Nonthermal plasma mist

Abstract

A cold plasma device for expressing a nonthermal plasma-treated fluid, the cold plasma device comprising: a probe, the probe comprising a conductor wire extending from a proximal end to a distal probe end and having a tip at the distal probe end; and a first passage having a first opening adjacent to the tip for receiving a fluid therein for dispensing the nonthermal plasma-treated fluid.

Description

NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 NONTHERMAL PLASMA MIST CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of US Provisional Patent Application No.63 / 554,305 filed on February 16, 2024, and claims the benefit of US Provisional Patent Application No.63 / 554,314 filed on February 16, 2024, with the United States Patent and Trademark Office, the contents of which are incorporated herein by reference in their entirety. FIELD OF THE INVENTION

[0002] The embodiments are directed toward devices using plasma-treated water, formation of plasma-treated water, devices for creating plasma-treated mist, and methods of use of the same. BACKGROUND OF THE INVENTION

[0003] Plasma-treated fluids have certain unique properties based on the introduction of certain reactive species and radicals into the fluid. Within the prior art, single electrodes are utilized to create low volumes of fluid that are plasma-treated. A high voltage electrode, typically with a quartz glass barrier, ceramic barrier, or other dielectric barrier, is positioned at a specific distance from a fluid. The fluid, upon application of an electric field will jump to the electrode and charge the fluid.

[0004] However, it is critically important to manage the distance between the electrode and the fluid to prevent the fluid from jumping to the electrode and grounding the electrode. It is also important to control interaction of the fluid with plasma to maximize diffusion of plasma-generated reactive species and radicals into the fluid. Furthermore, as a single electrode, the volume which can be treated is small. Grids of electrodes may be utilized over a flat span of fluids, but again issues relate to the distance between the electrode and the fluid and to create such stable and level spaces for treating the fluid without spoiling the fluids. Accordingly, mass production of such fluids is all but impossible.

[0005] Applicant has created improvements to methods and systems that use plasma-treated fluids, particularly through the creation of mists or microdroplets of plasma-treated fluids, which can be advantageously applied to live tissues, particularly those of animal and human tissues, and which may be used for treatments of infection of a variety of microorganisms. Particular embodiments are directed toward the unique creation of dental devices, wound care devices, oral care, esophageal treatment, as well as those of the sinus, nasal passages, and reproductive tracts. Furthermore, the devices may be suitable for prophylaxis and sterilizing procedures before, during, and / or after surgical procedures. SUMMARY OF THE INVENTION

[0006] Methods of treatment of a microorganism by applying a quantity of fluids from a device, which are charged by the application of cold plasma to create, within the quantity of fluids, reactive species; and wherein the fluids are 1 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 formed into microdroplets through sufficient means wherein cold plasma is generated at a tip of an applicator device, and wherein fluids are expressed to contact the cold plasma. In a preferred embodiment, the fluid is precharged with cold plasma before being expressed. In certain preferred embodiments, the plasma-treated fluid is created by a first device and then added to a second device for creation of the plasma mist.

[0007] In a preferred embodiment, a cold plasma device for generating a nonthermal plasma mist comprising: a probe (18), said probe (18) comprising a conductor wire (14) extending from a proximal end to a distal probe end and having a tip (17) at said distal probe end; a first passage having a first opening adjacent to the tip (17) and a second passage having a second opening adjacent to the tip (17); said first passage or said second passage defined for receiving a fluid therein for dispensing said nonthermal plasma mist from the first opening or the second opening; and a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz.

[0008] In a further embodiment, the cold plasma device wherein the power source most preferably generates between 17,000 V and 37,000 V pulses of between 1 µs and 5 µs in duration applied at 1,000 Hz.

[0009] In a further embodiment, the cold plasma device wherein the conductor wire comprises an insulating material along a length of the probe from the proximal end to the distal probe end with a portion of noninsulated material at each end of the conductor wire.

[0010] In a further embodiment, the cold plasma device wherein the probe is connected to a pressurized gas and a wiring harness, said wiring harness connected to a power source.

[0011] In a further embodiment, the cold plasma device wherein a pressurized gas is configured to flow into the first passage.

[0012] In a further embodiment, the cold plasma device is defined to provide suction from the second opening adjacent to the tip and through the second passage.

[0013] In a further embodiment, the cold plasma device wherein the conductor wire is surrounded by an epoxy along a length of the probe from the proximal end to the distal probe end.

[0014] In a further embodiment, the cold plasma device wherein the tip comprises a conductive metal or metal alloy.

[0015] In a further embodiment, the cold plasma device wherein the tip comprises gallium or a gallium alloy.

[0016] In a further embodiment, the cold plasma device wherein the first passage and the second passage are attached to an outside portion of the probe or a recess within the probe or are comprised within the probe. 2 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0017] In a further embodiment, the cold plasma device wherein the first passage is provided with nitrogen gas or a nitrogen gas and nitric oxide gas mixture at a concentration of the nitric oxide of 5,000 ppm and a flow rate of between 0.01 standard liters per minute (SLPM) and 0.15 SLPM.

[0018] In a further embodiment, the cold plasma device wherein the first passage or second passage is defined to connect to a reservoir of fluid.

[0019] In a further embodiment, the cold plasma device wherein plasma mist is generated by taking a fluid within the first passage or second passage and passing said fluid through a microdroplet generator before being expressed from the first opening or second opening.

[0020] In a further embodiment, the cold plasma device comprising: a suction of between 0.1 SLPM and 10 SLPM of flow within the second passage; and / or a flow of nitrogen gas into the first passage; and / or a flow of a combination of nitrogen gas and nitric oxide, said nitric oxide at between 1,000 ppm and 10,000 ppm, having a standard liter per minute flow of 0.01 SLPM to 0.15 SLPM; and / or a flow of fluid wherein said fluid is optionally expelled as microdroplets.

[0021] In a preferred embodiment, use of the cold plasma device for use in treatment of sinusitis and / or nasal infection and / or Barrett’s esophagus and / or a combination thereof.

[0022] In a preferred embodiment, the fluids are expressed from a cold plasma device wherein the fluid is water. In a further preferred embodiment, the fluids expressed from a cold plasma device wherein the fluid expressed further comprises at least one additional additive.

[0023] In a preferred embodiment, a method of treatment of sinusitis comprising administering to a patient in need thereof an effective amount of nonthermal plasma mist, said plasma mist generated by any of the disclosed embodiments.

[0024] In a further embodiment, the method of treatment wherein the nonthermal plasma mist is administered by providing a flow of nitrogen gas to a tip of the probe.

[0025] In a further embodiment, the method of treatment wherein the nonthermal plasma mist is administered by providing a suction of air from an opening in a passage adjacent to a tip of the probe.

[0026] In a further embodiment, the method of treatment comprising a fluid reservoir and a microdroplet creator wherein fluid flows into the microdroplet creator and is expelled from the tip as microdroplets and preferably wherein a cold plasma is provided to contact the microdroplets.

[0027] In a further embodiment, the method of treatment wherein the first passage and the second passage are attached to an outside portion of the probe or a recess within the probe or are comprised within the probe.

[0028] In a preferred embodiment, a method of treatment of sinusitis comprising administering to a patient in need thereof an effective amount of nonthermal plasma-treated fluid, mist, said nonthermal plasma-treated fluid administered 3 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 by inserting a balloon catheter into a nasal cavity, said balloon catheter having a probe at a distal end of the balloon catheter, and applying a quantity of nonthermal plasma-treated fluid from the probe from the balloon catheter. In preferred embodiments, the method wherein the plasma-treated fluid is provided as a plasma-treated mist. In preferred embodiments, the method wherein the plasma-treated mist is generated by a microdroplet creation device.

[0029] In a preferred embodiment, a method of treatment of a nasal infection comprising administering to a patient in need thereof an effective amount of nonthermal plasma mistreated fluid, said nonthermal plasma-treated fluid administered by inserting a balloon catheter into a nasal cavity, said balloon catheter having a probe at a distal end of the balloon catheter, applying a quantity of nonthermal plasma-treated fluid from the probe from the balloon catheter. In preferred embodiments, the method wherein the plasma-treated fluid is provided as a plasma-treated mist. In preferred embodiments, the method wherein the plasma-treated mist is generated by a microdroplet creation device.

[0030] In a preferred embodiment, a method of treatment of a body tissue, said body tissue accessible by a balloon catheter, and comprising administering to a patient in need thereof an effective amount of nonthermal plasma-treated fluid, said nonthermal plasma-treated fluid administered by inserting the balloon catheter into or adjacent to the body tissue, said balloon catheter having a probe at a distal end of the balloon catheter, applying a quantity of nonthermal plasma-treated fluid from the probe from the balloon catheter. In preferred embodiments, the method wherein the plasma-treated fluid is provided as a plasma-treated mist. In preferred embodiments, the method wherein the plasma- treated mist is generated by a microdroplet creation device.

[0031] In a preferred embodiment, a method of providing an antimicrobial nonthermal plasma mist to a tissue comprising administering to a patient in need thereof an effective amount of nonthermal plasma mist, said nonthermal plasma mist administered by generating a plurality of microdroplets, said microdroplets being formed by a microdroplet device, and wherein the microdroplets are charged with oxidative species by contacting fluid of the microdroplets with a cold plasma before creation of the microdroplets, after creation of the microdroplets, or both and applying a quantity of nonthermal plasma mist to the tissue.

[0032] In a further embodiment, the device or method comprising a fluid supply line and a microdroplet generator; wherein said fluid supply line provides fluid to the microdroplet generator; wherein upon formation microdroplets are contacted by cold plasma; and preferably wherein the microdroplet generator is a sonicator, nebulizer, nozzle, atomizer, or combinations thereof.

[0033] In a preferred embodiment, an endoscope comprising a probe at its distal end sufficient to express a plasma- treated fluid from said distal end. 4 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0034] In a preferred embodiment, an endoscope comprising a balloon at its distal end and an outlet further distal to the balloon for expressing plasma-treated fluids or plasma mist and optionally further comprising a probe suitable for creating quantities of plasma to treat fluids expressed from the outlet.

[0035] In a further embodiment, the device or method that is a laparoscope.

[0036] In a preferred embodiment, an irrigator, said irrigator expressing plasma-treated fluid.

[0037] In a preferred embodiment, an irrigator, said irrigator comprising a plasma probe, said irrigator further comprising an activation feature and a fluid line, said fluid line exiting adjacent to the plasma probe, and wherein fluid flows and plasma is generated upon activating the activation feature.

[0038] In a preferred embodiment, a plasma device comprising: a fluid supply; a microdroplet creator and a plasma treatment component; and wherein upon flow of fluid from the fluid supply, the fluid is formed into a plurality of microdroplets via the microdroplet creator and the fluid and / or the microdroplets are contacted by cold plasma.

[0039] In a preferred embodiment, a system for creating plasma mist for therapeutic treatment comprising: a power supply; a plasma probe; a fluid supply, a microdroplet creator, and an activation switch; wherein upon changing the activation switch from an off position to an on position, the fluid supply is activated, the microdroplet creator is activated, and the power supply provides the necessary plasma in pulses to generate cold plasma; wherein the cold plasma contacts microdroplets of fluid creating plasma mist; and wherein the plasma mist is provided for therapeutic treatment.

[0040] In a preferred embodiment, a method of treating a patient in need thereof with an antimicrobial plasma mist comprising generating the plasma mist and applying the plasma mist to a patient in need thereof.

[0041] In a further embodiment, the method of treatment wherein the system further comprises a balloon catheter wherein the plasma mist is expelled from a tip distally positioned on the balloon catheter.

[0042] In a preferred embodiment, a cold plasma device for generating a nonthermal plasma mist, the cold plasma device comprising: a probe (18), said probe (18) comprising a conductor wire (14) extending from a proximal end to a distal probe end and having a tip (17) at said distal probe end; a first passage having a first opening adjacent to the tip (17); said first passage defined for receiving a fluid therein for dispensing said nonthermal plasma mist from the first opening; and a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz.

[0043] In a further embodiment, the cold plasma device wherein the power source most preferably generates between 17,000 V and 37,000 V pulses of between 1 µs and 5 µs in duration applied at 1,000 Hz.

[0044] In a further embodiment, the cold plasma device wherein the conductor wire comprises an insulating material along a length of the probe from the proximal end to the distal probe end with a portion of noninsulated material at each end of the conductor wire. 5 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0045] In a further embodiment, the cold plasma device wherein the probe comprises a second passage, said second passage being connected to a harness, said harness comprising a feature suitable for supplying pressurized gas to said tip.

[0046] In a further embodiment, the cold plasma device wherein the conductor wire is surrounded by an epoxy along a length of the probe from the proximal end to the distal probe end.

[0047] In a further embodiment, the cold plasma device wherein the tip comprises a conductive metal or metal alloy.

[0048] In a further embodiment, the cold plasma device wherein the tip comprises gallium or a gallium alloy.

[0049] In a further embodiment, the cold plasma device wherein the first passage and the second passage are attached to an outside portion of the probe or a recess within the probe or are comprised within the probe.

[0050] In a further embodiment, the cold plasma device wherein the first passage is provided with nitrogen gas or a mixture of nitrogen gas and nitric oxide gas at a concentration of the nitric oxide gas of 5,000 ppm and a flow rate of between 0.01 standard liters per minute (SLPM) and 0.15 SLPM.

[0051] In a further embodiment, the cold plasma device wherein the first passage is defined to connect to a fluid supply.

[0052] In a further embodiment, the cold plasma device wherein plasma mist is generated by taking a fluid within the first passage and passing said fluid through a microdroplet generator before being expressed from the first opening.

[0053] In a further embodiment, the cold plasma device comprising: a suction of between 0.1 SLPM and 10 SLPM of flow within the second passage; and / or a flow of nitrogen gas into the first passage; and / or a flow of a combination of nitrogen gas and nitric oxide, said nitric oxide at between 1,000 ppm and 10,000 ppm, having a standard liter per minute flow of 0.01 SLPM to 0.15 SLPM; and / or a flow of fluid wherein said fluid is optionally expelled as microdroplets.

[0054] In a further embodiment, the cold plasma device wherein the fluid is pretreated with a cold plasma.

[0055] In a further embodiment, the cold plasma device wherein the fluids are expressed to contact cold plasma generated by the device, thereby generating the plasma mist.

[0056] In a preferred embodiment, use of the cold plasma device for use in treatment of sinusitis and / or nasal infection and / or Barrett’s esophagus and / or combinations thereof.

[0057] In a preferred embodiment, a cold plasma device for generating a nonthermal plasma mist, the cold plasma device comprising: a probe (18), said probe (18) comprising a conductor wire (14) extending from a proximal end to a distal probe end and having a tip (17) at said distal probe end; a first passage having a first opening adjacent to the tip (17), a second passage having a second opening adjacent to the tip (17), and a third passage having a third opening adjacent to 6 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 the tip (17); said first passage defined for receiving a fluid therein for dispensing said nonthermal plasma mist from the first opening, the second passage defined for supplying a pressured gas, and the third passage defined to provide a suction from said third opening; and a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz.

[0058] In a preferred embodiment, a method of generating a nonthermal plasma-treated fluid, the method comprising: (a) an applicator device comprising a probe (18), said probe (18) comprising a conductor wire (14) extending from a proximal end to a distal probe end and having a tip (17) at said distal probe end; (b) a first passage having a first opening adjacent to the tip (17); (c) said first passage defined for receiving a fluid therein, said first passage connected thereto to a fluid source; (d) a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz sufficient to generate nonthermal plasma; and (e) expressing the fluid from said first passage, whereby the fluid passes through the nonthermal plasma, generating the nonthermal plasma fluid.

