JP2013201966A - Heat cycle device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a heat cycle device which can make the temperature of heat conductors reach a set temperature in a short time.SOLUTION: A heat cycle device includes: a mounting part which is filled with a reaction liquid and a liquid having a specific gravity different from that of the reaction liquid and immiscible in the reaction liquid and on which a reaction container, including a flow passage along the opposed inner walls of which the reaction liquid moves, is mounted; and heat conductors which conduct heat. It includes: a temperature gradient forming part which forms a temperature gradient in a direction of movement of the reaction liquid with respect to the flow passage when the reaction container is mounted on the mounting part; a driving mechanism which allows the mounting part and the temperature gradient forming part to rotate about an axis of rotation having a component perpendicular to the direction in which the gravity acts and a component perpendicular to the direction in which the reaction liquid moves in the flow passage, when the reaction container is mounted on the mounting part; and an air blowing mechanism which sends air to at least the heat conductors.

Description

  The present invention relates to a heat cycle apparatus.

  In recent years, gene-based medical care such as gene diagnosis and gene therapy has attracted attention due to the development of gene utilization technology, and many methods using genes for variety discrimination and variety improvement have been developed in the field of agriculture and livestock. . Techniques such as PCR (Polymerase Chain Reaction) are widely used as techniques for utilizing genes. Today, PCR has become an indispensable technique for elucidating information on biological materials.

  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 (reaction solution) to a thermal cycle (temperature cycle). The thermal cycle is a process in which two or more stages of temperature are periodically applied to the reaction solution. In PCR, a technique of applying a two-stage or three-stage thermal cycle is common.

  In PCR, generally, a container for performing a biochemical reaction, which is called a tube or a biological sample reaction chip (also called a biochip, a reaction container, or the like) is used. However, in the conventional method, there are problems that a large amount of reagents and the like are required, and that the apparatus becomes complicated in order to realize a thermal cycle necessary for the reaction, and that the reaction takes time. Therefore, a biochip and a reaction apparatus are required for performing PCR accurately and in a short time using a very small amount of reagent or specimen.

  In order to solve such a problem, Patent Document 1 discloses that a biological sample reaction chip filled with a reaction solution and a liquid that is not mixed with the reaction solution and has a specific gravity smaller than that of the reaction solution is rotated in the horizontal direction. A biological sample reaction device is disclosed in which a reaction liquid is moved and subjected to a thermal cycle by rotating around an axis.

JP 2009-136250 A

  In the biological sample reaction apparatus disclosed in Patent Document 1, when the temperature of the heat conductor is increased (the temperature of the heat conductor is increased), an excessive temperature increase (overshoot) occurs and the target temperature is reached. It took time.

  The present invention has been made in view of the above problems, and one of the objects according to some aspects thereof is a heat cycle device capable of causing the temperature of a heat conductor to reach a set temperature in a short time. Is to provide.

  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 In one aspect of the thermal cycle apparatus according to the present invention, a reaction solution and a liquid having a specific gravity different from that of the reaction solution and immiscible with the reaction solution are filled and the reaction solution is opposed to the reaction solution. A mounting portion for mounting a reaction vessel including a flow path that moves along the inner wall, and a heat conductor that conducts heat, and when the reaction vessel is mounted on the mounting portion, A temperature gradient forming part that forms a temperature gradient in a direction in which the reaction solution moves, and the mounting part and the temperature gradient forming part have a component perpendicular to the direction in which gravity acts, and the mounting part A drive mechanism for rotating the flow path around a rotating shaft having a component perpendicular to the direction in which the reaction solution moves, and a blower mechanism for blowing air to at least the heat conductor. ,including.

  According to the thermal cycle apparatus of this application example, the rotation shaft has a component perpendicular to the direction in which gravity acts, and the reaction liquid is passed through the flow path of the reaction container when the reaction container is attached to the attachment portion. Since the drive mechanism has a component perpendicular to the moving direction, the drive mechanism rotates the mounting portion, so that the lowest point or the highest point in the direction in which gravity acts in the flow path of the reaction vessel mounted on the mounting portion The position of changes. Thereby, the reaction solution moves in the flow path in which the temperature gradient is formed by the temperature gradient forming unit. Therefore, a thermal cycle (temperature cycle) can be applied to the reaction solution.

  According to the heat cycle device of this application example, since it has a blower mechanism, the efficiency of heat exchange between the heat conductor and the environment (the space around the heat conductor) is improved. As a result, when the temperature of the heat conductor is raised to the target temperature, so-called overshoot (overheating) can be suppressed, so that the target temperature can be reached in a shorter time. Therefore, according to the thermal cycle apparatus of this application example, the time required for the thermal cycle (temperature cycle) can be shortened as compared with a thermal cycle apparatus that does not include a blower mechanism.

  Application Example 2 In Application Example 1, the heat conductor may further include a heat radiating portion that dissipates heat.

  According to the heat cycle device of this application example, since the heat conductor has the heat radiating portion, the heat exchange between the heat conductor and the environment is further improved. As a result, overshoot can be suppressed when the temperature of the heat conductor is raised from the low temperature side and stabilized at the target temperature. Therefore, when starting the device or increasing the temperature of the heat conductor from the low temperature side and stabilizing it at the target temperature, the time until it becomes possible to perform PCR thermal cycling is shortened. Can do.

  Application Example 3 In Application Example 1 or Application Example 2, the temperature gradient forming unit heats the first region of the flow path to the first temperature when the reaction vessel is mounted on the mounting unit. A conductor, and a second heat conductor that heats the second region of the flow path to a second temperature higher than the first temperature when the reaction vessel is attached to the attachment portion, The air blowing mechanism may blow air to at least the first heat conductor.

  The thermal cycle device according to this application example includes a first heat conductor that heats the first region of the flow path to the first temperature, and a second heat conductor that heats the second region of the flow path to the second temperature. Therefore, when the reaction vessel is attached to the attachment portion, the first region and the second region of the flow path can be heated to different temperatures. Therefore, a more accurate thermal cycle can be applied to the reaction solution.

  The thermal cycle apparatus of this application example can be suitably used for RT-PCR, and can reduce the time required for RT-PCR.

  Application Example 4 In Application Example 3, the first heat conductor may include a first heat radiating portion made of fins.

  In the heat cycle device according to this application example, the first heat conductor has a first heat radiating portion made of a fin, and the first heat radiating portion is a fin. Therefore, the structure of the first heat radiating portion is simple. Therefore, it is possible to easily manufacture a heat cycle device that can shorten the time required for the heat cycle.

The figure which shows typically the principal part of the thermal cycle apparatus which concerns on 1st Embodiment. The figure which shows typically the principal part of the thermal cycle apparatus which concerns on 1st Embodiment. The figure which shows typically the principal part of the thermal cycle apparatus which concerns on 2nd Embodiment. The figure which shows typically the principal part of the thermal cycle apparatus which concerns on 2nd Embodiment. The perspective view which shows typically the outline of the thermal cycle apparatus which concerns on 3rd Embodiment. The disassembled perspective view which shows typically the principal part of the heat cycle apparatus which concerns on 3rd Embodiment. The top view of the 1st heat conductor which concerns on 3rd Embodiment, and a 1st thermal radiation part. The side view of the 1st heat conductor which concerns on 3rd Embodiment, and a 1st thermal radiation part. Sectional drawing of the 1st heat conductor which concerns on 3rd Embodiment, and a 1st thermal radiation part. The side view of the 1st heat conductor which concerns on 3rd Embodiment, and a 1st thermal radiation part. The graph which shows the result of an experiment example. The graph which shows the result of an experiment example.

  Several embodiments of the present invention will be described below. The embodiment described below is an example of the present invention, and the present invention is not limited to the following embodiment at all, and various embodiments that are carried out without departing from the spirit of the present invention are described. Variations are also included. Note that not all of the configurations described below are necessarily essential components of the present invention.

1. 1. First embodiment 1.1. Thermal Cycle Device The thermal cycle device 100 of the present embodiment includes a mounting unit 10, a temperature gradient forming unit 20, a drive mechanism 30, and a blower mechanism 60. More specifically, in the thermal cycle apparatus 100 of the present embodiment, the reaction liquid 11 and the reaction liquid 11 are filled with a liquid 12 having a specific gravity different from that of the reaction liquid 11 and immiscible with the reaction liquid 11, and the reaction liquid 11 faces each other. When the reaction vessel 15 is attached to the attachment portion 10 including the attachment portion 10 to which the reaction vessel 15 including the flow passage 13 moving along the inner wall is attached and the heat conductor 22 that conducts heat, In contrast, the temperature gradient forming unit 20 that forms a temperature gradient in the direction in which the reaction solution 11 moves, the mounting unit 10 and the temperature gradient forming unit 20 have components perpendicular to the direction in which gravity acts, and A drive mechanism 30 that rotates the flow path 13 around a rotation axis R having a component perpendicular to the direction in which the reaction solution 11 moves when the reaction vessel 15 is attached to the attachment unit 10, and at least the heat conductor 22. A blowing mechanism 60 for blowing air Including the. In the thermal cycle apparatus 100 of the present embodiment, the temperature gradient forming unit 20 heats the first region 131 of the flow path 13 to the first temperature when the reaction vessel 15 is mounted on the mounting unit 10. A body 221 and a second heat conductor 222 that heats the second region 132 of the flow path 13 to a second temperature higher than the first temperature when the reaction container 15 is mounted on the mounting unit 10, and a blower mechanism 60 blows air to at least the first heat conductor 221.

