Apparatus and method for removing biofilm from metallic devices

Abstract

A method and apparatus for removing biofilm from or reducing bacterial adhesion to a metallic medical device 40 outside a human or animal body. The method includes connecting a first electrode 50 to a surface of the medical device 40, exposing a target area on the surface of the medical device 40 to an electrolyte fluid 14, positioning a second electrode 20 proximate the target area, and providing electrical power between the first electrode 50 and the second electrode 20 such that electrolysis occurs in the electrolyte fluid, the electrical power including a plurality of electrical pulses, a potential difference between the first electrode and the second electrode being at least 1 V, and a current density applied in each electrical pulse being at least 1 V per 1 cm of the target area. 2 The maximum is 15A per

Description

[Technical field]

[0001] The present disclosure relates to an apparatus and method for removing biofilm and / or bacteria from metallic medical devices. [Background technology]

[0002] Infection, whether acute or chronic, is a common complication after implantation of a prosthesis or osteosynthesis material in a patient, which is associated with high morbidity, very high mortality and high economic costs for the available treatments.

[0003] Despite many advances in sterilization techniques and systemic and local prophylactic antibiotic therapy in recent years, infection rates remain between 0.3% and 25%, depending on the type of intervention and size of implant used. Although the exact pathophysiology of orthopedic hardware infection is unclear, it is known that infection of orthopedic hardware is preceded by 1) contamination of the surgical site, 2) bacterial adherence, and 3) biofilm formation on the prosthetic material.

[0004] Currently available methods are unable to destroy all of the biofilm present on the surface of the implant, and its presence necessitates removal of the metal material after several weeks of infection to remove the entire bacterial load and cure the infection.

[0005] The antibacterial usefulness of electric fields has been known since the beginning of the last century, with methods known for sterilizing milk using low frequency alternating current (AC). In scientific fields outside of medicine, such as industrial water and food processing, high voltage electric fields are routinely used to "sterilize" or kill a variety of microorganisms and pathogens.

[0006] Electric fields have also been demonstrated to have the ability to enhance the bactericidal effect of certain antibiotics. Since then, several in vitro studies have been conducted demonstrating the ability of low-energy electric fields (alternating and direct current) to inhibit bacterial growth of different strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Staphylococcus epidermidis. Electric fields have also been demonstrated to be effective in treating osteomyelitis caused by Staphylococcus epidermidis in rabbits (US Pat. No. 5,399,633).

[0007] However, the application of DC leads, among other things, to electrolysis of water, which leads to changes in the pH of the medium, the release of free radicals and various ions that may be cytotoxic, especially for long-term exposure to DC current. In addition, there are galvanic corrosion effects (on the anode) that make it impossible to apply it directly to orthopedic implants. For this reason, the application of this current to the human body can only be carried out under very controlled conditions, making the applicability of the study very limited.

[0008] Various studies have been published that demonstrate the ability to modify electrostatic forces and alter bacterial adhesion to biomaterials or to degrade already formed and attached biofilms (US Pat. No. 5,399,633).

[0009] US Pat. No. 5,399,433 discloses a catheter (urinary or intravascular) that is resistant to infection through the use of electric fields.

[0010] An electric field can be applied to the surface of the medical device to repel the biofilm from the surface by ionic forces. However, this method cannot repel all bacteria on the surface of the medical device, and the process of removing the biofilm may take several hours or more. Thus, the electric field affects the liquid solution (synovial fluid or blood) in which the metallic implant is placed, causing coagulation of the medium and the formation of bacterial clumps.

[0011] Another proposed method involves placing the medical device in an electrolyte solution and applying a direct current to the solution, where the electrolytic reaction results in a pH change and the formation of antimicrobial molecules (e.g., HCl, which has antimicrobial properties). This process directly reduces the viability of the bacteria in the medium, killing them, but again, the medical device must be placed in the electrolytic medium for hours or days to kill the bacteria in the biofilm, and the potential cytotoxic effects on the host cells are not controlled. [Prior art documents] [Patent documents]

[0012] [Patent Document 1] U.S. Patent No. 5,312,813 [Patent Document 2] U.S. Patent No. 6,663,634 [Patent Document 3] US Patent Application Publication No. 2013 / 0041238 Summary of the Invention [Problem to be solved by the invention]

[0013] Thus, there is a need to provide a device that more effectively removes biofilms from or reduces bacterial adhesion to medical devices, and there is also a need to provide a device that removes biofilms from or reduces bacterial adhesion to medical devices that reduces the duration of the removal process. [Means for solving the problem]

[0014] According to a first aspect of the invention, there is provided an in vitro method of removing biofilm from or reducing bacterial adhesion to a metallic medical device outside a human or animal body, comprising connecting a first electrode to a surface of the medical device, exposing a target area on the surface of the medical device to an electrolyte fluid, positioning a second electrode proximate to the target area, and providing electrical power between the first and second electrodes such that electrolysis occurs in the electrolyte fluid, the electrical power comprising a plurality of electrical pulses, a potential difference between the first and second electrodes being at least 1 V and a current density applied in each electrical pulse being at least about 100 Å per 1 cm of the target area. 2 A method is provided in which the current is a maximum of 15A per

[0015] In a preferred embodiment, the applied current density is 1 cm 2 of the target area. 2 0.1A to 15A per cm of the target area, preferably 2 In another preferred embodiment, the applied current density is 0.1 A to 5 A per cm 2 of the target area. 2 The current is 0.2A to 2A.

[0016] According to a first aspect of the present invention, there is provided another in vitro method of removing biofilm from or reducing bacterial adhesion to a metallic medical device outside a human or animal body, the method comprising connecting a first electrode to a surface of the medical device, exposing a target area on the surface of the medical device to an electrolyte fluid, positioning a second electrode proximate to the target area, and providing electrical power between the first and second electrodes such that electrolysis occurs in the electrolyte fluid, the electrical power comprising a plurality of electrical pulses, wherein the potential difference between the first and second electrodes is at least 1 V, the current applied in each electrical pulse is up to 2 A, and each electrical pulse has a duration of less than 1 second.

[0017] In a preferred embodiment, the step of providing power between the first electrode and the second electrode comprises providing a potential difference of 1 V to 50 V, preferably 10 V to 30 V, and the step of providing power between the first electrode and the second electrode further comprises providing a current of 0.5 A to 1 A.

[0018] In another preferred embodiment, each electrical pulse has a duration of 0.05 seconds to 0.2 seconds.

[0019] In another preferred embodiment of any of the in vitro methods of the first aspect of the invention, the second electrode is an anode comprising a sacrificial metal, preferably comprised of silver, and / or the electrolyte fluid comprises one or more of a disinfectant, an antibacterial agent or an antibiotic, or the second electrode is an anode comprising a non-corrodible metal and no sacrificial metal, and the method further comprises isolating the bacteria from the electrolyte fluid after power is provided.

[0020] According to a second aspect of the present invention, there is provided an apparatus for removing biofilm from a metallic medical device, comprising: a fluid output connectable to a source of electrolyte fluid, the fluid output providing electrolyte fluid for cleaning a target area of ​​the medical device; a first electrode for electrically connecting to the medical device; a second electrode configured to be positioned proximal to the fluid output; and a power source for providing electrical power between the first and second electrodes, the power source being configured to provide intermittent electrical pulses between the first and second electrodes such that electrolysis occurs on a surface of the metallic device, the potential difference between the first and second electrodes being at least 1 V and the current density applied with each electrical pulse being at least about 1 cm of the target area. 2 A device is provided that provides a maximum of 15A per

[0021] In a preferred embodiment, the power source is configured to apply a current density of 1 cm of the target area. 2 0.1A to 15A per cm of the target area, preferably 2 The device is configured to provide intermittent electrical pulses of 0.1 A to 5 A per pulse.

[0022] In another preferred embodiment, the power source is configured to apply a current density of 1 cm 2 The device is configured to provide intermittent electrical pulses of 0.2A to 2A per pulse.

[0023] According to a second aspect of the present invention, there is provided another apparatus for removing biofilm from a metallic medical device, the apparatus comprising: a fluid output connectable to a source of electrolyte fluid, the fluid output providing electrolyte fluid for cleaning a target area of ​​the medical device; a first electrode for electrically connecting to the medical device; a second electrode configured to be positioned proximal to the fluid output; and a power source for providing power between the first and second electrodes, the power source configured to provide intermittent electrical pulses between the first and second electrodes such that electrolysis occurs on a surface of the metallic device, the potential difference between the first and second electrodes being at least 1 V, the current applied in each electrical pulse being at most 2 A, and each electrical pulse having a duration of less than 1 second.

[0024] In a preferred embodiment, the power supply is configured to provide intermittent electrical pulses with a potential difference between 1V and 50V, preferably between 10V and 30V, and a current between the first and second electrodes between 0.5A and 1A.

[0025] In another preferred embodiment, the power source is configured to provide each electrical pulse having a duration between 0.05 seconds and 0.2 seconds.

[0026] In another preferred embodiment of any of the devices of the second aspect of the invention, the device further comprises a controller configured to control the supply of electrolyte fluid from the fluid source to the fluid output.

[0027] In another preferred embodiment, the fluid output and / or the first electrode and / or the second electrode are removably connectable to the device via a detachment mechanism.

[0028] In another preferred embodiment, the fluid output comprises a tubular body, optionally curved such that the longitudinal axis of the tubular body at the proximal end is offset from the longitudinal axis of the tubular body at the distal end by more than 0 degrees to 90 degrees, or the fluid output comprises a porous sponge or a conical cap at its distal end.

[0029] In another preferred embodiment, the first or second electrode and the fluid output are provided on a single detachable body connectable to the device, more preferably both the first and second electrodes are provided on a single detachable body.

[0030] In another preferred embodiment, the power source is configured to provide an intermittent direct current between the first electrode and the second electrode.

[0031] In another preferred embodiment, the device further comprises a source of electrolyte fluid connected to the fluid applicator, the fluid being saline, and optionally the fluid comprising one or more of a disinfectant, an antibacterial agent, or an antibiotic.

[0032] In another preferred embodiment, the apparatus further comprises a pump configured to provide the electrolyte fluid at a predetermined pressure to the fluid output.

[0033] In another preferred embodiment, the fluid output and the first electrode and / or the second electrode are configured to be connected to a handheld portion, the handheld portion comprising a user-actuated element for activating the supply of fluid and / or power.

