JP2013044661A - Thermal cycle device and abnormality determination method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a thermal cycle device capable of determining whether or not a reaction liquid is in a state in which a desired thermal cycle can be applied to the reaction liquid, and further to provide an abnormality determination method of the thermal cycle device.SOLUTION: The thermal cycle device includes: a mounting section for mounting a reaction vessel that is filled with a reaction liquid and a liquid having a specific gravity different from that of the reaction liquid and not mixed with the reaction liquid and includes a flow passage being moved along an inner wall which the reaction liquid faces; a temperature gradient forming section for forming a temperature gradient with respect to the flow passage in a direction in which the reaction liquid is moved; a driving mechanism for switching dispositions of the mounting section and the temperature gradient forming section between a first disposition and a second disposition having a lowest position of the flow passage in a direction in which gravity acts different from that of the first disposition; a detecting section for detecting intensity of light having a predetermined wavelength; and a determining section for determining whether or not a state of the reaction vessel is abnormal on the basis of the intensity of light detected by the detecting section. Either the reaction liquid or the liquid not mixed with the reaction liquid filled in the reaction vessel includes a fluorescent material emitting light having the predetermined wavelength.

Description

  The present invention relates to a heat cycle device and an abnormality determination method.

  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, in the conventional method, there are problems that a large amount of reagents and the like are required, and that the apparatus becomes complicated in order to realize a thermal cycle necessary for the reaction, and that the reaction takes time. Therefore, a biochip and a reaction apparatus are required for performing PCR accurately and in a short time using a very small amount of reagent or specimen.

  In order to solve such a problem, Patent Document 1 discloses that a biological sample reaction chip filled with a reaction liquid and mineral oil is rotated around a horizontal rotation axis so that Discloses a biological sample reaction apparatus that moves a reaction solution and performs thermal cycling.

JP 2009-136250 A

  In the biological sample reaction apparatus described in Patent Document 1, in order to apply a desired thermal cycle to the reaction solution, the reaction solution needs to move in the mineral oil. However, for example, if the reaction solution sticks in the biochip and does not move, or if there is a problem in mounting the biochip on the biological sample reaction device, there is a possibility that the desired heat cycle cannot be applied to the reaction solution. .

  The present invention has been made in view of the above problems, and according to some aspects of the present invention, whether or not a desired thermal cycle cannot be applied to a reaction solution, that is, a reaction vessel. It is possible to provide a heat cycle apparatus and an abnormality determination method that can determine whether or not the state of the battery is abnormal.

(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 along the inner wall facing the reaction liquid. A temperature gradient that forms a temperature gradient in the direction in which the reaction solution moves with respect to the flow path when the reaction container including the moving flow path is mounted and the reaction container is mounted on the mounting position. When the reaction vessel is attached to the forming portion and the attaching portion, the placement of the attaching portion and the temperature gradient forming portion is the first placement and the lowest point of the flow path in the direction in which gravity acts. Based on a drive mechanism that switches between a second arrangement different in position from the first arrangement, a detection unit that detects the intensity of light of a predetermined wavelength, and the intensity of the light detected by the detection unit To determine whether the state of the reaction vessel is abnormal That includes a determining unit, wherein the one of the filled in the reaction vessel reaction mixture and the liquid immiscible with the reaction solution includes a fluorescent substance that emits light of the predetermined wavelength.

  The “reaction container state” in the present specification includes the state of the reaction container mounted in the mounting part, the amount of the reaction liquid in the reaction container, and the state of movement of the reaction liquid.

  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 the present embodiment, the detection unit can detect the intensity of light having a predetermined wavelength emitted from the fluorescent substance contained in either the reaction liquid filled in the reaction container or the liquid immiscible with the reaction liquid. . The determination unit can determine whether or not the state of the reaction vessel is abnormal based on the intensity of light of a predetermined wavelength detected by the detection unit. Therefore, it is possible to realize a thermal cycle apparatus that can determine whether or not a desired thermal cycle cannot be applied to the reaction solution.

(2) In the above-described heat cycle apparatus, when the placement of the mounting portion and the temperature gradient forming portion is the first placement or the second placement, the detection portion is in the direction in which gravity acts. You may detect the intensity | strength of the said light of the area | region containing the lowest point of a flow path.

  Since the reaction solution moves in the flow path toward the vicinity of the lowest point in the direction in which gravity acts, when the mounting portion and the temperature gradient forming portion are in the first arrangement or the second arrangement, the gravity solution The reaction solution moves to a region including the lowest point of the flow path in the acting direction. Therefore, by detecting the intensity of light of a predetermined wavelength in the vicinity of the lowest point of the flow path in the direction in which gravity acts, the determination unit can more accurately determine whether there is an abnormality in the movement of the reaction liquid. Can be judged. Therefore, it can be more accurately determined whether or not the state of the reaction vessel is abnormal.