  FIG.1 and FIG.2 is a figure which shows typically the principal part of the thermal cycle apparatus 100 which concerns on this embodiment.

1.1.1. Reaction Container First, the reaction container 15 attached to the heat cycle apparatus 100 will be described. The reaction vessel 15 is filled with a reaction liquid 11 and a liquid 12 having a specific gravity different from that of the reaction liquid 11 and immiscible with the reaction liquid 11 (hereinafter referred to as “liquid 12”). The reaction vessel 15 includes a flow path 13 in which the reaction solution 11 moves along the opposing inner wall.

  The liquid 12 has a specific gravity smaller than that of the reaction liquid 11 and is not miscible with the reaction liquid 11. As the liquid 12, for example, a liquid that is not miscible with the reaction liquid 11 and has a higher specific gravity than the reaction liquid 11 may be employed. In the example shown in FIGS. 1 and 2, the reaction vessel 15 includes a flow path 13 and a sealing body 14. The flow path 13 is filled with the reaction solution 11 and the liquid 12 and is sealed with a sealing body 14.

  The channel 13 is formed so that the reaction solution 11 moves along the opposing inner walls. Here, the “opposite inner walls” of the flow channel 13 mean two regions of the wall surface of the flow channel 13 that are in a positional relationship facing each other. “Along” means a state where the distance between the reaction solution 11 and the wall surface of the flow path 13 is short, and includes a state where the reaction solution 11 contacts the wall surface of the flow path 13. Therefore, “the reaction solution 11 moves along the opposing inner wall” means that the reaction solution 11 is in a state where the distance between the two regions of the wall surface of the flow path 13 that are in a facing positional relationship is short. Means "move". In other words, the distance between the two inner walls facing each other in the flow path 13 is such a distance that the reaction solution 11 moves along the inner wall.

  When the flow path 13 of the reaction vessel 15 has such a shape, the direction in which the reaction liquid 11 moves in the flow path 13 can be regulated, so that the path through which the reaction liquid 11 moves in the flow path 13 can be defined to some extent. Thereby, the time required for the reaction solution 11 to move in the flow path 13 can be limited to a certain range. Therefore, the distance between the two inner walls facing each other in the flow path 13 is preferably a variation in thermal cycle conditions applied to the reaction liquid 11 caused by a variation in the time during which the reaction liquid 11 moves in the flow path 13. It is preferable that the accuracy of the reaction can be satisfied, that is, the result of the reaction can satisfy the desired accuracy. More specifically, the distance in the direction perpendicular to the direction in which the reaction solution 11 moves between the two inner walls facing each other in the flow path 13 is such that two or more droplets of the reaction solution 11 do not enter. Is desirable.

  In the example shown in FIGS. 1 and 2, the outer shape of the reaction vessel 15 is a cylindrical shape, and a flow path 13 having a longitudinal direction in the direction along the central axis of the column (the vertical direction in FIGS. 1 and 2) is provided. Is formed. The shape of the flow path 13 is a cross section in a direction perpendicular to the longitudinal direction of the flow path 13, that is, a cross section perpendicular to the direction in which the reaction solution 11 moves in a region of the flow path 13 (this is the cross section of the flow path 13. “Cross section”) is a circular column. Therefore, in the reaction vessel 15, the opposed inner wall of the flow channel 13 is a region including two points on the wall surface of the flow channel 13 facing each other across the center of the cross section of the flow channel 13. The “movement direction in which the reaction liquid 11 moves” is the longitudinal direction of the flow path 13.

  The shape of the cross section of the flow path 13 is not limited to a circle, but may be any shape such as a polygon or an ellipse as long as the reaction solution 11 can move along the opposing inner walls. For example, when the cross section of the flow path 13 of the reaction vessel 15 is polygonal, the “opposite inner wall” is opposed to the flow path when the cross section inscribed in the flow path 13 is assumed to be a circular flow path. It shall be an inner wall. That is, the flow path 13 may be formed so that the reaction solution 11 moves along the opposing inner wall of the virtual flow path inscribed in the flow path 13 and having a circular cross section. Thereby, even when the cross section of the flow path 13 is a polygon, the path | route to which the reaction liquid 11 moves can be prescribed to some extent. Therefore, the time required for the reaction solution 11 to move can be limited to a certain range. Furthermore, the cross-sectional shape of the flow path 13 does not necessarily have to be constant in the longitudinal direction, and the flow path 13 may have a tapered shape such as a truncated cone or a tapered portion, for example. Also good. Further, the shape of the flow path 13 and the shape of the reaction vessel 15 can be designed in consideration of the manufacturing advantages of the reaction vessel 15. That is, for example, when the reaction container 15 is made of a polymer and the reaction container 15 is manufactured by injection molding, the shape of the flow path 13 and the shape of the flow path 13 are set so that the mold can be easily taken out from the mold. The shape of the reaction vessel 15 can be designed.

  The flow path 13 includes a first region 131 and a second region 132. The first region 131 and the second region 132 are regions that are controlled to have different temperatures when the reaction vessel 15 is mounted on the mounting unit 10 of the thermal cycle apparatus 100. In the present embodiment, a region that is in thermal contact with the first thermal conductor 221 is referred to as a first region 131, and a region that is in thermal contact with the second thermal conductor 222 is referred to as a second region 132. The first region 131 and the second region 132 of the flow path 13 of the reaction vessel 15 are temperature controlled by being in thermal contact with the first thermal conductor 221 and the second thermal conductor 222, respectively.

  The first region 131 is a region including one end portion in the longitudinal direction of the flow path 13, and the second region 132 is a region including the other end portion in the longitudinal direction of the flow path 13. In the example shown in FIGS. 1 and 2, a region surrounded by a dotted line including an end portion on the side relatively far from the sealing body 14 in the flow channel 13 is the first region 131. A region surrounded by a dotted line including an end portion on the side relatively close to the sealing body 14 is a second region 132.

  In the thermal cycle apparatus 100 according to the present embodiment, at least the first thermal conductor 221 of the temperature gradient forming unit 20 heats the first region 131 of the flow path 13 of the reaction vessel 15 to the first temperature, and the temperature gradient forming unit 20. The second heat conductor 222 heats the second region 132 of the flow path 13 of the reaction container 15 to the second temperature, so that the temperature of the reaction liquid 11 moves in the direction of movement with respect to the flow path 13 of the reaction container 15. Form a gradient.

  The flow path 13 is filled with the liquid 12 and the reaction liquid 11. Since the liquid 12 is not miscible with the reaction liquid 11, that is, does not mix, the reaction liquid 11 is held in the liquid 12 in the form of droplets as shown in FIGS. 1 and 2. . Since the specific gravity of the reaction liquid 11 is larger than that of the liquid 12, the reaction liquid 11 is located in the lowermost region in the direction in which gravity acts in the flow path 13. In FIGS. 1 and 2, the direction in which gravity acts is indicated by an arrow g.

  As the liquid 12, for example, dimethyl silicone oil or paraffin oil can be used. The reaction liquid 11 is a liquid containing components necessary for the reaction. When the reaction is PCR, the reaction solution 11 includes DNA (target nucleic acid) amplified by PCR, DNA polymerase necessary for amplifying DNA, primers, and the like. For example, when PCR is performed using oil as the liquid 12, the reaction liquid 11 is preferably an aqueous solution containing the above components.

1.1.2. Mounting Unit The thermal cycle apparatus 100 according to this embodiment includes a mounting unit 10 to which the reaction vessel 15 is mounted. The mounting part 10 has a structure for mounting the reaction container 15. In the example shown in FIGS. 1 and 2, a part of the first heat conductor 221 and a part of the second heat conductor 222 constitute the mounting portion 10. Although not shown, the mounting unit 10 may be configured to include other configurations, for example, a member that serves as a guide or a spacer when mounting the reaction vessel 15, or a member for fixing the reaction vessel 15. In the example of FIGS. 1 and 2, the mounting portion 10 has a slot structure in which the reaction vessel 15 is inserted and mounted.

  The number of mounting portions 10 provided in the first thermal conductor 221 and the second thermal conductor 222 is not particularly limited. When the number of mounting parts 10 is plural, a plurality of reaction containers 15 can be respectively mounted. In the present embodiment, an example in which the mounting unit 10 has a slot structure is shown, but the mounting unit 10 may have a structure that can hold the reaction vessel 15. For example, a structure in which the reaction container 15 is fitted in a recess that matches the shape of the reaction container 15 or a structure in which the reaction container 15 is sandwiched and held may be employed.

1.1.3. Temperature Gradient Forming Unit The temperature gradient forming unit 20 of the thermal cycle apparatus 100 of the present embodiment includes a first thermal conductor 221 and a second thermal conductor 222 provided with the mounting unit 10. When the reaction vessel 15 is mounted on the mounting unit 10, the temperature gradient forming unit 20 is described as a moving direction in which the reaction solution 11 moves with respect to the flow path 13 (in the present specification, simply referred to as “the moving direction”). Is a configuration that forms a temperature gradient. 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 reaction solution 11 moves” means to form a state in which the temperature changes along the moving direction in which the reaction solution 11 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 FIGS. 1 and 2, the temperature gradient forming unit 20 includes a first thermal conductor 221 and a second thermal conductor 222.

1.1.3.1. Thermal Conductor The first thermal conductor 221 and the second thermal conductor 222 are provided with at least a part of the mounting portion 10. As a result, the first heat conductor 221 and the second heat conductor 222 have the first region 131 and the second region 132 of the flow path 13 of the reaction vessel 15 respectively when the reaction vessel 15 is attached to the attachment unit 10. Control is performed so as to be the first temperature and the second temperature, respectively.

