CAPILLAR ELECTROPHORESIS DEVICE

Abstract

Capillary electrophoresis device for analyzing a sample by electrophoresis using a capillary (02), wherein the device comprises the following: a heater (62) which heats the capillary (02), an electrode holder (05) which holds capillary electrodes of the capillary (02) and is connected to a high-voltage unit, and a conductive element (63) which is at least partially made of metal and is grounded to a low potential, wherein the electrode holder (05) and the conductive element (63) are in contact with an insulating element (64) arranged between them and a non-conductive heat storage plate (100) is arranged between the conductive element (63) and the insulating element (64).

Description

Technical field

[0001] The present invention relates to an electrophoresis device, wherein a capillary and, in particular, a technique for reducing its size and the risk of discharge are used. Technical background

[0002] In recent years, the application of DNA analysis has rapidly spread from research applications to clinical settings such as hospitals. A method for DNA analysis involves the electrophoresis of DNA fragments from a sample, which is used for criminal investigations, determining blood relationships, and diagnosing diseases.

[0003] In capillary electrophoresis, a capillary filled with a separation medium is kept at a constant temperature, and a high voltage is applied, causing charged DNA to be cleaved for each base length. The capillary is then irradiated with excitation light, and the fluorescence emitted by the fluorescent dye marker of the DNA passing through the capillary is detected, allowing the base sequence of the sample to be read.

[0004] In recent years, the requirements have diversified along with the increasing number of users. One requirement is to reduce the size of the device, and another is to obtain the results of DNA analysis as quickly as possible.

[0005] To reduce the size of a device, it is considered to actively eliminate additional space within the device itself. If a conductive part with a potential difference exists near the cathode end of a capillary, there is a possibility that a discharge will occur in peripheral parts of the capillary. A prior art capillary electrophoresis device was designed such that no conductive parts are located near the cathode end of a capillary to prevent discharges. However, if the size of the device is reduced, the conductive part will inevitably be located near the cathode end of the capillary, thus increasing the possibility of a discharge.

[0006] This is a problem that is also addressed in PTL 1, and PTL 1 discloses a structure in which, even in a case where a conductive part is located near a cathode end of a capillary, the spatial distance or creepage distance from the electrode of the capillary to the conductive part increases.

[0007] Regarding the achievement of rapid DNA analysis, it should be noted that a method for shortening the time required to initiate electrophoresis and a method for increasing the electrophoresis rate itself are being considered. PTL 2 discloses an electrophoresis device comprising a capillary, a support structure in which the capillary is arranged on a surface, a heater for temperature control in direct contact with the capillary, an optical system, and a high-voltage power supply. The structure, in which the capillary is in direct contact with the heater, allows the time required to raise the temperature to a predetermined value during electrophoresis analysis to be reduced.

[0008] PTL 2 is an effective means of obtaining the analysis result quickly by shortening the time required to initiate capillary electrophoresis. Additionally, a method involving the application of a high voltage to a capillary is available for obtaining the analysis result quickly by achieving rapid capillary electrophoresis. However, applying a high voltage further increases the aforementioned potential difference, and there is a possibility of discharge occurring in the capillary's outer regions. Citation listPatent literature PTL 1: JP 2010-249579 A PTL 2: JP 2006-284530 A

[0009] A capillary electrophoresis device in which an aluminum plate serving as a conductive element is directly provided with an insulating film is disclosed in US 2006 / 0 000 714 A1. Another capillary electrophoresis device similar to the invention is also disclosed in US 7 958 736 B2. Summary of the inventionTechnical problem

[0010] As described above, reducing the size of a capillary electrophoresis device and achieving rapid DNA analysis presents the common problem of needing to counteract discharges. Applying a high voltage to a capillary increases the risk of discharge to its edges. To reduce this risk, a large spatial distance, or creepage distance, must be ensured between the capillary electrode and the conductive edge. However, simply ensuring this distance increases the internal capacitance of the device to the same extent, thus negating the reduction in device size.

[0011] To ensure a large creepage distance, a common method involves giving parts with complex shapes to increase their surface area. Another method is to increase the creepage distance by roughening areas when simple surface shapes suffice. However, the risk of discharge increases or decreases depending on the presence or absence of cut marks, forming marks, or similar features on the surface of the parts, as well as on the atmospheric temperature and humidity within the device. Due to a phenomenon known as creep path formation, the location where a discharge has occurred acts as a discharge path, and further discharges are likely to occur there. Therefore, simply by designing components in a complex manner, it is difficult to effectively counteract discharges.

