WO2022230448A1 - 分注装置、及び検体処理測定システム - Google Patents
分注装置、及び検体処理測定システム Download PDFInfo
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- WO2022230448A1 WO2022230448A1 PCT/JP2022/012830 JP2022012830W WO2022230448A1 WO 2022230448 A1 WO2022230448 A1 WO 2022230448A1 JP 2022012830 W JP2022012830 W JP 2022012830W WO 2022230448 A1 WO2022230448 A1 WO 2022230448A1
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- Prior art keywords
- dispensing
- tips
- nozzles
- mounting
- dispensing device
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- 238000012545 processing Methods 0.000 title claims description 38
- 239000012491 analyte Substances 0.000 title 1
- 230000007246 mechanism Effects 0.000 claims abstract description 83
- 229910052751 metal Inorganic materials 0.000 claims description 55
- 239000002184 metal Substances 0.000 claims description 55
- 230000005291 magnetic effect Effects 0.000 claims description 22
- 238000003825 pressing Methods 0.000 claims description 19
- 150000007523 nucleic acids Chemical class 0.000 claims description 14
- 102000039446 nucleic acids Human genes 0.000 claims description 14
- 108020004707 nucleic acids Proteins 0.000 claims description 14
- 238000010438 heat treatment Methods 0.000 claims description 9
- 238000001816 cooling Methods 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 239000000284 extract Substances 0.000 claims description 2
- 238000003780 insertion Methods 0.000 claims description 2
- 230000037431 insertion Effects 0.000 claims description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 21
- 238000005259 measurement Methods 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000006249 magnetic particle Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 6
- 230000002093 peripheral effect Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000011109 contamination Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 208000025721 COVID-19 Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 210000003097 mucus Anatomy 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 241000711573 Coronaviridae Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000003302 ferromagnetic material Substances 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229910001172 neodymium magnet Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1065—Multiple transfer devices
- G01N35/1074—Multiple transfer devices arranged in a two-dimensional array
Definitions
- the present invention relates to a pipetting device to which a plurality of pipetting tips can be attached collectively, and a sample processing and measuring system equipped with this pipetting device.
- PCR polymerase chain reaction
- samples containing pathogens saliva, nasopharyngeal mucus, etc.
- nucleic acids DNA or RNA
- pathogens are detected based on the amplified nucleic acids. is detected. Since the end of 2019, the world has been exposed to the pandemic of the new coronavirus (COVID-19).
- the PCR method is used for the detection of COVID-19.
- the PCR method is mainly performed manually, but it is difficult to continuously perform a large amount of inspection processing manually, and there is a possibility that erroneous operation and contamination may occur during the processing process. be.
- a dispensing head device 10 includes a plurality of dispensing nozzles 16 arranged on a plane at predetermined intervals.
- the dispensing head device 101 attaches a plurality of dispensing tips 18 to a plurality of dispensing nozzles 16 to perform dispensing to a plurality of wells 4 a of the microplate 4 .
- the dispensing tip is attached to the dispensing nozzle by pressing the lower end of the dispensing nozzle with an elastic member such as an O-ring attached into the upper opening of the dispensing tip.
- an elastic member such as an O-ring attached into the upper opening of the dispensing tip.
- the dispensing nozzle is provided with an elastic member such as an O-ring to improve close contact with the dispensing tip. If the dispensing tip is repeatedly attached to and detached from the dispensing nozzle, the elastic member will deteriorate, causing liquid and gas to leak from between the dispensing nozzle and the dispensing tip, or the dispensing tip to fall from the dispensing nozzle. may occur. Therefore, it is necessary to replace the elastic member periodically.
- Patent Document 1 for a plurality of pipetting nozzles arranged at predetermined intervals on a plane, it is necessary to replace the elastic member such as an O-ring after removing each pipetting nozzle from the pipetting device. , and the maintenance of the dispensing nozzle was time-consuming.
- an object of the present invention is to provide a pipetting device capable of collectively attaching a plurality of pipetting tips to a plurality of pipetting nozzles, and a sample processing and measuring system equipped with this pipetting device.
- a pipetting device capable of collectively attaching a plurality of pipetting tips to a plurality of pipetting nozzles
- a sample processing and measuring system equipped with this pipetting device.
- the elastic members of the plurality of dispensing nozzles are less likely to deteriorate, and the plurality of dispensing nozzles can be easily attached.
- An object of the present invention is to provide an apparatus and a sample processing and measurement system equipped with this pipetting apparatus.
- 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 for mounting a plurality of dispensing tips in the first direction and the second direction at predetermined intervals; an attachment mechanism for attaching the mounting body on which the plurality of dispensing tips are placed to the side of the dispensing main body in order to attach the plurality of dispensing tips to the plurality of dispensing nozzles; a removal mechanism for removing the placement body on which the plurality of dispensing tips are placed from the side of the dispensing main body;
- a dispensing device comprising: a controller that controls operations of the plurality of dispensing nozzles, the attaching mechanism, and the removing mechanism.
- the placement body includes a placement plate on which the plurality of dispensing tips are placed at predetermined intervals in the first direction and the second direction, and a placement plate frame surrounding at least a part of the periphery of the placement plate. and a dispensing device.
- the dispensing device wherein the loading plate is rectangular, and the loading plate frame surrounds three sides of the rectangle.
- the attachment mechanism includes one or more attachment magnets provided on one of the placement plate frame and the dispensing main body, and one or more attachment magnets provided on the other of the placement frame and the dispensing main body.
- a dispensing device comprising a plurality of metal bodies.
- the attachment mechanism includes one or more attachment magnets provided on one of the placement body and the dispensing main body, and one or more attachment magnets provided on the other of the placement body and the dispensing body.
- a dispensing device comprising: [Aspect 7] In the dispensing device according to aspect 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; The dispensing device, wherein the plurality of metal bodies are arranged to surround the other of the plurality of dispensing tips and the plurality of dispensing nozzles.
- the attachment mechanism includes one or a plurality of first magnets provided on one of the placement body and the dispensing body, and one or more magnets provided on the other of the placement body and the dispensing body.
- a dispensing device comprising a plurality of second magnets;
- the plurality of first magnets are arranged to surround one of the plurality of dispensing tips and the plurality of dispensing nozzles, The dispensing device, wherein the plurality of second magnets are arranged to surround the other of the plurality of dispensing tips and the plurality of dispensing nozzles.
- the removal mechanism includes a remover that applies a force to the mounting body in a direction in which the mounting body separates from the dispensing main body, and a remover moving mechanism that moves the remover.
- the magnetic force applying unit includes a comb portion composed of a plurality of projecting pieces, a plurality of comb magnets arranged on each of the plurality of projecting pieces; a comb moving mechanism that moves the plurality of comb portions in a direction of insertion or withdrawal between the plurality of dispensing nozzles.
- the dispensing device wherein the plurality of dispensing nozzles includes an elastic member that contacts the plurality of dispensing tips.
- Aspect 15 a first dispensing unit that dispenses the primary sample from the primary sample container into the secondary sample container; a processing unit that extracts nucleic acid from the secondary sample in the secondary sample container; and a heating and cooling unit for amplifying the extracted nucleic acid.
- a sample processing and measuring device comprising a repeating heating section, a measuring section that measures the amplified nucleic acid, and a second dispensing section that dispenses a reagent or solution to at least the processing section,
- a sample processing and measuring apparatus, wherein the second pipetting unit is the pipetting device according to any one of aspects 1 to 14.
- the pipetting device of the present invention and the sample processing and measuring system equipped with this pipetting device can collectively attach and detach a plurality of pipetting tips to and from a plurality of pipetting nozzles.
