JP5939392B2 - Container and thermal cycle equipment - Google Patents

Description

  The present invention relates to a container and a heat cycle apparatus.

  In the field of biochemistry, a technique of PCR (Polymerase Chain Reaction) has been established. Recently, the accuracy and detection sensitivity of amplification in the PCR method have improved, and it has become possible to amplify, detect, and analyze a very small amount of sample (DNA, etc.). PCR is a technique for amplifying a target nucleic acid by subjecting a solution (reaction solution) containing a nucleic acid (target nucleic acid) to be amplified and a reagent to thermal cycling. As a thermal cycle of PCR, a method of performing a thermal cycle at two or three stages of temperatures is common.

  On the other hand, the diagnosis of infectious diseases such as influenza in the medical field is currently mainly performed using a simple test kit such as immunochromatography. However, in such a simple test, accuracy may be insufficient, and it is desired to apply PCR that can expect higher test accuracy to diagnose infection. In general outpatients and the like in medical institutions, the time that can be spent on examinations is limited to a short time because the examination time is limited. For this reason, for example, the inspection of influenza is carried out in a short time by a simple inspection such as immunochromatography at the expense of the accuracy of the inspection.

  Under such circumstances, it has been necessary to shorten the time required for the reaction in order to realize a test by PCR that can expect higher accuracy in the medical field. As an apparatus for performing a PCR reaction in a short time, for example, Patent Document 1 discloses a reaction for a biological sample filled with a reaction solution and a liquid that is phase-separated from the reaction solution and has a specific gravity smaller than that of the reaction solution. A biological sample reaction apparatus is disclosed in which a reaction liquid is moved to perform a thermal cycle by rotating a chip around a horizontal rotation axis (Patent Document 1). Further, as a method of PCR, a method using magnetic beads (Patent Document 2), or using magnetic beads as a droplet moving means, and moving the droplets in a temperature change region on the substrate, the PCR heat There is a disclosure of a method of performing a cycle (Patent Document 3).

JP 2009-136250 A JP 2009-207459 A JP 2008-012490 A

  In the apparatus using the action of gravity as described in Patent Document 1 above, when adopting a method of performing PCR thermal cycling at three stages of temperature, the container filled with the PCR reaction solution has a complicated shape. It was necessary to provide a flow path. Further, in a container used for subjecting a minute amount of liquid to a temperature cycle as described in Patent Document 1, the smaller the diffusion of heat in the container, the easier it is to partition the temperature-controlled region. The temperature distribution changes rapidly, and the accuracy and efficiency of the temperature cycle is improved. However, for example, if the flow path in the container is expanded or contracted, such as by providing a constriction or a step in the container, the influence of the convection of the contents (for example, oil) may increase in the expanded diameter part of the flow path. there were. Therefore, the change in the temperature distribution in the container may be difficult to form or slow down.

  One of the objects according to some aspects of the present invention is to provide a container capable of accurately and efficiently applying a three-stage temperature cycle to a small amount of liquid by simple operations such as tilting and reversal. It is in. Another object of some aspects of the present invention is to provide a thermal cycle apparatus that can easily perform a three-stage temperature cycle using the above-described container.

  SUMMARY An advantage of some aspects of the invention is to solve at least a part of the problems described above, and the invention can be implemented as the following aspects or application examples.

  [Application Example 1] One aspect of the container according to the present invention has a longitudinal direction, a container body having one longitudinal end opened and the other end closed, and a container projecting into the container body. A container including a protrusion and sealing the one end of the container, wherein the container is orthogonal to the longitudinal direction when the container is sealed by the cover A first region including the protrusion in a cross section; a second region having a diameter-increased portion connected to the other end side of the first region and a diameter-reduced portion on the other end side; and the other end of the second region. A third region connected to the side, and when the container is sealed by the lid, the first region, the second region, and the space inside the third region are in communication with each other. It is a container.

  According to the container according to this application example, when a liquid droplet that is temperature-controlled in the container and a liquid that is phase-separated from the liquid droplet and has a specific gravity smaller than the liquid droplet are introduced, tilting, reversal, etc. By a simple operation, a three-stage temperature cycle can be efficiently applied to a small amount of liquid, and a heat cycle can be accurately applied.

  In the container according to this application example, when the container is sealed with the lid, the internal space is communicated along the longitudinal direction through the first region, the second region, and the third region of the container. Therefore, when a droplet to be temperature-controlled in the container and a liquid phase-separated from the droplet and a liquid having a specific gravity smaller than the droplet are introduced, the droplet moves in the internal space by the action of gravity. (Drop). And since the container which concerns on this application example has a 2nd area | region which has an enlarged diameter part and a reduced diameter part, when moving a droplet from a 1st area | region to a 3rd area | region, the inclination angle of a container is adjusted. As a result, the droplet can be stopped in the second region.

  Further, in the container according to this application example, since the projection of the lid body exists in the first region of the container, the volume of the space in the container in the first region of the container can be reduced, so that the liquid in the first region can be reduced. Convection can be suppressed. Thereby, temperature control can be made more precise in the first region, and the temperature of the droplet can be controlled more accurately. Therefore, when the droplet is used as a PCR reaction solution and the temperature is controlled by setting the first region, the second region, and the third region to appropriate temperatures, a three-stage thermal cycle is accurately performed on the reaction solution. Can be easily applied.

  Application Example 2 In Application Example 1, the inner wall of the third region of the container may be positioned on the inner side of the inner wall of the first region in a plan view from the longitudinal direction.

  Since the container of this application example has a container with a simple structure, for example, various molding methods such as balloon molding and injection molding can be easily applied and manufacturing is easy.

  Application Example 3 In Application Example 1 or Application Example 2, in the first region and the third region of the vessel body, the area of the region surrounded by the inner wall of the vessel body in a cross section orthogonal to the longitudinal direction is constant. It may be.

According to the container of this application example, when liquid droplets to be temperature-controlled in the container and a liquid phase-separated from the liquid droplets and having a specific gravity smaller than that of the liquid droplets are introduced by the action of gravity. Drops can be moved (dropped) in the space inside the container with a smoother motion.

  Application Example 4 In any one of Application Examples 1 to 3, the lengths of the first region and the third region of the container in the longitudinal direction are the lengths of the second region in the longitudinal direction. It may be longer than the length.

