CAPILLARY CARTUCE AND COMPOSITION METHOD FOR IT

The capillary cartridge addresses inconsistent tip positioning by using a capillary retaining element with a tapered and rotation limiting design, ensuring precise alignment and reducing stress-related issues, thus improving the reliability and efficiency of capillary electrophoresis devices.

DE112023006473T5Pending Publication Date: 2026-03-26HITACHI HIGH TECH CORP +1
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Patent Information

Authority / Receiving Office
DE · DE
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-08-04
Publication Date
2026-03-26

AI Technical Summary

Technical Problem

Existing capillary fixation methods in capillary electrophoresis devices result in inconsistent tip positioning, leading to potential breakage and reduced separation efficiency due to stress and deformation of the capillary during assembly, which affects the precision and reliability of the electrophoresis process.

Method used

A capillary cartridge design that utilizes a capillary retaining element with a first hole section, a tapered section, and a rotation limiting section, allowing precise alignment and fixation of the capillary tip without deformation, using a pressure surface to secure the capillary to the block unit.

Benefits of technology

Ensures accurate positioning of the capillary tip, reducing assembly-induced stress and breakage, thereby enhancing the consistency and reliability of electrophoresis results by minimizing variations in tip position and rotation.

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Abstract

A capillary cartridge comprises: a capillary; a capillary retainer attached at a predetermined distance from one end of the capillary; and a block unit comprising a first element in which a main flow channel is formed, and a second element connected to the first element, the block unit holding the capillary retainer by clamping it between the first and second elements. The capillary retainer further comprises a first perforated section through which the capillary passes, a first tapered section coaxial with the first perforated section, and a first rotation-limiting section having a pressure surface with a predetermined projecting shape.The first element comprises a second tapered section, which is connected to and coaxial with the main flow channel, and a second rotation-limiting section, which is connected to the second tapered section. The capillary is further connected to the block unit when the pressure surface of the first rotation-limiting section is pressed against a pressure surface of the second element in a state where the rotation-limiting sections of the capillary retaining element and the first element are fitted together and the tapered sections of the capillary retaining element and the first element are in contact with each other.
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Description

Technical field

[0001] This invention relates to a capillary cartridge and a method for its composition. State of the art

[0002] In a capillary electrophoresis apparatus, electrophoresis of a sample is performed in a tiny tube called a capillary. During electrophoresis, the sample is gradually separated as it moves through the capillary, and the sample contents are optically analyzed at a detection window that is partially positioned along the capillary.

[0003] Sleeves are frequently used to connect capillaries to devices (see, for example, patent literature 1). The capillary is generally fixed to a block containing a flow channel via a sleeve as follows.

[0004] An external thread is formed on the outer circumferential surface of the sleeve, and a tapered surface is formed coaxially with this. The sleeve has a through-hole section that is slightly larger than the capillary. When the capillary is guided through this through-hole section in the sleeve, a tiny gap exists between the inner circumferential surface of the through-hole section in the sleeve and the outer circumferential surface of the capillary, allowing the sleeve to move freely along the length of the capillary.

[0005] The block also features a through-hole section that is coaxial with the flow channel, an internal thread formed on the inner circumferential surface of the through-hole section, and a tapered surface that is also coaxial with the through-hole section. By screwing the external thread of the sleeve clockwise into the internal thread of the block, the external and internal threads engage, and the sleeve is gradually inserted into the block. List of literature on patent literature

[0006] Patent literature 1: Japanese publication no. 2012-98309 Summary of the invention: Technical problem

[0007] When connecting a capillary to a device, the capillary can be fixed so that it protrudes 1 to 2 mm from the sleeve into the flow channel. In this case, the procedure simply ensures that the capillary is securely held by the sleeve, and the position of the capillary tip is not controlled; that is, it can be in any position. In contrast, there are cases where it is necessary to position the tip of the capillary precisely within the flow channel into which the capillary is inserted. In such cases, the following procedure is used to fix the capillary over the sleeve.

[0008] When the sleeve is screwed clockwise into the block, the tapered surface of the sleeve comes into contact with the tapered surface of the block. At this stage, the capillary inserted into the hole in the sleeve can move freely axially along the hole in the sleeve. Therefore, the length of the capillary protruding from the sleeve can be checked using a microscope or similar instrument, and the amount of the capillary protrusion is adjusted by moving the capillary relative to the sleeve.

[0009] As the sleeve is screwed further clockwise into the block, a component force is generated in a direction normal to the axis of rotation of the sleeve, corresponding to the taper angle of the tapered surface. The sleeve is thereby subjected to stress and deformed by the component force in the direction normal to the tapered surface, causing the section of the hole drilled into the sleeve to become uniformly smaller and the gap between the sleeve and the capillary to disappear. Furthermore, the sleeve deforms as it is screwed into the block to secure the capillary.

