WO2019181655A1 - Récipient de stockage, couvercle de récipient de réactif, récipient de réactif et cartouche de réactif - Google Patents

Récipient de stockage, couvercle de récipient de réactif, récipient de réactif et cartouche de réactif Download PDF

Info

Publication number
WO2019181655A1
WO2019181655A1 PCT/JP2019/010055 JP2019010055W WO2019181655A1 WO 2019181655 A1 WO2019181655 A1 WO 2019181655A1 JP 2019010055 W JP2019010055 W JP 2019010055W WO 2019181655 A1 WO2019181655 A1 WO 2019181655A1
Authority
WO
WIPO (PCT)
Prior art keywords
container
reagent
thickness
well
lid
Prior art date
Application number
PCT/JP2019/010055
Other languages
English (en)
Japanese (ja)
Inventor
芳朋 筒井
とも子 三田
秀一 明石
鈴木　利幸
大上　創一
Original Assignee
凸版印刷株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from JP2018051606A external-priority patent/JP7003763B2/ja
Priority claimed from JP2018051627A external-priority patent/JP7059725B2/ja
Priority claimed from JP2018060500A external-priority patent/JP7043921B2/ja
Application filed by 凸版印刷株式会社 filed Critical 凸版印刷株式会社
Priority to CN201980020417.5A priority Critical patent/CN111902722A/zh
Publication of WO2019181655A1 publication Critical patent/WO2019181655A1/fr

Links

Images

Classifications

    • 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
    • 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