  According to the container of this application example, the temperature controlled regions in the first region, the second region, and the third region can be easily separated from each other, so that, for example, the degree of freedom of arrangement of a temperature control heater or the like is increased. Can do.

  Application Example 5 In any one of Application Examples 1 to 4, the inner wall of the second region of the container may be tapered.

  According to the container of this application example, since the shape of the second region of the container is simpler, for example, various molding methods such as balloon molding and injection molding can be easily applied, and manufacturing is further facilitated. Can be

  [Application Example 6] One aspect of the heat cycle apparatus according to the present invention includes a mounting unit for mounting a container, a first temperature control unit, a second temperature control unit, a third temperature control unit, a rotation mechanism, The container has a longitudinal direction, one end of the longitudinal direction is opened and the other end is closed, and the one end of the container body can be sealed, and the container body is sealed And a lid provided with a protrusion that protrudes into the interior of the container body, the container body having the longitudinal direction when the container body is sealed by the lid body A first region including the protrusion in a cross section orthogonal to the first region, a diameter-enlarged portion connected to the other end side of the first region, a second region having a reduced-diameter portion on the other end side, and the second region A third region connected to the other end side of the first region, and when the container is sealed by the lid, the first region, A region where the space inside the region and the space inside the third region are continuous, and when the container is mounted on the mounting portion, the first temperature control unit of the first region of the container The temperature is controlled, the second temperature control unit controls the temperature of the second region, the third temperature control unit controls the temperature of the third region, the rotation mechanism includes the mounting unit and each of the It is a thermal cycle device that rotates a temperature control unit around a rotation axis having a component orthogonal to the direction in which gravity acts.

  According to the thermal cycle device of this application example, when the container is mounted, the temperatures of the first region, the second region, and the third region of the container can be controlled, and the action of gravity can be performed by the rotation mechanism. The container can be rotated around an axis of rotation having a component orthogonal to the direction of movement. As a result, the direction in which gravity acts with respect to the longitudinal direction of the container can be freely changed. For example, the liquid droplet in which temperature control is performed in the container, and the liquid droplet are phase-separated and have a specific gravity higher than that of the liquid droplet. When a small liquid is introduced, a three-stage temperature cycle can be efficiently applied to a small amount of liquid by a simple operation such as tilting and reversal, and a heat cycle can be accurately performed. Therefore, for example, when a droplet is used as a PCR reaction solution and the first region, the second region, and the third region are set to appropriate temperatures, the reaction solution can be easily subjected to a three-stage thermal cycle. Can do.

Sectional drawing which shows the container which concerns on embodiment notionally. The schematic diagram which shows the inclination shape of the 2nd area | region of the container which concerns on embodiment. The schematic diagram which shows arrangement | positioning of the container which concerns on embodiment. The schematic diagram which shows a mode that the container which concerns on embodiment is inclined. The schematic diagram which shows a mode that the container which concerns on embodiment is inclined. Sectional drawing which shows the container which concerns on embodiment typically. Sectional drawing which shows typically sealing operation of the container which concerns on embodiment. The schematic diagram which shows a mode that the container which concerns on embodiment is inclined. The schematic diagram of the thermal cycle apparatus which concerns on embodiment. The figure which shows the mode of rotation of the heat cycle apparatus which concerns on embodiment. The figure which shows the mode of rotation of the heat cycle apparatus which concerns on embodiment.

  Several embodiments of the present invention will be described below. The embodiments described below illustrate examples of the present invention. The present invention is not limited to the following embodiments, and includes various modified embodiments that are implemented within a range that does not change the gist of the present invention. Note that not all of the configurations described below are essential configurations of the present invention.

1. Container The container 100 according to the present embodiment includes a container body 10 and a lid body 20.

  FIG. 1 is a diagram conceptually showing a container 100 that is an embodiment of a container according to the present invention. FIG. 2 is an enlarged view showing the vicinity of the second region 12 of the container 100, and is a schematic diagram for explaining the inclination angle θ of the inner side surface of the vessel body 10. FIG. 3 is an enlarged view of the vicinity of the second region 12 of the container 100, and is a schematic diagram for explaining the inclination angle α of the container 100. 4 and 5 are diagrams schematically showing the state of inclination of the container 100. FIG.

1.1. The container body 10 has a longitudinal direction. The vessel body 10 has a shape extending along the longitudinal direction, and has a tubular shape with one end opened and the other end closed. That is, the container body 10 has a shape that can hold a liquid inside when the opened one end side is disposed on the opposite side to the direction in which the gravity acts. The container 10 has a length enough to form three temperature-controlled regions in the longitudinal direction.

  The container 10 has the 1st area | region 11, the 2nd area | region 12, and the 3rd area | region 13 in order from the open | released one end side in the longitudinal direction.

  The first region 11 is formed with a first space 101 through which liquid can flow in the longitudinal direction of the container body 10 when the liquid is introduced into the container body 10 and sealed by the lid body 20. It is an area. Further, the first region 11 is a region including the protrusion 21 of the lid body 20 in a cross section orthogonal to the longitudinal direction when the container body 10 is sealed by the lid body 20. The first region 11 may or may not be connected to the opening at the end on one end side of the vessel body 10. That is, the first region 11 may extend from the position of the opening on one end side of the container body 10 to the other end side of the container body 10, or from the position separated from the opening of the container body 10 by a given interval. It may extend to the end side. In the vessel 10, the position serving as the starting point of the first region 11 extending to the other end side is located at the root of the protrusion 21 of the lid 20. Moreover, in the 1st area | region 11 of the container 10, the area of the area | region enclosed by the inner wall of the container 10 in the cross section orthogonal to a longitudinal direction may be constant. In this manner, when the droplet D and the droplet D are phase-separated into the container 100 and the liquid L having a specific gravity smaller than that of the droplet D is introduced, the droplet D is placed inside the container 100 by the action of gravity. It is possible to easily move the space.

The length in the longitudinal direction of the first region 11 coincides with the length in the longitudinal direction of the protrusion 21 of the lid 20, but the length is not particularly limited, and is, for example, 1 mm or more and 10 cm or less, 5 mm or more and 5 cm or less. be able to. Further, for example, when the thickness is 10 mm or more and 3 cm or less and 15 mm or more and 2 cm or less, interference with the temperature of other regions when controlling the temperature of the first space 101 formed inside the container 100 can be suppressed. The steepness of the temperature change with the region can be improved.