- FIG. 1 is an upper perspective view showing a sample processing and measurement system according to a first embodiment of the present invention
- FIG. FIG. 2 is a front view showing the sample processing and measurement system of FIG. 1
- FIG. 2 is a schematic top view showing a stage of the sample processing and measurement system of FIG. 1
- FIG. 2A is a top view showing the dispensing range of the first pipetting unit
- FIG. 4B is a top view showing the dispensing range of the second pipetting unit of the sample processing and measuring system of FIG. 1
- FIG. 2 is an upper perspective view showing the second dispensing section (dispensing device) of FIG. 1
- FIG. 6 is a bottom perspective view showing the second dispensing section of FIG. 5;
- FIG. 6 is an upper perspective view showing the placement body of the dispensing tip of FIG. 5; 6A and 6B are an upper perspective view showing the second pipetting unit in FIG. 5 without a pipetting tip attached, and FIG. 8B showing an upper perspective view with a pipetting tip attached.
- FIG. 6 shows (a) a lower perspective view with the dispensing tip attached, and (b) a lower perspective view with the dispensing tip not attached, showing the second dispensing unit of FIG. 5 .
- FIG. 6 shows (a) a side view, (b) a front view of a state in which the magnetic force applying portion is retracted, and (c) a front view of a state in which the magnetic force applying portion is protruded, showing the second dispensing portion of FIG. 5 .
- FIG. 9(b) is a partially cutaway side view showing the second pipetting unit of Fig. 9(a);
- FIG. 11 is an enlarged cross-sectional view of the vicinity of a dispensing nozzle showing a fourth modification of the first embodiment;
- FIG. 11 is an upper perspective view showing a second dispensing section according to a second embodiment of the present invention;
- 13 is an upper perspective view showing a state in which a plurality of dispensing tips are attached by the second dispensing section of FIG. 12;
- FIG. FIG. 13 is an upper perspective view showing the second dispensing tip rack and a plurality of dispensing tips of FIG. 12;
- FIG. 15 is an exploded perspective view of the second dispensing tip rack of FIG. 14;
- FIG. 11 is a front view showing the operation of the second dispensing section according to the second embodiment;
- FIG. 11 is an upper perspective view showing a second dispensing section according to a third embodiment of the present invention;
- FIG. 18 is a front view showing the second pipetting unit of FIG. 17;
- FIG. 18 is an exploded perspective view showing the second dispensing part of FIG. 17;
- FIG. 19 shows (a) a horizontal cross-sectional view and (b) a vertical cross-sectional view along line bb showing the second pipetting unit of FIG. 18 ;
- FIG. 11 is a front view showing the operation of the second dispensing section according to the second embodiment;
- FIG. 11 is a front view showing the operation of the second dispensing section according to the second embodiment;
- the specimen is a biologically relevant substance, preferably a body fluid collected from a living body (e.g., saliva, nasopharyngeal mucus, etc.), or any dissolvable tissue can be used.
- a biologically relevant substance preferably a body fluid collected from a living body (e.g., saliva, nasopharyngeal mucus, etc.), or any dissolvable tissue can be used.
- the x-direction, y-direction, and z-direction in this embodiment correspond to the first direction, the second direction, and the third direction, respectively, in the claims.
- the sample processing and measurement system 1000 includes a base 100 having a stage for supporting each part, a first pipetting unit 200 for pipetting the primary sample from the primary sample container into the secondary sample container (well), the first pipetting unit 200 and /or a moving mechanism 300 for moving the second pipetting unit 400 in the x direction, a second pipetting unit (piping device) 400 for pipetting secondary samples from secondary sample containers and performing PCR-related processing, and a first It is composed of a first dispensing tip housing section 500 that houses a plurality of dispensing tips for the dispensing section 200, and a control section (computer) 600 that controls the operations of each section 200-400.
- the base 100 includes a fixed stage 105, a movable stage 120 that can move in the y direction, and a movement mechanism (belt and motor) 122 for the movable stage 120.
- a control unit 600 controls the operation of the moving mechanism 122 .
- a parent sample storage unit 110 is provided on a fixed stage 105 on the upper surface of the base 100 .
- the primary sample storage unit 110 includes multiple primary sample container racks 114 that store multiple primary sample containers 112 in a row in the y direction.
- the first pipetting unit 200 is a pitch change type pipetting device having a plurality of pipetting nozzles arranged in a row.
- the first pipetting unit 200 can preferably have 12 pipetting nozzles.
- the first pipetting unit 200 includes a plurality of pipetting nozzles (a plurality of first pipetting nozzles) 205 arranged in a row in the y direction, and a nozzle between the pipetting nozzles 205.
- a pitch conversion mechanism 210 that converts the pitch in the y direction of the pipette, and a support portion 220 that supports the entire first dispensing section 200 on the movement mechanism 300 so as to be movable in the x direction.
- the control section 600 controls the operation of the drive motor of the pitch conversion mechanism 210 .
- the pitch conversion mechanism 210 includes a plurality of guide rods 206 for sliding the plurality of dispensing nozzles 205 in the y direction, a link mechanism connected to each of the plurality of dispensing nozzles 205 and capable of extending and contracting in the y direction, and a link mechanism. and a link drive for driving.
- this pitch conversion mechanism for example, the pitch conversion mechanism described in FIG. 5 of International Publication No. 2016/031705 by the inventor of the present application can be used.
- the pitch conversion mechanism 210 corresponds to the first pitch corresponding to the arrangement of the multiple primary sample containers 112 arranged on the primary sample container rack 114 and the arrangement of the multiple secondary sample containers (wells) arranged on the PCR plate. It can be stretched and contracted between the second pitch.
- the first pitch eg 22.5 mm
- the second pitch eg 9.0 mm
- the moving mechanism 300 includes rails 310 that movably support the first pipetting unit 200 and/or the second pipetting unit 400, and the first pipetting unit 200. It is composed of a moving first belt 320, a first motor 330 that drives the first belt, a second belt 340 that moves the second dispensing section 400, and a second motor 350 that drives the second belt 340. be.
- the controller 600 controls operations of the first motor 330 and/or the second motor 350 .
- a primary sample storage unit 110 is provided on the fixed stage 105 .
- a second pipetting tip storage unit 121 that stores a plurality of pipetting tips for the second pipetting unit 400, and a PCR plate or A processing unit 122 that accommodates a microplate and executes processing, and a heating unit (thermal cycler) 123 that stores a PCR plate containing a plurality of extracted nucleic acids extracted from secondary samples in the processing unit 122 and executes PCR.
- a reagent storage unit 124 for containing reagents used for processing of secondary samples, amplification of nucleic acids, detection of amplified nucleic acids, etc., and a disposal tank 125 for discarding solutions that are no longer needed after processing.
- the PCR plate or microplate preferably has 96 (8 ⁇ 12) wells approximately evenly spaced in the xy directions.
- the heating unit 123 repeats heating and cooling to amplify the extracted nucleic acid.
- a universal cooling unit 126 and/or a PCR plate storage unit 127 for storing PCR plates may preferably be provided on the movable stage 120 .
- the movable stage 120 can be provided with a cooling mechanism (cooling block) 128 on the lower surface side of the general-purpose cooling section 126 .
- the control unit 600 controls operations of the heating unit 123 and the cooling mechanism 128 .
- the sample processing and measurement system 1000 may preferably include an ID reader for reading the primary sample ID provided in the primary sample container and the rack ID of the primary sample container rack, and/or a real-time PCR module for performing real-time PCR. .
- FIG. 4(a) shows a state in which the movable stage 120 has moved forward (away from the moving mechanism 300 in the y direction).
