Therapeutic device for cell therapy or cell stimulation

Abstract

A therapeutic device for cell stimulation or cell therapy comprises a housing accommodating electrodes, a generator for generating high-frequency pulses, a processor unit comprising a control, regulation and calculation module, a memory unit, a control element, a controllable modulator by means of which the generator can be controlled. A voltage pulse sequence comprising a plurality of voltage pulses can be generated by means of the modulator, wherein the frequency of the voltage pulse sequence can be at least partially non-constant.

Description

Technical Field

[0001] This invention relates to a therapeutic device for cell therapy or cell stimulation. Background Technology

[0002] Existing technologies include therapeutic devices that utilize physiological electrical stimulation (also referred to as electrotherapy in the literature). This type of therapeutic device is based on the principle of delivering electrical energy to biological cells. This technology is used in medicine for so-called high-frequency therapy. It combines an electric field generated by an RF generator with a delivery device for delivering RF power in pulses to the cells to achieve cell stimulation.

[0003] The therapeutic device according to the invention is applicable in the fields of health applications, fitness, beauty, pain relief, wound healing, cell therapy, or further cellular stimulation for human or animal treatment.

[0004] Document DE 2822892 A1 illustrates an example of such a therapeutic device, namely a device for maintaining a negative potential in human, animal, and plant cells and / or for permeating substances into the cells. A generator, influenced by control circuitry, can produce high-frequency pulses with adjustable repetition frequency and duration, and the circuitry generates DC voltages and pulsating DC voltages for ionization, as well as pulses of a specific shape and variable repetition frequency for inductive electrotherapy of the tissue to be treated. Treatment sessions are performed at predetermined time intervals.

[0005] Although acceptable results have been achieved with respect to its intended use, the following disadvantages exist for the user during operation:

[0006] - The device is cumbersome to use during therapy because it requires a wired power source.

[0007] - The energy level needs to be set manually via the power supply unit.

[0008] - The pulse frequency for energy transfer can only vary within a very small range, specifically from 10 Hz to 1000 Hz.

[0009] - The emitted energy is unaffected in its signal form.

[0010] Any of these factors limits the long-term success of the therapy; local application of case-specific pulsed forms is not possible, thus requiring numerous repeated treatments and / or having limited effect on cells. The treatment head, containing electrodes, has a diameter of approximately 17 cm and a height of approximately 10 cm. An antenna is arranged within the treatment head, which is configured as an electrically insulating plastic plate on its surface, with a conductive cover arranged circularly on the patient side. A helical conductive cover is connected at its ends to a tuning capacitor on the opposite surface.

[0011] A therapeutic device powered by a direct current is known from EP 2397187 A1. Using this device, a magnetic field is generated to induce an electric current that stimulates electrical signals in nerve bundles of the body, which can then stimulate molecules, organs, or tissues of a biological object. Due to the associated relatively high energy consumption, methods are sought for the local treatment of biological materials containing living cells with reduced energy consumption.

[0012] For example, according to DE10324926 B3, a pin-shaped electrode is provided for this purpose, which is connected to an AC high-voltage generator. The electrode has a circular tip covered by a dielectric. In one aspect, the dielectric is used to insulate the electrode 3; in another aspect, the dielectric is used to dielectrically prevent gas discharge, which can be ignited by applying an alternating high voltage to the electrode between the dielectric and the surface of the biomaterial, and generating cold plasma on the surface of the biomaterial. Ceramic, glass, or plasma-resistant plastics can be used as the dielectric. The free oxygen in the plasma has a chemical effect on the biomaterial to kill unwanted microorganisms, bacteria, and degenerated tissue on the surface of the biomaterial.

[0013] DE 10 2008 045 830 A1 or EP 2 163 143 B1 discloses an apparatus for treating a subject with plasma generated via electrodes and counter-electrodes. A dielectric is arranged between the subject and the electrodes, such that plasma is generated by discharge through a dielectric barrier gas, and this plasma is applied to the subject. According to an embodiment, the electrodes consist of an ionized gas (e.g., a rare gas, an inert gas, or a gas mixture), which is generated by ionizing the gas by applying a high voltage greater than the gas's breakdown voltage, and thus exists as plasma. The gas therefore becomes conductive and can itself be used as an electrode.

[0014] Document US6866082 A discloses a handheld device comprising electrodes for generating a gas discharge in the air between the electrodes and the body part to be treated. The electrodes are configured as a glass body filled with neon, which is electrically coupled to a high-voltage transformer via a foil. Oxygen in the air between the electrodes and the body part to be treated is stimulated to form ozone by a spark generated by the discharge of a capacitor located in the device. The neon-filled glass body provides insulation to the transformer circuitry by allowing the neon gas to escape, thus preventing electric shock in the event of damage caused by glass breakage. Summary of the Invention

[0015] Based on the prior art, the object of the present invention is to provide a therapeutic device that overcomes the shortcomings of the prior art. Specifically, the object of the present invention is to develop a more easily operable therapeutic device whose pulse rate and / or energy output and / or signal form can be individually customized for the desired treatment or therapy by adjusting the pulse rate and / or energy output and / or signal form over a wide range.

[0016] This objective is achieved by the features of claim 1. Advantageous embodiments of the treatment device are the subject of claims 2 to 17.

[0017] A therapeutic device for cell stimulation or cell therapy according to the present invention includes a housing housing electrodes, a generator for generating high-frequency voltage pulses, a processor unit including control, regulation, and calculation modules, a memory unit, at least one operating element, and a controllable modulator by which the generator can be controlled. A voltage pulse sequence comprising multiple voltage pulses can be generated by the modulator, whereby the frequency and duration of the voltage pulses can be adjusted as needed by the modulator. The electrodes, generator, processor unit, memory unit, operating element, and modulator are arranged within the housing. The electrodes comprise a glass body containing a cavity in which gas is contained. The electrodes include a first end that can be coupled to the modulator. The electrodes include a second dome-shaped end, wherein the gas can be induced into a non-thermal primary plasma state by a voltage pulse applied to the electrodes, wherein a secondary plasma can be generated by the ionization of air present near the second end of the electrodes.

[0018] The gas may specifically include inert gases such as helium, neon, and argon. The gas is contained within a glass body, i.e., the gas is enclosed within a cavity of the glass body. The gas is ionized by introducing a voltage pulse, thereby enabling a gas discharge from the electrode to the body site to be treated. The gas forms a primary plasma, which can be generated by applying a voltage, i.e., by transmitting a sequence of voltage pulses. The glass body acts as a dielectric barrier. Secondary plasma can be obtained at a second end of the electrode via the primary plasma, allowing air to be ionized and thus become conductive, and enabling coupling with the body site to be treated. The high voltage generated by the primary plasma exceeds the breakdown voltage, which in particular generates free oxygen or ions in the air surrounding the electrode end, which interact with the surface of the body site to be treated, thereby inducing cell stimulation. The body site forms a cathode. Specifically, a gas discharge occurs to form secondary plasma if the air gap between the cathode and the first end of the glass body is less than 3 mm. According to an embodiment, the electrode may include an antimicrobial coating.

[0019] Plasma is defined as a physical state of matter in which charged particles with both positive and negative charges exist in a gaseous phase. The sum of the positive and negative charges is equal, so they compensate for each other in the volume under consideration, meaning the overall charge state is neutral. Plasma also contains atoms or molecules with neutral charges; however, they can exist in states excited by electrons, vibrations, or rotation, and are therefore called excited-state particles or reactive particles.

[0020] Non-thermal plasma is a plasma in which the temperature describing the distribution of the kinetic energy of electrons in the plasma (hereinafter referred to as the electron temperature) is higher than the temperature describing the distribution of the kinetic energy of ions in the plasma (hereinafter referred to as the ion temperature). If the ion temperature is in the range of 25°C to a maximum of 100°C (and inclusive), then non-thermal plasma is called cold plasma.

[0021] Therefore, the treatment device according to embodiments of the present invention comprises a direct atmospheric cold plasma treatment device. Secondary cold plasma is generated via electrodes containing primary plasma. The generation of secondary cold plasma has the advantage of little or no heating of the body part to be treated. Therefore, the cells of the body part to be treated are not exposed to any unacceptable thermal effects that would otherwise lead to damage to the cells or their components.

[0022] The treatment device responds to touch by varying the intensity of the plasma, allowing the intensity to be altered based on the holding position. The highest intensity was observed in the tests when the device was held close to the opposite ends of the electrodes. In the measurements described below, the device was therefore encased in grounded aluminum foil to eliminate any influence from manual operation of the device on the measurement results.

[0023] According to one embodiment, the generator is designed as a Tesla coil. The voltage provided by the energy storage unit is converted into the generator's input voltage by a modulator. According to one embodiment, the maximum frequency is in the range of 10 Hz to 100 Hz, and includes 100 Hz. According to one embodiment, the maximum voltage at the modulator's output is in the range of 8 V to 65 V, and includes 65 V. The modulator may include a transformer through which the voltage provided by the energy storage unit can be converted into the input voltage required by the generator. According to one embodiment, the voltage at the generator's output is in the range of 5 kV to 25 kV, and includes 25 kV.

[0024] According to an embodiment, a modulator can be used to adjust the frequency or amplitude. The amplitude and / or frequency of the voltage can be modulated by the modulator. According to an embodiment, the frequency of the voltage pulse sequence is at least partially not constant. According to an embodiment, the voltage amplitude increases during the time period t2-t1, remains constant during the time period t3-t2, and decreases during the time period t4-t3, wherein the duration of the voltage pulse sequence corresponds to the time period t4-t1.

[0025] Specifically, the frequency can increase during the time period t2-t1, remain constant during the time period t3-t2, and decrease during the time period t4-t3.

[0026] Therefore, any combination of voltage and frequency can be adjusted by the modulator. Thus, any desired pulse sequence can be adjusted by the modulator. The pulse sequence is transmitted to the generator, where it is converted into a pulse sequence with a correspondingly higher voltage. The high voltage is then applied to the electrodes.

[0027] According to one embodiment, an energy storage unit disposed within the housing is provided to supply power to the operating therapeutic device, enabling wireless operation of the device. The housing may include a display element through which specific therapeutic methods and operational data can be displayed.

[0028] According to an embodiment, the electrode includes a sensor through which current or voltage emitted via the electrode can be recorded as a measurement value, wherein the measurement value can be digitized into measurement data, wherein the measurement data can be stored in a memory unit, and wherein the computing module of the processor unit is configured to determine the time profile of the energy delivered by the electrode and / or the energy emitted by the electrode.

[0029] Specifically, the processor unit's control module is configured to control the modulator based on measurement data, particularly for controlling a constant energy output and / or for signal form-independent control, enabling the generation of any desired signal form, such as a combination of amplitude modulation and frequency modulation, within the generator. The measurement data is configured to control the course of the therapy via the processor unit's control module.

[0030] According to an embodiment, measurement data in the processor unit can be linked to a timestamp, wherein the timestamp-linked measurement data is configured to be stored in a memory unit for storing the process of the therapy.

[0031] According to an embodiment, the housing can be configured as one of the poles of a capacitor for capacitive coupling.

[0032] The energy storage unit can be configured as a rechargeable element, such as a lithium-ion element or a supercapacitor. Specifically, battery charging can be configured to operate the treatment device for a duration of up to 50 minutes. The treatment device can operate continuously for a period of up to 25 minutes. If the energy storage unit is cooled, or if the operation of the treatment device is interrupted for a period of approximately 30 minutes, the operating time can be extended.

[0033] According to an embodiment, the housing includes an inner side containing a conductive or conductive surface, such as conductive plastic or plastic coated with a conductive material. The outer side of the housing is configured as an electrical insulator. Specifically, the housing may contain or be composed of plastic. For example, the housing may contain or be composed of ABS. Specifically for applications in the food industry, the housing may contain or be composed of PLA (polylactic acid).

