JP6664046B2 - Plasma irradiation processing apparatus, evaluation apparatus and evaluation method thereof, control apparatus and control method thereof, and method of manufacturing film - Google Patents

Description

  The present invention relates to a plasma irradiation apparatus, an evaluation apparatus and an evaluation method thereof, a control apparatus and a control method thereof, and a film manufacturing method.

  Patent Literature 1 discloses a plasma irradiation apparatus used in the industrial field, the medical field, and the like.

International Publication 2012/005132

  Conventionally, when evaluating a plasma irradiation apparatus, electromagnetic waves, light, and the like emitted from plasma itself have been measured. This method, for example, evaluates the state of the plasma to be irradiated, and cannot estimate the relationship between the plasma and the effect on the irradiation target.

  According to one aspect of the present invention, a plasma generation unit that generates plasma, a measurement unit that measures a current value flowing through the irradiation target while irradiating the irradiation target with the plasma, and the current There is provided a plasma irradiation processing apparatus including an evaluation unit for creating a correlation between a value and a coagulation ability of the plasma.

  According to another aspect of the present invention, a plasma generation unit that generates plasma, a measurement unit that measures a current value flowing through the irradiation target while the plasma is irradiated on the irradiation target, and a power supply Controlling the voltage using control information indicating the relationship between the voltage supplied from the and the current value and the coagulation result of the irradiation target, and a control unit that switches a mode related to coagulation of the irradiation target. A processing device is provided.

  According to another aspect of the present invention, there is provided an evaluation method of a plasma irradiation processing apparatus, wherein a current value of a current flowing through the irradiation target object by a measuring unit while the plasma is irradiated to the irradiation target object. Measuring, by an evaluation unit, creating a relationship between the current value and the coagulation ability of the plasma, and by using the relationship, by the evaluation unit, evaluate the performance of the plasma irradiation processing apparatus. And an evaluation method including:

  According to another aspect of the present invention, there is provided an evaluation method of a plasma irradiation processing apparatus, wherein a current value of a current flowing through the irradiation target object by a measuring unit while the plasma is irradiated to the irradiation target object. By measuring and, by the evaluation unit, to create a relationship between the voltage and the current value supplied from the power supply to the plasma irradiation processing apparatus, using the relationship, by the evaluation unit, the plasma Evaluating the performance of the irradiation processing apparatus.

  According to another aspect of the present invention, there is provided a method for controlling a plasma irradiation processing apparatus, wherein a current value of a current flowing through the irradiation target object by a measuring unit while the plasma is being irradiated on the irradiation target object. And controlling the voltage using control information indicating a relationship between a voltage supplied from the power supply to the plasma irradiation apparatus and the current value and a solidification result of the irradiation target, and controlling the voltage to control the irradiation target. A control method including switching a mode relating to coagulation of an object.

  According to another aspect of the present invention, creating a correlation between the current value flowing through the irradiation target by irradiating the plasma with the irradiation target and the coagulation ability of the plasma, and using the correlation And controlling the voltage supplied from the power supply to the plasma irradiation apparatus.

  According to another aspect of the present invention, information on the current value flowing through the irradiation target while irradiating the irradiation target with plasma, and information on the solidification result of the irradiation target, An evaluation device for creating a correlation between the current value and the coagulation ability of the plasma is provided.

  According to another aspect of the present invention, a voltage supplied from a power supply to the plasma irradiation processing apparatus, a current value flowing through the irradiation target while the target is irradiated with plasma, A control device is provided that outputs the set value of the voltage to the plasma irradiation processing device using control information indicating a relationship with a solidification result of the object.

FIG. 1 is a schematic configuration diagram illustrating an example of a plasma irradiation processing apparatus according to a first embodiment. (A) is an example of a detected current waveform and a voltage waveform in the present embodiment, (b) is an example of a detected current waveform and an induced current waveform in the present embodiment, and (c) is an example of the detected current waveform and the induced current waveform in the present embodiment. An example of a current value flowing through a sample. 4 is a graph illustrating a relationship between a current value and hemoglobin concentration in the embodiment. 4 is an image of the sample according to the present embodiment after plasma irradiation. 4 is an image of the sample according to the present embodiment after plasma irradiation. 4 is an image of the sample according to the present embodiment after plasma irradiation. 4 is an image of the sample according to the present embodiment after plasma irradiation. 4 is a graph showing a relationship between electric power (W) and the amount of albumin deposited in the embodiment. 7 is a graph showing the number of red blood cells before and after plasma irradiation in the present embodiment. 4 is an example of a flow until a product is shipped in the present embodiment. In the present embodiment, an example of a graph in which a horizontal axis indicates a set voltage and a vertical axis indicates a current value. FIG. 4 is a schematic configuration diagram illustrating an example of a plasma irradiation processing apparatus according to a second embodiment. 13 is an example of control information according to the second embodiment. 6 is an example of a flowchart of setting voltage correction when the device is used in the embodiment.

  Hereinafter, the present embodiment will be described with reference to the accompanying drawings. The attached drawings show specific embodiments, but these are for understanding the present invention, and are not used for interpreting the present invention in a limited manner.

  Hereinafter, an example of an embodiment of a medical plasma irradiation processing apparatus will be described, but the apparatus may be applied to a purpose other than medical use (eg, a food field).

The inventor of the present application has searched for a measurable physical quantity derived from plasma, and based on the measurement result of the physical quantity (eg, an electrical parameter, etc.), has obtained the following new findings regarding the correlation between the plasma and the effect generated on the irradiation target. Obtained.
(1) When plasma flare is applied to whole blood, there is a correlation between the amount of current flowing through the sample (blood) and the amount of hemolysis.
(2) When plasma flare is applied to a PBS (Phosphate buffered saline) diluted solution of red blood cells, there is a correlation between the amount of current flowing through the sample and the amount of hemolysis.
(3) The larger the amount of hemolysis, the greater the amount of coagulated product generated.

