Non-contact, non-invasive treatment device

Abstract

The invention relates to a non-contact non-invasive device for generating a gas flow having a low- temperature atmospheric pressure plasma and directing the gas flow towards an affected area (P1). The device comprising a guide member (10) having an inlet opening and an outlet opening (104A), configured to guide the gas flow towards the affected area (P1), the inlet opening being connected to a plasma source gas supply outlet (106), a low-frequency voltage application circuit (2) configured to generate low-frequency, high voltage electric current flowing through the gas flow towards the affected area (P1), a high-frequency voltage application circuit (3) configured to generate high-frequency electric current flowing through the gas flow towards the affected area (140A), a first electrode (6) and a second electrode mechanism (540) located at the guide member (10) and around the gas flow, the second electrode mechanism (540) comprising a plurality of electrode elements, wherein the plurality of electrode elements is arranged to be separated by a dielectric medium, and the plurality of electrode elements is configured to form phase-shifted counter electrode pairs.

Description

[0001] NON-CONTACT, NON-INVASIVE TREATMENT DEVICE

[0002] TECHNICAL FIELD

[0003] The present invention relates to a non-contact, non-invasive treatment device, particularly to a radiofrequency (RF) coupling method for dual frequency system for irradiating atmospheric pressure plasma onto a lesion for treatment. The invention also relates to a method of treatment of a patient

[0004] BACKGROUND ART

[0005] Conventionally, methods of treating a lesion in a living body have included methods of irradiating plasma onto the lesion and methods of irradiating electromagnetic waves onto the lesion. For example, J P2017504404A discloses a device that applies a voltage between an insulating electrode arranged on the surface or inside of a target tissue and an electrode provided to face the insulating electrode to generate local plasma discharge and apply electric field treatment to the target tissue. Furthermore, JP2017504404A shows that when a conductive disc electrode is used as the electrode, the magnitude of the electric field within the tissue is inversely proportional to the radius of the electrode, indicating the need to reduce the radius of the electrode to generate a high electric field.

[0006] For example, in the case of cancer that has progressed to the point of forming a wound by breaking through the skin and forming a cancerous skin ulcer, bacteria infect the wound and produce an unpleasant odor. In the case of cancerous skin ulcers with symptoms such as bleeding, exudation, and pain as the main clinical conditions, contact-type treatment devices cannot be applied to the lesion, making care treatment difficult and significantly reducing the patient's quality of life (QOL). In such cases of refractory skin ulcers with bleeding, exudation, and pain, which are accompanied by bacterial infection, a treatment device that can treat the wound and sterilize it non-invasively is needed. Furthermore, when the ulcer spreads extensively, a treatment device that can reliably treat the entire lesion is required. However, the wider the treatment area, the more difficult it is to perform uniform treatment stably.

[0007] The present invention has been made in view of the above problems and aims to provide a non-contact, non- invasive treatment device for non-invasive treatment by uniformly irradiating low-temperature atmospheric pressure plasma onto the entire lesion.

[0008] BRIEF DESCRIPTION OF THE INVENTION

[0009] The present invention relates to a non-contact non-invasive device for generating a gas flow having a low- temperature atmospheric pressure plasma and directing the gas flow towards an affected area. The device comprising a guide member, a low-frequency, high voltage application circuit, a high-frequency voltage application circuit, a first electrode and a second electrode mechanism.

[0010] The guide member having an inlet opening and an outlet opening and is configured to guide the gas flow towards the affected area, the inlet opening being connected to a plasma source gas supply outlet. The low-frequency voltage application circuit is configured to generate low-frequency electric current flowing through the gas flow towards the affected area. The high-frequency voltage application circuit is configured to generate high-frequency electric current flowing through the gas flow towards the affected area.

[0011] The first electrode and the second electrode mechanism are located at or in connection with the guide member and around the gas flow. The second electrode mechanism comprising a plurality of electrode elements, wherein the plurality of electrode elements is arranged to be separated by a dielectric medium, and the plurality of electrode elements is configured to form phase-shifted counter electrode pairs.

[0012] According to the configuration of the present invention, by applying a low-frequency, high voltage with the low-frequency voltage applying circuit to the plasma source gas supply outlet in which plasma raw material gas is supplied, and by applying a high-frequency voltage with the high-frequency voltage applying circuit, a wide and uniform low-temperature atmospheric pressure plasma can be irradiated onto the surface of the lesion.

[0013] Irradiation with low-temperature atmospheric pressure plasma can cause the cancer cells on the surface of the lesion and bacteria, which are the cause of infection, to die, as well as promote blood coagulation on the lesion surface and facilitate wound healing. Furthermore, the inventors confirmed that low-temperature atmospheric pressure plasma generated by applying high-frequency voltage is more effective in killing cancer cells.

[0014] For example, the dielectric medium separating the plurality of electrode elements can be glass, air, or other suitable medium.

[0015] According to the configuration of the present invention, the electrodes of the phase-shifted counter electrode pairs are arranged to be alternatively connected to a radio-frequency circuit via phase shifting capacitors.

[0016] The phase-shifted counter electrode pairs are opposite pairs of the plurality of electrode elements of the second electrode. The phase shifting capacitor is configured to phase shift the phase-shifted counter electrode pairs by 90 degrees.

[0017] According to the configuration of the present invention, the phase shifting capacitor is configured to generate a homogeneous radio frequency (RF) plasma discharge by creating a phase shift (here a 90 degree phase shift) of voltage and current. For example, the pair of sine-waves having alternating mutually-exclusive minima and maxima.

[0018] According to the configuration of the present invention, the second electrode mechanism is located downstream of the first electrode, and the low-temperature atmospheric pressure plasma is generated by applying the low-frequency, high voltage generated by the low-frequency voltage application circuit to the first electrode, and applying high-frequency voltage generated by the high-frequency voltage application circuit to the second electrode mechanism.

[0019] By flowing radiofrequency (RF) current to the lesion through low-temperature atmospheric plasma, noncontact and non-invasive treatment with RF current can be performed on the surface and interior of the lesion. This allows for the accumulation of RF energy inside the lesion to promote blood circulation and induce apoptosis in cancer cells on the surface and interior of the lesion. According to the configuration of the present invention, a wide and uniform low-temperature atmospheric pressure plasma is irradiated, including the low-temperature atmospheric pressure plasma generated at the first electrode in the gas flow.

[0020] In addition, a high-frequency electric field is formed around the plasma raw material gas supply outlet or the flow path of the gas flow, which allows for the maintenance of generated plasma and the generation of plasma. Furthermore, since there are separate electrodes for applying low-frequency voltage and high-frequency voltage, it is possible to reduce design constraints related to the size of the plasma raw material gas supply outlet, the time and distance for maintaining low-temperature atmospheric pressure plasma, and impedance, thus achieving a highly versatile treatment device suitable for treating affected areas.

[0021] According to the configuration of the present invention, the non-contact, non-invasive device further includes a gas supply device. The gas supply device is configured to supply plasma source gas to the guide member through the plasma source gas supply outlet and to generate the gas flow directed towards the outlet opening, wherein the low-frequency, high voltage application circuit is further configured to apply low- frequency, high voltage to the gas flow and the high-frequency voltage application circuit is further configured to apply high-frequency voltage to the gas flow.

[0022] In the present invention, preferably, a guide member is provided that defines an outlet opening and has a plasma raw material gas supply outlet formed inside, and the plasma raw material gas supply outlet is configured such that the cross-sectional area of the internal space decreases toward the downstream.

[0023] Preferably, the second electrode mechanism is located near the outlet opening of the first electrode, it is possible to apply high-frequency voltage at a lower position where the impedance of the low-temperature atmospheric pressure plasma in the plasma raw material gas supply space is lower compared to when high- frequency voltage is applied near the first electrode.

[0024] This allows easy matching of the impedance between the high-frequency voltage applying circuit and the low-temperature atmospheric pressure plasma in the plasma raw material gas supply space, enabling the irradiation of plasma to the affected area while flowing RF current to the affected area through low-temperature atmospheric pressure plasma. By flowing RF current to the affected area through low-temperature atmospheric pressure plasma, non-contact and non-invasive treatment of the affected area surface and interior with RF current is possible, promoting blood circulation. In the affected area and inducing apoptosis in cancer cells on the affected area surface and interior.