[0059] In a further embodiment, the method further comprising a microdroplet generator, said microdroplet generator receiving the fluid from the fluid source and generating microdroplets which are expressed from the first opening, and wherein said microdroplets are passed through the nonthermal plasma.

[0060] In a preferred embodiment, a method of expressing a plasma-treated fluid from a device, the method comprising: (a) generating a quantity of plasma-treated liquid by applying a nonthermal plasma to said plasma-treated liquid by applying between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s for a duration of between 5 minutes and 120 minutes applied at 100 Hz to 10,000 Hz adjacent to said plasma-treated liquid; (b) capturing the plasma-treated liquid into a vessel; (c) withdrawing the plasma-treated liquid from the vessel; and (d) expressing a quantity of the plasma-treated liquid from the device.

[0061] In a further embodiment, the method wherein the plasma-treated liquid is expressed from the device as a microdroplet.

[0062] In a further embodiment, the method wherein microdroplets are created by a sonicator, a nebulizer, a nozzle, an atomizer, or combinations thereof.

[0063] In a further embodiment, the method wherein the device further comprises a probe sufficient to receive a voltage to create a nonthermal plasma and wherein the nonthermal plasma is generated adjacent to an opening of the device wherein the plasma-treated liquid is expressed.

[0064] In a preferred embodiment, a method of treatment of sinusitis, the method comprising administering an effective amount of nonthermal plasma-treated fluid to a patient in need thereof. 7 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0065] In a further embodiment, the method further comprising wherein said nonthermal plasma-treated fluid is administered by expressing a quantity of fluid from a device and applying a quantity of cold plasma from a probe within the device wherein the fluid comes into contact with the cold plasma.

[0066] In a further embodiment, the method wherein the nonthermal plasma-treated fluid is a plasma mist.

[0067] In a further embodiment, the method wherein the nonthermal plasma-treated fluid is created by providing a flow of nitrogen gas to a tip of the probe.

[0068] In a further embodiment, the method wherein the nonthermal plasma-treated fluid is administered by providing a suction of air from an opening in a passage adjacent to a tip of the probe.

[0069] In a further embodiment, the method wherein the nonthermal plasma-treated fluid is generated from a probe (18), said probe (18) comprising: a conductor wire (14) extending from a proximal end to a distal end and having a tip (17) at said distal end; a first passage having a first opening adjacent to the tip (17) for expressing the fluid; and a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz.

[0070] In a further embodiment, the method wherein the conductor wire comprises an insulating material along a length of the probe from the proximal end to the distal end with a portion of noninsulated material at each end of the conductor wire.

[0071] In a further embodiment, the method wherein the probe is connected to a pressurized gas or a fluid supply and a wiring harness said, wiring harness connected to a power source, and wherein at least a second passage supplies the pressurized gas.

[0072] In a further embodiment, the method comprising at least a third passage, said third passage defined to provide suction from a second opening adjacent to the tip and through the third passage.

[0073] In a further embodiment, the method wherein the first passage and the second passage are attached to an outside portion of the probe or a recess within the probe or are comprised within the probe.

[0074] In a further embodiment, the method wherein the first passage or the second passage is connected to a fluid supply line, wherein a microdroplet generator is provided in line with the fluid supply line, and wherein fluid is treated with cold plasma.

[0075] In a further embodiment, the method comprising: a suction of between 0.1 SLPM and 10 SLPM within the second passage; and / or a flow of nitrogen gas into the first passage; and / or a flow of a combination of nitrogen gas and nitric oxide, said nitric oxide at between 1,000 ppm and 10,000 ppm, having a standard liter per minute flow of 0.01 SLPM to 0.15 SLPM. 8 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0076] In a further embodiment, the method wherein the conductor wire is surrounded by an epoxy along a length of the probe from the proximal end to the distal end.

[0077] In a further embodiment, the method wherein the tip comprises a conductive metal or metal alloy, which is preferably gallium or a gallium alloy.

[0078] In a further embodiment, the method comprising a fluid reservoir and a microdroplet creator wherein fluid flows into the microdroplet creator and is expelled from the tip as microdroplets and preferably wherein a cold plasma is provided to contact the microdroplets.

[0079] In a further embodiment, the method wherein the first passage is provided with a mixture of nitrogen gas and nitric oxide at a concentration of the nitric oxide at 5,000 ppm and a flow rate of between 0.01 SLPM and 0.15 SLPM.

[0080] In a preferred embodiment, a method of treatment of sinusitis, the method comprising administering an effective amount of nonthermal plasma-treated fluid to a patient in need thereof, said nonthermal plasma-treated fluid administered by inserting a balloon catheter into a nasal cavity, said balloon catheter defining a lumen comprising a fluid supply line, and applying a quantity of nonthermal plasma-treated fluid from the fluid supply line at a distal end of the balloon catheter.

[0081] In a further embodiment, the method further comprising a probe at the distal end, the probe sufficient to generate cold plasma, and wherein the method comprises applying a voltage to the probe sufficient to generate a cold plasma, which is generated while expressing the nonthermal plasma-treated fluid from the fluid supply line.

[0082] In a further embodiment, the method further comprising a plasma mist generator wherein the nonthermal plasma-treated fluid is transformed by the plasma mist generator into a plasma-treated mist.

[0083] In a preferred embodiment, a method of treatment of a nasal infection, the method comprising administering an effective amount of nonthermal plasma mist to a patient in need thereof, said nonthermal plasma mist administered by inserting a balloon catheter into a nasal cavity, said balloon catheter having a probe at a distal end of the balloon catheter, and applying a quantity of nonthermal plasma mist from the probe from the balloon catheter.

[0084] In a preferred embodiment, a method of treatment of a body tissue, said body tissue accessible by a balloon catheter, the method comprising administering an effective amount of nonthermal plasma mist to a patient in need thereof, said nonthermal plasma mist administered by inserting the balloon catheter into or adjacent to the body tissue, said balloon catheter having a probe at a distal end of the balloon catheter, and applying a quantity of nonthermal plasma mist from the probe from the balloon catheter.

[0085] In a preferred embodiment, a method of providing an antimicrobial nonthermal plasma mist to a tissue, the method comprising administering an effective amount of nonthermal plasma mist to a patient in need thereof, said 9 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 nonthermal plasma mist administered by generating a plurality of microdroplets, said microdroplets being formed by a microdroplet device, and wherein the microdroplets are charged with oxidative species by contacting fluid of the microdroplets with a cold plasma before creation of the microdroplets, after creation of the microdroplets, or both and applying a quantity of nonthermal plasma mist to the tissue.

[0086] In a further embodiment, the method wherein the cold plasma is administered by providing a flow of nitrogen gas to a tip of the probe.

[0087] In a further embodiment, the method wherein the cold plasma is administered by providing a suction of air from an opening in a passage adjacent to a tip of the probe.

[0088] In a further embodiment, the method wherein the cold plasma is generated from a probe (18), said probe (18) comprising: a conductor wire (14) extending from a proximal end to a distal end and having a tip (17) at said distal end; a first passage having a first opening adjacent to the tip (17) and a second passage having a second opening adjacent to the tip (17); and a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz.

[0089] In a further embodiment, the method wherein the probe is connected to a fluid supply line, said fluid supply line providing fluid to said probe, and wherein the fluid supply line is connected to a reservoir containing a plasma-treated fluid.

[0090] In a further embodiment, the method wherein the first passage and the second passage are attached to an outside portion of the probe or a recess within the probe or are comprised within the probe.

[0091] In a further embodiment, the method wherein the first passage is provided with nitrogen gas or a mixture of nitrogen gas and nitric oxide.

[0092] In a further embodiment, the method wherein the fluid provided within the probe is treated with cold plasma to create a plasma mist, said plasma mist being expelled from the tip of the probe.

[0093] In a further embodiment, the method wherein the first passage is provided with a mixture of nitrogen gas and nitric oxide at a concentration of the nitric oxide of 5,000 ppm and a flow rate of between 0.01 SLPM and 0.15 SLPM.

[0094] In a further embodiment, the method comprising: a suction of between 0.1 SLPM and 10 SLPM of flow within the second passage; and / or a flow of nitrogen gas into the first passage; and / or a flow of a combination of nitrogen gas and nitric oxide, said nitric oxide at between 1,000 ppm and 10,000 ppm, having a standard liter per minute flow of 0.01 SLPM to 0.15 SLPM.

[0095] In a further embodiment, the method comprising administering the cold plasma once a day, twice a day, three times a day, every other day, or on an as-needed basis. 10 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0096] In a further embodiment, the device or method wherein the probe is rigid at the tip.

[0097] In a further embodiment, the device or method wherein the probe is flexible along at least a portion of a length of the probe.

[0098] In a further embodiment, the device or method wherein a flexible probe comprises an insulating coating.

[0099] In a further embodiment, the device or method wherein the first passage and / or the second passage comprise at least one opening disposed along a length of the first passage and / or the second passage which extends beyond the tip of the probe between the tip and an end of the first passage or the second passage.

[0100] In a further embodiment, the device or method wherein the tip of the probe comprises a channel connecting a gas supply channel to a suction channel.

[0101] In a further embodiment, the device or method comprising a treatment chamber, said treatment chamber having an opening disposed to be placed onto a surface creating the treatment chamber.

[0102] In a further embodiment, the device or method wherein the treatment chamber comprises a plurality of openings in a wall of the chamber.

[0103] In a further embodiment, the device or method wherein the treatment chamber comprises a plurality of probes within the treatment chamber.

[0104] In a further embodiment, the device or method comprising: a fluid supply line and a microdroplet generator; wherein said fluid supply line provides fluid to the microdroplet generator; wherein upon formation microdroplets are contacted by cold plasma; and preferably wherein the microdroplet generator is a sonicator, a nebulizer, a nozzle, an atomizer, or combinations thereof.

[0105] In a preferred embodiment, an endoscope comprising a probe at its distal end.

[0106] In a preferred embodiment, an endoscope comprising a balloon at its distal end and an outlet further distal to the balloon for expressing plasma-treated fluids or plasma mist and optionally further comprising a probe suitable for creating quantities of plasma to treat fluids expressed from the outlet.

[0107] In a further embodiment, the device or method wherein the device is a laparoscope.

[0108] In a preferred embodiment, an irrigator, said irrigator expressing plasma-treated fluid.

[0109] In a preferred embodiment, an irrigator, said irrigator comprising a plasma probe, said irrigator further comprising an activation feature and a fluid line, said fluid line exiting adjacent to the plasma probe, and wherein fluid flows and plasma is generated upon activating the activation feature.

[0110] In a preferred embodiment, a plasma device comprising: a fluid supply; a microdroplet creator and a cold plasma generating component; and wherein upon flow of fluid from the fluid supply, the fluid is formed into a plurality of microdroplets via the microdroplet creator and the fluid and / or the microdroplets are contacted by cold plasma. 11 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0111] In a preferred embodiment, a system for creating plasma mist for therapeutic treatment, the system comprising: a power supply; a plasma probe; a fluid supply, a microdroplet creator, and an activation switch; wherein upon changing the activation switch from an off position to an on position, the fluid supply is activated, the microdroplet creator is activated, and the power supply provides the necessary plasma in pulses to generate cold plasma; wherein the cold plasma contacts microdroplets of fluid creating plasma mist; and wherein the plasma mist is provided for therapeutic treatment.

[0112] In a preferred embodiment, a method of treating a patient in need thereof with an antimicrobial plasma mist, the method comprising generating the antimicrobial plasma mist and applying the antimicrobial plasma mist to a patient in need thereof.

[0113] In a further embodiment, the method further comprising a balloon catheter wherein the antimicrobial plasma mist is expelled from a tip distally positioned on the balloon catheter.

[0114] The disclosure, including descriptions, drawings, and claims, describes one or more embodiments of the invention. Many other features, objects, and advantages of the invention will be apparent to one of ordinary skill in the art from the disclosure. Given the disclosure, and in light of the prior art, it is another objective of the invention to improve upon, and overcome the inefficiencies, limitations, and constraints of the prior art.

[0115] Use of a device for creating a plasma-treated fluid wherein said plasma-treated fluid is further utilized for treatment of a medical ailment and preferably wherein the medical ailment comprises a reduction in the quantity of microbes on a tissue surface. BRIEF DESCRIPTION OF THE FIGURES

[0116] FIG.1A is an illustration of a device used to produce cold plasma mist via an applicator.

[0117] FIG.1B depicts a plasma probe having a gas and vacuum line adjacent to the plasma probe tip.

[0118] FIG.1C depicts a cross section of plasma probe having a gas and vacuum line adjacent to the plasma probe tip.

[0119] FIG.2 depicts a graphical representation of treatment time for 1 second, 5 seconds, 10 seconds, and 15 seconds for different gases relating to inactivation of E. coli.

[0120] FIG.3A depicts a graphical chart depicting the amount of ozone generated by a plasma probe with various gases and FIG.3B depicts only those of N2, N2:NO 0.05, and N2:NO 0.10 concentration without air as a reference to depict the quantity of ozone at appropriate scape.

[0121] FIG.4 depicts a graphical representation of the temperature of a metallic test element being subjected to the various forms of cold plasma for a given duration.

[0122] FIG.5 depicts a flowchart of a method for treating a patient with cold plasma mist in the throat or nose. 12 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0123] FIG.6 depicts a representation of a treatment of the tonsils using a cold plasma device.

[0124] FIG.7A depicts an embodiment of a cold plasma probe wherein the probe comprises two tubes that open at the tip, with corresponding recesses at the base.

[0125] FIG.7B depicts a variant of the two tubes that open at the top, with the tubes positioned adjacent to the length of the probe and having a tip recess.

[0126] FIG.7C depicts a rear portion of a probe such as the exemplar from FIG.7A.

[0127] FIG.7D depicts a tip end of a probe with two tubes within the tip body open at the end of the body with the openings having a noncircular opening.

[0128] FIG.8 depicts a graphical chart identifying that spraying plasma pretreated water over certain time periods has a different log reduction and can increase to a greater than five-log reduction of bacteria upon an increase in dwell time from twenty to thirty seconds.

[0129] FIGS.9A, 9B, and 9C depict that plasma creates submicron droplets of fluid.

[0130] FIG.10A depicts an eye patch apparatus for using plasma mist, FIG.10B depicts a nasal cannula apparatus for using plasma mist, FIG.10C depicts a face mask apparatus for using plasma mist, and FIG.10D depicts a nebulizer for use with a plasma-treated fluid to administer plasma mist.

[0131] FIG.11A depicts a probe system for applying plasma-treated fluid or plasma mist.

[0132] FIG.11B depicts a dental sonication probe.

[0133] FIGS.11C and 11D depict plasma irrigation tools.

[0134] FIG.12A depicts a balloon catheter, with the distal end of the catheter having a tip end to expel plasma mist, with FIG.12B depicting an embodiment wherein cold plasma is generated at the tip end, which can be used with or without fluids, to create plasma mist and FIGS.12C and 12D depicting an endoscope and a laparoscope that can be used in conjunction with cold plasma creating tools.

[0135] FIG.13 depicts a balloon catheter with a balloon at the distal end and two ports at the proximal end.

[0136] FIGS.14A and 14B depict examples of balloon sinuplasty utilizing cold plasma or plasma mist or plasma- treated fluids.

[0137] FIG.15 depicts a graphical chart of cold plasma inactivation of Streptococcus pyogenes based on different gas mixtures. DETAILED DESCRIPTION OF THE INVENTION

[0138] The disclosures of this patent application, including the descriptions, drawings, and claims, describe one or more embodiments of the invention in more detail. Many other features, objects, and advantages of the invention will be apparent from these disclosures to one of ordinary skill in the art, especially when considered in light of a more exhaustive 13 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 understanding of the numerous difficulties and challenges faced by the art. While there are many alternative variations, modifications, and substitutions within the scope of the invention, one of ordinary skill in the art should consider the scope of the invention from a review of any claims that may be appended to applications and patents based hereon, including any amendments made to those claims in the course of prosecuting this and related applications.