For example, in the field of plasma medicine, there are the following multiple (eg, three) categories of surgical procedures.
(Category 1) Use of thermal action using Energy Device ... energy device (high-frequency electrocoagulation, ultrasonic coagulation, laser coagulation, etc.) (Category 2) Surgical Hemostats: Serum protein components (such as albumin) Coagulation (Category 3) Adhesive and Tissue Sealing: Coagulation with hemolysis (formation of red blood cell clot)

  The following embodiments utilize a correlation between a current value flowing through a sample (an irradiation target, an irradiation target) and a plasma coagulation ability when a generated plasma is irradiated on a sample (eg, blood). This is a technique for evaluating or controlling plasma with respect to the above categories.

  The coagulation ability of plasma includes, for example, the ability of plasma to coagulate a sample. As an example, the coagulation ability of plasma includes causing a chemical reaction in a sample (eg, film formation by polymerization in the case of protein) and activating a coagulation factor in the sample (eg, blood in the case of blood). Activation of coagulation factors, etc.), and formation of a membrane-like structure (eg, a hemolytic membrane in the case of blood, a membrane-like structure by an aggregate), and the like. The above-described plasma coagulation ability is an example, and various coagulation capacities may be included as the plasma coagulation ability.

[First Embodiment]
FIG. 1 is a schematic configuration diagram illustrating an example of a plasma irradiation processing apparatus (plasma irradiation system) according to the first embodiment. As an example, the plasma irradiation processing apparatus 1 includes a plasma generation unit (plasma generation device) 2, a power supply and gas source 3, a stage (sample mounting unit) 4, a detection unit 5, and a processing device 6.

  The sample 7 is introduced into the sample holding unit 8. As an example, the sample 7 is blood, and the sample holding unit 8 is a well plate. The sample holding unit 8 is arranged on the stage 4. A copper foil (not shown) is attached to the stage 4.

  The power supply and gas source 3 supply voltage and gas to the plasma generation unit 2. The power supply and the power supply in the gas source 3 are grounded. The copper foil of the stage 4 and the ground side of the power supply are connected via an electric wire 9. The detection unit 5 is disposed on the electric wire 9. As an example, the detection unit 5 is a current sensor, for example, a Rogowski coil. As another example, the detection unit 5 may be a current probe. As another example, the detection unit 5 may be configured by a resistor and a differential amplifier. In this configuration, the detection unit 5 can evaluate the current value by measuring the voltage applied between the resistors of the resistor via the differential amplifier.

  The plasma generation unit 2 generates plasma (plasma flare) having a low atmospheric pressure based on a gas and a voltage supplied from a power supply and a gas source 3. The plasma generation unit 2 includes a discharge tube 10 for generating plasma. An inert gas is introduced into the discharge tube 10 from a power source and a gas source in the gas source 3. As an example, the inert gas is helium. Glow discharge is generated by introducing helium gas into the discharge tube 10 and applying a voltage to the discharge tube 10. The plasma generation unit 2 generates plasma by glow discharge, and can irradiate the plasma corresponding to the plurality of categories described above.

  The processing device 6 includes a control unit 11, a measurement unit 12, an evaluation unit 13, a storage unit 14, and a user interface 15. Each of the processing units 11, 12, and 13 of the processing device 6 may be realized by hardware means, for example, by designing an integrated circuit, or may be realized by software means by which a processor executes a program corresponding to the processing. May be done.

  In FIG. 1, the control unit 11, the measurement unit 12, the evaluation unit 13, and the storage unit 14 are illustrated in a form included in one processing device 6, but this is for the purpose of simplifying the description. Yes, and is not limited to this configuration. The components of the processing device 6 may be realized on a separate device. As an example, the processing of the measurement unit 12 is executed on the first device, the output result of the measurement unit 12 is input to the second device via a network or a storage medium, and the evaluation result of the evaluation unit 13 is input to the second device. Processing may be performed. As an example, the function of the evaluation unit 13 may be realized as one device as an evaluation device (first device). As another example, the function of the control unit 11 may be implemented as one device as a control device (second device).

  In FIG. 1, the plasma generation unit 2 and the processing device 6 are illustrated as separate blocks, but all or at least a part of the components of the processing device 6 may be incorporated in the plasma generation unit 2 itself.

  The storage unit 14 is, for example, a recording device such as a memory and a hard disk, or a recording medium such as an SD card and a DVD. The storage unit 14 stores input information to each of the processing units 11, 12, and 13 of the processing device 6 and output information from each of the processing units 11, 12 and 13 (eg, a current measurement result and a processing result). Is stored.

  The user interface 15 includes an input unit such as a mouse and a keyboard, and a display unit such as a display. Various information may be input to the processing units 11, 12, and 13 of the processing device 6 using the input unit of the user interface 15. Further, the display unit of the user interface 15 may display output information from each of the processing units 11, 12, and 13 of the processing device 6, and the like.

  The control unit 11 controls each component of the device. For example, the control unit 11 is connected to the power supply and the gas source 3 and controls a set voltage of the power supply and the power supply in the gas source 3. The control unit 11 can control the voltage applied from the power supply to the discharge tube 10 to control the coagulation ability of the plasma. The control unit 11 can irradiate the plasma corresponding to the plurality of categories described above by controlling the voltage applied to the discharge tube 10.

  The measurement unit 12 is connected to the detection unit 5. The measurement unit 12 measures a current value of a current flowing through the stage 4 via the sample 7. In the following, for example, the current value flowing to the stage 4 via the sample 7 is described as “current value”, and the current value actually detected by the detection unit 5 is described as “detected current value”.

  The measurement current value detected by the detection unit 5 is input to the measurement unit 12. As an example, the detected current value is input to the measurement unit 12 via an amplifier and an AD converter. Further, a voltage value applied to the discharge tube 10 is also input to the measuring unit 12. As an example, the voltage value is input to the measurement unit 12 via an amplifier and an AD converter. FIG. 2A is an example of a diagram in which the waveform of the detection current actually detected by the detection unit 5 and the waveform of the voltage applied to the discharge tube 10 are superimposed. As an example, the measurement unit 12 includes an FPGA (field-programmable gate array). For example, the processing of the measurement unit 12 described below may be realized on an FPGA.

