Systems and methods for treating respiratory infections and lung cancer using cold atmospheric pressure plasma

Abstract

1. A system for performing cold atmospheric pressure plasma treatment of respiratory infections or lung cancer, the system comprising: a source of carrier gas; a cold atmospheric pressure plasma generator connected to the source of carrier gas; a source of compressed air; a humidifier connected to the source of compressed air; a source of oxygen; a ventilator having an input connected to the output of the humidifier and the source of oxygen; a mixer having an inner chamber formed from a dielectric; an active electrode inside the inner chamber; and an outer electrode connected to ground, the mixer having a fluid input port connected to the gas output of the cold atmospheric pressure plasma generator and the output of the ventilator; and a delivery member connected to the output of the mixer for delivering the combined humidified air and cold atmospheric pressure plasma to the patient's respiratory system.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of the filing dates of U.S. Provisional Patent Application No. 63 / 008,510, filed April 10, 2020, U.S. Provisional Patent Application No. 63 / 010,565, filed April 15, 2020, U.S. Provisional Patent Application No. 63 / 014,657, filed April 23, 2020, and U.S. Provisional Patent Application No. 63 / 033,561, filed June 2, 2020.

[0002] The above provisional patent applications are hereby incorporated by reference in their entireties.

[0003] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT none

[0004] The present invention relates to systems and methods for using cold atmospheric pressure plasma to treat respiratory infections, lung cancer, pneumonia, or other cancers of the respiratory system. [Background technology]

[0005] Plasma medicine has been recognized as a new scientific field after intense research efforts in the application of low-temperature or cold atmospheric plasma. Keidar M, Beilis II, “Plasma Engineering: application in aerospace, nanotechnology and bionanotechnology,” Oxford: Elsevier; 2013. Cold atmospheric plasmas (CAP) are known to generate various chemically active species, including reactive oxygen species (ROS) and reactive nitrogen species (RNS). Chauvin, J., Judee, F., Yousfi, M. et al. “Analysis of reactive oxygen and nitrogen species generated in three liquid media by low temperature helium plasma jet,” Sci Rep 7, 4562 (2017). CAP is a cocktail containing ROS and RNS in combination with transient electric fields, UV, and charged species.

[0006] CAP has already been found to be effective in wound healing, skin diseases, hospital hygiene, sterilization, antifungal treatment, dental care, and cosmetic target cell / tissue removal. One of the most recent applications of CAP is in cancer treatment. M. Keidar et al. “Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy,” British Journal of Cancer (2011) 105(9), 1295-1301. As an ionized gas with a temperature close to room temperature, cold atmospheric pressure plasma (CAP) has demonstrated its promising capabilities in cancer treatment by inducing selective death of cancer cells in vitro. See Yan D, Sherman JH and Keidar M, “Cold atmospheric plasma, a novel promising anti-cancer treatment modality,” Oncotarget.8 15977-15995 (2017); Keidar M, “Plasma for cancer treatment,” Plasma Sources Sci.Technol.24 33001 (2015); Hirst AM, Frame FM, Arya M, Maitland NJ and O'Connell D, “Low temperature plasmas as emerging cancer therapeutics: the state of play and thoughts for the future,” Tumor Biol.37 7021-7031 (2016). CAP treatment on several subcutaneous xenograft tumors and melanoma in mice also demonstrated its potential clinical application.See Keidar M, Walk R, Shashurin A, Srinivasan P, Sandler A, Dasgupta S, Ravi R, Guerrero-Preston R and Trink B, “Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy,” Br. J. Cancer. 105 1295-301 (2011); Chernets N, Kurpad DS, Alexeev V, Rodrigues DB and Freeman TA, “Reaction chemistry generated by nanosecond pulsed dielectric barrier discharge treatment is responsive for the tumor eradication in the B16 melanoma mouse model,” Plasma Process. Polym. 12 1400-1409 (2015).

[0007] Furthermore, various experiments have been carried out in relation to the effect of CAP on viruses. In J. Zimmerman et al., “Effects of cold atmospheric plasmas on adenoviruses in solution,” J. Phys., D: 44 (2011) 505201, the authors reported successful inactivation of adenovirus, a non-enveloped double-stranded DNA virus, in solution using surface microdischarge technology working in air. In X. Su et al., “Inactivation Efficacy of Nonthermal Plasma- Activated Solutions Against Newcastle Disease Virus,” Applied and Environmental Microbiology, May 2018, vol. 84, issue 9, the authors reported an investigation into the inactivation efficacy of Newcastle Disease Virus by non-thermal plasma-activated solutions. In T. Xie et al., “Inactivation of airborne viruses using a packed bed non-thermal plasma reactor,” J. Phys. Appl. Phys. 52 (2019), the authors report a study of the effectiveness of a packed bed dielectric barrier discharge (DBD) NTP reactor to inactivate bacteriophage MS2 in aerosols. See also U.S. Patent Publication No. 2020 / 0016286, entitled “Production of Immune-response Stimulating Aerosols by Non-thermal Plasma Treatment of Airborne Pathogens.”

[0008] Several different systems and methods have been disclosed for performing cold atmospheric plasma (CAP) treatment. For example, U.S. Patent No. 10,213,614 discloses a two-electrode system for CAP treatment of cancer cells.

[0009] Another example cold atmospheric pressure plasma system is disclosed in US Pat. No. 9,999,462. The disclosed system has two units, namely a conversion unit (CU) and a cold plasma probe (CPP). The conversion unit is connected to an electrosurgical generator (ESU) output and converts the ESU signal into a signal suitable for performing a cold atmospheric pressure plasma procedure. The cold plasma probe is connected to the conversion unit output. At the end of the cold plasma probe, a cold plasma is generated that is thermally harmless to living tissue, i.e. the plasma cannot cause burns to the tissue. However, this cold plasma is lethal to cancer cells while leaving normal cells unaffected. The disclosed cold plasma conversion unit is unique in that it utilizes a high voltage transformer to upconvert the voltage (1.5-50 kV), downconvert the frequency (<300 kHz), and downconvert the power (<30 W) of the high voltage output from the electrosurgical unit (U.S. Patent No. 9,999,462).

[0010] Further research has shown that these CAP systems can be used to stimulate media, which can then be used for cancer treatment.For example, U.S. Patent No. 10,479,979 discloses a method for preparing CAP stimulated media for use in cancer treatment.Another method for preparing CAP stimulated media is disclosed in U.S. Patent Publication No. 2019 / 0279849.

[0011] Additionally, various systems and methods for controlling gas flow and an integrated gas assisted electrosurgical generator having a graphical user interface are disclosed in WO2018 / 191265 entitled “Electrosurgical Gas Control Module” and WO2019199281 entitled “Gas Enhanced Electrosurgical Generator.”

[0012] Various medical ventilator systems have been disclosed. Medical ventilators typically have a source of pressurized oxygen that is fluidly connected to a patient through a conduit. For example, U.S. Patent No. 10,350,374 discloses a medical system having a ventilator coupled to a breathing circuit. Some ventilator systems add means for monitoring patient data. For example, U.S. Patent No. 8,554,298 discloses a system and method for managing ventilation of a patient ventilated by a medical ventilator, and in particular, for integrating oximeter data with the medical ventilator. Another example is U.S. Patent Publication No. 20150034082, which discloses a ventilator-extracorporeal membrane gas-exchange (ECGE) system. Yet another example is U.S. Patent Publication No. 20170164873, which discloses a medical ventilator with pneumonia and pneumonia bacterial disease analysis capabilities by using gas recognition.

[0013] Still other systems include means for supplying medical gases with the aid of a ventilator. US 2013 / 0092159 discloses a method and a device for supplying at least one medical gas to a patient receiving artificial ventilation with the aid of a ventilator. The gas mixture provided by the ventilator's breathing gas flow and the medical gas added to that flow is fed to a connection piece, such as a Y-piece or Y-connector, from which a patient feed line leads to the mechanically ventilated patient, from which a further line branches off. By means of this further line at least the gas exhaled by the patient and the proportion of the breathing gas introduced by the ventilator into the first line and the medical gas delivered to the first line that was not inhaled by the patient are discharged via a second line. For example, US 20150059743 discloses a ventilator for supplying a mixture of oxygen and a medical gas other than oxygen to a patient. Summary of the Invention [Means for solving the problem]

[0014] In a preferred embodiment, the present invention is a system and method for using cold atmospheric pressure plasma to treat respiratory infections or cancers of the respiratory system, in particular to treat patients with COVID-19.

[0015] In a preferred embodiment, the present invention is a system for performing plasma treatment of respiratory infections. As used herein, "plasma treatment of respiratory infections" refers to the use of plasma to generate active species that are delivered to the respiratory system of a patient. The system includes a source of carrier gas, a humidifier connected to the source of carrier gas, a source of feed gas, a humidifier connected to the source of feed gas, a plasma generator configured to plasmatize the carrier gas into a plasma, a mixer, and a fluid delivery member connected to an output of the mixer to deliver the active species generated in the mixer to a patient. The mixer has an inner chamber formed from a dielectric, an active electrode inside the inner chamber and connected to an electrical output of the plasma generator, and an outer electrode connected to ground, and the mixer has a first fluid input port connected to a source of carrier gas and a second fluid input connected to a source of feed gas. The structure of the mixer forms a dielectric barrier discharge system for generating plasma. The carrier gas can include at least one of helium, argon, nitrogen, and oxygen. The delivery member may be, for example, an endotracheal tube, a nasal cannula, or a face mask. The source of feed gas may comprise one of a ventilator and a continuous positive airway pressure device and may include a mixture of air and oxygen.

