1. Field of the Invention
The present invention relates to medical implants and, more particularly, to a self-assembled monolayer coating on electrically conductive regions of a medical implant.
2. Related Art
A variety of medical implants deliver electrical energy to tissue of a patient to stimulate that tissue. Examples of such implants include pace makers, auditory brain stem implants (ABI), Functional Electrical Stimulators (FES), Spinal Cord Stimulators, cochlear implants etc.
In a cochlear implant, an array of electrodes are implanted into the patient's cochlea. The electrode array is connected to a stimulator unit that is operationally connected to a signal processing unit. In operation, audio signals from the environment are received from a microphone and delivered to the signal processing unit for audio processing. These processed signals are used by the stimulator unit to generate electrical signals for delivery to the cochlea via the electrode array. As such, a cochlear implant allows for electrical signals to be applied directly to the auditory nerve fibers of a patient, thereby allowing the brain to perceive a sound.
The generation and delivery of the electrical stimulating signals requires energy provided by, for example, a battery. Energy drain of such a power source can severely affect the effectiveness and performance of a medical implant. As would be appreciated, the drain of energy of the power source is related to the energy consumption of the device, and a power source that is drained more quickly necessitates more frequent recharging or replacement. In some instances, this may require surgery, which is highly undesirable for the patient.
According to one aspect of the present invention, a medical implant for providing electrical stimulation to a patient's tissue is provided. The medical implant comprises: at least one electrically conductive region; and a coating of self assembled monolayer (SAM) attached at least a portion of the conductive region, wherein the SAM is configured to inhibit the attachment of impedance-inducing material to the coated portion of the at least one conductive region.
According to another aspect of the present invention, a method of reducing energy consumption of a medical implant having at least one electrically conductive region for stimulating tissue of a patient is provided. The method comprises: coating at least a part of the at least one electrically conductive region with a self assembled monolayer (SAM) that inhibits attachment of impedance-inducing material to the at least one electrically conductive region.
According to a still other aspect of the present invention, a cochlear implant is provided. The cochlear implant comprises: a stimulator unit configured to generate electrical stimulation signals; an electrode array having at least one electrode contact configured to deliver the stimulation signals to a patient's tissue; and a coating of self assembled monolayer (SAM) on the electrode contact, wherein the SAM is configured to inhibit the attachment of impedance-inducing material to the electrode contact.
The various aspects of the present invention will now be described in detail with reference to the following figures in which:
FIG. is an illustration of an electrode contact surface contour with a SAM coating, in accordance with embodiments of the present invention;
Aspects of the present invention are generally directed to a medical implant comprising at least one conductive region having a self-assembled monolayer (SAM) disposed thereon. The SAM is configured to inhibit the attachment of organic material to the coated portion of the at least one conductive region. Specifically, the organic material, as described below, is material that increases the impedance at the tissue/electrode interface when compared to an tissue/electrode interface that does not have the organic material. As is known in the art, a SAM is an organized layer of amphiphilic molecules in which one end of the molecule, known as the “head group” shows a special affinity for a substrate. SAMs also consist of a tail with a functional group at the terminal end.
An electrode contact tissue/interface interface exists between each electrode contact 30 and the electrolytes in the cochlear fluids of the patient. The term electrode contact/tissue interface is used throughout this specification to mean the interface between the stimulating electrode contact and the tissue to be stimulated. In the case of a cochlear implant, this is the interface between the electrode contact and the auditory nerve fiber tissue being stimulated.
This interface results from the difference in the conducting mediums (electron flow in the metal electrode contact 30) and to ionic flow in the cochlear fluid. With constant stimulus, a thin layer of water molecules is formed at the electrode contact 30 surfaces, and nearby is a diffused layer of hydrated ions. This forms the electric double layer.
There are two primary charge transfer mechanisms for delivery of the stimulation signals to the patient. The first charge transfer mechanism is known as capacitive charge transfer and is achieved by charging the double layer that acts like a capacitance due to separation of charge. However, this alone cannot provide effective stimulation of the nerves. The other charge transfer mechanism is the faradaic reaction which involves surface chemical reactions that may be reversible or irreversible. Irreversible reactions are not desirable in medical implants because harmful chemical species can diffuse into the biological system. For that reason, a set of biphasic pulses is delivered in neural stimulation. As can be seen in
When a foreign object such as a medical implant is implanted into the body, various physiological reactions, such as immune response, occur in response to the presence of the foreign body. These responses may include the build up of impedance-increasing materials, such as fibrous tissue encapsulations or protein adhesions or other attachments, on the surface of the implant. Such organic materials increase the impedance at the tissue/electrode interface (i.e. the location where the electrode contacts, or is adjacent to, the tissue), when compared to a tissue/electrode interface that does not include the organic materials.
