阅读说明：本技术 毛细管阵列单元 (Capillary array unit ) 是由 有留克洋 大浦刚 刈屋俊一 于 2019-09-02 设计创作，主要内容包括：本发明提供一种构成为装拆作业简单的毛细管阵列单元,毛细管阵列单元包括:毛细管；卡头,该卡头设置在毛细管的一端；毛细管头,该毛细管头设置在毛细管的另一端；检测部,该检测部设置在毛细管的一部分上；以及保持体,该保持体用于保持毛细管,保持体包括用于将毛细管保持为弯曲形状的第一保持部；用于将毛细管保持为直线形状的第二保持部；以及用于在规定方向上移动第二保持部的引导件。(The invention provides a capillary array unit which is simple in assembly and disassembly operation, and comprises a capillary; a chuck disposed at one end of the capillary tube; a capillary head disposed at the other end of the capillary; a detection portion provided on a part of the capillary tube; and a holding body for holding the capillary, the holding body including a first holding portion for holding the capillary in a bent shape; a second holding portion for holding the capillary in a linear shape; and a guide for moving the second holding portion in a prescribed direction.)

1. A capillary array unit, comprising:

a capillary tube;

the clamping head is arranged at one end of the capillary tube;

the capillary head is arranged at the other end of the capillary;

a detection unit provided in a part of the capillary; and

a holding body for holding the capillary tube,

the holder includes a first holding portion for holding the capillary in a curved shape, a second holding portion for holding the capillary in a linear shape, and a guide for moving the second holding portion in a predetermined direction.

2. The capillary array unit of claim 1,

the holding body has a fixing portion for detachably fixing the second holding portion.

3. The capillary array unit of claim 1,

there is a separator for holding the capillaries in a state of separation one by one.

4. The capillary array unit of claim 3,

a plurality of said separators are arranged in such a way that,

the capillaries pass through the separators such that each capillary crosses between adjacent separators.

5. The capillary array unit of claim 1,

the first holding portion includes a sliding portion that moves along the guide and a plate portion that holds the capillary in a straight line.

6. The capillary array unit of claim 5,

the plate portion has high thermal conductivity.

7. The capillary array unit of claim 5,

a portion of the plate portion is bent.

8. The capillary array unit of claim 5,

the capillary tube was fixed to the plate portion with an adhesive tape.

9. The capillary array unit of claim 8,

the adhesive tape has high thermal conductivity.

Technical Field

The present invention relates to a capillary array unit.

Background

Capillary electrophoresis is widely used as a technique for separating and analyzing various biological samples including deoxyribonucleic acid (DNA). One of the technical advantages is the superior heat dissipation characteristics that result from the ratio of the surface area to the volume of the capillary tube. This heat dissipation characteristic enables high-speed and high-resolution sample separation by electrophoresis using a high voltage.

In japanese patent laid-open No. 2009-174897, a method for fixing a capillary array having a high rigidity to a frame so as to simplify its mounting to a capillary electrophoresis device is disclosed.

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open publication No. 2009-174897

Disclosure of Invention

Technical problem to be solved by the invention

In a capillary electrophoresis device, when the kind of sample or application is changed, the capillary array is replaced correspondingly. The capillary array is replaced by the user.

The conventional capillary tube sags due to the weight of the detection unit and the array head. Sag is evident especially in less rigid capillary arrays. If the capillary tube is directly attached, the detection unit and the pump may come into contact with the device, thereby damaging the capillary tube. Therefore, in order to correct the sagging, the user holds the capillary tube with both hands and attaches and detaches the capillary tube while bending. The operation of attaching and detaching while bending is a burden to the user.

The present invention provides a capillary array unit configured to simplify attachment and detachment operations of a capillary array by maintaining the capillary array in a form that prevents damage to the capillary when the capillary array is attached to and detached from a device, regardless of the rigidity of the capillary.

Technical scheme for solving technical problem

The capillary array unit of the present invention includes a capillary; a load head disposed at one end of the capillary; a capillary head disposed at the other end of the capillary; a detection portion provided on a part of the capillary tube; and a holding body for holding the capillary, the holding body including a first holding portion for holding the capillary in a bent shape; a second holding portion for holding the capillary in a linear shape; and a guide for moving the second holding portion in a predetermined direction.

Effects of the invention

According to the present invention, the operation of attaching and detaching the capillary array is simplified.

Drawings

Fig. 1 is a diagram showing the basic structure of a capillary electrophoresis device of the present invention.

