Dispensing device and sample processing and measurement system
Patent Information
- Application Number
- JP2023517146
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2021-04-28
- Filing Date
- 2022-03-18
- Publication Date
- 2026-10-01
- Estimated Expiration
- 2042-03-18
Smart Images

Figure 0007927312000001 
Figure 0007927312000002 
Figure 0007927312000003
Abstract
Description
Technical Field
[0001] The present invention relates to a dispensing device to which a plurality of dispensing tips can be attached collectively, and a specimen processing and measurement system including the dispensing device. Background Art
[0002] For the detection of pathogens such as viruses, a PCR method using polymerase chain reaction (PCR), which has become widespread with the development of genetic engineering, is used. A specimen containing a pathogen (such as saliva or nasopharyngeal mucus) is collected with a commercially available collection kit, nucleic acid (DNA or RNA) is extracted from the specimen, the nucleic acid is amplified by the PCR method, and the pathogen is detected based on the amplified nucleic acid. Since the end of 2019, the world has been exposed to the pandemic of novel coronavirus (COVID-19). The PCR method is used for the detection of COVID-19.
[0003] The PCR method is mainly performed manually, but not only is it difficult to continuously perform a large amount of test processing manually, but also erroneous operations and contamination may occur during the processing steps.
[0004] When performing the PCR method, specimens are processed using a microplate or a PCR plate having a plurality of wells (for example, 96 wells) formed therein. For dispensing (suction and discharge) of specimens, solutions, and reagents into the wells, a dispensing nozzle equipped with a dispensing tip is used. Since the plurality of wells are arranged at predetermined intervals on the plane (xy direction) of the microplate or PCR plate, collective dispensing can be performed using a plurality of dispensing nozzles arranged corresponding to the number of wells. For example, as shown in FIGS. 1 and 2 of Patent Document 1, the dispensing head device 10 includes a plurality of dispensing nozzles 16 arranged at predetermined intervals on a plane. The dispensing head device 101 mounts a plurality of dispensing tips 18 on the plurality of dispensing nozzles 16, and performs dispensing to a plurality of wells 4a of the microplate 4. Prior Art Documents Patent Documents
[0005] [Patent Document 1] Japanese Patent Publication No. 2006-105754 [Overview of the Initiative] [Problems that the invention aims to solve]
[0006] Typically, a dispensing tip is attached to a dispensing nozzle by press-fitting the lower end of the nozzle, which is fitted with an elastic component such as an O-ring, into the upper opening of the dispensing tip. When the dispensing nozzle dispenses liquids such as samples or reagents, the lower end of the dispensing nozzle is pressed in with a relatively large force to ensure a tight seal with the upper opening of the dispensing tip, in order to prevent leakage of liquid and gas between the nozzle and the dispensing tip, and to prevent the dispensing tip from falling out of the nozzle.
[0007] In order to press-fit multiple dispensing tips, arranged at predetermined intervals on a plane, into multiple dispensing nozzles simultaneously, it becomes necessary to apply a force that is roughly equal across the entire plane from the direction normal to the plane, in proportion to the number of pairs of dispensing tips and nozzles. Applying such a force to multiple pairs of dispensing tips and nozzles has been difficult.
[0008] Furthermore, the dispensing nozzle is equipped with an elastic member such as an O-ring to improve the seal with the dispensing tip. Repeated attachment and detachment of the dispensing tip to the dispensing nozzle can cause the elastic member to deteriorate, potentially leading to leakage of liquid and gas between the dispensing nozzle and the dispensing tip, or the dispensing tip falling off the nozzle. Therefore, it is necessary to replace the elastic member periodically. However, as described in Patent Document 1, for multiple dispensing nozzles arranged at predetermined intervals on a plane, it is necessary to replace the elastic member such as the O-ring after removing each individual dispensing nozzle from the dispensing device, making maintenance of the dispensing nozzles time-consuming.
[0009] Therefore, the present invention aims to provide a dispensing device capable of simultaneously attaching multiple dispensing tips to multiple dispensing nozzles, and a sample processing and measurement system equipped with this dispensing device. Alternatively, the present invention aims to provide a dispensing device in which the elastic members of multiple dispensing nozzles are less likely to deteriorate when multiple dispensing tips are simultaneously attached to multiple dispensing nozzles, and in which the attachment of multiple dispensing nozzles is easy, and a sample processing and measurement system equipped with this dispensing device. [Means for solving the problem]
[0010] Each embodiment of the present invention is configured as follows. [Aspect 1] A dispensing device comprising a plurality of dispensing nozzles arranged at predetermined intervals in a first direction and a second direction, A dispensing body that supports the plurality of dispensing nozzles, A mounting body on which multiple dispensing tips are placed at predetermined intervals in the first and second directions, In order to attach the plurality of dispensing tips to the plurality of dispensing nozzles, a mounting mechanism is provided for attaching the aforementioned mounting body on which the plurality of dispensing tips are placed to the dispensing body side, A removal mechanism for removing the aforementioned mounting unit on which the multiple dispensing tips are placed from the dispensing body side, A dispensing device comprising a plurality of dispensing nozzles, a mounting mechanism, and a control unit that controls the operation of the removal mechanism.
[0011] [Aspect 2] In the dispensing device described in Embodiment 1, The dispensing device comprises a mounting plate on which the plurality of dispensing tips are mounted at predetermined intervals in a first direction and a second direction, and a mounting plate frame that surrounds at least a portion of the periphery of the mounting plate. [Aspect 3] In the dispensing device described in Embodiment 2, The aforementioned mounting plate is rectangular, and the mounting plate frame described above surrounds three sides of the rectangle in a dispensing device. [Aspect 4] In the dispensing device described in embodiment 2 or 3, The mounting mechanism comprises one or more mounting magnets provided on one of the above-described mounting plate frame and the above-described dispensing body, and one or more metal bodies provided on the other of the above-described mounting frame and the above-described dispensing body, in a dispensing device.
[0012] [Aspect 5] In the dispensing device described in any one of embodiments 2 to 4, The aforementioned mounting plate frame is suspended from the dispensing body side, and is part of the dispensing device. [Aspect 6] In the dispensing device described in any one of the embodiments 1 to 5, The mounting mechanism comprises one or more mounting magnets provided on one of the above-described mounting body and the above-described dispensing body, and one or more metal bodies provided on the other of the above-described mounting body and the above-described dispensing body, in a dispensing device. [Aspect 7] In the dispensing device described in embodiment 4 or 6, The plurality of mounting magnets are arranged to surround one of the plurality of dispensing tips and the plurality of dispensing nozzles. A dispensing device in which the plurality of metal bodies are arranged to surround the other of the plurality of dispensing tips and the plurality of dispensing nozzles.
[0013] [Aspect 8] In the dispensing apparatus described in any one of the embodiments 1 to 3, The dispensing device comprises a mounting mechanism consisting of one or more first magnets provided on one of the above-described mounting body and the dispensing body, and one or more second magnets provided on the other of the above-described mounting body and the dispensing body. [Aspect 9] In the dispensing apparatus described in Embodiment 8, The plurality of first magnets are arranged to surround one of the plurality of dispensing tips and the plurality of dispensing nozzles. A dispensing device in which the plurality of second magnets are arranged to surround the other of the plurality of dispensing tips and the plurality of dispensing nozzles. [Aspect 10] In the dispensing device described in any one of the embodiments 1 to 10, A dispensing apparatus, wherein the removing mechanism comprises: a remover configured to apply a force to the placing body in a direction in which the placing body separates from a dispensing main body; and a remover moving mechanism configured to move the remover.