Definitions

  • the present invention relates to a storage container for storing a dispensing pipette, a reagent container lid, a reagent container using a reagent container lid, and a reagent cartridge in which a reagent containing minute beads (particles) is stored.
  • This application includes Japanese Patent Application No. 2018-051627 filed in Japan on March 19, 2018, Japanese Patent Application No. 2018-060500 filed in Japan on March 27, 2018, and March 19, 2018 Claim priority based on Japanese Patent Application No. 2018-051606 filed in Japan, the contents of which are incorporated herein.
  • nucleic acid can be extracted from a sample such as a biological sample collected from a patient, and genetic differences such as single nucleotide polymorphisms can be detected to predict drug sensitivity in advance. Sex has been suggested.
  • reagents necessary for extracting nucleic acid from the subject are contained in the reagent cartridge, and each time the nucleic acid is extracted from the subject, these reagents are used up, and the used reagent cartridge is discarded (for example, Patent Document 1).
  • Dispensing pipettes used for reagent dispensing are also discarded after each use, just like reagent cartridges, to prevent cross-contamination between specimens and to prevent the spread of infection sources ( For example, see Patent Document 2).
  • the dispensing pipette described in Patent Document 2 is stored in a dispensing pipette tip rack (accommodating container) and discarded together with the accommodating container.
  • Patent Document 1 describes a nucleic acid analyzer that supplies a whole blood sample collected from a patient to a cartridge and performs purification of the nucleic acid and analysis of the nucleic acid using the cartridge. Yes.
  • the burden on the user in nucleic acid analysis can be reduced by reducing the portion depending on the user's manual work.
  • the reproducibility of nucleic acid analysis can be improved without variation in the nucleic acid recovery rate due to the difference in skill of users.
  • Patent Document 3 describes a reagent container applicable to the above-described nucleic acid analyzer.
  • the reagent container described in Patent Document 3 has a plurality of reagent storage units in which reagents are stored.
  • the opening of each reagent container is sealed until use by a coating film having an aluminum layer and a seal layer, and is pierced by a pipette tip or the like when used.
  • polymer beads are usually hydrophobic and have a high protein binding capacity.
  • Silica beads are easy to modify such as functional group addition and particle surface change.
  • Magnetic beads are suitable for screening that captures only a specific substance using magnetic force.
  • an antibody designed to bind to the target antigen is immobilized on the magnetic bead surface.
  • Add magnetic beads having antibodies on the surface to a solution in which antigens and impurities are mixed and stir.
  • a magnet is brought close to a container containing a solution of an antigen bound to magnetic beads, the antigen bound to the magnetic beads is attracted to the magnet.
  • an antigen solution with few impurities can be obtained by adding a washing process such as replacing the solution in the container with a solution containing no impurities.
  • Such screening suggests the possibility of predicting drug sensitivity in advance by extracting nucleic acid from a specimen such as a biological sample collected from a patient and detecting a genetic difference such as a single nucleotide polymorphism. Has been.
  • reagents necessary for extracting nucleic acid from the subject are contained in the reagent cartridge, and each time the nucleic acid is extracted from the subject, these reagents are used up, and the used reagent cartridge is discarded (for example, Patent Document 1).
  • Patent Document 4 describes a specimen pretreatment cartridge that separates and extracts nucleic acids by adsorbing magnetic beads adsorbed with nucleic acids to the inner wall of a housing portion using a magnet. By using the sample pretreatment cartridge, the time required for nucleic acid extraction can be shortened.
  • the container described in Patent Document 2 has a shape in which a plurality of dispensing pipettes can be easily stored and taken out.
  • the storage container itself is a disposable container, it has a simple structure and is configured to be self-supporting by a thin plate-like leg portion provided on the outer periphery of the storage portion of the dispensing pipette.
  • the storage container does not necessarily have a stable and self-supporting structure.
  • the coating film described in Patent Document 3 has an advantage that it can be suitably broken by a pipette tip or the like by reducing the thickness of the aluminum layer and the seal layer.
  • the covering film described in Patent Document 3 emphasizes ease of breakthrough, the sealing strength may not always be sufficient, and there is room for improvement. Although details will be described later, the inventor has also found other improvements.
  • the polymer beads have a high affinity with the resin container and are easily adsorbed. Also, since the magnetic beads are strongly attracted to the inner wall surface of the housing part by the magnet, some magnetic beads are housed when separating the magnetic beads adsorbed on the inner wall of the housing part away from the housing part. In some cases, the magnetic beads could not be efficiently recovered due to continued adsorption on the inner wall of the part. Patent Document 4 does not describe the characteristics of the inner wall of the housing portion that can efficiently recover the magnetic beads. In response to these problems, measures have been taken such as reducing the unevenness of the inner wall surface of the housing portion or performing a water-repellent surface treatment.
  • the fine beads are an effective material as a bio-based reagent, they may remain adsorbed in the container due to the influence of the size and material.
  • Many of the reagents are expensive, and when the amount of the reagent remaining in the container is large, the increased amount of the used reagent causes an increase in cost.
  • the amount of minute beads remaining in the container is large, the amount of substance extraction may be insufficient when extracting a low-concentration substance.
  • a first object of the present invention is to provide a storage container that stores a dispensing pipette and that can stably stand on its own.
  • the second object of the present invention is to provide a reagent container lid material that achieves a high level of ease of breakthrough and sealing strength against the container.
  • a third object of the present invention is to provide a reagent container in which the reagent container is securely sealed with a lid material, and the lid material using a pipette tip or the like can be easily broken through.
  • a fourth object of the present invention is to provide a reagent cartridge including a specimen container having an inner wall that is difficult to adsorb minute particles such as polymer beads and magnetic beads.
  • the storage container includes a main body having a plurality of storage portions and a plurality of leg portions, and each of the plurality of storage portions has an opening only on the upper surface of the main body, The plurality of openings are arranged in a first direction and a second direction different from the first direction, and the plurality of leg portions connect the two accommodating portions adjacent to each other in the first direction. And a second leg portion that connects the two accommodating portions adjacent to each other in the second direction, and each of the plurality of leg portions includes the plurality of legs with respect to a downward direction in a height direction.
  • the protrusions protrude from each of the storage portions, and the protrusions form a bottom surface parallel to the top surface.
  • the first direction and the second direction may intersect perpendicularly.
  • the said opening may be arrange
  • the openings of the housing portions may be arranged at all the intersections of the lattice.
  • the main body further includes a marker, and the opening of the receiving portion and the marker are disposed at any of the intersections of the lattice, and the marker may be disposed at a position other than the center of the intersection of the lattice. Good. At least one of the opening and the marker in the housing portion may be arranged at all the intersections of the lattice.
  • the said accommodating part may have a 1st accommodating part and a 2nd accommodating part from which an internal diameter differs.
  • the lid material for a reagent container includes a base material layer having a thickness of 10 ⁇ m or more and 20 ⁇ m or less, and a metal layer having a thickness of 5 ⁇ m or more and 10 ⁇ m or less arranged on one side in the thickness direction of the base material layer. And a heat-sealing layer provided opposite to the base material layer in the metal layer and having a thickness of 2 to 3 times the thickness of the base material layer.
  • the thickness of the heat sealing layer may be 20 ⁇ m or more and 35 ⁇ m or less.
  • the thickness of the heat-fusible layer may be 1 to 2 times the sum of the thickness of the base material layer and the thickness of the metal layer.
  • the reagent container according to the third aspect of the present invention includes a container main body having a plurality of reagent storage portions in which reagents are stored, and the plurality of reagent storages by heat sealing the heat sealing layer to the container main body.
  • a reagent cartridge is a reagent cartridge, and includes a main body having a subject container for dispensing a solution containing particles, and an average length of curved elements on the inner wall of the subject container.
  • the roughness defined by is 1/50 times to 2/3 times the outer diameter of the particles.
  • the roughness defined by the average length of the curved element of the inner wall of the subject container may be 1/20 times to 1/2 times the outer diameter of the particles. 1/100 or less may be sufficient as the contact area of the said particle
  • the distance between the particle and the inner wall in a portion where the particle and the inner wall are not in contact may be 10 nm or more.
  • the particles may be magnetic beads.
  • the storage container can be made stable and independent. Further, the reagent container lid according to the above aspect of the present invention achieves both high ease of breakthrough and high sealing strength for the container.
  • the reagent container is securely sealed by the lid material, and the lid material using a pipette tip or the like can be easily pierced.
  • the reagent cartridge according to the above aspect of the present invention it is difficult for minute particles to be adsorbed on the inner wall of the subject container.
  • FIG. 3 is a cross-sectional view taken along a line AA ′ perpendicular to the Y axis in the dispensing pipette rack shown in FIG. 2.
  • FIG. 3 is a cross-sectional view taken along the line BB ′ perpendicular to the X axis in the dispensing pipette rack shown in FIG. 2.
  • FIG. 1 is a perspective view showing an entire configuration of a dispensing pipette rack 200 according to the present embodiment and a reagent cartridge 100 used together with the dispensing pipette rack 200.
  • a dispensing pipette rack 200 shown in FIG. 1 accommodates a dispensing pipette tip 201 and a drilling pipette tip 202.
  • the reagent cartridge 100 stores a reagent for extracting nucleic acid from the subject.
  • the sample is loaded into the reagent cartridge 100, and the reagent cartridge 100 and the dispensing pipette rack 200 are attached to a nucleic acid extraction apparatus (not shown), whereby the nucleic acid extraction operation using the dispensing pipette tip 201 is performed by the machine. Can be implemented automatically.
  • the reagent cartridge 100 includes a main body 101 formed in a box shape having an opening, and a claw portion 102 formed so as to protrude laterally from the outer surface of the main body 101.
  • the claw portion 102 is used for fixing the reagent cartridge 100 to the nucleic acid extraction apparatus.
