Patent Application
20130202479
The present invention relates to a plasma sterilization apparatus which inactivates adhesive bacteria and floating (airborne) bacteria in facilities and space such as bioclean rooms (herein after, referred to as BCR) requiring removal of microorganisms; more particularly, the present invention relates to monitoring technology capable of detecting activeness or inactiveness of bacteria in real time.
Expectations have been raised for achieving regenerative medicine using artificially cultured cells and tissues to regenerate damaged skin, cornea, internal organs, etc. for functional recovery of patients. The number of patients having target diseases is expected to be 20,000 per year even when only those having cornea regeneration are considered and thus practical application of technology has been longed for. It is expected that participation of pharmaceutical companies will also become obvious in the future and regenerative medicine will grow into a new medical industry.
BCR, in which aseptic manipulation can be carried out, is essential in clinical studies and thus establishment of sterilization techniques for surface adhesive bacteria has been an important problem to maintain the indoor environment in the BCR. Conventional sterilization has been carried out by formalin fumigation inside a room but that usage has become prohibited because it is harmful to human body since its carcinogenicity is pointed out. Therefore, other adhesive bacteria sterilization techniques substituting formalin are desired.
To study on a novel sterilization method of surface adhesive bacteria inside a BCR, sterilization methods of surface adhesive bacteria which have been generally used in medical practice or medical-related manufacturers have been researched and roughly classified as follows.
i) Sterilization methods by heating such as dry-heat sterilization, high-pressure steam sterilization, and boiling water sterilization;
ii) Radiation sterilization methods by radiation (γbeam etc.), ultraviolet rays (near 254 nm wavelength), electron beam, etc.; and
iii) Gas sterilization methods by ethylene oxide gas, hydrogen peroxide gas, etc.
Although there are various sterilization methods depending on material, shape, etc. of the sterilized subject as exemplified above, application of the sterilization methods mentioned above in a BCR is considered to be difficult. For example, since the floor in a BCR is a resin-based material, the heat sterilization methods which raise temperature to about 120° C. cannot be used. Also, the process time is a problem in the radiation sterilization methods because its sterilization ability is low and thus radiation for several tens of minutes to several hours is required.
With regard to the gas sterilization methods, since they are harmful to human body same as formalin and require several hours to one day for degassing, using the gas sterilization methods has become avoided. Against such a background, sterilization methods using plasma as a novel sterilization method capable of low-temperature and high-speed processing and not using harmful substances have been getting attentions.
When performing the sterilization treatment in a BCR, a cultivation test using culture media is generally used as a method for determining presence and activeness/inactiveness of bacteria; however, the determination requires time for about several days. Therefore, it is impossible to know when and where contamination due to bacteria occurs in the BCR in real time and thus, currently, the sterilization process of the whole room by formalin has been empirically carried out in a cycle of once every few weeks.
As described above, there is a tendency that fumigation inside a room by formalin is prohibited because formalin is harmful to human body and substitute means such as plasma have been studied. However, it is impossible to irradiate plasma on the whole BCR room at one time, and thus it will be possible to sterilize the whole BCR room effectively if existing position of bacteria is detected and irradiated and the irradiation time is decided when inactiveness is determined.
If such sterilization is achieved, only specific portions where bacteria are increased in a BCR need the sterilization work and it will become unnecessary to make a complete stop (all the workers are evacuated) of the BCR for a few days for sterilization. In addition, it is possible to increase power for plasma generation only at a portion where bacteria exist and thus it will be possible to carry out sterilization on the whole BCR room with low power.
As a method of determining inactivation of bacteria in real time, Patent Document 1 discloses a method of measuring oxygen radicals in the plasma treatment using an optical detector. Changes of oxygen radicals desorbed from bacteria are observed by plasma and determination of extinction of bacteria is made when the changes of oxygen radicals become constant as bacteria are completely disappeared (bacteria are decomposed by various radicals generated by the plasma. The smaller the radius of bacteria by the decomposition, the smaller the amount of oxygen radicals desorbed; thus, timing at which the amount of generated oxygen radicals becomes constant when bacteria are completely disappeared).