[0025] According to the configuration of the present invention, the non-contact, non-invasive device according further includes a transformer. The transformer is connected to the high-frequency voltage application circuit and the second electrode mechanism, wherein the transformer is configured to amplify the high-frequency voltage applied to the second electrode mechanism.

[0026] According to the configuration of the present invention, since the transformer can amplify the voltage applied by the high-frequency voltage applying circuit and apply it to the second electrode, it is possible to apply RF current to the plasma raw material gas supply outlet even when the impedance of the low-temperature atmospheric pressure plasma is relatively high. This allows for the flow of RF current to the affected area through low-temperature atmospheric pressure plasma, enabling non-contact and non-invasive treatment of the affected area surface and interior with RF current.

[0027] In the present invention, preferably, the transformer is a resonant transformer comprising a first coil and a second coil, with the first coil connected to the high-frequency voltage application circuit and the second coil connected to the plurality of electrode elements.

[0028] According to the configuration of the present invention, by constructing the transformer with the first coil and the second coil, it is possible to apply high voltage to the second electrode mechanism with a relatively simple structure.

[0029] In the present invention, preferably, the guide member forms an inlet opening and an outlet opening being connected to the plasma raw material gas supply outlet includes a convergence part configured to reduce the cross-sectional area of the internal space toward the downstream and an extension part that communicates with the convergence part and the outlet opening, with the first coil and the second coil provided around the extension part.

[0030] In the present invention, preferably, the guide member further comprising a focusing portion configured to form a reverse conical space, and an extension portion configured to continuously extends downward from the focusing portion. The guide member is further configured to have a decreasing cross-sectional area in the downstream direction of the gas flow.

[0031] According to the configuration of the present invention described above, the impedance of the low- temperature atmospheric pressure plasma generated in the extension portion is matched with the high- frequency voltage application circuit.

[0032] Furthermore, the low-temperature atmospheric pressure plasma generated by the guide member can be inductively coupled with RF energy. Additionally, the low-temperature atmospheric pressure plasma generated by the guide member is focused, allowing high-density and uniform low-temperature atmospheric pressure plasma, including gas, to be irradiated onto the affected area.

[0033] According to the configuration of the present invention the guide member is further configured to define the outlet opening and an internal space of gas flow formed inside. The focusing portion is further configured to decrease the cross-sectional area of the internal space of the gas flow downstream, and the extension portion is adapted to be in communication with the focusing portion focusing portion and the outlet opening. The first coil and the second coil are configured to surround the extension portion. The plurality of electrode elements of the second electrode mechanism are configured to surround the extension portion.

[0034] In the present invention, it is preferable to further have a magnetic field generation mechanism that generates a magnetic field crossing the flow of gas inside the guide member.

[0035] When the current flowing in the plasma becomes large, the plasma tends to concentrate in the central part due to the pinch effect. However, according to the configuration of the present invention described above, the magnetic field generated by the magnetic field generation mechanism disturbs the pinch effect and can homogenize the low-temperature atmospheric pressure plasma.

[0036] In the present invention, it is preferable to further have a gas temperature control mechanism that includes a temperature sensor for measuring the temperature of the gas flow ejected toward the affected area and controls the temperature of the gas flow ejected toward the affected area based on the temperature measured by the temperature sensor.

[0037] When the treatment device continues to operate, the temperature of the low-temperature atmospheric pressure plasma rises, which can cause burns and the like when the low-temperature atmospheric pressure plasma is irradiated onto the affected area. However, according to the configuration of the present invention described above, the gas temperature control mechanism can maintain the temperature of the low-temperature atmospheric pressure plasma irradiated onto the affected area at a constant level, preventing burns and the like.

[0038] According to the present invention, it is possible to provide a non-contact, non-invasive treatment device for uniformly irradiating the entire affected area with low-temperature atmospheric pressure plasma.

[0039] Thus, in a preferred embodiment, the invention relates to a non-contact non-invasive device for generating a gas flow having a low-temperature atmospheric pressure plasma and for directing the gas flow towards an affected area Pl, wherein the device comprises: a guide member 10 having an inlet opening and an outlet opening 104A, configured to guide the gas flow towards the affected area Pl, the inlet opening being connected to a plasma source gas supply outlet 106, a low-frequency, high voltage application circuit 2 configured to generate low-frequency, high voltage in order to ionize the gas flow, flowing towards the affected area Pl, a high-frequency voltage application circuit 3 configured to generate high-frequency electric current flowing through the gas flow towards the affected area Pl, a first electrode 6 and a second electrode mechanism 540 located at the guide member 10 and around the gas flow, the second electrode mechanism 540 comprising a plurality of electrode elements 546, wherein the plurality of electrode elements 546 is arranged to be separated by a dielectric medium, and the plurality of electrode elements 546 is configured to form phase-shifted counter electrode pairs.

[0040] Preferably, the electrodes of the phase-shifted counter electrode pairs are arranged to be alternatively connected to a radio-frequency circuit via a phase shifting capacitor 550, wherein the phase shifting capacitor 550 is configured to phase shift the phase-shifted counter electrode pairs by 90 degrees.

[0041] More preferably, the phase shifting capacitor 550 is configured to generate a homogeneous radio frequency RF plasma discharge by creating a 90 degree phase shift of voltage and current.

[0042] In a preferred embodiment in the non-contact, non-invasive device of the invention the second electrode mechanism 540 is located downstream of the first electrode 6, and the low-temperature atmospheric pressure plasma is generated by applying the low-frequency, high voltage generated by the low-frequency, high voltage application circuit 2 to the first electrode 6, and applying high-frequency voltage generated by the high-frequency voltage application circuit 3 to the second electrode mechanism 540.

[0043] In a preferred embodiment the non-contact, non-invasive device of the invention comprises a gas supply device 4 configured to supply plasma source gas 40 to the guide member 10 through the plasma source gas supply outlet 106 and to generate the gas flow directed towards the outlet opening 104A, wherein the low-frequency, high voltage application circuit 2 is further configured to apply low-frequency, high voltage to the gas flow; and the high-frequency voltage application circuit 3 is further configured to apply high-frequency voltage to the gas flow.

[0044] Preferably, the low-frequency, high voltage source 22 is supplied with power from the first power source 20 and generates a voltage of low-frequency high voltage. Preferably, the low frequency in the range of 10 to 100 kHz, e.g. a frequency of 10-25 kHz and a voltage of 10-20 k\Z is generated.

[0045] Preferably, the high-frequency voltage source 26 is supplied with power from the second power source 24 and generates a high-frequency voltage. Specifically, in this embodiment, a high frequency preferably in the range of 12 to 15 MHz, e.g. a frequency of 13.56 MHz and a voltage of 5 k\Z is generated.

[0046] In a preferred embodiment the non-contact, non-invasive device of the invention comprises a transformer 7 connected to the high-frequency voltage application circuit 3 and the second electrode mechanism 540, wherein the transformer 7 is configured to amplify the high-frequency voltage applied to the second electrode mechanism 540.

[0047] Preferably, in the non-contact, non-invasive device the transformer 7 is a resonant transformer and further comprises a first coil 542 connected to the high-frequency voltage application circuit 3 and a second coil 544 connected to the plurality of electrode elements 546.

[0048] Preferably, in the non-contact, non-invasive device the guide member 10 comprises a focusing portion 102 configured to form a reverse conical space, and an extension portion 104 configured to continuously extends downward from the focusing portion 102, wherein the guide member 10 is further configured to have a decreasing cross-sectional area in the downstream direction of the gas flow.

[0049] Preferably, the guide member 10 is further configured to define the outlet opening 140A and an internal space of gas flow formed inside, the focusing portion 102 is further configured to decrease the cross-sectional area of the internal space of the gas flow downstream, and the extension portion 104 is adapted to be in communication with the focusing portion focusing portion 102 and the outlet opening 104A, wherein the first coil 542 and the second coil 544 are configured to surround the extension portion 104, and wherein plurality of electrode elements 546 of the second electrode mechanism 540 are configured to surround the extension portion 104. Preferably, in the non-contact, non-invasive device also comprises a magnetic field generator mechanism 12 configured to generate a magnetic field crossing the gas flow inside the guide member 10.