  • a sample well (subject storage portion) 110 into which a subject such as a biological sample is put, a reagent well portion 120 in which a reagent for extracting nucleic acid from the subject is stored, A waste liquid well (waste liquid storage unit) 130 for discarding an unnecessary solution separated in the step of extracting nucleic acid from the subject and a recovery well 140 for recovering the nucleic acid extracted from the subject are integrally provided.
  • the reagent cartridge 100 includes an extraction filter cartridge 150 containing a carrier that adsorbs nucleic acids.
  • the reagent cartridge 100 is provided with a holding portion 160 in which the extraction filter cartridge 150 is accommodated.
  • the reagent well section 120 includes a plurality of reagent wells (reagent storage sections) 121, 122, 123, 124, 125, 126, an oil well (oil storage section) 127, and an oil removal section 128.
  • the openings of the plurality of reagent wells 121 to 126 and the openings of the oil well 127 and the oil removing portion 128 are sealed by the sealing film 104 shown in FIG.
  • the sealing film 104 prevents gas from entering the reagent wells 121 to 126 and the oil well 127.
  • the sealing film 104 is formed of a material that can be pierced by a dispensing pipette tip 201 or a drilling pipette tip 202 described later.
  • the sealing film 104 can be formed of, for example, a metal thin film or a plastic film.
  • a biological fluid such as a cell membrane that dissolves a biological material such as a cell membrane, and a biological material such as a cytoplasm that cannot be completely dissolved by the dissolution fluid 121A and clogs the carrier.
  • washing solution 123A for washing away unnecessary substances other than nucleic acids adsorbed on the carrier
  • washing solution 124A washing solution 124A
  • elution solution 125A for eluting nucleic acid from the carrier
  • diluting solution 126A for adjusting the nucleic acid concentration in the elution solution.
  • oil well 127 for example, a well-known oil 127A used in a PCR reaction by being stacked on a reaction solution is accommodated.
  • oil 127A for example, mineral oil or silicon oil can be preferably used.
  • the oil removing unit 128 is a member for removing the oil 127A adhering to the outer surface of the dispensing pipette tip 201 when supplying the oil 127A to the dispensing pipette tip 201, and has a filter (not shown) inside.
  • the waste liquid well 130 has a shape corresponding to the outer shape of the bottom of the extraction filter cartridge 150, and is a recess that can support the extraction filter cartridge 150.
  • the extraction filter cartridge 150 is configured not to fall within the reagent cartridge 100.
  • the recovery well 140 is a recess having a shape capable of supporting the extraction filter cartridge 150 in the same manner as the waste well 130.
  • the bottom of the recovery well 140 has a shape that can store the nucleic acid solution eluted from the carrier of the extraction filter cartridge 150 by the eluent 125A.
  • the waste liquid well 130 and the recovery well 140 are provided adjacent to each other in the reagent cartridge 100.
  • the arrangement of the waste liquid well 130 and the recovery well 140 shortens the flow line of the extraction filter cartridge 150 when the extraction filter cartridge 150 is moved to the recovery well 140 after the extraction filter cartridge 150 is washed in the waste liquid well 130. It is an arrangement for. Thereby, the possibility that the extraction filter cartridge 150 passing over the reagent cartridge 100 contaminates the reagent cartridge 100 or the like can be reduced.
  • the extraction filter cartridge 150 has an extraction filter unit (not shown) inside.
  • This extraction filter unit is a member for temporarily adsorbing nucleic acids contained in the sample dispensed from the sample well 110.
  • ⁇ Dispensing pipette rack> As shown in FIG. 1, a plurality of pipette tips 201 and a pipette tip 202 for punching are accommodated in the pipette rack 200 (accommodating container).
  • the dispensing pipette tip 201 is a member for dispensing and stirring the liquid stored in the reagent cartridge 100.
  • the liquid stored in the reagent cartridge 100 is dispensed or agitated by any of the plurality of dispensing pipette tips 201, and no cross contamination occurs between the liquids by the dispensing pipette tips 201.
  • the drilling pipette tip 202 is a member that is used to pierce the sealing film 104 that seals the openings of the reagent wells 121 to 126, the oil well 127, and the oil removal unit 128 to make a hole. After making a hole in the sealing film 104 on each well using the pipetting tip 202 for making a hole, the dispensing pipette tip 201 is inserted into each well through this hole.
  • the dispensing pipette rack 200 is also a container for collecting the used dispensing pipette tips 201 and the drilling pipette tips 202, and is used as infectious waste after the use of the dispensing pipette tips 201 in the nucleic acid extraction apparatus. Dispensing pipette tips 201 and drilling pipette tips 202 can be discarded along with the dispensing pipette rack 200.
  • FIG. 2 is a plan view of the dispensing pipette rack 200.
  • the dispensing pipette rack (container) 200 includes a main body 210 formed in a box shape having no bottom surface.
  • the main body 210 is integrally formed with a plurality of accommodating portions 220 that can accommodate the dispensing pipette tips 201 or the drilling pipette tips 202, the leg portions 230, and the markers 240.
  • the main body 210 has an upper surface 210a formed in a substantially square shape, and the four corners of the side surface of the main body 210 are subjected to R chamfering from the viewpoint of ease of holding.
  • the housing part 220 is a cavity having an opening only on the upper surface 210a of the main body 210, as shown in FIGS.
  • the accommodating portion 220 includes a first accommodating portion 221 that can accommodate the dispensing pipette tip 201 and a second accommodating portion 222 that can accommodate the pipette tip 202 for punching.
  • the housing part 220 includes seven first housing parts 221 and one second housing part 222.
  • three openings 221a of seven first accommodating portions 221, openings 222a of one second accommodating portion 222, and one marker 240 is formed in a grid of 3 rows and 3 columns. Specifically, the centers of the seven openings 221a, the one opening 222a, and the one marker 240 coincide with one of the intersections of the lattice L of 3 rows and 3 columns.
  • one direction (row direction) in which the lattice L extends is referred to as a “first direction”
  • the other direction (column direction) is referred to as a “second direction”.
  • the first direction and the second direction intersect perpendicularly.
  • the centers of the seven openings 221a, one opening 222a, and one marker 240 are arranged in a first direction and a second direction different from the first direction, as shown in FIG.
  • the first direction of the lattice L in which the opening of the accommodating portion 220 is arranged is the “X axis”
  • the direction orthogonal to the X axis on the upper surface 210a is the “Y axis”
  • the X axis is the direction orthogonal to the X axis on the upper surface 210a
  • the height direction of the main body 210 orthogonal to the Y axis is also referred to as “Z axis”.
  • the second direction coincides with the Y-axis direction.
  • the opening 222a and the marker 240 of the second housing portion 222 are formed at a position corresponding to one of the corners of the lattice L of 3 rows and 3 columns, as shown in FIG. As shown in FIG. 2, the opening 222a and the marker 240 of the second housing portion 222 are formed in the same position in the first direction (X axis) and at different positions in the second direction (Y axis). .
  • FIG. 3 is a cross-sectional view taken along the line AA ′ perpendicular to the Y axis in the dispensing pipette rack 200 shown in FIG.
  • AA ′ cross section three first accommodating portions 221 are arranged in the X-axis direction.
  • FIG. 4 is a cross-sectional view taken along the line BB ′ perpendicular to the X axis in the dispensing pipette rack 200 shown in FIG.
  • the BB ′ cross section one first accommodating portion 221 and one second accommodating portion 222 are arranged in the Y-axis direction.
  • the first accommodating portion 221 is a substantially cylindrical cavity having a circular opening 221a on the upper surface 210a of the main body 210, as shown in FIG. As shown in FIG. 3, the first housing portion 221 is closed at the bottom surface (the tip portion on the opposite side of the top surface in the Z-axis direction).
  • the first accommodating portion 221 is easy to accommodate the dispensing pipette tip 201 whose inner diameter is smaller toward the lower side in the Z-axis direction and whose outer diameter is smaller toward the tip.
  • the second housing portion 222 is a substantially cylindrical cavity having a circular opening 222 a on the upper surface 210 a of the main body 210. As shown in FIG. 4, the second housing portion 222 is closed at the bottom surface portion (the tip portion on the opposite side of the top surface in the Z-axis direction).
  • the second accommodating portion 222 has an inner diameter that is smaller toward the lower side in the Z-axis direction, and can easily accommodate the drilling pipette tip 202 whose outer diameter is smaller toward the tip.
  • the outer diameter of the drilling pipette tip 202 is larger than the outer diameter of the dispensing pipette tip 201. Therefore, as shown in FIG. 4, the inner diameter of the second housing part 222 is larger than the inner diameter of the first housing part 221.
  • the first storage portion 221 and the second storage portion 222 have the same length in the Z-axis direction from the top surface 210a to the bottom surface portion of the main body 210, as shown in FIGS.
  • the leg portion 230 includes a first leg portion 231 and a second leg portion 232.
  • the first leg portion 231 and the second leg portion 232 are thin plate members.
  • the first leg portion 231 connects the two accommodating portions 220 adjacent in the first direction (X axis).
  • the 2nd leg part 232 connects the two accommodating parts 220 adjacent to a 2nd direction (Y-axis).
  • the leg portion 230 has a protruding portion 230 b that protrudes downward in the Z-axis direction from the bottom surface portions of the first housing portion 221 and the second housing portion 222.
  • the protruding portion 230b of the portion 230 forms the same plane (referred to as “bottom surface P”).
  • the bottom surface P is parallel to the top surface 210 a of the main body 210.
  • the dispensing pipette rack 200 can stand on its own by grounding the bottom surface P formed by the protruding portions 230b of the plurality of leg portions 230 on a desk or the like.
  • the leg portion 230 is provided between the upper surface 210a and the bottom surface P in the Z-axis, as shown in FIGS. Therefore, the leg part 230 can fix each accommodating part 220 so that the relative position of each accommodating part 220 may not move in the whole from the upper surface 210a to the bottom face part.
  • the curved deformation of the elongated accommodating portion 220 can be suitably prevented. Therefore, the dispensing pipette tip 201 and the drilling pipette tip 202 can be stably accommodated in the accommodating portion 220.
  • FIG. 5 is a bottom view of the main body 210 as viewed from the bottom surface P side.
  • the leg portion 230 connects the accommodating portions 220 adjacent to each other in the first direction (X axis), and the second leg portion 232 is adjacent to the second direction (Y axis).
  • the matching accommodating part 220 is connected.
  • the leg portion 230 is formed only inside the outermost housing portion 220 and is not formed outside the outermost housing portion 220. Therefore, when the user picks up the pipetting pipette rack 200, the leg portion 230 is unlikely to come into contact with the user's hand.
  • the leg portion 230 formed in a thin plate shape can suitably prevent the user's hand from being damaged.
  • the marker 240 is a two-dimensional code including information such as type and expiration date.
  • the marker 240 can also be used to prevent an error between the first direction and the second direction when the user handles the dispensing pipette rack 200.
  • the marker 240 is formed at a corner (upper right corner in FIG. 2) of the 3 ⁇ 3 grid L, and is formed at a point other than the center at the intersection of the 3 ⁇ 3 grid L. .
