Apparatus and method for removing biofilms from metal devices

Abstract

A method and apparatus for removing a biofilm from a metallic medical device (40) outside a human or animal body or reducing bacteria adhering to the metallic medical device. The method comprises: connecting a first electrode (50) to a surface of a medical device (40); exposing a target area on the surface of the medical device (40) to the electrolytic fluid (14); placing a second electrode (20) in the vicinity of the target area; and providing electrical power between the first electrode (50) and the second electrode (20) such that electrolysis occurs in the electrolysis fluid; wherein the electrical power comprises a plurality of electrical pulses, where the potential difference between the first electrode and the second electrode is at least 1 V, and where the current density applied in each electrical pulse is up to 15 A per square centimeter of target area.

Description

Technical Field

[0001] The present disclosure relates to an apparatus and method for removing biofilm and / or bacteria from a metal medical device. Background Art

[0002] Infection, whether acute or chronic, is a common complication in patients following implantation of prosthetic or osteosynthetic materials. This complication is associated with significant morbidity and mortality, and the economic costs of available treatments are high.

[0003] Despite many advances in aseptic practices and systemic and local prophylactic antibiotic therapy in recent years, infection rates still range from 0.3% to 25%, depending on the type of intervention and the size of the implant used. Although the exact pathophysiology of orthopedic implant infection is unknown, it is known that any orthopedic implant infection is preceded by 1) surgical site contamination, 2) bacterial adhesion, and 3) biofilm formation on the prosthetic material.

[0004] It is the presence of this biofilm that necessitates the removal of the metal several weeks after infection to eliminate the entire bacterial load and thereby cure the infection, as currently available methods are unable to destroy all biofilm on the implant surface.

[0005] The antimicrobial effects of electric fields have been known since the beginning of the last century: the use of low-frequency alternating current (AC) to sterilize milk is known. In scientific fields outside of medicine, such as industrial water and food processing, high-voltage electric fields are often used to "sterilize" or kill various microorganisms and pathogens.

[0006] Further evidence was provided that electric fields could enhance the bactericidal effect of certain antibiotics. Since then, several in vitro studies have demonstrated that low-energy electric fields (AC and DC) can inhibit bacterial growth of different strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Staphylococcus epidermidis. The effectiveness of electric fields in treating osteomyelitis caused by Staphylococcus epidermidis has also been demonstrated in rabbits (US5312813).

[0007] However, the application of direct current produces, among other things, the electrolysis of water, which in turn leads to changes in the pH of the medium, the generation of free radicals and the release of various ions that can be cytotoxic, especially when exposed to direct current for a long time. In addition, direct current can also produce electro-corrosive effects (at the anode), which makes it impossible to apply direct current directly to orthopedic implants. This is why this type of current can only be applied under strictly controlled conditions on the human body, and therefore its applicability for research is very limited.

[0008] Various studies have been published showing their ability to modify electrostatic forces, alter bacterial adhesion to biomaterials or even deconstruct already formed and adhered biofilms (US 6,663,634 B2).

[0009] US2013 / 0041238A1 discloses a catheter (urethral catheter or intravascular catheter) that uses an electric field to prevent infection.

[0010] An electric field can be applied to the surface of a medical device in order to repel the biofilm from the surface by ionic forces. However, this method cannot repel all bacteria from the surface of the medical device, and the process of removing the biofilm may take several hours or longer. Therefore, the electric field affects the liquid solution (synovial fluid or blood) where the metal implant is placed and causes the medium to coagulate and the formation of bacterial clumps.

[0011] Another proposed approach is to place the medical device in an electrolytic solution and apply a direct current to the solution, where the electrolytic reaction produces a pH change and forms antimicrobial molecules (such as HCl) with antimicrobial properties. This process directly reduces the viability of bacteria in the medium and kills the bacteria, but again, the medical device must be placed in the electrolytic medium for several hours or days to kill bacteria in the biofilm, and potential cytotoxic effects on host cells are not controlled.

[0012] Therefore, it is necessary to provide a device that can more effectively remove biofilm on medical devices or reduce bacteria adhering to medical devices. It is also necessary to provide a device that can shorten the removal process time to remove biofilm from medical devices or reduce bacteria adhering to medical devices. Summary of the invention

[0013] According to a first aspect of the present invention, there is provided an in vitro method for removing biofilm from a metal medical device outside the human or animal body or reducing bacteria adhering to the metal medical device, comprising: connecting a first electrode to the surface of the medical device; exposing a target area on the surface of the medical device to an electrolytic fluid; placing a second electrode near the target area; providing power between the first electrode and the second electrode so that electrolysis occurs in the electrolytic fluid; wherein the power comprises a plurality of electric pulses, wherein the potential difference between the first electrode and the second electrode is at least 1 V; and wherein the current density applied in each electric pulse is up to 15 A per square centimeter of the target area.

[0014] In a preferred embodiment, the applied current density is 0.1 A to 15 A per square centimeter of target area, preferably 0.1 A to 5 A per square centimeter of target area. In another preferred embodiment, the applied current density is 0.2 A to 2 A per square centimeter of target area.

[0015] According to a first aspect of the present invention, another in vitro method for removing biofilm from a metal medical device outside the human or animal body or reducing bacteria adhering to the metal medical device is provided, comprising: connecting a first electrode to the surface of the medical device; exposing a target area on the surface of the medical device to an electrolytic fluid; placing a second electrode near the target area; providing electricity between the first electrode and the second electrode so that electrolysis occurs in the electrolytic fluid; wherein the electricity includes a plurality of electric pulses, wherein the potential difference between the first electrode and the second electrode is at least 1V; and wherein the current applied in each electric pulse is up to 2A, and wherein the duration of each electric pulse is less than 1 second.

[0016] In a preferred embodiment, the step of providing power between the first electrode and the second electrode comprises providing a potential difference of 1V to 50V, preferably 10V to 30V, and the step of providing power between the first electrode and the second electrode further comprises providing a current of 0.5A to 1A.

[0017] In another preferred embodiment, the duration of each electric pulse is 0.05 seconds to 0.2 seconds.

[0018] In another preferred embodiment of any in vitro method of the first aspect of the invention, the second electrode is an anode comprising a sacrificial metal, preferably silver, and / or wherein the electrolytic fluid comprises one or more of a disinfectant, an antibacterial agent or an antibiotic agent; or the second electrode is an anode comprising a non-corrosive metal and free of a sacrificial metal, wherein the method further comprises separating bacteria from the electrolytic fluid after providing electricity.

[0019] According to a second aspect of the present invention, there is provided an apparatus for removing biofilm from a metal medical device, comprising: a fluid output connectable to an electrolytic fluid source, the fluid output for supplying electrolytic fluid to clean a target area of ​​the medical device; a first electrode for electrically connecting to the medical device; a second electrode configured to be placed near the fluid output; and a power source for supplying power between the first electrode and the second electrode; wherein the power source is configured to provide intermittent electrical pulses between the first electrode and the second electrode so that electrolysis occurs on the surface of the metal device, wherein the potential difference between the first electrode and the second electrode is at least 1 V, and wherein the current density applied in each electrical pulse is up to 15 A per square centimeter of the target area.

[0020] In a preferred embodiment, the power source is configured to provide intermittent electrical pulses, wherein the applied current density is 0.1 A to 15 A per square centimeter of target area, preferably 0.1 A to 5 A per square centimeter of target area.

[0021] In another preferred embodiment, the power source is configured to provide intermittent electrical pulses, wherein the applied current density is between 0.2A and 2A per square centimeter of the target area.

[0022] According to a second aspect of the present invention, another apparatus for removing biofilm from a metal medical device is provided, comprising: a fluid output device connectable to an electrolytic fluid source, the fluid output device being used to supply electrolytic fluid to clean a target area of ​​the medical device; a first electrode for being electrically connected to the medical device; a second electrode configured to be placed near the fluid output device; and a power source for supplying power between the first electrode and the second electrode; wherein the power source is configured to provide intermittent electric pulses between the first electrode and the second electrode so that electrolysis occurs on the surface of the metal device, wherein the potential difference between the first electrode and the second electrode is at least 1 V; and wherein the current applied in each electric pulse is up to 2 A, and wherein the duration of each electric pulse is less than 1 second.

[0023] In a preferred embodiment, the power supply is configured to provide intermittent electrical pulses, wherein the potential difference is 1 V to 50 V, preferably 10 V to 30 V, and the current between the first electrode and the second electrode is 0.5 A to 1 A.

[0024] In another preferred embodiment, the power supply is configured to provide each electrical pulse with a duration of 0.05 seconds to 0.2 seconds.

[0025] In another preferred embodiment of any apparatus of the second aspect of the present invention, the apparatus further comprises a controller configured to control the supply of the electrolytic fluid from the fluid source to the fluid output device.

[0026] In another preferred embodiment, the fluid output device and / or the first electrode and / or the second electrode are removably connected to the device via a detachment mechanism.

[0027] In another preferred embodiment, the fluid output device comprises a tubular body, optionally wherein the tubular body is curved so that the longitudinal axis of the proximal end of the tubular body is offset greater than 0 to 90 degrees from the longitudinal axis of the distal end of the tubular body, or wherein the fluid output device comprises a porous sponge or a conical cap at its distal end.