Fig. 2A is a front view of a capillary array unit of the present invention.

Fig. 2B is a side view of a capillary array unit of the present invention.

Fig. 2C is a diagram of a separator.

Fig. 3A is a diagram showing the capillary array unit when the second frame is fixed by the fixing portion.

Fig. 3B is a diagram showing the shape of the capillary array unit when the capillary head is connected to the pump mechanism.

Fig. 4 is a diagram showing the mounting of the cartridge of the present invention to an oven.

Fig. 5 is a view showing a capillary array unit after a capillary electrophoresis device of the present invention is mounted with a cartridge.

Fig. 6A shows a diagram of a capillary array unit after the capillary head is installed in the present invention.

Fig. 6B is a diagram showing details of the mounting of the capillary head of the present invention to a block.

Detailed Description

FIG. 1 is a schematic diagram showing the basic structure of a capillary electrophoresis apparatus. The capillary electrophoresis device has: a capillary electrophoresis part 1, the capillary electrophoresis part 1 comprising one or more capillaries; an optical detection unit 2 for optically detecting the sample separated by the electrophoretic medium in the capillary tube by the optical detection unit 2; and a polymer injection mechanism 3, the polymer injection mechanism 3 injecting a highly viscous polymer solution (hereinafter referred to as polymer) as an electrophoresis medium into the capillary.

The capillary electrophoresis part 1 has a capillary array 110, an oven (thermostatic bath) 115, a buffer container 112, and a high-voltage power supply 114.

The capillary array 110 includes one or more capillaries. The capillary tube is a quartz tube, and is externally coated with polyimide resin. Examples of the capillary include a highly rigid capillary having an outer diameter of 320 μm and an inner diameter of 50 μm and a polyimide coating thickness of 20 μm, and a flexible capillary having an outer diameter of 125 μm and an inner diameter of 50 μm and a polyimide coating thickness of 12.5. mu.m. Therefore, the outer diameter of the polyimide coating was 360 μm.

One end of the capillary array 110 is a capillary head 203 formed by bundling and bonding the capillaries. The other end of capillary array 110 is held by chuck 202. Chuck 202 is secured to oven 115.

The chuck 202 is provided with a tubular cathode electrode 204. The capillary tube passes through the cathode electrode 204 and protrudes from the lower end of the cathode electrode 204. Thereby, the capillary cathode end 206 is immersed in the buffer solution in the buffer container 112.

Oven 115 houses capillary array 110 and regulates the temperature of capillary array 110. The peltier element is used as a heat source of the oven 115, and the temperature can be set from a temperature lower than room temperature to a high temperature of 50 ℃.

The polymer injection mechanism 3 includes a pump 103 having a piston, a block 104 having a flow path inside, a polymer container 101 for storing a polymer, and a buffer container 107 for storing a buffer solution. The anode 106 is immersed in the buffer solution in the buffer container 107. The inner diameter of the flow path in the block 104 is 0.5 to 2mm, which is several times to several tens times larger than the inner diameter of the capillary tube. This is to avoid voltage loss during electrophoresis.

The pump 103, the capillary head 203 and the two tubes 104a, 104b are connected to the block 104. The pump 103, the capillary head 203, and the two tubes 104a and 104b are connected to each other via a flow path in the block 104. A first tube 104a is connected between the block 104 and the polymer in the polymer container 101. The first pipe 104a is provided with a check valve 102. The second pipe 104b is connected between the block 104 and the buffer solution in the buffer container 107. The second pipe 104b is provided with an electrically operated cushion valve 105.

A polymer having sufficient capacity for continuous operation is stored in the polymer container 101. The shape of the polymer container 101 is flexibly changed so that even when the polymer is sucked from the polymer container 101, the inside of the polymer container does not become a negative pressure. The polymer container 101 is disposed at a position lower than the buffer container 107. This is to avoid backflow of the polymer from the polymer container 101 to the buffer container 107 due to the pressure caused by the difference in level. Conversely, backflow of polymer or buffer into polymer container 101 is prevented by check valve 102. The liquid levels of the buffers in the two buffer containers 112, 107 are maintained at the same level.

When polymer is injected into the capillaries of capillary array 110, the electrically operated cushion valve 105 closes. Accordingly, the flow path between the capillary array 110 and the buffer container 107 is closed. The polymer in the polymer container 101 is injected into the capillary by driving the pump 103. When electrophoresis is performed, the buffer valve 105 is opened to connect the flow path between the capillary array 110 and the buffer container 107.