[0034] The treatment device features an improved signal output that can be configured or pre-programmed by the user depending on the type of therapy. The device is also easier to operate due to its integrated energy storage unit, which enables wireless operation.

[0035] According to the present invention, these advantages can be obtained through at least one of the following features:

[0036] - Variable signal curves, such as the variable frequency of a high-frequency field emitted through electrodes.

[0037] - Controlling the intensity of the delivered energy, thereby generally keeping the delivered power constant and independent of the position and / or type of the electrodes.

[0038] - Operation is improved by an energy storage unit arranged in the casing, which has its own internal power source and is operated by an energy battery, typically a rechargeable battery.

[0039] New, previously unused physical principles in therapeutic applications can facilitate and improve wireless applications. According to one embodiment, capacitive coupling is used, allowing energy from a high-frequency field to flow from the user to the object being treated. In this embodiment, electrodes are capacitively coupled to the user, connecting the user and the object being treated. The capacitive coupling between the user's body and the object ensures potential equilibrium.

[0040] The advantages of this invention, including controllable, programmable energy delivery in the form of adjustable signals, lead to the optimization of various forms of therapy.

[0041] According to an exemplary form of therapy, energy is delivered over a large surface via a variable pulse frequency, while simultaneously modulating the signal form. This influences the concept of the skin effect, as is known to those skilled in the art. Due to the skin effect, most electrons arriving at the treatment subject via a high-frequency voltage emitted through electrodes are forced to the surface of the treatment subject. At lower amplitude and / or frequency modulation (AM / FM), the skin effect is reduced, resulting in more targeted penetration depth and duration of energy delivery.

[0042] Users can change the modulation by activating the control elements of the treatment device and / or by using the treatment device configured according to the type of therapy, which reads the desired modulation from the memory unit.

[0043] In another embodiment, energy output is measured by sensors, such as by measuring voltage and / or current, and the measurement results are fed to a processor unit. The processor unit includes a control module that can be used to control different states according to the treatment method.

[0044] According to an embodiment, the energy output is modulated during modulation in such a way that the energy output follows a signal form that can be independently selected or retrieved from a memory cell.

[0045] According to the embodiments, the energy delivery is stable regardless of the electrodes used, the different coupling factors of the capacitive coupling used wirelessly during therapy, or the form of the modulated signal.

[0046] In another variation, the measured values ​​determined by the sensor can be provided as signals to a processor unit, which can then process the measured values ​​into measurement data. Specifically, the units or measured variables mentioned below can be calculated using a computing module. If needed, these units can be displayed via a display element, output via an interface for information exchange, or stored in a memory unit.

[0047] These units may include at least one element from the following list:

[0048] - The total energy delivered within a given time interval

[0049] - Signal form and modulation type (AM / FM) during therapy

[0050] - The time interval between electrode removal and one or more interruptions

[0051] - Internal energy management regulations

[0052] - Detection of defective electrodes

[0053] Other computations are conceivable, recording and registering the therapeutic progress for each patient. Other computations are also conceivable, including external data read in via an interface, which increments and records the success of the therapy. For this purpose, the processor unit can perform any type of computation, typically control and / or statistical computations.

[0054] The calculation results can then be fed into the control module of the processor unit, influencing the signal curve and / or modulation. Therapeutic data can be used to generate learning effects from earlier treatments for later treatments. This therapeutic data can be transmitted to other treatment devices via an interface for information exchange, thereby ensuring continuous improvement in quality with each use of the treatment device according to the invention.

[0055] Capacitive coupling can be achieved by coupling the user and the object of treatment to a conductive surface on the housing of the treatment device. For this purpose, it is conceivable that the housing itself is designed to be conductive, that is, it has at least one conductive or conductive surface, or that the housing has a conductive or conductive surface internally. The conductive or conductive surface itself can be configured as a wire, surface, or three-dimensional object.

[0056] The energy storage unit can be powered by a charging system. In one variation, this charging system includes a contact plug and can obtain the required energy from a commercial charging station. In another possible variation, the energy storage unit is charged via an inductive circuit mounted in the housing. This inductive circuit forms the secondary coil of a transmission transformer. Therefore, when the treatment device is in the effective field of the charging station, an energy flow can be generated through the primary coil built into the charging station. Such charging systems are now standardly available in the electronics industry. Attached Figure Description

[0057] The invention will be explained in more detail using exemplary embodiments shown in the accompanying drawings. It is shown that:

[0058] Figure 1a : A schematic diagram of the first embodiment of the treatment device.

[0059] Figure 1b : A schematic diagram of the second embodiment of the treatment device,

[0060] Figure 1c : A schematic diagram of the components of the second embodiment of the treatment device.

[0061] Figure 2: Simplified circuit diagram of a known treatment device.

[0062] Figure 3 : Figure 1a A simplified circuit diagram of the treatment device.

[0063] Figure 4a: Possible voltage-time curves for the known treatment device in Figure 2.

[0064] Figure 4b: Curves of possible frequencies of the known treatment device in Figure 2 over time.

[0065] Figure 5a : Figure 3 The possible voltage curve of the treatment device over time,

[0066] Figure 5b : Figure 3 The possible frequency curve of the treatment device over time,

[0067] Figure 6a Used for Figure 1b or Figure 1c The first part of the two-piece outer shell of the treatment device,

[0068] Figure 6b :according to Figure 1b or Figure 1c A view of a first variant of the electrodes used in a treatment device.

[0069] Figure 6c Used for Figure 1b or Figure 1c The second part of the two-piece housing of the treatment device,

[0070] Figure 6d View of the second variant of the electrode.

[0071] Figure 6e View of the third variant of the electrode.

[0072] Figure 6f : Figure 1b or Figure 1c A view of the treatment device.

[0073] Figure 6g The longitudinal section of the fourth variant of the electrode.

[0074] Figure 7 : Passing through it, there are arranged Figure 1b or Figure 1c A partial cross-section of the electrode housing of the treatment device.

[0075] Figure 8a : pass through Figure 6a The radial section of the first part of the outer shell,

[0076] Figure 8b : pass through Figure 6c The radial cross-section of the second part of the outer shell,

[0077] Figure 9 A measuring device used to measure leakage current in patients.

[0078] Figure 10a Graph showing the functional relationship between patient leakage current and the distance of the first treatment device from the cathode.

[0079] Figure 10b : A graph showing the functional relationship between the patient's leakage current and the distance of the second treatment device from the cathode.

[0080] Figure 10c Graph showing the functional relationship between patient leakage current and the distance of the third treatment device from the cathode.

[0081] Figure 10d The functional relationship between temperature profile and the distance between the electrodes and cathode of the second treatment device.

[0082] Figure 11 A measuring device used to determine the composition of secondary plasma generated by a treatment device.

[0083] Figure 12a : A diagram showing the composition of the secondary plasma in the first treatment device.

[0084] Figure 12b : A diagram showing the composition of the secondary plasma in the second treatment device.

[0085] Figure 12c : A diagram showing the composition of the secondary plasma in the third treatment device.

[0086] Figure 13 The spectrum of the third treatment device compared to the first treatment device.

[0087] Figure 14 A measuring device used to determine the reactive substances formed during discharge.

[0088] Figure 15 An exemplary spectrum of the first treatment device determined by FTIR spectroscopy.

[0089] Figure 16 Graph of current measured under HI settings

[0090] Figure 17a Regarding the functional relationship between pH value and treatment time when the first treatment device is set to LO (Lower Flow),

[0091] Figure 17b Regarding the functional relationship between pH value and treatment time when the first treatment device is set to HI,

[0092] Figure 17c Regarding the functional relationship between pH value and treatment time when the second treatment device is in water,

[0093] Figure 17d Regarding the functional relationship between pH value and treatment time when the second treatment device is in NaCl,

[0094] Figure 17e The functional relationship between pH value and treatment time when the first electrode of the third treatment device is in water.

[0095] Figure 17f The functional relationship between pH value and treatment time when the second electrode of the third treatment device is in water.

[0096] Figure 18a For the first treatment device, the functional relationship between the concentration of H2O2 and the treatment time is as follows:

[0097] Figure 18b For the second treatment device, the concentration of H2O2 in the water,

[0098] Figure 18c For the second treatment device, the concentration of H2O2 in NaCl,

[0099] Figure 19 When the first treatment device is in H2O and NaCl, NO2 - The functional relationship between concentration and treatment time.

[0100] Figure 20 : Determine the results of the MTT assay for the cytotoxicity of the first treatment device.

[0101] Figure 21 : Determine the results of the MTT assay for the cytotoxicity of the second treatment device.

[0102] Figure 22a The results of the MTT assay were used to determine the cytotoxicity of the first electrode of the third treatment device.

[0103] Figure 22b The results of the MTT assay were used to determine the cytotoxicity of the second electrode of the third treatment device.

[0104] Figure 23 : An illustration of an agar plate used for testing the inhibition zone of an LSE electrode against Staphylococcus aureus.

[0105] Figure 24 A bar chart showing the results of the inhibition zone test of the LSE electrode against Staphylococcus aureus.

[0106] Figure 25 : An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a first therapeutic device targeting the bacteria Staphylococcus aureus.

[0107] Figure 26 : An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a first therapeutic device targeting the bacteria Staphylococcus epidermidis.

[0108] Figure 27 : An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a first therapeutic device targeting the bacteria Escherichia coli.

[0109] Figure 28 : An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a first therapeutic device targeting the bacterium Pseudomonas aeruginosa.

[0110] Figure 29 : An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a first therapeutic device targeting Candida albicans.

[0111] Figure 30 A bar chart showing the results of tests on the inhibition zones of all microorganisms at the EWC electrode of the first treatment device.

[0112] Figure 31 : An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a second therapeutic device targeting the bacteria Staphylococcus aureus.

[0113] Figure 32: An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a second therapeutic device targeting the bacteria Staphylococcus epidermidis.

[0114] Figure 33 : An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a second therapeutic device targeting Escherichia coli.

[0115] Figure 34 : An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a second therapeutic device targeting the bacterium Pseudomonas aeruginosa.

[0116] Figure 35 : An illustration of an agar plate used for testing the inhibition zone of the EWC electrode in a second therapeutic device targeting Candida albicans.

[0117] Figure 36 A bar chart showing the results of tests on the inhibition zones of all microorganisms at the EWC electrode of the second treatment device.

[0118] Figure 37 : An illustration of an agar plate used for testing the inhibition zone of a third therapeutic device against Staphylococcus aureus.

[0119] Figure 38 : An illustration of an agar plate used for testing the inhibition zone of a third therapeutic device against Staphylococcus epidermidis.

[0120] Figure 39 : An illustration of an agar plate used for testing the inhibition zone of a third therapeutic device against the bacteria Escherichia coli.

[0121] Figure 40 : An illustration of an agar plate used for testing the inhibition zone of a third therapeutic device against the bacterium Pseudomonas aeruginosa.

[0122] Figure 41 : An illustration of an agar plate used for testing the inhibition zone of a third therapeutic device against Candida albicans.

[0123] Figure 42 : A bar chart showing the results of tests on the inhibition zones of all microorganisms in the third treatment device. Detailed Implementation

[0124] Figure 1a A first embodiment of a therapeutic device for cell therapy is schematically shown, including electrodes 1, a generator 3 for generating high-frequency pulses, a processor unit 6 including control, regulation and calculation modules, a memory element 9 and an operating element 5.

[0125] The treatment device may include at least one interface 8 for exchanging information.

[0126] The treatment device also includes a memory unit 9 and a controllable modulator 4 for the control generator 3. The energy supply for operating the treatment device is provided by an internal energy storage unit 10.

