Patent Description:
Implantable active devices require a protection method to protect the implant electronics from bodily fluids present in human or animal bodies. Bodily fluids typically contain ions that may cause electrochemical reactions, like corrosion, in the presence of an electric current. Encapsulation is thus a critical component for the design of a medical device - it acts as a barrier between these ionic fluids and critical electronic/electric interfaces to reduce and/or prevent degradation of the implant electronics.

Polyimides are popular for use as a substrate material for the microfabrication of electronics, and attempts have been made to encapsulate polyimides with silicone rubber encapsulants, such as polydimethylsiloxane rubber (PDMS). As described in "<NPL>, bonding these two flexible materials remains a crucial challenge - the resistance to fluid ingress may be reduced by the encapsulant delaminating to some degree from the substrate. The degree of bonding was increased by functionalizing the surfaces of the PDMS and polyimide substrates with mercaptosilanes and epoxysilanes, respectively, for the formation of a thiolepoxy bond in the click reaction. It was also increased by functionalizing one or both surfaces with mercaptosilane and introducing an epoxy adhesive layer between the two surfaces.

US patent application <CIT> describes a method of adhering a protective layer applied to a substrate region of an implantable medical device (IMD) to form a covered Substrate region. The method includes obtaining the IMD, depositing an intermediate layer on a portion of the substrate region of the IMD such that the intermediate layer binds to the portion of the Substrate region to create a modified substrate region, and depositing the protective layer after depositing the intermediate layer onto the intermediate layer and adhering the protective layer to the intermediate layer. In an embodiment of the present invention, this method enhances the sealing characteristics of the protective layer by, for example, reducing the likelihood of delamination of the protective layer from the IMD relative to IMDs prepared by certain other methods.

"<NPL> describes a hybrid multimodal deep brain probe made out of a thin-film polyimide electrode and flexible silicone rubber substrate. The engineered combination of two technologies resulted in a device as flexible as commercial DBS probes, but including the benefits from thin-film technology such as higher contact density, high resolution in fabrication and capability of applying various coatings for specific applications.

US patent application <CIT> describes a hybrid composite for medical devices that interface with biological tissues. The hybrid composite comprises at least one first layer of conformable polymeric material, a second layer of insulating polymeric material, and one or more active components and/or one or more passive components, wherein the one or more active components and/or the one or more passive components are partially or completely embedded in the first layer of conformable polymeric material or the second layer of insulating polymeric material. Preferably, the conformable polymeric material is an elastomer, a hydrogel or a biodissolvable polymer and the insulating polymeric material is parylene or silicon carbide. A method of forming the inventive hybrid composite is also provided.

<CIT> describes an implantable medical device formed on a flexible substrate formed of liquid crystal polymer. The device comprises an equipment module, electrode array and interconnection module comprising conductors there between. The components are encapsulated using silicone or liquid crystal polymer.

Although PDMS can be substantially biocompatible, causing minimal tissue reaction while having a relative long period of biostability, it still has a relatively high permeability to moisture which can lead to degradation of the implant electronics. Many other encapsulants with a lower degree of moisture permeability may have a lower degree of biocompatibility. Recently, LCP's (Liquid Crystal Polymers) have been considered for use as a substrate for electronics, and there is also a need for improved bonding techniques between LCP and encapsulants.

It is an object of the invention to provide improved bonding to improve resistance to fluid ingress in implantable devices comprising flexible substrates.

The present invention is defined by the independent claims, while the dependent claims concern the preferred embodiments. Any "embodiment" or "example" which is disclosed in the description but is not covered by the claims should be considered as presented for illustrative purpose only.

According to a first aspect of the present disclosure, there is provided an implantable electrical device comprising: a flexible substrate having a first surface and one or more electrical conductors; a first biocompatible encapsulation layer; a first adhesion layer, disposed between the first surface and the first encapsulation layer; wherein: the first surface comprises a Liquid-Crystal Polymer (LCP), the first adhesion layer is configured and arranged to conform to the first surface and comprises a ceramic material; the first encapsulation layer comprises a silicone rubber (such as a polydimethylsiloxane (PDMS) rubber), and the first adhesion layer and the first encapsulation layer are configured and arranged to resist the ingress of fluids from a human or animal body into at least a portion of the first surface.

By providing a bilayer having an encapsulant comprising a silicone rubber and a conformal adhesion layer comprising ceramic materials, the adhesion layer appears to show significantly higher stability in ionic media, thereby providing relatively longer protection in case of any delamination or water permeation through the encapsulant. A silicone rubber, such as a PDMS, may further contribute to longer-lasting adhesion and defect reduction due to flowing in-between any defects and crevices in the adhesion layer - in particular, a silicone rubber, such as a PDMS with a relatively low viscosity may provide an even higher degree of defect reduction.

According to a further aspect of the current disclosure, there is provided an implantable electrical device, wherein the substrate further comprises a second surface, the electrical device further comprising: a second biocompatible encapsulation layer; and a second adhesion layer, disposed between the second surface and the second encapsulation layer; wherein: the second surface comprises a Liquid-Crystal Polymer (LCP); the second adhesion layer is configured and arranged to conform to the second surface <NUM> and comprises a ceramic material; the second encapsulation layer comprises a silicone rubber (such as a polydimethylsiloxane (PDMS) rubber), and the second adhesion layer and the second encapsulation layer are configured and arranged to resist the ingress of fluids from a human or animal body into at least a portion of the second surface.

One or more regions of a substrate surface may be protected by an encapsulant/adhesion layer. Each encapsulant/adhesion layer may be optimized separately or together to a predetermined degree.

According to a further aspect of the current disclosure, there is provided an implantable electrical device wherein the first surface and/or second surface comprise a substance selected from the group comprising: a polyimide, Parylene-C, SU-<NUM>, a polyurethane, or any combination thereof.

The encapsulant/adhesion layer may be optimized to protect a surface of many types of substrates. If the substrate is configured and arranged to be substantially flexible, the substrate may have a high degree of conformability. The high degree of 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 a flexible substrate.

According to another aspect of the current disclosure, there is provided an implantable electrical device, wherein the ceramic material is selected from the group comprising: HfO2, Al2O3, Ta2O3, SiC, Si3N4, TiO2, and any combination thereof.

These ceramic materials may be advantageously used as in an adhesion layer for a silicone rubber encapsulant layer, such as a PDMS encapsulant layer.

An adhesion layer may comprise more than one ceramic material. Multilayer stacks may be used comprising adjacent layers of similar and/or different ceramic materials. For example:.

According to yet another aspect of the current disclosure, there is provided an implantable medical device, comprising an implantable electrical device as described herein.

The implantable medical device is typically configured and arranged such that materials in direct contact with tissue are substantially biocompatible.