  For example, a liquid can be introduced into the first space 101. The shape of the first space 101 is not particularly limited. For example, the contour in a cross section orthogonal to the longitudinal direction of the first space 101 can be a circle, an ellipse, a polygon, a ring, a polygon, or the like. When the outer shape in the cross section orthogonal to the longitudinal direction of the first space 101 is an annular shape, for example, the inner wall surface of the first region 11 is circular in the cross section orthogonal to the longitudinal direction, and the protrusion 21 of the lid 20 This can be realized by making the cross section orthogonal to the longitudinal direction of the ring into a circular shape and the shape of the lid 20 such that the protrusion 21 is arranged so as not to contact the inner wall surface of the first region 11.

  Moreover, the area in the cross section orthogonal to the longitudinal direction of the 1st space 101 is not specifically limited. However, the area is such that the droplet D can move in the longitudinal direction of the first space 101 when, for example, the droplet D and a liquid phase-separated from the droplet D are introduced into the container 100. It is preferable to do.

  The first space 101 can communicate with the second space 102 inside the second region 12 of the container body 10 when the container body 10 is sealed by the lid body 20.

  The second region 12 is a region that forms a second space 102 in which the liquid can flow in the longitudinal direction of the container body 10 when the liquid is introduced into the container body 10. The second region 12 has an enlarged diameter portion 12a and a reduced diameter portion 12b.

  The enlarged diameter portion 12a of the second region 12 is a portion connected to the other end side of the first region 11 (the side opposite to the open end of the container body 10). The expanded diameter portion 12a is a portion having an expanded inner diameter in the second region 12 as compared with other portions. In the second region 12, the inner diameter (the area of the second space 102 in the cross section orthogonal to the longitudinal direction) decreases from the enlarged diameter portion 12a to the reduced diameter portion 12b.

  Here, the inner diameter of the second region 12 is simply expressed as an inner diameter, but the inner diameter of the second region 12 is a circle having the same area when the contour in a cross section perpendicular to the longitudinal direction of the second space 102 is other than a circle. It refers to the diameter of the case.

  For example, a liquid can be introduced into the second space 102. The shape of the outline of the cross section orthogonal to the longitudinal direction of the second space 102 is not particularly limited, and may be, for example, a circle, an ellipse, or a polygon. Moreover, it is preferable that the shape of the outline of the cross section orthogonal to the longitudinal direction of the second space 102 is smoothly connected to the first space 101 and the third space 103 in the enlarged diameter portion 12a and the reduced diameter portion 12b. In this way, when the droplet D and the liquid phase-separated from the droplet D are introduced into the container 100, the droplet D can easily move in the longitudinal direction.

  The area in the cross section orthogonal to the longitudinal direction of the second space 102 is not particularly limited. However, such an area is, for example, large enough to allow the droplet D to move from the first space 101 to the third space when the droplet D and a liquid that is phase-separated from the droplet D are introduced into the container 100. It is preferable to do.

  The enlarged diameter portion 12a is a portion that forms a region in which the cross section perpendicular to the longitudinal direction of the second space 102 formed therein is enlarged compared to other portions, and the reduced diameter portion 12b This is a portion that forms a region in which the cross section perpendicular to the longitudinal direction of the second space 102 formed in this is reduced compared to other portions. In the enlarged diameter portion 12a, the second space 102 communicates with the first space 101, and in the reduced diameter portion 12b, the second space 102 communicates with the third space 103.

The length in the longitudinal direction of the container 10 in the second region 12 is not particularly limited. For example, 1 mm
It can be 3 cm or less and 2 mm or more and 2 cm or less. Further, for example, when the thickness is 3 mm or more and 2 cm or less and 5 mm or more and 1 cm or less, interference with the temperature of another region when the temperature of the second space 102 is controlled is suppressed, or the steepness of temperature change with the other region is suppressed. Can be improved. Moreover, the thickness of the 2nd area | region 12 of the container 10 is not specifically limited, You may differ in the enlarged diameter part 12a and the reduced diameter part 12b. In the illustrated example, the enlarged diameter portion 12a and the reduced diameter portion 12b have substantially the same thickness.

  In addition, the length of the second region of the container 10 in the longitudinal direction may be shorter than the lengths of the first region 11 and the third region 13 in the longitudinal direction. In this way, when the temperature control is performed in each of the first region 11, the second region 12, and the third region 13, the controlled regions can be easily separated. For example, the temperature control heater and the like can be freely arranged. The degree can be increased.

  The aspect in which the inner diameter decreases from the enlarged diameter portion 12a toward the reduced diameter portion 12b is not particularly limited. For example, the inner diameter may decrease monotonously from the expanded diameter portion 12a toward the reduced diameter portion 12b, or may decrease with a maximum or minimum. That is, the inner wall of the second region 12 of the vessel body 10 may be tapered. In this way, the shape of the second region 12 of the vessel body 10 is further simplified, and various molding methods such as balloon molding and injection molding can be easily applied, and manufacturing is further facilitated. be able to.

  In other words, in the longitudinal direction of the container body 10, the direction from one end to the other end is positive, the longitudinal position with the end on one end side of the container body 10 as the origin is the position x, and the cutting is perpendicular to the longitudinal direction. When the area occupied by the contour of the inner wall of the body 10 on the surface is a function f (x), the absolute value | f ′ (x) | of the differential f ′ (x) by the position x of the function f (x) is the maximum. Is located in the second region 12.

  Since the second region 12 has the enlarged diameter portion 12a and the reduced diameter portion 12b, as a result, a side surface inclined with respect to the longitudinal direction of the container 100 is formed in the second space 102 inside the second region 12. . Due to the presence of such side surfaces, if the longitudinal direction of the container 100 is inclined at an appropriate angle with respect to the direction in which gravity acts, the liquid droplet D and the liquid droplet D are phase-separated inside the container 100, In addition, when a liquid having a specific gravity smaller than that of the droplet D is introduced, the second region 12 prevents the droplet D from falling (sliding or falling) from the first region 11 side to the third region 13 side in the container 100. Can be parked nearby.

  Here, the inclination angle θ of the side surface with respect to the longitudinal direction of the container 100 and the inclination angle α with respect to the direction in which gravity acts in the longitudinal direction of the container 100 are defined as shown in FIGS. The longitudinal direction of the container 100 is a chain line indicated by a symbol LD in the drawing.

