Abstract:
A reagent holding container is provided that is capable of storing a reagent in a stable state over a long period of time and simply delivering a held reagent. A reagent holding container having a flexible material and a perforable material, wherein a plunger functions both to deform the flexible material of the reagent holding container and perforate the perforable material of the reagent holding container.

Description:
TECHNICAL FIELD 
       [0001]    The present invention relates to a reagent holding container for storing a reagent, a liquid delivery device provided with the reagent holding container, and a reagent discharge method for discharging a reagent from the reagent holding container. 
       BACKGROUND ART 
       [0002]    A technique concerning a reagent holding container of related art is described in PTL 1. This publication describes a reagent holding container that includes a deformable upper structure and a pierceable bottom structure. In this publication, a piercing element provided below the pierceable bottom structure is pushed upward with a plunger to pierce the bottom structure while bending the deformable upper portion under the applied pressure of a plunger to discharge the reagent contained in the container. The precondition of this technique is that the plungers and the reagent are avoided from contact to prevent plunger contamination. 
         [0003]    PTL 2 also describes a technique concerning a reagent holding container of related art. This publication describes drying and holding a reagent in a bellows-shaped reagent holding container, dissolving the dried reagent in a sample delivered to the reagent holding container, and crushing the bellows-shaped reagent holding container to deliver a sample and reagent mixture. 
       CITATION LIST 
     Patent Literature 
       [0004]    PTL 1: JP-A-2013-064725 
         [0005]    PTL 2: JP-A-2011-158463 
       SUMMARY OF INVENTION 
     Technical Problem 
       [0006]    However, the technique disclosed in PTL 1 requires installing two plungers, one on the upper side of the reagent holding container to deform the upper portion of the container, and one on the lower side of the reagent holding container to pierce the bottom portion. This involves a complicated mechanism on. the liquid delivery device side where delivery of a reagent takes place. Another drawback is that the bottom piercing element installed adjacent the bottom portion of the reagent holding container poses the risk of piercing the bottom portion during the storage of the reagent holding container. The device of PTL 2 involves high manufacturing cost because the reagent is heated or vacuum. dried after being sealed in the reagent holding container. PTL 1 and PTL 2 also do not consider sealing a liquid reagent in the reagent holding container over extended time periods without causing the liquid to evaporate. 
         [0007]    The present invention was completed under these circumstances, and it is an object of the present invention to provide a reagent holding container that enables a reagent held therein to be delivered using a simple mechanism, and stably storing a reagent over extended time periods. 
       Solution to Problem 
       [0008]    A reagent holding container of the present invention is a reagent holding container that includes a deformable member and a pierceable member. The reagent holding container discharges a reagent held therein upon an external pressure mechanism deforming the deformable member and piercing the pierceable member. 
       Advantageous Effects of Invention 
       [0009]    The present invention can provide a reagent holding container that enables a reagent held therein to be delivered using a simple mechanism, and stably storing a reagent over extended time periods. 
         [0010]    Other objects, configurations, and advantages of the present invention will be more clearly understood from the descriptions of the embodiments below. 
     
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         [0011]    [ FIG. 1 ]  FIG. 1  is a cross sectional view of a reagent holding container according to First Embodiment 
           [0012]    [ FIG. 2A ]  FIG. 2A  is a cross sectional view representing the operation of the reagent holding container. 
           [0013]    [ FIG. 2B ]  FIG. 2B  is a cross sectional view representing the operation of the reagent holding container. 
           [0014]    [ FIG. 3 ]  FIG. 3  is a side view of a liquid delivery device provided with the reagent holding container. 
           [0015]    [ FIG. 4 ]  FIG. 4  is a block diagram of a sample processing apparatus using the liquid delivery device. 
           [0016]    [ FIG. 5A ]  FIG. 5A  is a side view representing the operation of the sample processing apparatus. 
           [0017]    [ FIG. 5B ]  FIG. 5B  is a side view representing the operation of the sample processing apparatus. 