The optical detection unit 2 includes a light source 111 and an optical detector 108. The optical detection unit 2 is disposed on the detection unit 205 provided in the capillary array 110. The detection unit 205 is mounted on the detection unit holder 116. The light source 111 generates laser light as excitation light. In the detection section 205, the coating of the capillary tube is removed, and the quartz tube is exposed. The detection unit 205 irradiates the detection target subjected to electrophoresis in the capillary with the excitation light from the light source 111. The detection object generates fluorescence. The fluorescence is detected by an optical detector 108.

The electrophoresis method will be explained. Although omitted in fig. 1, an autosampler for transporting the sample tray, buffer container 112, is included. The sample tray is disposed at the cathode end 206 of the capillary by an autosampler. First, the sample tray is placed under the cathode end 206 of the capillary, and then the sample tray is raised. The sample tray has a plurality of wells, and each well contains a sample including an inspection object such as a fluorescence-labeled DNA. The cathode end 206 of the capillary 201 is immersed in the sample in the well of the sample tray. Then, a high voltage of about several kV is applied between the anode electrode 106 and the cathode electrode 204 by the high voltage power supply 114. An object to be detected such as a fluorescence-labeled DNA is introduced into the capillary through the cathode end 206 of the capillary. Thereafter, as shown in FIG. 1, the cathode end 206 of the capillary is immersed in the buffer container 112. The detection object is separated while moving within the capillary. When the detection object labeled with fluorescence passes through the detection section 205, the detection object is irradiated with excitation light from the light source 111. The detection object is caused to generate fluorescence by the excitation light. The fluorescence is detected by an optical detector 108.

The operation of the polymer injection mechanism will be described. In the pump 103, the direction in which the piston is pushed into the chamber is described as the normal rotation of the motor, and the direction in which the piston is withdrawn is described as the reverse rotation of the motor. First, the cushion valve 105 is closed. Next, the motor is reversed. The piston is withdrawn and the polymer in the polymer reservoir 101 is drawn into the chamber of the pump 103 via the flow path in the block 104. Next, the motor is rotated forward. The piston is pushed in and the polymer in the chamber of the pump 103 is pushed into the flow path in the block 104. At this time, the polymer in the chamber of the pump 103 is prevented from flowing back into the polymer container 101 by the action of the check valve 102. Thus, the polymer flows into the capillary via the flow path in block 104 and out the cathode end 206 of the capillary. Finally, the buffer valve 105 is opened to prepare for electrophoresis.

Referring to fig. 2A, 2B and 2C, an example of the capillary array unit of the present invention is explained. Fig. 2A shows a front structure of the capillary array unit of the present example, and fig. 2B shows a side structure of the capillary array unit. In this example, the length of the capillary from the chuck to the detection unit is shown as 28 cm. The capillary array unit of the present example includes a capillary array 110, a first frame 300 for holding the capillary array 110, a second frame 301, a fixing portion 302 for detachably fixing the second frame, and guide pieces 311, 312. As shown in fig. 2A, the first frame 300 includes a first leg portion 303, a second leg portion 304, a bridge portion 305, and a support portion 313. The frame 300 is configured to hold the capillary array 110. The two leg portions 303, 304 are fixed to the chuck 202. The support portion 313 is connected to the capillary management label 306. One end of the capillary array 110 is a capillary head 203 formed by bundling and bonding the capillaries. The other end of capillary array 110, the cathode end, is held by a tubular electrode disposed in chuck 202.

The shaft 310 is disposed on the first frame 300. As shown in fig. 2B, the shaft 310 extends orthogonally to a surface constituting the first frame 300. A separator 324 is mounted on the shaft 310. The second frame 301 is provided with a slit 314. The slit 314 is provided with a groove perpendicular to the face constituting the second frame 301. A separator 325 is mounted on the slit 314.

The separators 324, 325 are film or plate-shaped, and are formed with holes 326 (see fig. 2C) in the same number as or larger than the number of capillaries. The bore 326 has an inner diameter slightly larger than the outer diameter of the capillary tube, for example about 1 mm. Each hole is penetrated by a capillary tube. Thus, all capillaries are held in a fixed shape by passing through the holes 326 of the separator. The second frame is configured to prevent the capillary head and the detection unit from sagging due to gravity, and is maintained in a state in which damage to the capillaries is prevented when the capillary array 110 is attached and detached.

