JP2011188749A - Temperature controller and electric power unit for temperature element - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To make the change in temperature of a DNA specimen (reaction solution) follow the predetermined temperature pattern in the PCR method. <P>SOLUTION: A temperature element 61 has a set of a p-type semiconductor 72P and an n-type semiconductor 72N arranged apart each other and a mounting part 81 to which a container of a DNA specimen is directly mounted, and is equipped with the followings: a metal well 71 joined to each of the p-type semiconductor 72P and the n-type semiconductor 72N; an electrode/heat radiation plate 73P, joined to the p-type semiconductor 72P, to which a voltage is impressed by a temperature control part 62; and an electrode/heat radiation plate 73N, joined to the n-type semiconductor 72N, to which a voltage is impressed by a temperature control part 62. When different voltages are impressed to the respective electrode/heat radiation plates 73P and 73N by the temperature control part 62 causing a potential difference between the p-type semiconductor 72P and the n-type semiconductor 72N, the metal well 71 spreads heat, while passing an electric current, from one side to another of the p-type semiconductor 72P and the n-type semiconductor 72N creating the Peltier effect. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a temperature control device applicable to a PCR method for amplifying a DNA specimen and a power supply device for a temperature element. In particular, the present invention relates to a temperature control device and a power supply device for a temperature element that can realize 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 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”. Further, with reference to the electrode plate 23P, the voltage applied so that the electrode plate 23P becomes a high potential and the electrode plate 23N becomes a low potential is hereinafter referred to as “a positive voltage is applied to the conventional Peltier element 1”. " Conversely, the application of a voltage so that the electrode plate 23P is at a low potential and the electrode plate 23N is at a high potential is hereinafter 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 negative 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, due to the negative voltage applied to the conventional Peltier element 1, the A surface portion becomes low temperature and the B surface portion becomes high temperature according to the value of the current flowing from the electrode plate 23N toward the electrode plate 23P. 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 positive voltage is applied to the conventional Peltier element 1, current flows in the opposite direction to that when the 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 positive voltage applied to the conventional Peltier element 1, the value of the current flowing from the electrode plate 23P toward the electrode plate 23N increases the temperature of the A surface region and the B surface region decreases. 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 amplifying apparatus including Patent Documents 1 and 2 is used, the DNA sample (reaction solution) is changed against the change of the current value according to the predetermined pattern of the time transition of the temperature target value in the PCR method. The temperature does not follow sufficiently. 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.

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 temperature element that heats or cools the DNA specimen by the Peltier effect (for example, the temperature element 61 in the embodiment);
A control unit (for example, the temperature control unit 62 in the embodiment) that performs energization control on the temperature element,
The temperature element is
A set of a p-type semiconductor (for example, the p-type semiconductor 72P in the embodiment) and an n-type semiconductor (for example, the n-type semiconductor 72N 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 p-type semiconductor is the first or second surface, and the n-type semiconductor is the first or second surface. A bonding portion (for example, the metal well 71 in the embodiment) that is bonded to each other on the second or first surface opposite to each other;
A first electrode portion (for example, an electrode and heat dissipation plate 73P in the embodiment) that is joined to the p-type semiconductor and to which a voltage is applied by the control unit;
A second electrode portion (for example, an electrode and heat dissipation plate 73N in the embodiment) that is joined to the n-type semiconductor and to which a voltage is applied by the control unit;
When a different voltage is applied to each of the first electrode part and the second electrode part by the control unit to cause a potential difference between the p-type semiconductor and the n-type semiconductor, the junction part Causes the Peltier effect by passing a current from one of the p-type semiconductor and the n-type semiconductor to the other and propagating the heat,
The control unit includes a constant current source (constant current source device 102 in the embodiment) having both a switching regulator (switching regulators 111P1 to 111M2 in the embodiment) and a linear regulator (linear regulators 113P and 113M in the embodiment).
The constant current source is:
If the absolute value of the output voltage of the switching regulator is greater than or equal to a threshold, the switching regulator is responsible for variable output control of a constant current,
When the absolute value of the output voltage of the switching regulator is less than the threshold, the linear regulator is responsible for variable output control of a constant current.
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.

  Further, according to the present invention, the constant current source has both a switching regulator and a linear regulator, and assigns the responsibility for the variable output control of the constant current according to the value of the output voltage of the switching regulator. As a result, it is possible to output a large current of, for example, about ± 30 A and a small voltage of, for example, about ± 0.3 V, and the power efficiency is dramatically improved as compared with the case where a conventional linear regulator is employed. .

  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, the temperature element is
A plurality of sets of the p-type semiconductor and the n-type semiconductor;
The p-type semiconductor (for example, the p-type semiconductor 72P1 and the p-type semiconductor 72P2 in the embodiment) of each of the plurality of sets is bonded to the first surface (for example, the side surface 71a in the embodiment) of the bonding portion. The n-type semiconductors (for example, the n-type semiconductor 72N1 and the n-type semiconductor 72N2 in the embodiment) of each of the plurality of sets are bonded to the second surface (for example, the side surface 71b in the embodiment) of the bonding portion. And
The p-type semiconductor of each of the plurality of sets is joined to the first electrode portion, and the n-type semiconductor of each of the plurality of sets is joined to the second electrode portion. It may be.