[0012] In addition to simply ensuring a distance, a method for achieving isolation by blocking a space is used. If the electrode of a capillary is attached while spatially separated from the outside, a space containing a high-voltage unit can be easily blocked. However, because the capillary is a consumable component that must be replaced after a certain number of electrophoresis cycles, the capillary electrode must also be located in a space accessible for replacement by a user, and spatial blockage is also difficult to achieve.

[0013] One object of the present invention is to solve the above problems and to provide a capillary electrophoresis device that reduces the discharge risk even with a partial configuration that has an insufficient spatial distance or creepage distance. Solution to the problem

[0014] To solve the aforementioned problem, the capillary electrophoresis device provided in claim 1 is offered for the analysis of a sample by electrophoresis using a capillary, according to the present invention. Further advantageous features are described in the dependent claims. Advantageous effects of the invention

[0015] According to the present invention, a capillary electrophoresis device can be provided which reduces the discharge risk even with a partial configuration that has an insufficient spatial distance or creepage distance. Brief description of the drawing

[0016] They show: Fig. 1 a schematic view of a configuration of a capillary electrophoresis device according to each embodiment, Fig. 2 a top view of the capillary electrophoresis device Fig. 1, Fig. 3 a sectional view of the device along a line AA in Fig. 2, Fig. 4 a view of a configuration of a capillary cartridge according to a first embodiment, which is not an embodiment of the invention but an example serving to illustrate the invention, Fig. 5 a detailed view of the capillary cartridge according to the first embodiment, Fig. 6 a schematic view of the attachment of the capillary cartridge according to the first embodiment, Fig. 7 a configuration near the capillary, whereby the risk of discharge is reduced, according to the first embodiment, Fig. 8 an example of a form of a conductive element according to the first embodiment, Fig. 9 a configuration view to illustrate the insulation treatment for the conductive element according to the first embodiment, Fig. 10 a configuration near a capillary, wherein the risk of discharge is reduced, according to a second embodiment, which is not an embodiment of the invention but an example serving to illustrate the invention, Fig. 11 a configuration near a capillary, wherein the risk of discharge is reduced, according to a third embodiment, which is not an embodiment of the invention but an example serving to illustrate the invention, Fig. 12 a configuration near a capillary, wherein the risk of discharge is reduced, according to a fourth embodiment as an embodiment of the invention, Fig. 13 a graphic 1 to illustrate the effect of the configuration of the third embodiment, Fig. 14 a graphic 2 to illustrate the effect of the configuration of the third embodiment, Fig. 15 a graphic 3 to illustrate the effect of the configuration of the third embodiment and Fig. 16 a graphic 4 to illustrate the effect of the configuration of the third embodiment. Description of embodiments

[0017] Various embodiments are described below as examples to aid in understanding the invention or as embodiments of the invention with reference to the drawings. In all drawings showing different embodiments, components that have the same function are designated by the same reference numerals or symbols. First embodiment

[0018] A first embodiment, which is not an embodiment of the invention but an example serving to illustrate the invention, is a capillary electrophoresis device that reduces the risk of discharge even in a partial configuration with insufficient spatial spacing or creepage distance. That is to say, the first embodiment is a capillary electrophoresis device for analyzing a sample by electrophoresis using a capillary and comprises a heater that heats the capillary, an electrode holder that holds the capillary electrodes and is connected to a high-voltage unit, and a conductive element that is at least partially made of metal and is grounded to a low potential, wherein the electrode holder and the conductive element are in contact with an intermediate structure, and the structure is an insulating element. The first embodiment is described below using the Fig. 1 to 9 described.

[0019] Fig. Figure 1 shows a configuration example of a capillary electrophoresis device according to the first embodiment. The device can be roughly divided into two units, namely an irradiation detection / thermostatic bath unit 40 at the upper section of the device and an automatic sampling unit 20 at the lower section of the device.

[0020] In the automatic sampling unit 20, which is an injection mechanism, a Y-axis drive body 23 is mounted on a sampling device base 21 and can be driven along the Y-axis. A Z-axis drive body 24 is mounted on the Y-axis drive body 23 and can be driven along the Z-axis. A sample tray 25 is mounted on the Z-axis drive body 24, and a user arranges an electrophoresis medium reservoir 28, an anode-side buffer liquid reservoir 29, a cathode-side buffer liquid reservoir 33, and a sample container 26 on the sample tray 25. The sample container 26 is arranged on the X-axis drive body 22, which is mounted on the sample tray 25, and only the sample container 26 can be driven along the X-axis on the sample tray 25. A fluid supply mechanism 27 is also mounted on the Z-axis drive body 24.The liquid supply mechanism 27 is located below the electrophoresis medium container 28.