However, although it is possible to determine disappearance of bacteria in the method described above, inactivation of bacteria which have been already generated before disappearance cannot be determined. Therefore, irradiation of plasma until bacteria are completely disappeared poses an increase in the process time. In addition, considering that the usage of the above-described method for the sterilization in a BCR, since a floor and walls inside the BCR are organic substance (main components: C, O, N), oxygen radicals may be desorbed from the floor and walls by irradiation of plasma; thus, it is expected to be difficult to determine the disappearing time of bacteria.
Patent Document 2 discloses a system, as an apparatus for monitoring dehydration operation during a freeze-drying process, of determining whether water (moisture) inside a chamber is completely dehydrated or not by generating plasma inside the chamber and paying attention to hydrogen radicals in the emission spectrum of the plasma. It is also disclosed that there is a sterilization effect as OH radicals are generated by generating plasma in a state that water exists inside the chamber.
However, the above-described way is originally a system for measuring the amount of water (=humidity) presenting inside the chamber for monitoring the dehydration state inside the chamber; thus, it is not a system of determining inactiveness by measuring reactive products generated from bacteria. In addition, although OH radicals are generated by generating plasma and thus an effect of sterilizing bacteria can be expected, water is detected when a large amount of water is contained in a gas for plasma generation when and thus it is difficult to measure spectrum of hydrogen desorbed from bacteria.
Patent Document 3 discloses, focusing on a light emission phenomenon correlated to plasma discharge, an air-cleaner apparatus capable of effectively controlling the generated amount of ions by estimating the generated amount of positive and negative ions based on the intensity of emission of light generated by the plasma discharge phenomenon. The emission intensity in a surface of ion-generating electrodes (plasma generating portions) is monitored and an output (generated amount of ions) of the ion-generating electrodes can be controlled based on detected emission information.
However, the above-described methods correspond to temporal changes of the electrodes and humidity changes in the discharge space by detecting light emission amount from the plasma and thus they cannot determine inactiveness of bacteria by taking notice of a specific emission spectrum.
As one example of the experiments made by the inventors, a case of yeast will be explained. Yeast forms tissues in a shell-like shape outside the cell cytoplasm and exhibits high resistant characteristics against sterilization by heat and ultraviolet rays. When Bacillus subtilis is irradiated with plasma, its outer shell is first altered and then its internal cell is altered. The inventors have taken attention to a phenomenon of increasing the light emission intensity of C2 around timing at which light emission of H attenuates like that in
Therefore, a preferred aim of the present invention is to provide a plasma sterilizer capable of highly efficient sterilization by determining presence and activeness/inactiveness of bacteria in real time by measuring a specific light emission spectrum of a component derived from an organism when performing sterilization using plasma.
To solve the above-mentioned problems, a plasma sterilizer of the present invention includes: a power supply outputting alternating-current voltage; a plasma source driven by the power supply; a light emission intensity detector detecting light emission intensity of hydrogen or hydroxyl group from a region in which a gas that is radicalized by the plasma source is present; and a controller controlling an output of the power supply based on the light emission intensity.
In addition, to solve the above-mentioned problems, a plasma sterilizer system of the present invention includes: a power supply outputting alternating-current voltage; a plasma source driven by the power supply; a light emission intensity detector detecting light emission intensity of hydrogen or hydroxyl group from a region in which a gas that is radicalized by the plasma source is present; a clock defining a detection time of the light emission intensity; and a controller controlling an output of the power supply based on the light emission intensity within a certain period measured by the clock.
Moreover, to solve the above-mentioned problems, a method of plasma sterilization of the present invention includes: a power supply outputting alternating-current voltage; a plasma source driven by the power supply; a light emission intensity detector detecting light emission intensity; and a controller performing control of changing an output of the power supply, the method including: a first step of applying the output of the power supply to the plasma source; a second step of generating a gas that is radicalized by the plasma source; a third step of detecting light emission intensity of hydrogen or hydroxyl group from a region in which the gas is present; and a fourth step of controlling the output of the power supply based on the light emission intensity.
According to the present invention, it is possible to highly efficiently sterilize upon a sterilization process using plasma.
Incidentally, the irradiation of the plasma as referred to herein is gas generated upon discharge and it is directed to a state in which freely moving charged particles are present and electrically neutral. That is, phenomena not only the discharging portion directly works on bacteria but also radicals generated by the discharge gives a sterilization effect on bacteria are included. Thus, the sterilization process can be performed when a generation region of radicals, instead of a discharge region, is present in the processing target surface 100.
