Electrophoresis equipment

Abstract

The purpose of the present invention is to provide an electrophoresis device in which, during replacement work of a capillary array, a detection unit is protected and high workability is provided. To achieve the purpose, the present invention is an electrophoresis device comprising a capillary array having one or more capillaries. The capillary array has: a load header provided at one end thereof; a capillary head provided at the other end; and a detection unit that is formed between the load header and the capillary head, and detects a sample that migrates in the capillary through electrophoresis. The electrophoresis device comprises: a holder to which the detection unit is attached; and a protection unit that protrudes with respect to an array surface of the capillary array. When the detection unit is attached to the protection unit, the inner surface of the holder is separated from the detection unit.

Description

[Technical Field]

[0001] The present invention relates to an electrophoresis device. [Background technology]

[0002] When changing the measurement method, the capillary array used in the capillary electrophoresis device is replaced by a different one depending on the user. However, because the weight of the detection unit and array head makes the capillary array prone to sagging, there is a possibility that the detection unit may come into contact with the device and be damaged during the replacement work. Therefore, Patent Document 1 discloses that, to facilitate the replacement work of the capillary array, a holder is provided to hold the capillaries, and this holder is composed of a slide part and a plate part (claim 5). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2020 / 50193 Summary of the Invention [Problem to be solved by the invention]

[0004] In the electrophoresis apparatus disclosed in Patent Document 1, the plate must be slid while maintaining a distance between the array holder and the capillary array detection unit so that the detection unit does not come into contact with the array holder, which does not provide high user operability.

[0005] An object of the present invention is to provide an electrophoresis apparatus that is easy to use and protects the detection unit during capillary array replacement. [Means for solving the problem]

[0006] In order to solve the above problem, the present invention provides an electrophoresis device comprising a capillary array having one or more capillaries, the capillary array having a load header provided at one end, a capillary head provided at the other end, and a detection unit formed between the load header and the capillary head for detecting samples undergoing electrophoresis within the capillaries, the device comprising: a holder to which the detection unit is attached; and a protective unit protruding from the arrangement surface of the capillary array, the protective unit separating the inner surface of the holder from the detection unit when the detection unit is attached. [Effects of the Invention]

[0007] According to the present invention, it is possible to provide an electrophoresis apparatus that is easy to use while protecting the detection unit during the capillary array replacement work. [Brief explanation of the drawings]

[0008] [Figure 1] Schematic diagram of an electrophoresis device according to an embodiment of the present invention. [Figure 2] FIG. 1 is a diagram showing the configuration of a capillary array unit according to Example 1. [Figure 3A] FIG. 1 is a diagram showing a state before the capillary array unit is attached to a block of an electrophoresis apparatus. [Figure 3B] FIG. 1 is a diagram showing the state after the capillary array unit is attached to the block of the electrophoresis device. [Figure 4] An exploded perspective view showing the configuration of the detection unit [Figure 5A] FIG. 1 is a plan view showing the configuration of the plate and capillary array around the detection unit. [Figure 5B] 1 is a cross-sectional view showing the configuration of the plate and capillary array around the detection unit. [Figure 6] A diagram showing the structure of the array holder in detail [Figure 7A] FIG. 1 is a cross-sectional view showing the positional relationship before the plate is slid relative to the array holder in Example 1. [Figure 7B] FIG. 10 is a cross-sectional view showing the positional relationship after the plate is slid relative to the array holder in Example 1. [Figure 8A] FIG. 10 is a cross-sectional view showing the positional relationship before the plate is slid relative to the array holder in Example 2. [Figure 8B] FIG. 10 is a cross-sectional view showing the positional relationship after the plate is slid relative to the array holder in Example 2. [Figure 9] FIG. 10 is a diagram showing the configuration of a capillary array unit in an electrophoresis apparatus according to a third embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0009] The configuration of an electrophoresis apparatus 101 according to an embodiment of the present invention will be described with reference to Fig. 1. Fig. 1 is a schematic diagram of the electrophoresis apparatus 101 according to this embodiment. As shown in Fig. 1, the electrophoresis apparatus 101 includes a capillary array 117 composed of one or more capillaries 102, a thermostatic bath 118 that maintains the capillaries 102 at a constant temperature, a high-voltage power supply 104 that applies a voltage to the capillaries 102, a pump mechanism 103 that injects a polymer into the capillaries 102, and a transport mechanism 125. The transport mechanism 125 is a mechanism for transporting a buffer container 121, a washing container 122, a waste liquid container 123, and a sample container 124 to a capillary cathode end 127.