  The detection current actually detected by the detection unit 5 (eg, Rogowski coil) includes a current flowing to the stage 4 via the sample 7 and an induced current caused by a voltage (fluctuating potential) applied to the discharge tube 10. And are included. Therefore, it is desirable to remove induced current, which is noise, by arithmetic processing. As an example, the measurement unit 12 calculates the current value of the current flowing through the sample 7 by subtracting the above-described induced current from the detected current value actually detected in the Rogowski coil. The measuring unit 12 adjusts the phase of the voltage waveform ((a) in FIG. 2) input to the measuring unit 12 to the detected current, and obtains the induced current from the voltage waveform. FIG. 2B is a diagram in which the waveform of the detected current and the waveform of the induced current obtained from the waveform of the voltage are superimposed. FIG. 2C shows a waveform obtained by subtracting the waveform of the induced current from the waveform of the detected current. As an example, the measurement unit 12 calculates a value obtained by dividing the area of the dotted triangle in FIG. 2C by the time corresponding to a half cycle of the current as the current value of the current flowing through the sample 7. If the influence of the induced current, which is noise, is small, the measurement unit 12 may output the detected current as a current value flowing to the stage 4 via the sample 7.

  As another example, the measurement unit 12 may calculate the power (W) from the current value and the voltage value. For example, the measurement unit 12 may calculate the power (W) by multiplying the current value and the voltage value in FIG.

  An example of measuring a current value will be described. As an example, the measurement unit 12 measures a current value of a current flowing to the stage 4 via the sample 7 while irradiating the sample 7 with plasma. Further, for example, the measurement unit 12 measures a current value of a current flowing to the stage 4 via the sample 7 to which the plasma generated by the plasma generation unit 2 is irradiated. As another example, the measurement unit 12 may measure a current value of a current flowing to the stage 4 via the sample 7 while irradiating the sample 7 other than blood with plasma. As yet another example, the measurement unit 12 may measure a current value of a current flowing through the stage 4 while irradiating the stage 4 in a state where the sample 7 is not arranged on the stage 4 with plasma. .

  In the sample 7 after the plasma irradiation, a solidification result generated by the plasma irradiation is measured (observed). For example, the coagulation result of the sample includes at least one of information on the amount of hemolyzed blood, information on the mass of clot in blood, and information on the number of red blood cells in blood. As an example, the information on the amount of hemolyzed blood is the hemoglobin concentration obtained by the hemoglobin colorimetry. Further, as an example, the information on the mass of the coagulated product in the blood is the amount of albumin deposited. The information on the number of red blood cells in the blood is the number of red blood cells obtained by the hemocytometer. For example, the coagulation ability of the plasma for the sample 7 is determined based on the coagulation result of at least one sample 7 described above.

  The information on the current value measured by the measurement unit 12 and the information on the coagulation result of the measured sample are input to the evaluation unit 13. The evaluation unit 13 calculates and creates a correlation (related information) between the current value measured by the measurement unit 12 and the coagulation result of the sample 7, and outputs the correlation. As an example, the process of creating the correlation (related information) in the evaluation unit 13 may be realized by spreadsheet software. The evaluation unit 13 may store the correlation information in the storage unit 14. For example, the evaluation unit 13 may include information on the correlation between the current value and the coagulation ability of the plasma, information on the correlation between the current value and the coagulation result of the sample 7, and the correlation between the voltage value and the current value. Is stored in the storage unit 14.

  In the present embodiment, there is a correlation between the voltage value applied to the discharge tube 10 and the current value measured by the measuring unit 12. For example, the value of the current value increases as the voltage value increases. Therefore, by using the correlation between the voltage value and the current value, it is possible to estimate how much current value flows to the stage 4 via the sample 7 when a certain voltage value is applied to the discharge tube 10. it can. The user can grasp how much voltage value is applied to the discharge tube 10, how much current value flows to the stage 4 via the sample 7, and as a result, how much coagulation result occurs in the sample 7. . As described above, the evaluation unit 13 in the present embodiment uses the discharge tube 10 to generate plasma based on the correlation between the current value and the coagulation result of the sample 7 and the correlation between the current value and the voltage value. And the coagulation result of the sample 7 can be grasped. Therefore, the evaluation unit 13 can grasp the correlation between the current value and the coagulation ability of the plasma. Based on the plurality of correlations described above, the evaluation unit 13 calculates and creates a correlation between the current value and the coagulation ability of the plasma. The plasma irradiation processing apparatus 1 evaluates the coagulation ability of the plasma using the correlation (eg, the correlation between the current value and the coagulation ability of the plasma, the correlation between the current value and the coagulation result of the sample 7). Or control becomes possible.

  FIG. 3 is an example of the relationship (eg, correlation) between the current value and the coagulation result of the sample 7, and is a graph showing the relationship between the above-described current value and the hemoglobin concentration. As the measured current value increases, the hemoglobin concentration increases. This indicates that the larger the current value, the larger the hemolysis amount of the blood, and indicates that there is a correlation between the current value and the hemolysis amount. It can also be said that there is a correlation between the current value and the number of red blood cells. This correlation can be used as a quantitative evaluation method for the above-described categorization.

  As an example, a graph (eg, related information) as shown in FIG. 3 may be displayed on the display unit of the user interface 15. The user can grasp the correlation between the current value and the coagulation result of the sample 7. For example, by using the correlation shown in FIG. 3, the user can grasp at what current value the coagulation result of the sample 7 corresponding to each of the above-described categories can be obtained. For example, in the graph of FIG. 3, at a current value of 0.8 mA, it can be understood that hemolysis and coagulation accompanied by the hemolysis have occurred as a result of coagulation by plasma irradiation. In FIG. 3, for example, when the current value is 0.4 mA or more, it is considered that hemolysis due to plasma irradiation and coagulation accompanying the hemolysis have occurred. In FIG. 3, for example, when the current value is 0.2 mA, there is a possibility that a slight hemolysis has occurred due to the plasma irradiation. The measurement conditions in FIG. 3 are such that a member corresponding to the counter electrode (eg, stage, sample holding portion 8 in some cases, etc.) has a shape of 75 mm (length) × 75 mm (width) × 70 μm (thickness). (Copper foil), and the distance between this member and the discharge tube is 10 mm.

