JP5896110B2 - Thermal cycle device and control method for thermal cycle device - Google Patents

Description

  The present invention relates to a heat cycle device and a control method for the heat cycle device.

  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.

  The PCR method is a technique for amplifying a target nucleic acid by subjecting a solution (reaction solution) containing a nucleic acid (target nucleic acid) to be amplified and a reagent to thermal cycling. The thermal cycle is a process in which two or more stages of temperature are periodically applied to the reaction solution. In the PCR method, a method of performing a two-stage or three-stage thermal cycle is common.

  In the PCR method, a container for performing a biochemical reaction, generally called a tube or a biological sample reaction chip (biochip), is used. However, the conventional methods have a problem that a large amount of reagents and the like are required, and the apparatus is complicated to realize a heat cycle necessary for the reaction, and 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 apparatus is disclosed in which a reaction solution is moved by rotating around an axis to perform a thermal cycle.

JP 2009-136250 A

  In order to apply a desired thermal cycle to the reaction solution in the biological sample reaction apparatus described in Patent Document 1, it is necessary for the reaction solution to move through the mineral oil. However, since the viscosity of the mineral oil becomes a resistance against the movement of the reaction liquid, the movement time of the reaction liquid varies depending on the mineral oil components, temperature, amount of the reaction liquid, and the like. Therefore, it has been difficult to bring the reaction solution to a desired temperature state for a desired time.

  The present invention has been made in view of the above problems, and according to some aspects of the present invention, a thermal cycle apparatus capable of bringing a reaction liquid into a desired temperature state over a desired time, and A method for controlling a thermal cycle apparatus can be provided.

(1) In the thermal cycle apparatus according to this embodiment, the reaction liquid and the reaction liquid have different specific gravities and are filled with a liquid that is immiscible with the reaction liquid, and the reaction liquid and the reaction liquid are immiscible. Any one of the liquids that do not include a fluorescent substance that emits light of a predetermined wavelength, and a mounting part that mounts a reaction vessel including a flow path that moves along the inner wall facing the reaction liquid; and When the reaction vessel is attached, a temperature gradient forming unit that forms a temperature gradient in the direction in which the reaction solution moves with respect to the flow path, and when the reaction vessel is attached to the attachment unit, the attachment unit Driving the temperature gradient forming section to switch between the first arrangement and a second arrangement in which the position of the lowest point of the flow path in the direction of gravity acts is different from the first arrangement. Mechanism and the predetermined wavelength from within the reaction vessel. And a control unit that controls the drive mechanism, and the control unit uses the drive mechanism to change the arrangement of the mounting unit and the temperature gradient forming unit from the first arrangement and the control unit. Based on a switching timing that is a timing for switching between the second arrangement and a detection timing that is a timing at which the intensity of the light detected by the detection unit changes across a reference value, the drive mechanism To determine a holding time that is a time for holding the placement of the mounting portion and the temperature gradient forming portion in at least one of the first placement and the second placement.

  According to this embodiment, the drive mechanism includes the mounting portion and the temperature gradient forming portion in the first arrangement, and the second arrangement is different from the first arrangement in the position of the lowest point of the flow path in the direction in which gravity acts. Switch between placement. As a result, the position of the lowest point in the direction in which gravity acts in the flow path of the reaction vessel mounted on the mounting portion changes. Therefore, since the reaction solution moves in accordance with gravity in the flow path in which the temperature gradient is formed by the temperature gradient forming unit, the reaction solution can be subjected to a heat cycle. Further, according to this embodiment, the switching timing that is the timing for switching the placement of the mounting portion and the temperature gradient forming portion between the first placement and the second placement by the drive mechanism, and the light detected by the detection portion The time until the reaction solution moves to an appropriate position can be estimated from the detection timing, which is the timing at which the intensity of the change changes across the reference value. According to this embodiment, since the holding time is determined based on the switching timing and the detection timing, it is possible to realize a thermal cycle apparatus that can bring the reaction liquid into a desired temperature state for a desired time.

(2) In the above heat cycle apparatus, the control unit determines the holding time based on a measuring unit that measures a time from the switching timing to the detection timing, and the time measured by the measuring unit. Determining means to perform.

  According to this embodiment, since the holding time is determined based on the time from the switching timing to the detection timing, the reaction liquid is not affected by the time until the reaction liquid moves to an appropriate position, and the reaction liquid is desired for a desired time. A heat cycle device that can be in a temperature state can be realized.

(3) In the thermal cycle apparatus according to this embodiment, the reaction liquid and the reaction liquid have different specific gravities and are not miscible with the reaction liquid, and the reaction liquid and the reaction liquid are miscible. Any one of the liquids that do not include a fluorescent substance that emits light of a predetermined wavelength, and a mounting part that mounts a reaction vessel including a flow path that moves along the inner wall facing the reaction liquid; and When the reaction vessel is attached, a temperature gradient forming unit that forms a temperature gradient in the direction in which the reaction solution moves with respect to the flow path, and when the reaction vessel is attached to the attachment unit, the attachment unit Driving the temperature gradient forming section to switch between the first arrangement and a second arrangement in which the position of the lowest point of the flow path in the direction of gravity acts is different from the first arrangement. Mechanism and the predetermined wavelength from within the reaction vessel. A detection unit that detects the intensity of the light and a control unit that controls the drive mechanism, wherein the control unit is a timing at which the intensity of the light detected by the detection unit changes across a reference value Until the predetermined time elapses from the timing, the drive mechanism holds the placement portion and the temperature gradient forming portion in at least one of the first placement and the second placement.

  According to this embodiment, the drive mechanism includes the mounting portion and the temperature gradient forming portion in the first arrangement, and the second arrangement is different from the first arrangement in the position of the lowest point of the flow path in the direction in which gravity acts. Switch between placement. As a result, the position of the lowest point in the direction in which gravity acts in the flow path of the reaction vessel mounted on the mounting portion changes. Therefore, since the reaction solution moves in accordance with gravity in the flow path in which the temperature gradient is formed by the temperature gradient forming unit, the reaction solution can be subjected to a heat cycle. Further, according to this embodiment, it is possible to estimate the timing at which the reaction liquid moves to an appropriate position from the detection timing that is the timing at which the intensity of light detected by the detection unit changes across the reference value. According to this embodiment, the arrangement of the mounting part and the temperature gradient forming part is held for a predetermined time with reference to the detection timing, so that a thermal cycle device capable of bringing the reaction liquid into a desired temperature state for a desired time is realized. it can.

(4) In the thermal cycle apparatus described above, when the detection unit is in the first arrangement, the light intensity from the region including the lowest point in the direction in which gravity acts in the flow path is determined. It may be detected.

  Thereby, when it becomes the 1st arrangement | positioning, it can be determined easily whether the reaction liquid moved to the vicinity of the lowest point in the direction which gravity acts in a flow path. Therefore, the detection timing can be determined more accurately.

(5) In the thermal cycle apparatus described above, the reaction solution filled in the reaction container includes the fluorescent material, and the control unit has the light intensity detected by the detection unit exceeding the reference value. The detected timing may be used as the detection timing.

  Since the fluorescent substance that emits light of a predetermined wavelength detected by the detection unit is contained in the reaction solution filled in the reaction container, the lowest position in the direction in which gravity acts in the flow path in the first arrangement. When the reaction solution moves near the point, the intensity of light detected by the detection unit increases. Therefore, the control unit can determine the detection timing more accurately by setting the timing when the intensity of light detected by the detection unit exceeds the reference value as the detection timing.

(6) In the above heat cycle apparatus, the liquid immiscible with the reaction liquid filled in the reaction vessel contains the fluorescent material, and the control unit has an intensity of the light detected by the detection unit. The detection timing may be a timing that falls below the reference value.

  Since the fluorescent substance that emits light of a predetermined wavelength detected by the detection unit is contained in a liquid that is not miscible with the reaction liquid filled in the reaction vessel, the action of gravity in the flow path in the first arrangement When the reaction solution moves in the vicinity of the lowest point in the direction in which the light is detected, the intensity of light detected by the detection unit decreases. Therefore, the control unit can determine the detection timing more accurately by setting the timing when the intensity of light detected by the detection unit falls below the reference value as the detection timing.

(7) In the control method of the thermal cycler according to this embodiment, the reaction solution is filled with a liquid having a specific gravity different from that of the reaction solution and immiscible with the reaction solution, and the inner wall facing the reaction solution A mounting portion for mounting a reaction container including a flow path that moves along the flow path, and when the reaction container is mounted on the mounting portion, a temperature gradient is formed in the direction in which the reaction solution moves with respect to the flow path. When the reaction vessel is attached to the temperature gradient forming part and the attachment part, the placement of the attachment part and the temperature gradient formation part is different from the first arrangement and the flow path in the direction in which gravity acts. And a driving mechanism that switches between a lower arrangement and a second arrangement that is different from the first arrangement, the control method of the thermal cycle apparatus comprising: the reaction liquid filled in the reaction vessel; and One of the liquids that is not miscible with the reaction liquid A fluorescent material that emits light of a predetermined wavelength is included, and the arrangement of the mounting part and the temperature gradient forming part is switched between the first arrangement and the second arrangement by the drive mechanism based on the switching timing. And detecting the detection timing, which is a timing at which the intensity of light having a predetermined wavelength from the reaction container changes across a reference value, the switching timing, and the detection timing. Determining a holding time, which is a time for holding the arrangement of the mounting part and the temperature gradient forming part in at least one of the first arrangement and the second arrangement by a mechanism.

  The switching timing, which is the timing at which the placement of the mounting portion and the temperature gradient forming portion is switched between the first placement and the second placement by the drive mechanism, and the light intensity detected in the detection step straddles the reference value. The time until the reaction solution moves to an appropriate position can be estimated from the detection timing that is the changing timing. According to the present embodiment, since the holding time is determined based on the switching timing and the detection timing in the determining step, a control method for the thermal cycle apparatus that can bring the reaction liquid into a desired temperature state for a desired time is realized. it can.

