Abstract:
A virus detection device includes a diffusion unit configured to diffuse a virus in a gas as an inspection target into an aqueous solution containing a fluorescent antibody specifically adsorptive to the virus by bringing the gas into contact with the aqueous solution and configured to adsorb the fluorescent antibody to the virus in the gas; an atomization unit configured to atomize the aqueous solution and generate a mist group of the aqueous solution in which the gas is diffused; a fluorescence measuring unit configured to measure a fluorescence intensity of the mist group; and an air current generator configured to form an air current flowing toward the fluorescence measuring unit from the atomization unit.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This Application is a Continuation of International Application No. PCT/JP2011/005767 filed on Oct. 14, 2011, which claims the benefit of Japanese Patent Application No. 2010-244474 filed on Oct. 29, 2010. The entire disclosure of the prior application is incorporated herein by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The present disclosure relates to a technique for detecting a virus. 
     BACKGROUND OF THE INVENTION 
     Recently, the wide spread of infectious diseases such as influenza and the expansion of a range of infection are considered as serious problems. In order to promptly solve the problems for public heath, there has been a demand for a highly precise and simple method for virus analysis. Currently, in quarantine inspection, a cleaning liquid after cleaning one&#39;s nasal cavity is analyzed. However, this inspection method has problems in sensitivity and time period for diagnosis. Further, in order to take measures against pandemic and bio terrors, viruses in the atmosphere need to be inspected constantly. In a manual inspection method conducted by a human being, such as inspecting the cleaning liquid from the nasal cavity, it is difficult to expect the automation of the virus analysis. As for the analysis of, e.g., an influenza virus in the atmosphere, there is a cultivation method for observing and analyzing colonies formed after culturing the virus adhered to a culture medium. However, this cultivation method has drawbacks in that it takes several days for the cultivation and it is difficult to automate the cultivation method. Thus, this cultivation method may not be useful when prompt analysis is required in such cases as dealing with a novel influenza, a foot-and-mouth disease virus, and the like. Additionally, there may be employed a method for detecting a virus in the atmosphere by trapping the virus in a liquid. In this method, however, due to low sensitivity of analysis in the liquid, the virus may not be precisely detected. 
     Under these circumstances, Non-Patent Document 1 describes a method for detecting a virus with high sensitivity in a short time period by selectively adsorbing a fluorescent antibody in a certain virus and then measuring fluorescence intensity. In the method of Non-Patent Document 1, however, a mucous membrane or saliva is analyzed as a sample and the analysis is not conducted automatically on a real time basis. Further, in the above method of Non-Patent Document 1, presence or absence of a virus is determined by detecting a variation difference in the fluorescence intensity, not by an absolute value of the fluorescence intensity. 
     Non-Patent Document 1: Hasegawa Makoto, “Development of High Sensitivity Pathogenic Organism Detection Method for Airport Quarantine and against Bio Terror,” [online], Oct. 8, 2008, New Energy and Industrial Technology Development Organization, [Searched on Jul. 6, 2010], Internet &lt;URL: http://www.nedo.go.jp/informations/press201008 — 1/201008 — 1.html&gt; 
     BRIEF SUMMARY OF THE INVENTION 
     In view of the foregoing problems, the present disclosure provides a technique for precisely detecting a virus in the atmosphere on a real time basis. 
     In accordance with one aspect of the illustrative embodiment, there is provided a virus detection device including a diffusion unit configured to diffuse a virus in a gas as an inspection target into an aqueous solution containing a fluorescent antibody specifically adsorptive to the virus by bringing the gas into contact with the aqueous solution and configured to adsorb the fluorescent antibody to the virus in the gas; an atomization unit configured to atomize the aqueous solution and generate a mist group of the aqueous solution in which the gas is diffused; a fluorescence measuring unit configured to measure a fluorescence intensity of the mist group; and an air current generator configured to form an air current flowing toward the fluorescence measuring unit from the atomization unit. 
     In accordance with another aspect of the illustrative embodiment, there is provided a virus detection method including diffusing a virus in a gas as an inspection target into an aqueous solution containing a fluorescent antibody specifically adsorbed to the virus by bringing the gas into contact with the aqueous solution, and adsorbing the fluorescent antibody to the virus in the gas; atomizing the aqueous solution and generating a mist group of the aqueous solution in which the gas is diffused; and measuring a fluorescence intensity of the mist group. 