- a dashed line area 200A indicates an area in which the row of the plurality of dispensing nozzles 205 of the first dispensing unit 200 (FIG. 1) can move.
- the plurality of dispensing nozzles 205 are arranged at the first pitch (small pitch), and the first dispensing tip storage unit 500, a portion of the primary sample storage unit 110, the dispensing tip disposal unit 130 , the first dispensing tip rack 121 , the pretreatment section 122 , and the reagent storage section 124 are included above.
- the dashed line area 200A preferably includes the entire upper side of the primary sample storage unit 110 with the plurality of dispensing nozzles 205 at the second pitch (large pitch).
- FIG. 4(b) shows a state in which the movable stage 120 has moved to the far side (direction approaching the moving mechanism 300).
- a dashed line area 400X indicates an area in which a group of multiple dispensing nozzles 436 (FIG. 5A) of the second dispensing section 400 can move.
- the dashed line area 400X includes above the dispensing tip disposal section 130, the first dispensing tip rack 121, the heating section 123, the waste liquid tank 125, and the PCR plate storage section 125, respectively.
- the plurality of dispensing nozzles 436 are arranged at predetermined intervals (substantially equal intervals in the xy direction) on the lower end plane (xy direction) of the sub-support portion 420 .
- the second dispensing section (dispensing device) 400 will be described with reference to FIGS. 5 to 9.
- the second pipetting unit 400 includes a plurality of pipetting nozzles corresponding to PCR plates or microplates having a plurality of wells.
- the second dispensing unit 400 includes an attachment mechanism for collectively attaching a plurality of dispensing tips 142 arranged at predetermined intervals in the xy direction to a plurality of dispensing nozzles 436, A removal mechanism is provided for collectively removing the plurality of arranged dispensing tips 142 from the plurality of dispensing nozzles 436 .
- the second pipetting unit 400 can preferably include 96 pipetting nozzles 436 arranged at approximately equal intervals in the xy direction, as shown in FIG. 5A.
- the second pipetting unit 400 includes a main support 410 that supports the entire second pipetting unit 400 so as to be movable in the x-direction with respect to the moving mechanism 300, and a main support 410 that supports the main support 410. It has a sub-support 420 that can move in the z-direction and a sub-support-moving motor 412 that moves the sub-support 420 in the z-direction.
- the sub-support part 420 includes a pipetting main body (cylinder block) 430, a plurality of plungers 438 movable in the z-direction with respect to the pipetting main body 430 in order to perform suction and ejection of a plurality of pipetting nozzles 436, and a plunger and a plunger motor 422 that moves a plurality of plungers 438 in the z-direction by moving the moving plate 439 in the z-direction.
- the dispensing main body 430 is fixed to the sub-support portion 420 .
- the controller 600 controls the operation of the sub-support moving motor 412 and/or the plunger motor 422 .
- FIG. 5 An attachment mechanism for collectively attaching a plurality of dispensing tips 142 to a plurality of dispensing nozzles 436 will be described.
- a second dispensing tip rack 140 and second dispensing tips 142 housed in the second dispensing tip rack 140 at predetermined intervals in the xy direction.
- a group and mounting bodies (catch plates) 144 on which the second dispensing tips 142 are mounted at approximately equal intervals in the xy direction are arranged.
- the second dispensing tip 142 has an upper end opening 142a with a larger outer diameter than the central portion.
- the mounting body 144 is provided with a plurality of through holes 144a that are arranged at predetermined intervals in the xy direction and penetrate 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 hole 144a of the mounting body 144, the second dispensing tip 142 has the lower end of the upper end opening 142a of the through hole 144a. placed around. Note that a plurality of dispensing tips 142 may be fixed to the mounting body 144 .
- the mounting body 144 includes one or more metal bodies (metal discs) 144b.
- One or more metal bodies 144 b are fixed to the mounting body 144 .
- the plurality of metal bodies 144b are preferably arranged so as to surround the plurality of dispensing tips 142 mounted on the mounting body 144.
- One or more metal bodies 144 b are preferably arranged on the periphery of the mounting body 144 .
- the one or more metal bodies 144b are preferably accommodated in one or more recesses 144c formed in the mounting body 144, respectively.
- a group of a plurality of dispensing nozzles 436 and one or a plurality of mounting magnets 432 are mounted on the lower surface of a dispensing body (cylinder block) 430 fixed to the sub-support portion 420. and are provided.
- a plurality of mounting magnets 432 are preferably arranged to surround a group of dispense nozzles 436 .
- the plurality of mounting magnets 432 attract the metal plates 144b of the plurality of placement bodies 144.
- a plurality of mounting magnets 432 preferably protrude from the bottom surface of dispensing body 430 in the z-direction.
- Mounting magnet 432 may preferably be cylindrical in shape.
- Mounting magnet 432 may preferably be a neodymium magnet.
- the mounting mechanism is composed of one or more mounting magnets 432 fixed to the dispensing main body 430 side and one or more metal bodies 144b fixed to the mounting body 144 side.
- FIG. 7A the plurality of dispensing tips 142 are accommodated in the second dispensing tip rack 140 with the plurality of dispensing tips 142 mounted on the mounting body 144 .
- a group of a plurality of dispensing nozzles 436 (FIG. 5A) of the second dispensing unit 400 descends from above the mounting body 144 toward the mounting body 144, and the plurality of nozzles fixed to the mounting body 144 When the metal body 144b is attracted to the plurality of magnet bodies 432 (FIG.
- the plurality of dispensing nozzles 436 are inserted into the upper end openings 142a of the plurality of dispensing tips 142, respectively, and the plurality of dispensing tips 142 and a plurality of dispensing nozzles 436 are in close contact with each other.
- the weight of the plurality of pipetting tips 142 is determined not by the plurality of pipetting nozzles 436 but by the plurality of magnet bodies 432 arranged beside the plurality of pipetting nozzles 436 via the plurality of metal bodies 144b of the mounting body 144. can support. Therefore, the plurality of dispensing nozzles 436 may be press-fitted into the upper end openings 142a of the plurality of dispensing tips 142 with a relatively small force that allows the plurality of dispensing tips 142 to adhere to each other.
- An elastic member (such as an O-ring) can preferably be provided on the outer peripheral surface of each of the plurality of dispensing nozzles 436 to make contact with the dispensing tip.
- a remover 434 is provided below the dispensing main body 430 so as to be movable in the z-direction with respect to the sub-support 420 .
- the remover 434 can collectively remove the plurality of dispensing tips 142 from the plurality of dispensing nozzles 436 as will be described later.
- the remover 434 has a substantially plate shape and includes a plurality of through holes. A plurality of dispensing nozzles 436 pass through a plurality of through holes of the remover 434 and are exposed downward. Plurality of dispensing nozzles 436 are not integrated with remover 434 .
- the sides of the dispensing body 430 are provided with a plurality of push rods (remove movers) movable in the z-direction relative to the sub-support 420 to push the remover 434 downward. mechanism) 437 is provided.
- the plurality of push 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 vertically together.
- the control unit 600 controls movement of the plurality of pressing rods 437 . As shown in FIG.
- the lower ends of the plurality of push rods 437 are respectively arranged near the plurality of mounting magnets 432 (mounting mechanism) to push the remover 434 downward.
- the removal mechanism is composed of a remover 434 , a plurality of push rods 437 and a mounting body 144 .
- the remover 434 applies a force to the placement body 144 in a direction in which the plurality of dispensing tips and the placement body 144 are separated from the dispensing main body 430 .