When performing sterilization inside a BCR, the target processing surface 100 is a floor and walls of the BCR and the target processing organism 101 is, for example, Bacillus subtilis.
By using or adding oxygen as a gas for generating the plasma 4, oxygen radicals are generated in the plasma 4. When the target processing organism 101 is irradiated with the plasma 4, desorption of hydrogen from the surface from cell walls of the target processing organism 101 by oxygen radicals is started. In this manner, the target processing organism 101 is inactivated as protein of the surface is altered.
Upon the start of the desorption, by measuring a light emission spectrum (e.g., 655 nm) of hydrogen in the plasma 4 by a spectrometer 5, a start time and an end time of the hydrogen desorption can be detected. When the hydrogen desorption ends, that is, when the light emission is hydrogen is attenuated and the light emission amount becomes constant, the target processing organism 101 is inactivated; if the hydrogen desorption can be detected, inactivation of the target processing organism 101 can be determined.
Detected information of the light emission intensity of hydrogen from the spectrometer 5 is transmitted to a control board 6 of the high-frequency power supply 2. When determining a presence of the target processing organism 101, the output power of the high-frequency power supply 2 may be set at a low level to reduce power consumption. Then, when a presence of the target processing organism 101 is recognized, the output power of the high-frequency power supply 2 is raised until inactivation of the target processing organism 101 is confirmed. In this manner, the generated amount of oxygen radicals in the plasma is increased to inactivate the target processing organism 101 at high speed.
Note that, when monitoring the target processing organism 101 by detecting a light emission spectrum of hydrogen, water may be detected if water etc. is attached to, for example, the target processing surface 100 in the BCR.
In this case, a light emission spectrum of a substance derived from an organism (e.g., phosphorus) may be detected together with the light emission spectrum of hydrogen. Phosphorus is a component contained in lipids of organisms and not contained in water or other organic substances. That is, presence of the target processing organism 101 may be determined by detecting the light emission spectrum of phosphorus to determine inactiveness of the target processing organism 101 from the light emission spectrum of hydrogen.
Further, although not illustrated here, when hydrogen of the outermost surface of yeast is desorbed, carbon etc. are desorbed subsequently. At this timing, yeast has been already inactivated and it is unnecessary to perform a sterilization process.
In the present invention, focusing on the fact that bacteria is inactivated at the timing at which hydrogen in a surface is desorbed, a light emission spectrum of hydrogen or hydroxyl (OH) is measured. Thus, inactivation of survivor bacteria can be determined earlier than monitoring desorption of carbon and thus a reduction of the process time and an improvement of process efficiency are achieved.
Note that, while
Note that, while a series of descriptions has been made in
The insulator 1 relates to characteristics of the generated plasma. When the plasma is generated by performing an atmospheric discharge from electrodes, an arc high-current discharge is made. However, a low-current glow discharge can be performed by using the insulator 1 and thus power can be reduced. Thus, the insulator 1 is provided to reduce the power of discharge and so the insulator 1 is not always necessary upon working of the present invention. Also, the volume of the discharge space can be reduced in glow discharge more than in other discharge systems and thus is suitable to small-sized apparatuses like the present invention.
The high-frequency power supply 2 controls the potential and frequency required in discharge. By a basic operation, the speed of inactivation of the target processing organism can be increased by increasing the magnitude of the potential and frequency. In addition, when a presence of the target processing organism 101 is not confirmed, the magnitude of the potential and frequency may be reduced. Further, the control may be performed with a potential and a frequency at which a low-current glow discharge can be generated even in the absence of the insulator 1. For example, a high-frequency voltage is controlled in discrete pulses to suppress the amount of current flowing in the plasma. In this manner, since there is also a case of reducing power by the high-frequency power supply 2, the insulator 1 for power reduction can be omitted.
Changing the shapes of the high-frequency electrode 3 and the ground electrode 3′ can change characteristics of the generated plasma. By changing electrode shapes, power of the apparatus can be reduced in the same manner as the insulator 1 and the high-frequency power supply 2 described above.
Note that the plasma is generated in accordance with an electric field formed by the high-frequency electrode 3 and the ground electrode 3′. Thus, when the high-frequency electrode 3 and the ground electrode 3′ are arranged to be close to the target processing surface 100, higher-density plasma can be irradiated on the target processing surface 100. However, the plasma may be at high temperature in some cases and thus a distance to some extent not posing a temperature degradation to the target processing surface 100 may be provided.