The separators 324, 325 separate the capillaries from each other and prevent the capillaries from being tangled with each other and tightly gathered in a bundle shape. In the present example, a plurality of separators are arranged, and the capillaries are passed through the separators in such a manner that the respective capillaries cross between the adjacent separators. By making the capillaries three-dimensionally cross, even in the case where the capillaries are short, the capillaries can be prevented from contacting each other.

The number of separators may be increased or decreased depending on the length of the capillary tube. Generally, the longer the capillary tube, the greater the number of separators. For example, when the length of the capillary tube is 36cm, the shaft is disposed in the shaft hole 320 opened in the bridge portion and the shaft hole 322 opened in the first frame 300, and the separator is installed. When the length of the capillary tube is 50cm, the shaft is disposed in the shaft hole 321, the shaft hole 322, and the shaft hole 323 opened in the first frame 300, and the separator is installed.

The capillary array 110 has a plurality of capillaries 201. The capillary array of this example has 8 capillaries 201.

The second frame 301 may move in a linear direction along the guide pieces 311, 312 provided on the first frame 300. The plate 307 is connected to the second frame 301. The capillary 201 is adhered to the plate 307 by capillary mount bands 308, 309 and the capillary 201 is restrained such that the capillary 201 does not sag due to the influence of gravity. The plate 307 is bent at multiple locations to increase rigidity. The plate 307 and the capillary fixation strips 308, 309 are preferably thin and of a material with good thermal conductivity in order to keep the temperature of the capillaries constant during electrophoresis. The plate 307 is a resin plate having a thickness of about 0.1 to 0.5mm, and the capillary fixing tapes 308 and 309 are single-sided adhesive tapes having a thickness of about 0.02 to 0.2 mm.

Referring to fig. 3A and 3B, the operation of the second frame 301 of the capillary array unit of the present invention will be described. Fig. 3A is a diagram of the diagram shown in fig. 2A as viewed from the opposite side. The linear portion 110A of the capillary array is configured by the second frame 301, the separator 325 provided on the second frame 301, the plate 307 connected to the second frame 301, and the capillary fixing bands 308, 309. The capillary head 203, the detection unit 205, the separator 325, the second frame 301, the second frame fixing unit 302, and the plate 307 are arranged on a straight line. When an external force in the direction indicated by arrow a is applied to the capillary head 203, the second frame 301 is released from the second frame fixing portion 302 and linearly moves along the guides 311 and 312 in the direction indicated by arrow a. Thereby, the capillary head 203 is connected to the mounting portion of the block 104 of the polymer injection mechanism 3, and the state shown in fig. 3B is obtained. Further, an external force in the direction indicated by the arrow B is applied to the capillary head 203. Then, the capillary head 203 is disconnected from the block 104, and linearly moved along the guides 311, 312 of the second frame 301 in the direction indicated by the arrow B. Thereby, the second frame 301 is restrained by the second frame fixing portion 302, and the state shown in fig. 3A is brought.

Next, referring to fig. 4, 5, 6A, and 6B, the mounting step of the capillary array 110 of the present invention will be explained. First, the chuck 202 is mounted on the oven 115. This is explained with reference to fig. 4. Fig. 4 shows a portion of the lower end of oven 115 and chuck 202. Illustration of the capillary array mounted to chuck 202 is omitted. A handle 207 is provided on the chuck 202. The user grasps the handle 207 and inserts the cartridge 202 into a recess in the oven 115. Grooves are provided on both side faces of the chuck 202, and protrusions are provided on the inner side of the concave portion of the oven 115. When the chuck 202 is inserted into the concave portion of the oven 115, the groove of the chuck 202 engages with the protrusion of the concave portion of the oven 115. As shown in fig. 5, since the second frame 301 is held by the second frame fixing portion 302, the capillary head 203 and the detection portion 205 do not interfere with each other at any portion of the electrophoresis apparatus. Therefore, this operation is simply to grasp the handle 207 and insert the chuck 202 into the recess of the oven 115, which is very easy.

Fig. 5 shows a state where the chuck 202 is mounted to the oven 115. The shape of the capillary array 110 shown in fig. 2A and 3A is maintained as it is. In this example, the capillary head 203 is disposed near the mounting portion of the block 104 of the polymer injection mechanism 3. The detection unit 205 is disposed near the mounting portion of the detection unit holder 116.

