WO2020065803A1 - 試料処理デバイスおよび装置 - Google Patents
試料処理デバイスおよび装置 Download PDFInfo
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- WO2020065803A1 WO2020065803A1 PCT/JP2018/035825 JP2018035825W WO2020065803A1 WO 2020065803 A1 WO2020065803 A1 WO 2020065803A1 JP 2018035825 W JP2018035825 W JP 2018035825W WO 2020065803 A1 WO2020065803 A1 WO 2020065803A1
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- reagent
- sample processing
- storage space
- flow path
- unit
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- 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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/56—Labware specially adapted for transferring fluids
- B01L3/565—Seals
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B3/00—Devices comprising flexible or deformable elements, e.g. comprising elastic tongues or membranes
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N37/00—Details not covered by any other group of this subclass
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/028—Modular arrangements
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/16—Reagents, handling or storing thereof
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/12—Specific details about materials
- B01L2300/123—Flexible; Elastomeric
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
Definitions
- the present invention relates to a sample processing device and an apparatus, and more particularly to a sample processing device and an apparatus for performing a liquid flowing operation by deforming an elastic film.
- the microfluidic system comprises a removable microfluidic device and control means, wherein the removable microfluidic device comprises at least one fluid chamber or a rigid layer and an elastic layer between both layers. It is described that a flow path is provided, and the control means is provided with a means for deforming the elastic layer by operating a fluid chamber or a fluid in the flow path.
- Patent Literature 2 describes a storage container, a flow cartridge, and a discharge mechanism in which liquid hardly remains when the storage liquid flows out.
- the microfluidic device described in Patent Literature 1 realizes inflow of fluid into or out of fluid chamber to which a flow path is connected by deformation of an elastic layer. There is no description about the sealing structure of the flow device. For this reason, when the inflow side upstream or the outflow side downstream of the fluid is in an open state, a desired flow operation can be performed, but when the device is used in a sealed state, the flow operation cannot be performed. Further, the configuration described in Patent Document 2 has a problem that it is not easy to control a small amount of outflow of liquid because a reagent pin is used.
- An object of the present invention is to solve the above problems and to provide a sample processing device and an apparatus for introducing a reagent with a small residual liquid amount in a sealed device and performing a flow operation by deformation of an elastic membrane. .
- the present invention has a reagent storage unit, an upper flow path through which liquid flows on the upper surface side, and a lower flow path through which liquid flows on the lower surface side.
- a processing unit communicating with the passage, and an elastic membrane sealing a lower surface side of the processing unit; a reagent storage unit configured to store a reagent between an upper member and an upper surface side of the processing unit; and a storage space.
- the upper member and the upper surface side of the processing unit have a bonding portion, wherein the bonding portion has at least a part of the bonding strength between the upper surface flow channel and the storage space more than other parts
- the present invention provides a sample processing device having a configuration including a low-strength joint having a low strength.
- the present invention provides a reagent storage unit, an upper flow path through which liquid flows on the upper surface side, and a lower flow path through which liquid flows on the lower surface side.
- a processing unit communicating with the flow path, and an elastic membrane for sealing the lower surface side of the processing unit, the reagent storage unit includes an upper member, a lower member, and a storage space for storing a reagent between the two members;
- the lower member is provided with a partially removed removal section above the upper surface flow path, and the joining section includes at least one portion between the removal section and the storage space.
- a sample processing device having a configuration in which a portion includes a low-strength bonding portion having lower bonding strength than other portions.
- the reagent storage unit an upper flow path through which liquid flows on the upper surface side, and a lower flow path through which liquid flows on the lower surface side, both ends of the upper flow path
- a processing unit that communicates with the different lower surface flow paths, a driving unit that controls air, an elastic film disposed between the processing unit and the driving unit, and whether the elastic film adheres to the processing unit or the driving unit.
- An air pressure control unit for switching wherein the reagent storage unit includes an upper member, a lower member, a storage space for storing the reagent between the two members, and a joining part for joining the two members around the storage space.
- At least a part of the lower member is joined to the upper surface side of the processing unit, the lower member is provided with a partially removed removal unit at the upper part of the upper surface flow path, and the joint is at least a portion between the removal unit and the storage space.
- FIG. 2 is a diagram illustrating an example of a sample processing device according to the first embodiment.
- FIG. 4 is a diagram illustrating an example of a reagent storage unit according to the first embodiment.
- FIG. 2 is a top view of the sealing film according to the first embodiment.
- FIG. 3 is a diagram illustrating an upper surface and a lower surface of the analysis chip according to the first embodiment.
- FIG. 2 is a diagram illustrating an upper surface and a side surface of the sample processing apparatus according to the first embodiment.
- FIG. 3 is a diagram illustrating a top surface and a side cross section of the sample processing device and the driving unit according to the first embodiment.
- FIG. 3 is an air piping system diagram for controlling the pressure of the driving unit according to the first embodiment.
- FIG. 4 is a diagram illustrating an example of an operation flow of the sample processing apparatus according to the first embodiment.
- FIG. 4 is a diagram illustrating an example of an analysis operation flow of the sample processing apparatus according to the first embodiment.
- FIG. 5 is an explanatory diagram of a reagent introduction operation of the sample processing apparatus according to the first embodiment.
- FIG. 5 is an explanatory diagram of a reagent introduction operation of the sample processing apparatus according to the first embodiment.
- FIG. 5 is an explanatory diagram of a reagent introduction operation of the sample processing apparatus according to the first embodiment.
- FIG. 4 is a diagram showing a reagent flow operation flow of the sample processing apparatus according to the first embodiment.
- FIG. 5 is an explanatory diagram of a reagent flowing operation of the sample processing apparatus according to the first embodiment.
- FIG. 7 is an explanatory diagram illustrating a continuation of the reagent flowing operation of the sample processing apparatus according to the first embodiment.
- FIG. 4 is a diagram showing a reagent flow operation flow of the sample processing apparatus according to the first embodiment.
- FIG. 5 is an explanatory diagram of a reagent flowing operation of the sample processing apparatus according to the first embodiment.
- FIG. 7 is an explanatory diagram illustrating a continuation of the reagent flowing operation of the sample processing apparatus according to the first embodiment.
- FIG. 5 is a diagram showing a sample flow operation flow of the sample processing apparatus according to the first embodiment.
- FIG. 4 is an explanatory diagram of a sample flowing operation of the sample processing apparatus according to the first embodiment.
- FIG. 7 is an explanatory diagram illustrating a continuation of the sample flowing operation of the sample processing apparatus according to the first embodiment.
- FIG. 3 is a diagram illustrating a stirring operation flow of the sample processing apparatus according to the first embodiment.
- FIG. 4 is an explanatory diagram of a stirring operation of the sample processing apparatus according to the first embodiment.
- FIG. 4 is a diagram illustrating a measurement operation flow of the sample processing apparatus according to the first embodiment.
- FIG. 10 is a side sectional view of the reagent storage unit according to the second embodiment.
- FIG. 13 is a diagram illustrating a configuration example of a reagent storage unit and a reagent pushing mechanism of a sample processing apparatus according to a third embodiment.
- FIG. 14 is a side sectional view of the reagent storage unit according to the fourth embodiment.
- a sealed device means a combination of a processing unit and a reagent storage unit in which liquid and air to be processed inside are not in contact with the outside.
- the present embodiment has a reagent storage unit, a processing unit having an upper flow path through which liquid flows on the upper surface side and a lower flow path through which liquid flows on the lower surface side, and both ends of the upper flow path communicating with different lower flow paths.
- a driving unit that controls air
- an elastic film disposed between the processing unit and the driving unit, and an air pressure control unit that switches whether the elastic film is in close contact with the processing unit or the driving unit
- the storage unit includes an upper member, a lower member, a storage space for storing a reagent between the two members, and a joint part where the two members are joined around the storage space, and at least a part of the lower member is a processing unit.