[0127] The housing 12 may contain at least one display element 7, through which therapeutic and operational data can be displayed.

[0128] Furthermore, the treatment device includes a sensor 2 that measures the voltage and / or current delivered via the electrode 1, thereby determining the energy delivered via the electrode 1 from the measured voltage or measured current. Therefore, the current and / or voltage delivered through the electrode 1 are recorded as measured values ​​by the sensor.

[0129] The measured values ​​are digitized and stored as measurement data in memory unit 9. The delivered energy can be determined from the measurement data by the calculation module of processor unit 6. The temporal profile of the energy emitted by electrode 1 can be determined by the calculation module of processor unit 6 from the current and / or voltage measurement data stored in memory unit 9 with timestamps. Alternatively, the determined voltage and / or current can also be recorded by a recording device and converted into measurement data, so that the temporal profile of the energy emitted by electrode 1 can be determined from the recorded voltage and current measurement data.

[0130] All components of the treatment device are housed within the outer casing 12.

[0131] Specifically, the housing 12 and / or the generator 3 can be configured such that the housing or the generator forms one pole of a capacitor, which enables capacitive coupling.

[0132] According to an embodiment, the therapy and operational data from the memory unit 9 are configured to be readable and writable. The data stored in the memory unit 9 can be used to influence the course of the therapy.

[0133] According to an embodiment, taking into account the measurement values ​​measured by sensor 2, the therapy and operational data can be calculated and processed into control instructions in processor unit 6, and the measurement values ​​can be stored as data in memory unit. The control instructions can be used to control modulator 4.

[0134] Specifically, modulator 4 can be controlled in such a way that the energy output is constant and independent of the signal form.

[0135] Specifically, modulator 4 can be controlled in such a way that any desired signal form is generated in generator 3; typically, a combination of amplitude and frequency modulation can be provided.

[0136] According to an embodiment, the housing 12 includes a conductive or conductive surface, such as conductive plastic or plastic coated with a conductive material.

[0137] According to an embodiment, the energy storage unit 10 can be configured as a rechargeable element, typically a lithium-ion element or a supercapacitor.

[0138] The energy delivered through electrode 1 can be used for cell stimulation or cell therapy.

[0139] Figure 1b A second embodiment of the treatment device 20 is shown, wherein... Figure 1a The same reference mark is used for parts that are the same or have the same effect.

[0140] The treatment device 20 includes electrodes 1, a generator 3 for generating high-frequency pulses, a processor unit 6 including control, regulation, and calculation modules, operating elements 5 and 15, and an energy storage unit 10. The electrodes 1, generator 3, processor unit 6, operating elements 5 and 15, and energy storage unit 10 are housed in a common housing 12 in the assembled state. Figure 1b The boundary of the system is schematically shown in the diagram.

[0141] The energy supply for operating the treatment device 20 is provided by an energy storage unit 10, also mounted in the housing 12. Specifically, the energy storage unit 10 may comprise a rechargeable battery. According to embodiments, the energy storage unit 10 may comprise a lithium-ion battery or a supercapacitor. The energy storage unit 10 can be charged using a charging device 16, which is known to those skilled in the art and therefore is not described in more detail in this illustration.

[0142] According to this embodiment, the operating elements 5 and 15 are rotatably arranged in the housing 12, which in Figure 1c As can be seen in the schematic diagram. The duration of each pulse can be adjusted using operating element 5. The height of the pulse (i.e., its amplitude) can be adjusted using operating element 15. According to this embodiment, a scale is attached to each of the operating elements 5 and 15, through which the set therapy and operation data can be displayed. In addition, the housing 12 may contain an optical display element, such as an LED light.

[0143] Furthermore, the treatment device includes a sensor 2 that measures the voltage and / or current delivered via the electrode 1, wherein the energy delivered via the electrode 1 can be determined by the measured voltage or the measured current. Therefore, the current and / or voltage delivered via the electrode 1 are recorded as measured values ​​by the sensor. The measured values ​​are digitized and stored as measurement data in the memory unit 9. The delivered energy can be determined from the measurement data by the calculation module of the processor unit 6. The temporal profile of the energy emitted by the electrode 1 can be determined by the calculation module of the processor unit 6 from the measured data of current and / or voltage stored in the timestamped memory unit 9. Alternatively, the determined voltage and / or current can also be recorded by a recording device and converted into measurement data, such that the temporal profile of the energy emitted by the electrode 1 can be determined from the recorded voltage and current measurement data.

[0144] According to an embodiment, taking into account the measurement values ​​measured by sensor 2, the therapy and operational data can be calculated and processed into control instructions in processor unit 6, and the measurement values ​​can be stored as data in memory unit. The control instructions can be used to control modulator 4.

[0145] Specifically, modulator 4 can be controlled in such a way that the energy output is constant and independent of the signal form. Specifically, modulator 4 can be controlled in such a way that any desired signal form can be generated within modulator 4, typically a combination of amplitude and frequency modulation. According to an embodiment, modulator 4 can be configured as a transformer. This transformer is used to generate the voltage required to ionize the gas in the electrode.

[0146] The input voltage of generator 3 can be in the range of 8 V to 65 V, and includes 65 V. The output voltage of modulator 4 is converted by generator 3 into a voltage in the range of, for example, 5 kV to 25 kV (and includes 25 kV). Therefore, the generator includes a high-voltage transformer. According to an embodiment, the high-voltage transformer is configured as a Tesla coil. The high-voltage transformer includes a primary winding for receiving power supplied by the modulator. Therefore, a primary winding voltage exists at the primary winding, for example, in the range of 8 V to 65 V, and includes 65 V. The high-voltage transformer includes a secondary winding at which a secondary winding voltage can be obtained. This secondary winding voltage is greater than the primary winding voltage. The secondary winding of the high-voltage transformer configured as a Tesla coil is arranged concentrically with the primary winding, which allows the high-voltage transformer to be designed in a particularly space-saving manner. The secondary winding voltage can be at least 100 times the primary winding voltage. Specifically, the secondary winding voltage can be 300 to 1000 times the primary winding voltage, and includes 1000 times. According to an embodiment, if the primary winding voltage is 65 V, then the secondary winding voltage is 25 kV. According to this exemplary embodiment, the secondary winding voltage is 385 times higher than the primary winding voltage.

[0147] The voltage pulse generated by modulator 4 is thus converted into a high-voltage pulse in generator 3 and fed to electrode 1, which contains anode 45. Anode 45 is located inside glass body 27. The anode contains a material from which charge carriers, particularly electrons and ions, can be released when a high voltage is applied. These charge carriers reach the gas-filled glass body 27.

[0148] Positively charged charge carriers move along the direction of the cathode 55. According to this embodiment, the cathode 55 is formed from the surface to be treated, as schematically shown. Negatively charged charge carriers move toward the anode. If the negatively charged charge carriers are sufficiently accelerated, they can release additional charge carriers when they strike the anode, which can then enter the internal gas-filled space. When electrons strike gas molecules, ions are generated, which move toward the cathode as positively charged charge carriers. If the applied voltage is in the range of 5 kV to 25 kV, and includes 25 kV, the number of charge carriers in the gas increases avalanche-like, causing the gas to be ionized and forming plasma. In this case, so-called cold plasma is obtained because the electrons are not generated by thermal radiation, but by secondary electrons generated from the contact of charge carriers with the anode material.

[0149] According to the present invention, the cathode 55 is located outside the glass body 27, so the electric field established in the electrode 1 also acts on charge carriers in the air, such as oxygen. The second end 22 of the electrode 1 acts as a dielectric barrier. Specifically, oxygen molecules can be ionized by the applied electric field, thereby forming a so-called secondary plasma. Specifically, when the distance between the cathode and the second end 22 of the electrode 1 is as high as 2 mm, a dielectric barrier discharge can be ignited in the air space.

[0150] In terms of its operating mode, the treatment device 20 corresponds to a capacitor, the first pole of which is formed by a housing 12, and the second pole of which is formed by the body part being treated. The first pole is formed by an electrode 1 containing an anode 45. The second pole is formed by a cathode 55. According to this embodiment, the housing 12 containing the electrode 1 forms one of the poles of the capacitor. During the therapy, a person holding the housing 12 in their hand brings the housing into contact with the opposite pole of the capacitor (the part of the patient's body to be treated), or at least approaches the capacitor in a manner that can form a secondary plasma.

[0151] Figure 1c An exploded view of the housing 12 is shown, in which electrodes 1, generator 3, modulator 4, processor unit 5, and energy storage unit 10 are arranged. The housing 12 contains the aforementioned operating elements 5 and 15.

[0152] According to an embodiment, the housing 12 includes a conductive or electrically conductive surface, such as conductive plastic or plastic coated with a conductive material.

[0153] The energy delivered through electrode 1 can be used for cell stimulation or cell therapy.

[0154] Figure 2 shows a simplified diagram of a treatment device according to EP 2397187 A1. This previously known treatment device is powered by a DC power supply 110 (e.g., a battery). Current flows from capacitor 104 to coil 103, generating an electromagnetic field when the connection to the DC power supply 110 is interrupted by switch 107. According to this embodiment, the coil is a potential-generating element for electrode 101. A potential difference is generated by the coil. Due to the potential difference, a voltage exists at electrode 101. This voltage is transmitted to the patient through electrode 101 in contact with the patient. Diode 106 prevents current from flowing back into the battery circuit. If switch 107 is closed, capacitor 104 can then be charged by battery 110. Since coil 103 acts as a resistor in this circuit, capacitor 104 is charged, and there is no potential difference at electrode 101. Due to the periodic opening and closing of switch 107, the potential difference at electrode 101 can fluctuate between zero and a maximum value that can be generated by the built-in coil 103, making pulsed operation possible. As a result, a pulsed voltage that can be used for therapeutic purposes is generated. When switch 107 is open, the direction of current flowing to the capacitor is opposite to the direction of current flow when switch 107 is closed. When switch 107 is closed, diode 106 prevents current from flowing back into the battery circuit. Therefore, the frequency of the pulse voltage is determined by the switching frequency of switch 107. Thus, a variable frequency pulse voltage can be generated using this treatment device, although the amplitude of the voltage is predetermined by the coil 103 used. The bleed resistor 105, connected in parallel with capacitor 104, is a component used to prevent electric shock when touching the treatment device after the DC power supply has been cut off. Capacitor 104 can be discharged through bleed resistor 105.

[0155] Figure 3 A circuit diagram of the therapeutic device according to the invention is shown in simplified form. The therapeutic device includes a generator 3 configured as a coil, which generates pulsed voltages directed through electrodes 1 to the area of ​​the patient's body to be treated. The pulse frequency and pulse duration can be adjusted by a modulator 4, configured as a switch according to this embodiment. When the switch is closed, a capacitor 13 can discharge through the coil. This means that a voltage is applied to the coil, thereby generating an electromagnetic field that produces a desired therapeutic effect on body cells in its vicinity. The ampere value can be adjusted using a potentiometer 11. As a result, the amplitude of the voltage applied to the coil can be varied.

[0156] As shown in this figure, when the switch is in the off position, no current can flow through the coil, meaning the coil does not generate an electromagnetic field. Capacitor 13 can be charged by energy storage unit 10, i.e., according to this embodiment, by a DC power supply. As in the prior art, the bleeder resistor 14 connected in parallel with capacitor 13 is a component used to prevent electric shock when the treatment device is touched after the DC power supply has been cut off. Capacitor 13 can be safely discharged through bleeder resistor 14.