           [0018]    [ FIG. 5C ]  FIG. 5C  is a side view representing the operation of the sample processing apparatus. 
           [0019]    [ FIG. 5D ]  FIG. 5D  is a side view representing the operation of the sample processing apparatus. 
           [0020]    [ FIG. 5E ]  FIG. 5E  is a side view representing the operation of the sample processing apparatus. 
           [0021]    [ FIG. 6A ]  FIG. 6A  is a cross sectional view representing the operation of a reagent holding container according to Second Embodiment. 
           [0022]    [ FIG. 6B ]  FIG. 6B  is a cross sectional view representing the operation of the reagent holding container according to Second Embodiment. 
           [0023]    [ FIG. 7A ]  FIG. 7A  is a cross sectional view representing the operation of a reagent holding container according to Third Embodiment. 
           [0024]    [ FIG. 7B ]  FIG. 7B  is a cross sectional view representing the operation of the reagent holding container according to Third Embodiment. 
           [0025]    [ FIG. 8A ]  FIG. 8A  is a side view representing the operation of a sample processing apparatus according to Fourth Embodiment 
           [0026]    [ FIG. 8B ]  FIG. 8B  is a side view representing the operation of the sample processing apparatus according to Fourth Embodiment. 
           [0027]    [ FIG. 8C ]  FIG. 8C  is a side view representing the operation of the sample processing apparatus according to Fourth Embodiment. 
           [0028]    [ FIG. 9A ]  FIG. 9A  is a cross sectional view representing the operation of a reagent holding container according to Fifth Embodiment. 
           [0029]    [ FIG. 9B ]  FIG. 9B  is a cross sectional view representing the operation of the reagent holding container according to Fifth Embodiment. 
       
    
    
     DESCRIPTION OF EMBODIMENTS 
       [0030]    Embodiments of the present invention are described below with reference to the accompanying drawings. The following embodiments are illustrative, and may be applied in other forms, including an embodiment based on a combination of different embodiments, and an embodiment based on a combination or replacements with known or common techniques. 
       Example 1 
       [0031]      FIGS. 1 and 2  illustrate a reagent holding container representing First Example. As shown in  FIG. 1 , a reagent container  1  is formed from a container base  10 , a bendable container portion  11 , and a pierceable container portion  15 . 
         [0032]    The material of the container base  10  is not particularly limited, and resin materials such as polystyrene, polypropylene, polycarbonate, and COP, and metallic materials such as aluminum, and stainless steel may be used. From the viewpoint of preventing evaporation of a reagent, it is preferable to use metallic materials such as aluminum and stainless steel. However, the same effect can be obtained by vapor depositing metal on resin material, or attaching a metal foil to resin material. 
         [0033]    The bendable container portion  11  may use flexible deformable materials, such as natural rubber, isoprene rubber, butadiene rubber, styrene-butadiene rubber, butyl rubber, nitrile rubber, ethylene propylene rubber, chloroprene rubber, acryl rubber, urethane rubber, and silicone rubber. Preferred for use is silicone rubber, which has both tensile strength and impact resilience. 
         [0034]    The pierceable container portion  15  may use an aluminum film, or a plastic film such as polypropylene, polyimide, polyester, nylon, polycarbonate, and PET. An aluminum film is preferred. for its ease of piercing, and the ability to prevent evaporation. A plastic film with vapor-deposited metal such as aluminum is more preferred because it generates less piercing debris. 
         [0035]    The bond between the container base  10  and the bendable container portion  11 , and between the container base  10  and the pierceable container portion  15  may be formed by thermocompression bonding or with a double-sided tape. 
         [0036]    The operation of the reagent container  1  is described below using  FIG. 2 .  FIG. 2(A)  shows a state in which the reagent container  1  is sealed with the bendable container portion  11  and the pierceable container portion  15 , with a reagent held inside the reagent container  1 . Pressing the bendable container portion  11  with a plunger  20  causes the bendable container portion  11  to bend downward as shown in  FIG. 2(B) . As the plunger  20  is pressed down further, the pierceable container portion  15  breaks, and the reagent inside the reagent container  1  is released out of the reagent container  1 . 