[0028] In another preferred embodiment, the first electrode or the second electrode and the fluid output device are provided on a single detachable body connectable to the device, more preferably wherein both the first electrode and the second electrode are provided on a single detachable body.

[0029] In another preferred embodiment, the power supply is configured to supply intermittent direct current between the first electrode and the second electrode.

[0030] In another preferred embodiment, the apparatus further comprises a source of electrolytic fluid connected to the fluid applicator, wherein the fluid is a saline solution; optionally wherein the fluid comprises one or more of a disinfectant, antimicrobial agent or antibiotic agent.

[0031] In another preferred embodiment, the apparatus further comprises a pump configured to provide the electrolytic fluid to the fluid output device at a predetermined pressure.

[0032] In another preferred embodiment, the fluid output device and the first electrode and / or the second electrode are configured to be connected to a handheld portion, and the handheld portion comprises a user-actuated element for actuating the fluid and / or power supply. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Embodiments will now be explained in detail, by way of non-limiting examples only, with reference to the accompanying drawings described below.

[0034] Figure 1A A schematic diagram showing an apparatus for removing biofilm from a metal medical device according to one or more embodiments;

[0035] Figure 1B A schematic diagram showing an apparatus for removing biofilm from a metal medical device according to one or more embodiments;

[0036] Figure 2 A schematic diagram showing an electronic controller of a device according to one or more embodiments;

[0037] FIG. 3A to FIG. 3F A schematic diagram showing a fluid output device of an apparatus according to one or more embodiments;

[0038] Figure 4 A schematic diagram showing an apparatus for removing biofilm from a metal medical device according to one or more embodiments;

[0039] Figure 5A A controller configured to provide power to a device according to one or more embodiments is shown;

[0040] Figure 5B Another controller configured to provide power to a device according to one or more embodiments is shown;

[0041] Figure 5C shows a configuration with Figure 5B A fluid output device for use with the controller shown;

[0042] Figure 6 a graph showing fluid pressure and current magnitude produced by an apparatus according to one or more embodiments; and

[0043] 7A to 7CExperimental data for reducing bacteria on metal devices using various methods according to one or more embodiments is presented.

[0044] Figures 8A to 8D Experimental images showing in vitro experiments to reduce bacteria on metal devices using methods according to one or more embodiments.

[0045] Figures 9A to 9D Experimental images of in vivo experiments using methods according to one or more embodiments to reduce bacteria on medical device implants are shown.

[0046] FIG. 10A to FIG. 10G Experimental images of another in vitro experiment showing the reduction of bacteria on a metal device using prior art methods and methods according to one or more embodiments. DETAILED DESCRIPTION

[0047] The present invention relates to a method and apparatus for removing biofilm on a metal medical device or reducing bacteria adhering to the metal on the medical device, which is configured to apply an electric pulse between two electrodes when one electrode is electrically connected to the metal medical device and when the metal device is exposed to an electrolytic fluid. The electric pulse (particularly a DC pulse) is applied to the metal device to mechanically lift bacteria or biofilm from the surface of the metal device by directly forming bubbles (when the medical device is electrically connected to a cathode and the electrolytic solution is a salt solution, the bubbles are hydrogen bubbles) on the surface of the metal device as electrolysis products, thereby reducing the adhesion of bacteria to a target area of ​​the medical device. The device can be configured to rinse or clean the device by intermittently supplying an electrolytic fluid to the target area of ​​the metal device. Intermittently supplying fluid to the target area further cleans away bacteria separated from the surface by the electric pulse and inhibits electrocoagulation and the formation of bacterial agglomerates.

[0048] As disclosed herein, the term "electrolytic fluid" may be considered to be any liquid containing an electrolyte such that electrolysis occurs when a DC voltage is applied between a cathode and an anode exposed to the electrolytic fluid. Thus, the electrolytic fluid may be a salt solution or any other type of buffer solution.

[0049] As disclosed herein, the term "exposed to an electrolytic fluid" may be considered to be any manner of providing the electrolytic fluid to the exposed element. This may include immersing the element in the electrolytic fluid or providing the electrolytic fluid to the exposed element by flowing the electrolytic fluid, such as by flowing the electrolytic fluid continuously or intermittently onto the element.

[0050] As disclosed herein, the term "metal medical device" may include any medical device that includes at least a portion made of metal. A metal device may be made of metal in whole or in part. The term "medical device" may be defined as any device that contacts the human or animal body when in use. A medical device may include a medical implant, a prosthesis, or any other device configured to be placed on or in the human or animal body.

[0051] As disclosed herein, the term "sacrificial metal" may be considered any metal whose surface dissolves into the electrolytic fluid when acting as an anode during an electrolysis process.

[0052] As disclosed herein, the term "non-corrosive metal" may be considered to be any metal whose surface will not dissolve into the electrolytic fluid when acting as an anode during an electrolysis process.

[0053] The methods disclosed herein can be used to remove biofilm from a medical device or reduce bacteria adhering to a medical device in vivo or in vitro. In other words, the methods disclosed herein can be used to remove biofilm from a medical device or reduce bacteria adhering to a medical device when the medical device is inside or on the body of a human or animal body or when the medical device is outside the body of a human or animal body.

[0054] Figure 1A A schematic diagram of an apparatus 1 for removing biofilm from a metal medical device 40 or reducing bacteria adhered to a metal medical device 40 is shown. The apparatus includes a fluid output device 10, a first electrode 50 for electrical connection to the metal device 40, a second electrode 20, a power source 22, and an optional controller 30. The fluid output device 10 is connectable to a fluid source 12 of an electrolytic fluid and is configured to supply an electrolytic fluid 14 from the fluid source 12 via a flow path 13 to clean a target area of ​​the medical device 40 with the electrolytic fluid. The electrode 20 is located near the fluid output device 10 and is connectable to the 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 supply power 24 between the electrodes 20, 50 so that electrolysis can occur between the electrodes 20, 50 in the presence of the electrolytic fluid. The controller 30 can be configured to control the supply of the fluid 14 from the fluid source 12 to the fluid output device 10, and can 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 electrode 20, such as Figure 5AAs shown, or no external controller may be provided for the fluid source 12 or the power source 22. In addition, the controller 30 may be configured to supply the fluid 14 intermittently or continuously. In use, electrolysis causes bubbles to be released from the surface of the target area of ​​the medical device 40, thereby mechanically separating the bacteria from the surface of the medical device 40. In an embodiment where the fluid is provided intermittently, intermittently providing the fluid 14 to the medical device 40 also provides intermittent cleaning of the target area so as to clean the separated bacteria from the surface of the medical device 40. Intermittent cleaning of the surface of the medical device 40 can prevent the removed bacteria 40 from condensing or forming bacterial clumps, for example, on the electrode 20, a portion of the target area, or a medium where the medical device 40 is placed. It is worth noting that in the apparatus and method disclosed herein, the step of cleaning the medical device 40 can occur simultaneously with the step of applying power to cause electrolysis, or these steps can occur sequentially. For example, in some embodiments, the medical device 40 can be immersed in the electrolytic fluid while supplying power to perform electrolysis. Subsequently, the medical device 40 can be cleaned with fluid from the fluid source 12. In other embodiments, cleaning and power may be provided simultaneously, such that the electrolytic fluid can both clean the device and provide electrolytic fluid for electrolysis at the same time.

[0055] The fluid output device 10 can be connected to any suitable fluid source 12. For example, the fluid output device 10 can be connected via one or more conduits to form a flow path from a fluid reservoir to the fluid output device 10. Additional components for regulating the flow of fluid from the fluid source 12 to the fluid output device 10 can be provided. For example, one or more pumps or valves can be provided to selectively provide fluid 14 to the fluid output device 10 at a desired pressure or fluid flow rate. In other embodiments, the fluid source 12 can provide the required pressure without using a pump. In a preferred embodiment, the fluid can be provided to the fluid output device 10 via a peristaltic pump so that the pump components are not exposed to the fluid. Therefore, the pump can be reused between cleanings. The connection can be a permanent connection, that is, the conduit is integral with the fluid source 12 and the fluid output device 10, or it can be detachable. For example, the conduit can be attached to the fluid source 12 and / or the fluid output device 10 by a detachment mechanism known in the art (e.g., a threaded connection, a friction fit, or an insertion connection).

[0056] The first electrode 50 and the second electrode 20 can be connected to any suitable power supply 22. For example, the electrodes 50, 20 can be connected via wires to form an electrical connection between the power supply 22 and the electrodes 50, 20. Additional electronic components can be placed between the power supply 22 and the electrodes 50, 20 to regulate the power supplied by the power supply 22 to the electrodes 50, 20. For example, the electrodes 50, 20 can be connected to the power supply 22 by a power converter, such as any DC-DC, AC-DC, DC-AC or AC-AC power converter. The power supply 22 may include a main power supply, one or more batteries, a constant voltage or constant current power supply, etc. The electrical connection between the electrodes 50, 20 and the power supply 22 is a permanent connection, that is, the wire forming the connection can be formed integrally with the electrodes 50, 20 and / or the power supply 22, or can be detachable. For example, the wire forming the connection can be attached to the power supply 22 and / or the electrodes 50, 20 by a disassembly mechanism known in the art (such as a threaded connection, a friction fit, a plug or an insertion connection).