- FIG. 8(a) the plurality of dispensing tips 142 are attached to the group of the plurality of dispensing nozzles 436 (FIG. 5A) while the plurality of dispensing tips 142 are held on the mounting body 144. It is In this state, when the control unit 600 moves the plurality of push rods 437 downward, the remover 434 also moves downward, and the lower surface of the remover 434 is aligned with the upper surface of the mounting body 144 and/or the upper end surface of the plurality of dispensing tips 142 . press . When the force by this pressing exceeds the force with which the plurality of mounting magnets 432 attracts the plurality of metal bodies 144b, as shown in FIG. Removed from multiple dispensing nozzles 436 .
- one or more mounting magnets 432 are fixed to the mounting body 144, one or more metal bodies 144b are fixed to the plurality of pressing rods 437, and the plurality of pressing rods 437 are integrated.
- the comb-shaped (comb-shaped) magnetic force applying section 414 included in the second dispensing section 400 of the present embodiment will be described.
- the method proposed by the inventor of the present application in International Publication No. 97/44671 can be preferably used. This technique 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 with respect to the dispensing tip.
- the second pipetting unit 400 of the present embodiment selectively exerts a magnetic force on the magnetic particles inside the plurality of pipetting tips 142 attached to the plurality of pipetting nozzles 436.
- a magnetic force applying unit 414 is provided.
- the magnetic force applying portion 414 includes a comb body 414a movable in the x direction with respect to the main support portion 410, and a comb body 414a for moving the comb body 414a in the x direction. , a comb portion 414b provided at the distal end of the main body 414a on the side of the plurality of dispensing tips 142, and each protruding piece of the comb portion 414b at predetermined intervals in the x direction. It is composed of a plurality of arranged comb magnets 414c (FIGS. 5(a) and 9(b)) and rails 414d for moving the comb bodies 414a in the x direction with respect to the main support portion 410.
- FIG. The controller 600 controls the operation of the comb body moving motor 416 .
- a plurality of comb portions are arranged between a plurality of rows of the plurality of dispensing tips 142 while the plurality of dispensing tips 142 are held by the dispensing body 430.
- a plurality of comb magnets 414c provided on each protruding piece of a plurality of comb portions 414b will attract magnetic particles in the solution within the plurality of dispensing tips 142. can be done.
- each protruding piece of the plurality of comb portions 414b is pulled out from between the rows of the plurality of dispensing tips 142.
- the plurality of comb magnets 414c provided on each protruding piece of the plurality of comb portions 414b do not exert a magnetic force on the magnetic particles in the plurality of dispensing tips 142, and the magnetic particles are removed from the plurality of dispensing tips 142. disperse in the solution inside.
- a plurality of metal bodies 144b fixed to the mounting body 144 are attracted by a plurality of mounting magnets 432 fixed to the dispensing main body 430 side as shown in FIG. .
- the magnetic force of the plurality of mounting magnets 432 may affect the plurality of comb magnets 414 c of the magnetic force applying section 414 and the magnetic particles within the dispensing tip 142 . Therefore, preferably, magnetic force shields (ferromagnetic material such as iron) can be provided on the side surfaces of the plurality of mounting magnets 432 and the side and lower surfaces of the plurality of metal bodies 144b.
- the O-ring alone does not support the load of the dispensing tip so that the dispensing tip does not drop from the dispensing nozzle.
- a dispensing tip is pressed into a dispensing nozzle fitted with an O-ring with a relatively large force so that the dispensing tip does not drop from the dispensing nozzle.
- the dispensing tip is repeatedly attached to and detached from the dispensing nozzle, the dispensing tip repeatedly slides against the O-ring, which deteriorates the O-ring and reduces the pressure force.
- the dispensing tip may come off from the dispensing nozzle, causing the liquid to splatter and cause contamination. Therefore, in order to maintain the pressure force of the O-ring, troublesome and delicate replacement or maintenance of the O-ring is required.
- the dispensing tip 142 is press-fitted into the dispensing nozzle 436 fitted with the O-ring with a relatively large force such that the dispensing nozzle 436 supports the load of the dispensing tip.
- the load of the dispensing tip 142 is applied to the mounting mechanism (mounting body 144, Since it is applied to the metal body 144b, the magnet 432, and the sub-support 420), it is not necessary to press the dispensing tip 142 into the dispensing nozzle 436 fitted with the O-ring with a relatively large force.
- the O-ring should have enough elastic force to seal the gap between the dispensing nozzle 436 and the upper end opening 142a of the dispensing tip 142 so that gas and liquid do not leak. good.
- the attachment mechanism of this embodiment when attaching the dispensing tip 142 to the dispensing nozzle 436, it is necessary to press-fit the dispensing tip 142 with a relatively large force into the dispensing nozzle 436 fitted with the O-ring. Therefore, the O-ring is less likely to deteriorate.
- the mounting mechanisms of the first to third embodiments include mounting bodies 144, 144A, and 144B of the dispensing tip 142, and 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 for attracting a plurality of metal bodies 144b, 144A1b, 144B1b.
- the plurality of mounting magnets 432 can be the plurality of first magnets 432, and the plurality of metal bodies 144b, 144A1b, 144B1b can be the plurality of second magnets.
- a pair of the first magnet and the second magnet are arranged so as to have different polarities while facing each other.
- the pair of magnets 432 and metal bodies 144b, 144A1b, 144B1b are in contact with each other.
- the pair of magnets 432 and the metal bodies 144b, 144A1b, 144B1b do not contact each other, and the dispensing tips 142 are separated in a state in which they face each other with a gap between them. It is attached to the injection nozzle 436 .
- the gap between the pair of magnets 432 and the metal bodies 144b, 144A1b, 144B1b is preferably 0.7-0.3 mm, more preferably about 0.5 mm.
- the attachment mechanism of the third modification is such that the pair of first and second magnets of the first modification do not contact each other, and are opposed to each other with a gap between them, and dispensing is performed.
- a tip 142 is attached to the dispensing nozzle 436 . Since the plurality of first magnets are not in contact with the plurality of second magnets and are attracted by magnetic force, the plurality of metal bodies 144b, 144A1b, 144B1b can be stably held by the plurality of mounting magnets 432. can.
- the gap between the pair of first and second magnets is preferably 0.7-0.3 mm, more preferably about 0.5 mm.
- the O-rings of the first to third embodiments of the present invention are preferably arranged on the inner peripheral surface of the upper end opening 142a of the dispensing tip 142 and the outer peripheral surface of the dispensing nozzle 436 as in the conventional O-rings. It is arranged on the outer peripheral surface of the dispensing nozzle 436 so as to be positioned between the .
- the O-ring 438 of the fourth modification is arranged on the lower surface 434a of the remover 434 surrounding the dispensing nozzle 436, as shown in FIG. When dispensing tip 142 is attached to dispensing nozzle 436 , O-ring 438 is positioned between lower surface 434 a and top opening 142 a of dispensing tip 142 .
- 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 section, and the configuration and operation of the other parts are the same as those of the sample processing system 1000. Since they are the same, drawings and descriptions of the configurations and operations of other parts are omitted.
- FIG. 1 A second dispensing section 400A according to the second embodiment will be described with reference to FIGS. 12 to 16.
- FIG. Portions common to the second pipetting unit 400A and the second pipetting unit 400 are given the same reference numerals as those of the second pipetting unit 400.
- FIG. The second pipetting unit 400A includes multiple pipetting nozzles 436 corresponding to a PCR plate or microplate having multiple wells.
- the second dispensing unit 400A includes an attachment mechanism for collectively attaching a plurality of dispensing tips 142 arranged at predetermined intervals in the xy direction to a plurality of dispensing nozzles 436 (FIG.
- the second pipetting unit 400 can preferably include 96 pipetting nozzles 436 arranged at approximately equal intervals in the xy direction, similar to FIG. 5A.