  In the example shown in FIGS. 1 and 2, the first heat conductor 221 is disposed at a position where the first region 131 of the flow path 13 of the reaction vessel 15 can be heated. Further, the second heat conductor 222 is disposed at a position where the second region 132 of the flow path 13 of the reaction vessel 15 can be heated.

  The first heat conductor 221 and the second heat conductor 222 can be controlled at different temperatures. In this case, it is preferable that the first thermal conductor 221 and the second thermal conductor 222 are arranged in a manner in which the thermal contact with each other is small. For example, the first thermal conductor 221 and the second thermal conductor 222 are preferably provided at positions that are separated from each other (positions that do not physically contact). Further, the first thermal conductor 221 and the second thermal conductor 222 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.

  The first heat conductor 221 and the second heat conductor 222 have a first heat source part 241 and a second heat source part 242 that generate heat, respectively, and can transfer the heat generated thereby to the reaction vessel 15. .

  The shapes of the first heat conductor 221 and the second heat conductor 222 are not particularly limited. The materials of the first thermal conductor 221 and the second thermal conductor 222 can be appropriately selected in consideration of conditions such as thermal conductivity, heat retention, and ease of processing. For example, since aluminum has high thermal conductivity and uneven heating is less likely to occur, the reaction vessel 15 can be efficiently and accurately heated. In addition, since aluminum can be easily processed, the first thermal conductor 221 and the second thermal conductor 222 can be accurately molded, and the accuracy of contact with the reaction vessel 15 can be increased. Therefore, a more accurate thermal cycle can be realized. In addition, the material of the 1st heat conductor 221 and the 2nd heat conductor 222 may use a copper alloy, for example, and may combine a some material. Specific examples of the first thermal conductor 221 and the second thermal conductor 222 include aluminum blocks.

  The first heat conductor 221 and the second heat conductor 222 are in thermal contact with the reaction vessel 15 when the reaction vessel 15 is attached to the attachment portion 10. As an aspect which contacts thermally, the 1st thermal conductor 221 and the 2nd thermal conductor 222, and the reaction container 15 are contacting directly, the 1st thermal conductor 221 and the 2nd thermal conductor 222 And the reaction vessel 15 may be in contact with each other via another thermally conductive member. In addition, a space may be provided between the first thermal conductor 221 and the second thermal conductor 222 and the reaction vessel 15 as long as heat can be appropriately transmitted. Thereby, when the reaction vessel 15 is heated by the first thermal conductor 221 and the second thermal conductor 222, the heat of the first thermal conductor 221 and the second thermal conductor 222 is stably transmitted to the reaction vessel 15. Therefore, the temperature of the predetermined region of the flow path 13 of the reaction vessel 15 can be stabilized.

  When the mounting part 10 is configured to include a part of the first heat conductor 221 and the second heat conductor 222 as in the present embodiment, the mounting part 10 is in direct contact with the reaction vessel 15. Is more preferable. Thereby, since the heat of the 1st heat conductor 221 and the 2nd heat conductor 222 can be stably transmitted to the reaction container 15, the temperature gradient of the flow path 13 of the reaction container 15 can be controlled efficiently.

  Further, when the mounting part 10 is configured to include a part of the first heat conductor 221 and the second heat conductor 222 as in the present embodiment, a mechanism for bringing the mounting part 10 into close contact with the reaction vessel 15. May be provided. The mechanism for bringing the mounting portion 10 into close contact with the reaction vessel 15 only needs to allow at least a part of the reaction vessel 15 to be in close contact with the mounting portion 10. For example, the reaction container 15 may be pressed against one wall surface of the mounting portion 10 by a spring attached to the member, for example, by adding another member. Thereby, since the heat of the temperature gradient formation part 20 can be more stably transmitted to the reaction vessel 15, the temperature of the reaction vessel 15 can be further stabilized.

  The temperature of the first heat conductor 221 and the second heat conductor 222 may be controlled by a temperature sensor and a 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 temperatures of the first heat conductor 221 and the second heat conductor 222 are preferably set so that the reaction vessel 15 is heated to a desired temperature. In the present embodiment, the first region 131 and the second region 132 of the flow path 13 of the reaction vessel 15 are controlled to target temperatures by controlling the temperature of the first thermal conductor 221 and the second thermal conductor 222. be able to. The temperatures of the first heat conductor 221 and the second heat conductor 222 are controlled so that the first region 131 and the second region 132 of the flow path 13 of the reaction vessel 15 are controlled to a desired temperature. For example, it may be controlled in consideration of the material and size of the reaction vessel 15.

1.1.4. Heat source unit The first heat source unit 241 and the second heat source unit 242 generate heat. The first heat source unit 241 and the second heat source unit 242 are provided on the first heat conductor 221 and the second heat conductor 222, respectively, and supply heat to the first heat conductor 221 and the second heat conductor 222. can do. As the first heat source unit 241 and the second heat source unit 242, for example, 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 is used. Can do. Moreover, you may provide a conducting wire and piping as needed, and you may connect to an external power supply etc. Among these, since the temperature control of the cartridge heater is easy, the temperature of the first heat conductor 221 and the second heat conductor 222 can be achieved by employing the cartridge heater for the first heat source unit 241 and the second heat source unit 242. Can be facilitated.

1.1.5. Driving mechanism The driving mechanism 30 has a component perpendicular to the direction in which the mounting unit 10 and the temperature gradient forming unit 20 act on the gravity, and the moving direction when the reaction vessel 15 is mounted on the mounting unit 10. This is a mechanism for rotating around a rotation axis R having a component perpendicular to (the direction in which the reaction liquid 11 moves). 1 and 2, only the rotation axis R is displayed, and the drive mechanism 30 is omitted.

  The direction “having a component perpendicular 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”. In this case, it is a direction having a component perpendicular to the direction in which gravity acts. The direction “having a component perpendicular to the moving direction” is expressed as a vector sum of “a component parallel to the moving direction” and “a component perpendicular to the moving direction”. This is a direction having a component perpendicular to the moving direction.

  Therefore, when the mounting unit 10 and the temperature gradient forming unit 20 are rotated around the rotation axis R in a state where the reaction vessel 15 is mounted on the mounting unit 10, the reaction solution 11 in the reaction vessel 15 is transferred to the flow path of the reaction vessel 15. 13 can be moved. In the example of FIG.1 and FIG.2, the rotating shaft R has shown the example perpendicular | vertical with respect to the direction where gravity acts. That is, in FIG. 1, the reaction liquid 11 is present in the first region 131 of the flow path 13 due to the action of gravity, and is in a state of being rotated by 180 ° around the rotation axis R with respect to the arrangement of FIG. In the example of FIG. 2, the reaction solution 11 exists in the second region 132 that is opposite to the first region 131 of the flow path 13 in the longitudinal direction due to the action of gravity. In the example of FIGS. 1 and 2, only the arrangement in which the longitudinal direction of the flow path 13 is parallel to the direction in which the gravity acts is illustrated, but the longitudinal direction of the flow path 13 is the direction in which the gravity acts. The reaction solution 11 can move in the flow path 13 if the arrangement is other than the arrangement perpendicular to the flow path 13. For this reason, the drive mechanism 30 does not necessarily have to be capable of being rotated by 180 ° or more around the rotation axis R. Further, the drive mechanism 30 may be configured to be able to rotate 360 ° or more around the rotation axis R.

  The drive mechanism 30 may rotate the mounting unit 10 and the temperature gradient forming unit 20 around the same rotation axis R. In other words, the rotation axis R that rotates the mounting unit 10 and the rotation axis R that rotates the temperature gradient forming unit 20 may be common (same).

  The drive mechanism 30 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 drive mechanism 30 has a motor, for example, the drive shaft of the motor can be rotated around the rotation axis R by the operation of the motor with the rotation axis R 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 10, It can set suitably in consideration of size reduction of an apparatus and interference with the other member in an apparatus. Note that the drive mechanism 30 is not limited to a motor, and for example, a handle, a mainspring, or the like may be employed.

  The heat cycle apparatus 100 may include a control unit (not shown). The control unit can control at least one of the drive mechanism 30 and the temperature gradient forming unit 20. The control unit may be configured to perform control by a dedicated circuit. In addition, the control unit functions as a computer and executes control by, for example, a CPU (Central Processing Unit) executing a control program stored in a storage device such as a ROM (Read Only Memory) or a RAM (Random Access Memory). It may be configured as follows. In this case, the storage device may have a work area for temporarily storing intermediate data and control results associated with the control.

1.1.6. Blower Mechanism The thermal cycle apparatus 100 of the present embodiment includes a blower mechanism 60 that sends air to at least the first thermal conductor 221. Examples of the air blowing mechanism 60 include a fan, a duct, and a combination thereof. The air blowing mechanism 60 sucks air (gas) around the heat cycle device 100 (first heat conductor 221) instead of a configuration in which air is sent toward the heat cycle device 100 (first heat conductor 221). It is good also as composition to do. The air blowing mechanism 60 may constitute a part of the temperature gradient forming unit 20. The air blowing mechanism 60 may blow air to the second heat conductor 222, other members, or the reaction vessel 10 attached to the attachment portion 15 in addition to the first heat conductor 221. In the example shown in FIGS. 1 and 2, the air blowing mechanism 60 is configured to send wind to both the first thermal conductor 221 and the second thermal conductor 222. Thereby, temperature control of areas other than the 1st field 131 of channel 13 may be performed. Further, the temperature of the second heat conductor 222 may be controlled. The air blowing mechanism 60 may function as a part of the temperature gradient forming unit 20.