[0016] The plasma generator preferably operates at a frequency within the range of 10 kHz to 200 kHz and an output peak voltage within the range of 3 kV to 6 kV. In a preferred embodiment, the plasma generator generates electrical energy having a frequency within 5 kHz of one of 40 kHz, 100 kHz, and 200 kHz. In another preferred embodiment, the plasma generator generates electrical energy having a frequency of 122 kHz. The plasma generator can be a combination high frequency electrosurgical generator and low frequency converter. The plasma generator can have a power module, a CPU for controlling the power module, a memory connected to the CPU, and a power source connected to the CPU. Still further, the plasma generator can have a touch screen display, a controller connected to the touch screen display, and a graphical user interface configured to display data on the touch screen display and receive input from a user through the touch screen display. The plasma generator can have a gas module. A source of carrier gas can be connected to the gas module, and the gas module controls the flow of the carrier gas to the mixer. The first humidifier can be connected between the gas module and the mixer, or can be connected between the gas module and the source of carrier gas.

[0017] In a preferred embodiment, the first humidifier is configured to humidify the carrier gas flowing from the carrier gas source to at least 70% humidity and the second humidifier is configured to humidify the feed gas flowing from the feed gas source to at least 50% humidity. For example, the first humidifier is configured to humidify the carrier gas flowing from the carrier gas source to 100% humidity and the second humidifier is configured to humidify the feed gas flowing from the feed gas source to at least 50% humidity.

[0018] In another embodiment, the present invention is a system for performing plasma treatment of the respiratory system. The system includes an electrical energy generator configured to generate electrical energy to plasmonize a carrier gas into a plasma, and a dielectric barrier discharge ("DBD") mixer. The DBD mixer includes an inner chamber formed from a dielectric, the inner chamber having a first input configured to fluidly connect to a source of humidified carrier gas, a second input configured to connect to a source of humidified feed gas, and an output configured to connect to a delivery member, an active electrode inside the inner chamber and connected to an electrical output of the electrical energy generator, and an outer electrode connected to ground. A plasma is generated in the inner chamber when electrical energy is provided from the electrical energy generator to the inner electrode while both the humidified feed gas and the humidified carrier gas flow into the inner chamber. The system can further include a first humidifier fluidly connected to the first input of the chamber in the dielectric barrier discharge assembly, and a second humidifier fluidly connected to the second input of the chamber in the dielectric barrier discharge assembly. Still further, the system may have a source of unhumidified helium fluidly connected to the input of the first humidifier and a source of unhumidified air fluidly connected to the input of the second humidifier.

[0019] Further aspects, features, and advantages of the present invention will be readily apparent from the following detailed description, by way of illustrating only preferred embodiments and implementations. The present invention is capable of other and different embodiments, and its several details can be modified in various obvious respects, all without departing from the spirit and scope of the present invention. Accordingly, the drawings and description are to be regarded as illustrative in nature and not restrictive. Additional objects and advantages of the present invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by the practice of the invention.

[0020] For a more complete understanding of the present invention, and the advantages thereof, reference is now made to the following description and the accompanying drawings. [Brief description of the drawings]

[0021] [Figure 1A] FIG. 2 is a block diagram of a cold atmospheric plasma system with a CAP joint mixer for the treatment of respiratory infections, according to a preferred embodiment, in which both the carrier gas and the feed gas are humidified.

[0022] [Figure 1B] FIG. 1B is a diagram of the system layout for the Dielectric Barrier Discharge assembly and connecting hoses of FIG.

[0023] [Figure 1C] FIG. 1B is a close-up view of the system layout for the Dielectric Barrier Discharge assembly and connecting hoses of FIG.

[0024] [Figure 1D] FIG. 1B is an exploded view of the system layout for the dielectric barrier discharge assembly and connecting hoses of FIG.

[0025] [Figure 1E] Figure 1B is a close-up exploded view of the system layout for the Dielectric Barrier Discharge assembly and connecting hoses of Figure 1A.

[0026] [Figure 1F] FIG. 1B is a close-up cross-sectional view of the system layout for the dielectric barrier discharge assembly and connecting hose of FIG. 1A.

[0027] [Figure 2A] FIG. 1 is an isometric view of a preferred embodiment of a CAP joint-mixer or dielectric barrier discharge (DBD) assembly, in accordance with a preferred embodiment of the present invention.

[0028] [Figure 2B] FIG. 1 is an exploded view of a preferred embodiment of a CAP joint-mixer or dielectric barrier discharge (DBD) assembly, in accordance with a preferred embodiment of the present invention.

[0029] [Figure 2C] FIG. 1 is a partial cross-sectional view of a preferred embodiment of a CAP joint-mixer or dielectric barrier discharge (DBD) assembly, in accordance with a preferred embodiment of the present invention.

[0030] [Figure 2D] FIG. 1 is a front view of a preferred embodiment of a CAP joint-mixer or dielectric barrier discharge (DBD) assembly, in accordance with a preferred embodiment of the present invention.

[0031] [Figure 2E] FIG. 1 is a rear view of a preferred embodiment of a CAP joint-mixer or dielectric barrier discharge (DBD) assembly, in accordance with a preferred embodiment of the present invention.

[0032] [Figure 2F] FIG. 1 is a top view of a preferred embodiment of a CAP joint-mixer or dielectric barrier discharge (DBD) assembly, in accordance with a preferred embodiment of the present invention.

[0033] [Figure 2G] FIG. 1 is a bottom view of a preferred embodiment of a CAP joint-mixer or dielectric barrier discharge (DBD) assembly, in accordance with a preferred embodiment of the present invention.

[0034] [Figure 2H] FIG. 1 is a left side view of a preferred embodiment of a CAP joint-mixer or dielectric barrier discharge (DBD) assembly, in accordance with a preferred embodiment of the present invention.

[0035] [Figure 2I]FIG. 1 is a right side view of a preferred embodiment of a CAP joint-mixer or dielectric barrier discharge (DBD) assembly in accordance with a preferred embodiment of the present invention.

[0036] [Figure 3A] 1 is a block diagram of a cold atmospheric pressure plasma generator according to a preferred embodiment of the present invention.

[0037] [Figure 3B] 1 is a block diagram of a plasma generator of an alternative preferred embodiment of the present invention.

[0038] [Figure 3C] 1 is a block diagram of a plasma generator of another alternative preferred embodiment of the present invention.

[0039] [Figure 3D] 1 is a block diagram of an integrated gas-enhanced electrosurgical generator having multiple gas modules in accordance with another alternative preferred embodiment of the present invention;

[0040] [Figure 4] FIG. 1 is a perspective view of an integrated gas-enhanced electrosurgical generator of a preferred embodiment of the present invention.

[0041] [Diagram 5] 1 is a flow diagram illustrating a method for treating a respiratory infection according to a preferred embodiment of the present invention, wherein both the carrier gas and the feed gas are humidified.

[0042] [Figure 6] FIG. 2 is a flow diagram showing a method for treating a respiratory infection according to a preferred embodiment of the present invention, where both the carrier gas and the feed gas are humidified and the CAP generator sweeps through multiple settings during a single treatment.

[0043] [Figure 7A]FIG. 2 is a block diagram of a cold atmospheric plasma system with a CAP joint mixer for treating respiratory infections according to a second preferred embodiment, in which the carrier gas is humidified.

[0044] [Figure 7B] 1 is a flow diagram showing a method for treating a respiratory infection according to a preferred embodiment of the present invention according to a second preferred embodiment, wherein the carrier gas is humidified.

[0045] [Figure 8A] FIG. 13 is a block diagram of a cold atmospheric plasma system with a CAP joint mixer for treating respiratory infections according to a third preferred embodiment, in which the feed gas is humidified.

[0046] [Figure 8B] FIG. 3 is a flow diagram showing a method for treating a respiratory infection according to a preferred embodiment of the present invention, wherein the feed gas is humidified.

[0047] [Figure 9] 1 is a block diagram of a cold atmospheric plasma system with a CAP joint mixer for endoscopic or laparoscopic use, according to a preferred embodiment.

[0048] [Figure 10A] Figure 1C is a graph of the concentration of H2O2 for a cold atmospheric plasma system for treating respiratory infections. [Figure 10B] Figure 1C is a graph of NO2- concentration for the cold atmospheric plasma system for treating respiratory infections.

[0049] [Figure 10C]1 is a graph of the viability of A549 cells treated according to the present invention with humidified O2 and air mixtures and various O2 percentages for up to 4 minutes.

[0050] [Figure 10D] 1 is a graph of the viability of A549 cells treated according to the present invention with humidified air / O2 mixture and dry He with 24% O2 for up to 17 minutes.

[0051] [Figure 10E] 1 is a graph of the viability of A549 cells treated according to the present invention with humidified helium and dry O2 and air mixture (with 24% O2) for up to 17 minutes.

[0052] [Figure 10F] 1 is a graph of the viability of A549 cells treated by a system according to the present invention for 5 or 10 minutes using a humidified air / O2 mixture (with 24% O2) and various helium humidities.

[0053] [Figure 10G] 1 is a graph showing the viability of lung cancer cells A549 48 hours after treatment with a system according to a preferred embodiment of the present invention using humidified air / O2 mixture and He+humidity 0-100% for 1-5 minutes.

[0054] [Figure 10H] 1 is a graph showing the viability of lung cancer cells A549 48 hours after treatment with a system according to a preferred embodiment of the present invention using a dry air / O2 mixture and He+humidity 0-100% for 1-5 minutes.