[0014] [Aspect 11] The dispensing apparatus according to Aspect 10, wherein A dispensing apparatus, wherein the remover presses an upper surface of the placing body and / or upper end surfaces of the plurality of dispensing tips, thereby removing the plurality of dispensing tips from the plurality of dispensing nozzles. [Aspect 12] The dispensing apparatus according to any one of Aspects 1 to 11, wherein A dispensing apparatus, comprising: a magnetic force applying unit configured to apply a magnetic force to an inside of each of the plurality of dispensing tips in a state where the plurality of dispensing tips placed on the placing body are attached to the plurality of dispensing nozzles.
[0015] [Aspect 13] The dispensing apparatus according to Aspect 12, wherein The magnetic force applying unit comprises: a comb portion constituted by a plurality of protruding pieces; a plurality of comb magnets respectively disposed on each of the plurality of protruding pieces; and a comb moving mechanism configured to move the plurality of comb portions in a direction of inserting or withdrawing the comb portions between the plurality of dispensing nozzles. [Aspect 12] The dispensing apparatus according to any one of Aspects 1 to 13, wherein A dispensing apparatus, wherein the plurality of dispensing nozzles each comprise an elastic member that contacts the plurality of dispensing tips. [Aspect 15] A sample processing and measuring apparatus, comprising: a first dispensing unit configured to dispense a parent sample from a parent sample container into a child sample container; a processing unit configured to extract nucleic acids from the child sample in the child sample container; a heating unit configured to repeat heating and cooling to amplify the extracted nucleic acids; a measuring unit configured to measure the amplified nucleic acids; and a second dispensing unit configured to dispense a reagent or a solution to at least the processing unit, wherein A sample processing and measuring apparatus, wherein the second dispensing unit is the dispensing apparatus according to any one of Aspects 1 to 14. [Effects of the Invention]
[0016] The dispensing device of the present invention, and the sample processing and measurement system equipped with this dispensing device, allow for the simultaneous attachment and removal of multiple dispensing tips to multiple dispensing nozzles. [Brief explanation of the drawing]
[0017] [Figure 1] This is an upper perspective view showing a sample processing and measurement system according to the first embodiment of the present invention. [Figure 2] Figure 1 is a front view showing the sample processing and measurement system. [Figure 3] Figure 1 is a schematic top view showing the stages of the sample processing and measurement system. [Figure 4] Figure 1 shows the sample processing and measurement system, with (a) a top view showing the dispensing range of the first dispensing section and (b) a top view showing the dispensing range of the second dispensing section. [Figure 5] Figure 1 is an overhead perspective view showing the second dispensing section (dispensing device). [Figure 5A] Figure 5 is a downward perspective view showing the second dispensing area. [Figure 6] Figure 5 is an overhead perspective view showing the mounting structure for the dispensing tip. [Figure 7] Figure 5 shows the second dispensing section: (a) an upward perspective view with the dispensing tip not attached, and (b) an upward perspective view with the dispensing tip attached. [Figure 8] Figure 5 shows the second dispensing section: (a) a downward perspective view with the dispensing tip attached, and (b) a downward perspective view without the dispensing tip attached. [Figure 9] Figure 5 shows the second dispensing section, (a) a side view, (b) a front view with the magnetic force application section retracted, and (c) a front view with the magnetic force application section protruding. [Figure 10] This is a partially cutaway side view showing the second dispensing section of Figure 9(a). [Figure 11] This is an enlarged cross-sectional view of the vicinity of the dispensing nozzle, showing a fourth modified example of the first embodiment. [Figure 12]This is an upper perspective view showing a second dispensing section according to a second embodiment of the present invention. [Figure 13] Figure 12 is an overhead perspective view showing the state in which multiple dispensing tips are attached to the second dispensing section. [Figure 14] Figure 12 is an overhead perspective view showing the second dispensing tip rack and multiple dispensing tips. [Figure 15] Figure 14 is an exploded perspective view of the second dispensing tip rack. [Figure 16] This is a front view showing the operation of the second dispensing unit according to the second embodiment. [Figure 17] This is an upper perspective view showing the second dispensing section according to the third embodiment of the present invention. [Figure 18] Figure 17 is a front view showing the second dispensing section. [Figure 19] Figure 17 is an exploded perspective view showing the second dispensing section. [Figure 20] Figure 18 shows (a) a horizontal cross-sectional view and (b) a vertical cross-sectional view along line bb, indicating the second dispensing area. [Figure 21] This is a front view showing the operation of the second dispensing unit according to the second embodiment. [Figure 22] This is a front view showing the operation of the second dispensing unit according to the second embodiment. [Modes for carrying out the invention]
[0018] Embodiments of the dispensing device and the sample processing and measurement system equipped with this dispensing device of the present invention will be described with reference to the drawings. In each figure, the same parts are denoted by the same reference numerals and their descriptions are omitted as appropriate. In each figure, the relative size and / or arrangement of each part is shown accurately in principle, but the present invention is not limited thereto. In each embodiment of the present invention, the sample is a biological substance, preferably a bodily fluid collected from a living organism (e.g., saliva, nasopharyngeal mucus, etc.), or any soluble tissue can be used. In this embodiment, the x, y, and z directions correspond to the first, second, and third directions of the claims, respectively.
[0019] (First Embodiment) [Basic Configuration of Sample Processing and Measurement System] The basic configuration of the sample processing and measurement system 1000 according to the first embodiment of the present invention will be explained with reference to Figures 1 and 2. The sample processing and measurement system 1000 consists of a base 100 equipped with a stage that supports each part, a first dispensing unit 200 that dispenses a parent sample from a parent sample container into a child sample container (well), a moving mechanism 300 that moves the first dispensing unit 200 and / or the second dispensing unit 400 in the x direction, a second dispensing unit (dispensing device) 400 that dispenses child samples from child sample containers and performs PCR-related processing, a first dispensing tip storage unit 500 that houses a plurality of dispensing tips for the first dispensing unit 200, and a control unit (computer) 600 that controls the operation of each part 200 to 400.
[0020] The base unit 100 comprises a fixed stage 105, a movable stage 120 that can move in the y-direction, and a moving mechanism (belt and motor) 122 for the movable stage 120. The control unit 600 controls the operation of the moving mechanism 122. The parent specimen storage unit 110 is provided on the fixed stage 105 on the upper surface of the base unit 100. The parent specimen storage unit 110 comprises a plurality of parent specimen container racks 114 that accommodate a plurality of parent specimen containers 112 in a single row in the y-direction.
[0021] The first dispensing unit 200 is a pitch-changing type dispensing device equipped with a plurality of dispensing nozzles arranged in a row. Preferably, the first dispensing unit 200 can be equipped with 12 dispensing nozzles. As shown in Figures 1 to 3, the first dispensing unit 200 includes a plurality of dispensing nozzles (a plurality of first dispensing nozzles) 205 arranged in a row in the y direction, a pitch changing mechanism 210 that changes the pitch in the y direction between the plurality of dispensing nozzles 205, and a support part 220 that supports the entire first dispensing unit 200 so that it can move in the x direction on a moving mechanism 300. The control unit 600 controls the operation of the drive motor of the pitch changing mechanism 210.
[0022] The pitch conversion mechanism 210 comprises a plurality of guide rods 206 that slide a plurality of dispensing nozzles 205 in the y-direction, a link mechanism connected to each of the plurality of dispensing nozzles 205 and expandable and contractible in the y-direction, and a link drive unit that drives the link mechanism. This pitch conversion mechanism can be, for example, the pitch conversion mechanism described in Figure 5 of the present inventor's International Publication No. 2016 / 031705. The pitch conversion mechanism 210 is expandable and contractible between a first pitch corresponding to the arrangement of a plurality of parent sample containers 112 arranged in the parent sample container rack 114 and a second pitch corresponding to the arrangement of a plurality of child sample containers (wells) arranged in the PCR plate. The first pitch (e.g., 22.5 mm) is preferably larger than the second pitch (e.g., 9.0 mm).