  The air blowing mechanism 60 may be configured integrally with the machine body of the heat cycle apparatus 100 or may be configured as a separate body. For example, as long as air can be blown to at least the first thermal conductor 221, it may be fixed to the casing 42 or may not be fixed. When including the ventilation mechanism 60 in the structure of the temperature gradient formation part 20, it is good also as a structure for providing a desired temperature gradient by providing a control part etc. and connecting to this and controlling a ventilation volume.

  When a fan is employed as the blower mechanism 60, for example, a commercially available DC fan motor, AC fan motor, fan, fan, or the like can be used. In FIG.1 and FIG.2, the ventilation mechanism 60 is drawn typically.

  The temperature of the air blown by the blower mechanism 60 may be the environmental temperature, or may be higher or lower than the environmental temperature. When the temperature of the wind blown by the blower mechanism 60 is higher than the environmental temperature, a heat source such as a heater or a heat exchanger may be added to the blower mechanism 60, and the temperature of the wind When the temperature is lower than the temperature, a cooling device such as a cooler or a heat exchanger that passes through the refrigerant may be added.

1.2. Example of Use of Thermal Cycler The thermal cycler 100 of the present embodiment can be suitably applied to reactions that require various PCRs and thermal cycles (temperature cycles).

  There is no restriction | limiting in particular as PCR which can apply the thermal cycle apparatus 100. FIG. However, since the heat cycle apparatus 100 has two heat conductors, the first heat conductor 221 and the second heat conductor 222, a heat cycle (temperature cycle) of two temperatures is easy. It is particularly suitable for (two-step temperature PCR). In addition, since at least the blower mechanism 60 for blowing air to the first heat conductor 221 is provided, RT-PCR can be achieved by setting the temperature of the first heat conductor 221 to a temperature relatively close to the environment (reverse transfer temperature). It can also be suitably applied to (Reverse Transcription Polymerase Chain Reaction).

  Specifically, when the temperature of the first thermal conductor 221 is raised from the low temperature side and stabilized at the target temperature, so-called overshoot (overheating) can be suppressed, and in a shorter time. The target temperature can be stabilized. Therefore, according to the thermal cycle apparatus 100, when starting the apparatus or increasing the temperature of the first thermal conductor 221 from the low temperature side and stabilizing it at the target temperature, the desired temperature of the PCR thermal cycle is achieved. Can be shortened. Also, the time can be shortened when the temperature of the first thermal conductor 221 is lowered from the high temperature side and stabilized at the target temperature.

  Therefore, compared with the case where the heat cycle apparatus 100 does not include the air blowing mechanism 60, the temperature of the first region 131 of the flow path 13 can be changed to an arbitrary temperature in a short time. For example, it is possible to shorten the time required for stabilization by changing to the annealing temperature, extension temperature, thermal denaturation temperature, and reverse transcription temperature of PCR, so that the thermal cycle by the operation of the drive mechanism 30 (movement of the reaction solution) is short. In addition to the increase in speed, it is possible to further increase the speed of PCR.

  Here, shuttle PCR refers to a technique in which the annealing reaction and the extension reaction are performed at the same temperature. In general, shuttle PCR can be realized by designing primers and polymerase. In shuttle PCR, the temperature for annealing / extension is about 60 ° C., and DNA can be amplified by repeating a thermal cycle (temperature cycle) with a heat denaturation temperature of around 95 ° C.

  In addition, when the virus is an RNA virus such as influenza, it cannot be amplified by PCR as it is. Therefore, RT-PCR (reverse transcription PCR) is performed. In RT-PCR, RNA is reverse transcribed into cDNA (Complementary DNA) with reverse transcriptase, and then amplified by PCR.

  In addition, a method of performing reverse transcription and PCR continuously by filling reverse transcriptase and polymerase into the same reaction container is called one-step RT-PCR. One-step RT-PCR has been used frequently in recent years because there is no need to transfer a reaction solution between reaction vessels.

  In one-step RT-PCR, the reverse transcription reaction is generally performed at a temperature of about 42 ° C. to 55 ° C. because the optimum temperature of the reverse transcriptase used is currently about 42 ° C. to 55 ° C. After the reverse transcription reaction, the temperature of the reaction solution is subsequently raised to a denaturation temperature of about 95 ° C. This separates RNA and reverse-transcribed cDNA into single strands (thermal denaturation), respectively, and inactivates reverse transcriptase. After that, DNA is amplified by repeating annealing / extension reaction and heat denaturation in the same manner as the above-described shuttle PCR. In the amplification reaction, the reverse transcriptase is inactivated at the heat denaturation temperature, so that inhibition of PCR by the reverse transcriptase is suppressed.

  An example in which RT-PCR is performed using the thermal cycle apparatus 100 of the present embodiment will be described. In this example, shuttle PCR is performed.

  First, the first thermal conductor 221 is set to the reverse transfer temperature, the second thermal conductor 222 is set to the thermal denaturation temperature, the reaction vessel 15 is mounted on the mounting portion 10, and the reaction solution 11 is passed through the first flow path 13. Arrange in the area 131. At this point, the reverse transcription reaction is started. Then, by operating the drive mechanism 30 and rotating it around the rotation axis R, the reaction solution 11 is moved to reach the second region 132 of the flow path 13 to perform heat denaturation (for example, FIG. 2). Embodiment). Here, the smaller the volume of the reaction solution 11 is, the easier it is to change the temperature. Therefore, the smaller the volume of the reaction solution 11 is, the shorter the temperature of the reaction solution 11 can be changed to the heat denaturation temperature. Then, the temperature of the first thermal conductor 221 is changed to the annealing / elongation temperature, and is rotated around the rotation axis R by the operation of the driving mechanism 30, thereby moving the reaction solution 11 and moving the first of the flow path 13. The region 131 is reached (for example, the mode of FIG. 1).

  Thereafter, the temperature of the first heat conductor 221 and the second heat conductor 222 is maintained, and the reaction liquid 11 is rotated around the rotation axis R by the operation of the drive mechanism 30 to cause the reaction solution 11 to be in the first region 131 and the second region. Move between regions 132. By repeating the rotation, a PCR thermal cycle (temperature cycle) can be applied to the reaction solution 11 a desired number of times.

  When a desired number of thermal cycles (temperature cycles) are completed, the reaction vessel 15 is removed and RT-PCR is completed. Thereafter, when RT-PCR is performed on the other reaction solution 11, the temperature of the first thermal conductor 221 is changed again to the temperature of reverse transcription, and the above operation is performed. On the other hand, RT-PCR can be performed sequentially.

  In the above example, RT-PCR is performed while the blower mechanism 60 is continuously operated. However, the blower mechanism 60 may be operated intermittently or may be operated so as to change the amount of blown air. Good.

  In addition to the above example, the thermal cycle apparatus 100 according to the present embodiment can be suitably applied to hot start PCR and real-time PCR by adding an appropriate configuration.

  In the above example, the heat denaturation temperature is about 95 ° C., the annealing / elongation temperature is about 60 ° C., and the reverse transfer temperature is 42 ° C. to 55 ° C. However, not only in such a temperature range, in the thermal cycle apparatus 100 of this embodiment, 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 to 68 ° C, or 60 ° C to 65 ° C, and the reverse transfer temperature to 35 ° C to 55 ° C, 37 ° C to 50 ° C, or 40 ° C to 48 ° C. In addition, the temperature of each heat conductor can be set according to the temperature required for various PCRs, including the temperature range required for the future development of enzymes and the like. And, for example, if the second thermal conductor 222 is on the high temperature side and the first thermal conductor 221 is on the low temperature side as in the one-step RT-PCR described above, the temperature on the low temperature side is, for example, 37 ° C. By changing the temperature within the range of 70 ° C. or lower, PCR according to the conditions can be performed.

1.3. Effects According to the heat cycle apparatus 100 of the present embodiment, the air blowing mechanism 60 that blows air to the first heat conductor 221 of the temperature gradient forming unit 20 is provided, and therefore, between the first heat conductor 221 and the environment. The efficiency of heat exchange is improved.

  As a result, when the temperature of the first thermal conductor 221 is raised from the low temperature side and stabilized at the target temperature, so-called overshoot (overheating) can be suppressed, and the target temperature can be reduced in a shorter time. Can be stabilized at temperature. Therefore, according to the thermal cycle apparatus 200, when the apparatus is started or when the temperature of the first thermal conductor 221 is increased from the low temperature side and stabilized at the target temperature, the PCR thermal cycle can be performed. It is possible to shorten the time until it becomes ready. Further, even if the temperature of the second heat conductor 222 is higher than the temperature of the first heat conductor 221 and the distance between both is affected by radiation, the temperature of the first heat conductor 221 is set to the set temperature. Can be stabilized. In addition, when the apparatus is small, the temperature of the first heat conductor 221 is easily affected by the temperature of the environment and the temperature of the second heat conductor 222. PCR can be performed.

  When reverse transcription PCR (RT-PCR) is performed in the thermal cycle apparatus 100 of the present embodiment, the first thermal conductor 221 is set to the optimum temperature for reverse transcriptase, and then the first thermal conductor 221 is elongated. If it is set to / annealing temperature, the time required for stabilization at the elongation / annealing temperature is shortened, and as a result, the time required for RT-PCR can be shortened. The time required for stabilization at the elongation / annealing temperature can be made shorter than the time required for the thermal denaturation reaction, and the waiting time for stabilizing the temperature of the first thermal conductor 221 for RT-PCR. Can be eliminated, and the subsequent shuttle PCR can be performed without delay. Such an effect is particularly remarkable when the difference between the environmental temperature and the annealing / elongation temperature is not large. That is, this is an effect obtained by improving the efficiency of heat exchange between the first thermal conductor 221 and the environment.