[0055] [Figure 11] FIG. 1 is a block diagram of a cold atmospheric plasma system with a CAP joint mixer for treating respiratory infections, according to another preferred embodiment, in which the carrier gas, feed gas, and third gas are humidified.

[0056] [Figure 12] 1 is a diagram of an alternative embodiment of a CAP joint mixer in which the air and oxygen feeds enter the CAP joint mixer at different locations, whereby at least one of the air and oxygen enters the CAP joint mixer downstream of the inner electrode.

[0057] [Figure 13A] 1 is a graph of the viability of A549 cells treated by a system according to a preferred embodiment of the present invention using a humidified air / O2 mixture.

[0058] [Figure 13B] 1 is a graph of the viability of A549 cells treated by a system according to a preferred embodiment of the present invention using humidified air and humidified O2 separately.

[0059] [Figure 14A] 1 is a graph of ozone production rate by a system according to a preferred embodiment of the present invention using humidified or dry air / O2 mixtures and He+humidity 0-100%.

[0060] [Figure 14B] 1 is a graph of ozone production rate by a system according to a preferred embodiment of the present invention using a mixture of humidified air and humidified O2 or separate humidified air and humidified O2 and humidified He at different voltages.

[0061] [Figure 14C] 1 is a graph of a first set of experimental results of ozone production rate by a system according to a preferred embodiment of the present invention using a mixture of humidified air and humidified O2 or separate humidified air and humidified O2 and humidified He at different voltages ranging from 35 to 40 V.

[0062] [Figure 14D]1 is a graph of a second set of experimental results of ozone production rates by a system according to a preferred embodiment of the present invention using a mixture of humidified air and humidified O2 or separate humidified air and humidified O2 and humidified He at different voltages ranging from 35 to 40 V, taken on a different day than the first set.

[0063] [Figure 15A] 1 is a graph of hydrogen peroxide (H2O2) generation rate by a system according to a preferred embodiment of the present invention. PBS was treated with CAP and gas mixtures (He, air, and O2), humidified air / O2, and humidified He2 for 8 or 15 minutes, either continuously or at predetermined intervals.

[0064] [Figure 15B] 1 is a graph of nitrite (NO2-) production rate by a system according to a preferred embodiment of the present invention. PBS was treated with CAP and gas mixtures (He, air, and O2), humidified air / O2, and humidified He for 8 or 15 minutes continuously and at predetermined intervals.

[0065] [Figure 15C] 1 is a graph of nitric acid (NO3-) production rate by a system according to a preferred embodiment of the present invention. PBS was treated with CAP and gas mixtures (He, air, and O2), humidified air / O2, and humidified He2 for 8 or 15 minutes continuously and at predetermined intervals. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0066] Cold atmospheric-pressure plasma (CAP) is a plasma that produces hydroxyl radicals ( · OH), singlet oxygen ( 1 O2), nitrogen ions (N2 +), atomic oxygen (O), as well as electrons, ions, and photons. The maximum concentration of these species can be achieved with an optimal amount of humidity in the gas. Upon interaction with biological fluids, the ROS and RNS generated by the CAP can be converted into hydrogen peroxide (HO), nitrite (NO), and nitrous acid (NO). 2- ), nitric acid (NO 3- ), Peroxynitrite (ONOO - ) can be formed. · OH, N2 + , 1 O2, O) are short half-life species, while H2O2, NO in the aqueous phase 2- , NO 3- , O.N.O. - are long half-life species. Long half-life species will further interact with intracellular species and metabolic pathways, inducing cell apoptosis. The present invention provides a system and method that can generate cold atmospheric plasma (non-thermal plasma) and deliver active species to a patient over a much longer distance than conventional systems. Conventional systems are typically used at a distance of 2-10 cm from the target tissue, but the present invention delivers plasma to a patient from a distance of more than 10 cm.

[0067] A cold atmospheric plasma system for treating respiratory infections according to a first preferred embodiment of the present invention is described with reference to FIG. 1. In this embodiment, the carrier gas is helium and the feed gas is air. A source of helium gas 110 is split into two lines 112, 114, each of which is controlled by a mass flow controller (MFC) 120. Line 112 is fluidly connected to a first humidifier 130. The helium gas flow (50-1000 mL / min) in line 112 passes through a H2O filled container (humidifier 130) and is then pumped to a mixing chamber 140. The helium gas flow in line 114 is pumped directly to the mixing chamber 140. Thus, the relative H2O saturation in the gas leaving the chamber 140 can be adjusted by the mass flow controllers 120 on lines 112, 114. Adjustment of the gas flow in the two lines 112, 114 allows fine adjustment of the overall flow rate and humidity of the gas flow exiting the chamber 140. Humidity can be in the range of 20% to 100%, with a preferred humidity of at least 70%. The total helium flow in this embodiment can vary from 0.5 L / min to 5 L / min in all cases. The humidity of the helium gas in the chamber 140 is measured by a calibrated high precision humidity and temperature meter 142. The humidified helium gas from the chamber 140 is delivered to an electrosurgical generator 300, referred to herein as a "cold atmospheric plasma (CAP) generator." A variety of electrosurgical generators are known in the art and can be used with the present invention. The gas delivered to the cold atmospheric plasma (CAP) generator 300 is referred to herein as a "carrier gas."

[0068] At the same time, the non-humidified air supply 150 (feed gas) is split into two lines 152, 154. Each line 152, 154 is controlled by a mass flow controller (MFC) 120. Line 152 is fluidly connected to a second humidifier 130. The air gas flow in line 152 passes through a H2O filled container (humidifier 130) and is then fed to the mixing chamber 140. The air gas flow in line 114 is fed directly to the mixing chamber 140. Thus, the relative H2O saturation in the air feed leaving the chamber 140 can be adjusted by the mass flow controller 120 on the lines 152, 154. Adjustment of the air flow in the two lines 152, 154 allows fine adjustment of the overall flow rate and humidity. Humidity can be in the range of 20% to 100%, with a preferred humidity of at least 70%. The humidity of the air in the chamber 140 is measured by a calibrated high precision humidity and temperature meter 142. The humidified air from the chamber 140 and oxygen from the oxygen supply 160 are provided to a respiratory delivery system 170, such as a ventilator, CPAP machine, BIPAP machine, or other known respiratory delivery system. The respiratory delivery system 170 will mix and condition the exhaust, oxygen, and CO2 and measure the pressure, flow, ratio, and frequency of the patient's intake. The output of the respiratory delivery system 170 is connected to a CAP joint mixer, for example, via tubing 174 and connector 176. In testing, it has been found effective to humidify the helium stream to 100% humidity and the air stream to 50% humidity.

[0069] The output of the CAP generator 300 and respiratory delivery system 170 are connected to a dielectric barrier discharge (DBD) assembly 200, referred to herein as the "CAP joint mixer." A ground cable 198 connects the outer electrode of the CAP joint mixer 200 to ground within the CAP generator 300. Although the ground cable 198 is shown separate from the tubing 194 in FIG. 1, other arrangements are possible where the ground cable 198 is coupled, for example, in a harness with the tubing 194. Due to the presence of H2O, the He + +e - Ionization of helium and H2O occurs simultaneously, which leads to chemical reactions. Cold plasma generates reactive species (H2O2, NO 2- , NO 3- , O.N.O. - , and 02 - ) is generated.

[0070] The output of the CAP joint mixer 200 is connected to a delivery member 190, which may be, for example, an endotracheal tube, an oxygen CPAP (continuous positive airway pressure), BIPAP (bilevel positive airway pressure), a ventilator face mask, or a nasal O2 cannula 190, to deliver active species 192 generated by the system, e.g., H2O2, NO2, 2- , NO 3- , O.N.O. - , and 02 - to the patient's respiratory system.

[0071] A preferred embodiment of a dielectric barrier discharge (DBD) assembly or CAP joint mixer 200 is described with reference to Figures 2A-2I. The DBD assembly 200 has a first inlet port 202 for receiving a flow of a first gas (e.g., a carrier gas), a second inlet port 204 for receiving a flow of a second gas (e.g., a feed gas), and an outlet port 206 through which gases and activated species generated within the DBD assembly exit the assembly. The assembly has a first housing 210 having a portion 212 that forms a chamber 212a within the first housing 210. At least the portion 212 that forms the chamber 212a is a dielectric material. In a preferred embodiment, the entire first housing 210 is formed of a dielectric material, although other embodiments are possible in which only a portion of the first housing 210, including the portion 212 that forms the chamber 212a, is formed of a dielectric material. In yet other embodiments, a dielectric material separate from the first housing 210 can surround the chamber 212a. The portion 212 of the first housing 210 forms an exit port 206 to which a delivery member, such as an endotracheal tube or other type of tube, can be connected. The invention is not limited to any particular type of delivery member or connection between the delivery member and the exit port 206. The first housing 210 has a first neck or connector portion 214 forming a first input port 202 for receiving a first gas, which in this embodiment is a carrier gas (e.g., helium), and a channel leading to the chamber 212a. The interior of the neck portion 214 is threaded to receive an inner electrode 230. The first housing 210 has a second neck or connector portion 216 forming a second input port 204 for receiving a second gas, which in this embodiment is a feed gas (e.g., an air / oxygen mixture), and a channel 216a leading to the chamber 212a. A second outer electrode 220 made of a conductive material, e.g., copper, surrounds the exterior of the dielectric forming the chamber 212a. As shown in FIGS. 2A and 2B, an outer insulating layer 219 covers an outer electrode 220 .The outer insulating layer 219 is not shown in Figure 2C. As shown in Figure 1, the outer electrode 220 is connected to ground. The housing 210 has a lip or ridge 218 that abuts the outer electrode 220. Within the upper portion of the lip or ridge 218 is a bore channel 218a that allows the outer electrode 220 to be connected to a ground wire 198 (see Figure 1) via a connecting wire 220a.