[0010] The capillary array 117 has a load header 129 at one end, a capillary head 112 at the other end, and a detection unit formed between the load header 129 and the capillary head 112 for detecting a sample undergoing electrophoresis in the capillaries 102. The capillary array 117 is composed of, for example, eight or twenty-four capillaries 102, and is replaced with capillaries of a different length when the measurement method is changed. Also, if a capillary 102 is damaged or its quality deteriorates, it is replaced with a new capillary array.

[0011] The capillary 102 is formed from a glass tube with an inner diameter of 50 μm and an outer diameter of 320 μm, and its surface is coated with polyimide to improve its strength. However, the polyimide coating has been removed from the detection unit 116 of the capillary 102, where the laser light is irradiated, to allow the internal light emission to easily leak to the outside. The interior of the capillary 102 is filled with a separation medium, which creates a migration difference during electrophoresis, by a pump mechanism 103. In this embodiment, a polymer, which is a highly viscous solution, is used as the separation medium.

[0012] The capillary cathode ends 127 are fixed through respective metallic hollow electrodes 126, and the tips of the capillaries 102 protrude about 0.5 mm from the hollow electrodes 126. All of the hollow electrodes 126 provided for each capillary 102 are mounted together on a load header 129. All of the hollow electrodes 126 are electrically connected to the high-voltage power supply 104 mounted in the main body of the device, and function as cathode electrodes when voltage is applied for electrophoresis, sample introduction, etc.

[0013] The capillary ends opposite the capillary cathode end 127 are bound together and glued by the capillary head 112. The capillary head 112 is connected to the block 107 in a pressure-tight and airtight manner. Then, new polymer is filled into the capillary 102 by the pump mechanism 103. The polymer in the capillary 102 is refilled for each measurement to improve the measurement performance.

[0014] The optical detection unit is composed of a light source 114 that illuminates the detection unit 116, an array holder 105 that holds the detection unit 116, and an optical detector 115 that detects the light emitted from the detection unit 116. When detecting a sample in the capillary 102 that has been separated by electrophoresis, the light source 114 illuminates the detection unit 116, and the light emitted from the detection unit 116 is detected by the optical detector 115.

[0015] The thermostatic bath 118 is covered with a heat insulating material, and its interior is controlled to a constant temperature by a heating and cooling mechanism 120. A fan 119 circulates and agitates the air inside the thermostatic bath 118, thereby maintaining the temperature of the capillary array 117 uniformly and constantly.

[0016] The pump mechanism 103 is composed of a plunger pump 106, a block 107, a check valve 108, an electric valve 113, a polymer container 109, and an anode buffer container 110. The block 107 is provided with a flow path that connects the plunger pump 106, the polymer container 109, the anode buffer container 110, and the capillary array 117. The flow path between the plunger pump 106 and the polymer container 109 is provided with a check valve 108 to prevent backflow of the polymer. The flow path between the block 107 and the anode buffer container 110 is provided with an electric valve 113. When the chamber 128 of the plunger pump 106 and the capillary array 117 are filled with polymer, the electric valve 113 closes to prevent the buffer solution from flowing in from the anode buffer container 110. When electrophoresis is performed, the electric valve 113 opens, and electricity is applied to the anode electrode 111 and the capillary cathode end 127.

