Extraction device and processing system for biologically-related substances

Abstract

An extracting device 200 comprises: a plurality of extraction vessels 210 for holding a solution containing magnetic particles and a sample; an oscillating mechanism 220 for causing the extraction vessels 210 to oscillate; a magnetic body which exerts a magnetic force on the extraction vessels 220; magnet moving mechanisms 258, 259 for moving the magnetic body between a contacting position in which the magnetic body is in contact with the extraction vessels 210 and a non-contacting position in which the magnetic body is not in contact with the extraction vessels 210; a temperature regulating unit for regulating the temperature of the extraction vessels 210; temperature regulating unit moving mechanisms 248, 249 for moving the temperature regulating unit between a contacting position in which the temperature regulating unit is in contact with the extraction vessels 210 and a non-contacting position in which the temperature regulating unit is not in contact with the extraction vessels 210; and a control portion for controlling the operation of each mechanism.

Description

[Technical field]

[0001] The present invention relates to an extraction device and processing system for biologically relevant substances, and more particularly to an extraction device and processing system for biologically relevant substances that separates biologically relevant substances including specific substances such as glycans by using magnetic particles and magnetic bodies. [Background technology]

[0002] Whole blood contains liver-derived transferrin and brain-derived transferrin, and the two have different sugar chain structures, making it possible to distinguish and separate them. It is known that brain (cerebrospinal fluid)-derived transferrin with a unique sugar chain is produced in early Alzheimer's dementia. In Patent Document 1, Hashimoto et al. propose using transferrin with a unique sugar chain as a marker for early Alzheimer's dementia.

[0003] Meanwhile, with regard to the extraction of biologically relevant substances, the present inventor has proposed a method and device in Patent Document 2. This method and device executes extraction of biologically relevant substances using magnetic particles that adsorb biologically relevant substances (nucleic acids), a dispensing tip that holds a solution containing the magnetic particles, and an external magnet that is movable relative to the dispensing tip. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 6680873 (WO2017 / 195778) [Patent Document 2] International Publication No. 97 / 44671 (EP0965842A1) Summary of the Invention [Problem to be solved by the invention]

[0005] Bio-related substances such as proteins (e.g., transferrin) can be extracted from a specimen such as whole blood using the method and device of Patent Document 2. However, the bio-related substances such as proteins extracted in this manner include those having different sugar chains bound to them.

[0006] Although glycans etc. that bind to bio-related substances can bind to antibodies (lectins etc.), the affinity between the glycans etc. and the antibodies is relatively weak. When a relatively vigorous process of suctioning and discharging a solution into a dispensing tip is performed, the bonds between the glycans etc. and the antibodies are destroyed, so that it is difficult to separate a bio-related substance containing a specific glycan etc. from bio-related substances containing different glycans etc. with the method and device of Patent Document 2.

[0007] Therefore, an object of the present invention is to provide an extraction device and a processing system capable of extracting biologically relevant substances including specific substances such as sugar chains by a relatively gentle processing. [Means for solving the problem]

[0008] Each aspect of the present invention is configured as follows. [Aspect 1] An extraction device for extracting a biologically relevant substance from a specimen using magnetic particles, comprising: a plurality of extraction vessels arranged along a first direction and holding a solution containing the magnetic particles and the specimen; One or more magnet bodies that exert a magnetic force on the plurality of extraction vessels; a magnet moving mechanism that moves the one or more magnet bodies between a contact position where the one or more magnet bodies are in contact with the one or more extraction vessels and a non-contact position where the one or more magnet bodies are not in contact with the one or more extraction vessels; A rocking mechanism that rocks the plurality of extraction vessels and the magnet moving mechanism; An extraction device comprising the rocking mechanism and a control unit that controls operation of the one or more magnet moving mechanisms.

[0009] [Aspect 2] 2. The extraction device of claim 1, further comprising: a nozzle section including a plurality of dispensing nozzles arranged along a first direction and a nozzle movement mechanism for moving the plurality of dispensing nozzles in a second direction different from the first direction; The rocking mechanism includes a rocking shaft extending in the first direction, Each of the plurality of extraction containers includes a container body that stores a solution and a lid that covers the container body, The extraction device, wherein the lid body has a circular dispensing opening or an elongated dispensing opening extending in the second direction. [Aspect 3] 3. The extraction device according to claim 2, An extraction device, wherein the container body has an inclined plane portion inclined with respect to the second direction. [Aspect 4] 4. The extraction device according to claim 3, further comprising: An extraction device, wherein the container body has a lowermost portion connected to the lower end of the inclined plane portion. [Aspect 5] 5. The extraction device according to claim 4, further comprising: The periphery of the bottom portion is sloped toward the bottom portion.

[0010] [Aspect 6] 6. The extraction device according to aspect 4 or 5, The lowermost portion is formed at a position shifted in the second direction from the center of the extraction vessel. [Aspect 7] 7. The extraction device according to any one of aspects 3 to 6, further comprising: An extraction device, wherein the magnet moving mechanism moves the one or more magnet bodies relative to the outer surface of the inclined plane portion. [Aspect 8] 2. The extraction device of claim 1, further comprising: The extraction vessel is provided on one side with a waste tube and a waste valve that adjusts the flow of liquid through the waste tube, and on the other side with a collection tube and a collection valve that adjusts the flow of liquid through the collection tube.

[0011] [Aspect 9] 3. The extraction device according to claim 1 or 2, The brewing device comprises a container body, the container body having a flat bottom surface and an inclined side surface connected to the flat bottom surface. [Aspect 10] 10. The extraction device according to any one of aspects 1, 8 to 9, further comprising: A temperature adjustment unit moving mechanism is provided for moving the one or more temperature adjustment units between a contact position where the one or more temperature adjustment units are in contact with the one or more extraction vessels and a non-contact position where the one or more temperature adjustment units are not in contact with the one or more extraction vessels; The extraction device, wherein the control unit controls the operation of the one or more temperature adjustment units. [Aspect 11] 11. The extraction device according to any one of the preceding aspects, further comprising: The extraction device, wherein the temperature adjustment unit is composed of a heater or a Peltier element, and a heat conductive portion disposed between the heater or the Peltier element and the container body.

[0012] [Aspect 12] 10. The extraction device according to any one of the preceding aspects, further comprising: An extraction device comprising a rocking body that is rocked by the rocking mechanism, the rocking body including the plurality of extraction containers, the one or more magnet bodies, the magnet moving mechanism, and the temperature adjustment unit. [Aspect 13] 13. The extraction device of any one of the preceding aspects, further comprising: The control unit oscillates the oscillating body with at least the magnet body in the contact position or the non-contact position. [Aspect 14] 14. The extraction device of any one of the preceding aspects, further comprising: The control unit controls the rocking mechanism to rock the extraction container at a tilt speed in a speed range of 0.8° / sec to 1.2° / sec.