[0021] The irradiation detection / thermostatic bath unit 40 comprises a thermostatic bath unit 41, which is the thermostatic bath, and a thermostatic bath door 43, and can maintain a constant internal temperature. An irradiation and detection unit 42, which is the irradiation detection section, is located behind the thermostatic bath unit 41 and can perform detection during electrophoresis. A user places a capillary cartridge, described in detail below, in the thermostatic bath unit 41. Electrophoresis is performed while the capillary is kept at a constant temperature in the thermostatic bath unit 41, and detection is performed by the irradiation and detection unit 42.Additionally, an electrode (anode) 44 is attached to the thermostatic bath unit 41 to apply a high voltage to ground when the high voltage for electrophoresis is applied. The thermostatic bath unit 41 is provided with a surface 50 for attaching the capillary cartridge, which will be described later.

[0022] As described above, the capillary cartridge is attached to the thermostatic bath unit 41. The electrophoresis medium reservoir 28, the anode-side buffer liquid reservoir 29, the cathode-side buffer liquid reservoir 33, and the sample reservoir 26 can be driven along the Y and Z axes by the automatic sampling unit 20, and only the sample reservoir 26 can be driven further along the X axis. The electrophoresis medium reservoir 28, the anode-side buffer liquid reservoir 29, the cathode-side buffer liquid reservoir 33, and the sample reservoir 26 can be automatically connected to any desired position within the capillary of the fixed capillary cartridge by the movement of the automatic sampling unit 20.

[0023] Fig. 2 shows a top view of the Fig. The capillary electrophoresis device shown in Figure 1. The anode-side buffer liquid container 29, arranged on the sample tray 25, has an anode-side wash bath 30, an anode-side electrophoresis buffer liquid bath 31, and an anode-side sample introduction buffer liquid bath 32. Additionally, the cathode-side buffer liquid container 33 has a waste liquid bath 34, a cathode-side wash bath 35, and a cathode-side electrophoresis buffer liquid bath 36.

[0024] The electrophoresis medium container 28, the anode-side buffer liquid container 29, the cathode-side buffer liquid container 33 and the sample container 26 are in the in Fig. 2 positional relationship shown. Therefore, the positional relationship between the anode side and the cathode side when connected to a capillary 02 of the capillary cartridge in the thermostatic bath unit 41 “electrophoresis medium container 28 - waste liquid bath 34”, “anode-side wash bath 30 - cathode-side wash bath 35”, “anode-side electrophoresis buffer liquid bath 31 - cathode-side electrophoresis buffer liquid bath 36” and “anode-side sample introduction buffer liquid bath 32 - sample container 26”.

[0025] Fig. 3 is a sectional view of the Fig. The capillary electrophoresis device shown in Figure 2 is arranged along a line AA. The electrophoresis medium container 28 is positioned on the sample tray 25. Additionally, the liquid supply mechanism 27 is arranged such that a piston embedded in the liquid supply mechanism 27 is located below the electrophoresis medium container 28.

[0026] During electrophoresis, the right side is in Fig. 3 to the cathode side of capillary 02 and the left side becomes the anode side. The automatic sampling unit 20 moves to a position “anode-side electrophoresis buffer liquid bath 31 - cathode-side electrophoresis buffer liquid bath 36”, as shown in Fig. As shown in Figure 2, a high voltage is applied to the capillary 02 on one electrode side (cathode side) 08, and a current flows from the electrode (anode) 44 through the cathode-side buffer liquid reservoir 33 and the anode-side buffer liquid reservoir 29 to the ground, thereby performing electrophoresis. A device structure can be provided in which the position of the sample holder 25 is fixed and the irradiation detection / thermostatic bath unit 40 is operated.

[0027] Fig. Figure 4 shows a schematic view of a configuration of the capillary cartridge according to the embodiment. The capillary cartridge 01 is designed to include the capillary 02, a support body 03, a heat dissipation body 04, an electrode holder 05, a detection unit 06, a capillary head 07, the electrode (cathode) 08, and a handle 09 as a handle section. Additionally, the electrode (cathode) 08 can have a structure in which the electrode is directly attached to the support body 03. Fig. 4 is the capillary cartridge 01 from the front of Fig. 4 in sequence support body 03 with handle 09, heat dissipation body 04 and capillary 02 arranged.

[0028] The capillary head 07 is an end section of the capillary 02 and serves as an injection or dispensing end, holding the capillary 02 in a bundle and filling it with the electrophoresis medium. According to the embodiment, when the capillary cartridge 01 is attached to the electrophoresis device, the capillary head 07 is connected to a container holding the electrophoresis medium, so that the capillary head 07 acts as the injection end. The capillary head 07 is installed in a bent position in the electrophoresis device.

