic headaches such as migraines, cluster headaches, and occipital neuralgia. The locations 830b, 840b for stimulation are located at the upper part (“above”) of the (external) inion.

[0238] In many cases, these will be the approximate locations 810, 820, 830a / 830b, 840a / 840b for the implantable stimulators 100, 101, 102, 103, 104, 105.

[0239] For each implant location 810, 820, 830a / 830b, 840a / 840b, a separate stimulation system can be used. In cases where the implant locations 810, 820, 830a / 830b, 840a / 840b are close together or even overlapping, a single stimulation system can be configured to stimulate at more than one implant location 810, 820, 830a / 830b, 840a / 840b.

[0240] Multiple stimulation devices 100, 101, 102, 103, 104, 105 can be operated individually, simultaneously, sequentially, or any combination thereof to provide the desired therapy.

[0241] Figure 7 A further configuration of the nerve is depicted, which can be stimulated using appropriately configured improved implantable stimulators 100, 101, 102, 103, 104, 105 to provide nerve stimulation for treating other disorders. Figure 5 and Figure 6 The locations (810, 820, 830, 840) depicted in Figure 7 are also depicted in

[0242] Based on the size of the area to be stimulated and the dimensions of the portion of the device to be implanted, an appropriate location is determined to provide the electrical stimulation required for treatment. The approximate implant locations for the portion of the stimulation device that includes the stimulation electrodes are depicted as the following regions:

[0243] - Location 810 for cortical stimulation for treating epilepsy;

[0244] - Location 850 for deep brain stimulation for treating tremor control in patients with Parkinson's disease; for treating dystonia, obesity, essential tremor, depression, epilepsy, obsessive-compulsive disorder, Alzheimer's disease, anxiety, bulimia, tinnitus, traumatic brain injury, Tourette's syndrome, sleep disorders, autism, bipolar disorder; and stroke recovery;

[0245] - Location 860 for vagus nerve stimulation for treating epilepsy, depression, anxiety, bulimia, obesity, tinnitus, obsessive-compulsive disorder, heart failure, Crohn's disease, and rheumatoid arthritis;

[0246] - Location 860 for carotid or carotid sinus stimulation for treating hypertension;

[0247] - Location 860 for hypoglossal and phrenic nerve stimulation for treating sleep apnea;

[0248] - Location 865 for cerebrospinal stimulation for treating chronic neck pain;

[0249] - Locations 870 for peripheral nerve stimulation for treating limb pain, migraine, and pain in the extremities;

[0250] - Locations 875 for spinal cord stimulation for treating chronic low back pain, angina, asthma, and general pain;

[0251] - Locations 880 for gastric stimulation for treating obesity, bulimia, and interstitial cystitis;

[0252] - Locations 885 for sacral nerve and pudendal nerve stimulation for treating interstitial cystitis;

[0253] - Locations 885 for sacral nerve stimulation for treating urinary incontinence and fecal incontinence;

[0254] - Locations 890 for sacral nerve modulation for bladder control treatment; and

[0255] - Locations 895 for peroneal nerve stimulation for treating gait or foot drop.

[0256] Other diseases that can be treated include gastroesophageal reflux disease, autoimmune diseases, inflammatory bowel disease, and inflammatory diseases.

[0257] The conformability and reduced thickness of the substrate 100 and the electrode arrays 200, 400 make one or more implantable stimulators 100, 101, 102, 103, 104, 105 highly advantageous for stimulating one or more nerves, one or more muscles, one or more organs, spinal cord tissue, brain tissue, one or more cortical surface regions, one or more sulci, and any combination thereof.

[0258] The implantable stimulators 100, 101, 102, 103, 104, 105 described above with respect to FIGS. 1 to 4 can generally be described as embodiments configured and arranged for improved conformability.

[0259] The stimulators 100, 101, 102, 103, 104, 105 can be further modified. In non-limiting examples:

[0260] - A portion of the foil substrate 300 and the pulse generator 500 can be embedded in one or more flexible biocompatible encapsulation layers, such as those described below. These layers can include: liquid crystal polymer (LCP), polydimethylsiloxane (PDMS), silicone polyurethane, polyimide, parylene, biocompatible polymers, biocompatible elastomers, and any combination thereof.

[0261] The implantable electrical devices 1100, 1101, 1102 described below with reference to FIGS. 8-12 can generally be described as embodiments configured and arranged to improve encapsulation. As described below, they can be included in implantable medical devices 1110, 1111 that are configured and arranged to provide a degree of stimulation.

[0262] Figure 11A A cross-section through an improved implantable electrical or electronic device 1100 is depicted. It includes:

[0263] - A substrate 1400 having a first surface 1410 and one or more electrical conductors 1210.

[0264] Optionally, the substrate 1400 can be substantially biocompatible. However, the use of one or more encapsulation layers 1310 can allow the use of substrates 1400 and electrical conductors 1210 that are not biocompatible, partially biocompatible, or significantly biocompatible.

[0265] Generally, the degree of biocompatibility of a material or layer can be determined by measuring the degree of tissue reaction and the length of time it is considered to be biostable. A low degree of tissue reaction and / or a long period of biostability indicate a high degree of biocompatibility.

[0266] The substrate 1400 is also configured and arranged to be substantially flexible. In other words, the substrate is largely compliant or flexible or compliant (or conformable). Parameters can be used to adjust the degree of flexibility, such as:

[0267] - The sizing of the components of the device 1100, and / or

[0268] - Incorporating materials and substances with desired properties, and / or

[0269] - The combination of materials and substances used, and / or

[0270] - The percentages of materials and substances used, and / or

[0271] - Including grooves, openings, holes, reinforcements.

[0272] Additionally or alternatively, those skilled in the art will recognize that for the substrate 300 described with reference to FIGS. 1-4, the above parameters can be used to adjust the degree of flexibility.

[0273] One or more electrical conductors 1210 are very schematically depicted and can be conductors embedded in or deposited on a substrate 1400, for example, by having a single polymer layer and applying a conductive material using deposition techniques known in the semiconductor industry. One or more conductors 1210 (such as metals) can be formed as needed, for example, in one or more conductive elements: wires, strands, foils, thin films, plates, and / or sheets. Optionally, one or more conductors can be positioned between the outer surfaces of the substrate 1400;

[0274] Device 1100 further includes:

[0275] - A first biocompatible encapsulation layer 1310 including polydimethylsiloxane (PDMS) rubber; and

[0276] - A first adhesion layer 1510.

[0277] In the context of the present disclosure, ceramics should be considered advanced ceramics and / or industrial ceramics, providing a relatively high degree of thermal stability, wear resistance, and corrosion resistance.

[0278] The most suitable ceramic materials are those that have a high degree of adhesion to the encapsulant layer and / or the substrate and can be applied as a relatively uniform coating to provide a relatively low moisture permeability. In this context, ceramic materials can be inorganic, non-metallic, or metallic, typically crystalline oxide, nitride, or carbide materials. Some elements such as carbon or silicon are also considered ceramics. Non-metallic ceramics can include non-metallic and metallic elements.

[0279] Optionally, the first adhesion layer 1510 can be substantially biocompatible, however, the use of one or more encapsulation layers 1310 can allow the use of one or more adhesion layers 1510 that are not biocompatible, partially biocompatible, or significantly biocompatible.

[0280] The first adhesion layer 1510 and the first encapsulation layer 1310 are configured and arranged to resist the entry of fluid from a human or animal body into at least a portion of the first surface 1410. This configuration and arrangement are further described below.

[0281] As Figure 11A shown, the extent of the adhesion layer 1510 / encapsulation layer 1310 in this cross-section can be less than the extent of the substrate 1400. Generally, the extent of the adhesion layer 1510 / encapsulation layer 1310 can be greater than, equal to, or less than the extent of the substrate 1400. The "greater than" embodiment of the adhesion layer and the encapsulation layer is described in Figure 11C . The additional "less than" embodiments of the adhesion layer and the encapsulation layer are described in Figure 11B and Figure 12A .

[0282] Typically, the portion of the first surface 1410 that is protected against fluid entry is equal to or less than the extent of the adhesion layer 1510 / encapsulation layer 1310.

[0283] As Figure 11A shown, the extent of the adhesion layer 1510 in this cross-section can be less than the extent of the encapsulation layer 1310, which can be advantageous in some configurations because the edges of the adhesion layer 1510 at least partially encapsulate 1310. Typically, the extent of the adhesion layer 1510 can be greater than, equal to, or less than the extent of the encapsulation layer 1310. Additional "less than" embodiments are described in Figure 11C and Figure 12A . The "equal" portion of the substrate is shown in Figure 12B .

[0284] In a preferred embodiment, the extent of the adhesion layer 1510 is equal to or greater than the extent of the encapsulation layer 1310, which can be advantageous in some configurations because the surface area of the encapsulant 1310 in direct contact with the surface 1410 of the substrate 1400 is significantly reduced. In some cases, this surface area can be substantially zero, further reducing the likelihood of fluid entry. "Substantially zero" embodiments are described in Figure 11C and a portion of the substrate is described in Figure 12B .

[0285] Figure 11B Another implantable electrical or electronic device 1101 is depicted. It is identical to the implantable electrical device 1100 depicted in Figure 11A , except that it further includes:

[0286] - A second surface 1420;

[0287] - A second biocompatible encapsulation layer 1320 comprising polydimethylsiloxane (PDMS) rubber; and

[0288] - A second adhesion layer 1520, which includes a ceramic material, disposed between the second planar surface 1420 and the second encapsulation layer 1320. The second adhesion layer 1520 is further configured and arranged to conform to the second surface 1420, in other words, it is a conforming layer.

[0289] The second adhesion layer 1520 and the second encapsulation layer 1320 are configured and arranged to resist fluid entry from the human or animal body into at least a portion of the second surface 1420. This configuration and arrangement are further described below.

[0290] The second encapsulation layer 1320 can be substantially the same as, highly similar to, or substantially different from the first encapsulation layer 1310.

[0291] The second adhesion layer 1520 can be substantially the same as, highly similar to, or substantially different from the first adhesion layer 1510.

[0292] Although the first surface 1410 and the second surface 1420 are depicted as Figure 11B opposite sides of the substrate in

[0293] - applying the first adhesion layer 1510 / encapsulation layer 1310 and the second adhesion layer 1520 / encapsulation layer 1320 to different regions of the first surface 1410;

[0294] - applying the first adhesion layer 1510 / encapsulation layer 1310 and the second adhesion layer 1520 / encapsulation layer 1320 to different regions of the second surface 1420;

[0295] - the first surface 1410 and the second surface 1420 are adjacent to each other;

[0296] - the first surface 1410 and the second surface 1420 are opposite to each other;

[0297] - the first surface 1410 and the second surface 1420 are at a predetermined angle to each other;

[0298] - the first surface 1410 and the second surface 1420 are substantially perpendicular to each other.

