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PLASMA DEVICE

20230181783 · 2023-06-15

    Inventors

    Cpc classification

    International classification

    Abstract

    There is described herein, a plasma device for the generation of oxygen and nitrogen species (RONS) and methods of generating RONS using the plasma device.

    Claims

    1. A plasma device for the generation of reactive oxygen, nitrogen species (RONS), the device comprising: a reservoir containing a carrier gas; a housing in fluid communication with the reservoir, wherein the reservoir includes air or water, or the housing includes an air or water inlet, said housing comprising at least one conduit formed from a dielectric material; first and second electrodes spaced along the at least one conduit wherein a plasma generation zone is provided in the spacing between the first and second electrodes; a power supply suitable to apply an electrical potential between the first and second electrodes sufficient to form a plasma through the ionisation of the carrier gas, and to form reactive oxygen nitrogen species from the water molecules; and at least one outlet for the plasma and the reactive oxygen nitrogen species formed.

    2. The device of claim 1, wherein the spacing between the first and second electrodes is more than 2 to 100 cm, there is a spacing between the one of the first and second electrodes closest to the outlet and the outlet of at least 0.5 cm, and wherein the or each conduit has an associated inner diameter or minimum inner width, and the ratio of the inner diameter or inner width of the or each conduit (Di) to the spacing between the first and second electrodes (d) is 0.0005 to 0.6, suitably wherein the spacing between the first and second electrodes is 15 to 20 cm and the ratio Di/d is 0.002 to 0.08.

    3. The device of claim 2, wherein the inter-electrode spacing is more than 2 cm and up to 20 cm and the ratio Di to d is 0.0025 to 0.6 or wherein the inter-electrode spacing is 10 to 30 cm and the ratio Di to d is 0.001 to 0.12.

    4. (canceled)

    5. The device of claim 2, wherein the inter-electrode spacing is 30 to 50 cm and the ratio Di to d is 0.001 to 0.04, or wherein the inter-electrode spacing is 50 to 100 cm and the ratio Di to d is 0.00025 to 0.03, generally 0.0005 to 0.024.

    6. (canceled)

    7. The device of claim 1, wherein the housing tapers along its length towards the outlet resulting in a substantially conical configuration.

    8. The device of claim 1, wherein the first electrode is connected to the positive terminal of the power supply and the second electrode is connected to the negative terminal of the power supply, and wherein the first electrode is provided within the conduit, and the second electrode is provided externally to the conduit, generally abutting an outer wall of the conduit.

    9. (canceled)

    10. The device of claim 1, wherein: the housing has a length, a first end towards the reservoir and a second end towards the outlet; the ratio of the inner diameter or inner width of the, or each conduit (Di) to the spacing between the first and second electrodes (d) is 0.0005 to 0.3; and the length of the housing between the first electrode and the second end is 11 to 25 cm, where there is a spacing of at least 0.5 cm between the second electrode and the second end.

    11. The device of claim 1 including more than one electrode connected to the negative terminal of the power supply or the ground, suitably two or three electrodes connected to the negative terminal of the power supply or the ground, or wherein each of the more than one electrode connected to the negative terminal of the power supply is provided externally to the conduit, generally abutting an outer wall of the conduit.

    12. (canceled)

    13. The device of claim 11, wherein the first electrode is connected to the positive terminal of the power supply, the spacing between the first electrode and the ground electrode furthest therefrom is 50 to 100 cm and the ratio of the inner diameter or inner width of the or each conduit (Di) to the spacing between the first (high voltage) electrode and the ground electrode furthest from the first electrode is 0.0005 to 0.024.

    14. The device of claim 10, wherein: the housing has a length, a first end towards the reservoir and a second end towards the outlet, the at least one conduit has an associated inner diameter or inner width of 0.5 to 5 mm, a first (high voltage) electrode is provided within the at least one conduit and more than one ground electrode is spaced along an outer surface of the at least one conduit, wherein a plasma generation zone is provided in the spacing along the length of the conduit between the first (high voltage) electrode and the ground electrode closest to the first (high voltage) electrode, wherein the spacing between the first (high voltage) electrode and the ground electrode closest to it is 2 to 7 cm and the spacing between the first (high voltage) electrode and the ground electrode furthest from it is 4 to 100 cm; the power supply is suitable to apply an electrical potential between the first (high voltage) electrode and the ground electrode closest to the first (high voltage) electrode sufficient to form a plasma through the ionisation of the carrier gas, and to form RONS such as hydrogen peroxide through the ionisation of the water molecules and optionally through ionisation of air; and the length of the housing between the first (high voltage) electrode and the end of the housing towards the at least one outlet is 11 to 25 cm, and there is a spacing of 0.5 to 2 cm between the ground electrode closest to the at least one outlet and the end of the housing towards the at least one outlet.

    15. The device as claimed in claim 1 wherein the section of the conduit or conduits between the first and second electrodes forms a helix around an axis of the plasma device extending in a longitudinal direction or undulates in a wave form along an axis of the plasma device extending in a longitudinal direction.

    16. The device of claim 1, wherein the housing includes more than one conduit, and the first and second electrodes are spaced along the more than one conduit wherein the plasma generation zone is provided within the more than one conduit in the spacing between the first and second electrodes, or wherein the housing comprises one to thirteen of the conduits.

    17. The device of claim 16, wherein some or all of the conduits extend in a longitudinal direction along the housing, along or parallel to the longitudinal axis of the housing, and/or wherein some or all of the conduits form a helix around an axis of the housing extending in a longitudinal direction.