(3) In the above-described thermal cycle apparatus, the reaction liquid filled in the reaction container includes the fluorescent material, and the determination unit is configured such that the mounting unit and the temperature gradient forming unit are arranged by the driving mechanism. When the intensity of the light detected by the detector does not exceed a reference value within a reference time after switching between the first arrangement and the second arrangement, the state of the reaction vessel is You may determine that it is abnormal.

  Since the fluorescent substance that emits light of a predetermined wavelength detected by the detection unit is contained in the reaction liquid filled in the reaction container, the reaction liquid is located near the lowest point in the direction of gravity in the flow path. In the case of movement, the intensity of light detected by the detection unit increases. In other words, if the light intensity does not exceed the reference value within the reference time, the state of the reaction vessel is likely to be abnormal. Therefore, when the intensity of light detected by the detection unit within the reference time does not exceed the reference value, the determination unit determines that the state of the reaction vessel is abnormal, so that the state of the reaction vessel is abnormal. It can be determined according to a predetermined standard.

(4) In the above heat cycle apparatus, the liquid that is immiscible with the reaction liquid filled in the reaction vessel contains the fluorescent material, and the determination unit is configured so that the mounting unit and the temperature gradient forming unit are driven by the drive mechanism. When the intensity of the light detected by the detection unit does not fall below a reference value within a reference time after the arrangement of is switched between the first arrangement and the second arrangement, It may be determined that the state of the reaction vessel is abnormal.

  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 lowest point in the direction in which gravity acts in the flow path When the reaction solution moves in the vicinity, the intensity of light detected by the detection unit becomes small. In other words, if the light intensity does not fall below the reference value within the reference time, the state of the reaction vessel is likely to be abnormal. Accordingly, when the intensity of light detected by the detection unit within the reference time does not fall below the reference value, the determination unit determines that the state of the reaction vessel is abnormal, so that the state of the reaction vessel is abnormal. It can be determined according to a predetermined standard.

(5) In the abnormality determination method according to this embodiment, the reaction liquid and the reaction liquid have different specific gravities and are immiscible with the reaction liquid, and are mixed with the reaction liquid and the reaction liquid. One of the liquids that does not contain a fluorescent substance that emits light of a predetermined wavelength, and a reaction container including a flow path that moves along the inner wall facing the reaction liquid is attached to the attachment part; and Forming a temperature gradient in the direction in which the reaction solution moves with respect to the flow path of the mounted reaction vessel, and arranging the mounting portion in the first arrangement and the direction in which gravity acts. The position of the lowest point of the flow path is switched between the second arrangement different from the first arrangement, the intensity of the light of the predetermined wavelength is detected, and the light detected in the detection Based on the strength of the reaction vessel, the state of the reaction vessel is abnormal Includes performing the whether the determination, the.

  According to this embodiment, the arrangement of the mounting portion is switched between the first arrangement and the second arrangement in which the position of the lowest point of the flow path in the direction in which the gravity acts is different from the first arrangement. . 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. Accordingly, since the reaction solution moves in accordance with gravity in the flow path where the temperature gradient is formed, the reaction solution can be subjected to a thermal cycle. Further, according to this embodiment, the intensity of light having a predetermined wavelength emitted from the fluorescent material contained in the reaction liquid filled in the reaction container or the liquid immiscible with the reaction liquid is detected. Therefore, it can be determined whether or not the state of the reaction vessel is abnormal based on the intensity of light of a predetermined wavelength. Therefore, it is possible to realize an abnormality determination method that can determine whether or not the desired heat cycle cannot be applied to the reaction solution.

(6) In the abnormality determination method described above, when performing the detection, the light in the region including the lowest point of the flow path in the direction in which gravity acts in the first arrangement or the second arrangement. You may detect the intensity | strength of.

  Since the reaction solution moves in the flow path toward the vicinity of the lowest point in the direction in which gravity acts, when the mounting portion is in the first arrangement or the second arrangement, the lowest point of the flow path The reaction solution moves to the region containing. Therefore, it is possible to more accurately determine whether or not there is an abnormality in the movement of the reaction liquid by detecting and determining the intensity of light having a predetermined wavelength in the vicinity of the lowest point of the flow path in the direction in which gravity acts. Therefore, it can be more accurately determined whether or not the state of the reaction vessel is abnormal.