- the lower member is provided with a partially removed removal portion at the upper part of the upper surface flow path, and at least a portion between the removed portion and the storage space has a stronger bonding strength than other portions.
- 4 is an embodiment of a sample processing apparatus having a weak configuration.
- a sample processing device in a sample processing device, blood, urine, a sample such as a liquefied sample such as a swab and a reagent are made to flow and mixed at a constant volume ratio, and optical measurement such as identification and quantification of a chemical substance is performed.
- a sample processing apparatus to be performed An example of a sample processing apparatus to be performed will be described.
- the analysis chip 10 which is a processing unit of the sample processing device 1, has an upper surface joined by a sealing film 21, and further, reagent storage units 80 and 85 are joined to the sealing film 21.
- the lower surface side of the analysis chip 10 is sealed with a membrane 20 which is an elastic film.
- a sealed device a combination of an analysis chip and a reagent storage unit as a processing unit in which such an elastic film and a sealing film or the like are in close contact with each other and do not allow fluid to enter and exit from the outside is called a sealed device.
- FIGS. 2A and 2B are a top view and a side cross-sectional view (BB cross section) of the reagent storage units 80 and 85 according to the first embodiment.
- the multi-liquid reagent storage unit 80 is composed of a multi-liquid upper film 81 and a multi-liquid lower film 82, and the convex portions of the multi-liquid upper film 80, namely, the first reagent chamber 810, the second reagent chamber 811, and the third reagent chamber 812, Different reagents can be retained.
- the double liquid lower film 82 has a reagent 3 film removal section 821 from which the film has been removed and missing.
- the joining portion means a portion where the two films are joined around the storage space.
- the hatched reagent 12 low-strength joint 831, reagent 23 low-strength joint 832, and reagent 3 low-strength joint 833 have a lower joint strength than the joints of the other parts, and flow out during transportation or storage.
- only the low-strength joints 831, 832, and 833 are peeled off by operations such as crushing the protrusions of the upper part of the multi-liquid upper film 80 from above, and communication between the reagent chambers or between the reagent chambers and the film remover is established.
- the reagent can be discharged.
- the single-liquid reagent storage unit 85 has the same structure, and is composed of a single-liquid upper film 86 and a single-liquid lower film 87.
- the reagent can be held in the reagent 4 chamber 850, which is a convex portion of the single-liquid upper film 86. It is.
- the single liquid lower film 87 has a reagent 4 film removing section 860. In the state where the reagent is held, the contact surfaces of the single liquid upper film 86 and the single liquid lower film 87 are joined except for the reagent 4 film removing section 860 to form a joint, but are hatched.
- the low-strength bonding portion 870 of the reagent 4 has a low bonding strength and does not flow out during transportation or storage, but only the low-strength bonding portion 870 is peeled off by an operation such as crushing the convex portion of the single-liquid upper film 85 from above.
- the communication between the reagent chamber and the film removing section allows the reagent to flow out.
- FIG. 2C shows the joined state of the single-liquid reagent storage unit 85.
- Portions 876 other than the reagent 4 chamber 850, the reagent 4 film removing unit 860, and the reagent 4 low-strength joining unit 870 are normal joints.
- a non-joining area 875 is partially provided only in the area of the reagent 4 low-strength joint 870.
- a solvent or an adhesive having a low adhesive strength may be used for the low-strength joint, or the bonding area may be reduced, or as shown in FIG.
- a non-joining area 875 where a solvent or an adhesive is not used in part may be provided.
- a double-sided tape may be used between the upper and lower members.
- the bonding strength may be reduced only in the region of the low-strength bonding portion, or, as shown in FIG. 2C, a non-bonding region 875 that does not partially use an adhesive may be provided.
- FIG. 3 is a top view of the sealing film 21 of the analysis chip 10 as the processing unit according to the first embodiment.
- the sealing film 21 has three through holes. That is, the reagent 3 through hole 221 is provided at a position corresponding to the reagent 3 film removing unit 821 of the multi-liquid reagent storage unit 80, and the reagent 4 through hole 260 is provided at a position corresponding to the reagent 4 film removing unit 860 of the single liquid reagent storing unit 85.
- a charging hole 280 is provided at a position corresponding to the charging section film 23.
- FIGS. 4A and 4B are a top view and a bottom view of the analysis chip 10.
- Wells 11, 12, 13 and an upper surface groove to be described later are provided on the upper surface side of the analysis chip 10, and a lower surface groove to be described later is provided on the lower surface side.
- 1 shows a top view and a side view of a sample processing apparatus according to a first embodiment.
- the sealing film 21, the analysis chip 10 and the membrane 20 are pressed against the driving unit 40 by the lid 50, and the reagent storage units 80 and 85 are mounted on the sealing film 21. Make up.
- the lid 50 is supported so as to be rotatable about the rotation support part 51.
- the lid 50 is in a state of being opened, and the two analysis chips 10 are juxtaposed.
- FIG. 5B shows a state in which the lid 50 is completely closed and is fastened to the housing 53 by the lock mechanism 54.
- the lid 50 is provided with an observation window 52 for observing the analysis result. Further, the lid 50 is provided with push-out mechanisms 55 and 57 used when the reagent flows out of the reagent storage units 80 and 85.
- An air pressure control unit 60 for controlling the air pressure in the drive unit 40 is provided below the housing 53, and an air pipe 70 is connected from the drive unit 40 to the air pressure control unit 60.
- the operation of the air pressure control unit 60 is controlled by a signal from an operation unit 61 such as a control computer outside the sample processing apparatus.
- FIG. 6A, 6B, 6C, and 6D are top views and side views of a state in which the sample processing device according to the first embodiment is in close contact with the driving unit 40 via the membrane 20. It is a sectional view (AA section), a side sectional view (BB section), and a side sectional view (CC section).
- FIG. 6 shows a state where the sample processing device is mounted on the sample processing apparatus shown in FIG. 5 and the drive unit 40 is pressed by the lid 50 via the membrane 20.
- FIG. 6A is a view from the upper surface side of the sample processing device.
- the well as the container on the upper surface side of the analysis chip and the circulation groove 901 as the air circulation channel are solid lines, and the groove 111 on the lower surface side of the analysis chip.
- the dents forming the recesses of the drive unit 40 are indicated by broken lines.
- the reagent storage units 80 and 85 and the sealing film 21 are omitted from FIG. 6A for the sake of easy viewing of the drawing, they are shown in FIG. All the functions will be described with reference to FIG. 6 (B) is an AA cross section of FIG. 6 (A), FIG. 6 (C) is a BB cross section of FIG. 6 (A), and FIG. 6 (D) is a FIG. 6 (A)
- the sample processing device and the drive unit 40 are in contact with each other via the membrane 20 in the CC cross section of FIG.
- the sample well 11 On the upper surface side of the analysis chip 10, the sample well 11, the stirring well 12, the disposal well 13, the vertical holes 911 and 912 for introducing the reagent, and the reagent shown in FIG. Circulation grooves 901, 902, 903, 904, 905, 906, 907, 908 and air reservoirs 915, 916 for the purpose of introduction of air and circulation of air.
- a plurality of grooves 111, 112, 113, 114, 115, 116, 121, 122, 123, 124, 125, 126, 131, 132 shown in FIG. , 133, 134, 141, 142, 143, 144, and 145 are provided.
- the membrane 20 is an elastic body made of a polymer compound such as rubber or resin.
- the membrane 20 is deformed by air pressure to move the fluid, and closes the fluid to the analysis chip 10 and the drive unit 40 to seal the fluid. doing.
- the driving unit 40 is provided with recesses 41, 42, 43, 44, 45, 46, 47, 48, 49, 4A, 4B, 4C, 4D, and 4E that form a plurality of recesses on the upper surface side that is in close contact with the membrane 20.
- Two types of tubes from each recess namely, pressurizing tubes 411,421,431,441,451,461,471,481,491,4A1,4B1,4C1,4D1,4E1, and depressurizing tubes 412,422,432,442.