    18. (canceled)

    19. The device of claim 1 including more than one outlet for the plasma and the reactive oxygen nitrogen species.

    20. A method of forming a plasma including reactive oxygen nitrogen species, the method comprising: providing the device of claim 1; providing a flow of the carrier gas comprising water molecules through the housing; and applying an electrical potential between the first and second electrodes to ionise the carrier gas to form a plasma and reactive oxygen nitrogen species, and wherein: the electrical potential is applied at a voltage of 0.5 to 30 kV(rms) and at a frequency of 1 kHz to 1 MHz.

    21. (canceled)

    22. The method of claim 20 including providing a surrounding gas between the electrode closest to the at least one outlet and the end of the housing towards the at least one outlet wherein the surrounding gas is selected from the group consisting of argon, helium, nitrogen, oxygen and mixtures thereof.

    23. A plasma treatment method for a patient in need thereof, the method comprising: providing a hydrogel on an anatomical region of interest of the patient; generating a plasma comprising reactive oxygen nitrogen species using the device of claim 1; and contacting a surface of the hydrogel with the plasma comprising reactive oxygen nitrogen species; wherein contact of the hydrogel with the plasma activates the hydrogel dressing.

    24. The method of claim 23, wherein the hydrogel includes therapeutic agents and activation of the hydrogel causes release of the therapeutic agents, and the anatomical region of interest is one or more of a wound, an infected area (for instance by micro-organisms or parasites) and a burn.

    25. (canceled)

    26. A method of deactivation of micro-organisms on a surface, the method comprising: generating a plasma comprising reactive oxygen nitrogen species using the device of claim 1; contacting the surface with the plasma comprising hydrogen peroxide, wherein the plasma has a temperature of 30 to 40° C., and is emitted from the device over an area of 0.5 cm.sup.2 to 10 cm.sup.2, generally 3 to 7 cm.sup.2 wherein the concentration of RONS in the plasma is from 1 to 1000 mM.

    27. (canceled)

    28. A system including the device claim 1 and a hydrogel dressing comprising therapeutic agents wherein the hydrogel dressing is activatable upon contact with a plasma comprising reactive oxygen nitrogen species to release the therapeutic agents.

    29-30. (canceled)

    Description

    [0300] The present invention will now be described by way of example only with reference to the associated figures in which:

    [0301] FIG. 1A shows an embodiment of the plasma device of the present invention comprising a housing extending along the longitudinal axis of the device;

    [0302] FIG. 1B shows an embodiment of the device of the present invention comprising a housing helically extending around the longitudinal axis of the device;

    [0303] FIG. 1C shows an embodiment of the device of the present invention comprising a housing extending along the longitudinal axis of the device for activating hydrogels and application to patients;

    [0304] FIG. 1D shows an embodiment of the device of the present invention comprising a housing helically extending around the longitudinal axis of the device for activating hydrogels and application to patients;

    [0305] FIG. 1E shows an embodiment of the device of the present invention including a plurality of conduits extending along the longitudinal axis of the device to provide a multi-jet device;

    [0306] FIG. 1F shows an embodiment of the device of the present invention including a plurality of conduits extending helically around the longitudinal axis of the device to provide a multi-jet device;

    [0307] FIG. 1G shows a schematic representation of the device of 1E used in the activation a hydrogel;

    [0308] FIG. 2A shows the concentration of hydrogen peroxide produced in accordance with Example 1 in plasma treated deionized water at different plasma exposure time;

    [0309] FIG. 2B shows a photo of the plasma jet according to the description in Example 1;

    [0310] FIG. 3A shows the concentration of hydrogen peroxide as measured from the plasma activated water prepared in accordance with Example 2;

    [0311] FIG. 3B shows a photo of the plasma jet according to the description in Example 2;

    [0312] FIG. 4A shows the concentration of hydrogen peroxide produced in plasma treated deionized water at different plasma exposure times in accordance with Example 3;

    [0313] FIG. 4B shows a photo of the plasma jet according to the description in Example 3;

    [0314] FIG. 5A shows the concentration of hydrogen peroxide produced in plasma treated deionized water at different plasma exposure times in accordance with Example 4;

    [0315] FIG. 5B shows a photo of the plasma jet according to the description in Example 4;

    [0316] FIG. 6 shows the concentration of nitrites produced in plasma treated deionized water at different plasma exposure times in accordance with Example 1;

    [0317] FIG. 7 shows the stability of the hydrogel against continuous plasma exposure time of two minutes in accordance with Example 6. The target with (B) argon plasma jet can tolerate the jet temperature whereas the (A) helium plasma jet burns it;

    [0318] FIG. 8 shows the relationship between the ratio of the inner diameter of dielectric tubes (Di) and the spacing between first and second electrodes (d) in accordance with Example 7;

    [0319] FIG. 9 provides a schematic representation of the device of the present invention with more than one ground electrode in accordance with Example 9 and 10;

    [0320] FIG. 10 provides schematic representations and photographs of the plasma jets in linear and helical configurations with one (10A and 10D), two (10B and 10E) and three (10C and 10F) ground electrodes in accordance with Example 9;

    [0321] FIG. 11 shows the measurement of the (A) concentrations of the hydrogen peroxide and (B) temperatures of the plasma jets in helical and linear configurations in accordance with Example 9. The plasma jets with one, two and three ground electrodes in both configurations are represented by E.sub.1, E.sub.1+E.sub.2 and E.sub.1+E.sub.2+E.sub.3 respectively;

    [0322] FIG. 12 shows the dimensions of the plasma jets for one, two and three ground electrodes in terms of ratio D.sub.i/d.sub.1 (FIG. 12A) and D.sub.i/d.sub.2 (FIG. 12B) in accordance with Example 10;

    [0323] FIG. 13A shows the schematic of the conical design of the multi jet plasma device in accordance with Example 11. FIG. 13B shows the photographs of the corresponding device with seven plasma jets operated individually (left) or together (right). The temperature of the plasma jet (bottom-right) measured with an infrared thermometer is below 30 degree celsius.