[0157] Figure 4a shows possible voltage-time curves for the known treatment device shown in Figure 2. The graphical representation in Figure 4a shows the functional relationship between voltage and time, with voltage in volts input on the vertical axis and time input on the horizontal axis. Voltage pulses can be generated using the previously known treatment device by opening switch 107 for a short period and then closing it again, such that current is supplied to the coil as long as the switch is closed, but the current supply is interrupted as long as the switch is open. For example, the switch can be closed for about 1 ms and then opened for 1 ms. As long as the switch is closed, voltage is generated by the current flowing through the coil. As long as the switch is open, no voltage is generated. This means that the time during which the switch is closed corresponds to a voltage pulse. If the switch is opened and closed several times, multiple voltage pulses can be generated, as illustrated in Figure 4a with an example of five voltage pulses. Subsequently, the switch can be opened for a longer period of time. No voltage is generated during this period because no current can flow through the coil. This period can be of any length. If treatment requires, another series of voltage pulses can be generated by opening and closing the switch several times within a short period of time.

[0158] Figure 4b shows the possible frequency response of the known treatment device shown in Figure 2 over time. The frequency, in Hertz, is entered on the vertical axis, and the time is entered on the horizontal axis. Each series of voltage pulses in Figure 4a corresponds to a frequency greater than zero, which is shown as a bar in Figure 4b. No voltage is generated as long as switch 107 is open because no current flows through the coil. Therefore, the frequency during this time period is zero Hertz.

[0159] Figure 5a An embodiment according to the present invention is shown. Figure 3 The possible voltage profile of the treatment device shown varies over time. Figure 5a The graphical representation shows the functional relationship between voltage and time, with voltage in volts input on the vertical axis and time input on the horizontal axis. Voltage pulses can be generated by the treatment device via an actuation modulator 4, for example, by opening the switch for a short period and then closing it again, so that current is supplied to the coil as long as the switch is closed, but the current supply is interrupted as soon as the switch is opened.

[0160] For example, the switch can be closed for approximately 1 ms and then open for 1 ms. The switch can also be open for 0.1 s and closed for 0.1 s. Specifically, the opening time can vary from 0.001 s to 0.1 s, and include 0.1 s. The closing time can also vary from 0.001 s to 0.1 s, and include 0.1 s. As long as the switch is closed, the current flowing through the coil generates a voltage. As long as the switch is open, no voltage is generated. This means that the time during which the switch is closed corresponds to a voltage pulse. If the switch is opened and closed several times, multiple voltage pulses can be generated, which... Figure 5a An example of 13 voltage pulses forming a voltage pulse sequence is shown. The switch can then be open for a longer period of time. No voltage is generated during this time because no current can flow through the coil. This period can be of any length. For example, the period can range from 0.1 s to 10 s, and includes 10 s. Specifically, the period can range from 0.1 s to 1 s, and includes 1 s. According to an embodiment, the time span can be 0.1 s. If treatment requires, at least one additional voltage pulse sequence can be generated by repeatedly opening and closing the switch within a short period of time. Two voltage pulse sequences are shown as examples in... Figure 5a As shown in the image.

[0161] for Figure 5a The given sequence of n voltage pulses shows that the voltage of each pulse increases during the time interval t2-t1 or t6-t5, remains constant during the time interval t3-t2 or t7-t6, and decreases during the time interval t4-t3 or t8-t7. If the time interval during which the switch is on corresponds to the time interval during which the switch is off, then the average pulse duration tm of the n voltage pulses corresponds to (t4-t1) / 2n.

[0162] If the duration ts of each of the n voltage pulses is different from the duration tp of each pause between voltage pulses, then the average pulse duration tm of the n voltage pulses and m pauses can be determined as follows. The duration of the voltage pulse sequence D corresponds to the sum of all tsi and all tpi. The i-th time interval of each of the voltage pulses 1 to n is denoted by tsi. The i-th time interval of each pause from 1 to m is denoted by tpi. The i-th voltage pulse extends, for example, over the time interval tsi, and the (i+1)-th voltage pulse extends over the time interval ts(i+1). For example, the i-th pause has the time interval tpi, and the (i+1)-th pause has the time interval tp(i+1). To obtain the average pulse duration tm, the duration of the voltage pulse sequence D is divided by the number of voltage pulses and pauses (n+m), where n corresponds to the number of voltage pulses and m corresponds to the number of pauses in the sequence of voltage pulses.

[0163] Therefore, according to this embodiment, the amplitude of the voltage pulse changes. Figure 5a The amplitude of the voltage pulse increases during the time period t2-t1. The amplitude of the voltage pulse remains constant during the time period t3-t2. The amplitude of the voltage pulse decreases during the time period t4-t3.

[0164] Figure 5b An embodiment according to the present invention is shown. Figure 3 The possible frequency response of the treatment device shown varies over time. Enter the frequency in Hertz on the vertical axis and the time on the horizontal axis. Figure 5a Each voltage pulse sequence in the sequence corresponds to a frequency greater than zero, which in Figure 5b It is shown as a trapezoid. No voltage is generated as long as the switch is open because no current can flow through the coil. Therefore, the frequency during the time interval between two adjacent voltage pulse sequences is zero Hertz. According to... Figure 5b The frequency of the voltage pulses in the first voltage pulse sequence increases during the time period t2-t1. The frequency of the voltage pulses remains constant during the time period t3-t2. The frequency of the voltage pulses decreases during the time period t4-t3. The frequency of the voltage pulses in the second voltage pulse sequence also increases during the time period t6-t5. The frequency of the voltage pulses remains constant during the time period t7-t6. The frequency of the voltage pulses decreases during the time period t8-t7.

[0165] In this regard, according to Figure 5a The diagram and the basis Figure 5b The illustrations are irrelevant. According to... Figure 5a The duration of the voltage pulse remains constant, therefore the corresponding frequency corresponds to... Figure 5b In the graphical representation, it will be constant.

[0166] according to Figure 5b In the variation shown, the time interval tsi decreases during the time interval t2-t1, remains constant during the time interval t3-t2, and increases during the time interval t4-t3.

[0167] for Figure 5b The second voltage pulse sequence shown has a time interval tsi that decreases during the time interval t6-t5, remains constant during the time interval t7-t6, and increases during the time interval t8-t7.

[0168] Figure 6a The first part 17 of the two-piece housing 12 of the treatment device 20 is shown.

[0169] Figure 6b An embodiment of a first variant of the electrode 1 located within the housing 12 is shown. Therefore, the electrode 1 can be removed from the housing 12 and replaced with another electrode if necessary. The electrode 1 includes a first segment 23 and a second segment 24, the first segment 23 having a length L1 and the second segment 24 having a second length L2. The first segment 23 extends from a first end 21 to a stop element 25. The second segment 24 extends from the stop element 25 to a second end 22 of the electrode 1.

[0170] Figure 6c The second part 18 of the two-piece housing 12 is shown.

[0171] Figure 6d An embodiment of a second variation of electrode 1 is shown. According to... Figure 6d The variant shown has a length L3 of the second segment 24 that is greater than according to Figure 6b The length L2 of the corresponding second segment 24. The length L1 of the first segment corresponds to the length L2 of the second segment 24. Figure 6b The length L1 is because the electrode 1 according to the second variant can be constructed in the housing 12 instead of the electrode 1 according to the first variant.

[0172] Figure 6e An embodiment of a third variation of electrode 1 is shown. According to... Figure 6d The variant shown has a length L4 of the second segment 24 that is greater than according to Figure 6b The length L2 of the corresponding second segment 24 is smaller than the length L3 of the second segment 24 of the electrode according to the second variant. This embodiment also only shows an exemplary configuration. Of course, the length L4 may deviate from this illustration. The length L1 of the first segment corresponds to the length L2 of the electrode according to the second variant. Figure 6bThe length L1 is such that the electrode 1 according to the third variant can be constructed into the housing 12 instead of the electrode 1 according to the first variant. The second end 22 of the electrode 1 is not formed as a rounded tip as shown in the previous embodiment, but includes an end formed as a flange-like protrusion. The electrode 1 is used when the gas discharge is to extend over a larger area on the object to be treated (in this illustration, over a circular area).

[0173] Figure 6f It shows that it contains according to Figure 6a and 6c The outer shell and according to Figure 6b , 6d The treatment device 20 for electrode 1 in one of the variations shown in 6e includes a two-piece housing 12 in which electrode 1 can be disposed. Electrode 1 is replaceable. To replace electrode 1, the first part 17 and the second part 18 of housing 12 can be separated from each other.

[0174] Figure 6g A fourth variant embodiment of electrode 1 is shown, illustrated in longitudinal section. Electrode 1 has a first end 21 configured for coupling to modulator 4. Electrode 1 has a second end 22 configured as a rounded tip. Electrode 1 includes a glass body 27 arranged within retaining element 26 such that at least the second end 22 protrudes beyond retaining element 26. Retaining element 26 extends within a housing to stop element 25 in the assembled state. According to this embodiment, stop element 25 is part of a tapered end section 28. Inside the tapered end section 28 is a support element 29 that supports the glass body 27 within retaining element 26.

[0175] The glass body 27 includes a tapered section 30 extending from the second end 22 to a tapered end section 28. The diameter of the tapered section increases continuously from the second end 22 to the tapered end section 28. In the region of the tapered end section 28, the glass body 27 includes a contraction 31, i.e., its diameter decreases in the region of the tapered end section 28, so as to widen again to a larger diameter in the intermediate section 38 adjacent to the tapered end section 28. The outer diameter of the glass body 27 in the intermediate section 38 may substantially correspond to the inner diameter of the intermediate section 38 of the retaining element 26. The section of the glass body 27, which is substantially cylindrical in design, will hereinafter be referred to as the central section 32.

[0176] The end section 33 of the glass body 27 is adjacent to the central section 32, and the end section includes a groove 34 and a coupling element 36 having a tip 37. The sealing element 35 is located in the groove 34 and rests on the inner wall of the middle section 38 of the retaining element 26.

[0177] A pin element 40 extends from tip 37 to the first end 21 of the electrode. Pin element 40 is connected to conductor element 39, which is conductive, allowing voltage pulses generated by modulator 4 and converted into high voltage by generator 3 to be transmitted to glass body 27 and the gas located therein. Pin element 40 is connected to conductor element 39, which extends from pin element 40 to bow element 41. Conductor element 39 can be configured as, for example, a wire or a sleeve. According to this embodiment, bow element 41 is part of conductor element 39. Pin element 40 and conductor element 39 are electrically insulated from the environment by retaining element 26. Retaining element 26 comprises or is composed of a non-conductive material (e.g., plastic). Conductor element 39 passes through the sheath of glass body 27 and enters the interior of glass body 27, reaching the anode 45 disposed there.

[0178] Furthermore, the pin element 40 is positioned by the positioning element 43 and centered on its axial position, thereby ensuring that the axis of the pin element 40 is aligned with the central axis of the glass body 27, i.e., the pin element 40 and the glass body 27 are arranged coaxially. The sleeve 39 is located inside the end section 44 of the retaining element 26 adjacent to the groove 42. An annular cavity is formed between the sleeve 39 and the end section 44.

[0179] Figure 7 A partial cross-section of the treatment device 20 is shown, wherein, according to Figure 6g The electrode 1 is housed within the housing 12. The electrode 1 is held within the housing 12 by a snap-fit ​​connection 19. The end of the housing 12 is positioned on a stop element 25, thereby holding the electrode 1 in the desired position within the housing.

[0180] exist Figure 7 An embodiment of the electrical coupling between electrode 1 and generator 3 is also shown, the generator specifically being configured as a Tesla coil. Generator 3 includes a connecting element 56 that contacts pin element 40. Pin element 40 contains a conductive material such that the high voltage generated by generator 3 can be transmitted through pin element 40 to conductor element 39 leading to anode 45. A spring element may be provided to ensure contact between pin element and terminal element 56.