[0010] Since the sleeve is screwed in for fixation after the amount of capillary protrusion has been set in this way, some variation in the capillary tip position is unavoidable, and controlling the magnitude of this variation is difficult. Furthermore, the end of the capillary can rotate along with the rotation of the sleeve, causing part of the capillary to be fixed to the block in a twisted state. In particular, the capillary can twist if the sleeve is tightened to the block with a large torque, thereby placing stress on the capillary and potentially leading to its breakage.

[0011] The present invention provides a capillary cartridge capable of precisely positioning the tip of the capillary and a method for assembling the same. Solution to the problem

[0012] To address the above problem, for example, the configurations described in the claims are adopted. The present application includes a variety of means for solving the above problems, and as an example, a capillary cartridge is provided comprising: a capillary; a first capillary retaining element attached at a position at a predetermined distance from one end of the capillary; and a first block unit comprising a first element in which a main flow channel is formed and a second element connected to the first element, wherein the first block unit holds the first capillary retaining element by clamping the first capillary retaining element between the first element and the second element.In the capillary cartridge, the first capillary retaining element comprises a first hole section through which the capillary passes, a first tapered section which is coaxial with the first hole section, and a first rotation limiting section which has a pressure surface with a predetermined protruding shape, wherein the first element comprises a second tapered section which is connected to and coaxial with the main flow channel, and a second rotation limiting section which is connected to the second tapered section.The capillary is also connected to the first block unit when the pressure surface of the first rotation limiting section is pressed through a pressure surface of the second element in a state in which the first rotation limiting section of the first capillary retaining element is fitted into the second rotation limiting section of the first element and the first tapered section of the first capillary retaining element is in contact with the second tapered section of the first element. Advantageous effects of the invention

[0013] A capillary cartridge capable of accurately positioning the capillary tip is provided, along with a method for assembling it. Further problems and novel features will become apparent from a description in this document and the accompanying drawings. Brief description of the drawings Fig. Figure 1 is a block diagram illustrating a schematic configuration of a capillary electrophoresis device. Fig. Figure 2 illustrates the main parts of a capillary cartridge. Fig. Figure 3A illustrates the configuration of an anode block unit. Fig. Figure 3B illustrates the configuration of the anode block unit. Fig. Figure 4 is a cross-sectional view of flow channels formed in an anode block. Fig. Figure 5 illustrates the configuration of a capillary sheath. Fig. Figure 6A illustrates the configuration of a cathode block unit. Fig. Figure 6B illustrates the configuration of the cathode block unit. Fig. Figure 7 is a cross-sectional view of flow channels formed in the cathode block. Fig. Figure 8 illustrates a state in which the tapered section of a capillary cathode head and the tapered section of the cathode block are connected in

[0014] Contact is available. Description of the embodiments

[0015] Fig. Figure 1 is a block diagram illustrating a schematic configuration of a capillary electrophoresis apparatus. A capillary cartridge (hereinafter referred to as the cartridge) 200 is attached to a capillary electrophoresis apparatus (hereinafter referred to as the electrophoresis apparatus) 100. Capillaries used in electrophoresis apparatuses can experience an accumulation of sample residues within the capillaries and a deterioration of their internal coatings due to repeated electrophoresis, resulting in reduced separation efficiency. For this reason, the electrophoresis apparatus 100 requires the cartridge 200 to be replaced after a certain number of electrophoresis runs. Even when replacing the cartridge 200, individual differences within the cartridge 200 must be minimized to ensure consistent analysis accuracy.First, the 200 cartridge will be described.

[0016] Fig. Figure 2 illustrates the main parts of a capillary cartridge. The cartridge 200 mainly comprises a gel unit 401, an anode block unit 410, a capillary sheath unit 420, and a cathode block unit 440. These are explained in more detail below.

[0017] The gel unit 401 is configured to store an aqueous polymer solution, which is a DNA separation medium, and to deliver the solution to the anode block unit 410. The inner circumferential surface of a gel syringe 401a and the outer circumferential surface of a gel piston 401b can slide against each other while maintaining a seal. By filling the gel syringe 401a with the aqueous polymer solution and moving the gel piston 401b in the A-direction, which corresponds to the longitudinal direction of the gel syringe 401a, the aqueous polymer solution stored in the gel syringe 401a is delivered via a gel coupler 401c to a gel tube 402.