[0299] Figure 11C Another implantable electrical or electronic device 1102 is depicted. It is the same as the Figure 11A implantable electrical device 1100 depicted in

[0300] - the substrate 1400 includes four protected surfaces, each surface being protected by another adhesion layer 1500 and another encapsulation layer 1300;

[0301] - for each protected surface, the extent of another adhesion layer 1500 is greater than the extent of the substrate 1400;

[0302] - for each protected surface, the extent of another encapsulation layer 1300 is greater than the extent of the substrate 1400; and

[0303] - for each protected surface, the extent of another adhesion layer 1500 is less than the extent of the encapsulation layer 1300.

[0304] Functionally, it can also be considered that another encapsulation layer 1300 includes Figure 11B the first encapsulation layer 1310 and the second encapsulation layer 1320 depicted in

[0305] Functionally, it can also be considered that another adhesion layer 500 includes Figure 11B the first adhesion layer 1510 and the second adhesion layer 1520 depicted in

[0306] Functionally, it can also be considered that the substrate 1400 depicted in Figure 11C includes the protected portions of the first surface 1410 and the second surface 1420 depicted in Figure 11B . However, the substrate 1400 depicted in Figure 11C includes two or more additional protected surfaces adjacent to such protected first or second surfaces.

[0307] Figure 11C Another encapsulation layer 1300 of Figure 11A or Figure 11B can be substantially the same as, highly similar to, or substantially different from the first encapsulation layer 1310 depicted in Figure 11C Another encapsulation layer 1300 of Figure 11B can be substantially the same as, highly similar to, or substantially different from the second encapsulation layer 1320 depicted in

[0308] Figure 11C Another adhesion layer 1500 of Figure 11A or Figure 11B can be substantially the same as, highly similar to, or substantially different from the first adhesion layer 1510 depicted in Figure 11C Another adhesion layer 1500 of Figure 11B can be substantially the same as, highly similar to, or substantially different from the second adhesion layer 1520 depicted in

[0309] Another embodiment 1102 may be advantageous because:

[0310] - The protected portion of the surface of the substrate 1400 to prevent fluid entry is less than the extent of another encapsulation layer 1300;

[0311] - The edges of another adhesion layer 1500 are substantially encapsulated by 1300; and

[0312] - The surface area of the encapsulant 1300 in direct contact with the surface of the substrate 1400 is close to or substantially zero.

[0313] Experiments were conducted to determine the suitability of specific adhesion layers 1510, 1520 to provide a high bond with PDMS.

[0314] A. Sample Preparation

[0315] Figure 10 Depicts a cross-section through the test sample 1130.

[0316] 1) Using Pt metallized IDC

[0317] An interdigitated capacitor (IDC) 1230 is used to evaluate the encapsulation performance. Approximately 600 nm of Pt (platinum) is sputtered on a 1-μm (1 micrometer) thick plasma-enhanced chemical vapor deposition (CVD) SiO2 layer 1435 with a 10-nm titanium adhesion layer in the middle. For more details on these IDCs 1230, see "Silicone rubber encapsulation for an endoscopically implantable gastrostimulator", Lonys, Vanhoestenberghe, Julemont, Godet, Delplancke, Mathys and Nonclercq, Med. Biol. Eng. Comput. 53 319-29, 2015. The SiO2 layer 1435 is disposed on a silicon substrate 1430.

[0318] 2) ALD coating

[0319] Atomic layer deposition (ALD) is a coating process that can be used to prepare nano-thick conformal coatings. Using an R-200 Advanced ALD reactor, the ALD coating is applied under a reduced pressure of approximately 1 mbar (1 hPa) (N2 atmosphere).

[0320] The R-200 Advanced from Picosun Oy, Finland, provides very high-quality ALD film deposition. The manufacturer recommends depositions applicable to include the following: Al2O3, TiO2, SiO2, Ta2O5, HfO2, ZnO, ZrO2, AlN, TiN, metals such as Pt or Ir.

[0321] It includes a remote microwave plasma generator with an adjustable power of 300 W - 3000 W, a frequency of 2.45 GHz, installed in the load chamber and connected to the reaction chamber. Up to 12 sources and 6 independent inlets can be used, and if the plasma option is selected, 7 independent inlets can be used. The precursor sources can include liquid, gaseous, and / or solid chemicals. The precursors can also include ozone and / or plasma. The remote plasma option allows metal deposition, thus greatly reducing the risk of short circuits and / or plasma damage. The processing temperature can generally be 50 °C - 500 °C. The plasma can typically be used up to approximately 450 °C or up to approximately 650 °C with a heated sample holder.

[0322] It includes a hot wall and a substantially separated inlet and instrumentation, providing relatively low particle (or substantially particle-free) processing suitable for a wide range of materials on wafers, 3D objects, and nanoscale features. It provides a high degree of uniformity, even on porous, through-porous, high aspect ratio (up to 1:2500), and nanoparticle samples using its proprietary Picoflow TM Diffusion enhancer. The enhancer provides a protective gas flow in the interstitial space to greatly reduce the back-diffusion of plasma species.

[0323] Suitable ALD processes for forming a monolayer containing a first and a second element can include:

[0324] - Loading a substrate as a sample into the reaction space;

[0325] - Introducing a quantity of a first molecule containing the first element into the reaction space, whereby at least a first portion of the first molecule adsorbs onto the surface of the substrate; and

[0326] - Introducing a quantity of a second molecule containing the second element into the reaction space, whereby at least a second portion of the second molecule reacts with the first portion on the surface of the substrate to form a monolayer of a compound containing the first and second elements.

[0327] Using the Picohot TM Source System (PH-300) and the PicoSolution option for the R-200 Advanced, the precursors are vaporized from stainless steel precursor bottles at elevated temperatures and at room temperature. The PicoHot TM 300 Source System allows the source to be heated up to 300 degrees Celsius, and the manufacturer recommends source chemicals with a vapor pressure of at least 2 mbar at the source temperature. The PicoSolution TM 600 Source System allows the use of liquid precursors, and the manufacturer recommends source chemicals with a vapor pressure of at least 10 mbar at the source temperature.

[0328] The thermal ALD process at 200 degrees Celsius is applied using a layer-by-layer deposition method, where two different precursor materials (separated by N2 purge to remove remaining molecules from the reaction space) are used to establish a HfO2 (hafnium dioxide) coating 1530, which is described in Figure 10 as a coating 1530 that substantially covers the outer surfaces of the substrate 1430, 1435, and the IDC sensor 1230.

[0329] At 200 degrees Celsius, an optional stabilization time of about 90 minutes is used. 10 layers of about 5 nm are applied to provide an ALD layer of about 50 nm.

[0330] ALD is thought to be beneficial for producing ultrathin conformal coatings with low defects and / or reduced pinhole formation. Additionally, the deposition temperature of ALD can be maintained below 200 °C, which is advantageous for devices incorporating sensitive metallization and / or polymers.

[0331] 3) PDMS encapsulation

[0332] Samples were encapsulated with a layer containing the substantially biocompatible PDMS (MED2-6215, NuSil Carpinteria, USA) 1330.

[0333] From nusil.com / product / med-6215_optically-clear-low-consistency-silicon e-elastomer:

[0334] MED-6215 is an optically clear low-consistency silicone elastomer. It is provided as a two-part, solvent-free, and relatively low-viscosity system. It cures thermally via an addition-curing chemical process. The mixing ratio is 10:1 (Part A: Part B).

[0335] MED-6215 is considered to be substantially biocompatible, and the manufacturer recommends that it can be used for human implantation for more than 29 days.

[0336] Uncured:

[0337]

[0338] Cured: at 150 °C (302 °F) for 15 minutes

[0339]

[0340]

[0341]

[0342] The manufacturer recommends using the silicone primer Nu-Sil MED1-161 as a primer to further improve the adhesion of MED-6215 to various substrates, including: metals (such as stainless steel, steel, copper, and aluminum), ceramic materials, rigid plastics, and other silicone materials.

[0343] MED-6215 is medical grade, in other words, substantially biocompatible and suitable for use in medical implantable devices. This is achieved by ensuring that all raw materials, intermediates, and finished products (medical grade) are produced in accordance with applicable GMP and / or appropriate regulatory standards (cGMP 21 CFR §820 (devices), cGMP 21 CFR §210 - 211 (drugs / API), and ISO 9001).

[0344] The encapsulation is carried out using a dip - coating process. An average relatively low viscosity (e.g., 4000 - 7000 cP (mPas)) seems to allow PDMS to flow more easily over the samples. The thickness of PDMS 1330 is estimated to be between 50 and 200 μm (micrometers).

[0345] B. Experimental setup

[0346] The lifetime reliability of the ALD coating can depend on factors such as the conformality, adhesion, and stability in ionic media of the coating. This is measured by the impedance of the IDC after an extended immersion test.

[0347] Extended immersion is carried out using phosphate - buffered saline (PBS) at approximately room temperature (about 23 °C).

[0348] The method described by Donaldson, Lamont, Shah Idil, Mentink, Perkins in "Apparatus to investigate the insulation impedance and accelerated life - testing of neural interfaces" published in J. Neural Eng, 2018, 10.1088 / 1741 - 2552 / aadeac is adopted to perform electrochemical impedance spectroscopy (EIS) to evaluate the performance of ALD and ALD - PDMS coatings.

[0349] The measurements are made using a Solartron Modulab and a potentiostat together with a frequency response analyzer. The measurements are carried out in a two - cell electrode configuration between the combs of the IDC structure. A Faraday cage is also used.

[0350] III. Results and discussion

[0351] A. Measurement results

[0352] After sample preparation and saline immersion, EIS measurements are carried out.

[0353] Figure 8A and Figure 8B Shows the EIS results 1700, 1710 for three samples.

[0354] Figure 8A depicts the Bode plot 1700, where the impedance magnitude ranges from 10 1 to 10 11 |Z| ohms along the vertical (Y) axis, and the frequency ranges from 10 -2 Hz to 10 5 Hz along the horizontal (X) axis:

[0355] - The bare IDC 1701 with exposed Pt metal forms an approximate straight line from about 10 -2 ,5×10 6 to 10 4 ,10 2 , followed by another straight line to 10 5 ,10 2 ;

[0356] - The IDC 1702 coated with HfO2 ALD forms an approximate straight line from 10 -2 ,10 9 to 10 5 ,10 3 ; and

[0357] - The IDC 1703 coated with an ALD-PDMS bilayer forms an approximate straight line from 10 -2 ,10 11 to 10 5 ,10 5 .