[0013] [Aspect 15] 15. The extraction apparatus of claim 14, further comprising: The control unit controls the rocking mechanism to rock the extraction container at a tilt angle in the angle range of ±15° to ±25°. [Aspect 16] 16. The extraction apparatus of claim 15, further comprising: The control unit controls the oscillating mechanism to repeat one oscillating operation configured by the speed range and the angle range multiple times. [Aspect 17] 17. An extraction device according to any one of claims 1 to 16, 1. A brewing apparatus comprising one or more temperature regulation units for regulating the temperature of said one or more extraction vessels. [Aspect 18] A processing system for processing the biologically relevant material, comprising the extraction device according to any one of aspects 1 to 17, The plurality of extraction vessels are arranged along the first direction; A plurality of dispensing nozzles arranged along the first direction; A plurality of cartridges for holding various reagents and / or solutions used in the extraction process; A processing system, wherein the plurality of cartridges are arranged along a second direction different from the first direction.

[0014] [Aspect 19] 19. The processing system of embodiment 18, comprising: A processing system comprising a nozzle unit that supports the plurality of dispensing nozzles movably along the second direction. [Aspect 20] 20. The processing system of embodiment 18 or 19, comprising: A processing system comprising a measurement unit that measures each of the plurality of biologically relevant substances extracted in the plurality of extraction containers. Effect of the Invention

[0015] The extraction device and processing system for biologically relevant substances of the present invention can extract biologically relevant substances bound to specific binding substances without destroying the binding structures of the biologically relevant substances and binding substances with relatively weak affinity by using a rocking mechanism. [Brief description of the drawings]

[0016] [Figure 1] 1 is a top view showing a system for extracting a biologically-relevant substance according to an embodiment of the present invention. [Figure 1A] FIG. 2 is a perspective view of the extraction system of FIG. 1. [Diagram 2] FIG. 2 is a perspective view showing an extraction vessel according to the first embodiment. [Diagram 3] 3A shows the extraction vessel of FIG. 2 in a top view with the valve open, in a top view with the valve closed, and in a side view with the valve closed. FIG. [Figure 4] FIG. 1 is a perspective view showing an extraction device according to a first embodiment. [Diagram 5] FIG. 5 is an exploded perspective view showing a rocker of the extraction device of FIG. 4. [Figure 6] 5A is a top view, FIG. 5B is a front view, and FIG. 5C is a cross-sectional view taken in the direction II of the extraction device shown in FIG. [Figure 7] 7 is a cross-sectional view showing the lifting and lowering state of the extraction device of FIG. 6(c). [Figure 8] FIG. 5 is a perspective view showing the brewing device of FIG. 4 in a swinging state. [Figure 9] FIG. 11 is a perspective view showing a first modified example of the extraction vessel. [Figure 10] 10A shows the extraction vessel of FIG. 9 in a top view with the valve open, in a top view with the valve closed, and in a side view with the valve closed. FIG. [Figure 11] FIG. 10 is a perspective view of an extraction device including the extraction vessel of FIG. [Figure 12] FIG. 11 is an exploded perspective view showing a second modified example of the extraction vessel. [Figure 13] 13A and 13B are top and bottom perspective views of the extraction vessel of FIG. 12. [Figure 14]13A-13C are (a) top, (b) side, and (c) bottom views of the extraction vessel of FIG. 12. [Figure 15] 13A and 13B are top perspective views showing the operation of the slide valve in FIG. 12, in which FIG. [Figure 16] 11A is a top perspective view of a partially disassembled oscillator according to a second embodiment, and FIG. 11B is a top perspective view of an assembled oscillator according to a second embodiment. [Figure 16A] 17 is a top perspective view showing a state in which the oscillator of FIG. 16 is oscillating. FIG. [Figure 17] 17 is a side view showing the rocking mechanism of the rocking body of FIG. 16. [Figure 18] 17 is a side view showing the magnet moving mechanism of the oscillator in FIG. 16. [Figure 19] 17A and 17B are diagrams showing the temperature adjustment unit of the oscillator of FIG. 16, in which (a) is a top view and (b) is a cross-sectional view taken along the line bb. [Figure 20] 17A and 17B are exploded and perspective views showing the extraction container of the rocker of FIG. 16, respectively; FIG. [Figure 21] 21A is a top view, FIG. 21B is a cross-sectional view taken along line bb, FIG. 21C is a cross-sectional view taken along line cc, and FIG. 21D is a cross-sectional view taken along line dd, showing the container body of the extraction container in FIG. 20. [Figure 22] 10A to 10C are cross-sectional views showing the position of a dispensing nozzle for each tilt state of an extraction container according to a second embodiment. [Figure 23] FIG. 2 is a schematic diagram showing the binding state between transferrin and lectin-immobilized magnetic beads. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Each embodiment of the extraction device and processing system for biologically relevant substances of the present invention will be described with reference to the drawings. In each drawing, the same parts are given the same reference numerals and the description will be omitted as appropriate. In Figures 1A to 22, the relative size and / or arrangement of each part is accurately illustrated in principle, but the present invention is not limited thereto.

[0018] In the embodiment of the present invention, the biologically relevant substance extracted from the specimen is transferrin bound to a specific sugar chain, but is not limited thereto and may be, for example, any component contained in a cell, an exosome, or any glycoprotein. The x direction and y direction of this embodiment correspond to the first direction and the second direction in the claims, respectively. The first extract (liver- and brain-derived transferrin) of this embodiment corresponds to the specimen in the claims, and the second extract (brain-derived transferrin) of this embodiment corresponds to the biologically relevant substance in the claims.

[0019] (overview) The extraction device and processing system for biologically relevant substances according to an embodiment of the present invention extracts a first extract (liver- and brain-derived transferrin) from a specimen such as whole blood using the method of Patent Document 2, and extracts or separates a second extract (brain-derived transferrin) from the first extract under relatively mild conditions (predetermined mild rocking conditions).

[0020] (Basic configuration of processing system) The basic configuration of a processing system 1000 according to the first and second embodiments of the present invention will be described with reference to Figs. 1 and 1A. As shown in Figs. 1 and 1A, the processing system 1000 includes a base 100 that supports each part. The base 100 includes an oscillating extractor 200 (200A) for extracting biologically relevant substances, a cartridge holder 104, a consumables holder 106, and a measuring part 400. The processing system 1000 according to the first embodiment includes the extractor 200 (Fig. 4) and an oscillating body 200S (Figs. 5 and 8), and the processing system 1000 according to the second embodiment includes the extractor 200A (Fig. 16) and an oscillating body 200SA (Figs. 16 and 17).

[0021] The extraction device 200 (200A) has a plurality of extraction containers 210 (210A) that can be swung on its upper surface. The cartridge holding section 104 has a plurality of lanes extending in the y direction, and holds a plurality of cartridges (first, second, and third cartridges 302, 304, 306) of different types in a row in each lane. The first cartridge 302 contains magnetic beads (magnetic particles) to which a first antibody that specifically binds to a protein such as transferrin TR is fixed, various solutions, various reagents, etc. The second cartridge 304 contains a second antibody to which a chemiluminescent or fluorescent substance is fixed and which specifically binds to a protein such as spherin TR, various solutions, various reagents, etc. The third cartridge 306 contains lectin-immobilized magnetic beads LMB (magnetic particles) to which a substance (lectin L) that binds to the sugar chain G of transferrin is fixed, various solutions, various reagents such as chemiluminescent reagents or fluorescent reagents, etc. The consumables holding section 106 holds consumables. The consumables include dispensing tips 502a (FIGS. 4, 11, 16, 22, etc.) and / or a punching tool for punching an aluminum seal of a cartridge.