[0050] Preferably, in the non-contact, non-invasive device also comprises a temperature sensor 140 configured to measure the temperature of the gas flow at the outlet opening 104A of the guide member 10, and a gas temperature control mechanism configured to control the temperature of the gas flow guided towards the affected area Pl based on the temperature measured by the temperature sensor 140. Preferably, in the non-contact, non-invasive device is adapted to uniformly irradiating the entire affected area Pl with low-temperature atmospheric pressure plasma.

[0051] The invention also relates to a method for killing cells by the device of the invention, wherein said method comprises placing the device over the cells to be killed, directing the gas flow towards the cells, generating a low-frequency electric current flowing through the gas flow towards the cells, generating high-frequency electric current flowing through the gas flow towards the cells, and irradiating the cells with a wide and uniform low-temperature atmospheric pressure plasma. The cells are preferably pathogenic cells.

[0052] The cells are preferably cells of a microorganism. The cells are preferably pathogenic cells.

[0053] The invention also relates to a method for the treatment of a subject, preferably a patient with the noncontact, non-invasive device of the invention, wherein said patient is in need of local treatment by a low- temperature atmospheric pressure plasma.

[0054] Preferably the subject, preferably patient is in need of killing cells present in or on her / his body locally, wherein said cells are present on an affected area, e.g. a lesion, on or in the body which is exposed or exposable to the plasma generated by the device of the invention. Preferably the cells are disease cells.

[0055] In an embodiment the patient has a neoplasm, and the disease cells are neoplastic cells. Preferably the cells are cancer cell or preferably tumor cells and the patient has a cancer, or preferably a tumor, respectively.

[0056] In an embodiment the patient has ulcer and the disease cells are tumor cells.

[0057] In an embodiment the patient has a bacterial infection and the disease cells are infecting bacterial cells.

[0058] In an embodiment the patient has inflammation and the disease cells are inflammatory cells or cells in inflammation state.

[0059] The patient is an animal. In a preferred embodiment the patient is a vertebrate, more preferably a mammal, in particular a human patient.

[0060] In the method of the invention the device of the invention is placed over the affected area in the patient, the device is operated wherein the gas flow is directed towards the affected area, a low-frequency electric current flowing through the gas flow is generated by the device, a high-frequency electric current flowing through the gas flow is generated by the device, thereby a wide and uniform low-temperature atmospheric pressure plasma is formed and the affected area is irradiated with the plasma.

[0061] According to the configuration of the present invention, by applying a low-frequency, high voltage with the low-frequency voltage applying circuit to the plasma source gas supply outlet in which plasma raw material gas is supplied, and by applying a high-frequency voltage with the high-frequency voltage applying circuit, a wide and uniform low-temperature atmospheric pressure plasma can be irradiated onto the affected area, preferably on surface of the lesion.

[0062] Preferably, the irradiation with the low-temperature atmospheric pressure plasma causes affected cells to die.

[0063] The cells caused to die include cells in the exposed or exposable lesion or on the surface of the lesion. The cells may be neoplastic cells, e.g. cancer cells, or preferably tumor cells.

[0064] Alternatively, the cells can be microorganism cells, e.g bacterial cells.

[0065] Alternatively, the cells can be pathogenic cells, e.g bacterial cells.

[0066] Pathogenic cells may cause of infection.

[0067] DEFINITIONS

[0068] A "subject" as used herein is an individual of an animal species, preferably a vertebrate, more preferably a mammalian or avian species, in particular a mammalian species, highly preferably the individual is a primate, a hominid or a human.

[0069] A "patient" is a subject who is or intended to be under medical or veterinarian observation, supervision, diagnosis or treatment.

[0070] A "treatment" of a subject refers to any process, action, application, therapy, or the like, wherein the subject or patient is under aid, in particular medical or veterinarian aid with the object of improving the sub-ject's or patient's condition, either directly or indirectly. Improving the subject's condition may include improv-ing an aesthetic condition (cosmetic treatment) and / or may include, in particular, restoring or maintaining nor-mal function of an organ or tissue, preferably at least partly restoring or maintaining health (medical or veteri-narian treatment). Treatment typically refers to the administration of an effective amount of a compound or composition described herein. Unless specified differently, a therapeutic treatment includes both medical or veterinarian treatment and prevention (or prophylaxis) i.e. prevention of the onset of a disease as well.

[0071] The term "effective dose" qualifies the dose of the atmospheric pressure plasma required to exert a desired effect on the cells or tissue, preferably cells or tissue of or in the patient. A "therapeutically effective dose" is sufficient to relieve or prevent (or prevent worsening of) one or more of the symptoms or characteristic parameters of a condition, e.g. a disorder or disease.

[0072] A "neoplasm" is a type of abnormal and excessive growth of tissue. (The process that occurs to form or produce a neoplasm is called "neoplasia".) The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor. Tumor cells often metastasize to various organs. "Cancer" is neoplasm which is a disease in which some of the body's cells grow uncontrollably and spread to other parts of the body. Preferably, cancer is a disease of uncontrolled proliferation by transformed cells subject to evolution by natural selection.

[0073] A number of neoplasms of each type are listed in (Kumar et al., 2017).

[0074] In situ neoplasms comprise in situ cancers of the oral cavity, esophagus, stomach, digestive organs, respiratory system, breast, genital organs, bladder, urinary organs, eye or endocrine glands; skin, and melanomas.

[0075] The singular forms "a", "an" and "the", or at least "a", "an", include plural reference unless the context clearly dictates otherwise.

[0076] The term "comprises" or "comprising" or "including" are to be construed here as having a non- exhaustive meaning and allow the addition or involvement of further features or method steps or components to anything which comprises the listed features or method steps or components. "Comprising" can be substituted by "including" if the practice of a given language variant so requires or can be limited to "consisting essentially of" if other members or components are not essential to reduce the invention to practice.

[0077] BRIEF DESCRIPTION OF THE DRAWINGS:

[0078] FIG. 1 shows a non-contact, non-invasive treatment device according to an embodiment of the present invention.

[0079] FIG. 2 shows a horizontal cross-sectional view of the shape of a first electrode comprising the non-contact, non-invasive treatment device, made of alumina ceramics dielectric and copper electrode.

[0080] FIG. 3 shows a horizontal cross-sectional view of the shape of another alumina ceramic dielectric and copper electrode comprising the first electrode of the non-contact, non-invasive treatment device according to the embodiment of the present invention.

[0081] FIG. 4 shows a configuration of the electrode elements according to an embodiment of the present invention.

[0082] FIG. 5A shows a photo of the electrode elements according to an embodiment of the present invention.

[0083] FIG. 5B shows a photo of electrode elements of a prior art electrode.

[0084] FIG. 6 shows a plasma system-prototype of the invention. On the left a plasma generator unit 500 according to the invention is shown whereas on the right the H\Z electronics and RF electronics modules are built up.

[0085] Fig. 7. A, Single frequency plasma irradiation. B, Dual frequency plasma irradiation.

[0086] Fig. 8. A, Untreated control cells. B, Cells treated with single frequency plasma. C, Cells treated with dual frequency plasma

[0087] Fig. 9. A, Mouse with tumor on the treatment table with temperature measurement probes inserted into the tumor core and the tumor skin surface. B, Plasma irradiation of the tumor.

[0088] Fig. 10. Representative temperature measurement graph of the irradiated skin surface (orange line) and the tumor core (red line) during the treatment.

[0089] Fig. 11 A-C, Tumor cross sections of the untreated control tumors. D-K, Tumor cross sections of the plasma- treated tumors. The arrows show the destroyed tumor tissue. DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

[0090] Hereinafter, embodiments of the non-contact, non-invasive treatment device of the present invention will be described in detail with reference to the drawings. The treatment device of the present invention generates low-temperature atmospheric pressure plasma and performs plasma treatment and RF treatment non-contact, non-invasively on intractable skin ulcers, cancerous skin ulcers, and the like. The treatment is not limited to humans and can also be applied to animals. Moreover, the applicable diseases are not limited to cancer, and can be applied to diseases that can be treated by plasma treatment and RF treatment.