(7) In the abnormality determination method described above, the reaction liquid filled in the reaction container includes the fluorescent material, and when performing the determination, the mounting portion is arranged in the first arrangement and the first arrangement. If the intensity of the light detected in the detection does not exceed a reference value within a reference time after switching between the two arrangements, it is determined that the state of the reaction vessel is abnormal. Also good.

  A fluorescent substance that emits light of a predetermined wavelength is contained in the reaction liquid filled in the reaction vessel, so if the reaction liquid moves near the lowest point of the flow path in the direction of gravity, it will be detected The intensity of the emitted light increases. In other words, if the light intensity does not exceed the reference value within the reference time, the state of the reaction vessel is likely to be abnormal. Therefore, if the intensity of the light detected within the reference time does not exceed the reference value, it is determined whether or not the state of the reaction container is abnormal by determining that the state of the reaction container is abnormal. It can be determined according to the criteria.

(8) In the abnormality determination method described above, the liquid that is immiscible with the reaction liquid filled in the reaction container contains the fluorescent material, and when the determination is performed, the placement of the mounting portion is the first. If the intensity of the light detected in the detection does not exceed a reference value within a reference time after switching between the second arrangement and the second arrangement, the state of the reaction vessel is abnormal. You may determine that there is.

  A fluorescent substance that emits light of a predetermined wavelength is contained in the reaction liquid filled in the reaction vessel, so if the reaction liquid moves near the lowest point of the flow path in the direction of gravity, it will be detected The intensity of the emitted light is reduced. In other words, if the light intensity does not fall below the reference value within the reference time, the state of the reaction vessel is likely to be abnormal. Therefore, when the intensity of the light detected within the reference time does not fall below the reference value, it is determined whether or not the state of the reaction vessel is abnormal by determining that the state of the reaction vessel is abnormal. It can be determined according to the criteria.

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 embodiment. The flowchart for demonstrating the abnormality determination method which concerns on embodiment. The flowchart for demonstrating the 1st specific example of an abnormality determination method. The graph which shows the intensity | strength of the light in the 1st specific example of an abnormality determination method. The flowchart for demonstrating the 2nd specific example of an abnormality determination method. The graph which shows the intensity | strength of the light in the 2nd specific example of an abnormality determination method.

  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 Driving mechanism 20 for switching the position of the lowest point of the flow path 110 between a second arrangement different from the first arrangement, a detection section 40 for detecting the intensity of light of a predetermined wavelength, and a detection section 40 And a determination unit 50 that determines whether or not the state of the reaction vessel 100 is abnormal based on the intensity of the light detected by. In addition, 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.

  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. In addition, 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 temperatures of the first heating unit 12 and the second heating unit 13 may be controlled by a temperature sensor (not shown) and a control unit 60 described 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. For example, as shown in FIG. 1B and FIG. 2, the structure in which the reaction vessel 100 and the mounting portion 11 are fitted with each other fits the protrusion 113 provided in the reaction vessel 100 into the recess 80 provided in the mounting portion 11. The structure 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. 3, 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” and “reaction of 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 portion 11, so that the gravity of the flow channel 110 of the reaction vessel 100 mounted on the mounting portion 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.

  When the placement of the mounting portion 11 and the temperature gradient forming portion 30 is the first placement or the second placement, the detection unit 40 includes the light in the region including the lowest point of the flow path 110 in the direction in which gravity acts. You may detect the intensity | strength of. 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 or the second arrangement, The reaction solution 140 moves to a region including the lowest point of the flow path 110 in the direction in which gravity acts. For this reason, 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 the gravity acts, thereby determining whether there is an abnormality in the movement of the reaction solution 140. Can be determined more accurately. Therefore, it can be more accurately determined whether or not the state of the reaction vessel 100 is abnormal.

  In addition, when the mounting unit 11 and the temperature gradient forming unit 30 are in the first arrangement or the second arrangement, a Selfoc lens or the like focused on the vicinity of the lowest point of the flow path 110 in the direction in which gravity acts. When the mounting part 11 and the temperature gradient forming part 30 are in the first arrangement or the second arrangement, the sensitivity to light from the vicinity of the lowest point in the direction in which gravity acts in the flow path 110 is increased. May be.

  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 the state of the reaction vessel 100. 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 device 1 includes a determination unit 50. The determination unit 50 determines whether or not the state of the reaction container 100 is abnormal based on the light intensity detected by the detection unit 40. The determination unit 50 may be configured to perform the determination described above by being realized by a dedicated circuit. Further, the determination unit 50 functions as a computer by executing a 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). The above-described determination may be performed. In this case, the storage device may have a work area for temporarily storing intermediate data and control results associated with the control.