  When the current value was 0.8 mA, the voltage applied to the discharge tube 10 (hereinafter, voltage value) was 13 V, and the plasma power was about 3 W. When the current value was 0.6 mA, the voltage value was 11.5 V, and the plasma power was about 2 W. When the current value was 0.4 mA, the voltage value was 10.5 V, and the plasma power was about 1.5 W. When the current value was 0.2 mA, the voltage value was 8.5 V, and the plasma power was about 0.7 W. Thus, there is a correlation between the voltage value applied to the discharge tube 10 and the current value measured by the measuring unit 12. Therefore, the evaluation unit 13 can also grasp the correlation between the voltage value applied to the discharge tube 10, the current value measured by the measurement unit 12, and the coagulation result of the sample 7. As a result, the evaluation unit 13 can grasp the correlation between the current value and the coagulation ability of the plasma.

  For example, when a voltage of 13 V is applied to the discharge tube 10, the current value is equivalent to 0.8 mA, and it can be estimated that hemolysis and coagulation accompanied by the hemolysis occur as a coagulation result by plasma irradiation. When a voltage of 10.5 V is applied to the discharge tube 10, the current value is equivalent to 0.4 mA, and it can be estimated that hemolysis and coagulation accompanied by the hemolysis occur as a result of coagulation by plasma irradiation. Also, considering the graph of FIG. 3, it can be seen that the solidification ability of the plasma at a voltage of 13V is higher than the solidification ability of the plasma at a voltage of 10.5V. From the graph of FIG. 3 and the relationship between the current value and the voltage value, the evaluation unit 13 creates a correlation between the current value and the coagulation ability of the plasma. For example, the evaluation unit 13 can evaluate the coagulation ability of the plasma using the correlation between the current value and the coagulation ability of the plasma. As an example, the evaluation unit 13 can determine the specifications of the plasma irradiation processing apparatus and perform evaluation (inspection) at the time of shipping using the correlation between the current value and the solidification ability of the plasma. For example, using the correlation between the current value and the coagulation ability of the plasma, the control unit 11 can control the coagulation ability of the plasma. As an example, the control unit 11 can control the voltage applied to the discharge tube 10 using the correlation between the current value and the coagulation ability of the plasma to control the coagulation ability of the plasma.

  FIG. 4 is an image after the sample 7 is irradiated with plasma by the plasma irradiation processing apparatus 1. The present example is an image obtained by irradiating a solution (hereinafter referred to as a sample) of erythrocytes isolated and purified from blood in PBS with low-temperature plasma by the plasma irradiation processing apparatus 1 under an atmospheric pressure environment. (A) is an optical microscope image of a sample after plasma irradiation, and (b) is an electron microscope image of the same sample. In the example of FIG. 4, the value of the current flowing through the sample is 0.8 mA, the plasma power is equivalent to 3 to 3.5 W, and the plasma irradiation time is 3 minutes. Hemolysis is caused by plasma irradiation by the plasma irradiation processing apparatus 1, and as a result, a film (hereinafter, hemolysis film) is formed uniformly. Arrow 41 indicates a portion where a uniform hemolytic film is formed by plasma irradiation. In this example, the thickness of the hemolytic film is relatively large, for example, the hemolytic film includes a portion whose thickness is greater than 20 μm. Hemolytic membranes include membrane structures derived from red blood cells.

  FIG. 5 is an image after plasma irradiation of the sample 7 by the plasma irradiation processing apparatus 1. In the present example, similarly to FIG. 4, an image was taken after irradiating a solution (hereinafter, a sample) of red blood cells isolated and purified from blood with PBS using a plasma irradiation processing apparatus 1 under low-pressure plasma under an atmospheric pressure environment. It is an image. (A) is an optical microscope image of a sample after plasma irradiation, and (b) is an electron microscope image of the same sample. In the example of FIG. 5, the current value flowing through the sample is 0.2 mA, the plasma power is equivalent to 0.5 to 0.7 W, and the plasma irradiation time is 3 minutes. The arrow 51 is a portion where hemolysis has not occurred. Arrows 52 and 53 indicate portions where hemolysis has occurred. An arrow 52 indicates a portion where erythrocytes have only caused hemolysis and no aggregates are present, and an arrow 53 indicates a portion where aggregates have occurred after hemolysis. In this example, a uniform hemolytic film is not formed, but a film-like structure is formed by aggregates by plasma irradiation. The coagulation ability of the plasma in FIG. 5 is lower than the coagulation ability of the plasma in FIG.

  FIG. 6 is an image after the sample 7 is irradiated with plasma by the plasma irradiation processing apparatus 1. This example is an image captured after irradiating low-temperature plasma to the whole blood (hereinafter, sample) by the plasma irradiation apparatus 1 under an atmospheric pressure environment. (A) is an optical microscope image of a sample after plasma irradiation, and (b) is an electron microscope image of the same sample. In the example of FIG. 6, the current value flowing through the sample is 0.8 mA, the plasma power is about 3 W, and the plasma irradiation time is 3 minutes. In this example, plasma irradiation is performed on whole blood (including blood cells and plasma), and a uniform hemolytic film is formed in substantially the same manner as in FIG. For example, the hemolytic membrane of FIG. 4 is composed of a single component (red blood cells in FIG. 4), while the hemolytic membrane of FIG. 6 is composed of multiple components (including components other than red blood cells). The arrow in the hemolytic membrane of FIG. 6 is derived from red blood cells.

  FIG. 7 is an image after the sample 7 is irradiated with plasma by the plasma irradiation processing apparatus 1. This example is an image captured after irradiating low-temperature plasma to the whole blood (hereinafter, sample) by the plasma irradiation apparatus 1 under an atmospheric pressure environment. (A) is an optical microscope image of a sample after plasma irradiation, and (b) is an electron microscope image of the same sample. In the example of FIG. 7, the current value flowing through the sample is 0.2 mA, the plasma power is about 0.7 W, and the plasma irradiation time is 3 minutes. In this example, a uniform hemolytic film is not formed, but a film-like structure is formed by aggregates by plasma irradiation. The coagulation ability of the plasma in FIG. 7 is lower than the coagulation ability of the plasma in FIG.

