Electrophoretic device

Abstract

To solve the above problem, an electrophoresis device of the present application includes: a capillary array including a capillary, a capillary head bundling one end of the capillary, an electrode holder holding an electrode provided at the other end of the capillary, and a detection portion provided at the capillary; a first heating portion heating the capillary; and an irradiation detection unit irradiating the detection portion with light and detecting fluorescence emitted from a fluorescently labeled sample in the capillary, wherein a second heating portion is provided to heat the detection portion.

Description

[0001] This application is a divisional application of application No. 201880096718.1, entitled "Electrophoresis device", filed on October 29, 2018. TECHNICAL FIELD

[0002] The present application relates to an electrophoresis device. BACKGROUND

[0003] In recent years, the scope of application of DNA analysis has rapidly expanded from research use to clinical fields such as hospitals. As a method of DNA analysis, there is a method of separating DNA fragments using electrophoresis, which is used for criminal investigation, determination of blood relationship, and disease diagnosis.

[0004] In Patent Literature 1, in order to reduce the temperature deviation between capillaries, an electrophoresis device is disclosed, which has: a multi-capillary array having a detection portion; a voltage application mechanism that applies a voltage to a power circuit including the sample introduction portion and the detection portion; a constant temperature tank that houses a portion or the entire portion of the multi-capillary array excluding the sample introduction portion; a first buffer container that houses a first buffer solution that impregnates the sample introduction portion; a first temperature control mechanism that adjusts the temperature of the first buffer solution; and a second temperature control mechanism that adjusts the temperature of the detection portion.

[0005] In Patent Literature 2, an electrophoresis device is disclosed, which is characterized by being provided with: a capillary array having a capillary and an optical detection portion for optically detecting a sample electrophoresed in the capillary; a constant temperature tank device including a main frame for housing the capillary array in order to maintain the capillary at a constant temperature and a door frame; a temperature control member provided to the main frame and having a hole; an optical detection portion holder disposed in the hole of the temperature control member and for holding the optical detection portion; and an optical detection portion holder cover for pressing the optical detection portion held in the detection portion, and a temperature propagation member is provided to the optical detection portion holder cover to contact the temperature control member.

[0006] Prior Art Documents

[0007] Patent Literature

[0008] Patent Literature 1: Japanese Patent Application Publication No. 2003-166976

[0009] Patent Literature 2: Japanese Patent Application Publication No. 2007-322367 SUMMARY

[0010] Problems to be Solved by the Invention

[0011] In order to improve the analysis performance of the electrophoresis device, it is necessary to heat the capillary at an appropriate temperature.

[0012] In Patent Literature 1, the vicinity of the detection section is heated by a second temperature control mechanism. However, temperature control of the detection section itself is not performed. In Patent Literature 2, a temperature propagation member transmits heat of a temperature control member to an optical detection section. However, sufficient temperature adjustment cannot be performed for the temperature propagation member.

[0013] An object of the present application is to improve the analysis performance of an electrophoresis device.

[0014] Solution to the problem

[0015] To solve the above problem, the electrophoresis device of the present application is provided with: a capillary array provided with a capillary, a capillary head bundling one end of the capillary, an electrode holder holding an electrode provided at the other end of the capillary, and a detection section provided at the capillary; a first heating section that heats the capillary; and an irradiation detection unit that irradiates the detection section with light and detects fluorescence emitted from a fluorescent marker sample in the capillary, the electrophoresis device being characterized by having a second heating section that heats the detection section.

[0016] Effects of the Invention

[0017] According to the present application, it is possible to improve the analysis performance of an electrophoresis device. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 is a diagram showing the structure of a capillary electrophoresis device.

[0019] Figure 2 is a plan view of a capillary electrophoresis device.

[0020] Figure 3 is an A-A sectional view of a capillary electrophoresis device.

[0021] Figure 4A is a diagram showing the structure of a capillary cartridge viewed from the capillary side.

[0022] Figure 4B is a diagram showing the structure of a capillary cartridge viewed from the holding section side.

[0023] Figure 5A is a diagram showing the structure of a constant-temperature tank.

[0024] Figure 5B is a diagram showing the structure of a constant-temperature tank in which a capillary cartridge is installed.

[0025] Figure 5C is a diagram showing the structure of a constant-temperature tank after a capillary cartridge is installed.

[0026] Figure 6A is a diagram showing the structure of a second temperature adjustment unit.

[0027] Figure 6B is a diagram showing an example of the second temperature adjustment unit.

[0028] Figure 6C is a side view of the second temperature adjustment unit.

[0029] Figure 7A is a diagram showing the surroundings of the detection section of the prior art.

[0030] Figure 7B is a diagram showing the surroundings of the detection section of the present application.

[0031] Figure 8A is a diagram showing the temperature distribution of the capillary array.