Alternatively, in this case, the temperature element is
A plurality of sets of the p-type semiconductor and the n-type semiconductor;
An insulator (for example, the insulator 91 in the embodiment) is inserted from the first surface (for example, the side surface 71a in the embodiment) of the joint portion to the second surface (for example, the side surface 71b in the embodiment). The connection part is divided into a plurality of regions (for example, the regions 201 and 202 in the embodiment),
For each of the plurality of regions, a pair in which the p-type semiconductor is bonded to the first surface side and the n-type semiconductor is bonded to the second surface side (for example, the p-type semiconductor 72P2 and the n-type in the embodiment) A second set of semiconductors 72N2), a set in which the n-type semiconductor is bonded to the first surface side and the p-type semiconductor is bonded to the second surface side (for example, the p-type semiconductor 72P1 and the n-type in the embodiment) 1st set of semiconductors 72N1) are alternately arranged,
A predetermined p-type semiconductor (for example, p-type semiconductor 72P2 in the embodiment) connected to the first surface is joined to the first electrode portion (for example, the electrode and heat dissipation plate 73P in the embodiment), A predetermined n-type semiconductor (for example, n-type semiconductor 72N1 in the embodiment) connected to the first surface is joined to a second electrode portion (for example, the electrode and heat dissipation plate 73N in the embodiment),
You may make it further have the 3rd electrode site | part (for example, electrode and heat sink 73PN in embodiment) which joins the said some group in series.

  In this case, a cooling unit (for example, the water cooling unit 63 in the embodiment) that cools at least one of the first electrode portion and the second electrode portion of the temperature element 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.

A power supply device (for example, the constant current power supply device 102 in the embodiment) for the temperature element of the present invention (for example, the temperature element 61 in the embodiment)
In a power supply device for 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 p-type semiconductor (for example, the p-type semiconductor 72P in the embodiment) and an n-type semiconductor (for example, the 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, and a bonding portion (for example, a metal well 71 in the embodiment) that is bonded to each of the p-type semiconductor and the n-type semiconductor;
A first electrode portion joined to the p-type semiconductor and applied with a voltage from the outside (for example, the electrode and heat dissipation plate 73P in the embodiment);
A second electrode portion (for example, an electrode and heat dissipation plate 73N in the embodiment) that is joined to the n-type semiconductor and to which a voltage is applied from the outside.
When a different voltage is applied from the outside to each of the first electrode part and the second electrode part to generate a potential difference between the p-type semiconductor and the n-type semiconductor, the junction part is: By causing a current to flow from one of the p-type semiconductor and the n-type semiconductor to the other and propagating heat, the Peltier effect is generated,
The power supply device
A constant current source device having both a switching regulator (switching regulators 111P1 to 111M2 in the embodiment) and a linear regulator (linear regulators 113P and 113M in the embodiment),
If the absolute value of the output voltage of the switching regulator is greater than or equal to a threshold, the switching regulator is responsible for variable output control of a constant current,
When the absolute value of the output voltage of the switching regulator is less than the threshold, the linear regulator is responsible for variable output control of a constant current.
It is a power supply device for temperature elements.

  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, according to the present invention, the constant current source has both a switching regulator and a linear regulator, and assigns the responsibility for the variable output control of the constant current according to the value of the output voltage of the switching regulator. As a result, it is possible to output a large current of, for example, about ± 30 A and a small voltage of, for example, about ± 0.3 V, and the power efficiency is dramatically improved as compared with the case where a conventional linear regulator is employed. .

  In this case, the mounting portion may be formed in the joint portion by being processed according to the shape of the object.

  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. It is a block diagram which shows schematic structure of the temperature control part of the DNA amplification apparatus of FIG. It is a block diagram which shows schematic structure of the constant current power supply device of the temperature control part 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. It is a schematic structure of the temperature element of FIG. 6, Comprising: It is a perspective view of a structure different from 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 series. It is a perspective view of schematic structure of the temperature element of FIG. 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, a current flows in the temperature element 61 due to a potential difference between voltages applied to the electrode and heat dissipation plates 73P and 73N. When the value of the current and its direction (polarity) are controlled by the temperature control unit 62, the degree to which the temperature element 61 heats or cools the object is adjusted. That is, temperature control using the temperature element 61 is 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, it is preferable that a material having high thermal conductivity and low electrical resistance is adopted as the material of 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 target material for joining the pair of the p-type semiconductor 72P and the n-type semiconductor 72N and the metal well 71. 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 temperature control part 62 which performs temperature control with respect to such a temperature element 61 is demonstrated.

FIG. 4 is a configuration diagram showing a schematic configuration of the temperature control unit 62.
As shown in FIG. 4, the temperature control unit 62 includes a temperature regulator 101, a constant current power supply device 102, an ammeter 103, a separate power supply 104, and a DC power supply 105.

  The temperature regulator 101 detects the temperature of the temperature element 61 and controls the detected temperature to be a target temperature. The details will be described later as the operation of the DNA amplification device 51. By changing the direction (polarity) and magnitude (value) of the current in the temperature element 61, the temperature element 61 heats the plastic tube 82 to the target temperature. Can be cooled. Therefore, the temperature regulator 101 sets a target value (hereinafter referred to as “current target value”) of the direction and magnitude of the current in the temperature element 61 and supplies it to the constant current power supply apparatus 102.