  The heat cycle apparatus 1 may include a control unit 60. The control unit 60 controls at least one of the drive mechanism 20 and the temperature gradient forming unit 30. Examples of control by the control unit 60 will be described in detail in the sections of “3. Control example of thermal cycle device” and “4. Abnormality determination method”. The control unit 60 may be configured to perform a control described later by being realized by a dedicated circuit. Further, the control unit 60 functions as a computer by, for example, a CPU (Central Processing Unit) executing a control program stored in a storage device (not shown) such as a ROM (Read Only Memory) or a RAM (Random Access Memory). 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 60 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, for example, among the first temperature, the second temperature, the duration of the first arrangement, the duration of the second arrangement, and the number of cycles of the thermal cycle as the heat cycle conditions , At least one may be set. The operation unit 25 is mechanically or electronically linked to the control unit 60, and settings in the operation unit 25 are reflected in the control by the control unit 60. 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 above items, for example, when one of a plurality of pre-registered thermal cycle conditions is selected, the control unit 60 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 with respect to light having a predetermined wavelength to such an extent that the 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 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, the liquid 130 may include a fluorescent material that emits light of a second wavelength different from the first wavelength. 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 substance that emits light of the first wavelength, the reaction liquid 140 may contain a fluorescent substance 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 the fluorescent substance is a fluorescent probe that binds complementarily to a specific DNA, the intensity of light of the second wavelength is measured. 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.

4). Abnormality Determination Method FIG. 5 is a functional block diagram of the heat cycle apparatus 1 according to the present embodiment. FIG. 6 is a flowchart for explaining the abnormality determination method according to the present embodiment.

  In the abnormality determination method according to the present embodiment, the reaction liquid 140 is filled with a liquid 130 having a specific gravity different from that of the reaction liquid 140 and immiscible with the reaction liquid 140, and one of the reaction liquid 140 and the liquid 130 is filled. Includes a fluorescent substance that emits light of a predetermined wavelength, and the reaction vessel 100 including the flow channel 110 that moves along the opposing inner wall of the reaction solution 140 is attached to the attachment portion 11 and attached to the attachment portion 11. A temperature gradient is formed in the direction in which the reaction solution 140 moves with respect to the flow path 110 of the reaction vessel 100, and the arrangement of the mounting portion 11 is changed between the first arrangement and the flow path 110 in the direction in which gravity acts. The position of the lowest point is switched between the second arrangement different from the first arrangement, the intensity of light of a predetermined wavelength is detected, and the reaction is performed based on the intensity of the light detected in the detection The state of the container 100 is Includes performing the determining whether or not a normal, the.

  In the example shown in FIG. 6, first, the reaction vessel 100 is mounted on the mounting portion 11 (step S100). 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. In addition, one of the reaction liquid 140 and the liquid 130 includes a fluorescent material that emits light of a predetermined wavelength.

  In the example shown in FIG. 6, after step S100, a temperature gradient is formed in the direction in which the reaction solution 140 moves with respect to the flow path 110 of the reaction vessel 100 attached to the attachment unit 11 (step S102). In the present embodiment, as shown in FIG. 5, the control unit 60 outputs control information D6 including information for controlling the temperature gradient forming unit 30 to the temperature gradient forming unit 30, and the temperature gradient forming unit 30 Based on the control information D <b> 6, a temperature gradient is formed in the direction in which the reaction solution 140 moves with respect to the flow path 110 of the reaction vessel 100 attached to the attachment unit 11.

  In the example shown in FIG. 6, after step S102, the placement of the mounting portion 11 is switched between the first placement and the second placement (step S104). In the present embodiment, as shown in FIG. 5, the control unit 60 outputs control information D3 including information for controlling the drive mechanism 20 to the drive mechanism 20, and the drive mechanism 20 is based on the control information D3. The arrangement of the mounting portion 11 is switched between the first arrangement and the second arrangement. In step S104, the number of times of switching the placement of the mounting portion 11 between the first placement and the second placement can be set to any number as necessary.

  In the example shown in FIG. 6, the intensity of light having a predetermined wavelength is detected after step S104 (step S106). In the heat cycle apparatus 1, the detection unit 40 detects the intensity of light having the first wavelength in the reaction vessel 100. In the present embodiment, as illustrated in FIG. 5, the detection unit 40 outputs detection result information D <b> 1 including information related to the detection result to the determination unit 50.

  In the example shown in FIG. 6, after step S106, it is determined whether or not the state of the reaction vessel 100 is abnormal based on the light intensity detected in step S106 (step S108). In the heat cycle apparatus 1, the determination unit 50 determines whether or not the state of the reaction vessel 100 is abnormal based on the intensity of light detected by the detection unit 40. In the present embodiment, as shown in FIG. 5, the determination unit 50 determines whether or not the state of the reaction vessel 100 is abnormal based on the detection result information D <b> 1 output by the detection unit 40. The determination result information D <b> 2 including the information related to the result of performing is output to the control unit 60.

