Fluid Exchange Electrodes and Related Systems

Abstract

The fluid exchange electrode is defined by a multi-layer electrode body that includes a conductive electrode material layer disposed within the electrode body and an ion conductive assembly that contacts the patient's skin. The electrolyte source is coupled to an inflow tube and is configured to allow a volume of electrolyte to be circulated through the electrode body, increasing the treatment duration and overall electrode life, and the temperature of the circulated electrolyte can be regulated. The circulated electrolyte can be discarded or, preferably, recirculated to the electrolyte source via a return or outflow tube. The fluid exchange electrodes described herein can be used as part of a treatment system that applies a DC voltage to remove bacteria from metal surgical implants.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the benefit of U.S. Patent Application No. 63 / 343,651, filed May 19, 2022, entitled "Fluid Exchangeing Electrode and Related System", which is hereby incorporated by reference in its entirety.

[0002] (Field of the Invention) This application generally relates to the field of surgically or orally implantable devices, and more specifically, to a novel design for electrodes and a treatment system employing the electrodes. In one version, the electrode / treatment system is used to provide DC voltage stimulation to enable the removal of biofilms and bacteria from the metal surface of an implant. According to at least one embodiment, the electrode circulates an electrolyte solution from an external reservoir to enable a longer safe treatment duration and an extended lifespan of the electrode.

Background Art

[0003] Metal implants are used for patients with many different injuries or medical problems. In particular, metal implants can be used for any individual who needs to replace one or more joints. According to one example, a metal implant can be used to replace a patient's hip or knee. According to yet another example, dental implants can be used to replace a patient's teeth. One of the potential problems with metal implants is that they tend to allow the growth of bacteria on the surface of the implant over time. This can increase the risk of infection in the patient, and the patient faces the risk of undergoing additional surgery to remove and replace the implant. To reduce the risk of infection, electrodes can provide electrical stimulation to an existing implant that inhibits the growth of bacteria. A system has been developed that can subcutaneously apply a sufficient cathodic current to a metal implant to cause an electrochemical reaction on the metal surface of the implant that can break down and kill the formed bacterial biofilm.

[0004] For an electrochemical process to occur, at least two electrodes, namely an anode and a cathode, are required in the electrolyte solution. The anode is the metal surface where the oxidation reaction occurs, and the cathode is another metal surface where the reduction reaction occurs. The reduction reaction essentially refers to the case where the substance in question gains electrons, thereby reducing the oxidation state of the molecule. The electrolytes in which the anode and cathode are present respectively provide an electrical connection by facilitating the flow of electrons transported by ion carriers such as sodium ions or potassium ions. Electrons are driven from the anode to the cathode via an electrical path through a potentiostat. A potentiostat is a device configured to pass a current from a counter electrode to a working electrode to keep the voltage of the working electrode at a constant value, and more preferably, is configured to keep it at a constant value compared to a stable reference electrode of the treatment system. In the case of cathodic voltage-controlled electrical stimulation (CVCES), the anode represents the counter electrode and the cathode represents the working electrode. Using a potentiostat, the user can determine which electrochemical process occurs on the working electrode and can determine at what rate that process occurs simply by adjusting the parameters of the applied voltage. The counter electrode has specific physical, electrical, and chemical requirements that must be met in order to adequately facilitate CVCES, particularly in a clinical environment where the health of a particular patient is involved.

[0005] CVCES technology in a clinical environment has been shown to be an effective way to combat bacterial biofilm infections on metal implants in the least invasive way possible without surgical intervention. In this setup, the patient's body acts as an electrochemical cell by using the metal implant as the working electrode (cathode), and the counter electrode attached to the patient's skin surface acts as the anode.

[0006] The counter electrode previously designed by the present applicant is described in International Publication No. WO 2021 / 178040 A1 (Title of Invention: Circumferential skin electrode for use with metal surgical implants). This design relates to a counter electrode that can be used in a CVCE-based treatment system. The circumferentially arranged electrode design has been found to increase the efficiency of treatment while maintaining patient safety parameters and presenting a minimally invasive profile. General components of this known electrode design include a lead wire, a conductive mesh layer, a conductive anode film layer, a buffer hydrogel layer, and a preferred geometry. An important feature of this design is that the electrode is shaped and configured to conform to substantially most or preferably the entire circumference of the patient's limb. This preferred geometry increases the treatment distribution on the implant and also increases the lifespan of the counter electrode. In conventional treatment systems, the counter electrode was a common patch that was locally placed only on one side of the implant. As a result, the natural tendency of the electrochemical reaction is stronger on the side of the implant closest to the electrode, thereby creating a non-uniform treatment on the implant. This non-uniform treatment occurs because the applied current naturally flows through the path of least resistance from the implant to the counter electrode. The distance between the counter electrode and the opposite side of the implant increases the natural resistance between the two electrode regions, and thus less current flows through it. There is a correlation between the anode-cathode distance and resistance. Resistance also varies depending on other factors in the treatment system such as muscle composition, fat composition, bone, skin hydration, and overall hydration.

[0007] Ultimately, this non-uniform treatment causes the side of the implant with the high-density cathodic reaction to receive a disproportionate amount of treatment compared to the low-density reaction side of the implant, thereby creating a clinical treatment that deviates from the ideal. Thus, using circumferentially arranged electrodes as described by the applicant in International Publication No. WO 2021 / 178040 A1, these resistivity coefficients can be normalized to a greater extent than conventional patch electrodes. More specifically, providing treatment using circumferentially arranged electrodes provides a more consistent and predictable treatment for disrupting any bacterial biofilm found on the implant. Consistent treatment is particularly important because if a portion of the biofilm does not receive appropriate treatment, the biofilm is simply more likely to regrow and continue to cause infection problems for the patient.

[0008] A second improvement shown by the circumferential design described in International Publication No. WO 2021 / 178040 A1 is that it shows improved safety for the patient's skin and tissue surrounding the implant compared to conventional patch electrodes. Depending on the amount of current entering the body, concentrating all of the current locally in one spot can cause severe chemical burns or thermal necrosis to local tissue, particularly the skin to which the patch electrode is adhered. Specifically, the counter electrode produces an accumulation of acidic by-products, and as the electrochemical reaction progresses over time, the acid becomes more concentrated. A low (i.e., acidic) pH is produced, and if in contact with the skin over a long period of time, the skin experiences chemical burns. The circumferential electrodes described above help mitigate this danger by virtue of their large surface area, thereby causing the current entering the body to be distributed much more widely across the electrode / skin surface. This latter feature then reduces the anodic current density, slows the decrease in pH per unit area, and results in a safer treatment for the patient.

[0009] The features of the counter electrode described in International Publication No. WO 2021 / 178040 A1 of the present applicant are very beneficial for promoting safe treatment of infected implants, but it has been found that there can still be limitations in long-term treatments, i.e., treatments lasting more than 3 hours. The extended treatment period causes excessive accumulation of acidic by-products within the hydrogel layer that contacts the skin with the conductive electrode surface, simply overcoming the ability of the electrode to distribute current over its large size. The conventional circumferential design describes its buffer system within the hydrogel that counteracts acidic by-products, but this feature also has limitations, especially over extended treatment periods. Additionally, at high treatment levels, this form of electrode has been observed to provide inadequate thermal regulation of heat generation in the patient's skin. Thus, while solving the fundamental problem of acidic by-product generation during the period of DC stimulation application, such as in CVCES treatments, there remains a need in the field of electrode design to also provide more effective means of thermal regulation at the electrode application site.

Summary of the Invention

[0010] The invention disclosed herein presents a novel method that significantly improves the treatment lifespan of the counter electrode component of an implant treatment system while maintaining important features of the electrode that are considered important for patient safety and treatment effectiveness.