In medical implants that deliver electrical stimulation via an electrode contact, such protein adhesions, attachments, bonds or adsorptions have been found to increase the impedance of the electrode contact/tissue interface. This increased impedance can reduce the volume of tissue that can be stimulated, thus reducing the effectiveness of the implant. Furthermore, increased impedance can result in a greater drain on power sources as the required power or energy consumption of the medical implant increases to compensate for the loss in signal. In the case of an internal battery as the power source, this will necessitate more frequent changing or recharging of the battery, which in some cases may result in additional surgery for the user. In one example, the power source or battery may be located in the stimulator 10 shown in
In embodiments of the present invention, this increase in impedance, and hence increased power drain or energy consumption, is reduced by the application of a self assembled monolayer (SAM) to a portion of the surface of an electrode contact 30.
In one form, unmasked regions of the implant may be exposed to the thiol solution to enable SAM 40 to assemble and adsorb to the implant. In one embodiment, platinum electrode contacts 30 adsorbs the thiol group due to the high affinity between platinum (and other transitional metals) and the sulphur group arranged at the head of SAM 40 resulting in a covalent bond between the two. The tail of SAM 40, arranged away from the medical implant, controls the functionality of the SAM 40 and can be varied to tailor the absorbance of proteins, cells and other physiological elements.
In one embodiment, SAM 40 may be represented by R—SH wherein the SH group undergoes deprotonation at the implant surface end and is covalently bound to electrode contact 30. The R group represents an alkane group, for example comprising 6 to 18 carbon atoms and terminated by a functional group, chosen depending on the purpose of the SAM binding. The terminal group of SAM 40 may be tailored to prevent or at least inhibit or alternatively, enhance tissue growth and protein attachment, adhesion, bonding or adsorption. As such, in embodiments of the invention, the terminal group of SAM 40 may comprise, but is not limited to, one or more of functional groups including COOH, CF3, CH3, CO2H, NH2, CH2OH, CO2CH3 and CH2H40 (ethylene oxide).
The majority of SAM 40 is orientated such that the tail is positioned away from the covalently bound head of the SAM. In particular, the thiol-based SAM 40 as used in the illustrated embodiment, is tightly packed and highly ordered due to electrostatic repulsive interactions between molecules in SAM 40. As such, once the medical implant is coated with SAM 40, the orientation of the molecule in addition to its terminal group preferably imparts electrostatic repulsive interactions between SAM 40 coated on the medical implant and the surrounding media, thereby deterring or inhibiting the attachment or adsorption of the impedance-inducing material, such as cells or protein, to the coated electrode contact 30. The reduction of protein adsorption (and thus impedance-inducing material) enables the medical implant to conserve charge transfer across the electrode contact/tissue interface by preventing electrode impedance fluctuations.
The thickness of SAM 40, in one form, less than 22 A, ideally results in no change to the impedance of the medical implant, and therefore no change to the efficiency of charge transfer between the implant and surrounding tissue. As such, minimal electrode impedance fluctuations may result in power saving, resulting in an increased battery life and subsequent cost savings across the life of the medical implant. This may also lead to a reduced frequency of explantation procedures for the patient.
Typically organic alkyls bearing mercapto group (thiols) can be used as SAM coatings. This is mainly due to the strong affinity that sulphur compounds have to transition metal surfaces such that the —SH group of thiol molecule undergoes deprotonation at the surface and forms a metal-sulphur covalent bond with the rest of the molecule being oriented away from the metal surface. Additionally, the interactions between the head group-substrate, end group-substrate, chain-chain, and end group-end group can be used to modify the degree of chemisorption and physisorption. These include long-chain carboxylic acids on metal oxides, organosilane species on hydroxylated glass, silicon oxides and aluminium oxides, and sulfides, disulfides, silanes, nitriles or organosulfurbased species on noble metal surfaces.
Surfaces may be engineered to either prevent or at least inhibit, or alternatively enhance tissue growth with an appropriate host response by choices of functional groups. For instance, keratinocytes have been found to grow on —COOH terminated SAMs, corneal epithelial cells tend to grow on —CF3, —CH3, —CO2H, and —NH2 terminated SAMs; and bovine aortic endothelial cells tend to grow on —CH3, —CH2OH, —CO2CH3, and —CO2H terminal SAMs While oligo (ethylene oxide) has universal resistance to protein adsorption regardless of the nature of the protein, thus inhibiting the attachment of this impedance-inducing material to the electrode contact.