(8) In the control method of the thermal cycler according to the present embodiment, the reaction liquid and the reaction liquid are filled with a liquid having different specific gravity and immiscible with the reaction liquid, and the inner walls facing the reaction liquid A mounting portion for mounting a reaction container including a flow path that moves along the flow path, and when the reaction container is mounted on the mounting portion, a temperature gradient is formed in the direction in which the reaction solution moves with respect to the flow path. When the reaction vessel is attached to the temperature gradient forming part and the attachment part, the placement of the attachment part and the temperature gradient formation part is different from the first arrangement and the flow path in the direction in which gravity acts. And a driving mechanism that switches between a lower arrangement and a second arrangement that is different from the first arrangement, the control method of the thermal cycle apparatus comprising: the reaction liquid filled in the reaction vessel; and One of the liquids that is not miscible with the reaction liquid A detection timing that includes a fluorescent substance that emits light of a predetermined wavelength, and that is a timing at which the intensity of light of a predetermined wavelength from the reaction vessel changes across a reference value; and a predetermined time from the detection timing Until at least one of the first arrangement and the second arrangement is held by the drive mechanism until the time elapses.

  The timing at which the reaction solution moves to an appropriate position can be estimated from the detection timing at which the intensity of the light detected in the detection step changes across the reference value. According to the present embodiment, in the holding step, the arrangement of the mounting part and the temperature gradient forming part is held for a predetermined time with reference to the detection timing, so that the reaction liquid can be kept in a desired temperature state for a desired time. A control method of the cycle device can be realized.

FIG. 1A is a perspective view illustrating a state in which the lid 70 of the thermal cycle apparatus 1 according to the embodiment is closed, and FIG. 1B illustrates a state in which the lid 70 of the thermal cycle apparatus 1 according to the embodiment is opened. FIG. FIG. 2 is a cross-sectional view schematically showing the main body 10 on a plane that passes through the line AA in FIG. 1A and is perpendicular to the rotation axis R; Sectional drawing showing the structure of the reaction container 100 with which the thermal cycle apparatus 1 which concerns on embodiment is mounted | worn. 4A is a cross-sectional view schematically showing a cross section in a plane perpendicular to the rotation axis R through the line AA in FIG. 1A in the first arrangement, and FIG. Sectional drawing which shows typically the cross section in the surface perpendicular to the rotating shaft R through the AA line | wire of FIG. The functional block diagram of the heat cycle apparatus 1 which concerns on a 1st specific example. The flowchart for demonstrating the control method of the heat cycle apparatus 1 which concerns on a 1st specific example. The graph which shows the intensity | strength of the light in the 1st specific example of the control method of the heat cycle apparatus. The other graph which shows the intensity | strength of the light in the 1st specific example of the control method of the heat cycle apparatus 1. FIG. The functional block diagram of the heat cycle apparatus 1 which concerns on a 2nd specific example. The flowchart for demonstrating the control method of the heat cycle apparatus 1 which concerns on a 2nd specific example. The graph which shows the intensity | strength of the light in the 2nd specific example of the control method of the heat cycle apparatus. The other graph which shows the intensity | strength of the light in the 2nd specific example of the control method of the heat cycle apparatus.

  DESCRIPTION OF EMBODIMENTS Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings. The embodiments described below do not unduly limit the contents of the present invention described in the claims. Also, not all of the configurations described below are essential constituent requirements of the present invention.

1. 1A is a perspective view showing a state in which the lid 70 of the thermal cycle apparatus 1 according to the present embodiment is closed, and FIG. 1B is a thermal cycle apparatus 1 according to the present embodiment. It is a perspective view showing the state which opened the lid 70 of. FIG. 2 is a cross-sectional view schematically showing the main body 10 on a plane that passes through the line AA in FIG. 1A and is perpendicular to the rotation axis R. In FIG. 2, an arrow g represents the direction in which gravity acts.

  In the heat cycle apparatus 1 according to this embodiment, the reaction liquid 140 and the reaction liquid 140 are filled with a liquid 130 having a specific gravity different from that of the reaction liquid 140 and immiscible with the reaction liquid 140. A mounting portion 11 for mounting a reaction vessel 100 including a flow channel 110 that moves in detail (details will be described later in the section of “3. Configuration of Reaction Container Mounted on Thermal Cycler According to Present Embodiment”); When the reaction vessel 100 is attached to the section 11, the direction in which the reaction solution 140 moves with respect to the flow path 110 (for details, refer to “2. Configuration of reaction vessel attached to thermal cycler according to this embodiment”). In the case where the reaction vessel 100 is mounted on the mounting unit 11 and the temperature gradient forming unit 30 that forms a temperature gradient (described later in the section), the arrangement of the mounting unit 11 and the temperature gradient forming unit 30 is the first arrangement. In the direction of gravity Drive mechanism 20 for switching the position of the lowest point of the flow path 110 between a second arrangement different from the first arrangement, and a detection unit for detecting the intensity of light of a predetermined wavelength from the reaction vessel 100 40 and a control unit 50 that controls the drive mechanism 20. In addition, either one of the reaction liquid 140 and the liquid 130 filled in the reaction container 100 includes a fluorescent material that emits light of the predetermined wavelength detected by the detection unit 40.

  In the example shown in FIG. 1A, the thermal cycle device 1 includes a main body 10 and a drive mechanism 20. As shown in FIGS. 1A, 1 </ b> B, and 2, the main body 10 includes a mounting portion 11 and a temperature gradient forming portion 30.

  The temperature gradient forming unit 30 forms a temperature gradient in the direction in which the reaction solution 140 moves with respect to the flow path 110 when the reaction vessel 100 is mounted on the mounting unit 11. 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 direction in which the reaction liquid 140 moves” means to form a state in which the temperature changes along the direction in which the reaction liquid 140 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. 1A, 1 </ b> B, and 2, the temperature gradient forming unit 30 includes the first heating unit 12 and the second heating unit 13. In the main body 10 of the heat cycle apparatus 1, the first heating unit 12 is disposed on the side far from the lid 70, and the second heating unit 13 is disposed on the side relatively near from the lid 70. A spacer 14 is provided between the first heating unit 12 and the second heating unit 13. In addition, as long as a temperature gradient is formed to such an extent that a desired reaction accuracy can be ensured, the number of heating units included in the temperature gradient forming unit 30 is arbitrary. For example, since the number of members to be used can be reduced by configuring the temperature gradient forming unit 30 with one heating unit, the manufacturing cost can be reduced.

  The first heating unit 12 heats the first region 111 of the reaction container 100 to the first temperature when the reaction container 100 is mounted on the mounting unit 11. In the example shown in FIG. 2, the first heating unit 12 is disposed in the main body 10 at a position for heating the first region 111 of the reaction vessel 100.

  The second heating unit 13 heats the second region 112 of the reaction container 100 to a second temperature different from the first temperature when the reaction container 100 is mounted on the mounting unit 11. In the example shown in FIG. 2, the second heating unit 13 is disposed in the main body 10 at a position for heating the second region 112 of the reaction vessel 100. The configuration of the second heating unit 13 is the same as that of the first heating unit 12 except that the region of the reaction vessel 100 to be heated and the heating temperature are different from those of the first heating unit 12.

  In the present embodiment, the second temperature is higher than the first temperature. For example, when the thermal cycler 1 is used for real-time PCR, the first temperature is about 63 ° C. (temperature for annealing and extension reaction), and the second temperature is about 95 ° C. (temperature for denaturing reaction). can do.

  The temperature gradient forming unit 30 includes a heat source unit 31 that generates heat and a heat conduction unit 32 that conducts heat generated in the heat source unit 31 to the mounting unit 11. In the example shown in FIG. 2, the first heating unit 12 of the temperature gradient forming unit 30 includes a first heater 12 a as the heat source unit 31 and a first heat block 12 b as the heat conduction unit 32. Yes. The second heating unit 13 of the temperature gradient forming unit 30 includes a second heater 13 a as the heat source unit 31 and a second heat block 13 b as the heat conduction unit 32.

  In the heat cycle apparatus 1, the first heater 12a and the second heater 13a are cartridge heaters, and are connected to an external power source (not shown) by conducting wires. The first heater 12a and the second heater 13a are not limited to this, and a carbon heater, a seat heater, an IH heater (electromagnetic induction heater), a Peltier element, a heating liquid, a heating gas, and the like can be used. In this embodiment, the 1st heater 12a is inserted in the 1st heat block 12b, and the 1st heat block 12b is heated when the 1st heater 12a generates heat. Similarly, the second heater 13a is inserted into the second heat block 13b, and the second heat block 13b is heated when the second heater 13a generates heat.

  The first heat block 12 b is a member that transfers heat generated from the first heater 12 a to the mounting unit 11 and the reaction vessel 100 mounted on the mounting unit 11. The second heat block 13 b is a member that transfers heat generated from the second heater 13 a to the mounting portion 11 and the reaction vessel 100 mounted on the mounting portion 11. In the heat cycle apparatus 1, the first heat block 12b and the second heat block 13b are aluminum blocks. Since the temperature control of the cartridge heater is easy, the temperature of the first heating unit 12 and the second heating unit 13 can be easily stabilized by using the first heater 12a and the second heater 13a as cartridge heaters. Therefore, a more accurate thermal cycle can be realized.

  The material of the heat block 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, the reaction vessel 100 can be efficiently heated by making the first heat block 12b and the second heat block 13b aluminum. Moreover, since heating unevenness hardly occurs in the heat block, a highly accurate thermal cycle can be realized. Further, since the processing is easy, the first heat block 12b and the second heat block 13b can be accurately molded, and the heating accuracy can be improved. Therefore, a more accurate thermal cycle can be realized. In addition, as a material of the heat block, for example, a copper alloy may be used, or a plurality of materials may be combined.

  The first heating unit 12 and the second heating unit 13 are preferably in contact with the reaction container 100 when the reaction container 100 is mounted on the mounting unit 11. Thereby, when the reaction vessel 100 is heated by the first heating unit 12 and the second heating unit 13, the heat of the first heating unit 12 and the second heating unit 13 can be stably transmitted to the reaction vessel 100. The temperature of the reaction vessel 100 can be stabilized. When the mounting part 11 is formed as a part of the first heating part 12 and the second heating part 13 as in this embodiment, it is preferable that the mounting part 11 contacts the reaction vessel 100. Thereby, since the heat of the 1st heating part 12 and the 2nd heating part 13 can be stably conveyed to reaction container 100, reaction container 100 can be heated efficiently.

  In addition, you may employ | adopt a heating mechanism from which the 1st heating part 12 and the 2nd heating part 13 differ. Further, the first heat block 12b and the second heat block 13b may be made of different materials.