[0139] It should be further understood that the various embodiments of this disclosure can be combined in whole or in part with one another. Thus, a feature in one embodiment or in one of the figures can be combined with another feature defined by another embodiment or another of the figures, without deviating from the scope of the disclosure.

[0140] As used herein, term “about” means within 10% of a stated number such that “about 100” means between 90 and 110.

[0141] As used herein, the term “air” means an ambient air in a given location.

[0142] As used herein the term “pathogens” shall mean microorganisms, bacterial spores, mycobacteria, viruses, nonlipid or small viruses, fungi, vegetative bacteria, and lipid or medium size viruses.

[0143] As used herein, the term “balloon” shall mean an inflatable component of a medical device.

[0144] Disinfection devices disclosed herein include a cold plasma generator. The term “cold plasma” as used herein refers to a plasma which is not in thermodynamic equilibrium, particularly that the temperature of the electrons is much higher than the temperature of ions and neutrals. The term “cold plasma” as used herein is synonymous with the terms “nonthermal plasma” and “nonequilibrium plasma.” The cold plasma generators of the disinfection devices disclosed herein may include any generator known to generate cold plasma. Examples of cold plasma generators which may be used for the disinfection devices disclosed herein include but are not limited to glow discharge, corona discharge, atmospheric pressure plasma jet, dielectric barrier discharge, surface discharge, micro hollow cathode discharge, plasma needle, and low-pressure plasma. Furthermore, the cold plasma generators considered for the disinfection devices disclosed therein may include pulsed cold plasma generators or continuous wave cold plasma generators. Each of these provides the necessary charges at the tip of a rigid or flexible probe of the present disclosure, which, in proximity to a body surface (functioning as a charge storing capacitor) allows for production of cold plasma with a simple handheld probe.

[0145] Cold plasma is best understood as a gas ionized by the application of high voltage. While there are many ways of generating plasma known to those skilled in the art, in this application we use 10,000 V–45,000 V pulses of 0.1 µs to 1 s in duration applied at 100 Hz to 10,000 Hz, and most preferably 17,000 V–37,000 V pulses of 1–5 µs in duration applied at 1,000 Hz. These high voltage pulses are delivered by special cables to the probe used by the medical professional. Depending on the gas atmosphere, different reactive species will be created at or near the tissue being treated. Applicant preferably uses ambient air, or intentional delivery of nitrogen gas alone, or with a small percentage of 14 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 nitric oxide. Because the tissue being treated is moist, Applicant also has nonzero quantities of water vapor. Thus, the species generated in this plasma will predominantly be the so-called reactive nitrogen species (RNS): NO, electronically excited NO, electronically excited N2, HNO, HNO2, HNO3, HNO4, and others, including OH radicals, generated from water.

[0146] Both pulsed and continuous wave dielectric barrier discharge cold plasma generators were used in the development of the disinfection devices disclosed herein and are known to function particularly well with the design considerations discussed herein. One advantage of dielectric barrier discharge cold plasma generators is their small size, making them easily configured, and deployed into small spaces and for use with tools, such as the probes detailed herein. Continuous wave dielectric barrier discharge cold plasma generators are advantageous due to their availability and lower costs as compared to pulsed dielectric barrier discharge cold plasma generators. Yet, a disadvantage of employing continuous wave dielectric barrier discharge cold plasma generators is that they generate considerably more ozone in a given disinfection process as compared to pulsed dielectric barrier discharge cold plasma generators. This discharge is less uniform and hotter, which can cause tissue damage. However, in some instances, tissue damage is desirable for therapeutic treatment. Herein, such ozone production may be contraindicated, and indeed, Applicant has detailed methodologies to virtually eliminate the presence of ozone in the plasma formation, while unexpectedly retaining the antimicrobial effects.

[0147] Probes are utilized to generate cold plasma in conjunction with the generator. The unique property of cold plasma, thus, is that we can create high concentrations of these reactive species, which are suitable for inactivating a wide variety of potential pathogens. Indeed, a wide spectrum of pathogens have been identified as being inactivated via the application of cold plasma for mere seconds.

[0148] The present embodiments detail new cold plasma probes and methods of delivery of cold plasma, plasma fluids and plasma mists for therapeutic use. The present embodiments provide a detail of new probe shapes and also features of the probes that provide unexpected improvements to plasma treatment, and which preferably generate plasma fluids and plasma mists for antimicrobial treatments.

[0149] The present embodiments detail probes used with a plasma generator that provide for therapeutic treatments using cold plasma, for treatment of an animal. The probes, when provided with a sufficient voltage, create cold plasma when treating a patient. Thus, for example, the probe may be placed into the mouth, and when the voltage is applied and the probe is adjacent to, for example, one millimeter away from the tonsils, cold plasma is created. The cold plasma then forms quantities of radical nitrogen and oxygen species, which have broad antimicrobial impacts. Applicant has unexpectedly identified that by adding fluids to this process, a plasma charged fluid, or a mist can be expressed onto targeted tissues, or used for irrigation of the same for antimicrobial and healing purposes. Thus, a mist or fluid could be 15 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 applied to the tonsils, or the mist or fluids could be applied to tissues within the nasal cavity which increases the reduction of microbial pathogens at the treatment site.

[0150] Application of cold plasma for five to ten seconds in a given location, as a nonlimiting example of a treatment time, can aid in removal of biofilms and / or destroy or inactivate surface and indwelling microorganisms, viruses, bacteria, fungi, etc. This treatment may also aid directly or indirectly in the activation of the host’s immune response, further assisting in the removal of the invading microbes and healing. However, in many cases, the area of the body to be treated limits visual access to the treatment site or swelling or other growths hinder access to the desired treatment site. For example, when considering swollen tonsils, which are being treated for tonsilitis, the tonsils may have significant surface area in contact with the cheek, throat, etc., and wherein microorganisms may be harbored in such contact surfaces. Application of cold plasma to adjacent surfaces may be insufficient to inactivate or kill the microorganisms that are hidden or behind a surface being in contact with the body itself, may not receive any of the reactive species generated from the cold plasma application, and thus will not be destroyed or inactivated. However, the removal of bacteria, bacterial films, and other adjacent microorganisms may still aid the body in then attacking and killing the remaining microorganisms, bacteria, or viruses.

[0151] Applicant, however, recognizes that the above paradigm represents an incomplete treatment, namely one that removes some, but not all of the surface level microorganisms, but leaves sufficient quantities of the microorganisms such that the underlying disease state is not eliminated. Such incomplete treatments may require additional treatments or even different treatments, including surgical procedures or medications such as an antibiotic or antiviral. However, by the inclusion of fluids to the cold plasma, treatment may be improved and provide a replacement for the prior antiquated procedures.

[0152] Plasma generation creates RONS species such as ozone (O3), hydroxyl radical (OH), hydrogen peroxide (H2O2), singlet oxygen (O2*), peroxynitrite radical (ONOO*), and others, and these species are conserved and protected by being dissolved into the fluid. The fluid can be stored or captured for subsequent use, thus becoming a plasma-treated fluid. In some embodiments, the fluid is provided as microparticles through one of various microparticle generators, creating plasma mists. However, preferably the plasma-treated fluid is created and immediately utilized, such as in the various devices and methods as detailed herein.

[0153] The present disclosure details devices and methods for treating tissues and surfaces with plasma-treated fluids, and in certain embodiments, to plasma-treated microdroplets. Plasma-treated fluids have unique properties in that the fluids are charged with numerous reactive species and radicals from plasma treatment and the formation of these radicals provides numerous potential beneficial uses. This treatment may also aid directly or indirectly in the activation of the host’s immune response, further assisting in the removal of the invading microbes and healing. 16 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0154] Fluids are often used in wound care, for example, where sterile water is used to clean a wound. However, plasma-treated fluids could go a step further and provide water or another fluid that is charged with reactive species and radicals which could further disinfect or oxidize tissue, bacteria, viruses, etc., in order to more thoroughly clean a skin surface. To date, it is impractical to create sufficient volumes of fluids for practical use, despite the potential benefits. Accordingly, the devices herein allow for production of such fluids to meet such need in a practical manner. In particular, the devices of the present embodiments and the methods of use of the same create plasma-treated fluids or plasma-treated microdroplets (a plasma mist), which are utilized for antimicrobial purposes.

[0155] The fluids suitable for use with these methods include water, water with additives (peracetic acid, chlorine- based disinfectants, alcohols, sulfur containing additives, e.g., certain amino acids, hydrogen peroxide, etc.), as well as other fluids like oils and alcohols, gels, foams, and mixtures comprising any of the above. One can even treat polymer mixtures to promote crosslinking and add oxidizers making the material antimicrobial. Such polymers may also exist in different forms and be utilized within the body for medical treatments.

[0156] In preferred embodiments, nonlimiting examples of additives include but are not limited to: sodium nitrate, peracetic acid, chlorine-based disinfectants, alcohols, hydrogen peroxide, sulfur containing compounds, such as sulfur containing amino acids including but not limited to methionine, and many other additives and combinations of additives may be added to water and treated by the device (10). Typically, such additives are included at between 0.01 millimolar (mM) and 5 M. Hydrogen peroxide is often provided in quantities of percentage as a 0.01% to 10% hydrogen peroxide mixture with the fluid, often being water.

[0157] In certain applications, the inclusion of a radical donor is especially warranted. A radical donor is a material that, in the presence of plasma, generates high quantities of highly reactive oxidizing radicals. In fact, a particularly useful embodiment of a treated fluid includes water having a sodium nitrate added thereto at a concentration of 25 mM. Sodium nitrate, when in the presence of plasma, generates high concentrations of peroxynitrate, which is a very strong oxidizer. Similar material may be included as a radical donor to increase the concentration of these very strong oxidizers to create fluid mixtures that have greater oxidation potential than without inclusion of such material. A highly preferred additive is a combination of two or more additives, for example sodium nitrate at 0.1 mM to 250 mM and hydrogen peroxide at 0.01% to 10% concentration. In certain applications, the additive is a radical donor, which is a material that, in the presence of plasma, generates high quantities of highly reactive radicals. Another nonlimiting example is hydrogen peroxide (about 0.01% to about 10%) and peracetic acid (from about 0.01 mM to about 250 mM) may both be added to a fluid such as water. In fact, a particularly useful embodiment of a treated fluid includes water having a sodium nitrate added thereto at a concentration of from 1 mM to about 100 mM, with a preferred concentration of 17 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 about 25 millimolar (mM). In many cases, hydrogen peroxide may be used in combination with one or more additional additives.

[0158] As one nonlimiting example, where sodium nitrate is added to a fluid (e.g., water) at a concentration of between 1 mM and 100 mM, the resultant plasma-treated fluid may contain high concentrations of peroxynitrate, which is a strong oxidizer. As another nonlimiting example, an additive can be sufficient to generate plasma-treated fluid that has a greater than one log reduction in the rate of killing of E. coli, as compared to the same fluid without the additive. For example, the addition of 25 mM sodium nitrate results in a plasma-treated fluid that has greater than one-log kill rate of E. coli, as compared to a fluid without the 25 mM addition. In other nonlimiting examples, plasma-treated fluids may be generated that have a desired pH (e.g., from about 2 to about 4.5), a desired concentration of radicals / reactive species such as H2O2 (e.g., between 10 ppm and 200 ppm), NO3−(e.g., between 20 and 500), and combinations thereof.

[0159] In an embodiment, storage of plasma-treated fluid may include cooling or even freezing or flash freezing the plasma-treated fluid (for example, as soon as is practicable), which may extend its shelf life.

[0160] In a nonlimiting example of plasma-treated water described below, tap water was plasma-treated in open air atmosphere using an embodiment of the plasma generating device. As is shown in Table 1, below, the most notable changes to the water are those to the pH and concentrations of certain radicals within the fluid, for example hydrogen peroxide H2O2 and nitrate (NO3−). To test the efficacy of the model, a device using a single static electrode and a single dielectric assembly having a length of either 30 millimeters (mm) or 60 mm was placed into a reservoir with tap water and rotated at speeds of 10, 60, 120, and 300 rotations per minute (RPM), for between 30 minutes and 60 minutes. The voltage between the rotational electrode and the static electrode was 22 kV. pH measurements were taken before treatment (time = 0) and at 5, 10, 20, 45, and 60 minutes of processing through the generated plasma, for example, as detailed in US Patent Application No.18 / 264,498, as a nonlimiting way to create such plasma-treated fluids. Hydrogen peroxide and nitrate measurements were taken after 60 minutes of treatment, as is noted in Table 1 below.

[0161] TABLE 1: Electrode, speed pH H2O2NO3−18 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 Electrode, speed pH H2O2NO3−Time (min) 0 5 10 20 45 60 m m, , hat reactive species (e.g., hydrogen ions) are being produced by plasma treating the water with the device. Moreover, the presence of other reactive species (e.g., H2O2, NO3−) also confirms that the device can successfully plasma-treat a fluid. A lower pH indicates a larger concentration of reactive species.

[0163] As is also indicated in Table 1, confirmation of the oxidative potential is shown by the oxidation of indigo carmine. In the examiner, the plasma generating device generates sufficient oxidation species to oxidate the indigo carmine. For example, an indigo carmine solution was a dark purple color before treatment, but after 120 minutes of treatment with the plasma generating device the solution in the reservoir turned clear, which is an indicator of a change in oxidative state.

[0164] The use of cold plasma itself provides for significant concentrations of radical species sufficient to inactivate or destroy many malignant microbes. Furthermore, charging fluids with cold plasma also shows a clear efficacy for treatment. However, Applicant has identified that microdroplets of fluids are superior to either option. Where a treatment provides cold plasma, such as through a probe that generates cold plasma at a given tissue location, applying cold plasma-treated microdroplets (plasma mist) provides for an unexpected improvement in efficacy.

[0165] Turning to FIG.1A, there is shown a preferred embodiment of a device (1) the cold plasma applicator (10). Preferred embodiments of the applicator (10) generate quantities of cold plasma (34) by generating a charge at the tip (17) of the probe (18) via the conductor wire (14) sufficient to generate the cold plasma (34). The conductor wire (14), for example, those depicted in FIG.1 C as nonlimiting examples, generally create the cold plasma (34) at a tip (17) and not along a portion of the shaft (19) so that precise application of cold plasma (34) can be delivered.

[0166] The cold plasma applicator (10) comprises an insulated conductor wire (14) such that the conductor wire (14) is insulated (55) along the length of the shaft (19) of the probe (18), and wherein the end of the insulated conductor wire (14) is provided in a reactive tip (17) such that the cold plasma (34) is generated at only the tip (17). One such example of the reactive tip (17) is that the tip (17) is filled with gallium, which is liquid at about 40°C, and, in connection with the conductor wire (14) which is noninsulated at the end of the conductor wire (14), creates the charge sufficient to generate the cold plasma (34). The tip (17) may be filled with another conductive metal or metal alloy, gallium and alloy with gallium, or a similar metal having a low melting point temperature are preferred. 19 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0167] As depicted in FIG.1A, and further detailed in additional embodiments, the applicator (10) holds the probe (18) and wherein a vacuum line (15) and a gas line (16) have openings adjacent to the tip (17). The gas line (16) is connected, such as via a connection harness (12), which may have multiple lines connected thereto, as depicted in FIG.1A, such as inclusion of a gas connection line (41) to a compressed gas (13), which delivers a quantity of gas at a specific flow rate, through to the gas line (16) within the probe. Preferably, this is utilized in conjunction with a regulator (42) that controls the quantity and flow rate of the gas. Simultaneously, e.g., connection line (49) may further include a vacuum line (15) connection to a vacuum pump (44) provides suction through the vacuum line (15) to pull gas from the tip (17). The regulator (42) and vacuum pump (44) may optionally operate with a filter (43). The two features of the gas line (16) and the vacuum line (15) work in concert to create improvements to the generated cold plasma (34), which is detailed herein. Namely, the mixture of gas provides for an increase in efficacy using certain gas mixtures, reduces the working temperature of the plasma at the target tissue, and dramatically reduces the production of ozone. The combination of maintaining and unexpectedly increasing the efficacy of treatments while simultaneously virtually eliminating the quantity of ozone production yields an unexpected result that provides for unique methods of treatment within the oral and nasal cavities that would be unavailable with typical plasma treatments due to the presence of and manufacture of ozone.