[0029] Fig. Figure 5 shows a detailed view of the capillary cartridge 01 according to the [reference to be added]. Fig. 4. The heat dissipation body 04 is attached to the support body 03 by means of adhesion or stickiness, chemical adhesion, a physical attachment mechanism, or the like. Additionally, the capillary 02 has an integral structure due to the attachment of the electrode holder 05 and the detection unit 06 to the support body 03. The electrode holder 05 holds the electrode (cathode) 08 and is designed such that an electrode holder fastening pin 10, formed in the electrode holder 05, passes through an electrode holder fastening hole 11 of the support body 03, thereby fastening it to the support body 03. In addition, the support body 03 has an exposure cell mounting frame 12 for attaching the detection unit 06, and the detection unit 06 is fitted into the exposure cell mounting frame 12 formed in the support body 03 and is thereby firmly connected to the support body 03.

[0030] Capillary 02 is a coated stagnant-flow channel for maintaining light shielding and strength. It is, for example, a quartz glass tube with an inner diameter of approximately 50 µm, coated with polyimide. The tube is filled with an electrophoresis medium, thus forming an electrophoresis path for sample separation. Because capillary 02 and heat dissipation body 04 are in close contact, heat generated by capillary 02 when a high voltage is applied can be dissipated by the heat dissipation body 04 to the side of the support body 03, preventing the temperature within capillary 02 from rising.

[0031] Electrode (cathode) 08 is present in proportion to the number of capillaries 02. A charged sample can be introduced into capillary 02 by applying a voltage, thus enabling electrophoresis separation for each molecular size. Electrode (cathode) 08 is a stainless steel tube with an inner diameter of, for example, approximately 0.1 to 0.5 mm, and capillary 02 is inserted into it.

[0032] The detection unit 06 is located at an intermediate section of capillary 02, and the capillaries 02 are arranged planarly with constant accuracy. The detection unit 06 is a section for detecting the fluorescence of a sample passing through capillary 02, and precise positioning relative to the device's detection system is required.

[0033] Fig. Figure 6 shows an example of a detailed view of the attachment of the capillary cartridge 01 according to the first embodiment. In the upper part of Fig. Figure 6 shows the condition before the capillary cartridge is attached to the thermostatic bath unit, and in the lower part of Fig. Figure 6 shows a state in which the capillary cartridge is attached to the thermostatic bath unit 41. When an exposure cell positioning pin 13 of the detection unit 06 is attached to the mounting surface 50 on the side of the electrophoresis device facing the thermostatic bath unit 41 and pressed against it through a positioning hole 14 of the support body 03, the detection unit 06 is temporarily secured by a clamp 51. Because a tapered electrode holder positioning pin 15 on the side of a device facing the thermostatic bath unit 41 is automatically inserted into an electrode holder positioning hole 16 of the support body 03 for attachment, the capillary cartridge 01 is simultaneously and temporarily attached to the thermostatic bath unit 41 in a single operation.The electrode holder positioning pin 15 and the electrode holder positioning hole 16 can be positioned in opposite locations. This means that the electrode holder 05 and the support body 03 can be attached by guiding the electrode holder positioning pin provided on one side through the electrode holder positioning hole provided on the other side.

[0034] Fig. Figure 7 shows a configuration example near capillary 02, where the discharge risk in the capillary electrophoresis device according to the first embodiment is reduced. A heating arrangement 60 is attached to a thermostatic bath base 67. Fig. 7 The heating arrangement 60 is separated from the thermostatic bathroom base 67 for ease of understanding. The same applies to the following.

[0035] The heating arrangement 60 comprises a heat-insulating material 61, a resistance heater 62, a conductive element 63, and a heat-dissipating rubber 64, which forms a structure consisting of an insulating element. These elements are joined together by a method such as bonding, welding, or screwing. According to the embodiment, heat generated by the resistance heater 62 is transferred through the conductive element 63 and the heat-dissipating rubber 64 to the capillary 02 of the capillary cartridge 01 to heat the capillary 02. Additionally, a heat-insulating material 61 is attached to the side of the heating arrangement 60 facing the thermostatic bath base 67, so that the heat from the resistance heater 62 is not dissipated.

[0036] It is desirable that the heat dissipation rubber 64 has excellent thermal conductivity because it is necessary to effectively transfer the heat generated by the resistance heater 62 to the capillary 02. Additionally, it is desirable that the heat dissipation rubber be made of a flexible material to prevent damage to the capillary 02 upon contact.

[0037] The temperature of the resistance heater 62 is controlled by a temperature sensor in the form of a thermistor, which is attached to the heating assembly 60. The mounting position of the thermistor, not shown in the drawing, can be on the heat-insulating material 61, on the resistance heater 62, on the conductive element 63, and on the heat dissipation rubber 64, but is preferably located on the heat dissipation rubber 64.