[0072] The inner electrode 230 is made of a conductive material and has a channel 240 within the inner electrode 230 through which a first gas (carrier gas) flows. The electrode 230 has a neck 232 that extends into the chamber 212a. The channel 240 extends through the neck 232 so that the first gas (carrier gas) can flow into the chamber 212a. The exterior of the electrode 230 has two threaded portions 230a, 230b and a lip or ridge 234. The threaded portion 230a engages the threaded interior of the neck 214 of the first housing 210 to secure the inner electrode 230 within the first housing 210. The ridge or lip 234 of the electrode 230 provides a stop when the electrode 230 is fully threaded into the neck 214.

[0073] The DBD assembly 200 further includes a second housing 250 having a channel therein through which a first gas (carrier gas) flows to a channel 240 in the inner electrode 230. The second housing 250 has a portion 252 having a threaded interior for engaging the threaded portion 230b of the electrode 230, thereby securing the second housing to the electrode 230 and the first housing 210. The second housing 250 has a recess at the end of the threaded portion 252 for receiving the electrode ridge or lip 234 and abutting the neck 214 of the first housing 210. The second housing 250 further includes a connector structure 254, 254a, 254b for connecting to a hose or other tubing 194 and a connector 196 for connecting the DBD assembly to the CAP generator 300. Within the second housing 250 is a tube 260 through which a first gas (carrier gas) flows. Within the tube 260 is an elongated electrode or wire that is connected (e.g., by solder) to a conductive connector 270. The conductive connector 270 abuts the inner electrode 230 and is thus electrically connected to the inner electrode 230.

[0074] As shown in FIG. 3A, an exemplary cold atmospheric plasma (CAP) generator 300 includes a power supply 302, a CPU (or processor or FPGA) 310, and a memory or storage 311. The system further includes a display 420 (FIG. 4), which may be the display of a tablet computer. The CPU 310 controls the system and receives input from a user through a graphical user interface that is displayed on the display 420. The CAP generator further includes a gas control module 1000 connected to a source 310 of CAP carrier gas, such as helium, for controlling the flow of carrier gas to the CAP joint mixer. The CAP generator 300 further includes a radio frequency (RF) power module 350 for generating radio frequency (RF) energy. The RF power module includes conventional electronic components as known for providing RF power in electrosurgical generators. The RF power module operates at frequencies between 10-200 kHz and output peak voltages of 3 kV-6 kV, and preferably close to (within 25% of) 40 kHz, 100 kHz, or 200 kHz. The gas module 1000 and RF power module 350 are connected to a connector 360 that allows the CAP joint mixer 200 (or CAP applicator 1100 of Figures 11A and 11B) to be connected to the generator 300 via a connector having an electrical connector 196a and a gas connector 196b.

[0075] As shown in Figure 3B, other arrangements for delivery of carrier gas and electrical energy can be used with the present invention. In Figure 3B, a source 110 of carrier gas (helium in this example) is provided to any type of gas control system 370 that delivers gas at a controlled flow rate to the CAP joint mixer 200. A conventional electrosurgical generator 350a delivers high frequency (HF) energy to a low frequency converter 350b, which outputs electrical energy having a frequency in the range of 10 kHz to 200 kHz and an output voltage in the range of 3 kV to 6 kV.

[0076] Another embodiment shown in FIG. 3C has a carrier gas source 110 connected to a conventional gas control system 370, which is in turn connected to a CAP joint mixer 200, and a conventional electrosurgical generator 351 also connected to the CAP joint mixer 200.

[0077] A generator housing 400 for a CAP-enabled gas-enhanced electrosurgical generator 300 according to a preferred embodiment of the present invention is shown in FIG. 4. The generator housing 400 has a housing 410 made of a sturdy material, such as plastic or metal, similar to the materials used for housings of conventional electrosurgical generators. The housing 410 has a removable cover 414. The housing 410 and cover 414 have means, such as screws, tongues, and grooves, or other structures, for removably securing the cover to the housing. The cover 414 can comprise only the top surface of the housing or multiple sides, such as the top, right, and left sides of the housing 410. The housing 410 can have multiple feet or legs attached to the bottom surface of the housing. The bottom surface of the housing 410 can have multiple vents for venting air from the interior of the gas-enhanced generator.

[0078] On the face of the housing 414 is a touchscreen display 420 and multiple connectors 432, 434 for connecting various accessories to the generator, such as an argon plasma probe, a hybrid plasma probe, a cold atmospheric plasma probe, or any other electrosurgical attachment. The face of the housing 410 is at an angle other than 90 degrees relative to the top and bottom faces of the housing 410 to provide easy viewing and use of the touchscreen display 420 by a user. One or more of the gas control modules can be mounted within the gas-enhanced electrosurgical generator 300.

[0079] The CAP-enabled gas-assisted electrosurgical generator has a graphical user interface (GUI) for controlling the components of the system using a touch screen display 420. The graphical user interface can control, for example, robotics, argon monopolar cut / coag, hybrid plasma cut, cold atmospheric plasma, bipolar, plasma sealer, hemodynamics, or voice activation. The graphical user interface can be used with fluorescence guided surgery. The graphical user interface (GUI) can further be used with guided images such as CT, MRI, or ultrasound. The graphical user interface can communicate with RFID (as may be found on various electrosurgical attachments) and can collect and store usage data in a storage medium. The graphical user interface communicates with a field-programmable gate array (FPGA), which can control an irrigation pump, an aspirator, a full bridge for adjusting power output, a flyback for regulating power (from DC to AC), and a foot pedal. The GUI further communicates with a database of data having associated predicted CAP settings or dosages via the CPU 310. The database storage can be in internal memory or other internal storage 311 or external storage.

[0080] A method for treating respiratory infections according to a preferred embodiment of the present invention, in which both the feed gas (air) and the carrier gas (helium) are humidified, is described with reference to FIG. 5. Pressurized feed gas (air) is provided to a humidifier 510. The pressurized air is humidified in the humidifier 520. Oxygen is added to the humidified air flow 530. The humidified air and oxygen flow are controlled by a ventilator or other respiratory delivery system 540. At the same time, a CAP carrier gas, such as helium, is provided to the humidifier 514. The carrier gas is humidified in the humidifier 522. The humidified carrier gas is provided to a CAP generator. The humidified CAP carrier gas from the CAP generator and the output of the ventilator are both provided to a CAP joint mixer 550, 552. Electrical energy is applied to an inner electrode in the CAP joint mixer 560. The output of the CAP joint mixer is then delivered to the patient's respiratory system, for example by a respiratory face mask, nasal cannula, or endotracheal tube 570.

[0081] In a study on the treatment of cancer using cold atmospheric plasma, it was found that CAP treatment reduced the viability of cancer cells in a dose-dependent manner. Rowe, W. et al. “The Canady Helios Cold Plasma Scalpel Significantly Decreases Viability in Malignant Solid Tumor Cells in a Dose-Dependent Manner,” Plasma, 2018.1(1):p. 177-188.

[0082] A method for treating respiratory infections according to another preferred embodiment of the present invention, in which both the feed gas (air) and the carrier gas (helium) are humidified, will be described with reference to Figure 6. In this embodiment, rather than applying electrical energy to the inner electrode in the CAP joint mixer at a single setting (e.g., 70V) for the entire treatment time (step 560 of Figure 5), the generator automatically sweeps through multiple settings, applying a first setting (e.g., 70V) 562 for a first time t1 while delivering power to the patient 570, and then applying a second setting (e.g., 40V) 564 for a second time t2 while delivering power to the patient 572.

[0083] An alternative embodiment of system 700, referred to herein as a "Helium Gas Humidity Adjustment Setup", is described with reference to FIG. 7A. A helium gas source 110 is split into two lines 112, 114, each of which is controlled by a mass flow controller (MFC) 120. The helium gas flow (50-1000 mL / min) in line 112 passes through a HO-filled container (humidifier 130) and is then pumped to a mixing chamber 140. The helium gas flow in line 114 is pumped directly to the mixing chamber 140. Thus, the relative HO saturation in the gas exiting the chamber 140 can be adjusted by the mass flow controllers 120 on the lines 112, 114. Adjustment of the gas flows in the two lines 112, 114 allows fine adjustment of the overall flow rate and humidity of the gas flows exiting the chamber 140. Humidity can be in the range of 20% to 100%, with a preferred humidity of at least 70%. The total helium flow in this embodiment can vary from 0.5 L / min to 5 L / min in all cases. In this helium gas humidification setup, the amount of helium HO vapor was varied during the experiment. The humidity of the helium gas in the chamber 140 was measured by a calibrated high-precision humidity and temperature meter 142 shown in FIG. 7A. The humidified helium gas from the chamber 140 is pumped to the CAP generator 300.