[0022] The measurement section 400 includes a plurality of measurement wells 402 that contain the second extract, a plurality of light receiving sections 404 that receive light from the plurality of measurement wells 402, and a measurement device (photomultiplier tube) 406 that measures the light from the plurality of light receiving sections 404 via optical fibers. Chemiluminescence, fluorescence, or the like can be used as the light from the measurement wells 402. The measurement wells 402 are preferably formed from a black material to block light.

[0023] The processing system 1000 includes a nozzle unit 500 that can move in the y direction above the upper surface of the base unit 100, a waste liquid tank 600 provided in the base unit 100, and a control unit (computer) 700 that controls the operation of each unit. An opening 600A (FIG. 1A) of the waste liquid tank 600 can be provided on the upper surface of the base unit 100. The nozzle unit 500 includes a plurality of dispensing nozzles 502 arranged in a line in the x direction corresponding to a plurality of lanes, a rail 504 that supports the nozzle unit 5002 having the plurality of dispensing nozzles 502 so as to be movable in the y direction, and a nozzle unit movement mechanism (movement motor) 506 that moves the nozzle unit 500. The control unit 700 controls the operation of the nozzle movement mechanism 506 that moves the nozzle unit 500 in the y direction, the piston motor 502c that drives the suction and discharge pistons 502b of the plurality of dispensing nozzles 502, and the lifting motor 510 that lifts and lowers the plurality of dispensing nozzles 502.

[0024] (First embodiment) [Extraction vessel for biologically-related substances] The extraction container 210 provided in the extraction device 200 according to the first embodiment will be described with reference to Figures 2 and 3. The extraction container 210 is composed of a container body 212 that contains the first extraction liquid dispensed from the dispensing tip 502a of the dispensing nozzle 502, a lid 214 fixed to the upper surface of the container body 212, a flexible waste liquid tube 216a provided on one narrow side surface of the container body 212, and a flexible collection tube 216b provided on the other narrow side surface of the container body 212. The flexible waste liquid tube 216a and the collection tube 216b have sufficient lengths to allow the container to be swung and rotated as described below.

[0025] The container body 212 has a flat bottom surface, and a pair of narrow side surfaces (inclined side surfaces) are connected at an incline to the flat bottom surface. Positioning protrusions 212a are formed on a pair of wide side surfaces of the container body 212. As described later, the positioning protrusions 212a are accommodated and fixed in a positioning recess 266 provided on the oscillating stage 260, and position the extraction container 210.

[0026] The cover 214 is a rectangular plate, and a dispensing port 214a is formed in the center (near the intersection of the diagonals) thereof. The first extract, various reagents, and / or various reagents are injected into the dispensing port 214a from the tip of a dispensing tip 502a attached to a dispensing nozzle 502 (described later).

[0027] The waste liquid tube 216a and the collection tube 216b are provided with a pair of clamping bodies 218 for clamping and closing the respective tubes. The waste liquid tube 216a and the pair of clamping bodies 218 form a waste liquid side pinch valve (waste liquid side pinch cock). The collection tube 216b and the pair of clamping bodies 218 form a collection side pinch valve (collection side pinch cock). As shown in FIG. 4, a valve drive motor 219 is provided for driving the pair of clamping bodies 218. The valve drive motor 219 is controlled by the control unit 700.

[0028] [Extraction equipment for biologically-related substances] The extraction device 200 according to the first embodiment will be described with reference to FIGS. 4 to 9. As shown in FIG. 4, the extraction containers 210 are arranged on a rocking stage 260 along the x direction. The extraction device 200 includes a rocking mechanism 220 that rocks the extraction containers 210, and a base (housing) 202 that supports the rocking mechanism 220. The rocking mechanism 220 includes a rocking motor 222, a rotating shaft 224 of the rocking motor 222, a rocking shaft 226 connected to the extraction containers 210, and a belt 228 that transmits the rotation of the rotating shaft 224 to the rocking shaft 226. The rocking shaft 226 extends in the x direction and is connected to the rocking stage 260 (rocking body 200S) that houses and fixes each extraction container 210.

[0029] 5 shows an exploded perspective view of the oscillating body (oscillating assembly) 200S of the extraction device 200. The oscillating body 200S is composed of a drive motor support part 230, a magnet support plate 240 attached to the drive motor support part 230 so as to be able to rise and fall (movable in the z direction), a temperature adjustment unit support plate 251 attached to the drive motor support part 230 so as to be able to rise and fall (movable in the z direction), and an oscillating stage 260 fixed to the drive motor support part 230 via multiple guide rods 269.

[0030] 5, the oscillating stage 260 has a plurality of accommodation openings 268 for respectively accommodating the plurality of extraction vessels 210, a first oscillating shaft 262 and a second oscillating shaft 264 for oscillating the oscillating stage 260, and a plurality of positioning recesses 266 for accommodating the positioning protrusions 212a of the plurality of extraction vessels 210. A plurality of valve drive motors 219 are fixed to the lower surface of the oscillating stage 260. The accommodation openings of the oscillating stage accommodate each of the extraction vessels 210 with the bottom surface of each of the extraction vessels 210 exposed downward.

[0031] A plurality of guide rods 269 extend downward from corners of the oscillating stage 260. One end of the first oscillating shaft 262 is oscillatably supported by a bearing formed on the base 202, and oscillates integrally with the oscillating shaft 226. The other end of the first oscillating shaft 262 is fixed to the oscillating stage 260. One end of the second oscillating shaft 264 is oscillatably supported by a bearing formed on the base 202. The other end of the second oscillating shaft 264 is fixed to the oscillating stage 260.

[0032] The oscillating body 200S holds the magnet support plate 240 and / or the temperature adjustment unit support plate 250 between the drive motor support part 230 and the oscillating stage 260 so that they can be raised and lowered (moved in the z direction) along the guide rods 269. Note that the temperature adjustment unit support plate 250 may be fixed to the guide rods 269 without being made capable of being raised and lowered.

[0033] The temperature adjustment unit support plate 250 includes a temperature adjustment unit 251. The temperature adjustment unit 251 has a plurality of through holes 258 penetrating in the z direction. The heating (temperature adjustment) operation of the temperature adjustment unit 251 is controlled by the control unit 700. The temperature adjustment unit 251 can be a heater 254 or a Peltier element 254. The heater 254 is composed of a sheet-like or flat-plate insulating material 252 arranged on the upper side of the temperature adjustment unit support plate 250, a sheet-like or flat-plate heater 254 arranged on the upper side of the insulating material 252, and a flat-plate heat conduction section (heat transfer block) 256 arranged on the upper side of the heater 254.

[0034] The Peltier element 254 has a lower heat absorbing and radiating surface (second heat absorbing and radiating surface) 252 and an upper heat absorbing and radiating surface (first heat absorbing and radiating surface) 256, and the heat absorbing and radiating operations are controlled by the control unit 700. When the temperature adjustment unit 251 is a Peltier element, the temperature adjustment unit support plate 250 can be provided with a plurality of heat radiating ports or a heat sink to promote the absorption and radiation of heat from the lower heat absorbing and radiating surface 252.