[0168] FIG.1A also depicts a reservoir (46) that provides fluids for use in the embodiments herein, with a fluid line (48) of the harness (12) connecting it to the probe (18). In certain embodiments, fluids are pretreated with cold plasma, creating a plasma-treated water. This plasma-treated water can then be applied via any one of the devices detailed herein.

[0169] In certain embodiments, the water is not pretreated with cold plasma but is treated by the devices detailed herein. Thus, the fluid in the reservoir may be untreated, such as directly connected to a fluid supply line, such as a tap water. In certain embodiments, the fluid is expressed as a “plasma mist” which is microdroplets of fluids that are charged by cold plasma. Advantageously, the microdroplets of fluids help to stabilize the reactive species and furthermore provides for tremendous surface area for increasing antimicrobial efficacy. Of course, the fluid may also be pretreated, and then also subsequently treated by the device.

[0170] FIG.1D shows a cross-sectional view of a variation of a harness (12), in which multiple of the lines are organized into a single harness, thus allowing for each of the various lines to be secured, e.g., to the control box (11), which itself would then be appropriately connected to the pressured gas tank (13) the regulator (42), the fluid reservoir (48), as well as the various voltage line, and vacuum lines. Thus, as depicted, a conductor wire (14) and a gas line (15), and suction line (16), as well as the fluid line (48), the connection line (49), and the gas connection line (41), as nonlimiting components of a harness. While a single harness component is depicted in FIG.1D, for the harness (12) it 20 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 would be obvious to one of ordinary skill in the art that one, two, or more different attachment lines can be utilized to create the necessary supply to the probe for its effective use.

[0171] The probe (18) and applicator (10) are connected to a control box (11) which provides for management of the electrical current, as well as operating and controlling vacuum and gas flow in certain embodiments. Essentially, the control box (11) may serve as a power supply, powering the probe (18), and depending on the harness and connections may also provide for control of gases, vacuum, and other features which can be optionally controlled by the control dials (4) which may be desirous to be displayed on the device display (6). Parameters are adjusted and current operating parameters are displayed on the device display (6). Different modes of action can be selected in the control box (11) via the control dials (4) and can be used to customize the intensity or temperature of the cold plasma so that a number of medical treatments can be achieved by altering voltage, wavelength, among other parameters. For example, cold plasma (34) from the applicator (10) can be used in the removal or reduction of biofilm from tissue, reduce the size of tissue, or in some cases, selectively injure tissue to achieve medical results. Those skilled in the art will recognize that a number of medical applications can be achieved by utilizing cold plasma and these are just some of the nonlimiting examples for illustrative purposes.

[0172] The applicator (10) is connected to the control box (11) via a connection harness (12), which allows the operator to easily manipulate the applicator (10) during operation. Within connection harness (12) there is at least one electrical connection, which can be multiple wires to complete that connection and optionally, a vacuum line (15) and / or a gas line (16), either of which may serve as a fluid line. Thus, the harness (12) may include multiple lines to control various elements of the device. In order to create plasma (34) at this temperature, a compressed gas (13) such as an inert or “noble” gas source and the like is used such as helium, nitrogen, nitric oxide, argon, and mixtures of gases in combination with such gases. Applicant identifies that a plurality of different noble gases and nontoxic gases may be suitable. A conductor wire (14) within the instrument is used to ionize the gas from the compressed gas source (13) and generate dielectric barrier discharge plasma. An integrated vacuum line (15) is utilized to capture any excess ozone particles that are generated that can cause harm to the patient. Here, vacuum line (15) means that suction is being provided to pull gases from the tip (17).

[0173] Preferred embodiments of the probe (18) are shaped in a manner to allow the physician or technician to maneuver easily in the desired region of the human subject in tight spaces such as the mouth, throat, esophagus, nasal cavity, paranasal sinuses, and ear. The probe (18) can be a single use, disposable probe or it can be a multiple use probe capable of being sterilized. The type of probe will be dictated by the medical treatment being provided. In one, nonlimiting example, a probe (18) is comprised of a conductor wire (14) that is coated with any type of insulation (55). The probe (18) may optionally be filled with degassed epoxy, or similar material, to limit movement of the conductor 21 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 wire (14) within the probe (18). In a preferred embodiment, the epoxy filled probe is then placed in a high-pressure chamber to further compress the epoxy as it cures to eliminate trapped air. The epoxy can fill some or all of the internal opening (78) from e.g., FIG.9C, and retain access to the conductor wire (14) such that an electronic connection can be made to provide the necessary power source. As those persons skilled in the art will readily recognize, the device (1) shown is for illustrative purposes and many other configurations of the device (1) can be used to achieve the same result such as with a separate control element like a foot pedal to operate.

[0174] FIG.1C is a cross-sectional detail of one nonlimiting configuration of probe (18) showing the more specific location of gas line (16) and vacuum line (15) as they run along probe (18) terminating at tip (17). Alternatively, gas line (16) and vacuum line (15) can terminate closer to or further from tip (17). In certain embodiments, the gas line (916) and the vacuum line (15) actually extend beyond the tip (17), creating a spacer between the tip (17) and the tissue to be treated. Within probe (18) is housed a conductor wire (14) optionally covered in insulation (55).

[0175] FIG.1B provides an example of the design of a testing apparatus. Here, the probe (18) is vertically mounted, with adjacent gas line (16) and vacuum line (15), being generally provided at a distance of about one millimeter to a sample Petri dish (52) with a layer of microorganisms / bacteria (54) grown on an agar layer (51) within the Petri dish (52). This setup was used to test the efficacy of the treatment on a sample species. The sample was prepared using a standard agar solution (51) to grow microorganisms / bacteria (54), specifically E. coli O157:H7 on Lysogeny broth. The total concentration of E. coli was 2 × 107colony-forming units (cfu) per milliliter of Lysogeny broth (LB). A voltage of 27 kV at 1,000 Hz was applied via the probe. All tests were performed at room temperature with the Petri dish (52) sitting on a grounding plate (56) that is connected to a grounding wire (58).

[0176] Interestingly, a further element is created by the application of pressurized gas being deployed to the tip (17) of a probe, such as depicted in FIG.1B. Applicant took a photograph at high speed of the plasma created in an example of air, but no suction, and compared that to the N2:NO 0.1 example with suction. Interestingly, the air example provided a beam of plasma that was merely 0.5 mm wide. This creates a “hot” spot for plasma formation and treatment. In comparison, providing the flow of the nitrogen and NO mixture, with suction, generated a plasma beam that was five times wider at 2.5 mm. This creates a broad, uniform treatment area of plasma, yet based on the studies herein, also provided significantly greater results in inactivating the microbes being treated. This plasma spread was an unexpected benefit of adding the controlled flow of gas at the tip that is combined with greater efficacy, lower temperature, and greatly reduced ozone formation.

[0177] Thus, further tests using controlled gases were preferred. FIG.2 is interesting for several reasons. First, is that it is widely understood that oxygen is generally necessary to provide sufficient quantities of reactive species. However, in view of FIG.2, what is clear is that at a time period of just one second, the combinations of nitrogen 22 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 gas (N2):nitric oxide (NO) each provided at least some inactivation, while air and N2alone produced no measurable inactivation. At a time of five seconds, all gases provided at least some inactivation, however, the combination of the N2:NO mixtures yielded larger inactivation circles. This continued again with both the ten- and fifteen-second experiments. In the case of a ten-second treatment, notably, all of the N2gases were dramatically and unexpectedly superior in inactivation than treatment with air alone. Accordingly, in all cases, the use of nitrogen gas alone or in combination with NO is at least equivalent in its inactivating power as compared to ambient air and indeed on average is superior to ambient air in all cases. The fact that the N2gas, alone or with NO, was even equivalent to the air mixture, yet alone superior to the air mixture was an unexpected surprise regarding the improved efficacy of treatment using the nitrogen gases.

[0178] This study was then repeated with a second bacterial species to ensure that the cold plasma reacted across different species as was previously reported in the literature, but also that it would retain efficacy with the nitrogen gas species. Table 2 depicts this test, and further details inclusions of NO at a lower and higher concentration.

[0179] TABLE 2: Time (sec) Air N2N2+ 0.01 NO N2+ 0.05 NO N2+ 0.10 NO N2+ 0.15 NO

[0180] What is immediately obvious from the data is that the presence of NO within any sample increases efficacy. Indeed, even the lowest concentration of NO provides a trend toward higher inactivation, and reaching toward quantities of 0.05 NO provides a significant increase in the efficacy. However, simultaneously, Applicant notes that the presence of more NO is not simply additive. Indeed, increasing the concentration up to 0.15 NO actually reduced efficacy meaningfully from the 0.10 NO concentration with N2. Accordingly, in certain embodiments, limiting the NO concentration from 0.01 to 0.15 is advantageous.

[0181] One of the major benefits of using nitrogen gas or a mixture of nitrogen gas and nitric oxide (“NO”), instead of ambient air, is the reduction in the presence of oxygen and thus dramatically reducing the formation of ozone from the cold plasma. Because the treatments are indicated and desired in the nose and mouth, patients would inherently be exposed to ozone. FIG.3A depicts a graphical representation showing the concentration of ozone in parts per million (“ppm”) over time when comparing four different gases. FIG.3B is provided as a supplement to show data and omitting the “air” as one of the gases, due to the significant differences in the ozone production. Indeed, when using air 23 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 alone, in FIG.3A it can be seen that at two minutes, ozone ppm is measured at about 4 ppm, and then at three minutes, the concentration of ozone reaches its near maximum concentration of between about 10–13 ppm, which appears to somewhat stabilize at between three to ten minutes of time.

[0182] In contrast, when looking at FIG.3B, ozone concentration again appears to stabilize at its maximum around three to four minutes, but this level is at or below 0.05 ppm, and at a time of three minutes is below this at about 0.03 ppm for all of the nitrogen-based gases tested. This is equivalent to 100 times the difference in the ozone measurement when comparing the air generated cold plasma to those created with the compressed gases. The amount of ozone produced in such examples is below the standards set by the EPA established in 2015, which is 0.070 ppm. This provides a unique antimicrobial solution that heretofore was unavailable due to the toxic presence of ozone at levels that may be effectively safe for therapeutic treatment.

[0183] Thus, Applicant has created a device that generates sufficient amounts of cold plasma that improves upon the inactivation properties of cold plasma as compared to creating cold plasma in ambient air, all the while dramatically reducing the concentrations of ozone produced, thus increasing safety of treatment within the ear and especially in the nose and throat.

[0184] Notably, however, the probes of the present disclosure can also be utilized in the presence of fluids. One is simply a plasma-treated fluid, which will be in liquid form and able to be utilized as any fluid would normally be used. Thus, when a saline rinse is used to clean a wound, instead the plasma-treated fluid can be utilized for the rinsing. Furthermore, the fluid can be microdroplets, that aid in increasing the surface area of disinfection and which can be used in all of the embodiments detailed herein. METHOD OF USE

[0185] Returning to FIG.1A, the probe (18) of the device (1) possesses a tip (17) at the distal end of the applicator (10), which creates cold plasma (34). The device is shaped such that a practitioner holding the applicator (10) can place the tip (17) into the mouth or into the nasal passages and, after activating the device (1) by selecting the desired voltage for the given treatment using the control dials (4) and the device display (6), create cold plasma (34) at the tip (17). The cold plasma (34) generates high concentrations of reactive species, which react with microbial species to inactive them. Use of the reservoir (46) then adds in the fluids necessary to create plasma mists to be optionally used in the various embodiments and methods of use.

[0186] Interestingly, the plasma created is of the present disclosure is referred to as “cold” plasma. This is because the formation of the plasma is warm but does not reach temperatures that could cause major burning, such as temperatures over 70°C or higher. However, even creating temperatures as high as 45°C can quickly cause discomfort or 24 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 even burns. This is especially true with sensitive skin, such as those within the mouth or nasal passages. Furthermore, even if the temperature is only at 40°C, such temperature can cause discomfort to a patient.

[0187] Applicant tested the temperature of the cold plasma, by testing its ability to heat a small metal plate placed one millimeter from the cold plasma and holding the device for up to ten minutes to determine the differences in temperature among the various gas mixtures being utilized. What was fascinating is that, in addition to the greater efficacy identified by using nitrogen gas or nitrogen and NO, a dramatic and unexpected reduction in temperature was realized. Indeed, after even a few minutes, the plasma created by using room / ambient air, with or without suction / vacuum, was dramatically different than those using any of the nitrogen mixtures. FIG.4 clearly depicts that while temperature is relatively similar at inception and at one minute, by the second minute, where the nitrogen gas examples were almost perfectly stable at between 22°C and 23°C, the air from the room, or simply without air, already showed an increase over this stable temperature and continued to rise significantly at each minute. When the device is then utilized within the nasal passages, the rapid increase in temperature may be sufficient to cause discomfort or damage these sensitive tissues with the air examples. However, with nitrogen gas, or mixtures using nitrogen gas, the temperature remains far below any threshold that could cause pain, discomfort, or burning of the tissue. Indeed, when looking at FIG.4 at ten minutes of time, the temperature for the probe without gas is nearly 20°C higher than when using nitrogen alone or in mixture.

[0188] Turning to FIG.5, which shows a flowchart (20) of the method in when the device (1) (from FIG.1A) is utilized for treatment of the throat. In the first step (21), the patient is examined by the physician to determine the correct course of treatment. Then, if necessary, the patient is treated with a local anesthetic, in the region that is to be treated in the next step (22). Once the anesthetic has set in, the device (1) (from FIG.1A) is adjusted to the desired operating parameters and positioned to effectively treat the desired region in the following step (23). Then, the device (1) (from FIG.1A) is used to treat the tissue for the appropriate amount of time with cold plasma, plasma mist, plasma-treated water, plasma-treated gel, and / or plasma-treated foam while providing a vacuum for excess ozone that is generated in the next step (24). Next, the results of the treatment are observed by the physician to determine the next course of action in the following step (25). Finally, the patient is released if no further treatment is needed in the last step (26). Otherwise, steps (21)–(25) may be repeated as necessary, with a treatment provided on a second, third, fourth, fifth, sixth, seventh, or at a different frequency as determined by the practitioner providing the treatment to the patient. Some protocols may need 2, 3, 4, 5, or more treatments that are spread out over the course of several days, several weeks, or longer.

[0189] Turning to FIG.6, which illustrates the applicator (10) comprising a probe (18) with a tip (17) treating the tonsils (30) of a patient, once the applicator (10) is positioned and calibrated, the conductor wire (14) (from FIG.1C) provides the necessary electrical charge to create the cold plasma (34) and / or plasma mist between the probe tip (17) and 25 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 the tissue, thus applying cold plasma and / or plasma mist to the affected area, in this case, the tonsils (30) of the patient. For this procedure, the control dials (4) (from FIG.1A) are set to allow the cold plasma (34) and / or plasma mist that is generated to be at room temperature that is adequate to sterilize and reduce or remove the microorganisms / biofilm (32) surrounding the tonsils (30) but avoids causing injury or discomfort to the tissue. Cold plasma (34) is applied to the tonsils (30) to treat the microorganisms / biofilm (32) that have developed on the tonsils (30). Those skilled in the art will recognize that the figure is for illustrative purposes and the applicator device may be in a different configuration or shape, and that the cold plasm / mist can also be plasma-treated water, plasma-treated foam, and / or plasma-treated gel.