  As shown in FIG. 2, the inner diameter of the second region 12 increases from the third region 13 toward the first region 11, and the inclined inner wall 12 c of the second space 102 is formed in the second region 12. It is formed. As shown in FIG. 2, the inclination angle θ of the inner wall 12 c is an angle at which the tangent to the inner wall 12 c is inclined with respect to the longitudinal direction of the container 100 when cut along a plane including the longitudinal direction of the container 100. The inclination angle θ takes a value exceeding 0 ° and not more than 90 °. In FIG. 2A, the inner wall 12c is drawn in a straight line in the cross section, but it may be a curved line as shown in FIG. 2B. In this case, the inclination angle θ of the inner wall 12c is The angle corresponds to the tangent to the portion of the inner wall 12c that is inclined most with respect to the longitudinal direction of the container 100.

On the other hand, as shown in FIG. 3 (a), the inclination angle α of the container 100 with respect to the longitudinal direction of gravity of the container 100 is parallel to the longitudinal direction G of the container 10 and the longitudinal direction of the vessel 10 is parallel. A case where the direction in which the first region 11, the second region 12, and the third region 13 are arranged in the same order is defined as 0 ° (360 °). 3B, the longitudinal direction of the body 10 is parallel to the direction G in which gravity acts, and the first region 11, the second region 12, and the third region 13 are provided. Is defined as 180 °. In this way, as shown in FIG. 4 (a), the inclination angle α with respect to the direction in which gravity acts in the longitudinal direction of the container 100 is defined.

  Referring to FIGS. 4A and 4B, the condition for keeping the droplet D near the second region 12 so as not to fall from the first region 11 side to the third region 13 side by the action of gravity is as follows. When the angle θ and the inclination angle α are used, 90 ° ≦ (θ + α). If the inclination angle θ of the side surface with respect to the longitudinal direction of the container 100 and the inclination angle α of the container 100 are selected so as to satisfy this relationship, the droplet D and the droplet D are phase-separated inside the container 100. In addition, when a liquid having a specific gravity smaller than that of the droplet D is introduced, the droplet D is kept in the vicinity of the second region 12 so that the droplet D does not fall from the first region 11 side to the third region 13 side in the container 100. Can do. Further, the tilt angle θ and the tilt angle α can be appropriately selected in consideration of the viscosity of the liquid L, the drop speed of the droplet D, and the like.

  The third region 13 is a region that forms a third space 103 in which the liquid can flow in the longitudinal direction of the container body 10 when the liquid is introduced into the container body 10. The third region 13 is connected to the reduced diameter portion 12 b of the second region 12. The third space 103 can communicate with the second space 102 inside the second region 12 of the vessel body 10.

  The length in the longitudinal direction of the container 10 in the third region 13 is not particularly limited, and can be, for example, 1 mm or more and 10 cm or less, 5 mm or more and 5 cm or less. In addition, for example, if it is 10 mm or more and 3 cm or less and 15 mm or more and 2 cm or less, interference with the temperature of other regions when the temperature of the third space 103 formed inside the container 100 is controlled, The steepness of the temperature change with the region can be improved.

  The shape of the third space 103 is not particularly limited. For example, the contour in the cross section orthogonal to the longitudinal direction can be a circle, an ellipse, a polygon, or the like. Moreover, the area in the cross section orthogonal to the longitudinal direction of the 3rd space 103 is not specifically limited. However, the area is large enough to allow the droplet D to move in the longitudinal direction of the third space 103 when, for example, the droplet D and the liquid L phase-separated from the droplet D are introduced into the container 100. Preferably. Moreover, in the 3rd area | region 13 of the container 10, the area of the area | region enclosed by the inner wall of the container 10 in the cross section orthogonal to a longitudinal direction may be constant.

  Further, the inner wall of the third region 13 of the container body 10 may be positioned inside the inner wall of the first region 11 of the container body 10 in a plan view from the longitudinal direction. In this way, since the structure of the container body 10 becomes simple, for example, various molding methods such as balloon molding and injection molding can be applied, and manufacturing can be facilitated.

  Examples of the material of the container 10 include polymer materials such as polypropylene, polycarbonate, polyacrylic acid, polymethacrylic acid, and polyethylene, and inorganic materials such as glass and metal. From the viewpoint of the heat resistance, thermal conductivity, and transparency of the container 10, the material of the container 10 is more preferably polypropylene or polycarbonate. Further, the container body 10 may be subjected to a surface treatment or the like. For example, when the droplet D and the liquid L phase-separated from the droplet D are introduced, the droplet D in the container body 10 is introduced. Movement can be facilitated.

1.2. Lid The lid 20 can seal the opening at one end of the vessel 10. The aspect in which the lid 20 seals one end of the container body 10 is not particularly limited, and the lid body 20 may be configured as a plug that fits inside the container body 10, or the lid body 20 may be a container body. It may be like a cap fitted to the outside of 10, or a combination of both. Further, a screw structure or a gasket such as an O-ring that fixes the lid 20 and the container body 10 may be fixed and sealed. In the example of FIG. 1, the lid 20 is like a plug that fits inside the vessel 10.

  The lid 20 includes a protrusion 21 that protrudes from the interior of the vessel body 10. The protrusion 21 is a portion excluding a portion that is responsible for sealing the container body 10 by the lid body 20, and is a portion that is inserted and disposed inside the container body 10 when the container body 10 is sealed. And when the container 10 is sealed, the area | region in which the protrusion 21 is located inside the container 10 is the 1st area | region 11 mentioned above.

  The length of the protrusion 21 in the longitudinal direction of the container 100 is not particularly limited as long as the second region 12 can be formed in the container 10. When the container 10 is sealed with the lid 20, the position where the protrusion 21 is arranged in the direction orthogonal to the longitudinal direction is not particularly limited. For example, in the example of FIG. 1, when the container body 10 is sealed by the lid body 20, the protrusion 21 is in contact with the inner side surface of the container body 10, but the protrusion 21 is in contact with the inner side surface of the container body 10. It does not have to be.