[0358] Figure 8B depicts the Bode plot 1710, where the phase ranges from 0 degrees to -90 degrees along the vertical (Y) axis, and the frequency ranges from 10 -2 Hz to 10 5 Hz along the horizontal (X) axis:

[0359] - The bare IDC 1711 with exposed Pt metal forms a curve passing through 10 -2 ,-20 to 10 0 ,-70 to 10 2 ,-80 to 10 -4 ,-20 to 10 -5 ,0;

[0360] - The IDC 1712 coated with HfO2 ALD forms a curve passing through 10 -2 ,-60 to 10 0 ,-80 to 10 2 ,-90 to 10 -4 ,-80 to 10 -5 ,-70; and

[0361] -IDC 1713 coated with a double layer of ALD-PDMS, forming a curve passing through 10 -2 , -80 to 10 0 , -90 to 10 2 , -90 to 10 -4 , -80 to 10 -5 , -90

[0362] For bare IDCs 1701, 1711, in the mid-frequency band (10 0 Hz - 10 3 Hz), the phase of 1711 seems to be relatively constant at about -80 degrees. At lower frequencies (about 10 -2 Hz), the polarization resistance seems to dominate, resulting in a phase of about -20 degrees. This can be considered to indicate that the metal is fully exposed to the electrolyte.

[0363] ALD-coated IDCs 1702, 1712 seem to show relatively high impedance values, indicating stronger capacitive behavior in the frequency range. This capacitance is thought to be due to the separation of the Pt metal and the electrolyte by the ALD layer acting as a dielectric. It can be considered that in the EIS results 1700, 1710, a fully conformal coating on the metal or a high resistance to fluid entry will result in substantially capacitive behavior.

[0364] For the ALD-PDMS double layers 1703, 1713, the results of impedance 1703 and phase 1713 show substantially capacitive behavior over substantially the entire frequency range, where the phase result 1713 approaches approximately -90°.

[0365] It is thought that any delamination or cracking of the ALD layer may expose more metal to the electrolyte, possibly resulting in significantly lower impedance and phase angles that are more prominently seen in the lower frequency region below 10 -1 Hz. In Figure 8A and Figure 8B , the comparison between ALD 1702, 1712 and ALD-PDMS double layers 1703, 1713 shows that for the double-layer encapsulated IDCs 1703, 1713, the impedance value 1703 is approximately two orders of magnitude higher. In addition, the phase result 1713 shows substantially more capacitive behavior.

[0366] In addition, the metal areas exposed due to ALD defects are also encapsulated with PDMS, where the specific resistance is about 10 15 Ohm.cm. It is thought that any significant delamination of PDMS from the ALD will allow water condensation, resulting in one or more conductive paths between the combs. This may result in below approximately 10 -1Lower impedance and phase angle are more significantly seen in the lower frequency region of Hz.

[0367] To track the changes in encapsulation and adhesion performance, EIS measurements were performed on all samples monthly. The impedance and phase angle at approximately 10 -2 Hz were selected as reference values for monitoring over time.

[0368] Figure 8C and Figure 8D Shows the adhesion evaluation results 1720, 1730 for two ALD samples and two ALD-PDMS samples after 450 days of immersion. Figure 8A and Figure 8B The results described in are considered the values measured at T = 0 days.

[0369] Figure 8C Depicts the adhesion evaluation result 1720, where the impedance magnitude ranges from 0 to 10 along the vertical (Y) axis 11 |Z| Ohm, and time ranges from 0 to 16 months along the horizontal (X) axis:

[0370] - Two IDCs 1722a, 1722b coated with HfO2 ALD, forming an approximate straight line from 0,10 9 to 16,10 9 Two samples provided essentially the same results, producing lines that essentially overlapped except for minimal deviations from 0 to 1 month and 15 to 16 months; and

[0371] - Two IDCs 1723a, 1723b coated with an ALD-PDMS bilayer, forming an approximate straight line from 0,10 11 to 16,10 11 Two samples provided essentially the same results, producing lines that essentially overlapped.

[0372] Figure 8D Describes the adhesive evaluation result 1730, where the phase ranges from -30 to -90 degrees along the vertical (Y) axis, and time ranges from 0 to 16 months along the horizontal (X) axis:

[0373] - The first IDC 1732a coated with HfO2 ALD, forming an approximate straight line from 0,-70 to 16,-65;

[0374] - The second IDC 1732b coated with HfO2 ALD, forming an approximate straight line from 0,-75 to 2,-63 to 4,-65 to 16,60;

[0375] - The first IDC 1733a coated with an ALD-PDMS bilayer forms an approximate straight line from 0, -83 to 2, -78 to 6, -80 to 16, -80.

[0376] - The second IDC 1733b coated with an ALD-PDMS bilayer forms an approximate straight line from 0, -80 to 2, -78 to 6, -77 to 10, -80 to 16, -78.

[0377] For the ALD-only samples 1722, 1732, the decrease in the phase angles 1732a, 1732b was measured after the first month of immersion, indicating that the fluid contacted the metal through one or more defects in the ALD layer. Substantially stable results were observed during the extended immersion period. This is considered to indicate the fairly high stability of the HfO2 adhesion layer in the ionic medium and the fairly high degree of adhesion of HfO2 to Pt over an extended period of time. A significant degradation of the HfO2 layer would be expected to show relatively high capacitive behavior, such as a significant decrease in the impedance magnitude 1720, which was not observed. Additionally, any significant delamination of the ALD layer from Pt would be expected to result in significantly higher resistive behavior, which results from the exposure of the metal to physiological saline, and this was also not observed.

[0378] Optical inspection of the ALD samples 1722, 1732 supported these conclusions, as no significant layer discoloration or degradation was observed.

[0379] For the ALD-PDMS bilayer samples 1723, 1733, substantially stable results were thus recorded over an extended period, indicating a relatively high degree of adhesion between the two layers and a significantly higher resistance to fluid ingress.

[0380] B. Conclusions

[0381] Pt is widely used in conductor and / or electrode regions due to its high biocompatibility and stability. However, in traditional systems, the long-term stability may be reduced due to the relatively weak adhesion of encapsulants such as PDMS, parylene, and epoxy resins to Pt.

[0382] Based on the results, it is considered that adding an adhesion layer containing one or more ceramic materials may be beneficial. In particular, an HfO2 ALD layer with an average thickness of about 25 nm to 100 nm, preferably about 50 nm, can provide a substantially stable intermediate adhesion layer between Pt and PDMS. Additionally, a relatively high degree of adhesion was also measured between the HfO2 layer and the SiO2 substrate, especially between the Pt forks.

[0383] In appropriate cases, substrates including other materials can thus be provided with SiO2 and / or Pt layers to improve adhesion to the HfO2 ALD layer.

[0384] The ALD-PDMS bilayer of the encapsulation layer 1330 and the adhesion layer 1530 appears to be particularly advantageous:

[0385] - The HfO2 ALD adhesion layer shows significantly higher stability in ionic media, thus providing relatively long resistance to delamination or water penetration through the PDMS encapsulation.

[0386] - PDMS, which has a relatively low average viscosity (e.g., 4000 to 7000 cP (mPas)) over a long period during encapsulation, can further contribute to more durable adhesion and defect reduction as it flows between any defects and openings in the ALD layer.

[0387] - PDMS-based materials are generally very suitable for implantation due to their relatively high degree of biocompatibility. Through appropriate selection and processing, many PDMS-type materials can be configured and arranged to be substantially biocompatible.

[0388] The polymer material contained in the substrate 1400 is preferably selected to be suitable for flexibility and includes one or more electrical conductors 1210. Preferably, the polymer substrate material has a high degree of biocompatibility and durability. Suitable polymer materials included in the substrate 1400 include those polymer materials described above for the conformal substrates related to FIGS. 1 to 4. In particular, polyimide, parylene C, SU-8, LCP, polyurethane, or any combination thereof can be used.

[0389] Preferably, the first surface 1410 and / or the second surface 1420 include a large amount of one or more liquid crystal polymers (LCPs). Optionally, the first surface 1410 and / or the second surface 1420 can be substantially composed of one or more LCPs. Optionally, the first surface 1410 and / or the second surface 1420 can be essentially composed of one or more LCPs.

[0390] The following table compares several physical and chemical properties of a typical polyimide and a typical LCP.

[0391]

[0392]

[0393] Advantageously, the substrate 1400 (e.g., including LCP) has a Young's modulus in the range of 2500 - 3600 MPa (2.5 - 3.6 GPa).

[0394] Optionally, the substrate 1400 may further include one or more electrical or electronic components configured to receive energy when electrical energy is applied to one or more electrical conductors 1210. For example, they may be inductively coupled, capacitively coupled, or directly connected. This is particularly advantageous for substrates including a large amount of one or more LCPs because PCB technology can be used. Preferably, biocompatible metals such as gold or platinum are used.

[0395] Preferably, the one or more encapsulation layers 1310, 1320 and the one or more adhesion layers 1510, 1520 are configured and arranged to resist fluid entry into at least a portion of the one or more surfaces 1410, 1420 adjacent to the one or more components.

[0396] For example, the one or more components may be active components, passive components, electronic components, integrated circuits (ICs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), analog components, digital components, surface mount devices (SMDs), through-hole packages, chip carriers, pin grid arrays, flat packages, small outline packages, chip scale packages, ball grid arrays, small-pin-count packages, flexible silicon devices, thin film transistors (TFTs), and any combination thereof.

[0397] The one or more electrical components may be configured and arranged to: resist corrosion, store charge, induct, sense, stimulate, amplify, process data, detect, measure, compare, switch, time, store data, count, oscillate, perform logic, add, generate stimulation pulses, and any combination thereof.

[0398] The substrate 1400 may further be configured and arranged to have the degree of conformability as described above. They may be foil-like (or film-like) and very closely follow the contour of the underlying anatomical features through flexibility. The very thin foil-like substrate 1400 has the additional advantage that they have increased flexibility.

[0399] The implantable electrical devices 1100, 1101 as described herein may be included in implantable medical devices 1110, 1111. For example, such medical devices 110, 1111 may be configured and arranged to provide a degree of sensing, stimulation, data processing, detection or measurement, data storage, oscillation, logic performance, stimulation pulse generation, or any combination thereof.

[0400] The embodiments described above with respect to FIGS. 1 to 4, in particular the implantable stimulators 101, 102, 103, 104, 105 may include the implantable electrical devices 1100, 1101, 1102.

[0401] AsFigure 12A As shown, an improved implantable medical device 1110 can be provided by modifying Figure 11A the implantable device 1100 shown. It is the same as the implantable electrical device 1100 depicted in Figure 11A , except in this cross-section:

[0402] - The substrate 1400 includes three protected surfaces, each protected by another adhesion layer 1500 and another encapsulation layer 1300; the three protected surfaces include two opposite protected surfaces and another adjacent surface;

[0403] - For the two opposite protected surfaces, the extent of the other adhesion layer 1500 is less than the extent of the substrate 1400. For the third adjacent protected surface, the extent of the other adhesion layer 1500 is greater than the extent of the substrate 1400;

[0404] - For the two opposite protected surfaces, the extent of the other encapsulation layer 1300 is less than the extent of the substrate 1400. For the third adjacent protected surface, the extent of the other encapsulation layer 1300 is greater than the extent of the substrate 1400; and

[0405] - For each protected surface, the extent of the other adhesion layer 1500 is less than the extent of the other encapsulation layer 1300.