[0011] Accordingly, according to at least one aspect of the present invention, a system for the treatment of a metal implant for the removal of bacteria is provided, the system comprising a device capable of generating a DC voltage, a working electrode coupled to the device capable of generating a DC voltage, the working electrode being the metal implant, and a counter electrode coupled to the device capable of generating a DC voltage. The counter electrode comprises a multi-layer electrode body having a layer of conductive electrode material disposed within a flow chamber of the electrode, and an ion-conductive assembly configured to directly contact the skin of the patient. An electrolyte source is coupled to the counter electrode and configured to enable a volume of electrolyte to flow through the electrode body.

[0012] According to at least another aspect, there is provided a fluid exchange electrode comprising: an electrode body; a conductive electrode material layer disposed within the electrode body; an ion conduction assembly configured to contact the skin surface of a patient; and an inflow tube and an outflow tube coupled within the electrode body, the inflow tube being configured to be connected to an electrolyte source that enables a volume of electrolyte solution to flow through the electrode body.

[0013] According to yet another aspect of the present invention, there is provided a method of extending the life of an electrode used in a biofilm removal treatment of an implant, the method comprising coupling an electrolyte source to the electrode and circulating an electrolyte solution within the electrode during the treatment, the electrode including an electrode body having an internal flow chamber disposed between a pair of insulating layers and a conductive electrode surface layer disposed within the defined flow chamber, the method further comprising providing a plurality of conductive perforations in one of the insulating layers and providing an ion conduction assembly under the insulating layer having the plurality of perforations and under the skin surface of the patient.

[0014] In summary, the present invention is based on a treatment system in which a DC current is applied to a metal implant, such as a knee or hip replacement, to electrochemically remove and destroy harmful bacterial biofilms from the metal surface of the implant. The treatment system requires at least two electrodes to effectively transfer the DC current from a voltage source to the metal implant. One of the electrodes (the working electrode) is the metal implant itself, which is connected to the voltage source by a subcutaneous attachment. A second electrode, called the counter electrode or return electrode, is directly adhered to the patient's skin in the vicinity of the implant. Since the treatment provides a DC current from one electrode to the other, acidic by-products are generated on the counter electrode that stimulate the surface through the conversion of electrons to the surrounding electrolyte. The treatment life of the counter electrode has been conventionally limited by the acidic accumulation in the hydrogel at the skin interface of the electrode, which can ultimately cause chemical burns to the patient's skin.

[0015] The disclosed invention provides a novel approach for continuously removing acidic by-products from electrodes via the circulation of an electrolyte solution. This fluid circulation significantly improves the lifespan of the electrodes by preventing the patient's skin from interacting with the acidic by-products. The fluid circulation further provides thermal regulation to skin sites where it has been observed that the temperature would otherwise rise to undesirable levels in the absence of the electrolyte solution. According to at least one embodiment, the counter electrode is defined by a multi-layer structure configured to allow the conductive electrolyte to flow into and out of the electrode body, thereby transporting acidic by-products away from the electrode and transporting fresh medium (fluid) to the electrode. Electrical conduction to the implant is not affected by this design, and important performance parameters are not sacrificed.

[0016] Several challenges were encountered in developing suitable electrode and system designs. These challenges are described in more detail in the "Detailed Description of the Invention" and include the following.

[0017] One challenge encountered by the present applicants was to create a method of isolating the skin interface hydrogel from the internal electrolyte flow without interrupting electrical conduction and without allowing water / high water content materials to come into direct contact with the skin. As is known, hydrogels swell significantly when in contact with water, which can negatively affect the mechanical integrity and adhesion of the hydrogel. Therefore, a material was needed that would allow electrical conduction through its body, prevent water from contacting the hydrogel, and not undergo its own redox reaction.

[0018] Another challenge encountered was to optimize the treatment or electrode system so that an excessive amount of electrolyte solution replacement was not required to achieve an extended electrode lifespan. This challenge was solved by incorporating additives into the electrolyte solution both initially and periodically during subsequent treatments to allow the electrodes to reach lifespan milestones by recycling the same electrolyte solution. Thus, the total volume can be made significantly smaller than the first prototype.

[0019] Furthermore, the upper and lower insulating layers of the electrodes that define the flow chamber should be fluidly sealed in a leak - proof manner. One potential problem area when maintaining this seal is the area of the extension wire that is connected to the potentiostat or other current - delivering device, and more specifically, the location where the extension wire protrudes through the electrode body. To overcome this challenge, a heat source with a tip can be used to ensure that the insulating layers are fused to each other in close proximity to the wire through which they extend.

[0020] Furthermore, since the insulating layers are each preferably made of a thin, flexible material, there was an issue that the layers forming the enclosed flow chamber within the electrode body were pinched together, potentially hindering the free flow of the circulating electrolyte. To solve this problem, a woven mesh sheet or layer was added between the insulating layers to add stability and support and prevent the flow of the electrolyte within the electrode from being hindered in the absence of such a structure.

[0021] This design significantly improves the lifespan of the return or counter electrode in a treatment system that provides DC stimulation to a metal implant. Prior art used to provide electrical stimulation to a metal implant has a limited duration or lifespan because acidic by - products accumulate at the interface between the hydrogel and the skin, posing a risk of chemical burns to the patient. The disclosed invention addresses this problem while maintaining the benefits of existing electrodes used for biofilm removal / eradication, including a treatment evenly dispersed on the metal surface of the implant itself and several safety - specific features used to maintain skin health.

[0022] One reason this disclosed design is unique is that the electrodes described herein use materials and features that are completely heterogeneous to the world of standard medical electrodes. Nevertheless, this new design meets a significant need in the field, particularly in treatment systems that rely on DC stimulation for the eradication of orthopedic and other implant infections.

[0023] Advantageously, the electrodes described herein are configured to enable a treatment of a much longer duration than known electrodes used for the same or similar purposes without affecting performance. Additionally, while the overall lifespan of the electrodes is increased, the safety of the patient is maintained if not improved.

[0024] These and other features and advantages will become readily apparent from the following detailed description, which should be read in conjunction with the accompanying drawings.

Brief Description of the Drawings

[0025] The accompanying drawings, which are incorporated herein and constitute a part of this specification, illustrate presently preferred embodiments of the invention and, together with the general description above and the detailed description below, serve to explain the features of the invention (like reference numerals represent like elements or steps).

Figure 1

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Figure 3a

Figure 3b

Figure 4a

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Figure 5a

Figure 5b

Figure 6

Best Mode for Carrying Out the Invention

[0026] The following description relates to certain specific embodiments of a novel electrode design made in accordance with aspects of the present invention. More particularly, the embodiments described are each specific to a counter electrode or return electrode configured for use in a CVES-based treatment system for eradicating or disrupting a biofilm from a surgical metal implant. However, from the following description, it will be apparent that the electrode designs described herein may be configured for use in other suitable applications. Further, throughout this detailed description, several terms are used to provide a suitable frame of reference with respect to the accompanying drawings. These terms, which may include "front", "rear", "back", "end", "proximal", "distal", "upper", "bottom", etc., are not intended to significantly limit or otherwise affect the intended scope of the present invention, except where specifically indicated as such.

[0027] The accompanying drawings are only intended to illustrate and present the prominent features of the present invention. Therefore, the drawings should not be relied upon by the reader for purposes of magnification, reduction, or similar purposes. With respect to the specific dimensions used for components throughout the following description, the range is intended to be ±15 percent. That is, 1.0 inch represents a range of 0.85 to 1.15 inches.

[0028] Referring to FIG. 1, a fluid exchange electrode 10 fabricated in accordance with a first embodiment of the present invention is shown, more specifically, a counter electrode or return electrode for use in a CVCES treatment system. The fluid exchange electrode 10 is defined by a plurality of layers that are combined to form a laminated structure. More specifically, the counter electrode 10 according to this particular embodiment includes a conductive electrode surface layer 14, an optional metal backing layer 18, an insulating backing 22 that seals the insulating layer 26, a mechanical support mesh layer 30, an ion conductive membrane layer 34, and at least one hydrogel layer. In this specifically shown embodiment, a pair of hydrogel layers are provided, namely an inner hydrogel layer 38 and an outer hydrogel layer 42, and the outer hydrogel layer 42 is configured to contact the patient's skin. Also, as further discussed herein, the ion conductive membrane layer 34 and at least one hydrogel layer (e.g., layers 38, 42) form the ion conductive assembly 32 of the electrode 10 described herein, which is disposed beneath the insulating layer 26.