[0023] As shown in Figures 1 and 4(a), the moving mechanism 300 consists of a rail 310 that movably supports the first dispensing unit 200 and / or the second dispensing unit 400, a first belt 320 that moves the first dispensing unit 200, a first motor 330 that drives the first belt, a second belt 340 that moves the second dispensing unit 400, and a second motor 350 that drives the second belt 340. The control unit 600 controls the operation of the first motor 330 and / or the second motor 350.
[0024] [Stage Configuration] The stage structure of the sample processing and measurement system 1000 will be explained using the schematic top view in Figure 3. A parent sample storage unit 110 is provided on the fixed stage 105. The movable stage 120 includes a second dispensing tip storage unit 121 that accommodates multiple dispensing tips for the second dispensing unit 400, a processing unit 122 that houses a PCR plate or microplate for processing (purifying, extracting) child samples and performs processing, a heating unit (thermal cycler) 123 that houses a PCR plate containing multiple extracted nucleic acids extracted from child samples by the processing unit 122 and performs PCR, a reagent storage unit 124 that houses reagents used for processing child samples, amplifying nucleic acids, and detecting amplified nucleic acids, etc., and a waste tank 125 for discarding solutions that are no longer needed after processing, etc. The PCR plate or microplate preferably has 96 (8x12) wells arranged at approximately equal intervals in the xy direction. The heating unit 123 repeatedly heats and cools in order to amplify the extracted nucleic acids.
[0025] Preferably, a general-purpose cooling unit 126 and / or a PCR plate storage unit 127 for storing PCR plates may be provided on the movable stage 120. The movable stage 120 may be provided with a cooling mechanism (cooling block) 128 on the lower side of the general-purpose cooling unit 126. The control unit 600 controls the operation of the heating unit 123 and the cooling mechanism 128. Furthermore, preferably, the sample processing and measurement system 1000 may be provided with an ID reader for reading the parent sample ID provided on the parent sample container and the rack ID of the parent sample container rack, and / or a real-time PCR module for performing real-time PCR.
[0026] Figure 4(a) shows the state in which the movable stage 120 has moved toward the front (away from the moving mechanism 300 in the y-direction). In Figure 4(a), the dashed area 200A indicates the area in which the row of multiple dispensing nozzles 205 of the first dispensing unit 200 (Figure 1) is movable. Preferably, the dashed area 200A includes the areas above the first dispensing tip housing unit 500, a part of the parent sample storage unit 110, the dispensing tip disposal unit 130, the first dispensing tip rack 121, the pre-processing unit 122, and the reagent storage unit 124, with the multiple dispensing nozzles 205 in a first pitch (small pitch) state. Preferably, the dashed area 200A also includes the area above the entire parent sample storage unit 110, with the multiple dispensing nozzles 205 in a second pitch (large pitch) state.
[0027] Figure 4(b) shows the movable stage 120 in the rearward position (towards the moving mechanism 300). In Figure 4(b), the dashed area 400X indicates the area in which the group of multiple dispensing nozzles 436 (Figure 5A) of the second dispensing unit 400 can move. The dashed area 400X includes the areas above the dispensing tip disposal unit 130, the first dispensing tip rack 121, the heating unit 123, the waste liquid tank 125, and the PCR plate storage unit 125. As shown in Figure 5A, the multiple dispensing nozzles 436 are arranged at predetermined intervals (approximately equal intervals in the x and y directions) on the lower end plane (x and y directions) of the sub-support unit 420.
[0028] [Second footnote section] The second dispensing unit (dispensing device) 400 will be described using Figures 5 to 9. The second dispensing unit 400 is equipped with multiple dispensing nozzles corresponding to a PCR plate or microplate having multiple wells. As will be described later, the second dispensing unit 400 is equipped with a mounting mechanism for attaching multiple dispensing tips 142 arranged at predetermined intervals in the x and y directions to multiple dispensing nozzles 436 all at once, and a removal mechanism for removing multiple dispensing tips 142 arranged at predetermined intervals in the x and y directions from multiple dispensing nozzles 436 all at once. Preferably, the second dispensing unit 400 can be equipped with 96 dispensing nozzles 436 arranged at approximately equal intervals in the x and y directions, as shown in Figure 5A.
[0029] As shown in Figure 5, the second dispensing unit 400 includes a main support unit 410 that supports the entire second dispensing unit 400 so that it can move in the x direction relative to the moving mechanism 300, a sub-support unit 420 that can move in the z direction relative to the main support unit 410, and a sub-support unit moving motor 412 that moves the sub-support unit 420 in the z direction. The sub-support unit 420 includes a dispensing body (cylinder block) 430, a plurality of plungers 438 that can move in the z direction relative to the dispensing body 430 for suction and discharge of a plurality of dispensing nozzles 436, and a plunger motor 422 that moves the plurality of plungers 438 in the z direction by moving a plunger moving plate 439 in the z direction. The dispensing body 430 is fixed to the sub-support unit 420. The control unit 600 controls the operation of the sub-support unit moving motor 412 and / or the plunger motor 422.
[0030] A mounting mechanism for attaching multiple dispensing tips 142 to multiple dispensing nozzles 436 at once will be described. As shown in Figure 5, below the dispensing body 430, there is a second dispensing tip rack 140, a group of second dispensing tips 142 housed at predetermined intervals in the x and y directions within the second dispensing tip rack 140, and a mounting body (catch plate) 144 for placing the second dispensing tips 142 at approximately equal intervals in the x and y directions.
[0031] As shown in Figure 6, the second dispensing tip 142 has an upper opening 142a with a larger outer diameter than the central portion. The mounting body 144 has a plurality of through holes 144a arranged at predetermined intervals in the x and y directions and penetrating in the z direction. Since the outer diameter of the upper opening 142a of the second dispensing tip 142 is larger than the inner diameter of the through holes 144a of the mounting body 144, the lower end of the upper opening 142a of the second dispensing tip 142 is placed around the through holes 144a. Note that multiple dispensing tips 142 may be fixed to the mounting body 144.
[0032] The mounting body 144 comprises one or more metal bodies (metal discs) 144b. One or more metal bodies 144b are fixed to the mounting body 144. The multiple metal bodies 144b are preferably arranged to surround a plurality of dispensing tips 142 placed on the mounting body 144. One or more metal bodies 144b are preferably arranged on the periphery of the mounting body 144. One or more metal bodies 144b are preferably housed in one or more recesses 144c formed in the mounting body 144.
[0033] As shown in the downward perspective view of Figure 5A, the lower surface of the dispensing body (cylinder block) 430 fixed to the sub-support 420 is provided with a group of dispensing nozzles 436 and one or more mounting magnets 432. Preferably, the multiple mounting magnets 432 are arranged to surround the group of dispensing nozzles 436.
[0034] Multiple mounting magnets 432 attract the metal plates 144b of multiple mounting bodies 144. The multiple mounting magnets 432 preferably protrude in the z direction from the lower surface of the dispensing body 430. The mounting magnets 432 can preferably be cylindrical in shape. The mounting magnets 432 can preferably be neodymium magnets.
[0035] The mounting mechanism consists of one or more mounting magnets 432 fixed to the dispensing body 430 and one or more metal bodies 144b fixed to the mounting body 144.
