JP2012150118A - Carrier-enclosing transformable container, processing device of carrier-enclosing transformable container, and method for processing carrier-enclosing transformable container - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a carrier-enclosing transformable container, a processing device of the carrier-enclosing transformable container, and a method for processing the carrier-enclosing transformable container capable of improving the efficiency of, enhancing the speed of, and facilitating processes such as handling and measurement of a carrier by retaining the carrier bonded or bondable with various types of substances such as biological substances, in a transformable container in a substantially stationary state.SOLUTION: The container includes: a containing part which can contain liquid and gas in the inside thereof surrounded with a wall face, a part of the wall face having a transformable wall face capable of undergoing a predetermined transformation without changing substantially the entire internal surface area of the wall face; an orifice part which is connected to the containing part and can undergo the inflow and outflow of a liquid sucked and discharged by the expansion and contraction of the inside by the transformation of the transformable wall face; and a carrier to which a predetermined substance enclosed in the containing part in a substantially stationary state is bonded or bondable.

Description

  The present invention relates to a carrier-enclosed deformed container, a carrier-enclosed deformed container processing apparatus, and a carrier-enclosed deformed container processing method.

  Conventionally, when a series of reaction processes using a large number of reagents and substances are performed on a target substance to be inspected, for example, the target substance is bound to a microcarrier such as a bead and accommodated in a test tube. Thereafter, various reagents and the like are injected into the test tube, the carrier is separated by some method, the carrier is moved to another container, and another reagent is injected or a treatment such as heating is performed. It was. For example, in the case where the carrier is a magnetic material, the separation is performed by adsorbing it on the inner wall of the test tube with a magnetic field.

  In addition, for example, in a process of examining a target substance using a flat carrier such as a preparation, on which various oligonucleotides are immobilized, the carrier itself is suspended in which a labeled target substance is suspended. Move the carrier to the measuring position of the measuring machine to move it into the liquid, dispense various reagents to the carrier itself, move the carrier itself into the washing liquid, or measure luminescence. The base sequence structure of the target substance was examined by performing a series of reaction processes.

  In order to carry out these treatments, it is necessary to separate the carrier itself and transfer the carrier itself, which has a problem that the treatment may be complicated and troublesome. In particular, when these carriers are transported by hand, a large burden is placed on the user and there is a risk of cross contamination. Further, when the carrier itself is transported by a machine, a large-scale device is required. In addition, when separating a nonmagnetic carrier, it is necessary to perform separation according to the size and specific gravity of the carrier, which has a problem that the processing is complicated and time-consuming.

  Therefore, instead of using a test tube or a planar carrier, a pipette tip provided with a liquid passage capable of passing a liquid, a nozzle to which the pipette tip is attached, and a magnetic field is applied to the liquid passage of the pipette tip. A device that performs a reaction process using a dispensing device invented by the present inventor having a magnetic device and a suction / discharge mechanism using a cylinder with a built-in plunger for sucking and discharging fluid in the pipette tip. there were.

  According to this method, a suspension in which a large number of magnetic particles with various substances held on the surface are suspended is sucked, and a magnetic field is applied during the suction to efficiently remove the magnetic particles from the liquid in the pipette tip. Separation and the like can be performed by adsorbing to the passage, but since the magnetic particles can pass through the liquid passage, the magnetic particles are adsorbed on the inner wall by applying a magnetic field in order to hold them in the pipette tip. There was a need. Therefore, in order to perform processing, it is necessary to combine suction / discharge control, adsorption control by a magnetic field, and pipette tip movement control. Further, when the carrier is non-magnetic particles, there is a problem that separation cannot be performed by the apparatus.

  Furthermore, a cylinder that drives a plunger is used as a suction / discharge mechanism. The mechanism such as a plunger is a high-precision processed part such as a syringe, and in particular, volume change in the cylinder is basically a dispensing tip. Therefore, it is necessary to transmit the plunger so that there is no looseness at the joint between the plunger and the driving device of the plunger. In addition, it is necessary to fit the nozzles of these suction / discharge mechanisms and dispensing tips so that there is no leakage of gas or liquid, and accuracy and structure for watertightness and airtightness are required for manufacturing and quality control. The In particular, when a plurality of dispensing tips are integrated and used, a large force is required to insert and fit a plurality of nozzles into a plurality of dispensing tips all at once. There was a risk that ring wear was severe and high quality control was required.

  Prevents cross-contamination due to contact between the nozzle and the gas or liquid in the dispensing tip when continuously performing processing by replacing multiple dispensing tips with the nozzle of the suction / discharge mechanism. There was a need to do.

  Furthermore, in order to control the suction and discharge of the dispensing tip, a cylinder having a capacity corresponding to the capacity of the dispensing tip is required, so that the device scale becomes large to handle a large volume of liquid. (Patent Documents 1 to 3).

  Also, hold beads with probes in small holes, then move them to capillaries or grooves and arrange the beads in the order determined for each type to create a probe bead array, or the order specified in the liquid flow Then, beads with probes were poured into and stored in grooves or capillaries to produce probe arrays in a predetermined order (Patent Document 4).

  Further, a system or method for detecting, analyzing and displaying a large number of analytes in a fluid sample in real time has at least one light source and at least one photodetector, and is substantially coplanar. A memory medium that is communicable with a computer, readable by a computer, and that stores computer instructions, the instructions processing and processing a biological sample using a flow cytometer Some included determination of the presence and amount of at least one analyte of interest in the biological sample at substantially the same time as the step (US Pat. No. 6,057,049).

  However, since the particles are very small for human handling (for example, several tens of μm to several mm), it is troublesome to accurately align a large number of particles in a groove or capillary in a predetermined order. It has the problem that it may be difficult to handle. In addition, there is a problem that there is a possibility that an accurate correspondence cannot be obtained due to the deviation of the arrangement of the particles. In addition, when particles suspended in a liquid are moved at high speed using a flow cytometer and measured with a photodetector, it is necessary to measure one particle per particle strictly. There has been a problem that the device structure becomes complicated and there is a possibility of performing complicated control.

Japanese Patent No. 3115501 International Publication WO 96/29602 International Publication No. WO 97/44671 JP 2000-346842 A Japanese National Patent Publication No. 14-534657

  Accordingly, a first object of the present invention is to enclose a carrier to which various substances such as biological substances are bound or capable of being bound in a container that can be deformed in a substantially stationary state, thereby handling the carrier and measuring it. It is an object to provide a carrier-enclosed deformed container, a carrier-enclosed deformed container processing apparatus, and a carrier-enclosed deformed container processing method that can make processing more efficient, faster, and easier.

  The second object of the present invention is to use a deformable container to automatically or consistently execute a series of processes such as transfer, reaction, and measurement of various substances in the deformable container. A carrier-enclosed deformation container, a carrier-enclosed deformation container, and a carrier-enclosed deformation that can be performed manually and can prevent cross-contamination due to contact between the liquid introduced into the container and the outside of the container as much as possible. To provide a container processing apparatus and a method for processing a carrier-enclosed deformed container.

  The third object of the present invention is to use a deformable container to contact a carrier having a large capacity (for example, 1 milliliter (cc) to several tens of milliliters) with a relatively small apparatus size. Provided are a carrier-enclosed deformed container, a carrier-enclosed deformed container processing apparatus, and a carrier-enclosed deformed container processing method capable of processing a liquid having a normal volume (for example, several tens of microliters to several hundreds of microliters). It is.

  A fourth object of the present invention is a carrier-enclosed deformable container capable of performing high-accuracy processing in spite of an apparatus configuration having a simple structure of a deformable container without using a complicated fluid mechanism, It is to provide a carrier-enclosed deformed container processing apparatus and a carrier-enclosed deformed container processing method.

  The fifth object of the present invention is to use a deformable container, so that accuracy for watertightness or airtightness is not required for production and quality control, and it can be provided at low cost, and the management burden can be reduced. It is possible to provide a carrier-enclosed deformed container, a carrier-enclosed deformed container processing apparatus, and a carrier-enclosed deformed container processing method.

  According to a first aspect of the present invention, there is provided a deformed wall surface that is capable of containing a liquid and a gas in an interior surrounded by a wall surface and that can be deformed in a predetermined manner without substantially changing the total inner surface area of the wall surface. A housing portion, a mouth portion communicating with the housing portion, a mouth portion through which the liquid sucked and discharged by expansion and contraction due to deformation of the deformed wall surface can flow in and out, and sealed in the housing portion in a substantially stationary state. It has a carrier to which a predetermined substance binds or can bind.

  Here, the “deformed wall surface” is a flexible wall surface that can be deformed and the surface area of the deformed wall surface is not substantially changed by the deformation. In other words, when the wall surface of the wall surface is substantially maintained before and after the deformation, for example, the folded wall surface is deformed so that it is stretched, or the wall surface in a relaxed state is deformed into a tensioned state. It is. Therefore, even in the wall surface incorporating the deformed wall surface, the total surface area does not change due to the deformation. The “part of the wall surface” is, for example, a wall surface portion excluding the vicinity of the inner mouth portion of the entire wall surface of the storage portion, and a non-deformable wall surface that does not deform is provided between the wall surface portion and the mouth portion. .

  Further, the “predetermined deformation” of the deformation wall surface is preferably a deformation whose internal volume is substantially determined according to the degree of deformation to be applied. That is, it is preferable that the inner volume is uniformly determined by expanding or contracting the interior surrounded by the wall surface according to the degree of pushing or pulling the deformed wall surface along a certain deformation direction or removing the force.

  The deformation wall surface may be urged in an expansion direction or a contraction direction inside due to the deformation. When urged in the expansion direction, it contracts by applying a force against the expansion direction and deforms in the expansion direction by removing the force. When urged in the contraction direction, it expands by applying a force in a direction opposite to the contraction direction, and deforms in the contraction direction by removing the force. Examples of the deformed wall surface include a wall surface on which an accordion is formed, a wall surface formed of an elastic body member such as rubber or a film member, or a spring having an elastic force in the deformation direction. The wall surface is formed of a flexible planar member or film member.

  Note that “suction / discharge” means suction or / and discharge. The material of the carrier-enclosed deformable container is, for example, polystyrene, polysulfone, polyethylene, polypropylene, polyester, polyvinyl, an acrylic resin, an elastic body such as rubber, other flexible materials, or a combination thereof. . The carrier-enclosed deformable container is preferably transparent or translucent. For example, polypropylene is used for the non-deformed wall, and polyethylene is used for the deformed wall.

  The size of the carrier-enclosed deformable container is, for example, several centimeters to several tens of centimeters in length from the mouth along the mounting opening or in the axial direction, and the volume depends on the length. For example, it is about several microliters to several tens of milliliters. The suction and discharge amount is, for example, about several microliters to several tens of milliliters depending on the volume.

  “Encapsulation” means that a container (for example, a carrier) accommodated in a container having a mouth portion capable of inflow and outflow of liquid is held so as not to flow out of the container through the mouth portion. .

  The “substantially stationary state” means that the carrier does not move freely in the container during measurement, but is substantially stationary so that it can be measured relative to each other or to the introduced liquid. Say. However, it need not be completely fixed.

  The “carrier to which a predetermined substance can be bound or bound” refers to a solid that is enclosed in the storage portion and to which the predetermined substance can be bound or bound, and includes, for example, a porous substance, a predetermined functional group, a predetermined carrier, and the like. It is made of an organic substance containing a natural product such as a resin, a fibrous substance or the like, a metal, a semiconductor, glass, silica or other inorganic substance. Examples of the shape of the carrier include a particle shape, a linear shape, a rod shape, a planar shape, and a block shape. In addition, the “predetermined substance” refers to various compounds including cells, nucleic acids such as DNA and RNA, genetic substances such as oligonucleotides, proteins such as immune substances, biological compounds such as peptides, amino acids, sugars, sugar chains, or cells. And living organisms such as bacteria, viruses and plasmids or living tissues. The “predetermined substance” includes not only one type but also a plurality of types. The biological compound is used for detection, capture, separation, extraction and the like of the binding of a biological compound as a receptor having a binding property to the biological compound as a ligand. Examples of the receptor include genetic materials such as nucleic acids, genetic materials such as nucleic acids having binding properties to proteins, sugar chains, peptides and the like, and biological materials such as proteins, sugar chains and peptides. In addition, a living body itself such as a cell, a virus, or a plasmid can be used as the biological compound or instead of the biological compound. The carrier has a binding property to the predetermined substance, for example, a ligand or a receptor, or a substance considered to have a binding property, for example, a receptor or a ligand, respectively. .

  “Binding” refers to associating at least one of the predetermined substances with the carrier directly or indirectly through another kind of substance. Examples of the bonding include, for example, covalent bonding, chemical adsorption, physical adsorption, hydrogen bonding, or electrical interaction. In addition, a predetermined chemical substance is bound to the carrier by chemical or physical adsorption, a specific reaction with a binding substance fixed to the carrier, or other methods. In addition, the carrier may be formed of a porous member, a concavo-convex member, or a fibrous member, thereby enhancing the ability to react with or bind to a biological substance.

  Examples of the material of the “carrier” include metals, semiconductors, metalloids such as semimetals, metal oxides, ceramics, glass, inorganic substances such as silica, resins such as rubber, latex, polystyrene, polypropylene, polyester, and acrylic, There are organic materials such as cellulose, polymer materials such as the above-mentioned fiber materials such as nylon, and natural materials such as natural fibers such as silk. More specifically, for example, taking a fiber material as an example, nylon or the like (3-nylon, 6-nylon, 6,6-nylon, 6,10-nylon, made of “polyamide polymer”, etc.) 7-nylon, 12-nylon, etc.), wholly aromatic polyamides such as PPTA (polyparaphenylene terephthalamide), and heterocycle-containing aromatic polymers. The carrier may be, for example, a fibrous body, a porous body, or a gel body.

For binding, the carrier is allowed to express or generate functional groups. For that purpose, for example, the functional group used for the binding of the biological substance is expressed or generated by hydrolyzing the peptide bond of the “polyamide polymer”. Examples of the functional group capable of binding to a biological substance include a carboxyl group —COOH, an amino group —NH ₂ , or a derivative group thereof. Here, the porous diameter suitable for the binding of the biological compound is, for example, several micrometers or less.

The “carrier” is a solid having a size that can be enclosed in the carrier-enclosed deformable container, and the binding position or the bondable position of the predetermined substance can be specified from the outside of the carrier-enclosed deformable container.
The carrier has a binding position or a bondable position corresponding to a predetermined position of one carrier with an interval, or a plurality of predetermined positions so that the predetermined substance can be bound or bindable. Corresponding to the carrier, for example, the joining position or the connectable position is enclosed in the container so that it can be specified by, for example, one-dimensional coordinates along the axial direction of the carrier-enclosed deformable container or in a random state. . Examples of such a carrier include one or a plurality of particulate carriers, spherical carriers, linear carriers, rod-shaped carriers, strip-shaped carriers, flat carriers, block-shaped carriers, and the like.

  In that case, a solution containing a predetermined substance labeled with a labeling substance composed of a luminescent substance such as a substance fixed to these carriers or a fluorescent substance that may be bound to the carrier itself is used as the chip-like container. The presence or absence of binding to these biological substances is measured by measuring the luminescence at each position by contacting with the carrier, thereby analyzing the structure, properties and presence of the target biological substance. can do.

  The size of the deformable container is, for example, the length between the intersections of the deformed wall surface and the mouth, or the length in the axial direction, along a straight line that passes through the mouth and is surrounded by the housing. From a centimeter to a few tens of centimeters, its volume is on the order of a few microliters to a few tens of milliliters, depending on its length.

  According to a second aspect of the present invention, the accommodating portion is surrounded by one or more deformable portions formed by the deformed wall surface and an undeformed wall surface that communicates with the deformable portion and is not deformed. The carrier is a carrier-enclosed deformable container enclosed in the non-deformable portion.

  Here, the deformed portion formed by the deformed wall surface is a portion that is deformed by applying an external force.

  “Measurable from the outside” means that the labeled state of each particulate carrier held in the carrier holding part can be specified from the outside.

  According to a third aspect of the present invention, there is provided the carrier-enclosed deformable container, wherein the accommodating portion has at least two deformable portions, and the maximum changeable amount of the accommodating portion based on deformation of the deformable wall surface of each deformable portion is different. is there.