- 452, 462, 472, 482, 492, 4A2, 4B2, 4C2, 4D2, 4E2 are connected to the air pipe 70 shown in FIG.
- FIG. 7 is an air piping system diagram for controlling the pressure of the driving unit 40 of the present embodiment, and these are installed in the air pressure control unit 60.
- the pressurizing pump 71 branches into 14 systems, and further branches into two systems via the pressurizing solenoid valves 711, 721, 731, 741, 751, 761, 771, 781, 791, 7A1, 7B1, 7C1, 7D1, and 7E1. , And a pressure pipe of the drive unit 40.
- the branch from the pressurizing electromagnetic valve to two systems is because the sample processing apparatus of the present embodiment is equipped with two analysis chips 10 as shown in FIG.
- the system is branched from the decompression pump 72 into 14 systems, and further divided into two systems via decompression solenoid valves 712, 722, 732, 742, 752, 762, 772, 782, 792, 7A2, 7B2, 7C2, 7D2, and 7E2. And is connected to the pressure reducing pipe of the driving unit 40.
- the air valve from the pump 71 to the drive unit 40 communicates with the pressurizing solenoid valve 711 and the like when energized, and the depression 41 and the like of the drive unit 40 are pressurized.
- the air pipe on the pump 71 side is closed, and the air pipe on the drive section 40 side can flow out to the outside, that is, the atmosphere side, and does not flow into the air pipe from the outside.
- the pressure reducing solenoid valve 712 and the like communicate with the air pipe from the pump 72 to the drive unit 40 when energized, and the depression 41 and the like of the drive unit 40 are reduced in pressure.
- the air pipe on the pump 72 side is closed, so that the air can flow into the air pipe on the drive unit 40 side from the atmosphere side, and does not flow out from the air pipe.
- the driving unit 40 is installed in the sample processing apparatus, and the air pipe 70 is connected.
- the device mounting 301 which is the first operation of the operation flow 301 to 309
- the operator attaches the membrane 20 to the analysis chip 10, peels off the input unit film 23 attached to the sealing film 21, and removes the sample for the sample.
- the sealed device is formed by charging the sample processing device into the well 11 and attaching the charging unit film 23 to the sample processing device.
- the charging section film 23 to be reattached does not need to be the same as the one that was first applied.
- the sealed device configured as described above is mounted on the drive unit 40 with the membrane 20 facing down, and the lid 50 is closed. This state is shown in FIG. Note that, here, the analysis chip 10 and the membrane 20 are separate and are attached by an operator. However, a method in which the analysis chip 10 and the membrane 20 are packaged integrally in advance may be used. .
- the operator selects a control procedure according to the analysis content by the operation unit 61 of FIG. 5A and starts the device operation.
- the sample processing apparatus starts an initialization operation 303, and performs an opening and closing operation of an electromagnetic valve, a pressurizing and depressurizing operation by a pump, and a pressure check if necessary. Thereafter, the pressure reducing solenoid valve 712 and the like are all closed with the pressure pump 71 and the pressure reducing pump 72 operating.
- the operator issues an instruction to start the analysis operation 306 from the operation unit 61, and the sample processing apparatus performs the analysis operation 307.
- the analysis result is stored in a memory in the sample processing apparatus, and displayed on a display or the like of the operation unit 61 as necessary.
- the operator When the analysis operation 307 is completed, the operator removes the sample processing device 1 and saves or discards it at device removal 308. If there is the next analysis, the process returns to the device mounting 301, mounts a new sample processing device, and performs the analysis. If there is no analysis, the operator performs an end operation 309 on the operation unit 61 and stops the apparatus.
- the reagents held in the reagent storage units 80 and 85 are introduced into the circulation grooves, which are the upper flow paths provided on the upper surface side of the analysis chip 10, using the pushing mechanisms 55 and 57.
- FIG. 10 is an enlarged side cross-sectional view of the periphery of the multi-liquid reagent storage unit 80 of the sample processing device, illustrating the operation of six pressurizing mechanisms constituting the multi-liquid pushing mechanism 55.
- FIG. 10A shows an initial state before reagent introduction, in which six pressurizing mechanisms 552 to 557 are located above the double-liquid reagent storage unit 80.
- the reagent one chamber pressurizing mechanism 552 is lowered to pressurize the reagent one chamber 810.
- the reagent 1 chamber 810 is crushed, and the internal pressure increases, thereby opening the reagent 12 low-strength welded portion 831, and the reagent 1 inside flows out to the reagent 2 chamber 811 side.
- the reagent 12 low-strength joint pressurizing mechanism 553 is lowered, and the reagent 12 low-strength joint 831 is pressurized.
- the reagent two chamber pressurizing mechanism 554 is lowered to pressurize the reagent two chamber 811.
- the reagent 2 chamber 811 is crushed and the internal pressure increases, thereby opening the low-strength welded portion 832 of the reagent 23, and the reagent 1 and the reagent 2 inside flow out to the reagent 3 chamber 812 side.
- the reagent 12 low-strength joint 831 is pressurized by the reagent 12 low-strength joint pressurizing mechanism 553, it does not open.
- each of the pressurizing mechanisms in the order of the reagent 23 low-strength joint pressurizing mechanism 555, the reagent 3 chamber pressurizing mechanism 556, and the reagent 3 low-strength joint pressurizing mechanism 557 Is lowered, and the reagent 23 low-strength joint 832, the reagent 3 chamber 812, and the reagent 3 low-strength joint 833 are sequentially pressurized, so that all the reagents are introduced into the reagent 3 circulation groove 901 from the reagent 3 film removing section 821. Is done.
- the number of reagent chambers in the multi-liquid reagent storage section 80 need not be three, but may be four or more or two. Alternatively, an empty reagent chamber in which no reagent is stored may be used.
- the purpose of the multi-liquid reagent storage unit 80 can be used for various purposes such as introduction of a trace amount of reagent and introduction of a dried reagent, in addition to sequential introduction of a plurality of reagents.
- the capacity of one reagent chamber 810 is made larger than the capacity of two reagent chambers 811, and a large amount of reagent 1 in one reagent chamber 810 is introduced into a second reagent chamber 811 holding a small amount of reagent 2.
- a dry reagent can be stored in the reagent 2 chamber 811 and introduced into the analysis chip 10 after dissolving with the liquid reagent in the reagent 1 chamber 810.
- the mixing operation shown in FIG. 11 may be performed.
- the reagent 3 low-strength joint pressurizing mechanism 557 is lowered, and the reagent 3 low-strength joint 833 is pressurized.
- the two chambers 811, the reagent 12 low-strength joint 831 and the reagent one chamber 810 are pressurized. Stop.
- the lowering of the reagent three chamber pressurizing mechanism 556 and the lowering of the reagent one chamber pressurizing mechanism 552 are repeated, so that the reagent is supplied to the reagent one chamber 810 and the reagent three. Reagents can be mixed by flowing between the chambers 812.
- the reagent 3 low-strength joint pressurizing mechanism 557 is lifted, and the reagent 1 chamber pressurizing mechanism 552, the reagent 12 low-strength joint pressurizer 553, the reagent 2 chamber pressurizing mechanism 554, and the reagent 23 low-strength joint press are added.
- the mixed reagent flows from the reagent 3 film removal section 821 to the reagent 3 circulation groove. 901.
- FIG. 12 is an enlarged side cross-sectional view around the single-liquid reagent storage unit 85 of the sample processing device, illustrating the operation of two pressurizing mechanisms constituting the multi-liquid pushing mechanism 57.
- FIG. 12 shows an initial state before the introduction of the reagent, in which the two pressurizing mechanisms are located above the single-liquid reagent storage unit 85.
- the reagent four chamber pressurizing mechanism 571 is lowered to pressurize the reagent four chamber 850.
- the reagent 4 chamber 850 is crushed, and the internal pressure increases, thereby opening the reagent 4 low-strength welded portion 870.