[0034] Embodiments will now be described in detail, by way of non-limiting examples only, with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0035] [Figure 1A] 1 is a schematic diagram of an apparatus for removing biofilm from a metallic medical device, according to one or more embodiments. [Figure 1B]1 is a schematic diagram of an apparatus for removing biofilm from a metallic medical device, according to one or more embodiments. [Diagram 2] FIG. 2 is a schematic diagram of an electronic controller of the device according to one or more embodiments. [Figure 3A] 1 is a schematic diagram of a fluid output of a device according to one or more embodiments. [Figure 3B] 1 is a schematic diagram of a fluid output of a device according to one or more embodiments. [Figure 3C] 1 is a schematic diagram of a fluid output of a device according to one or more embodiments. [Figure 3D] 1 is a schematic diagram of a fluid output of a device according to one or more embodiments. [Figure 3E] 1 is a schematic diagram of a fluid output of a device according to one or more embodiments. [Figure 3F] 1 is a schematic diagram of a fluid output of a device according to one or more embodiments. [Figure 4] 1 is a schematic diagram of an apparatus for removing biofilm from a metallic medical device, according to one or more embodiments. [Figure 5A] FIG. 2 illustrates a controller configured to provide power to a device, according to one or more embodiments. [Figure 5B] FIG. 2 illustrates another controller configured to provide power to a device, according to one or more embodiments. [Figure 5C] FIG. 5C shows a fluid output configured for use in conjunction with the controller shown in FIG. 5B. [Figure 6] 1 is a graph of fluid pressure and current amplitude generated by a device according to one or more embodiments. [Figure 7A] 13A-13D show experimental data for bacterial reduction on metallic devices using various methods according to one or more embodiments. [Figure 7B] 13A-13D show experimental data for bacterial reduction on metallic devices using various methods according to one or more embodiments. [Figure 7C]13A-13D show experimental data for bacterial reduction on metallic devices using various methods according to one or more embodiments. [Figure 8A] 13A-13C show experimental images of an in vitro experiment of bacterial reduction on a metallic device using a method according to one or more embodiments. [Figure 8B] 13A-13C show experimental images of an in vitro experiment of bacterial reduction on a metallic device using a method according to one or more embodiments. [Figure 8C] 13A-13C show experimental images of an in vitro experiment of bacterial reduction on a metallic device using a method according to one or more embodiments. [Figure 8D] 13A-13C show experimental images of an in vitro experiment of bacterial reduction on a metallic device using a method according to one or more embodiments. [Figure 9A] 13A-13C show experimental images of an in vivo experiment of bacterial reduction on a medical device implant using a method according to one or more embodiments. [Figure 9B] 13A-13C show experimental images of an in vivo experiment of bacterial reduction on a medical device implant using a method according to one or more embodiments. [Figure 9C] 13A-13C show experimental images of an in vivo experiment of bacterial reduction on a medical device implant using a method according to one or more embodiments. [Figure 9D] 13A-13C show experimental images of an in vivo experiment of bacterial reduction on a medical device implant using a method according to one or more embodiments. [Figure 10A] FIG. 13 shows experimental images of another in vitro experiment of bacterial reduction on a metallic device using a current art method and a method according to one or more embodiments. [Figure 10B] FIG. 13 shows experimental images of another in vitro experiment of bacterial reduction on a metallic device using a current art method and a method according to one or more embodiments. [Figure 10C]FIG. 13 shows experimental images of another in vitro experiment of bacterial reduction on a metallic device using a current art method and a method according to one or more embodiments. [Figure 10D] FIG. 13 shows experimental images of another in vitro experiment of bacterial reduction on a metallic device using a current art method and a method according to one or more embodiments. [Figure 10E] FIG. 13 shows experimental images of another in vitro experiment of bacterial reduction on a metallic device using a current art method and a method according to one or more embodiments. [Figure 10F] FIG. 13 shows experimental images of another in vitro experiment of bacterial reduction on a metallic device using a current art method and a method according to one or more embodiments. [Figure 10G] FIG. 13 shows experimental images of another in vitro experiment of bacterial reduction on a metallic device using a current art method and a method according to one or more embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] The present invention relates to a method and apparatus for removing biofilm or reducing bacterial adhesion on a metallic medical device, configured to apply an electric pulse between two electrodes when one electrode is electrically connected to the metallic medical device and the metallic device is exposed to an electrolyte fluid. The application of an electric pulse (specifically a DC pulse) to the metallic device forms gas bubbles (when the medical device is electrically connected to the cathode and the electrolyte solution is saline, the gas bubbles are hydrogen bubbles) directly on the surface of the metallic device as a product of electrolysis, thereby reducing bacterial adhesion to the target area of ​​the medical device by mechanically lifting the bacteria or biofilm from the surface of the metallic device. The apparatus can be configured to rinse or wash the device by intermittent supply of electrolyte fluid to the target area of ​​the metallic device. The intermittent supply of fluid to the target area further washes the bacteria detached from the surface by the electric pulse and inhibits electrocoagulation and the formation of bacterial clumps.

[0037] As disclosed herein, the term "electrolyte fluid" can be considered any liquid that contains an electrolyte such that electrolysis occurs when a DC voltage is applied between a cathode and an anode exposed to the electrolyte fluid. Thus, the electrolyte fluid can be saline or any other type of buffer solution.

[0038] As disclosed herein, the term "exposing to electrolyte fluid" can be considered any method of providing electrolyte fluid to exposed elements, including immersing the elements in the electrolyte fluid or providing the electrolyte fluid to the exposed elements by a flow of the electrolyte fluid, for example, by a continuous or intermittent flow of the electrolyte fluid over the elements.

[0039] As disclosed herein, the term "metallic medical device" can include any medical device that includes at least a portion made from metal. A metallic device may be made entirely or partially of metal. The term "medical device" can be defined as any device that interfaces with the human or animal body during use. A medical device can include a medical implant, prosthesis, or any other device configured to be placed on or in the human or animal body.

[0040] As disclosed herein, the term "sacrificial metal" may be considered to be any metal whose surface dissolves in the electrolyte fluid when acting as an anode during electrolysis.

[0041] As disclosed herein, the term "non-corroding metal" may be considered to be any metal whose surface does not dissolve in the electrolyte fluid when acting as an anode during electrolysis.

[0042] The methods disclosed herein can be used to remove biofilms from or reduce bacterial adhesion to medical devices in vivo or in vitro. In other words, the methods disclosed herein can be used to remove biofilms from or reduce bacterial adhesion to medical devices while the medical device is in or on the human or animal body, or outside the human or animal body.

[0043] FIG. 1A shows a schematic diagram of an apparatus 1 for removing biofilm or reducing bacterial adhesion to a metallic medical device 40. The apparatus comprises a fluid output 10, a first electrode 50 electrically connected to the metallic device 40, a second electrode 20, a power source 22, and optionally a controller 30. The fluid output 10 is connectable to a fluid source 12 of electrolyte fluid and configured to provide electrolyte fluid 14 from the fluid source 12 via a flow path 13 for flushing a target area of ​​the medical device 40 with the electrolyte fluid. The electrode 20 is positionable proximate to the fluid output 10 and connectable to a power source 22. The power source 22 is connectable to the first electrode 50 and the second electrode 20 via connections 54, 24. The apparatus 1 is configured to provide electrical power 24 between the electrodes 20, 50 such that electrolysis can occur between the electrodes 20, 50 in the presence of the electrolyte fluid. The controller 30 may be configured to control the supply of fluid 14 from the fluid source 12 to the fluid output 10 and may also control the supply of power 24 to the electrodes 20. Alternatively, a separate controller may be provided to control the supply of power 24 to the electrodes 20, as shown, for example, in FIG. 5A, or no external controller may be provided for either the fluid source 12 or the power source 22. The controller 30 may also be configured to supply the fluid 14 intermittently or continuously. In use, electrolysis causes bubbles to be released from the surface at the target area of ​​the medical device 40, thereby mechanically detaching bacteria from the surface of the medical device 40. In embodiments where the fluid is provided intermittently, the intermittent provision of the fluid 14 to the medical device 40 further provides intermittent washing of the target area to wash detached bacteria from the surface of the medical device 40. Intermittent cleaning of the surface of the medical device 40 prevents the removed bacteria 40 from coagulating or forming bacterial mass, for example, on the electrode 20, on a portion of the target area, or on the medium in which the medical device 40 is placed. It should be noted that in the devices and methods disclosed herein, the step of cleaning the medical device 40 may occur simultaneously with the step of applying power and causing electrolysis, or the steps may occur sequentially.For example, in some embodiments, the medical device 40 may be immersed in the electrolyte fluid while power is applied to cause electrolysis. The medical device 40 may then be washed with fluid from the fluid source 12. In other embodiments, the washing and power may be applied simultaneously to provide electrolyte fluid for electrolysis at the same time that the electrolyte fluid washes the device.

[0044] The fluid output 10 may be connectable to any suitable fluid source 12. For example, the fluid output 10 may be connected via one or more conduits that form a flow path from a fluid reservoir to the fluid output 10. Additional components may be provided to regulate the flow of fluid from the fluid source 12 to the fluid output 10. For example, one or more pumps or valves may be provided to selectively provide the fluid 14 to the fluid output 10 at a desired pressure or fluid flow rate. In other embodiments, the fluid source 12 may provide the required pressure without the use of a pump. In a preferred embodiment, the fluid may be provided to the fluid output 10 via a peristaltic pump so that pump components are not exposed to the fluid. Thus, the pump can be reused between cleanings. The connections may be permanent, i.e., the conduits may be integral with the fluid source 12 and the fluid output 10, or may be detachable. For example, the conduits may be attached to the fluid source 12 and / or the fluid output 10 by a detachment mechanism such as a threaded connection, a friction fit, or a stub connection, as known in the art.