- the second dispensing section 400A includes the same magnetic force applying section 414 as in the first embodiment.
- the second dispensing section 400A includes a main support section 410 that supports the entire second dispensing section 400A so as to be movable in the x direction with respect to the moving mechanism 300, and the main support section 410.
- a sub-supporting part 420 movable in the z-direction and a sub-supporting part moving motor 412 for moving the sub-supporting part 420 in the z-direction are provided.
- the sub-support part 420 includes a pipetting main body (cylinder block) 430, a plurality of plungers 438 movable in the z-direction with respect to the pipetting main body 430 in order to perform suction and ejection of a plurality of pipetting nozzles 436, and a plunger and a plunger motor 422 that moves a plurality of plungers 438 in the z-direction by moving the moving plate 439 in the z-direction.
- the dispensing main body 430 is fixed to the sub-support portion 420 .
- the controller 600 controls the operation of the sub-support moving motor 412 and/or the plunger motor 422 .
- the dispensing main body 430 below the dispensing main body 430 are a second dispensing tip rack 140A, a group of second dispensing tips 142 accommodated in the second dispensing tip rack 140A at predetermined intervals in the xy direction, and a second dispensing tip rack 140A.
- a rectangular mounting plate 144A2 on which chips 142 are placed at predetermined intervals in the xy direction, and a mounting plate frame 144A2 surrounding at least a portion (three sides of the rectangle) of the mounting plate 144A2 are arranged.
- 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 (U shape).
- the mounting plate frame 144A1 includes one or more metal bodies (metal discs) 144A1b, an upper concave portion 144A1c that accommodates the periphery of the mounting plate 144A2, and a second dispensing tip. and a lower recess 144A1d that accommodates the upper end of the side wall of the rack 140A.
- One or more metal bodies 144Ab are fixed to the mounting body frame 144A.
- the plurality of metal bodies 144Ab are preferably arranged so as to surround the plurality of dispensing tips 142 mounted on the mounting plate 144A2 as shown in FIG.
- the one or more metal bodies 144Ab are preferably arranged at corners and/or ends of the mounting body frame 144A1.
- the one or more metal bodies 144A1b are preferably accommodated in one or more recesses formed in the mounting body frame 144A1, respectively.
- the mounting plate 144A2 is provided with a plurality of through holes 144A2a that are arranged at predetermined intervals in the xy direction and pass through 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 hole 144A2a of the mounting plate 144A2, the second dispensing tip 142 has the lower end of the upper end opening 142a of the through hole 144A2a. placed around. Note that a plurality of dispensing tips 142 may be fixed to the mounting plate 144A2.
- the second dispensing tip rack 140A supports a mounting body 144A containing a plurality of dispensing tips 142, and can translate the mounting body 144A containing a plurality of dispensing tips 142 in the x direction. Therefore, no side wall is provided on the plane (yz plane) perpendicular to the x direction.
- a group of a plurality of dispensing nozzles 436 and one or a plurality of mounting magnets 432 are fixed to the sub-support portion 420 below the dispensing main body (cylinder block) 430 .
- a plurality of mounting magnets 432 are preferably arranged to surround a group of dispense nozzles in the xy plane. The multiple mounting magnets 432 attract the multiple metal plates 144A1b of the mounting body 144A.
- the mounting mechanism is composed of one or more mounting magnets 432 fixed to the dispensing main body 430 (sub-support portion 420) side and one or more metal bodies 144A1b fixed to the mounting body 144A side. be.
- FIG. 12 and 16(a) in a mounting state in which a plurality of dispensing tips 142 are mounted on the mounting body 144A, the plurality of dispensing tips 142 are placed on the second dispensing tip rack 140A. Contained.
- the group of the plurality of pipetting nozzles 436 of the second pipetting unit 400A descends toward the mounting body 144A from above the mounting body 144A in the mounting state of FIG. 16(a), the state shown in FIG.
- the plurality of metal bodies 144A1b fixed to the mounting body 144A are attracted to the plurality of magnet bodies 432 to be in the attracted state.
- a plurality of dispensing nozzles 436 are respectively inserted into the upper end openings 142a of the plurality of dispensing tips 142, and the plurality of dispensing tips 142 and the plurality of dispensing nozzles 436 respectively In close contact.
- the second dispensing section 400A attaches a plurality of dispensing tips 142 and becomes movable in the xy direction.
- the weight of the plurality of dispensing tips 142 is distributed not through the plurality of dispensing nozzles 436 but through the plurality of metal bodies 144A1b of the mounting body 144A.
- a plurality of magnets 432 (sub-supports 420) arranged laterally of the injection nozzle 436 support it. Therefore, the plurality of dispensing nozzles 436 may be press-fitted into the upper end openings 142a of the plurality of dispensing tips 142 with a relatively small force that allows the plurality of dispensing tips 142 to adhere to each other.
- An elastic member (such as an O-ring) can preferably be provided on the outer peripheral surface of each of the plurality of dispensing nozzles 436 to make contact with the dispensing tip.
- a remover 434 is provided on the lower surface of the dispensing main body 430 so as to be movable in the z direction.
- the remover 434 can collectively remove the plurality of dispensing tips 142 from the plurality of dispensing nozzles 436 as will be described later.
- the remover 434 has a substantially plate shape and includes a plurality of through holes. A plurality of dispensing nozzles 436 pass through a plurality of through holes of the remover 434 and are exposed downward. Plurality of dispensing nozzles 436 are not integrated with remover 434 .
- a plurality of push rods (remove moving mechanism) 437 movable in the z-direction are provided on the side surface of the dispensing main body 430 to push the remover 434 downward.
- the plurality of push rods 437 can preferably be rod actuators. Since the lower ends of the multiple pressing rods 437 are fixed to the remover 434 , the multiple pressing rods 437 and the remover 434 move vertically with respect to the sub-support 420 .
- the control unit 600 controls movement of the plurality of pressing rods 437 . As shown in FIG.
- the lower ends of the plurality of push rods 437 are arranged near the plurality of mounting magnets 432 (mounting mechanism), respectively, and push the remover 434 downward.
- the removal mechanism is composed of a remover 434, a plurality of push rods 437, and a mounting body 144A.
- the remover 434 applies force to the placement body 144A in a direction in which the plurality of dispensing tips 142 and the placement body 144A are separated from the dispensing main body 430 .
- the plurality of dispensing tips 142 are attached to the group of the plurality of dispensing nozzles 436 in a holding state in which the plurality of dispensing tips 142 are held on the mounting body 144A. .
- the control unit 600 moves the plurality of push rods 437 downward
- the remover 434 also moves downward, and the lower surface of the remover 434 is aligned with the upper surface of the mounting body 144A and/or the plurality of pressure rods.
- the upper end surface of the dispensing tip 142 is pressed. When the force due to this pressing exceeds the force with which the plurality of mounting magnets 432 attracts the plurality of metal bodies 144A1b, as shown in FIG. Removed from multiple dispensing nozzles 436 .
- the mounting body 144A is composed of the mounting plate 144A2 and the mounting body frame 144A2, the operator can separate the mounting body frame 144A2 from the mounting plate 144A2. After this separation, the mounting plate 144A2 on which the plurality of used dispensing tips 142 are mounted is discarded, and the mounting body frame 144A2 is placed on the mounting plate 144A2 on which the plurality of unused dispensing tips 142 are mounted. can be installed. This allows the mounting body frame 144A2 including the relatively expensive metal body 144A1b to be reused.
- 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 pipetting section, and the configuration and operation of the other parts are the same as those of the sample processing system 1000. Since they are the same, drawings and descriptions of the configurations and operations of other parts are omitted.