According to a further aspect of the current disclosure, there is provided a process for applying an encapsulation layer to a surface of a flexible substrate, the process comprising: providing a substrate having one or more electrical conductors and a first surface comprising a Liquid-Crystal Polymer (LCP); applying a first conformal adhesion layer, comprising a ceramic material, to at least a portion of the first surface; applying a first biocompatible encapsulation layer, comprising a silicone rubber (such as a polydimethylsiloxane (PDMS) rubber) to at least a portion of the first adhesion layer; wherein the first adhesion layer and the first encapsulation layer are configured and arranged to resist the ingress of fluids from a human or animal body into at least a portion of the first surface.

According to a still further aspect of the current disclosure, wherein the substrate has a second surface comprising a Liquid-Crystal Polymer (LCP), there is provided a process for further applying a second conformal adhesion layer, comprising a ceramic material, to at least a portion of the second surface; applying a second biocompatible encapsulation layer, comprising a silicone rubber (such as a polydimethylsiloxane (PDMS) rubber), to at least a portion of the second adhesion layer; wherein the second adhesion layer and the second encapsulation layer are configured and arranged to resist the ingress of fluids from a human or animal body into at least a portion of the second surface.

According to a yet further aspect of the current disclosure, there is provided a process wherein first adhesion layer and/or second adhesion layer is/are applied using an ALD process.

According to another aspect of the current disclosure, there is provided a process wherein the process further comprises: cleaning at least a portion of the first adhesion layer and/or second adhesion layer before applying the first and/or second encapsulation layer;
For example , the cleaning step may comprise: applying an alcohol, in particular ethanol, to at least a portion of the first adhesion layer and/or second adhesion layer; exposing at least a portion of the first adhesion layer and/or second adhesion layer to a plasma comprising O3 (Ozone); exposing at least a portion of the first adhesion layer and/or second adhesion layer to a plasma comprising O2; exposing at least a portion of the first adhesion layer and/or second adhesion layer to a silane; or any combination thereof.

According to a still further aspect of the current disclosure, there is provided a process wherein the first and/or second biocompatible encapsulation has an average viscosity in the range <NUM> to <NUM> mPas for a significant time period during the application to the first and/or second adhesion layers respectively.

Alternatively, the first and/or second biocompatible encapsulation has an average viscosity in the range <NUM> to <NUM> mPas for a significant time period during the application to the first and/or second adhesion layers respectively.

Advantageously, the first and/or second biocompatible encapsulation may be applied using a vacuum centrifugal casting.

Features and advantages of some embodiments of the present invention, and the manner in which the same are accomplished, will become more readily apparent upon consideration of the following detailed description of the invention taken in conjunction with the accompanying drawings, which illustrate preferred and exemplary embodiments, and which are not necessarily drawn to scale, wherein:.

In the following detailed description, numerous non-limiting specific details are given to assist in understanding this disclosure. It will be obvious to a person skilled in the art that the software methods may be implemented on any type of suitable controllers, memory elements, and/or computer processors.

<FIG> depicts a cross-section through an improved implantable electrical or electronic device <NUM>. It comprises:.

Optionally, the substrate <NUM> may be substantially biocompatible - however, the use of one or more encapsulation layers <NUM> may allow substrates <NUM> and electrical conductors <NUM> which are not biocompatible, partially biocompatible, or significantly biocompatible, to be used.

In general, the degree of biocompatibility of a material or layer may be determined by measuring the degree of tissue reaction and the length of period during which it is considered biostable. A low degree of tissue reaction and/or long period of biostability indicates a high degree of biocompatibility.

The substrate <NUM> is further configured and arranged to be substantially flexible - in other words, the substrate is pliant or flexible or compliant (or conformable) to a substantial degree. The degree of flexibility may be adapted using parameters, such as:.

Additionally or alternatively, the skilled person will realize that the degree of flexibility and/or conformability of one or more portions of the substrate <NUM> may be adapted using one or more of the suitable parameters described in this disclosure.

The one or more electrical conductors <NUM> are depicted very schematically - they may be conductors embedded in or deposited onto the substrate <NUM> - for example, by having a single polymer layer and applying conductive material using suitable deposition techniques known from the semiconductor industry. The one or more conductors <NUM>, such as a metal, may be formed as required - for example, in one or more conductive elements: wire, strand, foil, lamina, plate, and/or sheet. Optionally, the one or more conductors may be positioned between the outer surfaces of the substrate <NUM>;.

In the context of this disclosure, a ceramic should be considered as an advanced ceramic and/or an industrial ceramic, providing a relatively high degree of thermal stability, wearresistance and resistance to corrosion.

The most suitable ceramic materials are those with a high degree of adhesion to the encapsulant layer and/or substrate, and capable of being applied in a relatively uniform coating to provide a relatively low degree of permeability to moisture. A ceramic material in this context may be an inorganic, non-metallic or metallic, often crystalline oxide, nitride or carbide material. Some elements, such as carbon or silicon, are also considered ceramics. A non-metallic ceramic may comprise both non-metallic and metallic elements.

Optionally, the first adhesion layer <NUM> may be substantially biocompatible - however, the use of one or more encapsulation layers <NUM> may allow one or more adhesion layers <NUM> which are not biocompatible, partially biocompatible, or significantly biocompatible, to be used.

The first adhesion layer <NUM> and the first encapsulation layer <NUM> are configured and arranged to resist the ingress of fluids from a human or animal body into at least a portion of the first surface <NUM>. The configuration and arrangement are further described below.

As depicted in <FIG>, the extent of the adhesion/encapsulation layer <NUM>/<NUM> in this cross-section may be less than the extent of the substrate <NUM>. In general, the extent of the adhesion/encapsulation layer <NUM>/<NUM> may be larger than, equal to or less than the extent of the substrate <NUM>. A "larger than" embodiment for the adhesion and encapsulation layers is depicted in <FIG>. Further "less than" embodiments for the adhesion and encapsulation layers are depicted in <FIG> and <FIG>.

In general, the portion of the first surface <NUM> being protected against ingress of fluids is equal to or less than the extent of the adhesion/encapsulation layer <NUM>/<NUM>.

As depicted in <FIG>, the extent of the adhesion layer <NUM> in this cross-section may be less than the extent of the encapsulation layer <NUM> - in some configurations, this may be advantageous as the edges of the adhesion layer <NUM> are at least partially encapsulated <NUM>. In general, the extent of the adhesion layer <NUM> may be larger than, equal to or less than the extent of the encapsulation layer <NUM>. Further "less than" embodiments are depicted in <FIG> and <FIG>. An "equal to" portion of a substrate is depicted in <FIG>.