  The evaluation unit 13 can create a correlation (correlation information) between the current value and the coagulation ability of the plasma from the examples of FIGS. 4 to 7 and the correlation between the current value and the voltage value. The plasma irradiation processing apparatus 1 can evaluate the coagulation ability of the plasma or control the coagulation ability of the plasma using the correlation.

  FIG. 8 is a graph (eg, related information) showing the relationship between the plasma power (W) and the amount of albumin deposited when the voltage applied to the discharge tube 10 is 10 V, 13 V, and 15 V. For example, the amount of albumin deposited was determined by irradiating the albumin dispersion with plasma and measuring the mass of the film-like structure formed on the liquid surface of the albumin dispersion. Therefore, for example, FIG. 8 is a graph showing a relationship between a film-like structure as a result of solidification generated by plasma irradiation and plasma power. As shown in FIG. 8, the greater the plasma power, the greater the amount of albumin deposited. Further, as the voltage applied to the discharge tube 10 increases, the amount of albumin deposited increases. As described above, there is a correlation between the voltage value applied to the discharge tube 10 and the current value measured by the measurement unit 12. Therefore, from these relationships, the evaluation unit 13 can grasp the correlation between the current value and the coagulation ability of the plasma, as described above.

  FIG. 9 is a graph (eg, related information) showing a difference in the number of red blood cells before and after plasma irradiation when the current value is 0.8 mA. As the irradiation time increases, the number of red blood cells decreases (the amount of hemolysis increases), indicating that there is a correlation between the plasma irradiation time and the number of red blood cells. Also, as shown in FIGS. 3, 4 and 5, it can be seen that the greater the amount of hemolysis, the more uniform and dense the hemolysis film is formed. Therefore, the evaluation unit 13 uses FIG. By calculating the amount, the coagulation ability of the generated plasma under the use conditions can be evaluated. Similarly, the evaluation unit 13 can evaluate the coagulation ability of the plasma for each current value by calculating the hemolysis amount with respect to the plasma irradiation time when the current value is 0.2 mA or 0.6 mA.

  Further, as described above, there is a correlation between the voltage value applied to the discharge tube 10 and the current value measured by the measurement unit 12. Using this correlation, the evaluation unit 13 can also grasp the correlation between the voltage value applied to the discharge tube 10 and the solidification result of the sample 7. Therefore, the evaluation unit 13 may evaluate the coagulation ability of the plasma for each voltage value by calculating the amount of hemolysis with respect to the plasma irradiation time at a certain voltage value.

  Although a plurality of correlations have been described with reference to FIGS. 3 to 9, the plasma irradiation processing apparatus 1 in the present embodiment can easily increase the solidification ability of plasma from one or a combination of these correlations. Can be evaluated quickly.

<Film production method>
A film can be manufactured on an irradiation target using the above-described correlation. First, using the measuring unit 12, a current value flowing through the sample 7 while the plasma generating unit 2 irradiates the sample 7 with plasma is measured. Thereafter, the solidification result of the sample 7 after the plasma irradiation is measured (observed) by the plasma irradiation.

  Next, using the evaluation unit 13, a correlation between a current value flowing through the sample 7 by irradiating the sample 7 with plasma and a solidification result of the sample 7 is created. Next, using this correlation, a threshold value of a current value at which a membrane (eg, a hemolysed membrane, a membrane-like structure formed of aggregates) is generated after hemolysis of red blood cells (hereinafter, a current threshold for membrane generation) Ask for. The control unit 11 controls the voltage applied to the plasma generation unit 2 so that the current value measured by the measurement unit 12 satisfies the film formation current threshold. Thereby, a film (eg, a hemolytic film) can be formed on the sample 7. The present embodiment has been obtained based on a new finding from the correlation between the current value and the result of coagulation of the sample 7 that hemolysis occurs when a certain current value is exceeded. Therefore, preferably, the sample 7 is blood, and the current threshold value for membrane generation is set based on a value at which hemolysis occurs. According to this configuration, the plasma irradiation of the plasma irradiation processing apparatus 1 can generate a hemolyzed film or a film-like structure of aggregates in blood.

  The above-described threshold value of the current value is an example, and various threshold values may be set according to the coagulation ability of the plasma. For example, in the production of the above-mentioned film, the film-forming current threshold value set based on the correlation created in advance (the correlation between the current flowing through the sample 7 and the coagulation ability of the plasma) is controlled. The unit 11 acquires the data from the storage unit 14 and the like, and controls the voltage applied to the plasma generation unit 2 so that the control unit 11 satisfies the film formation current threshold, thereby forming a film on the sample 7. May be configured. The numerical values of the current values described with reference to FIGS. 3 to 9 are examples, and the film forming current threshold is not limited to the above numerical values. The current threshold value for film generation may change according to the sample 7 (eg, tissue), and may be set for each sample 7 (eg, tissue).

  In addition, as described above, there is a correlation between the voltage value applied to the discharge tube 10 and the current value measured by the measuring unit 12. Therefore, the evaluation unit 13 may use this correlation to determine a threshold value of a voltage value at which a desired film is generated (hereinafter, a film generation voltage threshold value). The control unit 11 may apply a voltage to the discharge tube 10 at a film generation voltage threshold value or a voltage value higher than the threshold value to control the coagulation ability of the plasma.

<Production>
FIG. 10 is an example of a flow until a product is shipped. For example, first, the manufacturer determines the specifications of the product (S61) and manufactures a prototype of the product (S62). Thereafter, the product is mass-produced (S63), and the product is shipped (S64). The plasma irradiation processing apparatus 1 in the present embodiment can solve the problems of each of the processes of S61 to S63.

<Specification determination (S61)>
According to the plasma irradiation processing apparatus 1, it is possible to estimate the coagulation ability of the plasma and determine the specifications of the apparatus. The measurement unit 12 measures a current flowing to the stage 4 via the sample 7 while irradiating the sample 7 with plasma. The evaluation unit 13 outputs a graph (eg, related information) indicating a correlation between the current value and the hemolysis amount (quantified by the hemoglobin colorimetry). The evaluation unit 13 creates a correlation between the current value and the coagulation ability of the plasma based on the output graph and the correlation between the current value and the voltage applied to the discharge tube 10. For example, using the correlation displayed on the user interface 15, the user can determine the specifications of the device (such as a set voltage of a power supply).