  Further, since the efficiency of heat exchange between the first heat conductor 221 and the environment is good, when the temperature of the first heat conductor 221 is lowered from a higher temperature to a temperature close to the temperature of the environment, the blower mechanism The temperature can be lowered in a shorter time compared to the case where 60 is not provided.

  Therefore, in particular, when performing RT-PCR a plurality of times using the thermal cycle apparatus 100 of the present embodiment, after performing RT-PCR with the first thermal conductor 221 set to the elongation / annealing temperature, In order to perform the next RT-PCR, the time required to stabilize the temperature of the first heat conductor 221 by changing it to the optimum temperature of the reverse transcriptase can be shortened. As a result, the total time of RT-PCR performed sequentially can be shortened.

  In addition, since the efficiency of heat exchange between the first heat conductor 221 and the environment is good, temperature control is facilitated when the temperature of the first heat conductor 221 is stabilized at a temperature close to the temperature of the environment. Can be stabilized sufficiently. In particular, when reverse transcription PCR (RT-PCR) is performed in the thermal cycle apparatus 100 of the present embodiment, if the first heat conductor 221 is set to the optimum temperature of the reverse transcriptase, Even when the optimum temperature is close to the environmental temperature, the temperature can be sufficiently stabilized, and the reverse transcription reaction can be performed stably.

  The above-described effects can be obtained regardless of whether the first temperature and the second temperature are high or low. However, if the first temperature is set lower than the second temperature, the blower mechanism 60 is at least the first temperature. The effect obtained by blowing air to the heat conductor 221 may be high.

1.4. Other configurations 1.4.1. First Heat Dissipation Unit The thermal cycle device 100 of the present embodiment may include a first heat dissipation unit 261 that dissipates heat of the first thermal conductor 221.

  The first heat radiation part 261 dissipates the heat of the first heat conductor 221. The first heat radiation part 261 dissipates the heat of the first heat conductor 221. The first heat radiating portion 261 is provided on the first heat conductor 221. The 1st thermal radiation part 261 can promote heat exchange between the 1st heat conductor 221 and environment (atmosphere etc.). A plurality of first heat radiating portions 261 may be provided on the first heat conductor 221. The position of the first heat conductor 221 where the first heat radiating portion 261 is provided is arbitrary as long as the first heat conductor 221 does not prevent the temperature gradient forming unit 20 from rotating. The first heat radiation part 261 can be appropriately selected and designed according to the shape and material of the first heat conductor 221.

  As the first heat radiating portion 261, air cooling fins (fins), a structure such as a heat sink, a cooling device such as a Peltier element, a pipe through a medium capable of transporting heat such as liquid or gas, and the like can be adopted. Of these, the fins are suitable as a heat radiating part in that they do not require wiring or piping, can be formed integrally with the first heat conductor 221, and can simplify the device configuration.

  When a fin is employed for the first heat radiating portion 261, the shape of the fin is not particularly limited. As shown in the figure, the first heat radiating portion 261 may be constituted by a fin having a cut in a surface different from the surface where the mounting portion 10 of the first heat conductor 221 opens. The fins may have any shape as long as the efficiency of dissipating the heat of the first thermal conductor 221 to the ambient gas is higher than when the fin has a flat surface. Here, the term “fin” refers to a structure having a surface on the surface of the object having a high efficiency for dissipating the heat of the object to the environmental gas as compared with the case where the surface is flat. A fin can also be referred to as a region having a large specific surface area in an object having a specific volume.

  A typical example of the fin shape is a thin plate shape or an assembly thereof. Such fins are obtained in consideration of, for example, the calculation of the efficiency of heat dissipation as described below, the material of the device, the structure, and the like in accordance with the purpose of the temperature and the like of the first thermal conductor 221 to be controlled. Can be designed based on.

  In general, the heat dissipation efficiency φ of a rectangular parallelepiped fin is expressed by the following equation.

_{φ = Q / Q ∞ = tanh} {m (h + δ / 2)} / {m (h + δ / 2)}
(Δ: fin thickness, h: fin height, m: (2α / δλ) ^1/2 , α: heat transfer coefficient between fin and air, F: fin cross-sectional area, λ: thermal conductivity)
Q is the heat transfer amount of the fin, and Q _∞ is the heat transfer amount of the fin in an ideal state where the entire fin has a uniform temperature. In an actual fin, the thermal conductivity is finite, and the temperature decreases due to heat dissipation from the root to the tip.

  The above equation means that the heat dissipation increases as the fin height increases, while the efficiency reaches a peak, and if the fin volume is the same, the heat dissipation increases with the addition of many thin fins. Yes. In general, the higher the fin height, the more difficult the processing becomes. Therefore, it is preferable to increase the fin height as much as possible.

  In addition, when the heat conductor 22 is formed of an aluminum-based material, there may be a limit due to machining accuracy. For example, the interval between δ and the fin may be limited to about 1 mm.

  About the thickness of a fin and the space | interval between fins, the following trial calculations can be illustrated.

Assuming that the thermal conductivity of aluminum is 204 W / mK and the heat transfer coefficient between aluminum and air is 116 W / m ² K, fins 7 mm high, 10 mm wide, 1 mm thick, 7 mm high, 10 mm wide, and thick With a 2 mm fin, the heat dissipation efficiency of a 1 mm thick fin is 98%, whereas the heat dissipation efficiency of a 2 mm thick fin is 99%. However, on the other hand, the amount of heat radiation can be increased by changing the distance between the fins. For example, the distance between the fins can obtain a heat radiation amount that is 50% higher for 2 mm than for 2 mm.

  For fins with a thickness of 1 mm, a width of 10 mm, and a height of 7 mm, and a fin with a thickness of 1 mm, a width of 10 mm, and a height of 14 mm, the efficiency of heat dissipation is 98% and 93%, respectively, and the heat dissipation area is doubled. A height of 14 mm is more advantageous. However, in the heat cycle apparatus 100 of the present embodiment, since a space for rotation around the rotation axis R is required, when a fin is employed as the first heat radiating portion 261, the height and shape of the fin are In view of this point, it can be designed appropriately.

  When the first heat radiating unit 261 is provided in the heat cycle apparatus 100, the efficiency of heat exchange between the first heat conductor 221 and the environment is improved. Thereby, when the temperature of the first thermal conductor 221 is raised from the low temperature side and stabilized at the target temperature, so-called overshoot (overheating) can be further suppressed, and the target can be achieved in a shorter time. The temperature can be stabilized. Therefore, when the apparatus is started up or when the temperature of the first thermal conductor 221 is increased from the low temperature side and stabilized at the target temperature, the time until the PCR thermal cycle can be performed is set. It can be shortened.

1.4.2. Second Heat Dissipation Part Although not shown, the heat cycle device 100 of the present embodiment may include a second heat dissipation part that dissipates the heat of the second heat conductor 222.

  The second heat radiating part dissipates heat of the second heat conductor 222. The second heat radiating portion is the same as the first heat radiating portion 261 described in the above-mentioned section “1.4.1. First heat radiating portion”. The detailed description is omitted by replacing “second heat radiating portion” and “first heat conductor 221” with “second heat conductor 222”. In the example of FIGS. 1 and 2, the second heat radiating portion is not formed.

  When the second heat radiating unit is provided in the heat cycle apparatus 100, the efficiency of heat exchange between the second heat conductor 222 and the environment is improved.

  Thereby, when the temperature of the second thermal conductor 222 is raised from the low temperature side and stabilized at the target temperature, so-called overshoot (overheating) can be further suppressed, and the target can be achieved in a shorter time. The temperature can be stabilized. Therefore, when the apparatus is started up or when the temperature of the second heat conductor 222 is increased from the low temperature side and stabilized at the target temperature, the time until a state where a PCR thermal cycle can be performed is obtained. It can be shortened.

  When the second heat radiating unit is provided in the heat cycle apparatus 200, the efficiency of heat exchange between the first heat conductor 221 and the second heat conductor 222 with the environment is improved. Therefore, the degree of freedom in setting the temperature when performing PCR can be increased. That is, the temperature of reverse transfer or the temperature of heat denaturation can be set for either the first heat conductor 221 or the second heat conductor 222.

  When the second heat conductor 222 is set to a higher temperature side (a side farther from the environment temperature) than the first heat conductor 221, heat exchange with the environment of the second heat conductor 222 is performed. Efficiency may be sufficient. In such a case, the second heat radiating portion may not be provided.

1.4.3. Fluorescence detector The thermal cycler 100 may include a fluorescence detector. Thereby, the thermal cycle apparatus 100 can be used for the use which performs PCR, for example, performing fluorescence detection like real-time PCR. When the heat cycle apparatus 100 includes a fluorescence detector, the number of fluorescence detectors is arbitrary. The position where the fluorescence detector is provided is arbitrary as long as the reaction solution 11 in the reaction vessel 15 can be optically measured. Furthermore, the structure which moves a fluorescence detector to the position which can measure the reaction liquid 11 in the reaction container 15 optically may be included. In the case where a fluorescence detector is provided in the thermal cycler 100 and the temperature of the first thermal conductor 221 is set to PCR annealing and extension temperature, the fluorescence detector is in the first region 131 of the flow path 13 of the reaction vessel 15. It is preferable to be provided so that light from can be detected. Thereby, fluorescence measurement suitable as real-time PCR can be performed.