[0035] The magnet support plate 240 is provided with a plurality of magnet pillars 242 extending in the z direction. The plurality of magnet pillars 242 as a whole can be referred to as a magnet body. The plurality of magnet pillars 242 are provided at positions aligned with the plurality of through holes 258 in the z direction. The plurality of magnet pillars 242 can be inserted into and removed from the plurality of through holes 258 in the z direction. The plurality of through holes 258 and the plurality of magnet pillars 242 are preferably arranged in a matrix. The plurality of magnet pillars 242 are preferably arranged such that the polarity of adjacent magnet pillars is reversed when viewed from the bottom surface of the extraction vessel 210.

[0036] 6(c), the drive motor support part 230 supports a magnet lifting motor 248 for lifting and lowering the magnet support plate 240, and a temperature adjustment unit lifting motor 258 for lifting and lowering the temperature adjustment unit support plate 251. The operations of the magnet lifting motor 248 and the temperature adjustment unit lifting motor 258 are controlled by the control part 700.

[0037] The rotating shaft of magnet lift motor 248 is a screw shaft, and a female screw portion at the lower end of magnet lift member 249 is attached to the screw shaft to form a ball screw mechanism. The upper end of magnet lift member 249 is fixed to magnet support plate 240. As a result, magnet support plate 240 (multiple magnet pillars 242) rises and falls together with magnet lift member 249 as the rotating shaft of magnet lift motor 248 rotates. The magnet moving mechanism is composed of magnet lift motor 248, magnet lift member 249, and magnet support plate 240.

[0038] The rotating shaft of the temperature adjustment unit lifting motor 258 is a screw shaft, and a female screw portion at the lower end of the temperature adjustment unit lifting member 259 is attached to this screw shaft to form a ball screw mechanism. The upper end of the temperature adjustment unit lifting member 259 is fixed to the temperature adjustment unit support plate 251. As a result, the temperature adjustment unit support plate 251 (heater 254) rises and falls together with the temperature adjustment unit lifting member 259 as the rotating shaft of the temperature adjustment unit lifting motor 258 rotates. The temperature adjustment unit moving mechanism is composed of the temperature adjustment unit lifting motor 258, the temperature adjustment unit lifting member 259, and the temperature adjustment unit support plate 251. It is also possible to fix the temperature adjustment unit 251 in contact with the bottom surface of the extraction container 210 without providing the temperature adjustment unit moving mechanism.

[0039] The raised and lowered states of the temperature adjustment unit 251 and the multiple magnetic pillars 242 will be described using Figure 7. Figure 7(a) shows the multiple magnetic pillars 242 in the lowered position (non-contact position) and the temperature adjustment unit 251 in the raised position (contact position). Figure 7(b) shows the multiple magnetic pillars 242 in the raised position and the temperature adjustment unit 251 in the lowered position. Figure 7(c) shows the multiple magnetic pillars 242 and the temperature adjustment unit 251 in the lowered position.

[0040] 7(a) and (c), when the multiple magnetic columns 242 are in the lowered position, the upper ends of the multiple magnetic columns 242 are spaced downward from the bottom surface of the extraction vessel 210, and the multiple magnetic columns 242 do not exert a magnetic force on the inside of the extraction vessel 210. As shown in FIG. 7(b), when the multiple magnetic columns 242 are in the raised position, the upper ends of the multiple magnetic columns 242 are in contact with the bottom surface of the extraction vessel 210, and the multiple magnetic columns 242 exert a magnetic force on the inside of the extraction vessel 210.

[0041] 7(a), when the temperature adjustment unit 251 is in the raised position, the upper surface of the temperature adjustment unit 251 abuts against the bottom plane of the extraction vessel 210, and the temperature adjustment unit 251 can heat or cool the extraction vessel 210. As shown in FIGS. 7(b) and (c), when the temperature adjustment unit 251 is in the lowered position, the upper surface of the temperature adjustment unit 251 is separated downward from the bottom plane of the extraction vessel 210, and the temperature adjustment unit 251 does not heat or cool the extraction vessel 210.

[0042] In this way, since the multiple magnetic pillars 242 (magnet support plate 240) and the temperature adjustment units 251 (temperature adjustment unit support plate 250) can be raised and lowered independently of each other, the control unit 700 can quickly switch between the following states (1) to (3). (1) As shown in FIG. 7(a), the extraction container 210 is heated or cooled while no magnetic force is applied to the extraction container 210; (2) As shown in FIG. 7(b), a state in which a magnetic force is applied to the extraction container 210 while the extraction container 210 is not heated or cooled; (3) As shown in FIG. 7(c), the extraction container 210 is not heated or cooled and no magnetic force is applied to the extraction container 210. (4) Although not shown in the figure, a state in which the extraction container 210 is heated or cooled while a magnetic force is applied to the extraction container 210.

[0043] Fig. 8 shows the oscillating state of the oscillating body 200S. The oscillating body 200S is oscillated around an oscillating axis 226 extending in the x-direction by the oscillating mechanism 220 in the arrangements shown in Figs. 8(a) and 8(b). Fig. 8(a) shows the waste liquid arrangement from the extraction container 210, and Fig. 8(b) shows the collection arrangement from the extraction container 210. In the waste liquid arrangement in Fig. 8(a), the waste liquid tube 216a side of the extraction container 210 is located downward, and if the valve 218 (valve 218A or 218B described later) is opened, the waste liquid can be discharged from the extraction container 210. In the collection arrangement of FIG. 8(b), the collection tube 216b side of the extraction container 210 is positioned downward, and when the valve 218 (valve 218A or 218B described below) is opened, the second extract can be dropped from the extraction container 210 into the second extract container 201 (FIG. 1) and collected.

[0044] [First modified example of extraction vessel] A first modified example of the extraction container according to the first embodiment will be described with reference to Figures 9 to 11. The extraction container 210A according to the first modified example is provided with a two-way valve 218A in a waste liquid tube 216a and a collection tube 216b instead of the pinch valve (a pair of clamping bodies) 218 ​​of the extraction container 210 in Figure 2. The two-way valve 218A is opened and closed by a valve drive motor 219.

[0045] [Second modified example of extraction vessel] A second modified example of the extraction container according to the first embodiment will be described with reference to Figures 12 to 14. The extraction container 210B according to the second modified example is provided with a slide valve 218B in the waste liquid pipeline and the collection pipeline instead of the pinch valve (pair of clamping bodies) 218 ​​of the extraction container 210 in Figure 2. The slide valve 218B opens and closes the waste liquid pipeline and the collection pipeline by sliding along the x direction. The extraction container 212 is provided with a laminate (aluminum) seal (lid) 214 that covers the top surface of the extraction container 212, and a perforation target label 214Ba is formed near the center of the laminate seal 214, and a dispensing port is formed by a punching tool.

[0046] The container body 212 is provided with a recess 217B that accommodates the waste liquid side and collection side slide valves 218B slidably in the x direction. The slide valves 218B are provided with a slide through hole 218B1 that penetrates in the y direction. A seal member 216Bc is disposed between the container body 212 and each recess 217B, and the seal member 216Bc has a through hole that penetrates in the y direction. The second extraction liquid container 201 is integrally molded on the outside of the collection side recess 217B. A seal member 216Bc is disposed between the collection side recess 217B and the second extraction liquid container 201, and the seal member 216Bc has a through hole that penetrates in the y direction. A joint 216Ba having a pipe extending in the y direction is disposed on the outside of the waste liquid side recess 217B. The outer end of the joint 216Ba is connected to a flexible waste liquid tube 216a.