- the reagent 4 inside the reagent 4 is removed from the reagent 4 film removing portion 860 through the central circulation groove shown in FIG. 905 and the reagent 4 circulation groove 908.
- the reagent 4 low-strength joint pressurizing mechanism 572 is lowered, and the reagent 4 low-strength welded portion 870 is pressurized, so that the reagent 4 remains in the analysis chip 10 without remaining liquid. Can be introduced.
- the reagent flow 312 in FIG. 9 will be described.
- the reagent introduced into the central circulation groove 905 and the reagent 3 circulation groove 901 and the reagent introduced into the central circulation groove 905 and the reagent 4 circulation groove 908 are caused to flow to the stirring well 12.
- FIG. 13 is a diagram showing a flow of a reagent flowing operation by opening and closing control of the pressurizing solenoid valve and the depressurizing solenoid valve of the sample processing apparatus of the present embodiment
- FIGS. 14A and 14B are explanatory diagrams of the reagent flowing operation.
- the solid arrows shown in FIGS. 14A and 14B indicate that the solenoid valves corresponding to the pressurizing pipes and the depressurizing pipes are open, and the solid arrows pointing upward indicate that the depression is pressurized when the pressurizing electromagnetic valve is opened. That is, the downward solid line arrow indicates that the depression is depressurized by opening the decompression solenoid valve.
- the solenoid valve is closed where no solid arrow is attached, but a dashed arrow is used to explain, in particular, that the solenoid valve is closed in the description of the drawing being referred to. That is, the upward dashed arrow indicates that the pressurizing solenoid valve has switched from open to closed, and the downward dashed arrow indicates that the pressure reducing solenoid valve has switched from open to closed.
- FIG. 14A and 14B show a part of the cross section AA or the cross section CC in FIG. 6, but the operation of the present embodiment is performed by showing a part of the central circulation groove 905 shown in the cross section BB by a broken line. explain. The direction of air flow in the central circulation groove 905 is indicated by a horizontal broken arrow.
- FIGS. 13A and 14A (section AA) (section AA) show that the reagent 31 is transferred from the multi-liquid reagent storage unit 80 described in FIGS. 10 and 11 to the central circulation groove 905 and the reagent 3 circulation groove 901 in FIG. This is the state immediately after the introduction.
- control of the electromagnetic valve was not described, but at the time of introduction of the reagent, the electromagnetic valve 721 for pressurizing the circulating seal dent was opened, and air was flowed in from the pressurizing pipe 421 for circulating sealing dent to thereby perform the circulating sealing. It is desirable to press the dent 42 to press the membrane 20 against the analysis chip 10 and prevent the reagent from flowing into the circulation sealing upstream groove 111 from the vertical hole 911 of the reagent 3.
- the initial air in the well or the circulation groove provided on the upper surface side of the analysis chip 10 expands by a volume corresponding to the sample sucked into the reagent sealing recess 43 or the like. Is much greater than the amount of expansion and the pressure drop is small. In particular, by providing the air reservoir 915 and the like, the volume of the initial air is increased (see FIG. 6A), and the pressure drop in the circulation groove becomes negligibly small.
- the electromagnetic valve 751 for agitating introduction dent pressurization is opened to allow air to flow from the agitation introduction dent pressurizing pipe 451.
- the stirring introduction recess 45 and opening the sample flow recess pressurizing solenoid valve 7B1 air flows into the sample flow recess pressurizing pipe 4B1 to pressurize the sample flow recess 4B.
- the membrane 20 is pressed against the analysis chip 10 to seal the stirring introduction upstream groove 115 and the sample flow downstream groove 133.
- the membrane 20 is pressed against the analysis chip 10 and pushes out the reagent 31 in the reagent flowing portion gap 443.
- the reagent sealing recess 43 and the sample flow recess 4B are pressurized, they flow out to the stirring introduction recess 45 side. Since the stirring introduction recess 45 is neither pressurized nor depressurized, the reagent 31 pushes open the stirring introduction section gap 453 which is a gap between the fluid chip 10 and the membrane 20, and flows out to the stirring well 12.
- FIG. 15 is a diagram showing a reagent flow operation flow by opening and closing control of the pressurizing solenoid valve and the depressurizing solenoid valve of the sample processing apparatus of the present embodiment
- FIGS. 16A and 16B are explanatory diagrams of the reagent flowing operation.
- FIG. 16A cross section CC in FIG. 16A is a state immediately after the reagent 32 is introduced into the central circulation groove 905 and the reagent 4 circulation groove 908 in FIG. 6 from the single-liquid reagent storage unit 85 described in FIG.
- the liquid is caused to flow by the switching operation of the electromagnetic valve similar to the operation described with reference to FIGS. 13, 14A, and 14B.
- FIG. 15B and FIG. 16A (cross section CC)
- air flows out of the reagent sealing depression decompression tube 4E2
- the reagent sealing is performed. Depressurize the depression 4E.
- a reagent sealing portion gap 4E3 is generated between the membrane 20 and the analysis chip 10, and the reagent 32 is drawn.
- air flows into the central circulation groove 905, and the pressure in the central circulation groove 905 hardly decreases.
- the stirring sealing dent 46 is pressurized by opening the stirring sealing dent pressurizing electromagnetic valve 761, and the detection introduction dent is formed.
- the detection introduction recess 47 is pressurized by opening the pressurizing solenoid valve 771.
- the membrane 20 is pressed against the analysis chip 10 to seal the stirring sealing downstream groove 125 and the detection introduction upstream groove 141.
- the reagent sealing depression 4E is pressurized by closing the reagent sealing depression pressure reducing electromagnetic valve 7E2 and opening the reagent sealing depression pressurizing electromagnetic valve 7E1.
- the fluid in the reagent sealing portion gap 4E3 returns to the reagent 4 vertical hole 912 side and seals the reagent sealing downstream groove 122.
- the reagent introduced into the circulation groove provided on the upper surface side of the analysis chip 10 is sucked into the grooves 112 and the like on the lower surface and the gaps 433 and the like.
- the circulation groove on the upper surface communicates with both ends and each groove on the lower surface in the middle, so that a dead end does not occur. Therefore, if the reagent is directly introduced into the circulation groove on the upper surface side, the entire amount can be sucked into the groove on the lower surface side.
- the film removing units 821 and 860 of the reagent storage units 80 and 85 are arranged in an upper part such as a circulation groove on the upper surface side of the analysis chip 10. In addition, there is no dead space between the reagent storage section and the circulation groove, and a trace amount of reagent can be flowed without residual liquid.
- FIG. 17 is a diagram showing a flow of a sample flowing operation by opening / closing control of the pressurizing solenoid valve and the depressurizing solenoid valve of the sample processing apparatus of the present embodiment
- FIGS. 18A and 18B are explanatory diagrams of the sample flowing operation.
- FIG. 18A shows a state in which the sample is dispensed into the sample well 11 and sealed with the input unit film 23.
- the liquid is caused to flow by the switching operation of the electromagnetic valve similar to the operation described with reference to FIGS.
- the sample flow dent 4B is depressurized by opening the sample flow dent pressure reducing solenoid valve 7B2. At this time, a sample flowing portion gap 4B3 is generated between the membrane 20 and the analysis chip 10, and the sample 33 is drawn.
- the reagent sealing dent 43 is pressurized by opening the reagent sealing dent pressurizing solenoid valve 731, and the reagent flow dent is formed.
- the reagent flow recess 44 is pressurized by opening the pressurizing solenoid valve 741.
- the membrane 20 is pressed against the analysis chip 10 to seal the reagent sealing downstream groove 113 and the reagent flow upstream groove 114.
- the sample sealing depression 4C is pressurized by closing the sample sealing depression depressurizing electromagnetic valve 7C2 and opening the sample sealing depression pressurizing electromagnetic valve 7C1.
- the fluid in the sample sealing portion gap 4C3 returns to the sample well 11 and seals the sample sealing downstream groove 132.