  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 intensity of light having a predetermined wavelength emitted from the fluorescent substance contained in the reaction liquid 140 filled in the reaction vessel 100 or the liquid 130 immiscible with the reaction liquid 140 is detected. Therefore, it can be determined whether or not the state of the reaction vessel 100 is abnormal based on the intensity of light of a predetermined wavelength. Therefore, it is possible to realize an abnormality determination method that can determine whether or not the desired heat cycle cannot be applied to the reaction solution.

  When performing the detection in step S106, the intensity of light from the region including the lowest point of the flow path 110 in the direction in which gravity acts in the first arrangement or the second arrangement may be detected. Since the reaction liquid 140 moves in the flow path 110 toward the vicinity of the lowest point in the direction in which the gravity acts, when the mounting portion 11 is in the first arrangement or the second arrangement, The reaction solution 140 moves to a region including the lowest point. Therefore, it is possible to more accurately determine whether or not there is an abnormality in the movement of the reaction solution 140 by detecting and determining the intensity of light of a predetermined wavelength in the vicinity of the lowest point of the flow path 110 in the direction in which gravity acts. it can. Therefore, it can be more accurately determined whether or not the state of the reaction vessel 100 is abnormal.

  Note that step S102 can be performed at any desired timing after step S100. That is, step S102 may be performed after step S104, may be performed after step S106, or may be performed after step S108.

  In the example shown in FIG. 6, the number of determinations in step S <b> 108 performed after the reaction container 100 is mounted on the mounting unit 11 is one. As a case where the state of the reaction vessel 100 is abnormal, either the case where the reaction vessel 100 itself containing the reaction liquid 140 and the liquid 130 is abnormal or the state where the reaction vessel 100 is attached to the mounting portion 11 is abnormal. It is considered that this is likely. In many of these cases, the presence or absence of an abnormality can be determined by performing one determination after step S104. Therefore, the presence or absence of abnormality can be determined with a small number of determinations.

  In addition, the number of times of performing the determination in step S108 performed after mounting the reaction container 100 on the mounting unit 11 may be a plurality of times. In this case, steps S104 to S108 are repeated a plurality of times in the flowchart shown in FIG. Accordingly, even when an abnormality occurs in the state of the reaction vessel 100 while repeating Step S104 a plurality of times, it is possible to determine whether or not there is an abnormality in Step S108 that is performed first after the abnormality has occurred.

4-1. First Specific Example of Abnormality Determination Method FIG. 7 is a flowchart for explaining a first specific example of the abnormality determination method. In the first specific example of the abnormality determination method for the heat cycle apparatus 1 shown in FIG. 7, the case where the reaction liquid 140 filled in the reaction vessel 100 contains a fluorescent material will be described. In addition, the same code | symbol is attached | subjected to the process same as the flowchart shown by FIG. 6, and detailed description is abbreviate | omitted.

  In the example shown in FIG. 7, first, the reaction vessel 100 is mounted on the mounting portion 11 (step S100). When the reaction container 100 is mounted on the mounting portion 11, the mounting portion 11 is in the first arrangement as shown in FIG. Next, a temperature gradient is formed in the direction in which the reaction solution 140 moves with respect to the flow path 110 of the reaction vessel 100 attached to the attachment unit 11 (step S102).

  In the example shown in FIG. 7, after step S102, the placement of the mounting portion 11 is switched between the first placement and the second placement (step S104). In the first specific example, as shown in FIG. 5, the control unit 60 outputs control information D3 for controlling the drive mechanism 20, and the drive mechanism 20 arranges the placement unit 11 based on the control information D3. After switching from the first arrangement to the second arrangement, the arrangement of the mounting portion 11 is switched from the second arrangement to the first arrangement. That is, the arrangement of the mounting portion 11 is switched twice between the first arrangement and the second arrangement. In addition, as illustrated in FIG. 5, the control unit 60 outputs control timing information D <b> 4 including information related to timing for switching the mounting unit 11 from the second arrangement to the first arrangement to the determination unit 50.

  In the example shown in FIG. 7, the intensity of light having a predetermined wavelength is detected after step S104 (step S106).