[0181] Figure 8a A radial section is shown passing through the first portion 17 of the housing 12, which is along... Figure 6a The section is cut off by a plane marked AA. The first portion 17 is provided with an edge 73, which is configured to rest on the shoulder 83 of the second portion 18. Edge 73 extends from a first end 71 of the first portion 17 to a second end 72 of the first portion 17, see also... Figure 6a .

[0182] Edge 73 includes at least one recess located between the first end 71 and the second end 72, the recess being in Figure 6a It is not visible because it is located inside the shell.

[0183] Figure 8b A radial section is shown passing through the second part 18 of the housing 12, which is along... Figure 6c The section 83 is cut from the plane marked BB. The shoulder 83 extends from the first end 81 of the second segment 18 to the second end 82 of the second segment 18. See also... Figure 6c .

[0184] The second segment 18 includes an annular element 84 at its second end 82, which is configured to receive the second end 72 of the first portion 17. In the assembled state, the electrode 1 is housed within the annular element 84.

[0185] According to this embodiment, the second portion 18 includes a latching element 85 at its first end, which is configured to be received in a corresponding recess in the first portion 17. The recess is located at the first end 71 of the first portion 17 on the inner side of the end wall. Figure 6a Invisible in the middle, and in Figure 8a It is also not visible in the middle because it is located in front of the cross-sectional plane; that is, in this diagram, it belongs to... Figure 8b The cut section.

[0186] Figure 8b The cross-sectional plane passes through the receiving opening of the charging device 16, which can be detachably connected to the lower side of the second part. Electrode 1, modulator 4, generator 3, processor unit including control, regulation, and calculation modules, optionally memory unit 9, and associated connections and wiring are located on the side of the second part 18 opposite to the receiving opening 86. Figure 1b Or illustrated schematically in 1c.

[0187] The first part 17 and the second part 18 can also be secured by a threaded connection. For this purpose, the first part includes a socket 77 with a threaded hole (not shown) that aligns with the socket 87 of the second part 18 when the first part 17 and the second part 18 are assembled to form the housing 12.

[0188] exist Figure 8bIn the middle, an additional recess 88 is provided immediately adjacent to the shoulder 83. A hook-shaped protrusion 89 abuts this recess 88. In the assembled state, the hook-shaped protrusion 89 engages in a corresponding recess 79 of the first part 17. Thus, the hook-shaped protrusion 89 snaps into the corresponding recess 79, resulting in the first part 17 covering the second part 18 at the connection point, thereby forming a double wall at the connection point, with a small air gap remaining between the double walls. Surprisingly, this thus achieves better protection against voltage at the connection line, ensuring that the operator of the device is not exposed to any danger from the applied voltage.

[0189] When operating the treatment device according to any embodiment, the amplitude of the voltage pulses can be adjusted via operating elements 5 and 15, and the frequency of the voltage pulses can also be adjusted. According to the embodiment, the voltage amplitude can vary within a range of 1 to 9. The frequency can range from 10 pulses per second to 100 pulses per second (and inclusive). Therefore, when amplitude 9 and 100 pulses per second are selected, the highest power setting is obtained. In the following measurement examples, the highest power setting is represented by HI. Therefore, when amplitude 1 and 10 pulses per second are selected, the lowest power setting is obtained. In the following measurement examples, the lowest power setting is represented by LO.

[0190] The ampere number of the pulses was recorded using a Teledyne Le Croy Waverunner 8254M oscilloscope with a voltage ratio of 10:1 across a 100 Ω resistor placed between the cathode and ground (Teledyne Le Croy, PP024). The optimal distance D between the plasma source and the cathode was 1 mm to 2 mm, including 2 mm, with the cathode formed as a copper element. For this distance, the amplitude varied between 10 pulses / s and 100 pulses / s. The pulsed current was stable and conformed to the treatment device specifications under all settings. Figure 16 In (Measurement Example 4), the voltage recording process lasted for a period of approximately 200 μs.

[0191] The effect of amplitude adjustment on the stability of the plasma source was investigated. For this purpose, the frequency of discharge peaks in the range of 10 Hz to 100 Hz (and inclusive) was examined using an oscilloscope. Analysis of the current pulses showed that, at the HI setting (amplitude 9 V, 100 pulses / s), there were up to 12 discharges per voltage pulse. The discharge operation was most stable at the highest frequency and amplitude of 100 Hz. Figure 16 As shown in the image.

[0192] Measurement Example 1

[0193] The patient leakage current (I) is determined according to the measurement specifications in DIN EN 60601-1 [2]. The measuring device is in... Figure 9 It is shown schematically in the middle. Figure 9 The circuit shown illustrates a low-pass filter describing the electrical response of the human body, with particular consideration given that higher frequency currents are classified as less harmful. Because the treatment device 20 is configured as a wireless device, it can only measure alternating current. Therefore, it will contain... Figure 9 The RC components of the circuit shown are connected to a Fluke 116 True RMS multimeter to determine the patient leakage current. The measuring device consists of an optical support to ensure that the planes between the cathode 55 and the second end 22 of the electrode 1, which forms the tip of the plasma source, are parallel. A micrometer screw is used to precisely set the distance. Therefore, the patient leakage current is measured as a function of the distance D between the second end 22 of the electrode 1 and the cathode 55, which is configured as a copper plate. The patient leakage current should not exceed a maximum value of 100 μA so that the therapeutic device can be used for medical purposes. The maximum (▼), minimum (▲), and average (●) values ​​of the patient leakage current are recorded for a period of 10 seconds. It is assumed here that the maximum value plays a decisive role in assessing the suitability for medical use.

[0194] according to Figure 10a The patient leakage current of the first treatment device (TV1) is plotted on the vertical axis in [μA], and the distance D between the second end 22 of electrode 1 and the copper plate forming the cathode 55 is plotted on the horizontal axis in [mm]. Figure 10a The limit of 100 [μA] was not reached at any distance, even at the maximum possible setting. The maximum value reached at a distance of 1.5 mm was 12 [μA]. Filament and stable air plasma were generated in the range of 0 mm to 3 mm. At greater distances, no plasma was formed, although patient leakage current was identified. For the lowest setting (LO), no patient leakage current was detected at all.

[0195] Figure 10bThe patient leakage current of the second treatment device (TV2) is shown. For this treatment device, the maximum, minimum, and average values ​​of the patient leakage current were recorded for a period of 10 seconds at an ambient temperature of 23°C and a relative humidity of 45%. The treatment device (TV2) shows the audible and measurable changes in the plasma as a function of the applied voltage. To achieve the highest intensity, the treatment device was encased in grounded aluminum foil. The maximum measurement duration for a single charge of the energy storage unit was 25 minutes. In the case of two charges, failure began to occur after approximately 50 minutes of operation, during which the casing temperature of the second treatment device (TV2) reached a maximum of 43°C. In the case of operation exceeding 50 minutes, the increase in operating temperature may lead to failure in the processor unit, which may partially impair the operation of the treatment device's control module, regulation module, or computing module. Therefore, additional measurements were performed after a cooling phase of approximately 30 minutes following two charging cycles.

[0196] The second treatment device (TV2) never reached a patient leakage current of 100 μA. The maximum patient leakage current was 11 μA. A stable secondary cold plasma was generated in air when the distance D between the second end 22 of electrode 1 and cathode 55 was 0 mm to 3 mm and included 3 mm. The discharge frequency decreased at distances greater than 2 mm, thereby reducing the patient leakage current. For the second treatment device (TV2), the plasma could not be detected visually or audibly at distances D > 3 mm, although a low patient leakage current was measured.

[0197] Figure 10c The patient leakage current of a third treatment device (TV3) including an LSE electrode is shown. For this treatment device, the maximum, minimum, and average values ​​of the patient leakage current were recorded for a period of 10 seconds at an ambient temperature of 23°C and a relative humidity of 49%.

[0198] The third treatment device (TV3) never reached a patient leakage current of 100 μA. The maximum patient leakage current was 23.5 μA when the LSE electrode was in contact with the cathode. A stable secondary cold plasma was generated in the air between the second plate-shaped end 22 of the LSE electrode 1 and the cathode 55 at a distance D of 0 mm to 3.5 mm and including 3.5 mm. The discharge became discontinuous at longer distances, although small patient leakage currents were measured.

[0199] Figure 10dThe temperature, expressed in degrees Celsius, varies with the distance D from the cathode to the electrode. Distance D is plotted on the horizontal axis, and temperature on the vertical axis. The room temperature at the time of measurement was 23°C, with a relative humidity of 51%. For the second treatment device (TV2), the highest measured temperature was 30 degrees Celsius. The temperature limit of 40 degrees Celsius was never reached.

[0200] Measurement Example 2

[0201] Optical emission spectroscopy (OES) is used to determine the spectral composition of optical plasma radiation. The corresponding measurement apparatus is... Figure 11 The diagram is schematically shown. Optical emission spectroscopy was performed in the ultraviolet (UV), visible (VIS), and near-infrared (NIR) regions using a calibrated AvaSpec 3648-USB2 120 fiber optic spectrometer from Avantes, Apeldoorn, NL, Netherlands. A cosine corrector 121 was used to determine plasma emission in order to increase the opening angle. To prevent the cosine corrector from direct contact with the plasma, a quartz window 122 (d = 2 mm) was attached to the electrode-facing side; this quartz window is transparent for wavelengths greater than 200 nm.

[0202] The supports required for the measuring device and the first, second and third treatment devices (TV1, TV2, TV3) have been omitted in this diagram.

[0203] Grounding wire 123 serves as cathode 55. Due to the small diameter of the wire (0.1 mm), wire 123 barely covers the plasma source. The distance D between the second end 22 of electrode 1 and cathode 55 is approximately 1.5 mm, as this value corresponds to the highest patient leakage current. Five spectra were recorded, and each spectrum was then analyzed using an integration time of 30 s. For medical applications, UV irradiance is of particular interest. The spectral irradiance E(λ) was measured in two ranges: UV-A (315–380 nm) and UV-B (280–315 nm). No emission was detected in the UV-C range (200–280 nm).

[0204] Figure 12a The complete spectrum of the first treatment device (TV1) is shown, which is determined by averaging five consecutive spectra, with each spectrum recorded for 30 seconds. Figure 12a The scale on the left-hand vertical axis is for the treatment device (TV1). The spectrum of the treatment device (TV1) shows the emission of neon (Ne) and nitrogen (N2). The measurements were performed at an ambient temperature of 22.7°C and a relative humidity of 61%.

[0205] Figure 12b The spectrum of the second treatment device (TV2) is shown. Measurements were taken at an ambient temperature of 23°C and a relative humidity of 50%; otherwise, measurements were taken in the same manner as the first treatment device (TV1).

[0206] Figure 12c The spectrum of the third treatment device (TV3) is shown. Measurements were taken at an ambient temperature of 22.5°C and a relative humidity of 48%; otherwise, measurements were taken in the same manner as for the first treatment device (TV1).

[0207] Figure 13 The spectrum of the third treatment device (TV3) compared to the first treatment device (TV1) is shown. Compared to (TV1), neon emission is higher, but nitrogen emission is lower. This can be explained by the larger area of ​​luminescent neon inside the LSE electrode. Through the electrodes of the first treatment device (TV1), focused discharge can occur on the cathode due to the geometry and the correlated amplification of the electric field at the second end designed as a tip. In contrast to (TV1), the discharge occurs at different locations on the grounding wire. Due to the position of the wire, the plasma cannot be fully recorded, hence the higher nitrogen emission of the first treatment device (TV1). Irradiance in the UV-A and UV-B ranges, and the effective irradiance of the third treatment device (TV3) at the measurement point with the highest intensity, are compared to the values ​​of the first treatment device (TV1). The irradiance levels are relatively low, as the spectrum has already indicated. The maximum daily treatment duration tmax is very high, approximately 1 hour. However, the UV-B value and effective irradiance intensity are higher than those of the first treatment device (TV1). This may be related to the higher neon emission, but measurements in the weighted region below 300 nm may also be affected by significant noise.