  Note that a cooling unit for cooling the second region 112 may be provided instead of the second heating unit 13. As the cooling unit, for example, a Peltier element can be used. Thereby, for example, even when the temperature of the second region 112 is difficult to decrease due to heat from the first region 111 of the reaction vessel 100, a desired temperature gradient can be formed in the flow path 110. Further, for example, the reaction liquid 140 can be subjected to a heat cycle in which heating and cooling are repeated.

  The temperature of the 1st heating part 12 and the 2nd heating part 13 may be controlled by the temperature sensor which is not illustrated, and the control part 50 mentioned later. It is preferable that the temperature of the 1st heating part 12 and the 2nd heating part 13 is set so that the reaction container 100 may be heated to desired temperature. In this embodiment, the first region 111 of the reaction vessel 100 is set to the first temperature by controlling the first heating unit 12 to the first temperature and the second heating unit 13 to the second temperature. The two regions 112 can be heated to a second temperature. In addition, the temperature of the 1st heating part 12 and the 2nd heating part 13 should just be controlled so that the 1st area | region 111 and the 2nd area | region 112 of the reaction container 100 may be heated to desired temperature. For example, by considering the material and size of the reaction vessel 100, the temperature of the first region 111 and the second region 112 can be heated to a desired temperature more accurately. Moreover, the temperature sensor in this embodiment is a thermocouple. The temperature sensor is not limited to this, and for example, a resistance temperature detector or a thermistor may be used.

  The mounting part 11 has a structure for mounting the reaction vessel 100. In the example shown in FIGS. 1B and 2, the mounting portion 11 of the heat cycle apparatus 1 has a slot structure in which the reaction vessel 100 is inserted and mounted. In the example shown in FIG. 2, the mounting unit 11 is a reaction container in a hole that passes through the first heat block 12 b of the first heating unit 12, the spacer 14, and the second heat block 13 b of the second heating unit 13, which will be described later. 100 is inserted. There may be a plurality of mounting portions 11 provided in the main body 10, and in the example shown in FIG. 1B, 20 mounting portions 11 are provided in the main body 10.

  In the present embodiment, the mounting unit 11 has a slot structure, but the mounting unit 11 may have a structure that can hold the reaction vessel 100. For example, a structure in which the reaction container 100 is fitted in a recess that matches the shape of the reaction container 100, or a structure in which the reaction container 100 is held therebetween may be employed.

  In the heat cycle apparatus 1 according to the present embodiment, the reaction vessel 100 and the mounting portion 11 are configured to be fitted together. The structure in which the reaction vessel 100 and the mounting portion 11 are fitted with each other is, for example, as shown in FIG. 1B and FIG. 2, in which the protruding portion 113 provided in the reaction vessel 100 is fitted into the recess provided in the mounting portion 11. Can be adopted. Thereby, the direction of the reaction vessel 100 with respect to the temperature gradient forming unit 30 can be kept constant. Therefore, since the change of the direction of the reaction vessel 100 during the thermal cycle can be suppressed, the temperature environment given to the reaction solution 140 can be controlled more precisely. Therefore, a more accurate thermal cycle can be applied to the reaction solution 140.

  Further, a mechanism for bringing the mounting portion 11 into close contact with the reaction vessel 100 may be provided. The mechanism for bringing the mounting portion 11 into close contact with the reaction vessel 100 only needs to allow at least a part of the reaction vessel 100 to be in close contact with the mounting portion 11. For example, the reaction container 100 may be pressed against one wall surface of the mounting portion 11 by a spring provided on the main body 10 or the lid 70. Thereby, since the heat of the temperature gradient formation part 30 can be more stably transmitted to the reaction container 100, the temperature of the reaction container 100 can be further stabilized.

  The mounting part 11 includes a first mounting part 11a and a second mounting part 11b for mounting the reaction vessel 100, respectively. When the mounting unit 11 is configured to be able to mount three or more reaction vessels 100, the first mounting unit 11a and the second mounting unit 11b include two reactions selected arbitrarily from the mounting unit 11. The part to which the container 100 is attached may be used.

  As shown in FIG. 2, the first mounting part 11 a and the second mounting part 11 b are provided in the heat conduction part 32 of the temperature gradient forming part 30. Further, the first mounting portion 11a and the second mounting portion 11b are provided at positions where the distance from the heat source portion 31 of the temperature gradient forming portion 30 is equal. Here, “the distances are equal” includes not only a completely parallel state but also a state in which the difference in distance is small enough to ensure a desired accuracy as a thermal cycler. In the example shown in FIG. 2, the distance between the first mounting portion 11a and the first heater 12a and the distance between the second mounting portion 11b and the first heater 12a are configured to be equal. Further, the distance between the first mounting portion 11a and the second heater 13a and the distance between the second mounting portion 11b and the second heater 13a are configured to be equal.

  According to the present embodiment, since the first mounting portion 11a and the second mounting portion 11b are provided at positions where the distance from the heat source unit 31 is equal, the heat from the heat source unit 31 passes through the heat conducting unit 32. Communicate evenly. Therefore, it is possible to realize a heat cycle device that can control the temperature with high accuracy. Moreover, when using the thermal cycle apparatus 1 for PCR, since the temperature variation of the reaction container 100 with which the 1st mounting part 11a and the 2nd mounting part 11b were mounted can be suppressed, the dispersion | variation in an amplification factor can be suppressed.

  As shown in FIG. 2, the direction in which the reaction solution 140 moves in the reaction vessel 100 attached to the first attachment portion 11a and the reaction solution 140 in the reaction vessel 100 attached to the second attachment portion 11b move. The direction to do may be parallel. Here, “parallel” includes not only a completely parallel state but also a state close to parallel to the extent that a desired accuracy can be secured as a heat cycle apparatus.

  According to this embodiment, the reaction liquid 140 in the reaction container 100 attached to the first attachment part 11a moves and the reaction liquid 140 in the reaction container 100 attached to the second attachment part 11b moves. Since the direction is parallel, when the placement of the mounting portion 11 is switched by the drive mechanism 20, the reaction solution 140 in the reaction vessel 100 mounted on the first mounting portion 11a and the second mounting portion 11b The reaction solution 140 in the reaction vessel 100 to be mounted moves at the same timing. In other words, the time at which the two reaction liquids 140 start moving can be synchronized. Therefore, the reaction vessel 100 attached to the first attachment part 11a and the reaction container 100 attached to the second attachment part 11b can be subjected to thermal cycles of the same time condition at the same timing. . The degree of “same” here is a range that does not affect the accuracy of the reaction.

  When the reaction vessel 100 is mounted on the mounting unit 11, the drive mechanism 20 changes the layout of the mounting unit 11 and the temperature gradient forming unit 30 to the lowest position of the flow path 110 in the direction in which gravity acts. Is switched between a second arrangement different from the first arrangement. The first arrangement and the second arrangement will be described in detail in the section “3. Control example of heat cycle apparatus”. In the heat cycle apparatus 1 according to the present embodiment, the drive mechanism 20 causes the mounting unit 11 and the temperature gradient forming unit 30 to have a component perpendicular to the direction in which gravity acts, and to react to the mounting unit 11. This is a mechanism for rotating the flow path 110 around the rotation axis R having a component perpendicular to the direction in which the reaction solution 140 moves when the container 100 is mounted.

  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 of “having a component perpendicular to the direction in which the reaction solution 140 moves through the flow path 110” refers to “the component parallel to the direction in which the reaction liquid 140 moves through the flow path 110” This is a direction having a component perpendicular to the direction in which the reaction solution 140 moves in the flow path 110 in the case of the vector sum of “component perpendicular to the direction in which the solution 140 moves”.

  In the heat cycle apparatus 1 according to the present embodiment, the drive mechanism 20 rotates the mounting unit 11 and the temperature gradient forming unit 30 on the same rotation axis R. In the present embodiment, the drive mechanism 20 includes a motor and a drive shaft (not shown), and is configured by connecting the drive shaft and the flange 16 of the main body 10. When the motor of the drive mechanism 20 is operated, the main body 10 is rotated with the drive shaft as the rotation axis R. The positional relationship between the rotating shaft R and the mounting portion 11 will be described in detail in the section “2. Positional relationship between the rotating shaft and the mounting portion”. The drive mechanism 20 is not limited to a motor, and for example, a handle, a mainspring, or the like can be employed.

  According to this embodiment, the rotation axis R has a component perpendicular to the direction in which gravity acts, and reacts with the flow path 110 of the reaction vessel 100 when the reaction vessel 100 is attached to the attachment portion 11. Since the shaft has a component perpendicular to the direction in which the liquid 140 moves, the drive mechanism 20 rotates the mounting unit 11, so that the gravity in the flow channel 110 of the reaction vessel 100 mounted on the mounting unit 11 is reduced. The position of the lowest point or the highest point in the acting direction changes. As a result, the reaction solution 140 moves in the flow path 110 where the temperature gradient is formed by the temperature gradient forming unit 30. Therefore, the reaction solution 140 can be heat cycled with a simple configuration.

  The heat cycle apparatus 1 includes a detection unit 40. The detection unit 40 detects the intensity of light having a predetermined wavelength from the reaction container 100. In the present embodiment, the detection unit 40 detects the intensity of light having the first wavelength. As the detection unit 40, various known photodetectors can be used. In the present embodiment, the detection unit 40 includes a fluorescence detector. The number of detectors included in the detector 40 is arbitrary as long as detection can be performed without any problem. In the example shown in FIG. 1A and FIG. 1B, the detection unit 40 includes a detector 41a and a detector 42a. In the example shown in FIGS. 1A and 1B, the detection unit 40 performs fluorescence detection by moving the detector 41a along the slide bar 41b. Similarly, the detection unit 40 detects the fluorescence by moving the detector 42a along the slide bar 42b.

  The detection unit 40 may detect the intensity of light from the region including the lowest point in the direction in which gravity acts in the flow path 110 when the first arrangement is achieved. Since the reaction solution 140 moves in the flow path 110 toward the vicinity of the lowest point in the direction in which gravity acts, when the mounting portion 11 and the temperature gradient forming portion 30 are in the first arrangement, the action of gravity. The reaction solution 140 moves to a region that includes the lowest point of the flow path 110 in the direction in which it flows. Therefore, the detection unit 40 detects the intensity of light having a predetermined wavelength in the vicinity of the lowest point of the flow path 110 in the direction in which gravity acts, so that the direction in which gravity acts in the flow path 110 in the first arrangement. It can be easily determined whether or not the reaction solution 140 has moved to the vicinity of the lowest point.