  • the position where the opening of the accommodating part 220 is arranged is not point-symmetric from the center at the intersection of the lattice L of 3 rows and 3 columns. Therefore, the user can recognize the first direction and the second direction by visually observing the position of the marker.
  • the housing part 220 is not formed at a place where the marker 240 is formed in the main body 210. Therefore, the user can grasp the position of the marker 240 and recognize the first direction and the second direction only by picking up the dispensing pipette rack 200 without looking at the marker 240. . Further, even when the dispensing pipette rack 200 is attached to a nucleic acid extraction apparatus or the like, a mechanism for preventing an error in the direction in which the dispensing pipette rack 200 is attached by using the asymmetric pipetting rack 200 (error) A mounting prevention mechanism) can be provided in a nucleic acid extraction device or the like.
  • the material forming the main body 101, the dispensing pipette rack 200 and the like is not particularly limited as long as it does not affect the sample, the reagent, or the like, but if a resin material including any of polypropylene, polycarbonate, and acrylic is used in particular. Good visible light permeability can be ensured, and the state of the solution can be confirmed.
  • a resin material including any of polypropylene, polycarbonate, and acrylic is used in particular. Good visible light permeability can be ensured, and the state of the solution can be confirmed.
  • polypropylene homopolypropylene or a random copolymer of polypropylene and polyethylene can be used.
  • an acryl the copolymer of monomers, such as polymethyl methacrylate or methyl methacrylate, and other methacrylic acid ester, acrylic acid ester, styrene, can be used.
  • tip can also be ensured.
  • the operation of the dispensing pipette rack 200 having the above-described configuration will be described.
  • the operation of the reagent cartridge 100 will be described by exemplifying the operation of attaching the reagent cartridge 100 and the dispensing pipette rack 200 to the nucleic acid extraction apparatus having a dispensing conveyance function for conveying the dispensing pipette tip 201 and extracting the nucleic acid. Will be explained.
  • a biological sample which is a subject
  • the reagent cartridge 100 loaded with the biological sample is mounted on the nucleic acid extraction apparatus.
  • the dispensing pipette rack 200 in which the dispensing pipette tip 201 and the drilling pipette tip 202 are accommodated is also attached to the nucleic acid extraction apparatus. If the nucleic acid extraction apparatus has the above-described erroneous mounting prevention mechanism, the user can prevent an error in the direction in which the dispensing pipette rack 200 is mounted.
  • the pipetting tip 202 for punching is transported from the pipetting pipette rack 200 by the dispensing transport mechanism of the nucleic acid extraction apparatus, and the sealing film 104 of the reagent well 121 of the reagent cartridge is pierced by the pipetting tip 202 for punching.
  • the dispensing transport mechanism of the nucleic acid extraction apparatus accommodates the holed pipette tips 202 in the dispensing pipette rack 200, and then transports the dispensing pipette tips 201 from the dispensing pipette rack 200.
  • various reagents stored in the reagent well 121 are dispensed and mixed using the dispensing pipette tip 201 by the dispensing conveyance mechanism of the nucleic acid extraction apparatus according to a predetermined procedure.
  • the cells in the biological sample supplied to the sample well 110 are lysed to obtain a cell lysate.
  • Dispensing pipette rack 200 can stand by itself stably by grounding a bottom surface P formed by protruding portions 230b of a plurality of leg portions 230 to a desk or the like. Since the protrusions 230b forming the bottom surface P are formed in a lattice shape, stability is increased when the bottom surface P is grounded to a desk or the like and the dispensing pipette rack 200 is placed, and blood contamination due to a fall or the like is prevented. It can prevent suitably.
  • Dispensing pipette rack 200 further includes a lid on top of upper surface 210a to prevent contamination and contamination of foreign matter before use, and to prevent contamination due to scattering of solution adhering to dispensing pipette tips after extraction. it can.
  • the dispensing pipette rack 200 can be easily made stable and independent.
  • the accommodating part 220 is fixed so as not to move relatively by the leg part, and the curved deformation of the elongated accommodating part 220 can be suitably prevented.
  • the dispensing pipette tip 201 and the drilling pipette tip 202 can be easily and stably housed in the housing portion 220 and easily taken out.
  • the leg portion 230 is formed only inside the outermost housing portion 220 as shown in FIG. Is not formed. Therefore, when the user picks up the pipetting pipette rack 200, the leg portion 230 is unlikely to come into contact with the user's hand.
  • the leg portion 230 formed in a thin plate shape can suitably prevent the user's hand from being damaged.
  • the dispensing pipette rack 200 can stably stand on its own by grounding the bottom surface P formed by the protruding portions 230b of the plurality of leg portions 230 to a desk or the like. It is.
  • the dispensing pipette rack 200 can recognize the first direction and the second direction by the marker 240 or the like.
  • the dispensing pipette rack 200 includes the main body 210, the first storage portion 221, the second storage portion 222, the leg portion 230, and the marker 240.
  • the aspect of the rack is not limited to this.
  • the dispensing pipette rack is provided with a main body having a leg portion and nine first storage portions without a second storage portion and a marker, and an opening of the first storage portion is a lattice of 3 rows and 3 columns on the top surface of the main body. It may be formed in a shape.
  • the opening of the accommodating portion 220 and the marker 240 are formed in a 3 ⁇ 3 lattice pattern on the upper surface 210a, but the manner of the accommodating portion and the marker is not limited to this.
  • the opening of the accommodating part and the marker may be formed on the upper surface of the main body, for example, in a 5 ⁇ 5 or 2 ⁇ 4 grid.
  • positioning aspect of the opening of an accommodating part is not limited to this.
  • the opening of the housing portion may be arranged in a lattice shape that does not intersect perpendicularly as long as the first direction and the second direction are not parallel to each other.
  • positioned was square shape
  • positioning aspect of the opening of an accommodating part is not limited to this.
  • the opening of the accommodating part 220 may be arrange
  • the opening of the accommodating part 220 was arranged at equal intervals in the 1st direction and the 2nd direction, the arrangement
  • the openings of the accommodating part 220 may be arranged at unequal intervals in the first direction and the second direction.
  • FIG. 6 is a bottom view of the main body 210 as seen from the bottom side of a dispensing pipette rack 200 ⁇ / b> B that is a modification of the dispensing pipette rack 200.
  • the accommodating part 220B of the dispensing pipette rack 200B includes three first accommodating parts 221 as shown in FIG.
  • first leg portion 231 that connects two storage portions 220B adjacent in the first direction
  • second leg portion 232 that connects two storage portions 220B adjacent in the second direction. There is also one.
  • the accommodating portion 220B is arranged in a first direction and a second direction different from the first direction, and the protruding portions of the leg portions (the first leg portion 231 and the second leg portion 232) extending in two directions are provided.
  • Dispensing pipette rack 200B can be made stable and independent by the bottom surface to be formed.
  • FIG. 7 is a bottom view seen from the bottom side of the dispensing pipette rack 200C.
  • Dispensing pipette rack 200C includes a main body 210 having a plurality of housing portions 220C capable of housing dispensing pipette tips 201 and the like, and leg portions 230C.
  • the housing part 220 ⁇ / b> C is a cavity having an opening only on the upper surface 210 a of the main body 210, like the housing part 220.
  • the accommodating portion 220 ⁇ / b> C includes 16 first accommodating portions 221 that can accommodate the dispensing pipette tips 201.
  • the accommodating portions 220C are formed in a 4 ⁇ 4 grid.
  • the leg portion 230C includes a first leg portion 231C and a second leg portion 232C.
  • the first leg portion 231 ⁇ / b> C connects two first accommodation portions 221 adjacent in the first direction (X axis).
  • the second leg portion 232C connects the two first accommodation portions 221 adjacent in the second direction (Y axis). Even if the accommodating part 220C is adjacent in the first direction, there is a portion that is not connected by the first leg part 231C (leg part 230C), and even if it is adjacent in the second direction, the second leg part 232C ( There are places that are not connected by legs 230C). However, there is no accommodating portion 220C that is not connected to any accommodating portion 220C.
  • the leg portion 230C has a protruding portion that protrudes downward in the Z-axis direction from the bottom surface portion of the housing portion 220C, and the protruding portions of the plurality of leg portions 230C form the same plane (“bottom surface P”).
  • the bottom surface P is parallel to the top surface 210 a of the main body 210.
  • Dispensing pipette rack 200C can stand on its own by grounding a bottom surface P formed by the protruding portions of a plurality of leg portions 230C on a desk or the like.
  • the dispensing pipette rack 200C has a portion of the leg 230 omitted in comparison with the dispensing pipette rack 200 according to the first embodiment, but the protrusions forming the bottom surface P are partially in a lattice shape. Since it is formed, the stability increases when the dispensing pipette rack 200C is placed with the bottom surface P grounded to a desk or the like, and contamination of blood due to a fall or the like can be suitably prevented.
  • the dispensing pipette rack 200C can be made stable and independent.
  • a part of the accommodating part 220C is fixed so as not to move relative to the leg part 230C, and the curved deformation of the elongated accommodating part 220C can be suitably prevented, and the dispensing pipette tip 201 can be stably accommodated in the accommodating part 220C. Easy to accommodate and take out.
  • the leg portion 230C is formed only inside the outermost housing portion 220C as shown in FIG. 7, and on the outside of the outermost housing portion 220C. Is not formed. Therefore, when the user picks up pipetting pipette rack 200C, leg portion 230C is unlikely to come into contact with the user's hand.
  • the leg portion 230C formed in a thin plate shape can suitably prevent the user's hand from being damaged.
  • FIG. 8 is a perspective view showing the reagent container 301 according to the present embodiment.
  • the reagent container 301 includes a container main body 400 formed in a box shape having an opening, and a lid member 310 attached to the container main body 400.
  • the container body 400 is made of resin or the like.
  • the container main body 400 includes a sample well 410 into which a specimen such as a biological sample is placed, a reagent well section 420 that contains a reagent for extracting nucleic acid from the specimen, and a step of extracting nucleic acid from the specimen.
  • the waste liquid well 430 for discarding the unnecessary solution separated in (1) and the recovery well 440 for recovering the nucleic acid extracted from the subject are integrally formed.
  • An extraction filter cartridge 450 containing a carrier that adsorbs nucleic acids is also attached to the container body 400.
  • the waste liquid well 430, the recovery well 440, and the extraction filter cartridge 450 are not essential components of the reagent container 301 and may not be provided.
  • the reagent well unit 420 includes a plurality of reagent storage units 421, 422, 423, 424, 425, 426, an oil well 427, and an oil removing unit 428.
  • the same reagent may be accommodated in a part or all of each reagent accommodating part, and different reagents may be accommodated.
