JP5822448B2 - Temperature control device and temperature element - Google Patents

Description

  The present invention relates to a temperature control device and a temperature element applicable to a PCR method for amplifying a DNA specimen. In particular, the present invention relates to a temperature control device and a temperature element capable of realizing high responsiveness of temperature control for a DNA specimen in a PCR method.

  In general, as a technique for amplifying DNA (Deoxyribonucleic acid, deoxyribonucleic acid), a PCR method (Polymerase chain Reaction) is known. The PCR method is a process of heating or cooling a reaction solution in which a primer, an enzyme, and deoxyribonucleoside triphosphate to be reacted with the DNA sample are added according to a predetermined pattern of a temperature target value over time. This is a technique for amplifying DNA by repeating.

  In a conventional DNA amplification apparatus that amplifies DNA by such a PCR method, an element having a Peltier effect (hereinafter referred to as a “Peltier element”) is used to heat or cool a DNA sample (reaction solution). (See Patent Documents 1 and 2). The Peltier effect is a phenomenon in which heat absorption occurs at a junction when a current is applied to a junction between different conductors, for example, a p-type semiconductor and an n-type semiconductor.

  FIG. 1 is a cross-sectional view showing a schematic configuration of a conventional Peltier element 1.

  The conventional Peltier element 1 is joined to the heat sink 21B, the electrode plates 23P and 23N to which a voltage is applied, the p-type semiconductor 24P and the electrode plate 23N joined to the electrode plate 23P in order from the lower side in FIG. A set of n-type semiconductors 24N, an electrode plate 22A joined to the set, and a heat dissipation plate 21A are stacked.

  In Patent Document 2, a set of metal plates a11 and a12 corresponding to the electrode plates 23P and 23N, a set of p-type semiconductor a4 and n-type semiconductor a3 corresponding to a set of p-type semiconductor 24P and n-type semiconductor 24N, and What consists of metal plate a2 equivalent to electrode plate 22A is called the Peltier element (refer FIG. 6 of patent document 2). However, the object to be controlled to be heated or cooled by the Peltier element referred to in Patent Document 2 is disposed with the heat conducting plates 12 and 22 interposed therebetween (see FIG. 1 of Patent Document 2). That is, in FIG. 1, the object to be controlled is a container 31, and the heat radiation plate 21A is interposed between the container 31 and the electrode plate 22A. It is equivalent that the heat conductive plates 12, 22 and the like are interposed between the metal plate a2 and the metal plate a2. In other words, the heat conductive plates 12, 22 and the like in Patent Document 2 correspond to the heat radiating plate 21A in FIG. Similarly, the lower surface portions of the radiation fins 51 and 52 in Patent Document 2 correspond to the radiation plate 21B of FIG. In summary, Patent Document 2 merely discloses that the temperature control for the temperature-controlled object is executed using the conventional Peltier element 1 of FIG. 1 as it is.

  Hereinafter, for simplification of description, the portion of the conventional Peltier element 1 on the upper surface side in FIG. 1, that is, the heat radiation plate 21 </ b> A and the electrode plate 22 </ b> A are collectively referred to as “A surface portion”. On the other hand, the part on the lower surface side in FIG. 1 of the Peltier element 1, that is, the heat radiation plate 21B and the electrode plates 23P and 23N are collectively referred to as “B surface part”. In addition, the voltage applied so that the electrode plate 23N becomes a high potential and the electrode plate 23P becomes a low potential with reference to the electrode plate 23N is hereinafter referred to as “a positive voltage is applied to the conventional Peltier element 1”. " On the contrary, the fact that the voltage is applied so that the electrode plate 23N is at a low potential and the electrode plate 23P is at a high potential is expressed as “a negative voltage is applied to the conventional Peltier element 1”.

  For example, as shown in FIG. 1, a container 31 containing a DNA sample (reaction solution) is disposed on the side of the A surface of the conventional Peltier element 1, more specifically, on the surface of the heat sink 21A. Suppose that

  In this case, when a positive voltage is applied to the conventional Peltier element 1, a current flows from the electrode plate 23N toward the electrode plate 23P. Specifically, the current flows in the order of the electrode plate 23N, the n-type semiconductor 24N, the electrode plate 22A, the p-type semiconductor 24P, and the electrode plate 23P. As a result, the A surface portion becomes a heat absorbing portion, and the B surface portion becomes a heat generating portion. Specifically, according to the value of the current flowing from the electrode plate 23N toward the electrode plate 23P due to the positive voltage applied to the conventional Peltier element 1, the A surface portion becomes low temperature and the B surface portion becomes high temperature. Temperature difference ΔT occurs. Thereby, the heat of the container 31 is absorbed by the A surface portion, and the container 31 is cooled.

  On the other hand, when a negative voltage is applied to the conventional Peltier element 1, current flows in the opposite direction to that when a positive voltage is applied. Specifically, the current flows in the order of the electrode plate 23P, the p-type semiconductor 24P, the electrode plate 22A, the n-type semiconductor 24N, and the electrode plate 23N. As a result, on the contrary to the case where a plus voltage is applied, the A surface portion becomes a heat generating portion, and the B surface portion becomes a heat absorbing portion. Specifically, depending on the value of the current flowing from the electrode plate 23P toward the electrode plate 23N due to the voltage value of the negative voltage applied to the conventional Peltier element 1, the A surface portion becomes high temperature and the B surface portion becomes low temperature. A temperature difference ΔT is generated. Thereby, the heat generated from the A surface portion is propagated to the container 31, and the container 31 is heated.

  Therefore, the temperature control for the DNA specimen in the PCR method can be realized by variably controlling the value of the current flowing between the electrode plate 23N and the electrode plate 23P so as to correspond to the predetermined pattern of the time transition of the temperature target value. become.

JP 2006-223292 A JP 2007-198718 A

  However, when the conventional DNA amplification apparatus including Patent Documents 1 and 2 is used, the temperature of the DNA sample (reaction solution) sufficiently follows the predetermined pattern of the time transition of the temperature target value in the PCR method. do not do. That is, the conventional DNA amplification apparatus including Patent Documents 1 and 2 cannot sufficiently obtain the temperature control responsiveness to the DNA specimen (reaction solution) in the PCR method.

The present invention has been made in view of such a situation, and an object thereof is to realize a high temperature control responsiveness to a DNA specimen in a PCR method.
In this specification, the term “high responsiveness” is used to mean that the response speed is high.

The temperature control device of the present invention (for example, the DNA amplification device 51 in the embodiment)
In a temperature control device for heating or cooling an object (for example, the plastic tube 82 in the embodiment),
A plurality of temperature elements (for example, temperature elements 61-1 and 61-2 in the embodiment) for heating or cooling the object by the Peltier effect;
A control unit (for example, the temperature control unit 62 in the embodiment) that performs energization control on the temperature element,
Each of the plurality of temperature elements includes:
A set of a first p-type semiconductor (e.g., p-type semiconductor 72P in the embodiment) and a first n-type semiconductor (e.g., n-type semiconductor 72N in the embodiment) that are spaced apart from each other;
A mounting portion (for example, the mounting portion 81 in the embodiment) for mounting the object is provided. The first p-type semiconductor is a first surface, and the second n-type semiconductor is a first surface facing the first surface. A bonding portion (for example, a metal well 71 in the embodiment) to be bonded to each other in the plane of 2;
A first p-side electrode portion (for example, an electrode and heat dissipation plate 73P in the embodiment) that is bonded to the first p-type semiconductor and to which a voltage is applied by the control unit;
A first n-side electrode portion (for example, an electrode and heat dissipation plate 73N in the embodiment) which is bonded to the first n-type semiconductor and to which a voltage is applied by the control unit;
Have
By connecting at least one of the first p-side electrode portion and the first n-side electrode portion of each of the plurality of temperature elements to the first n-side electrode portion or the first p-side electrode portion of another temperature element. A series connection of the plurality of temperature elements is configured,
The control unit executes a first control (for example, main temperature control in the embodiment) that applies different voltages to both ends of the series connection, and as a result, in each of the plurality of temperature elements, the first p-type semiconductor and When a potential difference is generated between the first n-type semiconductor and the junction, the junction portion causes the current to flow from one of the first p-type semiconductor and the first n-type semiconductor to the other and propagates heat, thereby causing the Peltier Produce an effect,
At least a part of the plurality of temperature elements (for example, the temperature element 61-2 in the embodiment) further includes:
A set of a second p-type semiconductor (eg, p-type semiconductor 172P in the embodiment) and a second n-type semiconductor (eg, n-type semiconductor 172N in the embodiment);
A second p-side electrode portion (for example, an electrode and heat dissipation plate 173P in the embodiment) that is bonded to the second p-type semiconductor and to which a voltage is applied by the control unit;
A second n-side electrode portion (for example, an electrode and heat dissipation plate 173N in the embodiment) that is bonded to the second n-type semiconductor and to which a voltage is applied by the control unit;
Have
The junction site is a third surface different from the second and second surfaces from the second p-type semiconductor, and a fourth surface opposite to the third surface from the second n-type semiconductor. Joined to each,
Independently of the first control, the controller further applies different voltages to the second p-side electrode part and the second n-side electrode part for each of at least some of the plurality of temperature elements. The second control to be applied (for example, sub temperature control in the embodiment) is executed,
As a result, when a potential difference is generated between the second p-type semiconductor and the second n-type semiconductor, the junction portion flows current from one of the second p-type semiconductor and the second n-type semiconductor to the other. Propagating heat to produce the Peltier effect,
It is a temperature control device.