  In addition, when the first arrangement is used, a self-focus lens or the like focused on the vicinity of the lowest point in the direction of the action of gravity in the flow path 110 is used. Sensitivity to light from the vicinity of the lowest point in the direction in which gravity acts in the path 110 may be increased. In the control example described later in the section “3. Control example of heat cycle device”, when the detection unit 40 is in the first arrangement, the detection unit 40 is the highest in the direction in which gravity acts in the flow path 110. A case where the intensity of light from a region including the lower point is detected will be described as an example.

  When performing fluorescence detection, the main body 10 is preferably provided with a measurement window 18 that can detect fluorescence inside the mounting portion 11. Thereby, since the member which exists between the detection part 40 and the reaction liquid 140 can be decreased, more suitable fluorescence measurement can be performed.

  The detection unit 40 can be used for fluorescence detection in a reaction such as real-time PCR, in addition to detection for the purpose of determining detection timing. In the example shown in FIG. 2, the measurement window 18 is provided in the first heating unit 12 provided on the side far from the lid 70. Thereby, when using the heat cycle apparatus 1 for reactions, such as real-time PCR which measures fluorescence on the low temperature (temperature which performs annealing and extension reaction) side, the influence of the sealing part 120 (after-mentioned) and the lid | cover 70 of reaction container 100 Appropriate fluorescence measurement can be performed without exposure. When fluorescence measurement is performed from the lid 70 side, it is preferable that the sealing portion 120 and the lid 70 of the reaction vessel 100 have a design that does not affect the measurement.

  The heat cycle apparatus 1 may include a control unit 50. The control unit 50 controls the drive mechanism 20. The control unit 50 may control the temperature gradient forming unit 30. An example of control by the control unit 50 will be described in detail in the section “3. Control example of thermal cycle device”. The control unit 50 may be configured to be realized by a dedicated circuit and perform control described later. The control unit 50 functions as a computer by executing a control program stored in a storage device (not shown) such as a ROM (Read Only Memory) or a RAM (Random Access Memory), for example, by a CPU (Central Processing Unit). However, it may be configured to perform control described later. In this case, the storage device may have a work area for temporarily storing intermediate data and control results associated with the control.

  As shown in FIG. 1A, FIG. 1B, and FIG. 2, the main body 10 of the heat cycle apparatus 1 is provided with a spacer 14 between the first heating unit 12 and the second heating unit 13. Yes. The spacer 14 is a member that holds the first heating unit 12 or the second heating unit 13. By providing the spacer 14, the distance between the first heating unit 12 and the second heating unit 13 can be determined more accurately. That is, the positions of the first heating unit 12 and the second heating unit 13 with respect to the first region 111 and the second region 112 of the reaction vessel 100 can be determined more accurately.

  The material of the spacer 14 can be appropriately selected as necessary, but is preferably a heat insulating material. Thereby, since the influence which the heat of the 1st heating part 12 and the 2nd heating part 13 mutually has can be decreased, temperature control of the 1st heating part 12 and the 2nd heating part 13 becomes easy. When the spacer 14 is a heat insulating material, when the reaction vessel 100 is attached to the attachment portion 11, the spacer 14 surrounds the reaction vessel 100 in a region between the first heating portion 12 and the second heating portion 13. Is preferably arranged. Thereby, since the heat radiation from the area | region between the 1st heating part 12 of the reaction container 100 and the 2nd heating part 13 can be suppressed, the temperature of the reaction container 100 is stabilized more. In the present embodiment, the spacer 14 is a heat insulating material, and in the example shown in FIG. 2, the mounting portion 11 is configured to penetrate the spacer 14. Thereby, when the reaction vessel 100 is heated by the first heating unit 12 and the second heating unit 13, the heat of the reaction vessel 100 is difficult to escape, so the temperatures of the first region 111 and the second region 112 are further stabilized. be able to.

  The heat cycle apparatus 1 may include a lid 70. In the example shown in FIGS. 1A and 2, the lid 70 is provided so as to cover the mounting portion 11. Since the cover 70 covers the mounting portion 11, when heat is applied by the first heating unit 12, heat radiation from the heat cycle device 1 to the outside can be suppressed, so that the temperature in the heat cycle device 1 can be stabilized. . The lid 70 may be fixed to the main body 10 by a fixing portion 71. In the present embodiment, the fixing portion 71 is a magnet. In addition, as the fixing | fixed part 71, not only this but a hinge and a catch clip may be employ | adopted, for example. In the example shown in FIGS. 1B and 2, a magnet is provided on a part of the surface of the main body 10 that comes into contact with the lid 70. The lid 70 is also provided with a magnet at a position where the magnet of the main body 10 comes into contact. When the mounting portion 11 is covered with the lid 70, the lid 70 is fixed to the main body 10 by magnetic force. Thereby, when the main body 10 is driven by the drive mechanism 20, it is possible to prevent the lid 70 from being removed or moved. Therefore, since the temperature in the heat cycle apparatus 1 can be prevented from changing due to the removal of the lid 70, a more accurate heat cycle can be applied to the reaction solution 140 described later.

  The main body 10 preferably has a highly airtight structure. If the main body 10 has a highly airtight structure, the air inside the main body 10 is difficult to escape to the outside of the main body 10, so that the temperature inside the main body 10 becomes more stable.

  The thermal cycle apparatus 1 preferably includes a structure that holds the reaction vessel 100 in a predetermined position with respect to the first heating unit 12 and the second heating unit 13. Thereby, a predetermined region of the reaction vessel 100 can be heated by the first heating unit 12 and the second heating unit 13. More specifically, the first region 111 of the flow path 110 constituting the reaction vessel 100 can be heated by the first heating unit 12 and the second region 112 can be heated by the second heating unit 13. In the present embodiment, the structure that determines the position of the reaction vessel 100 is the second heat block 13b.

  The structure for determining the position of the reaction vessel 100 may be any structure that can hold the reaction vessel 100 at a desired position. The structure for determining the position of the reaction vessel 100 may be a structure provided in the thermal cycler 1, a structure provided in the reaction vessel 100, or a combination of both. For example, it is possible to employ a screw, a plug-in type bar, a structure in which the protruding portion 113 is provided in the reaction vessel 100, or a structure in which the mounting portion 11 and the reaction vessel 100 are fitted. When using a screw or a rod, the holding position can be adjusted according to the reaction conditions of the thermal cycle, the size of the reaction vessel 100, etc. by changing the length of the screw, the length to be screwed in, or the position to insert the rod. You may do it.

  The heat cycle apparatus 1 may have a mechanism for keeping the temperature of the main body 10 constant. Thereby, since the temperature of the reaction vessel 100 becomes more stable, a more accurate thermal cycle can be applied to the reaction solution 140. As a mechanism for keeping the main body 10 warm, for example, a thermostatic bath can be adopted.

  The spacer 14 shown in FIGS. 1A, 1B, and 2 may be transparent. Thereby, when the transparent reaction container 100 is used for the heat cycle process, it is possible to observe how the reaction liquid 140 moves from the outside of the apparatus. Therefore, it can be visually confirmed whether the heat cycle process is performed appropriately. Accordingly, the degree of “transparency” here may be such that the movement of the reaction liquid 140 can be visually recognized when these members are employed in the heat cycle apparatus 1 and the heat cycle process is performed.

  In order to observe the inside of the heat cycle apparatus 1, the spacer 14 may be transparent or the spacer 14 may be omitted. As the number of members existing between the observer and the reaction container 100 to be observed decreases, the influence of light refraction by the object decreases, so that the inside can be easily observed. Moreover, since the number of members is reduced by eliminating the spacer 14, the manufacturing cost can be reduced.

  In the present embodiment, an example in which the heat cycle apparatus 1 includes the lid 70 has been described, but the lid 70 may be omitted. Thereby, since the number of members to be used can be reduced, manufacturing cost can be reduced.

  The heat cycle apparatus 1 may include a display unit 24 as shown in FIGS. 1 (A) and 1 (B). The display unit 24 is a display device, and displays various information related to the heat cycle device 1. For example, the control unit 50 may control the display unit 24. The display unit 24 may display the heat cycle conditions set by the operation unit 25 and the time and temperature measured during the heat cycle process. For example, when setting is performed by operating the operation unit 25, the input conditions are displayed, or the temperature measured by the temperature sensor during the heat cycle process, the first arrangement or the second arrangement has elapsed. You may display the time and the cycle number which performed the heat cycle. Further, when the heat cycle process is completed or when some abnormality occurs in the apparatus, the fact may be displayed. Furthermore, notification by voice may be performed. By performing notification by display or voice, the user of the apparatus can easily grasp the progress or termination of the thermal cycle process.

  The heat cycle apparatus 1 may include an operation unit 25 as shown in FIGS. 1 (A) and 1 (B). The operation unit 25 is a UI (user interface), and is a device that receives an operation for setting a heat cycle condition. By operating the operation unit 25, as the heat cycle conditions, for example, the first temperature, the second temperature, the holding time for holding the first arrangement, the holding time for holding the second arrangement, and heat You may be comprised so that at least 1 can be set among the cycle numbers of a cycle. The operation unit 25 is mechanically or electronically linked to the control unit 50, and settings in the operation unit 25 are reflected in the control by the control unit 50. As a result, the heat cycle condition applied to the reaction solution 140 can be changed, and therefore a desired heat cycle can be applied to the reaction solution 140. Even if the operation unit 25 can individually set any of the items described above, for example, when one of a plurality of thermal cycle conditions registered in advance is selected, the control unit 50 sets necessary items. You may do. In the example shown in FIGS. 1A and 1B, the operation unit 25 is a button type, and the heat cycle condition can be set by pressing the button for each item.

2. FIG. 3 is a cross-sectional view showing the configuration of the reaction vessel 100 attached to the thermal cycler 1 according to this embodiment. In FIG. 3, an arrow g represents the direction in which gravity acts.