  In the example shown in FIG. 7, after step S106, it is determined whether or not the state of the reaction vessel 100 is abnormal based on the light intensity detected in step S104 (step S108). When performing the determination in step S108 in the first specific example, after the placement portion 11 is switched between the first placement and the second placement (in the first specific example, the second placement is determined). The intensity of the light detected in step S106 within the reference time (in the first specific example, the first reference time) after switching from the first to the first arrangement) is a reference value (in the first specific example). When the first reference value V1) is not exceeded, it is determined that the state of the reaction vessel 100 is abnormal. In the first specific example, after the determination unit 50 of the heat cycle apparatus 1 switches the arrangement of the mounting unit 11 and the temperature gradient forming unit 30 between the first arrangement and the second arrangement by the drive mechanism 20. Within the reference time (first reference time) after switching from the second arrangement to the first arrangement, the intensity of light detected by the detection unit 40 becomes the reference value (first reference value V1). If not exceeded, it is determined that the state of the reaction vessel 100 is abnormal.

  Next, a specific example of step S108 will be described. In the example shown in FIG. 7, it is determined whether or not the light intensity detected in step S106 within the first reference time exceeds the first reference value V1 (step S202). In the first specific example, as shown in FIG. 5, the determination unit 50 determines whether the light intensity exceeds the first reference value V1 based on the detection result information D1 output from the detection unit 40. . Further, in the first specific example, as shown in FIG. 5, it is determined whether or not it is within the first reference time based on the control timing information D4 output from the control unit 60.

  If the intensity of light detected in step S106 within the first reference time exceeds the first reference value V1 (YES in step S202), it is determined that the state of the reaction vessel 100 is normal (step) S204). If the intensity of the light detected in step S106 does not exceed the first reference value V1 within the first reference time (NO in step S202), it is determined that the state of the reaction vessel 100 is abnormal ( Step S206).

  As the first reference time, a time sufficient for the reaction solution 140 to move from the second region 112 in the flow path 110 of the reaction vessel 100 to the first region 111 is set. The first reference time may be set in consideration of the structure of the flow path 110 of the reaction vessel 100, the viscosity of the liquid 130, the specific gravity difference between the liquid 130 and the reaction liquid 140, or may be set experimentally. Good.

  The timing for starting the measurement of the first reference time may be a timing at which the arrangement of the mounting portion 11 and the temperature gradient forming unit 30 starts to be switched by the driving mechanism 20 or a timing at which the switching of the mounting portion 11 and the temperature gradient forming unit 30 is finished. But you can. Hereinafter, a case where the timing for starting the measurement of the first reference time is the timing when the placement of the mounting unit 11 and the temperature gradient forming unit 30 is switched from the second placement to the first placement will be described as an example.

  FIG. 8 is a graph showing the light intensity in the first specific example of the abnormality determination method. 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 t0 is the timing when the placement of the mounting portion 11 and the temperature gradient forming portion 30 is switched from the second placement to the first placement. The time when the first reference time has elapsed from time t0 is time t2. FIG. 8 illustrates three states from the first state to the third state.

  In the first state, after the time t0, at time t1, which is a time within the first reference time, the intensity of light detected by the detection unit 40 exceeds the first reference value V1. Therefore, the determination unit 50 determines that the first state is a normal state.

  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 within the first reference time. Therefore, the determination unit 50 determines that the second state is an abnormal state. 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 time t0, the intensity of the light detected by the detection unit 40 is not high and is constant. Therefore, the determination unit 50 determines that the third state is an abnormal state. 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.

  According to the first specific example, since the fluorescent material that emits light of a predetermined wavelength detected by the detection unit 40 is included in the reaction solution 140 filled in the reaction vessel 100, the flow in the direction in which gravity acts is performed. When the reaction liquid 140 moves near the lowest point of the path 110, the intensity of the detected light increases. In other words, if the light intensity does not exceed the reference value (first reference value V1) within the reference time (first reference time), there is a high possibility that the state of the reaction vessel 100 is abnormal. Therefore, when the intensity of light detected within the reference time (first reference time) does not exceed the reference value (first reference value V1), it is determined that the state of the reaction vessel 100 is abnormal. Whether or not the state of the reaction vessel 100 is abnormal can be determined according to a predetermined criterion.

4-2. Second Specific Example of Abnormality Determination Method FIG. 9 is a flowchart for explaining a second specific example of the abnormality determination method. In the second specific example of the abnormality determination method of the heat cycle apparatus 1 shown in FIG. 9, a case where the liquid 130 filled in the reaction vessel 100 contains a fluorescent material will be described. In addition, the same code | symbol is attached | subjected to the process same as the flowchart shown by FIG.6 and FIG.7, and detailed description is abbreviate | omitted.

  In the second specific example shown in FIG. 9, the processes from step S100 to step S106 are the same as those in the first specific example described with reference to FIG.