[0208] The International Commission on Non-Ionizing Radiation Protection has published a method for determining effective irradiance because different wavelengths cause different levels of harm to human skin. The spectral weighting function S(λ) must be multiplied by the spectral irradiance E(λ) and integrated over the entire UV range from 200 nm to 380 nm to calculate the effective irradiance E according to the following formula. eff :

[0209]

[0210] Maximum daily exposure time t max D can be used according to the following formula. max =3 mJ / cm 2 The maximum daily dose, from the effective irradiance E effcalculate:

[0211] t max = D max / E eff

[0212] The UV-A and UV-B irradiance levels and effective irradiance E of the first, second, and third treatment devices (TV1, TV2, TV3) eff As shown in Table 1 below, irradiance levels are relatively low, as already indicated in the spectrum. There is no significant emission in the UV-C range. The maximum daily treatment duration is very high at 6 hours for the first treatment device and 5 hours for the second treatment device.

[0213]

[0214] Table 1

[0215] Measurement Example 3

[0216] In the third measurement example, FTIR spectroscopy was performed, therefore Fourier transform infrared absorption spectroscopy, hereinafter referred to as FTIR. FTIR is used to qualitatively and quantitatively determine the composition of reactive substances formed during discharge. Absorption in the infrared range (corresponding to the excitation of molecular vibrations and rotations) is a characteristic feature of heteronuclear molecules (e.g., various nitrogen oxides or ozone). This determination is made by measuring the background radiation intensity I0 and the radiation intensity I after sample absorption, both of which depend on the wavenumber ν. This allows the absorption coefficient A to be determined, where... For each substance i, the absorption coefficient A is affected by the length of the optical path, as well as the density n and the absorption cross section σ (which depends on the wavenumber). Plasma chemistry involves a complex network of reactions occurring at different timescales, so the composition of the substance is variable during discharge and converges to a steady-state mixture of long-lived components in the afterglow. Figure 15 The measurement results shown are related to the static state.

[0217] Figure 14A measuring apparatus for performing FTIR spectroscopy is shown. Gas processed by the treatment device 20, supplied to container 125 through indoor air inlet 126, is collected in gas collection chamber 127 and drawn into multi-pass absorption chamber (MPC) 128, which is connected to a Bruker Vertex 80V spectrometer 129. MPC 128 has an optical path length L of 32 m, thus allowing measurement of the low density n of the absorbed substance. Vacuum pump 130 allows indoor air to be introduced into container 125 and MPC 128. A pressure of 100 mbar is obtained in MPC 128 by vacuum pump 130 and by throttling the inflow through throttling valve 131. The highest performance combination (HI) and lowest performance combination (LO) of the corresponding treatment device 20 are measured. For all measurements, the air flow rate is 30 l / h and is measured and checked by an Omega SMA66C flow meter.

[0218] The grounded cathode 55 is placed in the container 125 at a distance D = 1 mm from the second end 22 of the electrode 1 of the treatment device 20.

[0219] Measurements covered a wavenumber range from 700 cm⁻¹ to 4000 cm⁻¹, with a resolution of 0.2 cm⁻¹. -1 It allows the detection of typical species of atmospheric cold plasma, namely O3, NO, NO2, N2O, N2O5, HNO3, HNO2, and H2O2. Changes in the concentrations of CO2 and H2O in indoor air were also recorded.

[0220] Figure 15 An exemplary spectrum of the first treatment device (TV1) is shown, with reference spectra inserted for the identified species O3, N2O, and NO2. Other absorption peaks are associated with CO2 and H2O, or with other absorption bands of the identified species. Figure 15 Plotting [cm] on the x-axis −1 Wavenumbers were plotted in units of λ, and the absorption coefficient A was plotted on the ordinate. Measurements were performed at 100 mbar at room temperature of 24°C and 55% relative humidity. At the maximum power (HI) setting on the treatment device, the airflow rate reached 30 l / h.

[0221] Specifically, the concentrations of long-lived oxygen and nitrogen species (RONS) generated by the treatment device were measured using FTIR spectroscopy. These species are considered one of the key mechanisms for achieving the desired therapeutic effect in medical applications. Reliable identification and accurate quantification of RONS are essential for compliance with DIN SPEC 91315. O3, N2O, and NO2 were measured as the species with the highest concentrations. Since the concentrations of N2O and NO2 were already in the range of 1 ppm, i.e., at the low end of the measurable range, it was no longer possible to reliably identify other species with even lower concentrations. The concentration of O3 was 15 ppm ± 4 ppm. The concentration of N2O was 1 ppm ± 0.05 ppm, and the concentration of NO2 was 2 ppm ± 0.5 ppm. These values ​​were determined for the highest power setting (HI) of the treatment device 20. No emission was detected for the lowest power setting (LO).

[0222] Measurement Example 5

[0223] To identify chemicals in the liquid phase for the treatment device, a saline solution was prepared in a 24-well titration plate consisting of 500 μl of water and 500 μl of NaCl salt solution. The second end 22 of electrode 1 was vertically positioned at a distance of 1 mm to 2 mm (including 2 mm) above the liquid surface. Plasma treatment was applied directly to the liquid surface for 10 s, 30 s, 60 s, 180 s, and 300 s.

[0224] To determine stability and compare reactive oxygen species (ROS) generated by the seven electrodes, H₂O₂ enrichment was determined immediately after plasma contact. Chemical parameters were also determined immediately after plasma contact.

[0225] The pH value was determined using the HANNA edge blu pH meter (Hanna Instruments) based on the glass electrode in water and NaCl.

[0226] Figure 17a The diagram illustrates the function of pH value (plotted on the vertical axis) versus the selected measurement duration (plotted on the horizontal axis) for the first treatment device (TV1). Here, for the LO setting of the treatment device (TV1), the measurements are determined for treatment durations of 0 s (reference), 10 s, 30 s, 60 s, 180 s, and 300 s. The left-hand column (black) corresponds to the pH value of H2O, and the corresponding right-hand column (gray) corresponds to the corresponding value of NaCl. For the LO settings of H2O and NaCl, the pH reading remains substantially constant, i.e., the pH reading does not change with increasing treatment time.

[0227] Figure 17bThe diagram illustrates the relationship between pH value (plotted on the ordinate) and the selected measurement duration (plotted on the abscissa) for the first treatment device (TV1). For the HI setting of the treatment device (TV1), the measurements were determined for treatment durations of 0 s (reference), 10 s, 30 s, 60 s, 180 s, and 300 s. The left-hand column (black) corresponds to the pH value of H2O, and the corresponding right-hand column (gray) corresponds to the corresponding value of NaCl. With increasing treatment duration, the pH values ​​of both H2O and NaCl decrease under the HI setting; that is, acidification in both liquids increases with increasing treatment duration. The acidification in both liquids is related to treatment duration: for H2O, the pH value decreases from 5.57 to 3.78, and for NaCl, the pH value decreases from 5.73 to 3.66.

[0228] Figure 17c The diagram shows the relationship between pH value (plotted on the vertical axis) and the selected measurement duration (plotted on the horizontal axis) when the treatment device (TV2) is in water. The measurements were determined for treatment durations of 0 s (reference), 10 s, 30 s, 60 s, 180 s, and 300 s.

[0229] Figure 17d The diagram shows the relationship between pH (plotted on the ordinate) and the selected measurement duration (plotted on the abscissa) when the treatment device (TV2) is in NaCl. The measurements were determined for treatment durations of 0 s (reference), 10 s, 30 s, 60 s, 180 s, and 300 s.

[0230] The pH values ​​measured by the second treatment device (TV2) decreased for both H2O and NaCl with increasing treatment duration, indicating increased acidification in both liquids with increasing treatment duration. The acidification in both liquids was related to treatment duration: for H2O, the pH reading decreased from 5.46 (+ / - 0.148) to 3.51 (+ / - 0.03), and for NaCl, the pH reading decreased from 5.87 (+ / - 0.3) to 3.44 (+ / - 0.04).

[0231] Figure 17e The diagram shows the relationship between pH value (plotted on the ordinate) and the selected measurement duration (plotted on the abscissa) for a treatment device (TV3) with the first electrode in water. Here, the measurements were determined for treatment durations of 0 s (reference), 10 s, 30 s, 60 s, 180 s, and 300 s. The pH value in the water decreased with increasing treatment time, indicating acidification. The average pH value decreased from 6.92 to 3.98.

[0232] Figure 17f The diagram shows the relationship between pH value (plotted on the ordinate) and the selected measurement duration (plotted on the abscissa) for a treatment device (TV3) with the second electrode in water. Measurements were determined for treatment durations of 0 s (reference), 10 s, 30 s, 60 s, 180 s, and 300 s. The pH value in the water decreased with increasing treatment time, indicating acidification. The average pH value decreased from 7.15 to 4.37.

[0233] Use commercially available Amplex Red reagent (10-acetyl-3,7-dihydroxyphenoxazine, molecular formula C). 14 H 11 NO4 (CAS name / number: 10H-phenoxazine-3,7-diol, 10-acetyl-119171-73-2, molecular weight 257.25) was used to determine the H2O2 concentration of the first and third treatment devices (TV1, TV3) by photometric sampling. Color reactions indicated the presence of H2O2. Absorption was photometrically quantified at 535 nm using an Infinite® M200 PRO Tecan microplate photometer. Four measurements (n=4) were performed for the HI and LO settings of the treatment device (TV1), except for electrode comparisons, where only one HI setting was used for n=3.

[0234] Figure 18a The graph shows the total concentration of H2O2 in [μM] plotted on the vertical axis as a function of treatment duration plotted on the horizontal axis. Only measurements were recorded at the HI setting of the first treatment device (TV1). For the LO setting, the H2O2 concentration was below the detection threshold and outside the minimum standard point. The left bar (black) corresponds to the H2O2 value of H2O, and the corresponding right bar (gray) corresponds to the corresponding H2O2 value of NaCl.

[0235] For both H₂O and NaCl, the total concentration increased with increasing treatment duration. After 10 s, the concentration of H₂O₂ in the water was 3 μM with a standard deviation of 0.1 ppm, reaching 44.35 μM with a standard deviation of 1.51 ppm after 300 s. After 10 s, the concentration of H₂O₂ in NaCl was 2.58 μM with a standard deviation of 0.08 ppm, reaching 42 μM with a standard deviation of 1.43 ppm after 300 s. The concentration in NaCl appeared lower than in the water, but the deviation remained within the standard deviation range.

[0236] Figure 18bThe diagram shows the relationship between the concentration of H2O2 in [μM] plotted on the ordinate and the treatment duration plotted on the abscissa for the second treatment device (TV2) in water. For the second treatment device, the H2O2 concentration was determined using a photometric assay series based on titanium oxysulfate (IV) (TiOSO4). TiOSO4 reacts in the presence of H2O2 to form a yellow-orange complex. Absorption was photometrically quantified at a wavelength of 407 nm using an Infinite® M200 PRO Tecan microplate photometer. Measurements were performed four times (n=4). The concentration was determined based on a standard curve of H2O2 at different dilutions. For very short exposure times (0 s, 10 s), these values ​​are below the detection limit and are therefore not included in the calculations or in Table 2.