[0018] The structure of the anode block unit 410 is further described with reference to the Fig. 3A, Fig. 3B and Fig. 4 described. The anode block unit 410 is configured to supply the aqueous polymer solution obtained through the gel tube 402 to a capillary 421 and to apply an anode-side voltage to the aqueous polymer solution in the capillary 421 for electrophoresis. For this purpose, the anode block unit 410 consists mainly of an anode block 411 in which flow channels 418 and 419 are formed (see Fig. 4) In this example, four connections are also provided for supplying and removing the aqueous polymer solution to and from the flow channels in the anode block 411, and one connection is provided for applying a voltage. It should be noted that the material of the anode block 411 is, for example, polymethyl methacrylate (PMMA).

[0019] The connections for supplying and discharging liquid also include a gel inlet connection 412 (see Fig. 2, Fig. 3B and Fig. 4), a capillary connection port 413 (see Fig. 3B and Fig. 4), a gel pump connection 414 (see Fig. 3B and Fig. 4) and a gel waste liquid connection 415 (see Fig. 3A and Fig. 4). The connection for applying a voltage also represents an anode electrode connection 416 (see Fig. 3B and Fig. 4) .

[0020] The gel inlet port 412 receives the aqueous polymer solution through the gel tube 402 and delivers the aqueous polymer solution to the flow channel 418, which is formed within the anode block 411. The gel inlet port 412 is connected via the flow channel 418 to the capillary connection port 413 and the gel pump port 414. The gel pump port 414 is further connected via the flow channel 419 to the gel waste liquid port 415. The gel pump port 414 also holds a gel pump 417. The inner circumferential surface of the gel pump port 414 and the outer circumferential surface of the gel pump 417 can slide against each other while maintaining the seal.By moving the gel pump 417 in the B direction, which corresponds to the longitudinal direction of the gel pump connection 414, pressure is exerted on the aqueous polymer solution supplied to the interior of the gel pump connection 414, and the aqueous polymer solution is delivered through the flow channel 418 to the capillary connection port 413. The capillary connection port 413 is connected to the capillary 421, to which a capillary anode head 422 is attached.

[0021] The gel waste liquid connection 415 directs unnecessary aqueous polymer solution remaining within the anode block 411 to an anode waste tank 501 (see Fig. 1) from, which is arranged outside the anode block 411. Additionally, an anode electrode 416e, which is connected to the anode electrode port 416, is provided in the flow channel between the flow channel 419 and the gel waste liquid port 415.

[0022] The structure of the capillary sheath unit 420 will be described below with reference to Fig. 5 described. The capillary sheath unit 420 has a multilayered structure comprising the capillary 421, a heat dissipation film 425, a heating unit 426, a heat-insulating material 427, and housings 428 and 429. These are each explained below.

[0023] The capillary 421 is a glass tube with an inner diameter of several tens of micrometers and an outer diameter of several hundred micrometers, the outer surface of which is protected by a polyimide coating. The capillary anode head 422 is located at the end of the capillary 421 on the side of the anode block unit 410, and a capillary cathode head 423 is located at the end of the capillary 421 on the side of the cathode block unit 440. Additionally, a slide 424 is positioned closer to the anode block unit than the center of the capillary 421, and the capillary 421 is attached to the endpoints 424a and 424b of the slide 424. Furthermore, a detection window 421a is provided in the capillary 421, located between the endpoints 424a and 424b of the slide 424. The detection window 421a is formed by removing the polyimide on the surface of the capillary 421 by several mm in the longitudinal direction of the capillary 421 in order to expose the glass tube.

[0024] The heat dissipation film 425 is made of a material with high thermal conductivity and improves the heat exchange efficiency between the capillary 421 and the heating unit 426. The capillary electrophoresis device utilizes the capillary's high heat dissipation capacity to reduce the effect of Joule heating generated during electrophoresis and to improve separation efficiency. Generally, methods for temperature control of capillaries include techniques such as using a temperature-controlled surface heater on the capillary surface or circulating air set to a constant temperature in a space where the capillary is installed. In the present embodiment, a surface heater is used as an example, although an air circulation system can also be employed.The heating unit 426 has a multilayered structure consisting of a surface heater 426a, a metal plate 426b, and an insulating film 426c. The surface heater 426a is controlled by a temperature sensor (not shown) installed on the heat-dissipating film 425, which sets the temperature of the heat-dissipating film 425 to a predetermined temperature. The metal plate 426b diffuses heat from the surface heater 426a across the surface, thus homogenizing the surface temperature. Furthermore, by using a metal with a high heat capacity as the material for the metal plate 426b, it is made less susceptible to disturbances such as fluctuations in the ambient air temperature. The insulating film 426c is also made of a material with high electrical resistance and prevents discharge from the capillary 421, to which a high voltage is applied, to the metal plate 426b.