    [0324] In the figures, the following reference numerals are used: [0325] 100 First electrode; high voltage electrode; needle electrode [0326] 110 Conduit; dielectric tube; [0327] 120 Carrier gas in [0328] 130 Housing for covering high voltage electrode and conduit(s) [0329] 140 Second electrode(s); Ground electrode (s) [0330] 150 Power supply [0331] 160 Distance of first ground electrode from the end of first electrode [0332] 165 Distance of the furthest ground electrode from the end of the first electrode [0333] 170 Distance of second ground electrode from the end of second electrode [0334] 180 Distance below the furthest ground electrode and end of the conduit (outlet) [0335] 185 Plasma jet output containing hydrogen peroxide and other reactive species [0336] 190 Width of the ground electrode [0337] 200 Wound infected with biofilm/cancer site [0338] 210 Hydrogel/dressing [0339] 220 Trajectory of antimicrobial agents [0340] 230 Hydrogen peroxide formed from plasma [0341] 240 Antimicrobials loaded into hydrogels [0342] 250 Released therapeutic agents

    [0343] FIG. 1A shows a schematic of the single jet plasma device, of the present invention including a first (high voltage) electrode, 100; a conduit covering the first electrode, 110; an inlet for the flow of carrier gas, 120 in fluid communication with a reservoir including flowmeter and the carrier gas reservoir (not shown). Water vapour molecules could be introduced to the housing, 130 by combining with the carrier gas through the same inlet, 120. The housing 130 contains a longitudinally extending quartz tube, 110, a high voltage electrode (HV electrode), 100 and second (ground) electrode, 140. A plasma generation zone, 160, is provided in the spacing between the HV electrode, 100 and the ground electrode, 140. Plasma and RONS may also be generated between the second (ground) electrode and the end of the conduit towards the output, 180. The positive terminal of the power supply, 150 is connected to the First (HV) electrode, 100 and negative terminal is connected to the second (ground) electrode, 140. Upon application of a sufficient electrical potential across the electrodes, 100, 140, plasma is formed through the ionisation of the carrier gas, and hydrogen peroxide is formed from the dissociation of water molecules present inside the quartz tube, 110. An outlet, 185, is provided for the plasma and the hydrogen peroxide formed. FIG. 1B shows a schematic of the single jet plasma device including a housing 130 in helical configuration. The device includes a first (high voltage) electrode, 100, a second (ground) electrode, 110; an inlet for the flow of carrier gas, 120 in fluid communication with a reservoir including flowmeter and the gas reservoir (not shown). Water vapour molecules would generally be introduced to the housing, 130 with the carrier gas through the same inlet, 120, and the carrier gas is generally combined with water vapour molecules in the reservoir. The housing 130 comprises a helical quartz tube, 110, initially extending along the longitudinal direction of the device, and subsequently extending around the longitudinal axis in a helix. Finally, the housing once again extends along the longitudinal direction of the device towards the outlet, 185. The device also includes a high voltage electrode (HV electrode), 100 and ground electrode, 140. A plasma generation zone, 160, is provided in the spacing between the HV electrode, 100 and the ground electrode, 140. Plasma and RONS may also be generated between the second (ground) electrode and the end of the conduit towards the output, 180. The positive terminal of the power supply, 150 is connected to the first (HV) electrode, 100 and the negative terminal of the power supply is connected to the second ground electrode, 140. Upon application of a sufficient electrical potential across the electrodes, plasma is formed through the ionisation of the carrier gas, and hydrogen peroxide is formed from the dissociation of water molecules present inside the quartz tube, 110. An outlet, 185, is provided for the plasma and the hydrogen peroxide formed.

    [0344] FIG. 1C shows a schematic of the single jet plasma device, of the present invention including a high voltage electrode, 100; a conduit covering the first electrode, 110; an inlet for the flow of carrier gas, 120 in fluid communication with a reservoir including flowmeter and the gas reservoir (not shown). Water vapour molecules would generally be introduced to the housing, 130 by combining with the carrier gas through1 the same inlet, 120. The housing 130 comprises a longitudinally extending quartz tube, 110. The housing contains a high voltage electrode (HV electrode), 100 and two ground electrodes, 140a, 140b. Plasma generation zones, 160, 170, are provided in the spacing between the HV electrode, 100 and the first ground electrode, 140a, and between the first ground electrode and the second ground electrode, 140b. Plasma and RONS may also be generated between the second ground electrode 140b and the end of the conduit towards the output, 180. The positive terminal of the power supply, 150 is connected to the HV electrode, 100 and negative terminal is connected to 140a, 140b which are connected to ground. Upon application of a sufficient electrical potential across the electrodes, plasma is formed through the ionisation of the carrier gas, and hydrogen peroxide is formed from the dissociation of water molecules present inside the quartz tube, 110. An outlet, 185, is provided for the plasma and the hydrogen peroxide formed.