[0091] Figure. 1 shows a non-contact, non-invasive treatment device according to an embodiment of the present invention. As shown in FIG. 1, the non-contact, non-invasive treatment device 1 of the present embodiment includes a gas supply device 4, a low-frequency high voltage applying circuit 2, a high-frequency voltage applying circuit 3, a first electrode 6, a grounding electrode 8, a guide member 10, a magnetic field generation mechanism 12, and a gas temperature control mechanism with a temperature sensor 140.

[0092] The first electrode 6 includes a flat alumina ceramic dielectric 60, a copper electrode 62 formed on the upper surface of the alumina ceramic dielectric 60, and an epoxy resin insulator 64 formed to cover the upper surface of these alumina ceramic dielectric 60 and copper electrode 62.

[0093] Note that the dielectric 60 is not limited to alumina ceramics and can for example also be made of quartz glass or barium titanate. Additionally, the first electrode 6 is not limited to copper and can be made of other good conductors (metals with electrical resistivity p in the range of 10 nQ-m to 100 nQ-m), such as aluminum, gold, titanium, graphene, etc.

[0094] Figure 2 is a horizontal cross-sectional view showing the shape of the alumina ceramic dielectric and copper electrode constituting the first electrode in the non-contact, non-invasive treatment device shown in Figure 1. As shown in Figure 2, the alumina ceramic dielectric 60 is circular in shape. In contrast, the copper electrode 62 has a shape where the tip extends radially from the center in equal angular intervals, with acute-angled triangles. The sharper the outer edge of the electrode that generates plasma, the higher the electric field intensity, making it easier to generate plasma. Therefore, in this embodiment, as shown in Figure 2, the copper electrode 62 has a shape where the tip extends radially from the center in equal angular intervals with acute-angled triangles, so the electric field intensity is increased, and plasma generation is promoted. The shape of the copper electrode is not limited to the shape shown in Figure 2, and, for example, it may be formed as a mesh electrode with multiple copper electrodes 162 arranged in a grid pattern, as shown in Figure 3. To achieve more uniform discharge, a square mesh shape is desirable for the copper electrode 162. Note that the shape of the copper electrode is not limited to this.

[0095] Referring back to Figure 1, the grounding electrode 8 is a plate-shaped electrode and is positioned below the affected area Pl, for example a patient or represented by a part of the patient to be treated. The first electrode 6 is positioned at a given distance from, e.g. above the affected area Pl, thereby sandwiching the affected area Pl between the first electrode 6 and the grounding electrode 8. Moreover, a guide member 10 is disposed between the first electrode 6 and the affected area Pl. Furthermore, a soft material that does not inhibit discharge between the first electrode 6 and the grounding electrode 8, such as a water-permeable material, may be provided between the grounding electrode 8 and the affected area Pl for purposes such as fixing and cooling the affected area Pl. By positioning the grounding electrode 8 on the exit opening side 104A relative to the first electrode 6, low-temperature atmospheric pressure plasma can be stably generated.

[0096] The low-frequency, high voltage applying circuit 2 includes a first power source 20 and a low-frequency voltage source 22 connected to the first power source 20. The low-frequency, high voltage source 22 is supplied with power from the first power source 20 and generates a voltage of low-frequency high voltage. Specifically, in this embodiment, a low frequency in the range of 10 to 100 kHz, e.g. a frequency of 10-25 kHz and a voltage of 10-20 k\Z is generated.

[0097] The high-frequency voltage applying circuit 3 includes a second power source 24 and a high-frequency voltage source 26 connected to the second power source 24. The high-frequency voltage source 26 is supplied with power from the second power source 24 and generates a high-frequency voltage. Specifically, in this embodiment, a high frequency preferably in the range of 12 to 15 MHz, e.g. a frequency of 13.56 MHz and a voltage of 5 k\Z is generated.

[0098] Note that, in this embodiment, low frequency refers to frequencies in the range of 10-100kHz, and high frequency refers to a frequency of 13.56MHz. Furthermore, low-frequency voltages are preferably in the range of 10-20k\Z, and 10k\Z is preferable as the upper limit for high-frequency voltages.

[0099] The guide member 10 is made of a funnel-shaped glass tube. The guide member 10 has a focusing portion 102 that forms a reverse conical space and an extension portion 104 that continuously extends downward from the focusing portion 102. The diameter of the extension portion 104 is preferably 5~100 mm, and in this embodiment, it is 100 mm. At a position corresponding to the side of the focusing portion 102 of the guide member 10 is connected to the plasma source gas supply outlet 106. A pipe 4A extending from the gas supply device 4 is connected to the plasma source gas supply outlet 106.

[0100] The focusing portion 102 is of a reverse conical shape, and the internal space in the horizontal direction of the focusing portion 102 narrows toward the extension portion 104. The focusing portion 102 is supplied with plasma raw gas from the gas supply device 4, and a voltage is applied to the plasma raw gas by the low-frequency voltage applying circuit 2 and the high-frequency voltage applying circuit 3.

[0101] At the lower part of the extension portion 104, an exit opening 104A that opens downward is formed. The guide member 10 is positioned above the affected area Pl so that the exit opening 104A faces the affected area Pl. On the opposite side of the exit opening 104A, the first electrode 6 is provided, and the alumina ceramic dielectric 60 of the first electrode 6 is disposed so as to block the upper part of the guide member 10.

[0102] The magnetic field generation mechanism 12 in this embodiment comprises a pair of neodymium magnets 120 and 122. These pair of neodymium magnets 120 and 122 are arranged so as to sandwich the extension portion 104 of the guide member 10 in the horizontal direction. These pair of neodymium magnets 120 and 122 are arranged so that the N-pole of one neodymium magnet 120 faces the S-pole of the other neodymium magnet 122. This generates a magnetic field that crosses the flow of gas in the extension portion 104 in the horizontal direction between these pair of neodymium magnets 120 and 122. The magnetic field generated by these pair of neodymium magnets 120 and 122 is preferably perpendicular to the gas flow. The magnetic field generation mechanism 12 is not limited to neodymium magnets, and the arrangement of neodymium magnets is not limited to a pair. A Halbach arrangement, a quadrupole arrangement, or a magnet ring may be used instead. The gas supply device 4 includes a gas source 40 and a flow control device 42 connected to the gas source 40. The gas source 40 is a gas source for plasma raw gas such as helium or argon. The flow control device 42 controls the flow rate of plasma raw gas supplied from the gas supply device 4 to the pipe 4A.

[0103] The gas temperature control mechanism includes a temperature sensor 140 and a gas temperature control device. The temperature sensor 140 is provided, for example, near the affected area Pl or near the exit opening 104A of the guide member 10 and measures the temperature of the gas sprayed toward the affected area Pl. The gas temperature control device is provided on the pipe 4A and, based on the temperature of the gas detected by the temperature sensor 140, feedback controls the temperature of the gas flowing through the pipe 4A from the gas source 40 so that the temperature of the plasma gas sprayed toward the affected area Pl is 20~40°C, which does not damage the normal tissue.

[0104] In this embodiment, the temperature of the gas flowing through the pipe 4A from the gas source 40 to the plasma source gas supply outlet 106is adjusted. However, the method of controlling the temperature of the gas sprayed toward the affected area Pl is not limited to this. For example, a cooling device may be provided on the opposite side of the guide member 10 of the first electrode 6, and alumina ceramic dielectric 60 of the first electrode 6 may be provided on the upper part of the guide member 10 so as to block the upper part of the guide member 10. A cooling device may be used that employs air circulation for air cooling, or a device that uses cooling water or cooling oil may be used. Additionally, a cooling mechanism may be provided in the guide member 10, or the gas supplied to the guide member 10 may be adjusted by mixing cooling gas.