[0025] The heat-insulating material 427 prevents the heat generated by the heating unit 426 from being dissipated outside the housings 428 and 429, thereby minimizing the influence of the outside air temperature on the temperature inside the capillary sleeve unit 420. The housings 428 and 429 contain the capillary 421, the heat-dissipating film 425, the heating unit 426, and the heat-insulating material 427 in a multi-layered structure.

[0026] For example, a silicone film can be used as a heat dissipation film 425, a polyimide heater as a surface heater 426a, an aluminum alloy as a metal plate 426b, a polyimide film as an insulating film 426c, a low-foam urethane film as a heat insulator, and ABS resin for the housings 428 and 429.

[0027] The structure of the cathode block unit 440 will be described below with reference to the Fig. 6A, Fig. 6B and Fig. 7 described. The cathode block unit 440 is configured to receive the aqueous polymer solution from the capillary 421, to receive the buffer solution for electrophoresis, to inject the sample DNA into the capillary 421, and to apply a cathode-side voltage to the aqueous polymer solution in the capillary 421 for electrophoresis. The cathode block unit 440 consists mainly of a cathode block 441 in which flow channels 450 and 451 are formed (see Fig. 7) In this example, four connections are provided for supplying and removing the aqueous polymer solution to and from the flow channels in the cathode block 441, two connections for applying a voltage and taking electrical measurements, and one connection for heating. It should be noted that the material of the cathode block 441 is also, for example, PMMA.

[0028] The connections for supplying and discharging liquid constitute a capillary connection 442 (see Fig. 6B and Fig. 7), a buffer solution inlet connection 443 (see Fig. 6A and Fig. 7), a sample inlet port 444 (see Fig. 6A, Fig. 6B and Fig. 7) and a waste liquid connection 445 (see Fig. 6A and Fig. 7). The connection for applying a voltage also represents a cathode electrode connection 446 (see Fig. 6B and Fig. 7) and the connection for electrical measurement is a measuring electrode connection 447 (see Fig. 6B and Fig. 7).

[0029] The connection for heating is furthermore a cathode heating connection 448 (see Fig. 6A).

[0030] Here, the flow channel 450, which connects the capillary connection port 442 and the waste liquid port 445, is referred to as the main flow channel, and the flow channel connecting the sample inlet port 444 and the main flow channel 450 is referred to as the sample flow channel. The flow channels are configured such that the connection point between the main flow channel 450 and the sample flow channel 451 is located closer to the sample inlet port 444. The flow resistance towards the upstream side of the main flow channel 450, i.e., the flow resistance towards the sample inlet port 444, is higher than the flow resistance towards the downstream side of the main flow channel 450, i.e., the flow resistance towards the waste liquid port 445, and the sample DNA introduced through the sample inlet port 444 flows mainly downstream of the main flow channel 450.

[0031] The capillary 421, with the attached capillary cathode head 423, is further connected to the capillary connection port 442. The method for connecting the capillary 421 to the capillary connection port 442 is described below. The capillary connection port 442 receives the aqueous polymer solution supplied by the capillary 421 and delivers the aqueous polymer solution to the main flow channel 450, which is formed within the cathode block 441. The buffer solution inlet port 443 also receives the buffer solution, which is supplied through a buffer solution tube, and delivers the buffer solution to the main flow channel 450, which is formed within the cathode block 441. The sample inlet port 444 then receives a solution containing sample DNA and buffer solution and delivers the solution containing sample DNA and buffer solution to the main flow channel 450 through the sample flow channel 451.The waste fluid port 445 also delivers excess buffer solution, aqueous polymer solution, and sample DNA that remain in the main flow channel 450 of the cathode block 441 to the outside of the cathode block 441. The waste fluid is collected in a cathode waste fluid tank 503 (see . Fig. 1) through a waste liquid tube 449 (see Fig. 6B) delivered, which is connected to the waste liquid connection 445.

[0032] One of the causes of individual differences in the cartridge 200 is the tip position of the capillary 421 in the flow channel of the cathode block 441. For example, in the cartridge 200, the measuring electrode port 447 determines the amount of sample DNA injected into the capillary 421. Specifically, the injection quantity is determined from the conductivity of the liquid between a cathode electrode 446e, connected to the cathode electrode port 446, and a measuring electrode 447e, connected to the measuring electrode port 447, taking advantage of the fact that the sample DNA is negatively charged. However, a variation in the tip position of the capillary 421 affects the determination result. Alternatively, since the capillary 421 is cooled in the flow channel by the sample DNA and buffer solution, variations in the length of the capillary 421 within the flow channel cause variations in the temperature influence on the capillary 421.Furthermore, if capillary 421 is inserted at an angle to the flow channel, an injection error is more likely to occur, resulting in insufficient injection of the sample DNA into capillary 421. To prevent such performance variations of the electrophoresis device, it is necessary to suppress variations in the tip position of capillary 421 within the flow channel of the block.