  In the example shown in FIG. 9, after step S106, it is determined whether or not the state of the reaction vessel 100 is abnormal based on the light intensity detected in step S104 (step S108). When the determination of step S108 in the second specific example is performed, after the placement of the mounting portion 11 is switched between the first placement and the second placement (in the second concrete example, the second placement is determined). The intensity of light detected in step S106 within a reference time (in the second specific example, the second reference time) after switching from the first to the first arrangement) is a reference value (in the second specific example). If the second reference value V2) does not fall below, it is determined that the state of the reaction vessel 100 is abnormal. In the second specific example, after the determination unit 50 of the heat cycle apparatus 1 switches the arrangement of the mounting unit 11 and the temperature gradient forming unit 30 between the first arrangement and the second arrangement by the drive mechanism 20. The intensity of light detected by the detection unit 40 within a reference time (second reference time) (after switching from the second arrangement to the first arrangement) becomes a reference value (second reference value V2). If not, it is determined that the state of the reaction vessel 100 is abnormal.

  Next, a specific example of step S108 will be described. In the example shown in FIG. 9, it is determined whether or not the intensity of the light detected in step S106 falls below the second reference value V2 within the second reference time (step S212). In the second specific example, as shown in FIG. 5, the determination unit 50 determines whether or not the light intensity is lower than the second reference value V2 based on the detection result information D1 output from the detection unit 40. . In the second specific example, as shown in FIG. 5, it is determined whether or not it is within the second reference time based on the control timing information D4 output from the control unit 60.

  If the light intensity detected in step S106 within the second reference time falls below the second reference value V2 (YES in step S212), it is determined that the state of the reaction vessel 100 is normal (step S214). If the light intensity detected in step S106 does not fall below the second reference value V2 within the second reference time (NO in step S212), it is determined that the state of the reaction vessel 100 is abnormal ( Step S216).

  As the second reference time, a time sufficient for the reaction solution 140 to move from the second region 112 in the flow path 110 of the reaction vessel 100 to the first region 111 is set. The second reference time may be set in consideration of the structure of the flow path 110 of the reaction vessel 100, the viscosity of the liquid 130, the specific gravity difference between the liquid 130 and the reaction liquid 140, or may be set experimentally. Good.

  The timing for starting the measurement of the second reference time may be a timing at which the arrangement of the mounting portion 11 and the temperature gradient forming unit 30 starts to be switched by the driving mechanism 20 or a timing at which the switching of the mounting portion 11 and the temperature gradient forming unit 30 is finished. But you can. In the following, a case where the timing for starting the measurement of the second reference time is a timing when the placement of the mounting unit 11 and the temperature gradient forming unit 30 is switched from the second placement to the first placement will be described as an example.

  FIG. 10 is a graph showing the light intensity in the second specific example of the abnormality determination method. The horizontal axis in FIG. 10 represents time, and the vertical axis represents the intensity of light detected by the detection unit 40.

  In the example shown in FIG. 10, time t <b> 10 is a timing when the placement of the mounting portion 11 and the temperature gradient forming unit 30 is switched from the second placement to the first placement. The time when the second reference time has elapsed from time t10 is time t12. FIG. 10 illustrates three states from the fourth state to the sixth state.

  In the fourth state, after time t10, at time t11, which is a time within the second reference time, the intensity of light detected by the detection unit 40 is lower than the second reference value V2. Therefore, the determination unit 50 determines that the fourth state is a normal state.

  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 within the second reference time. Therefore, the determination unit 50 determines that the fifth state is an abnormal state. 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 lowered but is constant. Therefore, the determination unit 50 determines that the sixth state is an abnormal state. 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.

  According to the second specific example, since the fluorescent material that emits light of a predetermined wavelength detected by the detection unit 40 is included in the liquid 130 filled in the reaction vessel 100, the flow path in the direction in which gravity acts. When the liquid 130 moves in the vicinity of the lowest point 110, the intensity of the detected light decreases. In other words, if the light intensity does not fall below the reference value (second reference value V2) within the reference time (second reference time), the state of the reaction vessel 100 is likely to be abnormal. Therefore, when the intensity of light detected within the reference time (second reference time) does not fall below the reference value (second reference value V2), it is determined that the state of the reaction vessel 100 is abnormal. Whether or not the state of the reaction vessel 100 is abnormal can be determined according to a predetermined criterion.

4-3. Other Modifications The control unit 60 may control the drive mechanism 20 based on the determination result of the determination unit 50. In the example illustrated in FIG. 5, the control information D <b> 3 may be output to the drive mechanism 20 based on the determination result information D <b> 2 output from the determination unit 50. For example, the control unit 60 may stop the operation of the drive mechanism 20 when the determination unit 50 determines that the state of the reaction vessel 100 is abnormal (when the determination result is abnormal). Thereby, when it is determined that the state of the reaction vessel 100 is abnormal, the subsequent thermal cycle process can be stopped.