[0406] Functionally, it can also be considered that the other encapsulation layer 1300 includes Figure 11B the first encapsulation layer 1310 and the second encapsulation layer 1320 shown.

[0407] Functionally, it can also be considered that the other adhesion layer 1500 includes Figure 11B the first adhesion layer 1510 and the second adhesion layer 1520 shown.

[0408] However, Figure 12A the substrate 1400 depicted in

[0409] Figure 12A includes another protected surface adjacent to such a protected first or second surface. Figure 11A or Figure 11B The other encapsulation layer 1300 in Figure 12A can be substantially the same as, highly similar to, or substantially different from the first encapsulation layer 1310 depicted in Figure 11B .

[0410] Figure 12A The other encapsulation layer 1300 in Figure 11A or Figure 11B can be substantially the same as, highly similar to, or substantially different from the second encapsulation layer 1320 depicted inFigure 12A Another adhesion layer 1500 can be substantially the same as, highly similar to, or substantially different from the second adhesion layer 1520 depicted in Figure 11B .

[0411] The medical device 1110 further includes:

[0412] - One or more stimulation electrodes 1220, which are configured and arranged to transmit energy to human or animal tissue when electrical energy is applied to one or more electrical conductors 1210. For example, they can be inductively coupled, capacitively coupled, or directly connected. In the example described, one or more stimulation electrodes 1220 are directly connected to one or more electrical conductors 1210. In many nerve stimulation applications, multiple electrodes 1220 may be required. These electrodes can be the same as, similar to, or different from the electrodes 200, 400 with respect to FIGS. 1 to 4 described above.

[0413] Optionally or additionally, one or more sensors 1230 can be provided similarly, and such sensors 1230 are configured to provide electrical signals and / or data to one or more electrical conductors 1210. For example, they can be inductively coupled, capacitively coupled, or directly connected. If a multi-layer substrate with electrical interconnects is provided, a higher degree of customization can be achieved. For example, it allows direct measurement of parameters related to operation, such as humidity, temperature, resistance, and electrical activity.

[0414] Typically, for nerve stimulation electrodes, one or more electrodes 1220 are configured and arranged to operate as ground electrodes or return electrodes, which can be one of the existing electrodes, or one or more additional electrodes such as the first electrodes 200a, 200b and the second electrodes 400a, 400b described with respect to FIGS. 1 to 4 as above.

[0415] Those skilled in the art will recognize that such stimulation electrodes 1220 and / or tissue sensors are preferably not completely covered by the encapsulation layer 1300 and / or the adhesion layer 1500, because their functions require a sufficiently high degree of electrical connection or exposure to the implant environment. For example, at least a portion of the stimulation electrodes 1220 and / or tissue sensors is masked during the encapsulation process to provide a conductive surface towards the tissue. Additionally or alternatively, parts of the device can be left unencapsulated.

[0416] Figure 12ADepicts device 1110, where substantially all of the stimulation electrodes 1220 are substantially uncovered. Additionally, in this cross-section, a portion of the substrate 1400 is substantially uncovered, thereby providing device 1110 with a substantially encapsulated portion and a substantially unencapsulated portion with one or more electrodes. In this cross-section, the extent of another adhesion layer 1500 for two opposite surfaces is less than the extent of another encapsulation layer 1300 for these surfaces, which may be advantageous because the edges of the another adhesion layer 1500 are at least partially encapsulated by 1300.

[0417] Applying such encapsulation to the implantable stimulator described above with respect to FIGS. 1 and 4 generally provides a substantially unencapsulated portion with one or more electrodes 200, 400, and a substantially encapsulated portion including the pulse generator 500.

[0418] Figure 12B Depicts another embodiment of medical device 1111. More specifically, it depicts a cross-section through a portion of the substrate 1400 including one or more electrodes 1220. Another medical device 1111 is the same as the device 1110 depicted in Figure 12A except that generally in this cross-section:

[0419] - The substrate 1400 includes four protected surfaces, each protected by another adhesion layer 1500 and another encapsulation layer 1300;

[0420] - For each protected surface, the extent of another adhesion layer 1500 is greater than the extent of the substrate 1400;

[0421] - For each protected surface, the extent of another encapsulation layer 1300 is greater than the extent of the substrate 1400; and

[0422] - For each protected surface, the extent of another adhesion layer 1500 is less than the extent of the encapsulation layer 1300.

[0423] In this cross-section, a "portion" of one or more stimulation electrodes 1220 is not completely covered to allow for electrical connection after implantation or exposure to the implant environment. Thus, in the region near the stimulation electrodes 1220, the above general statements do not fully apply. In particular, in this cross-section:

[0424] - Another adhesion layer 1500 has been applied to the surface of the substrate 1400 adjacent to the stimulation electrodes 1220 and also to the edge portions of the surfaces of the electrodes 1220. This can provide additional protection against ingress at any interface between the electrodes 1220 and the substrate 1400; and

[0425] -Another encapsulation layer 1300 has been applied to the surface of the substrate 1400 adjacent to the stimulation electrode 1220. However, it is not significantly applied to the edge portion of the surface of the electrode 1220.

[0426] In other words, in the cross-section at the edge portion of the surface of the electrode 1220, the extent of the another adhesion layer 1500 is substantially the same as the extent of the another encapsulation layer 1300.

[0427] In some configurations, this may be advantageous because the surface area of the another encapsulation layer 1300 in direct contact with the surface of the electrode 1220 is greatly reduced. In some cases, this surface area may be substantially zero.

[0428] Applying such an encapsulation to the implantable stimulator described above with respect to FIGS. 1 and 4 generally provides a basic encapsulation portion having a "portion" of one or more electrodes 200, 400, and a basic encapsulation portion including a pulse generator 500.

[0429] Optionally, if the extent of the another encapsulation layer 1300 at the edge portion of one or more electrodes 1220 in the cross-section is greater than the extent of the another adhesion layer 1500, then in some configurations, this may be advantageous because at least a portion of the edge of the another adhesion layer 1500 is encapsulated by 1300.

[0430] Thus, one or more stimulation electrodes 1220 and / or sensors are preferably included in the surface and configured and arranged to provide a tissue interface.

[0431] As described above, "included in the surface" means that the electrode 1220 is relatively thin (e.g., when the substrate conforms to the surface of a basic plane, the surface of the basic plane has an extent of 20 to 50 microns or less along a transverse axis substantially perpendicular to the longitudinal axis of the substrate. Even thinner electrodes can be used to further increase conformability, e.g., 1 micron or less) and is attached to (or at least partially embedded in) the surface.

[0432] This is particularly advantageous for substrates including a large amount of one or more LCPs because PCB / metallization techniques can be used to provide conductive regions that can be configured and arranged as electrodes 1220 and / or sensors 1230. As described above, conductive materials such as gold, platinum, platinum black, TiN, IrO2, iridium, and / or platinum / iridium alloys and / or oxides are preferably used. Conductive polymers such as Pedot can also be used. Preferably, biocompatible conductive materials are used.

[0433] As described above, for the electrode 1220, a thicker metal layer is generally preferred over a thinner metal layer because they can withstand body substances that can dissolve the metal. However, thicker metal layers generally increase the rigidity near the thicker layer (reducing conformability).

[0434] In the second set of experiments, the adhesion of NuSil's PDMS MED2-4213 to LCP substrates was investigated using two different substrates and two different PDMS casting processes.

[0435] Adhesion was evaluated using different methods: by peel testing after drying following PBS immersion at 60 degrees Celsius and by peel testing based on ASTM D1876.

[0436] From nusil.com / product / med2-4213_fast-cure-silicone-adhesive:

[0437] MED2-4213 is a two-part, translucent, thixotropic, relatively high extrusion rate, relatively high tear strength, relatively fast curing silicone adhesive. It is also substantially tin (Sn) free, reducing the cure's requirements for atmospheric humidity. It also does not contain significant amounts of cure by-products such as acetic acid or methanol.

[0438] MED2-4213 is considered to be substantially biocompatible, and the manufacturer recommends that it can be used for human implantation for up to 29 days. Typical chemical and physical properties include:

[0439] Uncured:

[0440]

[0441] Cured: at 150 °C for 15 minutes

[0442]

[0443]

[0444]

[0445] It may be advantageous if the first encapsulation layer (1310) and / or the second encapsulation layer (1320) has a tensile strength in the range of 6 to 8 MPa.

[0446] NuSil recommends that in many bonding applications (for substrates including aluminum, glass, PMMA, silicone), a silicone primer is not required to achieve adequate adhesion.

[0447] The manufacturer recommends using a primer when adhering to substrates including polyetherimide, PEEK, plastics, polycarbonate, polyimide, polysulfone, polyurethane, and stainless steel.

[0448] To study the adhesion properties of PDMS on LCPs with different processing methods and adhesion layers, two different test substrates were used:

[0449] - Type 1: A substrate of 3 layers of LCP with an ALD coating on one side

[0450] - Type 2: A laminated substrate of 2 layers of LCP with an ALD coating on one side

[0451] Generally speaking, when manufacturing implantable electrical devices, it is beneficial to perform as few steps as possible, which can reduce the risk of introducing contamination or transportation-related problems and can reduce one or more costs.

[0452] A process with relatively few steps can be based on overmoulding electronics directly mounted on a substrate (here LCP). Depending on the hardware configuration, the PDMS used may need to adhere well enough to surfaces such as:

[0453] - The ASIC passivation layer in the case of wire-bonding.

[0454] - The Si substrate in the case of an ASIC flip chip or ACF mount. The Si substrate is one of the relevant interfaces when using bare-die components. A bare-die integrated circuit is usually made from a wafer or substrate, i.e., a thin slice of crystalline silicon semiconductor. To manufacture a bare-die component, this material undergoes many microfabrication processes to become an integrated circuit, but one side always uses the raw material, usually crystalline silicon. The relevant interfaces include:

[0455] - ASIC interconnects.

[0456] - Gold from wire-bonding or stud bumps.

[0457] - ACF (anisotropic conductive film), which is usually epoxy-based and coated with gold particles, for applying bare-die components on bonding pads.

[0458] - The substrate, in this case, the substrate contains a large amount of LCP.

[0459] Prepare a type 1 LCP substrate using one or more of the following process steps:

[0460] a) Providing the substrate: These substrates are basic planar sheets of LCP with an average thickness of about 0.150 mm. The substrate consists of three layers: two layers of 0.050 mm of 3908, separated by a layer of 0.050 mm of ULTRALAM 3850.

[0461] The 3908LCP is available from Rogers Corporation (www.rogerscorp.com) and can be used as a bonding medium (adhesion layer) between copper, other LCP materials, and / or dielectric materials. It features a low and stable dielectric constant. It has a relatively low modulus, allowing for relatively easy bending for flexible applications, and has a relatively low moisture absorption.