  By making one of the maximum changeable amounts of the at least two deformation portions approximately equal to the volume of the narrow tube portion in which the carrier is enclosed or the volume of the region in which the carrier is enclosed, it is brought into contact with the carrier. It is possible to efficiently contact the carrier by preparing the necessary liquid, for example, the minimum necessary amount of the reagent solution or the sample suspension in each container and deforming it using the deforming part. it can. The cleaning liquid is brought into contact with not only the thin tube portion in which the carrier is enclosed but also the thick tube portion using the other deformed portion. In this way, it is possible to perform suction or discharge of liquid having at least two different volumes. In particular, when handling manually, switching of the capacity can be performed by selecting the deforming portion, not by adjusting the magnitude of the force applied to the deforming portion.

  According to a fourth aspect of the present invention, the deformable portion or the only deformable portion having the largest maximum changeable amount includes a straight line passing through the deformed wall surface through the inside of the mouth portion and the accommodating portion, and the deformed wall surface. It is a carrier-enclosed deformable container in which the deformable wall surface is formed to be deformable along the linear direction at the intersection.

  According to a fifth aspect of the present invention, there is provided a carrier-enclosed deformable container in which the carrier is a plurality of particulate carriers to which a plurality of types of chemical substances are bound or bindable and can be distinguished from the outside or a set of a plurality of particulate carriers. It is.

  The “particulate carrier” is a particulate solid having a size that can be introduced and held in the carrier holding part. In general, one of the particulate carriers or one set of the particulate carriers corresponds to one kind of the plurality of kinds of chemical substances that can be bound or bound thereto. The size of the particulate carrier is, for example, a size of 0.1 mm to several mm in diameter or diameter. In the space part in which the particulate carrier is enclosed, the volume of the space part excluding the enclosed particulate carrier is, for example, a volume of several microliters to several hundred microliters. By labeling the particulate carrier or the collection of particulate carriers according to the chemical substance to which they can bind or bind, it is not necessary to identify them by the arrangement position of the encapsulated particulate carrier or the assembly.

  The “aggregate of particulate carriers” is a collection of particulate carriers to which at least two particulate carriers belong, and the particulate carriers belonging to the aggregate are preliminarily set between the particulate carriers to which they belong by a predetermined number. It is specified by a predetermined distance, by a predetermined range in which the particulate carrier is located, or by a predetermined boundary, coating or case surrounding the particulate carrier to which it belongs. As a result, it is possible to handle a set of particulate carriers as if they were one particulate carrier. In addition, particulate carriers that have the function of immobilizing various substances, particulate carriers that have the function of discriminating, and other particulate carriers (in order to indicate the boundaries between sets or by labeling, etc.) (For shielding light etc.), functions can be dispersed for each particle to facilitate handling, and various other functions can be added. Further, if even a collection of particulate carriers can be clearly identified, the number of the particulate carriers belonging to it can be set freely, so that there is expandability, versatility, and diversity.

  According to a sixth aspect of the present invention, each particulate carrier of the plurality of particulate carriers or at least one particulate carrier belonging to a set of a plurality of particulate carriers is the kind of the chemical substance, the particulate carrier. Or a carrier-enclosed deformable container that is labeled so as to be distinguishable from each other before being introduced into the accommodating portion in accordance with each set of the particulate carriers.

  “At least one particulate carrier belonging to each particulate carrier of the plurality of particulate carriers or a set of each particulate carrier is the kind of chemical substance, each particulate carrier, or each particulate carrier. Because they are labeled so that they can be distinguished from each other according to the set of carriers, they can be distinguished from each other for the first time by forming an array by being introduced and held in the carrier holding part. There is no need to be.

  “Particulate carrier is identifiably labeled” means that the particulate carrier itself retains, binds, or is fixed to an identifiable labeling element, or the particulate carrier itself is identifiable. Means processed or formed. That is, it means that the cause of labeling is present in the particulate carrier, and is different from the case where the cause of labeling is present outside the particulate carrier, such as the arrangement and position of the particulate carrier. For example, by changing the size of the particulate carrier by forming the shape of the particulate carrier into a sphere, a cube, a cylinder, a quadrangular column, a cone, a pyramid, an unevenness, etc. By attaching to a carrier, various fluorescent materials, phosphorescent materials, chemiluminescent materials and other luminescent materials, various wavelengths of infrared rays, ultraviolet rays, radiation materials that emit electromagnetic waves of various wavelengths including radio waves, and various magnetic strengths Labeling is performed by providing a labeling element such as a magnetic substance on the particulate carrier. In that case, the labeling includes not only the case where the labeling element such as the luminescent substance, various electromagnetic radiation substances, and the magnetic substance is provided on the surface of the particulate carrier, but also the case where the labeling element is provided inside the particulate carrier. As a case where it is provided inside, there is a case where the particulate carrier is formed in a hollow shape, and is a particulate case or a particulate film in which these substances are accommodated or bundled. In that case, in the case of a luminescent material, the particulate case or particulate coating needs to be transparent or translucent. The particulate carrier already has a labeling element before being introduced and held in the carrier holding portion, or the particulate carrier itself is processed or formed so as to be distinguishable.

  The labeling element includes a binding substance that can specifically react with a predetermined luminescent substance that can be identified by measurement and that has not yet reacted with the luminescent substance or the like. . An example of such a binding substance is a receptor having a binding property to the ligand with respect to the luminescent substance or the like bound to the ligand. This labeling element is potentially labeled, and the labeling becomes obvious by reacting with the predetermined luminescent substance or the like. Therefore, when this labeling element is used, the particulate carrier is potentially labeled so that it can be distinguished from each other before being introduced into the carrier holding part, and the labeling manifests by the reaction after the introduction. Are also included in being labeled prior to introduction.

  Thereby, the mutually identified particulate carriers are arranged so as to be position-identifiable, or each particulate carrier or a set of particulate carriers can be identified without moving the particulate carriers in order. Thus, various substances fixed or fixable to the particulate carrier can be recognized. Therefore, for example, by bringing a suspension of a target substance labeled by another method that reacts or binds with the various substances into contact with the particulate carrier, the target substance is labeled and the particulate carrier is labeled. Thus, various substances to which the target substance is bound can be specified.

  That is, according to the present invention, each particulate carrier can be randomly, freely, arbitrarily or irregularly positioned without constituting an array arranged in a position or order corresponding to various substances. Alternatively, various substances that can be fixed or fixed by the particulate carrier can also be recognized by maintaining the order.

  According to a seventh aspect of the present invention, the carrier is bonded or bindable to a plurality of different predetermined positions where a plurality of types of chemical substances can be identified from the outside, and is formed in a linear shape, a rod shape, a flat plate shape, or a block shape. The carrier-enclosed deformed container. The “block shape” includes a spherical shape, a cylindrical shape, a cubic shape, a rectangular parallelepiped shape, a prismatic shape, and the like.

  Here, the carrier may be flexible or inflexible. These carriers are enclosed in the carrier-enclosed deformable container using an enclosure. As the enclosing portion, these carriers may be attached so as to be in contact with the liquid sucked into the carrier-enclosed deformable container, and an attachment for preventing the outflow from the mouth portion may be provided. In general, the chemical substance that can bind to or bind to each predetermined position on the carrier is one of the plurality of kinds.

  According to an eighth aspect of the present invention, the non-deformable portion includes a thick tube portion capable of storing a liquid therein, a thin tube portion or a thin thin layer portion thinner than that, and the thick tube portion and the thin tube portion or the thin layer portion. A transition portion provided between the thick tube portion and the thin tube portion or the thin layer portion; the mouth portion is provided in communication with the thin tube portion or the thin layer portion; A deformed container with a carrier enclosed in either the thin tube portion or the thin layer portion.

  In this case, if the particulate carriers are held in one row in the narrow tube or in one layer in the thin layer portion, by scanning the particulate carrier along the narrow tube, or Measurement is easier by capturing the entire thin layer as a flat image. Here, since it is a single row or a single layer, the cross-section perpendicular to the diameter or axial direction of the thin tube, or the cross-section in the thickness or normal direction of the thin layer portion, the particulate carrier is along the axial direction. Cannot pass each other or can not line two or more vertically in the axial direction. Alternatively, it is necessary to have a shape or size such that two or more of the particulate carriers cannot be arranged along the normal direction. That is, a capillary having an inner diameter or width and length that is larger than the liquid of the particulate carrier and smaller than twice the outer diameter, or a thin tube having a heat smaller than twice the outer diameter. It has a layer part.

  Then, each particulate carrier enclosed in the thin tube portion or the thin layer portion can be measured by scanning along the row or collectively. The outer diameter of such a particulate carrier is, for example, about 0.1 mm to 3 mm, and the capillary has an inner diameter of, for example, about 0.2 mm to 6 mm.

  The thin tube portion and the thick tube portion are not limited to a straight line shape, and may be a curved line shape. For example, a spiral that is rotated along a cylinder around an axis that connects the mouth and the opening for mounting, or that spirally rotates in a plane, is curved, or a U-shaped portion is You may have. The thin tube portion and the thick tube portion may not only have a circular or annular cross section in the direction perpendicular to the fluid flow direction, but may have a square cross section on the inner wall, for example. When the particulate carrier to be held is spherical, the vertexes of the quadrangle serve as grooves through which fluid can pass. Further, the thin layer portion is not limited to a planar shape, and may be a curved surface shape. In addition, the volume of the space in which the fluid can be stored in the narrow tube portion in which the carrier is sealed is, for example, about several microliters to several hundred microliters.

  A ninth aspect of the present invention is a carrier-enclosed deformable container having an enclosing portion that encloses the carrier in the accommodating portion in a state where the fluid can flow into the accommodating portion from the mouth portion.

  Here, as an example of the “enclosing portion”, when the mouth portion has a size that allows the carrier to pass through, the fluid can pass but the carrier cannot pass through the holding portion. In another type, there is one having one or more carrier passage blocking members provided so as to partition the accommodating portion with respect to the flow direction of the fluid.

  The “carrier passage blocking member” is formed by a member separate from the carrier-enclosed deformable container. A combination of both the wall of the carrier-enclosed deformable container and the processed wall of the carrier-enclosed deformable container may be used. The carrier passage blocking member allows a fluid to pass through by forming a gap with the inner wall surface of the container, but the size of the through-hole or the gap has a size or a shape that the particulate carrier cannot pass through. Is. For example, it is a penetrating porous member having a through hole and a member provided so as to partition a thin tube in a wheel shape, a cross shape, a single character shape, a radial shape, a net shape, or an annular shape. In the case of a permeable porous member, various particulate carriers having a size larger than the pore diameter can be surely enclosed. The “penetrating porous member” does not have to be a filter that captures any substance by adsorption or the like. However, in the case where the enclosing portion is a thin film filter such as a filter or a membrane, it is possible not only to prevent the carrier from flowing out from the mouth portion but also to capture a predetermined substance. When the enclosing part is provided separately from the carrier-enclosed deformable container, a member formed in a thin plate shape or thin film shape in which the fluid flow direction is thin, or a through hole having a large pore diameter under the condition that the carrier does not flow out is used. A porous porous member is used. The number of the carrier passage blocking members is preferably such that the particulate carrier is provided at least at one location on the mouth side in order to prevent the particulate carrier from flowing out from the mouth.

  In addition, the carrier can be easily enclosed and removed by providing the carrier passage blocking member provided separately in a detachable manner.

  Further, when the carrier-enclosed deformed container is processed by caulking as the enclosing portion, the pressure required for suction and discharge can be reduced by enlarging the opening under the condition that the carrier does not flow out. . As the one using the carrier-enclosed deformable container itself, in order to narrow the narrow tube, the holding portion is provided so as to partition with respect to the fluid flow direction. In some cases, one having two or more projecting portions projecting the wall surface, a short tubular stopper, or the like is used.

  Accordingly, the particulate carrier can be reliably enclosed by processing and deforming the carrier-enclosed deformable container without processing the particulate carrier.

  According to a tenth aspect of the present invention, the encapsulating portion includes an introduction hole formed in a wall surface of the accommodating portion so that the carrier can be introduced into the accommodating portion, and a cover enclosing the introducing hole It is a deformed container.

  In this case, it is preferable that the size of the introduction hole is larger than the size of the mouth portion. As a result, a carrier that cannot pass through the mouth portion can be enclosed in the housing portion.

  An eleventh aspect of the invention is a carrier-enclosed deformable container in which a portion of the non-deformable portion in which the carrier is encapsulated is detachably attached.

  Accordingly, the carrier can be easily sealed by attaching the portion to the carrier-enclosed deformable container body.

  A twelfth aspect of the invention is a carrier-enclosed deformable container in which a bellows is formed on the deformed wall surface. Here, the “belly bellows” is a planar member or a film-like member in which a wave or ridge having a peak and a valley formed along a direction that crosses a predetermined deformation direction substantially perpendicularly. It can be bent in the valley. When the planar member or film member having bellows formed on the cylindrical wall surface with the deformation direction as an axis is used, the wave or ridge shape is a straight line perpendicular to the deformation direction. Or it consists of the crest and trough of the circumference shape or closed curve shape (a curve also contains a straight line) contained in the plane perpendicular | vertical to this deformation direction.

  The bellows is formed, for example, so as to partition the entire wall surface of the housing portion into two across the deformation direction of the bellows. Therefore, the deformation direction substantially coincides with each normal direction of each plane including the corrugated waveform or each mountain or valley of the ridge.

  According to a thirteenth aspect of the present invention, there is provided a deformed wall surface that is capable of containing a liquid and a gas in an interior surrounded by the wall surface, and is capable of predetermined deformation without substantially changing the total inner surface area of the wall surface. An accommodating portion that communicates with the accommodating portion, a mouth portion through which the liquid sucked and discharged by the expansion and contraction due to the deformation of the deforming wall surface can flow in and out, and a predetermined substance accommodated in the accommodating portion. One or two or more carrier-enclosed deformable containers having a carrier that can be coupled or bondable, and one or two or more of the carrier-enclosed deformable containers are supported so that the mouth portion does not fluctuate due to deformation of the deformed wall surface. A carrier-enclosed deformed container processing apparatus having one or more carrier-enclosed heads that perform suction and discharge of liquid to the carrier-enclosed deformable container by deforming the deformed wall surface of the encapsulated deformable container. .

  Here, “supporting the carrier-enclosed deformable container so that the mouth portion does not fluctuate due to deformation of the deformed wall surface” means that the position and shape of the mouth portion are substantially the same due to deformation of the deformed wall surface. It is to be attached to the head so as not to fluctuate upward. This is because the plunger and the mouth that slide during suction and discharge are not independently formed as members as in the case of a cylinder-type dispensing tip. This is because the deformed wall surface and the mouth portion that are deformed into a continuous shape are continuous as members. For example, a support position such as a mounting position or a fixed position of the carrier-enclosed deformable container on the head is an undeformed wall surface that does not deform other than a deformed wall surface provided between the mouth portion and the deformed wall surface. The mouth portion is preferably supported so as to face downward.

  A fourteenth aspect of the invention includes a container group having a plurality of containers that can store liquids such as various solutions and suspensions, and a head moving unit that moves the carrier-sealed head relative to the container group. Furthermore, each container provided in the container group is a carrier-enclosed deformed container processing apparatus provided so that the mouth portions can be inserted all at once.

  In a fifteenth aspect of the invention, the container is a well, the container group is at least one microplate in which the well is arranged in a matrix, and the carrier-enclosed deformable container of the carrier enclosure head is arranged in a matrix. In addition, all the mouth portions provided in the carrier enclosing head are provided so that they can be simultaneously inserted into all or a part of the wells of the microplate, and at least one of the row spacing or column spacing of the mouth portions corresponds. The carrier is set to a natural number multiple of the row interval or column interval of the well, and at least one of the corresponding row number or column number of the mouth is the natural number of the row number or column number of the well. It is an enclosure deformation container processing apparatus.

  Here, the “matrix shape” means that a predetermined number of elements are provided at predetermined row intervals and column intervals along the two directions of the column direction and the row direction. The number of rows and the number of columns are each 2 or more. The column direction and the row direction are usually orthogonal, but are not necessarily limited thereto, and may be oblique. In addition, the case where the elements are staggered by shifting the arrangement by a distance of half the column interval or half the row interval between adjacent rows or columns is also included. The “row interval” is a distance in the column direction between a row in which one element arranged in a matrix is provided and a row in which elements adjacent in the column direction are provided, and the “column interval” is The distance in the row direction between a column provided with one element arranged in a matrix and a column provided with an element adjacent in the row direction.

  “All the mouths are provided so that they can be inserted into a part of the wells of the microplate all at once.” In general, the mouth matrix has fewer rows or columns than the well matrix. The mouth matrix and the well matrix have the same angle between the row direction and the column direction, and the row or column spacing of the mouth matrix is the natural value of the row or column spacing of the well matrix. It needs to be several times.