[0038] A low-potential section is brought into contact with the conductive element 63. This low-potential section is generally referred to as earth or ground (GND) and has a virtual zero potential by being connected to the power supply of the device. According to the embodiment, a grounding plate 66 is attached to the thermostatic bath base 67 when the low-potential section is brought into contact with the conductive element 63. The grounding plate 66 is grounded to the conductive element 63, while avoiding contact with the surfaces of the heat-insulating material 61 and the resistance heater 62. A grounding wire or a frame ground via the device frame can be used for the low-potential section instead of the grounding plate.

[0039] Fig. Figure 8 shows a structure that, as a specific example of the shape of the conductive element 63 according to the first embodiment, is provided with a chamfer 70. The conductive element 63 consists at least partially of metal and has excellent conductivity. A preferred example is a metal plate made of aluminum, iron, brass, stainless steel, or the like. Additionally, a resin plate in which a metal powder or a metal filler is mixed, an elastomer, or the like can be used. Furthermore, a metal surface applied to the resistance heater 62 and the heat dissipation rubber 64, a metal layer applied thereto, a thin metal film applied thereto, or the like can be used.

[0040] The conductive element 63 also has a zero potential by being grounded to the grounding plate 66, as described above. When the conductive element 63 has a zero potential, a reduction in the potential of edge parts and a determination of the point at which the potential drops with respect to a section to which a high voltage is applied are achieved, so that any shape can be used as long as the effect and function are maintained. A preferred example for achieving space savings is a single-plate shape. However, to avoid a concentration of the electric field, it is desirable to avoid a pointed shape as much as possible and to reduce the risk of discharge by providing a chamfer 70 or the like on a section that has an edge. In the specific example in Fig. 8 A plate shape formed along the heating arrangement 60 is used and a concentration of the electric field is avoided by beveling 70.

[0041] Fig. Figure 9 shows an example of a case in which the in Fig. Figure 8 shows that the conductive element 63 is subjected to an insulation treatment. It is desirable that the conductive element 63 be insulated so that no direct discharge occurs with respect to the conductive element 63. For example, in a preferred example, the entire conductive element 63 is covered with a polyimide layer, an insulating elastomer, a resin, or the like.

[0042] Fig. Figure 9 shows a specific example of a design where the thickness of the insulating element is varied proportionally to the distance from the high-voltage unit to achieve optimal insulation. One insulating material 80 is wound around the upper section of the conductive element 63 because the upper section is furthest from the high-voltage unit; two insulating materials 81 are wound around the intermediate section; and three insulating materials 82 are wound around the lower section, which is furthest from the high-voltage unit, so that the lower section has the greatest thickness. An insulating material in the form of a polyimide layer is generally expensive, and its thermal conductivity decreases as its thickness increases.Accordingly, this configuration allows for lower costs and prevents a reduction in thermal conductivity compared to using insulation material of a uniform thickness. Furthermore, instead of changing the number of windings of the insulation material, a graduated insulation performance and thermal conductivity can be achieved. Of course, insulation material of a uniform thickness can be used as long as the reduction in cost and thermal conductivity remains within acceptable limits. In such cases, however, it is necessary to implement an insulation treatment, grounding the conductive element 63 to the grounding plate 66. Additionally, the contact surface of the thermostatic bath base 67 and the conductive element 63 can protrude to ensure sufficient creepage distance with respect to the conductive element 63.

[0043] In the configuration according to the first embodiment, when electrophoresis is initiated using the capillary electrophoresis device, in which the Fig. 8 and Fig. 9 illustrated conductive element 63 in the thermostatic bath base 67 from Fig. 7 contains a high voltage applied to the high-voltage unit in the electrode holder 05 via an electrode plug 65. A discharge phenomenon occurs as a result of the potential difference, so that a discharge occurs with respect to the grounding plate 66 or the conductive element 63, which at that time has a zero potential. In the configuration according to the embodiment, however, the conductive element 63 and the thermostatic bath base 67 are in contact with the underside of the conductive element 63, and the thermostatic bath base 67 and the electrode holder 05 are in contact with each other, so that the electrode plug 65 is covered.

[0044] Because the thermostatic bath base 67 and the electrode holder 05 are insulating elements, the high-voltage unit and the low-voltage unit with zero potential are in contact with several insulated structures arranged between them. The potential from a section to which a high voltage is applied to the conductive element 63 with zero potential is then gradually reduced using the thermostatic bath base 67 as a dielectric. The conductive element 63, which is grounded to the grounding plate 66, which is a section with a low potential, has a virtual zero potential in the device, as does the grounding plate 66. In general, a high potential is generated at and in the vicinity of a section to which a high voltage is applied.Because the potential of parts located in and near the conductive element 63, which has a zero potential, is reduced, no discharge to parts other than the conductive element 63 occurs in the high-voltage unit of the electrode plug 65 and the electrode holder 05.