    [0345] FIG. 1D shows a schematic of the single jet plasma device in helical configuration, of the present invention including a high voltage electrode, 100; a conduit attached to the top portion of the helical tube, extending perpendicularly towards the top and covering the first electrode, 110; an inlet for the flow of carrier gas, 120 in fluid communication with a reservoir including flowmeter and the gas reservoir (not shown). Water vapour molecules would generally be introduced to the housing, 130 by combining with the carrier gas through the same inlet, 120. The housing 130 comprises a helical quartz tube, 110 extending around the longitudinal axis of the device. There is also provided a high voltage electrode (HV electrode), 100 and first and second ground electrodes, 140a and 140b. Plasma generation zones, 160, 170, are provided in the spacing between the HV electrode, 100 and the first ground electrode, 140a, and between the first ground electrode and the second ground electrode, 140b. Plasma and RONS may also be generated between the second ground electrode 140b and the end of the conduit towards the output, 180. The positive terminal of the power supply, 150 is connected to the HV electrode, 100 and negative terminal is connected to 140a, 140b which are connected to ground. Upon application of a sufficient electrical potential across the electrodes, plasma is formed through the ionisation of the carrier gas, and hydrogen peroxide is formed from the dissociation of water molecules present inside the quartz tube, 110. The bottom end of the helical tube is connected to another quartz tube extending perpendicularly in the vertical direction towards the bottom. An outlet, 185, is provided for the plasma and the hydrogen peroxide formed.

    [0346] FIG. 1E shows a device of the present invention including a plurality of conduits, 110, with a plurality of high voltage needle electrodes 100 extending in a longitudinal direction along the housing, 130. For communication with the gas reservoir, the device includes a plurality of inlets, 120. Water vapour molecules could be introduced to the housing, 130 by combining with the carrier gas through the same inlet, 120. The housing 130 comprises a plurality of quartz tubes extending in longitudinal direction, 110, a plurality of the high voltage electrodes (HV electrodes), 100 and ground electrodes, 140a, 140b. Plasma generation zones, 160, 170, are provided in the spacing between the HV electrode, 100 and the first ground electrode, 140a, and between the first ground electrode and the second ground electrode, 140b. Plasma and RONS may also be generated between the second ground electrode 140b and the end of the conduit towards the output, 180. The positive terminal of the power supply, 150 is connected to the HV electrodes, 100 and negative terminal is connected to 140a, 140b which are connected to ground. Upon application of a sufficient electrical potential across the electrodes, plasma is formed through the ionisation of the carrier gas, and hydrogen peroxide is formed from the dissociation of water molecules present inside the quartz tube, 110. A plurality of the outlets, 185, are provided in each conduits for the plasma and the hydrogen peroxide formed.

    [0347] FIG. 1F shows a schematic of the plasma device including a plurality of conduits, 110, some of which are in a helical configuration and some of which extend along the longitudinal axis of the device. There is also provided a plurality of high voltage needle electrodes 100 extending in a longitudinal direction along the housing, 130. The conduits are attached to the top portion of the helical tube, extending perpendicularly towards the top and covering each first electrodes, 110. A plurality of the inlets for the flow of carrier gas, 120 is provided for each conduits through fluid communication with a reservoir including flowmeter and the gas reservoir (not shown). Water vapour molecules could be introduced to the housing, 130 by combining with the carrier gas through the same inlet, 120. The housing 130 contains helical and/or straight conduits extending in longitudinal direction along its axis, 110, a high voltage electrode (HV electrodes), 100 and ground electrodes, 140. Plasma generation zones, 160, 170, are provided in the spacing between the HV electrode, 100 and the first ground electrode, 140a, and between the first ground electrode and the second ground electrode, 140b. Plasma and RONS may also be generated between the second ground electrode 140b and the end of the conduit towards the output, 180. The positive terminal of the power supply, 150 is connected to the HV electrode, 100 and negative terminal is connected to 140a, 140b which are connected to ground. Upon application of a sufficient electrical potential across the electrodes, plasma is formed through the ionisation of the carrier gas, and hydrogen peroxide is formed from the dissociation of water molecules present inside the tubes, 110. Bottom end of each helical tubes are connected to another straight tube extending perpendicularly in the vertical direction towards the bottom. A plurality of the outlets, 185, are provided in each conduits for the plasma and the hydrogen peroxide formed.

    [0348] FIG. 1G shows the device of FIG. 1E. A plasma composition including reactive oxygen species (including hydrogen peroxide) and reactive nitrogen species are emitted from the outlets, 185. The plasma composition contacts a hydrogel dressing, 210 provided on the surface of a wound infected with a biofilm, 200. The hydrogel dressing, 210 may be loaded with antimicrobial agents, 240 which are activated with the hydrogen peroxide, 230 released from the plasma. Additional therapeutic agents, 250 are released through activation reactions, which along with hydrogen peroxide travel inside the wound and contribute in wound healing through trajectory 220.

    [0349] In another embodiment of FIG. 1G, the hydrogel dressing may be removed and the wound with biofilm, 200 may be a cancer tumor.

    EXAMPLE 1

    Production of Hydrogen Peroxide by using a Plasma Device with a Single Ground Electrode in a Linear Quartz Tube (For Producing Hydrogen Peroxide in Plasma Treated Water)

    [0350] The schematic of the plasma device used for this example is shown in FIG. 1A. The fabrication of the plasma jet was done by inserting a stainless-steel needle (outer diameter: 0.90 mm, inner diameter: 0.60 mm, length: 51 mm) inside a quartz tube (inner diameter: 1.5 mm and outer diameter: 3 mm). This needle act as a high voltage electrode/first electrode. The second electrode made up of copper (width: 4 mm, thickness: 1 mm) was positioned at 17 cm below the tip of the high voltage needle electrode. The distance of 17 cm in this plasma jet was specifically determined through a separate experiment conducted to study the effect of inter-electrode spacing (varying from 0.5 cm to 17 cm) on the concentration of hydrogen peroxide. This was tested by constructing plasma jets of different tube lengths (results not shown in this patent) and the plasma jet with higher inter-electrode spacing generated highest concentration of hydrogen peroxide. The first electrode was connected to the positive terminal of the high voltage, high frequency power supply and the second electrode was grounded. The working gas was 99.99% pure argon gas regulated at a constant gas flow rate of 1.2 litres per minute (velocity: 11.32 m/s, Reynold's number: 1340) by using a rotameter. In this configuration, plasma was generated with an applied voltage of 10 kV p-p and frequency of 23.5 kHz.