  “At least one of the row interval or column interval of the mouth is set to a natural number multiple of 2 or more of the row interval or column interval of the corresponding well, and at least the number of rows or columns of the corresponding mouth is set. 1 is the natural fraction of the number of rows or columns of the wells ”. Therefore, the microplate has the same arrangement as the matrix arrangement of the mouth, and is at least a natural number that does not overlap each other (> 1) The matrix-like well array (hereinafter referred to as “well sub-matrix”) exists. Moreover, an arbitrary well element belonging to one well submatrix and a corresponding one well element belonging to a well submatrix adjacent thereto are not separated by more than the distance between wells adjacent to each other in the microplate. become.

  As a result, the working area is limited to one microplate having an area substantially equivalent to the carrier-encapsulating head, despite the fact that there are two or more independent well groups into which all the mouths of the carrier-encapsulating head can be inserted simultaneously. Therefore, the work area is not increased unnecessarily. In addition, the movement of the nozzle head between the well sub-matrices is repeated for at least (natural number of times (> 1) -1) times at the most by the distance of the row interval or the column interval, so that all well sub-matrices in the microplate The entire mouth portion of the carrier enclosing head can be positioned so as to be insertable.

  Since the natural number is 2 or more, at least either the number of well rows or the number of columns of the microplate must be a number having this natural number (> 1) as a divisor. For example, a natural number is "3" for a carrier-enclosed head in which mouths having a column interval with a column interval set to 3 times are arranged on a microplate in which matrix wells of 4 rows x 12 columns are arranged. Therefore, the number of columns in the mouth is four columns, which is 1/3 of 12 columns, which is the number of well columns. Thus, the well row number 12 has a divisor of “3”.

  A sixteenth aspect of the present invention further includes a control unit, and the control unit can insert all the mouth portions into wells belonging to the corresponding first well sub-matrix of the microplate with respect to the moving means. After being positioned at the same position, it is relatively moved between the carrier-encapsulating head and the microplate so that all the mouth portions can be simultaneously inserted into the wells belonging to the corresponding second well submatrix of the microplate. It is the support | carrier enclosure deformation | transformation container processing apparatus to be located.

  Here, only the case of having the “first well sub-matrix” and the “second well sub-matrix” is described because the number of well sub-matrices is at least the natural number (n> 1). It is. Further, when the wells of the microplate have a normal matrix arrangement, the row interval or the column interval distance of the wells of the microplate is set along the corresponding column direction or / and the row direction. By performing the relative movement between the carrier-encapsulating head and the microplate at least a natural number of times (n> 1), all the mouth portions can be simultaneously inserted into all the well sub-matrices in the microplate.

  When both the row interval and the column interval of the mouth part are natural number times (n> 1) and natural number times (m> 1) times the row interval and column interval of the well, The number of matrices is a total of nm per microplate.

  According to a seventeenth aspect of the present invention, each well sub-matrix along the movement path of the carrier enclosing head contains a liquid such as a solution or a suspension required in each process step according to the order of the steps. It is the support | carrier enclosure deformation | transformation container processing apparatus accommodated according to the order of this process.

  Here, the “movement path” is a path through which the carrier-enclosed head is sequentially moved in parallel to the whole well submatrix, and is preferably the path having the shortest distance along the movement path. Therefore, each well submatrix is selected in the order corresponding to the processing step, and necessary solutions such as reagents are accommodated. Further, for example, the wells belonging to the same well submatrix contain solutions or suspensions to be handled as the same type or the same amount, and the wells belonging to different well submatrixes are different or different from each other. The solution or suspension to be handled as a quantity is contained. This is because the suction and discharge operations of the carrier-enclosed deformable containers provided in the same carrier-encapsulating head are interlocked and substantially equivalent. Alternatively, when a large volume of liquid is handled, the same type of solution or suspension may be accommodated between wells belonging to different well sub-matrices.

  In an eighteenth aspect of the invention, the control unit is in a state in which the mouth part can be inserted into all wells belonging to each well group in the microplate in which the same mouth part provided in the carrier enclosure head can be inserted. The carrier-enclosed deformed container processing apparatus that sequentially moves the carrier-enclosed head so as to be positioned at the position.

  Each well group includes one well element belonging to each well submatrix without overlapping. Therefore, the number of well elements belonging to each well group is equal to the number of well sub-matrices existing in one microplate. That is, as a result, the mouths of the carrier-enclosed deformable containers can be simultaneously inserted into the corresponding wells in the whole well group. The number of wells belonging to each well group is at least the natural number (n> 1). If the row spacing and column spacing of the wells are both natural number multiples (n> 1, m> 1) in both the row spacing and column spacing of the mouth of the carrier-enclosed deformable container, they belong to each well group The number of wells is nm. In addition, the movement path | route in the well group of each mouth part is a path | route which passes all the well elements in this well group according to the order of a process process, and it is preferable that it is the shortest distance.

  In addition, it is preferable that partition walls that partition well groups in the microplate into which the same opening provided in the carrier sealing head can be inserted protrude from the upper surface of the microplate.

  As a result, for example, a number of different specimens to be processed can be processed in a state of being partitioned by the partition walls, so that once the mouth is moved into the region surrounded by the partition walls, The treatment can be performed without moving beyond the partition wall.

  Furthermore, the number of the carrier enclosing heads and the number of microplates are at least the natural number and the natural number, respectively. In that case, it can provide or control so that operation | movement of each carrier enclosure head may be interlocked.

  In a nineteenth aspect of the invention, the carrier-enclosed head has two or more magnets provided so as to be able to contact with and separate from the accommodating portion so that a magnetic field can be applied and removed simultaneously in the accommodating portion. This is a carrier-enclosed deformed container processing apparatus provided with magnetic means. Here, in general, when a magnetic field is applied, the case where magnetic particles as a carrier are accommodated in the carrier-enclosed deformable container, or a dispensing tip instead of the carrier-enclosed deformable container is provided on the carrier-enclosed head. This is the case.

  As the magnetic force means, for example, a mouth row or a mouth column having a row interval or a column interval set to a natural number multiple of 2 or more of the row interval or column interval of the wells arranged in a matrix. Between the mouth rows and between the mouth columns, and provided so as to be relatively movable along the row direction or the column direction, and extending along the row direction or the column direction. In addition, for example, each of the combs has (row number-1) or (column number-1) comb-tooth members of the carrier-enclosed deformable container and a support member connected at one end of the comb-tooth member. The tooth member is provided with magnets of several columns or several rows arranged at the column intervals or row intervals at positions corresponding to the respective carrier-enclosed deformable containers. When a magnetic field is applied to the carrier-enclosed deformable container, all the magnets are moved to the shortest distance to all of the carrier-enclosed deformable containers, and when the magnetic field is removed or weakened, all the magnets are The encapsulated deformable container may be completely withdrawn from the arranged head, or the magnets may be moved to a predetermined position in the middle of the predetermined interval of the carrier encapsulated deformable container. In addition to the case described above, the number of comb-teeth members may be such that the magnets arranged in one comb-teeth member affect each of the two carrier-enclosed deformable containers arranged on both sides thereof. The number of comb-tooth members is about half of the number.

  According to a twentieth aspect of the invention, there is provided the carrier-enclosed deformed container processing apparatus further including a light detection means for detecting a state in the housing portion in the carrier-enclosed head. Therefore, at least the non-deformable portion or the like of the carrier-enclosed deformable container needs to be formed of a translucent member. The “liquid state” includes the presence / absence of a liquid, the suction amount or the discharge amount of the liquid.

  In addition, as the light detection means, for example, the mouth row of the money carrier-enclosed deformable container having the row spacing or the column spacing set to a natural number multiple of 2 or more of the row spacing or column spacing of the well or the mouth portion Provided between the columns so as to be relatively movable along the row direction or the column direction, extending along the row direction or the column direction, and having a width that can be inserted between the mouth rows or between the mouth columns. In addition, for example, each of the comb teeth members has (number of rows-1) or (number of columns-1) comb teeth members of the mouth portion and a support member connected at one end of the comb teeth members. Each is provided with one light detection unit.

  In a twenty-first aspect of the invention, the light detecting means is disposed outside the non-deformable portion of the accommodating portion, and is disposed adjacent to the non-deformable portion so as to surround the periphery of the non-deformable portion. A terminal, or one or two or more light receiving terminals and at least one irradiation terminal, and moves relative to the non-deformable portion so as to scan the entire area of the non-deformable portion that can accommodate the inner particulate carrier. This is a carrier-enclosed deformed container processing apparatus that is possible.

  Here, since it is “movable relative to the non-deformable part”, both the case where the non-deformable part is moved and the case where the photodetecting means is moved may be moved.

  In a twenty-second aspect of the invention, the carrier-encapsulated head deforms the deformed wall surface along the linear direction at an intersection of the deformed wall surface and a straight line that passes through the mouth portion and the accommodating portion and passes through the deformed wall surface. This is a carrier-enclosed deformed container processing apparatus.

  In a twenty-third aspect of the invention, the carrier enclosing head advances and retreats all at once along a predetermined deformation direction of the carrier container supporting portion capable of supporting the two or more carrier enclosing deformable containers and the deforming wall surface of the carrier enclosing deformable container. A carrier-enclosed deformed container processing apparatus having an operable movable member.

  In a twenty-fourth aspect of the invention, the deformation of the deformation wall surface and / or the movement between the carrier enclosure head and the container group includes the number or structure of the carrier enclosure deformation containers, the liquid to be sucked and discharged, and the like. This is a carrier-enclosed deformed container processing apparatus having a control unit that controls the substance to be controlled, the amount thereof, the storage position, the temperature or the concentration thereof, the processing content, or an instruction.

  A twenty-fifth aspect of the invention is a carrier-enclosed deformation container processing apparatus in which a predetermined reference position is set for the deformation of the deformation wall surface, and the deformation of the deformation wall surface is controlled based on the reference position.

Here, the “predetermined reference position” is determined by the amount of liquid handled in the process, the capacity of the carrier-enclosed deformable container to be used, the content of the process, or the processing accuracy of the carrier-enclosed deformable container.
For example, when the amount of liquid handled in processing is very small (for example, in the order of several μl to several hundred μl), or when the capacity of the carrier-enclosed deformed container to be used is small, processing requires accuracy, or the carrier When the processing accuracy of the encapsulated deformable container is not high, the reference position is based on the position along the deformation direction of the movable member or deformed wall surface in which the carrier encapsulated deformed container has already been subjected to predetermined deformation. This makes it possible to perform highly accurate control. In this case, for example, it is preferable to set so that all of the predetermined maximum suction amount of the liquid into the carrier-enclosed deformable container with the predetermined maximum deformation amount can be discharged. Accordingly, it is possible to prevent the liquid from remaining in the carrier-enclosed deformable container due to the discharge of the liquid from the carrier-enclosed deformable container.

For example, a predetermined internal volume V determined by the deformation of the carrier-enclosed deformable container with reference to the position of the movable member or the deformed wall surface corresponding to the state is set as V ₀ and the volume inside the deformed container enclosed with the carrier is set in advance. _{1. When} the predetermined minimum internal volume V ₂ is set by deformation of the carrier-enclosed deformable container, the predetermined maximum suction amount V ₁ -V ₀ of the liquid into the carrier-enclosed deformable container is a predetermined maximum The reference position is set so that the relationship is smaller than the discharge amount V ₀ -V ₂ , that is, V ₁ −V ₀ ≦ V ₀ −V ₂ , that is, (V ₁ + V ₂ ) / 2 ≦ V _0. Is preferred.

  Here, since it is the “predetermined maximum deformation”, the physical maximum deformation is not necessarily required. Since the “maximum suction amount can be discharged”, the “maximum discharge amount” needs to be equal to or larger than the “maximum suction amount”. Thus, the processing can be performed without worrying about the remaining amount of liquid in the carrier-enclosed deformable container.

  On the other hand, when the amount of liquid to be handled is large (for example, in the order of several milliliters) and the processing does not require a high degree of accuracy, the position of the carrier-enclosed deformable container is not deformed and is used as a reference. Can be controlled. In such a case, for example, a position along the deformation direction (for example, a position 1 mm away from the chip) is taken as the reference position in a state where the movable member is not yet in contact with the carrier-enclosed deformation container. This is the case.

  In a twenty-sixth aspect of the invention, the mouth portion is provided at the lower end, the storage portion is provided above the mouth portion, and the inner wall surface is vertically partitioned by a part of the wall surface surrounding the accommodating portion. The carrier-enclosed deformed container processing apparatus is provided with a deformable wall surface that can be deformed in a direction so that the upper end of the receiving portion and the movable member can contact or connect to each other.

  In a twenty-seventh aspect of the invention, the accommodating portion has a deformable wall surface that can be contacted or connected to the movable member and can be deformed by the movable member, and can accommodate gas. A carrier-enclosed deformed container processing apparatus having a non-deformable portion that is formed of a non-deformed wall surface and that has the mouth at the tip and can store a liquid.

  In a twenty-eighth aspect of the present invention, a deformed wall surface that is capable of containing a liquid and a gas inside a wall surface and is capable of predetermined deformation without substantially changing the total inner surface area of the wall surface is a part of the wall surface. A receiving portion connected to the receiving portion, a mouth portion through which the liquid sucked and discharged by the expansion and contraction of the inner wall due to deformation of the deformation wall surface, and a predetermined substance stored in the receiving portion are combined. Or a supporting step for supporting the two or more carrier-enclosed deformable containers having a carrier that can be coupled to the carrier-encapsulating head so that the mouth does not fluctuate due to deformation of the deformed wall surface, and a moving step for moving the carrier-encapsulating head And a deforming step of inserting the mouth portion into a container in a container group and deforming the deformed wall surface all at once.

  A twenty-ninth aspect of the invention is a carrier-enclosed deformation container processing method in which the deformation step sets a predetermined reference position for deformation of the deformation wall surface and deforms the deformation wall surface with reference to the reference position.

  In a thirtieth aspect of the present invention, the mouth portion is provided at a lower end, and the deformed wall surface is provided so as to be deformable in a vertical direction on a part of a wall surface surrounding the housing portion. And a non-deformable portion that can communicate with the deformable portion and that does not have the deformable wall surface and has the mouth portion and can store liquid. The deformation step is a carrier-enclosed deformation container processing method including a step of bringing a movable member into contact with or connecting to an upper end surface of the housing portion and a step of lowering and / or raising the movable member.

  A thirty-first aspect of the invention is a carrier-enclosed deformation container processing method in which the movable member is raised and lowered by setting a predetermined reference position along the vertical direction in which the deformation wall surface is deformed and using the reference position as a reference. .

  In a thirty-second aspect of the invention, in the liquid, a magnetic substance capable of binding a predetermined substance or suspended with a predetermined substance is suspended, and the magnetic substance is applied by applying a magnetic field to the inside of the container or the container group. It is a processing method of a carrier-enclosed deformed container having a step of adsorbing and separating on the inner wall of the container or the container.

  According to a thirty-third aspect of the invention, there is provided a microplate having wells arranged in a matrix and one or more carrier-encapsulating heads having a mouth of a carrier-enclosed deformable container arranged in a matrix and capable of sucking and discharging fluid. At least one of the row interval or column interval of the mouth is set to a natural number multiple of 2 or more of the row interval or column interval of the well, and at least the number of rows or columns of the corresponding mouth 1 is a natural fraction of the number of rows or columns of the well, and the carrier enclosing head is moved relative to the microplate so that the well belongs to the first well submatrix in the microplate. A first step of positioning all the openings provided in each carrier enclosing head so that they can be inserted all at once, and a relative movement between the carrier enclosing head and the microplate; Serial the corresponding second carrier enclosing transformable container processing method and a second step of insertably positioned simultaneously to the wells belonging to the well submatrix within the microplate all mouth.

  Here, only the case of having “first step” and “second step” is described because the number of well sub-matrices is at least the natural number (n> 1). Therefore, when both the row interval and the column interval of the mouth are natural number times (n> 1) and natural number times (m> 1), respectively, the row interval and column interval of the well, Since the number of well sub-matrices is a total of nm per microplate, the number of steps is a total of nm per microplate.

  Further, in the case of a normal matrix arrangement, the carrier enclosing head and the microplate are arranged along the corresponding column direction or row direction by the distance corresponding to the row interval or column interval of the wells of the microplate. By performing the relative movement between them at least naturally several times (n> 1), all the mouth portions can be simultaneously inserted into all the well matrices in the microplate.

  In the first step, in order to perform the processing, the mouth portion is inserted into each well and sucked or discharged, and the mouth portion is extracted from the well. In the second step, as in the first step, an insertion step, a suction / discharge step, or an extraction step is provided. The required number of steps is determined according to at least the set natural number (n> 1), and has at least the natural number of steps.