[0017] The transport mechanism 125 is equipped with three electric motors and linear actuators (not shown), and is movable in three directions: up and down, left and right, and depth. One or more containers can be placed on the moving stage 130 of the transport mechanism 125. The moving stage 130 is also equipped with an electric grip 131, which can grasp and release each container. This allows the buffer container 121, washing container 122, waste container 123, and sample container 124 to be transported to the load header 129 as needed. Unnecessary containers are stored in a designated storage area within the device. [Example]

[0018] 2 is a diagram showing the configuration of a capillary array unit 201 according to the first embodiment. As shown in FIG. 2, the capillary array unit 201 of this embodiment includes a capillary array 117, a frame 202, and a plate 203 that slides relative to the frame 202. The capillaries 102 are held in a fixed shape by separators 204 provided on the frame 202 to prevent them from entangling with each other. The detection unit 116 and capillary head 112 of the capillary array 117 are supported on the plate 203 by a detection unit support part 223 and an array head support part 224 of the plate 203 to prevent them from sagging due to their own weight. Furthermore, the capillaries 102 attached to the plate 203 are bundled together by a bundling arm 222.

[0019] A wireless management tag 209 is attached to the frame 202, and records the serial number, manufacturing date, and number of uses (number of times electrophoresis has been performed) of the capillary array unit 201. The information recorded in the wireless management tag 209 is read or rewritten via a communication unit provided in the electrophoresis device.

[0020] FIG. 3A is a diagram showing the state before the capillary array unit 201 is attached to the block 107 of the electrophoresis device, and FIG. 3B is a diagram showing the state after the capillary array unit 201 is attached to the block 107 of the electrophoresis device.

[0021] Immediately after the capillary array unit 201 is inserted into the array holder 105, the plate 203 is fixed to the frame 202 by the fixing part 205, and the capillary head 112 is not attached to the block 107, as shown in Fig. 3A. Next, when the plate 203 is removed from the fixing part 205 and slid toward the block 107, the capillary head 112 is inserted into the block 107, and the detection part 116 is fitted into a predetermined attachment position in the array holder 105, as shown in Fig. 3B.

[0022] The configuration of the detection unit 116 will now be described in detail. FIG. 4 is an exploded perspective view showing the configuration of the detection unit 116. As shown in FIG. 4, the detection unit 116 is configured by combining, in order from the front side, a silicon substrate 212, a polyimide coating-removed portion 218 of the capillary array 117, a ceramic substrate 213, and a detection unit base 214. The silicon substrate 212 has a first window 215 for extracting fluorescence and a V-shaped groove 216 for aligning the capillary array 117. The ceramic substrate 213 has a second window 217 for reducing noise due to reflection of fluorescence and a measurement window 219 for irradiating the polyimide coating-removed portion 218 with laser light. The silicon substrate 212, the capillary array 117, and the ceramic substrate 213 are laminated and then fixed with an adhesive.

[0023] The detection unit base 214 is made of resin and is provided with a plurality of base protrusions 221 (protective portions) around its periphery that extend perpendicularly to the arrangement surface of the capillary array. Note that the base protrusions 221 have recesses 220 formed at positions that face the corners of the ceramic substrate 213, and the corners of the ceramic substrate 213 are fitted into these recesses 220, thereby positioning the ceramic substrate 213 and the like relative to the detection unit base 214. Furthermore, the base protrusions 221 not only protect the corners of the ceramic substrate 213, but also, as will be described later, prevent other device components from coming into contact with the silicon substrate 212.

[0024] Next, the configuration of the plate 203 that supports the detection unit 116 and the capillary head 112 will be described. Fig. 5A is a plan view showing the configuration of the plate 203 and the capillary array 117 around the detection unit 116, and shows the back side of the plate 203 etc. when the state in Fig. 3A is considered the "front". Fig. 5B is a cross-sectional view showing the configuration of the plate 203 and the capillary array 117 around the detection unit 116, and shows the plate 203 etc. as viewed vertically.

[0025] As shown in FIG. 5A, a plate-side thermally conductive sheet 225 is provided on the rear side of the plate 203, and the capillary array 117 is provided on the rear side of the plate 203. The plate-side thermally conductive sheet 225 suppresses excessive temperature rise of the capillaries by conducting heat generated in the capillaries when a high voltage is applied. In addition, when the array holder cover 227 is closed, the plate-side thermally conductive sheet 225 also serves to seal the periphery of the capillary array 117, thereby preventing external light from penetrating into the detection unit 116. Therefore, the plate-side thermally conductive sheet 225 is preferably made of a material that has thermal conductivity, insulation, and flexibility, and can be made of, for example, thermally conductive rubber.