  The shape of the protrusion 21 is not particularly limited. The shape of the protrusion 21 can be formed so that, for example, the area of the cross section orthogonal to the longitudinal direction of the container 100 in the first space 101 when sealed is constant. Moreover, when the shape or area of the cross section orthogonal to the longitudinal direction of the space inside the first region 11 of the container 10 has changed, the cross section orthogonal to the longitudinal direction of the protrusion 21 is corresponding to this. The area and shape may be changed. The shape of the cross section perpendicular to the longitudinal direction of the protrusion 21 is such that the droplet 10 and the liquid L phase-separated from the droplet D are introduced into the container 100 and the container 10 is sealed by the lid 20. In addition, it is not particularly limited as long as the droplet D can move in the first space 101, and it can have a shape in which curves and straight lines are arbitrarily combined. Examples of specific shapes of the protrusions 21 include a columnar shape, a prismatic shape, a plate shape, and the like.

  As one of the functions of the protrusion 21, the space formed by the inner wall surface of the first region 11 of the container body 10 is sealed by sealing the container body 10 before the container body 10 is sealed. 101. Thereby, the volume of the space inside the container 10 can be made small. Therefore, when a liquid or the like is introduced into the first space 101 in the container 100 and a temperature gradient is formed, convection of the liquid can be suppressed, and turbulence due to the convection of the temperature gradient can be suppressed.

  Examples of the material of the lid 20 include polymer materials such as polypropylene, polycarbonate, polyacrylic acid, polymethacrylic acid, and polyethylene, and inorganic materials such as glass and metal. From the viewpoint of the heat resistance and thermal conductivity of the lid 20, the material of the lid 20 is more preferably polypropylene or polycarbonate. Further, the lid 20 may be subjected to a surface treatment or the like. For example, when the droplet D and the liquid L phase-separated from the droplet D are introduced, the movement of the droplet D in the container 100 is performed. Can be made easier.

1.3. Inclination of the container FIG. 5 shows the droplet D in the container 100 when the droplet D and the liquid L that is phase-separated from the droplet D and has a specific gravity smaller than that of the droplet D are introduced. It is a figure which shows the mode of a movement typically.

  The volume of the droplet D is arbitrary as long as the shape of the droplet can be maintained in the liquid L. Since the specific gravity of the droplet D is larger than that of the liquid L, as shown in FIG. 5A, when the inclination angle α of the container 100 is 0 °, the third region 13 (third space of the container 100). 103). 5B, when the inclination angle α of the container 100 is 180 °, the container 100 falls to the end of the first region 11 (first space 101).

  Next, when the container 100 is tilted from the state of FIG. 5B to the tilt angle α satisfying the relationship of (90 ° −θ) ≦ α, as shown in FIG. Although falling (sliding, falling) from the first region 11 toward the third region 13, it can be stopped near the second region 12 by the action of the shape of the second region 12. In the example of the container 100, when the droplet D is moved from the first region 11 to the third region 13, the rotation direction is selected so that the droplet D moves along the inner wall of the container 10. Let

1.4. Operational Effect In the container 100 of this embodiment, the internal space communicates in the order of the first region 11, the second region 12, and the third region 13 along the longitudinal direction. That is, when the container 10 is sealed with the lid 20, the first space 101, the second space 102, and the third space 103 are in communication. Therefore, when the droplet D for temperature control in the container 100 and the liquid L having a specific gravity smaller than that of the droplet D are sealed by being phase-separated from the droplet D, the droplet is caused by the action of gravity. D can be moved (dropped) in the space in the container 100. And since the container 100 has the 2nd area | region 12 which has the enlarged diameter part 12a and the reduced diameter part 12b, when moving the droplet D from the 1st area | region 11 to the 3rd area | region 13 by the effect | action of gravity, a container The droplet D can be stopped in the second region 12 by adjusting the tilt angle α of 100. Furthermore, in the 1st area | region 11, since the protrusion 21 of the cover body 20 exists, since the volume of the space in the container 100 becomes small, the convection of the liquid L in the 1st space 101 can be suppressed. Thereby, the droplet D can be moved between each area | region where temperature control was carried out correctly by simple operation. Therefore, for example, when the droplet D is used as a PCR reaction solution and the first region 11, the second region 12, and the third region 13 are set to appropriate temperatures, a three-stage thermal cycle can be easily performed on the reaction solution. Can be applied.

2. Specific Example FIG. 6 is a schematic view showing a container 110 which is an embodiment of the container according to the present invention. FIG. 6B corresponds to a cross section taken along line I-I in FIG. FIG. 7 is a diagram schematically showing how the container body 10 is sealed by the lid body 20 in the container 110. FIG. 8 is a diagram schematically illustrating the inclination of the container 110. The container 110 according to the present embodiment includes the container body 10 and the lid body 20, but the same members and the like as those described in the container 100 described above are denoted by the same reference numerals and detailed description thereof is omitted. To do.

  The container 10 in the container 110 is the same as the container 10 described above in that it has a first region 11, a second region 12, and a third region 13. As shown in FIG. 6, the container 10 in the container 110 is formed by the point that the cavity 14 is formed when the container 10 is sealed by the lid 20 and the protrusion 21 of the lid 20. It differs from the above-mentioned vessel body 10 in that it is arranged without contacting the inner wall surface.

  The lid body 20 in the container 110 is the same as the lid body 20 in the container 100 described above in that the projections 21 are provided. However, the lid 20 in the container 110 has a shape that can form the cavity 14 when the vessel 10 is sealed. The cavity 14 has a size that can accommodate an excluded volume of the liquid L mainly by the protrusions 21 when the droplet D and the liquid L are introduced into the vessel body 10 and sealed by the lid body 20. . Then, as shown in FIG. 7, by appropriately setting the volume of the liquid L to be introduced (FIG. 7A), the first space 101, the second space 102, and the third space are sealed at the time of sealing. It is possible to seal the liquid L without causing the liquid L to overflow from the container 110 (FIG. 7B). Thus, in the container 110, since the cavity 14 is formed when the container body 10 is sealed by the lid body 20, bubbles are unlikely to be generated in the first space 101 and the like, and the liquid L The effect that it is hard to overflow can be acquired. Further, since the cavity 14 is present, a certain amount of error may be included when the liquid L is accommodated, and the degree of freedom of the amount of the liquid L is increased.