  According to the first invention, the thirteenth invention, or the twenty-eighth invention, a carrier to which various substances such as biological substances are bound or bindable is sealed in a deformable deformable container in a substantially stationary state, and the deformable By dynamically deforming the container, the liquid can be sucked and discharged. Therefore, without using a fluid dynamic mechanism such as a pipe for flowing a complicated liquid or gas such as a cylinder, the fluid can be sucked into the deformed container, contacted and discharged between the fluid and the carrier, and can be handled easily. Or using a device having a simple structure can be manufactured and processed inexpensively and easily.

  Further, since the deformed wall surface is deformed without changing the total inner surface area of the wall surface, liquid processing such as suction and discharge is performed, so that fitting, sliding, etc. between members constituting the wall surface are performed. Therefore, it is possible to obtain complete water tightness and air tightness and perform highly reliable processing without requiring high processing accuracy.

  In addition, various processes can be performed only by sucking and discharging a liquid while the carrier to which a predetermined substance is bound or bound is sealed in the container having a mouth, and by moving the carrier-enclosed deformable container, For example, since reaction, washing, temperature control, separation, stirring, dispensing, clarification, isolation, elution, and extraction can be performed, processing can be performed efficiently, quickly, and easily.

  Furthermore, according to the present invention, the reaction from the reaction with a predetermined substance bound to the carrier to the measurement can be carried out while being enclosed in the carrier-enclosed deformed container having only the mouth open. Since the predetermined substance can be carried out without touching other members or human hands, cross contamination can be prevented and reliable and reliable. In addition, by selecting the carrier-enclosed deformable container so as to have a shape suitable for the speed of the fluid and the amount of liquid to be handled, it is possible to cope with various treatments, so that there is versatility and diversity.

  In addition, according to the present invention, since the carrier is held in a substantially stationary state, it is not moved by applying a fluid force. Therefore, the carrier can be handled and handled by simple control without performing complicated synchronous control or the like. Measurement can be facilitated.

  According to the second invention, since the carrier is surrounded by the non-deformed wall surface, it is possible to avoid adverse effects on the carrier due to deformation and to perform measurement in a stable state from the outside, so that the reliability is high. .

  According to the third invention, it is possible to reliably perform suction and discharge of liquids having at least two different types of capacities in the accommodating portion, not by adjusting the magnitude of the force applied to the deforming portion, but by selecting the deforming portion. It becomes. In particular, since a small amount of liquid and a large amount of liquid are manually determined in advance and the other amounts can be reliably sucked and discharged, the reliability is high.

  According to the fourth invention, the carrier-enclosed deformable container is normally used while being fixed so as to support the mouth from below with the mouth facing downward, so that the deformation is performed along the vertical direction. By doing so, it is possible to easily and reliably prevent the mouth from being changed due to deformation.

  According to the fifth invention, the particulate carrier or the aggregate of particulate carriers uses the same particulate carrier consistently to fix, react, measure, etc. various substances. It is suitable for performing automatically.

  According to the sixth aspect of the present invention, the various substances held on the particulate carrier are not identified based on the position associated with the particulate carrier. It is not necessary to fix or maintain the order strictly and to measure strictly. In addition, since it is not moved by applying a fluid force but is held in a substantially stationary state, it is easy to handle and measure each particulate carrier with simple control without performing complicated synchronous control, etc. It can be made accurate.

  According to the present invention, it is possible to easily introduce and hold a plurality of particulate carriers to which various substances are bound or capable of being bound, without predetermining the position and order of the plurality of particulate carriers without holding them in advance. Therefore, since the process corresponding to the fixed carrier situation for the particulate carrier situation can be executed in a different place from the container, the efficiency of the process, the reliability of the process, and the certainty of the process can be improved.

  According to the present invention, a plurality of particulate carriers to which various substances are bound or capable of binding are labeled in advance before being held, and the particulate carriers are measured by holding the particulate carriers in an approximately stationary state at an arbitrary position. It is sufficient to measure the presence / absence of a substance, and the measurement is prepared because it is not necessary to measure a fine position coordinate.

  Furthermore, according to the present invention, it is possible to label each aggregate of particulate carriers having a plurality of particulate carriers. Therefore, the particulate carriers belonging to the aggregate share different functions for each particulate carrier by differentiating the particulate carrier on which various substances can be fixed or immobilized and the particulate carrier used for labeling. Can be made. Therefore, since the function can be specialized for each of the particulate carriers for labeling and immobilization, processing with higher accuracy can be performed.

  Moreover, since various labeling can be performed by freely setting the number of the particulate carriers belonging to the aggregate of the particulate carriers, there is expandability, diversity, and versatility.

  According to the seventh invention, since the plurality of types of chemical substances can be bonded or bonded to a plurality of positions on one carrier, the plurality of positions can be bonded to or bonded to a plurality of chemical substances, for example, The chemical substances at each position can be easily and reliably specified by performing a regular arrangement such as a constant interval and a fixed direction.

  According to the eighth invention, since the carrier is enclosed in the thin tube portion or the thin layer portion, for example, the particulate carriers are arranged in a row or a single layer in the thin tube portion or the thin layer portion. By holding, each particulate carrier can be held one-dimensionally or two-dimensionally and measured reliably. Moreover, the measurement can be facilitated by measuring so as to scan along the thin tube portion or the thin layer portion.

  Furthermore, if the fluid is introduced and discharged along the narrow tube portion, the contact with the fluid can be reliably performed. In addition, since the thin tube portion can be inserted into various containers provided outside, it is convenient for sucking and discharging liquid. In addition, according to the present invention, since the particulate carrier and the fluid can be processed in a state where they can always contact, the processing efficiency is high.

  According to the ninth aspect of the present invention, a state in which the carrier is sealed in advance in the container is provided by providing the sealing portion that seals the carrier in the storage portion in a state where the fluid can flow into the storage portion from the mouth portion. Compared to the case of manufacturing in (1), since the carrier can be sealed using the sealing part after the container is manufactured, the manufacturing is easy.

  According to the tenth invention, since the carrier can be introduced through the introduction hole provided in the housing portion and sealed with the lid portion, it is not necessary to introduce the carrier from the mouth portion, and the carrier does not pass as the mouth portion. By forming the size, the carrier can be surely sealed. Further, the carrier can be removed from the introduction hole.

  In the eleventh aspect of the present invention, it is possible to facilitate the introduction of the carrier into the accommodating portion by detachably attaching the portion in which the carrier is enclosed in the non-deformable portion. By preparing a plurality of such portions in advance, the processing can be performed efficiently.

  In a twelfth aspect, a bellows is provided as the deformed wall surface. This makes it possible to form a wall having a large deformation rate with a simple configuration. Moreover, since it can be formed with a rigid member, it is hard to break. Furthermore, the location and direction of bending are determined by deformation, and the regularity of deformation or the regularity due to deformation is high.

  According to the fourteenth invention, by using only a mechanical mechanism that does not come into contact with the gas liquid to be moved along the deformation direction, liquid processing such as suction, discharge, transfer, etc. is enabled. Since the portion that can come into contact with the liquid is almost limited to the closed space and the container in the carrier-enclosed deformable container, contamination can be reliably prevented.

  In addition, since the carrier-enclosed deformable container is supported so that it does not fluctuate depending on the force applied to the deformed wall by the mouth, accurate position control can be performed using the carrier-enclosed deformable container. By arranging a large number of containers closely, a rapid and efficient process can be performed.

  According to the fifteenth invention, the carrier-enclosed deformable container is supported so that the mouth portion does not fluctuate depending on the force applied for deformation of the deformed wall surface, and a plurality of carrier-enclosed deformable containers are simultaneously subjected to the same conditions. Therefore, accurate position control and highly reproducible suction / discharge control can be performed. Even if a carrier-enclosed deformed container is used, a large number of processes can be performed in parallel, which is efficient. Even when a large number of containers are closely arranged, a highly reliable process is performed. be able to.

  Since at least one of the row interval or column interval of the mouth portion is a natural number multiple of 2 or more of the row interval or column interval of the corresponding well, two or more wells are provided for one mouth portion. Can be matched. Therefore, two or more types of solutions can be stored in one microplate without newly providing a microplate, so that more types of solutions can be handled without increasing the work area. Can do.

  Further, since one mouth can correspond to two or more wells, one mouth can handle a liquid having a volume twice or more as large as the volume handled by one well. Furthermore, since a large space that can be used between adjacent mouths will appear, various functions, for example, a function of exerting a magnetic force in the mouths, without expanding the device scale for each mouth part, A mechanism for adding a function for detecting the state of the liquid in the mouth can be provided.

  According to the sixteenth or thirty-third invention, in addition to the effects of the thirteenth and fourteenth inventions, wells that can be handled at one time by one head overlap each other belonging to one microplate. Each well submatrix, and the distance between each well submatrix is only separated by a distance corresponding to the distance between adjacent wells of the microplate, so one well is required for each well submatrix. By accommodating each of the various solutions, the moving distance of the carrier-enclosed deformable container array head until one process is completed is short, and the process can be performed quickly and efficiently.

  According to the seventeenth aspect, a series of processes consisting of a plurality of processes for a large number of processing objects can be continuously executed consistently using one head for one microplate. High processing efficiency for work area. Further, since the moving distance of the head is short, the working efficiency is high.

  According to the eighteenth invention, each well group includes one well element belonging to each well submatrix without overlapping, and therefore, the mouth portion is inserted into all wells belonging to the well group. By making the movement possible, a series of processes consisting of at least the natural number (n> 1) steps are applied to a large number of objects with respect to one microplate. Because it can be performed in the plate, it is reliable and easy to manage.

  According to the nineteenth aspect or the thirty-second aspect, since the magnetic field is applied to and removed from the inside of the accommodating portion, the separation is achieved by adsorbing the magnetic particles in the liquid in which the magnetic particles are suspended. It can be done reliably. Further, a gap between adjacent mouth rows or adjacent mouth columns having a row interval or a column interval of the mouth provided in the head so as to be set to a natural number multiple of 2 or more of the row interval or the column interval of the liquid well. Since a magnet having a strong magnetic force can be provided by using a microplate with wells integrated in nectar, a strong magnetic field can be applied to and removed from each carrier-enclosed deformable container with a simple mechanism. .

  According to the twentieth invention, the suction and discharge states of the liquid are measured by detecting the state in the vicinity so as to surround the non-deformation portion of the accommodating portion of each carrier-enclosed deformation container, and the reliability High control can be performed.

  According to the twenty-first aspect, since the light receiving terminal and / or the irradiation terminal is provided so as to surround the vicinity of the non-deformable portion of the accommodating portion, light emission by the particulate carrier can be reliably captured. So reliable.

  According to the twenty-second aspect of the present invention, the fluid is deformed so as to pass through the mouth portion, so that the fluid can be reliably sucked and discharged through the mouth portion.

  According to the twenty-third aspect, by using only a mechanical mechanism that does not come into contact with the gas liquid to be processed that moves the movable member along the deformation direction, liquid processing such as suction, discharge, and transfer is enabled. Since the portion that can come into contact with the liquid is almost limited only to the closed space and the container in the carrier-enclosed deformable container, contamination can be reliably prevented.

  According to the twenty-fourth invention, since the deformation of the deformed wall surface and / or the movement of the head is controlled based on the structure of the carrier-enclosed deformable container and the like, the suction and discharge can be reliably performed. it can.

  According to the twenty-fifth, twenty-sixth or twenty-ninth invention, the deformation is controlled on the basis of a reference deformation state in which both expansion and contraction are possible due to wall surface deformation. In addition, it is possible to immediately cope with both the contraction and the contraction, and it is possible to perform a quick and efficient process. Further, by properly setting the reference deformation state, it is possible to prevent the liquid from remaining in the carrier-enclosed deformation container due to the discharge of the liquid.

  According to the twenty-sixth or thirtieth invention, the gas is accommodated in the deformed portion having the deformed wall surface, and the introduced liquid is stored in the non-deformed portion having no deformed wall surface. Therefore, the introduced liquid is not affected by the deformation of the deformed wall surface, and can prevent the liquid from adhering to the deformed wall surface to remain, and has high reliability in the case of performing a quantitative process.

It is sectional drawing and perspective view which show the support | carrier enclosure deformation | transformation container which concerns on the 1st Embodiment of this invention. It is sectional drawing and perspective view which show the carrier enclosure deformation | transformation container which concerns on the 2nd Embodiment of this invention. It is sectional drawing and the perspective view which show the support | carrier enclosure deformation | transformation container which concerns on the 3rd Embodiment of this invention. It is a perspective view which shows the optical sensor applied to the support | carrier enclosure deformation | transformation container which concerns on the 3rd Embodiment of this invention. A sectional view and a perspective view of a carrier enclosure deformation container concerning a 4th embodiment of the present invention are shown. It is a perspective view of the support | carrier enclosure deformation | transformation container processing apparatus which concerns on the 5th Embodiment of this invention. It is a figure which shows the microplate of the support | carrier enclosure deformation | transformation container processing apparatus which concerns on the 5th Embodiment of this invention. It is a side view which shows the comb-tooth light detection part and comb-tooth magnet which concern on the 5th Embodiment of this invention. It is a figure which shows the comb-tooth shaped light detection part which concerns on the 5th Embodiment of this invention. It is sectional drawing and a perspective view which show the support | carrier enclosure deformation | transformation container which concerns on the 6th Embodiment of this invention. It is sectional drawing and a perspective view which show the support | carrier enclosure deformation | transformation container which concerns on the 7th Embodiment of this invention. It is sectional drawing and a perspective view which show the support | carrier enclosure deformation | transformation container which concerns on the 8th Embodiment of this invention. It is sectional drawing and a perspective view which show the support | carrier enclosure deformation | transformation container which concerns on the 9th Embodiment of this invention. It is a flowchart which shows the carrier enclosure deformation | transformation container processing method which concerns on the 10th Embodiment of this invention.

  Subsequently, a carrier-enclosed deformable container, a carrier-enclosed deformed container processing apparatus, and a processing method thereof according to an embodiment of the present invention will be described with reference to the drawings.

FIG. 1 shows a carrier-enclosed deformable container 11 according to a first embodiment of the present invention.
As shown in FIG. 1 (a), the carrier-enclosed deformable container 11 can store a liquid and a gas inside a wall surface, and has a predetermined inner surface without substantially changing the entire inner surface area. An accommodating portion 12 having a deformable deformable wall surface in a part of the wall surface, and an opening through which the liquid sucked and discharged by expansion and contraction of the interior due to deformation of the deformable wall surface communicates with the accommodated portion 12 A part 13 and a plurality of particulate carriers 14 and 15 to which a predetermined substance sealed in a substantially stationary state in the housing part 12 can be combined or can be combined. The accommodating portion 12 is surrounded by one deformable portion 16 surrounded by the deformed wall surface and an undeformed wall surface that communicates with the deformable portion 16 and is not deformed, and communicates with the mouth portion 13 so that the inside can be measured from the outside. A non-deformable portion 17.

  The deformed portion 16 has a bellows 18 formed on the deformed wall surface. The bellows 18 is formed so as to partition the entire wall surface of the accommodating portion 12 or the deformed wall surface of the deformable portion 16 into two across the axial direction of the deformable portion 16 or the accommodating portion 12, which is the deformation direction. This portion has a vertex 19, and the other is provided at the boundary between the non-deformable portion 17 and the deformable portion 16 and the non-deformable portion 17, and supports the carrier-enclosed deformable container 11 mainly by hand or fingers. A flange 20 is provided which has a larger radius than the deforming portion 16 and the non-deforming portion 17 and protrudes outward. Therefore, the carrier-enclosed deformable container 11 is suitable for manual operation. The normal directions of the virtual planes including the peaks or valleys of the waveform of the bellows 18 substantially coincide with the axial direction. The bellows 18 is deformed along the linear direction (the axial direction) at the intersection of a straight line (axial line) that passes through the mouth portion 13 and the accommodating portion 12 and penetrates the deformed wall surface and the deformed wall surface. The wall surface is formed to be deformable.

  The non-deformable portion 17 includes a substantially cylindrical thick tube portion 21 capable of storing a liquid therein formed of a light-transmitting resin such as polypropylene, polyester, and polyethylene, and a substantially cylindrical thin tube portion 22 thinner than that. , And a funnel-shaped transition portion 23 provided between the thick tube portion 21 and the thin tube portion 22, and the mouth portion 13 is provided at the tip of the thin tube portion 22. After the particulate carriers 14 and 15 are sealed inside, the narrow tube portion 22 is fitted to the fitting portion 24 at the lower end of the transition portion 23 and attached by adhesion, heat welding, or the like. The narrow tube portion 22 is a resin that does not emit fluorescence when the particulate carriers 14 and 15 labeled with a fluorescent dye are measured, and is suitably formed of polypropylene that requires a certain level of strength. On the other hand, it is appropriate that the portion of the accommodating portion 12 excluding the deformable portion 16 and the thin tube portion 22 formed integrally with the deformable portion 16 is made of polyester having a certain degree of softness.