[0462] It can be used with one or more layers of 3850LCP to produce a substantially all-LCP multi-layer substrate that is substantially adhesive-free.

[0463] Typical values of the physical and chemical properties of 3908LCP include:

[0464] Mechanical properties

[0465]

[0466]

[0467] Thermal properties

[0468]

[0469] Electrical properties

[0470]

[0471]

[0472] Environmental properties

[0473]

[0474] The 3850 is available from Rogers Corporation (www.rogerscorp.com) and is a relatively high-temperature-resistant LCP. It can be provided as a double-sided copper-clad laminate for use as a laminate circuit material. The manufacturer recommends using these products as single or multi-layer substrates. The ULTRALAM 3850 circuit material features a relatively low and stable dielectric constant and low dielectric loss. It has a relatively low modulus, allowing for relatively easy bending for flexible applications, and has a relatively low moisture absorption.

[0475] It can be used with one or more layers of 3908LCP to produce a substantially all-LCP multi-layer substrate that is substantially adhesive-free.

[0476] Typical values of the physical and chemical properties of 3850LCP include:

[0477] Mechanical properties

[0478]

[0479]

[0480] Thermal properties

[0481]

[0482] Electrical properties

[0483]

[0484] Environmental properties

[0485]

[0486] Further prepare a type 1 LCP substrate using one or more of the following process steps:

[0487] b1) Optionally pre-clean at least a portion of the substrate with IPA and then dry. Another suitable alcohol may also be used.

[0488] b2) Apply an adhesion coating: Using ALD, apply the coating to the outer surface of the substrate, which in this case is the surface including the surface of 3908LCP. Ten alternating layers of approximately 5 nm of Al2O3 and approximately 5 nm of HfO2 result in a multi-layer of approximately 100 nm. The scope of the ALD coating is approximately the same as the scope of the substrate. Use the R-200 Advanced ALD reactor described above to apply the ALD coating. It is applied at a temperature significantly below the LCP melting temperature. For these type 1 LCP substrates, it is applied at approximately 125 degrees Celsius after an optional stabilization time of approximately 90 minutes.

[0489] For comparison, some samples omitted this step (in other words, directly applied PDMS to the LCP).

[0490] c) Clean at least a portion of the adhesion coating: As part of the preparation of the PDMS coating, perform an optional 10-minute ozone (O3) plasma treatment to clean the ALD surface. PDMS is applied within 15 minutes after the ozone cleaning. For comparison, some samples were not cleaned before the PDMS coating was applied.

[0491] UV O3 (ozone) plasma cleaning is suitable for dry, non-destructive atomic cleaning and the removal of organic contaminants. It uses intense 185 nm and 254 nm ultraviolet light. In the presence of oxygen, the 185 line generates ozone, while the 254 line excites the organic molecules on the surface. This combination promotes the rapid destruction and significant reduction of organic contaminants.

[0492] d) Applying an encapsulation coating: A PDMS coating of MED2-4213 with a thickness of approximately 500 μm to 1000 μm was applied on the ALD coating. The syringe was filled with MED2-4213 and mixed and degassed at a relatively high speed (2500 rpm) for three minutes. It was cured at 150 °C for 10 min and post-cured at 80 °C for 24 hours. The range of the PDMS coating is smaller than that of the ALD coating, so the ALD coating is exposed near the edge of the substrate (not covered by the encapsulant). After applying PDMS on the substrate, the substrate was placed on a preheated plate coated with PTFE (polytetrafluoroethylene), and a heavy object was pressed on top of it.

[0493] Therefore, 6 type 1 LCP samples were prepared:

[0494]

[0495] The pass / fail test for type 1 LCP substrates was defined manually:

[0496] - After curing the PDMS, a dry peel test (without soaking) was performed, and the degree of delamination was recorded.

[0497] - After the dry peel test, the samples were soaked in a 60 °C PBS solution for 1 day, 1 week, and 4 weeks, and the peel test was repeated to determine the second degree of delamination.

[0498] Three degrees of delamination were defined:

[0499] - Delamination: PDMS can be relatively easily removed from the substrate

[0500] - Partial delamination: PDMS can be relatively easily removed in some areas, but adheres relatively well in other areas

[0501] - Adhesion: PDMS basically does not delaminate

[0502] Phosphate-buffered saline (abbreviated as PBS) is a commonly used buffer solution in biological research. It is an aqueous salt solution containing disodium hydrogen phosphate, sodium chloride, and in some formulations, potassium chloride and potassium dihydrogen phosphate. The buffer helps to maintain a constant pH. The osmotic pressure and ionic concentration of the solution are chosen to match those of the human body (isotonic).

[0503]

[0504] Sample 1.1: Generally, PDMS has a low adhesion level to LCP.

[0505] Sample 1.2: PDMS cannot be peeled off from the surface in the dry state. After soaking for 24 hours, part of the PDMS can be peeled off from the substrate, although no water-filled voids were observed. After peeling off some PDMS, the rest adheres well to the substrate and cannot be peeled off anymore, even after an additional 1 or 2 weeks of soaking. It is suspected that the initial delamination was caused by local contamination or processing problems during the PDMS processing.

[0506] Sample 1.3: These samples showed good adhesion. Delamination was not reached until after two weeks of testing, under both dry and wet conditions.

[0507] Conclusion

[0508] - Generally, without any adhesion layer, the adhesion level of PDMS to LCP is low (Sample 1.1).

[0509] - In Sample 1.2 (coated with ALD and then encapsulated with PDMS, without O3 cleaning), PDMS cannot be peeled off from the surface in the dry state. After soaking for 24 hours, part of the PDMS can be peeled off from the substrate, although no water-filled voids were observed. After peeling off some PDMS, the rest adheres well to the substrate and cannot be peeled off anymore, even after an additional 2 weeks of soaking. Samples with more conformal ALD multilayers showed good adhesion even after soaking for two weeks.

[0510] - Sample 1.3 (coated with ALD and encapsulated with PDMS after the O3 cleaning step) showed the highest adhesion level. No substantial delamination was reached under either dry or wet conditions (after soaking for 2 weeks).

[0511] - An Al2O3 / HfO2 multilayer ALD layer with a total average thickness of about 50 nm - 200 nm, preferably about 100 nm, can provide a favorable intermediate adhesion layer between LCP and PDMS polymers.

[0512] Prepare a type 2 LCP laminated substrate using one or more of the following process steps:

[0513] a) Provide substrates: These substrates are LCP laminates with an average thickness of about 0.110 mm. The substrate consists of four layers: an outer copper connection pad, a layer of 0.050 mm of 3850, one or more inner copper conductors, and a layer of 0.025 mm of ULTRALAM3908:

[0514] a1) LCP approximately 50 um thick The 3850 board has a first copper layer on its first surface. The first copper layer is approximately 18 um thick. The first copper layer is configured and arranged to form copper connection pads, for example, by masking and etching, which can be considered to be included in the outer surface of the laminated substrate;

[0515] a2) The 3850 is further coated with another copper layer. The second layer is approximately 18 um thick. Optionally, it can be configured and arranged to form one or more conductors, for example, by masking and etching, which can be considered to be included in the inner surface of the laminated substrate. If inner conductors are not required, the another copper layer can be omitted or completely removed;

[0516] a3) LCP approximately 25 um thick The 3908 board is bonded to the inner surface of the 3850 layer and further bonded to one or more conductors.

[0517] Optionally, the laminate can be substantially planar.

[0518] b) Apply an adhesion coating:

[0519] b1) Optionally pre - clean at least a portion of the substrate using IPA and then dry. Another suitable alcohol can also be used.

[0520] b2) Apply a coating to the outer surface of the substrate using ALD. In this case, it is the surface including the 3908 LCP. It is not the outer surface of the substrate including one or more connection pads. Ten alternating layers of approximately 5 nm of Al2O3 and approximately 5 nm of HfO2 result in a multi - layer of approximately 100 nm. Use the R - 200 Advanced ALD reactor to apply the ALD coating. It is applied at a temperature well below the melting temperature of the LCP. For these type 1 LCP substrates, it is applied at approximately 125 degrees Celsius after an optional stabilization time of approximately 90 minutes. The extent of the ALD coating is approximately the same as the extent of the substrate.

[0521] b3) Apply an adhesion improver: NuSil's MED - 166 is a specially formulated primer recommended by the manufacturer for improving the adhesion of PDMS to various substrates, including: rigid plastics and other silicone materials. The manufacturer recommends that it is suitable for human implantation for a period greater than 29 days.

[0522] c) Clean at least a portion of the adhesion coating before encapsulation:

[0523] c1) Option 1: Clean with ethanol and then dry at 70 degrees Celsius for 4 hours. Another suitable alcohol can also be used.

[0524] c2) Option 2: Expose the ALD surface to a plasma containing O2.

[0525] O2 (oxygen) plasma refers to any plasma treatment carried out while actively introducing oxygen into the plasma chamber. Oxygen plasma is generated by utilizing an oxygen source on the plasma system.

[0526] Additionally or alternatively, ozone (O3) can be used.

[0527] d) Apply an encapsulation coating:

[0528] d1) Apply an encapsulation mask to simplify testing: Apply a Kapton tape (10 mm wide) to one edge to cover a small section, on which the tensile testing machine will be clamped during the peel test.

[0529] d2) Apply an encapsulation coating: A PDMS coating of MED2 - 4213 approximately 500 μm to 1000 μm thick is applied on top of the ALD coating. Vacuum centrifugal casting is used at 100 degrees Celsius with a PTFE - coated mold under a relatively low vacuum (e.g., 800 - 900 Pa (8 to 9 mbar)) to reduce the risk of air entrapment in the PDMS. Generally, applying a vacuum can facilitate the application of an adhesive coating of PDMS with an average viscosity in the range of 55000 - 100000 cP (mPas) over a fairly long period.

[0530] The area of the PDMS coating is approximately the same as that of the ALD coating. After removing the Kapton tape, a strip approximately 10 mm wide where the PDMS does not adhere to the ALD coating is provided.

[0531] e) Perform further processing: Cut the coated substrate with an area of approximately 100 mm × 75 mm into 7 pieces of approximately 100 mm × 10 mm for the peel test. Due to the removal of the Kapton tape, each piece has an area of approximately 10 mm × 10 mm and no PDMS coating at its edge.

[0532] Thus, 15 samples of type (2) are prepared:

[0533]

[0534] The peel test according to ASTM D1876 is applicable to testing type 2 LCP or laminated substrates. A peel testing machine is used to measure the peel force.

[0535] 4. Peel test results

[0536] Figure 9 Depicts Chart 1750, comparing the average tensile force under dry (unsoaked) conditions with the average tensile force after soaking in PBS at 60 °C for 24 hours. The LCP samples were coated with PDMS using different processes.

[0537] The average peel force from 0 to 18 N is plotted along the vertical (Y) axis, and the results are given for different samples along the horizontal (X) axis. For simplicity of explanation, the samples are ordered numerically: from left to right, samples 2.2, 2.2, 2.3, 2.4, and 2.5.