[0057] The power source 22 is configured to provide intermittent electrical pulses between the first electrode and the second electrode so that electrolysis occurs on the surface of the metal device 40, wherein the current applied in each electrical pulse is sufficient to cause bubbles to escape from the surface of the metal device during the electrical pulse. When the potential between the electrodes is greater than the decomposition potential required for electrolysis to occur, and the current applied in each electrical pulse is sufficient to cause bubbles to escape from the surface of the metal device during the electrical pulse, the bacteria or biofilm on the surface of the metal device is lifted off the surface of the device by the bubbles. It should be understood that the current and potential difference required for each electrical pulse to cause bubbles to escape from the surface of the metal device will depend on the equipment used, including the surface area of ​​the electrodes, the material of the electrodes used, the type of electrolytic fluid, etc. For a given device according to the present invention, it can be verified by visual confirmation whether the current supplied for each electrical pulse is sufficient to release the bubbles. For example, the medical device can be immersed in a container containing an electrolytic fluid, and it can be visually verified whether bubbles escape from the surface of the medical device in each pulse.

[0058] It is worth noting that the decomposition potential is defined as the minimum voltage between the anode and cathode (first electrode and second electrode) required for electrolysis to occur, which depends on the redox reaction occurring at the electrodes and therefore on the selected electrolyte solution and electrode metal. For saline solutions, the decomposition potential is 1V to 2V. According to Faraday's law, above the decomposition potential, the rate of gas generation at the electrode increases in proportion to the current. For saline solutions, currents greater than 0A to 2A are sufficient to cause bubbles to escape from the surface of the medical device in each pulse. Therefore, when using saline solutions, the following voltage and current ranges are preferred:

[0059] - a voltage of at least 1 V, preferably 1 V to 50 V, more preferably 10 V to 30 V;

[0060] - The current through the medical device is up to 2A, preferably between 0.5A and 1A.

[0061] However, it should be noted that these preferred values ​​are also feasible for other electrolytic fluids (such as buffer solutions). We also note that the so-called current up to 2A should be understood as greater than 0A and up to 2A, that is, there should be some current in any case.

[0062] As observed in Examples 1 to 3 described herein, it has been observed that multiple pulses of less than 1 second in duration are sufficient to at least partially detach the biofilm. A series of 100 electrical pulses, each 0.1 second in duration, can reduce the amount of biofilm on a substrate by several orders of magnitude ( Fig. 7A , “CH1-BF”). Similar effects were observed for 25 electrical pulses, each with a duration of 0.1 s ( Figure 7B , "CH1-BF"). It has therefore been observed that applying a series of short electrical pulses (i.e., pulse duration less than 1 second) is sufficient to remove biofilm, which means that the risks associated with prolonged electrical treatment (e.g., applying a constant current to a medical device for 30 seconds or more) (e.g., increased risk of prolonged exposure to free radicals or cytotoxic ions) are reduced. Applying the treatment in the form of a series of pulses rather than a single long pulse can reduce the accumulation of free radicals or cytotoxic ions on the medical device. The interval between electrical pulses (i.e., the time when no current flows) can be any suitable time interval, and is preferably less than 1 second, even more preferably 0.5 seconds.

[0063] The term "proximal" in relation to the second electrode 20 and the fluid output device 10 is to be understood as the second electrode 20 being positioned sufficiently close to the fluid output device 10 so that the desired bubbles (caused by electrolysis) escape from the surface of the target area on the medical device 40 during use. The distance between the second electrode 20 and the fluid output device 10 may depend on the parameters of the apparatus 1. For example, the apparatus 1 may be configured to output the fluid 14 from the fluid output device 10 in the form of a jet so that the fluid output device 10 is located further away from the target area than the electrode 20, while still applying the fluid 14 to the target area of ​​the medical device 40 and applying electricity to the target area to cause electrolysis. Furthermore, the power source may be a constant current source having a maximum voltage, a larger maximum voltage allowing the second electrode 20 to be further away from the surface of the medical device 40 while still achieving the current level required to release bubbles from the surface of the medical device 40 during each electrical pulse.

[0064] As disclosed herein, a fluid output device may be defined as any fluid port that delivers fluid 14 from a fluid source 12 to a destination. The fluid output device may include, for example, a nozzle.

[0065] The controller 30 can be any suitable controller, analog or electronic, for controlling the supply of fluid to the fluid output device 10 and / or the supply of power to the electrode 20. For example, the controller can be configured to control an actuated 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 device 10. For example, the controller can be configured to control a pump to intermittently supply fluid to the fluid output device 10 at a desired pressure. The controller 30 can also be configured to control the supply of power to the electrode. For example, the controller 30 can be an electronic controller that is configured to open and close the electrical connection 54, 24 between the power source 22 and the electrodes 50, 20. The controller 30 can be configured to control one or more electrical components between the power source 22 and the electrode, such as a converter, a variable resistor, etc. It should be understood that in any embodiment disclosed herein, the controller 30 can be powered by any power source and can be powered by the power source 22 or a different power source.

[0066] The device 1 may also include 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 transmitted from the source 60 to the target area via a flexible conduit, which may be positioned at the target area of ​​the medical device 40 and form a flow path 62. The negative pressure source 60 may be powered by any suitable internal or external power source, and may be powered by the power source 22. The negative pressure source 60 may be configured to operate intermittently or continuously so as to intermittently or continuously remove excess electrolytic fluid 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 the fluid 14 with the intermittent operation of the negative pressure source 60, so that the intermittent negative pressure source 60 operates for a predetermined period of time after the fluid output device 10 stops supplying the fluid 14 to the medical device 40. The negative pressure source 60 may output the received fluid to a reservoir (not shown).

[0067] Figure 1B A schematic diagram of an apparatus 1 for removing biofilm or reducing bacterial adhesion from a medical device 40 is shown. Figure 1B include Figure 1A , but provides a separate controller 320 that is connectable to the power source 22 and provides power 24 between the electrodes 50, 20.

[0068] It is worth noting that Figure 1A and 1B The associated device 1 performs two mechanical actions. First, the bacteria are lifted from the surface of the medical device 40 by the bubbles released from the electrolysis. Second, the pressure of the electrolytic fluid supplied by the fluid output device also causes the erosion of the biofilm or bacterial layer on the surface of the medical device 40.

[0069] The power source 22 is preferably a current source. In a preferred embodiment, the power source 22 is configured to provide electrical pulses of sufficient current so that each pulse releases bubbles from the surface of the medical device 40. According to Faraday's first law, the mass of an element deposited on an electrode is proportional to the charge. Therefore, the rate of gas generation on the surface of the medical device 40 is proportional to the current provided by the power source 22. Therefore, the amount of current that needs to be supplied 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 surface of the medical device 40 facing the second electrode 20. Therefore, both the cross-sectional area and the duration of the pulse will determine whether bubbles are released from the surface of the medical device 40 during each pulse. It has been observed that for a cross-sectional area of ​​177 mm 2 With a pulse duration of 0.1 s, a current of 500 mA was sufficient to observe bubbles escaping from the surface during each electrical pulse (i.e., about 2.82 mA / mm 2 The current density is sufficient to lift the bubbles off the surface of the medical device 40). However, a lower current density can be applied and the duration of each pulse can be extended, wherein the duration of the pulse is sufficient to allow the bubbles to escape from the surface of the medical device 40. The voltage range of the current source is preferably 0 to 15 V, preferably 0 to 30 V, and more preferably 0 to 50 V. A higher maximum voltage means that the electrode 20 can move farther from the surface of the medical device 40 while the current is maintained at the desired level.

[0070] As shown in Example 5, according to 1A current and 0.07cm 2 Medical device target area, current density can be 14.29A / cm 2 , and still be safe for the subject. Therefore, although the current density may vary depending on the size of the electrode, it is possible to establish a current greater than 0A / cm 2 And up to 15A / cm 2 More preferably, the current density can be 0.1A / cm 2 Up to 5A / cm 2 , even more preferably 0.2A / cm 2 Up to 2A / cm 2 The spatial dimension always refers to the area of ​​the medical device where electrolysis occurs during the pulse, also referred to as the target area of ​​the medical device, although in some embodiments it may be defined as the cross-sectional area of ​​the second electrode (40) when the voltage is insufficient to provide current to all areas of the device.

[0071] Figure 2A schematic diagram of an electronic controller 30 is shown. The electronic controller 30 includes one or more of a memory 34 and a processor 36. The memory 34 may contain instructions that, when executed using the processor 36, cause the fluid output device 10 and / or the electrode 20 to operate according to any suitable sequence, including the sequence of operations disclosed herein. The controller 30 is configured to control the supply of fluid 14 to the fluid output device 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 fluid components (e.g., valves, pumps, pump motors, etc.) in the flow path 13 and power conditioning components (e.g., power converters, variable resistors, etc.) in the electrical connections between the power source 22 and the electrodes 50, 20. In other embodiments, the controller 30 may be configured to communicate wirelessly with various components, such as via Bluetooth or any other suitable communication protocol, and the control connections 302 and 304 may be wireless. Figure 1B The controller 320 may have a similar configuration to control the supply of power to the electrodes 50 , 20 .