[0036] Using Figure 7, the operation of attaching multiple dispensing tips to multiple dispensing nozzles 142 will be explained. As shown in Figure 7(a), with multiple dispensing tips 142 placed on the mounting body 144, the multiple dispensing tips 142 are housed in the second dispensing tip rack 140. In this state, the group of multiple dispensing nozzles 436 of the second dispensing unit 400 (Figure 5A) descends from above the mounting body 144 toward the mounting body 144, and when the multiple metal bodies 144b fixed to the mounting body 144 are attracted to the multiple magnets 432 (Figure 5A), the multiple dispensing nozzles 436 are inserted into the upper end openings 142a of the multiple dispensing tips 142, and the multiple dispensing tips 142 and the multiple dispensing nozzles 436 come into close contact with each other.
[0037] The weight of the multiple dispensing tips 142 can be supported not by the multiple dispensing nozzles 436, but by the multiple magnets 432 positioned next to the multiple dispensing nozzles 436 via the multiple metal bodies 144b of the mounting body 144. Therefore, the multiple dispensing nozzles 436 only need to be pressed into the upper end openings 142a of the multiple dispensing tips 142 with a relatively small force that allows them to be tightly attached. Preferably, each of the multiple dispensing nozzles 436 can be provided with an elastic member (such as an O-ring) that contacts the dispensing tip.
[0038] Next, a removal mechanism for removing multiple dispensing tips 142 at once will be described. As shown in Figure 5A, a remover 434 is provided below the dispensing body 430 so as to be movable in the z direction relative to the sub-support 420. As will be described later, the remover 434 can remove multiple dispensing tips 142 from multiple dispensing nozzles 436 at once. The remover 434 is generally plate-shaped and has multiple through holes. The multiple dispensing nozzles 436 are exposed on the lower side after passing through the multiple through holes of the remover 434. The multiple dispensing nozzles 436 are not integrated with the remover 434.
[0039] Furthermore, as shown in Figures 5 and 5A, the side surface of the dispensing body 430 is provided with a plurality of pressing rods (remover movement mechanism) 437 that are movable in the z direction relative to the sub-support 420 in order to press the remover 434 downward. The plurality of pressing rods 437 can preferably be rod actuators. Since the lower ends of the plurality of pressing rods 437 are fixed to the remover 434, the plurality of pressing rods 437 and the remover 434 move up and down together. The control unit 600 controls the movement of the plurality of pressing rods 437. As shown in Figure 5A, the lower ends of the plurality of pressing rods 437 are each positioned near the plurality of mounting magnets 432 (mounting mechanism) and press the remover 434 downward. The removal mechanism consists of the remover 434, the plurality of pressing rods 437, and the mounting body 144. The remover 434 applies force to the mounting body 144 in a direction that separates the multiple dispensing tips and the mounting body 144 from the dispensing body 430.
[0040] Using Figure 8, the operation of the removal mechanism when removing multiple dispensing tips from multiple dispensing nozzles will be explained. As shown in Figure 8(a), with multiple dispensing tips 142 held on the mounting body 144, the multiple dispensing tips 142 are attached to a group of multiple dispensing nozzles 436 (Figure 5A). In this state, when the control unit 600 moves the multiple pressing rods 437 downward, the remover 434 also moves downward, and the lower surface of the remover 434 presses against the upper surface of the mounting body 144 and / or the upper end surfaces of the multiple dispensing tips 142. When this pressing force exceeds the force with which the multiple mounting magnets 432 attract the multiple metal bodies 144b, the mounting body 144 on which the multiple dispensing tips 142 are mounted is removed from the multiple dispensing nozzles 436, as shown in Figure 8(b).
[0041] As a modified example, one or more mounting magnets 432 may be fixed to the mounting body 144, and one or more metal bodies 144b may be fixed to multiple pressing rods 437 and integrated with the multiple pressing rods 437.
[0042] [Magnetic force application unit] The comb-shaped magnetic field application unit 414 of the second dispensing unit 400 of this embodiment will now be described. For the purification (pretreatment) of the sample in the second dispensing unit 400, the method proposed by the present inventors in International Publication 97 / 44671 can preferably be used. This method is performed using magnetic particles that adsorb target 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.
[0043] The second dispensing unit 400 of this embodiment includes a magnetic force application unit 414 to selectively apply magnetic force to magnetic particles inside the multiple dispensing tips 142 attached to the multiple dispensing nozzles 436.
[0044] As shown in Figures 5A and 9, the magnetic force application unit 414 consists of a comb body 414a that is movable in the x-direction relative to the main support unit 410, a comb body movement motor 416 provided on the main support unit 410 to move the comb body 414a in the x-direction, a comb portion 414b provided at the end of the body 414a on the side of the multiple dispensing tips 142, a plurality of comb magnets 414c (Figures 5(a) and 9(b)) arranged at predetermined intervals in the x-direction for each protruding piece of the comb portion 414b, and a rail 414d that moves the comb body 414a in the x-direction relative to the main support unit 410. The control unit 600 controls the operation of the comb body movement motor 416.
[0045] As shown in the comb insertion state in Figure 9(c), when multiple dispensing tips 142 are held in the dispensing body 430, and each protruding piece of the multiple comb portion 414b is inserted from the x direction between multiple rows of multiple dispensing tips 142, the multiple comb magnets 414c provided on each protruding piece of the multiple comb portion 414b can attract magnetic particles in the solution within the multiple dispensing tips 142.
[0046] As shown in the comb withdrawal state in Figure 9(b), when multiple dispensing tips 142 are held, and each protruding piece of the multiple comb portion 414b is pulled out in the x direction from between the rows of multiple dispensing tips 142, the multiple comb magnets 414c provided on each protruding piece of the multiple comb portion 414b do not exert a magnetic force on the magnetic particles in the multiple dispensing tips 142, and the magnetic particles are dispersed in the solution in the multiple dispensing tips 142.
[0047] In the state shown in Figure 9(c), the multiple metal bodies 144b fixed to the mounting body 144 are attracted by multiple mounting magnets 432 fixed to the dispensing body 430, as shown in Figure 10. The magnetic force of the multiple mounting magnets 432 may affect the multiple comb magnets 414c of the magnetic force application unit 414 and the magnetic particles in the dispensing tip 142. Therefore, it is preferable to provide magnetic shielding (ferromagnetic material such as iron) on the sides of the multiple mounting magnets 432 and on the sides and bottom surfaces of the multiple metal bodies 144b.
[0048] The function of the O-ring in the dispensing nozzle 436 in this embodiment will now be described. In this embodiment, the dispensing nozzle 436 does not rely solely on the O-ring to support the load of the dispensing tip and prevent it from falling out of the nozzle. In conventional examples, the dispensing tip is pressed into the dispensing nozzle fitted with an O-ring with a relatively large force to prevent it from falling out of the nozzle. However, repeated attachment and detachment of the dispensing tip to the nozzle causes the O-ring to deteriorate due to repeated sliding of the dispensing tip against the O-ring, resulting in a decrease in the pressurizing force. As a result of the decreased pressurizing force, the dispensing tip may fall out of the nozzle, causing liquid to splash and potentially leading to contamination. Therefore, in order to maintain the pressurizing force of the O-ring, complicated and delicate replacement or maintenance of the O-ring was required.