  • the type, composition, and the like of the reagent stored in each reagent storage unit can be selected as appropriate according to the application and usage method of the reagent container 301.
  • the lid 310 is a reagent container lid in this embodiment.
  • the lid member 310 is heat-sealed to the container main body 400 to seal the openings of the reagent storage part, the oil well, and the oil removal part of the reagent well part 420.
  • FIG. 9 shows a partially enlarged plan view of the lid member 310.
  • the lid 310 is heat-sealed only in the ring-shaped portion R1 around each well opening in the reagent well 420 in the container body 400.
  • FIG. 10 is a cross-sectional view schematically showing the lid member 310.
  • the lid member 310 includes a base material layer 311, a metal layer 312, and a heat sealing layer 313.
  • the base material layer 311 is formed of a resin such as polyethylene terephthalate (PET), nylon, stretched polypropylene, and the like, and the thickness thereof is, for example, 10 ⁇ m or more and 20 ⁇ m or less.
  • the metal layer 312 is formed of a metal such as aluminum, and is provided on one side of the base material layer 311 in the thickness direction. The thickness of the metal layer 312 is, for example, 5 ⁇ m or more and 10 ⁇ m or less.
  • the heat sealing layer 313 is formed of a resin that melts when heated, and is provided on the metal layer 312 on the side opposite to the base material layer 311.
  • the thickness of the heat sealing layer 313 is, for example, not less than 10 ⁇ m and not more than 35 ⁇ m.
  • the material of the heat-fusible layer 313 is appropriately determined according to the material of the container body 400. For example, low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), unstretched polypropylene (CPP), or the like is used. be able to.
  • the lid material for the reagent container is formed using a plurality of resin materials
  • the lid material is less likely to break through as the amount of the easily stretchable resin material increases. This is because the resin material is stretched and difficult to cut when the tip of the pipette tip or the like is pressed against the reagent container lid. From this point of view, it is preferable to form the lid for the reagent container using a lot of resin materials that are relatively difficult to stretch, such as PET.
  • many of the resins used for the heat-sealing layer are easily stretched, and it has been difficult to produce a reagent container lid material that achieves both high sealing strength and ease of breakthrough.
  • the thickness of the heat-sealing layer formed of a resin that is relatively easy to stretch is relatively difficult to stretch. It has been found that if the thickness is within a predetermined range, even if the heat-sealing layer has a certain thickness, the ease of breakthrough is not easily impaired.
  • the thickness of each layer is defined based on this finding.
  • the thermal fusion layer 313 by setting the thickness of the thermal fusion layer 313 to be not less than 2 times and not more than 3 times the thickness of the base material layer 311, the thermal fusion layer is about several tens of ⁇ m, which is described in Patent Document 3. Even when it is considerably thicker than the coating film, a reagent container lid member can be constructed that is easy to break through.
  • the inventors have also found that it is more preferable to set the thickness of the heat-fusible layer 313 to be 1 to 2 times the sum of the thickness of the base material layer 311 and the thickness of the metal layer 312. It was issued.
  • the lid 310 when the lid 310 is heat-sealed only at the ring-shaped portion around the well and attached to the container body, the entire contact surface is made by making the heat-sealing surface into a ring shape.
  • the well can be surely sealed as compared with the case of heat fusion.
  • the heat-sealed area is small, if even a slight separation occurs, the sealed state is released relatively easily. Even if the thickness of the heat-sealing layer 313 exceeds three times the thickness of the base material layer 311, the increase in the sealing strength is limited due to the small heat-sealing area.
  • the heat-sealed part has the function of applying tension to the lid attached to the container body, so if the area of heat fusion between the container body and the lid is small, the area responsible for the tension of the lid is also small. Become. Further, when the reagent container 301 is used, a plurality of wells in the normal reagent well section 420 are pierced. When the lid member that seals the well is broken through, the tension disappears at the portion of the well, so that the tension of the entire lid member 310 is slightly lowered even if the fusion of the ring-shaped portion is maintained.
  • the tension of the entire lid member 310 decreases, and when a pipette tip or the like is pressed, the stroke required to start applying force to the lid member gradually increases. If a certain amount of this is accumulated and further expansion of the cover material is applied, there is a possibility that the cover material will not be broken even if the pipette tip or the like is moved to the limit stroke of the analyzer.
  • the lid material according to the present embodiment is suitable for occurrence of such a situation that the lid material is not torn by setting the thickness of the heat sealing layer 313 to be not less than 2 times and not more than 3 times the thickness of the base material layer 311. Can be suppressed.
  • the base material layer 311 and the metal layer 312 are easy to tear when pierced, and the direction in which the tear extends is usually irregular. When a plurality of generated rifts merge, a part of the lid member may be cut off as a small piece and fall into the well. Since the direction of the fissure is difficult to control, it is not easy to reduce the risk of generating small pieces.
  • the thickness of the heat-fusible layer 313 is set to be equal to or more than one times the sum of the thickness of the base material layer 311 and the thickness of the metal layer 312, that is, the base material layer 311 and the metal layer 312.
  • the thickness of each layer is used as an index of combination, but the following matters can be considered as an index instead of the thickness of each layer.
  • the resin include elongation (rate), glass transition point (glass transition temperature), tensile strength, and rupture degree.
  • the metal include elongation (rate), tensile strength, and rupture degree.
  • the lid 310 according to the present embodiment is difficult to peel from the container body 400 until it is used by being applied to the container body 400. Therefore, the quality of the clean state in the sealed reagent container and the stored reagent is suitably maintained even when the container is dropped during transportation. Since the lid member 310 is easily pierced when the tip of the pipette tip or the like comes into contact with a certain pressure, the pipette tip or the like can quickly access the reagent container. Even when the piercing operation is performed a plurality of times, an excessive load is applied to the tip of the pipette tip or the like so that the tip of the pipette tip or the like is not easily rounded.
  • the heat-sealing layer 313 has a sufficient thickness, not only a high sealing strength is realized, but also the base material layer 311 and the metal layer 312 are partly broken when broken. Hateful. As a result, when a pipette tip or the like accesses the reagent storage unit, a situation such as a small piece of the lid member 310 falling into the reagent storage unit can be suitably suppressed.
  • each layer may be bonded via the adhesive layer 314 like the lid member 310A of the modified example (modified example 1B) shown in FIG. If this structure is employ
  • the adhesive layer that joins the base material layer 311 and the metal layer 312 and the adhesive layer that joins the metal layer and the heat sealing layer may be the same material or different materials. .
  • the thickness of the adhesive layer 314 does not have to be taken into consideration in the relationship of the thicknesses of the base material layer 311, the metal layer 312, and the heat fusion layer 313 described above.
  • the third embodiment of the present invention will be further described using experimental examples.
  • the present invention is not limited by the contents of the experimental examples.
  • a PET film having a thickness of 12 ⁇ m was prepared as a substrate and an aluminum foil having a thickness of 7 ⁇ m was prepared as a metal layer.
  • CPP films (4 types of 20 ⁇ m, 30 ⁇ m, 40 ⁇ m, and 50 ⁇ m) having different thicknesses were prepared as heat-sealing layers, and the respective layers were bonded together with an adhesive to produce a lid material for each experimental example.
  • the prepared lid member was fixed to the upper surface of a polypropylene container main body (well inner diameter: 9 mm) by heat fusion (180 ° C., 3 seconds).
  • the heat fusion was a ring-shaped region having a width of 1 mm around the well opening.
  • a metal pin is abutted against the container body with the lid attached, and the maximum amount of force applied to the pin before the lid is broken and the amount of movement (stroke) of the pin until the lid is broken are measured. did. The results are shown in FIG.
  • the maximum force value increases as the heat-fusible layer becomes thicker.
  • the maximum force value exceeded 9N.
  • a container sealed with a lid is set in an automatic analyzer and the lid is pierced with an arm that automatically attaches / detaches a piercing member such as a dispensing tip or pestle, the piercing member and the arm.
  • the stroke did not change greatly up to 30 ⁇ m and increased at 40 ⁇ m.
  • the thickness of the heat-sealing layer is more than 3 times the thickness of the base material layer.
  • FIG. 13 is a perspective view showing the overall configuration of the reagent cartridge 500 according to the present embodiment and the dispensing pipette tip 601 used together with the reagent cartridge 500.
  • the reagent cartridge 500 stores a reagent for extracting nucleic acid from the subject.
  • the nucleic acid extraction device can be mechanically performed using the dispensing pipette tip 601. it can.
  • the reagent cartridge 500 has a main body 501 formed in a box shape having an opening, and a claw portion 502 formed so as to protrude laterally from the outer surface of the main body 501.
  • the claw portion 502 is used for fixing the reagent cartridge 500 to the nucleic acid extraction apparatus.
  • the material for forming the main body 501 is not particularly limited as long as it does not affect the sample, the reagent, or the like. However, if a resin material containing any of polypropylene, polycarbonate, and acrylic is used, good visible light transmittance is obtained. Can be ensured, and the state of the solution can be confirmed. As polypropylene, homopolypropylene or a random copolymer of polypropylene and polyethylene can be used. Moreover, as an acryl, the copolymer of monomers, such as polymethyl methacrylate or methyl methacrylate, and other methacrylic acid ester, acrylic acid ester, styrene, can be used. Moreover, when using these resin materials, the heat resistance and intensity
  • a waste well 530 for discarding an unnecessary solution separated in the above step and a recovery well 540 for recovering a nucleic acid extracted from a subject are integrally provided.
  • the reagent cartridge 500 has a magnetism collecting well 528, and by making the magnet 700 adjacent to the magnetism collecting well 528, the magnetic beads B diffused in the magnetism collecting well 528 can be magnetized.
  • the reagent well section 520 includes a plurality of reagent wells 521, 522, 523, 524, 525, and 526 and a magnetic bead well 527.
  • the openings of the plurality of reagent wells 521 to 526 and the opening of the magnetic bead well 527 are sealed with a sealing film 504 shown in FIG.
  • the sealing film 504 suppresses gas intrusion into the reagent wells 521 to 526 and the magnetic bead well 527.
  • the sealing film 504 is formed of a material that can be broken by the dispensing pipette tip 601.
  • the sealing film 504 can be formed of, for example, a metal thin film or a plastic film.
  • the reagent wells 521, 522, 523, 524, 525, and 526 include a solution 521A that dissolves biological materials such as cell membranes, a solution 522A that dissolves biological materials such as cytoplasm that cannot be completely dissolved by the solution 521A, and a carrier.