[0072] 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 drive, floppy disk, tape, optical disk, etc. Similarly, the processor 36 may include one or more processing units, such as microprocessors, GPUs, CPUs, multi-core processors, etc. The controller 30 may also be implemented in the form of software, hardware, or any combination thereof to perform the sequence of operations disclosed herein.

[0073] The controller 30 may also be connected to a user interface 32, which is configured to select one or more parameters of the fluid supply control, such as the 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., which a user may use to select 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.

[0074] Figure 3AA fluid output device 10 for use with the apparatus 1 according to one or more embodiments is shown. The fluid output device 10 includes a tubular body 82 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 the target area on the medical device 40. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 so 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 disposed at or near the distal tip of the tubular body 82. The tubular body 82 may include a single orifice at its distal end to output the fluid so that the electrolytic fluid is output as a single jet, or the tubular body 82 may include multiple orifices at its distal end so that the electrolytic fluid is output as a fluid shower or spray. The tubular body 82 is curved so that the longitudinal axis A at the proximal end of the tubular body 82 is different from the longitudinal axis B at the distal end of the tubular body 82. The angle between the longitudinal axis A and the longitudinal axis B can be greater than a value between 0 and 90 degrees, more preferably between 60 and 90 degrees. The curved form of the tubular body 82 allows access to difficult-to-reach areas of the medical device, such as the posterior femoral condyle of a knee prosthesis. The tubular body 82 can also include a sponge at its distal tip (such as with respect to Figure 3C further details) or a conical cap (as described with respect to Figure 3D The length of the tubular body 82 may be 20 mm to 100 mm.

[0075] Figure 3B A fluid output device 10 for use with the apparatus 1 is shown according to one or more embodiments. The fluid output device 10 includes a tubular body 84 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 the target area on the medical device 40. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 so 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 disposed at or near the distal tip of the tubular body 84. The tubular body 84 may include a single orifice at its distal end to output the fluid so that the electrolytic fluid is output as a single jet, or the tubular body 84 may include multiple orifices at its distal end so that the electrolytic fluid is output as a fluid shower or spray. The tubular body 84 is straight so that the longitudinal axis of the tubular body 84 remains unchanged along its length. The tubular body 84 may also include a sponge at its distal tip (such as with respect to Figure 3C further details) or a conical cap (as described with respect to Figure 3D The length of the tubular body 84 may be 20 mm to 100 mm.

[0076] Figure 3CA fluid output device 10 for use with the apparatus 1 according to one or more embodiments is shown. The fluid output device 10 includes a tubular body 85 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 the target area on the medical device 40. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 so 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 disposed at or near the distal tip of the tubular body 85. The tubular body 85 may include a single orifice at its distal end to output the fluid so that the electrolytic fluid is output as a single jet, or the tubular body 85 may include multiple orifices at its distal end so that the electrolytic fluid is output as a fluid shower or spray. The fluid output device also includes a sponge 86 mounted at the distal end of the tubular body 85. The sponge 86 may be made of any deformable porous material (e.g., polyester). The sponge 86 may include a mesh of conductive material and may therefore be connected to the power source 22 and used as the electrode 20. The sponge 86 allows the fluid 14 to be distributed over a wide surface area of ​​the medical device 40 to be treated and suspends the electrolytic fluid 14 in the sponge 86 to ensure that current flows between the electrodes 50, 20. The tubular body 85 may be 20 mm to 100 mm in length.

[0077] Figure 3D A fluid output device 10 for use with the apparatus 1 is shown according to one or more embodiments. The fluid output device 10 includes a tubular body 87 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 the target area on the medical device 40. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 so 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 disposed at or near the distal tip of the tubular body 87. The tubular body 87 may include a single orifice at its distal end to output the fluid so that the electrolytic fluid is output as a single jet, or the tubular body 87 may include multiple orifices at its distal end so that the electrolytic fluid is output as a fluid shower or spray. The tubular body 87 may include a conical cap 88 at its distal tip for engaging with the surface of the medical device 40. The conical cap 88 may prevent the electrolytic fluid from leaking from the target area of ​​the medical device 40 when engaged. The length of the tubular body 87 may be 20 mm to 100 mm.

[0078] Figure 3E A fluid output device 10 is shown for use with the apparatus 1 according to one or more embodiments. Figure 3F Shows a cross section taken along line AA Figure 3E0048] A cross-sectional view of a fluid output device 10 is shown in FIG. The fluid output device 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 the target area on the medical device 40. The tubular body 89 may include a single orifice at its distal end to output the fluid so that the electrolytic fluid is output as a single jet, or the tubular body 89 may include multiple orifices at its distal end so that the electrolytic fluid is output as a fluid shower or spray. Optionally, the one or more fluid conduits are connected to the negative pressure source 60 so that the tubular body 89 also provides a fluid path 62 for the fluid extracted by the negative pressure source 60. The second electrode 20 is disposed at or near the distal tip of the tubular body 87. The second electrode 20 forms a ring-shaped structure within the tubular body 89, such as Figure 3F As shown. In some embodiments, the second electrode 20 may form only a portion of the annular structure. The fluid output device 10 also includes a first electrode 50 located radially inwardly within the second electrode 20. The first electrode may optionally be exposed from the distal tip of the tubular body 89 so that it can easily contact the medical device 40 to form a cathode connection. In other embodiments, the first electrode 50 is formed as an annular structure, and the second electrode 20 is disposed radially inwardly within the first electrode 50. Thus, a single detachable body may be provided that includes the first electrode 50, the second electrode 20, and the fluid output device 10 in its entirety. The fluid output device 10 may also include one or more of the following features: As described with respect to Figure 3A The curved shape; Figure 3C The sponge 86; and Figure 3D The conical cap 88 and the tubular body 89 may have a length of 20 mm to 100 mm.

[0079] It should be understood that in reference Figures 3A to 3F In any of the embodiments described above, the fluid output device 10 may include the first electrode 50 instead of the second electrode 20, and the second electrode 20 may be disposed on a separate element of the device.

[0080] In some embodiments, when the medical device 40 is located in the body, the device 1 can be suitable for minimally invasive percutaneous treatment. Specifically, the electrodes 50 and 20 may include a metal needle configured to be inserted into the body, so that the first electrode 50 is electrically connected to the medical device 40, and the second electrode 20 may be located near the target area of ​​the medical device 40. The fluid output device 10 may also include a needle for piercing the body and injecting an electrolytic fluid at the location of the medical device. Finally, the negative pressure source 60 may also include a needle for piercing the body and extracting the fluid at the location, and when the negative pressure source 60 and the fluid output device 10 are alternately operated, the negative pressure source 60 can use the flow path of the fluid output device 10. Once the needle is correctly placed, the electrolytic fluid can be injected into the location of the medical device 40, and an electric pulse can be applied to the electrolytic fluid to remove bacteria from the surface of the medical device 40. The negative pressure source 60 can then be operated to extract the electrolytic fluid containing the removed bacteria, thereby removing bacteria from the body and treating the infected site.

[0081] Figure 4 A schematic diagram of an apparatus 100 for removing biofilm or bacteria from a metal medical device 40 is shown. Figure 1A and 1B As in the case of the device 1 shown in FIG. 1 , the device 100 includes a fluid output device 10, a first electrode 50 for electrically connecting to a metal device 40, a second electrode 20, and an optional controller 30. The fluid output device 10 is connectable to a fluid source 12 and configured to supply an electrolytic fluid 14 to clean a target area of ​​the medical device 40. The electrode 20 is located near the fluid output device 10 and is connectable to a power source 22, optionally via a controller 320. The device 100 is configured to supply power 24 between the electrodes 50, 20 so that electrolysis occurs 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 so that electrolysis occurs at the surface of the metal device 40, wherein the current applied in each electrical pulse is sufficient to cause bubbles to escape from the surface of the metal device 40 during the electrical pulse. The controller 30 is configured to control the supply of the fluid 14 from the fluid source 12 to the fluid output device 10, and the controller 320 is configured to control the supply of the power 24 to the electrodes 50, 20. In the illustrated embodiment, the power source via controller 320 also powers controller 30 and motor 106, while in other embodiments, controller 30 and motor 106 are powered by separate power sources. Additionally, in some embodiments, controller 30 is configured to supply fluid 14 intermittently.