The example in which the target processing surface 100 is a floor of a BCR has been described. However, it is also compatible to sterilization of the walls by making a portion for performing sterilization crawl along wall surfaces. Other than making the apparatus itself moved along the sidewalls by magnetic force and adhesive force, the apparatus may be such that the portion on which the sterilized process is performed is moved along the wall surface.
The example that the target processing organism 101 is, for example, Bacillus subtilis has been described. The reason of exemplifying Bacillus subtilis is that Bacillus subtilis exhibits high resistance against sterilization by heat and ultraviolet rays and is thus used in biological indicators (BI) of this art. Thus, the present invention is also effective to bacteria having high resistance against sterilization by heat and ultraviolet rays and the range of bacteria which can be processed are wide in addition to Bacillus subtilis and yeast.
An example has been described that the gas for generating the plasma 4 is, for example, oxygen. However, it is not limited as long as the gas is for desorbing organic substances. The reason of selecting oxygen here is that oxygen exists in the atmosphere and also is highly effective in desorbing organic substances. By supplying oxygen from the atmosphere, it is not necessary for the plasma sterilization apparatus to take along a cylinder (tank) in which a desorbing gas is sealed and thus downsizing can be achieved. In addition, it is also unnecessary to replace the gas cylinder (tank) and thus there is an effect of reducing running costs.
Further, for forcible convection of the gas for generating the plasma 4 to the processing surface 100, a fan or the like for ventilation may be mounted. Depending on a presence or absence of a device for forcible convection and the strength of convention, more radicalized gas is present on the processing surface and thus the processing efficiency can be improved. In addition, when natural convection is utilized, while the processing efficiency is lowered than the case of having a device for forcible convention, the device for forcible convection can be omitted.
Inactivation of a target for detecting an intensity change in wavelength can be also determined even when a light emission spectrum of hydroxyl group (OH) is measured except for that of hydrogen. As illustrated in the detection result in
A light emission spectrum of each substance means a range of wavelength in which a satisfactory light emission intensity of each substance such as hydrogen, hydroxyl group or phosphorus can be obtained. Generally known regions of wavelengths of respective substances include near 410 nm to 490 nm or near 650 nm to 660 nm having a peak at 656 nm for hydrogen. In addition, near 302.1 nm to 308.9 nm for hydroxyl group, and near 215.4 nm to 255.5 nm or 919.4 nm to 1058.2 nm for phosphorus are typical. In this manner, the detection may be performed with selecting from a wavelength range in which satisfactory light emission intensity of each substance can be obtained.
The spectrometer 5 performs detection of light emission intensity of a waveform at which light emission intensity of each substance can be well obtained, using a color filter and a light-receiving element, and thus it is not always necessary to detect the entire visible light region. Since it is only necessary to be able to detect intensity of a specific wavelength, downsizing and cost reduction of the apparatus can be achieved. Also, in addition to directing the light-receiving unit of the spectrometer 5 directly to the target processing surface 100, further better detection sensitivity can be obtained by using a condenser lens and/or optical fiber. Particularly, when an optical fiber is interposed between the target processing surface 100 and a light-receiving unit of the spectrometer 5, it is not necessary to install the spectrometer 5 in a vicinity of the target processing surface 100 and thus the degree of freedom can be increased.
Although not illustrated in
A second embodiment of the present invention will be described hereinafter. Even when other plasma generating methods than that of the first embodiment is used, determination of presence and inactiveness of a target processing organism 101 by light emission spectrum of the present invention is possible.
For example,
A spectrometer 5 and a control board 6 are installed in the same manner as the first embodiment and an output of a high-frequency power supply 2 is controlled based on intensity information of a light emission spectrum of hydrogen. Note that, when it is possible to suppress the amount of current flowing in the plasma by controlling high-frequency voltage supplied from the high-frequency power supply 2 in a discontinuous pulse form, the temperature of the plasma will not be high to some extent to degrade the target processing surface 100 inside the BCR even without the insulator for protecting the electrode.