  According to the present invention, the junction portion provided in the temperature element is directly joined to the p-type semiconductor and the n-type semiconductor, and allows current to flow from one of the p-type semiconductor and the n-type semiconductor to the other and propagates heat. , Has the function of producing a Peltier effect. A mounting portion is provided at the bonding site, and a predetermined container containing a DNA sample can be directly mounted on the mounting portion. Therefore, the DNA specimen is directly heated or cooled by the joining part without interposing a delay element for the temperature control system (for example, the heat radiation plate 21A of the conventional Peltier element 1 in FIG. 1). As a result, compared with the case where the conventional Peltier device 1 is adopted, high responsiveness of temperature control is realized.

Furthermore, the second control for individually controlling the temperature for each of at least some of the plurality of temperature elements independently of the first control for simultaneously controlling the temperatures for the plurality of temperature elements connected in series. Is executed.
As a result, it is possible to absorb the influence of variation between the plurality of temperature elements and make the temperature changes of the plurality of temperature elements substantially the same.

  In this case, the object is a predetermined container used for accommodating a DNA (Deoxyribonucleic acid) sample, and the container is mounted on the mounting portion.

  By applying the present invention to the PCR method, it is possible to cause the temperature of the DNA specimen to follow the predetermined pattern of the time transition of the temperature target value. That is, high responsiveness of temperature control for a DNA sample in the PCR method can be realized.

  In this case, a cooling unit that cools at least one of the first p-side electrode part, the first n-side electrode part, the second p-side electrode part, and the second n-side electrode part of the temperature element (for example, in the embodiment) A water cooling unit 63) may be further provided.

  Furthermore, in this case, the temperature control device may be a portable device. A portable device refers to a device that can be freely carried by a human.

The temperature element of the present invention (for example, the temperature element 61 in the embodiment)
In a temperature element that heats or cools an object (for example, the plastic tube 82 in the embodiment) by the Peltier effect,
A set of a first p-type semiconductor (e.g., p-type semiconductor 72P in the embodiment) and a first n-type semiconductor (e.g., n-type semiconductor 72N in the embodiment) that are spaced apart from each other;
A set of a second p-type semiconductor (for example, the p-type semiconductor 172P in the embodiment) and a second n-type semiconductor (for example, the n-type semiconductor 172N in the embodiment) that are spaced apart from each other;
It has a mounting part (for example, mounting part 81 in the embodiment) for mounting the object, the first p-type semiconductor on the first surface, and the first n-type on the second surface facing the first surface. The semiconductor is joined to the second p-type semiconductor at a third surface different from the first surface and the second surface, and to the second n-type semiconductor at a fourth surface opposite to the third surface. A bonding site (for example, the metal well 71 in the embodiment);
A first p-side electrode portion (for example, an electrode and heat dissipation plate 73P in the embodiment) that is joined to the first p-type semiconductor and to which a voltage is applied from the outside;
A first n-side electrode portion (for example, an electrode and heat dissipation plate 73N in the embodiment) that is joined to the first n-type semiconductor and to which a voltage is applied from the outside;
A second p-side electrode portion (for example, an electrode and heat dissipation plate 173P in the embodiment) that is joined to the second p-type semiconductor and to which a voltage is applied from the outside;
A second n-side electrode portion (for example, an electrode and heat dissipation plate 173N in the embodiment) that is joined to the second n-type semiconductor and to which a voltage is applied from the outside;
With
First control (for example, main temperature control in the embodiment) in which a different voltage is applied from the outside between the first p-side electrode portion and the second n-side electrode portion is executed, and the first p-type semiconductor and the first When a potential difference is generated between the n-type semiconductor and the 1n-type semiconductor, the junction portion causes the Peltier effect to flow by passing current from one of the first p-type semiconductor and the first n-type semiconductor to the other and propagating heat. As well as
Second control (for example, sub-temperature control in the embodiment) in which a different voltage is externally applied between the second p-side electrode part and the second n-side electrode part is executed independently of the first control. When a potential difference is generated between the second p-type semiconductor and the second n-type semiconductor, the junction portion causes a current to flow from one of the second p-type semiconductor and the second n-type semiconductor to the other and generates heat. It is a temperature element that causes the Peltier effect by propagating.

  According to the present invention, the junction portion provided in the temperature element is directly joined to the p-type semiconductor and the n-type semiconductor, and allows current to flow from one of the p-type semiconductor and the n-type semiconductor to the other and propagates heat. , Has the function of producing a Peltier effect. A mounting portion is provided at the joining portion, and an object to be cooled or heated can be directly mounted on the mounting portion. Therefore, the object is directly heated or cooled by the joining portion without interposing a delay element for the temperature control system (for example, the heat radiation plate 21A of the conventional Peltier element 1 in FIG. 1). As a result, compared with the case where the conventional Peltier device 1 is adopted, high responsiveness of temperature control is realized. Therefore, by applying the temperature element according to the present invention to the PCR method, that is, by adopting a predetermined container that can contain a DNA sample as the object, a predetermined pattern of the time transition of the temperature target value in the PCR method On the other hand, the temperature of the DNA sample can be made to follow the temperature. That is, high responsiveness of temperature control for a DNA sample in the PCR method can be realized.

  Further, when such temperature elements are used in series connection, first control for controlling the temperature at once for a plurality of temperature elements connected in series, and each of at least some of the plurality of temperature elements In contrast, it is possible to execute the control independently of the second control that individually controls the temperature. As a result, it is possible to absorb the influence of variation between the plurality of temperature elements and make the temperature changes of the plurality of temperature elements substantially the same.

  According to the present invention, high responsiveness of temperature control for a DNA sample in the PCR method can be realized.

It is sectional drawing which shows schematic structure of the conventional Peltier device. It is a top view which shows schematic structure of the DNA amplification apparatus which concerns on one Embodiment of this invention. It is a perspective view which shows schematic structure of the metal well of the temperature element of the DNA amplification apparatus of FIG. FIG. 3 is a top view showing a schematic configuration of the temperature element of the DNA amplification apparatus of FIG. 2 when two sets of a p-type semiconductor and an n-type semiconductor are arranged in parallel. It is a perspective view of schematic structure of the temperature element of FIG. 6 is a schematic configuration of the temperature element of FIG. 4, and is a perspective view of a configuration different from that of FIG. 5. FIG. 3 is a top view showing a schematic configuration of the temperature element of the DNA amplification apparatus of FIG. 2 when two sets of a p-type semiconductor and an n-type semiconductor are arranged in series. It is a perspective view of schematic structure of the temperature element of FIG. FIG. 3 is a top view showing a schematic configuration of a DNA amplification apparatus according to an embodiment of the present invention, which is different from FIG. FIG. 10 is a diagram illustrating a result of temperature control performed on each of two temperature elements connected in series shown in FIG. 9 when performing a PCR test under the same conditions. FIG. 4 is a diagram showing a comparison between a case where the test of the PCR method under the same conditions is realized by using the conventional DNA amplification device including the conventional Peltier device of FIG. 1 and the case of using the DNA amplification device of FIG. is there.

  Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

  FIG. 2 is a top view showing a schematic configuration of the DNA amplification device 51 according to one embodiment of the present invention.

  The DNA amplification device 51 includes a temperature element 61, a temperature control unit 62, and a water cooling unit 63. The temperature element 61 includes a metal well 71, a set of a p-type semiconductor 72P and an n-type semiconductor 72N, electrode and heat dissipation plates 73P and 73N, and water pipes 74P and 74N, in order to cool or heat the object by the Peltier effect. Is provided.

  As shown in FIG. 2, a water pipe 74P is connected to the electrode / heat radiating plate 73P, and a water pipe 74N is connected to the electrode / heat radiating plate 73N. The water cooling section 63 cools each of the electrode / heat radiating plates 73P and 73N by keeping water flowing through each of the water pipes 74P and 74N, and keeps the temperature constant. That is, the electrode / heat radiating plates 73P and 73N have the same function as the heat radiating plate 21B of the conventional Peltier element 1 shown in FIG.

  Further, each of the electrode / heat radiating plates 73 </ b> P and 73 </ b> N is electrically connected to the temperature control unit 62, and a voltage is applied by the temperature control unit 62. That is, the electrode / heat radiating plate 73P has the same function as the electrode plate 23P of the conventional Peltier element 1 of FIG. 1, and the electrode / heat radiating plate 73N is the same as the electrode plate 23N of the conventional Peltier element 1 of FIG. It has the function of Hereinafter, these functions are referred to as “voltage applied functions”. Although details will be described later, the temperature control using the temperature element 61 is performed by controlling the polarity (current polarity) and the current value of the voltage applied to the electrode / heat dissipation plates 73P and 73N by the temperature control unit 62. Realized.

  As long as the electrode and heat dissipation plates 73P and 73N have a heat dissipation plate function and a voltage applied function, the materials and structures thereof may be arbitrary. However, a material having high thermal conductivity and low electrical resistance is suitable as a material for the electrode and heat sinks 73P and 73N in order to further exhibit the heat sink function and the voltage application function. In this embodiment, copper (Cu) is employed as such a material.

  One end of a p-type semiconductor 72P is joined to the electrode / heat sink 73P, while one end of an n-type semiconductor 72N is joined to the electrode / heat sink 73N. That is, the p-type semiconductor 72P has the same function as the p-type semiconductor 24P of the conventional Peltier element 1 of FIG. 1, and the n-type semiconductor 72N is the same as the n-type semiconductor 24N of the conventional Peltier element 1 of FIG. It has the function of

  The pair of the p-type semiconductor 72P and the n-type semiconductor 72N may have any material, structure, etc., as long as the Peltier effect is achieved. However, in the present embodiment, bismuttel which can obtain a larger Peltier effect is adopted as a material of a set of the p-type semiconductor 72P and the n-type semiconductor 72N.

  The other end of the p-type semiconductor 72P is directly joined to the side surface 71a of the metal well 71, while the other end of the n-type semiconductor 72N is directly joined to the side surface 71b facing the side surface 71a of the metal well 71. ing.

  Here, the term “direct bonding” or “direct mounting” in this specification refers to bonding or mounting that does not intervene what is a delay factor for the temperature control system (for example, the heat dissipation plate 21A of the conventional Peltier element 1 in FIG. 1). Means. Therefore, of course, there may be a case where a target material for joining the p-type semiconductor 72P and the n-type semiconductor 72N and the metal well 71 are interposed. Specifically, for example, in this embodiment, the surface of the set of the p-type semiconductor 72P and the n-type semiconductor 72N is plated with nickel, and further joined to the metal well 71 with a low melting point alloy such as GaIn. . That is, in this embodiment, nickel for plating and a low-melting-point alloy are employed as materials for joining the two. Note that the bonding method of the present embodiment is merely an example, and for example, a bonding method of plating with a metal other than nickel, a bonding method of double plating, a bonding method of using other materials as a low melting point alloy, a low melting point Various joining methods such as a joining method by soldering instead of an alloy can be employed.

  In other words, the metal well 71 has a function of directly joining a set of the p-type semiconductor 72P and the n-type semiconductor 72N, that is, a function similar to that of the electrode plate 22A of the conventional Peltier element 1 of FIG. That is, the function is a function that causes a Peltier effect by flowing current and propagating heat from one of the p-type semiconductor 72P and the n-type semiconductor 72N to the other. Hereinafter, this effect is referred to as “bridge and electrode function”.

  As long as the metal well 71 has a bridge and electrode function, its material, structure, etc. may be arbitrary. However, it is preferable that the metal well 71 is made of a material having a low electric resistance in order to further exhibit the bridge and electrode function. For example, copper (Cu) or aluminum (Al) is preferably used. is there. In addition, the aluminum here includes not only pure aluminum but also an aluminum alloy. In the present embodiment, a predetermined aluminum alloy is employed.

  What should be noted here is that a mounting portion 81 for directly mounting an object to be heated or cooled is provided on the upper surface 71 u of the metal well 71.

  FIG. 3 is a diagram showing a schematic configuration of a metal well 71 having such a mounting portion 81. Specifically, FIG. 3A is a side view showing a schematic configuration of a plastic tube 82 that is an example of an object directly attached to the attachment portion 81. FIG. 3B is a perspective view showing a schematic configuration of a metal well 71 having a mounting portion 81 to which such a plastic tube 82 can be directly mounted. Note that the various dimensions shown in FIG. 3 (locations where mm is described) are dimensions employed in the present embodiment and are merely examples.

  In the present embodiment, since the temperature element 61 is provided in the DNA amplifying apparatus 51, the object heated or cooled by the temperature element 61 is precisely a DNA specimen (reaction solution). However, since it is difficult to directly heat or cool the DNA specimen (reaction solution), it is accommodated in a plastic tube 82 as shown in FIG. 3A and heated or cooled. Therefore, in the following description, it is assumed that the object to be heated or cooled is the plastic tube 82 used for housing the DNA specimen (reaction solution).

  As shown in FIG. 3B, a concave portion that matches the shape of the lower portion of the plastic tube 82 (the portion in which the dimension of 12 mm in FIG. 3A is described) is the upper surface of the metal well 71 as the mounting portion 81. It is formed from the center of 71u to the inside downward. In other words, the mounting portion 81 is processed to mount the plastic tube 82.

  Thus, in the present embodiment, the plastic tube 82 used for housing the DNA specimen (reaction solution) is directly attached to the attachment portion 81. If the conventional Peltier device 1 of FIG. 1 is used as an example, the container 31 corresponds to the plastic tube 82 and the electrode plate 22A has a bridge and electrode function. 31 is equivalent to being directly mounted inside the electrode plate 22A without the heat sink 21A interposed.

  That is, when the container 31 is heated or cooled using the conventional Peltier device 1 of FIG. 1, the container 31 performs heat transfer with the electrode plate 22A having a bridge and electrode function through the heat radiating plate 21A. become. Therefore, in the temperature control system for heating or cooling the container 31 using the conventional Peltier element 1, the heat radiating plate 21A formed of ceramic or the like becomes a delay element. The responsiveness of temperature control using the conventional Peltier device 1 of FIG. 1 is deteriorated by this delay factor.

  On the other hand, in the temperature control system of this embodiment, that is, the temperature control system that heats or cools the plastic tube 82 using the temperature element 61, the plastic tube 82 is a delay element such as the conventional heat sink 21A. Heat can be directly exchanged with the metal well 71 having the function of a bridge and an electrode, without intervening. Therefore, the responsiveness of the temperature control of the present embodiment is higher than the case of using the conventional Peltier element 1 of FIG. Details of such effects will be described later with reference to FIG.