[0045] The first electrode 50 and the second electrode 20 may be connectable to any suitable power source 22. For example, the electrodes 50, 20 may be connected via electrical wiring that forms an electrical connection between the power source 22 and the electrodes 50, 20. Additional electronic components may be disposed between the power source 22 and the electrodes 50, 20 to regulate the power provided by the power source 22 to the electrodes 50, 20. For example, the electrodes 50, 20 may be connected to the power source 22 by a power converter, such as any DC-DC, AC-DC, DC-AC, or AC-AC power converter. The power source 22 may include a mains power source, one or more batteries, a constant voltage or constant current power source, or the like. The electrical connection between the electrodes 50, 20 and the power source 22 may be permanent, i.e., the electrical wiring that forms the connection may be integral with the electrodes 50, 20 and / or the power source 22, or may be removable. For example, the electrical wiring that makes the connections can be attached to the power source 22 and / or electrodes 50, 20 by a removable mechanism such as a threaded connection, a friction fit, a plug or stub connection, or the like, as is known in the art.

[0046] The power supply 22 is configured to provide intermittent electrical pulses between the first and second electrodes such that electrolysis occurs on the surface of the metallic device 40, and the current applied with each electrical pulse is sufficient to cause air bubbles to escape from the surface of the metallic device during the electrical pulse. If the potential between the electrodes is greater than the decomposition potential required for electrolysis to occur and the current applied with each electrical pulse is sufficient to cause air bubbles to escape from the surface of the metallic device during the electrical pulse, the bacteria or biofilm on the surface of the metallic device will be lifted from the surface of the device by the air bubbles. It will be understood that the current and potential difference required for each electrical pulse to cause air bubbles to escape from the surface of the metallic device will depend on the apparatus used, including the surface area of ​​the electrodes, the material of the electrodes used, the type of electrolyte fluid, etc. With a given apparatus according to the present invention, it can be verified by visual confirmation whether the current provided for each electrical pulse is sufficient to release air bubbles. For example, the medical device may be immersed in a container containing an electrolyte fluid, and it can be visually verified whether air bubbles escape from the surface of the medical device with each pulse.

[0047] It should be noted that the decomposition potential, defined as the minimum voltage between the anode and cathode (first and second electrodes) required for electrolysis to occur, depends on the redox reaction occurring at the electrodes and therefore on the electrolyte solution and electrode metal selected. For saline, the decomposition potential is 1V to 2V. Above the decomposition potential, the rate of gas generation at the electrodes increases proportionally to the current, according to Faraday's law. For saline, a current of more than 0A to 2A is sufficient for gas bubbles to escape from the surface of the medical device for each pulse. Thus, when saline is used, the following voltage and current ranges are used: The voltage is at least 1 V, preferably 1 V to 50 V, and more preferably 10 V to 30 V. The current passing through the medical device is up to 2A, preferably 0.5A to 1A; It is preferred.

[0048] However, it should be noted that these preferred values ​​are also achievable for other electrolyte fluids, such as buffer solutions, etc. Also, note that a current of up to 2 A is understood to be greater than 0 A up to 2 A, i.e., in either case, there will be some current.

[0049] As observed in Examples 1-3 described herein, multiple pulses with durations of less than 1 second were observed to be sufficient to at least partially detach the biofilm. A series of 100 electric pulses, each with a duration of 0.1 seconds, reduces the amount of biofilm on the substrate by several orders of magnitude (FIG. 7A, "CH1-BF"). A similar effect was observed for 25 electric pulses, each with a duration of 0.1 seconds (FIG. 7B, "CH1-BF"). Thus, it was observed that applying a series of short electric pulses (i.e., pulse durations of less than 1 second) is sufficient to remove the biofilm, which means that the risks associated with prolonged electrical treatments (e.g., constant current applied to a medical device for 30 seconds or more), such as increased risk of prolonged exposure to free radicals or cytotoxic ions, are reduced. Applying the treatment as a series of pulses rather than a single prolonged pulse reduces the accumulation of free radicals or cytotoxic ions in the medical device. The gap between the electric pulses (i.e., the time during which no current flows) may be any suitable time gap, preferably less than 1 second, and even more preferably 0.5 seconds.

[0050] The term "proximal" with respect to the second electrode 20 and the fluid output 10 should be understood to mean that the second electrode 20 and the fluid output 10 are positioned close enough so that the required gas bubbles (caused by electrolysis) escape from the surface at the target area on the medical device 40 during use. The distance between the second electrode 20 and the fluid output 10 may depend on the parameters of the device 1. For example, the device 1 may be configured to output the fluid 14 in a jet of fluid from the fluid output 10 such that the fluid output 10 is located further from the target area than the electrode 20, while still applying both the fluid 14 to the target area of ​​the medical device 40 and the power to cause electrolysis at the target area. The power source may also be a constant current source with a maximum voltage, where a larger maximum voltage allows the second electrode 20 to be held further away from the surface of the medical device 40 while still achieving the required level of current for the gas bubbles to be expelled from the surface of the medical device 40 during each electrical pulse.

[0051] As disclosed herein, a fluid output may be defined as any fluid port that delivers fluid 14 from the fluid source 12 to a target. The fluid output may include, for example, a nozzle.

[0052] The controller 30 may be any suitable controller, analog or electronic, that controls the supply of fluid to the fluid output 10 and / or the supply of power to the electrodes 20. For example, the controller may be configured to control an actuatable valve that is periodically opened and closed to open and close the fluid flow path 13 between the fluid source 12 and the fluid output 10. The controller may be configured to control a pump, for example, to intermittently supply fluid to the fluid output 10 at a desired pressure. The controller 30 may also be configured to control the supply of power to the electrodes. For example, the controller 30 may be an electronic controller configured to open and close the electrical connections 54, 24 between the power source 22 and the electrodes 50, 20. The controller 30 may be configured to control one or more electrical components, such as a transducer, a variable resistor, etc., between the power source 22 and the electrodes. It will be understood that in any of the embodiments disclosed herein, the controller 30 may be powered by any power source, and may be powered by the power source 22 or a different power source.

[0053] The apparatus 1 may further comprise a negative pressure source 60 configured to remove fluid from the target area. The negative pressure source 60 may be any suitable negative pressure source, such as a vacuum pump, a surgical suction device, or the like. Negative pressure may be transferred from the source 60 to the target area via flexible tubing that may be positioned at the target area of ​​the medical device 40 and form a fluid pathway 62. The negative pressure source 60 may be powered by any suitable internal or external power source, or may be powered by the power source 22. The negative pressure source 60 may be configured to operate intermittently or continuously such that excess electrolyte fluid is intermittently or continuously removed from the surface of the medical device 40. The negative pressure source 60 may be controlled by the controller 30 via any suitable control connection (not shown). The controller 30 may be configured to synchronize the intermittent supply of fluid 14 with the intermittent operation of the negative pressure source 60, such that the intermittent negative pressure source 60 operates for a predetermined period of time after the fluid output 10 stops supplying fluid 14 to the medical device 40. Negative pressure source 60 can output the received fluid to a storage reservoir (not shown).

[0054] Figure IB shows a schematic diagram of an apparatus 1 for removing biofilm from or reducing bacterial adhesion to a medical device 40. Figure IB includes the features disclosed in Figure IA, except that a separate controller 320 is provided that is connectable to a power source 22 and provides power 24 between the electrodes 50, 20.

[0055] It should be noted that two mechanical actions are performed by the device 1 described in relation to Figures 1A and 1B: first, bacteria are lifted from the surface of the medical device 40 by the gas bubbles released from the electrolysis, and second, the pressure of the electrolyte fluid provided by the fluid output causes erosion of the biofilm or bacterial layer on the surface of the medical device 40.

[0056] The power supply 22 is preferably a current source. In a preferred embodiment, the power supply 22 is configured to provide an electrical pulse of sufficient current such that gas bubbles are released from the surface of the medical device 40 during each pulse. According to Faraday's first law, the mass of an element deposited on an electrode is directly proportional to the charge. Thus, the rate of gas generation on the surface of the medical device 40 is proportional to the current provided by the power supply 22. Thus, the amount of current that needs to be provided for each pulse depends on the area of ​​the medical device 40 where electrolysis occurs during the pulse, which is generally determined by the cross-sectional area of ​​the second electrode 20 facing the surface of the medical device 40. Thus, both the cross-sectional area and the duration of the pulse determine whether gas bubbles are released from the surface of the medical device 40 during each pulse. If the current is 500 mA, then the gas bubbles will be released from the surface of the medical device 40 at a rate of 177 mm. 2 It has been observed that for a cross-sectional area of ​​100 nm and a pulse duration of 0.1 s duration, it is sufficient to observe gas bubbles escaping from the surface during each electrical pulse (i.e., a current density of approximately 2.82 mA / mm 2 (A current density of 0.5 V is sufficient for the bubbles to lift off the surface of the medical device 40). However, if the current density is lowered, the duration applied for each pulse can be longer, and the pulses have sufficient duration for the bubbles to escape from the surface of the medical device 40. The current source preferably has a voltage range of 0V to 15V, preferably 0V to 30V, and even more preferably 0V to 50V. A higher maximum voltage means that the electrode 20 can be moved farther from the surface of the medical device 40 while still maintaining the current at the required level.

[0057] As shown in Example 5, the current density is 0.07 cm according to a current of 1 A. 2 14.29A / cm for a medical device target area 2 and still be safe for the subject. Thus, the current density may vary depending on the size of the electrode, but may be less than 0 A / cm 2 Larger than 15A / cm 2 A safe range of current density can be established. More preferably, the current density is less than 0.1 A / cm. 2~5A / cm 2 , and even more preferably 0.2 A / cm 2 ~2A / cm 2 The spatial dimension always refers to the area of ​​the medical device where electrolysis occurs during the pulse, also known as the target area of ​​the medical device, but in some embodiments can be defined as the cross-sectional area of ​​the second electrode 40 when the voltage is not sufficient to provide current to the entire area of ​​the device.

[0058] FIG. 2 shows a schematic diagram of the electronic controller 30. The electronic controller 30 comprises one or more of a memory 34 and a processor 36. The memory 34 may include instructions that, when executed using the processor 36, cause the fluid output 10 and / or the electrodes 20 to operate according to any suitable sequence, including the sequences of operations disclosed herein. The controller 30 is configured to control the supply of fluid 14 to the fluid output 10 via a control connection 302. The controller 30 may be configured to control the supply of power 24 from the power source 22 via a control connection 304. It should be noted that the control lines 302 and 304 may be physical control lines (analog or electronic) configured to provide control signals to fluidic components (valves, pumps, pump motors, etc.) in the flow path 13 and power conditioning components (power converters, variable resistors, etc.) in the electrical connection between the power source 22 and the electrodes 50, 20. In other embodiments, the controller 30 may be configured to communicate with the various components wirelessly, for example via Bluetooth or any other suitable communication protocol, and the control connections 302 and 304 may be wireless. The controller 320 of FIG. 1B may have a similar configuration for controlling the supply of power to the electrodes 50, 20.