[0033] For this reason, the cartridge according to the present embodiment is configured such that a head (capillary retaining element) is attached to the capillary without using a sleeve to attach the capillary to the block unit, and the capillary is attached to the block unit via the head. The connection of the capillary 421 to the cathode block 441 is described below as an example.

[0034] The capillary cathode head 423 is attached to the capillary 421, and the length (protruding length) from the capillary cathode head 423 to the tip of the capillary is specified as x [mm].

[0035] As in Fig. As illustrated in Figure 6A, the capillary cathode head 423 is formed with a head rotation limiting section 423a and has a hole section 423b drilled through it to allow the capillary 421 to pass through. A tapered section 423c with a varying cross-sectional area is also formed coaxially with the hole section 423b. In this example, the head rotation limiting section 423a is rectangular with a long side and a short side. The diameter of the hole section 423b is also slightly larger than the diameter of the capillary 421, and the capillary 421 is guided through the hole section 423b, so that the protruding length is x mm. The capillary cathode head 423 is attached to the capillary 421, for example, by injecting adhesive between the inner circumferential surface of the hole section 423b and the outer circumferential surface of the capillary 421.

[0036] To connect the capillary 421, to which the capillary cathode head 423 is attached, to the cathode block 441, the capillary cathode head 423 is mounted while being pressed against the capillary connection port 442 by a cathode knob 431. The following explains how the capillary 421 is attached to the cathode block 441 via the capillary cathode head 423, which is broadly divided into the capillary cathode head 423, the cathode block 441, and the cathode knob 431.

[0037] As in Fig. As illustrated in Figure 6B, an external thread 442a is formed on the outer circumferential surface of the capillary connection port 442 of the cathode block 441. Furthermore, a rotation limiting section 442b and a tapered section 442c are formed within the capillary connection port 442. The rotation limiting section 442b has a rectangular shape, identical to the shape of the head rotation limiting section 423a shown above, and has long and short sides.

[0038] Additionally, as in Fig. 6A and Fig. Figure 6B illustrates an internal thread 431a formed on the inner circumferential surface of the cathode knob 431, and a hole section 431b is formed therein. The hole section 431b of the cathode knob 431 has a rectangular shape, which is identical to the preceding shape of the head rotation limiting section 423a, and has long and short sides.

[0039] The hole section 431b of the cathode knob 431 and the rotation limiting section 442b of the cathode block 441 are each slightly larger than the protruding shape of the head rotation limiting section 423a of the capillary cathode head 423. This allows the capillary cathode head 423 to pass through the hole section 431b of the cathode knob 431, and allows the head rotation limiting section 423a of the capillary cathode head 423 to fit into the rotation limiting section 442b of the cathode block 441.

[0040] The procedure for connecting the capillary 421 to the cathode block 441 is described below. First, the internal thread 431a of the cathode knob 431 is engaged with the external thread 442a of the cathode block 441, and then screwed in the D direction, which is clockwise, so that the engagement width is maximized (until the cathode knob 431 can no longer move). The cathode knob 431 is then rotated 180° in the E direction, which is counterclockwise. That is, the D direction represents the direction in which the cathode knob 431 is tightened, and the E direction is the direction in which the cathode knob 431 is loosened. Furthermore, the cathode knob 431 is rotated in the E-direction by an angle of less than 180°, so that the long side of the hole section 431b of the cathode knob 431 and the long side of the rotation limiting section 442b of the cathode block 441 assume the same phase.

[0041] In this state, the capillary 421 is inserted into the capillary connection port 442 of the cathode block 441. That is, the long side of the head rotation limiting section 423a of the capillary cathode head 423 and the long side of the rotation limiting section 442b of the cathode block 441 (and therefore the long side of the hole section 431b of the cathode knob 431) are brought into the same phase, and the capillary cathode head 423 attached to the capillary 421 is inserted into the capillary connection port 442 along the C-direction, which corresponds to the longitudinal direction of the capillary 421. As the capillary cathode head 423 is gradually inserted into the capillary connection port 442, the tapered section 423c of the capillary cathode head 423 also comes into contact with the tapered section 442c of the cathode block 441. The state at this point is described in Fig. 8 illustrates.