- FIG. 21(a) A second pipetting unit 400B according to the third embodiment will be described with reference to FIGS. 17 to 22.
- FIG. The second pipetting unit 400B includes a plurality of pipetting nozzles 436 (FIG. 21(a)) corresponding to PCR plates or microplates having a plurality of wells.
- the second pipetting unit 400B includes an attachment mechanism for collectively attaching a plurality of pipetting tips 142 arranged at predetermined intervals in the xy direction to a plurality of pipetting nozzles 436, A removal mechanism is provided for collectively removing the plurality of arranged dispensing tips 142 from the plurality of dispensing nozzles 436 .
- the second pipetting unit 400B can preferably include 96 pipetting nozzles 436 arranged at approximately equal intervals in the xy direction, as in FIG. 5A.
- the second dispensing section 400B has the same magnetic force applying section 414 as in the first embodiment.
- the second pipetting unit 400B includes a main support unit 410 that supports the entire second pipetting unit 400B so as to be movable in the x direction with respect to the moving mechanism 300, and a main support unit 410 that supports the main support unit 410. It has a sub-support 420 that can move in the z-direction and a sub-support-moving motor (not shown) that moves the sub-support 420 in the z-direction.
- the sub-support part 420 includes a pipetting main body (cylinder block) 430, a plurality of plungers 438 movable in the z-direction with respect to the pipetting main body 430 in order to perform suction and ejection of a plurality of pipetting nozzles 436, and a plunger A plunger motor (not shown) is provided for moving the plurality of plungers 438 in the z-direction by moving the moving plate 439 in the z-direction.
- the dispensing main body 430 is fixed to the sub-support portion 420 .
- the controller 600 controls the operation of the sub-support movement motor and/or the plunger motor.
- the mounting body 144B is composed of a mounting plate 144B2 and a mounting body frame 144B1.
- the mounting body frame 144B1 can preferably be formed in a U shape (U shape) as shown in FIG.
- the mounting plate frame 144B1 includes one or a plurality of metal bodies (metal disks) 144B1b, an upper concave portion 144B1c that accommodates the periphery of the mounting plate 144B2, and a a plurality of guide rods 144B1a protruding toward (in the z-direction).
- metal bodies 144Bb are fixed to the mounting body 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, respectively.
- the mounting body frame 144B1 Since the lower end of the guide rod 144B1a is fixed to the mounting body frame 144B1, the mounting body frame 144B1 is suspended from the sub-support 420 on the side of the dispensing main body 430 so as to be movable in the z direction.
- the plurality of metal bodies 144B1b are preferably arranged so as to surround the plurality of dispensing tips 142 mounted on the mounting plate 144A2 as shown in FIG. 20(a).
- the one or more metal bodies 144B1b are preferably arranged at the corners and/or ends of the carrier frame 144B1.
- the one or more metal bodies 144B1b are preferably accommodated in one or more recesses formed in the mounting body frame 144B1, respectively.
- the mounting plate 144B2 is provided with a plurality of through holes 144B2a that are arranged at predetermined intervals in the xy direction and pass through 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 hole 144B2a of the mounting plate 144B2, the second dispensing tip 142 has the lower end of the upper end opening 142a of the through hole 144B2a. placed around. Note that a plurality of 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 projecting portions 140Ba of the second dispensing tip rack 140Ba.
- the second dispensing tip rack 140B supports a mounting plate 144B2 containing a plurality of dispensing tips 142, and allows a mounting plate frame 144B1 to be integrally moved in the x-direction with the second pipetting unit 400B. Therefore, no side wall is provided on the plane (yx plane) perpendicular to the x direction.
- the second dispensing tip rack 140B has a pair of protrusions (pins) 140Ba extending in the z-direction from the upper end of its side wall. By inserting the protrusion 140Ba into the second through hole 144B2d (FIG. 19), the second dispensing tip rack 140A.
- the mounting plate 144B2 is positioned.
- a group of a plurality of dispensing nozzles 436 and one or a plurality of mounting magnets 432 are fixed to the sub-support portion 420 below the dispensing main body (cylinder block) 430 .
- a plurality of mounting magnets 432 are preferably arranged to surround a group of dispense nozzles 436 in the xy plane.
- the multiple mounting magnets 432 attract the multiple metal plates 144B1b of the mounting body 144B.
- the mounting mechanism is composed of one or more mounting magnets 432 fixed to the dispensing main body 430 side, and one or more metal bodies 144B1b fixed to the placement body 144B side.
- the plurality of dispensing tips 142 are accommodated in the second dispensing tip rack 140B in a mounted state in which the plurality of dispensing tips 142 are mounted on the mounting body 144B.
- the moving mechanism 300 moves the group of the plurality of dispensing nozzles 436 of the second dispensing section 400B toward the mounting body 144B in the x-direction, as indicated by the arrow in Step 1 .
- the plurality of dispensing nozzles 436 face the upper end openings of the plurality of dispensing tips 142 in the z direction. state.
- Step 2 the control unit 600 operates the sub-support moving motor 412 to lower the sub-support 420 until the plurality of magnets 432 and the plurality of metal bodies 144B1b are in contact with each other.
- 21(b) a plurality of magnet bodies 432 are in an attracted state in which a plurality of metal bodies 144B1b are attracted.
- the plurality of dispensing nozzles 436 are inserted into the upper end openings 142a of the plurality of dispensing tips 142, respectively, and the plurality of dispensing tips 142 and the plurality of dispensing nozzles 436 are in close contact with each other.
- Step 3 from the state shown in FIG. 21(b), as shown in FIG. With a plurality of dispensing tips 142 attached to 436, the second dispensing unit 400B becomes movable.
- the weight of the plurality of pipetting tips 142 is distributed not by the plurality of pipetting nozzles 436 but by the plurality of magnet bodies 432 ( A secondary support 420) may provide support. Therefore, the plurality of dispensing nozzles 436 may be press-fitted into the upper end openings 142a of the plurality of dispensing tips 142 with a relatively small force that allows the plurality of dispensing tips 142 to adhere to each other.
- An elastic member (such as an O-ring) can preferably be provided on the outer peripheral surface of each of the plurality of dispensing nozzles 436 to make contact with the dispensing tip.
- a remover 434 is provided on the lower surface of the dispensing main body 430 so as to be movable in the z direction.
- the remover 434 can collectively remove the plurality of dispensing tips 142 from the plurality of dispensing nozzles 436 as will be described later.
- the remover 434 has a substantially plate shape and includes a plurality of through holes. A plurality of dispensing nozzles 436 pass through a plurality of through holes of the remover 434 and are exposed downward. Plurality of dispensing nozzles 436 are not integrated with remover 434 .
- a plurality of pressing rods (remover moving mechanism) 437 movable in the z-direction are provided on the side surface of the dispensing main body 430 in order to press the remover 434 downward.
- the plurality of push 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 vertically together.
- the control unit 600 controls expansion and contraction of the plurality of pressing rods 437 . As shown in FIG.
- the lower ends of the plurality of push rods 437 are arranged near the plurality of mounting magnets 432 (mounting mechanism), respectively, and push the remover 434 downward.
- the removal mechanism is composed of a remover 434, a plurality of push rods 437, and a mounting body 144B.
- the remover 434 applies force to the placement body 144B in a direction in which the plurality of dispensing tips 142 and the placement body 144B are separated from the dispensing main body 430 .
- FIG. 22(d) The operation of the removal mechanism when removing a plurality of dispensing tips from a plurality of dispensing nozzles will be described using FIG.