[0026] The plate 203 has plate protrusions 207 (protective parts) that extend perpendicularly to the array surface of the capillary array 117 and protrude on the capillary head 112 side of the upper and lower edges of the plate-side thermal conduction sheet 225. The plate protrusions 207 come into contact with holder rails 208 provided on the array holder 105 side.

[0027] 6 is a diagram showing the details of the structure of the array holder 105, showing the array holder cover 227 in an open state. As shown in Fig. 6, the array holder 105 includes a holder-side thermally conductive sheet 226 provided on the surface that comes into contact with the capillary array 117, holder rails 208 that extend in the left-right direction and are arranged to face each other above and below the holder-side thermally conductive sheet 226, and an array holder cover 227 that covers the front side. The array holder 105 also has a window 228 that exposes the detection unit 116 of the capillary array 117.

[0028] The holder-side heat conduction sheet 226, like the plate-side heat conduction sheet 225 provided on the plate 203, suppresses an excessive temperature rise in the capillary while preventing external light from penetrating into the detection unit 116, and is made of heat conductive rubber or the like. The holder rail 208 abuts against the plate protrusion 207, and its sliding direction terminal end has an inclined portion 208a.

[0029] Next, the positional relationship between the array holder 105 and the plate 203 will be described with reference to Figures 7A and 7B. Figure 7A is a cross-sectional view showing the positional relationship before the plate 203 is slid relative to the array holder 105 in Example 1, and Figure 7B is a cross-sectional view showing the positional relationship after the plate 203 is slid relative to the array holder 105 in Example 1. Note that Figures 7A and 7B show the plate 203 and the array holder 105 viewed from the vertical direction with the array holder cover 227 open, and therefore the array holder cover 227 is not shown. The array holder 105 is attached to a unit housing 229, and the unit housing 229 is provided with a step 231 for maintaining the detection unit 116 and the condenser lens 230 at a predetermined distance. The functions realized in common in Examples 1, 2, and 3 are that before and during sliding of plate 203, detection unit 116 and array holder 105 are not in contact with each other, and a distance is maintained to prevent contamination or damage to detection unit 116, and that after sliding of plate 203, detection unit 116 is positioned at the position of window portion 228, and detection unit 116 is brought into contact with step 231, thereby maintaining a constant distance between detection unit 116 and condenser lens 230 and achieving the high-precision positioning required optically. Details of the structure for realizing these two opposing states before and after sliding of plate 203 are described below. First, when the plate 203 is inserted into the array holder 105 together with the capillary array 117, as shown in Fig. 7A, the plate protrusions 207 abut against the holder rails 208 of the array holder 105, restricting the movement of the plate 203 toward the rear side. When the plate 203 starts to slide in this state, the plate protrusions 207 slide along the front side of the holder rails 208, restricting the movement of the plate 203 toward the rear side. In other words, the detection units 116 of the capillary array 117 supported by the plate 203 are kept separated from the inner surface of the array holder 105, preventing contamination and damage.

[0030] When the plate protrusion 207 slides left and right and reaches the inclined portion 208a of the holder rail 208, the plate 203 gradually moves toward the rear side along the inclination. Then, when the plate protrusion 207 passes the end of the inclined portion 208a of the holder rail 208, the plate-side thermally conductive sheet 225 comes into contact with and presses against the holder-side thermally conductive sheet 226, sealing the periphery of the capillary array 117.

[0031] 7B, when plate 203 slides relative to array holder 105, detection unit 116 enters the attached state. Here, when detection unit 116 enters the attached state, the center position of detection unit 116 coincides with the center position of window portion 228 of array holder 105. Note that the protrusion dimension of holder rail 208 toward the front side is smaller than the protrusion dimension of plate protrusion 207 toward the rear side, so holder rail 208 is spaced apart from plate 203.

[0032] In addition, the distance (d1) between the plate protrusion 207 and the center of the detection unit 116 is longer than the distance (D1) between the sliding direction terminal end of the holder rail 208 and the center of the window portion 228 formed in the array holder 105, so the plate protrusion 207 will not come into contact with the holder rail 208 when in the attached state. Furthermore, the distance (d2) between the plate protrusion 207 and the load header 129 side end of the detection unit 116 is shorter than the distance (D2) between the sliding direction terminal end of the holder rail 208 and the anti-rail side end of the window portion 228. Therefore, immediately after the plate protrusion 207 passes over the inclined portion 208a of the holder rail 208, the load header 129 side end of the detection unit 116 can be prevented from coming into contact with the anti-rail side end of the window portion 228 of the array holder 105.