[0042] A pressure surface 423d of the capillary cathode head 423 is arranged further in the direction of the C-direction than a pressure surface 431c of the cathode knob 431, which engages with the cathode block 441. The pressure surface 423d of the capillary cathode head 423 represents the surface of the head rotation limiting section 423a, which faces the surface of the cathode knob 431 where the hole section 431b is provided (see Fig. 6B and Fig. 8) The pressure surface 431c of the cathode knob 431 also represents the surface of the cathode knob 431 in which the hole section 431b is provided, and which faces the pressure surface 423d of the capillary cathode head 423 (see Fig. 6A and Fig. 8) In addition, the capillary cathode head 423, the cathode block 441 and the cathode button 431 are designed such that a distance ε between the pressure surface 423d of the capillary cathode head 423 and the pressure surface 431c of the cathode button 431, which engages with the cathode block 441, becomes smaller at this time than a distance L that the cathode button 431 travels in the C direction when it is rotated by 180° in the D direction.

[0043] If the cathode knob 431 is removed from the in Fig.In the state illustrated in Figure 8, when the capillary cathode head 423 is rotated in the D-direction, the pressure surface 423d of the capillary cathode head 423 also comes into contact with the pressure surface 431c of the cathode knob 431. If the cathode knob 431 is then rotated further in the D-direction, it presses the capillary cathode head 423 against the cathode block 441 and fixes the capillary cathode head 423 in place. Since the relationship ε < L is established, the cathode knob 431 can reliably fix the capillary cathode head 423. At this point, the tapered section 423c of the capillary cathode head 423 and the tapered section 442c of the cathode block 441 come into line contact, thereby generating a sealing force. This enables fluid transfer between the capillary 421 and the cathode block 441 without leakage.

[0044] In this example, the shape of the head rotation limiting section 423a of the capillary cathode head 423 is a rectangle that is bilaterally symmetrical about the central axis of the hole section 423b, and the rotation limiting section 442b of the cathode block 441 and the hole section 431b of the cathode knob 431 have the same shape as the shape of the head rotation limiting section 423a. However, the shape is not limited to a rectangle as long as a compressive force is generated between the capillary cathode head 423 and the cathode knob 431 when the phase is shifted. Although the rectangle is bilaterally symmetrical, but, for example, if the shape does not have rotational symmetry, the method for mounting the capillary cathode head 423 on the cathode block 441 is uniquely determined so that the capillary 421 does not twist between the cathode block unit 440 and the anode block unit 410.In this case, however, it is necessary, after first engaging the internal thread 431a of the cathode knob 431 with the external thread 442a of the cathode block 441, to loosen the cathode knob 431 by 360° and then align the chamfer between the hole section 431b of the cathode knob 431 and the rotation limiting section 442b of the cathode block 441, which complicates the installation. In contrast, in the case of a figure with three-sided or four-sided symmetry, the amount of rotation of the cathode knob 431 can be reduced, which simplifies the installation. However, this increases the likelihood that the capillary cathode head 423 will be installed on the cathode block 441 in a rotated state relative to the original installation direction. In this case, the capillary 421 is twisted between the cathode block unit 440 and the anode block unit 410.In the case of two-sided symmetry, an incorrect assembly would also require that the capillary 421 be rotated by 180°, and therefore assembly errors are unlikely to occur.

[0045] The foregoing describes the method for connecting the capillary 421 to the cathode block 441. Similarly, the capillary anode head 422 is first mounted to the anode block 411 by attaching it to the anode block 411 while the capillary anode head 422 is pressed with an anode button 430. This mounting method is similar to the method for connecting the capillary 421 to the cathode block 441 and is therefore not described here.

[0046] The electrophoresis device 100 with the installed cartridge 200 is described with reference to Fig. As described in Figure 1, a central processing unit (CPU) 310 is configured to control the entire electrophoresis device 100 and is connected to a heating power supply unit 320, a high-voltage power supply unit 330, a pump unit 340, a linear actuator 350, a linear actuator 360, and the like. The heating power supply unit 320 also supplies power to the heating unit 426 of the capillary shell unit 420. The high-voltage power supply unit 330 applies a voltage to the aqueous polymer solution in the capillary 421 for electrophoresis and a high potential (HV) to the anode electrode terminal 416 of the anode block unit 410, as well as a reference potential (GND) to the cathode electrode terminal 446 of the cathode block unit 440. The pump unit 340 also supplies the buffer solution to the main flow channel 450 of the cathode block 441.It should be noted that a buffer solution tank 502, containing the buffer solution, is provided in the cartridge 200, and the pump unit 340 pumps the buffer solution in the buffer solution tank 502 towards the buffer solution inlet port 443 of the cathode block 441. The linear actuator 350 then drives the gel piston 401b of the gel unit 401. Additionally, the linear actuator 360 drives the gel pump 417 of the anode block unit 410.