[0105] Next, the operation of the non-contact non-invasive treatment device 1 in this embodiment will be described. When the non-contact non-invasive treatment device 1 is started, plasma feed gas is supplied from the gas source 40 in the gas supply device 4 to the focusing unit 102 of the guide member 10 via the pipe 4A. At this time, the flow rate of the plasma feed gas supplied from the gas supply device 4 is controlled by the flow rate control device 42.

[0106] Furthermore, when the non-contact non-invasive treatment device 1 is started, the low-frequency, high voltage source 22 of the low-frequency voltage application circuit 2 generates a low-frequency high voltage, and the high-frequency voltage source 26 generates a high-frequency low voltage.

[0107] Electric charges accumulate in the first electrode 6 and polarize positively and negatively. Consequently, atoms in the plasma feed gas in the vicinity of the first electrode 6 are ionized, and low-temperature atmospheric pressure plasma is generated due to the electric field generated around the first electrode 6, resulting in the generation of low-temperature atmospheric pressure plasma. The low-temperature atmospheric pressure plasma thus generated, along with the plasma source gas, reaches the extension portion 104.

[0108] This embodiment has the following advantages.

[0109] Furthermore, this embodiment includes a focusing unit 102 configured to reduce the cross-sectional area of the internal space downstream, with the focusing unit 102 having an outlet opening 104A of the guide member 10 arranged facing the affected area Pl. As a result, the low-temperature atmospheric pressure plasma generated in the focusing unit 102 and the extension unit 104 is focused, and high-density and uniform low- temperature atmospheric pressure plasma, including gas, can be irradiated onto the affected area Pl. When the current flowing in the low-temperature atmospheric pressure plasma becomes large, the low- temperature atmospheric pressure plasma converges due to the magnetic field generated by the current. In this regard, this embodiment includes the magnetic field generating mechanism 12 that generates a magnetic field so as to cross the flow of gas in the extension unit 104. Consequently, the magnetic field generated by the magnetic field generating mechanism 12 disturbs the pinch effect and allows uniformization of the low- temperature atmospheric pressure plasma.

[0110] When the non-contact non-invasive treatment device 1 continues to operate, the temperature of the low- temperature atmospheric pressure plasma rises overtime, which can cause burns and other problems when the low-temperature atmospheric pressure plasma is irradiated onto the affected area. In response to this, this embodiment includes a gas temperature control mechanism 14, including a temperature sensor 140 for measuring the temperature of the gas ejected toward the patient Pl and a gas temperature control unit 142 for controlling the temperature of the gas ejected toward the patient Pl based on the temperature measured by the temperature sensor 140. This keeps the temperature of the low-temperature atmospheric pressure plasma irradiated onto the patient Pz's affected area constant and prevents burns and other issues.

[0111] The present invention can be applied when low-frequency and high-frequency voltages are separately applied to the plasma feed gas supply outlet 106.

[0112] The non-contact non-invasive treatment device 1 of the present embodiment further includes a second electrode mechanism 540 and the second electrode 540 further comprising a plurality of electrode elements 546, wherein the plurality of electrode elements 546 is arranged to be separated by a dielectric medium, and the plurality of electrode elements 546 is configured to form phase-shifted counter electrode pairs.

[0113] The phase-shifted counter electrode pairs are arranged to be alternatively connected to a radio-frequency circuit via phase shifting capacitors 550.

[0114] Phase shifting capacitors 550 are configured to generate a homogeneous radio frequency plasma discharge by creating a 90 degrees phase shift of voltage and current, wherein a pair of sine-waves having alternating mutually-exclusive minima and maxima.

[0115] According to this embodiment, the following effects are achieved.

[0116] In this embodiment, low-temperature atmospheric pressure plasma is generated by applying both low- frequency and high-frequency voltages to the plasma feed gas in the focusing section 102 using the low- frequency voltage application circuit 2 and the high-frequency voltage application circuit 3. This allows for the wide and uniform irradiation of low-temperature atmospheric pressure plasma onto the affected area Pl. As a result, low-temperature atmospheric pressure plasma can be used to destroy cancer cells on the surface of the affected area Pl, eliminate bacteria causing infections, induce blood coagulation on the surface of the affected area Pl, and promote the healing of skin wounds.

[0117] In this embodiment, the high-frequency voltage application circuit 3 applies high-frequency voltage to the first electrode 6, generating RF current. The RF current to flow from the first electrode 6 to the plasma on the surface of the affected area Pl. This RF current accumulates RF energy in the interior of the affected area Pl, promoting blood circulation and inducing apoptosis in cancer cells on the surface and inside the affected area Pl. When the current flowing through the low-temperature atmospheric pressure plasma increases, the low- temperature atmospheric pressure plasma converges due to the magnetic field generated by the current (pinch effect). However, in this embodiment, a magnetic field generation mechanism 12 is provided that generates a magnetic field crossing the flow of gas within the elongation section 104 of the guide member 10. This magnetic field generated by the magnetic field generation mechanism 12 disrupts the pinch effect, allowing the low- temperature atmospheric pressure plasma to be uniform.

[0118] The low-frequency voltage application circuit 2 is connected to a high-frequency blocking filter 512, and the high-frequency blocking filter 512 is located between the low-frequency voltage source 22 and the copper electrode 62 of the first electrode 6.

[0119] The low-frequency voltage source 22 is powered by the first power source 20 and generates a low-frequency high voltage. Specifically, in this embodiment, it generates a voltage of 10-25 kHz and 10-20 k\Z, with a preferred range of 10k-20k\Z for low-frequency voltage. In this embodiment, low-frequency refers to frequencies between 10 kHz and 100 kHz.

[0120] The high-frequency blocking filter 512 is a filter that allows low-frequency current to pass while attenuating RF current. The high-frequency blocking filter 512 prevents RF current generated in the second electrode mechanism 540, as described later, from flowing into the circuit connected to the first electrode 6 and damaging the first power source 20. In this embodiment, a filter capable of blocking a frequency of 13.56 MHz is used.

[0121] In this embodiment the first electrode 6 is composed of alumina ceramic dielectric and copper electrodes. As shown in Figure 3, the alumina ceramic dielectric 60 is circular in shape. In contrast, the copper electrode 162 is a mesh-like electrode formed by intersecting multiple straight lines. Electrodes with sharper edges generate stronger electric fields and are more likely to induce plasma. In this shape, increasing the electric field strength promotes plasma generation. Furthermore, it is desirable for the mesh shape of the copper electrode 162 to be square, as this allows for uniform discharge across the entire electrode. The shape of the copper electrode is not limited to this configuration.

[0122] The second electrode mechanism 540 includes a first coil 542 connected to the high-frequency voltage application circuit 520, a second coil 544, which, together with the first coil 542, forms a resonant transformer, and electrode elements 546.

[0123] The first coil 542 has a larger radius than the second coil 544 and fewer windings than the second coil 544. The first coil 542 and the second coil 544 surround the extension portion 104 of the guide member 10 and are coaxially arranged. The first coil 542 is located near the upper end of the extension portion 104 of the guide member 10, and the second coil 544 is positioned below the first coil 542 with a gap between them. Although the first coil 542 is placed close to the second coil 544, they are not electrically connected.

[0124] Furthermore, when the non-contact non-invasive treatment device 1 is activated, the high-frequency voltage source 26 generates a high-frequency high-voltage voltage in the high-frequency voltage application circuit 520. When this voltage is applied to the first coil 542 of the second electrode mechanism 540, the second coil 544 resonates, and the applied voltage is increased proportionally to the number of turns of the second coil 544. The second coil 544 applies the increased high-frequency high-voltage voltage to the plurality of electrode elements 546.

[0125] The plurality of electrode elements 546 accumulates charges and polarizes positively and negatively due to the high-frequency high-voltage voltage. At this time, an electric field is generated around the plurality of electrode elements 546. The atoms in the plasma source gas that reaches the extension portion 104 are ionized by this electric field, resulting in the generation of low-temperature atmospheric pressure plasma. Additionally, by placing the plurality of electrode elements 546 near the exit opening 104A of the extension portion 104, i.e., in the vicinity of the extension portion 104, the high-frequency voltage is applied to the low-temperature atmospheric pressure plasma at a position where the impedance of the low-temperature atmospheric pressure plasma is low, allowing the RF current to reach the affected area Pl through the low-temperature atmospheric pressure plasma.