  Further, in the container 110, the side surface of the second space 102 inside the second region 12 of the container body 10 is tapered, and the angle formed by the tangent to the longitudinal direction of the container 110 is the longitudinal length of the container 110. It is changing along the direction. Even if it does in this way, the effect which stops dropping of droplet D can be acquired. That is, as shown in FIG. 8B, when a droplet D and a liquid L that is phase-separated from the droplet D and has a specific gravity smaller than that of the droplet D are introduced into the container 110, the droplet D Can be moved in the container 110, and the droplet D can be retained in the vicinity of the second region 12 if the inclination angle is appropriately selected.

  Since the specific gravity of the droplet D is larger than that of the liquid L, as shown in FIG. 8A, when the inclination angle α of the container 110 is 180 °, the first region 11 (first space of the container 110). 101). As shown in FIG. 8C, when the inclination angle α of the container 110 is 0 °, the container 110 falls to the end of the third region 13 (third space 103).

  Further, as shown in FIG. 8A, from the state where the inclination angle α of the container 110 is 180 °, as shown in FIG. 8B, the container 110 is in a relationship of (90 ° −θ) ≦ α. When tilted to a satisfying tilt angle α, the droplet D falls (slides, falls) from the first region 11 toward the third region 13, but cannot exceed the step due to the shape of the second region 12, Stops near the second region 12. In the example of the container 110, since the protrusion 21 is arranged at the center in a cross section orthogonal to the longitudinal direction, when the droplet D is moved from the first region 11 to the third region 13, the droplet D can be moved along the inner wall of the vessel 10.

3. Thermal Cycle Device The thermal cycle device 200 of the present embodiment includes a mounting unit 210 for mounting the above-described container 110, a first temperature control unit 221, a second temperature control unit 222, a third temperature control unit 223, and a rotation. Mechanism 230. When the container 110 is mounted, the first temperature control unit 221 controls the temperature of the first region 11 of the container 10, the second temperature control unit 222 controls the temperature of the second region 12, and the third The temperature control unit 223 controls the temperature of the third region 13, and the rotation mechanism 230 rotates the mounting unit 210 and each temperature control unit around a rotation axis having a component orthogonal to the direction in which gravity acts. Let

  FIG. 9 is a diagram schematically showing a main part of the heat cycle apparatus 200 according to the present embodiment. 10 and 11 are diagrams showing a state of rotation of the heat cycle apparatus 200. FIG.

  The heat cycle apparatus 200 of the present embodiment has a mounting part 210 for mounting the container 110. When the container 110 is mounted, the mounting unit 210 is configured so that the first region 11, the second region 12, and the third region 13 of the container 110 are the first temperature control unit 221, the second temperature control unit 222, and the third temperature, respectively. It is formed so that the temperature is controlled by contacting the control unit 223 thermally.

  The thermal cycle device 200 according to the present embodiment forms a temperature gradient along the first space 101, the second space 102, and the third space 103 of the container 110 (along the direction in which the droplet D moves). Can do. The first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223 control the temperature of some or all of the first region 11, the second region 12, and the third region 13, respectively. May be.

The mounting part 210 has a structure for mounting the container 110. In the example shown in FIG. 9, a part of each of the first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit constitutes the mounting unit 210. Although not shown, the mounting portion 210 may be configured to include other configurations, for example, members that serve as guides or spacers when mounting the container 110, and members that fix the container 110. In the example of FIG. 9, the mounting portion 210 has a slot structure in which the container 100 is inserted and mounted.

  The number of mounting parts 210 provided in the heat cycle apparatus 200 is not particularly limited. When there are a plurality of mounting parts 210, a plurality of containers 110 can be mounted respectively. Note that the mounting part 210 may have any structure that can hold the container 110. For example, a structure in which the container 110 is fitted in a recess that matches the shape of the container 110 or a structure in which the container 110 is held therebetween may be employed.

  The thermal cycle apparatus 200 of the present embodiment includes a first temperature control unit 221, a second temperature control unit 222, and a third temperature control unit 223 provided with a mounting unit 210.

  Each temperature control unit is configured to form a temperature gradient in the moving direction in which the droplet D moves when the container 110 is mounted on the mounting unit 210. Here, “forming a temperature gradient” means forming a state in which the temperature changes along a predetermined direction. Therefore, “to form a temperature gradient in the moving direction in which the droplet D moves” means to form a state in which the temperature changes along the moving direction in which the droplet D moves. “The state in which the temperature changes along the predetermined direction” is, for example, that the temperature may be monotonously high or low along the predetermined direction, or from a change in which the temperature increases along the predetermined direction. You may change on the way from the change which becomes low, or from the change which becomes low to the change which becomes high. In the example shown in FIG. 9, the temperature gradient is formed by the three temperature control units of the first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223. As long as it is formed, the number of temperature control units may be one, two, or four or more.

  The first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223 may each include a heat conductor such as a heat source and an aluminum heat block, for example. As the heat source, a heater (heating wire), a cartridge heater, a carbon heater, a sheet heater, an IH heater (electromagnetic induction heater), a heating liquid, a heating gas, or the like may be used. Moreover, each temperature control part may be equipped with a conducting wire or piping as needed, and may be connected to an external power source or the like. Among these, since the temperature control of the cartridge heater is easy, it is easy to stabilize the temperature of control by adopting the cartridge heater.

  The first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223 are the first region 11 and the second region of the container 10 of the container 110 when the container 110 is mounted on the mounting unit 210, respectively. 12 and the third region 13 are controlled to be the first temperature, the second temperature, and the third temperature, respectively.

  The first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223 can be controlled to different temperatures. In this case, it is preferable that each temperature control part is arrange | positioned in the aspect with small thermal contact with each other. For example, it is preferable to provide each temperature control part in the position away from each other (position which does not physically contact). Moreover, each temperature control part may be installed in the thermal cycle apparatus 200 in a state where thermal interference is reduced by a heat insulating member or the like.

  Each temperature control unit is in thermal contact with the container 110 when the container 110 is mounted on the mounting unit 210. As an aspect which contacts thermally, the aspect which each temperature control part and the container 110 are contacting directly, the aspect which contacts between the containers 110 via another heat conductive member, etc. Can be mentioned. Moreover, as long as heat can be appropriately transmitted, there may be a space between each temperature control unit and the container 110.

The temperatures of the first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223 may be controlled by a temperature sensor and control unit (not shown). As the temperature sensor, for example, a thermocouple can be used, but not limited thereto, for example, a resistance temperature detector or a thermistor may be used. The control unit may control the rotation mechanism.