[0047] The DNA to be tested is introduced into the electrophoresis apparatus 100 via a DNA sample inlet 390. The introduced test object undergoes processing, such as DNA amplification, in a reaction chamber 380 and is sent as sample DNA to the sample inlet 444 of the cathode block 441. It should be noted that the water and reagents required in the reaction chamber 380 are supplied by a water tank 504 and a reagent bottle 505 of the cartridge 200, respectively. The injection of the sample DNA into the capillary 421 is also determined based on the conductivity of the liquid between the cathode electrode 446e, which is connected to the cathode electrode port 446, and the measuring electrode 447e, which is connected to the measuring electrode port 447, as measured by an instrument amplifier 370, which is connected to the measuring electrode port 447.

[0048] Furthermore, it should be noted that the anode block unit 410 and the cathode block unit 440 are arranged such that both ends of the capillary are in the same plane with respect to the direction of gravity, thus preventing a difference in water level between the two ends of the capillary. For example, if the arrangement of the anode block unit 410, the capillary sleeve unit 420, and the cathode block unit 440 is installed horizontally along the length of the capillary 421 on the electrophoresis device 100, it is sufficient that the height of the base surface of the capillary connection port 413 of the anode block 411 and the height of the base surface of the capillary connection port 442 of the cathode block 441 are equal.

[0049] An example has been described in which a single capillary is arranged in the electrophoresis device 100, but it is also possible to arrange several capillaries in the electrophoresis device 100 by arranging several capillaries in the cartridge 200 or by allowing the electrophoresis device 100 to accommodate several cartridges 200.

[0050] It should be noted that the present invention is not limited to the embodiments described above and includes various modification examples. For instance, the embodiments described above have only been described in such detail to facilitate understanding of the present invention, and the present invention is not necessarily limited to those embodiments that include all the described configurations. Furthermore, a part of the configuration of one embodiment can be replaced by the configurations of other embodiments, and the configuration of one embodiment can also be supplemented by the configurations of other embodiments. In addition, a part of the configuration of each of the embodiments can also be supplemented, deleted, or replaced with respect to other configurations.For example, an example is illustrated here in which the cathode block 441 and the cathode knob 431, or the anode block 411 and the anode knob 430, are connected by the engagement of a threaded section provided on the outer circumferential surface with a threaded section provided on the inner circumferential surface. However, these can also be connected by the engagement of a latch. List of reference symbols

[0051] 100: Capillary electrophoresis device, 200: Capillary cartridge, 310: CPU, 320: Heater power supply unit, 330: High-voltage power supply unit, 340: Pump unit, 350, 360: Linear actuator, 370: Instrument amplifier, 380: Reaction chamber, 390: DNA sample inlet, 401: Gel unit, 401a: Gel syringe, 401b: Gel piston, 401c: Gel coupler, 402: Gel tube, 410: Anode block unit, 411: Anode block, 412: Gel inlet port, 413: Capillary connection port, 414: Gel pump port, 415: Gel waste liquid port, 416: Anode electrode port, 416e: Anode electrode, 417: Gel pump, 418, 419: Flow channel, 420: Capillary sleeve unit, 421: Capillary, 422: Capillary anode head, 423: Capillary cathode head, 423a: Head rotation limiting section, 423b: Hole section, 423c: Tapered section, 423d: Pressing surface, 424: Slide, 424a, 424b: End point, 425: Heat dissipation film, 426: Heating unit, 426a: Surface heater, 426b: Metal plate, 426c: Insulating film,427: Heat-insulating material, 428, 429: Housing, 430: Anode knob, 431: Cathode knob, 431a: Internal thread, 431b: Hole section, 431c: Pressing surface, 440: Cathode block unit, 441: Cathode block, 442: Capillary connection port, 442a: External thread, 442b: Rotation limiter section, 442c: Tapered section, 443: Buffer solution inlet port, 444: Sample inlet port, 445: Waste liquid port, 446: Cathode electrode port, 446e: Cathode electrode, 447: Measuring electrode port, 447e: Measuring electrode, 448: Cathode heater port, 449: Waste liquid tube, 450: Main flow channel 451: Sample flow channel, 501: Anode waste liquid tank, 502: Buffer solution tank, 503: Cathode waste liquid tank, 504: Water tank, 505: Reagent bottle, QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] JP 2012-98309

[0006]