[0084] At the same time, the non-humidified air tank 150 and the non-humidified oxygen tank 160 deliver air and oxygen, respectively, to a respiratory delivery system 170, such as a ventilator, a CPAP (Continuous Positive Airway Pressure) system, or a BIPAP (Bilevel Positive Airway Pressure) system. These are referred to as "feed gases." The respiratory delivery system 170 will mix and condition the air, oxygen, and CO2 and measure the pressure, flow, ratio, and frequency of the patient's inspiration. The outputs of the CAP generator 300 and the respiratory delivery system 170 are connected to a dielectric barrier discharge (DBD) assembly 200. The output of the CAP joint mixer 200 is connected to a delivery member 190, which can be, for example, an endotracheal tube, an oxygen CPAP (Continuous Positive Airway Pressure), a BIPAP (Bilevel Positive Airway Pressure), a ventilator face mask, or a nasal O2 cannula 190, and the active species 192 generated by the system, such as H2O2, NO2, and the like, are then delivered to the ventilator. 2- , NO 3- , O.N.O. - , and 02 - to the patient's respiratory system.

[0085] A method for treating a respiratory infection using the system of FIG. 7A is described with reference to FIG. 7B. A CAP carrier gas, such as helium, is provided to a humidifier 714. The carrier gas is humidified 722. The humidified carrier gas is provided to a CAP generator. At the same time, a pressurized feed gas (air) is provided 710. Oxygen is added to the air flow 730. The air and oxygen flow is controlled by a ventilator or other respiratory delivery system 740. The humidified CAP carrier gas from the CAP generator and the output of the ventilator are both provided to a CAP joint mixer 750, 752. Electrical energy is applied to an inner electrode in the CAP joint mixer 760. The output of the CAP joint mixer is then provided to the patient's respiratory system 770, for example, by a respiratory face mask, nasal cannula, or endotracheal tube.

[0086] Another embodiment of a cold atmospheric plasma system 800 for treating respiratory infections is described with reference to FIG. 8A. A helium gas supply 110 is fed to an electrosurgical generator 300. At the same time, a non-humidified air supply 150 (feed gas) is split into two lines 152, 154. Each line 152, 154 is controlled by a mass flow controller (MFC) 120. The air gas flow in line 152 passes through a H2O filled container (humidifier 130) and is then fed to a mixing chamber 140. The air gas flow in line 114 is fed directly to the mixing chamber 140. Thus, the relative H2O saturation in the air feed leaving the chamber 140 can be adjusted by the mass flow controllers 120 on the lines 152, 154. Adjustment of the air flow in the two lines 152, 154 allows fine adjustment of the overall flow rate and humidity. Humidity can be in the range of 20%-100%, with a preferred humidity of at least 70%. The humidity of the air in the chamber 140 is measured by a calibrated high precision humidity and temperature meter 142. The humidified air 140 from the chamber 140 and oxygen from the oxygen supply 160 are provided to a respiratory delivery system 170, such as a ventilator, CPAP machine, BIPAP machine, or other known respiratory delivery system. The respiratory delivery system 170 will mix and condition the exhaust, oxygen, and CO2 and measure the pressure, flow, ratio, and frequency of the patient's inhalation.

[0087] The output of the CAP joint mixer 200 is connected to a delivery member 190, which can be, for example, an endotracheal tube, oxygen CPAP (Continuous Positive Airway Pressure), BIPAP (Bilevel Positive Airway Pressure), ventilator face mask, or nasal O2 cannula 190, and delivers active species 192 generated by the system, e.g., H2O2, NO 2- , NO 3- , O.N.O. - , and 02 - to the patient's respiratory system.

[0088] A method for treating respiratory infections according to a preferred embodiment of the present invention, in which the feed gas (air) is humidified, is described with reference to FIG. 8B. Pressurized feed gas (air) is provided to a humidifier 810. Pressurized air is humidified in the humidifier 820. Oxygen is added to the pressurized air flow 830. The humidified air and oxygen flow are controlled by a ventilator or other respiratory delivery system 840. At the same time, a CAP carrier gas, such as helium, is provided to a CAP generator 812. The CAP carrier gas from the CAP generator and the output of the ventilator are both provided to a CAP joint mixer 850, 852. Electrical energy is applied to an inner electrode in the CAP joint mixer 860. The output of the CAP joint mixer is then provided to the patient's respiratory system 870, for example, by a respiratory face mask, nasal cannula, or endotracheal tube. Other embodiments of the present invention are possible in which the plasma is delivered to the patient through, for example, an endoscopic or laparoscopic device. Still further, in other embodiments, the present invention can treat cancer within the abdomen by delivering the output of a CAP joint mixer to the abdomen, for example, via a laparoscope or trocar.

[0089] A cold atmospheric plasma system for treating a patient via an endoscope or laparoscope according to a preferred embodiment of the present invention is described with reference to FIG. 9. A helium gas source 110 is split into two lines 112, 114, each of which is controlled by a mass flow controller (MFC) 120. The helium gas flow (50-1000 mL / min) in line 112 passes through a H2O filled container (humidifier 130) and is then pumped to a mixing chamber 140. The helium gas flow in line 114 is pumped directly to the mixing chamber 140. Thus, the relative H2O saturation in the gas leaving the chamber 140 can be adjusted by the mass flow controllers 120 on the lines 112, 114. Adjustment of the gas flows in the two lines 112, 114 allows fine adjustment of the overall flow rate and humidity of the gas flow leaving the chamber 140. Humidity can range from 20% to 100%, with a preferred humidity of at least 70%. Total helium flow in this embodiment can vary from 0.5 L / min to 5 L / min in all cases. The humidity of the helium gas in the chamber 140 is measured by a calibrated high precision humidity and temperature meter 142. The humidified helium gas from the chamber 140 is delivered to an electrosurgical generator 300. A variety of electrosurgical generators are known in the art and may be used with the present invention. The gas delivered to the cold atmospheric plasma (CAP) generator 300 is referred to herein as the "carrier gas."

[0090] At the same time, the non-humidified air supply 150 (feed gas) is split into two lines 152, 154. Each line 152, 154 is controlled by a mass flow controller (MFC) 120. The air gas flow in line 152 passes through a H2O filled container (humidifier 130) and is then fed to the mixing chamber 140. The air gas flow in line 154 is fed directly to the mixing chamber 140. Thus, the relative H2O saturation in the air feed leaving the chamber 140 can be adjusted by the mass flow controllers 120 on the lines 152, 154. Adjustment of the air flow in the two lines 152, 154 allows fine adjustment of the overall flow rate and humidity. Humidity can be in the range of 20% to 100%, with a preferred humidity of at least 70%. The humidity of the air in the chamber 140 is measured by a calibrated high-precision humidity and temperature meter 142. Humidified air 140 from chamber 140 and oxygen from oxygen supply 160 are connected to gas control system 171. In an alternative embodiment, an integrated gas-enhanced electrosurgical generator having multiple gas control modules 1000a, 1000b, 1000c as shown in Figure 3D can be used. In such a system, the flowing helium, air, and oxygen are all controlled by gas modules within a single housing and with a unified control system.

[0091] The output of the CAP generator 300 and the humidified air and oxygen from the gas control system 170 are connected to a dielectric barrier discharge (DBD) assembly 200, referred to herein as the "CAP joint mixer." A ground cable 198 connects the outer electrode of the CAP joint mixer 200 to a ground within the CAP generator 300. Although the ground cable 198 is shown separate from the tubing 194 in FIG. 1, other arrangements are possible where the ground cable 198 is coupled, for example, in a harness with the tubing 194. Due to the presence of H2O, the He + +e - Ionization of helium and H2O occurs simultaneously, which leads to chemical reactions. Cold plasma generates reactive species (H2O2, NO 2- , NO3- , O.N.O. - , and 02 - ) is generated.

[0092] The output of the CAP joint mixer 200 is connected to an elongated delivery member 190a, which can be, for example, a rigid or flexible tube sized to fit into the channel of any type of endoscope or laparoscope, whether that scope is a bronchoscope, colonoscope, or any other type of scope used in surgical applications.

[0093] The embodiment shown in FIG. 1A, in which both the feed gas (air) and the carrier gas (helium) are humidified, provides higher humidity in the CAP joint mixer than the embodiment in which only one of the feed gas and the carrier gas is humidified. Experiments have shown that in the embodiment of FIG. 1A, the increased humidity can reduce the treatment time required to achieve a 100% kill rate for lung cancer cells to 5 minutes, versus about 17 minutes for the embodiment in which only one of the feed gas and the carrier gas is humidified. Additionally, ozone production can be reduced from nearly 20 parts per million (ppm) for the embodiments of FIGS. 7A and 8A to less than 3 ppm (about 2 ppm) for the embodiment of FIG. 1A.

[0094] The gas control module 1000 according to the present invention is designed for gas-enhanced electrosurgical systems. Conventionally, gas-enhanced electrosurgical systems have an electrosurgical generator and a gas control unit with separate housings. Conventional gas control units typically control only a single gas, such as argon, CO2, or helium. The present invention uses a gas control module 1000 that can be used in a gas control unit or in a combination unit that functions both as an electrosurgical generator and as a gas control unit. Furthermore, multiple gas control modules according to the present invention can be combined in a single gas control unit or a combination generator / gas control unit to provide control of multiple gases and provide control for multiple types of gas-enhanced surgical procedures, such as argon gas coagulation, hybrid plasma electrosurgical systems, and cold atmospheric plasma systems.

[0095] Still further, although helium is the carrier gas used in the disclosed embodiments, other gases such as argon, nitrogen, oxygen, or air may be used as the carrier gas.

[0096] Although the preferred embodiment is described with respect to a ventilator, other medical respiratory devices, such as a continuous positive airway pressure (CPAP) system, may be used with the present invention.