         [0037]    Because the bendable container portion  11  is bent down in use, the bendable container portion  11  has a thickness of preferably 1 mm or less, desirably 0.5 mm or less when, for example, silicone rubber is used. On the other hand, the thickness should preferably be 0.1 mm or more to prevent breaking the silicon rubber upon being bent. 
         [0038]    For ease of breakage, the pierceable container portion  15  has a thickness of preferably 10 to 50 μm when, for example, an aluminum film is used. A thickness below 10 μm is not preferable because such a thin film is susceptible to cracking and easily breaks, and is not suited for storing reagent. 
         [0039]    The following describes a liquid delivery device with the reagent container  1  installed therein.  FIG. 3  is a detailed explanatory diagram of a liquid delivery device of the present invention.  FIG. 4  is a block diagram of a sample processing apparatus using the liquid delivery device. 
         [0040]    The configuration of the sample processing apparatus shown in  FIG. 4  is described first. A sample processing apparatus  30  is configured form a device mount  50  in which a liquid delivery device  40  is installed, and a top lid  60  that holds the liquid delivery device  40 , and seals the sample processing apparatus  30 . 
         [0041]    The liquid delivery device  40  has a top surface with air ports (described later), and the top lid  60  has air connectors  61 ,  62 , and  63  hat allow passage of air through the ports. 
         [0042]    The air connectors  61 ,  62 ,  63  contact the corresponding air ports on the top surface of the liquid delivery device  40  upon installing the liquid delivery device  40  on the device mount  50 , and sealing the sample processing apparatus  30  with the top lid  60  by bringing it into contact with the device mount  50 . This enables high pressure air to be guided into the liquid delivery device. The high pressure air generated in a pump  70  is held in an air chamber  80 , and adjusted to an almost constant pressure with a regulator  90 . The air adjusted to a constant pressure in the air chamber  80  is piped to the air connectors  61 ,  62 ,  63  via valves  101 ,  102 , and  103 , respectively. 
         [0043]    The valves  101 ,  102 , and  103  are controlled by a controller  110 , which selects the valves  101 ,  102 , and  103  to supply air to the air connectors  61 ,  62 ,  63  from the air chamber  80 , or release air to the atmosphere through the air connectors  61 ,  62 ,  63 , or closes all the valves  101 ,  102 , and  103 . 
         [0044]    A pressure sensor  120  for measuring the pressure inside the air chamber  80  is provided, as required. The controller  110  controls the valves  101 ,  102 , and  103  according to signals from the pressure sensor  120 . 
         [0045]    The liquid delivery device  40  is described below in detail.  FIG. 3  is a side view of the liquid delivery device  40 . 
         [0046]    As shown in the side view, the liquid delivery device  40  As configured form a sample tank  130 , a reagent tank  160 , a mixture tank  140 , a sampling tank  150 , and a channel  170 . The air ports ( 131 ,  141 , and  151  in the diagram) are disposed at the upper portions of the sample tank  130 , the mixture tank  140 , and the sampling tank  150 . The air ports  131 ,  141 ,  151  are provided at positions that contact the air connectors  61 ,  62 ,  63  shown in  FIG. 4 . The air thus enters the air ports  131 ,  141 ,  151  through the air connectors  61 ,  62 ,  63  via the valves  101 ,  102 , and  103 . In the reagent tank  160  is disposed a stop  161  that holds the reagent container  1 . 
         [0047]    Referring to  FIG. 5 , the following describes how a sample and a reagent are mixed in the liquid delivery device  40 . 
         [0048]      FIG. 5A  shows an initial, state in which a sample  132  has been injected into the sample tank  130  through the air port  131 . A reagent  162  is contained in the reagent container  1  installed in the reagent tank  160 . The mixture tank  140 , the sampling tank  150 , and the channel  170  are filled with air. The valves  101 ,  102 , and  103  (see  FIG. 4 ) are all closed. 