[0059] The memory 34 may include one or more volatile or non-volatile memory devices, such as DRAM, SRAM, flash memory, read-only memory, ferroelectric RAM, hard disk drives, floppy disks, magnetic tapes, optical disks, etc. Similarly, the processor 36 may include one or more processing units, such as a microprocessor, a GPU, a CPU, a multi-core processor, etc. The controller 30 may further be implemented in software, hardware, or any combination to perform the sequences of operations disclosed herein.

[0060] The controller 30 may further be connected to a user interface 32 configured to select one or more parameters of the fluid supply control, such as pressure, flow rate, pulse frequency, and pulse duration of the fluid supply. The user interface 32 may alternatively or additionally be configured to select one or more parameters of the power supply, such as voltage, current, and pulse rate and duration. The user interface 32 may include buttons, knobs, sliders, levers, wheels, touch screens, etc. that a user can use to select the parameters. The controller 320 may be connected to the same user interface or a separate user interface to select one or more parameters of the power supply, such as voltage, current, pulse rate, and duration of the cleaning operation.

[0061] 3A illustrates a fluid output 10 according to one or more embodiments for use with the apparatus 1. The fluid output 10 comprises a tubular body 82 comprising one or more fluid conduits. The one or more fluid conduits provide a fluid path for the fluid 14 from the fluid source 12 to a target area on the medical device 40. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 such that the tubular body 82 also provides a fluid path 62 for the fluid extracted by the negative pressure source 60. Optionally, the second electrode 20 is provided at or proximal to the distal tip of the tubular body 82. The tubular body 82 may comprise a single fluid output orifice at its distal end such that the electrolyte fluid is output as a single jet of fluid, or the tubular body 82 may comprise multiple orifices at its distal end such that the electrolyte fluid is output as a shower or spray of fluid. The tubular body 82 is curved such that the longitudinal axis A of the tubular body 82 at the proximal end of the tubular body is different from the longitudinal axis B of the tubular body 82 at the distal end of the tubular body 82. The angle between the longitudinal axis A and the longitudinal axis B may be between 0 degrees and 90 degrees, more preferably between 60 degrees and 90 degrees. The curved configuration of the tubular body 82 allows access to areas that are difficult for medical devices to reach, such as the posterior femoral condyles of a knee prosthesis. The tubular body 82 may further comprise a sponge at its distal tip, as described in more detail with respect to FIG. 3C, or a conical cap, as described in more detail with respect to FIG. 3D. The tubular body 82 may have a length of 20 mm to 100 mm.

[0062] 3B illustrates a fluid output 10 according to one or more embodiments for use with the apparatus 1. The fluid output 10 comprises a tubular body 84 comprising one or more fluid conduits. The one or more fluid conduits provide a fluid path for the fluid 14 from the fluid source 12 to a target area on the medical device 40. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 such that the tubular body 84 also provides a fluid path 62 for the fluid extracted by the negative pressure source 60. Optionally, the second electrode 20 is provided at or proximal to the distal tip of the tubular body 84. The tubular body 84 may comprise a single orifice of the fluid output at its distal end such that the electrolyte fluid is output as a single jet of fluid, or the tubular body 84 may comprise multiple orifices at its distal end such that the electrolyte fluid is output as a shower or spray of fluid. The tubular body 84 is straight such that the longitudinal axis of the tubular body 84 remains constant along its length. The tubular body 84 may further comprise a sponge at its distal tip, as described in more detail with respect to Figure 3C, or a conical cap, as described in more detail with respect to Figure 3D. The tubular body 84 may have a length of between 20 mm and 100 mm.

[0063] 3C illustrates a fluid output 10 according to one or more embodiments for use with the apparatus 1. The fluid output 10 comprises a tubular body 85 comprising one or more fluid conduits. The one or more fluid conduits provide a fluid path for the fluid 14 from the fluid source 12 to a target area on the medical device 40. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 such that the tubular body 85 also provides a fluid path 62 for the fluid extracted by the negative pressure source 60. Optionally, the second electrode 20 is provided at or proximal to the distal tip of the tubular body 85. The tubular body 85 may comprise a single orifice of the fluid output at its distal end such that the electrolyte fluid is output as a single jet of fluid, or the tubular body 85 may comprise multiple orifices at its distal end such that the electrolyte fluid is output as a shower or spray of fluid. The fluid output further comprises a sponge 86 attached to the distal end of the tubular body 85. The sponge 86 can be made of any deformable porous material, such as polyester. The sponge 86 may comprise a mesh of conductive material and therefore may be connected to a power source 22 and used as an electrode 20. The sponge 86 suspends the electrolyte fluid 14 within the sponge 86 to allow the fluid 14 to be distributed over a large surface area of ​​the medical device 40 being treated and ensures that the current flows between the electrodes 50, 20. The tubular body 85 may have a length of 20 mm to 100 mm.

[0064] 3D illustrates a fluid output 10 according to one or more embodiments for use with the apparatus 1. The fluid output 10 comprises a tubular body 87 comprising one or more fluid conduits. The one or more fluid conduits provide a fluid path for the fluid 14 from the fluid source 12 to a target area on the medical device 40. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 such that the tubular body 87 also provides a fluid path 62 for the fluid extracted by the negative pressure source 60. Optionally, the second electrode 20 is provided at or proximal to the distal tip of the tubular body 87. The tubular body 87 may comprise a single orifice of the fluid output at its distal end such that the electrolyte fluid is output as a single jet of fluid, or the tubular body 87 may comprise multiple orifices at its distal end such that the electrolyte fluid is output as a shower or spray of fluid. The tubular body 87 may comprise a conical cap 88 at its distal tip for interfacing with a surface of the medical device 40. The conical cap 88, when interfaced, can prevent leakage of electrolyte fluid away from the target area of ​​the medical device 40. The tubular body 87 can have a length of between 20 mm and 100 mm.

[0065] FIG. 3E illustrates a fluid output 10 according to one or more embodiments for use with the apparatus 1. FIG. 3F illustrates a cross-sectional view of the fluid output 10 shown in FIG. 3E along line AA. The fluid output 10 includes a tubular body 89 including one or more fluid conduits. The one or more fluid conduits provide a fluid path for the fluid 14 from the fluid source 12 to a target area on the medical device 40. The tubular body 89 may include a single fluid output orifice at its distal end such that the electrolyte fluid is output as a single jet of fluid, or the tubular body 89 may include multiple orifices at its distal end such that the electrolyte fluid is output as a shower or spray of fluid. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 such that the tubular body 89 also provides a fluid path 62 for the fluid extracted by the negative pressure source 60. A second electrode 20 is provided at or proximal to the distal tip of the tubular body 87. The second electrode 20 forms a ring inside the tubular body 89, as shown in FIG. 3F. In some embodiments, the second electrode 20 can form only a portion of the ring. The fluid output 10 further comprises a first electrode 50 located radially inside the second electrode 20. The first electrode may optionally be exposed from a distal tip of the tubular body 89 to easily contact the medical device 40 and form a cathodic connection. In other embodiments, the first electrode 50 is formed as a ring and the second electrode 20 is provided radially inside the first electrode 50. Thus, a single removable body may be provided that comprises all of the first electrode 50, the second electrode 20 and the fluid output 10. The fluid output 10 may further comprise one or more of the following features: a curved shape as described with respect to FIG. 3A, a sponge 86 as described with respect to FIG. 3C, and a conical cap 88 as described with respect to FIG. 3D. The tubular body 89 can have a length of between 20 mm and 100 mm.

[0066] It will be appreciated that in any of the embodiments described with reference to Figures 3A to 3F, the fluid output section 10 may comprise a first electrode 50 instead of the second electrode 20, and the second electrode 20 may be provided on a separate element of the device.

[0067] In some embodiments, the apparatus 1 may be suitable for minimally invasive percutaneous procedures when the medical device 40 is located within the body. Specifically, the electrodes 50 and 20 may comprise metal needles configured to be inserted into the body such that the first electrode 50 forms an electrical connection to the medical device 40 and the second electrode 20 is positionable proximate to a target area of ​​the medical device 40. The fluid output 10 may also comprise a needle that penetrates into the body and injects electrolyte fluid into the site of the medical device. Finally, the negative pressure source 60 may also comprise a needle that penetrates into the body and extracts fluid from the site, and the negative pressure source 60 may use the fluid path of the fluid output 10 when the negative pressure source 60 and the fluid output 10 are alternately operated. Once the needle is correctly positioned, the electrolyte fluid can be injected into the site of the medical device 40 and an electric pulse can be applied to the electrolyte fluid to remove bacteria from the surface of the medical device 40. Negative pressure source 60 may then be operated to extract the electrolyte fluid containing the removed bacteria, thereby removing the bacteria from the body and treating the site of infection.

[0068] FIG. 4 shows a schematic diagram of an apparatus 100 for removing biofilm or bacteria from a metallic medical device 40. As with the apparatus 1 shown in FIGS. 1A and 1B, the apparatus 100 comprises a fluid output 10, a first electrode 50 electrically connected to the metallic device 40, a second electrode 20, and optionally a controller 30. The fluid output 10 is connectable to a fluid source 12 and configured to provide an electrolyte fluid 14 for cleaning a target area of ​​the medical device 40. The electrode 20 is located proximal to the fluid output 10 and is connectable to a power source 22, optionally via a controller 320. The apparatus 100 is configured to provide electrical power 24 between the electrodes 50, 20 to cause electrolysis at the target area. The power source 22 is configured to provide intermittent electrical pulses between the first electrode 50 and the second electrode 20 to cause electrolysis at the surface of the metallic device 40, the current applied during each electrical pulse being sufficient to cause air bubbles to escape from the surface of the metallic device 40 during the electrical pulse. The controller 30 is configured to control the supply of fluid 14 from the fluid source 12 to the fluid output 10, and the controller 320 is configured to control the supply of power 24 to the electrodes 50, 20. In the illustrated embodiment, the power source via the controller 320 also powers the controller 30 and the motor 106, although in other embodiments the controller 30 and the motor 106 are powered by separate power sources. Additionally, in some embodiments the controller 30 is configured to supply the fluid 14 intermittently.