[0082] exist Figure 4In the embodiment shown, the fluid output device 10 and the electrode 20 are removably connected to the controller via a detachable mechanism. In the specific embodiment shown, the device includes a removable element 102 having a fluid conduit 102a, and the fluid output device 10 is located at the distal end of the conduit 102a. The removable element 102 may include a removable element 102 having a fluid conduit 102a. Figures 3A to 3D The removable element 102 may be any form of tubular body related to the removable element 102, and may also include a sponge or a conical cap at the distal tip. The removable element 102 also includes an electrode 20. The fluid output device 10 and the electrode 20 are removably connected to the body 110 by a detachment mechanism. For example, the removable element 102 may be connected to the body 110 by a threaded mechanism, a friction fit, or a barbed connection. It should be understood that any suitable detachment mechanism may be used, which has a first configuration in which the removable element 102 and the body 110 are mechanically connected and a second configuration in which the removable element 102 and the body 110 are not connected. When the removable element 102 and the body 110 are connected, the electrode 20 is connected to a wire that extends to the proximal end of the removable element 102 and forms an electrical connection with the wire in the body 110, so that the body 110 can be connected to the power source 22. The electrical connection can be formed by any suitable electrical connection, such as a plug and socket or a pin connection. The electrode 20 and the fluid output device 10 are configured to be detachable from the controller 30, allowing the electrode 20 and the fluid output device 10 to be replaced between bacteria or biofilm removal operations, so that cross contamination does not occur between medical devices. Although the removable element 102 includes the fluid output device 10 and the electrode 20, in other embodiments, the fluid output device 10 and the electrode 20 can be permanently connected to the controller 30 and the body 110, or only one of the fluid output device 10 and the electrode can be connected to the controller 30 by a detachable mechanism. The fluid output device 10 and the electrode 20 can be removably connected to the controller 30 by a separate detachable mechanism. The first electrode 50 can be removably connected to the power source 22 or the controller 320 by a similar detachable mechanism, so that the first electrode 50 can be replaced with another electrode to clean a different medical device. In other embodiments, the first electrode 50 can be permanently connected to the controller 320 or the power source 22. The first electrode 50 can be connected to the medical device by any suitable connection mechanism (e.g., an electric clip) or by an adhesive pad.

[0083] The apparatus 100 also includes a pump 104 connectable between the fluid source 12 and the fluid output device 10. The pump 104 can be any suitable pump, such as a positive displacement pump, a pulse pump, or a rotor dynamic 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 the motor 106 to actuate the pump 104. In other embodiments, the pump 104 is hydraulically actuated and the apparatus includes a hydraulic source for actuating the pump. The pump 104 is also configured to be connected to the fluid source 12 so as to receive the fluid 14 as an input to the pump. The pump 104 can be connected to the fluid source 12 independently of the body 110, such as Figure 4 As shown. For example, the pump 104 may include 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 flow 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 the flow path through the body 110. In some embodiments, the pump 104 is disposed within or on the body 110. In such embodiments, the body 110 is configured to be connected to the power source 22 and the fluid source 12, and when the removable element 102 is connected to the body 110, the removable element 102 forms a fluid connection between the output end of the pump 104 and the fluid output device 10 and forms an electrical connection between the power source 22 and the electrode 20 via the body 110.

[0084] exist Figure 4 In the illustrated embodiment, the controller 30 is configured to control the operation of the motor 106, thereby controlling the pump 104. Thus, the controller controls the flow of the fluid 14 to the fluid output device 10 by controlling the motor 106.

[0085] like Figure 4As shown, the body 110 can be ergonomically shaped so that it can be held in the hand of the user. The device 100 can also include a user-actuated element 108, such as a trigger, for actuating the supply of electrolytic fluid to the fluid output device 10. In an embodiment in which the controller 30 also controls the supply of electricity to the electrodes 50, 20, a user-actuated element 108 (or a separate user-actuated element) can also be provided for actuating the supply of electricity to the electrodes 50, 20. The user-actuated element 108 is connected to the controller 30. When the user sets the user-actuated element 108 to a first configuration, the controller 30 is configured to actuate the motor 106. When the user sets the user-actuated element 108 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, wherein the first configuration is achieved by pulling the trigger and the second configuration is achieved by releasing the trigger. The user-actuated element can be connected to, for example, a switch for turning the motor on and off, or the user-actuated element can be configured to send a start or stop signal to the controller 30 in the first configuration and the second configuration. In other embodiments, the user-actuated element 108 may include one or more buttons or levers, or may include a guided user interface on a touch screen, for example.

[0086] The device 100 may also include 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 or the like, and may be provided with or separately from the body 110. Negative pressure may be transmitted from a source 62 to the target area via a flexible conduit, which may be positioned at the target area of ​​the medical device 40 and form a flow path 62. The negative pressure source 60 may be powered by any suitable internal or external power source, and may be powered by the power source 22. The negative pressure source 60 may be configured to operate intermittently so as to intermittently remove excess electrolytic fluid 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 the fluid 14 with the intermittent operation of the negative pressure source 60, so that the negative pressure source 60 intermittently operates for a predetermined period of time after the fluid output device 10 stops supplying the fluid 14 to the medical device 40. The negative pressure source 60 may output the received fluid to a reservoir (not shown). The negative pressure source 60 may be contained within the body 110 and powered by a motor in the body 110 that is controlled by the controller 30, such as in the case of the pump 104. When the removable element 102 is attached to the body 110, the removable element 102 may include a second fluid conduit (not shown) extending from the fluid output device 10 through the removable element 102 to the negative pressure source 60.

[0087] For the device 100 , the surface area of ​​the electrode 20 used to determine the current density at the electrode 20 is the longitudinal cross-sectional area of ​​the electrode 20 at the distal end of the removable element 102 .

[0088] Figure 5A A controller 320 is shown for controlling the power supplied to the electrode 20. The controller 320 is powered by the power supply 22 (the power supply 22 may be external or internal to the controller 320) and may include a user interface 321 (e.g., a touch screen) for selecting parameters of the power supply, such as voltage, current, pulse rate, and duration. The controller 320 includes an output 326. For example, the output 326 may be connected to a power line electrically connected to the electrode 20. For example, in Figure 4 In the illustrated embodiment, the body 110 may be connected to an output 326 via a power cord that provides an electrical connection to the electrode 20 (and optionally powers the controller 30 and motor 106). The controller 320 may also 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 direct current pulse between the electrodes 50, 20 to enable electrolysis to occur.

[0089] Figure 5B Another controller 330 for controlling the supply of power to the electrode 20 is shown. The controller 320 is powered by the power source 22 (the power source 22 can be external or internal to the controller 320) and can include a user interface 321 (e.g., 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 can be connected to a power line electrically connected to the second electrode 20. The controller 330 can also include an electrical connection 328 for the first electrode 50, or the first electrode 50 can be permanently connected to the controller 330. The controller 330 is configured to provide a direct current pulse between the electrodes 50, 20 so that electrolysis can occur. The controller 330 also includes a pump 104 incorporated into the controller 330 so that the controller 330 also provides fluid to the fluid output device 10 (the pump 104 of the controller 330 can be connected to any suitable fluid source through the fluid connection of the controller 330, or the controller 330 can also include a fluid source). The pump can be, for example, a peristaltic pump so that the pump components are not exposed to the fluid. The pump 104 may include an output connector 329 for connecting to a proximal end of the fluid output device 10 .

[0090] Figure 5C A fluid output device 10 is shown that may be used in conjunction with a controller 330. Because the pump is incorporated into the controller 330, the fluid output device 10 does not have any moving parts. Figure 5CThe fluid output device 10 includes a tubular body 350 including one or more fluid conduits from the proximal end of the tube 350 to the distal end of the tube 50. The tubular body 350 may be, for example, Figures 3A to 3F The fluid output device 10 also includes a connector 351 located at the proximal end of the tubular body 350. The connector 351 is configured to cooperate with the output connector 329 to form a fluid connection between the pump 104 and one or more fluid conduits of the tubular body 350, so 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 can 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 device 10 may also include leads 352 and 353 for connecting 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 with the tubular body 350.

[0091] In any embodiment disclosed herein, the fluid 14 can be any electrolyte solution (e.g., a saline solution such as saline), and the device is configured to apply a direct current pulse between the electrodes 50 and 20. The second electrode 20 can be selected as a cathode or an anode, and the first electrode 50 can be connected to the medical device. Preferably, the first electrode 50 is a cathode so that the medical device 40 does not oxidize or corrode. The direct current power applied between the electrodes 50 and 20 causes electrolysis to occur in the target area. The bubbles formed at the target area of ​​the medical device lift the bacteria from the surface of the medical device, thereby reducing the adhesion of bacteria to the medical device and removing the biofilm from its surface. In some embodiments, the fluid output device is configured to provide fluid intermittently, which provides intermittent cleaning for the medical device 40 to prevent bacteria in the electrolytic fluid from accumulating on the surface. That is, the fluid output device 10 provides an electrolyte solution to allow electrolysis in the target area, and the separated bacteria can be further cleaned by the fluid intermittently supplied in the target area. The electrolyte solution fluid contains a solvent and an electrolyte. The solvent can include, for example, water. The electrolyte can include, for example, salt ions and / or silver ions. When the electrolyte solution contains silver ions, an antibacterial effect can be observed without the use of a sacrificial electrode (e.g., a silver electrode). The electrolyte solution may also include one or more of the following: a disinfectant (e.g., hypochlorous acid), an antibacterial agent (e.g., dissolved silver, gold, or copper ions), or an antibiotic therapeutic composition (the antibiotic therapeutic composition may include any suitable antibiotic composition known in the art, including but not limited to one or more of vancomycin, gentamicin, and clindamycin). The salt solution is advantageously biocompatible. It is noteworthy that the cleaning effect of electrolysis and periodic cleaning on the target area is generated by the bubbles generated during the electrolysis process to remove bacteria from the surface, and the removed bacteria are washed away by periodic cleaning. It has been observed that this process greatly shortens the cleaning time of the medical device compared to the process of indirectly killing bacteria using toxic chemicals generated during the electrolysis process.