[0032] Figure 8B is a diagram showing the arrangement of the thermostat and the capillary array.

[0033] Figure 9A is a diagram showing the temperature distribution of the capillary array of the prior art.

[0034] Figure 9B is a diagram showing the temperature distribution of Figure 8A

[0035] Figure 10A is a diagram showing the temperature distribution of the capillary array of the present application.

[0036] Figure 10B is a diagram showing the temperature distribution of Figure 9A

[0037] Figure 11 is a diagram showing the structure of the first temperature adjustment unit.

[0038] Figure 12 is a diagram showing the heater of the first temperature adjustment unit.

[0039] Figure 13A is a diagram showing an example of the heater of the first temperature adjustment unit of Example 2.

[0040] Figure 13B is a diagram showing an example of the heater of the first temperature adjustment unit of Example 2.

[0041] Figure 14A is a diagram showing an example of the surroundings of the detection section of Example 3.

[0042] Figure 14B is a diagram showing an example of the surroundings of the detection section of Example 3. DETAILED DESCRIPTION

[0043] ​​An embodiment of the present application will be described below with reference to the accompanying drawings.

[0044] Example 1

[0045] Figure 1 A device configuration diagram of a capillary electrophoresis device of Example 1 is shown. The device can be roughly divided into an irradiation detection / thermostatic bath unit 40 at the upper portion of the device and an automatic sampler unit 20 at the lower portion of the device.

[0046] In the automatic sampler unit 20, a Y-axis drive body 23 is mounted on a sampler base 21, a Z-axis drive body 24 is mounted on the Y-axis drive body 23, and a sample disk 25 is mounted on the Z-axis drive body 24. Thus, the sample disk can be driven in the Y-axis direction and the Z-axis direction by the Y-axis drive body 23 and the Z-axis drive body. A user places a running medium container 28, an anode-side buffer container 29, a cathode-side buffer container 33, and a sample container 26 on the sample disk 25. The sample container 26 is placed on an X-axis drive body 22 mounted on the sample disk 25, and the sample container 26 can be driven on the sample disk 25 only in the X-axis direction. A liquid supply mechanism 27 is also mounted on the Z-axis drive body 24. The liquid supply mechanism 27 is disposed below the running medium container 28.

[0047] The irradiation detection / thermostatic bath unit 40 is mainly composed of a thermostatic bath unit 41 and an irradiation detection unit 42. The thermostatic bath unit 41 can maintain the temperature inside constant. The irradiation detection unit 42, which is an irradiation detection portion, is mounted at the rear of the thermostatic bath unit 41. A user places a capillary cartridge 01 described later in the thermostatic bath unit 41 and fixes it inside the thermostatic bath unit 41. While the capillary is kept constant in temperature by the thermostatic bath unit 41, electrophoresis of a sample with added fluorescence is performed, and detection of the fluorescence imparted to the sample is performed by the irradiation detection unit 42. In addition, an electrode (anode) 43 for falling to GND when a high voltage for electrophoresis is applied is also mounted on the thermostatic bath unit 41. As described above, the running medium container 28, the anode-side buffer container 29, the cathode-side buffer container 33, and the sample container 26 can be driven in the YZ-axis direction by the automatic sampler unit 20, and only the sample container 26 can be driven in the X-axis direction. Thus, the running medium container 28, the anode-side buffer container 29, the cathode-side buffer container 33, and the sample container 26 can be automatically connected to the capillary of the capillary cartridge 01 fixed to the thermostatic bath unit 41 by the action of the automatic sampler unit 20.

[0048] Figure 2 A device configuration diagram of a capillary electrophoresis device of Example 1 is shown. The device can be roughly divided into an irradiation detection / thermostatic bath unit 40 at the upper portion of the device and an automatic sampler unit 20 at the lower portion of the device. Figure 1The diagram shows a top view of the capillary electrophoresis apparatus. The anode-side buffer container 29, placed on the sample tray 25, includes an anode-side cleaning tank 30, an anode-side electrophoresis buffer tank 31, and an anode-side sample introduction buffer tank 32. Additionally, the cathode-side buffer container 33 includes a waste liquid tank 34, a cathode-side cleaning tank 35, and a cathode-side electrophoresis buffer tank 36.

[0049] The electrophoresis medium container 28, the anode-side buffer solution container 29, the cathode-side buffer solution container 33, and the sample container 26 are arranged in the positional relationship shown in the figure. Thus, the positional relationship of the anode side to the cathode side when connected to the capillary 05 in the constant temperature bath unit 41 is "electrophoresis medium container 28 - waste liquid tank 34", "anode-side cleaning tank 30 - cathode-side cleaning tank 35", "anode-side electrophoresis buffer solution tank 31 - cathode-side electrophoresis buffer solution tank 36", and "anode-side sample introduction buffer solution tank 32 - sample container 26".