[0045] Here, as the structural size of the conductive element 63 increases, the potential of parts in the vicinity of the conductive element 63 is also slightly reduced. For example, the fact that the area of ​​the conductive element 63 is larger than the area of ​​an element to which a high voltage is applied by the capillary electrode held by the electrode holder is a factor that further improves the prevention of nearby discharges. Second embodiment

[0046] According to another second embodiment of a capillary electrophoresis device, which is not an embodiment of the invention but an example serving to illustrate the invention, the discharge risk is reduced even with a partial configuration that has an insufficient creepage distance or spatial distance.

[0047] As in Fig. The configuration elements shown in 10 are the same as in the one in Fig. In the first embodiment shown in Figure 7, the order of the conductive surface and the resistance heater 62, which are included in the heating arrangement 60, is different. Specifically, the conductive element 63 is arranged adjacent to the heat-insulating material 61, followed by the resistance heater 62. In this configuration, the distance between the conductive surface of the conductive element 63 and the thermostatic bath base 67 is reduced by switching the resistance heater 62 and the conductive surface of the conductive element 63. Consequently, the potential of the conductive surface of the conductive element 63 and the potential of the thermostatic bath base 67 are brought closer together than if the resistance heater 62 were located between them.By using the configuration according to the embodiment, it can be expected that the potential of the thermostatic bath base 67 and of parts near the thermostatic bath base can be further reduced. In addition, an insulating countermeasure is applied to the conductive element 63, so that, unlike in the first embodiment, a direct discharge with respect to the conductive element 63 does not occur.

[0048] As described in the first and second embodiments, the shape can be changed if the order of the components is altered to improve functionality. Third embodiment

[0049] According to a third embodiment of a capillary electrophoresis device, which is not an embodiment of the invention but an example serving to illustrate the invention, the discharge risk is reduced even with a partial configuration having insufficient creepage distance or spatial separation, and it furthermore has a thermal insulation function. That is to say, the third embodiment of a capillary electrophoresis device for analyzing a sample by electrophoresis using a capillary comprises a heater that heats the capillary, an electrode holder that holds capillary electrodes and is connected to a high-voltage unit, and a conductive heat storage plate that is at least partially made of metal and is grounded to a low potential, wherein the electrode holder and the conductive heat storage plate are in contact with a structure that is an insulating element.

[0050] According to the in Fig. In the embodiment shown in 11, the element shown in the Fig. In the embodiment shown in Figure 7, a conductive heat storage plate 90 with a heat storage function is used as the conductive element 63. The conductive heat storage plate 90, as the conductive element, comprises at least part of a metal and has excellent conductivity and high heat capacity. For example, with regard to conductivity and heat capacity, a metal plate with a thickness of approximately 1.0 mm to 10.0 mm made of aluminum, iron, brass, or stainless steel is preferred. Additionally, a resin plate in which a metal powder or a metal filler is mixed, and an elastomer with high heat capacity, are preferred. As in the first embodiment, an insulation measure is taken to prevent direct discharge with respect to the conductive heat storage plate 90.Additionally, as in the first embodiment, the conductive heat storage plate 90 and the electrode holder 05 are in contact with the heat dissipation rubber 64 as a structure formed from an insulating element.

[0051] In the configuration according to the embodiment, where the conductive heat storage plate 90 is used, it is possible, for example, to ensure that the temperature does not decrease significantly when replacing the capillary cartridge 01, even if a user opens or closes the thermostatic bathroom door 43. This is because the conductive heat storage plate 90, as a conductive element, reduces the risk of heat discharge and, due to its high heat capacity, stores sufficient heat generated by the resistance heater 62.

[0052] The effect of the embodiment is described with reference to the Fig. 13 to 16 with actual test results based on the configuration of the embodiment.

[0053] First is Fig. Figure 13 is a graph showing an ideal state in which no suspended metal is arranged around the electrode holder 05, to which a high voltage is applied, and all insulated structures with which the electrode holder 05 is in contact act as dielectrics. The horizontal axis represents a distance, and the vertical axis represents a potential, with the distance x of the position of the electrode holder 05, to which -20 kV is applied, assumed to be zero. As shown in the upper part of the diagram, the potential gradually drops from -20 kV to 0 kV, and no discharge occurs.

[0054] On the right side of Fig. Figure 14 shows the result of an electrophoresis test after the conductive heat storage plate 90 was removed from the configuration near the capillary according to the embodiment. Fig. 11 was removed. As shown in the graph, while the voltage applied to the device is changed stepwise from 0 kV to -20 kV, both the current value of the device's power supply and the current value of the capillary fluctuate considerably. Near 18 kV, a strong discharge occurs from the device's power supply and from the capillary. This is because a discharge from the electrode holder 05, to which a high voltage is applied, occurs in a gap of approximately 10 mm formed by the absence of the conductive heat storage plate 90.