[0029] In addition, the counter electrode 10 according to this particular embodiment includes several other components that are connected or otherwise coupled to the body of the electrode 10 described herein. These components include an electrical lead wire 54. The electrical lead wire 54 extends from an optional metal backing layer 14 to a potentiostat or other similar device (not shown in FIG. 1) that can generate a sufficient DC voltage for a CVCES-based implant treatment, as well as an inflow tube 46 and an outflow tube 50 configured to circulate or recirculate an electrolyte solution (synonymously referred to as "electrolyte" or "electrolyte solution" throughout this description) through the defined or formed portion of the electrode 10. Next, each of these various components of the electrode 10 will be described in more detail.

[0030] The basic component of any counter electrode design is the conductive electrode surface layer 14, which is intended to conduct electrical energy to the patient's body and internal metal implants, and thus represents the anode of the CVES-based treatment system. The conductive electrode surface layer 14 can be made from any inert conductive material that does not decompose or generate its own chemical by-products when functioning as the anode of the treatment system. According to the embodiments described herein, the conductive electrode surface layer 14 is made from a carbon vinyl sheet. Carbon vinyl is a common substrate material that can be used for stimulating electrodes largely due to its overall flexibility that allows it to easily conform to the patient's skin. Other suitable materials that can be similarly utilized for this purpose include chemically inert metals, which can include, for example, among others, platinum and rhodium. These alternative metals may be provided as a mesh (e.g., a grid of wires) or as a thin sheet. As will be described in more detail below, the conductive electrode surface layer 14 is connected to a potentiostat schematically shown as 130 in FIGS. 3a and 3b, or to a current from another power source that can provide sufficient electrical energy via an electrical lead wire 54 that can be adhered or epoxy-bonded to the surface of the conductive electrode surface layer 14 or an optional metal backing layer 18.

[0031] The optional metal backing layer 18 is preferably laminated on the side facing the upper side of the conductive electrode surface layer 14. This layer 18 can be made from a conductive metal foil or mesh that may contain copper or platinum, or alternatively, the metal backing layer 18 can utilize conductive ink. Since carbon vinyl usually does not have sufficient conductivity to evenly distribute current, the metal backing layer 30 is designed to assist in distributing the current generated from a potentiostat or similar device across the entire conductive electrode surface layer 14. Thus, if the conductive electrode surface layer 14 is not formed from a carbon vinyl sheet but from another metal with sufficient conductivity such as platinum or rhodium, the metal backing layer 18 is an optional component of the electrode 10. Ideally, according to this embodiment, the metal backing layer 18 has a smaller surface area or footprint than the conductive electrode surface layer 14. More specifically, the edges of the metal backing layer 18 are slightly recessed from the edges of the conductive electrode surface layer 14 to prevent contact with the electrolyte solution that would cause undesirable interactions in the electrochemical reaction.

[0032] To provide sufficient electrical insulation from the conductive electrode surface layer 14 to the patient or caregiver, an insulating backing 22 is applied over the conductive electrode surface layer 14 and the metal backing layer 18, thereby effectively sealing the metal backing layer 18 between the conductive electrode surface layer 14 and the insulating backing 22. The electrical lead wire 54 is adhered or otherwise attached to the metal backing layer 18 as shown in FIG. 1. If the metal backing layer 18 is not present, the electrical lead 54 is attached to the conductive electrode surface layer 14 and extends outward therefrom.

[0033] As further shown in FIG. 1, the insulating backing 22 may be sealed to the insulating layer 26 via an edge seal or peripheral seal shown as 58, where the insulating backing 22 preferably acts as a coating for the electrode 10 described herein. Further, the insulating backing 22 includes a dome-shaped or concave surface that creates a consistent cross-sectional height of a defined internal chamber having an open volume 62 that surrounds both the conductive electrode surface layer 14 and the metal backing layer 18, and both the conductive electrode surface layer 14 and the metal backing layer 18 are sealed to the inner ceiling of the defined internal chamber. The edge seal 58 enables the electrode 10 to be leak-proof and easily assembled during manufacture. Thus, an enclosed internal volume is provided through which the electrolyte 80 of FIG. 2 flows laterally and circulates through the electrode body via the inlet tube 46 and the outlet tube 50, and each of the inlet tube 46 and the outlet tube 50 is hermetically sealed between the insulating backing 22 and the insulating layer 26 by the peripheral seal 58. Both the insulating backing 22 and the insulating layer 26 may be composed of a suitable plastic such as polyvinyl chloride or PVC. The ports 88 formed in the edge seal 58 as depressions at each opposite end of the insulating backing 22 enable connection to external flow tubes that interact with a pump 150 as shown in FIGS. 3a and 3b, and an electrolyte reservoir 140 as shown in FIGS. 3a and 3b. More specifically, the external flow tubes are the inlet tube 46, the outlet tube 50, and the electrical lead 54.

[0034] According to this particular embodiment, the insulating layer 26 includes a pattern of spaced conductive through-holes 66 formed along the surface of the insulating layer 26 on the opposite side of the conductive surface. The through-holes 66 according to this particular embodiment are defined by a set of equally spaced circular openings, although it will be understood that the through-holes can take other convenient shapes including, but not limited to, elliptical, diamond-shaped, and polygonal cross-sections. This latter feature creates one or more open areas of a size sufficient to allow ionic electrical conduction through the encapsulated electrolyte 80 (FIG. 2) to the adjacent layers of the formed fluid exchange electrode 10. In this particular example, the diameter of the vias 66 is 0.5 inches, although it can range from about 0.01 inches to 5.0 inches. The spacing between each of the conductive vias 66 is, according to this particular embodiment, about 0.75 inches center to center, although this parameter can range from about 0.01 inches to 5.0 inches.

[0035] Also, between the conductive electrode surface layer 14 and the insulating layer 26, a mechanical support mesh layer 30 is disposed to prevent entrapment of the formed flow chamber defined by the internal (open) volume 62. Preferably, the mechanical support mesh layer 30 is made of a moisture-resistant plastic mesh of plastic wire strands woven in a lattice pattern and assembled thereto. Alternatively, the support mesh layer 30 can be formed by injection molding. In this particular embodiment, the diameter of these wire strands is 0.05 inches, although the diameter of the plastic wire strands can range from 0.001 inches to 0.25 inches. Disposed under the insulating layer 26 is an ion-conductive assembly 32 which, according to this embodiment, is composed of a specialized ion-conductive membrane layer 34, an inner hydrogel layer 38, and an outer hydrogel layer 42, each of which is described in more detail below.

[0036] Figure 2 shows how the electrolyte solution flows through the fluid exchange electrode 10 of FIG. 1. More specifically, a volume of electrolyte solution, schematically shown as 80, is provided between the conductive electrode surface layer 14 and the insulating layer 26. Although the composition of the electrolyte solution will be described in detail, generally speaking, the electrolyte solution is composed of water, a conductive metal salt, and a neutralizing agent mixed in solution respectively. The neutralizing agent may include a hydroxide salt, a buffer, or a combination of each. A thickening agent may also be present in the solution, which can make the electrolyte solution into a viscous gel. The directional flow of the electrolyte solution 80 is functionally indicated by the arrow 70. The electrolyte solution 80 enters the electrode 10 laterally through the inflow tube 46 and exits the electrode 10 through the outflow tube 50. The ion conversion of energy is functionally indicated by the downward arrow 84. The conversion is from the conductive electrode surface layer 14, through the encapsulated electrolyte solution 80, and further, according to this particular embodiment, through the ion conductive assembly 32 composed of the ion conductive membrane layer 34 and the hydrogel layers 38, 42 respectively, into the body of a patient (not shown) and interacts with an infected metal implant (also not shown in this figure). This electrical current is driven by an external potentiostat, galvanostat, or power source (not shown) through the coupled electrical lead 54. As described herein, the inflow tube 46 and the outflow tube 50 can be coupled to an electrolyte reservoir such as 130 in FIGS. 3a and 3b through appropriate tubes to create a fluid circuit for the electrode body, or the outflow tube 50 can be connected to a waste container (not shown).