Fig. 6A shows a state where the capillary head 203 is mounted on the block 104 of the polymer injection mechanism 3. Mounting the capillary head 203 to the block 104 moves the second frame 301 in a linear direction along the guides. Thus, the capillary head 203 is passed through the hole of the block 104 and mounted on the polymer injection mechanism 3. A handle 208 is provided adjacent the chuck. By moving the second frame by holding 208, the user can mount the capillary head 203 on the block without directly contacting the capillary. Details are described with reference to fig. 6B. At this time, as described with reference to fig. 3B, by moving the second frame in a linear direction along the guide, the capillary head 203 passes through the hole of the block 104. Next, the fastening screw 701 provided on the block 104 is tightened, and the sealing surface 702 of the capillary head 203 is pressed against the block 104. Thereby, the capillary head 203 and the block 104 are sealed, and the capillary head 203 is fixed to the block 104. As shown in fig. 5, the capillary head 203 is disposed near the mounting portion of the block 104 of the polymer injection mechanism 3. This operation allows the capillary head 203 to be inserted into the hole of the block 104 simply by moving the second frame 301 along the guides 311 and 312, and the capillary head can be easily attached.

Finally, the detecting unit 205 is mounted on the detecting unit holder 116. As shown in fig. 6B, when the capillary head 203 is connected to the block 104 of the polymer injection mechanism 3, the detection section 205 is disposed on the mounting portion of the detection section holder 116. Therefore, the detection unit 205 can be attached to the detection unit holder 116 only by closing the detection unit holder cover 117, and the detection unit can be easily attached.

Next, the step of detaching the capillary array of the present invention will be described with reference to fig. 4, 5, 6A, and 6B.

First, the detection unit holder cover 117 is opened, and the detection unit 205 is released from being fixed. Next, the capillary head 203 is detached from the block 104 of the polymer injection mechanism 3. This is explained with reference to fig. 6B. First, the fastening screw 701 is loosened to release the force that fastens the fixed capillary head 203. Next, the capillary head 203 is detached from the hole of the block 104 by moving the second frame 301 in a linear direction along the guides 311, 312. At this time, as described with reference to fig. 3, by moving the second frame 301 in the linear direction along the guides 311, 312, the second frame 301 is constrained by the second frame fixing portion 302. At this time, since the detection part 205 is already in the unfixed state, as shown in fig. 5, if the second frame 301 is moved to the second frame fixing part 302 side, the detection part 205 is also detached from the mounting part of the detection part holder 116. Therefore, this operation is simply to move the second frame 301 along the guide pieces 311, 312, which is very easy.

Finally, the chuck 202 is removed from the oven 115. This is explained with reference to fig. 4. Fig. 4 shows a portion of the lower end of oven 115 and chuck 202. Illustration of the capillary array attached to the chuck is omitted. A handle 207 is provided on the chuck 202. The user grasps the handle 207 to remove the chuck 202 from the oven 115. As shown in fig. 5, when the chuck is removed, the second frame 301 is held by the second frame fixing portion 302, and therefore the capillary head 203 and the detection portion 205 do not interfere with each other at any portion of the device. Therefore, this operation is simply to remove the chuck 202 from the oven 115 by grasping the handle 207, which is very easy.

As described above, according to the present example, when performing operations of attaching and detaching the capillary array 110 to and from the electrophoresis apparatus, the user does not need to attach and detach the capillary array 110 while bending the capillaries. Therefore, the capillary array can be easily attached and detached. Therefore, the capillary array can be easily replaced.

Although the examples of the present invention have been described above, it is easily understood by those skilled in the art that the present invention is not limited to the examples described above, and various changes may be made within the scope of the invention recited in the claims.

Description of the reference symbols

1 capillary electrophoresis unit, 2 optical detection unit, 3 polymer injection mechanism, 101 polymer container, 102 check valve, 103 pump, 104 block, 105 buffer valve, 106 electrode, 107 buffer container, 108 optical detector, 110 capillary array, 111 light source, 112 buffer container, 113 electrode, 114 high voltage power supply, 115 oven, 116 detection unit holder, 117 detector holder cover, 201 capillary, 202 cartridge, 203 capillary head, 204 cathode electrode, 205 detection unit, 206 cathode end, 207 cartridge handle, 208 handle, 300 first frame, 301 second frame, 302 fixing unit, 303 first foot unit, 304 second foot unit, 305 bridge portion 306 capillary management label, 307 plate, 308, 309 capillary fixing tape, 310 shaft, 311, 312 guide, 313 support unit, 314 slit, 310, 320, 321, 322 shaft hole, 324, 325 separator, 326 hole 701, fastening screw, and screw, 702 sealing the surface.