- FIG. 19 is a diagram showing a flow of a stirring operation by controlling the opening and closing of the pressurizing solenoid valve and the depressurizing solenoid valve of the sample processing apparatus of this embodiment
- FIG. 20 is an explanatory diagram of the stirring operation.
- FIG. 19 (A) and FIG. 20 (A) (cross section AA) show a state in which a plurality of liquid samples and a reagent merged in the stirring well 12 are held and the reagent flow depression pressurizing solenoid valve is held.
- the solenoid valve 741 and the detection introduction dent pressurizing solenoid valve 771 By opening the solenoid valve 741 and the detection introduction dent pressurizing solenoid valve 771, the cutout dent 44 and the detection introduction dent 47 are pressurized and sealed.
- the stirring introduction dent 45 is depressurized by opening the stirring introduction dent depressurizing solenoid valve 752, and the pressure is generated between the membrane 20 and the analysis chip 10.
- the liquid is drawn into the stirring introduction section gap 453 which is a gap to be formed.
- dashed arrows 921 and 922 air flows into the stirring well 12 through the central circulation groove 905 and the like.
- FIG. 21 is a diagram showing a measurement operation flow by opening and closing control of the pressurizing solenoid valve and the depressurizing solenoid valve of the sample processing apparatus of the present embodiment.
- the stirring sealing dent 46 is depressurized by opening the stirring outlet dent pressure reducing electromagnetic valve 762, and the mixed liquid held in the stirring well 12 after the stirring is completed is stirred with the stirring sealing upstream groove. Aspirate from 126. At this time, air flows into the stirring well 12 through the central circulation groove 905 and the like.
- the reagent flow depression pressurizing electromagnetic valve 7D1 is opened to pressurize and seal the reagent flow depression 4D, close the stirring sealing depression depressurization electromagnetic valve 762, and close the stirring sealing seal.
- the agitation sealing recess 46 is pressurized by opening the stop recess pressing solenoid valve 761. At this time, air flows out of the stirring well 12 through the central circulation groove 905 and the like.
- the detection unit introduction dent pressure reducing solenoid valve 772 is closed.
- the membrane 20 of the detection part introduction recess 47 tries to return to the lower surface side of the analysis chip 10 by elastic force, and pushes out the mixed liquid.
- the stirring sealing recess 46 and the reagent flowing recess 4D are sealed, the mixed liquid fills the detection unit introduction downstream groove 142, the detection groove 143, and the waste upstream groove 144 while disposing the mixed liquid without pressurization.
- the concave 48 moves to the gap between the membrane 20 and the analysis chip 10 and the waste downstream groove 145, and the excess mixed solution is pushed out to the waste well 13. At this time, air flows out of the disposal well 13 through the central circulation groove 905 and the like.
- the observation groove 52 is irradiated with observation light from the observation window 52 of FIG. 5 to acquire data.
- the above is the operation of the measurement 315 in FIG. 9, and the analysis operation 307 in FIG. 8 ends here.
- the detection groove 143 has a function of holding the liquid in a closed space, and in the first embodiment described in detail above, the analysis operation of irradiating the detection groove 143 with observation light from the observation window 52 and acquiring data is shown.
- the processing in the processing groove of the present embodiment is not limited to analysis and detection.
- the reaction may be performed by holding the liquid in the detection groove 143 and then recovered from the waste well 13, or the liquid may be held in the detection groove 143 to reduce the temperature. Processing other than optical measurement such as control may be performed.
- the reagent storage unit configured by using the upper surface member and the lower surface member is bonded to the sealing film of the analysis chip.
- the reagent storage section is formed by directly joining the upper member of the section to the sealing film of the analysis chip, or by also using the upper member of the reagent storage section as the sealing film of the analysis chip.
- the lower surface member or the lower surface member is configured so that the role of the sealing film doubles.
- the second embodiment has a reagent storage unit, an upper flow path through which liquid flows on the upper surface side, and a lower flow path through which liquid flows on the lower surface side, and both ends of the upper flow path communicate with different lower flow paths.
- an elastic membrane for sealing the lower surface side of the processing unit.
- the reagent storage unit includes a storage space for storing the reagent between the upper member and the upper surface side of the processing unit, and a flow path around the storage space and the upper surface.
- the sample processing has a joining portion that joins the upper member and the upper surface side of the processing section around the periphery, and the joining portion has a structure in which at least a portion between the upper surface flow path and the storage space has lower joining strength than other portions. 5 is an example of a device.
- FIG. 22 shows a configuration of a reagent introduction part of an analysis chip, which is a main part of the sample processing device of this example.
- a reagent chamber 850 is provided by directly joining the upper member 86 of the reagent storage unit 85 to the sealing film 21 of the analysis chip 10. That is, the role of the lower member of the reagent storage unit also serves as the sealing film of the analysis chip.
- the low-strength bonding portion 879 is provided between the reagent chamber 850 and the removing portion 260 of the sealing film 21.
- a reagent chamber 850 may be provided between the sealing film 21 of the analysis chip 10 and the analysis chip 10. That is, the role of the upper member of the reagent storage unit is also performed by the sealing film of the analysis chip.
- the low-strength bonding portion 878 is provided between the reagent chamber 850 and the circulation groove 905 which is the upper surface channel provided between the sealing film 21 and the analysis chip 10.
- the reagent storage section is a reagent chamber 850 that is a storage space for storing a reagent between the upper member that is the sealing film 21 and the upper surface side of the analysis chip 10 that is the processing section.
- the upper part of the analysis chip is joined to the upper surface of the analysis chip around the circulation groove 905 which is a flow path. At least a part between the upper flow path and the storage space is joined more than other parts. This is a configuration including a low-strength bonding portion 878 whose strength is weakened.
- the elasticity can be improved in the sealed device including the combination of the processing unit and the reagent storage unit in which the liquid to be processed inside and the air are not in contact with the outside.
- the flow operation can be performed by the deformation of the membrane, and the reagent can be introduced into the device with a small residual liquid amount.
- Example 3 is an example of the configuration of the sample processing device, the reagent storage unit of the sample processing apparatus, and the reagent pushing mechanism.
- FIG. 23 illustrates an example of the reagent storage unit and the reagent pushing mechanism according to the third embodiment.
- the upper member 881 and the lower member 882 that constitute the reagent chamber 880 of the reagent storage section are substantially identical to each other because the upper member 881 has a convex shape on the upper surface side and the lower member 882 has a convex shape on the lower surface side. It has an inverted shape.
- the pushing mechanism 883 also has a convex end, and the upper surface of the analysis chip 10 is also concave 884 so as to follow the convex shape of the lower member 882. In this state, when the push-out mechanism 883 is lowered and the reagent chamber 880 is crushed, the upper member 881 is inverted and comes into close contact with the lower member 882, and the reagent flows out without remaining liquid.
- the upper member 886 and the lower member 887 constituting the reagent chamber 885 are not formed in a simple convex shape, but are formed in a smooth surface from the convex portion of both members to the joint surface.
- the pushing mechanism 888 also has the same aspect at the tip, and when crushed, the upper member 886 smoothly turns over and comes into close contact with the lower member 887, so that the reagent flows out without residual liquid.
- a part of the convex portion of the upper member 890 constituting the reagent chamber 889 is depressed to form a depressed portion 891. Therefore, when crushed by the push-out mechanism 888, the upper part 890 is inverted by the depression 891 and closely adheres to the lower part 887, and the reagent flows out without remaining liquid.
- the depression 891 is a trigger for deformation when crushing, and has an effect of preventing uneven deformation. As long as a similar effect can be obtained, a part may be made flat or the curvature may be changed in addition to the shape of the depression.
- FIG. 23 shows a state where the reagent chamber 892 is crushed without any gap.
- the upper member 893 having this shape is manufactured and the reagent is held, the space of the upper member is widened, the reagent is stored and joined to the lower member, and when the reagent chamber 892 is crushed by the pushing mechanism 894, there is no gap.