  • a cleaning solution 523A and a cleaning solution 524A for washing away unnecessary substances other than the adsorbed nucleic acid, an elution solution 525A for eluting nucleic acid from the carrier, and a dilution solution 526A for adjusting the nucleic acid concentration in the eluate are accommodated.
  • the magnetic bead well 527 contains a magnetic bead solution 527A that is a solution containing magnetic beads B for adsorbing nucleic acids.
  • a magnetic bead solution 527A that is a solution containing magnetic beads B for adsorbing nucleic acids.
  • the surface of magnetic particles is covered with silica.
  • the particles constituting the magnetic beads B are, for example, iron oxide.
  • the waste liquid well 530 is a well for discarding an unnecessary solution.
  • the recovery well 540 is a well for storing the nucleic acid solution from which the nucleic acid has been eluted by the eluent 525A.
  • the magnetism collecting well 528 and the recovery well 540 are provided in a positional relationship adjacent to each other in the reagent cartridge 500. This arrangement is for shortening the flow line of the dispensing pipette tip 601 from the magnetism collecting well 528 to the waste liquid well 530 after the cleaning operation is performed in the magnetism collecting well 528. Thereby, the possibility that the dispensing pipette tip 601 passing over the reagent cartridge 500 contaminates the reagent cartridge 500 or the like can be reduced.
  • FIG. 14 is a cross-sectional view of the magnetism collecting well 528.
  • the magnetism collecting well (subject accommodating portion) 528 is a cavity having an opening only on the upper surface of the main body 501.
  • the cavity of the magnetic flux collecting well 528 is closed at the bottom surface (the portion opposite to the top surface in the height direction).
  • Van der Waals force is a force that adsorbs substances in the liquid. Van der Waals forces generate attractive forces in proportion to the -7th power of the distance between materials. Thus, it can be seen that when the distance between substances is small and the area is large, the adsorbing force increases rapidly. In the case of a bead close to a sphere whose shape is not uneven, the surface of the bead is close to a flat surface on a micro scale. When such shaped beads are pressed against the surface of the container having good smoothness, intermolecular forces such as van der Waals force increase rapidly, and as a result, they are adsorbed on the container surface.
  • Method A1 Fine fine irregularities are formed on the container surface or bead surface so as to reduce the contact area.
  • Method A2 The rigidity of the container surface and / or beads is increased.
  • Method A3 A repulsive force acts on the container surface and the beads.
  • it is necessary to select and change the material, which may increase the cost.
  • the surface state may affect the immobilization of the antibody, there is a risk of suppressing the bio-effect. Therefore, industrially, method A1 is desirable.
  • FIG. 15 shows (a) adsorption force (van der Waals force) between a smooth surface and beads, (b) gravity (specific gravity 2000 kg / m 3 ), and (c) resistance force of beads due to water flow and bead particle size ( It is the graph which showed the relationship with (bead diameter).
  • the bead particle size is 1 mm or less, the beads adsorb on the smooth surface against gravity, and when the bead particle size is 0.1 mm or less, It turns out that it becomes difficult to peel off from a smooth surface.
  • the particle size of the beads to be used is often 10 nm or more, as shown in FIG. 15, if the adsorption force (Van der Waals force) between the beads and the smooth surface is reduced to 1/100, the beads flow with water by stirring or the like. It turns out that adsorption
  • the contact area between the beads and the container surface may be 1/100 or less compared to the contact area on the smooth surface (Method A1). Furthermore, it is necessary to increase the distance between the bead surface and the container surface in the non-contact portion (Method B) so that the van der Waals force effect does not occur in the portion where the bead and the container surface are not in contact.
  • FIG. 16 is a graph showing the relationship between the distance between the bead and the container surface and the van der Waals force.
  • the distance may be 10 nm or more, and is preferably 100 nm or more.
  • the beads come into contact with the container surface with dots or lines, and the beads and the container surface are not in contact with each other.
  • the distance between the bead and the container surface in the portion can be increased (Method B).
  • the contact area between the bead and the container surface is set to 1/100 or less compared to the contact area on the smooth surface, and the bead and the container surface are in contact with each other.
  • the distance between the bead and the surface of the container in the unfinished portion may be 10 nm or more.
  • FIG. 17 is an enlarged cross-sectional view of the inner wall 528 s of the magnetism collecting well 528.
  • the contact area between the bead and the container surface varies depending on the size of the bead, the hardness between the bead and the container surface, and the degree of force when in contact.
  • RSm the roughness defined by the average length of the curve element defined by JIS
  • the surface roughness (RSm) is more preferably 1/20 or more.
  • FIG. 18 is a schematic diagram of polystyrene beads in contact with a smooth surface.
  • the contact area between the polystyrene beads and the smooth surface is influenced by elasticity, so that the circumferential portion having a length of about 5 to 20% of the bead diameter is formed.
  • the surface irregularities in the horizontal direction with respect to the contact surface may be equal to or larger than the bead diameter.
  • FIG. 19 is a schematic diagram of the magnetic beads B in contact with the inner wall 528s observed with a microscope. Considering that it is sufficient to reduce the contact area to 1/100 or less, from the result of observation with a microscope as shown in FIG. there were.
  • the surface roughness should be 1/50 or more of the bead diameter, and considering the surface roughness and bead variation, the wrinkle surface roughness is preferably 1/20 or more of the bead diameter.
  • the uneven pitch is smaller than the bead size (Method C).
  • the rough surface has a correlation between the surface roughness in the depth direction and the pitch of the unevenness in the planar direction. If the surface roughness (RSm) is 2/3 or less of the average particle diameter of the beads, the bead gets stuck due to the unevenness. It is desirable that the surface roughness (RSm) be 1 ⁇ 2 or less.
  • the inner wall 528s of the magnetism collecting well 528 has a surface roughness (RSm) of 1/50 times to 2/3 times the average bead diameter d of the magnetic beads B, and 1/20 times to 1 / It is more desirable that it is 2 times.
  • RSm surface roughness
  • the magnetic beads B are unlikely to enter the irregularities of the inner wall 528s and are difficult to adsorb.
  • the uneven structure on the surface of the container may be a random structure such as a rough surface or a regular structure such as a lattice. Further, the uneven structure on the surface of the container may be a structure that is supported by dots or a linear structure.
  • a generally used surface roughness measuring instrument is a device for measuring the surface roughness in the depth direction such as Ra, and the horizontal roughness has many variations, and further, the horizontal roughness and the depth direction are measured. Since the roughness has a correlation in the general rough surface, the average length roughness (RSm) of the curve element is replaced with the arithmetic surface roughness (Ra) which is the surface roughness in the depth direction.
  • the surface roughness may be controlled. As described above, when the depth of the irregularities on the bead or the container surface is 10 nm or less, the effect of reducing the van der Waals force due to the irregularities is reduced, so Ra needs to be 10 nm or more. .
  • the operation of the reagent cartridge 500 having the above-described configuration will be described.
  • the operation of the reagent cartridge 500 will be described by taking as an example the operation of mounting the reagent cartridge 500 in a nucleic acid extraction apparatus having a dispensing and carrying function for carrying the dispensing pipette tip 601 and extracting the nucleic acid.
  • 20 and 21 are diagrams showing the magnetic collection well 528 in the process of extracting nucleic acid.
  • a biological sample which is a subject
  • a biological sample which is a subject
  • the reagent cartridge 500 into which the biological sample is loaded is attached to the nucleic acid extraction apparatus.
  • the dispensing pipette tip 601 is conveyed by the dispensing conveyance mechanism of the nucleic acid extraction apparatus.
  • a certain amount of biological sample is aspirated from the sample well 510 and discharged into the reagent well 521.
  • the lysis solution 521A stored in the reagent well 521 and the biological sample are mixed to obtain a cell lysis solution in which the cells in the biological sample are lysed.
  • a cell lysate (not shown) is sucked from the reagent well 521 by the dispensing pipette tip 601 and dispensed to the magnetism collecting well 528.
  • the magnetic bead solution 527 A containing the magnetic beads B is attracted from the magnetic bead well 527 by the dispensing pipette tip 601 and dispensed to the magnetism collecting well 528.
  • the magnetic beads B and the cell lysate are mixed, and the nucleic acid is adsorbed to the magnetic beads B.
  • the nucleic acid extraction apparatus brings the magnet 700 close to the outer periphery of the magnetism collecting well 528 as shown in FIG.
  • the magnetic beads B inside the magnetism collecting well 528 are collected on the inner wall 528s of the magnetism collecting well 528 by the magnetic force of the magnet.
  • the nucleic acid extraction apparatus sucks the solution containing the cells and magnetic beads B in the biological sample put in the magnetism collecting well 528 with the dispensing pipette tip 601, and discards the sucked solution to the waste liquid well 530.
  • the magnetic beads B collected on the inner wall 528 s remain in the magnetic collection well 528.
  • the nucleic acid extraction apparatus dispenses the lysis solution 522A into the magnetism collecting well 528, and moves the magnet 700 disposed on the outer periphery of the magnetism collecting well 528 away from the magnetism collecting well 528.
  • the magnetic bead B adsorbed on the inner wall 528s is It is easily turbid.
  • the washing step is performed, the magnetic beads B are transferred to the recovery well 540, and the eluate 525A is further dispensed into the recovery well 540, whereby the nucleic acid adsorbed on the magnetic beads B is recovered.
  • the magnetic particles are difficult to be adsorbed on the inner wall of the accommodating portion, and the nucleic acid adsorbed on the magnetic particles can be efficiently recovered.
  • the present invention can be applied to various particles such as an ellipse, a polygon, and a fiber.
  • the particle diameter to be used may be the shortest particle diameter as the particle diameter.
  • the present invention can be applied to a storage container for storing a plurality of dispensing pipette tips, a reagent container lid, a reagent container, and a reagent cartridge for storing particles in a storage section.
  • Reagent cartridge 101 Main body 104 Sealing film 200, 200B, 200C Dispensing pipette rack (container) 201, 601 Dispensing pipette tip 202 Drilling pipette tip 210 Main body 210a (for dispensing pipette rack) Upper surface 220, 220B, 220C Housing portion 221 First housing portion 221a Opening 222 Second housing portion 222a Opening 230, 230C Leg 231, 231C First leg 232, 232 C Second leg 230 b Protrusion 240 Marker P Bottom L Lattice 301 Reagent container 310, 310 A Reagent container lid 311 Base material layer 312 Metal layer 313 Thermal fusion layer 314 Adhesive layer 400 Container body 421, 422, 423, 424, 425, 426 Reagent storage unit 501 (reagent cartridge) body 502 Nail part 510 Sample well 520 Reagent well part 521 Reagent well 522 Reagent well 523 Reagent well 524 Reagent