[0190] One of the key benefits of the cold plasma treatment is that its strong oxidizing potential is broadly antimicrobial. Thus, treatment of, especially diseases of the ear, nose, and throat, which may be highly variable to the given pathogen, the cold plasma can treat such broad pathogen species instead of having singular or limited function over one species or class such as viral, bacterial, microorganisms and / or fungal. Cold plasma has been shown to kill numerous pathogens, a nonlimiting list is provided in Table 3.

[0191] TABLE 3: Pathogen Plasma Type

[0192] The benefit of such broad spectrum antimicrobial material is immense. Indeed, many other species are inactivated or destroyed by cold plasma. Certain studies have shown that nonthermal plasma can inactivate 99.9% of airborne viruses through releasing energetic molecules, to kill the viruses in less than a second. Microorganisms such as bacteria are inactivated by destruction of their cell wall. Fungi are also inactivated with cold plasma, though they may be somewhat less sensitive than microorganisms, viruses and bacteria and may require additional time for inactivation. Nonetheless, spores were inactivated after treatment times of as little as one second for certain Aspergillus niger, Penicillium citrinum, Cladosporium cladosporioides, and Chaetomium sp. species. Certain Candida sp. were also inactivated at high rates after treatment times of less than ten minutes. Therefore, use of the materials allows for a broad inactivation of a wide variety of microbial species. 26 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0193] FIGS.7A, 7B, 7C, and 7D depict examples of a through conduit probe (70) that contains an internal passage, having a first and second passage. Such passages can be used for gas, fluids, and / or suction. Indeed, a third passage can be utilized, or added onto any of the embodiments. Turning to FIG.7A, one passage is the gas through conduit (71) and the other passage is the vacuum through conduit (72). In FIG.7A, these conduits are shown opposite each other on the through conduit probe (70) and in the plane of the distal end. However, the gas through conduit (71) and the vacuum through conduit (72) can be in any configuration within through conduit probe (70), and while through conduit probe (70) is shown as being straight in FIG.7A, one skilled in the art will appreciate that it can be in any shape and / or configuration necessary to perform the medical procedure including but not limited to being bent, rigid or flexible. These two passages / through conduits have the same general functionality as the tubes in that one passage / through conduit functions as a line to send air and / or gas to the tip (17), with the air and / or gas being pressurized to flow at a particular flow rate using the regulator (42) (from FIG.1A) which may optionally engage the filter (43) (from FIG.1A). This passage / conduit is generally referred to as the gas through conduit (71). The air and / or gas leaves the through conduit probe (70) via the gas exit (74a) at the tip (17). The opposite line then pulls the air / gas expelled from the gas exit (74a) at the tip (17) via the vacuum entry (75a) into the vacuum through conduit (72). The through conduit receiving end (73) of through conduit probe (70) connects the through conduit probe (70) to applicator (10) (from FIG.1A). In FIG.7A, the gas and / or air flow directly though the gas through conduit (71) and the vacuum through conduit (72) however, one skilled in the art will recognize that it may be advantageous to line these through conduits with other materials or run tubes or supply lines or return lines within the conduit. Thus, the designs are not so limited, but detail one solution to the problem of providing a pressurized particular gas to the tip via a supply line and pulling gas from a point adjacent to the supply line. This allows for creation of the desired reactive species, limits ozone production, and pulls created gases back via the suction side. By having the gas (71), tip (17), and suction / vacuum (72) in a plane, it forces the pressurized gas to pass directly over the tip (17) creating an even flow of plasma charged particles.

[0194] FIG.7A in particular shows the tip (17) end of through conduit probe (70) that has a rounded end. The gas exit (74a) and the vacuum exit (75b) are placed on opposing sides of the tip (17), with a rounded shape. By contrast the rectangular gas supply (76) and the rectangular vacuum (77) of FIG.7D are a more oval or rectangular shaped inlet and outlet. The purpose of the shape change is to encourage the spread of plasma at the tip (17), creating a broad treatment area. Again, rectangular gas supply (76) and rectangular vacuum (77) are shown opposite one another in FIG.7D, however one skilled in the art will recognize that they can be in any configuration that will optimally deliver plasma to the treatment area and while the gas through conduit (71) and the vacuum through conduit (72) are shown as straight and opposite one another, these can also be in any shape, location and / or configuration including spiraling within through conduit probe (70). The tip (17) may also be concave, having the gas exit and the vacuum entrance positioned beyond the 27 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 tip (17). Or the tip (17) may be any shape, but having the gas exit and the vacuum entrance positioned beyond the tip (17) provides that such features separate the tip from the surface to be treated, which can thus be easily controlled by simply touching the ends of the gas exit or vacuum entrance to the surface to be treated, leaving the proper distance between such surface and the tip (17).

[0195] FIG.7C depicts the rear of the through conduit probe (70) of FIG.7A where the probe terminates into the through conduit receiving end (73). The through conduit receiving end may optionally be threaded to connect it to the through conduit probe (70) and the applicator (10), or it can be attached via adhesive, or it can be molded so that the probe, receiving end and applicator are one piece, or the three components can be attached together via any other means generally known in the art. A suitable supply line can be inserted into the gas entry (74b) hole, and a second return line can be inserted into the vacuum exit (75b) hole. The internal opening (78) will hold the conductor wire (14) and will accept a banana clip style plug, to create the electrical contact between the conductor wire (14) with optional insulation (55), the banana clip (not shown) and the control box (11) (from FIG.1A). Notably, the particular design of the banana clip can be virtually any connector known to those of ordinary skill in the art. While this embodiment has described a supply line, a return line and / or a tube being inserted into the gas entry (74b) and the vacuum exit (75b), gas / air can flow directly through the gas through conduit (71) and the vacuum through conduit (72) without the use of an intermediary line or tube.

[0196] FIG.7C depicts the rear of the through conduit probe (70) of FIG.7A where the probe terminates into the through conduit receiving end (73). The through conduit receiving end may optionally be threaded to connect it to the through conduit probe (70) and the applicator (10), or it can be attached via adhesive, or it can be molded so that the probe, receiving end and applicator are one piece, or the three components can be attached together via any other means generally known in the art. A suitable supply line can be inserted into the gas entry (74b) hole, and a second return line can be inserted into the vacuum exit (75b) hole. The internal opening (78) will hold the conductor wire (14) and will accept a banana clip style plug, to create the electrical contact between the conductor wire (14) with optional insulation (55), the banana clip (not shown) and the control box (11) (from FIG.1A). Notably, the particular design of the banana clip can be virtually any connector known to those of ordinary skill in the art. While this embodiment has described a supply line, a return line and / or a tube being inserted into the gas entry (74b) and the vacuum exit (75b), gas / air can flow directly through the gas through conduit (71) and the vacuum through conduit (72) without the use of an intermediary line or tube.

[0197] FIG.7B depicts channel probe (80) being a variation wherein the orifice(s) that allows for the passage of air / gas from the compressed gas (13) (from FIG.1A) and the vacuum suction from the control box (11) (from FIG.1A) to the channel tip (84) is printed, molded, machined, or otherwise affixed to the outer side of the channel probe (80). As 28 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 shown in FIG.9B, the exterior gas supply line channel (82) and the exterior vacuum line channel (83) are on the outside surface of channel probe (80). The gas / air stream may flow directly within exterior gas supply line channel (82) and the vacuum suction can remove the emitted air / gas directly through the exterior vacuum line channel (83). Alternatively, as shown in FIG.7B, a vacuum line (15) can run through exterior vacuum line channel (83) to pull air / gas from the treatment site through the channel probe (80), through the shaft (19) of the applicator (10), and into the control box (11) all shown in FIG.1A. Similarly, a gas line (16) can run through the exterior gas supply line channel (82); while mostly obscured in FIG.7B, it is substantially in the form shown for vacuum line (15). While exterior gas supply line channel (82) and exterior vacuum line channel (83) are shown opposite each other in FIG.7B, they can be in any shape or configuration as needed to perform the necessary medical treatment. This can include vacuum line (15) and gas line (16) sharing a single exterior channel. Additionally, while one exterior gas supply line channel (82) and one exterior vacuum line channel (83) are shown on channel probe (80), one skilled in the art will appreciate that another embodiment may comprise only one of the aforementioned channels and / or lines or may further comprise a third or more channel. Each of the channels can be independently operated as desired for the given treatment. Alternatively, there can be any multiple exterior gas supply line channels (82) and exterior vacuum line channels (83) and these need not be in even pairs. For example, channel probe (80) may contain two exterior supply line channels (82) and four exterior vacuum line channels (83) or n exterior gas supply line channels (82) and n exterior vacuum line channels (83), as nonlimiting examples.

[0198] Furthermore, the channel tip (84) possesses a channel tip recess (81) that is defined to encourage air to flow from the gas line (16) around the channel tip (84) and into the vacuum line (15). This channel tip recess (81) encourages a more even or different disbursement of the plasma created at the channel tip (84). While FIG.7B shows only one channel tip recess (81) in a particular size and shape, it should be understood that there can be any plurality of channel tip recesses in any size, shape, and / or configuration so as to deliver the appropriate dosage of plasma to the treatment site.

[0199] In certain embodiments, it may be desirable to not only create plasma, but to create microdroplets of plasma charged fluids. The rationale for the use of plasma-treated fluids is that the reactive species created by the cold plasma are stabilized by water. Microdroplets are a highly effective way to create a quantity of fluid and, as depicted in FIG.8, water, which can be expressed or sprayed onto a surface to provide an even disbursement of the microdroplets. Such even distribution is desirable to ensure even spread of the antimicrobial microdroplets.

[0200] Accordingly, as depicted in FIG.8, the charged microdroplets can be sprayed over a surface inoculated with the given bacteria for a given period of time to reduce loads of pathogens. Notably, increasing the time of treatment from ten to thirty seconds dramatically increases the log reduction of the pathogens. The method of application of microdroplets onto tissues or surfaces is highly effective in evenly distributing the microdroplets over the surface of the 29 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 tissues to be treated and ensures that necessary log reduction in pathogenic loads as necessary for reducing microbial loads.

[0201] Indeed, the even coating of the microdroplets is effectively created by the small size of the microdroplets. In cases in which microdroplets are introduced into a plasma generator, the plasma in itself creates small diameter microdroplets of fluids and thus creates a higher efficiency of treatment to the pathogenic loads. In particular, the introduction of plasma creates coulombic explosion of microdroplets to reduce the radius of the incoming microdroplets. The microdroplets of the present disclosure are created and maintained along a bell curve for their size. By using plasma, much smaller droplets of the fluid are created than are initially created by the nozzles alone.

[0202] In order to disinfect and reduce the pathogenic load on a given surface, a sufficient concentration of reactive species is necessary. In some instances, Applicant recognizes that more than one treatment will be necessary. Thus, when using the different probes defined herein, treatment of a surface, such as a skin surface or tissues of the mouth or nose, multiple treatments may be necessary for desired efficacy. Such treatments may be performed as often as every few hours, every day, every other day, or on another more dispersed schedule as determined by an appropriate professional treating a patient.

[0203] FIGS.9A, 9B, and 9C detail the droplet explosion in plasma. Indeed, the even coating of the microdroplets is effectively created by the small size or the microdroplets. FIGS.9A and 9B depict that plasma in itself creates smaller diameter microdroplets of fluids and thus creates a higher efficiency of treatment to the pathogenic loads. This is evidenced by the greater amount of smaller sized particles in FIG.9B as compared to FIG.9A. The introduction of plasma creates coulombic explosion of droplets to reduce the radius of the droplets, as depicted by FIG.9C. Thus, when creating a plasma mist, the microdroplets of fluid are exploded in the presence of plasma, creating highly charged RONS (reactive oxygen and nitrogen species), which are bound into the microdroplets themselves. In certain embodiments, the microdroplets of the present disclosure are created and maintained along a bell curve for their size. By using plasma, much smaller droplets of the fluid are created than are initially created by the nozzles alone, or where a sonicator, or nebulizer, or atomizer are utilized to create microdroplets. Therefore, such devices can be suitable for reducing particle size of charged droplets. However, Applicant envisions that microdroplets are formed both by mechanical means, such as with the nozzle, sonicator, nebulizer, atomizer, etc., and then further refined in their size by the application of plasma.

[0204] FIGS.10A–10D depict various nonlimiting examples of devices and methods for delivering plasma mist or plasma-treated water, gel, foam, and / or other liquids to treat medical conditions. In FIG 10A, an eye cup / patch (1111) is attached to a connection harness (1112). The connection harness (1112) can be a tube that delivers plasma mist or water from another source such as control box (11) (from FIG.1) and can be hooked to or otherwise interact with one or more 30 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 features described herein. Alternatively, connection harness (1112) can act as a conduit containing any of the features described herein such as a probe with a conductor wire so that plasma mist or plasma-treated water can be produced directly at the treatment site. Eye cup / patch is placed over the patients infected eye and left there for a period of time while the plasma mist or plasma-treated water is delivered. The length of time will vary based upon the condition being treated. Nonlimiting examples of treatment using eye cup / patch (1111) include treating eye infections, such as conjunctivitis, keratitis, and cellulitis; styes; or as a preventative measure after eye surgery such as removal of a cataract.

[0205] FIG.10B shows a nonlimiting example of a nasal cannula (1114) which is attached to a flexible line (1113) which connects the nasal cannula (1114) to the external source generating the plasma mist as described in greater detail herein. The antimicrobial properties of the plasma mist delivered through the patient’s nose make it ideal for treating various bacterial and viral infections currently treated with antibiotics, antivirals, and other medications such as congested sinuses, colds, and allergies. The prescribed dosage duration and frequency depends on the condition.

[0206] FIG.10C depicts a nebulizer mask (1116) attached to a flexible line (1115) which connects the nebulizer mask (1116) to the external source generating the plasma mist as described in greater detail herein. The nebulizer mask (1116) is placed over the patient’s nose and mouth to deliver plasma mist to treat respiratory tract infections including, but not limited to the common cold, laryngitis, pharyngitis / tonsillitis, acute rhinitis, acute rhinosinusitis, acute otitis media, acute bronchitis, bronchiolitis, pneumonia and tracheitis. Additionally, the nebulizer mask (1116) can be used in conjunction with a patient on a ventilator to reduce the risk of ventilator-associated pneumonia (VAP).

[0207] FIG.10D depicts another embodiment of a nebulizer, being a handheld nebulizer wherein the plasma- treated fluid can be added to a nebulizing reservoir (1118) and then drawn up into the nebulizing chamber (1120) and by passing air through airline (1117) and over the nebulizing chamber (1120). The plasma mist then travels to mouthpiece (1119) where it is inhaled by the patient. In each of FIGS.10A, 10B, and 10C, a device such as depicted in FIG.10D can be utilized to create the plasma mist to the target tissues, as a nonlimiting way of getting the plasma mist to the target tissue.