[0069] In the embodiment shown in FIG. 4, the fluid output 10 and the electrodes 20 are removably connectable to the controller via a detachment mechanism. In the particular embodiment shown, the device comprises a detachable element 102 having a fluid conduit 102a, with the fluid output 10 located at the distal end of the conduit 102a. The detachable element 102 may comprise a tubular body having any of the configurations described in connection with FIGS. 3A-3D and may further comprise a sponge or conical cap at the distal tip. The detachable element 102 also comprises an electrode 20. The fluid output 10 and the electrodes 20 are removably connected to the body 110 via a detachment mechanism. For example, the detachable element 102 may be connected to the body 110 by a thread mechanism, a friction fit, or a stub-type connection. It will be appreciated that any suitable detachment mechanism may be used having a first configuration in which the detachable element 102 and the body 110 are mechanically connected and a second configuration in which the detachable element 102 and the body 110 are disconnected. When the removable element 102 and the body 110 are connected, the electrodes 20 are connected to wires that extend to the proximal end of the removable element 102 and form an electrical connection with electrical wiring in the body 110, which in turn can be connected to a power source 22. The electrical connection can be made by any suitable electrical connection, such as a plug and socket or pin connection. The electrodes 20 and the fluid output 10 are removably provided from the controller 30, allowing the electrodes 20 and the fluid output 10 to be replaced during a bacterial or biofilm removal operation, so that cross contamination does not occur between medical devices. Although the removable element 102 includes both the fluid output 10 and the electrodes 20, in other embodiments, the fluid output 10 and the electrodes 20 may be permanently connected to the controller 30 and the body 110, or only one of the fluid output 10 and the electrodes may be connected to the controller 30 by a detachment mechanism. The fluid output 10 and the electrodes 20 may instead be detachably connected to the controller 30 by a separate detachment mechanism.The first electrode 50 may be removably connectable to the power source 22 or controller 320 by a similar connection mechanism so that the first electrode 50 can be replaced with another electrode for cleaning a different medical device. In other embodiments, the first electrode 50 may be permanently connected to the controller 320 or power source 22. The first electrode 50 may be connectable to the medical device by any suitable connection mechanism, such as an electrical clip, or by an adhesive pad.

[0070] The device 100 further comprises a pump 104 connectable between the fluid source 12 and the fluid output 10. The pump 104 may be any suitable pump, such as a positive displacement pump, an impulse pump, or a rotodynamic pump. In a preferred embodiment, the pump is a peristaltic pump. In the illustrated embodiment, the pump 104 forms part of the removable element 102, and when the removable element 102 is connected to the body 110 via a detachment mechanism, the pump 104 forms a mechanical connection with an electric motor 106 that operates the pump 104. In another embodiment, the pump 104 is hydraulically operated, and the device comprises a hydraulic source that operates the pump. The pump 104 is also configured to be connected to the fluid source 12 to receive the fluid 14 as an input to the pump. The pump 104 may be connected to the fluid source 12 independently of the body 110, as shown in FIG. 4. For example, the pump 104 may comprise a fluid input port configured to receive a fluid conduit connected to the fluid source 12. In other embodiments, the fluid source 12 may be connected to the pump 104 through a fluid path in the body 110. For example, the body 110 may include a fluid input port configured to receive a fluid conduit connected to the fluid source 12, and the pump 104 may be configured to receive the fluid 14 via a fluid path through the body 110. In some embodiments, the pump 104 is provided in or on the body 110. In such embodiments, the body 110 is configured to be connected to both the power source 22 and the fluid source 12, and the removable element 102, when connected to the body 110, forms a fluid connection between the output of the pump 104 and the fluid output 10, and an electrical connection between the power source 22 and the electrode 20 via the body 110.

[0071] 4, the controller 30 is configured to control the operation of the motor 106 and thus the pump 104. The controller therefore controls the flow of fluid 14 to the fluid output 10 by controlling the motor 106.

[0072] As shown in FIG. 4, the body 110 may be ergonomically shaped so that it may be grasped by a user's hand. The device 100 may further include a user-actuated element 108, such as a trigger, for actuating the supply of electrolyte fluid to the fluid output 10. In embodiments in which the controller 30 also controls the supply of power to the electrodes 50, 20, the user-actuated element 108 (or a separate user-actuated element) may also be provided for actuating the supply of power to the electrodes 50, 20. The user-actuated element 108 is connected to the controller 30. When the user-actuated element 108 is set by the user to a first configuration, the controller 30 is configured to actuate the motor 106. When the user-actuated element 108 is set by the user to a second configuration, the controller 30 is configured to stop the motor 106. In the illustrated embodiment, the user-actuated element 108 is a spring-loaded trigger, and the first configuration is achieved by pulling the trigger and the second configuration is achieved by releasing the trigger. The user-actuated element may, for example, be connected to a switch that turns a motor on and off, or the user-actuated element may be configured to send start and stop signals to the controller 30 in a first and second configuration. In other embodiments, for example, the user-actuated element 108 may include one or more buttons or levers, or may include a navigated user interface on a touch screen.

[0073] The apparatus 100 may further comprise a negative pressure source 60 configured to remove fluid from the target area. The negative pressure source 60 may be any suitable negative pressure source, such as a vacuum pump, and may be provided with the body 110 or separate from the body 110. Negative pressure may be transferred from the source 62 to the target area via flexible tubing that may be positioned at the target area of ​​the medical device 40 and form a fluid pathway 62. The negative pressure source 60 may be powered by any suitable internal or external power source, or may be powered by the power source 22. The negative pressure source 60 may be configured to operate intermittently such that excess electrolyte fluid is intermittently removed from the surface of the medical device 40. The negative pressure source 60 may be controlled by the controller 30 via any suitable control connection (not shown). The controller 30 may be configured to synchronize the intermittent supply of fluid 14 with the intermittent operation of the negative pressure source 60, such that the intermittent negative pressure source 60 operates for a predetermined period of time after the fluid output 10 stops supplying fluid 14 to the medical device 40. The negative pressure source 60 may output the received fluid to a storage reservoir (not shown). The negative pressure source 60 may be contained within the body 110 and powered by a motor within the body 110 controlled by the controller 30, as in the case of the pump 104. The removable element 102 may include a second fluid conduit (not shown) that extends through the removable element 102 from the fluid output 10 to the negative pressure source 60 when the removable element 102 is attached to the body 110.

[0074] For device 100 , the surface area of ​​electrode 20 , which determines the current density at electrode 20 , is the longitudinal cross-sectional area of ​​electrode 20 at the distal end of detachable element 102 .

[0075] FIG. 5A shows a controller 320 that controls the power provided to the electrode 20. The controller 320 is powered by a power source 22 (which may be external or internal to the controller 320) and may include a user interface 321, such as a touch screen, for selecting parameters of the power source, such as voltage, current, pulse rate and duration. The controller 320 includes an output 326. For example, the output 326 may be connectable to a power cable that is electrically connected to the electrode 20. For example, in the embodiment shown in FIG. 4, the body 110 may be connectable to the output 326 via a power cable that provides an electrical connection to the electrode 20 (and optionally power to the controller 30 and motor 106). The controller 320 may further include an electrical connection 328 for the first electrode 50, or the first electrode 50 may be permanently connected to the controller 320. The controller 320 is configured to provide a DC electrical pulse between the electrodes 50, 20 such that electrolysis may occur.

[0076] 5B shows another controller 330 that controls the power provided to the electrodes 20. The controller 320 is powered by a power supply 22 (which may be external or internal to the controller 320) and may include a user interface 321, such as a touch screen, for selecting parameters of the power supply, such as voltage, current, pulse rate and duration. The controller 330 includes an output 326. For example, the output 326 may be connectable to a power cable electrically connected to the second electrode 20. The controller 330 may further include an electrical connection 328 for the first electrode 50, or the first electrode 50 may be permanently connected to the controller 330. The controller 330 is configured to provide DC electrical pulses between the electrodes 50, 20 so that electrolysis may occur. The controller 330 further comprises a pump 104 integrated into the controller 330 such that the controller 330 also provides fluid to the fluid output 10 (the pump 104 controller 330 may be connectable to any suitable fluid source via the fluid connections of the controller 330 or the controller 330 may further comprise a fluid source). The pump may be, for example, a peristaltic pump such that pump components are not exposed to the fluid. The pump 104 may comprise an output connector 329 that connects to a proximal end of the fluid output 10.

[0077] FIG. 5C illustrates a fluid output 10 that may be used in conjunction with a controller 330. Because the pump is integrated into the controller 330, the fluid output 10 does not include any moving parts. The fluid output 10 of FIG. 5C includes a tubular body 350 that includes one or more fluid conduits from a proximal end of the tube 350 to a distal end of the tube 50. The tubular body 350 may be, for example, any of the tubular bodies described with respect to FIGS. 3A-3F. The fluid output 10 further includes a connector 351 at a proximal end of the tubular body 350. The connector 351 is configured to mate with the output connector 329 to form a fluid connection between the pump 104 and the one or more fluid conduits of the tubular body 350 such that the pump 104 provides fluid to the distal end of the tubular body 350 through the one or more fluid conduits. The connector 351 may form any type of fluid connection with the output connector 329, such as a friction fit, a threaded fit, or the like. The fluid output portion 10 may further comprise leads 352 and 353 that connect to the electrical outputs 326 and 328 to electrically connect the electrodes 20 and / or 50 to the controller 330 when the electrodes 20 and / or 50 are provided in the tubular body 350.