[0237]

[0238] Table 2

[0239] In both water and NaCl, the concentration increased with increasing treatment duration. After short treatment durations of 10 s or 30 s, the H₂O₂ concentration was within the detection limit of the experimental setup (< 5 μM). Therefore, for treatment durations > 60 s, the standard deviation was higher. At a treatment duration of 300 s, the maximum concentration in water (81.04 μM) was higher than the maximum concentration in NaCl (51.17 μM).

[0240] Figure 18c The diagram shows the relationship between the concentration of H2O2 in [μM] on the vertical axis and the duration of treatment on the horizontal axis for the second treatment device (TV2) in NaCl.

[0241] For the first electrode of the third treatment device (TV3), in water, the concentration of H2O2 in [μM] was plotted as a function of the treatment duration plotted on the x-axis, and the concentration of H2O2 for the second electrode of the third treatment device was also plotted. Depending on the treatment duration, both electrodes were rich in H2O2, resulting in a concentration of 30 μM (1.015 ppm) for the first electrode and 18.34 μM (0.624 ppm) for the second electrode after a treatment duration of 300 s.

[0242] Nitrite and nitrate were determined using colorimetric reagents (Griess assay; Caymentchemicals) and microtiter plates. To measure the total nitrate / nitrite concentration, in the first step, nitrate was converted to nitrite using nitrate reductase, and in the second step, nitrite was converted to a deep purple azo compound by adding Griess reagent, where nitrite was determined in the absence of nitrate reductase conversion. Standard curves for both compounds were included in the test procedure. The accurate concentrations of nitrite and nitrate were determined by photometric measurements of the absorption coefficients at a wavelength of 540 nm using an Infinite® M200 PRO Tecan microplate spectrophotometer. Measurements were repeated twice for the first treatment device (TV1), where n=3, and twice for the second treatment device (TV2), where n=5.

[0243] Figure 19 The figure shows NO2 in [μM] plotted on the vertical axis for the first treatment device (TV1). - and / or NO3 - The total concentration is relative to the treatment duration plotted on the horizontal axis. Only measurements were recorded at the HI setting of treatment device 20; for the LO setting, NO2... - and NO3 - The concentration was below the detection threshold and outside the minimum standard point. Figure 19 In the middle, the left column (gray) corresponds to NO2 in H2O. - The measured values, and the corresponding right column (black) corresponds to NO3 in H2O. - The measured value for NO2. - and NO3 - The total concentration increases with increasing treatment duration. Therefore, the concentration curve set by HI shows the concentration of nitrate (NO3) in water. - ) and nitrite concentration (NO2) - The increase in nitrite depends on the duration of treatment. The proportion of nitrite in water is lower than the proportion of nitrate.

[0244] exist Figure 19 In the middle, the left column (black) corresponds to NO2 in H2O. - The measured values, and the corresponding right column (gray) corresponds to NO2 in NaCl. - The measured value. For NO2 in water. - NO2 in NaCl - The total concentration increases with increasing treatment duration. Therefore, the concentration curve set by HI shows the nitrite (NO2) concentration in water and NaCl. -The increase in nitrite depends on the duration of treatment. The concentration of nitrite appears to be lower in water than in NaCl.

[0245] Measurement Example 6

[0246] As described in DIN SPEC 91315, cytotoxicity was determined using the adherent skin fibroblast cell line GM00637 via an MTT assay (MTT determination). The yellow, water-soluble 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was converted to a blue-violet formazan, and the absorbance was monitored to determine cell viability. Absorbance was recorded at 550 nm using an Infinite® M200 PRO Tecan microplate spectrophotometer.

[0247] Cells were obtained from the Coriell Institute (Camden, New Jersey, USA) and stored in DMEM High Glucose w / L Glutamine (Corning®) medium containing 10% fetal bovine serum (FBS; Biochrome AG, Berlin, Germany) and supplemented with 1% penicillin / streptomycin (Corning®). Cultures were stored at 37°C and 5% CO2.

[0248] The day before processing, 0.5 × 10⁻⁶ ppm was added to each microtiter plate. 5 Cells were applied to a 24-well titration plate and seeded as described above. The number and volume of cells used were adapted to the 24-well titration plate according to DIN SPEC 91315, corresponding to the size of the plasma source in the treatment device.

[0249] Prior to plasma treatment, cell culture medium was removed, cells were washed twice with phosphate-buffered saline (pH 7.4), and covered with 150 μl of PBS. Cells were exposed to the plasma source for 10 s, 30 s, 60 s, 180 s, and 300 s (measured in triplicate). Untreated cells served as a control. Immediately after point plasma treatment, i.e., no more than 5 minutes after plasma treatment, 450 μl of fresh DMEM containing 13% FBS was added to each well (indentation). The cell culture plates were incubated for 48 hours. Subsequently, the supernatant medium was replaced with fresh DMEM containing 15 μl of MTT solution (5 mg / ml in PBS) and 10% FCS.

[0250] After 2 h, the MTT medium solution was removed, and the cells were washed twice with PBS, followed by the addition of 300 ml of cell lysis solution (DMSO / pure acetic acid / SDS). Finally, the uptake coefficient was monitored, and cytotoxicity was determined relative to a 100% untreated control. The IC-50 time, corresponding to 50% cell viability, was calculated.

[0251] Figure 20 The results of the MTT assay for the first treatment device (TV1) are shown, with treatment duration plotted on the x-axis and cytotoxicity as a percentage (%) plotted on the y-axis. Cells tolerated the plasma treatment well. After an exposure period of 300 s, cell viability remained at 65.5%, indicating that the IC-50 time of the treatment device was above 300 s. For all other treatment durations, viability was approximately 90%, with a slight decrease in viability as treatment time increased.

[0252] Figure 21 The results of the MTT assay for the second treatment device (TV2) are shown. The room temperature was 22.1°C, and the average relative humidity was 56.6% (range 51% to 60.3% and inclusive). Treatment duration is plotted on the x-axis, and cytotoxicity in percentage (%) is plotted on the y-axis. Cell viability decreased with increasing treatment duration, consistent with the increase in cytotoxicity with increasing plasma exposure duration. The calculated IC-50 time for the second treatment device was 65.14 s. After the longest treatment duration of 300 s, only an average of 26.5% of cells remained viable. The standard deviations for treatment durations of 60 s, 180 s, and 300 s were relatively high, >10%.

[0253] Table 3 shows the formation Figure 21 Basic measurement results:

[0254]

[0255] Table 3

[0256] The results of the MTT test of the first and second electrodes of the third treatment device (TV3) were as follows: Figure 22a and 22b The values ​​are shown in the figure. Treatment duration is plotted on the x-axis, and cytotoxicity as a percentage is plotted on the y-axis. After the longest treatment duration, cell viability decreased to 53.59% (+17.22%) for the first electrode and to 65.28% (+12.05%) for the second electrode. The IC-50 time was greater than 300 s for both electrodes.

[0257] Measurement Example 7

[0258] According to DIN SPEC 91315:2014-06, the antimicrobial efficacy of plasma sources in the form of LSE electrodes was determined using inhibition zone assays. Staphylococcus aureus DSM 799 / ATCC 6538 and Staphylococcus epidermidis DSM20044 / ATCC 14990 (DSM German Collection of Microorganisms and Cell Cultures; ATCC American Type Culture Collection) were used for measurements. Escherichia coli K-12 DSM 11250 / NCTC 10538 (NCTC National Collection of Type Cultures) was used for additional measurements. Pseudomonas aeruginosa DSM 50071 / ATCC 10145 was used for additional measurements. Candida albicans DSM1386 / ATCC 10321 was used for additional measurements.

[0259] For testing using the LSE electrode, 100 μl of Staphylococcus aureus bacteria (with a cell count of approximately 10) was used. 6 A solution ( / ml - colony forming units / ml) was distributed on a moist solid medium (soy casein digested agar, Carl Roth GmbH & Co. KG, Karlsruhe, Germany) and selectively treated using a plasma source-LSE electrode. Treatment times were 1 min, 2 min, 3 min, 4 min, or 5 min, with growth inhibition zone tests performed on the moist agar surface (N=6). The distance between the plasma source and the surface of the moist solid was approximately 1.5 mm. The cathode was located below the agar plate.

[0260] After incubating 84 mm diameter agar plates at 37°C, the dimensions of the growth inhibition zone were measured in mm, where the growth inhibition zone was defined as the area where no visible microbial growth was observed. If the growth inhibition zone was not circular, the average diameter was determined by measuring the maximum and minimum diameters. For comparison, agar plates were inoculated but without plasma treatment. Their conditions at times t=0 min to t=5 min are shown in the figure. Figure 23 middle.

[0261]

[0262] Table 4a

[0263]

[0264] Table 4b

[0265]

[0266] Table 4c

[0267] Therefore, treating the agar plates inoculated with bacteria as described above with the plasma source of the LSE electrode of the treatment device resulted in a growth inhibition zone for Staphylococcus aureus. The size of the zone depended on the treatment duration. In each case, six agar plates were treated with the plasma source for 1 min, 2 min, 3 min, 4 min, and 5 min. Figure 23 An exemplary instance is shown in the figure.

[0268] Figure 24 It is a graphical representation of the mean (MV) and the corresponding standard deviation (SD) in the bar chart based on Tables 4a to 4c, where the treatment duration is plotted on the horizontal axis and the average diameter in mm is plotted on the vertical axis.

[0269] With increasing treatment duration, the size of the growth inhibition zone only partially increases. Therefore, the effect of treatment duration on the size of the growth inhibition zone is less significant than its effect on ROS formation; see [link to relevant documentation]. Figure 22a and 22b The antimicrobial zone is slightly larger than the corresponding zone formed by ROS, thus an additional antimicrobial effect can be assumed. However, the number of residual colonies within the growth-inhibiting zone steadily decreases with increasing treatment duration.

[0270] In contrast, measurements using EWC electrodes for Staphylococcus aureus showed a diameter of 14 mm for a 1-minute treatment duration and 16 mm for a 5-minute treatment duration, including a 16 mm growth inhibition zone.

[0271] For testing of the first treatment device (TV1), 100 μl of the corresponding microbial solution (with a cell count of approximately 10) was used. 6 Colony-forming units ( / ml - colony-forming units / ml) were distributed on moist solid medium (soy casein digested agar, Carl Roth GmbH & Co. KG, Karlsruhe, Germany) and selectively treated with a plasma source-EWC electrode. Treatment times were 1 min, 2 min, 3 min, 4 min, or 5 min, with growth inhibition zone tests performed on the moist agar surface (N=6). The distance between the plasma source and the surface of the moist solid was approximately 1.5 mm. The cathode was positioned below the agar plate.

[0272] After incubating 84 mm diameter agar plates at 37°C, the dimensions of the growth inhibition zone were measured in mm, where the growth inhibition zone was defined as the area where no visible microbial growth was observed. If the growth inhibition zone was not circular, the average diameter was determined by measuring the maximum and minimum diameters.

[0273] For comparison, agar plates were inoculated, but without plasma treatment. Their results at times t=0 min to t=5 min are shown... Figure 25 middle.

[0274] For the bacteria Staphylococcus epidermidis, their behavior at times t=0 min to t=5 min is shown... Figure 26 middle.

[0275] For the bacteria *Escherichia coli*, their behavior at times t=0 min to t=5 min is shown... Figure 27 middle.

[0276] For the bacterium *Pseudomonas aeruginosa*, their behavior at times t=0 min to t=5 min is shown... Figure 28 middle.

[0277] For Candida albicans yeast, their behavior at times t=0 min to t=5 min is shown... Figure 29 middle.

[0278] Tables 5a, 5b, and 5c below show the measurements of Staphylococcus aureus at 25.4°C and 46% relative humidity for time intervals from t=0 min to t=5 min.