  Next, the operation of the above DNA amplification device 51 will be described.

  As described above, from a functional point of view, the electrode and heat dissipation plates 73P and 73N of the present embodiment have a heat dissipation plate function and a voltage applied function, so that the heat dissipation plate 21B and the electrode plate of the conventional Peltier element 1 of FIG. It corresponds to 23P and 23N. Therefore, the electrode and heat dissipation plates 73P and 73N behave the same as the B surface portion of the conventional Peltier element 1. Therefore, hereinafter, the electrode / heat dissipating plates 73P and 73N are appropriately referred to as “B surface portions” in the temperature element 61 of the present embodiment.

  On the other hand, from a functional point of view, the metal well 71 has a bridge and electrode function, and thus corresponds to the electrode plate 22A of the conventional Peltier element 1 shown in FIG. Therefore, the metal well 71 behaves the same as the A-plane portion of the conventional Peltier element 1. Therefore, hereinafter, the metal well 71 is appropriately referred to as an “A surface portion” in the temperature element 61 of the present embodiment. Here, it should be noted that the A surface portion of the temperature element 61 of the present embodiment is a delay element for the temperature control system, such as the heat sink 21A of the A surface portion of the conventional Peltier element 1. It is a point that does not exist.

  Further, in the present embodiment, the voltage is applied by the temperature control unit 62 so that the electrode / heat dissipation plate 73N is at a high potential and the electrode / heat dissipation plate 73P is at a low potential with reference to the electrode / heat dissipation plate 73N side. Hereinafter, this is expressed as “a positive voltage is applied to the temperature element 61”. Conversely, the voltage is applied by the temperature control unit 62 so that the electrode / heat sink 73N is at a low potential and the electrode / heat sink 73P is at a high potential. "Applied".

  In this case, when a positive voltage is applied to the temperature element 61 by the temperature control unit 62, a current flows from the right to the left in FIG. Specifically, the current flows in the order of the electrode / heat radiating plate 73N, the n-type semiconductor 72N, the metal well 71, the p-type semiconductor 72P, and the electrode / heat radiating plate 73P. As a result, the metal well 71 which is the A surface portion becomes the heat absorbing portion. That is, the heat generated from the plastic tube 82 (FIG. 3) directly attached to the metal well 71 which is the A-surface portion is directly absorbed by the metal well 71, thereby cooling the plastic tube 82.

  Specifically, according to the value (absolute value) of the current that flows due to the positive voltage applied to the temperature element 61, the metal well 71 that is the A-surface part becomes a low temperature, and the electrode and heat dissipation plate 73P that is the B-surface part. A temperature difference ΔT is generated such that 73N becomes high temperature.

  Here, the low temperature of the A surface portion does not mean a low temperature in an absolute sense, but means that the temperature is relatively low with respect to the temperature of the B surface portion. That is, as described above, the electrode / radiation plates 73P and 73N which are the B surface portions are water-cooled by the water-cooling unit 63 and maintained at a constant temperature. Hereinafter, such a constant temperature on the side of the electrodes and heat radiation plates 73P and 73N which is the B surface portion is referred to as a “reference temperature”. Therefore, the metal well 71 which is the A-plane portion is cooled to a temperature lower than the reference temperature by a temperature difference ΔT.

  Although the temperature difference ΔT has a certain limit, the temperature difference ΔT increases as the value (absolute value) of the current flowing by the plus voltage applied to the temperature element 61 increases. Accordingly, the temperature control unit 62 gradually increases the temperature difference ΔT by gradually increasing the value (absolute value) of such current, that is, the metal well 71 that is the A surface portion. The temperature can be lowered gradually. In this case, since the plastic tube 82 is directly cooled by the metal well 71, the responsiveness of the temperature control is high compared to the case where the plastic tube 82 is cooled via a delay element such as the conventional heat sink 21A of FIG. Become a thing. That is, in this embodiment, since the temperature control target value is given as a current value by the temperature control unit 62, the followability of the temperature drop of the object (plastic tube 82) with respect to the temperature control target value is high.

  After that, when the polarity of the output voltage is reversed by the temperature control unit 62, that is, when a negative voltage is applied to the temperature element 61, the current is the left in FIG. 2 in the direction opposite to the case where the positive voltage is applied. Flows from one side to the right. Specifically, the current flows in the order of the electrode / heat sink 73P, the p-type semiconductor 72P, the metal well 71, the n-type semiconductor 72N, and the electrode / heat sink 73N. As a result, the metal well 71, which is the A-surface portion, is now a heat generating portion. That is, the heat generated from the metal well 71 that is the A-surface portion is directly propagated to the plastic tube 82, whereby the plastic tube 82 is heated.

  More specifically, when a negative voltage is applied to the temperature element 61, the metal well 71, which is the A surface portion, is heated to a temperature higher than the reference temperature by a temperature difference ΔT. Although the temperature difference ΔT has a certain limit, the temperature difference ΔT increases as the value (absolute value) of the current flowing by the minus voltage applied to the temperature element 61 increases. Accordingly, the temperature control unit 62 gradually increases the temperature difference ΔT by gradually increasing the value (absolute value) of such current, that is, the metal well 71 that is the A surface portion. The temperature can be increased gradually. In this case, since the plastic tube 82 is directly heated by the metal well 71, the responsiveness of the temperature control is high as compared with the case where the plastic tube 82 is heated via a delay element such as the conventional heat sink 21A of FIG. Become a thing. In other words, the temperature control target value is given as a current value by the temperature control unit 62 here, so that the follow-up of the temperature rise of the object (plastic tube 82) with respect to the temperature control target value is high.

  Thus, the temperature control unit 62 can perform temperature control on the plastic tube 82 using the temperature element 61 by changing the polarity (current polarity) of the output voltage and the current value. Therefore, the PCR method can be easily realized by providing the temperature control unit 62 with a predetermined pattern of time transition of the output current as a predetermined pattern of time transition of the temperature target value. That is, the DNA specimen (reaction solution) stored in the plastic tube 82 is heated or cooled by the thermal cycle of the temperature element 61 that changes according to the predetermined pattern, and as a result, the DNA is amplified.

  It should be noted that the present invention is not limited to the present embodiment, and modifications, improvements, etc. within a scope that can achieve the object of the present invention are included in the present invention.

  For example, the number of pairs of p-type semiconductors and n-type semiconductors is only one pair such as the pair of p-type semiconductor 72P and n-type semiconductor 72n in the embodiment of FIG. It can be.

  For example, as shown in FIG. 4 to FIG. 8, two sets such as a first set of p-type semiconductor 72P1 and n-type semiconductor 72N1 and a second set of p-type semiconductor 72P2 and n-type semiconductor 72N2 may be employed.

  FIG. 4 is a top view showing a schematic configuration of the temperature element 61 when the first set and the second set are arranged in parallel. FIG. 5 is a perspective view of a schematic configuration of the temperature element 61. FIG. 6 is a schematic configuration of the temperature element 61, and is a perspective view of a configuration different from that of FIG. However, in FIG.5 and FIG.6, illustration of the electrode and heat sinks 73P and 73N is abbreviate | omitted. When it is necessary to individually distinguish the configurations of FIG. 5 and FIG. 6, the temperature element 61 having the configuration of FIG. 5 is particularly referred to as “temperature element 61a”, and the temperature element 61 having the configuration of FIG. This will be referred to as “element 61b”.

  As shown in FIG. 4, one end of the first set of p-type semiconductors 72P1 and the second set of p-type semiconductors 72P2 is joined to the electrode and heat dissipation plate 73P, and the other end is joined to the side surface 71a of the metal well 71. The On the other hand, one end of the first set of n-type semiconductors 72N1 and the second set of n-type semiconductors 72N2 are joined to the electrode / heat dissipation plate 73N, and the other end is joined to the side surface 71b of the metal well 71.