- a plurality of dispensing tips 142 are arranged in a group of a plurality of dispensing nozzles 436 while the plurality of dispensing tips 142 are held on the mounting plate 144B2 (mounting body 144B).
- Step 4 when the control unit 600 moves the plurality of pressing rods 437 downward, the remover 434 also moves downward, and the lower surface of the remover 434 is positioned on the mounting body 144B (mounting plate frame 144B1 and The upper surface of the mounting plate 144B2) and/or the upper end surfaces of the plurality of dispensing tips 142 are pressed.
- the mounting plate 144B2 is removed from the plurality of dispensing nozzles 436.
- the mounting plate frame 144B1 is moved downward by its own weight, and the mounting plate frame 144B1 and the mounting plate 144B2 are separated in the z direction.
- the state of FIG. 22(e) since the platen plate 144B2 is separated from the platen plate frame 144B1 in the z direction, the state of FIG. can do.
- the mounting plate frame 144B1 held on the side of the second dispensing section 400B can be pulled out from the mounting plate 144B2 held on the side of the second dispensing tip rack 140B.
- the mounting body 144B is composed of a mounting plate 144B2 and a mounting body frame 144B2.
- the mounting body frame 144B2 can be separated from 144B2 without manual intervention. After this separation, only the mounting plate 144B2 on which the plurality of used dispensing tips 142 are mounted is discarded, and a mounting body is placed on the mounting plate 144B2 on which the plurality of unused dispensing tips 142 are mounted.
- the frame 144B2 can be attached horizontally without manual intervention. This makes it possible to reuse the mounting body frame 144A2 provided with the relatively expensive metal body 144A1b while avoiding contamination of the specimen.
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Abstract
Description
[態様1]
第1方向及び第2方向に所定間隔で配置された複数の分注ノズルを備える分注装置であって、
前記複数の分注ノズルを支持する分注本体と、
複数の分注チップを前記第1方向及び前記第2方向に所定間隔で載置する載置体と、
前記複数の分注チップを前記複数の分注ノズルに装着するために、前記複数の分注チップを載置した前記載置体を前記分注本体側に取り付ける取付機構と、
前記複数の分注チップを載置した前記載置体を前記分注本体側から取り外す取外機構と、
前記複数の分注ノズル、前記取付機構、及び前記取外機構の動作を制御する制御部とを備える、分注装置。
態様1に記載の分注装置において、
前記載置体は、前記複数の分注チップを前記第1方向及び前記第2方向に所定間隔で載置する載置板と、前記載置板の周囲の少なくとも一部を取り囲む載置板枠とから構成される、分注装置。
[態様3]
態様2に記載の分注装置において、
前記載置板は矩形であり、前記載置板枠は前記矩形の3辺を取り囲む、分注装置。
[態様4]
態様2又は3に記載の分注装置において、
前記取付機構は、前記載置板枠及び前記分注本体の一方に設けられた、1つ又は複数の取付磁石と、前記載置枠及び前記分注本体の他方に設けられた、1つ又は複数の金属体とから構成される、分注装置。
態様2~4のいずれか一項に記載の分注装置において、
前記載置板枠は、前記分注本体側から吊り下げられている、分注装置。
[態様6]
態様1~5のいずれか一項に記載の分注装置において、
前記取付機構は、前記載置体及び前記分注本体の一方に設けられた、1つ又は複数の取付磁石と、前記載置体及び前記分注本体の他方に設けられた、1つ又は複数の金属体とから構成される、分注装置。
[態様7]
態様4又は6に記載の分注装置において、
前記複数の取付磁石は、前記複数の分注チップ及び前記複数の分注ノズルの一方を取り囲むように配置され、
前記複数の金属体は、前記複数の分注チップ及び前記複数の分注ノズルの他方を取り囲むように配置される、分注装置。
態様1~3のいずれか一項に記載の分注装置において、
前記取付機構は、前記載置体及び前記分注本体の一方に設けられた、1つ又は複数の第1磁石と、前記載置体及び前記分注本体の他方に設けられた、1つ又は複数の第2磁石とから構成される、分注装置。
[態様9]
態様8に記載の分注装置において、
前記複数の第1磁石は、前記複数の分注チップ及び前記複数の分注ノズルの一方を取り囲むように配置され、
前記複数の第2磁石は、前記複数の分注チップ及び前記複数の分注ノズルの他方を取り囲むように配置される、分注装置。
[態様10]
態様1乃至10のいずれか一項に記載の分注装置において、
前記取外機構は、前記載置体が前記分注本体から分離する方向に前記載置体に対して力を加えるリムーバと、前記リムーバを移動するリムーバ移動機構とを備える、分注装置。
態様10に記載の分注装置において、
前記リムーバが、前記載置体の上面及び/又は前記複数の分注チップの上端面を押圧することにより、前記複数の分注チップが前記複数の分注ノズルから取り外される、分注装置。
[態様12]
態様1乃至11のいずれか一項に記載の分注装置において、
前記載置体に載置された前記複数の分注チップが前記複数の分注ノズルに取り付けられた状態で、前記複数の分注チップのそれぞれの内部に磁力を及ぼす磁力付与部を備える、分注装置。
態様12に記載の分注装置において、
前記磁力付与部は、複数の突出片から構成されるコーム部分と、
前記複数の突出片のそれぞれに配置された複数のコーム磁石と、
前記複数のコーム部分を前記複数の分注ノズルの間に挿入または引き抜く方向に移動するコーム移動機構とを備える、分注装置。
[態様12]
態様1乃至13のいずれか一項に記載の分注装置において、
前記複数の分注ノズルは、前記複数の分注チップと接触する弾性部材を備える、分注装置。
[態様15]
親検体容器から親検体を子検体容器に分注する第1分注部と、子検体容器中の子検体から核酸を抽出する処理部と、前記抽出された核酸を増幅するために加熱冷却を繰り返す加熱部と、前記増幅された核酸を測定する測定部と、少なくとも前記処理部に試薬又は溶液を分注する第2分注部と、を備える検体処理測定装置において、
前記第2分注部は、態様1乃至14のいずれか一項に記載の分注装置である、検体処理測定装置。
[検体処理測定システムの基本構成]