The following is an example of the procedure for determining the specifications.
(1) Erythrocytes purified from whole blood are dissolved in PBS to obtain a 2.0 × 10 ⁹ RBCs / mL solution (sample 7).
(2) Add sample 7 to any well of the well plate.
(3) The control unit 11 irradiates the sample 7 with the atmospheric pressure low-temperature plasma generated by the plasma generation unit 2 for a predetermined time (determined time).
(4) The current value (first current value) flowing to the stage 4 via the sample 7 during the plasma irradiation is measured by the measuring unit 12.
(5) The procedures (1) to (4) are repeatedly executed while changing the set voltages of the power supply and the gas source 3 by the control unit 11.
(6) With respect to each sample 7 obtained by repeatedly executing the procedures (1) to (4), the hemoglobin concentration is determined by a hemoglobin colorimetric method.
(7) A set of the current value (first current value) measured in step (4) and the hemoglobin concentration obtained in step (6) are input to the evaluation unit 13. The evaluation unit 13 creates a graph showing a correlation between the current value and the hemoglobin concentration.
(8) The evaluation unit 13 creates a correlation between the current value and the coagulation ability of the plasma based on the created graph and the correlation between the current value and the voltage value applied to the discharge tube 10. Using the correlation, the user determines the specifications (such as the set voltage of the power supply) of the device.
(9) Remove the sample 7 from the stage 4. The control unit 11 irradiates the plasma generated by the plasma generation unit 2 to the stage 4 where the sample 7 is not arranged on the stage 4.
(10) While irradiating the plasma, the current value (second current value) flowing through the stage 4 without using the sample 7 is measured by the measuring unit 12. The evaluation unit 13 performs a comparison operation between the first current value and the second current value under the same irradiation condition (for example, a set voltage of a power supply). The evaluation unit 13 calculates correction information (for example, a correction value and a correction formula) for correcting the second current value to the first current value based on the comparison result (for example, a difference between the current values).
Thereafter, the specifications of another device are determined.
(11) The controller 11 irradiates the plasma generated by the plasma generator 2 to the stage 4 in a state where the sample 7 is not arranged on the stage 4.
(12) The current flowing through the stage 4 is measured by the measuring unit 12 while the sample 7 is not interposed during the plasma irradiation.
(13) The evaluation unit 13 corrects the current value measured in step (12) using the correction information calculated in step (10). The evaluation unit 13 estimates the coagulation ability of the plasma based on the graph created in the procedure (8) and the correlation between the corrected current value and the voltage value applied to the discharge tube 10. The user determines the specifications (such as the voltage applied by the power supply) of the device based on the estimated coagulation ability.

  The above procedure may be used for evaluation (inspection) for shipment of a product (eg, the plasma irradiation apparatus 1). For example, a reference value as to whether the performance required for the product is satisfied is determined in advance with reference to a graph, and the evaluation unit 13 sets the reference value (reference value) set according to the measured current value and the purpose of use of the device. May be evaluated in comparison with the range. For example, if the current value measured using the product falls within the set reference value, the product can be shipped.

  In order to confirm that the plasma generated by the plasma irradiation apparatus coagulated blood to form a film, histological analysis or observation with an electron microscope had to be performed. According to the present embodiment, it is possible to easily evaluate the solidification ability of plasma by plasma irradiation in a short time. As an example, erythrocytes isolated and purified from blood or a solution of erythrocytes isolated and purified in PBS are used as an indicator for evaluation. In this case, the evaluation unit 13 creates a correlation between the current value and the coagulation ability of the plasma. By utilizing this correlation, the solidification ability of the plasma irradiation apparatus 1 can be evaluated in real time or in a short time. In addition, the evaluation unit 13 can predict the formation of a stable blood coagulation film by using the correlation.

<Production of prototype (S62) and mass production (S63)>
According to the plasma irradiation processing apparatus 1, it is possible to estimate the coagulation ability of plasma without using the sample 7 derived from a living body (eg, blood), to evaluate a prototype, and to perform a pre-shipment inspection at the time of mass production. Become.

  For example, the following operation is performed in advance on a device serving as a reference for evaluation (for example, a device serving as a reference in specification determination S61). A predetermined amount (for example, 1 mL) of water is prepared as a sample 7. The control unit 11 controls the plasma generation unit 2, the power source and the gas source 3 to irradiate water as the sample 7 with plasma. Then, the measuring unit 12 measures the current value while irradiating the water with the plasma. Thereafter, the evaluation unit 13 creates information (eg, related information) indicating the relationship between the current value and the set voltage value while the water is being irradiated with the plasma. For example, the information is a graph in which a horizontal axis indicates a set voltage and a vertical axis indicates a current value. In addition, the storage unit 14 stores information on a reference range of the slope based on the slope of the fitting straight line of the created graph. FIG. 11 is an example of a case where a fitting straight line is obtained on a graph in which a horizontal axis indicates a set voltage and a vertical axis indicates a current value.

The following is an example of a product evaluation procedure in trial manufacture (S62) and mass production (S63).
(1) A predetermined amount (for example, 1 mL) of water is placed on the stage 4. The control unit 11 irradiates the atmospheric pressure low-temperature plasma generated by the plasma generation unit 2 to water.
(2) The measuring unit 12 measures a current value flowing to the stage 4 via water while irradiating the plasma.
(3) The control unit 11 executes the procedures (1) and (2) while changing the set voltage of the power supply and the gas source 3.
(4) The evaluation unit 13 creates information indicating the relationship between the set voltage value and the current value. For example, the information is information indicating a graph in which a horizontal axis indicates a set voltage and a vertical axis indicates a current value.
(5) The evaluation unit 13 determines whether or not the slope of the fitting straight line of the current value of the graph created in the procedure (4) falls within the above-described reference range.
(6) When the inclination falls within the reference range, the evaluation unit 13 determines that the apparatus (eg, the plasma irradiation processing apparatus 1) has passed. If the inclination deviates from the reference range, the evaluation unit 13 determines that the device is rejected, and the control unit 11 corrects the set voltage and the like, and compares the output variation due to the set voltage between the devices. So that it falls within a certain range.