[0037] Other suitable variations and modifications of the electrode design may also be considered. For example, another alternative configuration for the counter or return electrode design is the incorporation of dual parallel channels as shown in Figures 4a and 4b. In briefly describing this latter embodiment, it is noted that for convenience, similar components are given the same reference numbers. As with the electrode 10, the fluid exchange electrode 212 according to this embodiment is composed of multiple components formed into a laminated structure. More specifically, the electrode 212 includes a conductive electrode surface layer 216, an insulating layer 228 having a pattern of spaced apart conductive perforations 66, and an insulating backing 224 that forms a coating for the electrode 212, with the insulating layer 228 and insulating backing 224 combining to form an internal flow chamber. The electrode 212 described herein further includes an ion-conducting assembly 32 configured according to this embodiment with an optional metal backing layer 220 and a mesh or support layer 240, respectively, disposed within the sealed interior volume 226 of the formed flow chamber, as well as an ion-conducting membrane layer 34 and inner and outer hydrogel layers 38, 42. As with previous designs, the ion-conducting assembly 32 is disposed beneath an insulating layer 228.

[0038] A difference compared to the conventional fluid exchange electrode design 10 of FIG. 1 is that the inlet tube 229 and the outlet tube 232 are located on the same side of the electrode body. This latter configuration allows two parallel channels to be formed within the defined interior volume 226, ensuring a path for electrolyte to circulate through the electrode 212. Additionally, the mechanical support mesh layer 240, the conductive electrode surface layer 216, and the optional metal backing layer 220 according to this embodiment are each modified to assume a substantially U-shape with openings toward the parallel inlet tube 229 and outlet tube 232. An additional seal location is provided within the openings by recessed portions 227 of the insulating backing 224 between the channels of each of the U-shaped layers, and the insulating backing 224 is sealed to the insulating layer 228. This additional seal created by the recessed portions 227 creates parallel channels defined as part of the open interior volume 226 within the fluid exchange electrode 212.

[0039] Next, for each of the aforementioned electrode designs, the embodiments of the ion conductive assembly 32 disposed under the insulating layers 26, 228 will be described. One problem the applicant encountered during the development of the present invention was to maintain the integrity of the outer hydrogel layer 42 in contact with the skin, especially when the aqueous electrolyte solution 80 was in direct contact with the outer hydrogel layer 42. A hydrogel is typically a solid gel material composed of a fibrous mesh, water, and a conductive salt. These materials are commonly used to bring the stimulating surface of a sensor or electrode into contact with the skin. It is known behavior of hydrogels that they swell very much when in contact with an aqueous solution, and thus their mechanical durability and adhesiveness are impaired. The initial design intention of the present invention was to directly adhere the hydrogel layer to the outside of an insulating layer having conductive perforations 66 spaced apart, which could then be adhered to the patient's skin. Conduction could then proceed from the layer of conductive electrode material within the internal volume of the electrode, through the electrolyte solution 80 and the conductive perforations 66, and ultimately through the hydrogel layer(s) to the patient's skin. Of course, when the internal volume of the electrode was filled with an electrolyte in contact with the hydrogel, the hydrogel swelled to a level that impaired the usefulness of the electrode in a short period of time.

[0040] Accordingly, there is a recognized need for an additional ion-conductive membrane layer 34 disposed between the inner hydrogel layer 38 and the insulating layer 26 (direct contact via the conductive vias 66 of FIG. 1) that allows for ion conduction while also restricting water transport. By "ion conduction" it is meant that the ion-conductive membrane layer 34 cannot be formed from a piece of metal, for example, a metal requires that electrons be transported electrically rather than ionically, which causes redox reactions on each side of the metal and thus invalidates the purpose of the ion-conductive membrane layer since acid accumulates in the hydrogel. In this embodiment, the membrane layer 34 has a volume resistivity of less than 1,000 ohm-cm, although the ion-conductive membrane layer 34 may have a volume resistivity of less than 1,000,000 ohm-cm. In the embodiments described herein, the thickness of the ion-conductive membrane layer 34 is 100 to 200 micrometers, although it will be understood that the thickness of this layer 34 may be included within any of the ranges from 1 micrometer to 1 centimeter. As described herein, several classes of materials were evaluated and considered suitable for the application, although among the available options, certain classes of materials have different properties that lead to subsequent deficiencies in performance, utility, or manufacturability. More specifically, it was determined that the following classes of materials, namely, solid electrolytes, anion exchange membranes, and cation exchange membranes, could be considered.

[0041] Examples of solid electrolytes include NASICON or LISICON. Anion and cation exchange membranes commonly used in chlor-alkali production cells are additional options for the ion-conductive membrane layer 34. Anion exchange membranes are generally made from ionomers and are semi-permeable membranes designed to conduct anions such as hydroxide ions while rejecting gases such as oxygen or hydrogen and cations. Cation exchange membranes allow the transport of cations such as protons and sodium ions while blocking the conduction of anions such as hydroxide. This transport makes it possible to have a higher conductivity compared to anion transport membranes and provides minimal additional voltage requirements for CVCES-based or other treatment stimulation devices. Cation exchange membrane materials can very easily accept free electrons, making this material conductive. Thus, when this cation exchange material is laminated to a hydrogel, the water in the hydrogel, which consists of H+ ions and -OH groups, is separated as the cation exchange membrane absorbs the -OH groups and leaves excess H+ in the water, lowering the pH of the hydrogel. Also, as part of its conduction mechanism, when the cation exchange membrane material is exposed to water, the material self-organizes into nanocavities through which water can diffuse. The diffusion of water facilitates at least part of the proton transport, which is an important factor in its ion conductivity. Since the diffusion of water affects the mechanical and adhesion properties of the laminated hydrogel, many cation exchange membranes preferably have a limit on the length through which the counter electrode can flow saline before the hydrogel becomes saturated. Cation exchange membranes can be a preferred choice for use as ion-conductive membranes that separate the hydrogel from the electrolyte solution. These membranes have limitations such as allowing proton diffusion (which affects the requirements for electrolyte flow) and weak water diffusion, but these limitations are further explained by the design features of the electrodes described further below.

[0042] In certain embodiments described herein, the selection of the cationic membrane for use as the ion conductive membrane layer 34 is subject to certain limitations as described above. These limitations can be mitigated by the design considerations of at least one of the hydrogel layers 38, 42 in contact with the ion conductive membrane layer 34 that forms the ion conductive assembly 32. The electrodes according to the present invention can have at least one hydrogel layer disposed between the ion conductive membrane layer 34 and the patient's skin surface (not shown), and can have up to five hydrogel layers. As shown in the embodiments of FIGS. 1 and 2, two hydrogel layers 38 and 42 are provided, although an electrode design based on a single hydrogel layer can also be advantageous. It should be noted that certain hydrogel properties can be modified and advantageous effects can be achieved, if desired, by having different hydrogel layers laminated together. Parameters to be considered in electrode design include conductivity, pH, and levels of components that can affect mechanical properties. As seen in FIG. 1, the inner hydrogel layer 38 contacts the ion conductive membrane layer 34 to the outer hydrogel layer 42, and then the outer hydrogel layer 42 contacts directly the patient's skin surface (not shown) on which the electrode 10 is disposed.