  A plurality (20 in this example) of particulate carriers 14 and 15 are accommodated in a row in the narrow tube portion 22, and the narrow tube portion 22 is caulked at the upper throttle portion 25 and the lower throttle portion 26 to form a liquid. Is processed so as to be finely squeezed so that the outflow of the particulate carriers 14 and 15 is impossible, and is enclosed so that the particulate carriers 14 and 15 do not flow out of the region. Yes. The upper diaphragm 25 and the lower diaphragm 26 correspond to the enclosure.

  The particulate carriers 14 and 15 are composed of, for example, a set of a plurality of particulate carriers having a size of about 0.5 mm (two elements belong). At least one of the particulate carriers belonging to the aggregate of the particulate carriers is bound to or capable of binding a predetermined chemical substance, and emits light such as a fluorescent dye or a chemiluminescent substance to identify the chemical substance. A particulate carrier 14 labeled with a substance, which is made of, for example, a fiber material such as silica or nylon, and the other particulate carriers belonging to the aggregate are allowed to reach the neighboring particulate carrier. The particulate carrier 15 is formed of a light-shielding substance for prevention, for example, an opaque resin or metal, and the particulate carrier 14 and the particulate carrier 15 are alternately arranged. Here, the particulate carrier 14 is labeled so as to be distinguishable by a labeling substance such as a different fluorescence or a combination of different labeling substances or a quantity ratio thereof before introduction into the storage part 12. .

  Next, a carrier-enclosed deformable container according to the second embodiment of the present invention will be described with reference to FIG. Since the same reference numerals as those in FIG. 1 denote the same components, detailed description thereof will be omitted.

  As shown in FIG. 2 (a), the carrier-enclosed deformable container 27 can store a liquid and a gas inside a wall surface, and has a predetermined inner surface without substantially changing the entire inner surface area. A housing portion 28 having a deformable wall surface that can be deformed as a part of the wall surface, and a port that is in communication with the housing portion 28 and through which the liquid sucked and discharged by expansion and contraction of the inner wall due to deformation of the deformed wall surface A part 29 and a plurality of particulate carriers 14 and 15 to which a predetermined substance sealed in a substantially stationary state in the accommodating part 28 can be combined or can be combined. The accommodating portion 28 is surrounded by the one deformable portion 16 surrounded by the deformed wall surface, and is surrounded by a non-deformed wall surface that communicates with the deformable portion 16 and is not deformed. A non-deformable portion 30.

  The non-deformable portion 30 includes a substantially cylindrical thick tube portion 21 capable of storing a liquid inside formed of a translucent resin such as polypropylene, polyester, and polyethylene, and a substantially cylindrical thin tube portion 31 thinner than that. , And a funnel-shaped transition portion 23 provided between the thick tube portion 21 and the narrow tube portion 31, and the narrow tube portion 31 is connected to the fitting portion 24 whose upper end is at the lower end of the transition portion 23. It is fitted and detachably attached. The narrow tube portion 31 is suitably made of polypropylene that is a resin that does not emit fluorescence when measuring the particulate carriers 14 and 15 that are labeled with a fluorescent dye, and that requires a certain degree of strength.

  As described above, a plurality (20 in this example) of particulate carriers 14 and 15 are enclosed in a row in the narrow tube portion 31, and are fitted into the narrow tube portion 31 on the upper and lower sides thereof. Inserted, for example, stainless steel pipes 32 and 33 are attached. On the side of the pipes 32 and 33 that can come into contact with the particulate carrier, a slope that is cut obliquely with respect to the axial direction so that the particulate carriers 14 and 15 do not block the pipes 32 and 33. 34, 35. Note that the hole at the lower end of the lower pipe 33 corresponds to the mouth portion 29.

  Subsequently, a carrier-enclosed deformable container 36 according to a third embodiment of the present invention will be described with reference to FIG. Note that the same reference numerals as those in FIG. 1 or FIG.

  The carrier-enclosed deformable container 36 can accommodate a liquid and a gas in an interior surrounded by a wall surface, and a deformed wall surface capable of predetermined deformation without substantially changing the total inner surface area of the wall surface. An accommodating portion 37 that is partly provided, a mouth portion 38 that communicates with the accommodating portion 37 and that can be sucked and discharged by expansion and contraction of the inner wall due to the deformation of the deformed wall surface, and is substantially in the accommodating portion 41. It has a plurality of particulate carriers 14 and 15 to which a predetermined substance enclosed in a stationary state can bind or bind. The accommodating portion 41 includes deformed portions 39 and 40 and other non-deformed portions. The non-deformable portion includes a thick tube portion 42 that can store a liquid therein, a thin tube portion 43 that is thinner than the thick tube portion 42, and the thick tube portion 42 or A funnel-shaped transition portion 44 provided between the narrow tube portion 43 and the mouth portion 38 is provided at the lower end of the narrow tube portion 43. The particulate carriers 14 and 15 are provided in the narrow tube portion 43. In this example, the narrow tube portion 43 is formed integrally with the transition portion 44 and the large tube portion 42.

The two deformable portions 39 and 40 surrounded by the deformable wall surfaces are different in the maximum changeable amounts V ₃₉ and V _{40 of the} accommodating portion 37 based on the deformation of the deformable wall surfaces of the deformable portions ₃₉ and ₄₀ , and V ₃₉ << it is V _40. In this case, the size of the maximum changeable amount V ₄₀ is preferably set to be approximately equal to the volume of the space of the narrow tube portion 43 excluding the particulate carriers 14 and 15 enclosed in the thin tube portion 43.

The deforming portion ₃₉ having V ₃₉ having the largest maximum changeable amount is the straight line at the intersection of the deforming wall surface and the straight line passing through the inside of the mouth portion 38 and the accommodating portion 37 and passing through the deforming wall surface. The deformation wall surface is formed to be deformable along a direction (axial direction).

  The narrow tube portion 43 is formed integrally with the thick tube portion 42 and the transition portion 44 so as to communicate with the transition portion 44. A plurality (20 in this example) of particulate carriers 14 and 15 are accommodated in a row in the narrow tube portion 43, and the narrow tube portion 43 is caulked by the upper throttle portion 45 and the lower throttle portion 46. The liquid is allowed to flow out and in, but the particulate carriers 14 and 15 are processed so as to be finely squeezed so that the particulate carriers 14 and 15 are sealed so as not to flow out of the region. ing. The upper diaphragm portion 25 and the lower diaphragm portion 26 correspond to the enclosure portion.

  Subsequently, based on FIG. 4, light as light detection means for optically measuring the particulate carriers 14 and 15 enclosed in the narrow tube portion 43 in the carrier-enclosed deformable container 36 according to the third embodiment. The sensor 47 will be described. The optical sensor 47 is supported by a carrier-enclosed head (not shown) in a state where one carrier-enclosed deformable container 36 faces the mouth 38 downward and the deformed wall surface can be deformed and moved vertically. It is suitable for use in a state that has been used. It is assumed that particulate carriers 14 and 15 to which a fluorescent substance is bound as a labeling substance are arranged and enclosed in a row in the narrow tube portion 43 of the carrier-enclosed deformable container 36.

  FIG. 4A shows an optical sensor 47 attached to the thin tube portion 43 of the carrier-enclosed deformable container 36. The optical sensor 47 is provided so as to be able to contact and separate on a horizontal plane with respect to the thin tube portion 43 of the carrier-enclosed deformable container 36.

  The optical sensor 47 is provided in the carrier enclosing head. Here, it is assumed that a fluorescent substance is used as a labeling substance in the narrow tube portion 43 of the carrier-enclosed deformable container 36. The optical sensor 47 is capable of detecting the fluorescence, and can be combined in a cylindrical shape having a central hole 50 having an inner diameter through which the thin tube portion 43 can be penetrated at the center. Two semi-cylindrical segments 48 and 49 that are separable along a plane including an axis, and light that is attached to the segment 48 and that has an end face 52 on the inner surface of the central hole and that can emit predetermined excitation light And an optical fiber 54 attached to the segment 49 and provided with an end face 51 on the inner side surface of the central hole and capable of receiving light emitted from the central hole.

  As shown in FIG. 4B, the two segments 48 and 49 of the optical sensor 47 are provided with a hole through which the narrow tube portion 43 penetrates at the center thereof, and a support plate (not shown). The segments 48 and 49 are attached on the support plate so as to pass through the center hole and the hole, so that the narrow tube part 43 passes through the center hole and the hole. It is attached so as to sandwich the lower end of.

  The support plate (not shown) and the optical sensor 47 are scanned along the narrow tube portion 43 by moving the support plate (not shown) and the upper portion of the narrow tube portion 43 relatively upward from the lower end of the narrow tube portion 43. Light emission from the particulate carrier enclosed in the narrow tube portion 43 is measured.

FIG. 5 shows a carrier-enclosed deformable container 55 according to the fourth embodiment.
The carrier-enclosed deformable container 55 can store liquid and gas inside the wall surface, and the deformed wall surface capable of predetermined deformation without substantially changing the total inner surface area of the wall surface. An accommodating portion 56 provided in a part, a mouth portion 57 which communicates with the accommodating portion 56 and through which the liquid sucked and discharged by expansion and contraction due to deformation of the deformed wall surface can flow in and out, and in the accommodating portion 56 A plurality of (eight in this example) particulate carriers 14 to which a predetermined substance enclosed in a substantially stationary state can bind or can be bound are encapsulated. The accommodating portion 56 is surrounded by one deformable portion 67 surrounded by the deformed wall surface, and is surrounded by a non-deformed wall surface that is not deformed in communication with the deformable portion 67 and communicates with the mouth portion 57 so that the inside can be measured from the outside. And an undeformed portion 58.

  A bellows 59 is formed in the deformable portion 67. The bellows 59 has, as a deformation direction, a wave having peaks and valleys formed along a direction that substantially perpendicularly crosses the axial direction along the upper and lower sides of the accommodating portion 56, on the wall surface that surrounds the deformation direction in a cylindrical shape. Formed and bendable at the peaks and valleys. The shape of the wave peak or valley is a closed curve shape contained in a virtual plane perpendicular to the deformation direction. By pressing the upper end surface 60 of the deformable portion 67 with a predetermined movable member along the axial direction, the deformed portion 67 is contracted by bending the peaks and valleys of the bellows 59, and the deformed portion is released. It is restored to its original state by the elastic force of 67.

  The non-deformable portion 58 includes a substantially rectangular tube-shaped thick tube portion 61 capable of storing a liquid therein formed of a translucent resin such as polypropylene, polyester, and polyethylene, and a substantially cylindrical thin tube portion 62 thinner than that. And a transition portion 63 formed with a step provided between the thick tube portion 61 and the narrow tube portion 62. As an example of the substantially rectangular shape of the cross section perpendicular to the axial direction of the thick tube portion 61, the length of the long side is approximately twice the length of the short side.

  As described above, a plurality (eight in this case) of the particulate carriers 14 are enclosed in a row so as to be in contact with the introduced liquid, and the upper and lower sides are arranged in the narrow tube portion 62. The short tubes 64 and 65 having a cross-sectional shape (a cross-sectional shape other than a circle) through which the particulate carrier 14 does not pass and are not blocked by the fine tube portion 62 are fitted into the inner wall surface of the thin tube portion 62. Is provided.

  FIG. 6 is a perspective view of the carrier-enclosed deformed container processing apparatus 10 according to the fifth embodiment of the present invention. The carrier-enclosed deformed container processing apparatus 10 has 2 or more (96 in this example) carrier-enclosed deformable containers 55 according to the third embodiment of the present invention, with the mouth portion 57 facing downward. Arranged in a matrix of 12 rows × 4 columns in a set, supported so that the mouth portion 57 does not fluctuate due to deformation of the deformation wall surface, and simultaneously deforming the deformation wall surface of the carrier-enclosed deformation container 55, A carrier enclosing head 70 that simultaneously sucks and discharges liquid to and from the carrier enclosing deformed container 55 and two or more wells 75 that can store liquids such as various solutions and suspensions in a matrix of 12 rows × 8 columns. Two microplates 73 and 74 as an arrayed container group and a head moving unit (not shown) that moves the carrier-enclosed head 70 relative to the two microplates 73 and 74 as the container group. And have.

  The carrier-enclosed head 70 is capable of contacting and vertically moving with the entire upper end surface 60 of the carrier-enclosed deformable container 55 arranged in a matrix of 12 rows × 8 columns. Deformable and recoverable movable members 71 and 72 are included (in FIG. 6, the movable member 71 is shown in a state where it is removed upward in order to clearly indicate the arrangement state of the carrier-enclosed deformable containers. ). The movable members 71 and 72 are connected to, for example, a nut portion screwed into a ball screw provided along the vertical direction via an arm, and the ball screw is driven to rotate by a motor so that the nut portion is moved to the ball screw. This is done by translationally driving along the screw. The carrier enclosing head 70 is provided with, for example, two plates having 48 support holes horizontally formed in the matrix (12 rows × 4 columns) with the row interval and the column interval. The deformable container 55 is supported by being inserted into and fitted into the support holes. The shape of the support hole has a shape of a square hole corresponding to the 63 square tube portion of the carrier-enclosed deformable container 55 and is supported by an upper step portion. The plate can move up and down and horizontally as a part of the carrier enclosure head 70 by the moving part. The carrier enclosing head 70 is moved using, for example, a ball screw provided separately.

  Furthermore, a magnetic field is applied to the inside of the thin tube portion 62 of the non-deformable portion 58 of each of the carrier-enclosed deformable containers 55 in the group of carrier-enclosed deformable containers 55 arranged in a matrix in which the one movable member 71 is provided. A comb-like magnet 77 as a magnetic means for exerting a force, and a comb-like light detection unit 78 as a light detection means for detecting the state of the particulate carrier inside each carrier-enclosed deformable container 55. . Reference numeral 79 denotes a tray that is fixedly attached to the carrier sealing head 70 and supports the comb-shaped magnets 77 so as to be movable in the column direction.

FIG. 7A is a perspective view showing in detail a microplate 73 (74) having wells 75 arranged in a matrix of 12 rows × 8 columns.
The microplate 73 is configured by arranging 96 wells 75 and 76 of 12 rows × 8 columns on a substrate 80 in a matrix. Further, on the base body 80, the natural number “2” wells 75 arranged in the row direction corresponding to the column spacing of the array of the carrier-encapsulating deformation containers 55 of the corresponding carrier-encapsulating head 70, In order to partition each well group consisting of 76, three elongated thin plate-like partition walls 81 in the row direction and eleven in the column direction so as to protrude upward on the surface of the base body 80. Provided.

  FIG. 7B shows a first set of wells into which the mouths 57 of all the carrier-enclosed deformable containers 55 arranged in a matrix of the carrier-enclosed heads 70 corresponding to the microplate 73 can be inserted all at once. The well submatrix (well 75 represented by black circles in the figure) and the second well submatrix (well 76 represented by white circles in the figure). Therefore, the arrangement of the carrier-encapsulating deformation containers 55 of the carrier-encapsulating head 70 has a matrix corresponding to the arrangement of the first well sub-matrix (75, black circle) and the second well sub-matrix (76, white circle). Will be.

  Here, a well 75 represented by a black circle belonging to the first well submatrix (75, black circle) and a well 76 belonging to the second well submatrix (76, white circle) are adjacent to each other vertically in the figure. A pair of wells 75 and 76 indicate a well group 82 that is a set of wells that can be inserted by the same carrier-enclosed deformable container 55 among the carrier-enclosed deformable containers 55 provided in the corresponding carrier-enclosed head 70. It is. Accordingly, the carrier-enclosed deformable container 55 once positioned in the region surrounded by the partition wall 81 cannot move beyond the partition wall 81 until the processing for the microplate 73 (74) is completed. Absent.

  FIGS. 7C and 7D show an example of a microplate 83 corresponding to a carrier enclosure head according to another embodiment. The microplate 83 has 96 wells 85, 86, 87, 88 arranged in a matrix 84 in a matrix of 12 rows × 8 columns. Further, on the base 84, the natural number arranged in the column direction and the row direction corresponding to the row interval and the column interval of the array of the carrier-encapsulating deformation containers 55 of the corresponding carrier-encapsulating head (not shown), Three rows along the column direction so as to project upward on the surface of the base body 84 so as to partition each well group 90 composed of “4” wells 85, 86, 87, 88. Are provided with five elongated thin plate-like partition walls 89.