- the reagent can be squashed, and the reagent flows out without remaining liquid.
- the flow operation can be performed by deforming the elastic membrane in the sealed device of the sample processing device and the sample processing apparatus of the first embodiment, and the reagent can be introduced into the device with a smaller residual liquid amount. Becomes possible.
- Embodiment 4 is an embodiment of a configuration that enables protection of the reagent chamber of the contact type device.
- air chambers 896 and 897 are provided on both sides of the reagent chamber 895.
- the two air chambers 896 and 897 are larger than the reagent chamber 895.
- the shape of the air chambers 896 and 897 does not need to be hemispherical, but may be ribs or protrusions. Even if a substance is put in, a structure without space inside may be used. According to the present embodiment, similarly to the sample processing devices and sample processing apparatuses of Examples 1 to 3, it is possible to introduce a reagent into the device with a small residual liquid amount by a flow operation by deformation of an elastic membrane. Further, the reagent chamber can be protected.
- the membrane 20 is deformed by air pressure, air is circulated through the circulation groove when performing operations such as liquid feeding, quantitative measurement, and stirring, so that the change in air pressure in the well is reduced, and stable. Flow operation can be performed.
- both ends of the circulation groove on the upper surface side of the analysis chip communicate with each groove on the lower surface side and do not reach a dead end, if the reagent is directly introduced into the circulation groove on the upper surface side, the entire amount is reduced on the lower surface side. Can be sucked into the groove.
- the film removal section of the reagent storage section on the top of the circulation groove on the upper surface side of the analysis chip, there is no dead space between the reagent storage section and the circulation groove, and a trace amount of reagent can be applied to the analysis chip with a small amount of residual liquid. Can be introduced and fluidized.
- a processing unit having a lower flow path through which liquid flows on the lower surface and an upper flow path through which liquid flows on the upper surface, A storage space for storing a reagent between an upper member and the upper surface of the processing unit, and a joining portion in which the upper member and the upper surface of the processing unit are joined around the storage space and around the upper surface flow path.
- a reagent storage unit provided, An elastic film that seals the lower surface of the processing unit; With The bonding portion has at least a part between the upper surface flow path and the storage space having a lower bonding strength than other parts, A sample processing device, wherein both ends of the upper surface channel communicate with different lower surface channels.
- ⁇ List 2> An upper member, a lower member, a storage space for storing a reagent between the two members, and a joining portion in which the two members are joined around the storage space, a reagent storage portion provided with: A processing unit having a lower flow path through which liquid flows on the lower surface and an upper flow path through which liquid flows on the upper surface, An elastic film that seals the lower surface of the processing unit; With At least a portion of the lower member of the reagent storage unit is joined to the upper surface side of the processing unit, The lower member is provided with a removed portion partially removed above the upper surface flow path, At least a part of the joint between the removing part and the storage space has a weaker joint strength than other parts, A sample processing device, wherein both ends of the upper surface channel communicate with different lower surface channels.
- ⁇ List 3> An upper member, a lower member, a storage space for storing a reagent between the two members, and a joining portion in which the two members are joined around the storage space, a reagent storage portion provided with: A processing unit having a lower flow path through which liquid flows on the lower surface and an upper flow path through which liquid flows on the upper surface, A sealing member for sealing the upper surface side of the processing unit, An elastic film that seals the lower surface of the processing unit; With At least a portion of the lower member of the reagent storage unit is joined to the sealing member, The lower member and the sealing member are provided with a removed portion partially removed above the upper surface flow path, At least a part of the joint between the removing part and the storage space has a weaker joint strength than other parts, A sample processing device, wherein both ends of the upper surface channel communicate with different lower surface channels.
- a reagent storage unit A processing unit having an upper surface flow path through which liquid flows on the upper surface side and a lower surface flow path through which liquid flows on the lower surface side, and both ends of the upper surface flow path communicating with the different lower surface flow paths, A sealing member for sealing the upper side of the processing unit, An elastic film that seals the lower surface side of the processing unit,
- the reagent storage unit includes an upper member, a lower member, a storage space for storing a reagent between the two members, and a bonding portion for bonding the two members around the storage space, At least a part of the lower member is joined to the sealing member, and the lower member and the sealing member are provided with a removed part partially removed above the upper surface flow path, At least a part of the joint between the removal part and the storage space has lower joint strength than other parts,
- a sample processing device comprising:
- a processing unit having a lower flow path through which liquid flows on the lower surface and an upper flow path through which liquid flows on the upper surface, A storage space for storing a reagent between an upper member and the upper surface of the processing unit, and a joining portion in which the upper member and the upper surface of the processing unit are joined around the storage space and around the upper surface flow path.
- a reagent storage unit provided, A drive unit for controlling air, An elastic film disposed between the processing unit and the driving unit; An air pressure control unit that switches whether the elastic film is in close contact with the processing unit or in close contact with the driving unit,
- the bonding portion has at least a part between the upper surface flow path and the storage space having a lower bonding strength than other parts,
- a sample processing apparatus wherein both ends of the upper surface flow path communicate with different lower surface flow paths.
- ⁇ List 6> An upper member, a lower member, a storage space for storing a reagent between the two members, and a bonding portion for bonding the two members around the storage space, a reagent storage portion provided with: A processing unit having a lower flow path through which liquid flows on the lower surface and an upper flow path through which liquid flows on the upper surface, A drive unit for controlling air, An elastic film disposed between the processing unit and the driving unit; An air pressure control unit that switches whether the elastic film is in close contact with the processing unit or in close contact with the driving unit, With At least a portion of the lower member of the reagent storage unit is joined to the upper surface side of the processing unit, The lower member is provided with a removed portion partially removed above the upper surface flow path, At least a part of the joint between the removing part and the storage space has a weaker joint strength than other parts, A sample processing apparatus, wherein both ends of the upper surface channel communicate with different lower surface channels.
- ⁇ List 7> An upper member, a lower member, a storage space for storing a reagent between the two members, and a joining portion in which the two members are joined around the storage space, a reagent storage portion provided with: A processing unit having a lower flow path through which liquid flows on the lower surface and an upper flow path through which liquid flows on the upper surface, A sealing member for sealing the upper surface side of the processing unit, A drive unit for controlling air, An elastic film disposed between the processing unit and the driving unit; An air pressure control unit that switches whether the elastic film is in close contact with the processing unit or in close contact with the driving unit, With At least a portion of the lower member of the reagent storage unit is joined to the sealing member, The lower member and the sealing member are provided with a removed portion partially removed above the upper surface flow path, At least a part of the joint between the removing part and the storage space has a weaker joint strength than other parts, A sample processing apparatus, wherein both ends of the upper surface flow path communicate with different lower surface flow paths.
- a reagent storage unit A processing unit having an upper surface flow path through which liquid flows on the upper surface side and a lower surface flow path through which liquid flows on the lower surface side, and both ends of the upper surface flow path communicating with the different lower surface flow paths, A sealing member for sealing the upper side of the processing unit, A drive unit for controlling air, An elastic film disposed between the processing unit and the driving unit; An air pressure control unit that switches whether the elastic film is in close contact with the processing unit or in close contact with the driving unit,
- the reagent storage section includes an upper member, a lower member, a storage space for storing a reagent between the two members, and a joining portion for joining the two members around the storage space, and at least one of the lower members.