[0043] According to this embodiment, the inner hydrogel layer 38 and the outer hydrogel layer 42 exhibit a buffering system similar to that described in International Publication No. WO 2021 / 178040 A1, which is hereby incorporated by reference in its entirety. The buffering compound(s) present in the hydrogel layer(s) bind to any hydrogen ions that have diffused through the hydrogel layer and neutralize them. Thus, the pH at the patient skin interface cannot begin to decrease until the buffering capacity of the hydrogel is completely depleted, thus adding yet another layer of patient safety to enable the long-term use of the electrodes described herein. In at least one embodiment, the initial pH of the buffered hydrogel is 7, although this parameter can be varied in the range from mildly acidic (pH = about 5) to fully basic (pH = 12). In at least one embodiment, the buffering compound used in the hydrogel layers 38, 42 is magnesium acetate, although it is understood that other suitable buffering compounds can be selected for use.

[0044] In addition to introducing the electrolyte solution and the ion-conductive membrane layer 34 that flow according to the electrode design of the present invention, there are additional design considerations to counter the slow diffusion of water through the ion-conductive membrane layer 34. One such consideration is the cross-link density of the hydrogel. Polymer meshes or matrices are components of almost all hydrogels. These meshes are designed to trap water within them and enable the hydrogel to be in a solid form. A hydrogel is produced when an uncured liquid gel is exposed to irradiation that links the polymer chains together, thus creating a polymer matrix that cures the gel. Therefore, there is an inverse relationship between the cross-link density and both the gel adhesiveness and its ability to absorb water in its body. Thus, a gel exposed to higher irradiation during manufacture will have lower adhesiveness but higher resistance to mechanical changes from water. Knowing this, the inner hydrogel layer 38 can include a higher level of cross-link density than the outer hydrogel layer 42. By having the inner hydrogel layer 38 with a higher cross-link density, water diffusion through the ion-conductive membrane layer 34 is slowed due to the resistance of the highly linked hydrogel to mechanical swelling. This creates two factors that slow the transport of water to the skin interface (outer) hydrogel layer 42, one factor being the ion-conductive membrane layer 34 and the second factor being the highly cross-linked hydrogel. The inner hydrogel layer 38 can optionally have smaller size dimensions that allow the outer hydrogel layer 42 to seal both the ion-conductive membrane layer 34 and the inner hydrogel layer 38 at the outer boundary or edge to the insulating layer 26, so the loss of adhesion in the inner hydrogel layer 38 has less impact on the usefulness of the electrode 10 than the loss of adhesion of the outer hydrogel layer 42 that contacts the skin.

[0045] Another problem that exists relates to optimizing the flow rate and electrolyte parameters in order to effectively extend the treatment life while maintaining the usability of the electrodes for the patient. In this embodiment, the cation exchange membrane is used as the material for the ion conductive membrane layer 34, and thus allows protons (units of acid) to easily diffuse into the outer hydrogel layer 42 of the skin interface. The electrolyte flow must be optimized to dispose of these protons before they can reach the ion conductive membrane layer 34. This optimization can be done through a balance of two main parameters. Namely, the proton neutralizing compound and the electrolyte flow rate. First, the effect of the proton neutralizing compound in the electrolyte should be considered. Similar to the buffer compound in the hydrogel layer, the flowing electrolyte may also contain a compound that neutralizes protons. Neutralizing agents for this purpose may include chemical buffers, hydroxide salts, or combinations of each. Both of these types of neutralizing agents bind to protons and neutralize the acid, but depend on different mechanisms. More specifically, a buffer is an aqueous solution consisting of a mixture of a weak acid and its conjugate base. When there are excess hydrogen ions in the solution, the conjugate base protonates the hydrogen ions to become a weak acid. Alternatively, if the solution is too basic, the weak acid deprotonates its proton to form water and its conjugate base, thus maintaining the pH within a range specific to that compound. In a preferred embodiment, the buffer compound used in the flowing electrolyte is potassium bicarbonate, although it is understood that other buffer compounds may be selected.

[0046] Other neutralizing agents, namely hydroxide salts, are compounds that dissociate into hydroxide ions and cations. The ratio of hydroxide ions to protons in a solution literally determines the pH value of the solution. In a state where a large amount of hydroxide ions are dissolved in the flowing electrolyte, the protons generated at the anode combine with the free hydroxide to form water. Both agents are applicable for neutralizing protons, but the use of a buffer may be more desirable for safety reasons. This safety issue relates to how the volume of these agents affects the pH level of the flowing electrolyte. To maximize electrode life, it is beneficial to add as much buffer or hydroxide salt (limited by their solubility) as possible. In the case of hydroxide ions, dissolving as much hydroxide salt as possible would result in an undesirably high pH fluid. If the electrode is damaged and leaks, this fluid can cause significant irritation or damage to the skin. On the other hand, a buffer can be filled to volume, maintain a neutral pH, and still have the same neutralizing ability as the hydroxide salt. A buffer compound, hydroxide salt, or a combination of each can be used, but it is understood that the buffer compound is preferred.

[0047] Other important parameters of the flowing electrolyte that optimize treatment life and usability for the patient are the reservoir volume and the flow rate. To better understand the reservoir system as a whole, refer to Figure 3a, which schematically shows a patient's limb 104 (partially shown) having a metal implant 108 embedded in the joint space. Fully assembled fluid double-channel fluid exchange electrodes 212, such as those in Figures 4a and 4b, are shown as an example. The electrode 212 is adhered to the limb 104 as the counter electrode of a CVES-based treatment system. In this example, the electrode 212 is adhered to the patient's leg and is configured to provide a DC stimulus, represented by arrow 120, to the implant 108 through the connection of the electrode to a potentiostat 130 having electrical leads 54 and respective communication lines 134 and 136 to the implant 108. Details regarding an exemplary treatment system are provided in International Publication No. WO 2021 / 146238A1, which is incorporated herein by reference in its entirety. The inlet tube 228 and the outlet tube 232 of the electrode 212 are in contact with the electrolyte reservoir 140. The electrolyte 144 in the reservoir 140 is facilitated to pass through the electrode 212 via a pump 150. The pump 150 is configured to control the flow rate of the electrolyte solution 144 at a specific RPM value. As further shown in Figure 3a, the treatment life can be monitored, for example, using either the Coulomb (charge) counting software or firmware that may be provided on the potentiostat 130, or this monitoring can be achieved using an integrated pH sensor 160 in the electrolyte reservoir 140, where the pH sensor 160 can provide feedback to release more solid neutralizing agents, shown as 161, into the electrolyte reservoir 140.

[0048] The reservoir 140 of the electrolyte 144 can literally be of any size, and thus it is understood that the reservoir 140 can theoretically hold an electrolyte solution 144 of infinite volume. This is an ideal situation as there is an infinite supply of neutralizing agent and thus the electrode life can be infinite with respect to preventing acid accumulation in the membrane and the hydrogel layer. However, an infinite or very large volume reservoir is undesirable or not practical from the perspective of usability for patients. Further, the ideal situation from the perspective of usability is to have the smallest possible reservoir volume (less mobility restrictions, the device is lighter, etc.). Thus, the reservoir 140 is optimized to contain an electrolyte 144 with a reservoir volume of about 100 mL to 1 L in one preferred embodiment. However, it is understood that the volume of the reservoir 130 can functionally vary somewhere between about 10 mL and 1000 L of electrolyte.

[0049] In contrast to the buffer, when using an electrolyte solution containing a hydroxide salt, the contents of reservoir 140 can be sent to the electrodes by pump 150 programmed to operate at a specified flow rate. In one preferred embodiment, the flow rate of pump 150 can be determined by the level of current controlled by potentiostat 130. The aforementioned control is important because the amount of current generated through the electrode / treatment system determines the number of protons generated within fluid exchange electrode 212. If an inappropriate or insufficient amount of fresh electrolyte solution is pumped into electrode 212 (i.e., too much or too little fluid), the electrolyte solution volume within the electrode body may become too alkaline or too acidic because the rate of proton generation does not match the rate of proton neutralization. If the electrolyte solution becomes too acidic, risk factors for patient skin and electrode damage occur, whereas if the electrolyte solution within the electrode becomes too alkaline, it is only dangerous if the electrode is damaged and leaks. Therefore, if pump 150 can update its flow rate continuously or at least periodically to match the generation of new protons (determined by the current), the pH within fluid exchange electrode 212 can be effectively maintained at an appropriate level. Communication of the measured current to pump 150 is facilitated via a separate communication line 154. Alternatively, if electrolyte solution 144 uses a buffer solution, pump 150 can be programmed to operate at a constant flow rate.