  Here, the carrier enclosure head (not shown) corresponding to the microplate 83 is an enclosure of 12 carriers arranged in the row direction in each of the 4 rows in the carrier enclosure head 70 shown in FIG. It has 24 carrier-enclosed deformable containers 55 arranged in a matrix of 6 rows × 4 columns, in which 6 carrier-enclosed deformable containers 55 in which every other deformable container 55 is thinned out are arranged.

  As shown in FIG. 7 (d), the microplate 83 includes 24 all-carrier-encapsulating deformation containers 55 arranged in a matrix of corresponding carrier-encapsulating heads (not shown). A first well submatrix (well 85 represented by a white circle in the figure), a second well submatrix (well 86 represented by a black circle in the figure), and a third well, which are a set of wells that can be inserted simultaneously. A submatrix (well 87 represented by a cross character in the figure) and a fourth well submatrix (well 88 represented by a single line in the figure) are shown.

  Here, a well 85 represented by a white circle belonging to the first well submatrix, a well 86 represented by a black circle belonging to the second well submatrix, a well 87 represented by a cross character belonging to the third well submatrix, and A set of four wells 85, 86, 87, 88 of the well 88 represented by a single line belonging to the fourth well submatrix is encapsulated in a carrier provided in the corresponding carrier encapsulation head (not shown). Of the deformable containers 55, a well group 90, which is a set of wells that can be inserted by the same carrier-enclosed deformable container 55, is shown. Therefore, the carrier-enclosed deformable container 55 once positioned in the region surrounded by the partition wall 89 does not move beyond the partition wall 89 until the processing for the microplate 83 is completed. Absent.

  When four microplates 83 are prepared and four bundles in which the 24 carrier-enclosed deformable containers 55 are arranged in a matrix of 6 rows × 4 columns are prepared, a total of 96 carrier-enclosed deformable containers are provided. The number of wells is equal to the number of wells of one microplate 83 in total, and although not different from the case of FIG. 6, four microplates can be processed at the same time, so the efficiency is high. .

  Next, FIG. 8A is a perspective view showing the comb-shaped magnet 77 and the comb-shaped light detection unit 78 taken out. The comb-shaped magnets 77 are provided in the carrier-encapsulating head 70, and each of the carrier-encapsulated deformations is applied so that a magnetic field can be applied to and removed from the inside of the 48 carrier-encapsulated deformable containers 55 all at once. A total of 48 magnets 92 are arranged in a matrix of 12 rows × 4 columns provided so as to be able to contact with and separate from the container 55.

  The comb-shaped magnet 77 is arranged along the column direction between adjacent columns of the carrier-enclosed deformable container 55 having a column interval set to “2” times the natural number with respect to the column interval of the wells 75 and 76. The number of the carrier-enclosed deformable containers 55 (number of columns−1) is provided so as to be movable, extends along the row direction, and is provided in a width that can be inserted between adjacent rows of the carrier-enclosed deformable containers 55. Three substantially prismatic comb-tooth members 91, and two substantially prismatic comb-tooth ends 91a provided outside the comb-tooth member 91 and formed slightly wider than the comb-tooth member 91, 91b and a support member (not shown) that is connected at one end of the comb-tooth member 91 and the comb-tooth ends 91a and 91b and extends in the row direction, and the comb-tooth members 91 and the comb-tooth ends 91b Along the longitudinal direction, that is, the column direction, the wells 75, 76 The magnet 92 in which the number of rows (12) is arranged at intervals set to the row interval, and the guide rail provided along the longitudinal direction of the comb-tooth members 91, 91a, 91b, that is, the column direction. 93. The magnet 92 is provided on the same side surface of the comb-tooth member 91 and the comb-tooth end 91b, and the guide rail 93 is provided at a position far from the side surface. The guide rail 93 guides the movement of the comb-shaped light detection unit 78 that is movably provided on the upper surfaces of the comb-tooth members 91, 91a, 91b.

  FIG. 8B is a perspective view showing a comb-shaped magnet 94 and the comb-shaped light detection unit 78 according to another embodiment. The comb-shaped magnet 94 is provided in the carrier enclosing head (not shown) and encloses each carrier so that a magnetic field can be simultaneously applied to and removed from the inside of the carrier enclosing deformed container 55. A total of 24 magnets 92 are arranged in a matrix of 6 rows × 4 columns provided to the deformation container 55 so as to be able to contact and separate from each other. That is, unlike the comb-shaped magnet 77 of FIG. 8A, the number of the magnets 92 arranged at each comb-tooth member and the comb-tooth end is thinned out to a half of 12, so that the number is six. This corresponds to the above-described carrier enclosure head (not shown).

  FIG. 9 shows details of the comb-like light detection unit 78, and the comb-like light detection unit 78 is arranged on the comb-like magnet 77 provided on the carrier enclosing head 70. It is provided so as to be movable relative to the magnet 77, and detects the state inside each of the carrier-enclosed deformable containers 55.

  The comb-like light detection unit 78 is arranged in the column direction between adjacent carrier-enclosed deformable containers 55 having a column interval set to a natural number multiple of the column interval of the wells 75 and 76, that is, “2” times. Are provided so as to be movable with respect to the comb-shaped magnet 77 or the carrier-enclosed deformable container 55, and extend in the row direction so as to be inserted between adjacent rows of the carrier-enclosed deformable containers 55. Three substantially prismatic comb-tooth members 95 (number of rows −1) of the carrier-enclosed deformed containers 55 formed, and provided on the outer side of the comb-tooth members 95, slightly more than the comb-tooth members 95. Two substantially prismatic comb teeth 95a and 95b formed in a width, and a comb member 95 and a support member 96 connected at one end of the comb teeth 95a and 95b and extending in the row direction. The comb teeth member 95 and the comb teeth ends 95a and 95b each have 1 Light detecting hole 98 is provided bored along the row direction.

  One end of the optical fiber 99 from the light emitting unit 100 is provided in the photodetection hole 98 provided in the one comb-tooth member 95 or the comb-teeth ends 95a and 95b. The tip of the optical fiber 101 connected to the optical sensor 102 is inserted into the photodetection hole 98 of the comb-tooth member 95 and the comb-tooth ends 95a and 95b adjacent to each other through an elongated gap in which the rows are to be arranged. It is provided so as to face the gap between the member 95 or two adjacent comb teeth ends 95a and 95b.

Reference numeral 97 denotes a narrow groove provided in each of the comb-tooth members 95 and the comb-tooth ends 95a and 95b along the row direction that can slide by engaging with the guide rail 93.
In addition, the size and shape of the comb-tooth member 95, the comb-tooth ends 95a and 95b, and the support member 96 of the comb-tooth-shaped light detection unit 78 are the same as the size and shape of the comb-tooth magnet 77, respectively. Is formed.

  FIG. 10 shows a carrier-enclosed deformable container 103 according to a sixth embodiment of the present invention that is suitable for mounting on the carrier-enclosed head 70 of the carrier-enclosed deformed container processing apparatus 10. Note that the same reference numerals as those in FIG. 1 represent the same elements, and thus detailed description thereof is omitted.

  As shown in FIG. 10, the carrier-enclosed deformable container 103 can store liquid and gas inside the wall and can be deformed in a predetermined manner without substantially changing the total inner surface area of the wall. An accommodating portion 104 having a deformed wall surface in a part of the wall surface, a mouth portion 13 communicating with the accommodating portion 104 and capable of flowing in and out of liquid sucked and discharged by expansion and contraction of the interior by the deformed wall surface; The container 104 has a plurality of particulate carriers 14 and 15 to which a predetermined substance sealed in a substantially stationary state can be bonded or bonded. The accommodating portion 104 is surrounded by one deformable portion 107 surrounded by the deformed wall surface and a non-deformed wall surface that communicates with the deformable portion 107 and is not deformed, and communicates with the mouth portion 13 so that the inside can be measured from the outside. And a non-deformable portion 108.

  The deformable portion 107 is formed with a bellows 109. The bellows 109 is formed so as to divide the entire wall surface of the accommodating portion 104 or the deformed wall surface of the deformable portion 107 into two parts across the axial direction of the deformable portion 107 or the accommodating portion 104 which is the deformation direction. This portion has a vertex 110, and the other is provided at the boundary between the non-deformable portion 108 and the deformable portion 107 and the non-deformable portion 108, and supports the carrier-enclosed deformable container 103 to the carrier-enclosed head 70. For this purpose, a flange 111 having a smaller radius than the deforming portion 107 and protruding outward is provided. That is, the carrier-enclosed deformable container 103 is suitable for automation that is used by being mounted on the carrier-enclosed head 70. The normal directions of the virtual planes including the peaks or valleys of the waveform of the bellows 109 substantially coincide with the axial direction. The bellows 109 is deformed along the linear direction (the axial direction) at the intersection of a straight line (axial line) passing through the deformed wall surface through the mouth portion 13 and the accommodating portion 104 and the deformed wall surface. The wall surface is formed to be deformable.

  The non-deformable portion 108 includes the thick tube portion 21, the thin tube portion 22, and the transition portion 23. The thin tube portion 22 encloses the particulate carriers 105 and 106 and encloses the thin tube portion. After that, it is fitted to the fitting portion 24 at the lower end of the transition portion 23 and attached by adhesion, heat welding or the like. The narrow tube portion 22 is suitably formed of polypropylene that is a resin that does not emit fluorescence when measuring the particulate carriers 105 and 106 that are labeled with a fluorescent dye, and that requires a certain degree of strength.

  FIG. 11 shows a carrier-enclosed deformable container 113 according to the seventh embodiment of the present invention. As shown in FIG. 11, the carrier-enclosed deformable container 113 can accommodate a liquid and a gas in an interior surrounded by a wall surface, and can be subjected to a predetermined deformation without substantially changing the total inner surface area of the deformed surface. An accommodating portion 114 having a deformable wall surface in a part of the wall surface, and a mouth portion 13 communicating with the accommodating portion 114 and capable of inflow and outflow of liquid drawn and sucked out by the internal expansion and contraction by the deformable wall surface; The container 114 includes a rod-shaped carrier 118 having a plurality of coupling positions 115 to which a predetermined substance sealed in a substantially stationary state can be coupled or coupled. The accommodating portion 114 is surrounded by one deformable portion 107 surrounded by the deformable wall surface and a non-deformed wall surface that communicates with the deformable portion 107 and is not deformed, and communicates with the mouth portion 13 so that the inside can be measured from the outside. A non-deformable portion 120.

  As shown in FIG. 11, the rod-shaped carrier 118 has a plurality of bonding positions 115 to which a plurality of kinds of chemical substances can be bonded or bonded, and is hydrophobic such as oil-based ink provided between the bonding positions 115. The material is partitioned by the boundary 116. In the narrow tube portion 117, the rod-shaped carriers 118 are accommodated in a line along the vertical direction, and a small pipe 119 is provided inside the narrow tube portion 117 at the upper throttle portion 25 and the lower throttle portion 26. The thin tube portion 117 is caulked to allow the liquid to flow out and in, but is sealed so that the rod-shaped carrier 118 does not flow out. The upper throttle part 25, the lower throttle part 26, and the two pipes 119 correspond to the enclosing part.

  Next, FIG. 12 shows a carrier-enclosed deformable container 121 according to an eighth embodiment of the present invention suitable for mounting on the carrier-enclosed head 70 of the carrier-enclosed deformed container processing apparatus 10.

  As shown in FIG. 12, the carrier-enclosed deformable container 122 can accommodate a liquid and a gas inside the wall and can be deformed in a predetermined manner without substantially changing the total inner surface area of the wall. An accommodating portion 122 having a deformed wall surface in a part of the wall surface, a mouth portion 123 communicating with the accommodating portion 122 and capable of flowing in and out of liquid sucked and discharged by the expansion and contraction of the interior by the deformed wall surface; A predetermined substance sealed in a substantially stationary state in the accommodating portion 122 has a plurality of spherical carriers 124 to which the predetermined substance can be combined or can be combined. The accommodating portion 122 is enclosed by one deformable portion 125 surrounded by the deformed wall surface and the spherical carrier 124 and is surrounded by an undeformed wall surface that communicates with the deformable portion 125 and is not deformed, and communicates with the mouth portion 123. And the non-deformable portion 126 capable of measuring the inside from the outside.

  A bellows 127 is formed on the deformation wall surface of the deformation portion 125. The bellows 127 is formed so as to divide the entire wall surface of the accommodating portion 122 or the deformed wall surface of the deformable portion 125 into two across the axial direction of the deformable portion 125 or the accommodating portion 122 which is the deformation direction. An introduction hole 129 for introducing the spherical carrier 124 into the accommodating portion 122 is formed at the upper end of the upper portion of the upper portion. In addition, the introduction hole 129 closes the introduction hole 129 by attaching the lid portion 128 to the flange portion around the introduction hole 129 by adhesion or heat welding after the introduction of the spherical carrier 124.

  The other lower portion is provided at the boundary between the non-deformable portion 126 and the deformable portion 125 and the non-deformable portion 126 so that the carrier-enclosed deformable container 121 is supported by the carrier-enclosed head 70. A flange 130 that is used and has a smaller radius than the deforming portion 125 and protrudes outward is provided. That is, the carrier-enclosed deformable container 121 is suitable for automation used by being mounted on the carrier-enclosed head 70. The normal directions of the virtual planes including the peaks or valleys of the waveform of the bellows 127 substantially coincide with the axial direction. The bellows 127 is deformed along the linear direction (the axial direction) at the intersection of a straight line (axial line) passing through the deformed wall surface through the mouth 123 and the accommodating portion 122 and the deformed wall surface. The wall surface is formed to be deformable.

  The non-deformable portion 126 includes a substantially cylindrical thick tube portion 131 capable of storing a liquid inside formed of a translucent resin such as polypropylene, polyester, and polyethylene, and a substantially cylindrical thin tube portion 132 thinner than that. And a funnel-shaped transition portion 133 provided between the thick tube portion 131 and the thin tube portion 132, and the mouth portion 123 is provided at the tip of the thin tube portion 132. The thick tube portion 131 is filled with a plurality of spherical carriers having a diameter larger than the inner diameter of the narrow tube portion 132 that can capture the predetermined substance by adsorption or the like as a particulate filler for chromatography. ing. The transition portion 133 has an elliptical cross section perpendicular to the axial direction so as not to be blocked by the spherical carrier 124. Here, the “filler” is filled in a predetermined container selected for the purpose of adsorbing a target biological material contained in a predetermined fluid as a so-called mobile phase based on the principle of liquid chromatography. Insoluble stationary phase.

  FIG. 13 shows a carrier-enclosed deformable container 134 according to a ninth embodiment of the present invention that is suitable for mounting on the carrier-enclosed head 70 of the carrier-enclosed deformed container processing apparatus 10. Since the same reference numerals as those in FIG. 12 are the same as those shown in FIG. 12, detailed description thereof is omitted.

  As shown in FIG. 13, the carrier-enclosed deformable container 134 can accommodate a liquid and a gas inside the wall and can be deformed in a predetermined manner without substantially changing the total inner surface area of the wall. An accommodating portion 135 having a deformed wall surface as a part of the wall surface, a mouth portion 123 communicating with the accommodating portion 135 and capable of flowing in and out of liquid sucked and discharged by expansion and contraction of the interior due to the deformed wall surface, It has one spherical carrier 136 to which a predetermined substance sealed in a substantially stationary state can be combined or can be combined. The accommodating portion 135 is enclosed by one deformable portion 125 surrounded by the deformed wall surface and the spherical carrier 136 and is surrounded by a non-deformed wall surface that does not communicate with the deformable portion 125 and communicates with the mouth portion 123. And an undeformed portion 139 capable of measuring the inside from the outside.

  The non-deformable portion 139 includes a substantially cylindrical thick tube portion 140 that can store a liquid inside formed of a light-transmitting resin such as polypropylene, polyester, polyethylene, and the like, and a substantially cylindrical thin tube portion 132 that is thinner than that. And a funnel-shaped transition portion 133 provided between the thick tube portion 140 and the thin tube portion 132, and the mouth portion 123 is provided at the tip of the thin tube portion 132. The thick tube portion 140 has one spherical carrier having a diameter sufficiently larger than the inner diameters of the narrow tube portion 132 and the transition portion 133 and capable of capturing the predetermined substance by adsorption or the like as the filler. 136 is enclosed. The spherical carrier 136 is supported by two convex points 137 and 138 that protrude slightly inward from the wall surface of the thick tube portion 140 so as to pass through the axis of the thick tube portion 140. Since the convex points 137 and 138 are formed so as to be pushed in from the outside of the thick tube portion 140, the spherical carrier is in the radial direction obtained by rotating the radial direction connecting the two convex points by 90 degrees in a horizontal plane. And a gap is formed between the inner wall surface of the thick tube portion 140 and liquid can pass therethrough.