In the present embodiment, as the direction of current, there is a direction from the electrode / heat radiating plate 73P of the temperature element 61 toward the electrode / heat radiating plate 73N. When a current flows in this direction, the temperature element 61 operates to heat the plastic tube 82 (hereinafter referred to as “heating operation”). Therefore, hereinafter, this direction is referred to as “heating direction”.
As another current direction, there is a direction from the electrode / heat radiating plate 73N of the temperature element 61 toward the electrode / heat radiating plate 73P. When a current flows in this direction, the temperature element 61 performs an operation of cooling the plastic tube 82 (hereinafter referred to as “cooling operation”). Therefore, hereinafter, this direction is referred to as “cooling direction”.
Such a direction of the current is specified by the type of the output signal of the temperature regulator 101. That is, the temperature regulator 101 outputs the control signal SP when instructing the heating direction as the current direction. On the other hand, the temperature regulator 101 outputs a control signal SM from the temperature regulator 101 when instructing the cooling direction as the current direction.

  In the present embodiment, the current target value in the temperature element 61 is specified by the signal level of the control signal SP or SM output from the temperature control regulator 101. Specifically, for example, the control signals SP and SM are current signals that vary within a range of 4 to 20 mA. Therefore, the current target value in the temperature element 61 is specified by the current value of the control signal SP or SM.

  The constant current power supply device 102 is configured as a so-called constant current regulator (stabilized power supply device). The constant current power supply device 102 determines the direction and magnitude of the output current based on the control signal SP or SM output from the temperature regulator 101, and outputs the constant current having the determined direction and magnitude to the temperature element 61. .

  Here, in this embodiment, since the driving range of the temperature element 61 is ± 30 A, the constant current power supply device 102 outputs a constant current to the temperature element 61 within a range of ± 30 A. In this case, a conventional regulator can be employed if a DC current of ± 30 A is simply output. However, it is difficult to employ a conventional regulator as a power supply device for the temperature element 61 of the present embodiment. Hereinafter, the difficult reason will be described.

  That is, since the resistance RL of the temperature element 61 of the present embodiment is very low, the voltage applied to the temperature element 61, that is, the potential difference between the electrode and heat dissipation plates 73P and 73N is low. For example, if the resistance RL of the temperature element 61 is 10 mΩ, the voltage applied to the temperature element 61 is ± 0.3 V when simply calculated according to Ohm's law. As described above, for the temperature element 61 of the present embodiment, a power supply device capable of supplying a large current of ± 30 A to the temperature element 61 and applying a small voltage of about ± 0.3 V to the temperature element 61. Is required.

  Here, conventional regulators are broadly classified into switch-on regulators and linear regulators. The linear regulator is also referred to as a series regulator.

  Switching regulators have the advantage of better power efficiency compared to linear regulators, but can only output up to about 10% of the rated voltage when functioning as a constant current source. There is a demerit that it cannot be guaranteed. Due to the disadvantages of the switching regulator, it is very difficult to apply a small voltage of about ± 0.3 V to the temperature element 61 while functioning as a constant current source. Therefore, it is very difficult to employ the switching regulator as a power supply device for the temperature element 61.

  On the other hand, the linear regulator has a merit that it can be continuously varied from 0 V to a rated voltage even if it functions as a constant current source, but has a demerit that power efficiency is poor. It is not realistic to employ the linear regulator as a power supply device for the temperature element 61 due to the disadvantages. That is, the power efficiency is poor that the loss that is the difference between the input power and the output power is large. Since this loss is consumed as heat in the linear regulator, a radiator is required. Therefore, considering that the output voltage required for the temperature element 61 is as small as ± 0.3 V, a loss (efficiency) is very large in a general input voltage linear regulator. A very large radiator is required. Providing such a very large radiator is not practical from the viewpoint of installation environment such as space and from the viewpoint of cost.

  Therefore, the constant current power supply device 102 according to the present embodiment has both a switching regulator and a linear regulator, and distributes the responsibility for the constant current output variable control according to the value of the output voltage of the switching regulator. For example, when the output voltage value of the switching regulator is greater than or equal to the threshold value, the switching regulator is responsible for variable output control of the constant current, and when the output voltage value of the switching regulator is less than the threshold value, the linear regulator is Take charge of variable output control. Here, the threshold value is not particularly limited as long as it is equal to or higher than the minimum voltage value at which the switching regulator can guarantee operation as a constant current source, and 1 V is adopted in the present embodiment.

  Here, in the above description, only the resistance RL of the temperature element has been considered in order to focus on the voltage and current in the temperature element 61. However, paying attention to the switching regulator, it is necessary to further consider the wiring resistance and the like. As a result, even when the voltage applied to the temperature element 61 is ± 0.3V, the output voltage of the switching regulator is ± 1V. It is appropriate to exceed. As will be described in detail later, in order to simultaneously heat or cool the plurality of plastic tubes 82, a plurality of metal wells 71 are connected in series to increase the resistance RL of the temperature element 61, and the output of the switching regulator. It is appropriate that the voltage exceeds ± 1V. Thus, in the temperature control using the temperature element 61, the output voltage of the switching regulator sometimes exceeds ± 1V. In such a case, the constant current output variable control is responsible for the switching regulator, so that temperature control with high power efficiency is possible.