    [0351] The argon plasma jet was targeted to a 96-well plate filled with 350 μL of DI water. The distance from the end of the quartz tube to the top of the water surface was fixed to 3 mm. The concentration of hydrogen peroxide formed in the plasma activated water was measured by using commercially available OPD/HRP kit. For this, a calibration curve with known concentrations of H.sub.2O.sub.2 was constructed to determine the concentration of H.sub.2O.sub.2 formed by the plasma jet inside de-ionized water. The measurement kit employed was a mixture of o-phenylenediamine (OPD, CAS number: 95-54-5, Sigma Aldrich Corporation) and horseradish peroxidase (HRP, CAS number: 9003-99-0, Sigma Aldrich Corporation). In the presence of HRP, OPD reacts with H.sub.2O.sub.2 to form 2-3-diaminophenazine which gives fluorescence at 450 nm. For measuring the H.sub.2O.sub.2 concentration, an OPD tablet included in the kit was dissolved in 10 mL of DI water and 20 μL of HRP was added onto the solution. 5 μL of different concentrations of H.sub.2O.sub.2 were added onto different wells of a 96-well plate containing 195 μL of dissolved OPD/HRP and incubated for 15 minutes. The absorbance values measured with the plate reader (λ=450 nm) were proportional to the concentration of H.sub.2O.sub.2 and the obtained line of best fit was used to estimate the H.sub.2O.sub.2 concentration formed in plasma activated water.

    [0352] The concentration of hydrogen peroxide produced in plasma treated deionized water at different plasma exposure time is shown in FIG. 2A. As the plasma exposure time was increased from 1 minute to 5 minutes, the averaged concentration of hydrogen peroxide also increases from 1.25 mM to 18.90 mM. Increasing the plasma exposure time also increases the interaction of plasma species (mostly electrons, ions, streamers, UVs, etc.) generated inside/outside of the quartz tube with the water molecules present inside/outside of the quartz tube and/or in the well plate. The water molecules are dissociated into hydroxyl radicals which further combine to form hydrogen peroxide.

    [0353] A photograph of the plasma jet operated with the description as mentioned in this example is shown in FIG. 2B.

    EXAMPLE 2

    Production of Hydrogen Peroxide by using a Plasma Device with a Single Ground Electrode in a Helical Tube (For Producing Hydrogen Peroxide in Plasma Treated water)

    [0354] A helical quartz tube (inner diameter: 1.5 mm, outer diameter: 3 mm, helical diameter: 15 mm, pitch: 23 mm) as shown in FIG. 1B was constructed to generate plasma and measure the concentration of hydrogen peroxide in plasma treated deionized water. The top and bottom end of the helical tube were connected to quartz tubes which were perpendicular to the axis of the helix and their dimensions were identical to the helical tube. The fabrication of the plasma jet was done by inserting a stainless-steel needle (outer diameter: 0.90 mm, inner diameter: 0.60 mm, length: 30 mm) inside the top portion of the quartz tube. This needle act as a high voltage electrode/first electrode. The second electrode made up of copper (width: 4 mm, thickness: 1 mm) was positioned at 17 cm below the tip of the high voltage needle electrode. The plasma operation conditions and hydrogen peroxide detection methods were identical as described in Example 1. FIG. 3A shows the concentration of hydrogen peroxide as measured from the plasma prepared by treating 350 μL of deionized water in a 96-well plate at 3 mm gap distance below the end of the quartz tube. The concentration of hydrogen peroxide is seen to increase with the increase in the plasma exposure time from 1 minute to 5 minute. At 5 minutes plasma exposure time, the concentration of hydrogen peroxide is ca. 16.5 mM. Increasing the plasma exposure time also increases the interaction of plasma species (mostly electrons, ions, streamers, UVs, etc.) generated inside/outside of the quartz tube with the water molecules present inside/outside of the quartz tube and/or in the well plate. The water molecules are dissociated into hydroxyl radicals which further combine to form hydrogen peroxide. A photograph of the plasma jet operated with the description as mentioned in this example is shown in FIG. 3B.

    EXAMPLE 3

    Production of Hydrogen Peroxide by using a Plasma Device with Two Ground Electrodes in a Linear Quartz Tube (For Activating Hydrogels and Treatment of Wounds in Patients)

    [0355] The plasma device is intended to generate plasma and hydrogen peroxide for treatment of wounds in patients through activation of hydrogels loaded with therapeutic agents. The schematic of the plasma device used for this example is shown in FIG. 1C. The fabrication of the plasma jet was done by inserting a stainless-steel needle (outer diameter: 0.90 mm, inner diameter: 0.60 mm, length: 51 mm) inside a quartz tube (inner diameter: 1.5 mm and outer diameter: 3 mm). This needle act as a high voltage electrode/first electrode. The first ground electrode made up of copper (width: 4 mm, thickness: 1 mm) was positioned at 5.6 cm below the tip of the high voltage needle electrode. The second ground electrode with identical dimensions as the first one was placed at 5.4 cm below the first ground electrode. These distances were specifically determined to operate the plasma at room temperature. Though the hydrogen peroxide was produced in all regions below the high voltage electrode, the second electrode placed in this configuration helps the plasma plume to reach outside of the quartz tube. The first electrode (stainless steel needle) was connected to the positive terminal of the high voltage, high frequency power supply and both of the second electrodes were grounded. The working gas was 99.99% pure argon gas regulated at a constant gas flow rate of 1.2 litres per minute (velocity: 11.32 m/s, Reynold's number: 1340) by using a rotameter. In this configuration, plasma was generated with an applied voltage of 7 kV p-p and frequency of 23.5 kHz. The plasma generated in this condition is at room temperature.