  Such a disposition relationship between the first set and the second set is not particularly limited as long as they are in parallel. For example, in the temperature element 61a of FIG. 5, the first set and the second set are arranged in the vertical direction, respectively. For example, in the temperature element 61b of FIG. 6, the first set and the second set are respectively arranged in the horizontal direction. Further, the number of sets in parallel is not particularly limited to two sets of the first set and the second set shown in FIGS. 4 to 6 and may be three or more sets.

  FIG. 7 is a top view showing a schematic configuration of the temperature element 61 in the case where the first set and the second set are arranged in series. FIG. 8 is a perspective view showing a schematic configuration of the temperature element 61. However, in FIG. 8, the illustration of the electrode / heat dissipating plates 73P, 73N, and 73PN is omitted.

  When these first and second sets are joined in series, the currents of the first and second sets need to flow independently of each other without being mixed with other sets of currents. . For this reason, as shown in FIG. 7 and FIG. 8, the insulator 91 is inserted so as to divide the metal well 71 from the side surface 71 a to the side surface 71 b of the metal well 71. Thereby, the metal well 71 is divided into two regions 101 and 102.

  In the embodiment of FIGS. 7 and 8, the first set is bonded to the region 101 and the second set is bonded to the region 102. Specifically, for the first set, the n-type semiconductor 72N1 is bonded to the region 101 side of the side surface 71a of the metal well 71, and the p-type semiconductor 72P1 is connected to the region 101 side of the side surface 71b of the metal well 71. Be joined. On the other hand, for the second set, the p-type semiconductor 72P2 is bonded to the region 102 side of the side surface 71a of the metal well 71, and the n-type semiconductor 72N2 is connected to the region 102 side of the side surface 71b of the metal well 71. To be joined.

  In this case, since a voltage is applied to the first set of n-type semiconductors 72N1 and the second set of p-type semiconductors 72P2, the electrode / heat dissipating plate 73N is joined to the first set of n-type semiconductors 72N1, Electrode and heat dissipation plate 73P is joined to the second set of p-type semiconductor 72P2. In order to join the first set and the second set in series, that is, to pass a current from one of the first set of p-type semiconductor 72P1 and the second set of n-type semiconductor 72N2 to the other, An electrode and heat dissipation plate 73PN is joined to the p-type semiconductor 72P1 and the second set of n-type semiconductors 72N2.

  The relationship between the arrangement of the first set and the second set depends on the position where the electrically insulated regions 101 and 102 are formed in the metal well 71. For example, in the example of FIG. 8, since the areas 101 and 102 are formed in the left-right direction, the first set and the second set are arranged in the horizontal direction, respectively. For example, although not shown, when the regions 101 and 102 are formed in the vertical direction, the first set and the second set are arranged in the vertical direction, respectively. In other words, by arbitrarily changing the formation position of the regions 101 and 102 in the metal well 71, the arrangement relationship between the first group and the second group can be arbitrarily changed accordingly.

  Further, the number of series in the set is not particularly limited to two sets of the first set and the second set shown in FIG. 7 and FIG. 8, and may be three or more sets. However, in this case, the metal well 71 is formed with the number of electrically insulated regions corresponding to the number of sets. For each of the plurality of regions, a pair in which the p-type semiconductor 72P is bonded to the side surface 71a and the n-type semiconductor 72N is bonded to the side surface 71b, and an n-type semiconductor 72N is bonded to the side surface 71a and the p-type semiconductor 72P is bonded to the side surface 71b. Are alternately arranged. The electrode / heat dissipating plate 73N is bonded to a predetermined set of n-type semiconductors 72N bonded to the side surface 71a, and the electrode / heat dissipating plate 73P to another set of p-type semiconductors 72P bonded to the side surface 71a. Are joined. One or more electrode / heat radiating plates for joining a plurality of sets in series, such as the electrode / heat radiating plate 73PN, are also provided.

  As described above, several embodiments have been described as embodiments of the present invention from the viewpoint of a set of a p-type semiconductor and an n-type semiconductor. Of course, the present invention can take various embodiments from other viewpoints.

  For example, the cooling method of the electrode and heat radiating plate for maintaining the reference temperature of the temperature element 61 employs the water cooling method by the water cooling unit 63 in the embodiment of FIG. For example, a cooling method using a liquid other than water may be employed, or an air cooling method may be employed.

  Further, for example, the object to be cooled or heated by the temperature element 61 is the plastic tube 82 in the embodiment of FIG. 2, more precisely the DNA specimen (reaction solution) stored in the plastic tube 82, but the metal well 71 The object is not particularly limited as long as it is an object that can be directly mounted on the mounting portion 81. In other words, the shape and the number of the mounting portions 81 of the metal well 71 are not particularly limited to the example of FIG. 3 and can be arbitrarily changed according to the object to be cooled or heated. However, in this case, if the mounting portion 81 is processed in accordance with the shape of the object and is formed in the metal well 71, the response of heating or cooling to the object is further enhanced, which is preferable. It is.

  Further, for example, a plurality of metal wells 71 may be connected to heat or cool the plurality of plastic tubes 82, or the number of mounting portions 81 formed in the metal well 71 may be plural. . That is, in the embodiment of FIG. 2, the number of temperature elements 61 is one, but is not limited to this. For example, a plurality of temperature elements 61 including one or more metal wells 71 are prepared, and a plurality of temperature elements 61 are prepared. The element 61 can also be connected and used.

  Specifically, for example, as shown in FIG. 9, the temperature element 61-1 and the temperature element 61-2 may be connected in series.

  FIG. 9 is a top view showing a schematic configuration of a DNA amplification device 51 according to an embodiment of the present invention when two temperature elements 61-1 and 61-2 are connected in series.

  The DNA amplification device 51 includes two temperature elements 61-1 and 61-2, a temperature control unit 62, and a water cooling unit 63.

Each of the two temperature elements 61-1 and 61-2 includes a metal well 71, a set of a p-type semiconductor 72P and an n-type semiconductor 72N, and an electrode / heat sink to cool or heat the object by the Peltier effect. 73P, 73N and water pipes 74P, 74N are provided.
Each configuration of the two temperature elements 61-1 and 61-2 so far is basically the same as the temperature element 61 of the embodiment of FIG. Therefore, the description of these configurations is omitted.

  The temperature element 61-2 further includes a set of a p-type semiconductor 172P and an n-type semiconductor 172N, electrode and heat dissipation plates 173P and 173N, and water tubes 174P and 174N.

A water pipe 174P is connected to the electrode / heat radiating plate 173P, and a water pipe 174N is connected to the electrode / heat radiating plate 73N.
The water cooling section 63 cools each of the electrode / heat radiation plates 173P and 173N by keeping water flowing through each of the water pipes 174P and 174N, and keeps the temperature constant.
That is, the electrode / heat radiating plates 173P and 173N have the same function as the heat radiating plate 21B of the conventional Peltier element 1 shown in FIG.

  The temperature control unit 62 includes a main control unit 62a and a sub control unit 62b.

The main control unit 62a performs temperature control using each of the temperature elements 61-1 and 61-2 connected in series.
Specifically, the electrode / heat radiating plate 73N of the temperature element 61-1 and the electrode / heat radiating plate 73P of the temperature element 61-2 are electrically connected directly. And the temperature control part 62 is electrically connected between each of the electrode and heat sink 73P of the temperature element 61-1, and each of the electrode and heat sink 73N of the temperature element 61-2.
Therefore, the temperature control unit 62 controls the temperature using each of the temperature elements 61-1 and 61-2 by controlling the polarity (current polarity) and current value of the voltage applied to the electrode and heat dissipation plates 73P and 73N. Control can be performed. Such temperature control performed by the main control unit 62a is hereinafter referred to as “main temperature control”.
Thus, the temperature control unit 62 can perform heating or cooling of the temperature element 61-1 and the temperature element 61-2 simultaneously by performing the main temperature control.

  Here, in the temperature element 61-2, the pair of the p-type semiconductor 72 </ b> P and the n-type semiconductor 72 </ b> N becomes a path through which current flows when main temperature control is performed. Therefore, hereinafter, a set of the p-type semiconductor 72P and the p-type semiconductor 72N is referred to as a “main semiconductor set”. That is, the main control unit 62a performs main temperature control by controlling the current flowing in the series connection of the plurality of main semiconductor groups.