[0055] On the left side in Fig. Figure 14 illustrates the prediction of the phenomenon occurring at that time with regard to potential and electric field. Because the electric field becomes concentrated through the gap and exceeds the voltage resistance of the air, a discharge occurs. At that time, the potential decreases rapidly.

[0056] Next, on the right-hand side in Fig. 15 The result of the electrophoresis test is shown in a state in which the conductive heat storage plate 90 and the electrode holder 05 are provided and a gap of at most 1 mm is provided between the insulated structure arranged between the conductive heat storage plate and the electrode holder and the conductive heat storage plate 90. Compared with Fig. 14. Although no extreme fluctuations in current value occur, instead slight fluctuations in current value occur intermittently even in a low-voltage environment, and significant fluctuations in current value occur when voltages of -19 kV and -20 kV are applied.

[0057] On the left side in Fig. Figure 15 illustrates an example of the prediction of the phenomenon occurring at that time with regard to potential and electric field. Because the conductive heat storage plate 90 has a zero potential, the potential drops to the conductive heat storage plate, but no discharge occurs due to the insulation. Additionally, a concentration of the electric field occurs in a small gap of at most 1 mm, but no significant discharge occurs. This gap of at most 1 mm is, however, smaller than the gap at the [unclear - possibly a reference to a specific point or element]. Fig. As shown in example 14, intermittent fluctuations in the current value occur. Additionally, a discharge eventually occurs when a high voltage of -19 kV or above is applied.

[0058] Finally, on the right side in Fig. Figure 16 shows the result of the electrophoresis test with the structure according to the embodiment. The in Fig. The existing gap 15 is eliminated, and the conductive heat storage plate 90 and the electrode holder 05 are in continuous contact with a single insulated structure or multiple insulated structures located without a gap between them. No fluctuations in current value occur in either the power supply of the device or in the capillary.

[0059] On the left side in Fig. Figure 16 illustrates the prediction of the phenomenon occurring at that time with regard to potential and electric field. Because the conductive heat storage plate 90 has a zero potential, the potential drops towards the conductive heat storage plate; however, due to the insulation, no discharge occurs. Additionally, the structure, which is an insulating element because there is no gap, acts as a dielectric beyond the conductive heat storage plate 90, and the potential gradually decreases. Fourth embodiment

[0060] A fourth embodiment of a capillary electrophoresis device, as an embodiment of the invention, is configured such that the discharge risk is reduced even with a partial configuration that has an insufficient creepage distance or spatial separation, and furthermore incorporates a thermal insulation function. That is to say, the fourth embodiment of a capillary electrophoresis device comprises a heater that heats a capillary, a non-conductive heat storage plate, an electrode holder that holds the capillary electrodes of the capillary and is connected to a high-voltage unit, and a conductive element that is at least partially made of metal and is grounded to a low potential, wherein the electrode holder and the conductive element are in contact with intervening structures, and these structures are insulating elements.

[0061] As in Fig. As shown in 12, the conductive heat storage plate 90 has a heat storage function in the Fig. The structure shown in Figure 11 is replaced by a non-conductive heat storage plate 100, and the conductive element 63 is attached to it as a conductive surface. It is preferred, for example, to use a non-conductive heat storage plate 100 with a thickness of approximately 1.0 mm to 10.0 mm, which, with regard to its heat capacity, consists of an aluminum oxide or glass plate. Examples of the conductive element 63 to be attached to the non-conductive heat storage plate 100 include a metal plate made of aluminum, iron, brass, stainless steel, or the like; a resin plate in which a metal powder or a metal filler is mixed; an elastomer and an applied metal surface or metal layer; and a thin metal film, as mentioned in the preceding example. It is also desirable according to the embodiment that the conductive element 63 be insulated so that no direct discharge occurs in the conductive element 63.

[0062] In addition, Fig. 12 the conductive surface of the conductive element 63 is arranged between the resistance heater 62 and the non-conductive heat storage plate 100. However, it is desirable that the conductive element 63 be attached to a non-conductive heater formed by combining the resistance heater 62 and the conductive heat storage plate 90, for example a heater generally referred to as a ceramic heater or glass heater, which is insulated in such a way that no direct discharge occurs.

[0063] It can be assumed that, according to the present invention described above, the conductive element, which is grounded to a low potential generally referred to as earth or ground and consists at least partially of a metal, has a potential close to zero. In the part in contact with the conductive element via the insulating element, the insulating element acts as a dielectric, so that any potential difference that may occur can be gradually reduced.