In a preferred embodiment, the extent of the adhesion layer <NUM> is equal to or larger than the extent of the encapsulation layer <NUM> - this may be advantageous in certain configurations as the surface area of encapsulant <NUM> in direct contact with the surface <NUM> of the substrate <NUM> is greatly reduced. In some cases, this surface area may be substantially zero, further reducing the possibility of fluid ingress. A "substantially zero" embodiment is depicted in <FIG> and a portion of a substrate depicted in <FIG>.

<FIG> depicts another implantable electrical or electronic device <NUM>. It is the same as the implantable electrical device <NUM> depicted in <FIG>, except for further comprising:.

The second adhesion layer <NUM> and the second encapsulation layer <NUM> are configured and arranged to resist the ingress of fluids from a human or animal body into at least a portion of the second surface <NUM>. The configuration and arrangement are further described below.

The second encapsulation layer <NUM> may be substantially identical, similar to a high degree or substantially different to the first encapsulation layer <NUM>.

The second adhesion layer <NUM> may be substantially identical, similar to a high degree or substantially different to the first adhesion layer <NUM>.

Although the first surface <NUM> and second surface <NUM> are depicted as opposite faces of a substrate in <FIG>, other combinations are possible, such as:.

<FIG> depicts a further implantable electrical or electronic device <NUM>. It is the same as the implantable electrical device <NUM> depicted in <FIG>, except in this cross-section:.

Functionally, it may also be considered that the further encapsulation layer <NUM> comprises the first <NUM> and second <NUM> encapsulation layers depicted in <FIG>.

Functionally, it may also be considered that the further adhesion layer <NUM> comprises the first <NUM> and second <NUM> adhesion layers depicted in <FIG>.

Functionally, it may also be considered that the substrate <NUM> depicted in <FIG> comprises the protected portions of the first <NUM> and second <NUM> surfaces depicted in <FIG>. However, the substrate <NUM> depicted in <FIG>, comprises two or more further protected surfaces, adjacent to such a protected first or second surface.

The further encapsulation layer <NUM> of <FIG> may be substantially identical, similar to a high degree or substantially different to the first encapsulation layer <NUM> depicted in <FIG>. The further encapsulation layer <NUM> of <FIG> may be substantially identical, similar to a high degree or substantially different to the second encapsulation layer <NUM> depicted in <FIG>.

The further adhesion layer <NUM> of <FIG> may be substantially identical, similar to a high degree or substantially different to the first adhesion layer <NUM> depicted in <FIG>. The further adhesion layer <NUM> of <FIG> may be substantially identical, similar to a high degree or substantially different to the second adhesion layer <NUM> depicted in <FIG>.

The further embodiment <NUM> may be advantageous because:.

Experiments were performed to establish the suitability of a specific adhesion layer <NUM>, <NUM> to provide a high degree of bonding to a PDMS.

<FIG> depicts a cross-section through the test sample <NUM>.

Interdigitated capacitors (IDC) <NUM> were used to evaluate encapsulation performance - approximately <NUM> of Pt (Platinum) was sputtered on top of a <NUM> (<NUM> micron) thick plasma enhanced chemical vapor deposition (CVD) SiO2 layer <NUM> with an intermediate <NUM> titanium adhesion layer. More details on these IDC <NUM> are found in "<NPL>. The SiO2 layer <NUM> was provided on a silicon substrate <NUM>.

Atomic layer deposition (ALD) is a coating process that may be used to create nm-thick conformal coatings. The ALD coating was applied using the PICOSUN® R-<NUM> Advanced ALD reactor under reduced pressure (N2 atmosphere) of about <NUM> mbar (1hPa).

The R-<NUM> Advanced, from Picosun Oy, Finland, provides very high quality ALD film depositions. It is suggested by the manufacturer as suitable for depositions including: Al2O3, TiO2, SiO2, Ta2O5, HfO2, ZnO, ZrO2, AlN, TiN, metals such as Pt or Ir.

It comprises a remote microwave plasma generator, with adjustable <NUM> - <NUM> W power, <NUM> frequency, mounted to the loading chamber and connected to the reaction chamber. Up to twelve sources with six separate inlets may be used - seven if the plasma option is chosen. The precursor sources may comprise liquid, gaseous and/or solid chemicals. Precursors may also include ozone and/or plasma. The remote plasma option allows deposition of metals with a greatly reduced risk of short-circuiting and/or plasma damage. The processing temperature may in general be <NUM> - <NUM>. Plasma may generally be used up to approximately <NUM>, or up to approximately <NUM> with a heated sample holder.

It comprises a hot-wall and substantially separate inlets and instrumentation providing a relatively low particle (or substantially particle-free) processing adaptable on 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 <NUM>:<NUM>), and nanoparticle samples using their proprietary Picoflow™ diffusion enhancer. This enhancer provides a protective gas flow in an intermediate space to greatly reduce back-diffusion of the plasma species.

A suitable ALD process, for forming a monolayer comprising a first and second element, may comprise:.

Using the Picohot™ source system (PH-<NUM>) and PicoSolution options for the R-<NUM> Advanced, precursors were vaporized from stainless-steel precursor bottles at increased temperature and at room temperature. The Picohot™ <NUM> source system allows source heating up to <NUM> degr. C, and is suggested by the manufacturer to be suitable with source chemicals having a vapor pressure of at least <NUM> mbar at source temperature. The Picosolution™ <NUM> source system allows liquid precursors to be used, and are suggested by the manufacturer to be suitable with source chemicals having a vapor pressure of at least <NUM> mbar at source temperature.

Thermal ALD-processes at <NUM> degr. C were applied with layer-by-layer deposition method where the two different precursor materials (separated by N2 purge to remove surplus molecules from the reaction space) were used to build up a HfO2 (hafnium dioxide) coating <NUM> - this is depicted in <FIG> as a coating <NUM> substantially covering the external surfaces of the substrate <NUM>, <NUM> and the IDC sensors <NUM>.

An optional stabilization time of approximately <NUM> minutes was used at <NUM> degr. Ten layers of approximately <NUM> were applied to provide an ALD layer of approximately <NUM>.

It is believed that ALD may be advantageous to create an ultra-thin conformal coating with low defects and/or reduced pinhole formation. Also, the deposition temperature for ALD may be kept below <NUM> which is advantageous for devices incorporating sensitive metallization and/or polymers.

Samples were encapsulated with a layer comprising a substantially biocompatible PDMS (MED2-<NUM>, NuSil Carpinteria, USA) <NUM>.

From nusil. com/product/med-6215_optically-clear-low-consistency-silicone-elastomer:
MED-<NUM> is an optically clear, low consistency silicone elastomer. It is provided as twoparts which are solvent free and have a relatively low viscosity. It cures with heat via additioncure chemistry. The mix ratio is <NUM>:<NUM> (Part A: Part B).

MED-<NUM> is considered substantially biocompatible - the manufacturer suggests that it may be used in human implantation for a period of greater than <NUM> days.