[0050] Figure 3 express Figure 2 A-A sectional view. The swimming medium container 28 is placed on the sample tray 25. In addition, the liquid supply mechanism 27 is configured such that the plunger built into the liquid supply mechanism 27 is located below the swimming medium container 28.

[0051] During electrophoresis, capillary 05 Figure 3 The right side is the cathode side, and the left side is the anode side. The sample tray 25 is moved in such a way that the anode and cathode sides of the capillary are positioned as "anode-side electrophoresis buffer tank 31 - cathode-side electrophoresis buffer tank 36". A high voltage is applied to the capillary 05 on the cathode side, and the current flows through the cathode-side buffer container 33 and the anode-side buffer container 29, through the electrode (anode) 43 to GND, thereby performing electrophoresis. Alternatively, a device structure can be adopted in which the position of the sample tray 25 is fixed, while the irradiation detection / thermostat unit 40 is movable.

[0052] Figure 4A This is a schematic diagram showing a structure of the capillary box in this embodiment. The capillary box 01 consists of a capillary array 02, a separator 10, a support 03, a sheet 04, and a gripping part 11 (see reference). Figure 4B The capillary array 02 is composed of a capillary 05, a detection unit 06, a capillary head 07, an electrode (cathode) 08, and an electrode support 09. In this figure, the electrode (cathode) 08 is held in place by the electrode support 09, but it could also be constructed with the electrode (cathode) 08 directly fixed to the support 03. Furthermore, in this figure, the capillary box 01, starting from the front side of Figure 4, consists of a support 03 with a gripping part 11, a sheet 04, and the capillary array 02 arranged sequentially.

[0053] The components will be described. The capillary 05 is a narrow flow path in which a coating for maintaining light shielding and strength is implemented, such as a quartz glass tube of about 50 μm in inner diameter in which a polyimide coating is implemented. The tube is filled with a mobile medium, becoming a mobile path for mobile separation of a sample. The capillary head 07 is the end of the capillary 05, binds and holds the capillary 05, and is an injection end or an exhaust end in which the mobile medium is filled. The partition 10 is formed with a number of holes equal to the number of the capillary 05, the inner diameter of the hole is slightly larger than the inner diameter of the capillary 05, and one capillary 05 penetrates each hole. This separates the capillary 05 from each other, preventing the capillary 05 from being entangled with each other and gathered in a bundle. In addition, the partition 10 is a member having a seal-like portion with adhesive on one side, and functions to position the capillary 05 on the sheet 04 by being attached to the sheet 04 with the capillary 05 penetrating. The material of the partition 10 is preferably thin and soft so as not to be an obstacle when the capillary cartridge is fixed to the thermostat unit 41. For example, as the material of the partition 10, there are silicone, paper, film, and the like. The number of the partition 10 can be increased or decreased according to the length of the capillary 02.

[0054] The electrode (cathode) 08 is present in a number corresponding to the number of the capillary 05, and by applying a voltage, a charged sample can be introduced into the capillary 05, and mobile separation is performed for each molecular size. The electrode (cathode) 08 is, for example, a stainless steel tube of about 0.1 to 0.5 mm in inner diameter, and the capillary 05 is inserted therein. The detection portion 06 is located above the capillary 05, and the capillary 05 is arranged in a planar shape with a constant accuracy. The detection portion 06 is a site for detecting the fluorescence of a sample passing through the capillary 05, and needs to be aligned with high accuracy with the position of the detection system of the device.

[0055] The sheet 04 is preferably a soft sheet having a cushioning property. By using a sheet having a cushioning property, breakage of the capillary 05 can be prevented. Furthermore, by using a heat insulating material or a heat dissipating material for the sheet 04, heat insulating performance and heat dissipating performance can be obtained. For example, as the heat insulating material, there are polyurethane foam, foamed plastic such as polyethylene, fiber-based materials such as glass wool, and the like, and as the heat dissipating material, there are rubber or elastomers such as silicone, heat dissipating gel, and the like.

[0056] Figure 5A An example of the thermostat unit 41 will be described. As shown in Figure 5A FIG. 6, the thermostat unit 41 is composed of a thermostat base 60 and a thermostat door 61. The thermostat base 60 is provided with a first temperature adjustment unit 62 for temperature adjustment of the capillary 05. The first temperature adjustment unit 62 has a cutout portion 63. The irradiation detection unit 42 is disposed in the cutout portion 63. The thermostat door 61 is provided with a second temperature adjustment unit 64 for temperature adjustment of the detection portion 06 of the capillary. Details of the first temperature adjustment unit 62 and the second temperature adjustment unit 64 will be described later.