[0033] When the array holder cover 227 is closed, the capillary array 117 comes into close contact with the plate-side thermally conductive sheet 225 and the holder-side thermally conductive sheet 226, and the detection unit 116 is pressed against the step 231 and positioned at a predetermined distance.

[0034] When removing the capillary array 117 including the detection unit 116, the plate 203 is slid to the right in Fig. 7B. At this time, the plate protrusion 207 is gradually pushed toward the front side along the inclined portion 208a of the holder rail 208, so that the capillary array 117 supported by the plate 203 can be easily removed from the array holder 105. In addition, since the tip of the plate protrusion 207 has a curved shape, not only is the plate protrusion 207 less likely to get caught on the inclined portion 208a of the holder rail 208, but damage to the holder rail 208 can also be prevented. [Example]

[0035] Example 2 will be described with reference to Figures 8A and 8B. Figure 8A is a cross-sectional view showing the positional relationship before plate 203 is slid relative to array holder 105 in Example 2, and Figure 8B is a cross-sectional view showing the positional relationship after plate 203 is slid relative to array holder 105 in Example 2. Note that Figures 8A and 8B are viewed from the same perspective as Figures 7A and 7B related to Example 1.

[0036] In Example 1, the plate 203 has a plate protrusion and the array holder 105 has a rail, but in Example 2, the plate 203 has a rail and the array holder 105 has a holder protrusion 211.

[0037] First, when the plate 203 together with the capillary array 117 is inserted into the array holder 105, the plate rail 210 abuts against the holder protrusion 211 of the array holder 105, as shown in Fig. 8A, and therefore movement of the plate 203 toward the rear side is restricted. When the plate 203 starts to slide in this state, the plate rail 210 slides on the front side of the holder protrusion 211, and therefore movement of the plate 203 toward the rear side is restricted. In other words, the detection unit 116 of the capillary array 117 supported by the plate 203 is maintained separated from the inner surface of the array holder 105, and therefore contamination and damage are prevented.

[0038] When the plate rail 210 slides left and right and the inclined end of the plate rail 210 reaches the holder protrusion 211, the plate 203 gradually moves toward the rear side along the inclined end. Then, when the end of the plate rail 210 passes the holder protrusion 211 and slides further, the detection unit 116 enters the attached state, as shown in FIG. 8B.

[0039] When removing the capillary array 117 including the detection unit 116, the plate 203 is slid to the right in Fig. 8B. At this time, the plate rail 210 is gradually pushed forward along its inclination, so that the capillary array 117 supported by the plate 203 can be easily removed from the array holder 105. In addition, the tip of the holder protrusion 211 has a curved shape, which not only makes it difficult for the holder protrusion 211 to get caught on the inclination of the plate rail 210, but also prevents the plate rail 210 from being scratched. [Example]

[0040] 9 is a diagram showing the configuration of a capillary array unit in an electrophoresis apparatus according to Example 3. Unlike Examples 1 and 2, the capillary array unit of this example does not include a plate that supports a part of the capillary array 117. Therefore, the weight of the detection unit 116 or the capillary head 112 causes the unfixed parts to sag and come into contact with other components of the electrophoresis apparatus, which may contaminate or damage the detection unit 116.