  The rotation mechanism 230 has a component orthogonal to the direction in which the mounting portion 210, the first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223 act on gravity, and This is a mechanism for rotating around the rotation axis R having a component orthogonal to the moving direction of the droplet D when the container 100 is mounted on the mounting portion 210. 9 to 11, only the rotation axis R is displayed, and the rotation mechanism 230 is omitted.

  The direction “having a component orthogonal to the direction in which gravity acts” is the vector sum of “component parallel to the direction in which gravity acts” and “component perpendicular to the direction in which gravity acts”. It is a direction having a component orthogonal to the direction in which gravity acts in the case where it is expressed. In addition, the direction “having a component orthogonal to the moving direction of the droplet D” includes “a component parallel to the moving direction of the droplet D” and “a component orthogonal to the moving direction of the droplet D”. Is a direction having a component orthogonal to the moving direction of the droplet D.

  Therefore, when the mounting unit 210, the first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223 are rotated around the rotation axis R in a state where the container 110 is mounted on the mounting unit 210, the container 110 is rotated. The droplet D inside can move in the first space 101, the second space 102, and the third space 103 of the container 110. 9 to 11 show an example in which the rotation axis R is perpendicular to the direction in which gravity acts.

  It will be easily understood that the droplet D can move if the longitudinal direction of the container 110 is an arrangement other than an arrangement perpendicular to the direction G in which gravity acts (arrangement shown in the figure). For this reason, the rotation mechanism 230 does not necessarily need to be rotated by 180 ° or more around the rotation axis R, and the rotation mechanism 230 can be rotated by 360 ° or more around the rotation axis R. An aspect may be sufficient.

  The rotation mechanism 230 may rotate the mounting unit 210, the first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223 around the same rotation axis R. In other words, the rotation axis R that rotates the mounting unit 210 and the rotation axis R that rotates the first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223 may be the same (same). .

  The rotation mechanism 230 may include a motor and a drive shaft (not shown), and may be configured by connecting the drive shaft and a gear, a flange, or the like as necessary. When the rotation mechanism 230 has a motor, the rotation shaft R can be rotated around the rotation axis R by the operation of the motor, for example, with the drive shaft of the motor as the rotation axis R. Although there is no restriction | limiting in particular about the positional relationship of the rotating shaft R and the mounting part 210, It can set suitably in consideration of size reduction of an apparatus and interference with the other member in an apparatus. Note that the rotation mechanism 230 is not limited to a motor, and for example, a handle, a mainspring, or the like may be employed.

The heat cycle apparatus 200 may include a control unit (not shown). The control unit can control at least one of the rotation mechanism 230, the first temperature control unit 221, the second temperature control unit 222, and the third temperature control unit 223. The control unit may be configured to perform control by a dedicated circuit. The control unit is, for example, a CPU (Central Processing).
The Unit may function as a computer by executing a control program stored in a storage device such as a ROM (Read Only Memory) or a RAM (Random Access Memory), and may be configured to perform control. In this case, the storage device may have a work area for temporarily storing intermediate data and control results associated with the control.

  In the heat cycle apparatus 200 of the present embodiment, when the container 110 is mounted, the first temperature control unit 221 controls the temperature of the first region 11 of the container body 10 and the second temperature control unit 222 uses the second region 12. The third temperature controller 223 can control the temperature of the third region 13. In addition, in the heat cycle apparatus 200 of this embodiment, in addition to this, the rotation mechanism 230 moves the mounting part 210 and each temperature control part around a rotation axis having a component orthogonal to the direction in which gravity acts. Can be rotated. As a result, the thermal cycle apparatus 200 according to the present embodiment causes the droplet D and the liquid D having a specific gravity smaller than that of the droplet D to be introduced into the container 110 when the droplet D and the droplet D are phase-separated into the container 110. It can be moved within 110 and subjected to thermal cycling. Since the tilt angle α of the container 110 can be freely changed by the rotation mechanism 230, the container 110 can be tilted to the tilt angle α that satisfies the relationship of (90 ° −θ) ≦ α. The rotation can also be stopped by α (for example, the state shown in FIG. 11). Therefore, it is possible to easily subject the droplet D to a thermal cycle at three stages.

4). Method for Using Container Hereinafter, as an example of a method for using a container according to the present invention, an embodiment in which a PCR reaction solution is moved in the above-described container 110 using the above-described thermal cycle apparatus 200 and subjected to thermal cycling will be described as an example. To do.

  First, as shown in FIG. 7A, the PCR reaction liquid (droplet D) and oil (liquid L) are stored in the container 10 of the container 110 with the lid 20 removed. The reaction liquid has a volume such that it exists as a droplet in oil, and has such a size that the droplet can move in the first space 101, the second space 102, and the third space 103 formed in the container 110.

  Examples of the reaction solution for PCR include aqueous solutions such as sterilized water, distilled water, and ion-exchanged water that contain a target nucleic acid and contain at least one of an enzyme, dNTP, probe, primer, and buffer. Here, dNTP represents four types of deoxynucleotide triphosphate (a mixture of dATP (Deoxyadenosine triphosphate), dCTP (Deoxycytidine triphosphate), dGTP (Deoxyguanosine triphosphate), and dTTP (Thymidine triphosphate)). .

  The target nucleic acid is, for example, DNA or RNA (DNA: Deoxyribonucleic Acid and / or RNA: Ribonucleic Asid). The target nucleic acid is used as a PCR template. Examples of the sample containing the target nucleic acid include blood, nasal mucus, oral mucosa, and other various biological samples. The target nucleic acid may be purified from these samples by extraction or the like.

  Examples of the oil include one selected from silicone oil such as dimethyl silicone oil, paraffin oil and mineral oil, and mixtures thereof.

  After the PCR reaction solution and oil are stored in the container 10, the container 10 is sealed with the lid 20 as shown in FIG. Then, as shown in FIG. 10, the container 110 is mounted on the mounting portion 210 of the heat cycle apparatus 200.

In this example, an example will be described in which the thermal denaturation temperature in PCR is 95 ° C., the annealing temperature is 55 ° C., and the extension temperature is 55 ° C. However, the thermal cycle apparatus 200 of the present embodiment is not limited to such a temperature range. For example, the heat denaturation temperature is 70 ° C. or higher, 85 ° C. or higher, or 90 ° C. or higher, and the annealing / elongation temperature is 55 ° C. or higher and 70 ° C. Below, it is easy to set 55 ° C or higher and 68 ° C or lower, or 60 ° C or higher and 65 ° C or lower. The temperature required for various PCRs, including the temperature range required for future enzyme development. The temperature of each temperature control unit can be set according to. Further, for example, it can be applied to one-step RT-PCR or the like, and PCR according to conditions can be performed.