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un récipient de stockage comprenant un corps comprenant une pluralité de parties de stockage et une pluralité de parties pied. Chaque partie de la pluralité de parties de stockage comprend une ouverture uniquement sur la surface supérieure du corps. La pluralité d'ouvertures est agencée dans une première direction et une seconde direction différente de la première direction. La pluralité de parties pied comprend : une première partie pied reliant deux des parties de stockage adjacentes dans la première direction; et une seconde partie pied reliant deux des parties de stockage adjacentes dans la seconde direction. Chaque partie de jambe de la pluralité de parties pied comprend : une section en saillie faisant saillie à partir de chaque partie de stockage de la pluralité de parties de stockage vers le bas dans la direction de la hauteur. Les sections en saillie forment une surface inférieure parallèle à la surface supérieure.
PCT/JP2019/010055 2018-03-19 2019-03-12 Récipient de stockage, couvercle de récipient de réactif, récipient de réactif et cartouche de réactif WO2019181655A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201980020417.5A CN111902722A (zh) 2018-03-19 2019-03-12 收容容器、试剂容器用盖材料、试剂容器及试剂盒

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP2018-051606 2018-03-19
JP2018051606A JP7003763B2 (ja) 2018-03-19 2018-03-19 試薬カートリッジ
JP2018-051627 2018-03-19
JP2018051627A JP7059725B2 (ja) 2018-03-19 2018-03-19 収容容器
JP2018060500A JP7043921B2 (ja) 2018-03-27 2018-03-27 試薬容器用蓋材および試薬容器
JP2018-060500 2018-03-27