[0097] experiment A cold atmospheric plasma system for treating respiratory infections in which only air was humidified was used to treat 1 mL phosphate buffer saline (PBS) in a 12-well plate with the argon coagulation and spray generators operating at frequencies close to 100 kHz for 3 min each. The voltage was set to be 70 V. Both oxygen and air flows were set to be 1 LPM. The oxygen (O2) and air mixture was humidified by bubbling through DI water. The relative humidity (RH) of the mixture was about 80%. The flow rate of helium, the carrier gas for cold atmospheric plasma (CAP), was set to 3 LPM. Thus, the O2 percentage of the final output gas from the endotracheal tube was about 24% in the O2-air-helium mixture.

[0098] Among the cocktail of plasma-generated reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the treated solution, hydrogen peroxide (H2O2) and nitrite (NO 2- ) are the most commonly studied long half-life species. Their concentrations were measured in treated phosphate-buffered saline (PBS) with CAP on or off using the Griess Reagent System (Promega, G2930) and a colorimetric Hydrogen Peroxide Assay Kit (Sigma-Aldrich, MAK311-1KT). Results were read by a BioTek microplate reader at 550 nm and 595 nm for absorbance, respectively.

[0099] Electrosurgical generators typically have multiple modes of operation including a "cut" or incision mode of operation or a "coag" or coagulation mode of operation. The cut mode will typically have a low voltage waveform (e.g., 1 KV) with a high duty cycle, e.g., 100%. The coag mode of the electrosurgical generator typically creates a waveform with large amplitude but short duration "spikes" to achieve hemostasis (coagulation). For example, the coag mode on an electrosurgical generator may use a high voltage waveform with a 6% duty cycle. Different degrees of hemostasis (coagulation) can be achieved by utilizing various degrees of "blended" waveforms, e.g., 50% on / 50% off, 40% on / 60% off, or 25% on / 75% off. Electrosurgical generators also have an argon plasma coagulation mode or "argon coag" mode. Argon Plasma Coagulation (APC) utilizes plasma generated by ionization of a millimeter-diameter argon stream that exits an electrosurgical hand piece into the ambient air. Compared to cut mode, the argon coagulation mode on the generator can use higher voltages (e.g., 1 KV for cut mode vs. 4 KV for argon coag), less current (500 mA for cut vs. 200 mA for argon coag), and lower frequencies (390 KHz for cut vs. 30 KHz for argon coag). Electrosurgical generators also have a "Spray mode" that is similar to the argon coag mode (similar voltage and current), but has a random walk of frequencies, e.g., from 10-30 KHz, which allows the frequency to cover different tissue impedances.

[0100] H2O2 and NO in relation to the treatment of this system 2-The concentrations of H2O2 and NO2 are plotted in Figures 14A and 14B. With the CAP turned on, both species are higher when treated in Argon Coag mode compared to when treated in Spray mode. A gas-only treatment was also performed as a control. As shown in Figures 10A and 10B, with a 3-minute treatment, the Argon Coag mode at 70 V produced 90 μM H2O2 and 18 μM NO2. 2- whereas the 70V Spray mode generated 25 μM H2O2 and undetectable amounts of NO 2- The gas mixture alone does not produce significant amounts of ROS or RNS.

[0101] CAP plasma ventilator validation Cold atmospheric pressure plasma has been shown to inactivate airborne viruses (Xia, T. et al. "Inactivation of airborne viruses using a packed bed non-thermal plasma reactor" Journal of Physics D:Applied Physics, 2019. 52(25)) and inactivate the Hepatitis B virus while maintaining normal liver function during CAP treatment (Shi, X. -It has been reported that cold atmospheric plasma inhibits HIV-1 replication (Volotskova, O. et al., "Cold Atmospheric Plasma Inhibits HIV-1 Replication in Macrophages by Targeting Both the Virus and the Cells" PLoS One, 2016.11(10):p.e0165322), and inactivates Newcastle disease virus and avian influenza virus without destroying antigenic determinants for vaccine preparation (Wang, G. et al., "Non-thermal plasma for inactivated-vaccine preparation" Vaccine, 2016.34(8):p.1126-32). In this study, the CAP is combined with a ventilator system to achieve delivery of the CAP throughout the patient's respiratory system as well as treatment of the virus.

[0102] Wu et al. (Wu, Y. et al. "MS2 virus inactivation by atmospheric-pressure cold plasma using different gas carriers and power levels" Appl Environ Microbiol, 2015.81(3):p.996-1002) showed that ambient air as the carrier gas produced the highest level of inactivation at power levels of 20 and 24 W with gas carriers Ar-O2 (2%, vol / vol) and He-O2 (2%, vol / vol). Furthermore, air is the required input gas for all ventilators. Therefore, air as the carrier gas is the best option for CAP-equipped ventilators. Relative humidity (RH) as an important factor of air will be studied for the optimal configuration in addition to CAP treatment parameters including discharge voltage (V) and treatment time (t).

[0103] Reactive species generated by CAP The activated species generated by CAP can be identified in the plasma beam using optical emission spectroscopy (OES) and in aqueous solution by species-based kits.

[0104] Reactive species in plasma beams An optical emission spectrometer (Ocean Optics HR2000) is used to detect species in the plasma beam in the 200-900 nm range. The plasma emission is collected perpendicular to the plasma beam axis and axially at 1 mm increments using a collimating lens. The plasma emission is transmitted to the spectrometer via an optical fiber.

[0105] Reactive species in solution Kondeti et al. conducted a thorough investigation of species generated in CAP-treated saline and water based on their half-lives. Kondeti, V. et al., "Long-lived and short-lived reactive species produced by a cold atmospheric pressure plasma jet for the inactivation of Pseudomonas aeruginosa and Staphylococcus aureus," Free Radic Biol Med, 2018.124:p.275-287. Kondeti et al. concluded that when the plasma was not in direct contact with saline, long-lived species played a major role; whereas, when the plasma was in contact with liquid, short-lived species were more important. NO 2- The concentrations of long half-life species in CAP-treated solutions such as H2O2 and H2O2 can be measured in airflow-treated phosphate buffered saline (PBS) with CAP on or off using the Griess Reagent System (Promega, G2930) and a fluorometric hydrogen peroxide assay kit (Sigma-Aldrich, MAK165-1KT). Results will be read on a BioTek microplate reader at 540 nm for absorbance and 540 / 590 nm for fluorescence, respectively.

[0106] Ozone can be a concern for CAP-based respirators because of its potential harmful effects on human health. Ozone concentrations should be measured at the respirator exhaust and reduced by filters to meet air quality standards.

[0107] Effect of CAP on cells Lung cancer cell line A549 will be used for the efficacy of CAP treatment. Airflow only treatment will be used as a control group. Cell viability will be assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.

[0108] In conclusion, with a tailored configuration, CAP-based ventilators may benefit patients with respiratory diseases such as pneumonia, COVID-19, or lung cancer.

[0109] CAP Plasma and Virus Inactivation Validation Viruses that cause respiratory diseases, such as COVID-19 and severe acute respiratory syndrome (SARS), are transmitted by aerosolized droplets that contain the infectious virus. Cold atmospheric plasma (CAP) is a type of plasma that uses hydrogen peroxide (H2O2), singlet oxygen ( 1 O2), ozone (O3), nitric oxide ( · NO), and hydroxyl radicals ( · It generates a large number of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as OH, as well as electrons, ions, and photons. · OH, 1 O2, · NO, O2 · - , · NO2, and ONOO - are short half-life species, while H2O2, NO 2- , and NO 3-is a long half-life species. Various studies have shown that CAP can inactivate viruses and other pathogens. The possible inactivation mechanism of viruses by CAP is by generating a large number of free radicals, leading to high oxidation-reduction potential (ORP) and electrical conductivity. Reactive oxygen and nitrogen species can react with carbohydrates and initiate lipid peroxidation and cross-linking of fatty acid side chains, resulting in the alteration of chemical bonds and molecular structures. Both induce oxidative stress by causing protein peroxidation and inducing the destruction of the viral envelope, and singlet oxygen can rapidly react with cysteine ​​to generate the main product of cystine with disulfide (R-cys-SS-cys-R), and both selectively react with tyrosine, tryptophan, and histidine to generate hydroperoxides, leading to protein aggregation, and finally resulting in changes to the virus morphology. Moreover, both can damage the viral nucleic acid encoding the enzyme by oxidizing guanine, inducing cross-linking between guanine and lysine, which contributes to the reduction of gene expression and elimination of viral replication, thereby leading to viral inactivation. The cold plasma system of the present invention generates ionized cold plasma in a humidified setup to generate reactive species that are delivered to a virally infected patient via an endotracheal tube. The output of the system includes reactive oxygen species (ROS) and reactive nitrogen species (RNS), which will inactivate the viruses present in the patient's bronchial cells.

[0110] The human epithelial lung cancer cell line A549 (ATCC, CCL-185) was used to study the efficacy of the present invention. A549 cells were cultured at 10 5Cells were cultured at a density of 100 µg / well and treated for up to 17 min. The frequency was approximately 100 kHz. The voltage was set to be 70 V. The flow rate of helium, the carrier gas for cold atmospheric plasma (CAP), was set to 3 LPM. The total flow rate of oxygen (O2) and air was set to 2 LPM. The O2 percentage of the final output gas from the endotracheal tube was approximately 16, 24, and 32% in the O2-air-He mixture.

[0111] Feed gas, either O2 and air mixture or He, was humidified by bubbling through DI water. The relative humidity (RH) of the humidified gas was constantly measured by a humidity sensor.

[0112] Blue tetrazolium thiazolyl bromide (MTT) was purchased from Sigma-Aldrich (St. Louis, MO, USA), and the viability assay was performed 48 h after CAP treatment according to the manufacturer's protocol. Results were read by a BioTek microplate reader at 570 nm for absorbance.