  Further, in the constant current power supply apparatus 102 of the present embodiment, the linear regulator only needs to be in charge of variable output control of the constant current when the input voltage (output voltage of the switching regulator) is 1 V or less. Compared with, power loss is also reduced. For this reason, since a heat radiator is also small, a linear regulator can be easily installed in the constant current power supply apparatus 102 at low cost.

  Further details of the constant current power supply apparatus 102 will be described later with reference to FIG.

  The ammeter 103 monitors the output current of the constant current power supply apparatus 102 and presents the monitoring result to the user. The separate power source 104 converts AC 100 V of a commercial AC power source (not shown) into DC 12 V and supplies it as a driving power source for the constant current power source device 102. The DC power source 105 converts AC 100 V of a commercial AC power source (not shown) into DC 12 V and supplies it as an internal power source for the constant current power source device 102.

  Next, details of the constant current power supply apparatus 102 in the temperature control unit 62 having the above configuration will be described.

  FIG. 5 is a configuration diagram showing a schematic configuration of the constant current power supply apparatus 102 of the present embodiment.

  As shown in FIG. 5, the constant current power supply apparatus 102 includes switching regulators 111P1 to 111M2, diodes 112P1 to 112M2, linear regulators 113P and 113M, and current loop current / voltage converters 114P and 114M.

  As shown in FIG. 5, the constant current power supply apparatus 102 includes a parallel circuit 121P configured by connecting a series connection of the switching regulator 111P1 and the diode 112P1 and a series connection of the switching regulator 111P2 and the diode 112P2 in parallel. Yes. Of the parallel circuit 121P, one end on the switching regulator 111P1, 111M side is connected to the positive output terminal of the separate power source 104, and the other end on the diode 112P1, 112P2 side is connected to the input terminal of the linear regulator 113P. The output terminal of the linear regulator 113P is connected to the electrode / heat radiating plate 73P (FIG. 2) of the temperature element 61 via the ammeter 103. The electrode / heat radiating plate 73 </ b> N (FIG. 2) on the opposite side of the temperature element 61 is connected to the negative output terminal of the separate power supply 104 via the constant current power supply device 102.

  Therefore, although details will be described later as the operation of the DNA amplification device 51, when the temperature element 61 performs a heating operation, the current is supplied to the positive output terminal of the separate power source 104, the parallel circuit 121P, the linear regulator 113P, and the temperature element 61. It flows in the order of the electrode / heat dissipating plates 73P and 73N and the negative output terminal of the separate power source 104.

  The switching regulators 111P1 and 111P2 are configured as, for example, so-called DC-DC converters, and change the DC 12V voltage applied by the separate power source 104 to a DC voltage of 12V or less and output it. Since the switching regulators 111P1 and 111P2 function as constant current sources, the switching regulators 111P1 and 111P2 output a constant current having a value instructed by the current loop current-voltage converter 114P. That is, the switching regulators 111P1 and 111P2 perform constant current output variable control in accordance with an instruction from the current loop current-voltage converter 114P. However, when the output voltages of the switching regulators 111P1 and 111P2 become less than the threshold (1V), the responsibility for constant current output variable control is transferred from the switching regulators 111P1 and 111P2 to the linear regulator 113P.

  Each of the diodes 112P1 and 112P2 drops the output voltage of each of the switching regulators 111P1 and 111P2, and prevents backflow of the output current of each of the switching regulators 111P1 and 111P2.

  As shown in FIG. 2, the output currents of the diodes 112P1 and 112P2 are added together and output to the linear regulator 113P. That is, in the present embodiment, the rated current of the switching regulators 111P1 and 111P2 is 15A, while the rated current of the temperature element 61 is 30A as described above. For this reason, by connecting two switching regulators 111P1 and 111P2 having a rated current of 15A in parallel, 30A that is the rated current of the temperature element 61 is output.

  In other words, when a switching regulator with a rated current of 30 A can be employed, one switching regulator may be mounted on the constant current power supply device 102 instead of the parallel circuit 121P. In this case, the diode is not essential, but it may be connected in series in the subsequent stage of the switching regulator.

  Conversely, when the rated current of the temperature element 61 exceeds 30 A, for example 45 A, the series connection of the switching regulator 111P3 and the diode 112P3 may be further connected in parallel to the parallel circuit 121, although not shown. In short, the parallel number K of the parallel circuit 121 may be varied in accordance with the magnitudes of the rated current of the switching regulator 111PK and the rated current of the temperature element 61. Note that K is an integer value of 1 or more, and is 2 in the example of FIG.

  The linear regulator 113P is configured by using, for example, a field effect transistor (FET). As described above, when the output voltage of the switching regulators 111P1 and 111P2 becomes less than the threshold (1V), the constant current output variable control. Execute. The linear regulator 113P also has a function of a so-called FET switch, and switches the on / off state under the control of the current loop current / voltage converter 114M. That is, details will be described later as the operation of the DNA amplification device 51. When the temperature element 61 performs a heating operation, the linear regulator 113P is turned on, whereas when the temperature element 61 performs a cooling operation, Under the control of the current loop current / voltage converter 114M, the linear regulator 113P is turned off, and the output of the parallel circuit 121P is cut off.