  As described above, according to the plasma irradiation apparatus 1, the performance or the safety of the plasma irradiation apparatus 1 is evaluated using the relationship between the current value and the set voltage value during plasma irradiation. Can be. Note that the above procedure may be applied to the specification study.

  In the above-described embodiment, an example in which blood, water, and the stage 4 are used as the irradiation target has been described, but the present invention is not limited to this example. For example, the irradiation target may include a monomer, or a high-molecular or low-molecular polymer. As an example, the irradiation target includes a polymer having a two-stage solidification state. For example, some polymers have a first stage that aggregates under certain conditions, and a second stage that deforms (or discolors) at high temperatures without agglomeration above certain conditions. The processing device 6 measures a current value flowing through the irradiation target while the irradiation target including the polymer is irradiated with plasma by the plasma generation unit 2 and a solidification result thereof. A correlation with the coagulation ability of the plasma may be created.

[Second embodiment]
FIG. 12 is a schematic configuration diagram illustrating an example of a plasma irradiation processing apparatus according to the second embodiment. The same components as those in FIG. 1 are denoted by the same reference numerals and description thereof will be omitted.

  The plasma irradiation processing apparatus 1 includes an electrode pad (sample mounting section) 81. The electrode pad 81 is attached in contact with the irradiation target 82. As an example, the irradiation target 82 is a human body, and FIG. 12 shows an example in which an electrode pad 81 is attached to an arm or a foot of the human body.

  In this embodiment, the electrode pad 81 may not be directly attached to the human body. For example, a member corresponding to the electrode pad 81 may be attached to a part of an operating table to measure a current value. The patient may be placed on the operating table so that the patient comes into contact with the electrode pad 81. Further, as described below, when plasma irradiation is performed outside the patient, the irradiation target 82 may be arranged on the stage 4 as in FIG.

  FIG. 13 is an example of control information stored in the storage unit 14. As an example, the control information includes a relationship between a voltage supplied from a power supply, a current value flowing through the irradiation target 82 during irradiation of the irradiation target 82 with plasma, and a solidification result of the irradiation target 82. including. As an example, the control information includes a relationship between a voltage supplied from a power supply, a current value flowing through the irradiation target 82 while the plasma is irradiated to the irradiation target 82, and a coagulation ability of the plasma. The solidification result of the irradiation target and the solidification ability of the plasma are the same as those described in the first embodiment.

  The storage unit 14 stores one or a plurality of operation mode setting information (eg, recipe 91) as control information. The recipe (control information) 91 stores a relationship among a mode 92, a current value 93, and a set voltage 94. The mode 92 holds identification information of a mode regarding coagulation of the irradiation target 82. The current value 93 holds, for example, a current value measured at the time of specification determination. The set voltage 94 holds the set voltage when the current value 93 was measured. For example, the evaluation unit 13 creates the graph of FIG. 3 for each tissue (eg, a tissue A, a tissue B, etc.) as an irradiation target when determining the specifications. The control unit 11 can obtain a set voltage for each coagulation ability for each tissue based on a graph (correlation) created for each tissue.

  As an example, the control unit 11 can control the set voltage of the power supply using the recipe 91 and selectively or automatically switch the coagulation ability of the plasma on the irradiation target between mode 1 and mode 2. As an example, mode (eg, first mode) 1 is a mode in which red blood cells included in the irradiation target can be hemolyzed (or a mode in which red blood cells can be hemolyzed to form a membrane). As an example, mode (eg, second mode) 2 is a mode in which red blood cells cannot be lysed but serum protein components contained in the irradiation target can be coagulated. Here, two modes have been described, but the present invention is not limited to this. The recipe 91 may hold another mode, or may hold information on three or more modes.

  As an example, recipe 91 may include at least one mode for dosage form processing. For example, dosage form processing includes drug shape processing and biological product processing. As an example, the modes related to dosage form processing may include a mode of forming a hemolysed membrane and a mode of coagulation (film formation, formation of aggregates, and solidification) of other biological products.

  For example, the sample 7 is a solution of a biological preparation containing an antibody or a biomolecule as a main component. Using the evaluation unit 13, the relationship between the current value flowing through the sample 7 while the sample 7 is irradiated with plasma, the set voltage, and the coagulation result (film formation or solidification, etc.) of the biological agent is determined. The recipe data shown is created. The created relationship (recipe data) is stored in the storage unit 14 as a recipe 91 for a predetermined irradiation target (eg, tissue A). The control unit 11 controls the set voltage of the power supply using the recipe 91, and can switch to a mode relating to the molding process.

  As an example, the recipe 91 may include at least one mode relating to the ability of the plasma to coagulate the protein components. For example, the sample 7 is a protein component (albumin, collagen, etc.) or a solution containing the protein component. Here, a case where the sample 7 is an aqueous protein solution will be described. First, a protein solution is prepared by mixing a protein with an aqueous solvent. Next, the plasma generated by the plasma irradiation apparatus 1 is irradiated to the aqueous protein solution. Thereby, the protein in the protein aqueous solution is polymerized, and a protein film is formed. Here, using the evaluation unit 13, a recipe showing a relationship between a current value flowing through the sample 7 while irradiating the sample 7 with plasma, a set voltage, and a solidification result (solidification state) of a protein component. Data is created. The created relationship (recipe data) is stored in the storage unit 14 as a recipe 91 for a predetermined irradiation target (eg, tissue A). In this example, the recipe 91 includes mode information corresponding to category 2 (Surgical hemostats) and mode information corresponding to category 3 (Tissue sealant) in protein components such as albumin and collagen. The control unit 11 controls the set voltage of the power supply using the recipe 91, and can switch to a mode related to the coagulation ability of plasma for blood or red blood cells or a mode related to coagulation ability of plasma for protein components. According to such a configuration, the plasma irradiation processing apparatus 1 can switch the mode in the configuration of the liquid in which the protein component is dissolved or the configuration of the liquid containing the red blood cells to adjust the dosage form or generate a film. .