On the other hand, the sub-control unit 62b controls the temperature control using the temperature element 61-2 independently of the main temperature control by controlling the current flowing through the pair of the p-type semiconductor 172P and the n-type semiconductor 172N. And can be done in parallel.
Such temperature control performed by the sub-control unit 62b is hereinafter referred to as “sub-temperature control”.
In the temperature element 61-2, the pair of the p-type semiconductor 172P and the n-type semiconductor 172N serves as a path through which a current flows when the sub-temperature control is performed by the sub-control unit 62b. Therefore, hereinafter, a set of the p-type semiconductor 172P and the p-type semiconductor 172N is referred to as a “sub-semiconductor set”.

Specifically, in the temperature element 61-2, one end of the p-type semiconductor 172P is directly bonded to the side surface 71c orthogonal to the side surface 71a and the side surface 71b of the metal well 71, while one end of the n-type semiconductor 172N is The metal well 71 is directly bonded to the side surface 71d facing the side surface 71c.
The other end of the p-type semiconductor 172P is directly joined to the electrode / heat sink 173P, while the other end of the n-type semiconductor 172N is directly joined to the electrode / heat sink 173N.
And the sub control part 62b is electrically connected between each of the electrode and heat sink 173P and 173N of the temperature element 61-2.
Therefore, the sub control unit 62b controls the polarity of the voltage (current polarity) and the current value applied to the electrode / heat dissipation plates 173P and 173N, thereby performing temperature control using the temperature element 61-2 as sub temperature control. Can be performed independently and in parallel with the main temperature control. That is, the sub control unit 62a can perform heating or cooling of the temperature element 61-2 independently and in parallel with the main temperature control by performing the sub temperature control.

Here, it is assumed that only main control by the main control unit 62a is performed and sub control by the sub control unit 62b is prohibited.
In this state, even when the target temperatures of the temperature element 61-1 and the temperature element 61-2 are the same, the temperature element 61-1 and the temperature element 61-2 may have different temperatures. .
Focusing only on the input / output current of the main control unit 62a, it appears that the currents flowing in the series connection of the plurality of main semiconductor groups have the same current value of the same polarity, but actually, each temperature element 61-1. This is because the current value of the current flowing through each of the temperature elements 61-1 and 61-2 is different due to the individual difference or the critical resistance value between 61-2 and 61-2.
Therefore, in the present embodiment, the sub control unit 62b performs sub temperature control, that is, controls the current flowing through the temperature element 61-2 independently of and parallel to the current flowing through the main temperature control. The current values of the currents flowing through the temperature elements 61-1 and 61-2 are made to substantially coincide with each other.
As described above, each of the temperature elements 61-1 and 61-2 is finely adjusted not only by the main control by the main control unit 62a but also by the sub-control by the sub-control unit 62b. As a result, the temperatures of the temperature element 61-1 and the temperature element 61-2 can be substantially matched. Details of such an effect will be described with reference to FIG.

  FIG. 10 is a diagram showing a result of temperature control performed on each of the two temperature elements 61-1 and 61-2 connected in series shown in FIG. 9 when performing the PCR test under the same conditions. .

FIG. 10A shows DNA samples (reactions) in each of the temperature elements 61-1 and 61-2 when only the main control by the main control unit 62a is performed in a state where the sub control by the sub control unit 62b is prohibited. It is a figure which shows the time-sequential change of the temperature of a solution.
FIG. 10B shows the DNA sample (reaction solution) in each of the temperature elements 61-1 and 61-2 when the main control by the main control unit 62a and the sub control by the sub control unit 62b are performed in combination. It is a figure which shows the time-sequential change of temperature.
In FIG. 10, the vertical axis represents temperature (degrees) and the horizontal axis represents time (seconds).

10A and 10B, the temperature transition pattern of the temperature target value in the PCR method is as follows (A) to (B).
(A) First, the temperature target value is set to 123 degrees, and heated to 123 degrees and held at 123 degrees.
This period is a period 201a in FIG. 10A and a period 202a in FIG. 10B.
(B) Next, the temperature target value is switched to 37 degrees, cooled to 37 degrees, and held at 37 degrees.
This period is a period 201b in FIG. 10A and a period 202b in FIG. 10B.

The test conditions are as follows (a) to (c).
(A) In both tests, a 0.2 ml standard plastic tube 82 and a metal well 71 having two mounting portions 81 having a hole diameter of 9.6 mm were used.
(B) The temperature of the DNA specimen (reaction solution) was measured by inserting the same thermocouple into the plastic tube 82 in both tests.
(C) The rated current of the main control unit 62a is ± 30A, and the rated current of the sub control unit 62b is ± 10A.

When only the main control by the main control unit 62a is performed in a state in which the sub control by the sub control unit 62b is prohibited, the temperature element 61- in any of the periods 201a and 201b in FIG. The temperatures of 1,61-2 do not match.
Specifically, with respect to the temperature element 61-1, the temperature of the DNA sample (reaction solution) can change substantially following the temperature transition pattern of the temperature target value, whereas the temperature element 61-1. As for -2, it has not changed following.
That is, the temperature element 61-2 is 98 degrees in the period 201a of FIG. 10A with respect to the target of “holding at 123 degrees” in (A) of the temperature target value pattern, and the temperature target value It has not reached 123 degrees. Similarly, in the period 201b of FIG. 10A, the temperature element 61-2 is 22 degrees with respect to the target of “holding at 37 degrees” in (B) of the temperature target value pattern. The target value of 37 degrees has not been reached.

On the other hand, when the main control by the main control unit 62a and the sub control by the sub control unit 62b are performed in combination, as shown in FIG. 10B, the periods 202a and 202b in FIG. In any case, the temperatures of the temperature elements 61-1 and 61-2 are substantially the same.
Specifically, in both the temperature elements 61-1 and 61-2, the temperature of the DNA sample (reaction solution) can change substantially following the temperature transition pattern of the temperature target value.

As described above, each DNA amplification device 51 in the case of including one temperature element 61 with reference to FIG. 2 and in the case of including two temperature elements 61-1 and 61-2 with reference to FIG. 9 and FIG. As described above, the number of temperature elements 61 included in the DNA amplification device 51 is not particularly limited to these examples.
For example, M temperature elements 61 can be connected in series in a straight line.
In this case, temperature control (rough adjustment temperature control) of the entire M temperature elements 61 can be realized by adopting temperature control in which current flows in the direction connected in series as main temperature control.
On the other hand, as the sub-temperature control, by adopting a temperature control in which currents flow independently to each of the M temperature elements 61 in a direction substantially perpendicular to the series-connected direction, each of the M temperature elements 61 is provided. Individual temperature control (fine adjustment temperature control) can be realized independently of and in parallel with the main control.
If a predetermined one of the M temperature elements 61 is used as a reference element, sub-temperature control for the reference element can be omitted. That is, the example of FIG. 9 means that M = 2 and the temperature element 61-1 is a reference element.
The unit of sub temperature control need not be one temperature element 61 but may be two or more temperature elements 61.
In this way, by connecting the M temperature elements 61 in series and appropriately combining the main temperature control and the sub temperature control, the influence of variation among the M temperature elements is absorbed, and a plurality of temperature elements It becomes possible to make each temperature change substantially the same.
By appropriately combining the main temperature control and the sub temperature control, on the contrary, it is also easy to set different temperature target values for each of the plurality of temperature elements 61 and individually control the temperature. It becomes possible.

Further, there may be N pieces of serial connection of the M temperature elements 61.
In this case, the control unit 62 can execute the main temperature control and the sub temperature control independently of other units, with each of the N serial connections as a unit.
In other words, the temperature elements 61 can be arranged in a matrix of N rows and M columns. In this case, the direction in which the current flows can be divided into a row direction and a column direction. In this case, for example, the control unit 62 can perform main temperature control as control of current flowing in the row direction, and can also perform sub temperature control as control of current flowing in the column direction. In this way, individual temperature control for each of the row and column directions can be performed independently of each other.
Also in this case, by appropriately combining the main temperature control and the sub temperature control, it is possible to absorb the influence of the variation among the M temperature elements and make the temperature changes of the plurality of temperature elements substantially the same. It becomes possible.
By appropriately combining the main temperature control and the sub temperature control, on the contrary, it is also easy to set different temperature target values for each of the plurality of temperature elements 61 and individually control the temperature. It becomes possible.