[0049] In contrast, in this embodiment, there is no need to press-fit the dispensing tip 142 into the dispensing nozzle 436 fitted with an O-ring with a relatively large force such that the dispensing nozzle 436 supports the load of the dispensing tip. That is, since the upper end opening 142a of the dispensing tip 142 is placed around the through hole 144a of the mounting body 144, the load of the dispensing tip 142 is applied to the dispensing tip mounting mechanism (mounting body 144, metal body 144b, magnet 432, and sub-support 420), there is no need to press-fit the dispensing tip 142 into the dispensing nozzle 436 fitted with an O-ring with a relatively large force. Therefore, in the mounting mechanism of this embodiment, the complicated and delicate replacement or maintenance of the O-ring is unnecessary in order to maintain the press-fit force of the O-ring. Furthermore, in the mounting mechanism of this embodiment, the O-ring only needs to have enough elasticity to seal the space between the dispensing nozzle 436 and the upper end opening 142a of the dispensing tip 142 so that gas and liquid do not leak out. In the mounting mechanism of this embodiment, when attaching the dispensing tip 142 to the dispensing nozzle 436, it is no longer necessary to press the dispensing tip 142 into the dispensing nozzle 436 with a relatively large force, thus reducing the likelihood of the O-ring deteriorating.
[0050] [Differentiation] Various modifications applicable to the first to third embodiments will be described. The mounting mechanism of the first to third embodiments consists of mounting bodies 144, 144A, and 144B for the dispensing tip 142, a plurality of metal bodies 144b, 144A1b, and 144B1b provided on the mounting bodies 144, 144A, and 144B, and a plurality of mounting magnets 432 that attract the plurality of metal bodies 144b, 144A1b, and 144B1b. In contrast, the mounting mechanism of the first modification can have a plurality of first magnets 432 instead of a plurality of mounting magnets 432, and a plurality of second magnets instead of a plurality of metal bodies 144b, 144A1b, and 144B1b. The pair of first and second magnets are arranged so that they have different polarities when facing each other.
[0051] In the mounting mechanisms of the first to third embodiments, a pair of magnets 432 and metal bodies 144b, 144A1b, and 144B1b are in contact with each other. In contrast, in the mounting mechanism of the second modified example, the pair of magnets 432 and metal bodies 144b, 144A1b, and 144B1b do not come into contact with each other, and the dispensing tip 142 is attached to the dispensing nozzle 436 with a gap between them. Since the multiple metal bodies 144b, 144A1b, and 144B1b are attracted by magnetic force without coming into contact with the multiple mounting magnets 432, the multiple metal bodies 144b, 144A1b, and 144B1b can be stably held by the multiple mounting magnets 432. The gap between the pair of magnets 432 and the metal bodies 144b, 144A1b, and 144B1b can preferably be 0.7 to 0.3 mm, more preferably about 0.5 mm.
[0052] Similar to the second modified example, the mounting mechanism of the third modified example has the dispensing tip 142 attached to the dispensing nozzle 436 with the pair of first and second magnets of the first modified example not in contact with each other, but facing each other with a gap between them. Since the multiple first magnets are attracted by magnetic force without contacting the multiple second magnets, the multiple metal bodies 144b, 144A1b, and 144B1b can be stably held by the multiple mounting magnets 432. The gap between the pair of first and second magnets can preferably be 0.7 to 0.3 mm, more preferably about 0.5 mm.
[0053] In the first to third embodiments of the present invention, the O-ring is preferably positioned on the outer circumferential surface of the dispensing nozzle 436, similar to the conventional method, so as to be positioned between the inner circumferential surface of the upper end opening 142a of the dispensing tip 142 and the outer circumferential surface of the dispensing nozzle 436. In contrast, the O-ring 438 of the fourth modified example is positioned on the lower side surface 434a of the remover 434 surrounding the dispensing nozzle 436, as shown in Figure 11. When the dispensing tip 142 is attached to the dispensing nozzle 436, the O-ring 438 is positioned between the lower side surface 434a and the upper end opening 142a of the dispensing tip 142. Under this arrangement, when the dispensing tip 142 is attached to the dispensing nozzle 434, the dispensing tip 142 does not slide against the O-ring 438, thus preventing deterioration of the O-ring 438 due to sliding.
[0054] (Second embodiment) The sample processing system according to the second embodiment of the present invention differs from the sample processing system 1000 according to the first embodiment only in the second dispensing unit; the configuration and operation of the other parts are the same as those of the sample processing system 1000, therefore, drawings and descriptions of the configuration and operation of the other parts are omitted.
[0055] A second dispensing unit 400A according to the second embodiment will be described with reference to Figures 12 to 16. Parts of the second dispensing unit 400A that are common with the second dispensing unit 400 are denoted by the same reference numerals as those of the second dispensing unit 400. The second dispensing unit 400A is equipped with a plurality of dispensing nozzles 436 that correspond to a PCR plate or microplate having a plurality of wells. As will be described later, the second dispensing unit 400A is equipped with a mounting mechanism for attaching a plurality of dispensing tips 142 arranged at predetermined intervals in the x and y directions to a plurality of dispensing nozzles 436 (Figure 16) all at once, and a removal mechanism for removing a plurality of dispensing tips 142 arranged at predetermined intervals in the x and y directions from a plurality of dispensing nozzles 436 all at once. Preferably, the second dispensing unit 400 can be equipped with 96 dispensing nozzles 436 arranged at approximately equal intervals in the x and y directions, similar to Figure 5A. In the second embodiment, the second dispensing unit 400A is equipped with the same magnetic force application unit 414 as in the first embodiment.
[0056] As shown in Figures 12 and 13, the second dispensing unit 400A includes a main support unit 410 that supports the entire second dispensing unit 400A so as to be movable in the x direction relative to the moving mechanism 300, a sub-support unit 420 that is movable in the z direction relative to the main support unit 410, and a sub-support unit moving motor 412 that moves the sub-support unit 420 in the z direction. The sub-support unit 420 includes a dispensing body (cylinder block) 430, a plurality of plungers 438 that are movable in the z direction relative to the dispensing body 430 for suction and discharge of a plurality of dispensing nozzles 436, and a plunger motor 422 that moves the plurality of plungers 438 in the z direction by moving a plunger moving plate 439 in the z direction. The dispensing body 430 is fixed to the sub-support unit 420. The control unit 600 controls the operation of the sub-support unit moving motor 412 and / or the plunger motor 422.
[0057] A mounting mechanism for attaching multiple dispensing tips 142 to multiple dispensing nozzles 436 at once will be described. Below the dispensing body 430 are a second dispensing tip rack 140A, a group of second dispensing tips 142 housed at predetermined intervals in the x and y directions within the second dispensing tip rack 140A, a rectangular mounting plate 144A2 on which the second dispensing tips 142 are placed at predetermined intervals in the x and y directions, and a mounting plate frame surrounding at least a portion (three sides of the rectangle) of the mounting plate 144A2. 144A1 In the second embodiment, the mounting body 144A is composed of a mounting plate 144A2 and a mounting body frame 144A1. The mounting body frame 144A1 can preferably be formed in a U-shape.
[0058] As shown in Figures 14 and 15, the mounting plate frame 144A1 comprises one or more metal bodies (metal discs) 144A1b, an upper recess 144A1c that accommodates the peripheral edge of the mounting plate 144A2, and a lower recess 144A1d that accommodates the upper end of the side wall of the second dispensing tip rack 140A. One or more metal bodies 144Ab are fixed to the mounting frame 144A. Preferably, the multiple metal bodies 144Ab are arranged to surround the multiple dispensing tips 142 placed on the mounting plate 144A2, as shown in Figure 12. Preferably, one or more metal bodies 144Ab are arranged at the corners and / or ends of the mounting frame 144A1. Preferably, one or more metal bodies 144A1b are each housed in one or more recesses formed in the mounting frame 144A1.