[0208] FIG.11A depicts a probe system for applying plasma-treated fluid or plasma mist from the probe (1310). The probe (1310) has virtually the same functionality as previous examples and has a tip (17) and an outlet (1311) for fluids taken from the supply (136). Fluids travel from the supply (136) through the supply line (137). The probe (1310) can create plasma (34) at the tip (17), and plasma mist (1301) may be created, or expelled adjacent to the tip (17). An optional plasma treatment can be provided in line with the fluid, such that a plasma in-line treatment (138) can be performed, which will charge the water with plasma. Optionally, the supply (136) may be previously plasma charged water. In certain embodiments, a microdroplet creator (139) is provided adjacent to the probe. The microdroplet creator (139) takes fluid from the supply line (137) and through a feature such as a nozzle, a nebulizer, an atomizer, a 31 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 sonicator, or other microdroplet creation mechanism, takes the water from a flowing form into the microdroplets. The in-line plasma treatment (138) can be placed before or after the microdroplet creator (139). The microdroplets are then expressed as the plasma mist (1301), whether or not cold plasma (34) is created at the tip (17) of the probe (1310). Probe (1310) may optionally be attached to and / or controlled by control box (11) as described in FIG.1. Probe (1310) may also optionally contain a vacuum line (15) in the event that the medical provider deems that it is advantageous to remove any remaining plasma mist (1301) after the prescribed treatment time is complete.

[0209] Thus, three primary solutions exist when generating the plasma mist or plasma-treated fluid. The first is that the fluid is created in a separate device, and then a reservoir of plasma-treated fluid is expressed as a plasma-treated mist or a plasma-treated fluid. The second is that an untreated fluid can be passed through a cold plasma within the device, typically, when the fluid is expressed and cold plasma is present at the expression point, to treat the fluid as it leaves the treatment device. Finally, the fluid can be both pretreated and also cold plasma provided to the fluid as it is being expressed. Each such solution yields plasma-treated fluids or plasma mist as desired for the particular iteration.

[0210] While not shown in FIG.11A, there may be any plurality of supply (136), supply line (137), microdroplet creator (139) and outlet (1311) that allow the medical provider to administer combination treatments in conjunction with plasma mist (1301) and the additional supply (136) reservoirs can contain any active ingredient necessary to treat the medical condition. Additionally, tip (17) may comprise a plurality of outlets (1311) to deliver a more even concentration of plasma mist (1301) to the treatment area.

[0211] FIG.11B provides a unique approach toward an existing problem in the dental industry. A dental sonication probe (1303) having a vibrating calculus removal end (1302) is defined. Alternatively, the vibrating calculus removal end can be a piezoelectric generator or a piezo ultrasonic scaler. The sonication probe (1303) may contain one or all of the features of the probe system of FIG.11A to produce plasma mist (1301). Alternatively, plasma-treated water, either created within the sonication probe system or created separately at another location in the dental office, can be pumped to the end of the sonication probe (1303) as a fluid stream rather than a mist. This is particularly useful as the sonication probe (1303) normally requires the flow of fluids, typically water, to the calculus removal tip (1302) to reduce temperature when in use, due to the high frequency of vibrations and the duration of use in performing calculus removal from teeth. The benefit of the use of plasma-treated water, is that while performing a dental cleaning, the calculus removal tip (1302) maintains temperature, while also generating quantities of the antimicrobial reactive species, which are able to inactivate or destroy the microbes while performing the cleaning. Indeed, for many patients, dental cleanings yield a high enough risk to their health, such as from a prior surgical procedure or a current medical condition, that antibiotics are desired, warranted, and frequently given to these patients. This is done prophylactically to prevent such infections. However, by providing the antimicrobial species at the location of the dental cleaning, the microorganisms 32 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 that are present at the gum line, under the gum line, present in microorganisms and / or bacterial films on the tooth surfaces, gum surface, on or underneath the calculus, are able to be inactivated or destroyed, thus reducing the incidence of, or preventing the infection.

[0212] Thus, methods of cleaning of tooth surfaces, typically which include removal of tartar or calculus from the teeth comprise, moving the vibrating calculus removal tip (1302) to remove calculus, while providing, simultaneously or contemporaneously, a plasma liquid or plasma mist (1301) to cool the calculus removal tip (1302) and to apply the antimicrobial properties of the plasma fluid or plasma mist to the tooth, gum, and mouth surfaces. Dental sonication probe (1303) may optionally comprise a vacuum line (15) to remove any access plasma charged mist (1301) or plasma charged water from the treatment site as the practitioner deems appropriate.

[0213] FIGS.11C and 11D depict embodiments of irrigation tools. FIG.11C provides a nozzle (1304) at the distal art of the nozzle irrigator (1305). The connection harness (12) provides access to the necessary power, and / or fluids to expel plasma-treated fluids and / or plasma mist (1301) from the nozzle (1304) by depressing on the trigger (1307) or by another feature. FIG.11D provides a variant of the irrigation device, with a plasma irrigator (1306), yielding cold plasma (34) at the distal end. Like FIG.11C, the connection harness (12) provides power (1309) such as the conductor wire and / or fluid supply (1308) to the plasma irrigator (1306). However, FIG.11D provides for a plasma probe that includes a conductor wire to be within the plasma irrigator (1306) tool. When the trigger (1307) is depressed, it activates the power (1309) and the fluid supply (1308), either simultaneously or consecutively, to transmit the aforementioned components to the distal end. The trigger (1307) may optionally engage with control box (11) (from FIG.1) to regulate the delivery of power and fluid supply. Thus, as fluids are expressed at the distal end of the plasma irrigator (1306), cold plasma is also optionally applied, yielding quantities of plasma-treated mist (1301). Based upon the quantity of fluid being deployed, the pressure, and the presence or absence of a nozzle, the size of the microdroplets within the plasma mist (1301) can be controlled. Thus, where more fluid is desired, a greater rate of flow may be generated, which may increase the particle size of the plasma mist but may be necessary for the desired clinical output. The embodiment of FIGS.11C and 11D may include as many features of FIGS.1A and 11A as necessary in order to achieve the desired therapeutic effect.

[0214] In some instances, such as during or after a surgical procedure, it is necessary to provide antimicrobial materials to a patient, whether to skin adjacent to a wound site, to a wound itself, to an incision point, or to open wounds or open surgical cavities. Using the embodiments described herein, a practitioner can apply plasma charged fluids, cold plasma, or plasma mist to the site, which provides for broad antimicrobial effects. Thus, in instances where a broad spectrum antibiotic is typically applied, this material can be either entirely avoided, or the plasma fluid can be first applied and then the antibiotic following, or in the reverse order, to increase the chance of eliminating microbial infection at the 33 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 surgical or wound site. Furthermore, the application of cold plasma, in contrast to a broad spectrum antibiotic, provides not only the protective antimicrobial effects, but also may promote immune responses to aid in the treatment recovery. A simple example is to generate a quantity of plasma-treated fluid. This plasma-treated fluid is then provided into a reservoir, and an irrigator dispenses the plasma-treated fluid from the reservoir to the surface to be treated. Alternatively, this can be dispensed in a catheter, or another device to apply the fluid or as a plasma mist in a desired treatment location.

[0215] The irrigation probe described in FIGS.11C and 11D can also be used to deliver plasma-treated gel, hydrogel, or plasma-treated foam. Thus, the embodiments provide a better standard of care than current medical treatments using gels for example, when gel is applied to a resection cavity after surgery, or the device may function within the nasal cavity as hemostatic agents to help stop nose bleeds when applied topically to the nasal tissues at the source of the nosebleed, to promote wound healing, to help reduce bleeding secondary to surgical procedures such as rhinoplasty, septoplasty, and other intranasal and intrasinal surgical procedures.

[0216] FIG.12 provides a simple example of a balloon catheter (137) that may be suitable for the present embodiments. The balloon catheter (137) may be manufactured so that a probe (18), or tube sufficient to deploy the plasma-treated fluid or plasma mist are within the balloon catheter (137), or they can be sized to be insertable into a port (146, 147) within the balloon catheter. One of the ports (146, 147) can allow for manipulation of the probe (18) whether or not that is spraying plasma mist, cold plasma, or otherwise deploying plasma fluids at the tip (17). The other port (146, 147) is typically used to inflate or deflate the balloon. Thus, at the distal end (138), the balloon is situated and allows for inflating an area of treatment, while the tip (17) uses any of the features of the probes (18) detailed herein, to provide the treatment fluids or cold plasma. At the proximal end (139), the practitioner can manipulate the catheter and inflate, deflate, or otherwise provide tools into the ports of the catheter.

[0217] FIG.13A depicts an embodiment of a balloon catheter (144), having a balloon (140) provided at a distal end of the catheter. Balloon catheters (144) are known to those of ordinary skill in the art. They comprise an elongated insertion tube (145) that typically comprises the balloon (140) at about the last 0–2 inches from the distal end of the catheter. The balloon catheter (144) typically includes one or more ports at the proximal end wherein the balloon can be inflated through one of the ports. It is also possible to then insert an additional element into the insertion tube (145). In some cases, this is simply provided with fluid, and wherein the distal end can express fluid out of the tip of the catheter. However, as depicted in FIG.13A, instead of simply providing an end to express fluid, the embodiment herein comprises a cold plasma probe and the tip (17) of the probe can be used to create cold plasma. FIG.13A in particular allows for the creation of cold plasma or alternatively expressing plasma-treated fluids or of plasma mist (1301). The purpose of such cold plasma or plasma-treated fluids or plasma mist is to irrigate the area beyond the tip (17) and to simultaneously 34 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 provide broad antimicrobial impacts by the application of the cold plasma, the plasma-treated fluid, or the plasma mist (1301).

[0218] FIG.13B provides a cross-sectional view of the probe (18) that may be present within the balloon catheter (144). Depicted, as in prior example is the conductor wire (14), insulation (55), and having a first line (141) and a second line (142). The first line (141) and the second line (142) may also include a third line. The combination of lines provides for the probe to use gas under pressure, such as a nonoxygen gas, a suction side, or fluid line, or a combination of two or all three, in any orientation. By providing a voltage to the probe (18) cold plasma (34) can be created. The device can create cold plasma in the presence of fluid or microdroplets (1301) to be expressed out of the tip (17) of the balloon catheter.

[0219] FIG.13C depicts a classical endoscope (130) that possesses a camera (131) at the distal end (132), with the operator possessing the proximal end (133). A probe (18) having the desired features for the given application is present in the endoscope (130). The probe (18) may possess any one of or all of the features as detailed herein, and as such may create cold plasma, may use a nonoxygen gas, may use a suction / vacuum, and / or may be able to irrigate with fluids, plasma-treated fluids, or create or provide a plasma mist (1301). Thus, a practitioner utilizing the endoscope can identify locations of treatment and provide the necessary level of cold plasma and / or plasma mist (1301) or materials for the particular need.

[0220] FIG.13D then details a laparoscope (135) that has a cutting or clamping feature (134) at the distal end (132). Such features are well-known tools at the end of a laparoscope, which can be used to cut, grasp, collect cells, among other nonlimiting uses. The laparoscope may be used alone, or together with an endoscope, or the laparoscope may include a camera (131) to allow for visual processing at the end of the tool, and wherein the proximal end (133) is manipulated by the practitioner. The practitioner may then utilize the probe (18) to create cold plasma, or to otherwise aerate, with fluids, cold plasma-treated fluids, or to generate or express plasma mist (1301), as detailed throughout the embodiments as disclosed herein.

[0221] While additional tools are not depicted, it should be apparent to those of ordinary skill in the art that it is suitable to express plasma-treated fluids, plasma mists or cold plasma at the distal end of a device, such as but not limited to a cystoscope. When fluids must be expressed, these would be expressed through a tube or line within the device suitable for that purpose. Such embodiments create a new treatment paradigm by application of an antimicrobial fluid at the targeted tissues.

[0222] FIGS.14A and 14B depict examples of balloon sinuplasty utilizing cold plasma or plasma mist or plasma- treated fluids. In each of FIGS.14A and 14B, a ballon catheter is inserted into one of the nostrils with a patient under local or general anesthesia. The balloon is located into a portion of the nasal cavity that has been compromised such that 35 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 the nasal cavity has no or reduced draining. The balloon is inflated to open the nasal passage in that space. The nasal cavity being treated is then provided with cold plasma treatment.

[0223] FIG.14A details a particular embodiment that utilizes a balloon catheter procedure. An image of the sinus of the face includes: the right maxillary sinus (1203), the left maxillary sinus (1204), the ethmoid sinus (1205), the left frontal sinus (1207) and the right frontal sinus (1206). In FIG.14A, a balloon catheter (1201) of the present embodiment is depicted as inserted into the right maxillary sinus (1203). The balloon catheter (1201) would be inserted into the right maxillary sinus (1203) with the balloon (1202) deflated. Once the balloon (1202) is in the proper position, the balloon is then inflated, typically with air but this could also be any other gas readily available. The present invention provides a distinct advantage over the prior art as the balloon (1202) can open the necessary pathways and then plasma charged mist and / or pressurized plasma charged air can be deployed from the same device to provide therapeutic treatment. Similarly, a plasma-treated fluid, such as plasma-treated saline, can be used as an irrigation fluid within the sinus that is opened from the balloon. Those of ordinary skill in the art will recognize that multiple different styles of balloon catheters exist and can be used in the present embodiments.

[0224] A depicted in FIG.13A, once the balloon (1202) is inflated, the sinus passages in the right maxillary sinus (1203) are opened, which allows access to this area. Typically, this procedure is performed because in its present state, the area is unable to drain because of inflammation or disease. By opening the passage in this area of the sinus, a probe, e.g., like probe (18) can be inserted into the balloon catheter (1201) and can be activated to apply cold plasma (34) or plasma mist (1301), as shown in other figures, or otherwise flush or irrigate the sinus cavity with plasma-treated water. The purpose of such plasma application is to reduce bacterial biofilm and other microorganisms and / or to provide broad antimicrobial cold plasma, water, or microdroplets into the sinus cavity for inactivating or destroying pathogens and other microorganisms.

[0225] FIG.14B then provides a further example wherein the balloon catheter (1201) is inserted into the right frontal sinus (1206). In each of the examples, the method of treatment is typically to first provide a local anesthetic to the sinus passages; second insert the balloon catheter (1201) into the sinus area desired for treatment. Third, inflate the balloon (1202) to open the sinus passage, and then finally apply via the probe, a quantity of cold plasma, plasma-treated fluids, plasma mist or a combination thereof. Such treatment will allow for opening of the sinuses, draining of sinuses, and clearing bacterial biofilms, as well as pathogenic microbes present in such areas by the application of the cold plasma, plasma-treated fluids, or the plasma mist.

[0226] FIG.15 repeats the study as depicted in FIG.2 but with a different bacterium, Streptococcus pyogenes here in FIG.15. This bacterium was interesting to confirm the cold plasma’s ability to destroy a pathogen that is likely to form bacterial films in the body, specifically within the mouth and esophageal regions. As previously noted, cold plasma was 36 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 highly effective in inactivating the bacteria, and again the combination of N2and nitric oxide was more effective than N2alone. Even the mere presence of the nitric oxide improved trend lines of efficacy. However, efficacy is in a narrow window, and more nitric oxide does not continue to increase efficacy. Therefore, Applicant defines that at a 5,000-ppm nitric oxide, a flow rate of 0.01 SLPM to 0.15 SLPM provides the necessary improvement, and additional nitric oxide reduces efficacy as compared to ambient air.

[0227] The various embodiments provide for several options for this treatment, which can be broadly understood according to the present disclosure, each of which can be used alone or in combination with one another. A first option is that a probe can be inserted into the catheter and be positioned appropriately to generate cold plasma to reach the treatment site. Preferably, the probe is inserted such that the tip of the probe is past or adjacent to the balloon, and thus virtually within the now open cavity. Applying a voltage to the probe generates cold plasma, which is then present in the now open cavity to provide antimicrobial effects, such as removing biofilms or destroying or inactivating bacteria, viruses, fungi, and / or other pathogens. EXAMPLES

[0228] Plasma-treated fluids can be created before use in a method treatment by passing fluid through cold plasma. For example, a device that allows for fluid to pass through cold plasma and is collected can be effective for creating a suitable quantity of plasma-treated fluid. Typically, one would create the plasma-treated fluid and then use the plasma- treated fluid in whatever medical protocol, typically immediately after it was created.