  The current loop current-voltage converter 114P receives the control signal SP output from the temperature regulator 101 when the temperature element 61 performs a heating operation. The control signal SP is a current signal of 4 to 20 mA as described above. Therefore, the current loop current / voltage conversion unit 114P converts the control signal SP from a current form of 4 to 20 mA to a form of voltage of 1 to 5 V, and supplies the converted signal to the switching regulators 111P1 and 111P2 and the linear regulator 113M. The switching regulators 111P1 and 111P2 change the value of the output current within the range of 0 to 15A in accordance with the value of the voltage (a value within the range of 1 to 5V) supplied from the current loop current / voltage converter 114P. When the voltage is supplied from the current loop current-voltage converter 114P, the linear regulator 114M switches from the on state to the off state, and interrupts the output of the parallel circuit 121M.

  The parallel circuit 121M and the linear regulator 113M have basically the same configuration and function as the parallel circuit 121P and the linear regulator 113P, and the connection form is also the same. However, the drive timing of the parallel circuit 121M and the linear regulator 114M is opposite to the drive timing of the parallel circuit 121P and the linear regulator 113P. That is, when the temperature element 61 performs a heating operation, as described above, the voltage is supplied from the current loop current-voltage conversion unit 114P and the linear regulator 113M is turned off, so that the parallel circuit 121M and the linear regulator 113M Driving stops. On the other hand, when the temperature element 61 performs the cooling operation, the linear regulator 113M is turned on, so that the parallel circuit 121M and the linear regulator 113M are driven.

  The current loop current / voltage converter 114M receives the control signal SM output from the temperature regulator 101 when the temperature element 61 performs a cooling operation. The control signal SM is a current signal of 4 to 22 mA as described above. Therefore, the current loop current-voltage conversion unit 114M converts the control signal SM from the form of current of 4 to 20 mA to the form of voltage of 1 to 5 V, and supplies it to the switching regulators 111M1 and 111M2 and the linear regulator 113P. The switching regulators 111M1 and 111M2 change the value of the output current within the range of 0 to 15A in accordance with the voltage value (value within the range of 1 to 5V) supplied from the current loop current / voltage conversion unit 114M. As described above, when the voltage is supplied from the current loop current-voltage conversion unit 114M, the linear regulator 114P switches from the on state to the off state and blocks the output of the parallel circuit 121P.

  The configuration of the DNA amplification device 51 has been described above with reference to FIGS. 1 to 5. Next, the operation of the 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 this embodiment, the voltage is applied by the temperature control unit 62 so that the electrode / heat dissipation plate 73P is at a high potential and the electrode / heat dissipation plate 73N is at a low potential with reference to the electrode / heat dissipation plate 73P side. Hereinafter, this is expressed as “a positive voltage is applied to the temperature element 61”. On the contrary, the voltage is applied by the temperature control unit 62 so that the electrode / heat sink 73P is at a low potential and the electrode / heat sink 73N is at a high potential. "Applied".

That is, the case where the plus voltage is applied to the temperature element 61 means the case where the linear regulator 113P shown in FIG. 5 is turned on and the parallel circuit 121P and the linear regulator 113P are driven. In this case, the current flows in the order of the positive output terminal of the separate power source 104, the parallel circuit 121 </ b> P, the linear regulator 113 </ b> P, the electrode and heat dissipation plates 73 </ b> P and 73 </ b> N of the temperature element 61, and the negative output terminal of the separate power source 104. Since the linear regulator 114M is in an off state, the driving of the parallel circuit 121M and the linear regulator 113M is stopped.
On the other hand, the case where a negative voltage is applied to the temperature element 61 means the case where the linear regulator 113M shown in FIG. 5 is turned on and the parallel circuit 121M and the linear regulator 113M are driven. In this case, the current flows in the order of the positive output terminal of the separate power source 104, the parallel circuit 121 </ b> M, the linear regulator 113 </ b> M, the electrode and heat dissipation plates 73 </ b> N and 73 </ b> P of the temperature element 61, and the negative output terminal of the separate power source 104. Since the linear regulator 113P is in an off state, the driving of the parallel circuit 121P and the linear regulator 113P is stopped.

  When a negative voltage is applied to the temperature element 61 by such a 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.

  More specifically, according to the value (absolute value) of the current flowing through the temperature element 61, the metal well 71 that is the A-surface part has a low temperature, and the electrode and heat dissipation plates 73P and 73N that are the B-surface parts have a high temperature. Temperature difference ΔT occurs.

  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.

  This temperature difference ΔT increases as the value (absolute value) of the current flowing through the temperature element 61 increases, although a certain limit exists. The value of the current flowing through the temperature element 61, that is, the value of the current output from the constant current power supply device 102 is controlled based on the signal level of the control signal SM output from the temperature regulator 101 of FIG. Therefore, the temperature regulator 101 increases the value of the current output from the constant current power supply device 102 and flowing through the temperature element 61 by increasing the signal level of the control signal SM, and as a result, increases the temperature difference ΔT. Can continue. In this way, the temperature regulator 101 can lower the temperature of the metal well 71 that is the A-plane portion by increasing the signal level of the control signal SM. 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.