     In accordance with the illustrative embodiment, the virus in the gas as an inspection target is diffused into the aqueous solution containing the fluorescent antibody specifically adsorbed to a certain virus. Then, mist of the chemical liquid is generated and fluorescence intensity of the mist is measured. With this method, presence or absence of the certain virus in the gas can be detected automatically on a real time basis. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Non-limiting and non-exhaustive embodiments will be described in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments in accordance with the disclosure and are, therefore, not to be intended to limit its scope, the disclosure will be described with specificity and detail through use of the accompanying drawings, in which: 
         FIG. 1  is a schematic view illustrating a configuration of a virus detection device in accordance with an illustrative embodiment; 
         FIG. 2  is a longitudinal side view illustrating a part of a micro fluid chip used in the illustrative embodiment; 
         FIG. 3  is a longitudinal side view illustrating a fluorescence measuring unit used in the illustrative embodiment; 
         FIG. 4  is a conceptual view for describing a virus diffusion in a chemical liquid, adsorption of a fluorescent antibody and atomization of the chemical liquid in a diffusion unit; 
         FIG. 5  is a conceptual view for describing diffusion of dust in the atmosphere in a chemical liquid, adsorption of a fluorescent antibody and atomization of the chemical liquid in the diffusion unit; 
         FIG. 6  is a schematic view illustrating a virus detection device in accordance with a second illustrative embodiment; 
         FIG. 7  is a schematic view illustrating a virus detection device in accordance with a third illustrative embodiment; 
         FIG. 8  is a schematic view illustrating a virus detection device in accordance with a fourth illustrative embodiment; and 
         FIG. 9  is a schematic view illustrating an atomization unit and a fluorescence measuring unit of a virus detection device in accordance with a fifth illustrative embodiment. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Configuration of a virus detection device in accordance with an illustrative embodiment will be explained with reference to  FIGS. 1 to 3 . As illustrated in  FIG. 1 , the virus detection device includes a main pipeline  8  configured as a guide passage of an air current. A dust removing unit  1  is provided at an upstream end of the main pipeline  8 , and a suction pump  7  serving as an air current generator is provided at a downstream end of the main pipeline  8 . The dust removing unit  1  is configured to allow a virus V to pass therethrough and required to have an enough air current resistance to form a fast air current capable of generating atomization in the main pipeline  8 . To this end, the dust removing unit  1  is configured to capture relatively large-sized particles. Further, in the main pipeline  8 , there is provided an atomization unit  4  configured to generate mist of a chemical liquid supplied from a micro fluid chip  3  serving as a diffusion unit to be described later. 
     As illustrated in  FIG. 2 , the micro fluid chip  3  includes a cover  32  and a plate-shaped body  33 . A groove  31  is formed on a top surface of the plate-shaped body  33 . The groove  31  is covered by the cover  32  to serve as a diffusion flow path  31 . As illustrated in  FIG. 2 , the diffusion flow path  31  has a cross section in the form of two semicircles, which are arranged next to each other horizontally and partially overlapped with each other. A protrusion  30  is formed at a middle part of the flow path. The diffusion flow path  31  is partitioned by the protrusion  30  into a gas flow path  34  and a liquid flow path  35 . As for the dimension of the diffusion flow path  31 , a width (W) of the diffusion flow path  31  is set to be equal to or less than, e.g., about 1 mm; a depth (H) thereof is set to be, e.g., about 0.5 mm; and a height of a gap between the protrusion  30  and the cover  32  is set to be, e.g., about 0.2 mm. As illustrated in  FIG. 1 , in order to obtain sufficient contact time between the atmosphere and the chemical liquid and a contact area therebetween, the diffusion flow path  31  is formed to meander. Both ends of the diffusion flow path  31  are branched into two lines at branch points and reach end portions of the micro fluid chip  3  in this state. One end (upstream end) of the diffusion flow path  31  corresponds to an atmosphere inlet port  36  and a chemical liquid inlet port  37 . The other end (downstream end) of the diffusion flow path  31  corresponds to an exhaust port  38  and a chemical liquid outlet port  39 . 
     As illustrated in  FIG. 1 , a branch line  13  branched from the main pipeline  8  between the dust removing unit  1  and the atomization unit  4  is airtightly connected to the atmosphere inlet port  36  of the micro fluid chip  3 . A gas intake pump  11  as a gas introduction unit and an atmosphere flow rate controller  12  are provided at the branch line  13  in this order from the upstream side thereof. Connected to the chemical liquid inlet port  37  is a pipeline  23  led from a chemical liquid storage tank  2  that stores therein a chemical liquid, which is an aqueous solution containing a fluorescent antibody F. Further, a chemical liquid supply pump  21  as a liquid introduction unit and a chemical liquid flow rate controller  22  are provided at the pipeline  23  in this order from the chemical liquid storage tank  2 . The exhaust port  38  of the micro fluid chip  3  is connected to an outside of the virus detection device. The atmosphere introduced into the micro fluid chip  3  is exhausted through the exhaust port  38 . The chemical liquid outlet port  39  of the micro fluid chip  3  is connected to the aforementioned atomization unit  4  via a chemical liquid supply line  40 , which is a guide passage. 