  The control unit 60 may control the display unit 24 based on the determination result of the determination unit 50. In the example shown in FIG. 5, display information D <b> 5 including information related to contents to be displayed on the display unit 24 may be output to the display unit 24 based on the determination result information D <b> 2 output by the determination unit 50. The display unit 24 displays the specified content based on the display information D5. For example, when the determination unit 50 determines that the state of the reaction vessel 100 is abnormal (when the determination result is abnormal), the control unit 60 causes the display unit 24 to display a message indicating abnormality. Also good. As a result, the user can be notified of the occurrence of an abnormality.

  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, 15 conducting wire, 18 measurement window, 20 drive mechanism, 21 bearing, 23 observation window, 24 display part, 25 operation part, 30 temperature gradient formation part, 31 heat source part, 32 Heat conduction part, 40 detection part, 41a, 42a detector, 41b, 42b slide bar, 50 determination part, 60 control part, 70 lid, 71 fixing part, 80 recess, 100 reaction vessel, 110 flow path, 111 first region , 112 second region, 113 projecting portion, 120 sealing portion, 130 liquid, 140 reaction solution, D1 detection result information, D2 determination result information D3 control information, D4 control timing information, D5 display information, D6 control information, R rotational axis, V1 first reference value, V2 second reference value

Claims (8)

The reaction liquid is mounted with a reaction container having a specific gravity different from that of the reaction liquid and filled with a liquid immiscible with the reaction liquid, and including a flow path in which the reaction liquid moves along the opposing inner wall. And
A temperature gradient forming unit that 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 a predetermined wavelength;
A determination unit that determines whether or not the state of the reaction vessel is abnormal based on the intensity of the light detected by the detection unit;
Including
Either the reaction liquid filled in the reaction container or a liquid immiscible with the reaction liquid contains a fluorescent material that emits light of the predetermined wavelength. The thermal cycle apparatus according to claim 1, wherein
The detection unit includes a region including a lowest point of the flow path in a direction in which gravity acts when the mounting unit and the temperature gradient forming unit are arranged in the first arrangement or the second arrangement. A thermal cycle apparatus for detecting the intensity of the light. The thermal cycle apparatus according to claim 2, wherein
The reaction solution filled in the reaction vessel contains the fluorescent substance,
The determination unit is configured by the detection unit within a reference time after the arrangement of the mounting unit and the temperature gradient forming unit is switched between the first arrangement and the second arrangement by the driving mechanism. A thermal cycle apparatus that determines that the state of the reaction vessel is abnormal when the intensity of the detected light does not exceed a reference value. The thermal cycle apparatus according to claim 2, wherein
The liquid immiscible with the reaction liquid filled in the reaction vessel contains the fluorescent substance,
The determination unit is configured by the detection unit within a reference time after the arrangement of the mounting unit and the temperature gradient forming unit is switched between the first arrangement and the second arrangement by the driving mechanism. A thermal cycle device that determines that the state of the reaction vessel is abnormal when the intensity of the detected light does not fall below a reference value. 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 is light of a predetermined wavelength. Mounting a reaction vessel including a flow path that includes a fluorescent substance that emits a gas and the reaction solution moves along an opposing inner wall; and
Forming a temperature gradient in a direction in which the reaction solution moves with respect to the flow path of the reaction vessel attached to the attachment portion;
Switching the placement of the mounting portion between the first placement and a second placement in which the position of the lowest point of the flow path in the direction in which gravity acts is different from the first placement;
Detecting the intensity of light of the predetermined wavelength;
Determining whether the state of the reaction vessel is abnormal based on the intensity of the light detected in the detection;
An abnormality determination method including In the abnormality determination method according to claim 5,
An abnormality determination method for detecting the intensity of the light in a region including the lowest point of the flow path in a direction in which gravity acts in the first arrangement or the second arrangement when performing the detection. The abnormality determination method according to claim 6,
The reaction solution filled in the reaction vessel contains the fluorescent substance,
In performing the determination, the intensity of the light detected in the detection is within a reference time after the placement of the mounting portion is switched between the first placement and the second placement. An abnormality determination method for determining that the state of the reaction vessel is abnormal when the reference value is not exceeded. The abnormality determination method according to claim 6,
The liquid immiscible with the reaction liquid filled in the reaction vessel contains the fluorescent substance,
In performing the determination, the intensity of the light detected in the detection is within a reference time after the placement of the mounting portion is switched between the first placement and the second placement. An abnormality determination method for determining that the state of the reaction vessel is abnormal when the reference value is not exceeded.

Images