[0126] In this way, the generated plasma, along with the plasma source gas, passes through the extension portion 104 and is ejected from the exit opening 104A. Here, a magnetic field is generated to cross the flow of the mixed gas within the extension portion 104 by the magnetic field generation mechanism 12, and the pinch effect is disrupted by the magnetic field, resulting in uniformization of the low-temperature atmospheric pressure plasma within the mixed gas as it flows through the extension portion 104.

[0127] Further, the first electrode 6 and the plurality of electrode elements 546 are positioned to sandwich the affected area Pl, along with the grounding electrode 8. When voltage is applied between them, RF current reaches from the first electrode 6 and the plurality of electrode elements 546 to the surface of the affected area Pl, ensuring a stable flow of RF current in the affected area Pl.

[0128] The plurality of electrode elements 546 is a capacitive electrode made of multiple copper layers, e.g. multiple pieces of copper foil, and it is positioned downstream the second coil 544 to surround the extension portion 104 of the guide member 10.

[0129] The plurality of electrode elements 546 is connected to one terminal of the second coil 544, while the other terminal of the second coil 544 is grounded. The shape of the plurality of electrode elements 546 is not limited to this configuration and may involve any plurality of electrode elements arranged to be separated by a dielectric medium positioned around the gas flow, e.g. around the extension portion comprising the gas flow.

[0130] In this electrode arrangement of the second electrode mechanism 540, preferably at least three pairs of electrodes in the arrangement are shown in Figure 4. One of the opposite pairs of electrodes is connected to the radio-frequency circuit via phase shifting capacitors 550. Phase shifting capacitors 550 can be for example a ceramic multilayer capacitor with 390 pF capacitance and 3k\Z voltage. In the case of a given sine wave, only one of the electrode pairs of the phase-shifted counter electrode pairs is at maximum voltage (fire), while the other is at 0 voltage thanks to the 90-degree phase shift, while in the next cycle it is exactly the opposite. With this solution, the resulting radio-frequency plasma discharge became completely homogeneous and the frequent arc discharge disappeared.

[0131] According to this embodiment, the following effects are achieved: The present invention's configuration described above generates a wide and uniform low-temperature atmospheric pressure plasma by applying low- frequency voltage to the first electrode 6 and high-frequency voltage to the plurality of electrode elements 546. Because the low-frequency voltage applied to the first electrode 6 and the high-frequency voltage applied to the second electrode mechanism 540 are separate, it is possible to reduce design limitations related to the size of the plasma source gas supply space, the time and distance over which low-temperature atmospheric pressure plasma can be maintained, and the impedance. This makes it possible to create a versatile treatment device applicable to treating affected areas. Additionally, a high-frequency electric field is formed near the exit opening 104A of the guide member, activating the maintenance and generation of plasma.

[0132] Furthermore, the plurality of electrode elements 546 of the second electrode mechanism 540 is positioned near the extension portion 104, closer to the exit opening 104A, than the first electrode 6. This allows the high- frequency voltage to be applied at a position where the impedance of the low-temperature atmospheric pressure plasma in the plasma source gas supply space is low. As a result, impedance matching between the high-frequency voltage application circuit 520 on the output side and the low-temperature atmospheric pressure plasma in the guide member 10 on the input side becomes easier, allowing RF current to be applied to the affected area Pl while irradiating it with low-temperature atmospheric pressure plasma. This enables the accumulation of RF energy in the affected area, promoting blood circulation and inducing apoptosis in cancer cells on the surface and inside the affected area.

[0133] Additionally, there are a first coil 542 and a second coil 544 that forms a resonant transformer with the first coil 542. The plurality of electrode elements 546 is connected to the second coil 544. With this configuration, the first coil 542 and the second coil 544 can relatively easily amplify the high-frequency voltage applied to the plurality of electrode elements 546. Even when the impedance of the low-temperature atmospheric pressure plasma in the guide member 10 is relatively high, RF current can still be generated in the low-temperature atmospheric pressure plasma. Since RF current can reach the affected area Pl through the low-temperature atmospheric pressure plasma, treatment of the surface and interior of the affected area Pl is possible.

[0134] Furthermore, the first coil 542 and the second coil 544 of the second electrode mechanism 540 are provided to surround the extension portion 104. With this embodiment, impedance matching is achieved between the impedance of the low-temperature atmospheric pressure plasma generated in the extension portion 104 on the input side (guide member 10) and the impedance of the high-frequency voltage application circuit 520 on the output side. Moreover, RF energy can be inductively coupled to the low-temperature atmospheric pressure plasma, promoting blood circulation and inducing apoptosis in cancer cells on the affected area Pl.

[0135] Furthermore, according to the configuration of this embodiment, a high-frequency electric field is formed in the extension portion 104 of the guide member 10, causing ionized atoms and electrons to accelerate in the extension portion 104. Therefore, the low-temperature atmospheric pressure plasma generated by the first electrode is easily maintained, and electrons generated in the extension portion 104 can also generate low- temperature atmospheric pressure plasma by colliding with the plasma source gas.

[0136] Additionally, the low-temperature atmospheric pressure plasma generated by the focusing unit 102 is focused and ejected from the exit opening 104A, allowing high-density and uniform low-temperature atmospheric pressure plasma to be irradiated onto the patient Pl's affected area. When the current flowing in the plasma becomes large, the plasma converges due to the magnetic field generated by the current (pinch effect). In contrast, in this embodiment, a magnetic field generation mechanism 12 that generates a magnetic field crossing the flow of gas inside the extension portion 104 of the guide member 10 is provided. This allows the magnetic field generated by the magnetic field generation mechanism 12 to disrupt the pinch effect and make the low-temperature atmospheric pressure plasma uniform.

[0137] It should be noted that in this embodiment, the first electrode 6 is positioned to cover the upper part of the guide member 10, and the grounding electrode 8 is positioned below the patient P, but the present invention is not limited to this arrangement. As long as voltage can be applied to the plasma source gas supplied from the gas supply device, the arrangement can vary. Additionally, in this embodiment, the second electrode mechanism 540 is provided to surround the extension portion 104 of the guide member 10, but it may also be provided to surround the focusing unit 102.

[0138] The present embodiments resulting a RF plasma discharge to become completely homogeneous and the previously frequent arc discharge disappeared.

[0139] EXAMPLES

[0140] Example 1. - Example for the non-contact, non-invasive treatment device

[0141] Example 1.2 - Basic construction

[0142] A non-contact, non-invasive treatment device 1 is provided herein, which includes a gas supply device 4, a low-frequency high voltage applying circuit 2, a high-frequency voltage applying circuit 3, a first electrode 6, a grounding electrode 8, a guide member 10, a magnetic field generation mechanism 12, and a gas temperature control mechanism with a temperature sensor 140.

[0143] The first electrode 6 includes a flat alumina ceramic dielectric 60, a copper electrode 62 formed on the upper surface of the alumina ceramic dielectric 60, and an epoxy resin insulator 64 formed to cover the upper surface of these alumina ceramic dielectric 60 and copper electrode 62.

[0144] Figure 2 shows a horizontal cross-sectional view showing the shape of the circular alumina ceramic dielectric 60 and copper electrode 62 having a tip which extends radially from the center in equal angular intervals. This is the first electrode 6 in the device shown in Figure 1. The alumina ceramic dielectric 60 is circular in shape, whereas the copper electrode 62 is a mesh-like electrode.

[0145] The device also has a plate-shaped grounding electrode 8 which is positioned below the affected area Pl in the patient. The first electrode 6 is positioned at a given distance from, e.g. above the affected area Pl, thereby sandwiching the affected area Pl between the first electrode 6 and the grounding electrode 8.

[0146] The low-frequency, high voltage applying circuit 2 comprises a first power source 20 and a low-frequency voltage source 22 connected to the first power source 20. The low-frequency, high voltage source 22 is supplied with power from the first power source 20 and generates a voltage of low-frequency of 10-25 kHz and a high voltage of 10-20 k\Z.