- a part is joined to the sealing member, and the lower member and the sealing member are provided with a removed part partially removed above the upper surface flow path, At least a part of the joint between the removal part and the storage space has lower joint strength than other parts,
- a sample processing apparatus comprising:
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Abstract
Description
試料処理デバイス1の処理部である分析チップ10は、上面側が密封フィルム21で接合されており、さらに密封フィルム21に対して試薬保存部80、85が接合されている。分析チップ10の下面側は弾性膜であるメンブレン20で密封されている。上述したように本明細書において、このような弾性膜と密封フィルム等が密着し、外部との流体の出入りがない処理部としての分析チップと試薬保存部との組み合わせを密封型デバイスと呼ぶ。
複液試薬保存部80は、複液上部フィルム81と複液下部フィルム82で構成され、複液上部フィルム80の凸部である、試薬1室810、試薬2室811、試薬3室812に、それぞれ異なる試薬を保持することが可能である。複液下部フィルム82にはフィルムが除去され欠損している試薬3フィルム除去部821がある。各試薬が保持された状態で、試薬3フィルム除去部821の部分を除き複液上部フィルム81と複液下部フィルム82との接触面は接合されて接合部を形成している。すなわち、接合部とは保存空間の周囲で両フィルムを接合する部分を意味する。
加熱圧着する場合は、材料の組み合わせにより最適な温度、圧力、接合処理時間があるが、低強度接合部に対しては、低温度、低圧力、短時間の条件から選択する。あるいは図2の(C)に示すように、接合領域を限定してもよい。図2の(C)は、単液試薬保存部85の接合状態を示したもので、試薬4室850と試薬4フィルム除去部860と試薬4低強度接合部870以外の部分876は通常の接合部であり、試薬4低強度接合部870の領域だけ、部分的に非接合領域875を設けている。
図5の(A)、(B)は、実施例1に係る試料処理装置の上面図、側面図を示す。同図の試料処理装置では、密封フィルム21、分析チップ10及びメンブレン20が、蓋50により駆動部40に押し付けられ、密封フィルム21の上部に試薬保存部80、85が搭載され、密封型デバイスを構成している。
まず、図10の(B)に示すように、試薬1室加圧機構552を下降させ、試薬1室810を加圧する。試薬1室810は押しつぶされ、内圧が増加することにより試薬12低強度溶着部831を開き、内部の試薬1は試薬2室811側へ流出する。
次に、単液押出し機構57を用いた単液試薬保存部85からの試薬導入について、図12を用いて説明する。
図24に示すように、試薬室895の両側に空気室896,897を設ける。図24では2つの空気室896、897は試薬室895より大きい。このように試薬室を囲むように空気室からなる保護構造を設けることで,試薬を搭載した密着型デバイスを落下させたとしても,空気室896、897が試薬室を保護するため,試薬室895から試薬が流出することはない。なお,この保護構造は試薬室を保護することが目的であるため,空気室896、897の形状は半球状の形状である必要はなく,リブや突起などの形状でもよく,内部に空気以外の物質を入れても,内部に空間のない構造でもよい。
本実施例によれば、実施例1~3の試料処理デバイス、試料処理装置と同様、弾性膜の変形による流動操作により、試薬を少ない残液量でデバイス内に導入することが可能であり、更に試薬室の保護を図ることができる。
下面側で液体が流れる下面流路と上面側で液体が流れる上面流路を有する処理部と、
上部部材と前記処理部上面側との間に試薬を保存する保存空間と、前記保存空間の周囲および前記上面流路の周囲で前記上部部材と前記処理部上面側を接合した接合部と、を設けた試薬保存部と、
前記処理部下面側を密封する弾性膜と、
を備え、
前記接合部は、前記上面流路と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱く、
前記上面流路の両端は、異なる前記下面流路に連通することを特徴とする、試料処理デバイス。
上部部材と、下部部材と、両部材の間に試薬を保存する保存空間と、前記保存空間の周囲で両部材を接合した接合部と、を設けた試薬保存部と、
下面側で液体が流れる下面流路と上面側で液体が流れる上面流路を有する処理部と、
前記処理部下面側を密封する弾性膜と、
を備え、
前記試薬保存部の下部部材の少なくとも一部は前記処理部の上面側に接合され、
前記下部部材は一部が除去された除去部を前記上面流路の上部に備え、
前記接合部は、前記除去部と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱く、
前記上面流路の両端は、異なる前記下面流路に連通することを特徴とする、試料処理デバイス。
上部部材と、下部部材と、両部材の間に試薬を保存する保存空間と、前記保存空間の周囲で両部材を接合した接合部と、を設けた試薬保存部と、
下面側で液体が流れる下面流路と上面側で液体が流れる上面流路を有する処理部と、
前記処理部上面側を密封する密封部材と、
前記処理部下面側を密封する弾性膜と、
を備え、
前記試薬保存部の下部部材の少なくとも一部は前記密封部材に接合され、
前記下部部材および前記密封部材は一部が除去された除去部を前記上面流路の上部に備え、
前記接合部は、前記除去部と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱く、
前記上面流路の両端は、異なる前記下面流路に連通することを特徴とする、試料処理デバイス。
試薬保存部と、
上面側で液体が流れる上面流路と下面側で液体が流れる下面流路とを有し、前記上面流路の両端は異なる前記下面流路に連通する処理部と、
前記処理部の上面側を密封する密封部材と、
前記処理部の下面側を密封する弾性膜と、を備え、
前記試薬保存部は、上部部材と、下部部材と、両部材の間に試薬を保存する保存空間と、前記保存空間の周囲で前記両部材を接合する接合部とからなり、
前記下部部材の少なくとも一部は前記密封部材に接合され、前記下部部材および前記密封部材は一部が除去された除去部を前記上面流路の上部に備え、
前記接合部は、前記除去部と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱い、
ことを特徴とする試料処理デバイス。
下面側で液体が流れる下面流路と上面側で液体が流れる上面流路を有する処理部と、
上部部材と前記処理部上面側との間に試薬を保存する保存空間と、前記保存空間の周囲および前記上面流路の周囲で前記上部部材と前記処理部上面側を接合した接合部と、を設けた試薬保存部と、
空気を制御する駆動部と、
前記処理部と前記駆動部間に配置された弾性膜と、
前記弾性膜が前記処理部側へ密着するか前記駆動部側へ密着するかを切り替える空気圧制御部と、を備え、
前記接合部は、前記上面流路と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱く、
前記上面流路の両端は、異なる下面流路に連通することを特徴とする、試料処理装置。
上部部材と、下部部材と、両部材の間に試薬を保存する保存空間と、前記保存空間の周囲で両部材を接合する接合部と、を設けた試薬保存部と、
下面側で液体が流れる下面流路と上面側で液体が流れる上面流路を有する処理部と、
空気を制御する駆動部と、
前記処理部と前記駆動部間に配置された弾性膜と、
前記弾性膜が前記処理部側へ密着するか前記駆動部側へ密着するかを切り替える空気圧制御部と、
を備え、
前記試薬保存部の下部部材の少なくとも一部は前記処理部の上面側に接合され、
前記下部部材は一部が除去された除去部を前記上面流路の上部に備え、
前記接合部は、前記除去部と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱く、
前記上面流路の両端は、異なる前記下面流路に連通することを特徴とする、試料処理装置。
上部部材と、下部部材と、両部材の間に試薬を保存する保存空間と、前記保存空間の周囲で両部材を接合した接合部と、を設けた試薬保存部と、
下面側で液体が流れる下面流路と上面側で液体が流れる上面流路を有する処理部と、
前記処理部上面側を密封する密封部材と、
空気を制御する駆動部と、
前記処理部と前記駆動部間に配置された弾性膜と、
前記弾性膜が前記処理部側へ密着するか前記駆動部側へ密着するかを切り替える空気圧制御部と、
を備え、
前記試薬保存部の下部部材の少なくとも一部は前記密封部材に接合され、
前記下部部材および前記密封部材は一部が除去された除去部を前記上面流路の上部に備え、
前記接合部は、前記除去部と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱く、
前記上面流路の両端は、異なる前記下面流路に連通することを特徴とする、試料処理装置。