[0078] In any of the embodiments disclosed herein, the fluid 14 may be any electrolyte solution (e.g., a saline solution such as physiological saline), and the device is configured to apply a DC electrical pulse between the electrodes 50, 20. The second electrode 20 may be selected as a cathode or an anode, and the first electrode 50 is connectable to the medical device. Preferably, the first electrode 50 is a cathode so that oxidation or electrocorrosion of the medical device 40 does not occur. The DC power applied between the electrodes 50, 20 creates electrolysis at the target area. The bubbles formed at the target area of ​​the medical device lift bacteria from the surface of the medical device, reducing bacterial adhesion to the medical device and removing biofilm from the surface. In some embodiments, the fluid output is configured to provide fluid intermittently, which provides intermittent cleaning to the medical device 40 and prevents bacterial buildup in the electrolyte fluid at the surface. That is, the fluid output 10 provides an electrolyte solution that allows electrolysis at the target area, and the separated bacteria can be further washed away by the fluid intermittently supplied at the target area. The electrolyte solution fluid is composed of a solvent and an electrolyte. The solvent may include, for example, water. The electrolyte may include, for example, salt ions and / or silver ions. When the electrolyte solution contains silver ions, an antibacterial effect is observed without the need to use a sacrificial electrode, such as a silver electrode. The electrolyte solution may further include one or more of a disinfectant (such as hypochlorous acid), an antibacterial agent (such as dissolved silver ions, gold ions, or copper ions), or an antibiotic treatment composition (the antibiotic treatment composition may include any suitable antibiotic composition known in the art, including, but not limited to, one or more of vancomycin, gentamicin, and clindamycin). Advantageously, saline is biocompatible. It is noted that the cleaning effect of electrolysis and periodic washing at the target area results from the removal of bacteria from the surface by bubbles formed during electrolysis and the washing away of the removed bacteria by periodic washing. This process has been observed to significantly reduce the cleaning time of medical devices compared to processes that indirectly kill bacteria using toxic chemicals produced by the process of electrolysis.

[0079] The DC power is applied intermittently. When the fluid is output intermittently, at least one cycle of DC current may be provided to the electrodes for each cycle of fluid provided to the fluid output. Providing at least one cycle of DC current for each cycle of the fluid output ensures that bacteria are lifted from the surface of the medical device before the next fluid cleaning occurs. Preferably, the DC current and fluid are provided intermittently such that electrolysis occurs during the cleaning of the medical device with the fluid. FIG. 6 shows a graph of fluid pressure 602 applied to the fluid output over time compared to current amplitude 604 applied to the electrodes 20. For example, the pressure profile 602 may be provided by the pump 104 controlled by the controller 30 and the current profile 604 may be provided by the controller 320. The pressure profile 602 includes a series of pulses that provide cleaning of the medical device at a desired pressure. The current profile 604 provides intermittent periods of constant current following the fluid pressure pulses. The alternating fluid cleaning and electrolysis caused by the direct current provide efficient cleaning of the medical device.

[0080] In a preferred embodiment, the second electrode 20 is a sacrificial anode comprising a sacrificial metal. As disclosed herein, a sacrificial electrode can be defined as an electrode that disintegrates over time when a current is applied to the electrode in an electrolyte solution. The sacrificial electrode can be selected to release certain ions into the electrolyte solution that have antibacterial properties. Examples of suitable materials include silver and copper.

[0081] In a further preferred embodiment, the sacrificial anode comprises silver (Ag) such that the oxidation process at the anode from electrolysis releases silver ions into the target area of ​​the device 40. The silver ions increase the antimicrobial properties of the fluid exposed to the medical device, thus increasing the efficacy of the biofilm or bacteria removal process.

[0082] In other embodiments, the second electrode 20 does not include a sacrificial metal and includes a non-corroding metal so that little or no metallic ions are released into the electrolyte solution during electrolysis. This allows the post-electrolysis electrolyte solution containing the bacteria from the biofilm to be recovered. The bacteria can be isolated from the electrolyte solution and cultured so that the bacteria can be identified to guide treatment of the infection (e.g., an effective route of administration of antibiotics to the patient). An example of a suitable material includes platinum.

[0083] In any of the embodiments disclosed herein, the first electrode 50 can include one or more non-corroding metals, such as cobalt-chromium and titanium.

[0084] In any of the embodiments disclosed herein, the device may be configured to provide a fluid flow of electrolyte fluid to the fluid output of between 0.5 liters and 2 liters per minute, the flow may be continuous or intermittent, with a pulse rate of between 0 Hz and 100 Hz, more preferably between 0 Hz and 10 Hz.

[0085] In any of the embodiments disclosed herein, the device may be configured to provide DC pulses having a duration of 0.05 seconds to 0.2 seconds at a frequency of 0 Hz to 100 Hz, more preferably 0 Hz to 10 Hz. The device may be configured to provide a current of 0 A to 1.5 A.

[0086] In any of the embodiments disclosed herein, the fluid output unit 10 may be removably connectable to the controller 30 via a detachment mechanism as disclosed in other embodiments. The fluid output unit 10 and the electrodes 20 may be provided on the same detachable body.

[0087] Any of the embodiments disclosed herein may include a pump located between the fluid source 12 and the fluid output 10, with the controller configured to control the pump to provide fluid at a predetermined pressure to the fluid output 10.

[0088] Any of the embodiments disclosed herein can include one or more user interfaces for selecting operating parameters of the fluid and electrical supplies.

[0089] In any of the embodiments disclosed herein, the fluid output section 10 and the first electrode 50 and / or the second electrode 20 may be connectable to a handheld portion, the handheld portion comprising a user-actuated element for actuating the supply of fluid and / or power.

[0090] Any of the devices disclosed herein can be used to implement the following method of removing biofilm from or reducing bacterial adhesion to a metallic medical device inside or outside the human or animal body, the method comprising: connecting a first electrode (e.g., electrode 50) to a surface of the medical device; exposing a target area on a surface of the medical device to an electrolyte fluid (e.g., using a fluid output 10); Positioning a second electrode (e.g., electrode 20) proximal to the target area; providing electrical power between the first electrode and the second electrode (e.g., using a power source 22) to cause electrolysis to occur in the electrolyte fluid; The electrical power includes multiple electrical pulses, the current applied in each electrical pulse being sufficient to cause air bubbles to escape from the surface of the medical device.

[0091] It should be noted that the method is not limited to being applied by the device disclosed above. For example, the method can be implemented by immersing a medical device in a reservoir or container of electrolyte fluid, connecting a first electrode to the surface of the immersed medical device, placing a second electrode proximal to a target area of ​​the medical device, and providing the necessary electrical pulse between the electrodes so that electrolysis occurs on the surface of the medical device. It should be noted that in embodiments in which the medical device is thus immersed in a reservoir of electrolyte fluid, the method can further include a step of washing the medical device with electrolyte fluid, for example, by using a fluid output as disclosed herein to wash the device with the fluid.

[0092] The fluid may be any of the electrolyte solutions disclosed herein.

[0093] Exposing the target area to the electrolyte fluid may include intermittently washing the metallic device with the electrolyte fluid. The washing and the electrical pulses may be applied in alternation (e.g., as shown in FIG. 6). The fluid and the electrical pulses may be applied according to any of the embodiments disclosed herein.

[0094] The second electrode may be any sacrificial anode disclosed herein, preferably the anode is composed of silver.

[0095] In some embodiments, the second electrode is free of sacrificial metals and includes a non-corroding metal such that little or no metallic ions are released into the electrolyte solution during electrolysis. This allows for recovery of the electrolyte solution after electrolysis that includes bacteria from the biofilm. The method can then include isolating the bacteria from the electrolyte fluid after power is provided. The bacteria can be isolated from the electrolyte solution and cultured so that the bacteria can be identified to guide treatment of the infection (e.g., an effective route of administration of antibiotics to the patient).

[0096] The above methods may also be applied to medical devices in vitro. Additionally, the above methods may also be applied directly to target areas on or in the human or animal body. EXAMPLES

[0097] Example 1 FIG. 7A shows experimental data of bacterial reduction on a metallic device in the first embodiment.

[0098] In the first example, nine cathode bases (three groups "CH1", three groups "CH2", and three groups "CH3") containing plates made of cobalt-chromium (CoCr) and nine corresponding anode plates also made of cobalt-chromium (CoCr) were used. The plates were 1.54 cm 2 The plates were discs with a surface area of ​​100 μm. Before use, the plates were sterilized with UV light for 30 minutes. The cathode base was immersed in 3 mL of each well. The wells were filled with a culture medium of trypticase soy broth (TSB) supplemented with 0.25% concentration of glucose. A 1 / 100 dilution of Staphylococcus epidermidis strain was used in the culture medium. The plates were incubated at 37° C. for 24 hours. After 24 hours of incubation, the culture medium was removed from the wells and each well was washed three times with sterile phosphate buffered saline (PBS 1X). Each well was then filled with 3 mL of saline solution so that the saline electrically connected the respective anode and cathode. Several control plates were also incubated in the same manner. A series of electrical pulses were applied between each anode and cathode (a control plate was not exposed to any current) such that electrolysis occurred within the wells and gas bubbles escaped from the surface of the cathode:

[0099] TIFF2025510395000002.tif43170

[0100] After the series of electric pulses, the saline was removed from the wells (this removed saline was used to measure the number of bacteria in planktonic state after the pulse as described below) and each well (including the control wells) was washed again three times with sterile PBS 1X. The biofilm attached to the cathode was removed with a sterile spatula and then homogenized in 900 μL of saline. One hundred microliters of the different serial dilutions were plated on Mueller Hinton (MH) agar plates for CFU / mL counting. The data was calculated as CFU / cm according to the following formula: 2 was converted to. CFU / cm 2 = (CFU / mL × dilution factor) / (disk area)

[0101] In addition, following the dilution method described above, the number of bacteria in suspension (i.e., not attached to the surface of the cathode) after a series of electric pulses was also measured by measuring the amount of bacteria contained in the saline solution removed from the wells immediately after the electric pulse (or the corresponding time in control experiments). The data were then converted into CFU / cm according to the formula above. 2 was converted to.

[0102] FIG. 7A shows the average CFU / cm of removed biofilm from the control, CH1, CH2, and CH3 groups, respectively. 2 values ​​(bars for control BF, CH1-BF, CH2-BF and CH3-BF) and CFU / cm of planktonic bacteria from control, CH1, CH2 and CH3 groups, respectively. 2 Values ​​("Control planktonic" and "C_plan_DP") are shown. With p-values ​​less than 0.0001, it can be seen that significant (by several orders of magnitude) elimination of biofilm occurred for all groups compared to the control wells ("Control BF"). Similarly, it can be seen that significant (by several orders of magnitude) elimination of planktonic bacteria occurred for all groups.

[0103] Example 2 FIG. 7B shows experimental data of bacterial reduction on metallic devices in the second embodiment.