Publications (1)

Publication Number Publication Date
WO2019181655A1 true WO2019181655A1 (fr) 2019-09-26

Family

ID=67986404

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2019/010055 WO2019181655A1 (fr) 2018-03-19 2019-03-12 Récipient de stockage, couvercle de récipient de réactif, récipient de réactif et cartouche de réactif

Country Status (2)

Country Link
CN (1) CN111902722A (fr)
WO (1) WO2019181655A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115175765A (zh) * 2020-02-25 2022-10-11 海利克斯拜恩德股份有限公司 用于流体系统的试剂载体

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6228372A (ja) * 1985-07-22 1987-02-06 テクノール・ホールデイングス　インコーポレイテツド ビン収納容器
JPH05240869A (ja) * 1992-02-28 1993-09-21 Suzuki Motor Corp 血液等の凝集パターン出力装置
WO2007080230A1 (fr) * 2006-01-13 2007-07-19 Finnzymes Instruments Oy Plaque de microtitration, son procédé de fabrication et kit associé
JP3150430U (ja) * 2009-02-03 2009-05-21 ビョコード イセル フランス ソシエテ アノニム 生体液分析用ユニットキュベット及び体外分析用自動分析装置
JP3172204U (ja) * 2011-09-26 2011-12-08 勝時 西森 鑑賞器具
US20140154734A1 (en) * 2012-05-22 2014-06-05 Diversified Biotech System and method for high throughput tissue sample extraction
JP2015023822A (ja) * 2013-07-26 2015-02-05 株式会社古河電工アドバンストエンジニアリング ウィルス検査方法、ウィルス検査装置およびウェルプレート

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3156550B2 (ja) * 1995-07-11 2001-04-16 株式会社日立製作所 試薬管理の方法および装置
US20040014097A1 (en) * 2002-05-06 2004-01-22 Mcglennen Ronald C. Genetic test apparatus and method
WO2011004653A1 (fr) * 2009-07-09 2011-01-13 凸版印刷株式会社 Trousse d'extraction d'acide nucléique, procédé d'extraction d'acide nucléique et appareil d'extraction d'acide nucléique
TWI523950B (zh) * 2009-09-30 2016-03-01 凸版印刷股份有限公司 核酸分析裝置
CN105242056B (zh) * 2014-06-04 2019-01-22 东曹株式会社 容器收纳托盘和自动分析装置

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6228372A (ja) * 1985-07-22 1987-02-06 テクノール・ホールデイングス　インコーポレイテツド ビン収納容器
JPH05240869A (ja) * 1992-02-28 1993-09-21 Suzuki Motor Corp 血液等の凝集パターン出力装置
WO2007080230A1 (fr) * 2006-01-13 2007-07-19 Finnzymes Instruments Oy Plaque de microtitration, son procédé de fabrication et kit associé
JP3150430U (ja) * 2009-02-03 2009-05-21 ビョコード イセル フランス ソシエテ アノニム 生体液分析用ユニットキュベット及び体外分析用自動分析装置
JP3172204U (ja) * 2011-09-26 2011-12-08 勝時 西森 鑑賞器具
US20140154734A1 (en) * 2012-05-22 2014-06-05 Diversified Biotech System and method for high throughput tissue sample extraction
JP2015023822A (ja) * 2013-07-26 2015-02-05 株式会社古河電工アドバンストエンジニアリング ウィルス検査方法、ウィルス検査装置およびウェルプレート

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115175765A (zh) * 2020-02-25 2022-10-11 海利克斯拜恩德股份有限公司 用于流体系统的试剂载体
CN115175765B (zh) * 2020-02-25 2024-05-07 海利克斯拜恩德股份有限公司 用于流体系统的试剂载体

Also Published As

Publication number Publication date
CN111902722A (zh) 2020-11-06

Similar Documents

Publication Publication Date Title
US10101354B2 (en) Method for prevention of contamination during disposing of liquid by pipet array
TW201107754A (en) Kit, method and apparatus for nucleic acid extraction operation
JPWO2006132074A1 (ja) 液体交換方法、それを用いた成分抽出方法、複合容器および自動分析装置
US9932574B2 (en) Suspension container for binding particles for the isolation of biological material
WO2016011134A1 (fr) Cartouche microfluidique avec guide de pipetage
EP2257820B1 (fr) Élément de test, appareil de test et methode d'immunodiagnostic ayant un couvercle perforable consistant en une feuille affaiblié.
JP2010508090A (ja) 貫通可能な隔壁キャップ
TW201326819A (zh) 分注裝置所用的吸管尖頭組及使用該吸管尖頭組朝試劑匣膜開孔之方法
JP2008209330A (ja) 磁気分離器およびそれを用いた分析装置
JP6934039B2 (ja) 免疫測定装置
CN114011479B (zh) 跨界面磁性分离
KR20200103626A (ko) 자성 입자 수집 방법 및 시험 세트
WO2019181655A1 (fr) Récipient de stockage, couvercle de récipient de réactif, récipient de réactif et cartouche de réactif
JP5625305B2 (ja) 試薬カートリッジ及び核酸精製キット
WO2016148235A1 (fr) Récipient, kit de purification d'acides nucléiques, et procédé de fabrication de récipient
JP2010099036A (ja) 生体高分子溶液処理用容器及び生体高分子溶液処理方法
JP6672790B2 (ja) 試薬カートリッジ及び核酸精製キット
JP2011189270A (ja) マイクロプレートおよび分離方法
JP2010151551A (ja) 試料前処理装置
JP7003763B2 (ja) 試薬カートリッジ
WO2019131217A1 (fr) Procédé de gestion de fluide, dispositif de gestion de fluide utilisé dans celui-ci et système de gestion de fluide
EP2423688B1 (fr) Conteneur de suspension pour des particules de liaison pour l'isolation de matériel biologique
WO2008001691A1 (fr) Procédé de traitement d'échantillon
JP2019162062A (ja) 収容容器
JP7015076B1 (ja) マイクロプレートシール器具

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19772440

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19772440

Country of ref document: EP

Kind code of ref document: A1