[0059] The mounting plate 144A2 has a plurality of through holes 144A2a arranged at predetermined intervals in the x and y directions and penetrating in the z direction. Since the outer diameter of the upper end opening 142a of the second dispensing tip 142 is larger than the inner diameter of the through holes 144A2a of the mounting plate 144A2, the lower end of the upper end opening 142a of the second dispensing tip 142 is placed around the through holes 144A2a. Multiple dispensing tips 142 may be fixed to the mounting plate 144A2.
[0060] The second dispensing tip rack 140A supports a mounting body 144A that houses multiple dispensing tips 142, and in order to allow the mounting body 144A that houses multiple dispensing tips 142 to move in the x-direction, it does not have side walls on the plane perpendicular to the x-direction (yz-plane).
[0061] As shown in Figure 16, below the dispensing body (cylinder block) 430, a group of dispensing nozzles 436 and one or more mounting magnets 432 are fixed to the sub-support 420. Preferably, the multiple mounting magnets 432 are arranged to surround the group of dispensing nozzles in the xy plane. The multiple mounting magnets 432 attract multiple metal plates 144A1b of the mounting body 144A.
[0062] The mounting mechanism consists of one or more mounting magnets 432 fixed to the dispensing body 430 (sub-support part 420) and one or more metal bodies 144A1b fixed to the mounting body 144A.
[0063] Using Figure 16, the operation of attaching multiple dispensing tips 142 to multiple dispensing nozzles 142 will be explained. As shown in Figures 12 and 16(a), in the mounted state in which multiple dispensing tips 142 are placed on the mounting body 144A, the multiple dispensing tips 142 are housed in the second dispensing tip rack 140A. In the mounted state shown in Figure 16(a), when the group of multiple dispensing nozzles 436 of the second dispensing unit 400A descends from above the mounting body 144A toward the mounting body 144A, as shown in Figure 16(b), the multiple metal bodies 144A1b fixed to the mounting body 144A are attracted to the multiple magnets 432, resulting in an attracted state. In the attracted state shown in Figure 16(b), the multiple dispensing nozzles 436 are inserted into the upper end openings 142a of the multiple dispensing tips 142, and the multiple dispensing tips 142 and the multiple dispensing nozzles 436 are in close contact with each other. Furthermore, when the entire second dispensing unit 400A is raised in the z direction by the sub-support moving motor 412 from the state shown in Figure 16(b), the second dispensing unit 400A becomes movable in the x and y directions with multiple dispensing tips 142 attached, as shown in Figures 13 and 16(c).
[0064] In the state shown in Figures 16(c) and 16(d), the weight of the multiple dispensing tips 142 is supported not by the multiple dispensing nozzles 436, but by multiple magnets 432 (sub-supports 420) positioned next to the multiple dispensing nozzles 436 via multiple metal bodies 144A1b of the mounting body 144A. Therefore, the multiple dispensing nozzles 436 only need to be pressed into the upper end openings 142a of the multiple dispensing tips 142 with a relatively small force sufficient to ensure close contact between them. Preferably, each of the multiple dispensing nozzles 436 can be provided with an elastic member (such as an O-ring) that contacts the dispensing tip.
[0065] Next, a removal mechanism for removing multiple dispensing tips 142 at once will be described. As shown in Figures 13 and 16(c), a remover 434 is provided on the lower surface of the dispensing body 430 so as to be movable in the z direction. As will be described later, the remover 434 can remove multiple dispensing tips 142 at once from multiple dispensing nozzles 436. The remover 434 is generally plate-shaped and has multiple through holes. The multiple dispensing nozzles 436 are exposed on the lower side after passing through the multiple through holes of the remover 434. The multiple dispensing nozzles 436 are not integrated with the remover 434.
[0066] Furthermore, as shown in Figures 13 and 16, the side surface of the dispensing body 430 is provided with a plurality of pressing rods (remover movement mechanism) 437 that are movable in the z direction to press the remover 434 downward. The plurality of pressing rods 437 can preferably be rod actuators. Since the lower ends of the plurality of pressing rods 437 are fixed to the remover 434, the plurality of pressing rods 437 and the remover 434 move up and down together with respect to the sub-support 420. The control unit 600 controls the movement of the plurality of pressing rods 437. As shown in Figure 13, the lower ends of the plurality of pressing rods 437 are each positioned near the plurality of mounting magnets 432 (mounting mechanism) and press the remover 434 downward. The removal mechanism consists of the remover 434, the plurality of pressing rods 437, and the mounting body 144A. The remover 434 applies force to the mounting body 144A in a direction that separates the multiple dispensing tips 142 and the mounting body 144A from the dispensing body 430.
[0067] Using Figure 16, the operation of the removal mechanism when removing multiple dispensing tips from multiple dispensing nozzles will be explained. As shown in Figure 16(c), in a holding state in which multiple dispensing tips 142 are held on the mounting body 144A, the multiple dispensing tips 142 are attached to a group of multiple dispensing nozzles 436. In the holding state shown in Figure 16(c), when the control unit 600 moves the multiple pressing rods 437 downward, the remover 434 also moves downward, and the lower surface of the remover 434 presses against the upper surface of the mounting body 144A and / or the upper end surfaces of the multiple dispensing tips 142. When this pressing force exceeds the force with which the multiple mounting magnets 432 attract the multiple metal bodies 144A1b, the mounting body 144A on which the multiple dispensing tips 142 are placed is removed from the multiple dispensing nozzles 436, as shown in Figure 16(d).
[0068] In the second embodiment, the mounting body 144A is composed of a mounting plate 144A2 and a mounting frame 144A2, so that the operator can separate the mounting frame 144A2 from the mounting plate 144A2. After this separation, the mounting plate 144A2 on which the used dispensing tips 142 are mounted can be discarded, and the mounting frame 144A2 can be attached to the mounting plate 144A2 on which the unused dispensing tips 142 are mounted. This makes it possible to reuse the mounting frame 144A2, which has a relatively expensive metal body 144A1b.
[0069] (Third embodiment) The sample processing system according to the third embodiment of the present invention differs from the sample processing system 1000 according to the first embodiment only in the second dispensing unit; the configuration and operation of the other parts are the same as those of the sample processing system 1000, therefore, drawings and descriptions of the configuration and operation of the other parts are omitted.
[0070] A second dispensing unit 400B according to a third embodiment will be described with reference to Figures 17 to 22. Parts of the second dispensing unit 400B that are common to the second dispensing unit 400 are denoted by the same reference numerals as those of the second dispensing unit 400. The second dispensing unit 400B includes a plurality of dispensing nozzles 436 (Figure 21(a)) corresponding to a PCR plate or microplate having a plurality of wells. As will be described later, the second dispensing unit 400B includes a mounting mechanism for attaching a plurality of dispensing tips 142 arranged at predetermined intervals in the x and y directions to a plurality of dispensing nozzles 436 all at once, and a removal mechanism for removing a plurality of dispensing tips 142 arranged at predetermined intervals in the x and y directions from a plurality of dispensing nozzles 436 all at once. Preferably, the second dispensing unit 400B can include 96 dispensing nozzles 436 arranged at approximately equal intervals in the x and y directions, similar to Figure 5A. In the third embodiment, the second dispensing unit 400B includes the same magnetic force application unit 414 as in the first embodiment.