[0057] Using Figure 5B An example of mounting the capillary cartridge 01 to the thermostat bath base 60 is described in detail. The protruding portion formed in the support body 03 as the insertion portion 56 is inserted into the opening portion of the thermostat bath base 60 as the support body insertion port 55. At the same time, the electrode holder positioning pin 51 of the thermostat bath base 60 is made to enter the electrode holder positioning hole 52 while the support body foot portion 53 formed in the support body is made to be placed in the support body foot receiving portion 54 formed in the thermostat bath base 60, thereby mounting the capillary cartridge 01. By the insertion of the support body 03, the floating of the capillary cartridge 01 due to the partial contact of the support body 03 when the thermostat bath door 61 is closed is prevented. Furthermore, by closing the thermostat bath door 61, the capillary cartridge 01 is pressed against the heater 62 as the mounting surface and is fixed.

[0058] Using Figure 5C An example of mounting the capillary cartridge 01 to the thermostat bath base 60 is described in detail. The protruding portion formed in the support body 03 as the insertion portion 56 is inserted into the opening portion of the thermostat bath base 60 as the support body insertion port 55. At the same time, the electrode holder positioning pin 51 of the thermostat bath base 60 is made to enter the electrode holder positioning hole 52 while the support body foot portion 53 formed in the support body is made to be placed in the support body foot receiving portion 54 formed in the thermostat bath base 60, thereby mounting the capillary cartridge 01. By the insertion of the support body 03, the floating of the capillary cartridge 01 due to the partial contact of the support body 03 when the thermostat bath door 61 is closed is prevented. Furthermore, by closing the thermostat bath door 61, the capillary cartridge 01 is pressed against the heater 62 as the mounting surface and is fixed.

[0059] The following uses Figure 6A , Figure 6B and Figure 6C The structure of the second temperature adjustment unit 64 for realizing the above-described situation is described.

[0060] Figure 6Ais a view showing the structure of the second temperature adjustment unit 64. The second temperature adjustment unit 64 is composed of a heater 70, a pressing block 71 for transmitting heat of the heater 70 to the detection section 06, a base plate 72 for mounting the heater 70, and an anti-reflection sheet 73. Figure 6B shows the appearance after the second temperature adjustment unit 64 is assembled. The second temperature adjustment unit 64 is mounted to the thermostat door 61 in such a manner that it directly contacts the detection section 06 of the capillary tube when the thermostat door 61 is closed. The second temperature adjustment unit 64 temperature-adjusts the detection section 06 from the side opposite to the direction in which the irradiation detection unit 42 detects fluorescence. The second temperature adjustment unit 64 transmits heat of the heater 70 to the pressing block 71 which contacts the detection section 06, and temperature-adjusts the detection section 06. In order to efficiently transmit heat of the heater 70, it is preferable that the area of the surface of the pressing block 71 which contacts the detection section 06 is equal to the area of the detection section 06, and the material of the pressing block 71 is preferably a material having a high thermal conductivity such as aluminum or copper. Further, it is preferable that the anti-reflection sheet 73 is provided to the pressing block 71. If the anti-reflection sheet 73 is not provided, fluorescence emitted from a sample which passes through the capillary tube 05 can be reflected to the pressing block 71. If the reflected fluorescence reaches the detection section 06, problems such as an increase in background noise occur, resulting in a decrease in detection accuracy. By providing the anti-reflection sheet 73, the problems such as an increase in background noise can be alleviated. The color of the pressing block 71 is preferably a color which alleviates reflection, such as black.

[0061] Figure 6C shows the second temperature adjustment unit 64 provided to the thermostat door 61. A spring 74 is provided between the second temperature adjustment unit 64 and the thermostat door 61. A guide 75 is provided to the thermostat door 61 in such a manner that it surrounds the second temperature adjustment unit 64 and the spring 74. By having the guide 75, the second temperature adjustment unit 64 can move only in a predetermined direction by the spring 74. The guide 75 can be provided separately from the thermostat door 61 as shown in Figure 6C , or the thermostat door 61 can be provided in a shape which functions as the guide 75. When the thermostat door 61 is closed, the second temperature adjustment unit 64 is pressed against the detection section 06 of the capillary tube. A gap is provided between the second temperature adjustment unit 64 and the guide 75, and therefore the second temperature adjustment unit 64 can move within the range of the gap. Therefore, when the thermostat door 61 is closed, the pressing block 71 and the detection section 06 can be brought into surface contact, and heat of the heater 70 can be efficiently transmitted to the detection section 06. Further, the detection section 06 pressed by the second temperature adjustment unit 64 is pressed against the irradiation detection unit 42. Thus, positioning of the detection section 06 is also performed.