Claims

[1] A capillary cartridge comprising: a capillary; a first capillary retaining element that is attached at a position at a predetermined distance from one end of the capillary; and a first block unit comprising a first element in which a main flow channel is formed and a second element connected to the first element, wherein the first block unit holds the first capillary retaining element by clamping the first capillary retaining element between the first element and the second element, wherein the first capillary retaining element comprises a first hole section through which the capillary passes, a first tapered section which is coaxial with the first hole section, and a first rotation limiting section which has a pressure surface with a predetermined projecting shape, wherein the first element comprises a second tapered section connected to and coaxial with the main flow channel, and a second rotation limiting section connected to the second tapered section, wherein the capillary is connected to the first block unit when the pressure surface of the first rotation limiting section is pressed through a pressure surface of the second element in a state in which the first rotation limiting section of the first capillary retaining element is fitted into the second rotation limiting section of the first element and the first tapered section of the first capillary retaining element is in contact with the second tapered section of the first element. [2] The capillary cartridge according to claim 1, wherein the first element comprises a sample flow channel for introducing a sample into the main flow channel and a cathode electrode which is provided in the main flow channel and configured to apply a cathode-side voltage to an aqueous polymer solution introduced into the capillary, and one end of the capillary is located closer to the cathode electrode than a connection point between the main flow channel and the sample flow channel. [3] The capillary cartridge according to claim 2, wherein the first element comprises a measuring electrode which is provided in the main flow channel between the cathode electrode and the junction point, The injection of the sample into the main path is determined based on the conductivity of the liquid between the cathode electrode and the measuring electrode, and one end of the capillary is positioned between the cathode electrode and the measuring electrode. [4] The capillary cartridge according to claim 3, further comprising: a second capillary retaining element, which is attached at a position at a predetermined distance from the other end of the capillary; and a second block unit comprising a third element in which a flow channel is formed and a fourth element connected to the third element, wherein the second block unit holds the second capillary retaining element by clamping the second capillary retaining element between the third element and the fourth element, wherein the second capillary retaining element comprises a second hole section through which the capillary passes, a third tapered section which is coaxial with the second hole section, and a third rotation limiting section which has a pressure surface with a predetermined projecting shape, wherein the second element comprises a fourth tapered section connected to and coaxial with the flow channel, and a fourth rotation limiting section connected to the fourth tapered section, wherein the capillary is connected to the second block unit when the pressure surface of the third rotation limiting section is pressed through a pressure surface of the second element in a state in which the third rotation limiting section of the second capillary retaining element is fitted into the fourth rotation limiting section of the second element and the third tapered section of the second capillary retaining element is in contact with the fourth tapered section of the second element, the second element comprises an anode electrode which is provided in the flow channel and configured to apply an anode-side voltage to the aqueous polymer solution introduced into the capillary, and there is no difference in water level between one end and the other end of the capillary. [5] The capillary cartridge according to claim 4, wherein one end and the other end of the capillary are arranged in the same plane with respect to a direction of gravity. [6] The capillary cartridge according to claim 1, wherein the protruding shape of the pressure surface of the first rotation limiting section of the first capillary retaining element is bilaterally symmetrical about a central axis of the first hole section. [7] A method for assembling a capillary cartridge with a block unit and a capillary, the method comprising: Attaching a capillary retaining element to a position at a predetermined distance from one end of the capillary, wherein the capillary retaining element comprises a first hole section through which the capillary passes, a first tapered section which is coaxial with the first hole section, and a first rotation limiting section which has a pressure surface with a predetermined projecting shape, wherein the block unit comprises a first element in which a main flow channel is formed, and a second element which is connected to the first element, wherein the first element comprises a second tapered section connected to and coaxial with the main flow channel, and a second rotation limiting section connected to the second tapered section; Bringing the first element and the capillary retaining element into a state in which the first rotation limiting section is fitted into the second rotation limiting section and the first tapered section is in contact with the second tapered section; and Pressing the pressure surface of the first rotation limiting section of the capillary retaining element with a pressure surface of the second element to connect the capillary to the block unit. [8] The method according to claim 7, wherein the first element has an outer circumferential surface on which a first thread section is formed, and the second element has an inner circumferential surface on which a second thread section is formed, wherein the first element and the second element are connected by the first thread section engaging with the second thread section, the second element comprises a second hole section with the predetermined protruding shape, the second rotation limiting section of the first element has the predetermined protruding shape, and with the second rotation limiting section of the first element and the second hole section of the second element aligned in phase, in a state in which the first element and the second element are connected, the capillary is introduced into the main flow channel of the first element. [9] The method according to claim 8, further comprising: Screw the second element into the first element in such a way that the second rotation limiting section of the first element and the second hole section of the second element are phase-shifted relative to each other; and Pressing the pressure surface of the first rotation limiting section of the capillary retaining element with the pressure surface of the second element. [10] The method according to claim 8, wherein the foregoing shape of the pressure surface of the first rotation limiting section of the first capillary retaining element is bilaterally symmetrical about a central axis of the first hole section.

Citation Information

Patent Citations

  • JAPANISCHEOFFENLEGUNGSSCHRIFTNR.2012-98309