[0071] As shown in Figure 17, the second dispensing unit 400B includes a main support unit 410 that supports the entire second dispensing unit 400B so as to be movable in the x direction relative to the moving mechanism 300, a sub-support unit 420 that is movable in the z direction relative to the main support unit 410, and a sub-support unit moving motor (not shown) that moves the sub-support unit 420 in the z direction. The sub-support unit 420 includes a dispensing body (cylinder block) 430, a plurality of plungers 438 that are movable in the z direction relative to the dispensing body 430 for suction and discharge of a plurality of dispensing nozzles 436, and a plunger motor (not shown) that moves the plurality of plungers 438 in the z direction by moving a plunger moving plate 439 in the z direction. The dispensing body 430 is fixed to the sub-support unit 420. The control unit 600 controls the operation of the sub-support unit moving motor and / or the plunger motor.
[0072] A mounting mechanism for attaching multiple dispensing tips 142 to multiple dispensing nozzles 436 at once will be described. Below the dispensing body 430, a second dispensing tip rack 140B, a group of second dispensing tips 142 housed at predetermined intervals in the x and y directions within the second dispensing tip rack 140B, a rectangular mounting plate 144B2 on which the second dispensing tips 142 are placed at predetermined intervals in the x and y directions, and a mounting plate frame 144B1 surrounding at least a portion (3 sides) of the mounting plate 144B2. In the second embodiment, the mounting body 144B consists of the mounting plate 144B2 and the mounting body frame 144B1. The mounting body frame 144B1 can preferably be formed in a U-shape (U-shape), as shown in Figure 19.
[0073] As shown in Figure 19, the mounting plate frame 144B1 comprises one or more metal bodies (metal discs) 144B1b, an upper recess 144B1c that accommodates the peripheral edge of the mounting plate 144B2, and a plurality of guide rods 144B1a that protrude upward (in the z direction) from the mounting frame 144B. One or more metal bodies 144Bb are fixed to the mounting frame 144B1. The upper ends of the guide rods 144B1a are attached to the sub-supports 420 so as to be movable in the z direction through openings provided in the sub-supports 420. Since the lower ends of the guide rods 144B1a are fixed to the mounting frame 144B1, the mounting frame 144B1 is suspended from the sub-support 420 on the dispensing body 430 side so as to be movable in the z direction.
[0074] The multiple metal bodies 144B1b are preferably arranged to surround the multiple dispensing tips 142 placed on the mounting plate 144A2, as shown in Figure 20(a). One or more metal bodies 144B1b are preferably positioned at the corners and / or ends of the mounting frame 144B1. One or more metal bodies 144B1b are preferably housed in one or more recesses formed in the mounting frame 144B1.
[0075] The mounting plate 144B2 has a plurality of through holes 144B2a arranged at predetermined intervals in the x and y directions and penetrating in the z direction. Since the outer diameter of the upper end opening 142a of the second dispensing tip 142 is larger than the inner diameter of the through holes 144B2a of the mounting plate 144B2, the lower end of the upper end opening 142a of the second dispensing tip 142 is placed around the through holes 144B2a. Multiple dispensing tips 142 may be fixed to the mounting plate 144B2. The mounting plate 144B2 has a pair of second through holes 144B2d that accommodate the protrusions 140Ba of the second dispensing tip rack 140Ba.
[0076] The second dispensing tip rack 140B supports a mounting plate 144B2 containing multiple dispensing tips 142, and does not have side walls on the plane perpendicular to the x-direction (yx plane) in order to allow the mounting plate frame 144B1 to move in parallel in the x-direction integrally with the second dispensing section 400B. The second dispensing tip rack 140B is provided with a pair of projections (pins) 140Ba extending in the z-direction from the upper end of its side wall. By inserting the projections 140Ba into the second through-hole 144B2d (Figure 19), the mounting plate 144B2 is positioned relative to the second dispensing tip rack 140A.
[0077] As shown in Figure 18, below the dispensing body (cylinder block) 430, a group of dispensing nozzles 436 and one or more mounting magnets 432 are fixed to the sub-support 420. Preferably, the multiple mounting magnets 432 are arranged to surround the group of dispensing nozzles 436 in the xy plane. The multiple mounting magnets 432 attract multiple metal plates 144B1b of the mounting body 144B.
[0078] The mounting mechanism consists of one or more mounting magnets 432 fixed to the dispensing body 430 side and one or more metal bodies 144B1b fixed to the mounting body 144B side.
[0079] The operation of attaching multiple dispensing tips 142 to multiple dispensing nozzles 142 will be explained using Figures 17 and 21. As shown in Figure 17, in the mounted state in which multiple dispensing tips 142 are placed on the mounting body 144B, the multiple dispensing tips 142 are housed in the second dispensing tip rack 140B. In the mounted state shown in Figure 17, as indicated by the arrow in Step 1, the moving mechanism 300 moves the group of multiple dispensing nozzles 436 of the second dispensing unit 400B toward the mounting body 144B from the x direction. When the mounting plate 144B2 is housed in the mounting plate frame 144B1, as shown in Figure 21(a), the multiple dispensing nozzles 436 are in a facing state in which they face the upper end openings of the multiple dispensing tips 142 in the z direction.
[0080] Starting from the opposing state shown in Figure 21(a), in Step 2, the control unit 600 operates the sub-support unit moving motor 412 to lower the sub-support unit 420 until the multiple magnets 432 and the multiple metal bodies 144B1b come into contact, resulting in the state shown in Figure 21(b). In the state shown in Figure 21(b), the multiple magnets 432 are attracted to the multiple metal bodies 144B1b. In this attracted state, the multiple dispensing nozzles 436 are inserted into the upper end openings 142a of the multiple dispensing tips 142, and the multiple dispensing tips 142 and the multiple dispensing nozzles 436 are in close contact with each other. Furthermore, in Step 3, starting from the state shown in Figure 21(b), the entire second dispensing unit 400B is raised in the z direction by the sub-support unit moving motor 412, as shown in Figure 21(c), so that the second dispensing unit 400B can move with the multiple dispensing nozzles 436 attached to the multiple dispensing tips 142.
[0081] The weight of the multiple dispensing tips 142 can be supported not by the multiple dispensing nozzles 436, but by the multiple magnets 432 (sub-supports 420) positioned next to the multiple dispensing nozzles 436 via the multiple metal bodies 144B1b of the mounting body 144B. Therefore, the multiple dispensing nozzles 436 only need to be pressed into the upper end openings 142a of the multiple dispensing tips 142 with a relatively small force that allows them to be tightly attached. Preferably, each of the multiple dispensing nozzles 436 can be provided with an elastic member (such as an O-ring) that contacts the dispensing tip.
[0082] Next, a removal mechanism for removing multiple dispensing tips 142 at once will be described. As shown in Figure 19, a remover 434 is provided on the lower surface of the dispensing body 430 so as to be movable in the z direction. As will be described later, the remover 434 can remove multiple dispensing tips 142 at once from multiple dispensing nozzles 436. The remover 434 is generally plate-shaped and has multiple through holes. The multiple dispensing nozzles 436 are exposed on the lower side after passing through the multiple through holes of the remover 434. The multiple dispensing nozzles 436 are not integrated with the remover 434.
[0083] Furthermore, as shown in Figures 17 and 19, the side surface of the dispensing body 430 is provided with a plurality of pressing rods (remover movement mechanism) 437 that are movable in the z direction to press the remover 434 downward. The plurality of pressing rods 437 can preferably be rod actuators. Since the lower ends of the plurality of pressing rods 437 are fixed to the remover 434, the plurality of pressing rods 437 and the remover 434 move up and down together. The control unit 600 controls the extension and retraction movement of the plurality of pressing rods 437. As shown in Figure 17, the lower ends of the plurality of pressing rods 437 are each positioned near the plurality of mounting magnets 432 (mounting mechanism) and press the remover 434 downward. The removal mechanism consists of the remover 434, the plurality of pressing rods 437, and the mounting body 144B. The remover 434 applies force to the mounting body 144B in a direction that separates the multiple dispensing tips 142 and the mounting body 144B from the dispensing body 430.