  As an example, the recipe 91 may include a mode for shaping a two-dimensional or three-dimensional structure of protein components. For example, when the plasma generated by the plasma irradiation apparatus 1 is irradiated on the aqueous protein solution, the protein in the aqueous protein solution is polymerized, and a protein film is formed. At this time, the protein films can be laminated to form a three-dimensional structure of the protein component. Here, recipe data showing the relationship between the current value flowing through the sample 7 while irradiating the sample 7 with the plasma, the set voltage, and the solidification result of the protein component (forming of a three-dimensional structure) is created. Then, it is stored in the storage unit 14 as a recipe 91 for a predetermined irradiation target (eg, tissue A). The control unit 11 controls the set voltage of the power supply using the recipe 91, and can switch to a mode related to, for example, molding of a three-dimensional structure of a red blood cell component or a protein component. According to such a configuration, a two-dimensional structure or a three-dimensional structure can be formed by solidification using plasma using a living body having a protein component as a material. In addition, this molding process of the three-dimensional structure may be applied to measurement control of the ink jet unit of the three-dimensional printer.

  As illustrated in FIG. 13, the recipe 91 is stored in the storage unit 14 for each irradiation target (eg, biological tissue), and thus the control unit 11 uses the above-described mode and recipe to execute the irradiation target. The set voltage can be controlled for each object (eg, for each tissue).

  Next, correction when the apparatus is used will be described. FIG. 14 is an example of a flowchart for setting voltage correction when the apparatus is used. The recipe 91 in the storage unit 14 holds information on the current value 93 of each mode. As an example, the evaluation unit 13 can evaluate the performance and safety of the plasma irradiation apparatus 1 using the current value 93 as a reference value.

  The control unit 11 inputs a set voltage value to the power source and the power source of the gas source 3 (S101). The plasma generation unit 2 generates plasma based on the set voltage (S102). The evaluation unit 13 compares the current value measured by the measurement unit 12 with the current value 93 of the recipe 91, which is the reference value (S103). The evaluation unit 13 determines whether the current value is within the range of the reference value or deviates from the reference value (S104). As an example, the evaluation unit 13 determines whether the difference between the current value and the reference value is larger than a threshold value, thereby determining whether the difference is within the reference range. If it deviates from the reference value, the control unit 11 corrects the set voltage value of the power supply based on the determination result of the evaluation unit 13 (S105).

  According to this configuration, the control unit 11 controls the output of the plasma irradiation processing apparatus 1 in accordance with the ever-changing current value when irradiating the living body with plasma, and performs the performance (coagulation ability) as a medical device and Safety (protection of organs, nerve cells, etc.) can be ensured.

  As another example, when the current value deviates from the reference value, the control unit 11 may stop the plasma output from the plasma generation unit 2. As shown in FIG. 9, the amount of hemolysis increases as the plasma irradiation time increases. When blood coagulation proceeds, the resistance of the irradiation target 82 increases, and the measured current value decreases. As an example, when a certain irradiation time has elapsed and the current value is smaller than the reference value, the control unit 11 may stop the plasma output. According to this configuration, by controlling the output of the plasma irradiation processing apparatus 1 in accordance with the resistance value of the irradiation target 82, the control unit 11 can ensure safety as a medical device.

  As another example, the evaluation unit 13 may determine the performance degradation of the plasma irradiation processing apparatus 1 based on a comparison result (computation result) between the current value measured by the measurement unit 12 and the reference value. Good. When the current value deviates from the reference value, the control unit 11 may stop the plasma output from the plasma generation unit 2 due to performance degradation. According to this configuration, the evaluation unit 13 can detect the performance degradation and secure the safety as a medical device.

  As another example, when blood coagulation progresses, the resistance of the irradiation target 82 increases, and the measured current value decreases. Therefore, the evaluation unit 13 determines the current value measured by the measurement unit 12. The progress or degree of coagulation of the sample (the coagulation state of the sample) may be estimated based on the result of comparison (calculation result) with the reference value. According to this configuration, the evaluation unit 13 can detect a change in the current value and predict the formation of a stable blood coagulation membrane.

  Although the present embodiment has been described with reference to the accompanying drawings, it is needless to say that the present invention is not limited to such an example. The combination of each component shown in the above-described example is an example, and various changes can be made based on design requirements and the like without departing from the gist of the present invention.

  The processing of the processing device 6 may be realized by a program code of software for realizing those functions. In this case, a storage medium storing the program code is provided to the apparatus, and the computer (or CPU or the like) of the apparatus reads the program code stored in the storage medium. In this case, the program code itself read from the storage medium realizes the function of the above-described embodiment, and the program code itself and the storage medium storing the program code constitute the present invention. As another example, a part of the processing device 6 may be realized by hardware using electronic components such as an integrated circuit.

  Furthermore, in the above-described embodiment, the control lines and the information lines are those that are considered necessary for the description, and do not necessarily indicate all the control lines and the information lines on the product. All components may be connected to each other.

DESCRIPTION OF SYMBOLS 1 ... Plasma irradiation processing apparatus 2 ... Plasma generation part 3 ... Power supply and gas source 4 ... Stage 5 ... Detection part 6 ... Processing apparatus 7 ... Sample 8 ... Sample holding part 9 ... Electric wire 10 ... Discharge tube 11 ... Control part 12 ... Measurement Unit 13 Evaluation unit 14 Storage unit 15 User interface 81 Electrode pad 82 Irradiation target 91 Recipe

Claims (4)

A plasma generation unit for generating plasma;
To satisfy a film forming current threshold set based on a correlation between a current value flowing through the irradiation target and the coagulation ability of the plasma while the plasma is irradiated on the irradiation target. And a control unit for controlling a voltage applied to the plasma generation unit. The plasma irradiation apparatus according to claim 1,
A plasma irradiation apparatus, comprising: a storage unit that stores a plurality of film generation current thresholds having different values according to the irradiation target. The plasma irradiation apparatus according to claim 1 or 2,
A plasma irradiation processing apparatus comprising: an evaluation unit configured to estimate a progress or a degree of solidification of the irradiation target based on a comparison result between the current value flowing through the irradiation target and a reference value. The plasma irradiation apparatus according to any one of claims 1 to 3,
The plasma irradiation processing apparatus, wherein the control unit stops the output of the plasma from the plasma generation unit based on a comparison result between the current value flowing through the irradiation target and a reference value.

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