[0064] Because the electrode holder that holds the capillary electrodes is connected to the high-voltage unit, it has a high potential. Accordingly, the potential can be gradually reduced as long as the electrode holder and the conductive element remain in contact via the insulating element, even when a high voltage is applied to the capillary via the electrode.

[0065] If sufficient creepage or spatial distance is provided between the electrode holder and the low-potential structure, no discharge occurs between them. If sufficient distance is not ensured to reduce size, it is assumed that an insulating element is provided between them. However, if a gap is formed between the insulating element and the electrode holder or the low-potential body, a discharge occurs in the gap. This is because, in a case where the insulating element acts as a dielectric, the potential gradient in the dielectric gradually decreases. Since the potential gradient between the insulating element and the gap is steep compared to a case where nothing is provided between them, a discharge easily occurs.Accordingly, it is desirable that the electrode holder and the conductive element be in continuous contact with a single insulating element or several insulating elements arranged without a gap between them.

[0066] Because the structure has no dielectric properties when it is not an insulating element, it does not function to gradually reduce a potential difference. Accordingly, the structure consists of an insulating element made up of a single layer or multiple layers.

[0067] Furthermore, in a case where the conductive element is simply a metal plate or an applied metal surface and is not grounded to earth or mass, the conductive element is, for example, a metal suspended in the air, so that the potential difference does not decrease and is maintained at a constant level. Additionally, in a case where no conductive element is present, the drop-off point of the high potential of the high-voltage unit is not defined. Then, depending on the surface condition of the edge parts or a change in distance during a drive, a discharge occurs or the discharge section changes. Therefore, it is difficult to take countermeasures against a discharge if the conductive element according to the present invention, which consists at least partially of metal and is grounded to a low potential, and a surface having a metal grounded to the low potential do not exist.

[0068] The present invention is not limited to the embodiments described above and includes various modification examples. For instance, the embodiments described above have been detailed for a better understanding of the present invention and are not necessarily limited to having all the described configurations. Additionally, a part of a configuration of one embodiment can be replaced by a configuration of another embodiment, and a configuration of another embodiment can be added to a configuration of one embodiment. Furthermore, a part of a configuration of each embodiment can be added to, removed from, or replaced by other configurations. Reference symbol list

[0069] 01: Capillary cartridge, 02: Capillary, 03: Support body, 04: Heat dissipation body, 05: Electrode holder, 06: Detection unit, 07: Capillary head, 08: Electrode (cathode), 09: Handle, 10: Electrode holder mounting pin, 11: Electrode holder mounting hole, 12: Exposure cell mounting frame, 13: Exposure cell positioning pin, 14: Positioning hole, 15: Electrode holder positioning pin, 16: Electrode holder positioning hole, 20: Automatic sampling unit, 21: Sampling device 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: Electrophoresis medium container, 29: anode-side buffer liquid container, 30: anode-side wash bath, 31: anode-side electrophoresis buffer liquid bath, 32: anode-side sample introduction buffer liquid bath, 33: cathode-side buffer liquid container, 34: waste liquid bath,35: cathode-side wash bath, 36: cathode-side electrophoresis buffer liquid bath, 40: irradiation detection / thermostatic bath unit, 41: thermostatic bath unit, 42: irradiation and detection unit, 43: thermostatic bath door, 44: electrode (anode), 50: mounting surface, 51: clamp, 60: heating assembly, 61: heat-insulating material, 62: resistance heater, 63: conductive element, 64: heat dissipation rubber, 65: electrode connector, 66: grounding plate, 67: thermostatic bath base, 70: chamfer, 80: one insulating material, 81: two insulating materials, 82: three insulating materials, 90: conductive heat storage plate, 100: non-conductive heat storage plate

Claims

[1] Capillary electrophoresis device for analyzing a sample by electrophoresis using a capillary (02), the device comprising: a heater (62) which heats the capillary (02), an electrode holder (05) which holds capillary electrodes of the capillary (02) and is connected to a high-voltage unit, and a conductive element (63) which consists at least partially of metal and is grounded to a low potential, wherein the electrode holder (05) and the conductive element (63) are in contact with an insulating element (64) arranged therebetween and a non-conductive heat storage plate (100) is arranged between the conductive element (63) and the insulating element (64). [2] Capillary electrophoresis device according to claim 1, wherein the insulating element (64) consists of a single layer or multiple layers. [3] A capillary electrophoresis device according to claim 1, wherein the conductive element (63) has an area larger than the area of ​​an element to which a high voltage is applied by the capillary electrode. [4] A capillary electrophoresis device according to claim 1, wherein the conductive member (63) is beveled.

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