  After that, when the polarity of the output voltage is inverted by the temperature control unit 62, that is, when a positive voltage is applied to the temperature element 61, the current is the opposite of the case where a negative 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.

  Specifically, when a positive voltage is applied to the temperature element 61, the metal well 71, which is the A-plane part, is heated to a temperature higher than the reference temperature by a temperature difference ΔT. This temperature difference ΔT increases as the value (absolute value) of the current flowing through the temperature element 61 increases, although a certain limit exists. The value of the current flowing through the temperature element 61, that is, the value of the current output from the constant current power supply device 102 is controlled based on the signal level of the control signal SP output from the temperature regulator 101 of FIG. Therefore, the temperature regulator 101 increases the value of the current output from the constant current power supply device 102 and flowing through the temperature element 61 by increasing the signal level of the control signal SP, and as a result, the temperature difference ΔT is increased. Can continue. As described above, the temperature regulator 101 can increase the temperature of the metal well 71 that is the A-plane portion by increasing the signal level of the control signal SP. 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.

  As described above, the temperature control unit 62 can perform temperature control on the plastic tube 82 using the temperature element 61 by changing the direction and magnitude of the output current. Therefore, the PCR method can be easily realized by giving the predetermined pattern of the time transition of the output current to the temperature regulator 101 of the temperature controller 62 as the predetermined pattern of the temporal 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. 6 to FIG. 10, 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 can be adopted.

  FIG. 6 is a top view showing a schematic configuration of the temperature element 61 when such a first set and a second set are arranged in parallel. FIG. 7 is a perspective view of a schematic configuration of the temperature element 61. FIG. 8 is a schematic configuration of the temperature element 61, and is a perspective view of a configuration different from that in FIG. However, in FIG.7 and FIG.8, illustration of the electrode and heat sink 73P and 73N is abbreviate | omitted. When it is necessary to individually distinguish the configurations of FIG. 7 and FIG. 8, the temperature element 61 having the configuration of FIG. 7 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. 6, the first set of p-type semiconductors 72P1 and the second set of p-type semiconductors 72P2 have one end joined to the electrode and heat dissipation plate 73P and the other end 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.

  The arrangement 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. 7, the first set and the second set are arranged in the vertical direction. For example, in the temperature element 61b of FIG. 8, 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. 6 to 8, and may be three or more sets.

  FIG. 9 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. 10 is a perspective view showing a schematic configuration of the temperature element 61. However, in FIG. 10, illustration of the electrode and heat radiation 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 FIGS. 9 and 10, 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 201 and 102.

  In the embodiment of FIGS. 9 and 10, the first set is joined to the region 201 and the second set is joined to the region 202. Specifically, for the first set, the n-type semiconductor 72N1 is bonded to the region 201 side of the side surface 71a of the metal well 71, and the p-type semiconductor 72P1 is connected to the region 201 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 202 side of the side surface 71a of the metal well 71, and the n-type semiconductor 72N2 is connected to the region 202 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 of the arrangement of the first set and the second set depends on the position where the electrically insulated regions 201 and 202 are formed in the metal well 71. For example, in the example of FIG. 10, since the areas 201 and 202 are formed in the left-right direction, the first set and the second set are respectively arranged in the horizontal direction. For example, although not shown, when the areas 201 and 202 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 201 and 202 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 sets in series is not particularly limited to two sets of the first set and the second set shown in FIGS. 9 and 10 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.

  Further, for example, the cooling method of the electrode and heat radiating plate for maintaining the reference temperature of the temperature element 61 is a water cooling method by the water cooling unit 63 in the embodiment of FIG. In addition, 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.

In other words, 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 wells 71 may be plural. Also good.
In this case, for example, when a plurality of plastic tubes 82 are arranged in a matrix, the metal well 71 is divided by an insulator as described above, and the direction of current flow can be divided into a row direction and a column direction. it can. Thereby, individual temperature control for each of the row direction and the column direction can be executed independently of each other.
Specifically, for example, N plastic tubes 82 can be connected in N rows (N is an integer value of 2 or more) in one column, that is, in a straight line. In this case, temperature control of the entire N plastic tubes 82 (rough adjustment temperature control) can be realized by temperature control in the row direction. On the other hand, individual temperature control (fine adjustment temperature control) for each of the N plastic tubes 82 can be realized by temperature control in the row direction.
Thus, when heating or cooling the plurality of plastic tubes 82, the resistance of the metal well 71 of the temperature element 61 increases, so that the output voltages of the switching regulators 111P1 to 111M2 of the constant current power supply apparatus 102 are also increased. It often increases and exceeds the threshold (1V). In such a case, since the switching regulators 111P1 to 111M2 are in charge of constant current output variable control, the power efficiency during temperature control is improved.

  The present invention can provide the following effects (1) to (4), for example, regardless of the various embodiments.