2. Second Embodiment 2.1. Thermal Cycle Device The thermal cycle device 200 of the present embodiment includes a mounting unit 10, a temperature gradient forming unit 20, a drive mechanism 30, and a blower mechanism 60. More specifically, in the thermal cycle apparatus 200 of the present embodiment, the reaction liquid 11 and the reaction liquid 11 are filled with a liquid 12 having a specific gravity different from that of the reaction liquid 11 and immiscible with the reaction liquid 11, and the reaction liquid 11 faces each other. When the reaction vessel 15 is attached to the attachment portion 10 including the attachment portion 10 to which the reaction vessel 15 including the flow passage 13 moving along the inner wall is attached and the heat conductor 22 that conducts heat, In contrast, the temperature gradient forming unit 20 that forms a temperature gradient in the direction in which the reaction solution 11 moves, the mounting unit 10 and the temperature gradient forming unit 20 have components perpendicular to the direction in which gravity acts, and A drive mechanism 30 that rotates the flow path 13 around a rotation axis R having a component perpendicular to the direction in which the reaction solution 11 moves when the reaction vessel 15 is attached to the attachment unit 10, and at least the heat conductor 22. A blowing mechanism 60 for blowing air Including the.

  In the thermal cycle apparatus 200 of the present embodiment, in the thermal cycle apparatus 100 described in the first embodiment, the temperature gradient forming unit 20 uses two thermal conductors (the first thermal conductor 221 and the second thermal conductor 222). In contrast to the thermal cycle device 100 of the first embodiment, the temperature gradient forming unit 20 includes a single thermal conductor 22. Other configurations and modified embodiments are the same as those of the heat cycle apparatus 100 of the first embodiment, and the same reference numerals are given to the same members and the like, and detailed description thereof is omitted.

  3 and 4 are diagrams schematically showing a main part of the thermal cycle apparatus 200 according to the present embodiment.

2.1.1. Reaction container The reaction container 15 attached to the heat cycle apparatus 200 of the present embodiment is the same as the reaction container 15 described in the first embodiment, and detailed description thereof is omitted. The difference is that the two regions 132 are not defined.

  The channel 13 has a first region 131. The first region 131 is a region in which the temperature is controlled when the reaction vessel 15 is mounted on the mounting unit 10 of the heat cycle apparatus 200. In the present embodiment, a region that is in thermal contact with the thermal conductor 22 is referred to as a first region 131.

  The first region 131 is a region including one end portion in the longitudinal direction of the flow path 13. In the example shown in FIGS. 3 and 4, a region surrounded by a dotted line including an end portion on the side farther from the sealing body 14 in the flow path 13 is the first region 131.

  In the thermal cycle device 200 according to the present embodiment, the heat conductor 22 of the temperature gradient forming unit 20 heats the first region 131 of the flow path 13 of the reaction vessel 15 to the first temperature, whereby the flow of the reaction vessel 15 is increased. A temperature gradient is formed in the direction in which the reaction solution 11 moves with respect to the path 13.

2.1.2. Mounting Unit The thermal cycle apparatus 200 according to the present embodiment includes the mounting unit 10 to which the reaction vessel 15 is mounted. The mounting part 10 of the heat cycle apparatus 200 of the present embodiment is the same as the mounting part 10 of the heat cycle apparatus 100 described in the first embodiment, and detailed description thereof is omitted, but the first embodiment is 1 The two heat conductors 22 are different in that they constitute the mounting portion 10.

  The number of mounting portions 10 provided on the heat conductor 22 is not particularly limited. When the number of mounting parts 10 is plural, a plurality of reaction containers 15 can be respectively mounted.

2.1.3. Temperature Gradient Forming Unit The temperature gradient forming unit 20 includes a heat conductor 22 provided with the mounting unit 10. The temperature gradient forming unit 20 is configured to form a temperature gradient in the moving direction in which the reaction solution 11 moves with respect to the flow path 13 when the reaction vessel 15 is mounted on the mounting unit 10. In the example shown in FIGS. 3 and 4, the temperature gradient forming unit 20 is configured by the heat conductor 22, and when the reaction vessel 15 is mounted on the mounting unit 10, the flow path 13 is far from the first region 131. A temperature gradient is formed such that the temperature becomes lower.

2.1.3.1. Thermal Conductor The thermal conductor 22 is provided with at least a part of the mounting portion 10. Thereby, the heat conductor 22 controls the first region 131 of the flow path 13 of the reaction vessel 15 to a target temperature when the reaction vessel 15 is attached to the attachment unit 10. In the example shown in FIGS. 3 and 4, the heat conductor 22 is disposed at a position where the first region 131 of the flow path 13 of the reaction vessel 15 can be heated.

  The heat conductor 22 includes a heat source unit 24 that generates heat, and heat generated thereby can be transmitted to the reaction vessel 15.

  The shape of the heat conductor 22 is not particularly limited. In addition, the material of the thermal conductor 22, specific examples, the mode of contact with the reaction vessel 15, the mode of temperature control, etc. are all the same as the first thermal conductor 221 and the second thermal conductor 222 described in the first embodiment. It is the same.

2.1.3.2. Heat source unit The heat source unit 24 generates heat. The heat source unit 24 is provided in the heat conductor 22 and can supply heat to the heat conductor 22. Specific examples of the heat source unit 24 are the same as those of the first heat source unit 241 and the second heat source unit 242 of the first embodiment.

2.1.4. Drive Mechanism The drive mechanism 30 of the thermal cycle apparatus 200 of the present embodiment is the same as the drive mechanism 30 described in the first embodiment, and thus detailed description thereof is omitted.

  3 and 4, only the rotation axis R is displayed, and the drive mechanism 30 is omitted. When the mounting unit 10 and the temperature gradient forming unit 20 are rotated around the rotation axis R in a state where the reaction vessel 15 is mounted on the mounting unit 10, the reaction solution 11 in the reaction vessel 15 is transferred to the flow path 13 of the reaction vessel 15. Can move along. 3 and 4 show an example in which the rotation axis R is perpendicular to the direction in which gravity acts. That is, in FIG. 3, the reaction liquid 11 exists in the first region 131 of the flow path 13 due to the action of gravity, and is in a state rotated by 180 ° around the rotation axis R with respect to the arrangement of FIG. 3. In the arrangement of FIG. 4, the reaction solution 11 exists in a region other than the first region 131 of the flow path 13 due to the action of gravity.

2.1.5. Blower Mechanism The thermal cycle apparatus 200 according to the present embodiment includes a blower mechanism 60 that sends air to at least the heat conductor 22. A specific example of the blower mechanism 60 is the same as that described in the first embodiment. 3 and 4, the air blowing mechanism 60 is schematically drawn. The air blowing mechanism 60 may constitute a part of the temperature gradient forming unit 20. The air blowing mechanism 60 may blow air only to the heat conductor 22 or may blow air to members other than the heat conductor 22. Thereby, the temperature control of the first region 131 of the flow path 13 may be performed. Further, the temperature control of the region other than the first region 131 may be performed. The temperature of the wind blown by the blower mechanism 60 is the same as in the first embodiment.

  A specific example of the blower mechanism 60 is the same as that described in the first embodiment. 3 and 4, the air blowing mechanism 60 is schematically drawn. The air blowing mechanism 60 may constitute a part of the temperature gradient forming unit 20.

2.2. Example of Use of Thermal Cycler The thermal cycler 200 of the present embodiment can be suitably applied to reactions that require various PCRs and thermal cycles (temperature cycles).

  There is no restriction | limiting in particular as PCR which can apply the thermal cycle apparatus 200. FIG. Since the heat cycle apparatus 200 includes the heat conductor 22 and the air blowing mechanism 60, the efficiency of heat exchange between the heat conductor 22 and the environment is high. Therefore, the time for changing the temperature of the heat conductor 22 to a desired temperature and the time for stabilization at the desired temperature can be shortened.

  The thermal cycle apparatus 200 of the present embodiment forms a temperature gradient with the thermal conductor 22 and the environment (gas), so that thermal cycle of two temperatures (temperature cycle) is easy and is particularly suitable for shuttle PCR. is there. Moreover, since it has the ventilation mechanism 60, if it sets the temperature of the heat conductor 22 to the temperature (reverse transcription temperature) comparatively close to the temperature of an environment, it can apply suitably also to RT-PCR.

  An example in which one-step RT-PCR is performed using the thermal cycle apparatus 200 of the present embodiment will be described. In this example, shuttle PCR is performed.

  In the thermal cycle apparatus 200, since the temperature gradient forming unit 20 is configured by the heat conductor 22 and the environment, the air blowing mechanism 60 blows air to an area other than the first area 131 of the flow path 13 to set the temperature of the area. Can be controlled. First, the temperature of the region other than the first region 131 of the flow path 13 is adjusted to the temperature for reverse transfer by the blowing mechanism 60, and the temperature of the heat conductor 22 is set to the heat denaturation temperature. Subsequently, the drive mechanism 30 sets the reaction solution 11 in a region other than the first region 131 of the flow path 13 (for example, the state of FIG. 4). As a result, the reverse transcription reaction proceeds. Next, the drive mechanism 30 is operated so that the reaction solution 11 is present in the first region 131 of the flow path 13 (for example, the state shown in FIG. 3), thereby performing a heat denaturation reaction. While the heat denaturation reaction is in progress, the temperature or intensity of the air blown by the blower mechanism 60 is changed to adjust the temperature of the region other than the first region 131 of the flow path 13 to the annealing / extension temperature. To do. Then, the drive mechanism 30 is operated so that the reaction solution 11 exists in a region other than the first region 131 of the flow path 13 (for example, the state of FIG. 4) and the reaction solution 11 in the first region 131 of the flow path 13. By repeating the state in which there exists (for example, the state of FIG. 3), the annealing / elongation reaction and the thermal denaturation reaction are repeated. In this way, one-step RT-PCR can be performed.