[0050] Figure 6 shows experimental data collected using a benchtop prototype of a version of the fluid exchange electrode that details at least some of the advantageous effects of the present invention. The prototype electrode used in the experiment included an orthopedic implant cathode chamber separated from the fluid exchange electrode by 3% agar containing 0.9% NaCl, which represents human tissue in terms of mechanical and electrical values. Hydrogel and ion conductive membrane layers were applied to the agar surface as they would be found in a clinical setting. Behind the membrane layer, a sealed flow cell or chamber was established to analyze how the electrolyte through which current flows from the anode interacts. In this flow cell, the anode current, pump flow rate, concentration of neutralizing agent, and treatment time can be adjusted to assist in understanding and optimizing the electrode.

[0051] Referring to the graph of Figure 6, five exemplary experiments or tests were conducted, and the results were provided in graph 500, where the pH of the sealed flow chamber was tracked over 6 hours. In each of these specific experiments, the initial pH value in the chamber was approximately 7. At time 0, a 200 mA DC stimulus was turned on (for all of the shown experiments), and an external coupled pump was turned on to the RPM values indicated by the key of the graph. More specifically, the following RPM values were used: 50 rpm, 5 rpm, 15 rpm, 10 rpm, and 10 rpm, which are represented by trend lines 504, 508, 512, 516, and 520, respectively. For all tests except trend line 520 (10 rpm buffer), the inflowing electrolyte had a pH of 12. As collected from Figure 6, at higher RPM values (higher flow rates) such as 50 rpm and 15 rpm, referring to trend lines 504, 512, the inflow of the pH 12 electrolyte overwhelms the production of protons at the anode, the total volume becomes alkaline, and if the electrode is punctured or otherwise allowed to leak, a danger is created.

[0052] Furthermore, at 5 rpm, proton production overwhelms the slow influx of the basic electrolyte, becoming too acidic and potentially diffusing through the membrane layer and ultimately reaching the skin surface. At 10 RPM, referring to trendline 516, the pH balance initially rises but then begins to decrease towards acidic levels. At around 150 minutes, a boost of solid NaOH was added to the filling chamber, and as the NaOH dissolved, the pH rose to 10 and then decreased again in a similar pattern. The addition of the NaOH boost illustrates how the chamber pH can be maintained within an acceptable range by monitoring the solution pH, such as by using a pH sensor and control system with software that can later add a soluble neutralizer. This feature can be automated by incorporating it into the electrode system. For the remaining tests, referring to trendline 520, it is clear that both the chamber electrolyte and the incoming electrolyte are buffered with potassium bicarbonate, maintaining the pH stably at around 8 throughout the test. This trendline shows the advantage of using a buffer. However, at a certain extrapolated point, the buffer ultimately reaches its capacity and then the pH begins to decrease. After analyzing this data, it is clear that flow rate is more important when using a hydroxide salt and less important when using a buffer. In the case of a buffer, the pH remains stable until the buffer capacity of the total volume (reservoir + electrode) is exceeded, unless the pump flow rate becomes exceptionally slow before the internal volume of the electrode begins to exceed its buffering capacity and new buffer can flow in.

[0053] Another negative aspect of conventional electrode designs used for cathode DC voltage treatment of implant biofilms is that they inadequately reduce skin heat increase, especially at higher treatment levels. In addition to each of the aforementioned advantages, the design described herein provides an excellent mechanism for cooling the heat increase at the interface between the skin and the electrode. The tissue between the implant through which the treatment current flows and the electrode body is thought to heat according to the conventional rule that circuit components with higher resistance dissipate greater heat loss. Skin, having a greater resistance compared to muscle or other body fluids, is thought to experience a higher temperature rise in the presence of high treatment currents. This is evident in tests conducted using previous generation electrodes without a fluid flow component, as measured using temperature probes at different parts of the tissue. The design described herein, having a certain circulating volume of electrolyte solution, has been shown to substantially increase the cooling effect of the outer plate compared to previous generations under the same test parameters. The mechanism behind the increased cooling efficiency is thought to be the fact that skin heat can be absorbed not only by the thin hydrogel provided between the stimulation surface of the conventional known design and the skin, but also by a large volume of fluid. Also, since the fluid is constantly flowing with respect to the reservoir, the volume of the heat sink is limited to the volume within the electrode compartment but extends to the total volume between the electrode and the reservoir.

[0054] Further design improvements related to the electrode system, and more specifically to the electrolyte reservoir, can enhance the already improved thermal regulation characteristics of the fluid exchange electrode design. The thermal regulation of the skin can be further improved when the fluid volume is cooled to a lower temperature. To do this, according to at least one version shown in FIG. 3b, where like parts are labeled with the same reference numbers for clarity, the system can incorporate a cooling element 170 within the electrolyte reservoir 140 that can control the fluid temperature. This cooling element 170 can exist in a plurality of forms including, but not limited to, a compressor or a refrigeration unit using chemicals, or a thermoelectric device. Ideally, the fluid should be as cold as possible (without freezing) to achieve the maximum result. However, depending on how much treatment current is flowing through the tissue, maximum cooling is not always necessary and can simply be a waste of power. For this latter reason, the system may further employ a temperature sensor 174 and a software feedback mechanism 178 shown schematically, and the software feedback mechanism 178 may include a controller. The software feedback mechanism 178 can actively take the system's temperature measurements and, if necessary, control the cooling element 170 to keep the skin at the desired temperature. The temperature sensor 174 may preferably be located within the skin-hydrogel interface or alternatively may be disposed either within the body of the electrode 212 or within the electrolyte reservoir 140. The aforementioned arrangement of the thermal regulation features can be arranged separately as shown in the system of FIG. 3b or can be included in the system configuration of FIG. 3a.

[0055] Using the electrode design of FIG. 1 as an example for electrode manufacturing, the first step in assembling this design is to attach the metal backing layer 18, more specifically its bottom surface, to the upper surface of the conductive electrode surface layer 14. To do this, the material must be cut and measured to a specific size configuration and often must be arranged such that there is a uniform boundary of the conductive electrode surface layer 14 that extends beyond the periphery of the metal backing layer 18 on all sides, which is often referred to as an "island arrangement". As described above, by recessing the metal backing layer 18 in this way, the electrolyte solution 14 of FIG. 2, which is typically made of copper or silver and could potentially corrode the metal backing layer 18, is prevented from contacting the metal backing layer 18. The metal backing layer 18 can be attached to the conductive electrode surface layer 18 using a strong conductive adhesive that can be spread evenly.

[0056] The next step is to connect the electrical lead 54 to the metal backing layer 18 so as to ensure electrical contact with the surface of the metal backing layer 18. Again, the metal backing layer 18 must be sealed so as to limit contact with the electrolyte solution 80 (FIG. 2) passing therethrough. To address this problem, a water-resistant adhesive can be used on the extended boundary of the conductive electrode surface layer 14 and sealed to the "ceiling" of the insulating backing 22, with the metal backing layer 18 laminated therebetween. After aligning the inlet tube 46 and the outlet tube 50, in the correct orientation according to the following configuration, the edge or boundary 58 can be sealed except for the opening for inserting the mechanical support mesh layer 30. Alternatively, if the selected configuration is the dual-channel electrode 212 characterized in FIGS. 4a and 4b, a central seal should not be performed at this stage. These layers can preferably be adhered using a heat source. Next, the mechanical support mesh layer 30 can be disposed within the opening formed between the conductive electrode surface layer 14 and the insulating layer 26. Then, the remaining openings are sealed and closed. During this latter step, it should be ensured that the connection of the end of the electrical lead wire 54 is outside the seal layer. Separating the partially assembled unit, according to these specific designs, the ion-conductive membrane layer 34 is then sealed to the inner hydrogel layer 38, ensuring that there are equally extended boundaries of the remaining hydrogel layer 38. No additional adhesive is required when attaching these two layers. Next, the outer hydrogel layer 42 is aligned and attached to the inner hydrogel layer 38. As previously described, the hydrogel "layer" can be a single layer having one hydrogel, or can include multiple hydrogel portions as described in this embodiment, or can be separate discrete hydrogel layers. Finally, the partially assembled unit is attached to the hydrogel assembly. An adhesive compatible with the insulating layer 26 is applied, and this adhesive is applied to the boundary of the inner hydrogel layer 38 to seal the boundary of the inner hydrogel layer 38 to the insulating layer 26, completing the ion-conductive assembly 32. When assembled, the ion-conductive membrane layer 34 is beneath the insulating layer 26 and is disposed in direct contact with the insulating layer 26.