[0538] For each sample, the vertical length of each bar represents the average peel force in Newtons (N). For each bar, an "I" - shaped line is also depicted to indicate the variation measured in the tensile force values used to determine the average. For each sample, an unfilled bar is depicted on the left - hand side, showing the average tensile force under dry conditions, and a shaded bar is depicted on the right - hand side, showing the average tensile force after soaking in PBS at 60 °C for 24 hours.

[0539] For sample 2.1, the unfilled bar 1761a is depicted as approximately 4 N, with a relatively small degree of variation. The value after soaking is not described.

[0540] For sample 2.2, the unfilled bar 1762a is depicted as approximately 13 N, with an average degree of variation. The shaded bar 1762b is depicted as approximately 14 N, with a relatively high degree of variation.

[0541] For sample 2.3, the unfilled bar 1763a is depicted as approximately 5 N, with a relatively small degree of variation. The shaded bar 1763b is depicted as approximately 7 N, with an average degree of variation.

[0542] For sample 2.4, the unfilled bar 1764a is depicted as approximately 7 N, with a relatively small degree of variation. The shaded bar 1764b is depicted as approximately 7.5 N, with an average degree of variation.

[0543] For sample 2.5, the unfilled bar 1765a is depicted as approximately 8 N, with a relatively small degree of variation. The shaded bar 1765b is depicted as approximately 8 N, with an average degree of variation.

[0544] The measured average peel force is:

[0545]

[0546] A seemingly stable overmolding encapsulation process was achieved, with essentially no or very few air bubbles in the PDMS. In 7 samples, obvious delamination at the LCP / PDMS interface was observed in 3 samples directly after overmolding. For this reason, a peel test was applied to obtain a more qualitative measurement of the adhesion strength.

[0547] Sample 2.1: Without additional primer or cleaning, the PDMS had a very low degree of adhesion to the LCP (about 4N - 1761a).

[0548] Sample 2.2: The substrate with primer seemed to have a relatively high degree of adhesion (about 13N - 1762a compared to about 4N - 1761a). During the test, some areas had a higher degree of adhesion, resulting in the PDMS cracking before being completely peeled off the sample. The average tensile force after the soak test seemed relatively high, about 14N - 1762b, but a relatively high degree of deviation was also observed.

[0549] Sample 2.3: By adding ALD multilayers, especially the HfO2 - Al2O3 multilayer ending with HfO2, the dry adhesion seemed to be improved (from about 4N - 1761a to about 5N - 1763a). The results 1763a under dry conditions seemed to have a very low degree of deviation. The average tensile force after the soak test seemed relatively high, about 7N - 1763b.

[0550] Sample 2.4: O2 plasma activation also seemed to increase the adhesion (about 7N - 1764a compared to about 4N - 1761a). The average tensile force after the soak test seemed slightly higher, about 7.5N - 1764b.

[0551] Sample 2.5: Plasma activation seemed to further improve the adhesion (about 8N - 1765a compared to about 4N - 1761a). The average tensile force after the soak test at 8N - 1765b seemed about the same. A small increase in deviation - 1765b was observed after soaking.

[0552] Conclusion

[0553] - A relatively high degree of adhesion was observed when using a primer. For example, NuSil's MED - 166 can be used. But it may not be very preferred in some applications. In particular, for implantable devices, it is beneficial to use significantly biocompatible materials, and more preferably materials that are essentially biocompatible (with a high degree of biocompatibility). Although the manufacturer of MED - 166 recommends that it is suitable for implantation for more than 29 days, the primer is usually an epoxy adhesive using volatile solvents. This may increase the risk of contamination due to insufficient evaporation and / or the need for additional process steps to ensure sufficient solvent removal.

[0554] In addition, for implantable devices, a high degree of quality control is often required to limit the risk of defects. The primer typically must be applied using a spraying process, which can be difficult to perform with a high degree of reliability. This reliability issue is thought to be the cause of some of the observed delamination.

[0555] - An Al2O3 / HfO2 multi-layer ALD layer with a total average thickness of about 50 nm - 200 nm, preferably about 100 nm, can provide a favorable intermediate adhesion layer between LCP and PDMS polymers. Generally, the ceramic layer has a thickness less than,

[0556] - The ALD coating used, made of materials suitable for implantable electrical devices, improves the adhesion of PDMS to LCP.

[0557] - The ALD multi-layer stack not only improves adhesion but also improves barrier properties to protect the surface area from moisture ingress. This is better than a primer, as primers typically have a high degree of moisture permeability.

[0558] Based on the improved adhesion between PDMS and a surface containing a large amount of Pt, SiO2, and LCP, an adhesion layer containing a ceramic material may be advantageously used for a wide range of substrate materials. In particular, the adhesion of PDMS can be improved when the first surface 1410 and / or the second surface 1420 includes a large amount of substances selected from the group consisting of: liquid crystal polymer (LCP), polyimide, parylene-C, SU-8, polyurethane, or any combination thereof. These substances can be included in the flexible substrate.

[0559] In appropriate cases, substrates including other materials can thus be provided with a layer of such materials to improve adhesion to the HfO2 ALD layer.

[0560] Those skilled in the art will also recognize that adhesion can be improved by optionally or additionally applying a conformal coating to such a substrate, for example, by an ALD process, to apply a SiO2 (silicon dioxide) layer.

[0561] PDMS is generally a silicone rubber with siloxane as the basic repeating unit. The methyl groups are replaced by various other groups (such as phenyl, vinyl, or trifluoropropyl, depending on the type of PDMS), thereby connecting the organic groups to the inorganic backbone.

[0562] Based on the improved adhesion of PDMS using one or more adhesion layers including HfO2 and / or Al2O3, an adhesion layer including a suitable ceramic material can be advantageously used for a wide range of substrate materials.

[0563] A suitable ceramic surface contains a relatively rich amount of hydroxyl groups. It is believed that the high degree of adhesion is due to the fact that oxygen in a suitable type of PDMS can form strong bonds with the hydroxyl groups on the suitable ceramic surface. This can be chemical bonding, hydrogen bridge bonding, or some combination.

[0564] Suitable ceramics include:

[0565] - Carbides, such as silicon carbide (SiC);

[0566] - Oxides, such as aluminum oxide (Al2O3);

[0567] - Nitrides, such as silicon-containing nitrides (SixNy or SiNxOy) and especially silicon nitride (Si3N4); and

[0568] - Many other materials, including mixed oxide ceramics that can act as superconductors.

[0569] In particular, the adhesion of PDMS can be improved when the ceramic material is selected from the group consisting of: HfO2, Al2O3, Ta2O3, TiO2, and any combination thereof.

[0570] It is also desirable that diamond-like carbon can be advantageously used to improve adhesion.

[0571] The adhesion can be further increased by activating the surface of the ceramic layer, for example, by applying alcohol, especially ethanol; using a plasma containing O3 (ozone) and / or containing O2; treating with silane; or any combination thereof.

[0572] The adhesion layer can be a bilayer or multilayer, where one or more layers can be configured and arranged for a relatively high degree of adhesiveness, and one or more layers can be configured and arranged for a relatively high degree of corrosion resistance (impermeability).

[0573] For example, a layer containing Al2O3 is believed to provide a relatively high degree of adhesiveness. For example, a layer containing HfO2 is believed to provide a relatively high degree of corrosion resistance.

[0574] Figure 5 and Figure 6 Examples of nerves that can be stimulated using one or more suitably configured improved medical devices 1110, 1111 are also described. The improved medical devices 1110, 1111 are configured to provide nerve stimulation to treat, for example, headache, chronic headache, or primary headache. In particular, if the substrate is substantially flexible (or conformable), it can better conform to the curved surface of the head and / or skull. This means that the comfort of the user of the implantable medical devices 1110, 1111 can be increased by applying one or more of the above-described features for improving conformability.

[0575] In many cases, these will be the approximate locations 810, 820, 830, 840 of one or more implantable medical devices 110, 111.

[0576] For each implant location 810, 820, 830a / 830b, 840a / 840b, a separate stimulation device 110, 111 may be used. In cases where the implant locations 810, 820, 830a / 830b, 840a / 840b are close to or even overlap, a single stimulation device 110, 111 may be configured to stimulate at more than one implant location 810, 820, 830a / 830b, 840a / 840b.

[0577] Multiple implantable medical devices 110, 111 may operate individually, simultaneously, sequentially, or any combination thereof to provide the desired treatment.

[0578] Figure 7 Further examples are depicted of nerves that may be stimulated using one or more suitably configured and improved implantable medical devices 110, 111 to provide nerve stimulation for treating other conditions.

[0579] The description herein should not be construed as prescribing a fixed order for performing the method steps described therein. Instead, the method steps may be performed in any feasible order. Similarly, the examples used to explain the algorithms are presented as non-limiting examples and are not intended to represent the only implementation of these algorithms. Those skilled in the art will be able to conceive of many different ways to implement the same functionality provided by the embodiments described herein.

[0580] For example, one or more features for improving conformability may be applied to embodiments configured and arranged for improving encapsulation. In some embodiments, it may be advantageous to apply features that improve encapsulation but reduce conformability.

[0581] For example, one or more features for improving encapsulation may be applied to embodiments configured and arranged for improving conformability. In some embodiments, it may be advantageous to apply features that improve conformability but reduce encapsulation.

[0582] Many types of implantable distals of stimulation devices are described. However, this does not exclude the rest of the device from being implanted. This should be interpreted to mean that at least the electrode portion of the distal is preferably configured and arranged to be implanted.

[0583] Although the invention has been described in connection with specific exemplary embodiments, it should be understood that various changes, substitutions, and alterations obvious to those skilled in the art may be made to the disclosed embodiments without departing from the spirit and scope of the invention as set forth in the appended claims.

[0584] In a non - limiting example,

[0585] - One or more electrodes 200a, 200b, 1220 of a first type are included in the first surfaces 310, 1410, and one or more electrodes 400a, 400b, 1220 of a second type are included in the second surfaces 320, 1420; or

[0586] - One or more electrodes 200a, 200b, 1220 of a first type are included in the first surfaces 310, 1410, and one or more electrodes 400a, 400b, 1220 of a second type are also included in the first surfaces 310, 1410; or

[0587] - One or more electrodes 200a, 200b, 1220 of a first type are included in the second surfaces 320, 1420, and one or more electrodes 400a, 400b, 1220 of a second type are included in the first surfaces 310, 1410; or

[0588] - One or more electrodes 200a, 200b, 1220 of a first type are included in the second surfaces 320, 1420, and one or more electrodes 400a, 400b, 1220 of a second type are also included in the second surfaces 320, 1420; or

[0589] - Any combination thereof.

[0590] By providing relatively large higher - electrode surfaces 200, 400, 1220, the stimulators 100, 101, 102, 103, 104, 105, 1100, 1101, 1102 can operate at lower energy / lower power. This can be advantageous in applications using high - frequency and / or burst stimulation.