    [0356] The argon plasma jet was targeted to a 96-well plate filled with 350 μL of DI water. The distance from the end of the quartz tube to the top of the water surface was fixed to 3 mm. The concentration of hydrogen peroxide formed in the plasma activated water was measured by using commercially available OPD/HRP kit. For this, a calibration curve with known concentrations of H.sub.2O.sub.2 was constructed to determine the concentration of H.sub.2O.sub.2 formed by the plasma jet inside de-ionized water. The measurement kit employed was a mixture of o-phenylenediamine (OPD, CAS number: 95-54-5, SigmaAldrich Corporation) and horseradish peroxidase (HRP, CAS number: 9003-99-0, SigmaAldrich Corporation). In the presence of HRP, OPD reacts with H.sub.2O.sub.2 to form 2-3-diaminophenazine which gives fluorescence at 450 nm. For measuring the H.sub.2O.sub.2 concentration, an OPD tablet included in the kit was dissolved in 10 mL of DI water and 20 μL of HRP was added onto the solution. 5 μL of different concentrations of H.sub.2O.sub.2 were added onto different wells of a 96-well plate containing 195 μL of dissolved OPD/HRP and incubated for 15 minutes. The absorbance values measured with the plate reader (λ=450 nm) were proportional to the concentration of H.sub.2O.sub.2 and the obtained line of best fit was used to estimate the H.sub.2O.sub.2 concentration formed in plasma activated water.

    [0357] The concentration of hydrogen peroxide produced in plasma treated deionized water at different plasma exposure time is shown in FIG. 4A. As the plasma exposure time is increased from 1 minute to 5 minutes, the averaged concentration of hydrogen peroxide also increases from 0.75 mM to 3.34 mM. Increasing the plasma exposure time also increases the interaction of plasma species (mostly electrons, ions, streamers, UVs, etc.) generated inside/outside of the quartz tube with the water molecules present inside/outside of the quartz tube and/or in the well plate. The water molecules are dissociated into hydroxyl radicals which further combine to form hydrogen peroxide.

    [0358] A photograph of the plasma jet operated with the description as mentioned in this example is shown in FIG. 4B.

    Example 4

    Production of hydrogen peroxide by using a plasma device with two ground Electrodes in a Helical Quartz Tube (For Activating Hydrogels and Treatment of Wounds in Patients)

    [0359] A helical quartz tube (inner diameter: 1.5 mm, outer diameter: 3 mm, diameter: 15 mm, pitch: 23 mm) as shown in FIG. 1D was constructed to generate plasma and hydrogen peroxide for treatment of wounds in patients through activation of hydrogels loaded with therapeutic agents. The top and bottom end of the helical tube were connected to quartz tubes which were perpendicular to the axis of the helix and their dimensions were identical to the helical tube. The fabrication of the plasma jet was done by inserting a stainless-steel needle (outer diameter: 0.90 mm, inner diameter: 0.60 mm, length: 30 mm) inside the top portion of the quartz tube. This needle act as a high voltage electrode/first electrode. The first ground electrode made up of copper tape (width: 4 mm) was positioned at 5.6 cm below the tip of the high voltage needle electrode outside of the helical tube. The second ground electrode identical to the first one was placed at 5.4 cm below the first ground electrode. Plasma was generated with an applied voltage of 7 kV p-p and frequency of 23.5 kHz. The plasma generated in this condition is at room temperature. The other parameters for plasma generation and hydrogen peroxide detection were the same as described in Example 3. FIG. 5A shows the concentration of hydrogen peroxide as measured from the plasma treated prepared by treating 350 μL, of deionized water in a 96-well plate at 3 mm gap distance below the end of the quartz tube. The concentration of hydrogen peroxide is seen to increase with the increase in the plasma exposure time from 1 minute to 5 minute. At 5 minutes plasma exposure time, the concentration of hydrogen peroxide is ca. 4.10 mM. Increasing the plasma exposure time also increases the interaction of plasma species (mostly electrons, ions, streamers, UVs, etc.) generated inside/outside of the quartz tube with the water molecules present inside/outside of the quartz tube and/or in the well plate. The water molecules are dissociated into hydroxyl radicals which further combine to form hydrogen peroxide.

    [0360] A photograph of the plasma jet operated with the description as mentioned in this example is shown in FIG. 5B.

    EXAMPLE 5

    Production of Additional Reactive Species having Biocidal/Virucidal Effects

    [0361] By controlling the electrode distance, applied voltage, working/surrounding gas, etc., the plasma source can be used for the production of nitrates, nitrites, peroxynitrates, etc. All these reactive species also possess strong biocidal and virucidal effects. The measurement of nitrites was performed by using the Griess reagent in the same conditions as in example 1 for the plasma jet with straight tube. It can be seen in FIG. 6 that the concentration of NO.sub.2 increases from 1 μM to 8 μM as the plasma treatment time is increased from 1 minute to 5 minutes. Short lived reactive species including atomic oxygen and nitric oxide-γ has also been detected using the technique of optical emission spectroscopy (not included in the patent). All these species including hydrogen peroxide and derivatives of oxygen/nitrogen (ozone, nitrous acid, peroxynitrate, etc.) can have a strong bactericidal/virucidal effects. Any person skilled in art can think of other reactive species for this purpose.