         [0049]      FIG. 5B  shows a state in which a plunger guide  21  (see  FIG. 4 ) is inserted into the reagent tank  160 , and the reagent container  1  is pressed against the Liquid delivery device  40 . With the plunger guide  21  held in this state, the reagent container  1  becomes tightly coupled to the liquid delivery device  40 . This makes it possible to prevent liquid leakage from the channel  170  to the reagent tank  160 . 
         [0050]      FIG. 5C  shows a state in which the plunger  20  (see  FIG. 4 ) is inserted into the reagent tank  160 , and bending the bendable container portion  11  of the reagent container  1  downward, and piercing the pierceable container portion  15 . The channel  170  may be depressed in a portion directly below the reagent tank  160  as shown in the diagram so that the plunger  20  can fully discharge the reagent  162  inside the reagent container  1 . By opening the valve  102 , the air inside the channel  170  is released into the air port  141 , and the reagent  162  inside the reagent container  1  is sent to inside the channel  170  toward the mixture tank  140 . 
         [0051]      FIG. 5D  shows a state in which the valve  101  is opened to supply air into the sample tank  130  through the air port  131 , and deliver the sample  132  inside the sample tank  130  and the reagent  162  in the channel  170  to the mixture tank  140 . Here, the sample  132  and the reagent  162  can be prevented from finding their way to the sampling tank  150  by opening the valve  103  and supplying air to the sampling tank  150  through the air port  151 . The sample  132  and the reagent  162  inside the mixture tank  140  become mixed by bubbling with air supplied to the mixture tank  140  through the air ports  131  to  151 . 
         [0052]      FIG. 5E  shows a state in which the valve  102  is opened to supply air through the air port  132 , and deliver the mixture of the sample  132  and the reagent  162  in the mixture tank  140  to the sampling tank  150 . Here, the sample  132  and the reagent  162  can be prevented from finding their way to the sample tank  130  by opening the valve  101  and supplying air to the sample tank  130  via the air port  131 . Finally, all valves are closed. to finish the liquid delivery operation. 
         [0053]    As described above, the present invention simplifies the mechanism on the liquid delivery device side with the dual function of the plunger deforming the flexible material of the reagent holding container, and piercing the pierceable material of the reagent holding container. Because the reagent container, the plunger (piercing mechanism), and the channel are distant away from each other in the initial state, there is no risk of the reagent container being pierced during the storage of the liquid delivery device, and liquid leakage can be prevented. 
       Example 2 
       [0054]      FIG. 6  represents another example of the present invention. This example does not differ from Example 1 with respect to the reagent container formed from the container base, the bendable container portion, and the pierceable container portion, but differs from Example 1 in the configuration that more actively prevents evaporation of reagent through the bendable container portion. 
         [0055]      FIG. 6  represents a reagent holding container of Second Example. As shown in  FIG. 6 , the reagent container  1  is formed from a container base  10 , a bendable container portion  11 , and pierceable container portions  12  and  15 . 
         [0056]    The container base  10 , the bendable container portion  11 , and the pierceable container portions  12  and  15  are made of the same materials used in Example 1. The feature of Example 2 lies in the double structure of the bendable container portion  11  and the pierceable container portion  12  in one of the sealing surfaces of the container base  10 . The most preferred material for the pierceable container portion  12  is an aluminum film for its ease of piercing, and the ability to prevent evaporation, as described in Example 1. The aluminum film used for the pierceable container portion  12  is more inert to the reagent than the rubber materials used for the bendable container portion  11 . Second Example using an aluminum film for the pierceable container portion can thus be said as being suited in situations where the reagent is corrosive to the rubber material of the bendable container portion  11 . instead of layering the pierceable container portion  12  on the bendable container portion  11 , aluminum or other such metal may be vapor deposited on the bendable container portion  11  to make a configuration without the pierceable container portion  12 . 