[0047] 15(a) shows that the waste liquid side and sampling side slide valves 218B are in an open state, and FIG. 15(b) shows that the waste liquid side and sampling side slide valves 218B are in a closed state. Each slide valve 218B is switched between an open state and a closed state by moving a pair of protrusions provided on the lower surface by a drive motor 219. The control unit 700 controls the drive motor 219 of the waste liquid side slide valve 218B and the drive motor 219 of the sampling side slide valve 218B independently.

[0048] The slide valve 218B is preferably made of elastic silicone rubber, and is press-fitted into the recess 217B, thereby enabling a simple structure to increase adhesion to the container body 212. The slide valve 218B has two holes formed in the z direction on its bottom surface, and two pins (protrusions) are inserted into the two holes from below the recess 217B. By simultaneously moving these pins in the opening (or closing) direction by the drive motor 219, it becomes possible to prevent an increase in sliding resistance and the occurrence of leaks due to deformation (compression / expansion) during operation of the slide valve 218B.

[0049] The parts around the slide valve 218B (pad 215, laminate (aluminum) seal 214, joint 216Ba) can be made of the same polypropylene as the container body 212. By integrating the contact surfaces of the laminate seal 214 and the container body 212 by welding, it is possible to prevent liquid leakage from the seal joint surface.

[0050] [Extraction processing by processing system] The processing system 1000 of the first embodiment performs the following steps to separate multiple first extracts (mixtures of liver- and brain-derived transferrin) from multiple samples such as relatively large volumes (5 to 10 ml) of whole blood.

[0051] First, a first extracting liquid extraction step is performed. In the first extracting liquid extraction step, the control unit 700 of the processing system 1000 moves the multiple dispensing nozzles 502 of the nozzle unit 500 in the y direction above the multiple first cartridges 302. Next, in accordance with the method of Patent Document 2, the multiple dispensing nozzles 502 perform suction and discharge using the binding between the first antibody-immobilized magnetic beads and lectin to separate multiple first extracts (transferrin) from multiple specimens such as whole blood. Glycoproteins such as transferrin contained in the first extract contain proteins with different sugar chains. The multiple first extracts are respectively held in multiple first extract wells.

[0052] A preparation step is executed for extracting a second extract from a first extract. In the preparation step, the control unit 700 transfers the first extract from the first extract wells to the extraction containers 210 using the dispensing nozzles 502. The dispensing nozzles 502 dispense the first extract from the dispensing tips 502a into the extraction containers 210 via the dispensing ports 214a of the extraction containers 210.

[0053] Furthermore, in the preparation step, the control unit 700 transfers the lectin-immobilized magnetic beads LMB, various solutions, various reagents, and the like, which are held in each of the second cartridges 304, into the extraction containers 210 in a predetermined procedure using the dispensing nozzles 502. As the lectin L, for example, a lectin that specifically binds to brain-derived transferrin TR, as described in Patent Document 1, can be used.

[0054] Next, the rocking step is performed. In the rocking step, as shown in FIG. 8, in a state in which the magnetic beads to which lectin is immobilized and a plurality of first extraction solutions are contained in each extraction container 210, the control unit 700 rocks the rocking body 200S of the extraction device 200 under a gentle predetermined rocking condition. The gentle predetermined rocking condition means that the pressure applied to the solution is lower than that applied by the suction and discharge by the dispensing nozzle. The gentle predetermined rocking condition will be described later in the examples. The rocking condition is composed of the following rocking angle, rocking period, and / or rocking time. The rocking angle of the rocking body 200S can be preferably in the range of ±45 degrees, more preferably in the range of ±30 degrees, with respect to the horizontal direction. The rocking period of the rocking body 200S can be preferably 5 to 30 seconds, more preferably 3 to 10 seconds. These rocking angles and rocking periods can be arbitrarily combined. The rocking time is composed of a plurality of rocking periods.

[0055] In the first embodiment, when the oscillator 200S shown in FIG. 8 is oscillated, the control unit 700 is placed in an oscillation configuration in which the multiple magnet pillars 242 are lowered and the temperature adjustment unit 251 is raised, as shown in FIG. 7(a).

[0056] In the rocking arrangement, no magnetic force is applied to the inside of the extraction container 210, and the inside of the extraction container 210 is cooled. The cooling temperature of the extraction container 210 by the temperature control unit 251 (Peltier element) can be in the range of 2 to 8° C., more preferably 3 to 5° C., and further preferably about 4° C. As shown in FIG. 23, brain-derived transferrin TR and lectin L (lectin-immobilized magnetic beads LMB) can bind with relatively weak affinity at such a cooling temperature.

[0057] When the oscillating body 200S is oscillated under the above-mentioned oscillating conditions, oscillating arrangement, and cooling temperature, the brain-derived transferrin TR binds to the lectin-immobilized magnetic beads LMB with relatively weak affinity, while the liver-derived transferrin is in a free state in the solution, as shown in Fig. 23. In this free state, in the first embodiment, the control unit 700 stops the oscillating body 200S at a horizontal position, and, as shown in Fig. 7(b), lowers the temperature adjustment unit 251 while raising the multiple magnet pillars 242 to the magnetic bead adsorption arrangement.

[0058] Next, a waste liquid process is performed. In the waste liquid process of the first embodiment, while maintaining the magnetic bead adsorption arrangement of Fig. 7(b), the control unit 700 tilts the rocker 200S at a predetermined angle (for example, 45 to 90 degrees) so that the waste liquid tube 216a is located below as shown in Fig. 8(a), and opens the waste liquid valve (pinch valve (pair of clamps) 218, two-way valve 218A, or slide valve 218B) using the valve drive motor 219. The lectin-immobilized magnetic beads LMB to which brain-derived transferrin is bound are magnetically adsorbed to the inner bottom surface of the extraction container 210, while the solution in which liver-derived transferrin is liberated flows out of the extraction container 210 through the waste liquid tube 216a and is dropped and transferred to the waste liquid tank 600.

[0059] After the waste liquid step is performed, the control unit 700 returns the rocking body 200S to the horizontal state. The control unit 700 further dispenses a washing liquid from the dispensing port 214a in order to wash the liver-derived transferrin, and then the rocking step and the waste liquid step are performed in this order.

[0060] Next, the lectin separation process is performed. In the lectin separation process of the first embodiment, the control unit 700 returns the oscillator 200S to a horizontal state, and sets the temperature adjustment unit 251 in the raised state and the multiple magnetic pillars 242 in the lowered state, as shown in FIG. 7(a), for lectin separation.

[0061] In the lectin separation configuration, the control unit 700 rocks the rocking body 200S while controlling the temperature inside the extraction container 210 to a predetermined temperature using the temperature adjustment unit 251. When the solution inside the extraction container 210 is controlled to a predetermined temperature, the three-dimensional structure of the lectin and / or brain-derived transferrin changes, causing separation of the lectin-immobilized magnetic beads and brain-derived transferrin.