     The atomization unit  4  includes a part  81  of the main pipeline  8  of which diameter is sharply narrowed; and the chemical liquid supply line  40  inserted into the part  81  of the main pipeline  8 . The chemical liquid supply line  40  serves as a guide passage through which the chemical liquid from the micro fluid chip  3  is flown. 
     A fluorescence measuring unit  5  is provided at a downstream side of the atomization unit  4 . As illustrated in  FIG. 3 , the fluorescence measuring unit  5  includes a case  56  of, e.g., a quadrangle shape. The case  56  forms a space through which an air current including mist M flows. Light transmitting windows  52   a  and  52   b  made of, e.g., quartz are arranged at the case  56 , for example, at top and bottom (or right and left) surfaces thereof such that the light transmitting windows  52   a  and  52   b  face each other. Disposed outside one light transmitting window  52   a  is a light emitting unit  51  that irradiates a laser beam having a wavelength deviated from a wavelength of fluorescence emitted from the fluorescent antibody F into the case  56 . Further, disposed outside the other light transmitting window  52   b  is an optical filter  53  that blocks light having a wavelength deviated from the wavelength of fluorescence emitted from the fluorescent body F. Disposed at a further outer position with respect to the light transmitting window  52   b  is a light receiving unit  54  that receives the fluorescence of the fluorescent antibody F to convert the fluorescence into an electrical signal. The light receiving unit  54  outputs a signal level, e.g., an electric current, corresponding to the intensity of the light received from the optical filter  53  to a received light output measuring unit  55 . For example, the received light output measuring unit  55  converts the electric current into a voltage and compares the voltage signal Ia with a preset threshold value Is. If it is determined that the voltage signal Ia is larger than the threshold value Is, the received light output measuring unit  55  may output an alarm indicating virus detection or display the virus detection on a non-illustrated display unit. 
     Since the voltage signal Ia is a signal corresponding to the intensity of the received light, the threshold value Is may be determined as follows. That is, the threshold Is is set to a value between a fluorescence intensity when no virus V exists in the atmosphere; and a fluorescence intensity when the mist M, in which the fluorescent antibody F is adsorbed a virus V in the atmosphere, passes through the case  56 . The fluorescence intensity when no virus V exists in the atmosphere corresponds to an intensity of fluorescence from a fluorescent antibody F adhered to a dust D contained in the atmosphere passing through the case  56  or a fluorescent antibody F contained in the mist M of the chemical liquid. The fluorescent antibody F is specifically adsorbed to the virus V. Thus, roughly speaking, when the virus V exists, a density of the fluorescent antibody F becomes higher than a density of the fluorescent antibody when no virus V exists, as illustrated in  FIGS. 4 and 5  to be described later. Accordingly, there is generated a difference in fluorescence intensity between the two cases when the virus V exists and when no virus V exists. 
     At a downstream side of the fluorescence measuring unit  5 , there is provided a chemical liquid collecting unit  6  formed of, for example, a mesh member for capturing mist M of the chemical liquid. Further, the suction pump  7  is provided at a downstream side of the chemical liquid collecting unit  6 . A separated gas is exhausted to an outside of the device via, e.g., a non-illustrated filter for adsorbing and removing a virus. 
     Now, an operation of the virus detection device in accordance with the present illustrative embodiment will be explained. First, the atmosphere (exterior air) is introduced into the main pipeline  8  via the dust removing unit  1  by the suction pump  7 . There is generated an air current that flows through the atomization unit  4 , the fluorescence measuring unit  5  and the chemical liquid collecting unit  6  in this order. The air current is exhausted via the suction pump  7  and the non-illustrated filter. Here, the dust removing unit  1  removes a large-sized dust in the atmosphere that may block the diffusion flow path  31  of the micro fluid chip  3  or interrupt fluorescence detection in the fluorescence measuring unit  5 . A part of the atmosphere introduced into the main pipeline  8  is flown into the atmosphere inlet port  36  of the micro fluid chip  3  by the gas intake pump  11 . The chemical liquid containing the fluorescent antibody F is flown from the chemical liquid storage tank  2  into the chemical liquid inlet port  37  of the micro fluid chip  3  by the chemical liquid supply pump  21 . 