         [0057]    The bond between the container base  10  and the pierceable container portion  12 , and between the pierceable container portion  12  and the bendable container portion  11  may be formed by thermocompression bonding, or with a double-sided tape. 
         [0058]    The operation of the reagent container  1  is described below using  FIG. 6 .  FIG. 6(A)  shows a state in which the reagent container  1  is sealed with the bendable container portion  11  and the pierceable container portion  12 , and the pierceable container portion  15 , with a reagent held inside the reagent container  1 . Pressing the bendable container portion  11  with the plunger  20  bends the bendable container portion  11  downward as shown in  FIG. 6(B) , and pierces the pierceable container portion  12 . As the plunger  20  is pressed down further, the pierceable container portion  15  breaks, and the reagent inside the reagent container  1  is released out of the reagent container  1 . 
         [0059]    With the same basic structure described, in Example 1, Second Example can be said as a convenient liquid delivery method that enables discharge of a reagent with the single plunger. The double structure of the bendable container portion and the pierceable container portion can provide chemical resistance while preventing reagent evaporation. 
       Example 3 
       [0060]      FIG. 7  represents another example of the present invention. This example does not differ from Example 2 with respect to the double structure of the bendable container portion and the pierceable container portion in one of the sealing surfaces of the container base, but differs from Example 2 in the configuration that prevents the piercing debris of the pierceable container portion from entering the channel. 
         [0061]      FIG. 7  represents the reagent holding container of Third Example. As shown in  FIG. 7 , the reagent container  1  is formed from a container base  10 , a bendable container portion  11 , and pierceable container portions  12  and  15 . 
         [0062]    The container base  10 , the bendable container portion  11 , and the pierceable container portions  12  and  15  are made of the same materials used in Examples 1 and 2. The feature of Example 3 is that the double structure of the bendable container portion  11  and the pierceable container portion  12  in one of the sealing surfaces of the container base  10  contacts the container base  10  on the side of the bendable container portion  11 . The material of the bendable container portion  11  is preferably rubber material, as described in Example 1. The present example is thus effective when the reagent stored in the reagent container  1  is inert to the rubber material of the bendable container portion  11 . Instead of layering the bendable container portion  11  on the pierceable container portion  12 , aluminum or other such metal may be vapor deposited on the side of the bendable container portion  11  opposite the reagent contacting surface to make a configuration without the pierceable container portion  12 . 
         [0063]    The operation of the reagent container  1  is described below using  FIG. 7 .  FIG. 7(A)  shows a state in which the reagent container  1  is sealed with the bendable container portion  11  and the pierceable container portion  12 , and the pierceable container portion  15 , with a reagent held inside the reagent container  1 . Pressing the bendable container portion  11  with the plunger  20  pierces the pierceable container portion  12 , and bends the bendable container portion  11  downward as shown in  FIG. 7(B) . As the plunger  20  is pressed down further, the pierceable container portion  15  breaks, and the reagent inside the reagent container  1  is released out of the reagent container  1 . 
         [0064]    With the same basic structure described in Examples 1 and 2, Third Example can be said as a convenient liquid delivery method that enables discharge of a reagent with the single plunger. An advantage of the bendable container portion contacting the container base in the double structure of the bendable container portion and the pierceable container portion in one of the sealing surfaces of the container base is that debris can be prevented from entering the channel upon piercing the pierceable container portion, and that the reagent is unlikely to remain in the reagent container. 
       Example 4 
     Piercing with Channel Projection 
       [0065]      FIG. 8  represents another example of the present invention. This Example differs from Example 1 in that the bendable container portion is deformed with the plunger whereas the pierceable container portion is pierced with a projection from the channel side (the projection having, a channel therein). 
         [0066]    Referring to  FIG. 8 , the following describes how the reagent is delivered in Example 4.  FIG. 8A  shows an initial state in which the reagent container  1  held in the reagent tank  160  with a stop  161  is storing a reagent  162  without touching a reagent tank projection  165  provided at the bottom portion of the reagent tank  160 . 