[0062] When the lectin separation process is completed, a transferrin recovery process is performed. In the transferrin recovery process of the first embodiment, while maintaining the magnetic bead adsorption arrangement of Fig. 7(b), the control unit 700 tilts the rocker 200S at a predetermined angle (e.g., 45 to 90 degrees) so that the collection tube 216b is positioned downward as shown in Fig. 8(b), and opens the collection valve (pinch valve (pair of clamps) 218, two-way valve 218A, or slide valve 218B) using the valve drive motor 219. The lectin-immobilized magnetic beads that are not bound to brain-derived transferrin are magnetically adsorbed to the inner bottom surface of the extraction container 210, while the solution containing brain-derived transferrin (second extraction liquid) flows out of the extraction container 210 and is dropped and transferred to the second extraction liquid container 201.

[0063] The control unit 700 moves the second extract aspirated into the multiple dispensing tips 502a to the multiple measurement wells 402. A detection reagent is dispensed from the third cartridge 306 into the multiple measurement wells 402. The detection reagent can be a second antibody to which a chemiluminescent or fluorescent substance is immobilized and which binds to a protein (transferrin). Thereafter, the control unit 700 uses the detector (PMT, etc.) 406 of the detection mechanism 400 to detect or quantify brain-derived transferrin in the second extract in the multiple measurement wells 402.

[0064] Second embodiment [Extraction device] The extraction device 200A according to the second embodiment will be described with reference to Figs. 16 and 16A. The extraction device 200A includes a rocking body 200SA supported to be rockable around a rocking shaft 226 with respect to a base (housing) 202. The rocking body 200SA includes a rocking mechanism 220 equivalent to the rocking mechanism 220 of the first embodiment. The rocking body 200SA includes a cover 203, a temperature adjustment unit (heating block) 270 that supports multiple extraction containers 210 in a temperature-adjustable manner, and a pair of arc-shaped bodies 229 that rock integrally with the temperature adjustment unit 270. The multiple extraction containers 210A are arranged along the x direction as shown in Figs. 1, 16, and 16A.

[0065] As shown in Fig. 16A and Fig. 17, the oscillating body 200SA can be in (a) a horizontal state, (b) a first inclined state (state rotated counterclockwise), and (c) a second inclined state (state rotated clockwise). The oscillating body 200SA further includes an oscillating gear (external gear) 226g that rotates together with the oscillating shaft 226. The oscillating gear 226g meshes with an internal gear 229g provided on the inner curved surface of an arc-shaped body 229. The outer curved surface of the arc-shaped body 229 is supported by a plurality of support rollers 204 rotatably supported on the base 202.

[0066] When the oscillating mechanism 220 operates, the oscillating gear 226g rotates together with the oscillating shaft 226, and the internal gear 229g of the arc-shaped body 229 that meshes with the oscillating gear 226g rotates, causing the oscillating body 200SA to rotate from state (a) to state (b) in Figures 16A and 17, and from state (a) to state (c).

[0067] [Magnet movement mechanism] A magnet moving mechanism 280 according to the second embodiment will be described with reference to Fig. 18. The magnet moving mechanism 280 is provided on the rocking body 200SA and rocks integrally with the rocking body 200SA. The magnet moving mechanism 280 is composed of a magnet support 284 that supports a plate-shaped magnet body 282, a link mechanism 286 that moves the magnet body 282 and the magnet support 284 relative to the outer surface of the inclined flat surface portion 212A2 of the reaction vessel 210A, and a magnet moving motor 288 that drives the link mechanism 286.

[0068] Fig. 18(a) shows a state in which the magnetic body 282 is in contact with the inclined flat surface portion 212A2 of the reaction vessel 210A. Fig. 18(b) shows a state in which the magnetic body 282 is separated from the inclined flat surface portion 212A2 of the reaction vessel 210A. Fig. 18(c) shows a cross-sectional view of the state of Fig. 18(a). The magnet moving mechanism 280 can move the magnetic body 282 in the direction of the arrow between the states (a) and (b).

[0069] [Temperature control unit] A temperature adjustment unit 270 according to the second embodiment will be described with reference to FIG. 19. The temperature adjustment unit 270 is composed of a metal body (heat conducting portion) 271, a temperature adjustment body (sheet-shaped heating body or Peltier element) 272 provided on the outer surface of the metal body 271, a plurality of openings 274 provided on the lower surface of the metal body 271 to movably accommodate a plurality of magnet bodies 282, a plurality of container accommodating portions 276 provided on the upper surface of the metal body 271 to accommodate a plurality of extraction containers 210A, and a temperature sensor 278 provided on the outer surface of the metal body 271. As shown in FIG. 18(c), the metal body 271 is disposed between the temperature adjustment body 272 and the container body 212A. When the temperature adjustment body 272 is a Peltier element, the Peltier element has a first heat absorption / radiation surface that can contact the container body 212A of the extraction container 210A via the metal body 271, and a second heat absorption / radiation surface that does not contact the container body 212A of the extraction container 212A.

[0070] [Extraction container] An extraction container 210A according to the second embodiment will be described with reference to FIGS. 20 to 23. The extraction container 210A is composed of a container body 212A that contains the first extraction liquid dispensed from a dispensing nozzle 502, and a lid 214A fixed to the upper surface of the container body 212A. The lid 214A is a rectangular plate, and a long and narrow dispensing port (slit) 214Aa extending in the longitudinal direction of the lid 214A is formed in its central portion (near the intersection of the diagonals). As shown in FIG. 20(b), a dispensing tip 502a attached to the dispensing nozzle 502 is inserted into the inside of the extraction container 210A through the dispensing port 214Aa. The inserted dispensing tip 502a dispenses the first extraction liquid, various reagents, and / or various reagents into the inside of the extraction container 210A. Furthermore, the inserted dispensing port 214Aa aspirates the waste liquid and / or the second extraction liquid from inside the extraction container 210A. The elongated dispensing port 214Aa preferably extends in a direction (y direction) perpendicular to the axis (x direction) of the oscillation shaft 226. Note that a circular dispensing port may be used instead of the elongated dispensing port 214Aa. The circular dispensing port may have a diameter equal to the longitudinal length of the elongated dispensing port 214Aa. For example, the circular dispensing port may have a length equal to the x-direction width inside the container body 212A.

[0071] As shown in FIG. 21, the bottom surface of the container body 212A includes an inclined flat surface portion 212A2 inclined in the y direction and a lowermost portion 212A1 connected to the lower end of the inclined flat surface portion 212A2. The periphery of the lowermost portion 212A1 is inclined toward the lowermost portion (FIG. 21(c)). Since the lowermost portion 212A1 is formed at a position shifted in the y direction from the center of the extraction container 210A (dispensing port 214Aa) in a horizontal state, the solution inside the extraction container 210A moves as shown in FIGS. 22(a) to 22(c) with the rotational movement of the rocking body 200SA. FIG. 22 shows a state in which the magnet body 282 contacts the inclined flat surface portion 212A2 of the container body 210A. In FIG. 22, (a) shows a state in which the lid 214A of the extraction container 210A is horizontal, (b) shows a state in which the extraction container 210A is rotated counterclockwise, and (c) shows a state in which the extraction container 210A is rotated clockwise.

[0072] 22(a) to (c), the dispensing port 214Aa is a long and narrow hole or a sufficiently large hole in the y direction, so that the dispensing tip 502a of the dispensing nozzle 502 can be inserted into the extraction container 210A. As shown in FIG. 22(b), when the extraction container 210A is rotated, the inclination angle of the inclined plane 212A2 increases, and the solution in the extraction container 210A is concentrated at the bottom part 212A1. This allows the dispensing tip 502a of the dispensing nozzle 502 to aspirate more solution from the bottom part 212A1 of the extraction container 210A without waste.