[0591] High - frequency operation may require the pulse generator 500 to provide more energy. In applications where energy / power is critical, for example, in a non - limiting example, if an increased operating life is desired from the power source for the pulse generator 500, any reduction in the required power can be advantageous. High - frequency operation can be considered to generate electrical stimulation pulses having a frequency of 1000 Hz or higher, preferably 1500 Hz or higher, more preferably 2000 Hz or higher, and even more preferably 2500 Hz or higher.

[0592] In an embodiment, experiments with burst stimulation have been performed, such as Burst Occipital Nerve Stimulation for Chronic Migraine and Chronic Cluster Headache published by Garcia-Ortega et al. in Neuromodulation 2019; 22:638-644, DOI: 10.1111 / ner.12977.

[0593] For burst operation, the pulse generator 500 is also configured and arranged to generate electrical stimulation pulses in the form of a group of stimulation pulses.

[0594] In a non-limiting example, a group of stimulation pulses (or burst) can include 2 to 10 pulses, more preferably 2 to 5 stimulation pulses. The stimulation pulses in a group can have a repetition frequency of more than 500 Hz, typically 1000 Hz or higher. The group can repeat at more than 5 Hz (usually 40 Hz or more).

[0595] As with high-frequency operation, burst operation may require the pulse generator 500 to provide more energy, and any reduction in the required power can be advantageous.

[0596] Additionally, the rate of charge balance restoration can also increase with lower impedance. By using relatively thin foil substrates 300, 1400, the stimulation between the first type of electrodes 200, 1220 included in one surface 310, 1410, 320, 1420 and the second type of electrodes 400, 1220 included in the other surface 310, 1410, 320, 1420 results in a relatively short current path in the tissue, reducing the impedance.

[0597] Similarly, the stimulation between the substrate 300, 1400 and the first type of electrodes 200, 1220 included in one surface 310, 1410, 320, 1420 and the adjacent second type of electrodes 400, 1220 included in the same surface 310, 1410, 320, 1420 provides a relatively short path through the tissue.

[0598] Although certain illustrative embodiments have been described, it is apparent that many alternatives, modifications, substitutions, and variations will become apparent to those skilled in the art in light of the foregoing description without departing from the spirit and scope of the invention as set forth in the appended claims.

[0599] The present invention encompasses every possible combination of the various features of each of the disclosed embodiments. One or more of the elements described in connection with the various embodiments may be implemented in a more separated or more integrated manner than explicitly described, or even in some cases removed or presented as inoperable, which is useful depending on the particular application.

[0600] Particularly advantageous feature combinations include the following non - limiting examples:

[0601] (i). An implantable stimulator 100, 101, 102, 103, 104, 105, 1110, 1111, comprising:

[0602] - A pulse generator 500 for generating one or more electrical therapeutic stimulation pulses;

[0603] - A conformable foil - like substrate 300, 1400 having a longitudinal axis 600 extending from the pulse generator 500 to the distal end of the substrate 300, 1400, the substrate 300, 1400 including one or more adjacent polymer substrate layers, the substrate having a first planar surface 310, 1410 and a second planar surface 320, 1420;

[0604] - An electrode array 200, 400, 1220 adjacent to the distal end, having first electrodes 200a, 200b, 1220 and second electrodes 400a, 400b, 1220 included in the first surface 310, 1410 or the second surface 320, 1420, each electrode 200, 400, 1220 in operation being configurable to deliver therapeutic energy to and / or receive therapeutic energy from human or animal tissue;

[0605] The implantable stimulator 100, 101, 102, 103, 104, 105, 1110, 1111 further comprises:

[0606] - One or more electrical interconnects 250, 1210 between the pulse generator 500 and the first electrodes 200a, 200b, 1220 and the second electrodes 400a, 400b, 1220 for delivering electrical energy as one or more electrical therapeutic stimulation pulses to the first electrodes 200a, 200b, 1220 and / or the second electrodes 400a, 400b, 1220;

[0607] One or more electrical interconnects 250, 1210 are included (or positioned) between a first surface 310, 1410 and a second surface 320, 1420, and the conformable foil substrate 30, 1400 has a maximum thickness of 0.5 millimeters or less in proximity to the first electrodes 200a, 200b, 1220 and the second electrodes 400a, 400b, 1220, the thickness being determined by the vertical distance between corresponding points on the first planar surface 310, 1410 and the second planar surface 320, 1420.

[0608] (ii). An implantable stimulator 100, 101, 102, 103, 104, 105, 1110, 1111, comprising:

[0609] - A substrate 300, 1400, the substrate including a top surface 310, 1410 and a bottom surface 320, 1420;

[0610] - A pulse generator 500 positioned along a first portion of the substrate 300, 1400, the pulse generator 500 being configured to generate at least one stimulation pulse;

[0611] - An electrode array 200, 400, 1220, including at least two electrodes 200, 400, 1220 positioned along a second conformable portion of the substrate 300, 1400;

[0612] - A plurality of electrical interconnects 250, 1210 that electrically couple the pulse generator 500 to at least two electrodes of the electrode array 200, 400, 1220, wherein the plurality of electrical interconnects 250, 1210 are located between the top surface 310, 1410 and the bottom surface 320, 1420 of the substrate 300, 1400; and

[0613] - An encapsulation layer that covers at least a portion of a first portion of the substrate 300, 1400;

[0614] Wherein, the maximum thickness of the substrate 300, 1400 in the second portion is equal to or less than 0.5 millimeters.

[0615] (iii). An implantable electrical device 100, 101, 102, 103, 104, 105, 1100, 1101, 1102, comprising:

[0616] - A substrate 300, 1400 having a first surface 310, 1410 and one or more electrical conductors 250, 1210;

[0617] - A first biocompatible encapsulation layer 1300, 1310, 1320;

[0618] - First adhesion layers 1500, 1510, 1520, which are disposed between the first surfaces 310, 1410 and the first encapsulation layers 1300, 1310, 1320;

[0619] Wherein:

[0620] - Substrates 300, 1400 are configured and arranged to be substantially flexible;

[0621] - First adhesion layers 1500, 1510, 1520 are configured and arranged to conform to the first surfaces 310, 1410 and comprise a ceramic material;

[0622] - First encapsulation layers 1300, 1310, 1320 comprise polydimethylsiloxane (PDMS) rubber, and

[0623] - First adhesion layers 1500, 1510, 1520 and first encapsulation layers 1300, 1310, 1320 are configured and arranged to resist fluid entry from a human or animal body into at least a portion of the first surfaces 300, 1410.

[0624] (iv). A method for applying encapsulation layers 1300, 1310, 1320 to surfaces 310, 1410, 320, 1420 of a substantially flexible substrate 300, 1400, the method comprising:

[0625] - Providing a substrate 300, 1400 having a first surface 310, 1410 and one or more electrical conductors 250, 1210;

[0626] - Applying a first conformable adhesion layer 1500, 1510, 1520 comprising a ceramic material to at least a portion of the first surface 310, 1410;

[0627] - Applying a first biocompatible encapsulation layer 1300, 1310, 1320 comprising polydimethylsiloxane (PDMS) rubber to at least a portion of the first adhesion layer 1500, 1510, 1520;

[0628] Wherein, the first adhesion layers 1500, 1510, 1520 and the first encapsulation layers 1300, 1310, 1320 are configured and arranged to resist fluid entry from a human or animal body into at least a portion of the first surfaces 310, 1410.

[0629] (v). An implantable stimulator 100, 101, 102, 103, 104, 105, 1110, 1111, comprising:

[0630] Substrates 300, 1400, which include a first surface 310, 1410 and a second surface 320, 1420, wherein the thickness of the substrates 300, 1400 is defined by the first surface 310, 1410 and the second surface 320, 1420;

[0631] A pulse generator 500, which is configured to generate at least one stimulation pulse;

[0632] At least two electrodes 200, 400, 1220 positioned along a conformable portion of the substrates 300, 1400;

[0633] A plurality of electrical interconnects 250, 1210, which electrically couple the pulse generator 500 to the at least two electrodes 200, 400, 1220;

[0634] Encapsulation layers 1300, 1310, 1320 that at least partially cover the substrates (300, 1400); and

[0635] Adhesion layers 1500, 1510, 1520 at at least one location between the encapsulation layers 1300, 1310, 1320 and the substrates 300, 1400;

[0636] Wherein the thickness of the substrates 300, 1400 along the conformable portion is equal to or less than 0.5 millimeters.

[0637] (vi). An implantable stimulator 100, 101, 102, 103, 104, 105, 1110, 1111, comprising:

[0638] Substrates 300, 1400, which include a top surface 310, 1410 and a bottom surface 320, 1420;

[0639] A pulse generator 500 positioned along a first portion of the substrates 300, 1400, which is configured to generate at least one stimulation pulse;

[0640] At least two electrodes 200, 400, 1220 positioned along a second conformable portion of the substrates 300, 1400;

[0641] A plurality of electrical interconnects 250, 1210, which electrically couple the pulse generator to the at least two electrodes 200, 400, 1220;

[0642] Wherein the plurality of electrical interconnects 250, 1210 are located between the top surface 310, 1410 and the bottom surface 320, 1420 of the substrates 300, 1400;

[0643] Encapsulation layers 1300, 1310, 1320, which cover at least a portion of a first portion of substrates 300, 1400; and

[0644] Adhesion layers 1500, 1510, 1520 at at least one location between encapsulation layers 1300, 1310, 1320 and substrates 300, 1400;

[0645] Wherein, the maximum thickness of substrates 300, 1400 in the second portion is equal to or less than 0.5 millimeters.

[0646] (vii). Implantable stimulators 100, 101, 102, 103, 104, 105, 1110, 1111 according to any disclosed example, wherein the maximum thickness of implantable stimulators 100, 101, 102, 103, 104, 105, 1110, 1111 near the pulse generator 500 is equal to or less than 5 millimeters, or equal to or less than 4 millimeters, or equal to or less than 3 millimeters, and this thickness is determined by the vertical distance between corresponding points on the outer planar surface.