試薬保存部と、
上面側で液体が流れる上面流路と下面側で液体が流れる下面流路とを有し、前記上面流路の両端は異なる前記下面流路に連通する処理部と、
前記処理部の上面側を密封する密封部材と、
空気を制御する駆動部と、
前記処理部と前記駆動部間に配置された弾性膜と、
前記弾性膜が前記処理部側へ密着するか前記駆動部側へ密着するかを切り替える空気圧制御部と、を備え、
前記試薬保存部は、上部部材と、下部部材と、両部材の間に試薬を保存する保存空間と、前記保存空間の周囲で前記両部材を接合する接合部とからなり、前記下部部材の少なくとも一部は前記密封部材に接合され、前記下部部材および前記密封部材は一部が除去された除去部を前記上面流路の上部に備え、
前記接合部は、前記除去部と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱い、
ことを特徴とする試料処理装置。
Claims (15)
- 試薬保存部と、
上面側で液体が流れる上面流路と下面側で液体が流れる下面流路を有し、前記上面流路の両端は異なる前記下面流路に連通する処理部と、
前記処理部の下面側を密封する弾性膜と、を備え、
前記試薬保存部は、上部部材と前記処理部の上面側との間に試薬を保存する保存空間と、前記保存空間の周囲および前記上面流路の周囲で前記上部部材と前記処理部の上面側を接合する接合部とからなり、
前記接合部は、前記上面流路と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱い低強度接合部を含む、
ことを特徴とする試料処理デバイス。 - 請求項1に記載の試料処理デバイスであって、
前記上部部材が密封フィルムからなる、
ことを特徴とする試料処理デバイス。 - 請求項1に記載の試料処理デバイスであって、
前記低強度接合部は、部分的な非接合領域を含む、
ことを特徴とする試料処理デバイス。 - 請求項1に記載の試料処理デバイスであって、
前記上部部材と前記処理部の上面側との間に、前記保存空間を保護する保護構造を有する、
ことを特徴とする試料処理デバイス。 - 請求項1に記載の試料処理デバイスであって、
前記処理部の上面側を密封する密封部材を更に備え、
前記保存空間は、前記上部部材と前記密封部材との間に形成され、
前記接合部は、前記上部部材と前記密封部材とを接合し、
前記密封部材は、一部が除去された除去部を前記上面流路の上部に備える、
ことを特徴とする試料処理デバイス。 - 試薬保存部と、
上面側で液体が流れる上面流路と下面側で液体が流れる下面流路を有し、前記上面流路の両端は異なる前記下面流路に連通する処理部と、
前記処理部の下面側を密封する弾性膜と、を備え、
前記試薬保存部は、上部部材と、下部部材と、両部材の間に試薬を保存する保存空間と、前記保存空間の周囲で両部材を接合する接合部とからなり、
前記下部部材は一部が除去された除去部を前記上面流路の上部に備え、
前記接合部は、前記除去部と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱い低強度接合部を含む、
ことを特徴とする試料処理デバイス。 - 請求項6に記載の試料処理デバイスであって、
前記低強度接合部は、部分的な非接合領域を含む、
ことを特徴とする試料処理デバイス。 - 請求項6に記載の試料処理デバイスであって、
前記上部部材と前記下部部材との間に、前記保存空間を保護する保護構造を有する、
ことを特徴とする試料処理デバイス。 - 請求項6に記載の試料処理デバイスであって、
前記処理部の上面側を密封する密封部材を備え、
前記密封部材は、前記下部部材の除去部に対応する位置が除去されている、
ことを特徴とする試料処理デバイス。 - 請求項6に記載の試料処理デバイスであって、
前記保存空間を形成する前記上部部材は上面側に凸形状であり、前記下部部材は下面側に凸形状である、
ことを特徴とする試料処理デバイス。 - 試薬保存部と、
上面側で液体が流れる上面流路と下面側で液体が流れる下面流路を有し、前記上面流路の両端は異なる前記下面流路に連通する処理部と、
空気を制御する駆動部と、
前記処理部と前記駆動部の間に配置された弾性膜と、
前記弾性膜が前記処理部へ密着するか前記駆動部へ密着するかを切り替える空気圧制御部と、を備え、
前記試薬保存部は、上部部材と、下部部材と、両部材の間に試薬を保存する保存空間と、前記保存空間の周囲で前記両部材を接合する接合部とからなり、
前記下部部材の少なくとも一部は前記処理部の上面側に接合され、前記下部部材は一部が除去された除去部を前記上面流路の上部に備え、
前記接合部は、前記除去部と前記保存空間の間の少なくとも一部が他の部分よりも接合強度が弱い低強度接合部を含む、
ことを特徴とする試料処理装置。 - 請求項11に記載の試料処理装置であって、
前記試薬保存部と、前記処理部と、前記弾性膜とで密封型デバイスを構成する、
ことを特徴とする試料処理装置。 - 請求項12に記載の試料処理装置であって、
前記保存空間と前記低強度接合部を加圧する押出し機構を更に備える、
ことを特徴とする試料処理装置。 - 請求項13に記載の試料処理装置であって、
操作部を更に備え、
前記操作部からの指示に基づき、前記押出し機構により前記保存空間と前記低強度接合部を加圧し、前記試薬保存部から前記上面流路に試薬を導入する、
ことを特徴とする試料処理装置。 - 請求項14に記載の試料処理装置であって、
前記保存空間を形成する前記上部部材は上面側に凸形状であり、前記下部部材は下面側に凸形状であり、
前記保存空間を加圧する前記押出し機構は、先端が下面側に凸形状である、
ことを特徴とする試料処理装置。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007162899A (ja) * | 2005-12-16 | 2007-06-28 | Pentax Corp | マイクロバルブ |
JP2013519884A (ja) * | 2010-02-12 | 2013-05-30 | ノースウエスタン ユニバーシティ | サンプル取得、処理及び反応のためのアッセイカード |
US20150190802A1 (en) * | 2014-01-07 | 2015-07-09 | Daktari Diagnostics, Inc. | Fluid delivery devices, systems, and methods |
WO2015186454A1 (ja) * | 2014-06-05 | 2015-12-10 | 株式会社日立ハイテクノロジーズ | 生化学用試薬類保存デバイス、及び生化学用分析装置 |
JP2017096819A (ja) * | 2015-11-26 | 2017-06-01 | 株式会社日立ハイテクノロジーズ | 保存容器、流動カートリッジ、および吐出機構 |
WO2018020924A1 (ja) * | 2016-07-25 | 2018-02-01 | 株式会社日立ハイテクノロジーズ | 気泡除去構造、気泡除去方法、及び攪拌方法 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007162899A (ja) * | 2005-12-16 | 2007-06-28 | Pentax Corp | マイクロバルブ |
JP2013519884A (ja) * | 2010-02-12 | 2013-05-30 | ノースウエスタン ユニバーシティ | サンプル取得、処理及び反応のためのアッセイカード |
US20150190802A1 (en) * | 2014-01-07 | 2015-07-09 | Daktari Diagnostics, Inc. | Fluid delivery devices, systems, and methods |
WO2015186454A1 (ja) * | 2014-06-05 | 2015-12-10 | 株式会社日立ハイテクノロジーズ | 生化学用試薬類保存デバイス、及び生化学用分析装置 |
JP2017096819A (ja) * | 2015-11-26 | 2017-06-01 | 株式会社日立ハイテクノロジーズ | 保存容器、流動カートリッジ、および吐出機構 |
WO2018020924A1 (ja) * | 2016-07-25 | 2018-02-01 | 株式会社日立ハイテクノロジーズ | 気泡除去構造、気泡除去方法、及び攪拌方法 |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022074730A1 (ja) * | 2020-10-06 | 2022-04-14 | 株式会社日立ハイテク | 試料処理デバイス、試料処理装置及び試料の処理方法 |
GB2613115A (en) * | 2020-10-06 | 2023-05-24 | Hitachi High Tech Corp | Sample processing device, sample processing apparatus, and sample processing method |
JP7475474B2 (ja) | 2020-10-06 | 2024-04-26 | 株式会社日立ハイテク | 試料処理デバイス、試料処理装置及び試料の処理方法 |
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