The manufacturer suggests silicone primer Nu-Sil MED1-<NUM> as a primer to further improve adhesion of MED-<NUM> to various substrates including: metals (such as stainless steel, steel, copper and aluminum), ceramic materials, rigid plastics, and other silicone materials.

MED-<NUM> is available in medical grade - in other words, substantially biocompatible and suitable for use in a medical implantable device. This is realized by ensuring all raw materials, intermediates, and finished products (for Medical Grade) are manufactured with applicable GMP and/or appropriate regulatory standards: cGMP <NUM> CFR § <NUM> (Device), cGMP <NUM> CFR § <NUM>-<NUM>(Drug/API) and ISO <NUM>.

A dip-coating process was used for the encapsulation. The average relatively low viscosity, for example, <NUM> to <NUM> cP (mPas), appears to have allowed the PDMS to more easily flow over the sample. The thickness of the PDMS <NUM> was estimated to be between <NUM> and <NUM> (micron).

The lifetime reliability of ALD coatings may depend on factors such as the conformality and adhesion of the layer, and its stability in ionic media. This was measured using the IDC's impedance after an extended soak test.

Extended soaking used phosphate buffered saline (PBS) at approximately room temperature (approx.

Electrochemical impedance spectrometry (EIS) was carried out to evaluate the performance of the ALD and ALD-PDMS coatings using the methods described in "<NPL>.

Measurements used a Solartron Modulab with a potentiostat in combination with a frequency response analyzer. Measurements were performed in a two-cell electrode configuration between the combs of the IDC structure. A Faraday cage was also used.

After sample preparation and submersion in saline, EIS measurements were performed.

<FIG> show the EIS results <NUM>, <NUM> for three samples.

<FIG> depicts Bode plots <NUM>, with impedance magnitude along the vertical (Y) axis from <NUM><NUM> to <NUM><NUM> |Z| Ohm, and frequency along the horizontal (X) axis from <NUM>-<NUM> to <NUM><NUM> Hz:
a bare IDC with exposed Pt metal <NUM>, forming an approximately straight line from approx. <NUM>-<NUM>, <NUM>×<NUM><NUM> to <NUM><NUM>, <NUM><NUM>, followed by a further straight line to <NUM><NUM>, <NUM><NUM> ;.

<FIG> depicts Bode plots <NUM>, with phase along the vertical (Y) axis from <NUM> to -<NUM> degrees, and frequency along the horizontal (X) axis from <NUM>-<NUM> to <NUM><NUM> Hz:.

For the bare IDC <NUM>, <NUM>, in the middle frequency band (<NUM><NUM>Hz - <NUM><NUM>Hz), the phase <NUM> appears to be relatively constant at approximately -<NUM> degr. At lower frequencies (approx. <NUM>-<NUM> Hz), the polarization resistance appears to be dominant, resulting in a phase of approximately - <NUM> degr. It is believed that this indicates the metal fully exposed to an electrolyte.

The ALD-coated IDC <NUM>, <NUM>, appeared to show relatively higher impedance values - this suggests a more capacitive behavior across the frequency range. This capacitance is believed to be caused by the Pt metal and electrolyte being separated by an ALD layer, which acts as a dielectric. It is believed that a fully conformal coating on the metal, or high resistance to fluid ingress, would result in a substantially capacitive behavior in the EIS results <NUM>, <NUM>.

For the ALD - PDMS bilayer <NUM>, <NUM>, the impedance <NUM> and phase <NUM> results show a substantially capacitive behavior across substantially the whole frequency range, with phase results <NUM> close to approximately -<NUM>°.

It is believed that any delamination or cracking of the ALD layer may expose more metal to the electrolyte, possibly resulting in a substantially lower impedance and phase angle that is more significantly seen in the lower frequency regions <<NUM>-<NUM> Hz. In <FIG>, a comparison between the ALD <NUM>, <NUM> and ALD-PDMS bilayer <NUM>, <NUM> shows an approximately two orders of magnitude higher impedance value <NUM> for the bilayer encapsulated IDC <NUM>, <NUM>. Furthermore, the phase results <NUM> show a substantially more capacitive behavior.

Additionally, metal areas exposed due to ALD defects are also encapsulated with the PDMS, with a specific resistance of approximately <NUM><NUM> Ohm. It is believed that any significant delamination of the PDMS from ALD would allow water condensation, resulting in one or more conductive paths between the combs. This may result in a lower impedance and phase angle more significantly seen in the lower frequency regions of approximately <<NUM>-<NUM> Hz.

To track changes in the encapsulation and adhesion performance, monthly EIS measurements were done on all samples. The impedance and phase angle at approximately <NUM>-<NUM> Hz were selected as the reference value to monitor over time.

<FIG> show the adhesion evaluation results <NUM>, <NUM> for two ALD samples and two ALD-PDMS samples over the four hundred and fifty days of soaking. The results depicted in <FIG> were considered as the values measured at T=<NUM> days.

<FIG> depicts adhesion evaluation <NUM>, with impedance magnitude along the vertical (Y) axis from <NUM> to <NUM><NUM> |Z| Ohm, and Time along the horizontal (X) axis from <NUM> to <NUM> months:.

<FIG> depicts adhesive evaluation <NUM>, with phase along the vertical (Y) axis from -<NUM> to -<NUM> degrees, and Time along the horizontal (X) axis from <NUM> to <NUM> months:.

For the ALD-only samples <NUM>, <NUM>, a drop in the phase angle 732a, 732b was measured after the first month of soaking, suggesting that fluid came into contact with the metals through one or more defects in the ALD layer. Substantially stable results were observed during the extended soaking. This is believed to indicate a substantially high stability of the HfO2 adhesion layer in ionic media and a substantially high degree of adhesion of HfO2 to Pt over an extended period of time. Significant deterioration of the HfO2 layer would be expected to show a relatively higher capacitive behavior, such as a significant drop in the impedance magnitude <NUM> - this was not observed. Additionally, any significant delamination of the ALD layer from Pt would be expected to result in a substantially more resistive behavior, originating from the metal being exposed to saline - this was also not observed.

Optical inspections of the ALD samples <NUM>, <NUM> supported these conclusions as no significant layer discoloration or degradation were observed.

For the ALD-PDMS bilayer samples <NUM>, <NUM>, substantially stable results were thus recorded over an extended period, suggesting a relatively high degree of adhesion between the two layers, and a substantially higher resistance to the ingress of fluids.

Pt is widely used as for conductors and/or electrode regions due to its high degree of biocompatibility and stability. However, long term stability may be reduced in conventional systems due to the relatively weak adhesion of encapsulants, such as PDMS, parylene and epoxy to Pt.