[0647] (viii) An implantable stimulator according to any disclosed example, wherein:

[0648] - The pulse generator 500 is positioned along a first portion of substrates 300, 1400;

[0649] - The electrode arrays 200, 400, 1220 are positioned along a second conformable liquid crystal polymer (LCP) portion of substrates 300, 1400;

[0650] - A plurality of electrical interconnects 250, 1210 are positioned on a first conformable LCP layer of substrates 300, 1400 using electroplating and / or semiconductor deposition techniques, and at least one second conformable LCP layer of substrates 300, 1400 is fixed to the first layer to cover the plurality of electrical interconnects 250, 1210;

[0651] - The encapsulation layers 1300, 1310, 1320 are biocompatible, cover a first portion and at least a portion of a second portion of substrates 300, 1400, the encapsulation layers 1300, 1310, 1320 include polydimethylsiloxane (PDMS) and have a tensile strength in the range of 6 to 8 MPa;

[0652] - One or more biocompatible adhesion layers 1500, 1510, 1520 conform to substrates 300, 1400 and are located between encapsulation layers 1300, 1310, 1320 and substrates 300, 1400, wherein one or more adhesion layers 1500, 1510, 1520 include a ceramic portion having an average thickness in the range of 25 nm to 200 nm, which is applied using atomic layer deposition (ALD), and include at least one first layer containing TiO2 and at least one second layer adjacent to the at least one first layer and containing Al2O3;

[0653] - A second portion of the substrate has a Young's modulus in the range of 2500 to 3600 MPa;

[0654] - One or more adhesion layers 1500, 1510, 1520 and encapsulation layers 1300, 1310, 1320 are configured to resist fluid entry onto substrates 300, 1400;

[0655] - The thickness of substrates 300, 1400 along the second portion is equal to or less than 0.2 mm;

[0656] - The thickness of stimulators 100, 101, 102, 103, 104, 105, 1110, 1111 along the first portion is equal to or less than 4 mm; and

[0657] - The pulse generator 500 includes an energy receiver configured to wirelessly receive energy from an energy transmitter.

[0658] Reference numerals:

[0659] 100, 101, 102 implantable stimulators

[0660] 103, 104, 105 additional embodiments of implantable stimulators

[0661] 200a, 200b one or more stimulating electrodes

[0662] 250 one or more stimulating electrical interconnection layers

[0663] 300 conformable foil substrate

[0664] 400a, 400b one or more return electrodes

[0665] 500 pulse generator

[0666] 600 longitudinal axis

[0667] 700 first horizontal axis

[0668] 750 second horizontal axis

[0669] 810 Locations for left supraorbital nerve or cortical stimulation

[0670] 820 Locations for right supraorbital stimulation

[0671] 830a / 830b Locations for left occipital nerve stimulation

[0672] 840a / 840b Locations for right occipital nerve stimulation

[0673] 850 Locations for deep brain stimulation

[0674] 860 Locations for vagus nerve, carotid artery, carotid sinus, phrenic nerve or hypoglossal nerve stimulation

[0675] 865 Locations for cerebrospinal stimulation

[0676] 870 Locations for peripheral nerve stimulation

[0677] 875 Locations for spinal cord stimulation

[0678] 880 Locations for gastric stimulation

[0679] 885 Locations for sacral and pudendal nerve stimulation

[0680] 890 Locations for sacral nerve modulation

[0681] 895 Locations for peroneal nerve stimulation

[0682] 910 Left supraorbital nerve

[0683] 920 Right supraorbital nerve

[0684] 930 Left greater occipital nerve

[0685] 940 Right greater occipital nerve

[0686] 1100, 1101, 1102 Improved implantable electrical or electronic devices

[0687] 1110, 1111 Improved implantable medical devices

[0688] 1130 Test substrate

[0689] 1210 One or more electrical conductors

[0690] 1220 One or more stimulating electrodes

[0691] 1230 One or more sensors

[0692] 1300 Another biocompatible encapsulation layer

[0693] 1310 First biocompatible encapsulation layer

[0694] 1320 Second biocompatible encapsulation layer

[0695] 1330 Third biocompatible encapsulation layer

[0696] 1400 Substrate

[0697] 1430 Silicon substrate

[0698] 1435 SiO2 (Silicon dioxide) layer

[0699] 1410 First surface

[0700] 1420 Second surface

[0701] 1500 Another adhesion layer

[0702] 1510 First adhesion layer

[0703] 1520 Second adhesion layer

[0704] 1530 Third adhesion layer

[0705] 1700 Bode plot represented as impedance magnitude

[0706] 1701 Impedance magnitude for a bare IDC with exposed Pt metal

[0707] 1702 Impedance magnitude for an IDC coated with HfO2 ALD

[0708] 1703 Impedance magnitude for an IDC coated with an ALD-PDMS bilayer

[0709] 1710 Bode plot represented as phase angle

[0710] 1711 Phase angle for a bare IDC with exposed Pt metal

[0711] 1712 Phase angle for an IDC coated with HfO2 ALD

[0712] 1713 Phase angle for an IDC coated with an ALD-PDMS bilayer

[0713] 1720 Adhesion monthly performance represented as impedance magnitude

[0714] 1722a, 1722b Impedance magnitude for an IDC coated with HfO2 ALD

[0715] 1723a, 1723b Impedance magnitude for an IDC coated with an ALD-PDMS bilayer

[0716] 1730 Adhesion monthly performance expressed as phase angle

[0717] 1732a, 1732b Phase angles of IDCs coated with HfO2 ALD

[0718] 1733a, 1733b Phase angles of IDCs coated with ALD-PDMS bilayer 810 Positions for left supraorbital nerve or cortical stimulation

[0719] 1750 Chart comparing average pull forces under dry conditions and after soaking

[0720] 1761 Average peel force of sample 2.1

[0721] 1762 Average peel force of sample 2.2

[0722] 1763 Average peel force of sample 2.3

[0723] 1764 Average peel force of sample 2.4

[0724] 1765 Average peel force of sample 2.5.

Claims

1. An implantable stimulator, comprising: A pulse generator configured to generate at least one stimulation pulse; A conformable foil substrate having a longitudinal axis extending from the pulse generator to a distal end of the substrate, the substrate including one or more adjacent polymer substrate layers, the substrate having a first planar surface and a second planar surface; And An electrode array near the distal end of the substrate, the electrode array having a first electrode and a second electrode, the first electrode and the second electrode being included in the first planar surface or the second planar surface, positioned along a conformable portion of the substrate, each electrode being configurable in operation to deliver therapeutic energy to and / or receive therapeutic energy from human or animal tissue during use; The implantable stimulator further comprises: One or more electrical interconnects between the pulse generator and the first electrode and the second electrode for delivering electrical energy as one or more electrical therapeutic stimulation pulses to the coupled first electrode and / or the second electrode; Wherein the one or more electrical interconnects are located between the first planar surface and the second planar surface of the substrate; Wherein the conformable foil substrate has a maximum thickness of 0.5 millimeters or less near the first electrode and the second electrode, the thickness being determined by the vertical distance between corresponding points on the first planar surface and the second planar surface, and Wherein the substrate and the pulse generator are embedded in one or more flexible biocompatible encapsulation layers including polydimethylsiloxane (PDMS).

2. The implantable stimulator according to claim 1, the implantable stimulator further comprising an adhesion layer adjacent to at least a portion of the substrate, the adhesion layer including a ceramic material.

3. The implantable stimulator according to claim 2, wherein, The substrate includes more than one adjacent substrate layer, and the adhesion layer is located between the substrate layers.

4. The implantable stimulator according to claim 2, the implantable stimulator further comprising one or more additional adhesion layers, the one or more adhesion layers including the ceramic material.

5. The implantable stimulator according to claim 4, wherein, The one or more additional adhesion layers are located between the substrate layers.

6. The implantable stimulator according to claim 1, wherein, The conformable foil substrate has a maximum thickness of 0.3 millimeters, or 0.2 millimeters, or 0.1 millimeters near the electrode array.

7. The implantable stimulator according to claim 1, wherein, The implantable stimulator has a maximum thickness of 5 millimeters, or 4 millimeters, or 3 millimeters near the pulse generator.

8. The implantable stimulator according to claim 1, wherein: The substrate has a surface included in a plane whose lateral extent is substantially perpendicular to the longitudinal axis; Wherein the conformable portion of the substrate has a maximum planar width, the width being determined by the vertical distance between corresponding points along the lateral extent on the outer surface edges of the substrate; and Wherein the ratio of the maximum planar width to the maximum thickness near the at least two electrodes is equal to or greater than 7:1, or equal to or greater than 10:1, or equal to or greater than 15:1, or equal to or greater than 30:1, or equal to or greater than 50:

1.

9. The implantable stimulator according to claim 1, wherein, The conformable portion of the substrate includes one or more layers of liquid crystal polymer (LCP).

10. The implantable stimulator according to claim 1, wherein, The encapsulation layer includes polydimethylsiloxane (PDMS), silicone polyurethane, polyimide, parylene, biocompatible polymers, biocompatible elastomers, and any combination thereof.

11. The implantable stimulator according to claim 1, wherein: The pulse generator is positioned along a first portion of the substrate; The electrode array is positioned along a second conformable liquid crystal polymer (LCP) portion of the substrate; Wherein, the plurality of electrical interconnects are positioned on the first conformable LCP layer of the substrate using electroplating and / or semiconductor deposition techniques, and at least one second conformable LCP layer of the substrate is fixed to the first conformable LCP layer to cover the plurality of electrical interconnects; The implantable stimulator further includes: One or more adhesion layers adjacent to the substrate; and An encapsulation layer covering the first portion of the substrate, the encapsulation layer including polydimethylsiloxane (PDMS); Wherein, the thickness of the substrate along the second portion is equal to or less than 0.2 mm; Wherein, the thickness of the implantable stimulator along the first portion is equal to or less than 3 mm; Wherein, the pulse generator includes an energy receiver configured to wirelessly receive energy from an energy transmitter.

12. The implantable stimulator according to claim 1, wherein, The implantable stimulator further includes: An encapsulation layer at least partially covering the substrate; and A biocompatible adhesion layer at at least one location between the encapsulation layer and the substrate.

13. The implantable stimulator according to claim 12, wherein, The encapsulation layer covers at least a portion of the conformable portion of the substrate, and wherein the adhesion layer is between at least a portion of the conformable portion of the substrate and the encapsulation layer.

14. The implantable stimulator according to claim 12, wherein, The adhesion layer includes a ceramic material selected from the group consisting of: HfO2, Al2O3, Ta2O3, Si3N4, TiO2, or any combination thereof.

15. The implantable stimulator according to claim 12, wherein, The conformable portion of the substrate has a Young's modulus in the range of 2500 to 3600 MPa.

16. The implantable stimulator according to claim 12, wherein, The encapsulation layer has a tensile strength in the range of 6 to 8 MPa.

17. The implantable stimulator according to claim 12, wherein, The ceramic portion of the adhesion layer has an average thickness in the range of 25 nm to 200 nm.

18. The implantable stimulator according to any one of claims 1 to 17, capable of being configured to stimulate one or more nerves, one or more muscles, one or more organs, spinal cord tissue, brain tissue, one or more cortical surface regions, one or more sulci, and any combination thereof.

19. The implantable stimulator according to any one of claims 1 to 17, capable of being configured to treat headache, chronic headache, primary headache, incontinence, occipital neuralgia, sleep apnea, hypertension, gastroesophageal reflux disease, inflammatory diseases, limb pain, leg pain, back pain, lower back pain, phantom pain, chronic pain, epilepsy, overactive bladder, post-stroke pain, obesity, autoimmune diseases, rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, and any combination thereof.

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