[0057] As described above, the configuration of the fluid exchange electrode 10 is characterized in FIG. 1 that defines a straight or linear flow into a defined flow chamber within the electrode body via the inlet tube 46 and the outlet tube 50. Alternatively, FIGS. 4a and 4b show a configuration having parallel flow paths defined within the electrode body, the structure being fluidly sealed at each of the four sides of the insulating layers 22, 26 of FIG. 1, which can be done using simple tools. However, it will be understood that these configurations can be easily deformed into longer devices such as those shown as electrodes 312 and 412, as shown in FIGS. 5a and 5b. These configurations have the same assembly process and layered structure as electrode 212, electrode 312 having a longer length dimension to allow for greater surface area contact with the patient's skin, and electrode 412 having a greater width dimension than the width dimension of electrode 212. Having the ability to manufacture fluid exchange electrodes with different lengths and widths allows the electrodes to adhere around the limbs or limbs of patients of different sizes. By extending the electrodes around most of the perimeter of the patient's limb, a treatment that is uniformly distributed with respect to the implant itself is provided. However, unlike the prior art described in the applicant's International Publication No. WO 2021 / 178040A1, the fluid exchange electrode has the ability to neutralize and eliminate acid accumulation regardless of the size of the surface area, and thus does not rely on a large surface area of the stimulation surface to extend the life of the electrode. For this reason, the fluid exchange electrodes described herein do not necessarily have to be a completely circumferential wrap. That is, the fluid exchange electrode can be fabricated as a plurality of smaller electrode shapes or nodes that can be more strategically placed around the limb or implant to promote uniform treatment and optimize space.

[0058] Although the present invention has been described with respect to specific variations and exemplary figures, those skilled in the art will recognize that the present invention is not limited to the variations or figures described. Further, if the above methods and steps indicate specific events occurring in a specific order, those skilled in the art will recognize that the order of the specific steps can be modified and that such modifications are in accordance with variations of the present invention. Further, some of the steps may be performed simultaneously in a parallel process, if possible, or sequentially as described above. Accordingly, as long as there are variations of the present invention that are within the scope of the spirit of the present disclosure or equivalent to the present invention found in the claims, it is intended that this patent also encompasses those variations.

[0059] As long as the claims recite the phrase "at least one of" with respect to a plurality of elements, this is intended to mean at least one or more of the recited elements and is not limited to at least one of each element. For example, "at least one of element A, element B, and element C" is intended to indicate element A alone, or element B alone, or element C alone, or any combination thereof. "At least one of element A, element B, and element C" is not intended to be limited to at least one of element A, at least one of element B, and at least one of element C.

[0060] The terms used in this specification are for the purpose of describing particular embodiments only and are not intended to be limiting. As used in this specification, the singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Further, "comprise" (and any form of comprise such as "comprises" and "comprising"), "have" (and any form of have such as "has" and "having"), "include" (and any form of include such as "includes" and "including"), and "contain" (and any form of contain such as "contains" and "containing") are to be further understood as open-ended conjunctive verbs. As a result, a method or apparatus that "comprises", "has", "includes", or "contains" one or more steps or elements possesses those one or more steps or elements but is not limited to possessing only those one or more steps or elements. Similarly, a step of a method or an element of an apparatus that "comprises", "has", "includes", or "contains" one or more features possesses those one or more features but is not limited to possessing only those one or more features. Further, an apparatus or structure configured in a certain way is at least configured in that way but may also be configured in ways not recited.

[0061] All means or steps, plus function elements, in the following claims, corresponding structures, materials, acts, and equivalents, if any, are intended to include any structure, material, or act for performing the functions in combination with other claimed elements specifically claimed. The descriptions set forth herein are presented for purposes of illustration and description but are not intended to be exhaustive or limited to the forms disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the present disclosure. Embodiments are chosen and described in order to best explain the principles and practical applications of one or more aspects described herein, as well as to enable others of ordinary skill in the art to understand the disclosure for various embodiments with various modifications that are suited to the particular uses contemplated and are in accordance with the following appended claims. Additional embodiments include any one of the embodiments described above and explained in any and all exhibits and other materials submitted herewith, one or more of whose components, functionality, or structure are exchanged with, thereby replaced by, or thereby enhanced by one or more of the components, functionality, or structure of the different embodiments described above.

[0062] This detailed description uses examples to disclose the invention, including the best mode, and to enable a person of ordinary skill in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims and can include other examples that occur to a person of ordinary skill in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims or if they include equivalent structural elements that do not differ substantially from the literal language of the claims. It is understood that other suitable modifications and variations will be readily apparent and understandable to those of ordinary skill in the art reading the foregoing detailed description and will be further understood from the claims listed below.

Description of the Reference Numerals

[0063] List of parts in FIGS. 1 - 6 10 pair or return (fluid exchange) electrodes 14 Conductive electrode surface layer 18 Metal backing layer 22 Insulating backing 26 Insulating layer 30 Mesh support layer 32 Ion conductive assembly 34 Ion conductive membrane layer 38 Inner hydrogel layer 42 Outer hydrogel layer 46 Inflow tube 50 Outflow tube 54 Conductive wire 58 Edge seal 62 Internal (open) volume 66 Pattern of conductive perforations 70 Arrow 80 Electrolyte or electrolyte solution 84 Arrow 88 Port 104 Leg, patient 108 Implant 120 Arrow, charge / current 130 Potentiostat 134 Line 136 Line 140 Electrolyte reservoir 144 Volume of electrolyte or electrolyte solution 150 Pump 154 Line 160 pH sensor 161 Neutralizing agent 164 Buffer 170 Cooling element 174 Temperature sensor 178 Software feedback mechanism 212 Fluid exchange electrode 216 Conductive electrode material layer 220 Metal backing layer 224 Insulating backing 226 Open chamber 227 Recess 228 Insulating layer 229 Inflow pipe 232 Outflow pipe 240 Mesh support layer 312 Electrode 412 Electrode 500 Graph 504 Trend line 508 Trend line 512 Trend line 516 Trend line 520 Trend line

Claims

1. A fluid exchange electrode, comprising an electrode body, a conductive electrode material layer disposed within the electrode body, an ion conductive assembly configured to contact the skin surface of a patient, an inlet tube and an outlet tube coupled inside the electrode body, the inlet tube being configured to connect to an electrolyte source to enable a volume of electrolyte to flow through the electrode body, the inlet tube and the outlet tube; and a fluid exchange electrode including the same.

2. The electrode according to claim 1, wherein the conductive electrode material layer is formed from at least one selected from the group consisting of carbon vinyl, platinum, and rhodium.

3. The electrode according to claim 1, further comprising an insulating layer and an insulating coating combined to define a flow chamber within the electrode body to which the inlet tube and the outlet tube are attached, the conductive electrode material layer being disposed within the flow chamber.

4. The electrode according to claim 3, wherein the insulating layer includes a plurality of spaced conductive perforations.

5. The electrode according to claim 3, further comprising a support layer disposed between the conductive electrode material layer and the insulating layer.

6. The electrode according to claim 4, wherein the inlet tube and the outlet tube are disposed on both sides of the electrode body.