[0062] Figure 7A Figure 7B ​​The temperature control near the detection unit 06 will be explained. The support 03 of the capillary box 01 is omitted, and only the capillary 05 and the detection unit 06 are described. Figure 7A This diagram illustrates the temperature regulation around the detection section as described in Patent Document 1. The capillary 05 near the detection section 06 is regulated by heaters (or conductive components) 92 and 93 located in the main body 91 and the cover 94. On the other hand, the detection section 06 is pressed against the irradiation detection unit 42 by a spring 95 located in the cover 94, thus not regulating the temperature of the detection section 06. Therefore, the detection section 06 has a lower temperature than the capillary near the detection section 06, which is sandwiched between heaters 92 and 93. Figure 8B The temperature regulation near the detection unit 06 of the present invention will be described. As mentioned above, the present invention provides a second temperature regulation unit 64 with a heater 70 for directly heating the detection unit 06. A spring 74 is provided between the thermostatic tank door 61 and the second temperature regulation unit 64. When the thermostatic tank door 61 is closed, the second temperature regulation unit 64 presses the detection unit 06 against the irradiation unit 42, and the detection unit 06 and the second temperature regulation unit 64 also come into contact. As a result, the detection unit 06 can be heated from the side opposite to the side where the irradiation detection unit 42 is provided by the second temperature regulation unit 64. The capillary 05 near the detection unit 06 is heated by being sandwiched between the first temperature regulation unit 62 with a heater 81 and the thermostatic tank door 61, as in Patent Document 1. Details of the first temperature regulation unit 62 will be described later. In this embodiment, the second temperature regulation unit 64 for heating the detection unit 06 is provided in the thermostatic tank door 61. The second temperature regulation unit 64 only needs to be able to heat the detection unit 06 from the side opposite to the side where the irradiation detection unit 42 is provided. The second temperature regulating unit 64 can be provided on the door 61 of the thermostatic bath as in this embodiment, or an additional mounting component, such as a door, can be provided for providing the second temperature regulating unit 62 on the base 60 of the thermostatic bath.

[0063] Next, the temperature of the capillary array O2 and the electrophoresis results during electrophoresis will be explained. For example... Figure 8A As shown, the area from the electrode holder 09 of the capillary array 02 to the detection unit 06 is designated as region 1, the detection unit 06 as region 2, and the area from the detection unit 06 to the capillary head 07 as region 3. The capillary array 02 is as follows... Figure 8B The temperature control unit 41 is configured to... Figure 8AThe region of the first temperature adjustment unit that adjusts the temperature of the region 1 is set as region 1', the position where the detection unit of the region 2 is arranged is set as region 2', and the region of the first temperature adjustment unit 62 that adjusts the temperature of the region 3 is set as region 3'. The regions 1 and 3 of the capillary array 02 are adjusted in temperature by the first temperature adjustment unit 62 provided in the constant-temperature bath base 61. The detection unit 06 of the region 2 is positioned in the cutout portion 63 of the first temperature adjustment unit 62 where the irradiation detection unit 42 is arranged, and therefore, cannot be adjusted in temperature by the first temperature adjustment unit. Therefore, the detection unit 06 of the region 2 is adjusted in temperature by the second temperature adjustment unit 64 provided in the constant-temperature bath door 61.

[0064] The temperature distribution of the capillary array 02 when the capillary array 02 is adjusted in temperature by only the first temperature adjustment unit 64 as in the past will be described using the case where the capillary array 02 is adjusted in temperature to 60°C. The regions 1 and 3 become the set temperature, i.e., 60°C. The detection unit 06 of the region 2 is not adjusted in temperature because it is not in contact with the first temperature adjustment unit 64 as described above, and therefore, the temperature of the region 2 is lower than that of the regions 1 and 3. Figure 9A The migration result at this time is shown in FIG. 6. The regions 1 and 3 are adjusted in temperature to 60°C, and the detection unit 06 of the region 2 is not adjusted in temperature. Figure 9B The migration result in the temperature distribution of the capillary array 02 shown in FIG. 6 is shown in FIG. 7. The regions 1 and 3 are adjusted in temperature to 60°C, and the detection unit 06 of the region 2 is not adjusted in temperature. Figure 9B In the migration result of the capillary array 02, the detected fluorescence intensity gradually decreases. If the fluorescence intensity decreases, the detection sensitivity on the long-base side deteriorates, and there is a problem in that it can not be possible to detect in the case of a small amount of sample. Therefore, it was found through re-study that the decrease in fluorescence intensity is related to the temperature difference between the regions 2 and 3 of the capillary array 02, and the smaller the temperature difference between the regions 2 and 3, the more uniform the fluorescence intensity. Figure 10A The temperature distribution of the capillary array 02 in which the temperature difference between the regions 2 and 3 is set to be small is shown in FIG. 8, Figure 10B The migration result when the temperature distribution of the capillary array 02 is Figure 10A The migration result when the temperature distribution of the capillary array 02 is Figure 10B As is clear from the migration result shown in FIG. 6, the fluorescence intensity does not decrease, and the fluorescence intensity is uniform. It is clear that if the temperature difference between the regions 2 and 3 is reduced, the fluorescence intensity becomes uniform. The smaller the temperature difference between the regions 2 and 3, the better, and if the temperature difference is within 7 degrees, a practically uniform signal intensity can be obtained. In addition, the temperature of the regions 2 and 3 is preferably around 45 degrees. If the temperature of the regions 2 and 3 is too low, the separation of the sample can be reduced, and the separation time can become long. In addition, in order to make the regions 1, 2, and 3 uniform at a high temperature, a high output is required. Therefore, the temperature of the regions 2 and 3 is preferably around 45 degrees.