本発明の第1の実施形態に係る検体処理測定システム1000の基本構成を、図1及び図2を用いて説明する。検体処理測定システム1000は、各部を支持するステージを備える基部100と、親検体容器から親検体を子検体容器(ウェル)に分注する第1分注部200と、第1分注部200及び/又は第2分注部400をx方向に移動する移動機構300と、子検体容器から子検体を分注してPCRに関する処理を行う第2分注部(分注装置)400と、第1分注部200用の複数の分注チップを収容する第1分注チップ収容部500と、各部分200~400の動作を制御する制御部(コンピュータ)600とから構成される。
検体処理測定システム1000のステージ構造を図3の模式上面図を用いて説明する。固定ステージ105上には、親検体保管部110が設けられている。可動ステージ120上には、第2分注部400用の複数の分注チップを収容する第2分注チップ収容部121と、子検体の処理(精製、抽出)を実行するためのPCRプレート又はマイクロプレートを収容して処理を実行する処理部122と、処理部122で子検体から抽出された複数の抽出核酸を収容したPCRプレートを収容してPCRを実行する加熱部(サーマルサイクラー)123と、子検体の処理、核酸の増幅、及び増幅核酸の検出等に用いる試薬を収容する試薬保管部124と、処理等で不要となった溶液を廃棄する廃棄槽125とを備えている。PCRプレート又はマイクロプレートは、好ましくはxy方向に略等間隔で配置された96個(8x12)のウェルを有する。加熱部123は、抽出された核酸を増幅するために、加熱及び冷却を繰り返す。
第2分注部(分注装置)400を図5~図9を用いて説明する。第2分注部400は、複数のウェルを有するPCRプレート又はマイクロプレートに対応した複数の分注ノズルを備える。第2分注部400は、後述するように、xy方向に所定間隔で配置された複数の分注チップ142を複数の分注ノズル436に一括して取付ける取付機構と、xy方向に所定間隔で配置された複数の分注チップ142を複数の分注ノズル436から一括して取外す取外機構とを備えている。第2分注部400は、好ましくは、図5Aに示すように、xy方向に略等間隔で配置した96個の分注ノズル436を備えることができる。
本実施形態の第2分注部400が備えるコーム状(櫛状)の磁力付与部414を説明する。第2分注部400における検体の精製(前処理)は、好ましくは本願発明者によって国際公開97/44671号に提案された手法を用いることができる。この手法は、標的核酸を吸着する磁性粒子と、磁性粒子を含む溶液を保持する分注チップと、分注チップに対して移動可能な外部磁石とを用いて実行される。
複数の取付磁石432の磁力が、磁力付与部414の複数のコーム磁石414cや分注チップ142内の磁性粒子に影響を及ぼす場合がある。そこで、好ましくは、複数の取付磁石432の側面及び複数の金属体144bの側面及び下面に、磁力遮蔽体(鉄等の強磁性体材料)を設けることができる。
第1~第3の実施形態に適用可能な各変形例を説明する。第1~第3の実施形態の取付機構は、分注チップ142の載置体144、144A、144Bと、載置体144、144A、144Bに設けられた複数の金属体144b、144A1b、144B1bと、複数の金属体144b、144A1b、144B1bを吸着する複数の取付磁石432とから構成されている。これに対して、第1変形例の取付機構は、複数の取付磁石432を複数の第1磁石432とし、複数の金属体144b、144A1b、144B1bを複数の第2磁石とすることができる。一対の第1磁石及び第2磁石は、両者が対向する状態で互いに極性が異なるように配置されている。
本発明の第2の実施形態に係る検体処理システムは、第1の実施形態に係る検体処理システム1000と第2分注部のみが相違し、他の部分の構成及び動作は検体処理システム1000と同じであるため、他の部分の構成及び動作の図面及び説明は省略する。
本発明の第3の実施形態に係る検体処理システムは、第1の実施形態に係る検体処理システム1000と第2分注部のみが相違し、他の部分の構成及び動作は検体処理システム1000と同じであるため、他の部分の構成及び動作の図面及び説明は省略する。
100 基部
142 分注チップ
144 載置体(キャッチプレート)
144a 貫通孔
144b 金属体(金属ディスク)
144c 凹部
120 可動ステージ
200 第1分注部
205 分注ノズル(第1分注ノズル)
210 ピッチ変換機構
300 移動機構
400 第2分注部(分注装置)
432 取付磁石
434 リムーバ
436 分注ノズル(第2分注ノズル)
438 O-リング
414 磁力付与部
414b コーム部分
414c コーム磁石
500 第1分注チップ収容部
600 制御部
400A 第2分注部(分注装置)
144A 載置体
144A1 載置板枠
144A2 載置板
400B 第2分注部(分注装置)
144B 載置体
144B1 載置板枠
144B2 載置板
Claims (15)
- 第1方向及び第2方向に所定間隔で配置された複数の分注ノズルを備える分注装置であって、
前記複数の分注ノズルを支持する分注本体と、
複数の分注チップを前記第1方向及び第2方向に所定間隔で載置する載置体と、
前記複数の分注チップを前記複数の分注ノズルに装着するために、前記複数の分注チップを載置した前記載置体を前記分注本体側に取り付ける取付機構と、
前記複数の分注チップを載置した前記載置体を前記分注本体側から取り外す取外機構と、
前記複数の分注ノズル、前記取付機構、及び前記取外機構の動作を制御する制御部とを備える、分注装置。 - 請求項1に記載の分注装置において、
前記載置体は、前記複数の分注チップを前記第1方向及び前記第2方向に所定間隔で載置する載置板と、前記載置板の周囲の少なくとも一部を取り囲む載置板枠とから構成される、分注装置。 - 請求項2に記載の分注装置において、
前記載置板は矩形であり、前記載置板枠は前記矩形の3辺を取り囲む、分注装置。 - 請求項2又は3に記載の分注装置において、
前記取付機構は、前記載置板枠及び前記分注本体の一方に設けられた、1つ又は複数の取付磁石と、前記載置枠及び前記分注本体の他方に設けられた、1つ又は複数の金属体とから構成される、分注装置。 - 請求項2~4のいずれか一項に記載の分注装置において、
前記載置板枠は、前記分注本体側から吊り下げられている、分注装置。 - 請求項1~5のいずれか一項に記載の分注装置において、
前記取付機構は、前記載置体及び前記分注本体の一方に設けられた、1つ又は複数の取付磁石と、前記載置体及び前記分注本体の他方に設けられた、1つ又は複数の金属体とから構成される、分注装置。 - 請求項4又は6に記載の分注装置において、
前記複数の取付磁石は、前記複数の分注チップ及び前記複数の分注ノズルの一方を取り囲むように配置され、
前記複数の金属体は、前記複数の分注チップ及び前記複数の分注ノズルの他方を取り囲むように配置される、分注装置。 - 請求項1~3のいずれか一項に記載の分注装置において、
前記取付機構は、前記載置体及び前記分注本体の一方に設けられた、1つ又は複数の第1磁石と、前記載置体及び前記分注本体の他方に設けられた、1つ又は複数の第2磁石とから構成される、分注装置。 - 請求項8に記載の分注装置において、
前記複数の第1磁石は、前記複数の分注チップ及び前記複数の分注ノズルの一方を取り囲むように配置され、
前記複数の第2磁石は、前記複数の分注チップ及び前記複数の分注ノズルの他方を取り囲むように配置される、分注装置。 - 請求項1乃至9のいずれか一項に記載の分注装置において、
前記取外機構は、前記載置体が前記分注本体から分離する方向に前記載置体に対して力を加えるリムーバと、前記リムーバを移動するリムーバ移動機構とを備える、分注装置。 - 請求項10に記載の分注装置において、
前記リムーバが、前記載置体の上面及び/又は複数の分注チップの上端面を押圧することにより、前記複数の分注チップが前記複数の分注ノズルから取り外される、分注装置。 - 請求項1乃至11のいずれか一項に記載の分注装置において、
前記載置体に載置された前記複数の分注チップが前記複数の分注ノズルに取り付けられた状態で、前記複数の分注チップのそれぞれの内部に磁力を及ぼす磁力付与部を備える、分注装置。 - 請求項12に記載の分注装置において、
前記磁力付与部は、複数の突出片から構成されるコーム部分と、
前記複数の突出片のそれぞれに配置された複数のコーム磁石と、
前記複数のコーム部分を前記複数の分注ノズルの間に挿入または引き抜く方向に移動するコーム移動機構とを備える、分注装置。 - 請求項1乃至13のいずれか一項に記載の分注装置において、
前記複数の分注ノズルは、前記複数の分注チップと接触する弾性部材を備える、分注装置。 - 親検体容器から親検体を子検体容器に分注する第1分注部と、子検体容器中の子検体から核酸を抽出する処理部と、前記抽出された核酸を増幅するために加熱冷却を繰り返す加熱部と、前記増幅された核酸を測定する測定部と、少なくとも前記処理部に試薬又は溶液を分注する第2分注部と、を備える検体処理測定装置において、
前記第2分注部は、請求項1乃至14のいずれか一項に記載の分注装置である、検体処理測定装置。
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