    EXAMPLE 6

    Heat Tolerance of the “Tissue” Surrogate against Plasma Exposure

    [0362] Treating thermally sensitive materials without rastering over the surface is an important challenge for successful application of plasma jets in medicine. In this example, the plasma jet as described in example 3 was used to treat an agarose gel which acts as a surrogate for real tissues. 0.5% agarose was heated in DI water and transferred to a petri dish before it solidified to form a gel. Firstly, the conventional helium plasma jet at 4 mm distance below the nozzle of the glass tube was targeted to the agarose gel (FIG. 7(A)). After two minutes of plasma exposure time, the centre of the gel in contact with the plasma jet was observed to be burnt. Next, the argon plasma jet (FIG. 7(B)) as described in example 3 was used to treat the agarose gel. The gel appeared to cope well and no burning was observed until continuous two minutes plasma exposure time at the same point. This suggests that the plasma jet as described in this patent is well suited for treating thermally sensitive materials.

    EXAMPLE 7

    Dimensions of the Plasma Device with a Single Ground Electrode

    [0363] We investigated the relationship between the ratio of the inner diameter of dielectric tubes (Di) and the spacing between first and second electrodes (d). Dielectric tubes with different inner diameters were constructed. The inner diameters of the tubes ranged from 0.5 to 12 mm (Di). We experimented with different inter-electrode spacings (d) ranging from 20 mm to 50 cm. The experiments were conducted with a device including a single ground electrode, and two ground electrodes. A preferred ratio of Di:d of less than 0.6 was identified. The results are summarised in FIG. 8.

    EXAMPLE 8

    Minimum Volume of the Plasma Generation Zone

    [0364] We assessed the minimum volume of the plasma generation zone for devices of different inner diameters. The distance between the first electrode (HV) and the second ground electrode (d) or the distance between the first electrode (HV) and the furthest ground electrode (d.sub.2) were varied from 4 to 20 cm. The inner diameters of the tubes were varied from 0.5 mm to 12 mm. We created devices having 1, 7 and 9 conduits (or jets) formed from these dielectric tubes. The results are summarised in the table below.

    TABLE-US-00005 D.sub.i d or d.sub.2 1-jet 7-jet 9-jet Range [cm] [cm] [cm.sup.3] [cm3] [cm3] Smallest 0.05 4 0.007854 0.0549779 0.0706858 0.05 10 0.019635 0.1374447 0.1767146 0.05 15 0.0294524 0.206167 0.2650719 0.05 20 0.0392699 0.2748894 0.3534292 Typical 0.15 4 0.0706858 0.4948008 0.6361725 0.15 10 0.1767146 1.2370021 1.5904313 0.15 15 0.2650719 1.8555032 2.3856469 0.15 20 0.3534292 2.4740042 3.1808626 0.5 4 0.7853982 5.4977871 7.0685835 0.5 10 1.9634954 13.744468 17.671459 0.5 15 2.9452431 20.616702 26.507188 0.5 20 3.9269908 27.488936 35.342917 Largest 1.2 4 4.5238934 31.667254 40.715041 1.2 10 11.309734 79.168135 101.7876 1.2 15 16.9646 118.7522 152.6814 1.2 20 22.619467 158.33627 203.5752

    EXAMPLE 9

    Comparison of Plasma Jets with One (E.SUB.1.), Two (E.SUB.1.+E.SUB.2.+E.SUB.3.) and Three (E.SUB.1.+E.SUB.2.+E.SUB.3.) Ground Electrodes with Linear and Helical Designs

    [0365] The schematic of the plasma device with more than one ground electrode (in linear configuration) is shown in FIG. 9. This schematic was applied to develop plasma devices up to three ground electrodes in linear and helical configurations. These are shown in FIG. 10A to 10F. For both linear and helical configurations of the tube, a stainless steel needle of length 22 mm was inserted inside the quartz tubes through the top end. This needle acted as a high voltage electrode/first electrode. The first ground electrode was formed from copper (width: 5 mm, thickness: 1 mm), positioned 5 cm below the tip of the high voltage needle electrode (FIG. 10A and 10D). A second ground electrode with identical dimensions to the first ground electrode described above was placed at 5.1 cm below the first ground electrode (FIG. 10B and 10E). The third ground electrode, with identical dimensions to the first ground electrode described above, was positioned at 3.5 cm below the second ground electrode (FIG. 10C and 10F). The total length of both the linear and helical tubes below the high voltage electrode/ first electrode was 23 cm. The working gas was 99.99% pure argon gas regulated at a constant gas flow rate of 1.0 litres per minute by using a rotameter. In this configuration, plasma was generated with an applied voltage of 7 kV p-p and frequency of 23.5 kHz. The photograph provided in FIG. 10A and 10D show that with one ground electrode, most of the plasma is inside the quartz tube. The addition of a second ground electrode increases the length of the plasma outside of the quartz tube FIG. 10B and 10E. With the addition of the third ground electrode, the length of the plasma plume is slightly increased (see FIG. 10C and 10F).

    [0366] The concentration of H.sub.2O.sub.2 and temperature of all the plasma jets as shown in FIGS. 11A to 11F were also compared. The plasma jets were targeted to a 96-well plate filled with 350 μL of DI water. The distance from the end of the quartz tube to the top of the water surface was fixed to 3 mm. The concentration of hydrogen peroxide formed in the plasma activated water was measured by using commercially available o-phenylenediamine (OPD)/horseradish peroxidase (HRP) kit. For this, a calibration curve with known concentrations of H.sub.2O.sub.2 was constructed to determine the concentration of H.sub.2O.sub.2 formed by the plasma jet inside de-ionized water. The measurement kit employed was a mixture of o-phenylenediamine (OPD, CAS number: 95-54-5, SigmaAldrich Corporation) and horseradish peroxidase (HRP, CAS number: 9003-99-0, SigmaAldrich Corporation). In the presence of HRP, OPD reacts with H.sub.2O.sub.2 to form 2-3-diaminophenazine which gives fluorescence at 450 nm. For measuring the H.sub.2O.sub.2 concentration, an OPD tablet included in the kit was dissolved in 10 mL of DI water and 20 μL of HRP was added onto the solution. 20 μL of different concentrations of H.sub.2O.sub.2 were added onto different wells of a 96-well plate containing 180 μL of dissolved OPD/HRP and incubated for 15 minutes. The absorbance values measured with the plate reader (μ=450 nm) were proportional to the concentration of H.sub.2O.sub.2 and the obtained line of best fit was used to estimate the H.sub.2O.sub.2 concentration formed in plasma activated water.