[0065] As is clear from the migration result shown in FIG. 6, the fluorescence intensity does not decrease, and the fluorescence intensity is uniform. It is clear that if the temperature difference between the regions 2 and 3 is reduced, the fluorescence intensity becomes uniform. The smaller the temperature difference between the regions 2 and 3, the better, and if the temperature difference is within 7 degrees, a practically uniform signal intensity can be obtained. In addition, the temperature of the regions 2 and 3 is preferably around 45 degrees. If the temperature of the regions 2 and 3 is too low, the separation of the sample can be reduced, and the separation time can become long. In addition, in order to make the regions 1, 2, and 3 uniform at a high temperature, a high output is required. Therefore, the temperature of the regions 2 and 3 is preferably around 45 degrees. Figure 9ACompared to the case without temperature regulation, when a temperature transfer member, as in Patent Document 2, is used to transfer heat from the first temperature regulation unit 62 to the detection unit, the temperature of region 2 increases. However, while this can be considered a slight improvement in reducing fluorescence intensity, the detection unit 06 cannot be sufficiently heated by the temperature transfer member, and the fluorescence intensity does not become uniform. Therefore, instead of heating the detection unit 06 by transferring heat from the first temperature regulation unit 62 to the detection unit, it is necessary to provide a second temperature regulation unit 64, as in this invention, to heat the region 06 with higher output precision in a way that reduces the temperature difference between region 2 and region 3.

[0066] Next, use Figure 11 The first temperature regulating unit 62, which is used to heat region 1' of the capillary array 02 to a high temperature and region 3' of the low temperature, is described. Figure 11 In the illustration, for ease of understanding, the first temperature regulating unit 62 is shown separated from the thermostatic bath base 60.

[0067] The first temperature regulation unit 62 consists of a heat insulation sheet 80, a heater 81, a heat transfer plate 82, and a heat conduction sheet 83, which are fixed to each other by methods such as bonding, welding, and threaded fixing.

[0068] In order to regulate the temperature of zone 1 of the capillary array 02 at a high temperature and regulate the temperature of zone 3 at a low temperature, the heater 80 is composed of zone 1' of the high-temperature region and zone 3' of the low-temperature region (see reference). Figure 12 Additionally, a non-heating region 85 is provided between region 1' and region 3' to prevent the temperature of region 1' from being transferred to region 3'. Although details are not shown, the heater 81 has heating resistance wires arranged on a base component such as a polyimide film, silicone, or ceramic. The heat output can be adjusted by the thickness and density of the heating resistance wires; when they are sparsely arranged, the heat output is reduced. Thus, a single heater 81 can have both high-temperature and low-temperature regions. In this embodiment, only one heater 81 is used, but different heaters can also be provided for regions 1' and 3'. Furthermore, the heat output of the heater is not limited to two levels; it can also be divided into three or more levels based on the heat dissipation.

[0069] The heat generated by the heater 81 is transmitted to the capillary tubes 05 of the capillary tube block 01 through the heat transmission plate 82 and the heat conduction sheet 83, and the capillary tubes 05 are heated. In order to prevent the heat of the heater 81 from being dissipated, a heat insulating sheet 80 is installed on the side of the thermostat base 60 of the first temperature adjustment unit 62. The heat transmission plate 82 is provided in order to uniformly spread the heat generated by the heater 81 to the heat conduction sheet 83, and is preferably a metal material having high thermal conductivity, such as aluminum or copper, etc. The heat conduction sheet 83 is required to efficiently transmit the heat generated from the heater to the capillary tubes 05, and thus excellent thermal conductivity is desirable. In addition, in order to prevent the contacted capillary tubes 05 from being damaged, a soft material is preferable. Furthermore, the order of the heat transmission plate 82 and the heater 81 can be reversed, and the first temperature adjustment unit 62 can also be arranged in the order of the heat insulating sheet 81, the heat transmission plate 82, the heater 81, and the heat conduction sheet 83.