[0092] The DC power is applied intermittently. When the fluid is output intermittently, at least one DC current cycle can be provided to the electrode for each fluid cycle provided to the fluid output device. Providing at least one DC current cycle for each cycle of the fluid output device can ensure that bacteria are removed from the surface of the medical device before the next fluid cleaning. Preferably, the DC current and fluid are provided intermittently so that electrolysis occurs between fluid cleanings of the medical device. Figure 66 shows a graph of fluid pressure 602 applied to a fluid output device versus time compared to a current amplitude 604 applied to electrode 20. For example, pressure curve 602 may be provided by pump 104 controlled by controller 30, while current curve 604 may be provided by controller 320. Pressure curve 602 includes a series of pulses that provide cleaning of a medical device at a desired pressure. Current curve 604 provides intermittent constant current cycles following fluid pressure pulses. Alternating fluid cleaning and electrolysis caused by direct current provides effective cleaning of the medical device.

[0093] 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 decomposes over time when an electric current is applied to the electrode in an electrolytic solution. The sacrificial electrode can be selected to release specific ions having antimicrobial properties into the electrolytic solution. Examples of suitable materials include silver and copper.

[0094] In a further preferred embodiment, the sacrificial anode comprises silver (Ag) so that the electrolytic oxidation process at the anode releases silver ions to the target area of ​​the device 40. The silver ions enhance the antimicrobial properties of the fluid exposed to the medical device. Thus, the effectiveness of the biofilm or bacteria removal process is enhanced.

[0095] In other embodiments, the second electrode 20 does not contain a sacrificial metal, but rather a metal that is not susceptible to corrosion, such that almost no metal ions are released into the electrolytic solution during the electrolysis process. This allows the electrolytic solution containing bacteria from the biofilm to be recovered after electrolysis. The bacteria can be isolated from the electrolytic solution and cultured to identify the bacteria, thereby guiding the treatment of the infection, such as administering an effective course of antibiotics to the patient. Examples of suitable materials include platinum.

[0096] In any of the embodiments disclosed herein, the first electrode 50 may include one or more metals that are not susceptible to corrosion, such as cobalt-chromium and titanium.

[0097] In any embodiment disclosed herein, the apparatus may be configured to provide a flow rate of between 0.5 liters and 2 liters of electrolytic fluid per minute to the fluid output device. The flow rate may be continuous or intermittent, with a pulse rate between 0-100 Hz, more preferably 0-10 Hz.

[0098] In any embodiment disclosed herein, the device may be configured to provide a DC pulse with a duration of 0.05 seconds to 0.2 seconds and a frequency of 0-100 Hz, more preferably 0-10 Hz. The device may be configured to provide a current between 0A and 1.5A.

[0099] In any of the embodiments disclosed herein, the fluid output device 10 may be removably connected to the controller 30 via a detachment mechanism disclosed in other embodiments. The fluid output device 10 and the electrode 20 may be provided on the same detachable body.

[0100] Any of the embodiments disclosed herein may include a pump located between the fluid source 12 and the fluid output device 10 , wherein the controller is configured to control the pump to provide fluid to the fluid output device 10 at a predetermined pressure.

[0101] Any of the embodiments disclosed herein may include one or more user interfaces to select operating parameters of the fluid supply and the power supply.

[0102] In any embodiments disclosed herein, the fluid output device 10 and the first electrode 50 and / or the second electrode 20 may be connected to a handheld portion, wherein the handheld portion includes a user-actuated element for actuating the delivery of fluid and / or power.

[0103] Any of the devices disclosed herein can be used to implement the following method of removing biofilm from a metal medical device inside or outside the human or animal body or reducing bacteria adhered to the metal medical device:

[0104] • attaching a first electrode (e.g., electrode 50) to a surface of a medical device;

[0105] • exposing a target area on the surface of the medical device to an electrolytic fluid (eg, using fluid output device 10);

[0106] • placing a second electrode (e.g., electrode 20) near the target area;

[0107] • providing power between the first electrode and the second electrode so that electrolysis occurs in the electrolytic fluid (eg, using power source 22);

[0108] - wherein the electrical force comprises a plurality of electrical pulses, wherein the current applied in each electrical pulse is sufficient to cause the gas bubbles to escape from the surface of the medical device.

[0109] It is worth noting that the method is not limited to application by the above disclosed device. For example, the method can be implemented by immersing the medical device in a reservoir or container of electrolytic fluid, connecting a first electrode to the surface of the immersed medical device, placing a second electrode near the target area of ​​the medical device, and providing the required electrical pulses between the electrodes to cause electrolysis to occur on the surface of the medical device. It is worth noting that in embodiments where the medical device is immersed in an electrolytic fluid reservoir in this manner, a step of washing the medical device with the electrolytic fluid can also be included, such as by using a fluid output device disclosed herein to wash the device with the fluid.

[0110] The fluid can be any electrolyte solution disclosed herein.

[0111] Exposing the target area to the electrolytic fluid may include intermittently rinsing the metal device with the electrolytic fluid. The rinsing and electrical pulses may be applied alternately (e.g., Figure 6 The fluid and electrical pulses may be applied according to any of the embodiments disclosed herein.

[0112] The second electrode can be any sacrificial anode disclosed herein, and preferably the anode is composed of silver.

[0113] In some embodiments, the second electrode does not contain a sacrificial metal, but rather a metal that is not susceptible to corrosion, such that virtually no metal ions are released into the electrolytic solution during the electrolysis process. This allows the electrolytic solution containing bacteria from the biofilm to be recovered after the electrolysis. The method may then include separating the bacteria from the electrolytic fluid after providing power. The bacteria may be separated from the electrolytic solution and cultured to identify the bacteria, thereby guiding treatment of the infection, such as administering an effective course of antibiotics to the patient.

[0114] The above method can also be applied to an in vitro medical device. In addition, the above method can also be directly applied to a target area on or inside the human or animal body.

[0115] Example 1

[0116] Fig. 7A The experimental data of the reduction of bacteria on the metal device in the first embodiment is shown.

[0117] In the first embodiment, nine cathode substrates (three for the "CH1" group, three for the "CH2" group, and three for the "CH3" group) were used, which were composed of plates made of cobalt-chromium (CoCr) and nine corresponding anode plates also made of cobalt-chromium (CoCr). These plates were 1.54 cm 2 disk. Before use, the plate was sterilized with UV light for 30 minutes. The cathode substrate was immersed in the corresponding well of 3 mL. The wells were filled with TSB (Tryptic Soy Broth) medium supplemented with 0.25% glucose concentration. A 1 / 100 dilution of Staphylococcus epidermidis strain was used in the medium. The plate was incubated at 37°C for 24 hours. After 24 hours of incubation, the medium was removed from the wells and each well was washed three times with sterile phosphate buffered saline (PBS1X). Each well was then filled with 3 mL of saline solution so that the saline electrically connected the corresponding anode and cathode. Multiple control plates were also incubated in the same manner. The following series of electrical pulses were applied between the corresponding anode and cathode so that electrolysis occurred in the wells and bubbles escaped the cathode surface (the control plate was not exposed to current):

[0118] hole Voltage (V) Pulse duration (s) Pulse interval time (s) Total pulse number CH1 15 0.1 0.5 100 CH2 15 0.1 0.5 150 CH3 15 0.1 0.5 200

[0119] After a series of electric pulses, the salt solution was removed from the wells (this removed salt solution was used to measure the amount of bacteria in the planktonic state after the pulse, as described below), and each well (including the control well) was washed again three times with sterile PBS 1X. The biofilm adhering to the cathode was removed with a sterile scraper and then homogenized in 900 μL of the salt solution. 100 microliters of different serial dilutions were plated on Müller Hinton (MH) agar plates for CFU / mL counting. The data were converted to CFU / cm according to the following formula 2 :

[0120]

[0121] In addition, the amount of bacteria in the planktonic state (i.e. not attached to the cathode surface) after a series of electric pulses was also measured by measuring the amount of bacteria contained in the saline solution directly removed from the wells after the electric pulse (or at the corresponding time in control experiments), following the previous dilution method. The data were converted to CFU / cm according to the above formula 2 .

[0122] Fig. 7A The average CFU / cm2 of biofilm removed from each of the control, CH1, CH2, and CH3 groups is shown. 2 Values ​​(bars, control BF, CH1-BF, CH2-BF and CH3-BF), and CFU / cm of planktonic bacteria in the control, CH1, CH2 and CH3 groups, respectively 2 Values ​​("Control Planktonic" and C_plan_DP"). It can be seen that the biofilms in all groups were significantly (several orders of magnitude) removed compared to the control wells ("Control BF"), with p values ​​less than 0.0001. Similarly, it can be seen that the planktonic bacteria in all groups were significantly (several orders of magnitude) removed.

[0123] Example 2

[0124] Figure 7B The experimental data of the reduction of bacteria on the metal device in the second embodiment is shown.