  Further, the target to be subjected to the main temperature control and the sub temperature control, which is arranged in a matrix of N rows and M columns, does not need to be the temperature element 61, and any temperature element capable of producing the Peltier effect is not required. Can be adopted.

  The present invention can provide the following effects (1) to (4), for example, regardless of the various embodiments. The configurations disclosed in (1) to (4) realize the temperature control device according to the present invention.

(1) The metal well 71 provided in the temperature element 61 according to the present invention directly joins the p-type semiconductor 72P and the n-type semiconductor 72n, and current flows from one of the p-type semiconductor 72P and the n-type semiconductor 72n to the other. And has the function of causing the Peltier effect by propagating heat. The metal well 71 is provided with a mounting portion 81 to which a cooling or heating object can be directly mounted. Therefore, the object is directly heated or cooled by the metal well 71 without interposing a delay element for the temperature control system (for example, the heat radiation plate 21A of the conventional Peltier element 1 in FIG. 1). That is, the metal well 71 is a heat path that propagates along with the current flowing from one of the p-type semiconductor 72P and the n-type semiconductor 72n to the other. Therefore, when the heat propagating through the path is directly supplied to the object, the object is heated, and the heat generated from the object is directly supplied to the path, so that the object is Is cooled. As a result, compared with the case where the conventional Peltier device 1 is adopted, high responsiveness of temperature control is realized.

(2) Due to the structure of the temperature element 61 according to the present invention, it becomes possible to improve the temperature accuracy by almost an order of magnitude compared with the prior art. That is, the conventional Peltier device 1 of FIG. 1 has a structure having only one set of the p-type semiconductor 24P and the n-type semiconductor 24N for the sake of simplicity of explanation, but the conventional Peltier device applied to the PCR method is A plurality of such sets are provided, and the plurality of sets are connected in series. For this reason, in the conventional Peltier element, the electrical resistance and thermal resistance of each interface (contact surface) between the p-type semiconductor or the n-type semiconductor and the heat sink are not uniform, and this is out of phase and thermal response. It was a factor to slow down. In contrast, the temperature element 61 according to the present invention has the number of interfaces between the p-type semiconductor 72P or the n-type semiconductor 72N and the metal well 71, as described above with reference to FIGS. Is extremely low, the degree of influence that slows down the thermal response is much lower than in the prior art. As a result, it is possible to improve the temperature accuracy by an order of magnitude compared to the conventional case.

(3) It is known in principle that the thermal response due to the Peltier effect increases as the current increases. Here, the temperature element 61 according to the present invention reduces the number of pairs of the p-type semiconductor 72P and the n-type semiconductor 72N as compared with the conventional Peltier element including the conventional Peltier element 1 of FIG. Since the area (contact area) of the interface with the hitting metal well 71 is increased, a much larger current can be handled. For this reason, by passing a large current through the temperature element 61 according to the present invention, the thermal response is further enhanced.

(4) Furthermore, a plurality of temperature elements 61 according to the present invention can be prepared, and the plurality of temperature elements 61 can be connected in series. In this case, the control unit 62 according to the present invention individually controls the main temperature control for controlling the temperature for the plurality of temperature elements 61 connected in series at the same time, and individually for each of at least some of the plurality of temperature elements 61. The sub-temperature control for controlling the temperature can be performed independently of each other.
Thereby, it is possible to absorb the influence of the variation between the plurality of temperature elements 61 and make the temperature changes of the plurality of temperature elements 61 substantially the same.
Conversely, it is possible to easily control the temperature individually by setting different temperature target values for each of the plurality of temperature elements 61.

  By applying the temperature element 61 having such various effects to the PCR method, that is, by adopting the plastic tube 82 used for accommodating the DNA specimen as the object, the temperature target value in the PCR method can be obtained. It becomes possible to change the temperature of the DNA specimen by following the predetermined pattern of the time transition. That is, as shown in FIG. 11, high responsiveness of temperature control of the DNA specimen in the PCR method can be realized. As a result, the time required for one process is shortened, and it is possible to improve the processing efficiency and power saving.

  FIG. 11 shows a case where a PCR method test under the same conditions was performed using a conventional DNA amplification apparatus including the conventional Peltier element 1 and a DNA amplification apparatus 51 including the temperature element 61 according to the present invention. FIG.

  FIG. 11A is a diagram showing a time-series change in temperature of a DNA sample (reaction solution) when a PCR method test is performed using a conventional DNA amplification device including the conventional Peltier element 1. FIG. 11B is a diagram showing a time-series change in the temperature of the DNA specimen (reaction solution) when the PCR method test is performed using the DNA amplification device 51 including the temperature element 61 according to the present invention. In FIG. 11, the vertical axis represents temperature (degrees) and the horizontal axis represents time (seconds).

The time transition pattern of the temperature target value in the PCR method in both tests is as follows (A) to (C).
(A) First, the temperature target value is set to 94 degrees, and the temperature is heated to 94 degrees and held at 94 degrees for 30 seconds.
This period is a period 301a in FIG. 11A and a period 301b in FIG. 11B.
(B) Next, the temperature target value is switched to 55 degrees, cooled to 55 degrees, and held at 55 degrees for 30 seconds.
This period is a period 302a in FIG. 11A and a period 302b in FIG. 11B.
(C) Next, the temperature target value is switched to 72 degrees, heated to 72 degrees, and held at 72 degrees for 60 seconds.
This period is a period 303a in FIG. 11A and a period 303b in FIG. 11B.

The test conditions are as follows (a) to (c).
(A) In both tests, a 0.2 ml standard plastic tube 82 and a metal well 71 having two mounting portions 81 having a hole diameter of 9.6 mm were used. However, in the test employing the conventional Peltier element 1, the metal well 71 was disposed at a predetermined position on the surface of the heat radiating plate 21A, that is, at the drawing position of the container 31 shown in FIG. That is, in the test employing the conventional Peltier element 1, the metal well 71 does not exhibit the bridge / electrode function but only functions as a mounting portion for mounting the plastic tube 82.
(B) The temperature of the DNA specimen (reaction solution) was measured by inserting the same thermocouple into the plastic tube 82 in both tests.
(C) In the PCR method test using the DNA amplification device 51 including the temperature element 61 according to the present invention, the output current of the temperature control unit 62 was as follows. That is, in the period 301b of FIG. 11B, the heating period (period in which the temperature is raised to 94 degrees) is 19.6 A, and the temperature holding period (period in which the temperature is maintained at 94 degrees) is 10.4 A. It was. In the period 302b of FIG. 11B, the cooling period (period in which the temperature is lowered to 55 degrees) is 18.1A, and the temperature holding period (period in which the temperature is maintained at 55 degrees) is 5.4A. In the period 303b of FIG. 11B, the heating period (period in which the temperature was raised to 72 degrees) was 18.5A, and the temperature holding period (period in which the temperature was maintained at 72 degrees) was 7.3A.

  When the PCR method test was performed using a conventional DNA amplification device including the conventional Peltier device 1, the waveform was dull in any of the periods 301a to 303a in FIG. The temperature of the DNA sample (reaction solution) does not change following the pattern of the target value over time. That is, there is a delay until the temperature of the DNA sample (reaction solution) reaches the temperature target value (94 degrees in the period 301a, 55 degrees in the period 302a, 72 degrees in the period 303a). As a result, with respect to the target of “holding at 94 degrees for 30 seconds” in (A) of the temporal transition pattern of the temperature target value, in the period 301a of FIG. Second and the target have not been achieved. Similarly, in the period 302a of FIG. 11A, the time within 55 ° ± 0.5 ° is used for the target of “holding at 55 ° C. for 30 seconds” in the time transition pattern of the temperature target value (B). The target has not been achieved for 20 seconds. With respect to the target of “holding at 72 degrees for 60 seconds” in (C) of the time transition pattern of the temperature target value, in the period 302a in FIG. 11A, the time within 72 degrees ± 0.5 degrees is 56 seconds. The goal has not been achieved.