Surfaces may also be engineered to either prevent or at least inhibit, or alternatively, to enhance tissue growth with an appropriate host response by the choice of surface finishes. A roughened surface has a larger surface area compared with a smooth surface and consequently a larger conducting surface area. Additionally the smoothness of the curves can be used to affect adhesion of biofilm. For instance, macro roughness with smooth curves and overall micro smoothness plus incorporation of SAMS will provide a high conducting surface, and prevent or at least inhibit, biofilm growth and protein adhesion.
Alternatively, 4-carboxyphenyl group could be used in place of a thiol group to bind the SAM onto the surface of an electrode contact 30. Similar to the thiol, in these embodiments the SAM would be covalently bonded and provide long term stability in terms of protein fouling at the neural stimulating surface. Various terminal functional groups can be incorporated to engineer the surface for a specific host response.
Another type of coupling mechanism for monolayers are silanes. Silanes covalently bond to oxides on surfaces (rather than directly to the metal) and may be of benefit if using substrate materials other than platinum. Once again the terminal functional groups can be tailored for specific applications.
Various methods may be used to coat electrode contact 30 with SAM 40. In one method, as shown in
In one embodiment, each individual electrode contact may be coated with the SAM and then assembled into an array of electrode contacts and incorporated into a lead. One method of assembling the array and lead is described in U.S. Pat. No. 6,421,569 entitled “Cochlear Implant Electrode Array” incorporated by reference herein.
In another embodiment, an integral electrode contact “spine and comb” arrangement may be constructed as described in International Patent Application No. PCT/US2008/083794 (WO2009/065127) entitled “Electrode Array and Method of Forming an Electrode Array”, incorporated by reference herein. The electrode assembly may then be coated as described above with reference to
In a further alternative, the already-formed lead or carrier member 20 may be masked as will be understood by the person skilled in the art, to leave exposed electrode contacts for coating as previously described. In another embodiment, if a second SAM is used to coat the lead, the electrode contacts may then be masked to prevent coating with the second SAM, and the lead coated as described above.
In the illustrated embodiment of
In further embodiments (not illustrated), the SAM may be combined with an anti-microbial coating to reduce protein fouling of implant surfaces. The anti-fouling coating may include, but is not limited to, silver ions, antibiotics, drugs, peptide coatings and poly-ethylene glycol coatings. The coating may be hydrophobic or hydrophilic.
In certain embodiments of the present invention, the conductive regions of the medical implant be biocompatible metals such as titanium, palladium, tantalum, iridium, gold and carbon-nano tubes. In these embodiments, a SAM may be applied thereto. Additionally, SAMs could also be applied over biocompatible conductive or insulative polymeric materials such as silicone and polyurethane carbon nano particle reinforced composites as well as other biocompatible materials such as alumina for blocking protein adsorption.
The benefit of SAMs on electrode surfaces to substantially prevent an increase in impedance has been discussed above. It would be appreciated that in some cases, protein blocking would also be beneficial over the implantable medical device as a whole such as the intra-cochlear portion of the implantable medical device. For instance SAMs can minimize trauma to the cochlea during explantation as a consequence of blocking protein adsorption and fibrous tissue growth on the electrode lead or carrier member. The use of the overall SAM coating of the device may be used as required depending upon circumstances such as the likelihood of explantation in a particular patient.
In accordance with embodiments of the present invention, SAMs may also be applied to conducting surfaces of extra cochlear electrodes (ECE) as shown in
In one embodiment of the present invention, the SAM may be tailored to block protein adsorption on a cochlear implant. In this case, the intra-cochlear portion (either the entire surface or simply a portion of one or more of the conductive electrode pads or contacts) of the medical implant may be coated with a SAM terminated by a functional group known to have resistance to protein adsorption. An example of such a group is ethylene oxide, a group that has universal resistance to protein adsorption regardless of the nature of the protein. The functional group is however not solely limited to ethylene oxide and alternate groups may be used to obtain a similar result.
The presence of SAMs on the electrode contact also reduces the DC bias level between electrode contacts. A high DC bias is likely due to organic residues on the electrode surface. This may also provide an effective cleaning protocol for neural stimulation applications.