[0104] In a second example, nine cathode bases (three groups "CH1", three groups "CH2", and three groups "CH3") containing plates made of cobalt-chromium (CoCr) and nine corresponding anode plates made of silver (Ag) were used. The plates were 1.54 cm 2 The plates were discs with a surface area of ​​100 μm. Before use, the plates were sterilized with UV light for 30 minutes. The cathode base was immersed in 3 mL of each well. The wells were filled with a culture medium of trypticase soy broth (TSB) supplemented with 0.25% concentration of glucose. A 1 / 100 dilution of the S. epidermidis strain was used in the culture medium. The plates were incubated at 37°C for 24 hours. After 24 hours of incubation, the culture medium was removed from the wells and each well was washed three times with sterile phosphate buffered saline (PBS 1X). Each well was then filled with 3 mL of saline solution so that the saline electrically connected the respective anode and cathode. Several control plates were also incubated in the same way. The following series of electric pulses were applied between each anode and cathode (control plates were not exposed to electric current) so that electrolysis occurred in the wells and air bubbles escaped from the surface of the cathode:

[0105] TIFF2025510395000003.tif46170

[0106] After the series of electric pulses, the saline was removed from the wells (this removed saline was used to measure the number of bacteria in planktonic state after the pulse as described below) and each well (including the control wells) was washed again three times with sterile PBS 1X. The biofilm attached to the cathode was removed with a sterile spatula and then homogenized in 900 μL of saline. One hundred microliters of the different serial dilutions were plated on Mueller-Hinton (MH) agar plates for CFU / mL counting. The data was calculated as CFU / cm according to the following formula: 2 was converted to. CFU / cm 2 = (CFU / mL × dilution factor) / (disk area)

[0107] In addition, following the dilution method described above, the number of bacteria in suspension (i.e., not attached to the surface of the cathode) after a series of electric pulses was also measured by measuring the amount of bacteria contained in the saline solution removed from the wells immediately after the electric pulse (or the corresponding time in control experiments). The data were then converted into CFU / cm according to the formula above. 2 was converted to.

[0108] FIG. 7B shows the average CFU / cm of removed biofilm from the control, CH1, CH2, and CH3 groups, respectively. 2 values ​​(bars for control BF, CH1-BF, CH2-BF and CH3-BF) and CFU / cm of planktonic bacteria from control, CH1, CH2 and CH3 groups, respectively. 2 Figure 1 shows the results of the elimination of biofilm (by several orders of magnitude) for all groups compared to the control wells (by "Control BF") with p-values ​​less than 0.0055. Similarly, it can be seen that significant (by several orders of magnitude) elimination of planktonic bacteria occurred for all groups. As the number of pulses increases, the reduction in biofilm and planktonic bacteria increases significantly.

[0109] It should be noted that the high ability of the electric pulses to detach the biofilm is observed with only 25 electric pulses of 0.1 second duration, 0.5 seconds apart, over a very short period of time, less than 30 seconds, achieving an 8 order of magnitude reduction over the control.

[0110] Example 3 FIG. 7C shows experimental data of bacterial reduction on metallic devices in the third embodiment.

[0111] In a third example, nine cathode bases (three groups "CH1", three groups "CH2", and three groups "CH3") containing plates made of cobalt-chromium (CoCr) and nine corresponding anode plates made of silver (Ag) were used. The plates were 1.54 cm 2The plates were disks with a surface area of ​​100 nm. Before use, the plates were sterilized with UV light for 30 minutes. The cathode base was immersed in 3 mL of each well. The wells were filled with a culture medium of trypticase soy broth (TSB) supplemented with 0.25% concentration of glucose. A 1 / 100 dilution of the Staphylococcus epidermidis strain was used in the culture medium. The plates were incubated at 37°C for 24 hours. After 24 hours of incubation, the culture medium was removed from the wells and each well was washed three times with sterile phosphate buffered saline (PBS 1X). Each well was then filled with 3 mL of saline solution so that the saline electrically connected the respective anode and cathode. Several control plates were also incubated in the same manner. An electric pulse was applied between each anode and cathode of groups CH1 and CH3, resulting in electrolysis in the wells and air bubbles escaping from the surface of the cathode. After the electric pulse, the saline solution was removed from the wells of group CH1, and each well of group CH1 was washed again three times with sterile PBS 1X (including the control wells). The biofilms attached to the cathode of CH1 were each removed with a sterile spatula and then homogenized in 900 μL of saline. 100 microliters of different serial dilutions were plated on Mueller-Hinton (MH) agar plates for CFU / mL counting. The data was calculated as CFU / cm according to the following formula: 2 was converted to. CFU / cm 2 = (CFU / mL × dilution factor) / (disk area)

[0112] The cathode plates of groups CH2 and CH3 were removed from the wells and washed with a pressurized jet of saline, ensuring to avoid cross-contamination of the plates due to splashing. After the pressurized washing was completed, the biofilms attached to the cathodes of CH2 and CH3 were removed with a sterile spatula, respectively, and then homogenized in 900 μL of saline. 100 microliters of the different serial dilutions were plated on Mueller-Hinton (MH) agar plates for CFU / mL counting. The data were converted into CFU / cm according to the above formula. 2 was converted to.

[0113] Thus, the CH1 plate was exposed to electrolysis only, the CH2 plate was exposed to only cleaning using a pressurized jet of fluid, and the CH3 plate was exposed to both electrolysis and cleaning using a pressurized jet. The parameters for electrolysis and cleaning were as follows:

[0114] TIFF2025510395000004.tif45170

[0115] FIG. 7C shows the average CFU / cm for biofilms removed from the control, CH1, CH2, and CH3 groups, respectively. 2 Values ​​(control BF, Pulse 25, Pistol and Pulse 25 + Pistol bars) and CFU / cm for planktonic bacteria from the control 2 Values ​​("control suspension") are shown. Control suspension bacterial counts were measured as in Examples 1 and 2. It can be seen that application of only 25 electric pulses results in a reduction in biofilm of about 7.8 orders of magnitude compared to the control, compared to a reduction of about 4.7 orders of magnitude when washing alone is used. The combination of electric pulses and washing resulted in a reduction in biofilm of about 9.9 orders of magnitude.

[0116] Example 4 Figure 8A shows a set of wells in which different medical implants 40 of Ti, sintered Ti and Cr-Co were cultured with a certain biofilm, while Figures 8B-8D show the biofilm removal on Ti, Ti sintered and Cr-Co medical implants 40, respectively, during the in vitro method according to the present procedure.

[0117] In a fourth example, E. coli biofilms were grown and developed in Ti, Ti-sintered and Cr-Co 1.4 cm wide plates for 72 hours to form mature biofilms, which were stained with purple crystals so that the biofilms could be easily identified by their darker color, as shown in Figures 8B-8D, stage I, and then dehydrated for another 72 hours to increase their adhesiveness.

[0118] After this was done, separation was attempted using physiological serum, but this was not possible.

[0119] Then, a pulse of 1 A (2 pulses per second, each pulse lasting 0.25 seconds) was applied (see Phase II of Figures 8B-8D), which successfully detached the entire biofilm in less than 10 seconds, as shown in Phase III of Figures 8B-8D, and the stained biofilm was completely removed from the medical implant 40. The 1.4 cm wide disc plate was 1.54 cm wide. 2 , which is 0.65 A / cm 2 This means that a current density of

[0120] This in vitro experiment demonstrates that the in vitro method for removing biofilm according to the present invention can effectively remove biofilm on medical implants in a short period of time.

[0121] Example 5 Figure 9A shows a medical implant 40 for a rabbit knee made of Cr-Co with a diameter of just 3 mm. Figure 9B shows a portion of an apparatus used to remove biofilm from a metallic medical device, the apparatus comprising a controller 320 and a first electrode 20. The controller 320 comprises a user interface 321 and an output 326 connectable to a power cable electrically connected to the electrode 20.

[0122] In a fifth example, an in vivo study was performed. Two New Zealand white rabbits were implanted in both knees with a specially designed Cr-Co prosthesis 40 as shown in Figure 9C under standard aseptic procedures and antibiotic prophylaxis with a single dose of cefazolin 10 mg / kg. Prior to implantation of the prosthesis, the prosthesis was immersed in a 0.3 McFarland inoculum of Staphylococcus aureus ATCC 25923 for 30 seconds.

[0123] In the first animal (control), the joint was closed immediately after saline flushing. In the second animal (case), both prostheses were treated with current pulses (1 A, 2 pulses per second) for 40 seconds with a 30% time interval, saline flushing, and the joint was closed, as shown in Figure 9D. The 3 mm prosthesis was closed with a 0.07 cm 2 , which is 14.29 A / cm 2 This means that a current density of

[0124] After 72 hours, both animals were reoperated to obtain tissue, bone and prosthetic explant samples for culture. In all samples, quantitative cultures were pre-vortexed and sonicated in 1 ml BHI. Absence of contamination was confirmed by MALDI-TOF MS (VITEK-MS) and identification of isolated colonies with an automated antibiogram (VITEK-2).

[0125] In all samples studied, the log10(ufc / cm) in control animals treated with a dose of cefazolin isolate S. aureus 2 The bacterial counts expressed as log10(ufc / mL) in the right leg prosthesis were 9.38 and in the left leg 8.86. The bacterial counts expressed as log10(ufc / mL) in the bone and periprosthetic tissue biopsies were 2.70 and 2.72 in the right leg and 3.24 and 3.87 in the left leg, respectively. In animals in which an electric field was applied to the implant after its placement in addition to a dose of cefazolin, all samples (prosthesis, bone and periprosthetic tissue biopsies) were negative and it was not possible to isolate the inoculated strain of Staphylococcus aureus after 14 days of incubation in sonicated broth. The results can be seen in the table below.

[0126] TIFF2025510395000005.tif48170

[0127] This in vivo model suggests that application of an electric field to artificial implants in combination with cefazolin is potentially effective in preventing the development of IPA following exposure of the implants to an inoculum of S. aureus ATCC 25923.

[0128] Example 6 In a sixth example, another in vivo study was performed in which two New Zealand White rabbits were implanted with specially designed Cr-Co prostheses under standard aseptic procedures and antibiotic prophylaxis with a single dose of cefazolin 10 mg / kg.

[0129] Then, an inoculum of Staphylococcus aureus ATCC (10 5 The rabbits were provided with 0.5 mL to 1 mL of serum containing 0.01% ucc / mL of IgG and the infection was allowed to proceed by placing them in the compartment for 4 days.