[0113] The viability of A549 cells treated by the present invention was plotted as shown in Figures 10C-10E. Figure 10C shows the viability of A549 cells treated by the present invention setup with air mixture humidity control for up to 4 minutes. The viability of A549 cells gradually decreased with increasing treatment time. With 4 minutes of treatment, the viability decreased to 60% (compared to no treatment). Increasing the oxygen percentage in the gas mixture showed a weakening effect of the treatment from Figure 10C.

[0114] The same setup with 24% O in the feed gas was then used to treat cells for up to 17 min (Figure 10D). Cell viability decreased to values ​​below 40% after 10 min of treatment compared to no treatment, and cells were completely eliminated after 17 min of treatment.

[0115] When treated with a setup in which only helium was humidified by helium humidification for 17 minutes, all cancer cells were also eliminated by CAP treatment (data shown in FIG. 10E).

[0116] Effect of treatment with humidified air / O2 mixtures and humidified helium A549 cells were treated with 100% humidified air / O2 mixture (1:1 v / v) at a flow rate of 2 LPM (O2 fraction 24%). Helium flow was 3 LPM and humidity was set at 0%, 50% and 100%.

[0117] The A549 cells without treatment were firmly attached to the culture dish and the nuclei were intact. The control in this experiment was treated with a mixture of air / O2 and He for 10 minutes. The cells did not show any morphological changes compared to the untreated cells.

[0118] When the humidity was set to 0% (dry helium), cells began to shrink within 5 minutes of treatment with the cold plasma system, but a significant amount of cells remained viable. After increasing the treatment time to 10 minutes, cell death was identified.

[0119] When the He humidity was increased to 50%, cells showed shrinkage and membrane blebbing at 5 min treatment time. Cell shrinkage was more severe at 10 min treatment time and dead cells were visualized in a floating pattern.

[0120] When the He humidity was increased to 100% for 5 or 10 min treatment, almost all cells were fragmented and non-viable.

[0121] MTT viability assay was performed on the cells. The results are shown in FIG. 10F. 0% He humidity (dry He) and 5 min treatment time reduced viability to 60%, and at 10 min, viability was reduced to 40% compared to no treatment. When He humidity was set to 50% or 100%, there were no viable cells at 5 or 10 min treatment.

[0122] A more comprehensive study was performed to determine the minimum treatment time required for the elimination of A549 cells. A549 cells were treated with humidified or dry air / O2 mixture (1:1 v / v) at a flow rate of 2 LPM (O2 fraction 24%) for 1 to 5 minutes. Helium flow was 3 LPM and humidity was set at 0%, 50%, and 100%. Images were taken 24 hours after CAP treatment.

[0123] Phase contrast images of A549 cells treated with humidified or dry air / O2 mixtures and He at various humidities for 1-5 minutes were taken by a system according to a preferred embodiment of the present invention. When the He humidity was set to 0% (dry helium), the cell number began to decrease at 5 minutes of treatment, but the cell morphology did not change significantly; when the He humidity was set to 50%, the cell number began to decrease at 4 minutes of treatment; when the He humidity was set to 100%, the cell number began to decrease at 2 minutes of treatment, and the cell membrane and nucleus began to shrink significantly at 4 minutes of treatment. Air / O2 humidity did not induce significant morphological changes.

[0124] MTT viability assay was performed on the cells (Figures 10G and 10H). 0% He humidity (dry He) induced less cell death compared to no treatment, even in 5 min treatment. When He humidity was set to 50%, cell viability gradually decreased with increasing treatment time. About 50% cells were viable in 5 min treatment. When He humidity was set to 100%, 3 min CAP treatment could reduce viability to less than 50%, and 4 min CAP treatment completely eliminated cells. Air / O2 humidity did not result in significant difference in viability data. Based on these results, it can be concluded that helium humidification is a crucial factor for the cold plasma system to eradicate lung cancer cells.

[0125] Separating the oxygen stream from the air stream A cold atmospheric pressure plasma system for treating respiratory infections according to a first preferred embodiment of the present invention is described with reference to FIG. 11. A helium gas source 110 is split into two lines 1112, 1114, each of which is controlled by a mass flow controller (MFC) 1120. The helium gas flow (50-1000 mL / min) in line 1112 passes through a HO-filled container (humidifier 1130a) and is then pumped to a mixing chamber 1140a. The helium gas flow in line 1114 is pumped directly to the mixing chamber 1140a. Thus, the relative HO saturation in the gas leaving the chamber 1140a can be adjusted by the mass flow controllers 1120 on the lines 1112, 1114. Adjustment of the gas flow in the two lines 1112, 1114 allows fine adjustment of the overall flow rate and humidity of the gas flow exiting the chamber 1140a. Humidity can be in the range of 20% to 100%, with a preferred humidity of at least 70%. The total helium flow in this embodiment can vary from 0.5 L / min to 5 L / min in all cases. The humidity of the helium gas in the chamber 1140a can be measured, for example, by a calibrated high precision humidity and temperature meter (not shown). The humidified helium gas from the chamber 1140a is delivered to an electrosurgical generator 300, referred to herein as a "cold atmospheric plasma (CAP) generator." A variety of electrosurgical generators are known in the art and can be used with the present invention. The gas delivered to the cold atmospheric plasma (CAP) generator 300 is referred to herein as a "carrier gas."

[0126] At the same time, the non-humidified air supply 1150 (feed gas) is controlled by a mass flow controller (MFC) 1120. The air gas flow passes through a second H2O filled container (humidifier 1130b) and is then pumped into the mixing chamber 1140b. At the same time, a source of non-humidified pressurized third gas 1160, in this case oxygen, is connected to a third H2O filled container (humidifier 1130c). The humidified third gas (oxygen) is pumped into the chamber 1140b where it mixes with the humidified air. Thus, the relative oxygen percentages leaving the chamber 1140b can be adjusted by the mass flow controllers (MFC) 1120 on the air and oxygen lines. The respective humidity of the air and oxygen can be in the range of 20% to 100%, with a preferred humidity of at least 70%. The humidity of the mixture in chamber 1140b can be measured, for example, by a calibrated high precision humidity and temperature gauge (not shown), and the oxygen content can be measured, for example, by an oxygen sensor. The humidified air and oxygen from chamber 1140b is provided to a respiratory delivery system 1170, such as a ventilator, CPAP machine, BIPAP machine, or other known respiratory delivery system. The respiratory delivery system 1170 will mix and condition the exhaust, oxygen, and CO2 and measure the pressure, flow, ratio, and frequency of the patient's inspiration. The output of the respiratory delivery system 170 is connected, for example, to a CAP joint mixer via tubing 1174 and connector 1176.

[0127] The output of the CAP generator 300 and respiratory delivery system 1170 is connected to a dielectric barrier discharge (DBD) assembly 200, referred to herein as the "CAP joint mixer." A ground cable 1198 connects the outer electrode of the CAP joint mixer 200 to a ground within the CAP generator 300. Although the ground cable 1198 is shown separate from the tubing 1194 in FIG. 11, other arrangements are possible where the ground cable 1198 is coupled, for example, in a harness with the tubing 1194. Due to the presence of H2O, the He + +e- Ionization of helium and H2O occurs simultaneously, which leads to chemical reactions. Cold plasma generates reactive species (H2O2, NO 2- , NO 3- , O.N.O. - , and 02 - ) is generated.

[0128] The output of the CAP joint mixer 200 is connected to a delivery member 1190, which can be, for example, an endotracheal tube, oxygen CPAP (Continuous Positive Airway Pressure), BIPAP (Bilevel Positive Airway Pressure), ventilator face mask, or nasal O2 cannula 1190, and delivers active species 1192 generated by the system, e.g., H2O2, NO 2- , NO 3- , O.N.O. - , and 02 - to the patient's respiratory system.

[0129] Ozone Measurement Ozone (O3) generated by the system according to the preferred embodiment of the present invention was measured at the end of the endotracheal tube by an ozone detector (Forensics detectors, CA). Measurements were performed using all the settings tested above, i.e., the CAP was set at 70 V with humidified or dry air / O2 mixture (1:1 v / v) at a flow rate of 2 LPM (O2 fraction 24%), the helium flow rate was 3 LPM, and humidity was set at 0%, 50%, and 100%. The ozone levels were shown in Figure 14A. At the same helium humidity, dry air / O2 yielded higher O3 levels compared to humidified air / O2. Higher humidity of helium generated higher concentrations of O3, which resulted in a stronger reducing effect on cells, as previously shown in Figures 10G and 10H. This correspondence indicates that O3 is the critical species in the cocktail generated by the system according to the preferred embodiment of the present invention. Figure 14B shows that the ozone production rate decreased significantly at lower voltages. Therefore, to be on the safe side, 35 or 40 V, instead of 70 V, were used to test cell viability (Figures 13A and 13B). The O3 production rate was higher when air and O2 were delivered to the system as a mixture (Figure 14B) compared to separate air and O2 injection (Figure 14B).

[0130] However, the cold plasma system with the settings shown above, i.e., CAP set at 70V with humidified or dry air / O2 mixture (1:1 v / v) at a flow rate of 2 LPM (24% O2 fraction), helium flow rate at 3 LPM, and humidity set at 0%, 50%, and 100%, generated large amounts of ozone (data shown in section 2) that exceeded the safety limits according to OSHA standards. To reduce ozone generation, lower voltages (35-40V) were utilized to treat the cells. Because the presence of oxygen in the air / O2 mixture stimulates ozone generation, air and O2 enter the joint CAP mixer and are fused separately to reduce O3 formation. Viability data for A549 cells treated with settings having lower O3 levels (i.e., lower voltage and separation of air and O2) are shown in Figures 14A and 14B.