From the results, it is believed that adding an adhesion layer comprising one or more ceramic materials may be advantageous. In particular, an HfO2 ALD layer with an average thickness of approximately <NUM> to <NUM>, preferably approximately <NUM>, may provide a substantially stable intermediate adhesion layer between Pt and the PDMS. Additionally, a relatively high degree of adherence was also measured between the HfO2 layer and the SiO2 substrate - in particular between the Pt forks.

Where appropriate, a substrate comprising other materials may thus be provided with a layer of SiO2 and/or Pt to improve adhesion to the HfO2 ALD layer.

The ALD-PDMS bilayer of an encapsulation layer <NUM> and adhesion layer <NUM> appears particularly advantageous:.

Polymeric materials comprised in the substrate <NUM> are selected for suitability to be flexible, and to comprise the one or more electrical conductors <NUM>. Preferably, the polymeric substrate materials have a high degree of biocompatibility and durability. Suitable polymer materials, including LCP (Liquid Crystal Polymer) films, are described in "<NPL>), In particular, Table <NUM> is included here as reference, depicting the properties of a polyimide (UBE U-Varnish-S), Parylene C (PCS Parylene C), a PDMS (NuSil MED-<NUM>) similar to the PDMS polymers described above, SU-<NUM> (MicroChem SU-<NUM><NUM> & <NUM> Series), and an LCP (Vectra MT1300). A polyurethane may also be used.

According to the claimed invention the first surface of the flexible substrate comprises a liquid-crystal polymer. Preferably, the first and/or second surface <NUM>, <NUM> comprise a significant amount of one or more Liquid Crystal Polymers (LCP's). Optionally, the first and/or second surface <NUM>, <NUM> may substantially consist of one or more LCP's. Optionally, the first and/or second surface <NUM>, <NUM> may essentially consist of one or more LCP's.

LCP's are chemically and biologically stable thermoplastic polymers with relatively low moisture penetration properties. They are non-fibrous. Advantageously, LCP may be thermoformed allowing component covers with complex shapes to be provided.

At room temperature, thin LCP films have mechanical properties similar to steel. This is important as implantable devices <NUM>, <NUM> must be strong enough to be implanted, strong enough to be removed (explanted) and strong enough to follow any movement of the neighboring anatomical features and/or structures without significant deterioration.

LCP belongs to the polymer materials with the lowest permeability for gases and water. LCP can be bonded to itself, allowing multilayer (two or more adjacent polymeric substrate layers) constructions with a substantially homogenous structure. A substrate <NUM> comprising two or more polymeric substrate layer may be modified (physically and/or chemically), such that it appears to be one layer of polymeric substrate. The table below compares several physical and chemical properties of a typical polyimide and a typical LCP.

In contrast to LCP, polyimides are thermoset polymers, which require adhesives for the construction of multilayer substrates. Polyimides are thermoset polymer material with high temperature and flexural endurance. LCP's are chemically and substantially biologically-stable thermoplastic polymers.

LCP may be used, for example, to provide multilayers with several layers of <NUM> (micron) thickness. Optionally, the one or more electrical conductors <NUM> may be comprised in one or more interconnect layers. Such electrical interconnect layers may be provided by metallization of LCP on one or more surfaces using techniques from the PCB industry, such as metallization with copper. Electro-plating may also be used. If the substrate <NUM> is a multilayer, one or more electrical interconnections <NUM> may be comprised between adjacent polymeric substrate layers. The polymeric substrate layers may also be considered adjacent when one of more adhesion layers are used between them.

An electrical interconnection <NUM> in the context of this disclosure is not configured or arranged to be, in use, in contact with human or animal tissue. For example, by embedding the one or more interconnections <NUM> in one or more layers of a low conductance or insulating polymer, such as LCP.

Lamination may also be used to provide a substrate <NUM> with the desired physical and chemical properties, and/or to provide a convenient method of manufacture. For example, a substrate <NUM> may comprise three laminated polymer layers: two high temperature thermoplastic layers with a low-temperature layer in between, and high-temperature layers towards the outer surfaces.

In another example, two layers of silicone may be provided as polymeric substrate layers: a first layer of silicone is provided, metal is patterned on a surface of the first layer, and a second layer of silicone is added over the metal patterning by, for example, jetting, dispensing, over-moulding, and/or spin-coating.

Advantageously, the substrate comprising an LCP, has a Young's modulus in the range <NUM> to <NUM> MPa (<NUM> to <NUM> GPa).

Optionally, the substrate <NUM> may further comprise one or more electrical or electronic components configured to receive energy when electrical energy is applied to the one or more electrical conductors <NUM>. For example, they may be inductively-coupled, capacitively-coupled or directly connected. This is particularly advantageous with substrates comprising significant amounts of one or more LCP's as PCB-techniques may be used. Preferably, a biocompatible metal such as gold or platinum is used.

Preferably, one or more encapsulation layers <NUM>, <NUM> and one or more adhesion layers <NUM>, <NUM> are configured and arranged to resist the ingress of fluids to at least a portion of one or more surfaces <NUM>, <NUM> proximate the one or more components.

For example, the one or more components may be an active component, a passive component, an electronic component, an integrated circuit (IC), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), an analog component, a digital component, a surface-mount device (SMD), a through-hole package, a chip carrier, a pin grid array, a fat package, a small outline package, a chip scale package, a ball grid array, a small-pin-count package, a flexible silicon device, a thin-film transistor (TFT), and any combination thereof.

The one or more electrical components may be configured and arranged to: resist, 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.

Conformable foil-like (or film-like) substrates <NUM> may be configured and arranged to follow the contours of underlying anatomical features very closely by being flexible. Very thin foil-like substrates <NUM> have the additional advantage that they have increased flexibility.

Advantageously, an LCP may be thermoformed allowing complex shapes to be provided. Very thin (and subsequently very conformable) and very flat (highly planar) layers of an LCP may be provided. For fine tuning of shapes, a suitable laser may also be used for cutting.

For example, a conformable foil-like substrate <NUM> comprising a significant amount of LCP may have a thickness in the range <NUM> microns (um) to <NUM> microns (um), preferably <NUM> microns (um) to <NUM> microns (um). For example, values of <NUM> (micron), <NUM>, <NUM>, or <NUM> may be provided.

An implantable electrical device <NUM>, <NUM> as described herein may be comprised in an implantable medical device <NUM>. For example, such a medical device <NUM> may be configured and arranged to provide a degree of sensing, stimulation, data processing, detection or measurement, data storage, oscillation, logic performance, stimulation pulses generation, or any combination thereof.

As depicted in <FIG>, an improved implantable medical device <NUM> may be provided by modifying the implantable device <NUM>, depicted in <FIG>. It is the same as the implantable electrical device <NUM> depicted in <FIG>, except in this cross-section:.

However, the substrate <NUM> depicted in <FIG>, comprises a further protected surface, adjacent to such a protected first or second surface.