7. The electrode according to claim 4, wherein the inlet tube and the outlet tube are each disposed in a parallel relationship on one side of the electrode.

8. The electrode according to claim 4, wherein the ion conductive assembly is disposed under the defined flow chamber.

9. The ion-conductive assembly includes an ion-conductive membrane layer disposed between one or more hydrogel layers and the insulating layer, and the conductive perforations of the ion-conductive membrane layer enable ion conduction to the membrane layer. The electrode according to claim 8.

10. The ion-conductive membrane layer is made of at least one of the group consisting of a cation exchange membrane, an anion exchange membrane, or a solid electrolyte. The electrode according to claim 9.

11. The ion-conductive membrane layer is made of a cation exchange membrane. The electrode according to claim 10.

12. The electrode according to claim 3, further comprising a metal backing layer disposed between the conductive electrode material layer and the insulating coating.

13. The extension lead is attached to one of the metal backing layer and the conductive electrode material layer, and the extension lead is configured to be attached to a voltage source. The electrode according to claim 12.

14. The one or more hydrogel layers are connected to the ion-conductive membrane layer. The electrode according to claim 9.

15. At least one of the one or more hydrogels is buffered. The electrode according to claim 14.

16. The buffer is magnesium acetate. The electrode according to claim 15.

17. There are two or more hydrogels, and the hydrogel connected to the ion-conductive membrane layer has a higher cross-linking density than the hydrogel configured to contact the skin surface of the patient. The electrode according to claim 15.

18. A system for treating a metal implant for the removal of bacteria, the system comprising: A device capable of generating a DC voltage, The working electrode coupled to the device capable of generating a DC voltage, the working electrode being the metal implant, The counter electrode coupled to the device capable of generating a DC voltage, A conductive electrode material layer disposed within the flow chamber of the electrode, A counter electrode comprising a multi-layer electrode body having an ion conductive assembly configured to make direct contact with the skin of a patient, and An electrolyte source coupled to the counter electrode and configured to allow a volume of electrolyte to flow through the electrode body, A system comprising. **Claim 19** The system according to claim 18, further comprising a pump coupled to the electrolyte source and configured to facilitate flow to the counter electrode. **Claim 20** The system according to claim 19, wherein the counter electrode includes an inlet tube and an outlet or return tube, each of which is coupled to the electrolyte source. **Claim 21** The system according to claim 19, wherein the counter electrode includes an inlet tube and an outlet tube, the inlet tube being connected to the electrolyte source and the outlet tube being connected to a waste container. **Claim 22** The system according to claim 18, wherein the electrolyte includes at least one dissolved salt. **Claim 23** The system according to claim 22, wherein the at least one dissolved salt is sodium chloride. **Claim 24** The system according to claim 22, wherein the electrolyte further includes at least one neutralizing agent. **Claim 25** The system according to claim 21, wherein the at least one neutralizing agent is at least one of a hydroxide salt and a buffer. **Claim 26** The system according to claim 21, wherein the electrolyte is cooled to enhance heat regulation of the skin of the patient to which the electrode is attached.

27. The system according to claim 26, wherein the electrolyte is cooled to a temperature between 30 degrees Fahrenheit and 98 degrees Fahrenheit.

28. The system according to claim 18, wherein the electrolyte is a viscous gel.

29. The system according to claim 18, wherein the conductive electrode material layer is made from one of the group consisting of carbon vinyl, platinum, and rhodium.

30. The system according to claim 29, wherein the flow chamber is defined by an insulating layer and an insulating coating sealed to each other.

31. The system according to claim 30, wherein the counter electrode further comprises a support sheet disposed within the flow chamber to prevent collapse of the flow chamber.

32. The system according to claim 18, further comprising an electrical lead coupling the counter electrode to the device capable of generating a DC voltage, the electrical lead being attached to either the conductive surface electrode layer or a metal backing sheet disposed in contact with the conductive surface electrode layer.

33. The system according to claim 30, wherein the insulating layer includes a plurality of conductive perforations, and the ion conductive assembly of the counter electrode includes an ion conductive membrane layer attached to the insulating layer and at least one hydrogel layer.

34. The system according to claim 33, wherein the at least one hydrogel layer is connected to the ion conductive membrane layer.

35. The system according to claim 34, wherein the ion conductive assembly is made from one of the group consisting of a cation exchange membrane, an anion exchange membrane, or a solid electrolyte.

36. The system according to claim 35, wherein the ion conductive membrane layer is made from a cation exchange membrane.

37. The system according to claim 19, wherein the electrolyte source is a reservoir.

38. The system according to claim 37, wherein the reservoir holds about 1 mL to 1000 L of electrolyte.

39. The system according to claim 38, wherein the reservoir holds about 100 mL to 1 L of electrolyte.

40. The system according to claim 37, comprising a pH sensor disposed within the reservoir and configured to detect a change in a neutralizing agent.

41. The electrolyte includes at least one of a buffer and a hydroxide salt, and the system is configured to automatically add a neutralizing agent to the reservoir based on a change detected by the pH sensor or based on an indication of a change for replacement of the electrolyte within the reservoir. The system according to claim 40.

42. The fluid reservoir includes a cooling element configured to actively cool the electrolyte to maintain and regulate the temperature of the electrolyte to optimize heat mitigation of the patient's skin. The system according to claim 37.

43. The system according to claim 42, wherein the cooling element is part of a sealed system using a chemical refrigerant.

44. The system according to claim 42, wherein the cooling element is a thermoelectric cooling device.

45. The system according to claim 42, further comprising a temperature sensor disposed within the reservoir and configured to detect a change in the temperature of the electrolyte within the reservoir.

46. The system according to claim 43, comprising a closed-loop feedback mechanism having the temperature sensor and a controller coupled to the temperature sensor, the controller being configured to control the chemical refrigerant to adjust the temperature of the electrolyte.

47. The system according to claim 37, wherein the apparatus configured to apply a DC voltage is further configured to monitor charge through the counter electrode.

48. The system according to claim 47, further comprising a controller configured to automatically add a neutralizing agent based on the monitored charge at the counter electrode or further comprising control logic indicating that replacement of the electrolyte in the reservoir is necessary.

49. The system according to claim 40, wherein the electrolyte is not buffered and contains at least one hydroxide salt, and the system further comprises control logic for adjusting the flow rate of the pump based on the monitored current from the apparatus capable of generating a DC voltage.

50. A method for extending the life of an electrode used in a biofilm removal treatment of an implant by a cathodic DC current, the method comprising: coupling an electrolyte source to the electrode; circulating an electrolyte solution through the electrode during treatment, and the electrode includes an electrode body having an internal flow chamber disposed between a pair of insulating layers and a conductive electrode surface layer disposed within the defined flow chamber, the method further comprising: providing a plurality of conductive perforations in one of the insulating layers; providing an ion conductive assembly under the insulating layer having the plurality of perforations and under the skin surface of the patient.

51. The method according to claim 50, wherein the ion conductive assembly includes an ion conductive membrane layer and one or more hydrogel layers, and the hydrogel layer is configured to be in direct contact with the skin surface of the patient. Claim 52 The method according to claim 51, wherein the ion conductive membrane layer is made from one of the group consisting of a solid electrolyte, a cation exchange membrane, and an anion exchange membrane. Claim 53 The method according to claim 52, wherein the ion conductive membrane layer is made from a cation exchange layer. Claim 54 The method according to claim 53, wherein the electrolyte contains at least one dissolved salt. Claim 55 The method according to claim 54, wherein the at least one dissolved salt is sodium chloride. Claim 56 The method according to claim 54, wherein the electrolyte further contains at least one neutralizing agent. Claim 57 The method according to claim 56, wherein the at least one neutralizing agent is at least one of a hydroxide salt and a buffer. Claim 58 The method according to claim 50, wherein the electrolyte is directed to flow through the electrode and the used electrolyte is recycled to the electrolyte source. Claim 59 The method according to claim 50, wherein the electrolyte is directed to flow through the electrode and the used electrolyte is directed to a waste container.

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