  The reaction vessel 100 is filled with a reaction liquid 140 and a liquid 130 having a specific gravity different from that of the reaction liquid 140 and immiscible with the reaction liquid 140 (hereinafter referred to as “liquid 130”). It includes a flow path 110 that moves along the inner wall. In the present embodiment, the liquid 130 is a liquid having a specific gravity smaller than that of the reaction liquid 140 and immiscible with the reaction liquid 140. As the liquid 130, for example, a liquid that is not miscible with the reaction liquid 140 and has a higher specific gravity than the reaction liquid 140 may be employed. In the example shown in FIG. 3, the reaction vessel 100 includes a flow path 110 and a sealing portion 120. The flow path 110 is filled with the reaction liquid 140 and the liquid 130 and is sealed by the sealing portion 120. The reaction vessel 100 is made of a material that is transparent to light having a predetermined wavelength (transmits light having a predetermined wavelength) to such an extent that the fluorescence detection performed by the detection unit 40 is not hindered. .

  The channel 110 is formed so that the reaction solution 140 moves along the opposing inner walls. Here, the “opposite inner walls” of the flow channel 110 mean two regions of the wall surface of the flow channel 110 that are in a positional relationship facing each other. “Along” means a state in which the distance between the reaction solution 140 and the wall surface of the channel 110 is short, and includes a state in which the reaction solution 140 is in contact with the wall surface of the channel 110. Therefore, “the reaction solution 140 moves along the opposing inner walls” means that the reaction solution 140 is in a state in which the distance is close to both of the two regions on the wall surface of the flow path 110 that face each other. Means "move". In other words, the distance between the two inner walls facing each other in the flow path 110 is such a distance that the reaction solution 140 moves along the inner wall.

  When the flow path 110 of the reaction vessel 100 has such a shape, the direction in which the reaction liquid 140 moves in the flow path 110 can be regulated, so that the path through which the reaction liquid 140 moves in the flow path 110 can be defined to some extent. Thereby, the time required for the reaction solution 140 to move in the flow path 110 can be limited to a certain range. Therefore, the distance between the two inner walls facing each other in the flow path 110 is desired to be a variation in the heat cycle conditions applied to the reaction liquid 140 caused by a variation in the time during which the reaction liquid 140 moves in the flow path 110. 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 140 moves between two opposing inner walls of the flow path 110 is such that two or more droplets of the reaction solution 140 do not enter. Is desirable.

  In the example shown in FIG. 3, the outer shape of the reaction vessel 100 is a cylindrical shape, and a flow path 110 having a longitudinal direction in the direction along the central axis (the vertical direction in FIG. 3) is formed. The shape of the flow path 110 is a cross section in a direction perpendicular to the longitudinal direction of the flow path 110, that is, a cross section perpendicular to the direction in which the reaction solution 140 moves in a region of the flow path 110 (this is the cross section of the flow path 110). “Cross section”) is a circular column. Therefore, in the reaction vessel 100, the opposed inner walls of the flow channel 110 are regions including two points on the wall surface of the opposed flow channel 110 across the center of the cross section of the flow channel 110. Further, “the direction in which the reaction liquid 140 moves” is the longitudinal direction of the flow path 110.

  The shape of the cross section of the flow path 110 is not limited to a circle, but may be any shape such as a polygon or an ellipse as long as the reaction solution 140 can move along the opposing inner walls. For example, when the cross section of the flow path 110 of the reaction vessel 100 is polygonal, the “opposite inner wall” is the opposite of the flow path when the cross section inscribed in the flow path 110 is assumed to be a circular flow path. It shall be an inner wall. That is, the flow path 110 may be formed so that the reaction solution 140 moves along the opposing inner walls of the virtual flow path inscribed in the flow path 110 and having a circular cross section. Thereby, even when the cross section of the flow path 110 is a polygon, the path | route for the reaction liquid 140 to move between the 1st area | region 111 and the 2nd area | region 112 can be prescribed | regulated to some extent. Therefore, the time required for the reaction solution 140 to move between the first region 111 and the second region 112 can be limited to a certain range.

  The first region 111 of the reaction vessel 100 is a partial region of the flow path 110 that is heated to the first temperature by the first heating unit 12. The second region 112 is a partial region of the flow path 110 that is different from the first region 111 and is heated to a second temperature different from the first temperature by the second heating unit 13. In the example shown in FIG. 3, the first region 111 is a region including one end portion in the longitudinal direction of the flow path 110, and the second region 112 includes the other end portion in the longitudinal direction of the flow path 110. It is an area. In the example shown in FIG. 3, a region surrounded by a dotted line including an end portion on the side relatively close to the sealing portion 120 in the flow channel 110 is the first region 111, and the sealing portion in the flow channel 110. A region surrounded by a dotted line including an end portion on the side far from 120 is a second region 112. In the thermal cycle apparatus 1 according to the present embodiment, the first heating unit 12 of the temperature gradient forming unit 30 heats the first region 111 of the reaction vessel 100 to the first temperature, and the second heating unit of the temperature gradient forming unit 30. 13 heats the second region 112 of the reaction vessel 100 to the second temperature, thereby forming a temperature gradient in the direction in which the reaction solution 140 moves with respect to the flow path 110 of the reaction vessel 100.

  The flow path 110 is filled with the liquid 130 and the reaction liquid 140. Since the liquid 130 is immiscible with the reaction liquid 140, that is, does not mix, the reaction liquid 140 is held in the liquid 130 in the form of droplets as shown in FIG. Since the specific gravity of the reaction liquid 140 is larger than that of the liquid 130, the reaction liquid 140 is located in the lowermost region in the direction in which gravity acts in the flow path 110. As the liquid 130, for example, dimethyl silicone oil or paraffin oil can be used. The reaction liquid 140 is a liquid containing components necessary for the reaction. When the reaction is PCR, the reaction solution 140 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 130, the reaction solution 140 is preferably an aqueous solution containing the above-described components.

  The reaction liquid 140 or the liquid 130 filled in the reaction container 100 includes a fluorescent material that emits light having a predetermined wavelength (first wavelength in the present embodiment) detected by the detection unit 40. That is, the fluorescent substance that emits light of the first wavelength is included only in one of the reaction solution 140 and the liquid 130. Therefore, the position of the reaction liquid 140 in the reaction vessel 100 can be estimated by detecting the intensity of the light having the first wavelength by the detection unit 40. The fluorescent substance may be a fluorescent probe that binds complementarily to a specific DNA or a fluorescent dye that emits fluorescence.

  When the reaction solution 140 includes a fluorescent material that emits light of the first wavelength, for example, as a fluorescent probe, the liquid 130 includes a fluorescent material that emits light of a second wavelength different from the first wavelength. May be. Thereby, for example, the amount of the liquid 130 filled in the reaction vessel 100 can be estimated by measuring the intensity of light of the second wavelength.

  When the liquid 130 contains a fluorescent material that emits light of the first wavelength, the reaction solution 140 may contain a fluorescent material that emits light of a second wavelength different from the first wavelength. Thus, for example, when the reaction solution 140 is a reaction solution for PCR and a fluorescent substance that emits light of the second wavelength is a fluorescent probe that binds complementarily to a specific DNA, By measuring the light intensity, the amount of specific DNA contained in the reaction solution 140 can be estimated.

3. Example of Control of Thermal Cycle Device Next, an example of a thermal cycle processing procedure of the thermal cycle device 1 according to this embodiment will be described. In the following, when the drive mechanism 20 mounts the reaction vessel 100 on the mounting part 11, the mounting part 11 and the temperature gradient forming part 30 are placed in the first arrangement and in the direction in which gravity acts in the flow path 110. A description will be given by taking as an example control for rotating the second point between a second arrangement different from the first arrangement.

  4A is a cross-sectional view schematically showing a cross section in a plane perpendicular to the rotation axis R through the line AA in FIG. 1A in the first arrangement, and FIG. 2 is a cross-sectional view schematically showing a cross section in a plane perpendicular to the rotation axis R through the line AA in FIG. 4A and 4B, the white arrow indicates the direction of rotation of the main body 10, and the arrow g indicates the direction in which gravity acts.

  As shown in FIG. 4A, the first arrangement is an arrangement in which the end of the flow path 110 that is relatively far from the sealing portion 120 is the lowest point in the direction in which gravity acts. . That is, the first arrangement is an arrangement in which, when the reaction vessel 100 is attached to the attachment portion 11, the first region 111 of the reaction vessel 100 is positioned at the lowermost portion of the flow path 110 in the direction in which gravity acts. In the example shown in FIG. 4A, in the first arrangement, the reaction liquid 140 having a specific gravity greater than that of the liquid 130 exists in the first region 111. Therefore, the reaction liquid 140 is placed under the first temperature.

  As shown in FIG. 4B, the second arrangement is an arrangement in which the end of the flow path 110 that is relatively close to the sealing portion 120 is the lowest point in the direction in which gravity acts. . That is, the second arrangement is an arrangement in which, when the reaction vessel 100 is attached to the attachment portion 11, the second region 112 of the reaction vessel 100 is positioned at the lowermost portion of the flow path 110 in the direction in which gravity acts. In the example shown in FIG. 4B, the reaction liquid 140 having a specific gravity greater than that of the liquid 130 exists in the second region 112 in the second arrangement. Accordingly, the reaction solution 140 is placed under the second temperature.

  The driving mechanism 20 rotates the mounting unit 11 and the temperature gradient forming unit 30 between the first arrangement and a second arrangement different from the first arrangement, so that the reaction liquid 140 is caused by the action of gravity. The first region and the second region of the flow path 110 are moved. Therefore, by switching the repeated arrangement, the reaction solution 140 is alternately exposed to the first temperature and the second temperature, so that the reaction solution 140 can be subjected to a heat cycle.

  Further, in the heat cycle apparatus 1 according to the present embodiment, the state of the reaction vessel 100 held in the first arrangement and the reaction vessel 100 held in the second arrangement by switching the arrangement of the mounting portion 11. The state can be switched. Therefore, since the reaction liquid 140 can be held at a predetermined temperature while holding the reaction vessel 100 in the first arrangement or the second arrangement, a thermal cycle device capable of easily controlling the heating time can be provided.

  The drive mechanism 20 rotates in the opposite direction between the first arrangement and the second arrangement, and when the drive mechanism 20 rotates from the second arrangement to the first arrangement. May be rotated. This eliminates the need for a special mechanism for reducing the twisting of wiring such as a conductive wire caused by rotation. Therefore, it is possible to realize a heat cycle device suitable for downsizing. Further, the number of rotations when rotating from the first arrangement to the second arrangement and the number of rotations when rotating from the second arrangement to the first arrangement are less than one rotation (the rotation angle is 360 °). Less). Thereby, the degree to which the wiring is twisted can be reduced.