The medical device <NUM> further comprises:.

Optionally or additionally, one or more sensors <NUM> may similarly be provided - such sensors <NUM> are configured to be provided electrical signals and/or data to the one or more electrical conductors <NUM>. For example, they may be inductively-coupled, capacitively-coupled or directly connected. If a multilayer substrate with electrical interconnections is provided, a high degree of customization is possible. For example, allowing direct measurements of parameters relevant for operation, such as humidity, temperature, electrical resistance and electrical activity.

Typically with neural-stimulation electrodes, one or more electrodes <NUM> are configured and arranged to operate as a ground or return electrode - this may be one of the existing electrodes or one or more further electrodes.

The skilled person will realize that such a stimulation electrode <NUM> and/or a tissue sensor is preferably not completely covered by an encapsulation layer <NUM> and/or an adhesion layer <NUM> as a sufficiently high degree of electrical connection or exposure to the implant environment are required for their function. For example, at least part of a stimulation electrode <NUM> and/or tissue sensor is masked during the encapsulation process to provide a conductive surface towards tissue. Additionally or alternatively, portions of the device may not be encapsulated.

<FIG> depicts a device <NUM> where substantially all of a stimulation electrode <NUM> is substantially not covered. In addition, in this cross-section, a portion of the substrate <NUM> is substantially not covered, providing a device <NUM> with a substantially encapsulated portion, and a substantially unencapsulated portion with one or more electrodes <NUM>.

The extent of the further adhesion layer <NUM> in this cross-section for the two opposite surfaces is less than the extent of the further encapsulation layer <NUM> for these surfaces - this may be advantageous as the edges of the further adhesion layer <NUM> are at least partially encapsulated <NUM>.

Applying this encapsulation to implantable stimulators generally provides a substantially unencapsulated portion with one or more electrodes <NUM>, and a substantially encapsulated portion comprising a pulse generator and/or electronics.

<FIG> depicts a further embodiment of a medical device <NUM>. More particularly, it depicts a cross-section through a portion of the substrate <NUM> comprising one or more electrode <NUM>. The further medical device <NUM> is the same as the device <NUM> depicted in <FIG> except, in general, in this cross-section:.

In this cross-section, "a part" of the one or more stimulation electrodes <NUM> is not completely covered to allow electrical connection or exposure to the implant environment after implantation. So, in the regions close to the stimulation electrodes <NUM>, the general statements made above do not all apply completely. In particular, in this cross-section:.

In other words, in this cross-section at the edge portions of the surface of the electrodes <NUM>, the extent of the further adhesion layer <NUM> is approximately the same as the extent of the further encapsulation layer <NUM>.

This may be advantageous in certain configurations as the surface area of further encapsulation layer <NUM> in direct contact with the surface of the electrodes <NUM> is greatly reduced. In some cases, this surface area may be substantially zero.

Optionally, it may be advantageous if the extent of the further encapsulation layer <NUM> in this cross-section at an edge portion of one or more electrodes <NUM> is greater than the extent of the further adhesion layer <NUM> - in some configurations, this may be advantageous as the edges of the further adhesion layer <NUM> are at least partially encapsulated <NUM>.

So, the one or more stimulation electrodes <NUM> and/or sensor are preferably comprised in a surface, configured and arranged to provide a tissue interface.

"Comprised in a surface" means that the electrodes <NUM> are relatively thin (for example, when the substrate conforms to a substantially planar surface, having an extent along a transverse axis. approximately perpendicular to a longitudinal axis of the substrate, of <NUM> to <NUM> microns or less. Thinner electrodes may also be used to further increase the degree of conformability, for example <NUM> micron or less), and attached to (or at least partially embedded in) the surface.

This is particularly advantageous with substrates comprising significant amounts of one or more LCP's as PCB/metallization-techniques may be used to provide conductive regions, which may be configured and arranged to be electrodes <NUM> and/or sensors <NUM>. Preferably, a conductive material is used such as gold, platinum, platinum black, TiN, IrO<NUM>, iridium, and/or platinum/iridium alloys and/or oxides. Conductive polymers, such as Pedot, may also be used. Preferably, bio-compatible conductive materials are used.

Thicker metal layers are generally preferred over thinner metal layers for electrodes <NUM> because they can be subjected to bodily substances that may dissolve the metal. However, thicker metal layers typically increase rigidity (reduce conformability) proximate the thicker layer.

In a second set of experiments, adhesion of PDMS MED2-<NUM> from NuSil to an LCP substrate was investigated using two different substrates and two different PDMS casting processes.

Different methods were used to evaluate the adhesion: adhesion evaluation by Peel-test dry, after PBS soaking at <NUM> degr. C, and a Peel-test based on ASTM D1876.

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

It may be advantageous if the first (<NUM>) and/or second (<NUM>) encapsulation layers have/has a tensile strength in the range <NUM> to <NUM> MPa.

NuSil suggests that in many bonding applications (for a substrate comprising Aluminum, Glass, PMMA, Silicone) the use of a silicone primer to improve suitable adhesion is not required.

Use of a primer is suggested by the manufacturer when adhering to substrates comprising Polyetherimide, PEEK, Plastic, Polycarbonate, Polyimide, Polysulphone, Polyurethane, and Stainless steel.

In order to study the adhesion properties of the PDMS on LCP with different processing methods and adhesion layers, two different test substrates were used:.

In general, it is advantageous to perform as few steps as possible when manufacturing an implantable electrical device - this may reduce the risk of introducing contamination or transport related issues, and it may reduce one or more costs.

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

ULTRALAM® <NUM> LCP is available from Rogers Corporation (www. rogerscorp. com) and may be used as a bonding medium (adhesive layer) between copper, other LCP materials and/or dielectric materials. It is characterized by low and stable dielectric constant. It has a relatively low modulus, allowing relatively easy bending for flex applications, and relatively low moisture absorption.

It may be used with one or more layers of ULTRALAM® <NUM> LCP to create substantially adhesive-less substantially all-LCP multi-layer substrates.

Typical values for physical and chemical properties of ULTRALAM® <NUM> LCP include:.

ULTRALAM® <NUM> is available from Rogers Corporation (www. rogerscorp. com) and is a relatively high-temperature resistant LCP. It may be provided as a double copper clad laminate for use as laminate circuit materials. The manufacturer suggests these products for use as a single layer or a multilayer substrate. ULTRALAM <NUM> circuit materials are characterized by a relatively low and stable dielectric constant, and dielectric loss. It has a relatively low modulus, allowing relatively easy bending for flex applications, and relatively low moisture absorption.

b1) an optional pre-cleaning of at least a portion of the substrate using IPA, followed by drying. Another suitable alcohol may also be used.

b2) Applying an adhesion coating: using ALD, a coating was applied to an outer surface of the substrate - in this case a surface comprising ULTRALAM® <NUM> LCP. Ten alternating layers of approximately <NUM> Al2O3 and of approximately <NUM> HfO2, resulted in an approximately <NUM> multilayer. The extent of the ALD coating was approximately the same as the extent of the substrate. The ALD coating was applied using the PICOSUN® R-<NUM> Advanced ALD reactor described above. It was applied at a temperature substantially lower than the melting temperature of the LCP. For these TYPE <NUM> LCP substrates, it was applied at approximately <NUM> degr C after an optional stabilization time of approximately <NUM> minutes.