[0073] [Extraction processing by processing system] The processing system 1000 of the second embodiment performs the following steps to separate multiple first extracts (mixtures of liver- and brain-derived transferrin) from multiple samples such as relatively large volumes (5 to 10 ml) of whole blood.

[0074] First, a first extracting liquid extraction step is performed. In the first extracting liquid extraction step, the control unit 700 of the processing system 1000 moves the multiple dispensing nozzles 502 of the nozzle unit 500 in the y direction above the multiple first cartridges 302. Next, in accordance with the method of Patent Document 2, the multiple dispensing nozzles 502 perform suction and discharge using the dispensing tips 502a of the multiple dispensing nozzles 502 by using the bond between the first antibody-immobilized magnetic beads and lectin to separate multiple first extracts (transferrin, etc.) from multiple specimens such as whole blood. Glycoproteins such as transferrin contained in the first extract contain proteins with different sugar chains. The multiple first extracts are respectively held in multiple first extract wells.

[0075] A preparation step is performed to extract a second extract from a first extract. In the preparation step, the control unit 700 transfers the first extract from the first extract wells to the extraction containers 210A using the dispensing nozzles 502. Specifically, the dispensing tips 502a of the dispensing nozzles 502 dispense the first extract into the extraction containers 210A via the respective dispensing ports 214Aa of the extraction containers 210A.

[0076] Furthermore, in the preparation step, the control unit 700 transfers, in a predetermined procedure, the lectin-immobilized magnetic beads LMB, various solutions, various reagents, and the like held in each of the second cartridges 304 into the extraction containers 210A using the dispensing tips 502a of the dispensing nozzles 502. As the lectin, for example, a lectin that specifically binds to brain-derived transferrin, as described in Patent Document 1, can be used.

[0077] Next, the rocking step is performed. In the rocking step, as shown in FIG. 16A and FIG. 17, in a state where the magnetic beads to which lectin is immobilized and a plurality of first extraction solutions are accommodated in each extraction container 210A, the control unit 700 rocks the rocking body 200SA of the extraction device 200A under a gentle predetermined rocking condition. The gentle predetermined rocking condition means that the pressure applied to the solution is lower than that of the suction and discharge by the dispensing nozzle. The gentle predetermined rocking condition will be described later in the examples. The rocking condition is composed of the following rocking angle, rocking period, and / or rocking time. The rocking angle of the rocking body 200S can be preferably in the range of ±45 degrees, more preferably in the range of ±30 degrees, with respect to the horizontal direction. The rocking period of the rocking body 200S can be preferably 5 to 30 seconds, more preferably 3 to 10 seconds. These rocking angles and rocking periods can be arbitrarily combined. The rocking time is composed of a plurality of rocking periods.

[0078] In the rocking arrangement, no magnetic force is applied to the inside of the extraction container 210A, and the extraction container 210A is cooled using a Peltier element 272 (FIG. 18(c)) and / or a cooling fan 290 (FIG. 17), etc. The cooling temperature of the extraction container 210A by the Peltier element 272 and / or the cooling fan 290 can be in the range of 2 to 8° C., more preferably 3 to 5° C., and even more preferably about 4° C. As shown in FIG. 23, brain-derived transferrin TR and lectin L (lectin-immobilized magnetic beads LMB) can bind with relatively weak affinity at such a cooling temperature.

[0079] When the oscillation of the oscillator 200SA is performed under the above-mentioned oscillation conditions, oscillation arrangement, and cooling temperature, the brain-derived transferrin TR binds to the lectin-immobilized magnetic beads LMB with a relatively weak affinity, while the liver-derived transferrin is in a free state in the solution. In this free state, in the second embodiment, the control unit 700 stops the oscillation of the oscillator 200SA at a horizontal position, and raises the magnet body 282 to the magnetic bead adsorption arrangement as shown in FIG. 18(a).

[0080] Next, the waste liquid process is performed. In the waste liquid process of the second embodiment, the control unit 700 tilts the extraction container 210A to the state shown in FIG. 22(b) while maintaining the magnetic bead adsorption arrangement of FIG. 18(a). In the state of FIG. 22(b), the lectin-immobilized magnetic beads LMB to which brain-derived transferrin TR is bound are magnetically adsorbed to the inner surface of the inclined flat surface portion 212A2 of the extraction container 210A, while the solution in the extraction container 210A is aspirated by the dispensing nozzle 502 using the dispensing tip 502a inserted from the dispensing port 214Aa. The solution aspirated by the dispensing tip 502a is discharged into the opening 600A of the waste liquid tank 600.

[0081] After the waste liquid step is performed, the control unit 700 returns the rocking body 200SA to the horizontal state (FIG. 22(a)). In order to further wash the liver-derived transferrin, the control unit 700 dispenses a washing liquid from the dispensing port 214Aa, and then the rocking step and the waste liquid step are performed in this order.

[0082] Next, the lectin separation process is performed. In the lectin separation process of the second embodiment, the control unit 700 returns the oscillator 200SA to a horizontal state, and moves the magnet body 282 away from the inclined flat surface portion 212Aa to the lectin separation arrangement as shown in FIG. 18(b).

[0083] In the lectin separation configuration, the control unit 700 rocks the rocking body 200SA while controlling the temperature inside the extraction container 210A to a predetermined temperature using the temperature adjustment unit 270 and / or the cooling fan 290. When the solution inside the extraction container 210A is controlled to a predetermined temperature, the three-dimensional structure of the lectin and / or brain-derived transferrin TR changes, causing separation of the lectin-immobilized magnetic beads MLB and brain-derived transferrin.

[0084] When the lectin separation process is completed, a transferrin recovery process is performed. In the transferrin recovery process of the second embodiment, while maintaining the magnetic bead adsorption arrangement of Fig. 18(a), the control unit 700 tilts the extraction container 210A to the state of Fig. 22(b), whereby the lectin-immobilized magnetic beads LMB that are not bound to brain-derived transferrin are magnetically adsorbed to the inner surface of the inclined flat surface portion 212A2 of the extraction container 210A, while the solution containing brain-derived transferrin (second extraction liquid) is sucked from the bottom portion 212A1 using the dispensing tip 502a attached to the dispensing nozzle 502.

[0085] The control unit 700 moves the nozzle unit 500 to move the second extract aspirated into the multiple dispensing tips 502a of the multiple dispensing nozzles 502 to the multiple measurement wells 402. A detection reagent is dispensed from the third cartridge 306 to the multiple measurement wells 402. The detection reagent can be a second antibody to which a chemiluminescent or fluorescent substance is immobilized and which binds to a protein (transferrin). Thereafter, the control unit 700 uses the detector (PMT, etc.) 406 of the detection mechanism 400 to detect or quantify brain-derived transferrin in the second extract in the multiple measurement wells 402.

[0086] [Lectin-immobilized magnetic beads] The capture of brain-derived transferrin TR using the lectin-immobilized magnetic beads LMB used in the first and second embodiments will be described. As shown in Fig. 23, lectin L, which specifically binds to brain-derived transferrin TR, is immobilized on the surface of the lectin-immobilized magnetic beads LMB. Transferrin TR is a glycoprotein, and has a sugar chain G extending from a protein P. At a cooled temperature (e.g., about 4°C), lectin L binds to the sugar chain G with weak affinity, allowing transferrin TR to be captured using the lectin-immobilized magnetic beads LMB.