     The atmosphere flow rate controller  12  and the chemical liquid flow rate controller  22  set a flow rate of the atmosphere flown into the atmosphere inlet port  36  and a flow rate of the chemical liquid flown into the chemical liquid inlet port  37 , respectively, to appropriate values obtained in advance through experiments. Accordingly, the atmosphere and the chemical liquid introduced into the micro fluid chip  3  flow side by side while forming an interface on the protrusion  30  of the diffusion flow path  31 . That is, the atmosphere flows through the gas flow path  34  in the diffusion flow path  31  toward the exhaust port  38 . The chemical liquid flows through the liquid flow path  35  in the diffusion flow path  31  toward the chemical liquid outlet port  39 . When the atmosphere and the chemical liquid flow within the micro fluid chip  3  in this way, a virus V in the atmosphere is diffused into the chemical liquid via the interface. The fluorescent antibody F in the chemical liquid is specifically adsorbed to the virus V. The atmosphere and the chemical liquid are separated from each other at a branch point near the outlet of the diffusion flow path  31 . Then, the atmosphere is exhausted to the outside of the device via the exhaust port  38 , and the chemical liquid is flown into the atomization unit  4  through the chemical liquid outlet port  39  and the chemical liquid supply line  40  serving as the guide passage. 
     In the atomization unit  4 , the chemical liquid sent from the micro fluid chip  3  through the chemical liquid supply line  40  is atomized by the air current. Here, the air current has been already speeded up as the main pipeline is sharply narrowed. That is, the chemical liquid is attracted from the outlet of the chemical liquid supply line  40  toward the high-speed air current to be groups of mist M. Then, the groups of mist M of the chemical liquid ride on the air current and are guided to the fluorescence measuring unit  5  through the guide passage of the main pipeline  8  at the downstream side of the atomization unit  4 . 
     In the fluorescence measuring unit  5 , e.g., an ultraviolet laser beam is irradiated from the light emitting unit  51  toward the case  56  through which the atomized chemical liquid flows. At this time, the fluorescent antibody F in the atomized chemical liquid fluoresces by the ultraviolet laser beam. The ultraviolet laser beam is blocked by the optical filter  53 , while light having a wavelength of fluorescence is detected by the light receiving unit  54 . The detected light intensity at this time is in proportion to a volumetric density of the fluorescent antibody F in the mist M of the chemical liquid. If no virus V exists in the mist M of the chemical liquid, as illustrated in  FIG. 5 , a fine dust D in the atmosphere may be introduced into the mist M. Thus, even though the florescent antibody F adheres to the dust D, the density of the fluorescent antibody F may be much lower than the density of the fluorescent antibody F adsorbed to the virus V. Accordingly, the light intensity detected by the light receiving unit  54  may be smaller than the preset threshold value Is. Meanwhile, if a virus V exists in the mist M of the chemical liquid, the fluorescence intensity detected by the light receiving unit  54  may become higher than the threshold value Is. In this case, the received light output measuring unit  55  notifies the detection of the virus V. 
     The mist M having passed through the fluorescence measuring unit  5  is gas-liquid separated in the chemical liquid collecting unit  6 . The separated chemical liquid is collected, whereas the separated gas is exhausted to the outside of the device by the suction pump  7  provided at the downstream of the chemical liquid collecting unit  6 . 
     In accordance with the above-described illustrative embodiment, the virus V in the atmosphere as a target of inspection is diffused in the chemical liquid (aqueous solution) containing the fluorescent antibody F that is specifically adsorbed to the certain virus V. The mist M of the chemical liquid is generated and the fluorescence intensity of the mist M is measured. When the virus V exists, the fluorescent antibody F is specifically adsorbed to the virus V so that the number of the fluorescent antibodies F in the mist M is increased. Accordingly, the intensity of the fluorescence emitted from the mist M when the virus V exists becomes greater than the intensity of the fluorescence emitted from the mist M when no virus V exists. The laser beam is blocked by the optical filter  53 , and the intensity of the fluorescence that has transmitted the optical filter  53  is measured and compared with the fluorescence intensity (threshold value) corresponding to the intensity of the fluorescence emitted from the mist M when no virus V exists. Accordingly, the virus V contained in the atmosphere can be detected with high precision on a real time basis. In addition, since the virus detection can be automatically performed, the virus V can be monitored constantly. Hence, when used in an airport or the like, the virus detection device in accordance with the present illustrative embodiment will be very effective because a virus V can be detected promptly and an immediate countermeasure thereto can be taken. 