[0125] In the second embodiment, nine cathode substrates (three for the "CH1" group, three for the "CH2" group, and three for the "CH3" group) were used, which were composed of plates made of cobalt-chromium (CoCr) and nine corresponding anode plates made of cobalt-chromium (CoCr). These plates were 1.54 cm 2disk. Before use, the plate was sterilized with UV light for 30 minutes. The cathode substrate was immersed in the corresponding well of 3 mL. The wells were filled with TSB (Tryptic Soy Broth) medium supplemented with 0.25% glucose concentration. A 1 / 100 dilution of Staphylococcus epidermidis strain was used in the medium. The plate was incubated at 37°C for 24 hours. After 24 hours of incubation, the medium was removed from the wells and each well was washed three times with sterile phosphate buffered saline (PBS1X). Each well was then filled with 3 mL of saline solution so that the saline electrically connected the corresponding anode and cathode. Multiple control plates were also incubated in the same manner. The following series of electrical pulses were applied between the corresponding anode and cathode so that electrolysis occurred in the wells and bubbles escaped the cathode surface (the control plate was not exposed to current):

[0126] hole Voltage (V) Pulse duration (s) Pulse interval time (s) Total pulse number CH1 15 0.1 0.5 25 CH2 15 0.1 0.5 50 CH3 15 0.1 0.5 100

[0127] After a series of electric pulses, the salt solution was removed from the wells (this removed salt solution was used to measure the amount of bacteria in the planktonic state after the pulse, as described below), and each well (including the control well) was washed again three times with sterile PBS 1X. The biofilm adhering to the cathode was removed with a sterile scraper and then homogenized in 900 μL of the salt solution. 100 microliters of different serial dilutions were plated on Müller Hinton (MH) agar plates for CFU / mL counting. The data were converted to CFU / cm according to the following formula 2 :

[0128]

[0129] In addition, the amount of bacteria in the planktonic state (i.e. not attached to the cathode surface) after a series of electric pulses was also measured by measuring the amount of bacteria contained in the saline solution directly removed from the wells after the electric pulse (or at the corresponding time in control experiments), following the previous dilution method. The data were converted to CFU / cm according to the above formula 2 .

[0130] Figure 7B The average CFU / cm2 of biofilm removed from each of the control, CH1, CH2, and CH3 groups is shown. 2 Values ​​(bars, control BF, CH1-BF, CH2-BF and CH3-BF), and CFU / cm of planktonic bacteria in the control, CH1, CH2 and CH3 groups, respectively 2 Values ​​("Control Planktonic" and C_plan_DP"). It can be seen that biofilms were significantly (several orders of magnitude) removed in all groups compared to the control wells ("Control BF"), with p values ​​less than 0.0055. Similarly, it can be seen that planktonic bacteria were significantly (several orders of magnitude) removed in all groups. The removal of biofilm and planktonic bacteria increased significantly with increasing pulse number.

[0131] Remarkably, the high ability of electric pulses to detach biofilms was observed with only 25 electric pulses of 0.1 second duration every 0.5 seconds, representing an 8-order-of-magnitude reduction compared to the control group in a very short time of less than 30 seconds.

[0132] Example 3

[0133] Figure 7C The experimental data of the reduction of bacteria on the metal device in the third embodiment is shown.

[0134] In the third embodiment, nine cathode substrates (three for the "CH1" group, three for the "CH2" group, and three for the "CH3" group) were used, which were composed of plates made of cobalt-chromium (CoCr) and nine corresponding anode plates made of silver (Ag). These plates were 1.54 cm 2 The disc. Before use, the plate was sterilized with UV light for 30 minutes. The cathode substrate was immersed in the corresponding well of 3mL. The wells were filled with TSB (Tryptic Soy Broth) medium supplemented with 0.25% glucose. A 1 / 100 dilution of Staphylococcus epidermidis strain was used in the medium. The plate was incubated at 37°C for 24 hours. After 24 hours of incubation, the medium was removed from the wells and each well was washed three times with sterile phosphate buffered saline (PBS1X). Each well was then filled with 3mL of saline solution so that the saline electrically connected the corresponding anode and cathode. Multiple control plates were also incubated in the same manner. An electric pulse was applied between the anode and cathode of each CH1 and CH3 group so that electrolysis occurred in the wells and bubbles escaped from the cathode surface. After the electric pulse, the saline solution was removed from the wells of the CH1 group, and each well of the CH1 group was washed again three times with sterile PBS1X (including the control wells). The biofilm adhering to the CH1 cathode was removed separately with a sterile scraper and then homogenized in 900μL of saline solution. 100 μl of different serial dilutions were plated on Müller Hinton (MH) agar plates for CFU / mL counting. The data were converted to CFU / cm according to the following formula: 2 :

[0135]

[0136] The cathode plates of the CH2 and CH3 groups were removed from the wells and spray-cleaned with pressurized saline solution, making sure to avoid cross-contamination of the plates by splashing. After the pressure cleaning was completed, the biofilm attached to the CH2 and CH3 cathodes was removed separately with a sterile scraper and then homogenized in 900 μL of saline solution. 100 μL of different serial dilutions were inoculated on Müller Hinton (MH) agar plates for CFU / mL counting. The data were converted to CFU / cm according to the above formula2 .

[0137] Therefore, the CH1 plate was only electrolyzed, the CH2 plate was only cleaned with a pressurized jet, and the CH3 plate was electrolyzed and cleaned with a pressurized jet at the same time. The parameters for electrolysis and cleaning were as follows:

[0138]

[0139] Figure 7C The average CFU / cm2 of biofilm removed by the control, CH1, CH2, and CH3 groups is shown. 2 Values ​​(bars, control BF, pulse 25, gun, and pulse 25 + gun), and CFU / cm of planktonic bacteria in the control 2 Values ​​("control planktonic"). The number of planktonic bacteria in the control was measured in the same manner as in Examples 1 and 2. It can be seen that the application of only 25 electric pulses can reduce the biofilm by about 7.8 orders of magnitude compared to the control, while the biofilm is reduced by about 4.7 orders of magnitude when only cleaning is used. The combination of electric pulses and cleaning can reduce the biofilm by about 9.9 orders of magnitude.

[0140] Example 4

[0141] Fig. 8A A set of wells is shown in which different Ti, Ti sintered and Cr-Co medical implants (40) were incubated with a biofilm. Figures 8B to 8D The elimination of biofilm on Ti, Ti sintered and Cr-Co medical implants (40) during in vitro methods according to the present procedures are shown respectively.

[0142] In the fourth example, biofilms of E. coli were grown and developed on 1.4 cm wide Ti plates, Ti sintered plates, and Cr-Co plates for 72 hours to form mature biofilms, which were stained with crystal violet so that the biofilms could be easily identified by their darker color, as shown in FIG. Figures 8B to 8D The sample was then dehydrated for another 72 hours to increase its adhesion.

[0143] After completion, attempts were made to separate it with physiological serum, but this was impossible.

[0144] Subsequently, a pulse of 1 A (2 pulses per second, each pulse duration 0.25 seconds) was applied (see Figures 8B-8D Phase II), successfully detaching the entire biofilm in less than 10 seconds after application, such as Figures 8B to 8D The target area for the 1.4 cm wide circular plate is 1.54 cm 2 , which means that the applied current density is 0.65A / cm2 .

[0145] The in vitro experiment shows that the in vitro method for removing biofilm of the present invention can effectively remove the biofilm on the medical implant in a short time.

[0146] Example 5

[0147] Fig.9A A medical implant (40) for a rabbit knee is shown, which is made of Cr-Co with a diameter of only 3 mm. Fig. 9B A portion of an apparatus for removing biofilm from a metal medical device is shown, 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 cord to which the electrode 20 is electrically connected.

[0148] The fifth embodiment was tested in vivo. Under standard aseptic conditions, two New Zealand white rabbits were implanted with specially designed Cr-Co prostheses (40) at their knees. Fig. 9C As indicated, antibiotic prophylaxis was performed with a single dose of cefazolin 10 mg / kg. Prior to implantation, the prosthesis was immersed in a 0.3 McFarland inoculum of Staphylococcus aureus ATCC25923 for 30 seconds.

[0149] In the first animal (control), the joints were closed directly after washing with saline. In the second animal (case), both prostheses were treated with pulsed current (1A, 2 pulses per second) with a 30% interval for 40 seconds, washed with saline and closed, as Fig.9D The target area for a 3 mm implant is 0.07 cm 2 , which means that the applied current density is 14.29A / cm 2 .

[0150] After 72 hours, both animals underwent reoperation and tissue, bone and prosthetic implant samples were cultured. Quantitative cultures from all samples were previously vortexed and sonicated in 1 ml BHI. The absence of contamination was confirmed by MALDI-TOF MS (VITEK-MS) and automated antibiogram of isolated colonies (VITEK-2).

[0151] In control animals treated with one dose of cefazolin, S. aureus was isolated from all study samples and was isolated from the right leg prosthesis at a log10(ufc / cm 2) was 9.38 in the right leg and 8.86 in the left leg. Bacterial counts expressed as log10 (ufc / mL) in 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 to which an electric field was applied in addition to a dose of cefazolin after implantation, all samples (prosthesis, bone and periprosthetic tissue biopsies) were negative and the inoculated Staphylococcus aureus strain could not be isolated after 14 days of incubation in broth treated with ultrasound. The results are shown in the following table:

[0152]

[0153] This in vivo model suggests that the application of electric fields to prosthetic implants in combination with cefazolin may have the efficacy to prevent implant-associated infections (IPAs) following exposure of the implants to an inoculum of S. aureus ATCC25923.