  Then, the case where the support | carrier enclosure deformation | transformation container processing method which concerns on 10th Embodiment using the support | carrier enclosure deformation container processing apparatus 10 which concerns on 5th Embodiment is applied to SNPs detection reaction is demonstrated.

  As schematically shown in FIG. 14, the method includes four SNPs (Single Nucleotide Polymorphysms) of four specimen genes (ATase exon6, ATase exon8, CYP2C19 exon5, CYP2D6 exon1) collected from 96 subjects. This is applied to the process for detecting polymorphisms (2 types in this case). In this process, the sample gene is extracted and amplified, and the sample preparation step S1 as a preparation step for preparing the ASPE product by the ASPE method, which will be described later, and the particulate carrier 14 to be enclosed in the carrier-enclosed deformed container 55 are used. Encapsulation step S2 in which a plurality of types (eight types in this example) of particulate carriers 14 to which tag DNA, which will be described later, which is a probe for detection is bound, are prepared and enclosed in the carrier-enclosed deformable container 55; It has a binding reaction step S3 for performing a binding reaction between the carrier 14 and the ASPE product, and a detection step S4 for detecting the binding reaction result.

  As shown in FIG. 14 (a), the sample preparation process in step S1 includes, for example, a sampling process for collecting samples such as oral mucosa, blood, and nails from 96 subjects, and the oral mucosa. An amplification step of extracting the amplified DNA and amplifying the DNA by PCR; a purification step of purifying the DNA; and an ASPE product preparation step of preparing the ASPE product using the ASPE described later.

  In the collecting step, a liquid in which the oral mucosa and the like collected from 96 subjects are suspended is accommodated in a microplate (not shown) having 96 wells (not shown). A deformed container in which no carrier is sealed in the carrier-enclosed deformable container 55 is attached to the carrier-encapsulating head 70, and each well (not shown) is covered with a porous material or a material such as silica. The broken magnetic particle suspension is sucked, transferred, and discharged simultaneously.

  By moving the movable members 71 and 72 up and down repeatedly, suction and discharge are repeated, the DNA is bound to and captured by the magnetic particles, and the comb-shaped magnet 77 is brought close to the deformation containers to generate a magnetic field therein. In the applied state, the movable members 71 and 72 are moved up and down to adsorb and separate the magnetic particles capturing the DNA on the inner walls of the deformation containers. The DNA is extracted by separating the DNA from the magnetic particles that have captured the separated DNA, and stored in each well of the microplate.

  Next, the extracted DNA is amplified by PCR using predetermined primers so as to obtain the four DNAs, and is accommodated in each of the 96 wells of the microplate. In each well containing the amplified DNA suspension, in order to remove contaminants including residues such as primers and oral mucosa, a new suspension of magnetic particles is used, and a new deformed container is used as the carrier. The DNA is captured by the magnetic particles by being attached to the sealing head 70 and moved up and down using the movable members 71 and 72 to perform suction and discharge, and in the deformation container 55 using the comb-like magnet 77. The magnetic particles are attracted to the inner wall of the deformation container 55 by applying a magnetic field, and separated and purified.

  Next, an ASPE product 148 for determining the four SNPs for each sample gene is prepared using ASPE (Allele-specific primer extension method).

  As shown in FIG. 14 (b), the base sequence 144 complementary to the base sequence 143 of a single-stranded tag DNA 142 described later has a base sequence 144 at the 3 'end, and the base sequence 145 of the SNP has a 5' end. For the sequence between 144 and base 145, a synthetic DNA consisting of several tens of bases of a single strand designed so as to be a base sequence complementary to the nearest sequence of SNP of each of the four genes is prepared as a primer. A total of 8 types of primers, 2 types for each of the 4 genes, 2 types for each of the 4 genes, and 8 types of tag DNA 142 having a predetermined base sequence different from each other. 1 and the base of the corresponding SNP are included. Using the primer and Dig-dUTP146 instead of the base “T” as a base, the DNA is extended and amplified by the PCR method based on each gene for each specimen. Then, extension amplification is performed only for the primers corresponding to the DNA polymorphism type of the specimen, and the ASPE product 148 is prepared for each of the 96 specimens.

  The prepared ASPE product 148 is stored in the well group of the first submatrix to which the well 75 (black circle) of the microplates 73 and 74 belongs. On the other hand, the second submatrix well group to which the wells 76 (white circles) of the microplates 73 and 74 belong contains a cleaning solution to be used in the detection step of step S4 described later. Further, two similar microplates (not shown) contain the AP-labeled Dig antibody 147 that specifically binds to the Dig-dUTP 146 in the first submatrix, and the second submatrix contains Contains the substrate solution 149 (CDP-Star).

  In this example, a mixture of all eight types of the ASPE product 148 is accommodated in each well 75 for each specimen. For example, a mixture of two types of the ASPE product 148 is added to each well 75. The processing may be performed by preparing four sets of necessary microplates such as the microplates 73 and 74 containing the substrate solution in the second partial matrix.

  In step S2, the particulate carrier 14 to be accommodated in the carrier-enclosed deformable container 55 is produced and enclosed. As shown in FIG. 14B, the particulate carrier 14 to be produced is, for example, one in which a tag DNA 142 having a predetermined base sequence 143 that is coated with avidin 141 and biotinylated is bound. Here, as the particulate carrier 14, for example, a size of about 1 mm in diameter is used, and various resins such as nylon (manufactured by Polysciences) are used. In addition, for example, ceramics (manufactured by Chiba Ceramic Co., Ltd., alumina 1.88 mm diameter) can be used. When using the light shielding particles, for example, color glass having a diameter of 2.0 mm is used.

  Further, the base sequence 143 of each tag DNA 142 and the complementary base sequence 144 contained in the primer have different base sequences 143 and 144 for each polymorphic base that may be a SNP of each gene. To synthesize. Then, in the processing according to the present embodiment, eight types of base sequences 143 and 144 are required for two types of possible polymorphic bases in each of four SNPs, so that there are eight types. The particulate carrier 14 is produced. For example, the first particulate carrier and the second particulate carrier correspond to the gene ATase exon6, and use Tag1 (base C) and Tag3 (base T) as the tag DNA 142. The particulate carrier and the fourth particulate carrier correspond to the gene ATase exon8, and use Tag4 (base A) and Tag2 (base G) as the tag DNA 142, and use the fifth particulate carrier and The sixth particulate carrier corresponds to the gene CYP2C19 exon5, and uses Tag7 (base A) and Tag6 (base G) as the tag DNA 142, and the seventh particulate carrier and the eighth particulate carrier. The carrier corresponds to the gene CYP2D6 exon1 and uses Tag9 (base C) and Tag10 (base T) as the tag DNA 142.

  The eight types of particulate carriers 14 bound to the eight biotinylated tag DNA 142 having the predetermined base sequence 143 thus prepared are arranged in a predetermined order from the first particulate carrier described above. 96 of the eight particulate carriers arranged in the order of the particulate carriers are produced in each of the carrier-enclosed deformable containers 55, and attached to the carrier-enclosed head 70 in a matrix. The particulate carrier 14 is encapsulated, for example, by fitting the short tubes 64 and 65 to the upper and lower portions of the array of the thin tube portions 62 of the carrier-enclosed deformable containers 55. The 96 carrier-enclosed deformable containers 55 enclosing the plurality of particulate carriers 14 are arranged in two sets of 12 rows × 4 columns matrix. In the case where the plurality of types of particulate carriers are formed so as to be distinguishable from each other using a labeling substance for each type, the arrangement order of the particulate carriers in the narrow tube portions 62 is not particularly required. . When light-shielding particles are used, for example, the reaction particulate carrier and the light-shielding particles are alternately arranged.

  As the thin tube portion 62, for example, the thin tube portion 62 made of polypropylene is used. As the size of the thin tube portion 62, for example, when a 1.0 mm diameter ceramic is used as the particulate carrier, for example, a 1.1 mm diameter round shape is used. In addition, when a ceramic having a diameter of 1.88 mm is used, a round shape having a diameter of 2.0 mm is used. Furthermore, in order to use the 2.0 mm glass beads as the light shielding particles, a 2.2 mm diameter round shape is used.

In step S <b> 3, the mouth portions 57 of the carrier-encapsulating deformable containers 55 arranged in a matrix of two sets of the carrier-encapsulating heads 70 are connected to the microplates 73 and 74 using a moving unit (not shown). It is moved to a position where it can be inserted into the first submatrix comprising each well 75. Next, the mouth portion 57 is simultaneously inserted into the wells 75 of the microplates 73 and 74 by the moving portion (not shown). For the deformation of the carrier-enclosed deformation container 55, a predetermined reference position is set, and the deformation of the deformation wall surface is controlled based on the reference position. That is, the position of the movable members 71 and 72, in the reference state, a state of contact with the upper end surface 60, and an interior volume of the maximum deformation container and V _1, the internal volume of minimum deformation vessel When V ₂ is set, the volume V ₀ in the reference state is determined so that V ₁ −V ₀ ≦ V ₀ −V ₂ , that is, (V ₁ + V ₂ ) / 2 ≦ V ₀ , so that the suction amount ( By setting the reference amount so that (V ₁ -V ₀ ) is smaller than the discharge amount (V ₀ -V ₂ ), it is possible to prevent the amount of sucked liquid from remaining in the carrier-enclosed deformable container 55. Can do. That is, the movable member 71 and 72 is in a state where the internal volume of the carrier enclosing transformable container 55 presses the upper end surface 60 of the carrier enclosing deformable container 55 such that V _0.

  Next, after inserting the mouth portion 57 into the well 75 corresponding to the first partial matrix belonging to each well 75 of the microplates 73 and 74, the movable members 71 and 72 are moved upward to By sucking the mixed solution of the ASPE product 148 accommodated for each specimen into the carrier-enclosed deformable container 55, the liquid and each particulate carrier 14 are brought into contact with each other, and the base sequence 143 of the tag DNA 142, When there is a corresponding ASPE product 148 for each particulate carrier 14 by causing a hybridization reaction between the base sequence 143 of the ASPE product 148 and the complementary base sequence 144, ASPE product 148 will be bound.

  Next, in step S4, using a moving unit (not shown), the carrier-enclosed head 70 is moved to the second partial matrix of the microplates 73 and 74 in which the cleaning liquid is stored as the moving path. The mouth portion 57 is moved to the well 76 belonging to the second submatrix by being moved by the column interval in the row direction and inserted all at once. Next, by using the movable members 71 and 72 to move upward and downward from the reference position, the suction and discharge are repeatedly washed. Thereafter, the carrier encapsulation head 70 is moved to a microplate (not shown) containing the AP-labeled Dig antibody 147 that specifically binds to the Dig-dUTP 146, and the mouth portion 57 is positioned in wells (not shown) belonging to the first submatrix and inserted simultaneously, and suction and discharge are repeated using the movable members 71 and 72, whereby the Dig-dUTP 146 and the AP label Dig antibody 147 is bound. Then, the ASPE product 148 in which the AP-labeled Dig antibody 147 is bound to only the type corresponding to the existing polymorphism in each particulate carrier 14 of each specimen is bound to the particulate carrier 14. Preferably, after further cleaning with a cleaning liquid, the carrier sealing head 70 is moved by a column interval in the row direction as the moving path using the moving unit (not shown), and the mouth portion 57 is moved to the mouth 57. It is placed in wells (not shown) belonging to the second submatrix and inserted all at once. Next, by moving the substrate liquid 149 upward and downward from the reference position using the movable members 71 and 72, the substrate liquid 149 is repeatedly sucked and discharged into the carrier-enclosed deformable container 55, thereby causing the substrate liquid 149 to repeat. Is caused to react with the Dig to cause chemiluminescence. At that time, the light emission from the particulate carrier 14 encapsulated is detected using the comb-like light detector 78 provided in the carrier encapsulating head 70. In order to detect chemiluminescence, the comb-tooth member 95 and the comb-tooth ends 95a and 95b of the comb-tooth-shaped light detection unit 78, the light detection holes 98 along the column direction, and the carrier-enclosed deformable containers are used. By sequentially moving every 55 rows (four) and moving the carrier-enclosed deformable container 55 upward, light is received by the optical fiber 101 for each of the particulate carriers 14 and detection is performed repeatedly. The measurement result for the gene of a certain sample is shown in the photograph of step S4 in FIG. Regarding the gene of this specimen, since only very weak luminescence was detected for the first particulate carrier, the sixth particulate carrier, and the seventh particulate carrier, the SNP of the gene ATase exon6 of this specimen was detected. Is base A, the SNP of gene ATase exon8 is base A / G, the SNP of gene CYP2C19 exon5 is base A, and the SNP of gene CYP2D6 exon1 is base T Recognize.

  Each embodiment described above is specifically described in order to better understand the present invention, and does not limit other embodiments. Therefore, changes can be made without changing the gist of the invention. For example, in the above-described embodiment, the deformation is mainly performed by the bellows, but, for example, it can be realized by using a deformed wall surface having a shape other than the bellows or an elastic body such as rubber as a material of the deformed wall surface. it can. Further, the shape of the carrier-enclosed deformable container is not limited to that described above, and may have a step in the thick tube portion or the thin tube portion.

  In addition, the arrangement of the carrier-encapsulated deformable container in the carrier-encapsulated head is not limited to the above-described arrangement, for example, 4, 6, 8, 12, 96, 384 arranged in a line or matrix There is. In addition, as the treatment, only the detection of SNPs using hybridization for DNA has been described. However, the present invention is not limited to this. For example, the treatment can also be used for detection of a protein using an antigen-antibody reaction. In addition, as the carrier-encapsulating head, only when 48 sets of 48 encapsulated deformable containers using one movable member are used, and processing is performed using 4 microplates having 96 wells. However, the present invention is not limited to this case. For example, four sets using one movable member for 24 carrier-enclosed deformable containers and eight microplates having 96 wells are used. It is also possible to perform the processing that was performed.

  The carrier-enclosed deformed container, the carrier-enclosed deformed container processing apparatus, and the carrier-enclosed deformed container processing method according to the present invention are fields that require processing of solutions containing various biological materials, such as industrial fields, foods, agricultural products, and fisheries. Agricultural fields such as processing, pharmaceutical fields, hygiene, insurance, immunity, diseases, medical fields that deal with genetics, fields such as chemistry or biology, etc. The present invention is particularly effective when a series of processes using a large number of reagents and substances are continuously performed in a predetermined order.

DESCRIPTION OF SYMBOLS 10 Carrier enclosure deformation container processing apparatus 11, 27, 36, 55, 103, 113, 121, 134 Carrier enclosure deformation container 14, 15 Particulate carrier 18, 59, 109, 127 Bellows
70 Carrier enclosing head

“Measurable from outside” means that the labeled state of each particulate carrier held in the non-deformable part can be specified from the outside.

The “particulate carrier” is a particulate solid having a size that can be introduced and held in the non-deformable portion . In general, one of the particulate carriers or one set of the particulate carriers corresponds to one kind of the plurality of kinds of chemical substances that can be bound or bound thereto. The size of the particulate carrier is, for example, a size of 0.1 mm to several mm in diameter or diameter. In the space part in which the particulate carrier is enclosed, the volume of the space part excluding the enclosed particulate carrier is, for example, a volume of several microliters to several hundred microliters. By labeling the particulate carrier or the collection of particulate carriers according to the chemical substance to which they can bind or bind, it is not necessary to identify them by the arrangement position of the encapsulated particulate carrier or the assembly.

“At least one particulate carrier belonging to each particulate carrier of the plurality of particulate carriers or a set of each particulate carrier is the kind of chemical substance, each particulate carrier, or each particulate carrier. Because they are labeled so that they can be distinguished from each other depending on the set of carriers, they can be distinguished from each other for the first time by forming an array by being introduced and held in the non-deformable part. There is no need to be.