[0229] Another embodiment takes either pretreated plasma-treated fluid, or untreated fluids, such as water, and creates microdroplets of fluid, through any known mechanisms to create such microdroplets as detailed herein, and passes these microdroplets through cold plasma, usually at the top of the probe in the embodiments detailed herein. By expressing microdroplets through the cold plasma, the microdroplets are charged with the reactive oxygen and nitrogen species. Applicant has detailed this as a plasma mist, which possesses antimicrobial properties suitable for use in the various embodiments herein.

[0230] Thus, in certain embodiments, fluids are expressed via a device suitable for creating microdroplets and treated with cold plasma to create plasma mist. One nonlimiting example is to provide a tube with an exit adjacent to the tip (17) of a probe (18) that is creating cold plasma, which allows the contact between the microdroplets and the cold plasma.

[0231] In some instances, the embodiments simply utilize plasma-treated fluid and create from this the plasma mist. One example is to use a device such as a nebulizer wherein the plasma-treated fluid can be added to a nebulizing reservoir (1118) and then drawing the plasma-treated fluid up into the nebulizing chamber (1120) by passing air through airline (1117) and over the nebulizing chamber (1120). The plasma mist then travels to mouthpiece (1119) where it is 37 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 inhaled by the patient. Air passed into the nebulizer and a patient can then inhale the plasma mist. Alternatively, this same plasma-treated fluid can be expressed from a nozzle, or via any number of microdroplet creating devices and expressed to the patient for treatment.

[0232] In another embodiment, an applicator or irrigator is used to spray plasma-treated fluids into wounds or onto a surface, or to apply the plasma-treated mist in the same manner.

[0233] In certain embodiments, it may be advantageous to place a “cup” like structure over a treatment site, such that the plasma, plasma-treated fluid, or plasma mist are held within the chamber to increase the dwell time and / or efficacy of the cold plasma, plasma fluid, or plasma-treated mist. As noted in the figures, increasing dwell time yields an increase in the kill rate. Thus, increasing the dwell time at the treatment site to greater than 10 seconds or 20–60 seconds or to more than 60 seconds advantageously increases efficacy in treatment. EXAMPLE 1: TREATING MULTICOMPONENT SINUS SAMPLES WITH PLASMA-TREATED MIST

[0234] Five samples from patients were obtained by a nasal swab of the patient. Two swabs were taken, one being used to inoculate different plates and a second swab used to confirm the bacterial diversity. Each sample was numbered and the corresponding sample tested to confirm the bacterial and viral diversity. Samples from patients one and five returned with normal nasal flora, while samples from patients two, three, and four returned abnormal flora. Patient two sample included MRSA, patient three sample included Staphylococcus aureus; and patient four included Streptococcus pneumoniae.

[0235] All steps are performed at room temperature, unless otherwise indicated. Each sample was placed in a 50 mL sample tube and filled with 20 mL PBS. The tube was then agitated to combine.

[0236] A series of presterilized plates were used and each test plate was then inoculated with 1 mL per plate, and the samples maintained at 5°C for 2 hours. The plates were then ready for treatment. Each sample was plated 15 times, allowing for five different materials to be tested, each in triplicate. A total of 75 plates were created and tested.

[0237] In order to apply the test solutions to each plate, a set of refillable spray bottles was obtained, sufficient to expel 100 µL of fluid per pump. The purpose of the pump was to expel fluids with a consistent droplet size onto the plates in order to accurately test the ability of each of the materials to destroy the bacterial samples. The following materials were thus tested in triplicate on each of the three swabs: 0.9% saline, fluticasone, amoxicillin, plasma-treated 0.9% saline, and plasma-treated 0.9% saline with L-methionine (0.1% by weight).

[0238] For each tray, a single 100 µL spray was expressed over the inoculated samples. Each was then covered and incubated for 24 hours at 37°C before reading was completed of the colony forming units.

[0239] Table 4 depicts five different patient totals using standard available sinus treatments. 38 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0240] TABLE 4: Saline Fluticasone AmoxicillinP1: Normal 8 11 9 4 3 7 0 2 0

[0241] Each of the results depicts the number of colony forming units in the table. The term normal for patients 1 and 5 refers to an ordinary diversity of nasal flora, while those for patients 2, 3, and 4 identify the specific abnormal bacteria present in the samples. Listed below the totals are the averages and the standard deviations for each of the tests performed in triplicate.

[0242] Table 5 depicts two different treatments using saline that is treated with nonthermal plasma, and saline with a 0.1% addition of L-methionine by weight. 39 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0243] TABLE 5: Plasma Plasma w / L-MethionineP1: Normal 5 0 3 7 6 4

[0244] Patients 1–5 are the same as are present in Table 4 above, and again the results define the number of colony forming units counted. Table 5 shows a remarkable difference in the treatments as compared to the Table 4 results. First, when comparing the saline, which can function here as a negative control, the differences yield an unexpectedly superior antimicrobial treatment. Furthermore, when simply comparing the plasma treatments to a standard of care, such as the fluticasone treatment, which is available in branded and generic treatment options. Finally, the positive control, the amoxicillin, demonstrates that the model is effective when providing a high quantity of topical administration of this drug, such that even the MRSA was reduced. Notably, the amoxicillin was the most effective in treatment, as it was virtually able to eliminate all of the different bacterial strains, except for the antibiotic-resistant strains. However, it should be noted that the concentration of the amoxicillin used was equal to 0.1% by weight, and was directly applied to the surfaces of bacteria, which is not done clinically, as amoxicillin is typically administered either orally or through IV application, thus, the effective dose is many times greater than an ordinary amoxicillin dose. Accordingly, the amoxicillin functions as a positive control, suitable to kill virtually all bacterial species present.

[0245] The standard of care would be the use of the corticosteroid, fluticasone. Thus, when determining effectiveness of the treatment, a plasma-treated saline was many times more effective than an untreated saline rinse. Furthermore, this treatment was also significantly more effective than a leading OTC corticosteroid, used to treat symptoms of nasal irritation and nasal inflammation, which are primarily due to bacterial infection. Finally, while the amoxicillin was slightly more effective, its dose was provided at a number sufficient to eliminate even resistant bacteria, 40 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 thus being higher than a typical does provided for general administration. Thus, the plasma-treated fluid shows significant and unexpected improvements, specifically over common treatment plans.

[0246] However, a further improvement, of almost double the efficacy was created by the small addition of methionine at 0.1% by weight, to the 0.9% saline solution. This allows for sulfur compounds to be created upon treatment by cold plasma, increasing the diversity and quantity of the reactive species in the treated fluids. Specifically, this was most effective against the Staphylococcus species specifically. Indeed, as with prior data, the inclusion of peroxides, or of certain additives provides for the creation of these additional reactive species which increases effectiveness of the treatment.

[0247] The combined reading of the Tables shows a dramatic and unexpected treatment, that is otherwise novel in the medical space. No other suggestion of using plasma-treated fluids is known. Here, the evidence shows that both common nasal fluora as well as abnormal nasal fluora are dramatically reduced as compared to ordinary saline rinses, which have been used for hundreds of years for nasal infection. Furthermore, the plasma-treated saline was many times more effective than using a modern drug. Only a topical administration of a high quantity of antibiotics was more effective, which was intended as the positive control of the system. Notably, such broad application, typically systemically, would then disrupt the entire microbial balance of the patient, and lead to risks of antibiotic resistance. Thus, the present solutions are suggested to provide a new treatment solution that can reduce the use of antibiotics and prevent the unwanted effects of whole-body microbial imbalance as well as antibiotic resistance from the frequent use of antibiotics. METHODS OF USE AND METHODS OF PROVIDING THERAPEUTIC TREATMENT TO TISSUES

[0248] The embodiments herein can be utilized for applying cold plasma to tissues desiring treatment with the cold plasma. A primary treatment methodology is that cold plasma is utilized as a broad antimicrobial treatment, which can eliminate not just a singular microorganism as is common with many therapeutics. Furthermore, cold plasma is nontoxic, and possesses efficacy for a short amount of time, and then the fluids are resolved back into primarily water and oxygen. Thus, in comparison to previously known treatments that may leave residual materials or residual toxins, the methods and use of cold plasma detailed herein do not leave any such residual material or toxins. Therefore, application of plasma- treated fluids can be used on both topical skin surfaces or within a body.

[0249] One primary treatment is a method of treating nasal infection by irrigating the sinus with a plasma-treated fluid. As provided by Table 5, the plasma-treated fluid was particularly effective at reducing the presence of certain bacterial strains which are commonly found in diseases nasal tissues. The most common treatment is a simple OTC corticosteroid, or saline rinses, but each is shown to be significantly and unexpectedly less effective than plasma- treated saline solutions of the present disclosure. 41 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0250] In treating a patient with nasal irrigation, a method of treatment provides for creating the plasma-treated fluid by one of the devices or methods described herein. Applying a quantity of the plasma-treated fluid to the target tissues within the sinus and irrigating the sinus with the plasma-treated fluid. The irrigating, whether with a plasma- treated fluid, or specifically with a plasma-treated mist, provides for both a rinsing of pus or other matter deriving from localized or systemic infection. Furthermore, the antimicrobial aspect then destroys bacteria by contact, and the reactive particles further generate localized immune responses to aid in removing the infection. Typically, a treatment may be from about 10 mL to up to 1 L of rinse in the sinus, preferably between about 10 mL and about 250 mL, and preferably between about 20 mL to about 100 mL for a given treatment.

[0251] One particularly suitable treatment paradigm is to treat lesions or infections on the dermis. The dermal skin layers are susceptible to various irritations, whether as a rash, a wart, facial or body blemishes (acne vulgaris) and related or similar skin issues, and other known diseases and disorders of the skin. Cold plasma may be applied to these areas on the skin, and the treatment is sufficient to reduce the duration of the skin disorders, Treatment may be provided in the form of cold plasma application for a few seconds to durations of multiple minutes. In other embodiments, the treatment is preferably using plasma-treated fluids, which may be used as a wash or a rinse as nonlimiting uses. Finally, microdroplets charged with plasma may be Applied onto the desired treatment region.

[0252] Cold plasma, plasma-treated fluids, plasma-treated gels, plasma-treated foam, and / or plasma mist (plasma microdroplets) can also be utilized in the nasal cavity and passages to remove or reduce microorganisms and bacterial biofilm, shrink diseased tissue, and / or eliminate or reduce microorganisms, bacterial, fungal, viral, or other microbial issues within the nasal passage. One of the key treatments, as detailed previously in FIG.15A, allows for a unique approach to balloon sinuplasty, which is to open sinus passages with the balloon and then to apply the cold plasma or the plasm-treated fluids (e.g., to irrigate the sinus), or to apply plasma mist to aid in the removal of biofilms or infection within the nasal passages. Nasal treatments may require multiple treatments or application of cold plasma materials, whether every few hours, every day, every other day, or as desired by the medical professional.

[0253] A particular type of treatment is treatment of the esophagus for Barrett’s esophagus. Here, when a procedure is performed, the cells can be collected, but then the cold plasma, plasma-treated fluids, or plasma mist can be provided at the treatment site. Thus, if the test for Barrett’s esophagus is determined to be positive, it may not be further necessary to perform another treatment because the practitioner has already treated the site.

[0254] Endoscopy allows for practitioners to insert a thin scope into the body and to visualize and / or provide certain treatments with the endoscope. Some treatments may include visualization only, or collection of sample tissues, or providing treatments via the endoscope. Applicant has detailed herein that cold plasma materials can be used in conjunction with an endoscope to provide for the antimicrobial effects of the cold plasma where desired along the 42 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 pathway of the endoscope. Thus, such treatments may be suitable for any type of endoscope or process that may use an endoscope including within sinus, throat, esophagus, stomach, rectum, vagina, and even possibly within urinary or venous systems as practical.

[0255] Endoscopes are inserted into a body opening, while laparoscopes are inserted into an opening created by a small incision. Such laparoscopic procedures are widely used by doctors to perform a number of surgical procedures. Just as with the endoscope, cold plasma, plasma-treated fluids, and plasma mists can be provided with the laparoscope to aid in providing antimicrobial materials to the treatment site.

[0256] In some embodiments, treating dermal skin is desired, where a wound or opening is present. Where a wound is required to be cleaned, using an irrigator to flush the wound with plasma-treated fluids can perform the necessary washing but also provide antimicrobial effects with the plasma-treated fluid.

[0257] In some instances, the device can be placed around a wound to allow for additional dwell time from the cold plasma, plasma fluids, or plasma mist to the desired treatment site. For example, a balloon or a plug can isolate a portion of the nasal cavity. Plasma-treated fluids can be inserted into the isolated cavity and the fluids or plasma mist can be introduced into this cavity for a given treatment time, such as a few seconds, or a few minutes. Once the treatment time is completed, the balloon or plug can be removed and the fluids appropriately drained from the sinus.

[0258] Finally, in some embodiments, open wounds, such as from a surgical procedure may need to be washed or cleaned with antimicrobial materials, and wherein plasma fluids or plasma mist can be directly applied to the surgical site. Methods of treatment thus allow for application of the antimicrobial material which may replace or be added to standard antibiotic or antimicrobial treatments before, during, or after the surgical procedure.

[0259] In some embodiments, wounds, or disease on the lips, within the mouth, or adjacent to the mouth or lips can be treated with cold plasma. For example, mouth sores, ulcers, lips, herpes, and oral thrush could all be effectively treated with cold plasm or the plasma fluid or plasma mist.

[0260] Eye treatments both before and after eye surgery, as well as common childhood eye diseases such as conjunctivitis, can be commonly treated with broad antimicrobial or antibacterial products. However, cold plasma, or the plasma-treated fluids or mist or could replace these materials to reduce the severity of or incidence of eye infections. Other eye infections, including but not limited to blocked ducts may also benefit from cold plasma treatment to reduce microorganisms, bacterial films, and bacterial loads.

[0261] Lung diseases are also common and may be viral or bacterial in nature. Providing antimicrobial plasma mist may be sufficient to remove microorganisms and / or bacterial biofilms that damage lung tissue. Therefore, it is envisioned that a device, such as a nebulizer could generate plasma mist to be inhaled into the lungs for treating such maladies. 43 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500

[0262] In other embodiments, plasma mist, plasma-treated water, and / or plasma-treated gel to tumors, both malignant and benign, cancerous, and noncancerous. Treatment can be delivered directly to the tumor before it is removed from the patient. Alternatively or in conjunction with the foregoing, once the tumor is resected, the probe can be used to deliver cold plasma, plasma mist, plasma-treated water, plasma-treated foam, and / or plasma-treated gel to the resection cavity to treat any remaining cancerous or other suspicious cells left behind from the resection. Treatment can be performed during the resection surgery, at a follow-up visit after surgery or both. The embodiments described herein provide an elegant solution for various head and neck cancers and / or other noncancerous diagnostics as well as any other cancer that can be treated with cold plasma.

[0263] In certain embodiments, the fluids can be defined by their viscosity at room temperature, i.e., at 20°C–25°C. For example, it may be suitable to use a given material that has a higher viscosity than another. In certain embodiments, such materials may be best called a plasma gel wherein the plasma gel may possess certain adhesive properties, increasing the dwell time for treatment of the tissues. Those of ordinary skill in the art will recognize that numerous gel-like materials are used for delivery of therapeutics into the sinus cavity, as a nonlimiting example. Here, the gel could be pretreated or treated as if it were a plasma mist and be treated upon delivery to the desired site.