[0154] Example 6

[0155] In the sixth embodiment, another in vivo experiment was conducted. Under standard aseptic measures, two New Zealand white rabbits were implanted with a specially designed Cr-Co prosthesis and a single dose of cefazolin 10 mg / kg was used for antibiotic prophylaxis.

[0156] Provide 0.5mL to 1mL of ATCC inoculum containing Staphylococcus aureus (10 5 ufc / ml) of serum, and the rabbits were housed for 4 days to allow the infection to progress.

[0157] After 4 days of infection progression, the first rabbit (control) and the second rabbit (case) were treated differently. The control rabbits underwent extensive surgical cleansing and flushing with rich physiological serum for 1 minute, representing a typical intervention of debridement, antibiotics, and implant retention (DAIR). The case rabbits underwent extensive surgical cleansing and flushing with rich physiological serum and current pulses (1A, 2 pulses per second, 30% duty cycle) for 1 minute.

[0158] After the cleaning procedure, control and case rabbits were monitored for 4 days, with cefazolin doses maintained to prevent sepsis and progression of infection to soft tissues.

[0159] Finally, the prosthesis was removed under sterile conditions, and further samples of joint fluid, periarticular tissue, bone, and blood cultures were collected.

[0160] The results showed that in the control animals, the bacterial counts expressed as log10 (ufc / mL) per prosthesis at a 1 / 10 dilution (regardless of the data on the prosthesis surface) were significantly higher than those in the case animals, as shown in the following table:

[0161]

[0162] The results show that electric fields applied according to one or more embodiments of the present invention are very effective in treating joint prosthesis infections, with improved results 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 the recolonization of bacteria present in the soft tissue around the joint. However, the counts were much lower than in the prostheses of the control rabbits treated with DAIR alone (no electric fields).

[0163] Example 7

[0164] Fig. 10A A portion of a device for removing biofilm from a metal medical device according to one or more embodiments of the present invention is shown, including: a controller 320 and a first electrode 20. The controller 320 includes a user interface 321 and outputs 326 and 328, the output 326 can be connected to a power line configured to be electrically connected to the electrode 20, and the output 328 can be connected to a power line configured to be electrically connected to the reference electrode 50.

[0165] Seventh Example Another in vitro experiment was conducted. Figures 10B to 10G A set of wells is shown in which different Ti, Ti sintered and Cr-Co medical implants (40) were incubated with a biofilm. Figures 10B to 10D The biofilm status before and after pulsed fluid-based biofilm removal procedures on Ti, Ti sintered, and Cr—Co medical implants ( 40 ) are shown, respectively. Figures 10E to 10G The biofilm states before and after the biofilm removal procedure according to the present invention are respectively shown on Ti, Ti sintered and Cr—Co medical implants ( 40 ), respectively.

[0166] E. coli biofilms were grown and developed on Ti plates, Ti sintered plates, and Cr-Co plates for 72 h to form mature biofilms, which were stained with crystal violet, so that the biofilms could be easily identified by their darker color, e.g. Figures 10B to 10G As shown in stage I of (stage I). Subsequently, in order to increase its adhesion, it is dehydrated for another 72 hours.

[0167] First, three implants (Ti, Ti sintered, and Cr-Co implants) were treated in a pulsed manner using an electrolytic fluid according to the prior art ( Figures 10B to 10D ). Use a commercial fluid gun to deliver the electrolytic fluid at high and low purge flow rates.

[0168] Then, use Fig. 10A In the present invention, the device according to one or more embodiments of the present invention treats three other implants (Ti, Ti sintered and Cr-Co), specifically, a sponge ( Figures 10E to 10G). The current pulses provided were 1A, 2 pulses per second, and a duty cycle of 50%, providing the electrolytic fluid at its minimum flow rate.

[0169] like Figures 10B to 10G As shown in Phase II of the experiment, the results show that in the implants treated with the pulsed electrolytic fluid alone, the biofilm could not be removed regardless of the low or high irrigation flow rate. On the other hand, using the device and method according to the present invention, the biofilm was completely removed in less than 5 seconds after application (for each implant).

[0170] All of the above are fully within the scope of the present disclosure and are to be considered as forming the basis for alternative embodiments applying one or more combinations of the above features, without being limited to the specific combinations disclosed above.

[0171] In view of this, there will be many alternatives for implementing the teachings of the present disclosure. Those skilled in the art will be able to modify and adjust the above disclosure to suit their own circumstances and requirements within the scope of the present disclosure, while retaining some or all of the technical effects of the above disclosure (whether disclosed or derivable from the above) according to their general knowledge in the art. All such equivalents, modifications or adjustments are within the scope of the present disclosure.

Claims

1. An in vitro method for removing biofilm from a metal medical device outside the human or animal body or reducing bacteria adhering to the metal medical device, comprising: connecting a first electrode to a surface of the medical device; exposing a target area on a surface of the medical device to an electrolytic fluid; placing a second electrode proximate the target area; providing power between the first electrode and the second electrode so that electrolysis occurs in the electrolytic fluid; Wherein the electrical force comprises a plurality of electrical pulses, wherein the potential difference between the first electrode and the second electrode is at least 1 V, and wherein the current density applied in each electrical pulse is up to 15 A per square centimeter of the target area.

2. The method according to claim 1, wherein the applied current density is 0.1 A to 15 A per square centimeter of target area, preferably 0.1 A to 5 A per square centimeter of target area.

3. The method according to claim 1 or 2, wherein the applied current density is 0.2A to 2A per square centimeter of target area.

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

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

6. The method according to claim 4 or 5, wherein the duration of each electric pulse is 0.05 seconds to 0.2 seconds.

7. A method according to any one of claims 1 to 6, wherein the second electrode is an anode, the anode comprising a sacrificial metal, preferably silver, and / or wherein the electrolytic fluid comprises one or more of a disinfectant, antimicrobial or antibiotic agent; or The second electrode is an anode comprising a non-corrosive metal and free of a sacrificial metal, wherein the method further comprises separating bacteria from the electrolytic fluid after providing the power.

8. An apparatus for removing biofilm from a metal medical device, comprising: a fluid output device connectable to a source of electrolytic fluid, the fluid output device for supplying electrolytic fluid to cleanse a target area of ​​the medical device; a first electrode for electrical connection to the medical device; a second electrode configured to be placed proximate to the fluid output device; as well as a power source for supplying power between the first electrode and the second electrode; The power supply is configured to provide intermittent electrical pulses between the first electrode and the second electrode such that electrolysis occurs on the surface of the metal device, wherein the potential difference between the first electrode and the second electrode is at least 1V, and wherein the current density applied in each electrical pulse is up to 15A per square centimeter of target area.

9. The apparatus according to claim 8, wherein the power source is configured to provide intermittent electrical pulses, wherein the applied current density is 0.1 A to 15 A per square centimeter of target area, preferably 0.1 A to 5 A per square centimeter of target area.

10. The apparatus of claim 8 or 9, wherein the power source is configured to provide intermittent electrical pulses, wherein the applied current density is between 0.2A and 2A per square centimeter of target area.

11. An apparatus for removing biofilm from a metal medical device, comprising: a fluid output device connectable to a source of electrolytic fluid, the fluid output device for supplying electrolytic fluid to clean a target area of ​​the medical device; a first electrode for electrical connection to the medical device; a second electrode configured to be placed proximate to the fluid output device; as well as a power source for supplying power between the first electrode and the second electrode; wherein the power supply is configured to provide intermittent electric pulses between the first electrode and the second electrode such that electrolysis occurs on the surface of the metal device, wherein the potential difference between the first electrode and the second electrode is at least 1V; and wherein the current applied in each electric pulse is up to 2A, and wherein the duration of each electric pulse is less than 1 second.

12. The device according to claim 11, wherein the power supply is configured to provide intermittent electrical pulses, wherein the potential difference is 1V to 50V, preferably 10V to 30V, and the current between the first electrode and the second electrode is 0.5A to 1A.

13. The apparatus of claim 11 or 12, wherein the power supply is configured to provide each electrical pulse with a duration of 0.05 seconds to 0.2 seconds.

14. The apparatus according to any one of claims 8 to 13, wherein the apparatus further comprises a controller configured to control the supply of the electrolytic fluid from the fluid source to the fluid output device.

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

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

17. Apparatus according to claim 16, wherein the fluid output means comprises a porous sponge or a conical cap at a distal end thereof.

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

19. The apparatus of claim 18, wherein both the first electrode and the second electrode are disposed on the single detachable body.

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

21. Apparatus according to any one of claims 8 to 20, wherein the apparatus further comprises a source of electrolytic fluid connected to the fluid applicator, wherein the fluid is a saline solution; optionally wherein the fluid comprises one or more of a disinfectant, antimicrobial agent or antibiotic agent.

22. The apparatus according to any one of claims 8 to 21, wherein the apparatus further comprises a pump configured to provide the electrolytic fluid to the fluid output device at a predetermined pressure.

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

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