[0087] (Modification of Temperature Control Unit) In the first embodiment, the temperature adjustment unit 251 is configured to rotate integrally with the rocking body 200S and to heat or cool the inside of the extraction container 210 by contacting the bottom of the container body 212. In the second embodiment, the temperature adjustment unit 270 is configured to rotate integrally with the rocking body 200SA and to heat or cool the inside of the extraction container 210A by contacting the inclined flat surface (bottom surface) 212A2 of the container body 212A. In contrast, the temperature adjustment unit according to the modified example does not rotate integrally with the rocking body 200S or 200SA, but can be one or more air conditioners (air conditioners) provided in the base (housing) 202 of the extraction device 200 or 200A or in the base (housing) 100 of the system 1000. By providing the temperature adjustment unit not on the rocking body side but on the base side, the rocking body 200S or 200SA is made lighter and the structure of the rocking mechanism is simplified. EXAMPLES

[0088] The processing process of the nozzle part 500 and the rocking body 200S or 200SA according to the first and second embodiments is exemplarily shown in Table 1. The processing process of Table 1 is executed according to a control program executed in advance by the control part 700. As shown in Table 1, the rocking parameters that define the processing process are defined by the tilt angle of the extraction container 200 or 200A (tilt angle of the lid body 214 or 214A), the tilt speed of this tilt angle, the acceleration of this tilt angle, the deceleration of this tilt angle, the number of repetitions or time of each step, and the waiting time between repetitions.

[0089] [Table 1]

[0090] The "gentle predetermined rocking condition" mentioned in the first and second embodiments is exemplarily specified in step 2 of Table 1. The rocking condition of step 2 can be changed within a predetermined range as follows. The tilt angle of step 2 can be set in an angle range of ±15° to ±25° with respect to the horizontal state of the container body (lid body) (FIGS. 11, 16, and 22(a)). The tilt speed of step 2 can be set in a speed range of 0.8° / sec to 1.2° / sec. The acceleration or deceleration of step 2 can be set in a range of 0.03° / sec to 0.06° / sec. The number of repetitions of step 2 can be set in a range of 7 to 13. The waiting time between repetitions of step 2 can be set in a range of 1.0 to 3.0 seconds. Each rocking parameter can be arbitrarily combined. [Explanation of symbols]

[0091] 1000 Processing Systems 100 base 200 Extraction device 200S Oscillator 210 Extraction vessel 214a Dispensing nozzle 216a Waste liquid pipeline 216b Collection pipe 220 Swing Mechanism 242 Magnet Pillar 251 Temperature Control Unit 400 Detection mechanism 500 Nozzle section 502 Dispensing nozzle 200A extraction device 200SA Oscillator 210A Extraction vessel 270 Temperature Control Unit (Heating Block) 280 Magnet moving mechanism 282 Magnet

Claims

1. An extraction device for extracting a biologically relevant substance from a specimen using magnetic particles, comprising: a plurality of extraction vessels arranged along a first direction and holding a solution containing the magnetic particles and the specimen; One or more magnet bodies that exert a magnetic force on the plurality of extraction vessels; a magnet moving mechanism that moves the one or more magnet bodies between a contact position where the one or more magnet bodies are in contact with the plurality of extraction containers and a non-contact position where the one or more magnet bodies are not in contact with the plurality of extraction containers; A rocking mechanism that rocks the plurality of extraction vessels and the magnet moving mechanism; A control unit that controls the operation of the rocking mechanism and the one or more magnet moving mechanisms; a nozzle section including a plurality of dispensing nozzles arranged along the first direction and a nozzle moving mechanism that moves the plurality of dispensing nozzles in a second direction different from the first direction; The swing mechanism includes a swing shaft extending in the first direction, Each of the plurality of extraction containers includes a container body that stores a solution and a lid that covers the container body, The lid body has a dispensing port, An extraction device, wherein the container body has an inclined flat surface or a inclined side surface inclined with respect to the second direction.

2. 2. The extraction device according to claim 1, An extraction device, wherein the container body has a lowermost portion connected to the lower end of the inclined plane portion.

3. 3. The extraction device according to claim 2, The periphery of the bottom portion is sloped toward the bottom portion.

4. 3. The extraction device according to claim 2, The lowermost portion is formed at a position shifted in the second direction from the center of the extraction vessel.

5. 2. The extraction device according to claim 1, An extraction device, wherein the magnet moving mechanism moves the one or more magnet bodies relative to the outer surface of the inclined plane portion.

6. 2. The extraction device according to claim 1, The extraction vessel is provided on one side with a waste tube and a waste valve that adjusts the flow of liquid through the waste tube, and on the other side with a collection tube and a collection valve that adjusts the flow of liquid through the collection tube.

7. 2. The extraction device according to claim 1, The brewing device comprises a container body, the container body comprising a flat bottom surface and the sloping side surface connected to the flat bottom surface.

8. 2. The extraction device according to claim 1, A temperature adjustment unit moving mechanism is provided for moving the one or more temperature adjustment units between a contact position where the one or more temperature adjustment units are in contact with the plurality of extraction containers and a non-contact position where the one or more temperature adjustment units are not in contact with the plurality of extraction containers; The extraction device, wherein the control unit controls the operation of the one or more temperature adjustment units.

9. 2. The extraction device according to claim 1, The extraction device, wherein the temperature adjustment unit is composed of a heater or a Peltier element, and a heat conductive portion disposed between the heater or the Peltier element and the container body.

10. 2. The extraction device according to claim 1, An extraction device comprising a rocking body that is rocked by the rocking mechanism, the rocking body including the plurality of extraction containers, the one or more magnet bodies, the magnet moving mechanism, and the temperature adjustment unit.

11. 2. The extraction device according to claim 1, The control unit oscillates the oscillating body with at least the magnet body in the contact position or the non-contact position.

12. 2. The extraction device according to claim 1, The control unit controls the rocking mechanism to rock the extraction vessel at a tilt speed in a speed range of 0.8° / sec to 1.2° / sec.

13. 13. The extraction device according to claim 12, The control unit controls the rocking mechanism to rock the extraction container at a tilt angle in the angle range of ±15° to ±25°.

14. 14. The extraction device according to claim 13, The control unit controls the rocking mechanism to repeat one rocking motion constituted by the tilt speed and the tilt angle a plurality of times.

15. 2. The extraction device according to claim 1, A brewing apparatus comprising one or more temperature regulating units for regulating the temperature of said plurality of brewing vessels.

16. A processing system for processing the biologically relevant material, comprising the extraction device according to claim 1, The plurality of extraction vessels are arranged along the first direction; A plurality of dispensing nozzles arranged along the first direction; a plurality of cartridges for holding various reagents and / or solutions used in the extraction process; The processing system, wherein the plurality of cartridges are arranged along a second direction different from the first direction.

17. 17. The processing system of claim 16, A processing system comprising a nozzle section that supports the plurality of dispensing nozzles movably along the second direction.

18. 17. The processing system of claim 16, A processing system comprising a measurement unit that measures each of the plurality of biologically relevant substances extracted in the plurality of extraction containers.

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