[0147] The high-frequency voltage applying circuit 3 includes a second power source 24 and a high-frequency voltage source 26 connected to the second power source 24wherein in this example a frequency of 13.56 MHz and a voltage of 5 k\Z is generated. With the help of the specially designed, funnel-shaped (of reverse conical shape) primary ionization chamber having a focusing portion 102, homogeneous helium plasma with a large surface (4cm2) and volume can be produced.

[0148] At the lower part of the extension portion 104, an exit opening 104A that opens downward is formed. The guide member 10 is positioned above the affected area Pl so that the exit opening 104A faces the affected area Pl. On the opposite side of the exit opening 104A, the first electrode 6 is provided, and the alumina ceramic dielectric 60 of the first electrode 6 is disposed so as to block the upper part of the guide member 10.

[0149] A pair of neodymium magnets 120 and 122 are arranged so as to sandwich the extension portion 104 and so that the N-pole of one neodymium magnet 120 faces the S-pole of the other neodymium magnet 122, whereby the magnetic field, perpendicular to the gas flow, crosses the flow of gas in the extension portion 104.

[0150] The temperature of the gas flowing through the pipe 4A from the gas source 40 to the plasma source gas supply outlet 106 is adjusted. When the non-contact non-invasive treatment device 1 is started, plasma feed gas is supplied from the gas source 40 in the gas supply device 4 to the funnel-shaped focusing unit 102 of the guide member 10 via the pipe 4A. and the low-frequency high voltage, and the high-frequency low voltage are generated resulting in the accumulation of electric charges, and ionization of atoms in the first electrode 6.

[0151] The process leads to the generation of low-temperature atmospheric pressure plasma which, along with the plasma source gas, reaches the extension portion 104.

[0152] Treatment by the device is shown in Example 3

[0153] This embodiment has the following advantages.

[0154] In this example, when the current flowing in the low-temperature atmospheric pressure plasma becomes large, the low-temperature atmospheric pressure plasma converges and the magnetic field crosses the flow of gas in the extension unit 104. Consequently, the magnetic field generated by the magnetic field generating mechanism 12 disturbs the pinch effect and allows uniformization of the low-temperature atmospheric pressure plasma. Moreover, a gas temperature control mechanism 14 is applied to avoid raising of the temperature.

[0155] Example 1.2 - The second electrode

[0156] The non-contact non-invasive treatment device 1 of the present embodiment includes a second electrode mechanism 540 and the second electrode 540 comprising electrode elements 546 arranged to be separated by a dielectric medium, and configured to form phase-shifted counter electrode pairs, alternatively connected to a radio-frequency circuit via phase shifting capacitors 550. These phase shifting capacitors 550 are configured to generate a homogeneous radio frequency plasma discharge by creating a 90 degree phase shift of voltage and current, wherein a pair of sine-waves having alternating mutually-exclusive minima and maxima. Thereby, wide and uniform irradiation of low-temperature atmospheric pressure plasma onto the affected area Pl is achieved.

[0157] In this electrode arrangement of the second electrode mechanism 540 three pairs of electrodes in the arrangement as shown in Figure 4. One of the opposite pairs of electrodes is connected to the radio-frequency circuit via phase shifting capacitors 550. The phase shifting capacitors 550 is in this example a ceramic multilayer capacitor with 390 pF capacitance and 3k\Z voltage. In the case of a given sine wave, only one of the electrode pairs of the phase-shifted counter electrode pairs is at maximum voltage (fire), while the other is at 0 voltage thanks to the 90-degree phase shift, while in the next cycle it is exactly the opposite. With this solution, the resulting radio-frequency plasma discharge became completely homogeneous and the frequent arc discharge disappeared.

[0158] Example 1.3 -The operation of the device

[0159] The high-frequency voltage application circuit 3 applies high-frequency voltage to the first electrode 6, generating RF current. The RF current to flow from the first electrode 6 to the plasma on the surface of the affected area Pl. This RF current accumulates RF energy in the interior of the affected area Pl, promoting blood circulation and inducing apoptosis in cancer cells on the surface and inside the affected area Pl.

[0160] When the non-contact non-invasive treatment device 1 is activated, the high-frequency voltage source 26 generates a high-frequency high-voltage voltage in the high-frequency voltage application circuit 520. When this voltage is applied to the first coil 542 of the second electrode mechanism 540, the second coil 544 resonates, and the applied voltage is increased proportionally to the number of turns of the second coil 544. The second coil 544 applies the increased high-frequency high-voltage voltage to the plurality of electrode elements 546.

[0161] The plurality of electrode elements 546 accumulates charges and polarizes positively.

[0162] The generated plasma, along with the plasma source gas, passes through the extension portion 104 and is ejected from the exit opening 104A. Here, a magnetic field is generated to cross the flow of the mixed gas within the extension portion 104 by the magnetic field generation mechanism 12, and the pinch effect is disrupted by the magnetic field, resulting in uniformization of the low-temperature atmospheric pressure plasma within the mixed gas.

[0163] The present embodiments resulting a RF plasma discharge to become completely homogeneous and the previously frequent arc discharge disappeared.

[0164] The RF current accumulates RF energy in the interior of the affected area, and inducing apoptosis in cancer cells on the surface and inside the affected area Pl.

[0165] As a result, low-temperature atmospheric pressure plasma can be used to destroy cancer cells on the surface of the affected area Pl, eliminate bacteria causing infections, induce blood coagulation on the surface of the affected area Pl, and promote the healing of skin wounds.

[0166] Example 2 - Biological effects of the plasma system in vitro

[0167] Example 2.1 - Materials and methods

[0168] Cells

[0169] 4T1 murine mammary carcinoma cell line was used for the in vitro experiment. Cells were maintained in Dulbecco's Modified Eagle's Medium (high glucose), supplemented with 10% calf serum and 1% antibiotic- antimycotic solution in a standard 25 cm2cell culture flask in a standard incubator at 37 °C in 5% CO2. 24 hours before the plasma treatment, the cells were transferred into a 35 mm, small Petri dish.

[0170] Plasma treatment

[0171] We wanted to compare the biological response induced by the plasma system in both single frequency and dual frequency modes. The first treatment was performed in single frequency mode, when we excited the plasma only using the low-frequency high-voltage (20kHz, 15k\Z) system. In the second treatment, in addition to the low-frequency excitation, we also coupled 20W, 13.56MHz radiofrequency energy to the primarily generated plasma. In both treatments, we irradiated the cell cultures in the Petri dishes for 120 seconds, which were covered with the previously detailed cell-maintaining medium to a height of about 8mm. The Helium gas flow rate were 20L / min in both treatments. Based on previous test measurements, the 20W RF energy does not cause a significant temperature increase in the cell layer. (Data not shown) After the treatments, the cells were returned to the incubator, and after 24 hours, microscopic images were taken using an inverted phase contrast microscope. Photos of the plasma treatments are shown in the Fig. 7.

[0172] Example 2.2 - Biological effects of the plasma system in vitro

[0173] Microscopic examination performed 24 hours after plasma treatment showed no morphological differences in the cell culture in the case of plasma treatment performed in single frequency mode compared to the untreated control sample. However, treatment performed in dual frequency mode resulted in an extremely high degree of tumor cell death. The characteristic morphological signs of cell death, such as cell shrinkage, rounding, detachment from the substrate, and cell disintegration are clearly observed in the sample. Morphological microscopic images of the cells are shown in Fig. 8.

[0174] Example 3 - Biological effects of the plasma system in in vivo tumor model

[0175] Example 3.1 - Materials and methods

[0176] Animal model

[0177] For the experiment, 6-8 week old female Balb / C mice were used. For tumor induction, 4T1 cell line was used, of which 1 million cells were injected in a volume of lOOuL under the skin of the right thigh of the mice. Plasma treatment was performed on the 12th day after tumor induction, when the tumor size reached 8-10mm.