[0279]

[0280] Table 5a

[0281]

[0282] Table 5b

[0283]

[0284] Table 5c

[0285] Tables 6a, 6b, and 6c below show the measurements of Staphylococcus epidermidis bacteria at 25.6°C and 44% relative humidity over time t=0 min to t=5 min.

[0286]

[0287] Table 6a

[0288]

[0289] Table 6b

[0290]

[0291] Table 6c

[0292] Tables 7a, 7b, and 7c below show the measurements of Escherichia coli at 24.5°C and 49% relative humidity for periods from t=0 min to t=5 min.

[0293]

[0294] Table 7a

[0295]

[0296] Table 7b

[0297]

[0298] Table 7c

[0299] Tables 8a, 8b, and 8c below show the measurements of Pseudomonas aeruginosa at 25.6°C and 44% relative humidity for times from t=0 min to t=5 min.

[0300]

[0301] Table 8a

[0302]

[0303] Table 8b

[0304]

[0305] Table 8c

[0306] Tables 9a, 9b, and 9c below show the measurements of the microorganism Candida albicans at 25.1°C and 47% relative humidity for periods from t=0 min to t=5 min.

[0307]

[0308] Table 9a

[0309]

[0310] Table 9b

[0311]

[0312] Table 9c

[0313] Gram-positive bacteria Staphylococcus aureus (15.08 mm - 18.33 mm) and Staphylococcus epidermidis (15.92 mm - 25.88 mm) showed the largest inhibition zone diameter, while Gram-negative bacteria Escherichia coli (12.54 mm - 15.46 mm) and Pseudomonas aeruginosa (9.96 mm - 12.63 mm) and yeast Candida albicans (10.83 mm - 16.17 mm) were less affected by plasma treatment with EWC electrodes.

[0314] Figure 30 The diameter values ​​of the bacteria Staphylococcus aureus (column B1), Staphylococcus epidermidis (column B2), Escherichia coli (column B3), Pseudomonas aeruginosa (column B4), and Candida albicans (column B5) are compared. Treatment duration in minutes is plotted on the x-axis, and the diameter of the inhibition zone in mm is plotted on the y-axis. For each series of tests, the decrease in antimicrobial efficacy was recorded in the following order:

[0315] Staphylococcus epidermidis > Staphylococcus aureus > Escherichia coli = Candida albicans > Pseudomonas aeruginosa

[0316] In some cases, the size of the growth inhibition zone increases with the duration of treatment.

[0317] As with the first treatment device (TV1), the same microbial growth inhibition zone test was performed on the second treatment device (TV2).

[0318] For the bacteria Staphylococcus aureus, their condition at time t=0 min to t=5 min is shown... Figure 31 middle.

[0319] For the bacteria Staphylococcus epidermidis, their behavior at times t=0 min to t=5 min is shown... Figure 32 middle.

[0320] For the bacteria *Escherichia coli*, their behavior at times t=0 min to t=5 min is shown... Figure 33 middle.

[0321] For the bacterium *Pseudomonas aeruginosa*, their behavior at times t=0 min to t=5 min is shown... Figure 34 middle.

[0322] For Candida albicans yeast, their behavior at times t=0 min to t=5 min is shown... Figure 35 middle.

[0323] Figure 36The diameter values ​​of the bacteria Staphylococcus aureus (column B1), Staphylococcus epidermidis (column B2), Escherichia coli (column B3), Pseudomonas aeruginosa (column B4), and Candida albicans (column B5) are compared. Treatment duration in minutes is plotted on the x-axis, and the diameter of the inhibition zone in mm is plotted on the y-axis. Gram-positive bacteria Staphylococcus aureus (14.17 mm - 15.92 mm) and Staphylococcus epidermidis (14.25 mm - 15.67 mm) showed the largest inhibition zone diameters, while Gram-negative bacteria Escherichia coli (11.92 mm - 12.58 mm) and Pseudomonas aeruginosa (8.17 mm - 11.33 mm), and Candida albicans (10.54 mm - 13.17 mm) were less affected by plasma treatment with EWC electrodes.

[0324] For each series of tests, the decline in antimicrobial efficacy was recorded in the following order:

[0325] Staphylococcus epidermidis = Staphylococcus aureus > Escherichia coli > Candida albicans > Pseudomonas aeruginosa.

[0326] The size of the growth inhibition zone increased with increasing treatment duration. An increase from 5% for Escherichia coli to 28% for Pseudomonas aeruginosa was observed over a timeframe from 1 to 5 minutes.

[0327] As with the first treatment device (TV1), the same microbial growth inhibition zone test was performed on the third treatment device (TV3).

[0328] For the bacteria Staphylococcus aureus, their condition at time t=0 min to t=5 min is shown... Figure 37 middle.

[0329] For the bacteria Staphylococcus epidermidis, their behavior at times t=0 min to t=5 min is shown... Figure 38 middle.

[0330] For the bacteria *Escherichia coli*, their behavior at times t=0 min to t=5 min is shown... Figure 39 middle.

[0331] For the bacterium *Pseudomonas aeruginosa*, their behavior at times t=0 min to t=5 min is shown... Figure 40 middle.

[0332] For Candida albicans yeast, their behavior at times t=0 min to t=5 min is shown... Figure 41 middle.

[0333] Figure 42 The diameter values ​​of the bacteria Staphylococcus aureus (column B1), Staphylococcus epidermidis (column B2), Escherichia coli (column B3), Pseudomonas aeruginosa (column B4), and Candida albicans (column B5) are compared. Treatment duration in minutes is plotted on the x-axis, and the diameter of the inhibition zone in mm is plotted on the y-axis. The Gram-positive bacterium Staphylococcus aureus (41.67 mm - 46.42 mm) shows the largest diameter of the inhibition zone. The second Gram-positive bacterium Staphylococcus epidermidis (36.42 mm - 41.83 mm) and the Gram-negative strains Escherichia coli (35.50 mm - 41.00 mm), Pseudomonas aeruginosa (35.00 mm - 38.75 mm), and Candida albicans (18.42 mm - 39.00 mm) are less affected by plasma treatment. For Candida albicans yeast, no growth inhibition zone was identified in any of the five Piper dishes at longer treatment times (t=3 min, 4 min, 5 min).

[0334] For each series of tests, the decline in antimicrobial efficacy was recorded in the following order:

[0335] Staphylococcus aureus > Staphylococcus epidermidis = Escherichia coli > Candida albicans (lasting 1 min and 2 min) > Pseudomonas aeruginosa.

[0336] In some cases, the size of the inhibition zone increases with the duration of treatment. Results for Staphylococcus aureus are comparable and therefore consistent.

[0337] Table 10 shows a comparison of measurement results from the above-described measurement examples for the first, second, and third treatment devices (TV1, TV2, TV3). Any officially prescribed limits (L) are also included in the orientation overview. Results for patient leakage current (I), temperature, UV radiation, and exhaust gas concentrations are within safety limits.

[0338]

[0339] Table 10

[0340] It will be apparent to those skilled in the art that many other variations are possible besides the described embodiments without departing from the concept of the invention. Therefore, the subject matter of the invention is not limited to the foregoing description and is determined by the scope of protection defined by the claims. For the interpretation of the claims or the specification, the broadest possible reading of the claims is decisive. Specifically, the terms “comprising” or “including” should be interpreted in a non-exclusive sense as referring to an element, component, or step, thereby indicating that the element, component, or step may be present or used, and may be combined with other elements, components, or steps not expressly mentioned. When a claim relates to an element or component in a group that may consist of A, B, C, up to N elements or components, this language should be interpreted as requiring only a single element from that group, not a combination of A and N, B and N, or any other combination of two or more elements or components from that group.

Claims

1. A therapeutic device for cell stimulation or cell therapy, comprising a housing (12) including electrodes (1), a generator (3) for generating high-frequency voltage pulses, a processor unit (6) including control, regulation and calculation modules, a memory unit (9), at least one operating element (5, 15), and a controllable modulator (4) for controlling the generator (3), wherein a voltage pulse sequence comprising multiple voltage pulses can be generated by the modulator (4), wherein the frequency and duration of the voltage pulses can be adjusted by the modulator (4), wherein the electrodes (1), the generator (3), the processor unit (6), and the... The memory unit (9), the operating element (5), and the modulator (4) are arranged in the housing (12), wherein the electrode (1) comprises a glass body (27) containing a cavity containing gas, wherein the electrode (1) includes a first end (21) configured to be coupled to the modulator (4), wherein the electrode includes a dome-shaped second end (22), wherein the gas can be converted into a non-thermal primary plasma state by a voltage pulse transmitted to the electrode (1), wherein the secondary plasma can be generated by ionizing the air present in the region surrounding the second end (22) of the electrode (1).

2. The treatment device according to claim 1, characterized in that, The frequency of the voltage pulse sequence is at least partially not constant.

3. The treatment device according to any one of claims 1 or 2, characterized in that, The voltage amplitude increases during the time period t2-t1, remains constant during the time period t3-t2, and decreases during the time period t4-t3, wherein the duration of the voltage pulse sequence corresponds to the time period t4-t1.

4. The treatment device according to any one of claims 1 or 2, characterized in that, The frequency increases during the time period t2-t1, remains constant during the time period t3-t2, and decreases during the time period t4-t3.

5. The treatment device according to claim 1, characterized in that, The maximum frequency is in the range of 10Hz to 100Hz, including 100Hz.

6. The treatment device according to claim 1, characterized in that, The voltage at the output of the modulator (4) is in the range of 8V to 65V, including 65V.

7. The treatment device according to claim 1, characterized in that, The voltage at the output terminal of the generator (3) is in the range of 5kV to 25kV, including 25kV.

8. The treatment device according to claim 1, characterized in that, An energy storage unit (10) disposed in the housing (12) is configured to supply energy for the operation of the treatment device, enabling the treatment device to operate wirelessly.

9. The treatment device according to claim 1, characterized in that, The housing (12) includes a display element (7) through which therapeutic and operational data can be displayed.

10. The treatment device according to claim 1, characterized in that, The electrode (1) includes a sensor (2) through which the current or voltage emitted via the electrode (1) can be recorded as a measurement value, which can be digitized into measurement data, wherein the measurement data can be stored in the memory unit (9), wherein the computing module of the processor unit (6) is configured to determine the timing of the delivered energy and / or the energy delivered by the electrode (1).

11. The treatment device according to claim 10, characterized in that, The control module of the processor unit (6) is configured to control the modulator (4) based on the measurement data, for controlling a constant energy output and / or for signal form-independent control, so that any desired signal form can be generated in the generator (3).

12. The treatment device according to claim 11, characterized in that, The measurement data is configured to control the course of the therapy via the control module of the processor unit (6).

13. The treatment device according to claim 12, characterized in that, The measurement data in the processor unit (6) can be linked to a timestamp, wherein the measurement data linked to the timestamp is configured to be stored in the memory unit for storing the process of the therapy.

14. The treatment device according to claim 1, characterized in that, The housing (12) is configured as one of the poles of a capacitor for capacitive coupling.

15. The treatment device according to claim 8, characterized in that, The energy storage unit (10) is configured as a rechargeable element.

16. The treatment device according to claim 15, characterized in that, The energy storage unit includes a negative electrode, which is configured as one of the poles of a capacitor for capacitive coupling.

17. The treatment device according to claim 1, characterized in that, The housing (12) includes an inner side, which contains a conductive or electrically conductive surface.

18. The treatment device according to claim 11, characterized in that, The signal form is a combination of amplitude modulation and frequency modulation.

19. The treatment device according to claim 15, characterized in that, The energy storage unit (10) is configured as a lithium-ion element or a supercapacitor.

20. The treatment device according to claim 17, characterized in that, The inner side contains conductive plastic or plastic coated with a conductive material.

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