  In the above example, RT-PCR is performed while the blower mechanism 60 is continuously operated. However, the blower mechanism 60 may be operated intermittently or may be operated so as to change the amount of blown air. Good.

  In addition to the above example, the thermal cycle apparatus 200 of the present embodiment can be suitably applied to hot start PCR and real-time PCR by adding an appropriate configuration.

2.3. According to the heat cycle apparatus 200 of this embodiment, since it has the heat conductor 22 of the temperature gradient formation part 20 and the ventilation mechanism 60 which ventilates at least the heat conductor 22, between the heat conductor 22 and the environment. The efficiency of heat exchange is improved. Therefore, according to the heat cycle apparatus 100, the heat conductor 22 can be shifted to the set temperature in a shorter time.

  In particular, when the temperature of the environment and the set temperature of the heat conductor 22 are close, the effect of the blower mechanism 60 becomes significant. Thereby, the overshoot in the case of the change of the temperature of the heat conductor 22 is further suppressed, and the temperature drop rate of the heat conductor 22 can be increased. Therefore, when PCR is performed using the thermal cycling apparatus 100, the temperature can be controlled more precisely, and the time required for PCR can be shortened.

2.4. Other configurations 2.4.1. Heat Dissipation Part The heat cycle device 200 of the present embodiment may be provided with a heat dissipation part on the heat conductor 22. The heat dissipating part is the same as the first heat dissipating part 261 described in the section “1.4.1. First heat dissipating part” of the first embodiment. By replacing “heat radiation part” and “first thermal conductor 221” with “thermal conductor 22”, a detailed description is omitted. In the example of FIGS. 3 and 4, the heat radiating part is not shown.

  When the heat cycle unit 200 is provided with a heat radiating unit, the efficiency of heat exchange between the heat conductor 22 and the environment is improved. As a result, when the temperature of the heat conductor 22 is increased from the low temperature side and stabilized at the target temperature, overshoot can be further suppressed and the target temperature can be stabilized in a shorter time. . Therefore, when the apparatus is started up or when the temperature of the heat conductor 22 is raised from the low temperature side and stabilized at the target temperature, the time until a state where a PCR thermal cycle can be performed is shortened. be able to.

2.4.2. Fluorescence detector The thermal cycle apparatus 200 may include a fluorescence detector (not shown). Thereby, the thermal cycle apparatus 200 can be used for the use which performs PCR, for example, performing fluorescence detection like real-time PCR. The fluorescence detector is the same as that described in “1.4.3. Fluorescence detector” in the first embodiment.

3. Third Embodiment 3.1. Thermal cycle apparatus In the thermal cycle apparatus 300 according to the third embodiment, members having the same functions as those of the thermal cycle apparatus 100 of the first embodiment and the thermal cycle apparatus 200 of the second embodiment are denoted by the same reference numerals. Detailed description thereof will be omitted.

  FIG. 5 is a perspective view schematically showing an outline of a heat cycle apparatus 300 according to the third embodiment. FIG. 6 is an exploded perspective view schematically showing a main part of the thermal cycler 300 according to the third embodiment. FIG. 7 is a plan view of the first thermal conductor 221 and the first heat radiating portion 261 of the thermal cycle apparatus 300 according to the third embodiment (viewed from the second thermal conductor 222 side). FIG. 8 is a side view of the first heat conductor 221 and the first heat radiation part 261 of the heat cycle apparatus 300 according to the third embodiment as viewed from the first heat radiation part 261 side. FIG. 9 is a cross-sectional view taken along the line AA in FIGS. 7 and 10. FIG. 10 is a side view of the first thermal conductor 221 and the first heat radiating portion 261 of the thermal cycle apparatus 300 according to the second embodiment as seen from a direction parallel to the rotation axis R.

  In the heat cycle apparatus 300 according to the third embodiment, the reaction liquid 11 and the reaction liquid 11 are filled with a liquid 12 having a specific gravity different from that of the reaction liquid 11 and immiscible with the reaction liquid 11, and the inner wall facing the reaction liquid 11. A mounting portion 10 for mounting the reaction vessel 15 including the flow path 13 that moves along with the heat conductor 22 that conducts heat, and when the reaction vessel 15 is mounted on the mounting portion 10, The temperature gradient forming unit 20 that forms a temperature gradient in the direction in which the reaction solution 11 moves, and the mounting unit 10 and the temperature gradient forming unit 20 have components perpendicular to the direction in which gravity acts and are mounted. When the reaction vessel 15 is mounted on the part 10, the drive mechanism 30 rotates the flow path 13 around the rotation axis R having a component perpendicular to the direction in which the reaction solution 11 moves, and at least the heat conductor 22 is blown. And a blower mechanism 60 that includes The temperature gradient forming unit 20 includes a first thermal conductor 221 that heats the first region 131 of the flow path 13 to a first temperature when the reaction vessel 15 is attached to the attachment unit 10, and the reaction vessel 15 in the attachment unit 10. And a second heat conductor 222 that heats the second region 132 of the flow path 13 to a second temperature higher than the first temperature when mounted, and the blower mechanism 60 blows air to at least the first heat conductor 221. Has a configuration.

  The mounting part 10 in the heat cycle apparatus 300 of the third embodiment is the same as the heat cycle apparatus 100 of the first embodiment except that a plurality of mounting portions 10 are provided. The reaction vessel 15 is the same as described in the first embodiment. The temperature gradient forming unit 20 in the thermal cycle apparatus 300 of the third embodiment is the same as the thermal cycle apparatus 100 except that a plurality of mounting units 10 are provided on the first thermal conductor 221 and the second thermal conductor 222. . In the thermal cycle apparatus 300, the temperature gradient forming unit 20 includes the first thermal conductor 221 and the second thermal conductor 222, as in the first embodiment.

  As shown in FIGS. 5 and 6, the first thermal conductor 221 in the thermal cycle apparatus 300 of the third embodiment is provided with a part of the mounting portion 10. Thereby, the first heat conductor 221 can control the first region 131 of the flow path 13 of the reaction container 15 to a target temperature when the reaction container 15 is attached to the attachment unit 10. In addition, as shown in FIG. 6, the first heat conductor 221 and the second heat conductor 222 have a first heat source part 241 and a second heat source part 242 that generate heat, respectively, and react the generated heat. Can be conveyed to the container 15. The first heat conductor 221 and the second heat conductor 222 are in thermal contact with the reaction vessel 15 when the reaction vessel 15 is attached to the attachment portion 10. The temperature of the first heat conductor 221 and the second heat conductor 222 may be controlled by a temperature sensor and a control unit (not shown).

  As shown in FIGS. 5 and 6, in the thermal cycle apparatus 300 of the present embodiment, holes for inserting the cartridge heaters 25 are formed in the first thermal conductor 221 and the second thermal conductor 222, respectively. By inserting the heater 25, the first heat source unit 241 and the second heat source unit 242 are configured. From the cartridge heater 25, a lead wire 23 including a reel 27 having a mode in which twisting hardly occurs when the main body 40 is rotated by the drive mechanism 30 is drawn out.

  In the heat cycle apparatus 300 of the present embodiment, two first heat radiating portions 261 are provided on the first heat conductor 221. In this embodiment, the 1st thermal radiation part 261 is an air cooling fin (fin). As shown in FIGS. 7 to 10, the fin has a shape in which a cut is made in the first thermal conductor 221.

  The drive mechanism 30 of the heat cycle apparatus 300 of the third embodiment is the same as that described in the first and second embodiments, but the first heat conductor is formed by the housing 42, the fixing member 44, and the flange 46. This is a mechanism for rotating the main body 40 in which the 221 and the second heat conductor 222 are positioned around the rotation axis R. In the heat cycle apparatus 300, the drive mechanism 30 includes a motor 32.

  The housing 42 is provided for installing the heat cycle apparatus 300 on a floor surface or the like, and the shape, material, and the like are arbitrary. The fixing member 44 and the flange 46 are provided for positioning and installing at least the first heat conductor 221 and the second heat conductor 222 and for positioning the rotation axis R. The shape, material, and the like of the fixing member 44 and the flange 46 are arbitrary. In the example of the first heat conductor 221 in FIGS. 7 to 10, a retaining hole 48 for connecting to the fixing member 44, the flange 46, and the like is drawn.

  Even when the members such as the casing 42, the fixing member 44, and the flange 46 cover the reaction vessel 15, as long as these members are transparent, the transparent reaction vessel 15 is used for thermal cycle processing. The state in which the reaction solution 11 moves from the outside of the apparatus can be observed. Therefore, it can be visually confirmed whether the heat cycle process is performed appropriately. Here, the degree of “transparency” may be such that the movement of the reaction liquid 11 can be visually recognized when these members are employed in the heat cycle apparatus 200 and the heat cycle process is performed.

  The heat cycle apparatus 300 according to the third embodiment includes a blower mechanism 60 that sends air to at least the first heat conductor 221. The example of the ventilation mechanism 60 is the same as that described in the first embodiment and the second embodiment. In the example of FIG. 5, a DC fan motor 62 is illustrated as the blower mechanism 60.