Another advantage of using SAMs is that the design of the medical implant may be altered as a result. For instance, because the impedance of the electrode contact/tissue interface is reduced, the size of the electrode contacts may also be reduced. Accordingly, a greater number of electrode contacts may be incorporated into the electrode array, potentially providing a further increase in the performance of the implant.
In the embodiments of
According to an aspect of the present invention, a portion of one or more of the electrically conductive regions (electrode contacts 30) of implantable component 100 may be coated with a SAM to reduce, prevent or inhibit attachment of the impedance-inducing material thereto.
According to another aspect, at least a portion of the electrically non-conductive region of implantable component 100, such as part of the casing of the stimulator 10, and/or part of lead 20 may also be coated with a second SAM that attracts the impedance-inducing material, to enhance securement of the implant within the patient.
Without any SAM coating for an electrode contact, the inter-operative impedance is typically about 1 to about 5 kOhm (in common ground (CG), and is between about 3 and about 7 kOhm when measured in monopolar modes. In post implantation the impedance is about 3 to about 6 kOhm for CG, but would be higher for MP These measurements were performed with clinical software, and the increase in impedance after implantation is due to fibrous tissue encapsulation. These measurements are shown in
The above estimate was confirmed by additionally recent Custom Sound measurements in saline. These indicate about 1.93 kOhm without SAM coating and about 3.94 kOhm with the SAM coating (both values for impedance in Monopolar MP1+2), which confirms a doubling of impedance with the SAM coating. These measurements were performed with electrode contacts with a larger surface area compared to intra-cochlear electrode contacts.
Test Method: EIS measurements (as conductance graph in
Influence Electrolyte: It appears that impedance values taken in saline and intra-operatively are comparable. This assumption is based on measurements performed in saline and known and available intra-operative data.
Influence of electrode surface areas: The impedance increases with decreasing surface area:
The impedance was about 1.93 kOhm for a 2 mm2 surface area electrode compared to about 3.55 kOhm for a 0.2 mm2 electrode contact (comparable to cochlear implant intra-cochlear electrode contact). Both measurements were taken under the same conditions (in saline, at room temperature, MP1+2 mode using clinical software).
Based on the above, it is assumed that the impedance of a SAM coated cochlear implant electrode contact is about 5.5 kOhm, which is still at the lower end of the scale for the MP impedance (which is between about 4.5 and about 8.5 kOhm in adults).
The references provided above indicate that the increase in the impedance due to the SAM is much less compared with the increase in impedance post implantation.
The data presented in
The above results demonstrate that the coating repels or at least inhibits protein and cell attachment and thus inhibits the impedance-inducing material.
The various aspects of the present invention may be applied to any suitable cochlear implant, as well as any other medical implant that uses electrodes and electrical stimulation, including Auditory Brain Stem Implants, Deep Brain Stem Implants, Cardiac Pacemakers, Intraocular Retinal Prostheses, etc.
It will be understood that the term “comprise” and any of its derivatives (e.g. comprises, comprising) as used in this specification is to be taken to be inclusive of features to which it refers, and is not meant to exclude the presence of any additional features unless otherwise stated or implied.
The reference to any prior art in this specification is not, and should not be taken as, an acknowledgement of any form of suggestion that such prior art forms part of the common general knowledge.
Although an illustrative embodiment of the present invention has been described in the foregoing detailed description, it will be understood that the invention is not limited to the embodiment disclosed, but is capable of numerous rearrangements, modifications and substitutions without departing from the scope of the invention as set forth and defined by the following claims.
The above illustrations show a medical implant capable of being coated with a self assembled monolayer (SAM). It will be appreciated that the illustrations are representative only, and that the size of the monolayer in any illustration is not intended to be an accurate depiction of its true size relative to the medical implant or SAM.
The invention described and claimed herein is not to be limited in scope by the specific preferred embodiments herein disclosed, since these embodiments are intended as illustrations, and not limitations, of several aspects of the invention. Any equivalent embodiments are intended to be within the scope of this invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. All documents, patents, journal articles and other materials cited in the present application are hereby incorporated by reference.
Number | Date | Country | Kind |
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2008904592 | Sep 2008 | AU | national |
The present application is a national stage application of International Application No. PCT/AU2009/001158, filed Sep. 4, 2009, and claims the benefit of Australian Provisional Patent Application No. 2008904592, filed Sep. 4, 2008. The content of these applications are hereby incorporated by reference herein.
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/AU2009/001158 | 9/4/2009 | WO | 00 | 6/29/2011 |