[0084] Using Figure 22, the operation of the removal mechanism when removing multiple dispensing tips from multiple dispensing nozzles will be explained. As shown in Figure 22(d), with multiple dispensing tips 142 held on the mounting plate 144B2 (mounting body 144B), the multiple dispensing tips 142 are attached to a group of multiple dispensing nozzles 436. In this state, as shown in Step 4, when the control unit 600 moves the multiple pressing rods 437 downward, the remover 434 also moves downward, and the lower surface of the remover 434 presses against the upper surface of the mounting body 144B (both the mounting plate frame 144B1 and the mounting plate 144B2) and / or the upper end surfaces of the multiple dispensing tips 142.
[0085] When this pressing force exceeds the attractive force between the multiple mounting magnets 432 and the multiple metal bodies 144A1b, the mounting plate 144B2, on which the mounting plate frame 144B1 and the multiple dispensing tips 142 are mounted, is removed from the multiple dispensing nozzles 436, as shown in Figure 22(e). In the state shown in Figure 22(c), preferably, the mounting plate frame 144B1 moves downward due to its own weight, and the mounting plate frame 144B1 and the mounting plate 144B2 separate in the z direction. In the state shown in Figure 22(e), since the mounting plate 144B2 is separated from the mounting plate frame 144B1 in the z direction, the state shown in Figure 17 can be achieved by horizontally moving the second dispensing unit 400B in the x direction. Furthermore, even if the mounting plate frame 144B1 and the mounting plate 144B2 are not separated in the z direction in the state shown in Figure 22(c), the mounting plate frame 144B1, which is held on the second dispensing unit 400B side, can be pulled out from the mounting plate 144B2, which is held on the second dispensing tip rack 140B side, by moving the second dispensing unit 400B in the x direction.
[0086] In the third embodiment, the mounting body 144B consists of a mounting plate 144B2 and a mounting frame 144B2, and the mounting frame 144B2 can be separated from the mounting plate 144B2 without manual intervention by moving the second dispensing section 400B horizontally (x direction). After this separation, only the mounting plate 144B2 on which the used dispensing tips 142 are mounted can be discarded, and the mounting frame 144B2 can be attached horizontally to the mounting plate 144B2 on which the unused dispensing tips 142 are mounted without manual intervention. This makes it possible to reuse the mounting frame 144A2, which has a relatively expensive metal body 144A1b, while avoiding contamination of the sample. [Explanation of Symbols]
[0087] 1000 Sample Processing and Measurement System 100 base 142 dispensing tips 144 Mounting body (catch plate) 144a Through hole 144b Metal body (metal disk) 144c recess 120 movable stages 200 First dispensing section 205 Dispensing nozzle (No. 1 dispensing nozzle) 210 Pitch conversion mechanism 300 Moving mechanism 400 Second dispensing section (dispensing device) 432 Mounting Magnet 434 Remover 436 Dispensing nozzle (Second dispensing nozzle) 438 O-ring 414 Magnetic force application section 414b Comb part 414c Comb Magnet 500 First dispensing tip housing 600 Control Unit 400A Second dispensing section (dispensing device) 144A Mounting body 144A1 Mounting plate frame 144A2 Mounting plate 400B Second dispensing section (dispensing device) 144B Mounting body 144B1 Mounting plate frame 144B2 Mounting plate
Claims
1. A dispensing device comprising a plurality of dispensing nozzles arranged at predetermined intervals in a first direction and a second direction, A dispensing body that supports the plurality of dispensing nozzles, A mounting body on which multiple dispensing tips are placed at predetermined intervals in the first and second directions, In order to attach the plurality of dispensing tips to the plurality of dispensing nozzles, a mounting mechanism is provided for attaching the aforementioned mounting body on which the plurality of dispensing tips are placed to the dispensing body side, A removal mechanism for removing the aforementioned mounting unit on which the multiple dispensing tips are placed from the dispensing body side, The system comprises a control unit that controls the operation of the plurality of dispensing nozzles, the mounting mechanism, and the removal mechanism, The dispensing device comprises a mounting plate on which the plurality of dispensing tips are mounted at predetermined intervals in a first direction and a second direction, and a mounting plate frame that surrounds at least a portion of the periphery of the mounting plate, wherein the mounting plate is rectangular, and the mounting plate frame surrounds three sides of the rectangle.
2. In the dispensing apparatus according to claim 1, The mounting mechanism comprises one or more mounting magnets provided on one of the above-described mounting plate frame and the above-described dispensing body, and one or more metal bodies provided on the other of the above-described mounting plate frame and the above-described dispensing body, in a dispensing device.
3. In the dispensing device according to claim 1 or 2, The aforementioned mounting plate frame is suspended from the dispensing body side, and is part of the dispensing device.
4. In the dispensing device according to claim 2, The plurality of mounting magnets are arranged to surround one of the plurality of dispensing tips and the plurality of dispensing nozzles. A dispensing device in which the plurality of metal bodies are arranged to surround the other of the plurality of dispensing tips and the plurality of dispensing nozzles.
5. In the dispensing device according to any one of claims 1 to 4, The dispensing device comprises a mounting mechanism consisting of one or more first magnets provided on one of the above-described mounting body and the dispensing body, and one or more second magnets provided on the other of the above-described mounting body and the dispensing body.
6. In the dispensing apparatus according to claim 5, The plurality of first magnets are arranged to surround one of the plurality of dispensing tips and the plurality of dispensing nozzles. A dispensing device in which the plurality of second magnets are arranged to surround the other of the plurality of dispensing tips and the plurality of dispensing nozzles.
7. In the dispensing device according to any one of claims 1 to 6, The removal mechanism comprises a remover that applies force to the aforementioned object in a direction that separates the aforementioned object from the dispensing body, and a remover moving mechanism that moves the remover, in a dispensing device.
8. In the dispensing apparatus according to claim 7, A dispensing device in which the remover presses the upper surface of the holder and / or the upper end surfaces of the plurality of dispensing tips, thereby removing the plurality of dispensing tips from the plurality of dispensing nozzles.
9. In the dispensing apparatus according to any one of claims 1 to 8, A dispensing device comprising a magnetic force application unit that applies magnetic force to the interior of each of the multiple dispensing tips, with the multiple dispensing tips placed on the mounting body attached to the multiple dispensing nozzles.
10. In the dispensing apparatus according to claim 9, The magnetic force application part comprises a comb portion composed of a plurality of protruding pieces, Multiple comb magnets arranged on each of the multiple protruding pieces, A dispensing device comprising a comb moving mechanism that moves the plurality of comb portions in a direction to insert or withdraw between the plurality of dispensing nozzles.
11. In the dispensing apparatus according to any one of claims 1 to 10, A dispensing device comprising the plurality of dispensing nozzles and elastic members that come into contact with the plurality of dispensing tips.
12. A sample processing and measuring device comprising: a first dispensing unit for dispensing a parent sample from a parent sample container into a child sample container; a processing unit for extracting nucleic acids from the child sample in the child sample container; a heating unit for repeatedly heating and cooling to amplify the extracted nucleic acids; a measuring unit for measuring the amplified nucleic acids; and a second dispensing unit for dispensing reagents or solutions to at least the processing unit, The specimen processing and measuring device wherein the second dispensing unit is the dispensing device according to any one of claims 1 to 11.
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