3-1. First Specific Example of Control Method of Thermal Cycle Device FIG. 5 is a functional block diagram of the thermal cycle device 1 according to the first specific example. FIG. 6 is a flowchart for explaining a control method of the thermal cycler 1 according to the first specific example.

  In the control method of the heat cycle apparatus 1 according to the first specific example, the mounting mechanism 11 and the temperature gradient forming unit 30 are arranged between the first arrangement and the second arrangement by the drive mechanism 20 based on the switching timing. Based on the switching, detection of the detection timing, which is the timing at which the intensity of light of a predetermined wavelength from the reaction vessel 100 changes across the reference value, the switching timing, and the detection timing, the drive mechanism 20 And determining a holding time which is a time for holding the placement of the mounting portion 11 and the temperature gradient forming portion 30 in at least one of the first placement and the second placement.

  In the example shown in FIG. 5 and FIG. 6, the control unit 50 of the thermal cycle apparatus 1 causes the drive mechanism 20 to place the mounting unit 11 and the temperature gradient forming unit 30 between the first arrangement and the second arrangement. Based on the switching timing that is the switching timing and the detection timing that is the timing at which the intensity of the light detected by the detection unit 40 changes across the reference value, the mounting mechanism 11 and the temperature gradient forming unit are driven by the drive mechanism 20. A holding time, which is a time for holding 30 arrangements in at least one of the first arrangement and the second arrangement, is determined. For example, the control unit 50 may determine the holding time by adding a preset time to the time from the switching timing to the detection timing. Further, for example, the control unit 50 estimates the time required for the reaction solution 140 to move the remaining distance in the flow path 110 based on the time from the switching timing to the detection timing, and at the estimated time, The holding time may be determined by adding the time from the switching timing to the detection timing and a preset time.

  In the example shown in FIG. 5, the control unit 50 measures the time from the switching timing to the detection timing, and the determining means 54 determines the holding time based on the time measured by the measuring means 52. And. In the example illustrated in FIG. 5, the control unit 50 includes a drive mechanism control unit 56 that controls the drive mechanism 20. The measurement unit 52, the determination unit 54, and the drive mechanism control unit 56 may be configured to be realized by a dedicated circuit and perform control described later. The measuring means 52, the determining means 54, and the drive mechanism control means 56 are, for example, a CPU (Central Processing Unit) stored in a storage device (not shown) such as a ROM (Read Only Memory) or a RAM (Random Access Memory). The computer may function as a computer by executing a control program, and may be configured to perform control described later.

  In the example shown in FIG. 6, first, the arrangement of the mounting portion 11 and the temperature gradient forming portion 30 is switched between the first arrangement and the second arrangement by the drive mechanism 20 based on the switching timing (step S100). ). In the first specific example, as shown in FIG. 5, the drive mechanism control means 56 of the control unit 50 drives the drive mechanism control information D5 including information for controlling the drive mechanism 20 based on the switching timing. Output to mechanism 20. Further, the drive mechanism control unit 56 outputs switching timing information D4 including information related to the switching timing to the measuring unit 52. Note that the switching timing may be, for example, a timing at which the placement of the mounting unit 11 and the temperature gradient forming unit 30 is started by the drive mechanism 20 or a timing at which the switching of the mounting unit 11 and the temperature gradient forming unit 30 is finished.

  In the example shown in FIG. 6, after step S <b> 100, a detection timing that is a timing at which the intensity of light having a predetermined wavelength from the reaction container 100 changes across the reference value is detected. The reference value may be designed in consideration of the amount of the fluorescent substance contained in the reaction solution 140 or the liquid 130, or may be determined experimentally.

  More specifically, first, after step S100, the intensity of light having a predetermined wavelength (in this embodiment, the first wavelength) from the inside of the reaction vessel 100 is detected (step S102). In the first specific example, the measurement unit 52 of the control unit 50 receives from the detection unit 40 input of detection result information D1 including information related to the intensity of light of the first wavelength detected by the detection unit 40.

  After step S102, it is determined whether or not the intensity of the first wavelength light detected by the detection unit 40 has changed across the reference value (step S104). If the intensity of the first wavelength light detected by the detection unit 40 does not change across the reference value (NO in step S104), steps S102 and S104 are performed again. When the intensity of the light of the first wavelength detected by the detection unit 40 changes across the reference value (YES in step S104), step S106 described later is performed with this timing as the detection timing.

  For more specific examples of the detection step, refer to the sections “3-1-1. Reaction liquid 140 contains a fluorescent substance” and “3-1-2. Liquid 130 contains a fluorescent substance”. Detailed.

  In the example shown in FIG. 6, after step S <b> 104, the arrangement of the mounting portion 11 and the temperature gradient forming unit 30 is changed between the first arrangement and the second arrangement by the drive mechanism 20 based on the switching timing and the detection timing. A holding time, which is a time for holding at least one of them, is determined (step S106). In the example shown in FIG. 5, the switching timing is first determined based on the switching timing determined based on the switching timing information D4 and the detection timing determined based on the detection result information D1. The time from the detection timing to the detection timing is measured as the first time, and the first time information D2 including the information related to the first time is output to the determination unit 54. Next, the holding time is determined based on the time from the switching timing to the detection timing. In the example shown in FIG. 6, the holding time is a time for holding the first arrangement. For example, the holding time may be obtained by adding the first time to the second time, which is the time during which the reaction solution 140 should be placed under the first temperature. The determination unit 54 outputs holding time information D3 including information about the holding time to the drive mechanism control unit 56. The drive mechanism control means 56 controls the subsequent drive mechanism 20 based on the holding time information D3.

  According to the present embodiment, the placement of the mounting portion 11 is between the first placement and the second placement in which the position of the lowest point of the flow path 110 in the direction in which gravity acts is different from the first placement. Can be switched with. As a result, the position of the lowest point in the direction in which gravity acts in the flow path 110 of the reaction vessel 100 attached to the attachment unit 11 changes. Therefore, since the reaction solution 140 moves in accordance with gravity in the flow path 110 where the temperature gradient is formed, the reaction solution 140 can be subjected to a heat cycle. In addition, according to the present embodiment, the switching timing that is the timing at which the arrangement of the mounting unit 11 and the temperature gradient forming unit 30 is switched between the first arrangement and the second arrangement by the drive mechanism 20, and the detection unit 40. It is possible to estimate the time until the reaction solution 140 moves to an appropriate position from the detection timing that is the timing at which the intensity of the light detected by the step changes across the reference value. According to the first specific example, since the holding time is determined based on the switching timing and the detection timing, the thermal cycle device capable of bringing the reaction liquid 140 into a desired temperature state over a desired time and control of the thermal cycle device The method can be realized.

  Further, according to the first specific example, in order to reliably perform a desired thermal cycle, it is not necessary to set a long holding time with a margin, so that the thermal cycle can be performed in a short time.

  In addition, according to the first specific example, since the holding time is determined based on the time from the switching timing to the detection timing, the reaction liquid 140 is not affected by the time until the reaction liquid 140 moves to an appropriate position. It is possible to realize a thermal cycle apparatus and a control method for the thermal cycle apparatus that can achieve a desired temperature state over a desired time.

3-1-1. Case where Reaction Solution 140 Contains a Fluorescent Substance Next, a first specific example will be described in more detail with respect to a case where the reaction solution 140 filled in the reaction vessel 100 contains a fluorescent material.

  FIG. 7 is a graph showing the light intensity in the first specific example of the control method of the heat cycle apparatus 1. In FIG. 7, the horizontal axis represents time, and the vertical axis represents the intensity of light detected by the detection unit 40.

  In the example shown in FIG. 7, the time t0 is the timing (switching timing) when the placement of the mounting portion 11 and the temperature gradient forming unit 30 is switched. FIG. 7 illustrates three states from the first state to the third state. In the example shown in FIG. 7, the control unit 50 uses the timing when the intensity of the light detected by the detection unit 40 exceeds the reference value as the detection timing. Further, the reference value for determining the detection timing is the first reference value V1.

  In the first state, after time t0, at time t1, the intensity of light detected by the detection unit 40 exceeds the first reference value V1. Therefore, the measuring means 52 of the control unit 50 measures the first time, which is the time from the switching timing to the detection timing, using the time t1 as the detection timing. The determining unit 54 determines the holding time by adding a preset second time to the first time measured by the measuring unit 52.

  Since the fluorescent substance that emits light of a predetermined wavelength (in this embodiment, the first wavelength) detected by the detection unit 40 is contained in the reaction solution 140 filled in the reaction vessel 100, the first In the arrangement, when the reaction solution 140 moves near the lowest point in the direction in which gravity acts in the flow path 110, the intensity of the light detected by the detection unit 40 increases. Therefore, the control unit 50 can determine the detection timing more accurately by setting the timing when the intensity of light detected by the detection unit 40 exceeds the reference value as the detection timing.

  In the second state, after the time t0, the intensity of light detected by the detection unit 40 increases, but does not exceed the first reference value V1. Examples of the second state include a case where the reaction vessel 100 is not correctly attached to the attachment unit 11 and a case where the amount of the reaction solution 140 filled in the reaction vessel 100 is insufficient.

  In the third state, after the time t0, the intensity of light detected by the detection unit 40 is not increased and is constant. For example, when the reaction vessel 100 is not attached to the attachment portion 11, or when the reaction vessel 100 is not filled with the reaction solution 140, the reaction solution 140 is in the second region of the reaction vessel 100. There is a case where it has adhered to the inner wall such as 112 and has not moved to the first region 111.

  When the first reference value V1 is not exceeded within a predetermined time as in the second state and the third state, the control unit 50 displays a message on the display unit 24 indicating that an abnormality has occurred. It may be displayed or the operation of the drive mechanism 20 may be stopped. Thereby, it is possible to notify the user that the heat cycle apparatus 1 is in a state where the desired heat cycle cannot be applied to the reaction solution 140.

3-1-2. When Liquid 130 Contains a Fluorescent Material Next, the first specific example will be described in more detail with respect to the case where the liquid 130 filled in the reaction vessel 100 includes a fluorescent material.