  Here, the first temperature control unit 221 is controlled to 55 ° C. to perform an annealing reaction on the reaction liquid in the first space 101, and the second temperature control unit 222 is controlled to 72 ° C. to react in the second space 102. It is assumed that an extension reaction is performed on the liquid, and the third temperature controller 223 is controlled to 95 ° C. to perform a heat denaturation reaction on the reaction liquid in the third space 103.

  Then, by operating the rotating mechanism 230, the reaction solution is moved as shown in FIG. 10B (α = 180 °). In this state, the reaction liquid (droplet D) is in the first region 11 (first space 101), and an annealing reaction is performed at 55 ° C. Next, the rotation mechanism 230 is operated, and as shown in FIG. 11, the rotation mechanism 230 is rotated to an inclination angle α that satisfies the relationship of (90 ° −θ) ≦ α and stopped. At this time, as shown in FIG. 11 and FIG. 8B, the reaction solution moves in the container 100 by gravity and stops near the second region 12. Here, the extension reaction is carried out at 72 ° C. When the rotation mechanism 230 is further operated (α = 0 °) to move the reaction solution (the state shown in FIG. 10A), the reaction solution moves to the third region 13 (the third space 103). In this state, the heat denaturation reaction is performed. Then, when the rotation mechanism 230 is operated (α = 180 °), the initial state (FIG. 10B) is returned, and the reaction solution is moved to the first region 11 (first space 101), and continues to the next state. An annealing reaction can be performed. Thereby, a thermal cycle can be applied to the PCR reaction solution.

  The direction of rotation by the rotation mechanism 230 is arbitrary as long as the reaction liquid can be retained in the second region 12. Further, the first temperature control unit 221 is controlled to 95 ° C. to perform a thermal transformation reaction on the reaction liquid in the first space 101, and the second temperature control unit 222 is controlled to 55 ° C. to react in the second space 102. An annealing reaction may be performed on the solution, and the third temperature control unit 223 may be controlled to 72 ° C. to perform an extension reaction on the reaction solution in the third space 103, or may be performed on the PCR reaction solution. These conditions may be appropriately changed in consideration of the power cycle.

  The present invention is not limited to the above-described embodiments, and various modifications can be made. For example, the present invention includes substantially the same configuration (for example, a configuration having the same function, method and result, or a configuration having the same purpose and effect) as the configuration described in the embodiment. In addition, the invention includes a configuration in which a non-essential part of the configuration described in the embodiment is replaced. In addition, the present invention includes a configuration that exhibits the same operational effects as the configuration described in the embodiment or a configuration that can achieve the same object. In addition, the invention includes a configuration in which a known technique is added to the configuration described in the embodiment.

DESCRIPTION OF SYMBOLS 10 ... Container body, 11 ... 1st area | region, 12 ... 2nd area | region, 12a ... Expanded diameter part, 12b ... Reduced diameter part, 12c ... Inner wall, 13 ... 3rd area | region, 14 ... Cavity, 20 ... Lid body, 21 ... Projection, 100, 110 ... Container, 101 ... First space, 102 ... Second space, 103 ... Third space, 200 ... Thermal cycle device, 210 ... Mounting portion, 221 ... First temperature control portion, 222 ... Second temperature Control unit, 223 ... third temperature control unit, 230 ... rotating mechanism, D ... droplet, L ... liquid, R ... rotating shaft

Claims (6)

A container having a longitudinal direction, one end of the longitudinal direction being opened and the other end being closed;
A lid that includes a projection that projects from the interior of the container, and seals the one end of the container;
A container for a thermal cycler comprising:
The vessel is
When the container is sealed by the lid, a first region including the protrusion in a cross section orthogonal to the longitudinal direction;
A second region having a diameter-increased portion connected to the other end side of the first region and a diameter-reduced portion on the other end side;
A third region connected to the other end of the second region;
Including
When sealing the vessel body by the lid, said first region, said second region, and Ri Do a state inside the space of the third region is in communication,
The third region is a container in which an area of a region surrounded by an inner wall of the vessel body in a cross section orthogonal to the longitudinal direction is constant . In claim 1,
The container in which the inner wall of the said 3rd area | region of the said container is located inside the inner wall of the said 1st area | region in planar view from the said longitudinal direction. In claim 1 or claim 2,
The container in which the area of the area | region enclosed by the inner wall of the said container in the cross section orthogonal to the said longitudinal direction is constant in the said 1st area | region of the said container. In any one of Claims 1 thru | or 3 ,
The container in which the length in the longitudinal direction of the first region and the third region of the container is longer than the length of the second region in the longitudinal direction. In any one of Claims 1 thru | or 4 ,
The inner wall of the second region of the vessel is a tapered shape. A container,
A mounting portion capable of mounting the container,
A first temperature control unit;
A second temperature control unit;
A third temperature control unit;
A rotation mechanism;
Including
The container is
A container having a longitudinal direction, one end of the longitudinal direction being opened and the other end being closed;
A lid provided with a projection capable of sealing the one end of the vessel body and protruding and arranged inside the vessel body when the vessel body is sealed;
A container having
The vessel is
When the container is sealed by the lid, a first region including the protrusion in a cross section orthogonal to the longitudinal direction;
A diameter-enlarged portion connected to the other end side of the first region, a second region having a reduced-diameter portion on the other end side,
A third region connected to the other end of the second region;
Including
When sealing the vessel body by the lid, said first region, said second region, and Ri Do a state inside the space of the third region are continuous,
The third region is a container in which an area of a region surrounded by an inner wall of the vessel body in a cross section orthogonal to the longitudinal direction is constant ,
When the container is mounted on the mounting portion,
The first temperature control unit controls the temperature of the first region of the container,
The second temperature control unit controls the temperature of the second region;
The third temperature controller controls the temperature of the third region;
The rotation mechanism is a thermal cycle device that rotates the mounting unit and each temperature control unit around a rotation axis having a component orthogonal to a direction in which gravity acts.

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