(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. Accordingly, the object propagating through the path is directly supplied to the object, thereby heating the object, and the heat generated from the object is directly supplied to the path, thereby the object. 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) The constant current source for driving the temperature element 61 according to the present invention is required to output a large current of about ± 30 A and a small voltage of about ± 0.3 V. However, even if a conventional switching regulator is simply applied, it is difficult to meet this requirement. On the other hand, even if a conventional linear regulator is simply applied, it is possible to meet the request itself, but the power efficiency is low and it is not practical. Therefore, the constant current power supply device 102 according to the present invention has both a switching regulator and a linear regulator, and distributes the responsibility of constant current output variable control according to the value of the output voltage of the switching regulator. For example, when the output voltage value of the switching regulator is greater than or equal to the threshold value, the switching regulator is responsible for variable output control of the constant current, and when the output voltage value of the switching regulator is less than the threshold value, the linear regulator is Take charge of variable output control. As a result, it is possible to output a large current of about ± 30 A and a small voltage of about ± 0.3 V, and the power efficiency is dramatically improved as compared with the case where a conventional linear regulator is employed.

  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 201a in FIG. 11A and a period 201b 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 202a in FIG. 11A and a period 202b 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 203a in FIG. 11A and a period 203b 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 with a hole diameter of 96 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 and electrode function but only functions as a mounting portion for mounting the plus check tube 82. On the other hand, in the test employing the temperature element 61 according to the present invention, the metal well 71 has a thinner size, that is, a smaller volume than the size shown in FIG. 3B. In addition, as the temperature detection unit (sensor) in the temperature adjuster 101, a highly accurate and highly responsive one was adopted at the time of filing this application.
(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 amplifying apparatus 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 201b in 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 202b 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 203b 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 a PCR method test was performed using a conventional DNA amplification apparatus including the conventional Peltier element 1, the temperature was clearly observed in any of the periods 201a to 203a 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 specimen (reaction solution) reaches the temperature target value (94 degrees in the period 201a, 55 degrees in the period 202a, 72 degrees in the period 203a). 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 201a of FIG. Second and the target have not been achieved. Similarly, in the period 202a of FIG. 11A, the time within 55 ° ± 0.5 ° is set 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 not been achieved for 20 seconds. With respect to the target of “holding at 72 degrees for 60 seconds” in the time transition pattern of the temperature target value (C), in the period 202a of 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 in the A-plane portion of the conventional Peltier element 1, that is, the temperature change in the electrode plate 22A having a 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 201b to 203b 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 201b, 55 degrees in the period 202b, 72 degrees in the period 203bc). As a result, with respect to the target of “holding at 94 degrees for 30 seconds” in the pattern (A) of the time transition of the temperature target value, in the period 201b of FIG. Seconds and the target have been achieved. Similarly, in the period 202b of FIG. 11B, 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 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 203b of FIG. 11B, 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 time for the test of the PCR method is shortened by the period 204b 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 5 including the temperature element 61 according to the present invention, the temperature of the DNA specimen (reaction solution) can follow the time 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.

  Heretofore, the DNA amplification device 51 including the temperature element 61 according to the present invention has been described. For this reason, the constant current power supply device 102 of FIG. 5 is adopted as the power supply device of the temperature element 61. However, the constant current power supply device 102 of FIG. 5 can be widely used not only as a power supply device for the temperature element 61 but also as a power supply device using various electric and electronic devices operating with direct current as a load.

  Here, in the constant current power supply device 102 of FIG. 5, when the output voltages of the switching regulators 111P1 to 111M2 are equal to or higher than a threshold (1 V in the above example), the switching regulators 111P1 to 111M2 perform constant current output variable control. By taking charge, I try to increase power efficiency. On the other hand, when the output voltages of the switching regulators 111P1 to 111M2 are less than the threshold value, the linear regulators 113P and 113M are in charge of variable control of the output current, thereby obtaining a large current and a small voltage (particularly a voltage less than the threshold value). It is possible to supply a constant current stably to a load that is applied.

  Therefore, it is preferable to employ the constant current power supply device 102 of FIG. 5 as a power supply device for a load that requires a large current and a small voltage. For example, as such a load, there is a “biological tissue cutting / adhesion device (see FIG. 1)” disclosed in Japanese Patent Application No. 2009-56483 filed earlier by the present applicant.

  That is, according to the specification attached to the application of Japanese Patent Application No. 2009-56483, the biological tissue cutting / adhesion device is disposed on each of the semiconductor portions 2 and 3 facing each other and the semiconductor portions 2 and 3 respectively. The electrode-and-heat exchanging parts 5 and 6, and the joining part 4 interposed between the semiconductor part 2 and the semiconductor part 3 to join the semiconductor part 2 and the semiconductor part 3 and having thermal conductivity; A cutting / adhesion site which is composed of at least electrodes 8 and 9 disposed in the electrode / heat exchange section 5 and the electrode / heat exchange section 6 respectively, and protrudes to the outside of the semiconductor sections 2 and 3 in the joint section 4. 15 is formed, while an electric circuit 10 including a current source 18 that supplies a direct current from the electrodes 8 and 9 to the semiconductor units 2 and 3 and a converter 20 that changes the direction of the current, water and the like circulate. And the heat exchange medium circulation path 20 that flows through the heat exchange medium circulation path 20 And a pump 28 and reservoir 29, the heat exchange medium circulation path 20 is assumed to path through the interior of the electrode Ken'netsu exchange portions 5 and 6 were taken. In this case, the constant current power supply device 102 of FIG. 5 is referred to as “the electric circuit 10 including the current source 18 that supplies a direct current from the electrodes 8 and 9 to the semiconductor units 2 and 3 and the converter 20 that changes the direction of the current”. It is preferable to adopt it.