[0041] 9, the base protrusion 221 of the detection unit base 214 according to this embodiment is positioned facing a corner of the silicon substrate 212 or the ceramic substrate 213, and the distance from the arrangement surface of the capillary array 117 to the tip of the base protrusion 221 is longer than the distance from the arrangement surface of the capillary array 117 to the surface of the detection unit 116 (silicon substrate 212). Therefore, the base protrusion 221 according to this embodiment also serves to separate the inner surface of the array holder 105 from the detection unit 116 (particularly the silicon substrate 212) when the detection unit 116 is attached to the array holder 105. However, when the detection unit 116 finally reaches the window portion 228, the detection unit 116 and the step 231 need to be in contact with each other, not separated from each other. Therefore, a hole for fitting base protrusion 221 is provided on the detecting unit pressing surface of step 231, and only when detecting unit 116 reaches window 228 does it fit into the hole, causing detecting unit 116 to come into contact with step 231 and position detecting unit 116 at a predetermined distance from condenser lens 230. Furthermore, base protrusion 221 of this embodiment is configured to be likely to come into contact with not only array holder 105 but also other components of the electrophoresis device before detecting unit 116 does, so that contact with detecting unit 116 is avoided and damage and contamination of silicon substrate 212 and polyimide coating removal portion 218 can be prevented.

[0042] The present invention is not limited to the above-described embodiments, but includes various modifications. For example, it is possible to replace part of the configuration of one embodiment with the configuration of another embodiment, or to add the configuration of another embodiment to the configuration of one embodiment. Furthermore, it is possible to add, delete, or replace part of the configuration of each embodiment with another configuration. [Explanation of symbols]

[0043] 101...electrophoresis apparatus, 102...capillary, 103...pump mechanism, 104...high-voltage power supply, 105...array holder, 106...plunger pump, 107...block, 108...check valve, 109...polymer container, 110...anode buffer container, 111...anode electrode, 112...capillary head, 113...motorized valve, 114...light source, 115...optical detector, 116...detection unit, 117...capillary array, 118...thermostat, 119...fan, 120...heating / cooling mechanism, 121...buffer container, 122...washing container, 123...waste container, 124...sample container, 125...transport mechanism, 126...hollow electrode, 127...capillary cathode end, 128...chamber, 129...load header, 130...moving stage, 131...grip, 201...capillary Ray unit, 202...frame, 203...plate, 204...separator, 205...fixing portion, 206...guide, 207...plate protrusion, 208...holder rail, 208a...inclined portion, 209...wireless management tag, 210...plate rail, 211...holder protrusion, 212...silicon substrate, 213...ceramics substrate, 214...detection unit base, 215...first window, 216...V Groove, 217...second window, 218...polyimide coating removal portion, 219...measurement window, 220...recess, 221...base protrusion, 222...binding arm, 223...detection unit support portion, 224...array head support portion, 225...plate side heat conduction sheet, 226...holder side heat conduction sheet, 227...array holder cover, 228...window portion, 229...unit housing, 230...condenser lens, 231...step

Claims

1. An electrophoresis apparatus comprising a capillary array having one or more capillaries, the capillary array having a load header provided at one end, a capillary head provided at the other end, and a detection unit formed between the load header and the capillary head for detecting a sample electrophoresing in the capillaries, a holder to which the detection unit is attached, a plate to support a part of the capillary array including the detection unit, and a protective part protruding from an arrangement surface of the capillary array, the protective portion formed on the plate abuts against a rail formed on the holder, The protective part separates the inner surface of the holder from the detection part when the detection part is attached, and the protective part slides along the front side of the rail and then moves to the rear side.

2. 2. The electrophoresis device according to claim 1, An electrophoresis device in which the rail has an inclined end in the sliding direction.

3. 2. The electrophoresis device according to claim 1, a distance between the protection portion and the center of the detection portion is longer than a distance between an end portion of the rail in the sliding direction and a center of a window portion formed in the holder; a distance between the protection portion and an end of the detection portion, Here, the end is an end of the detection unit that is closer to the load header. An electrophoresis device in which the distance is shorter than the distance between the end of the rail in the sliding direction and the end of the window portion on the side opposite to the rail.

4. An electrophoresis apparatus comprising a capillary array having one or more capillaries, the capillary array having a load header provided at one end, a capillary head provided at the other end, and a detection unit formed between the load header and the capillary head for detecting a sample electrophoresing in the capillaries, a holder to which the detection unit is attached, and a protective unit that protrudes from an arrangement surface of the capillary array, the protection portion is positioned facing a corner of the detection portion, the distance from the arrangement surface of the capillary array to the tip of the protection part is longer than the distance from the arrangement surface of the capillary array to the surface of the detection part; The protection section separates the inner surface of the holder from the detection section when the detection section is attached.

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