[0070] In order to adjust the temperature of the zone 1 of the capillary tube array 02 at a high temperature and the temperature of the zone 3 at a low temperature, not only the heater 81 but also the heat transmission plate 82 needs to be divided into the zone 1' and the zone 3'. Even if the heater 81 is provided with a high-temperature region and a low-temperature region, if the heat transmission plate 82 is common to the high-temperature region and the low-temperature region, the heat of the high-temperature region will be transmitted to the low-temperature region, and the temperature of the low-temperature region will be increased. Therefore, the heat transmission plate 82 of the present application is divided into the zone 1' and the zone 3'. Furthermore, it is preferable to provide a heat insulating block 84 between the heat transmission plate 82 of the zone 1' and the heat transmission plate 82 of the zone 3' in order to prevent the heat of the zone 1' from being transmitted to the zone 3'.

[0071] The temperature control of the heater 81 is performed by a temperature sensing sensor such as a thermistor installed in the first temperature adjustment unit 62. The installation position of the omitted thermistor can be any one of the heat insulating sheet 80, the heater 81, the heat transmission plate 82, and the heat conduction sheet, but is desirable to be on the heat dissipation rubber 64 which contacts the capillary tubes 05. In the case where the heater 81 is one as in the present application, the temperature control is performed commonly to the zone 1' and the zone 3', and thus the temperature control can be performed at a low cost compared to the case where two heaters are provided.

[0072] Example 2

[0073] In Example 1, the heater 81 which divides the heat generation amount into two levels of the zone 1' and the zone 3' is shown, but the heat generation amount of the heater 81 can be divided into three or more levels. Except for the heater 81, the other is the same as Example 1.

[0074] Figure 13AA heater 81 of the present embodiment is shown. The thermostat bath unit 41 is not completely closed, and thus there is a case where the temperature is affected by the ambient temperature. In particular, the capillary tube head 07 and the electrode holder 09 protrude from the lower side of the zones 3' and 4' to the outside of the thermostat bath unit 41, and thus the thermostat bath unit 41 is slightly open. Therefore, the lower side of the first temperature adjusting unit 62 is easily affected by the ambient temperature. Therefore, the heater of the present embodiment is provided with the zone 4' having a larger heat generation amount than the zone 1' on the lower side of the zone 1'. By increasing the heat generation amount of the zone 4' having a large heat dissipation amount, the detection portion 06 can be heated more uniformly from the electrode holder 09 of the capillary tube array 02. In addition, as shown in Figure 13B the drawing, the zone 4' having a larger heat generation amount than the zone 1' can be provided according to the heat dissipation amount not only on the lower side of the zone 1' but also in a manner surrounding the zone 1'.

[0075] Embodiment 3

[0076] In Embodiment 1, an example in which the detection portion 06 is heated from the side opposite to the side on which the irradiation detection unit 42 is provided using the second temperature adjusting unit 64 is shown. In the present embodiment, the detection portion 06 is heated from the side of the irradiation detection unit 42 using the heater 100 provided on the irradiation detection unit 42. Figure 14A Figure 14B An example in which the detection portion 06 is heated from the side of the irradiation detection unit 42 by providing a heater on the irradiation detection unit 42 is described.

[0077] Figure 14A Temperature adjustment in the vicinity of the detection portion of the present embodiment is shown. The second temperature adjusting unit 64 provided on the thermostat bath door 61 is replaced with the detection portion presser 101, and a heater 100 is provided on the irradiation detection unit 42, and otherwise the same as Embodiment 1. The present application does not heat the detection portion 06 by the second temperature adjusting unit 64 provided on the thermostat bath door 61, but heats the detection portion 06 by the heater 100 provided on the irradiation detection unit 42. The heater 100 is provided on the irradiation detection unit 42 so as to avoid the position where the fluorescence from the detection portion 06 enters the irradiation detection unit 42. The heater 100 is fixed to the detection unit 42 by adhesion, welding, screwing, or the like. When the thermostat bath door 61 is closed, the detection portion 06 is pushed against the irradiation detection unit 42 by the detection portion presser 101 provided on the thermostat bath door 61. Thus, the detection portion 06 comes into contact with the heater 100 provided on the irradiation detection unit 42, and the detection portion 06 is heated by the heater 100. The detection portion 06 is pressed by the detection portion presser 101, but the detection portion 06 can also be directly pushed against the irradiation detection unit 42 by the spring 74. When the heater 100 is provided on the detection unit 42, the heater 100 directly contacts the casting of the detection unit 42, and thus the temperature easily decreases, and thus a high output is required, but the detection portion can be heated with a simpler structure. In addition, when the detection portion 06 is heated from the side of the irradiation detection unit 42, a heater for heating the detection portion 06 can not be newly provided, but the heater 100 provided on the irradiation detection unit 42 can be used as is.​Figure 14B In this case, the heater provided at the irradiation detection unit 42 is commonly used with the first temperature adjustment unit 62.