  The thermal cycle apparatus 300 according to the third embodiment includes a fluorescence detector 50. The fluorescence detector 50 is provided at a position where the reaction container 15 can be desired from the first heat conductor 221 side when the reaction container 15 is mounted on the mounting unit 10. The thermal cycle apparatus 300 has a rail 52 that allows the fluorescence detector 50 to move to a position suitable for each of the eight reaction vessels 15. The fluorescence detector 50 can be moved along the rail 52, and the position of the fluorescence detector 50 may be configured to be moved by a motor or the like. Furthermore, the position of the fluorescence detector 50 may be connected to a control unit (not shown) and controlled to be moved to a desired position in real-time PCR or the like.

  Moreover, in the heat cycle apparatus 300, for example, a heat insulating material (not shown) can be disposed in an appropriate part. Thereby, the temperature of the reaction vessel 15 may be further stabilized. The heat cycle apparatus 300 may include a structure that holds the reaction vessel 15 in a predetermined position with respect to the first heat conductor 221 and the second heat conductor 222. The structure that determines the position of the reaction vessel 15 may be any structure that can hold the reaction vessel 15 at a desired position. The structure for determining the position of the reaction vessel 15 may be a structure provided in the heat cycle apparatus 300, a structure provided in the reaction vessel 15, or a combination of both. For example, a screw, a plug-type rod, a structure in which a reaction container 15 is provided with a protrusion, a structure in which the mounting part 10 and the reaction container 15 are fitted, and a nail that determines the end point of insertion of the reaction container 15 are the first heat conduction. For example, it may be provided on at least one of the body 221 and the second heat conductor 222. When using a screw or a rod, the holding position can be adjusted in accordance with the reaction conditions of the thermal cycle, the size of the reaction vessel 15 and the like by changing the length of the screw, the length to be screwed in, and the position to insert the rod. You may do it.

3.2. Operational effect The heat cycle apparatus 300 of the third embodiment has the air blowing mechanism 60 similar to that described in the first embodiment, and has the same effect as described in the first embodiment. According to the heat cycle apparatus 300 of the third embodiment, the air blowing mechanism 60 that blows air to the first heat conductor 221 of the temperature gradient forming unit 20 is provided, and therefore, between the first heat conductor 221 and the environment. The efficiency of heat exchange is improved, and the same effects as described in the first embodiment can be achieved. Moreover, since the 1st heat radiating part 261 is provided in the 1st heat conductor 221 of the temperature gradient formation part 20, the heat exchange between the 1st heat conductor 221 and the environment is made efficient. Thereby, when changing the preset temperature of the 1st heat conductor 221 from a certain temperature to another temperature, what is called overshoot can further be suppressed. Further, the time required for changing the temperature of the first thermal conductor 221 from a temperature away from the environmental temperature to a temperature close to the environmental temperature can be further shortened. Therefore, according to the thermal cycle apparatus 300 of the third embodiment, the thermal cycle of one PCR can be further shortened, and the next reaction solution can be used even when performing multiple PCRs sequentially with the apparatus. In contrast, the time until the PCR can be started can be further shortened. In particular, when the environmental temperature is room temperature and the temperature of the first heat conductor 221 is set to the optimum temperature of the reverse transcriptase, the optimum temperature of the reverse transcriptase is close to room temperature, so the first heat conduction The time required for changing the temperature of the body 221 from the other temperature to the optimum temperature of reverse transcriptase can be shortened, and the above effect becomes particularly remarkable. Therefore, according to the thermal cycle apparatus 300 of the third embodiment, it is possible to shorten the inspection time by PCR.

4). Experimental Example According to the first thermal conductor 221 of the third embodiment, a heat dissipating part (fin) having a thickness of 1 mm, a height and a width of 10 mm to 15 mm, respectively, as shown in FIGS. A heat conductor (hereinafter referred to as heat conductor A) was manufactured by shaving. Moreover, the same shape heat conductor (henceforth heat conductor B) which did not cut out the thermal radiation part was manufactured. A cartridge heater was used as a heat source for each heat conductor, and connected to a controller capable of PID control together with a thermocouple. PID is an abbreviation for Proportinal, Integral, and Differential, and PID control is one of control methods combining proportionality, integration, and differentiation.

Then, using a cooling fan having a maximum air volume of 0.42 m ³ / min and a maximum static pressure of 31.9 Pa, a fan estimated to have an air volume of about 0.25 to 0.35 m ³ / min from duct loss or the like (Sanyo Electric) The model 109P0624H602) was adopted as a blower mechanism and installed so that the wind hits the heat conductor, and the temperature control experiment of the heat conductor was conducted. The environmental temperature was 23 ° C.

With respect to the temperature increase from 42 ° C. to 63 ° C. and the temperature decrease from 63 ° C. to 42 ° C., the time change of the temperature of the heat conductor was measured under the following conditions.
(Experiment 1) The fan is not operated with respect to the heat conductor B (Experiment 2) The fan is operated with respect to the heat conductor B (Experiment 3) The fan is not operated with respect to the heat conductor A (Experiment 3) 4) The fan is operated with respect to the heat conductor A The above experimental results are collectively shown in the graphs of FIGS. 11 and 12.

  Referring to the graph of FIG. 11, when the fan is operated for both the heat conductor B without fins and the heat conductor A with fins (Experiment 2 and Experiment 4), the temperature rises to 63 ° C. It can be seen that the time to reach is significantly reduced compared to the case where the fan is not operated (Experiment 1 and Experiment 3). Furthermore, when it has a fin (experiment 4), it turned out that the time required for temperature rising is shortest. Specifically, the time from the start of temperature rise until it stabilizes at 63 ± 1 ° C. was approximately 2 minutes and 30 seconds in Experiment 1 and approximately 2 minutes and 33 seconds in Experiment 3, whereas it was approximately 55 seconds in Experiment 2. In Experiment 4, it was about 18 seconds. It was also confirmed that the temperature was stable after reaching 63 ° C.

  Further, in the graph of FIG. 12, when the fan is operated for both the heat conductor B having no fins and the heat conductor A having fins (Experiment 2 and Experiment 4), the temperature is 42 when the temperature is lowered. It can be seen that the time until the temperature reaches 0 ° C. is significantly shortened compared to the case where the fan is not operated (Experiment 1 and Experiment 3). Specifically, the time from the start of temperature decrease until it stabilizes at 42 ± 1 ° C. was 50 minutes or more in Experiment 1 and Experiment 3 (which did not reach 42 ° C.), whereas it was about 3 in Experiment 2. Minute, in Experiment 4, it was about 4 minutes 24 seconds.

  From the above experimental results, it was confirmed that according to the heat cycle apparatus of the present invention, the time required for the heat conductor to reach a desired temperature was very short. Therefore, the heat cycle device having the blower mechanism can achieve a short heat cycle. Moreover, since the thermal cycle apparatus of this invention can control the temperature of a heat conductor more accurately, it turned out that PCR with higher precision can be performed.

  In addition, each embodiment and experimental example which were mentioned above are examples, Comprising: This invention is not necessarily limited to these. For example, a plurality of embodiments can be combined as appropriate.

  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 ... Mounting part, 11 ... Reaction liquid, 12 ... Liquid, 13 ... Flow path, 131 ... 1st area | region, 132 ... 2nd area | region, 14 ... Sealing body, 15 ... Reaction container, 20 ... Temperature gradient formation part, 22 DESCRIPTION OF REFERENCE SYMBOLS: Heat conductor, 23 ... Lead wire, 24 ... Heat source part, 25 ... Cartridge heater, 26 ... Heat radiation part, 27 ... Reel, 221 ... First heat conductor, 222 ... Second heat conductor, 241 ... First heat source , 242 ... second heat source part, 261 ... first heat radiating part, 30 ... drive mechanism, 32 ... motor, 40 ... main body, 42 ... housing, 44 ... fixing member, 46 ... flange, 48 ... retaining hole, 50 ... Fluorescence detector, 52 ... rail, 60 ... air blowing mechanism, 62 ... DC fan motor, R ... rotating shaft

Claims (4)

The reaction liquid is mounted with a reaction container having a specific gravity different from that of the reaction liquid and filled with a liquid immiscible with the reaction liquid, and including a flow path in which the reaction liquid moves along the opposing inner wall. And
A temperature gradient forming unit that includes a heat conductor that conducts heat, and forms a temperature gradient in a direction in which the reaction solution moves with respect to the flow path when the reaction vessel is mounted on the mounting unit;
When the mounting portion and the temperature gradient forming portion have a component perpendicular to the direction in which gravity acts, and the reaction vessel is mounted on the mounting portion, the reaction solution moves through the flow path. A drive mechanism that rotates about a rotation axis having a component perpendicular to the direction;
A blower mechanism for blowing air to at least the heat conductor;
Including a heat cycle device. In claim 1,
The thermal conductor is a thermal cycle device further having a heat radiating part for radiating heat. In claim 1 or claim 2,
The temperature gradient forming unit includes:
A first thermal conductor that heats the first region of the flow path to a first temperature when the reaction vessel is mounted on the mounting portion;
A second heat conductor that heats the second region of the flow path to a second temperature higher than the first temperature when the reaction vessel is mounted on the mounting portion;
Including
The air blowing mechanism is a heat cycle device that blows air to at least the first heat conductor. In claim 3,
The first thermal conductor is a thermal cycle device having a first heat radiating portion made of fins.

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