[0131] When air and O2 are added to the system as a mixture (FIG. 13A), the ability of CAP in reducing cancer viability is higher compared to when air and O2 are separately integrated into the system (FIG. 13B). 8 min of CAP treatment at 40 V with air / O2 mixture or 15 min of CAP treatment at 40 V with air and O2 separate could reduce cancer cell viability to less than 5 percent.

[0132] Detection of reactive species in treated media The system according to the preferred embodiment of the present invention was used to treat 1 mL phosphate buffered saline (PBS) in a 12-well plate with argon coagulation mode for 8 or 15 minutes, either continuously or at intervals. For interval treatment, CAP was administered in a 3+3+2 or 4+4+4+3 minute format with a 5 minute break between each interval. The voltage was set at 35 or 40V. Helium, O2, and air were all humidified. Helium flow rate was set at 3 LPM. Oxygen and air flow rates were both set at 1 LPM.

[0133] Among the cocktail plasma-generated reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the treated solution, hydrogen peroxide (H2O2), nitrite (NO 2- ), and nitric acid (NO 3- ) are the most commonly studied long half-life species. Their concentrations were measured in treated PBS with CAP on or off using a colorimetric hydrogen peroxide assay kit (Sigma-Aldrich, MAK311-1KT), the Griess Reagent System (Promega, G2930), and a colorimetric nitrite / nitrate assay kit (Sigma-Aldrich 23479). Results were read by a BioTek microplate reader at 595 nm, 550 nm, and 540 / 570 nm for absorbance, respectively.

[0134] H2O2, NO 2- , and NO 3- The concentrations of HO and NO were plotted against the HO concentration at 40V. The previous viability data demonstrated that 8 min of continuous treatment with the air and O2 mixed setup or 15 min of continuous treatment with the air and O2 separated setup at 40V were both capable of reducing A549 viability to less than 5%. As shown in Figures 15A-15C, 8 min of the air and O2 mixed setup at 40V was sufficient to reduce A549 viability to less than 5% for the 3+3+2 min interval treatment with 470 μM HO, 12.5 μM NO, and 15 min of HO and NO. 2- , and 2.2 μM NO 3- Compared to 725 μM H2O2 and 11.9 μM NO 2- , and 3.3 μM NO 3- whereas a continuous 15 min of air and O2 separation setup at 40 V produced 952 μM H2O2, 45 μM NO2, and 4+4+4+3 min interval treatments. 2- , and 12 μM NO 3- Compared to 806 μM H2O2 and 33 μM NO 2- , and 4.3 μM NO 3- Nitric acid (NO 3-) were too low to be detected in most of the settings. Gas mixtures alone do not generate significant amounts of ROS or RNS.

[0135] For the 8 min continuous treatment, H2O2 was generated in 1 mL of medium by CAP treatment with a gas flow of 5 LPM. The detected species were: 724×10 -6 mol / l×34g / mol=24.6×10 -3 mg / mL = 24.6 g / m of H2O2 3 was generated by a 40L gas mixture. H2O2 level is 24.6×10 -3 / 40=0.615×10 -3 mg / L=0.615mg / m 3 That is, For 3+3+2 minute intervals, the H2O2 level was 0.4mg / m 3 That is, For 15 minutes of continuous treatment, the H2O2 level is 0.365mg / m 3 That is, For 4+4+4+3 minute treatment, the H2O2 level was 0.43 mg / m 3 It is.

[0136] In all cases, 0.615, 0.4, 0.38, and 0.42 mg / m 3 is 1.4 mg / m 3 , which is below the NIOSH and OSHA permissible exposure limits for H2O2 (https: / / www.cdc.gov / niosh / npg / npgd0335.html).

[0137] The foregoing description of preferred embodiments of the present invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the invention. The embodiments were chosen and described to explain the principles of the invention and its practical application, so as to enable those skilled in the art to utilize the invention in various embodiments as suited to the particular uses contemplated. It is intended that the scope of the invention be defined by the appended claims and their equivalents. Each of the above documents is incorporated herein by reference in its entirety.

Claims

1. 1. A system for performing plasma treatment of a respiratory infection, comprising: a source of carrier gas (110); a first humidifier (130) connected to said source (110) of carrier gas; a source of feed gas (150); a second humidifier (130) connected to said source (150) of feed gas; a plasma generator (300) configured to energize the carrier gas into a plasma; a mixer (200) having an inner chamber formed from a dielectric, an active electrode (230) inside the inner chamber and connected to an electrical output of the plasma generator (300), and an outer electrode (220) connected to ground, the mixer (200) having a first fluid input port (202) connected to the source (110) of carrier gas and a second fluid input (204) connected to the source (150) of feed gas; a fluid delivery member (190) connected to an output (206) of the mixer (200) for delivering active species generated within the mixer (200) to a patient; 1. A system for performing plasma treatment of a respiratory infection, comprising:

2. 10. The system for performing plasma treatment of respiratory infections of claim 1, wherein the carrier gas comprises at least one of helium, argon, nitrogen, and oxygen.

3. The system for performing plasma treatment of a respiratory infection of claim 1 , wherein the delivery member (190) comprises an endotracheal tube.

4. The system for performing plasma treatment of a respiratory infection of claim 1 , wherein the delivery member (190) comprises one of a nasal cannula and a mask.

5. 10. The system for performing a plasma procedure of claim 1, wherein the source of feed gas comprises one of a ventilator and a continuous positive airway pressure device.

6. 6. The system for performing plasma treatment of respiratory infections as recited in claim 5, wherein the feed gas comprises a mixture of air and oxygen.

7. 2. The system for performing plasma treatment of respiratory infections as recited in claim 1, wherein the plasma generator (300) is configured to operate at a frequency in the range of 10 kHz to 200 kHz and an output peak voltage in the range of 3 kV to 6 kV.

8. 2. The system for performing a plasma procedure of claim 1, wherein the plasma generator (300) generates electrical energy having a frequency within 25 kHz of one of the following frequencies: 40 kHz, 100 kHz, and 200 kHz.

9. The system for performing plasma treatment of respiratory infections according to claim 1 , wherein the plasma generator (300) comprises a high frequency electrosurgical generator and a low frequency converter.

10. The plasma generator (300) A power module (350); A CPU (310) for controlling the power module (350); A memory (311) connected to the CPU (310); A power supply (302) connected to the CPU (310); 2. A system for performing plasma treatment of a respiratory infection as described in claim 1, comprising:

11. The plasma generator (300) a touchscreen display (420); a controller connected to said touchscreen display (420); a graphical user interface configured to display data on the touchscreen display (420) and to receive input from a user through the touchscreen display (420); 11. The system for performing plasma treatment of a respiratory infection of claim 10, further comprising:

12. The plasma generator (300) Gas module (1000) 11. The system for performing plasma treatment of a respiratory infection of claim 10, further comprising:

13. 13. The system for performing plasma treatment of respiratory infections as described in claim 12, wherein the source of carrier gas (110) is connected to the gas module (1000), and the gas module (1000) controls the flow of the carrier gas to the mixer (200).

14. The system for performing plasma treatment of respiratory infections as recited in claim 13, wherein the first humidifier (130) is connected between the gas module (1000) and the mixer (200).

15. 14. The system for performing plasma treatment of respiratory infections as described in claim 13, wherein the first humidifier (130) is connected between the gas module (1000) and the source (110) of carrier gas.

16. 2. The system for performing plasma treatment of respiratory infections of claim 1, wherein the first humidifier (130) is configured to humidify a carrier gas flowing from the source (110) of carrier gas to at least 70% humidity, and the second humidifier (130) is configured to humidify a feed gas flowing from the source (150) of feed gas to at least 50% humidity.

17. 2. The system for performing plasma treatment of respiratory infections of claim 1, wherein the first humidifier (130) is configured to humidify a carrier gas flowing from the source (110) of carrier gas to 100% humidity and the second humidifier (130) is configured to humidify a feed gas flowing from the source (150) of feed gas to at least 50% humidity.

18. 1. A system for performing plasma treatment of a respiratory infection, comprising: an electrical energy generator (300) configured to generate electrical energy to energize the carrier gas into a plasma; and a dielectric barrier discharge assembly (200), the dielectric barrier discharge assembly (200) comprising: an internal chamber formed from a dielectric material, the internal chamber having a first input (202) configured to fluidly connect to a source of humidified carrier gas (110), a second input (204) configured to connect to a source of humidified feed gas (150), and an output (206) configured to connect to a delivery member (190); an active electrode (230) within the inner chamber and connected to an electrical output of the electrical energy generator; and An outer electrode (220) connected to ground Equipped with The system comprises: a first humidifier (130) fluidly connected to the first input (202) of the internal chamber in the dielectric barrier discharge assembly (200); a second humidifier (130) fluidly connected to the second input (204) of the inner chamber in the dielectric barrier discharge assembly (200); Further equipped 1. A system for performing plasma treatment of respiratory infections, wherein plasma is generated in the inner chamber when electrical energy is supplied from the electrical energy generator to the inner electrode while both a humidified feed gas and a humidified carrier gas flow into the inner chamber.

19. a source of helium (110) connected to the input of the first humidifier; a source of air (150) connected to the input of the second humidifier; 20. The system for performing plasma treatment of a respiratory infection of claim 18, further comprising:

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