By using the configuration of
In addition, a schematic diagram to be still another example of the configuration of the plasma sterilization apparatus of the present invention is illustrated in
In the present structure, plasma is generated being stuck to the surface of the insulator 1 and thus the insulator 1 is put directly close to the target processing surface 100. In this manner, plasma can be generated in a large area and thus a wide area of the target processing surface 100 can be processed in a lump. A measurement method of light emission spectrum here is the same as that of
A third embodiment of the present invention will be described hereinafter.
As a result, hydrogen radicals generated per a unit time are increased and light emission detection of hydrogen is made easier. Also, required time of inactivation can be also shortened.
A fourth embodiment of the present invention will be described hereinafter.
A self-moving plasma sterilization apparatus is illustrated in
In
Further, during irradiation of plasma 4 to the target processing organism 101, the status in a sterilization processing may be displayed to the outside by display means 9 like LEDs etc. provided to the above-described apparatus 102. Further, the apparatus 102 may be back to a charging space installed in the BCR by autonomous moving after moving around in the whole BCR. Timing of operating the apparatus 102 is once in a few hours or once in a day depending on a required cleanness of the BCR.
Although it is possible to operate the apparatus 102 even while a worker(s) is at work, the apparatus 102 may be operated in night time when a worker(s) leaves from the BCR. In this manner, it is not necessary to completely stop the operation of the BCR for a few days for the sterilization processing and thus it is possible to keep the inside always clean.
In addition, by combining rotation information of a motor of a moving portion with the logger function, it is possible to map where contaminated parts are present on the field. For the mapping, a sensor for obtaining position information may be suitably provided. By comparing the mapping information thus obtained and a result of an arrangement plan of work tables and staff in the BCR, an easily contaminated location 104 or easily contaminated time can be specified depending on the arrangement. By performing the sterilization work with weighting assigned to the specified space and time, the BCR can be operated at a further lower contamination level.
Moreover, by performing control for suppressing factors of letting bacteria being present on the floor surface soar with respect to the specified space and time, possibility of attachment of bacteria onto samples in the BCR can be lowered. More specifically, control is performed so as not to cause convection of air in the specified location and time with respect to an air convection apparatus (e.g., air conditioning apparatus) 105. Alternatively, a display monitor or the like may be embedded in a system to display the specified location and time and an alarm function may be provided so that moving of measurement devices and a person(s) inside the BCR are deterred.
A fifth embodiment of the present invention will be described hereinafter.
For example, a plasma sterilization apparatus same as that in
In this manner, the target processing organism 101 floating in the air can be inactivated. Note that, although the floating target sometimes passes through the processing box being incompletely inactivated during one passing through the processing box, by installing the processing box to an air outlet or the like of an air conditioner in the BCR, the air in the room are sure to pass through the inside of the processing box 103 and so every target processing organisms 101 is inactivated after repeating passing through the processing box 103.
Further, it is more preferable that light emission information of the target processing organism 101 floating in the BCR is output from the spectrometer 5 and the amount of air flow of the air convection apparatus in the BCR is controlled. For example, when the target processing organism 101 is increased, increasing the high-frequency power supply 2 or the amount of air flow of the air convection apparatus can kill the target processing organism 101 in BCR at a higher speed.
Note that, upon generation of plasma, the above-described plasma sterilization apparatuses in
As described in the foregoing, according to the present invention, it is possible to irradiate plasma only on necessary portions by detecting presence of bacteria in a sterilization processing using plasma. In addition, it is possible to decide irradiation time by determining inactivation and to sterilize the entire BCR room highly efficiently. In this manner, it is only necessary to perform the sterilization work targeting on bacteria in an active state in the BCR and thus it is not necessary to completely stop operation of the BCR for the sterilization processing. In addition, the output power of the power supply can be increased for generating plasma at portions where bacteria in an active state are present and thus sterilization inside the BCR can be performed at low power.
Further, the sterilization technology of surface-attached bacteria using plasma suggested by the present invention is targeted on in-room sterilization of mainly BCRs for regenerative medicine; however, it can be diverted to manufacturing facilities of medical supplies and food supplies and hospital facilities which require elimination of microorganisms. Moreover, it can be also diverted to sterilization of floating bacteria as well as surface-attached bacteria and thus it can be applied to sterilization in homes, refrigerators and so forth for domestic home appliances etc.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/JP2010/068550 | 10/21/2010 | WO | 00 | 4/8/2013 |