[0178] Plasma treatment

[0179] Plasma treatment was performed in dual frequency operation mode with the following parameters:

[0180] Initial plasma generation: 15k\Z, 25kHz

[0181] Helium flow rate: 30 slm (standard liter / minute)

[0182] Radiofrequency power: 10W (13.56MHz)

[0183] The experimental setup of the plasma system for the in vivo study is shown in Fig. 6.

[0184] Before the treatment, the tumor area was shaved. The treatment was performed under inhalation anaesthesia. (2% Isoflurane) During the treatment, the skin temperature of the plasma-irradiated area was measured to prevent overheating of the skin surface. When the skin surface temperature reached the critical temperature of 42 °C, the plasma irradiation was turned off and allowed to cool down to the physiological level. The irradiation-cooling cycle was repeated 5 times during the treatment. A multi-channel optical thermometer system (Luxtron-Lumasense FOT kit) was used for temperature measurement. In addition to the skin surface, the temperature of the tumor core was also measured. Images of in vivo plasma treatment are shown in Fig. 9., as well as representative temperature measurement graph in Fig. 10.

[0185] Sampling

[0186] 48 hours after treatment, the animals were euthanized, the tumor was removed and fixed in 10% buffered formalin solution for 24 hours. After fixation, they were embedded in paraffin blocks and standard histological sections were prepared. After standard hematoxylin-eosin staining, they were examined with a biological microscope. Example 3.2 - Results of the treatment

[0187] Compared to untreated control tumors, which have only a few small necrotic areas on the section plane, plasma-treated tumors have large necrotic areas on the section planes in all cases. Tumor tissue destruction is observed not only directly under the plasma-treated skin layer, but also in deeper tissue layers. It is possible to destroy a significant part of the tumor, even far from the tumor surface, where direct plasma treatment did not reach the tumor tissue. Histomorphological images of the tumor cross sections are shown in Fig. 11. where the arrows show the destroyed tumor tissue.

[0188] Conclusions

[0189] 1. A stable operating dual-frequency plasma system has been successfully developed which suitable for conducting basic research experiments.

[0190] 2. Plasma treatment in dual frequency mode is extremely effective in destroying tumor cells in vitro.

[0191] 3. The first in vivo experimental results proved the correctness of our concept, that is, significant tumor cell destruction can be achieved even under the surface layer of the treated tumor. This tumor killing effect extends far beyond the tumor surface, effectively targeting deep tumor tissue layers for destruction.

[0192] Reference signs

[0193] 1: Non-contact non-invasive treatment device

[0194] 2: Low-frequency, high voltage application circuit

[0195] 3: High-frequency voltage application circuit

[0196] 4: Gas supply device

[0197] 4A: Pipe

[0198] 5: Plasma generator unit

[0199] 6: First electrode

[0200] 8: Grounding electrode

[0201] 10: Guide member

[0202] 12: Magnetic field generation mechanism

[0203] 20: First power supply

[0204] 22: Low-frequency, high voltage source

[0205] 24: Second power supply

[0206] 26: High-frequency voltage source

[0207] 40: Gas source

[0208] 42: Flow control device

[0209] 60: Dielectric (e.g., alumina ceramic)

[0210] 62: copper electrode

[0211] 64: Insulator (e.g., epoxy resin)

[0212] 102: Focusing portion

[0213] 104: Extension portion

[0214] 104A: Exit opening

[0215] 106: Plasma source gas supply outlet

[0216] 120: Neodymium magnet

[0217] 122: Neodymium magnet

[0218] 140: Temperature sensor

[0219] 500: Plasma generator unit

[0220] 512: High-frequency blocking filter

[0221] 540: Second electrode mechanism

[0222] 542: First coil

[0223] 544: Second coil

[0224] 546: A plurality of electrode elements

[0225] 550: Phase shifting capacitors

[0226] 600: Electronics

[0227] Pl: Affected area

Claims

CLAIMS1. A non-contact non-invasive device for generating a gas flow having a low-temperature atmospheric pressure plasma and for directing the gas flow towards an affected area (Pl), wherein the device comprises: a guide member (10) having an inlet opening and an outlet opening (104A), configured to guide the gas flow towards the affected area (Pl), the inlet opening being connected to a plasma source gas supply outlet (106), a low-frequency, high voltage application circuit (2) configured to generate low-frequency, high voltage in order to ionize the gas flow, flowing towards the affected area (Pl), a high-frequency voltage application circuit (3) configured to generate high-frequency electric current flowing through the gas flow towards the affected area (Pl), a first electrode (6) and a second electrode mechanism (540) located at the guide member (10) and around the gas flow, the second electrode mechanism (540) comprising a plurality of electrode elements (546), wherein the plurality of electrode elements (546) is arranged to be separated by a dielectric medium, and the plurality of electrode elements (546) is configured to form phase-shifted counter electrode pairs.

2. The non-contact, non-invasive device according to claim 1, wherein the electrodes of the phase-shifted counter electrode pairs are arranged to be alternatively connected to a radiofrequency circuit via a phase shifting capacitor (550), wherein the phase shifting capacitor (550) is configured to phase shift the phase-shifted counter electrode pairs by 90 degrees.

3. The non-contact, non-invasive device according to claim 2, wherein the phase shifting capacitor (550) is configured to generate a homogeneous radio frequency (RF) plasma discharge by creating a 90 degree phase shift of voltage and current.

4. The non-contact, non-invasive device according to claim 1, wherein the second electrode mechanism (540) is located downstream of the first electrode (6), and the low-temperature atmospheric pressure plasma is generated by applying the low-frequency, high voltage generated by the low-frequency, high voltage application circuit (2) to the first electrode (6), and applying high-frequency voltage generated by the high-frequency voltage application circuit (3) to the second electrode mechanism (540).

5. The non-contact, non-invasive device according to claim 1 further comprising a gas supply device (4) configured to supply plasma source gas (40) to the guide member (10) through the plasma source gas supply outlet (106) and to generate the gas flow directed towards the outlet opening (104A), wherein the low-frequency, high voltage application circuit (2) is further configured to apply low-frequency, high voltage to the gas flow; and the high-frequency voltage application circuit (3) is further configured to apply high-frequency voltage to the gas flow.

6. The non-contact, non-invasive device according to claim 1 further comprisinga transformer (7) connected to the high-frequency voltage application circuit (3) and the second electrode mechanism (540), wherein the transformer (7) is configured to amplify the high-frequency voltage applied to the second electrode mechanism (540).

7. The non-contact, non-invasive device according to claim 6, wherein the transformer (7) is a resonant transformer and further comprises a first coil (542) connected to the high-frequency voltage application circuit (3) and a second coil (544) connected to the plurality of electrode elements (546).

8. The non-contact, non-invasive device according to claim 1, wherein the guide member (10) comprises a focusing portion (102) configured to form a reverse conical space, and an extension portion (104) configured to continuously extends downward from the focusing portion (102), wherein the guide member (10) is further configured to have a decreasing cross-sectional area in the downstream direction of the gas flow.

9. The non-contact, non-invasive device according to claim 8, wherein the guide member (10) is further configured to define the outlet opening (140A) and an internal space of gas flow formed inside, the focusing portion (102) is further configured to decrease the cross-sectional area of the internal space of the gas flow downstream, and the extension portion (104) is adapted to be in communication with the focusing portion focusing portion (102) and the outlet opening (104A), wherein the first coil (542) and the second coil (544) are configured to surround the extension portion (104), and wherein plurality of electrode elements (546) of the second electrode mechanism (540) are configured to surround the extension portion (104).

10. The non-contact, non-invasive device according to claim 1 further includes a magnetic field generator mechanism (12) configured to generate a magnetic field crossing the gas flow inside the guide member (10).

11. The non-contact, non-invasive device according to claims 1 further includes a temperature sensor (140) configured to measure the temperature of the gas flow at the outlet opening (104A) of the guide member (10), and a gas temperature control mechanism configured to control the temperature of the gas flow guided towards the affected area (Pl) based on the temperature measured by the temperature sensor (140).

12. A non-contact, non-invasive treatment device according to any of claims 1 to 11 adapted to uniformly irradiating the entire affected area (Pl) with low-temperature atmospheric pressure plasma.

Images