For comparison, this step was omitted for some of the samples (in other words, the PDMS was applied directly to the LCP).

c) Cleaning at least a portion of the adhesion coating: as preparation for the PDMS coating, an optional ten-minute ozone (O3) plasma treatment was performed to clean the ALD surface. The PDMS was applied within fifteen minutes from the ozone cleaning. For comparison, some samples were not cleaned before the PDMS coating was applied.

UV O3 (ozone) plasma cleaning is suitable for dry, non-destructive atomic cleaning and removal of organic contaminants. It uses intense <NUM> and <NUM> ultraviolet light. In the presence of oxygen, the <NUM> line produces Ozone and while the <NUM> line excites organic molecules on the surface. This combination drives the rapid destruction and decimation of organic contaminants.

d) Applying an encapsulation coating: a PDMS coating of approximately <NUM> to <NUM> of MED2-<NUM> was applied on top of the ALD coating. A syringe was filled with MED2-<NUM>, and mixed & degassed at relatively high speed (<NUM> rpm) for three minutes. It was cured at <NUM> degr C for <NUM> and post-cured at <NUM> degr C for <NUM> hours. The extent of the PDMS coating was less than the extent of the ALD coating, whereby the ALD coating was exposed (not covered by encapsulant) close to the edge of the substrate. After applying the PDMS on the substrate, the substrate was placed on the PTFE (polytetrafluorethylene)-coated pre-heated plate, and a weight was pressed on top of it.

So, six samples of TYPE <NUM> LCP were prepared:.

A Pass/ Fail test was defined for the TYPE <NUM> LCP substrates by hand:.

Three degrees of delamination were defined:.

Phosphate-buffered saline (abbreviated PBS) is a buffer solution commonly used in biological research. It is a water-based 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 osmolarity and ion concentrations of the solutions are selected to match those of the human body (isotonic).

Samples <NUM>: the PDMS could not be peeled from the surface in dry state. After twenty-four hours of soaking, part of the PDMS could be peeled from the substrate, although no moisture filled voids were observed. After peeling away some of the PDMS, the rest stuck so well to the substrate it could not be peeled off any further, not even after <NUM> or <NUM> weeks of additional soaking. It was suspected that the initial delamination was due to local contamination during PDMS processing or processing issues.

Samples <NUM>: these samples showed good adhesion. No delamination was achieved in dry and wet conditions until after two weeks of testing.

Optionally, the laminated sheets may be substantially planar.

O2 (oxygen) plasma refers to any plasma treatment performed while actively introducing oxygen gas to the plasma chamber. Oxygen plasma is created by utilizing an oxygen source on a plasma system.

Additionally or alternatively, ozone (O3) may be used. d) Applying an encapsulation coating:.

The extent of the PDMS coating was approximately the same as the extent of the ALD coating. After removing the Kapton tape, a strip of approximately <NUM> wide was provided where the PDMS was not attached to the ALD coating.

e) Performing further processing: the coated substrate of approximately 100x75mm area was cut into <NUM> pieces of approximately 100x10mm for Peel-testing. Each piece had an area of approximately 10x10mm without the PDMS coating at is edge due to Kapton tape removal.

So, fifteen samples of type (<NUM>) were prepared:.

Peel-test according to ASTM D1876 was adapted for testing the TYPE <NUM> LCP or laminated substrates). A Peel-tester was used to measure the lamination force.

<FIG> depicts a graph <NUM> comparing the average pull force under dry (not soaked) conditions with the average pull forces after <NUM> hours of soaking at <NUM> degr. The samples of LCP were coated with PDMS using different processes.

Average peel force is plotted along the vertical (Y) axis from <NUM> to <NUM> N, and the results are indicated for the different samples along the horizontal (X) axis. To simplify interpretation, the order of the samples chosen is numerical: from left to right, samples <NUM>, <NUM>, <NUM>, <NUM> and <NUM>.

For each sample, the vertical length of each bar indicates the average peel force in Newtons (N). For each bar, an "I" shaped line is also depicted to indicate the variation measured in the pull force values used to determine the average. For each sample, an unfilled bar is depicted on the left-hand side showing the average pull force under dry conditions, and a hatched bar on the right-hand side showing the average pull force after <NUM> hours of soaking at <NUM> degr.

For sample <NUM>, an unfilled bar 761a is depicted of approx. 4N, with a relatively small degree of variation. No value after soaking is depicted.

For sample <NUM>, an unfilled bar 762a is depicted of approx. 13N, with an average degree of variation. A hatched bar 762b is depicted of approx. 14N, with a relatively high degree of variation.

For sample <NUM>, an unfilled bar 763a is depicted of approx. 5N, with a relatively small degree of variation. A hatched bar 763b is depicted of approx. 7N, with an average degree of variation.

For sample <NUM>, an unfilled bar 764a is depicted of approx. 7N, with a relatively small degree of variation. A hatched bar 764b is depicted of approx. 5N, with an average degree of variation.

For sample <NUM>, an unfilled bar 765a is depicted of approx. 8N, with a relatively small degree of variation. A hatched bar 765b is depicted of approx. 8N, with an average degree of variation.

It appears that a stable overmolding encapsulation process was achieved, showing substantially none, or very few, air bubbles in the PDMS. Substantial delamination of the LCP/PDMS interface was observed on <NUM> out of <NUM> samples directly after overmolding. For this reason, the Peel-test was applied to get a more qualitative measure of the adhesion strength.

Samples <NUM>: without additional priming or cleaning, the PDMS had a very low degree (approx. 4N - 761a) of adhesion to LCP.

Samples <NUM>: substrates with a primer appeared to have a relatively high degree of adhesion (approx. 13N - 762a - compared to approx. 4N - 761a). During the test, some regions had a higher degree of adhesion, which resulted in the PDMS rupturing before peeling the samples completely. The average pull force after the soaking test appeared to be higher at approx. 14N - 762b, but a relatively high degree of deviation was also observed.

Samples <NUM>: by adding an ALD multilayer, specifically the HfO2-Al2O3 multilayer ending with HfO2, the degree of dry adhesion appeared improved (from approx. 4N - 761a - to approx. 5N - 763a). The results under dry conditions - 763a - appears to have a very low degree of deviation. The average pull force after the soaking test appeared to be higher at approx.