[0130] After the infection had progressed for 4 days, the first rabbit (control) and the second rabbit (case) were treated differently. The control rabbit underwent extensive surgical cleaning and irrigation with abundant saline for 1 min, which corresponds to a typical intervention of debridement, antibiotics and implant retention (DAIR). The case rabbit underwent extensive surgical cleaning and irrigation with abundant saline and electrical current pulses (1 A, 2 pulses per second with a duty cycle of 30%) for 1 min.

[0131] After the cleaning procedure, both control and case rabbits were monitored for 4 days and maintained on cefazolin to prevent the development of sepsis and soft tissue infection.

[0132] Finally, the prostheses were explanted under sterile conditions and further samples of synovial fluid, periarticular tissue, bone and blood cultures were taken.

[0133] The results, as shown in the table below, show that in control animals the bacterial counts expressed as log10(ufc / mL) in a 1 / 10 dilution of each prosthesis (data not taking into account the prosthesis surface) were significantly higher than in case animals.

[0134] TIFF2025510395000006.tif29170

[0135] The results showed that the applied electric field according to one or more embodiments of the present invention is highly effective in treating joint prosthesis infections and improves outcomes compared to when only DAIR (debridement, antibiotics, and implant retention) is performed. The bacterial counts on the right knee of the case rabbit can be explained by recolonization from bacteria present in the periarticular soft tissue. However, the counts were much lower than in the prostheses of the control rabbits treated with DAIR only (no electric field).

[0136] Example 7 10A shows a portion of an apparatus used to remove biofilm from a metallic medical device in accordance with one or more embodiments of the present invention, the apparatus including a controller 320 and a first electrode 20. The controller 320 includes a user interface 321, an output 326 connectable to a power cable configured to electrically connect to the electrode 20, and an output 328 connectable to a power cable configured to electrically connect to a reference electrode 50.

[0137] In the seventh example, another in vitro test was carried out. Figures 10B-10G show a set of wells in which different medical implants 40, Ti, sintered Ti and Cr-Co, were cultured with a certain biofilm. Figures 10B-10D show the biofilm condition before and after the pulsating fluid based biofilm removal procedure was performed on the Ti, Ti sintered and Cr-Co medical implants 40, respectively. Figures 10E-10G show the biofilm condition before and after the biofilm removal procedure according to the invention was performed on the Ti, Ti sintered and Cr-Co medical implants 40, respectively.

[0138] E. coli biofilms were grown and developed for 72 hours in Ti, sintered Ti and Cr-Co plates to form mature biofilms, which were stained with purple crystals so that the biofilms could be easily identified by their darker color (stage I) as shown in Figure 10B-G, stage I. They were then dehydrated for another 72 hours to increase their adhesiveness.

[0139] First, three implants (Ti, Ti-sintered, and Cr-Co) were treated with electrolyte fluid in a pulsed manner according to the prior art (FIGS. 10B-10D). The electrolyte fluid was delivered at high and low flushing flows using a commercially available fluid pistol.

[0140] Next, three other implants (Ti, Ti-sintered, and Cr-Co) were treated using the device according to one or more embodiments of the present invention of FIG. 10A, specifically using a sponge at the distal end of the fluid output (FIGS. 10E-10G). The current pulses provided were 1 A, 2 pulses per second with a 50% duty cycle, and the electrolyte fluid was provided at its minimum flow rate.

[0141] As shown in Phase II of Figures 10B-10G, implants treated with pulsed electrolyte fluid alone demonstrated that either low or high flushing flows were unable to detach the biofilm, whereas using the device and method according to the present invention, the biofilm was completely removed in less than 5 seconds of application (for each implant).

[0142] All of the above is fully within the scope of the present disclosure and is considered to form the basis of alternative embodiments in which one or more combinations of the features described above are applied, without being limited to the specific combinations disclosed above.

[0143] In light of this, there are many alternatives for implementing the teachings of the present disclosure. It is expected that a person skilled in the art, in light of common general knowledge in the art, can modify and adapt the above disclosure to suit their own circumstances and requirements while retaining some or all of the technical effects of the above disclosure, either disclosed or derivable from the above. All such equivalents, modifications, or adaptations are within the scope of the present disclosure.

Claims

1. 1. An in vitro method for removing biofilm from or reducing bacterial adhesion to a metallic medical device outside the human or animal body, comprising: connecting a first electrode to a surface of the medical device; exposing a target area on the surface of the medical device to an electrolyte fluid; placing a second electrode proximate the target area; providing electrical power between the first electrode and the second electrode such that electrolysis occurs in the electrolyte fluid; the power comprises a plurality of electrical pulses, a potential difference between the first electrode and the second electrode being at least 1 V, and a current density applied in each electrical pulse being at least 1 cm ２ The method is such that the maximum current is 15A per ohm.

2. The current density applied is within 1 cm of the target area. ２ 0.1A to 15A per cm 2 of the target area, preferably ２ 2. The method of claim 1, wherein the current is 0.1 A to 5 A per second.

3. The current density applied is within 1 cm of the target area. ２ The method according to claim 1 or 2, wherein the temperature is 0.2A to 2A per saturation.

4. 1. An in vitro method for removing biofilm from or reducing bacterial adhesion to a metallic medical device outside the human or animal body, comprising: connecting a first electrode to a surface of the medical device; exposing a target area on the surface of the medical device to an electrolyte fluid; placing a second electrode proximate the target area; providing electrical power between the first electrode and the second electrode such that electrolysis occurs in the electrolyte fluid; wherein the power comprises a plurality of electrical pulses, a potential difference between the first electrode and the second electrode is at least 1 V, a current applied in each electrical pulse is up to 2 A, and each electrical pulse has a duration of less than 1 second.

5. 5. The method of claim 4, wherein the step of providing power between the first electrode and the second electrode comprises providing a potential difference of 1 V to 50 V, preferably 10 V to 30 V, and the step of providing power between the first electrode and the second electrode further comprises providing a current of 0.5 A to 1 A between the first electrode and the second electrode.

6. The method according to claim 4 or 5, wherein each electrical pulse has a duration of between 0.05 seconds and 0.2 seconds.

7. the second electrode is an anode comprising a sacrificial metal, preferably comprised of silver, and / or the electrolyte fluid comprises one or more of a disinfectant, an antibacterial agent or an antibiotic; or the second electrode is an anode comprising a non-corroding metal and no sacrificial metal, and the method further comprises isolating bacteria from the electrolyte fluid after the electrical power is provided. The method according to any one of claims 1 to 6.

8. 1. An apparatus for removing biofilm from a metallic medical device, comprising: a fluid output connectable to a source of electrolyte fluid, the fluid output providing the electrolyte fluid for irrigating a target area of ​​the medical device; a first electrode electrically connecting to the medical device; the second electrode configured to be disposed proximate to the fluid output; a power source that supplies power between the first electrode and the second electrode; the power source is configured to provide intermittent electrical pulses between the first electrode and the second electrode to cause electrolysis at the surface of the metallic device, a potential difference between the first electrode and the second electrode being at least 1 V, and a current density applied with each electrical pulse being at least about 1 cm of the target area. ２ The device has a maximum current of 15A per

9. The power source is configured to apply a current density of 1 cm of the target area. ２ 0.1A to 15A per cm 2 of the target area, preferably ２ 9. The apparatus of claim 8, configured to provide intermittent electrical pulses of between 0.1 A and 5 A per pulse.

10. The power source is configured to apply a current density of 1 cm of the target area. ２ 10. The apparatus of claim 8 or 9, configured to provide intermittent electrical pulses of between 0.2A and 2A per pulse.

11. 1. An apparatus for removing biofilm from a metallic medical device, comprising: a fluid output connectable to a source of electrolyte fluid, the fluid output providing the electrolyte fluid for irrigating a target area of ​​the medical device; a first electrode electrically connecting to the medical device; the second electrode configured to be disposed proximate to the fluid output; a power source that supplies power between the first electrode and the second electrode; wherein the power source is configured to provide intermittent electrical pulses between the first and second electrodes such that electrolysis occurs at the surface of the metallic device, wherein a potential difference between the first and second electrodes is at least 1 V, a current applied in each electrical pulse is up to 2 A, and each electrical pulse has a duration of less than 1 second.

12. 12. The apparatus of claim 11, wherein the power supply is configured to provide intermittent electric pulses with a potential difference between 1 V and 50 V, preferably between 10 V and 30 V, and a current between the first and second electrodes of 0.5 A to 1 A.

13. 13. Apparatus according to claim 11 or 12, wherein the power source is configured to provide each electrical pulse having a duration of between 0.05 seconds and 0.2 seconds.

14. 14. The apparatus of any one of claims 8 to 13, further comprising a controller configured to control the supply of electrolyte fluid from the fluid source to the fluid output.

15. A device according to any one of claims 8 to 14, wherein the fluid output portion and / or the first electrode and / or the second electrode are removably connectable to the device via a detachment mechanism.

16. 16. The device of any one of claims 8 to 15, wherein the fluid output comprises a tubular body, optionally curved such that a longitudinal axis of the tubular body at a proximal end is offset from the longitudinal axis of the tubular body at a distal end by more than 0 degrees to 90 degrees.

17. 17. The device of claim 16, wherein the fluid output comprises a porous sponge or a conical cap at its distal end.

18. A device according to any one of claims 8 to 17, wherein the first electrode or the second electrode and the fluid output are provided on a single detachable body connectable to the device.

19. 20. The device of claim 18, wherein both the first electrode and the second electrode are provided on the single detachable body.

20. 20. The apparatus of any one of claims 8 to 19, wherein the power supply is configured to provide an intermittent direct current between the first electrode and the second electrode.

21. 21. The apparatus of any one of claims 8 to 20, further comprising a source of electrolyte fluid connected to the fluid applicator, the fluid being saline, and optionally the fluid comprising one or more of a disinfectant, an antibacterial agent, or an antibiotic.

22. 22. An apparatus according to any one of claims 8 to 21, further comprising a pump configured to provide the electrolyte fluid at a pressure to the fluid output.

23. 23. The device of any one of claims 8 to 22, wherein the fluid output and the first electrode and / or the second electrode are configured to be connected to a handheld portion, the handheld portion comprising a user-actuated element for actuating the supply of fluid and / or power.

Images