[0264] Accordingly, Applicant has defined that the broad antimicrobial effects of cold plasma, plasma-treated fluids, and plasma mist can be used in numerous ways for their antimicrobial potential. 44 4921-5597-5699, v.4

Claims

NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 What is claimed is:

1. A cold plasma device for generating a nonthermal plasma mist, the cold plasma device comprising: a probe (18), said probe (18) comprising a conductor wire (14) extending from a proximal end to a distal probe end and having a tip (17) at said distal probe end; a first passage having a first opening adjacent to the tip (17); said first passage defined for receiving a fluid therein for dispensing said nonthermal plasma mist from the first opening; and a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz.

2. The cold plasma device of claim 1 wherein the power source most preferably generates between 17,000 V and 37,000 V pulses of between 1 µs and 5 µs in duration applied at 1,000 Hz.

3. The cold plasma device of claim 1 wherein the conductor wire comprises an insulating material along a length of the probe from the proximal end to the distal probe end with a portion of noninsulated material at each end of the conductor wire.

4. The cold plasma device of claim 1 wherein the probe comprises a second passage, said second passage being connected to a harness, said harness comprising a feature suitable for supplying pressurized gas to said tip.

5. The cold plasma device of any one of claims 1 to 4 wherein the conductor wire is surrounded by an epoxy along a length of the probe from the proximal end to the distal probe end.

6. The cold plasma device of any one of claims 1 to 5 wherein the tip comprises a conductive metal or metal alloy.

7. The cold plasma device of any one of claims 1 to 6 wherein the tip comprises gallium or a gallium alloy.

8. The cold plasma device of any one of claims 4 to 7 wherein the first passage and the second passage are attached to an outside portion of the probe or a recess within the probe or are comprised within the probe.

9. The cold plasma device of any one of claims 4 to 8 wherein the first passage is provided with nitrogen gas or a mixture of nitrogen gas and nitric oxide gas at a concentration of the nitric oxide gas of 5,000 ppm and a flow rate of between 0.01 standard liters per minute (SLPM) and 0.15 SLPM.

10. The cold plasma device of any one of claims 1 to 9 wherein the first passage is defined to connect to a fluid supply. 45 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 11. The cold plasma device of any one of claims 1 to 10 wherein plasma mist is generated by taking a fluid within the first passage and passing said fluid through a microdroplet generator before being expressed from the first opening.

12. The cold plasma device of any one of claims 4 to 11 comprising: a suction of between 0.1 SLPM and 10 SLPM of flow within the second passage; and / or a flow of nitrogen gas into the first passage; and / or a flow of a combination of nitrogen gas and nitric oxide, said nitric oxide at between 1,000 ppm and 10,000 ppm, having a standard liter per minute flow of 0.01 SLPM to 0.15 SLPM; and / or a flow of fluid wherein said fluid is optionally expelled as microdroplets.

13. The cold plasma device of any one of claims 1 to 12 wherein the fluid is pretreated with a cold plasma.

14. The cold plasma device of any one of claims 1 to 13 wherein the fluids are expressed to contact cold plasma generated by the device, thereby generating the plasma mist.

15. Use of the cold plasma device of any one of claims 1 to 14 for use in treatment of sinusitis and / or nasal infection and / or Barrett’s esophagus and / or combinations thereof.

16. A cold plasma device for generating a nonthermal plasma mist, the cold plasma device comprising: a probe (18), said probe (18) comprising a conductor wire (14) extending from a proximal end to a distal probe end and having a tip (17) at said distal probe end; a first passage having a first opening adjacent to the tip (17), a second passage having a second opening adjacent to the tip (17), and a third passage having a third opening adjacent to the tip (17); said first passage defined for receiving a fluid therein for dispensing said nonthermal plasma mist from the first opening, the second passage defined for supplying a pressured gas, and the third passage defined to provide a suction from said third opening; and a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz.

17. A method of generating a nonthermal plasma-treated fluid, the method comprising: a. an applicator device comprising a probe (18), said probe (18) comprising a conductor wire (14) extending from a proximal end to a distal probe end and having a tip (17) at said distal probe end; b. a first passage having a first opening adjacent to the tip (17); c. said first passage defined for receiving a fluid therein, said first passage connected thereto to a fluid source; 46 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 d. a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz sufficient to generate nonthermal plasma; and e. expressing the fluid from said first passage, whereby the fluid passes through the nonthermal plasma, generating the nonthermal plasma fluid.

18. The method of claim 17 further comprising a microdroplet generator, said microdroplet generator receiving the fluid from the fluid source and generating microdroplets which are expressed from the first opening, and wherein said microdroplets are passed through the nonthermal plasma.

19. A method of expressing a plasma-treated fluid from a device, the method comprising: a. generating a quantity of plasma-treated liquid by applying a nonthermal plasma to said plasma- treated liquid by applying between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s for a duration of between 5 minutes and 120 minutes applied at 100 Hz to 10,000 Hz adjacent to said plasma-treated liquid; b. capturing the plasma-treated liquid into a vessel; c. withdrawing the plasma-treated liquid from the vessel; and d. expressing a quantity of the plasma-treated liquid from the device.

20. The method of claim 19 wherein the plasma-treated liquid is expressed from the device as a microdroplet.

21. The method of claim 20 wherein microdroplets are created by a sonicator, a nebulizer, a nozzle, an atomizer, or combinations thereof.

22. The method of claim 19 wherein the device further comprises a probe sufficient to receive a voltage to create a nonthermal plasma and wherein the nonthermal plasma is generated adjacent to an opening of the device wherein the plasma-treated liquid is expressed.

23. A method of treatment of sinusitis, the method comprising administering an effective amount of nonthermal plasma-treated fluid to a patient in need thereof.

24. The method of claim 23 further comprising wherein said nonthermal plasma-treated fluid is administered by expressing a quantity of fluid from a device and applying a quantity of cold plasma from a probe within the device wherein the fluid comes into contact with the cold plasma.

25. The method of claim 23 wherein the nonthermal plasma-treated fluid is a plasma mist.

26. The method of claim 24 wherein the nonthermal plasma-treated fluid is created by providing a flow of nitrogen gas to a tip of the probe.

27. The method of claim 26 wherein the nonthermal plasma-treated fluid is administered by providing a suction of air from an opening in a passage adjacent to a tip of the probe. 47 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 28. The method of claim 23 wherein the nonthermal plasma-treated fluid is generated from a probe (18), said probe (18) comprising: a conductor wire (14) extending from a proximal end to a distal end and having a tip (17) at said distal end; a first passage having a first opening adjacent to the tip (17) for expressing the fluid; and a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz.

29. The method of claim 28 wherein the conductor wire comprises an insulating material along a length of the probe from the proximal end to the distal end with a portion of noninsulated material at each end of the conductor wire.

30. The method of claim 28 wherein the probe is connected to a pressurized gas or a fluid supply and a wiring harness said, wiring harness connected to a power source, and wherein at least a second passage supplies the pressurized gas.

31. The method of claim 30 comprising at least a third passage, said third passage defined to provide suction from a second opening adjacent to the tip and through the third passage.

32. The method of claim 30 wherein the first passage and the second passage are attached to an outside portion of the probe or a recess within the probe or are comprised within the probe.

33. The method of claim 30 wherein the first passage or the second passage is connected to a fluid supply line, wherein a microdroplet generator is provided in line with the fluid supply line, and wherein fluid is treated with cold plasma.

34. The method of claim 30 comprising: a suction of between 0.1 SLPM and 10 SLPM within the second passage; and / or a flow of nitrogen gas into the first passage; and / or a flow of a combination of nitrogen gas and nitric oxide, said nitric oxide at between 1,000 ppm and 10,000 ppm, having a standard liter per minute flow of 0.01 SLPM to 0.15 SLPM.

35. The method of claim 28 wherein the conductor wire is surrounded by an epoxy along a length of the probe from the proximal end to the distal end.

36. The method of claim 28 wherein the tip comprises a conductive metal or metal alloy, which is preferably gallium or a gallium alloy. 48 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 37. The method of claim 28 comprising a fluid reservoir and a microdroplet creator wherein fluid flows into the microdroplet creator and is expelled from the tip as microdroplets and preferably wherein a cold plasma is provided to contact the microdroplets.

38. The method of claim 28 wherein the first passage is provided with a mixture of nitrogen gas and nitric oxide at a concentration of the nitric oxide at 5,000 ppm and a flow rate of between 0.01 SLPM and 0.15 SLPM.

39. A method of treatment of sinusitis, the method comprising administering an effective amount of nonthermal plasma-treated fluid to a patient in need thereof, said nonthermal plasma-treated fluid administered by inserting a balloon catheter into a nasal cavity, said balloon catheter defining a lumen comprising a fluid supply line, and applying a quantity of nonthermal plasma-treated fluid from the fluid supply line at a distal end of the balloon catheter.

40. The method of claim 39 further comprising a probe at the distal end, the probe sufficient to generate cold plasma, and wherein the method comprises applying a voltage to the probe sufficient to generate a cold plasma, which is generated while expressing the nonthermal plasma-treated fluid from the fluid supply line.

41. The method of claim 39 further comprising a plasma mist generator wherein the nonthermal plasma- treated fluid is transformed by the plasma mist generator into a plasma-treated mist.

42. A method of treatment of a nasal infection, the method comprising administering an effective amount of nonthermal plasma mist to a patient in need thereof, said nonthermal plasma mist administered by inserting a balloon catheter into a nasal cavity, said balloon catheter having a probe at a distal end of the balloon catheter, and applying a quantity of nonthermal plasma mist from the probe from the balloon catheter.

43. A method of treatment of a body tissue, said body tissue accessible by a balloon catheter, the method comprising administering an effective amount of nonthermal plasma mist to a patient in need thereof, said nonthermal plasma mist administered by inserting the balloon catheter into or adjacent to the body tissue, said balloon catheter having a probe at a distal end of the balloon catheter, and applying a quantity of nonthermal plasma mist from the probe from the balloon catheter.

44. A method of providing an antimicrobial nonthermal plasma mist to a tissue, the method comprising administering an effective amount of nonthermal plasma mist to a patient in need thereof, said nonthermal plasma mist administered by generating a plurality of microdroplets, said microdroplets being formed by a microdroplet device, and wherein the microdroplets are charged with oxidative species by contacting fluid 49 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 of the microdroplets with a cold plasma before creation of the microdroplets, after creation of the microdroplets, or both and applying a quantity of nonthermal plasma mist to the tissue.

45. The method of any one of claims 42 to 44 wherein the cold plasma is administered by providing a flow of nitrogen gas to a tip of the probe.

46. The method of any one of claims 42 to 45 wherein the cold plasma is administered by providing a suction of air from an opening in a passage adjacent to a tip of the probe.

47. The method of any one of claims 42 to 46 wherein the cold plasma is generated from a probe (18), said probe (18) comprising: a conductor wire (14) extending from a proximal end to a distal end and having a tip (17) at said distal end; a first passage having a first opening adjacent to the tip (17) and a second passage having a second opening adjacent to the tip (17); and a power source generating between 10,000 V and 45,000 V at a pulse of between 0.1 µs and 1 s in duration applied at 100 Hz to 10,000 Hz.

48. The method of any one of claims 42 to 47 wherein the probe is connected to a fluid supply line, said fluid supply line providing fluid to said probe, and wherein the fluid supply line is connected to a reservoir containing a plasma-treated fluid.

49. The method of any one of claims 42 to 48 wherein the first passage and the second passage are attached to an outside portion of the probe or a recess within the probe or are comprised within the probe.

50. The method of any one of claims 42 to 49 wherein the first passage is provided with nitrogen gas or a mixture of nitrogen gas and nitric oxide.

51. The method of any one of claims 42 to 50 wherein the fluid provided within the probe is treated with cold plasma to create a plasma mist, said plasma mist being expelled from the tip of the probe.

52. The method of any one of claims 42 to 51 wherein the first passage is provided with a mixture of nitrogen gas and nitric oxide at a concentration of the nitric oxide of 5,000 ppm and a flow rate of between 0.01 SLPM and 0.15 SLPM.

53. The method of any one of claims 42 to 52 comprising: a suction of between 0.1 SLPM and 10 SLPM of flow within the second passage; and / or a flow of nitrogen gas into the first passage; and / or a flow of a combination of nitrogen gas and nitric oxide, said nitric oxide at between 1,000 ppm and 10,000 ppm, having a standard liter per minute flow of 0.01 SLPM to 0.15 SLPM. 50 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 54. The method of any one of claims 17 to 53 comprising administering the cold plasma once a day, twice a day, three times a day, every other day, or on an as-needed basis.

55. The device or method of any prior claim wherein the probe is rigid at the tip.

56. The device or method of any prior claim wherein the probe is flexible along at least a portion of a length of the probe.

57. The device or method of any prior claim wherein a flexible probe comprises an insulating coating.

58. The device or method of any prior claim wherein the first passage and / or the second passage comprise at least one opening disposed along a length of the first passage and / or the second passage which extends beyond the tip of the probe between the tip and an end of the first passage or the second passage.

59. The device or method of any prior claim wherein the tip of the probe comprises a channel connecting a gas supply channel to a suction channel.

60. The device or method of any prior claim comprising a treatment chamber, said treatment chamber having an opening disposed to be placed onto a surface creating the treatment chamber.

61. The device or method of claim 60 wherein the treatment chamber comprises a plurality of openings in a wall of the chamber.

62. The device or method of claim 60 wherein the treatment chamber comprises a plurality of probes within the treatment chamber.

63. The device or method of any prior claim comprising: a fluid supply line and a microdroplet generator; wherein said fluid supply line provides fluid to the microdroplet generator; wherein upon formation microdroplets are contacted by cold plasma; and preferably wherein the microdroplet generator is a sonicator, a nebulizer, a nozzle, an atomizer, or combinations thereof.

64. An endoscope comprising a probe of any prior claim at its distal end.

65. An endoscope comprising a balloon at its distal end and an outlet further distal to the balloon for expressing plasma-treated fluids or plasma mist and optionally further comprising a probe of any prior claim suitable for creating quantities of plasma to treat fluids expressed from the outlet.

66. The device or method of any prior claim wherein the device is a laparoscope.

67. An irrigator, said irrigator expressing plasma-treated fluid. 51 4921-5597-5699, v.4NONTHERMAL PLASMA MIST PATENT DOCKET No.: ION01.0004.500 68. An irrigator, said irrigator comprising a plasma probe of any prior claim, said irrigator further comprising an activation feature and a fluid line, said fluid line exiting adjacent to the plasma probe, and wherein fluid flows and plasma is generated upon activating the activation feature.

69. A plasma device comprising: a fluid supply; a microdroplet creator and a cold plasma generating component; and wherein upon flow of fluid from the fluid supply, the fluid is formed into a plurality of microdroplets via the microdroplet creator and the fluid and / or the microdroplets are contacted by cold plasma.

70. A system for creating plasma mist for therapeutic treatment, the system comprising: a power supply; a plasma probe; a fluid supply, a microdroplet creator, and an activation switch; wherein upon changing the activation switch from an off position to an on position, the fluid supply is activated, the microdroplet creator is activated, and the power supply provides the necessary plasma in pulses to generate cold plasma; wherein the cold plasma contacts microdroplets of fluid creating plasma mist; and wherein the plasma mist is provided for therapeutic treatment.

71. A method of treating a patient in need thereof with an antimicrobial plasma mist, the method comprising generating the antimicrobial plasma mist and applying the antimicrobial plasma mist to a patient in need thereof.

72. The method of treatment of claim 71 further comprising a balloon catheter wherein the antimicrobial plasma mist is expelled from a tip distally positioned on the balloon catheter. 52 4921-5597-5699, v.4

Images