[0078] Symbol explanation

[0079] 01 - capillary cartridge, 02 - capillary array, 03 - support body, 04 - sheet, 05 - capillary, 06 - detection section, 07 - capillary head, 08 - electrode (cathode), 09 - electrode holder, 10 - partition, 11 - grip section, 20 - autosampler unit, 21 - sampler base, 22 - X-axis drive body, 23 - Y-axis drive body, 24 - Z-axis drive body, 25 - sample tray, 26 - sample container, 27 - liquid supply mechanism, 28 - running medium container, 29 - anode-side buffer container, 30 - anode-side washing tank, 31 - anode-side electrophoresis buffer tank, 32 - anode-side sample introduction buffer tank, 33 - cathode-side buffer container, 34 - waste tank, 35 - cathode-side washing tank, 36 - cathode-side electrophoresis buffer tank, 40 - irradiation detection / thermostatic chamber unit, 41 - thermostatic chamber unit, 42 - irradiation detection unit, 43 - electrode (anode), 51 - electrode holder positioning pin, 52 - electrode holder positioning hole, 53 - support body foot portion, 54 - support body foot receiving portion, 55 - support body insertion port, 56 - insertion portion, 60 - thermostatic chamber base, 61 - thermostatic chamber door, 62 - first temperature adjustment unit, 63 - cutout portion, 64 - second temperature adjustment unit, 70 - heater, 71 - pressing block, 72 - base plate, 73 - anti-reflection sheet, 74 - spring, 75 - guide, 80 - heat insulation sheet, 81 - heater, 82 - heat transfer plate, 83 - heat conduction sheet, 84 - heat insulation block, 85 - non-heating area, 91 - main body portion, 92 - heater, 93 - heater, 94 - cover portion, 95 - spring, 100 - heater, 101 - detection section pressing member.

Claims

1. An electrophoresis apparatus comprising: a capillary array including capillaries, a capillary head bundling one end of the capillaries, an electrode holder holding an electrode provided at the other end of the capillaries, and a detection section provided at the capillaries; a heating section heating at least the capillaries; and an irradiation detection unit irradiating light to the detection section and detecting fluorescence emitted from a fluorescent marker sample in the capillaries, wherein the electrophoresis apparatus is characterized in that the heating section has a structure that independently temperature-regulates a first region, a second region, and a third region, the first region is a region of the capillary array from the electrode holder to the detection section, the second region is a region of the capillary array in which the detection section is disposed, the third region is a region of the capillary array from the detection section to the capillary head, the temperature is regulated so that the temperature of the second region and the third region is lower than the temperature of the first region, and the temperature difference between the second region and the third region is smaller than the temperature difference between the second region and the first region.

2. The electrophoresis apparatus according to claim 1, wherein the temperature difference between the second region and the third region is regulated to be 7 degrees or less.

3. The electrophoresis apparatus according to claim 1, wherein the temperature of the second region and the third region is regulated to be about 45 degrees.

4. The electrophoresis apparatus according to claim 1, wherein the heating section is configured to include a first temperature regulating unit and a second temperature regulating unit, the first region and the third region are temperature-regulated by the first temperature regulating unit, and the second region is temperature-regulated by the second temperature regulating unit.

5. The electrophoresis apparatus according to claim 4, wherein the first temperature regulating unit has: a first heat source; and a heat transfer plate that transfers heat of the first heat source to the capillaries, and the first heat source is configured to include: a first heat source region that temperature-regulates the third region; and a second heat source region that temperature-regulates the first region and has a larger heat generation amount than the first heat source region.

6. The electrophoresis apparatus according to claim 5, wherein the heat transfer plate is configured to include a first heat transfer plate that contacts a high-temperature portion, and a second heat transfer plate that contacts a low-temperature portion.

7. The electrophoresis apparatus according to claim 6, wherein a heat insulating material is provided between the first heat transfer plate and the second heat transfer plate.

8. The electrophoresis apparatus according to claim 4, wherein the second temperature regulating unit has a second heat source, and a block that transfers heat of the second heat source to the detection section.

9. The electrophoresis apparatus according to claim 8, wherein an anti-reflection sheet is provided on a surface of the block that contacts the detection section.

10. The electrophoresis apparatus according to claim 8, wherein the block is black.

11. The electrophoresis apparatus according to claim 8, wherein ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ The surface of the block that contacts the detection portion is the same size as the detection portion.

12. The electrophoresis apparatus according to claim 4, wherein the electrophoresis apparatus is configured to further include a case having a main body portion and a door portion, the first temperature adjustment unit is provided in the main body portion, the second temperature adjustment unit is provided in the door portion.

13. The electrophoresis apparatus according to claim 12, wherein a spring is provided in the door portion in front of the second temperature adjustment unit.

14. The electrophoresis apparatus according to claim 13, wherein a guide member is provided in the door portion in front of the second temperature adjustment unit.

15. The electrophoresis apparatus according to claim 4, wherein the detection portion is located between the irradiation detection unit and the second temperature adjustment unit.

16. The electrophoresis apparatus according to claim 4, wherein the second temperature adjustment unit is provided in the irradiation detection unit.

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