Samples <NUM>: O2-plasma activation also appeared to increase the adhesion (approx. 7N - 764a - compared to approx. 4N - 761a). The average pull force after the soaking test appeared to be slightly higher at approx.

Samples <NUM>: plasma activation appeared to further improve the degree of adhesion (approx. 8N - 765a - compared to approx. 4N - 761a). The average pull force after the soaking test appeared to be approximately the same at 8N - 765b. A small increase in deviation - 765b - was observed after soaking.

In addition, for implantable devices, a high degree of quality control is often required to limit the risk of defects. Primers must typically be applied using a spray coating process, which may be difficult to perform with a high degree of reliability. It is believed that such reliability issues were the cause of the partial delamination observed.

Based upon the improved adhesion between a PDMS and surfaces comprising a significant amount of Pt, SiO2 and an LCP, an adhesion layer comprising a ceramic material may be advantageously used for a wide range of substrate materials. In particular, adhesion of a PDMS may be improved where a first surface <NUM> and/or second surface <NUM> comprises a significant amount of a substance selected from the group comprising: a Liquid-Crystal Polymer (LCP), a polyimide, Parylene-C, SU-<NUM>, a polyurethane, or any combination thereof. These substances may be comprised in a flexible substrate.

Where appropriate, a substrate comprising other materials may thus be provided with a layer of such a material to improve adhesion to the HfO2 ALD layer.

The skilled person will also realise that adhesion may be improved by optionally or additionally applying a conformal coating to such a substrate, for example with an ALD process, applying a layer of SiO2 (silicon dioxide).

PDMS is, in general, a silicone rubber, with siloxane as the basic repeating unit. Methyl groups are substituted by a variety of other groups, for example, phenyl, vinyl or trifluoropropyl groups, depending on the type of PDMS, enabling the linkage of organic groups to an inorganic backbone.

Based upon the improved adhesion to a PDMS using one or more adhesion layers comprising HfO2 and/or Al2O3, an adhesion layer comprising a suitable ceramic material may be advantageously used for a wide range of substrate materials.

Suitable ceramic surfaces are relatively rich in hydroxyl groups. It is believed that the high degree of adhesions is due to oxygen in suitable PDMS-types can form strong bonds with the hydroxyl groups on the suitable ceramic surface. This may be chemical bonding, hydrogenbridge bonding or some combination.

many other materials, including the mixed oxide ceramics that can act as superconductors.

In particular, adhesion of a PDMS may be improved where the ceramic material is selected from the group comprising: HfO2, Al2O3, Ta2O3, TiO2, and any combination thereof.

It is also expected that Diamond-like carbon may be advantageously used to improve adhesion.

Adhesion may be further improved by activating the surface of the ceramic layer - for example, by applying an alcohol, in particular ethanol; using a plasma comprising O3 (Ozone) and/or comprising O2; treating with a silane; or any combination thereof.

An adhesion layer may be a bi-layer or multilayer, in which one or more layers may be configured and arranged for a relatively high degree of adhesion, and one or more layers may be configured and arranged for a relatively high degree of corrosion resistance (impermeability).

For example, it is believed that a layer comprising Al2O3 provides a relatively high degree of adhesion. For example, it is believed that a layer comprising HfO2 provides a relatively high degree of corrosion resistance.

<FIG> depict examples of nerves that may be stimulated using one or more suitably configured improved medical devices <NUM>, <NUM>, configured to provide neurostimulation to treat, for example, headaches, chronic headaches or primary headaches. In particular, if the substrate is substantially flexible, it may conform better to the curved surfaces of the head and/or skull. This means that the comfort to the user of an implantable medical device <NUM>, <NUM> may be increased.

<FIG> depicts the left supraorbital nerve <NUM> and right supraorbital nerve <NUM> which may be electrically stimulated using a suitably configured device. <FIG> depicts the left greater occipital nerve <NUM> and right greater occipital nerve <NUM> which may also be electrically stimulated using a suitably configured device.

Depending on the size of the region to be stimulated and the dimensions of the part of the device to be implanted, a suitable location is determined to provide the electrical stimulation required for the treatment. Approximate implant locations for the part of the stimulation device comprising stimulation electrodes are depicted as regions:.

In many cases, these will be the approximate locations <NUM>, <NUM>, <NUM>, <NUM> for the one or more implantable medical devices <NUM>, <NUM>.

For each implant location, <NUM>, <NUM>, <NUM>, <NUM> a separate stimulation device <NUM>, <NUM> may be used. Where implant locations <NUM>, <NUM>, <NUM>, <NUM> are close together, or even overlapping a single stimulation device <NUM>, <NUM> may be configured to stimulate at more than one implant location <NUM>, <NUM>, <NUM>, <NUM>.

A plurality of implantable medical devices <NUM>, <NUM> may be operated separately, simultaneously, sequentially or any combination thereof to provide the required treatment.

<FIG> depict further examples of nerves that may be stimulated using one or more suitably configured improved implantable medical devices <NUM>, <NUM> to provide neurostimulation to treat other conditions. The locations depicted in <FIG> (<NUM>, <NUM>, <NUM>, <NUM>) are also depicted in <FIG>.

The descriptions thereof herein should not be understood to prescribe a fixed order of performing the method steps described herein. Rather the method steps may be performed in any order that is practicable. Similarly, the examples used to explain the algorithm are presented as non-limiting examples, and are not intended to represent the only implementations of these algorithms. The person skilled in the art will be able to conceive many different ways to achieve the same functionality as provided by the embodiments described herein.

For example, one or more features that improve conformance may be applied to embodiments that are configured and arranged for improved encapsulation. In some embodiments, it may be advantageous to apply features that improve encapsulation but reduce conformance.

For example, one or more features that improve encapsulation may be applied to embodiments that are configured and arranged for improved conformance. In some embodiments, it may be advantageous to apply features that improve conformance but reduce encapsulation.

Claim 1:
An implantable electrical device (<NUM>, <NUM>, <NUM>), comprising:
a flexible substrate (<NUM>) having a first surface (<NUM>) and one or more electrical conductors (<NUM>);
a first biocompatible encapsulation layer (<NUM>);
a first adhesion layer (<NUM>), disposed between the first surface (<NUM>) and the first encapsulation layer (<NUM>);
wherein:
the first surface (<NUM>) comprises a Liquid-Crystal Polymer (LCP);
the first adhesion layer (<NUM>) is configured and arranged to conform to the first surface (<NUM>) and comprises a ceramic material;
the first encapsulation layer (<NUM>) comprises a silicone rubber, and
the first adhesion layer (<NUM>) and the first encapsulation layer (<NUM>) are configured and arranged to resist the ingress of fluids from a human or animal body into at least a portion of the first surface (<NUM>).