  Thus, in the conventional DNA amplifying apparatus including the conventional Peltier element 1, the reason why the temperature of the DNA sample (reaction solution) cannot follow the time transition pattern of the temperature target value is as follows. That is, as described above, the temperature change at the A-plane portion of the conventional Peltier element 1, that is, the temperature change at the electrode plate 22A having the bridge and electrode function, is a heat radiating plate 21A (see FIG. 1). This is because the signal is transmitted to the plastic tube 82 attached to the metal well 71.

On the other hand, when the PCR method test is performed using the DNA amplification device 51 including the temperature element 61 according to the present invention, the waveform is steep in any of the periods 301b to 303b in FIG. 11B. As is clear from the above, the temperature of the DNA sample (reaction solution) changes substantially following the temporal transition pattern of the temperature target value. That is, there is almost no delay until the temperature of the DNA sample (reaction solution) reaches the temperature target value (94 degrees in the period 301b, 55 degrees in the period 302b, 72 degrees in the period 303bc). As a result, with respect to the target of “holding at 94 degrees for 30 seconds” in (A) of the temporal transition pattern of the temperature target value, the time within 94 degrees ± 0.5 degrees is 30 in the period 301b of FIG. 11B. Seconds and the target have been achieved. Similarly, in the period 302b of FIG. 11B, the time within 55 ° ± 0.5 ° is used for the target of “holding at 55 ° C. for 30 seconds” in (B) of the time transition pattern of the temperature target value. The target has been achieved for 30 seconds. With respect to the target of “holding at 72 degrees for 60 seconds” in (C) of the time transition pattern of the temperature target value, in the period 303b of FIG. 11A, the time within 72 degrees ± 0.5 degrees is 60 seconds. The goal has been achieved.
Furthermore, it should be noted that not only the goal of ± 0.5 degrees has been achieved, but a much higher accuracy of ± 0.01 degrees has been achieved. Furthermore, the total test time of the PCR method is shortened by the period 304b in FIG. 11B.

  In FIG. 11B, the plot points are spaced apart when the temperature rises or falls because the temperature gradient becomes steep, that is, the temperature control response is improved and the temperature rises or falls in a short time. This is because it has become possible. Also, the reason why the plot line width appears to be narrow at a constant temperature is because the accuracy of temperature control is improved and blurring is reduced. In addition, it is presumed that the use of the metal well 71 having a smaller thickness than the size shown in FIG. 3B, that is, a smaller volume, contributes to the improvement of temperature accuracy.

  In this way, in the DNA amplification device 51 including the temperature element 61 according to the present invention, the temperature of the DNA sample (reaction solution) can follow the temporal transition pattern of the temperature target value as follows. is there. That is, as described above, since the metal well 71 itself has a bridge and electrode function and operates as the A surface portion, the temperature change at the A surface portion becomes a delay element like the heat sink 21A. This is because it is directly transmitted to the plastic tube 82 without any interposition.

51 DNA amplification device 61, 61a, 61b Temperature element 62 Temperature control unit 62a Main control unit 62b Sub control unit 63 Water cooling unit 71 Metal well 72P, 72P1, 72P2 p-type semiconductor 72N, 72N1, 72N2 n-type semiconductor 73P, 73N, 73PN Electrode / heatsink 74P, 74N Water tube 81 Mounting part 91 Insulator 101, 102 region 172P p-type semiconductor 172N n-type semiconductor 173P, 173N Electrode / heatsink 174P, 174N water tube

Claims (6)

In a temperature control device that heats or cools an object,
A plurality of temperature elements for heating or cooling the object by the Peltier effect;
A control unit that performs energization control on the temperature element, and
Each of the plurality of temperature elements includes:
A set of a first p-type semiconductor and a first n-type semiconductor that are spaced apart from each other;
A bonding portion having a mounting portion for mounting the object, wherein the first p-type semiconductor is bonded to the first surface and the first n-type semiconductor is bonded to the second surface facing the first surface; The site,
A first p-side electrode portion joined to the first p-type semiconductor and applied with a voltage by the control unit;
A first n-side electrode portion bonded to the first n-type semiconductor and applied with a voltage by the control unit;
Have
By connecting at least one of the first p-side electrode portion and the first n-side electrode portion of each of the plurality of temperature elements to the first n-side electrode portion or the first p-side electrode portion of another temperature element. A series connection of the plurality of temperature elements is configured,
The control unit performs a first control to apply different voltages to both ends of the series connection, and as a result, in each of the plurality of temperature elements, between the first p-type semiconductor and the first n-type semiconductor. When a potential difference occurs, the junction site causes the Peltier effect by flowing current and propagating heat from one of the first p-type semiconductor and the first n-type semiconductor to the other,
At least some of the plurality of temperature elements further includes:
A set of second p-type semiconductor and second n-type semiconductor;
A second p-side electrode portion joined to the second p-type semiconductor and applied with a voltage by the control unit;
A second n-side electrode portion bonded to the second n-type semiconductor and applied with a voltage by the control unit;
Have
The junction site is a third surface different from the first surface and the second surface from the second p-type semiconductor, and a fourth surface facing the third surface from the second n-type semiconductor. Joined to each other in terms of
Independently of the first control, the controller further applies different voltages to the second p-side electrode part and the second n-side electrode part for each of at least some of the plurality of temperature elements. Execute the second control to be applied,
As a result, when a potential difference is generated between the second p-type semiconductor and the second n-type semiconductor, the junction portion flows current from one of the second p-type semiconductor and the second n-type semiconductor to the other. Propagating heat to produce the Peltier effect,
Temperature control device. There are a plurality of series connection of the temperature elements,
The control unit performs the first control and the second control independently of other units, with each of the plurality of series connections as a unit.
The temperature control apparatus according to claim 1. The object is a predetermined container used for containing a DNA (Deoxyribonucleic acid) specimen,
The temperature control apparatus according to claim 1, wherein the mounting portion is processed to mount the container. 4. The cooling unit according to claim 1, further comprising: a cooling unit that cools at least one of the first p-side electrode part, the first n-side electrode part, the second p-side electrode part, and the second n-side electrode part of the temperature element. The temperature control apparatus according to claim 1. The temperature control device according to any one of claims 1 to 4, wherein the temperature control device is a portable device. In a temperature element that heats or cools an object by the Peltier effect,
A set of a first p-type semiconductor and a first n-type semiconductor that are spaced apart from each other;
A set of a second p-type semiconductor and a second n-type semiconductor, which are spaced apart from each other;
A mounting portion for mounting the object; the first p-type semiconductor on a first surface; the first n-type semiconductor on a second surface opposite to the first surface; the first surface; A junction part for joining the second p-type semiconductor on a third surface different from the second surface, and a second n-type semiconductor on a fourth surface opposite to the third surface;
A first p-side electrode portion joined to the first p-type semiconductor and applied with a voltage from the outside;
A first n-side electrode portion joined to the first n-type semiconductor and applied with a voltage from the outside;
A second p-side electrode portion joined to the second p-type semiconductor and applied with a voltage from the outside;
A second n-side electrode portion joined to the second n-type semiconductor and applied with a voltage from the outside;
With
A first control in which a different voltage is applied from the outside between the first p-side electrode portion and the first n-side electrode portion is executed, and a potential difference is generated between the first p-type semiconductor and the first n-type semiconductor. When it occurs, the junction site causes the Peltier effect by flowing current and propagating heat from one of the first p-type semiconductor and the first n-type semiconductor to the other, and
Second control in which a different voltage is applied from the outside between the second p-side electrode part and the second n-side electrode part is performed independently of the first control, and the second p-type semiconductor and the second control part When a potential difference is generated between the second n-type semiconductor and the junction, the junction portion causes a current to flow from one of the second p-type semiconductor and the second n-type semiconductor to the other and propagates heat, thereby causing the Peltier effect. Give rise to,
Temperature element.

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