  FIG. 8 is another graph showing the light intensity in the first specific example of the control method of the thermal cycler 1. The horizontal axis in FIG. 8 represents time, and the vertical axis represents the intensity of light detected by the detection unit 40.

  In the example shown in FIG. 8, the time t <b> 10 is the timing (switching timing) when the placement of the mounting unit 11 and the temperature gradient forming unit 30 is switched. FIG. 8 illustrates three states from the fourth state to the sixth state. In the example illustrated in FIG. 8, the control unit 50 uses the timing when the light intensity detected by the detection unit 40 falls below the reference value as the detection timing. Further, the reference value for determining the detection timing is the second reference value V2.

  In the fourth state, after time t10, at time t11, the intensity of light detected by the detection unit 40 is lower than the second reference value V2. Therefore, the measuring means 52 of the control unit 50 measures the first time, which is the time from the switching timing to the detection timing, using the time t11 as the detection timing. The determining unit 54 determines the holding time by adding a preset second time to the first time measured by the measuring unit 52.

  Since the fluorescent material emitting light of a predetermined wavelength (first wavelength in the present embodiment) detected by the detection unit 40 is contained in the liquid 130 filled in the reaction container 100, the first arrangement When the reaction solution 140 moves in the vicinity of the lowest point in the direction in which gravity acts in the flow path 110, the intensity of light detected by the detection unit 40 decreases. Therefore, the control unit 50 can determine the detection timing more accurately by setting the timing when the intensity of light detected by the detection unit 40 falls below the reference value as the detection timing.

  In the fifth state, after the time t10, the intensity of light detected by the detection unit 40 decreases, but does not fall below the second reference value V2. Examples of the fifth state include a case where the reaction vessel 100 is not correctly attached to the attachment unit 11 and a case where the amount of the reaction solution 140 filled in the reaction vessel 100 is insufficient.

  In the sixth state, after the time t10, the intensity of light detected by the detection unit 40 is not small but constant. As a case where the sixth state is reached, for example, when the reaction vessel 100 is not attached to the attachment portion 11, when the reaction vessel 100 is not filled with the reaction solution 140, the reaction solution 140 is in the second region of the reaction vessel 100. There is a case where it has adhered to the inner wall such as 112 and has not moved to the first region 111.

  As in the fifth state and the sixth state, when the value does not fall below the second reference value V2 within a predetermined time, it is assumed that an abnormality has occurred, and the control unit 50 displays a message on the display unit 24 indicating an abnormality. It may be displayed or the operation of the drive mechanism 20 may be stopped. Thereby, it is possible to notify the user that the heat cycle apparatus 1 is in a state where the desired heat cycle cannot be applied to the reaction solution 140.

3-2. Second Specific Example of Thermal Cycle Device Control Method FIG. 9 is a functional block diagram of a thermal cycle device 1 according to a second specific example. FIG. 10 is a flowchart for explaining a control method of the thermal cycler 1 according to the second specific example.

  The control method of the thermal cycler 1 according to the second specific example is to detect a detection timing that is a timing at which the intensity of light having a predetermined wavelength from the inside of the reaction vessel 100 changes across the reference value, and to detect a predetermined timing from the detection timing. Holding the placement of the mounting portion 11 and the temperature gradient forming portion 30 in at least one of the first placement and the second placement by the drive mechanism 20 until the time elapses.

  In the example shown in FIGS. 9 and 10, the control unit 50 of the heat cycle apparatus 1 has passed a predetermined time from the detection timing, which is the timing at which the light intensity detected by the detection unit 40 changes across the reference value. Until this occurs, the arrangement of the mounting portion 11 and the temperature gradient forming unit 30 is held in at least one of the first arrangement and the second arrangement by the drive mechanism 20.

  In the example shown in FIG. 9, the control unit 50 includes a timing determination unit 58 that determines a detection timing based on the detection result of the detection unit 40 and a drive mechanism control unit 56 that controls the drive mechanism 20. Yes. The drive mechanism control unit 56 and the timing determination unit 58 may be configured to be realized by a dedicated circuit and to perform control described later. The drive mechanism control means 56 and the timing determination means 58 have a control program stored in a storage device (not shown) such as a ROM (Read Only Memory) or a RAM (Random Access Memory) by a CPU (Central Processing Unit), for example. It may be configured to function as a computer by executing and to perform control described later.

  In the example shown in FIG. 10, first, the arrangement of the mounting portion 11 and the temperature gradient forming unit 30 is switched between the first arrangement and the second arrangement by the drive mechanism 20 based on the switching timing (step S200). ). In the second specific example, as shown in FIG. 9, the drive mechanism control means 56 of the control unit 50 drives the drive mechanism control information D5 including information for controlling the drive mechanism 20 based on the switching timing. Output to mechanism 20. Note that the switching timing may be, for example, a timing at which the placement of the mounting unit 11 and the temperature gradient forming unit 30 is started by the drive mechanism 20 or a timing at which the switching of the mounting unit 11 and the temperature gradient forming unit 30 is finished.

  In the example shown in FIG. 10, after step S200, a detection timing that is a timing at which the intensity of light of a predetermined wavelength from the inside of the reaction vessel 100 changes across the reference value is detected. The reference value may be designed in consideration of the amount of the fluorescent substance contained in the reaction solution 140 or the liquid 130, or may be determined experimentally.

  More specifically, first, after step S200, the intensity of light having a predetermined wavelength (in the present embodiment, the first wavelength) from the reaction vessel 100 is detected (step S202). In the second specific example, the timing determination unit 58 of the control unit 50 receives from the detection unit 40 input of detection result information D1 including information related to the intensity of light of the first wavelength detected by the detection unit 40.

  After step S202, it is determined whether or not the intensity of the first wavelength light detected by the detection unit 40 has changed across the reference value (step S204). If the intensity of the first wavelength light detected by the detection unit 40 has not changed across the reference value (NO in step S204), steps S202 and S204 are performed again. When the intensity of the light of the first wavelength detected by the detection unit 40 changes across the reference value (in the case of YES in step S204), this timing is determined as the detection timing and includes information regarding the detection timing. The detection timing information D6 is output to the drive mechanism control means 56.

  For more specific examples of the detection step, refer to the sections “3-2-1. When the reaction solution 140 contains a fluorescent substance” and “3-2-2. When the liquid 130 contains a fluorescent substance”. Detailed.

  In the example shown in FIG. 10, after step S <b> 204, the mounting mechanism 11 and the temperature gradient forming unit 30 are arranged in the first arrangement and the second arrangement by the drive mechanism 20 until a predetermined time elapses from the detection timing. At least one of them is held (step S206). In the example shown in FIGS. 9 and 10, the drive mechanism control unit 56 of the control unit 50 performs the mounting unit 11 and the temperature by the drive mechanism 20 until a predetermined time elapses from the detection timing based on the detection timing information D6. The drive mechanism control information D5 is output to the drive mechanism 20 so that the arrangement of the gradient forming unit 30 is maintained in the first arrangement.

  According to the present embodiment, the placement of the mounting portion 11 is between the first placement and the second placement in which the position of the lowest point of the flow path 110 in the direction in which gravity acts is different from the first placement. Can be switched with. As a result, the position of the lowest point in the direction in which gravity acts in the flow path 110 of the reaction vessel 100 attached to the attachment unit 11 changes. Therefore, since the reaction solution 140 moves in accordance with gravity in the flow path 110 where the temperature gradient is formed, the reaction solution 140 can be subjected to a heat cycle. Further, according to the present embodiment, the timing at which the reaction solution 140 moves to an appropriate position can be estimated from the detection timing that is the timing at which the intensity of light detected by the detection unit 40 changes across the reference value. According to the second specific example, the placement of the mounting part 11 and the temperature gradient forming part 30 is held for a predetermined time with reference to the detection timing, so that the reaction solution 140 can be brought to a desired temperature state for a desired time. A heat cycle device and a control method for the heat cycle device can be realized.

  In addition, according to the second specific example, in order to reliably perform a desired thermal cycle, it is not necessary to set a long time for holding the arrangement with a margin, so that the thermal cycle can be performed in a short time. it can.

3-2-1. When Reaction Solution 140 Contains a Fluorescent Substance Next, the second specific example will be described in more detail with respect to the case where the reaction solution 140 filled in the reaction vessel 100 contains a fluorescent material.

  FIG. 11 is a graph showing the light intensity in the second specific example of the control method of the thermal cycler 1. In FIG. 11, the horizontal axis represents time, and the vertical axis represents the intensity of light detected by the detection unit 40.

  In the example shown in FIG. 11, the time t20 is the timing (switching timing) when the placement of the mounting unit 11 and the temperature gradient forming unit 30 is switched. FIG. 11 illustrates three states from the seventh state to the ninth state. In the example shown in FIG. 11, the control unit 50 uses the timing when the intensity of the light detected by the detection unit 40 exceeds the reference value as the detection timing. Further, the reference value for determining the detection timing is the first reference value V1.

  In the seventh state, after time t20, at time t21, the light intensity detected by the detection unit 40 exceeds the first reference value V1. Therefore, the timing determination means 58 of the control unit 50 determines time t21 as the detection timing. The drive mechanism control unit 56 causes the drive mechanism 20 to hold the first arrangement from the detection timing determined by the timing determination unit 58 until the preset third time elapses. Is output.

  Since the fluorescent substance that emits light of a predetermined wavelength (in this embodiment, the first wavelength) detected by the detection unit 40 is contained in the reaction solution 140 filled in the reaction vessel 100, the first In the arrangement, when the reaction solution 140 moves near the lowest point in the direction in which gravity acts in the flow path 110, the intensity of the light detected by the detection unit 40 increases. Therefore, the control unit 50 can determine the detection timing more accurately by setting the timing when the intensity of light detected by the detection unit 40 exceeds the reference value as the detection timing.

  In the eighth state, after time t20, the intensity of light detected by the detection unit 40 increases, but does not exceed the first reference value V1. Examples of the eighth state include a case where the reaction vessel 100 is not correctly attached to the attachment unit 11 and a case where the amount of the reaction solution 140 filled in the reaction vessel 100 is insufficient.

  In the ninth state, after the time t20, the intensity of the light detected by the detection unit 40 does not increase and is constant. For example, when the reaction vessel 100 is not attached to the attachment portion 11, or when the reaction vessel 100 is not filled with the reaction solution 140, the reaction solution 140 is in the second region of the reaction vessel 100. There is a case where it has adhered to the inner wall such as 112 and has not moved to the first region 111.