51 DNA amplification device 61, 61a, 61b Temperature element 62 Temperature 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 and heat dissipation plate 74P, 74N Water pipe 81 Mounting portion 91 Insulator 101 Temperature regulator 102 Constant current power supply device 103 Ammeter 104 Separate power supply 105 DC power supply 111P1, 111P2, 111M1, 111M2 Switching regulator 112P1, 112P2, 112M1, 112M2 Diode 113P1, 113M Linear regulator 114P, 114M Current Loop Current-Voltage Converter 201, 202 Area

Claims (8)

In a temperature control device that heats or cools an object,
A temperature element for heating or cooling the object by the Peltier effect;
A control unit that performs energization control on the temperature element, and
The temperature element is
A set of p-type and n-type semiconductors spaced apart from each other;
A mounting portion for mounting the object, wherein the p-type semiconductor is the first or second surface, and the n-type semiconductor is the second or first surface facing the first or second surface. A bonding portion to be bonded to each other in a plane;
A first electrode portion joined to the p-type semiconductor and applied with a voltage by the control unit;
A second electrode part joined to the n-type semiconductor and to which a voltage is applied by the control unit;
When a different voltage is applied to each of the first electrode part and the second electrode part by the control unit to cause a potential difference between the p-type semiconductor and the n-type semiconductor, the junction part Causes the Peltier effect by passing a current from one of the p-type semiconductor and the n-type semiconductor to the other and propagating the heat,
The control unit has a constant current source having both a switching regulator and a linear regulator,
The constant current source is:
If the absolute value of the output voltage of the switching regulator is greater than or equal to a threshold, the switching regulator is responsible for variable output control of a constant current,
When the absolute value of the output voltage of the switching regulator is less than the threshold, the linear regulator is responsible for variable output control of a constant current.
Temperature control device. The object is a predetermined container used for containing a DNA (Deoxyribonucleic acid) specimen,
The temperature control device according to claim 1, wherein the mounting portion is processed to mount the container. The temperature element is
A plurality of sets of the p-type semiconductor and the n-type semiconductor;
The p-type semiconductor of each of the plurality of sets is bonded to the first surface of the bonding portion, and the n-type semiconductor of each of the plurality of sets is bonded to the second surface of the bonding portion. Are joined,
The p-type semiconductor of each of the plurality of sets is joined to the first electrode portion, and the n-type semiconductor of each of the plurality of sets is joined to the second electrode portion. Item 3. The temperature control device according to Item 1 or 2. The temperature element is
A plurality of sets of the p-type semiconductor and the n-type semiconductor;
The insulator is inserted into the second surface from the first surface of the joint portion, so that the joint portion is divided into a plurality of regions,
For each of the plurality of regions, a set in which the p-type semiconductor is bonded to the first surface side and the n-type semiconductor is bonded to the second surface side, and the n-type semiconductor on the first surface side And a pair of joining the p-type semiconductors on the second surface side by alternately joining,
The predetermined p-type semiconductor connected to the first surface is joined to the first electrode portion, and the predetermined n connected to the first surface is connected to the second electrode portion. Type semiconductor is joined,
The temperature control apparatus according to any one of claims 1 to 3, further comprising a third electrode portion that joins the plurality of sets in series. The temperature control device according to any one of claims 1 to 4, further comprising a cooling unit that cools at least one of the first electrode portion and the second electrode portion of the temperature element. The temperature control device according to any one of claims 1 to 5, wherein the temperature control device is a portable device. In a power supply for a temperature element that heats or cools an object by the Peltier effect,
The temperature element is
A set of p-type and n-type semiconductors spaced apart from each other;
A bonding portion for mounting the object, and a bonding portion for bonding to each of the p-type semiconductor and the n-type semiconductor;
A first electrode portion joined to the p-type semiconductor and applied with a voltage from the outside;
A second electrode portion joined to the n-type semiconductor and applied with a voltage from the outside,
When a different voltage is applied from the outside to each of the first electrode part and the second electrode part to generate a potential difference between the p-type semiconductor and the n-type semiconductor, the junction part is: A temperature element that causes the Peltier effect by flowing current from one of the p-type semiconductor and the n-type semiconductor to the other and propagating heat;
The power supply device
A constant current source device having both a switching regulator and a linear regulator,
If the absolute value of the output voltage of the switching regulator is greater than or equal to a threshold, the switching regulator is responsible for variable output control of a constant current,
When the absolute value of the output voltage of the switching regulator is less than the threshold, the linear regulator is responsible for variable output control of a constant current.
Power supply for temperature element. The power supply device for a temperature element according to claim 7, wherein the mounting portion is processed in a shape corresponding to a shape of the object and is formed in the joint portion.

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