“Particulate carrier is identifiably labeled” means that the particulate carrier itself retains, binds, or is fixed to an identifiable labeling element, or the particulate carrier itself is identifiable. Means processed or formed. That is, it means that the cause of labeling is present in the particulate carrier, and is different from the case where the cause of labeling is present outside the particulate carrier, such as the arrangement and position of the particulate carrier. For example, by changing the size of the particulate carrier by forming the shape of the particulate carrier into a sphere, a cube, a cylinder, a quadrangular column, a cone, a pyramid, an unevenness, etc. By attaching to a carrier, various fluorescent materials, phosphorescent materials, chemiluminescent materials and other luminescent materials, various wavelengths of infrared rays, ultraviolet rays, radiation materials that emit electromagnetic waves of various wavelengths including radio waves, and various magnetic strengths Labeling is performed by providing a labeling element such as a magnetic substance on the particulate carrier. In that case, the labeling includes not only the case where the labeling element such as the luminescent substance, various electromagnetic radiation substances, and the magnetic substance is provided on the surface of the particulate carrier, but also the case where the labeling element is provided inside the particulate carrier. As a case where it is provided inside, there is a case where the particulate carrier is formed in a hollow shape, and is a particulate case or a particulate film in which these substances are accommodated or bundled. In that case, in the case of a luminescent material, the particulate case or particulate coating needs to be transparent or translucent. The particulate carrier already has a labeling element before being introduced and held in the non-deformable portion , or the particulate carrier itself has been processed or formed in an identifiable manner.

The labeling element includes a binding substance that can specifically react with a predetermined luminescent substance that can be identified by measurement and that has not yet reacted with the luminescent substance or the like. . An example of such a binding substance is a receptor having a binding property to the ligand with respect to the luminescent substance or the like bound to the ligand. This labeling element is potentially labeled, and the labeling becomes obvious by reacting with the predetermined luminescent substance or the like. Therefore, when this labeling element is used, the particulate carrier is potentially labeled so that they can be distinguished from each other before being introduced into the non-deformation part , and the labeling manifests by the reaction after the introduction. Are also included in being labeled prior to introduction.

Here, as an example of the "encapsulation", when the mouth portion has the carrier level allowing passage, such that fluid is the carrier but can pass through is not pass through, the said non-deformable portion On the other hand, there is one having one or more carrier passage blocking members provided so as to partition the housing portion with respect to the fluid flow direction.

Further, when the carrier-enclosed deformed container is processed by caulking as the enclosing portion, the pressure required for suction and discharge can be reduced by enlarging the opening under the condition that the carrier does not flow out. . As the one using the carrier-enclosed deformable container itself, in order to narrow the narrow tube so as to be narrowed, a projecting portion protruding in the center direction of the tube or the non-deformed so as to partition with respect to the fluid flow direction is used. In some cases, one having one or two or more projecting parts projecting from the wall surface of the part, a short tubular stopper, or the like is used.

Next, in step S4, using a moving unit (not shown), the carrier-enclosed head 70 is moved to the second partial matrix of the microplates 73 and 74 in which the cleaning liquid is stored as the moving path. The mouth portion 57 is moved to the well 76 belonging to the second submatrix by being moved by the column interval in the row direction and inserted all at once. Next, by using the movable members 71 and 72 to move upward and downward from the reference position, the suction and discharge are repeatedly washed. Thereafter, the carrier encapsulation head 70 is moved to a microplate (not shown) containing the AP-labeled anti- Dig antibody 147 that specifically binds to the Dig-dUTP 146, and the mouth The portion 57 is positioned in wells (not shown) belonging to the first submatrix and inserted all at once, and suction and discharge are repeated using the movable members 71 and 72, whereby the Dig-dUTP 146 and the AP Labeled anti- Dig antibody 147 is allowed to bind. Then, the ASPE product 148 in which the AP-labeled anti- Dig antibody 147 is bound to only the type corresponding to the existing polymorphism in each particulate carrier 14 of each specimen is bound to the particulate carrier 14. Preferably, after further cleaning with a cleaning liquid, the carrier sealing head 70 is moved by a column interval in the row direction as the moving path using the moving unit (not shown), and the mouth portion 57 is moved to the mouth 57. It is placed in wells (not shown) belonging to the second submatrix and inserted all at once. Next, by moving the substrate liquid 149 upward and downward from the reference position using the movable members 71 and 72, the substrate liquid 149 is repeatedly sucked and discharged into the carrier-enclosed deformable container 55, thereby causing the substrate liquid 149 to repeat. Is caused to react with the Dig to cause chemiluminescence. At that time, the light emission from the particulate carrier 14 encapsulated is detected using the comb-like light detector 78 provided in the carrier encapsulating head 70. In order to detect chemiluminescence, the comb-tooth member 95 and the comb-tooth ends 95a and 95b of the comb-tooth-shaped light detection unit 78, the light detection holes 98 along the column direction, and the carrier-enclosed deformable containers are used. By sequentially moving every 55 rows (four) and moving the carrier-enclosed deformable container 55 upward, light is received by the optical fiber 101 for each of the particulate carriers 14 and detection is performed repeatedly. The measurement result for the gene of a certain sample is shown in the photograph of step S4 in FIG. Regarding the gene of this specimen, since only very weak luminescence was detected for the first particulate carrier, the sixth particulate carrier, and the seventh particulate carrier, the SNP of the gene ATase exon6 of this specimen was detected. Is the base T, the SNP of gene ATase exon8 is base A / G, the SNP of gene CYP2C19 exon5 is base A, and the SNP of gene CYP2D6 exon1 is base T Recognize.

Claims (33)

A container having a deformed wall surface in a part of the wall surface, which is capable of storing liquid and gas inside the wall surface, and capable of predetermined deformation without substantially changing the total inner surface area of the wall surface;
An opening through which the liquid sucked and discharged by the expansion and contraction of the internal portion due to the deformation of the deformation wall surface communicates with the accommodating portion can flow in and out;
A carrier-enclosed deformable container having a carrier to which a predetermined substance sealed in a substantially stationary state is bound or capable of binding.   The housing portion is surrounded by one or more deformed portions formed by the deformed wall surface and a non-deformed wall surface that communicates with the deformable portion and is not deformed, communicates with the mouth portion, and can measure the inside from the outside. The carrier-enclosed deformable container according to claim 1, further comprising a deformable portion, wherein the carrier is enclosed in the non-deformable portion.   The carrier-enclosed deformable container according to claim 2, wherein the accommodating portion has at least two deformable portions, and is formed so that a maximum changeable amount of the accommodating portion based on deformation of a deformed wall surface of each deformable portion is different.   The deformable portion or the only deformable portion having the largest maximum changeable amount is in the direction of the straight line at the intersection of the straight line that passes through the deformed wall surface through the mouth and the accommodating portion and the deformed wall surface. The carrier-enclosed deformable container according to any one of claims 2 and 3, wherein the deformable wall surface is formed along the deformable wall.   5. The carrier according to any one of claims 1 to 4, wherein the carrier is a plurality of particulate carriers to which a plurality of types of chemical substances are bound or bindable and can be distinguished from the outside, or a set of a plurality of particulate carriers. A carrier-enclosed deformable container as described in 1.   Each particulate carrier of the plurality of particulate carriers or at least one particulate carrier belonging to a set of each particulate carrier is the kind of chemical substance, each particulate carrier, or each particulate carrier. The carrier-enclosed deformable container according to claim 5, wherein the container-enclosed deformable container is labeled so as to be distinguishable from each other before being introduced into the accommodating portion according to each set.   The carrier is formed in a linear shape, a rod shape, a flat plate shape, or a block shape, in which a plurality of kinds of chemical substances can be bonded or bonded to a plurality of predetermined different positions that can be distinguished from the outside. The carrier-enclosed deformable container according to claim 4.   The non-deformable portion includes a thick tube portion capable of storing liquid therein, a narrower tube portion or a thin thin layer portion thinner than the thick tube portion, and the thick tube portion and the thin tube portion or the thin layer portion communicating with the thick tube portion. And the transition portion provided between the thin tube portion or the thin layer portion, the mouth portion is provided in communication with the thin tube portion or the thin layer portion, and the carrier is the thin tube portion or the thin layer portion. The carrier-enclosed deformable container according to any one of claims 1 to 7, which is enclosed in any one of the thin layer portions.   The carrier-enclosed deformable container according to any one of claims 1 to 8, further comprising an enclosing portion that encloses the carrier in the housing portion in a state where the fluid can flow into the housing portion through the mouth portion.   The carrier enclosure according to claim 9, wherein the enclosing unit includes an introduction hole formed in a wall surface of the accommodating part so that the carrier can be introduced into the accommodating part, and a lid part that closes the introducing hole. Deformation container.   The carrier-enclosed deformable container according to any one of claims 1 to 10, wherein a portion of the non-deformable portion in which the carrier is enclosed is detachably attached.   The carrier-enclosed deformable container according to any one of claims 1 to 11, wherein a bellows is formed on the deformed wall surface.   An accommodating portion having a deformed wall surface in a part of the wall surface that can store a liquid and a gas inside the wall surface and is capable of predetermined deformation without substantially changing the total inner surface area of the wall surface; An opening through which the liquid sucked and discharged by the expansion and contraction of the internal portion due to deformation of the deformation wall surface communicated with the storage portion can flow in and out, and a predetermined substance stored in the storage portion can be combined or combined One or more carrier-enclosed deformable containers having a carrier, and one or more carrier-enclosed deformable containers are supported so that the mouth does not fluctuate due to deformation of the deformed wall surface, and the deformation of the carrier-enclosed deformable container A carrier-enclosed deformed container processing apparatus having one or more carrier-enclosed heads that perform liquid suction and discharge on the carrier-enclosed deformable container by deforming a wall surface.   A container group having a plurality of containers capable of storing liquids such as various solutions and suspensions, and a head moving unit that moves the carrier-sealed head relative to the container group; The carrier-enclosed deformed container processing apparatus according to claim 13, wherein each container provided in the group is provided so that the mouth portions can be inserted all at once.   The container is a well, the container group is at least one microplate in which the well is arranged in a matrix, and the carrier-encapsulated deformable container of the carrier-encapsulated head is arranged in a matrix, All of the provided mouth portions are provided so as to be able to be inserted into all or a part of the wells of the microplate all at once, and at least one of the row interval or column interval of the mouth portion is the row interval of the corresponding wells or 15. The carrier according to claim 14, wherein each carrier is set to a natural number multiple of a column interval, and at least one of the corresponding number of rows or columns of the mouth portion is the natural number of the number of rows or columns of the well. Enclosed deformed container processing device.   The control unit further includes a control unit, and the control unit is positioned so that all the mouth portions can be inserted into the wells belonging to the corresponding first well sub-matrix of the microplate at the same time with respect to the moving unit. 16. The apparatus according to claim 15, wherein all of the mouths are moved relative to each other between the carrier enclosing head and the microplate so that all the mouth portions can be simultaneously inserted into the wells belonging to the corresponding second well submatrix of the microplate. The carrier-enclosed deformed container processing apparatus as described.   In each well sub-matrix along the movement path of the carrier enclosing head, a liquid such as a solution or a suspension required in each process step is stored according to the process order. 17. The carrier-enclosed deformed container processing apparatus according to claim 16, which is accommodated in a unit.   The control unit is positioned so that the mouth part can be inserted into all wells belonging to each well group in the microplate into which the same mouth part provided in the carrier sealing head can be inserted. 18. The carrier-enclosed deformed container processing apparatus according to claim 13, wherein the carrier-enclosed head is sequentially moved.   The carrier-enclosed head is provided with a magnetic means having two or more magnets provided so as to be able to contact with and separate from the housing portion so that a magnetic field can be applied to and removed from the housing portion all at once. The carrier-enclosed deformed container processing apparatus according to any one of claims 13 to 18.   20. The carrier-enclosed deformed container processing apparatus according to any one of claims 12 to 19, wherein the carrier-enclosed head further includes a light detection unit that detects a state in the housing portion.   The light detecting means is one or two or more light receiving terminals arranged in the vicinity of the non-deformable portion so as to surround the non-deformable portion outside the non-deformable portion of the receiving portion, or 1 or 2 21. The carrier-enclosed deformable container according to claim 20, which has the light receiving terminal and at least one irradiation terminal, and is relatively movable so as to scan the entire region of the non-deformable portion that can accommodate the inner particulate carrier. Processing equipment.   13. The carrier encapsulating head deforms the deformed wall surface along the straight line direction at an intersection of the deformed wall surface and a straight line that passes through the deformed wall surface through the inside of the mouth portion and the receiving portion. Item 22. The carrier-enclosed deformed container processing device according to any one of Items 21.   The carrier enclosing head includes a carrier container supporting portion capable of supporting the two or more carrier enclosing deformable containers, and a movable member capable of moving forward and backward simultaneously along a predetermined deformation direction of the deforming wall surface of the carrier enclosing deformable container. 23. The carrier-enclosed deformed container processing apparatus according to claim 13, comprising:   The deformation of the deformed wall surface and / or the movement between the carrier-enclosed head and the container group, the number or structure of the carrier-enclosed deformable containers, the liquid to be sucked and discharged, the substance contained therein, the amount thereof, The carrier-enclosed deformed container processing apparatus according to any one of claims 13 to 23, further comprising a control unit that performs control based on the storage position, the temperature or the concentration thereof, the processing content, or an instruction.   25. The carrier-enclosed deformation container processing apparatus according to claim 13, wherein a predetermined reference position is set for the deformation of the deformation wall surface, and the deformation of the deformation wall surface is controlled based on the reference position. .   The mouth portion is provided at a lower end, the storage portion is provided above the mouth portion, and a deformable portion that can be deformed in a vertical direction by partitioning an inner wall surface of a part of a wall surface that surrounds the housing portion. 26. The carrier-enclosed deformed container processing apparatus according to claim 13, wherein a wall surface is provided, and an upper end of the receiving portion and the movable member are provided so as to be in contact with or connectable to each other.   The accommodating portion is formed of a deformable portion capable of contacting or connecting to the movable member and having a deformable wall surface that can be deformed by the movable member and capable of accommodating gas, and a non-deformed wall surface that is in communication with the deformable portion and is not deformed. 27. The carrier-enclosed deformed container processing apparatus according to any one of claims 13 to 26, further comprising a non-deformable portion having the mouth portion at a tip thereof and capable of storing liquid. An accommodating portion having a deformed wall surface in a part of the wall surface that can store a liquid and a gas inside the wall surface and is capable of predetermined deformation without substantially changing the total inner surface area of the wall surface; A mouth portion that communicates with the accommodating portion and through which the liquid sucked and discharged by the expansion and contraction of the inner wall due to the deformation of the deforming wall surface can flow in and out, and a carrier to which a predetermined substance accommodated in the accommodating portion can be combined or combined A support step of supporting two or more carrier-enclosed deformable containers having a carrier-enclosed head so that the mouth does not fluctuate due to deformation of the deformed wall surface;
A moving step of moving the carrier enclosing head;
And a deforming step of deforming the deformed wall surfaces simultaneously by inserting the mouth into a container in a container group.   29. The carrier-enclosed deformation container processing method according to claim 28, wherein in the deformation step, a predetermined reference position is set for deformation of the deformation wall surface, and the deformation wall surface is deformed based on the reference position.   The mouth portion is provided at a lower end, the deformation wall surface is provided so as to be deformable in a vertical direction on a part of a wall surface surrounding the housing portion, and the housing portion is provided above the mouth portion, A deformable portion having the deformable wall surface and capable of containing gas; and a non-deformable portion communicating with the deformable portion and not having the deformable wall surface and having the mouth portion and capable of storing liquid. 30. The carrier-enclosed deformable container process according to claim 28 or 29, wherein the step includes a step of bringing a movable member into contact with or connecting to an upper end surface of the housing portion, and a step of lowering and / or raising the movable member. Method.   The carrier-enclosed deformation container processing method according to claim 30, wherein the moving member is raised and lowered by setting a predetermined reference position along the vertical direction in which the deformation wall surface is deformed and using the reference position as a reference.   A magnetic substance capable of binding a predetermined substance or bonded to a predetermined substance is suspended in the liquid, and the magnetic substance is applied to the container or the container by applying a magnetic field to the container of the container or the container group. 32. The method for treating a carrier-enclosed deformed container according to claim 28, further comprising a step of adsorbing and separating the inner wall of the carrier.   A microplate in which wells are arranged in a matrix, and one or more carrier-encapsulating heads having a mouth of a carrier-enclosed deformable container in which a fluid can be sucked and discharged and arranged in a matrix. At least one of the row interval or column interval of the portion is set to a natural number multiple of 2 or more of the row interval or column interval of the well, and at least one of the corresponding row number or column number of the mouth is a row of the well The carrier-encapsulating head, which is the natural fraction of the number or the number of columns, is moved relative to the microplate so that each carrier-encapsulating head is moved to a well belonging to the first well submatrix in the microplate. A first step of positioning all provided mouths so that they can be inserted all at once, and relatively moving between the carrier-enclosed head and the microplate, Second step and carrier enclosing transformable container processing method with which insertably positioned in unison in the corresponding second wells belonging to the well submatrix in Lee black plate.

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