    [0367] The concentration of hydrogen peroxide produced in plasma treated deionized water at plasma exposure time of 2 minutes is shown in FIG. 11A for both linear and helical configurations. For linear plasma jet, the concentration of H.sub.2O.sub.2 with one ground electrode (E.sub.1) is ca. 167 μM. With the addition of a second ground electrode (E.sub.1+E.sub.2), the concentration is increased to ca. 423 μM. This further increased to ca. 585 μM with the addition of a third ground electrode (E.sub.1+E.sub.2+E.sub.3).

    [0368] A similar trend is observed with the helical configuration but the concentrations were slightly lower than the linear configuration.

    [0369] The temperatures of the plasma jets were measured with a mercury at 5 mm position below the end of the quartz tube. The bulb of the thermometer was wrapped by a tape and it was treated by the plasma jet continuously for up to one minute. The readings at the end of plasma treatment were noted. The results are shown in FIG. 11B. The temperature of the target point increases slightly with the addition of second and third ground electrodes for both linear and helical configurations. With three ground electrodes, the temperatures of linear and helical jets are found to be 42.5 and 34 degree Celsius. The slightly lower temperature with the helical jet is attributed to the configuration of the plasma design.

    EXAMPLE 10

    Dimensions of the Plasma Device with More than One Ground Electrode

    [0370] The schematic of the plasma device with more than one ground electrode (in linear configuration) is represented in FIG. 9. We used this schematic to identify the dimensions of the devices that could be operated by including more than one ground electrode. The inner diameters of the tubes ranged from 0.5 to 12 mm (Di). The dimensions of the devices could be summarised in terms of two parameters: (i) ratio of inner diameter of the tube (D.sub.1) to the distance between the first electrode (high voltage, HV) and the closest ground electrode (d.sub.1) (=Di/d.sub.1), (ii) ratio of inner diameter of the tube (D.sub.i) to the distance between the first electrode (HV) and the furthest ground electrode (d.sub.2), (=Di/ d.sub.2). The results are summarised in FIG. 12A and 12B.

    EXAMPLE 11

    A Multi-Jet Plasma Device in Conical Configuration and its Temperature Measurement

    [0371] FIG. 13A shows the schematic of the conical device of the present invention including a plurality of conduits, 110, with a plurality of high voltage needle electrodes 100 extending in a longitudinal direction along the housing, 130. For communication with the gas reservoir, the device includes a plurality of inlets, 120. Water vapour molecules could be introduced to the housing, 130 by combining with the carrier gas through the same inlet, 120. The housing 130 comprises a plurality of quartz tubes extending in longitudinal direction, 110, a plurality of the high voltage electrodes (HV electrodes), 100 and ground electrodes, 140a, 140b. Plasma generation zones, 160, 170, are provided in the spacing between the HV electrode, 100 and the first ground electrode, 140a, and between the first ground electrode and the second ground electrode, 140b. Plasma and RONS may also be generated between the second ground electrode 140b and the end of the conduit towards the output, 180. The positive terminal of the power supply, 150 is connected to the HV electrodes, 100 and negative terminal is connected to 140a, 140b which are connected to ground. Upon application of a sufficient electrical potential across the electrodes, plasma is formed through the ionisation of the carrier gas, and hydrogen peroxide is formed from the dissociation of water molecules present inside the quartz tube, 110. A plurality of the outlets, 185, are provided in each conduits for the plasma and the hydrogen peroxide formed.

    [0372] The schematic in FIG. 13A was utilised to fabricate a conical configuration of the plasma device. This is shown in FIG. 13B. It consists of seven individual quartz tubes (inner diameter: 1.5 mm, outer diameter: 3 mm) inserted inside seven holes of a conical housing (inner diameter: 3.20 mm). A high voltage needle electrode (stainless steel) was inserted inside each quartz tubes and sealed inside the housing using torr-seal. Ground electrodes made up of copper (thickness: 1 mm) were wrapped outside each of the seven tubes at positions of 30 mm and 60 mm below the tip of the high voltage electrode. The distance of the each nozzles of the quartz tubes from the end of second ground electrode was 30 mm. FIG. 14B (left) shows the photographs of the individual plasma jets operated with argon gas and FIG. 14B (right) shows the photograph of the device with all 7-jets operated together. The operating parameters for the plasma device were: applied voltage: ˜8 kV p-p, frequency: 23.5 kHz, Ar flow rate: 5 standard litres per minute. The temperature of the plasma plume was measured using an infrared thermometer (bottom photograph on the right) and it was found to be less than 30 degree Celsius. This was true for all seven plasma jets operated individually or together. This confirms that the conical design of the multi-jet plasma device could be suitable for the treatment of thermally sensitive materials including hydrogel dressings.

    [0373] The conical design of the multi-jet would reduce the interaction of the individual jets with each other and reduce electrode heating thereby operating the plasma jet at room temperature. The temperature of the jet would further be reduced by operating the jet in dimming mode.

    [0374] Various modifications and variations of the described aspects of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes of carrying out the invention which are obvious to those skilled in the relevant fields are intended to be within the scope of the following Claims.