     In the above-described illustrative embodiment, the atmosphere forming the air current in the main pipeline  8  and the atmosphere in contact with the chemical liquid in the micro fluid chip  3  are supplied from an identical system after passing through the dust removing unit  1 . However, besides the dust removing unit  1  in the main pipeline  8 , it may be possible to provide an additional dust removing unit and supply the atmosphere to the micro fluid chip  3  through a separate line from the main pipeline  8 . 
     In the illustrative embodiment of  FIG. 1 , the micro fluid chip  3  is provided. However, as illustrated in  FIG. 6 , without providing the micro fluid chip  3 , the atomization unit  4  may be provided by submerging one end of the chemical liquid supply line  40  in the chemical liquid storage tank  2  and inserting the other end of the chemical liquid supply line  40  into the narrow part  81  of the main pipeline  8 , as in the above-described illustrative embodiment. In this case, a negative pressure is generated at the other end of the chemical liquid supply line  40  due to the air current formed in the main pipeline  8  by the suction pump  7 . Accordingly, the chemical liquid in the chemical liquid storage tank  2  is attracted into the main pipeline  8  via the chemical liquid supply line  40  to be atomized (i.e., mist of the chemical liquid is generated). When the virus V in the atmosphere passes through the atomization unit  4 , the virus V is introduced into the mist of the chemical liquid generated at the other end of the chemical liquid supply line  40 . Accordingly, since the virus V is diffused into the chemical liquid through the atomization unit  4 , the atomization unit  4  also functions as the diffusion unit in accordance with this illustrative embodiment. Further, in this illustrative embodiment, the same effect as achieved in the above-described illustrative embodiment may also be obtained. 
     In the illustrative embodiment where the atomization unit  4  also functions as the diffusion unit, the chemical liquid supply pump  21  may be provided on the way of the chemical liquid supply line  40 , as illustrated in  FIG. 7 . In this case, the chemical liquid in the chemical liquid storage tank  2  may be supplied into the atomization unit  4  through a liquid supplying operation of the chemical liquid supply pump  21 . 
     In the illustrative embodiment of  FIG. 1 , the micro fluid chip  3  is used as the diffusion unit. However, as shown in  FIG. 8 , an aeration tank  90  may be used as the diffusion unit. In this configuration, the atmosphere may be brought into contact with a chemical liquid in the aeration tank  90  by an air diffusion device  91  so that a virus V in the atmosphere is diffused into the chemical liquid. In  FIG. 8 , a reference numeral  93  refers to a ventilation port. In this configuration, one end of a chemical liquid supply line  40  may be submerged in the aeration tank  90 , and the chemical liquid may be attracted from the other end of the chemical liquid supply line  40  by an air current generated by the suction pump  7 , so that the chemical liquid may be atomized. Here, it may be also possible to provide a chemical liquid flow rate controller on the way of the chemical liquid supply line  40 , as depicted in  FIG. 7 . 
     In accordance with another illustrative embodiment, as shown in  FIG. 9 , a virus detection device may include a dual pipeline  96  having an inner pipeline  94  and an outer pipeline  95 . An opening at a leading end of the inner pipeline  94  may be narrowed, and a leading end of the dual pipeline  96  may be connected to the case  56  of the fluorescence measuring unit  5 . A suction pipeline  97  may be connected to a surface of the case  56  facing the leading end of the dual pipeline  96 . In this configuration, a chemical liquid may be supplied into the inner pipeline  94  of the dual pipeline  96 , and the atmosphere may flow through the outer pipeline  95 . The chemical liquid may be flown into the inner pipeline  94  by a non-illustrated chemical liquid flow rate controller. By driving the suction pump  7 , the atmosphere may be attracted into the outer pipeline  95 . The chemical liquid from the inner pipeline  94  may be atomized into mist groups by an air current of the atmosphere. The mist groups may be dispersed into the case  56  and pass through a light transmitting region in which a laser beam is emitted from the light emitting unit  51 . In this embodiment, the leading end of the dual pipeline  96  functions as the diffusion unit and the atomization unit. 
     In the above-described embodiments, the atmosphere may be exterior air or may be expiration of a human being. In the latter case, one end of a pipeline for introducing the atmosphere may be expanded to have a bugle shape. By blowing from the bugle-shaped part of the pipeline, the expiration of the human being may be introduced into the pipeline.