  When the first reference value V1 is not exceeded within a predetermined time as in the eighth state and the ninth state, the control unit 50 displays a message indicating that an abnormality has occurred on the display unit 24 as an abnormality has occurred. It may be displayed or the operation of the drive mechanism 20 may be stopped. Thereby, it is possible to notify the user that the heat cycle apparatus 1 is in a state where the desired heat cycle cannot be applied to the reaction solution 140.

3-2-2. Case where the liquid 130 contains a fluorescent material Next, a case where the liquid 130 filled in the reaction vessel 100 contains a fluorescent material will be described in more detail.

  FIG. 12 is another graph showing the light intensity in the second specific example of the control method of the thermal cycler 1. The horizontal axis in FIG. 12 represents time, and the vertical axis represents the intensity of light detected by the detection unit 40.

  In the example shown in FIG. 12, time t30 is the timing (switching timing) at which the placement of the mounting portion 11 and the temperature gradient forming portion 30 is switched. FIG. 12 illustrates three states from the tenth state to the twelfth state. In the example shown in FIG. 12, the control unit 50 uses the timing when the intensity of the light detected by the detection unit 40 falls below the reference value as the detection timing. Further, the reference value for determining the detection timing is the second reference value V2.

  In the tenth state, after time t30, at time t31, the intensity of light detected by the detection unit 40 is lower than the second reference value V2. Therefore, the timing determination unit 58 of the control unit 50 determines the time t31 as the detection timing. The drive mechanism control unit 56 causes the drive mechanism 20 to hold the first arrangement from the detection timing determined by the timing determination unit 58 until the preset third time elapses. Is output.

  Since the fluorescent material emitting light of a predetermined wavelength (first wavelength in the present embodiment) detected by the detection unit 40 is contained in the liquid 130 filled in the reaction container 100, the first arrangement When the reaction solution 140 moves in the vicinity of the lowest point in the direction in which gravity acts in the flow path 110, the intensity of light detected by the detection unit 40 decreases. Therefore, the control unit 50 can determine the detection timing more accurately by setting the timing when the intensity of light detected by the detection unit 40 falls below the reference value as the detection timing.

  In the eleventh state, after the time t30, the intensity of light detected by the detection unit 40 is reduced, but does not fall below the second reference value V2. For example, when the reaction vessel 100 is not correctly attached to the attachment portion 11, the amount of the reaction solution 140 filled in the reaction vessel 100 is insufficient.

  In the twelfth state, after time t30, the intensity of the light detected by the detection unit 40 is not small but constant. As a case where the twelfth state is reached, for example, when the reaction vessel 100 is not attached to the attachment portion 11, when the reaction vessel 100 is not filled with the reaction solution 140, the reaction solution 140 is in the second region of the reaction vessel 100. There is a case where it has adhered to the inner wall such as 112 and has not moved to the first region 111.

  As in the eleventh state and the twelfth state, when the value does not fall below the second reference value V2 within a predetermined time, the control unit 50 displays a message to the effect that an abnormality has occurred on the display unit 24. It may be displayed or the operation of the drive mechanism 20 may be stopped. Thereby, it is possible to notify the user that the heat cycle apparatus 1 is in a state where the desired heat cycle cannot be applied to the reaction solution 140.

  In addition, embodiment mentioned above and a modification are examples, Comprising: It is not necessarily limited to these. For example, a plurality of embodiments and modifications 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 1 Thermal cycle apparatus, 10 Main body, 11 Mounting part, 11a 1st mounting part, 11b 2nd mounting part, 12 1st heating part, 12a 1st heater, 12b 1st heat block, 13 2nd heating part, 13a 2nd heater, 13b 2nd heat block, 14 spacer, 18 measurement window, 20 drive mechanism, 21 bearing, 22 slide bar, 23 observation window, 24 display section, 25 operation section, 30 temperature gradient forming section, 31 heat source section, 32 heat conduction unit, 40 detection unit, 41a, 42a detector, 41b, 42b slide bar, 50 control unit, 52 measurement unit, 54 determination unit, 56 drive mechanism control unit, 58 timing determination unit, 70 lid, 71 fixing unit , 100 reaction vessel, 110 flow path, 111 first region, 112 second region, 113 projecting portion, 120 sealing portion, 130 Liquid, 140 reaction liquid, D1 detection result information, D2 first time information, D3 holding time information, D4 switching timing information, D5 drive mechanism control information, D6 detection timing information, R rotating shaft, V1 first reference value, V2 first 2 reference values

Claims (8)

The reaction liquid and the reaction liquid have different specific gravities and are filled with a liquid that is immiscible with the reaction liquid, and either the reaction liquid or the liquid immiscible with the reaction liquid emits light of a predetermined wavelength. A mounting portion for mounting a reaction vessel including a fluorescent substance that emits and including a flow path through which the reaction solution moves;
A temperature gradient forming unit that 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 reaction vessel is attached to the attachment part, the arrangement of the attachment part and the temperature gradient forming part is the first arrangement, and the position of the lowest point of the flow path in the direction in which gravity acts is the first position. A drive mechanism that switches between a second arrangement different from the one arrangement;
A detection unit for detecting the intensity of light of the predetermined wavelength from within the reaction vessel;
A control unit for controlling the drive mechanism;
Including
The controller is
From the switching timing that is a timing for switching the placement of the mounting portion and the temperature gradient forming portion between the first placement and the second placement by the driving mechanism, the light detected by the detection portion By adding a preset second time to the first time that is the time until the detection timing at which the intensity changes across the reference value, the drive mechanism causes the mounting portion and the temperature gradient forming portion to A thermal cycle apparatus that determines a holding time, which is a time during which an arrangement is held in at least one of the first arrangement and the second arrangement. The thermal cycle apparatus according to claim 1, wherein
The controller is
Measuring means for measuring the first time;
Determining means for determining the holding time by adding a preset second time to the first time measured by the measuring means;
Including a heat cycle device. The reaction liquid and the reaction liquid have different specific gravities and are filled with a liquid that is immiscible with the reaction liquid, and either the reaction liquid or the liquid immiscible with the reaction liquid emits light of a predetermined wavelength. A mounting portion for mounting a reaction vessel including a fluorescent substance that emits and including a flow path through which the reaction solution moves;
A temperature gradient forming unit that 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 reaction vessel is attached to the attachment part, the arrangement of the attachment part and the temperature gradient forming part is the first arrangement, and the position of the lowest point of the flow path in the direction in which gravity acts is the first position. A drive mechanism that switches between a second arrangement different from the one arrangement;
A detection unit for detecting the intensity of light of the predetermined wavelength from within the reaction vessel;
A control unit for controlling the drive mechanism;
Including
The controller is
From the switching timing that is the timing of switching the placement of the mounting portion and the temperature gradient forming portion between the first placement and the second placement by the drive mechanism,
From the detection timing that is a timing at which the intensity of the light detected by the detection unit changes across a reference value to a timing at which a preset third time elapses,
A thermal cycle device, wherein the mounting mechanism and the temperature gradient forming unit are held in at least one of the first arrangement and the second arrangement by the driving mechanism. In the heat cycle apparatus according to any one of claims 1 to 3,
The said detection part is a heat cycle apparatus which detects the intensity | strength of the said light from the area | region containing the lowest point in the direction which gravity acts in the said flow path when it becomes the said 1st arrangement | positioning. In the heat cycle apparatus according to any one of claims 1 to 4,
The reaction solution filled in the reaction vessel contains the fluorescent substance,
The said control part is a thermal cycle apparatus which makes the detection timing the timing when the intensity | strength of the said light detected by the said detection part exceeded the said reference value. In the heat cycle apparatus according to any one of claims 1 to 4,
The liquid immiscible with the reaction liquid filled in the reaction vessel contains the fluorescent substance,
The said control part is a thermal cycle apparatus which makes the said detection timing the timing when the intensity | strength of the said light detected by the said detection part fell below the said reference value. A mounting portion for mounting a reaction vessel including a flow path through which the reaction liquid and the reaction liquid have different specific gravity and are immiscible with the reaction liquid and are filled with the reaction liquid;
A temperature gradient forming unit that 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 reaction vessel is attached to the attachment part, the arrangement of the attachment part and the temperature gradient forming part is the first arrangement, and the position of the lowest point of the flow path in the direction in which gravity acts is the first position. A drive mechanism that switches between a second arrangement different from the one arrangement;
A control method for a heat cycle apparatus including:
Either one of the reaction liquid filled in the reaction container and the liquid immiscible with the reaction liquid contains a fluorescent substance that emits light of a predetermined wavelength,
Based on the switching timing, the arrangement of the mounting part and the temperature gradient forming part is switched between the first arrangement and the second arrangement by the driving mechanism;
Detecting a detection timing that is a timing at which the intensity of light of a predetermined wavelength from within the reaction vessel changes across a reference value;
By adding a second time set in advance to a first time that is a time from the switching timing to the detection timing, the mounting mechanism and the temperature gradient forming unit are arranged by the driving mechanism in the first arrangement. And determining a holding time that is a time for holding at least one of the second arrangements;
A control method for a thermal cycle device. A mounting portion for mounting a reaction vessel including a flow path through which the reaction liquid and the reaction liquid have different specific gravity and are immiscible with the reaction liquid and are filled with the reaction liquid;
A temperature gradient forming unit that 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 reaction vessel is attached to the attachment part, the arrangement of the attachment part and the temperature gradient forming part is the first arrangement, and the position of the lowest point of the flow path in the direction in which gravity acts is the first position. A drive mechanism that switches between a second arrangement different from the one arrangement;
A control method for a heat cycle apparatus including:
Either one of the reaction liquid filled in the reaction container and the liquid immiscible with the reaction liquid contains a fluorescent substance that emits light of a predetermined wavelength,
Detecting a detection timing that is a timing at which the intensity of light of a predetermined wavelength from within the reaction vessel changes across a reference value;
From the switching timing that is the timing of switching the placement of the mounting portion and the temperature gradient forming portion between the first placement and the second placement by the drive mechanism,
From the detection timing to a timing at which a preset third time elapses,
Holding the placement of the mounting portion and the temperature gradient forming portion in at least one of the first placement and the second placement by the drive mechanism;
A control method for a thermal cycle device.

Images