         [0067]      FIG. 8B  shows a state in which the plunger guide  21  (see  FIG. 4 ) is inserted in the reagent tank  160 , and the reagent container  1  is pressed against the liquid delivery device  40 . Here, the pierceable container portion  15  of the reagent container  1  (see  FIG. 2 ) is pierced by the reagent tank projection  165 . With the plunger guide  21  held in this state, the reagent container  1  becomes tightly coupled to the liquid delivery device  40 . This makes it possible to prevent liquid leakage from the channel  170  to the reagent tank  160 . 
         [0068]      FIG. 8C  shows a state in which the plunger  20  (see  FIG. 4 ) is inserted in the reagent tank  160 , and pressing down the bendable container portion  11  (see  FIG. 2 ) of the reagent container  1 . In response, the reagent  162  inside the reagent container  1  flows into the channel  170  via a projection channel  166 . 
         [0069]    As described above, the difference from Example 1 is that the deformation of the bendable container portion, and the piercing of the pierceable container portion are separately performed. By making the inner diameter of the projection channel  166  smaller, the dead volume between the reagent container  1  and the liquid delivery device  40  can be reduced to prevent the reagent from remaining in the reagent container  1 . 
       Example 5 
       [0070]      FIG. 9  represents another example of the present invention. This Example differs from the other examples in that the bendable container portion is raised upward in the initial state. 
         [0071]    The operation of the reagent container  1  of Example 5 is described below using  FIG. 9 .  FIG. 9(A)  shows a state in which the reagent container  1  is sealed with the bendable container portion  11  and the pierceable container portion  15 , with the reagent held inside the reagent container  1 . The plunger guide  21  presses the peripheries of the container base  10  against the liquid delivery device  40  (the liquid delivery device  40  is not shown). Pressing the bendable container portion  11  with the plunger  20  bends the bendable container portion  11  downward, and the pierceable container portion  15  breaks as the plunger  20  is pressed down further, releasing the reagent inside the reagent container  1  out of the reagent container  1 . 
         [0072]    The bendable container portion and the pierceable container portion are not necessarily required to have flat surfaces, provided that there is a portion (the container base in this example) that can be pressed against the liquid delivery device with the plunger guide as in this example. 
         [0073]    The present invention is not limited to the examples described above, and includes various modifications. For example, the foregoing detailed descriptions of the examples above are given to facilitate understanding of the present invention, and are not necessarily limited to an embodiment that includes all the configurations described above. Some of the configurations of any of the examples may be replaced with the configurations of other examples, or the configurations of any of the examples may be added to the configurations of other examples. Additions, deletions, or replacements of some of the configurations of examples are also possible. 
       REFERENCE SIGNS LIST 
       [0074]      1  Reagent container 
         [0075]      10  Container base 
         [0076]      11  Bendable container portion 
         [0077]      12 ,  15  Pierceable container portion 
         [0078]      20  Plunger 
         [0079]      21  Plunger guide 
         [0080]      30  Sample processing apparatus 
         [0081]      40  Liquid delivery device 
         [0082]      50  Device mount 
         [0083]      60  Top lid 
         [0084]      61 ,  62 ,  63  Air connectors 
         [0085]      70  Pump 
         [0086]      80  Air chamber 
         [0087]      90  Regulator 
         [0088]      101 ,  102 ,  103  Valves 
         [0089]      110  Controller 
         [0090]      120  Pressure sensor 
         [0091]      130  Sample tank 
         [0092]      131 ,  141 ,  151  Air ports 
         [0093]      132  Sample 
         [0094]      140  Mixture tank 
         [0095]      150  Sampling tank 
         [0096]      160  Reagent tank 
         [0097]      161  Stop 
         [0098]      162  Reagent 
         [0099]      165  Reagent tank projection 
         [0100]      166  Projection channel 
         [0101]      170  Channel