CN101109760B - Chemical reaction cartridge, method of producing chemical reaction cartridge, and mechanism for driving chemical reaction cartridge - Google Patents

Chemical reaction cartridge, method of producing chemical reaction cartridge, and mechanism for driving chemical reaction cartridge Download PDF

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Publication number
CN101109760B
CN101109760B CN200710148081XA CN200710148081A CN101109760B CN 101109760 B CN101109760 B CN 101109760B CN 200710148081X A CN200710148081X A CN 200710148081XA CN 200710148081 A CN200710148081 A CN 200710148081A CN 101109760 B CN101109760 B CN 101109760B
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China
Prior art keywords
pond
flow channel
roller
solution
chemical reaction
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CN200710148081XA
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Chinese (zh)
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CN101109760A (en
Inventor
田名纲健雄
片仓久雄
三森裕示
平松仁
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Yokogawa Electric Corp
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Yokogawa Electric Corp
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Priority claimed from JP2004204085A external-priority patent/JP4379716B2/en
Application filed by Yokogawa Electric Corp filed Critical Yokogawa Electric Corp
Publication of CN101109760A publication Critical patent/CN101109760A/en
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087Multiple sequential chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0633Valves, specific forms thereof with moving parts
    • B01L2400/0655Valves, specific forms thereof with moving parts pinch valves

Abstract

A chemical reaction cartridge includes a vessel having at least one part made of an elastic body, in which a plurality of chambers formed in the vessel so as to be connected or arranged connectably through a flow path, and an external force is applied to the elastic body from an outside of the vessel to move a fluid substance in the flow path or the chambers or in both the flow path and the chambers so as to perform a chemical reaction, wherein at least one of the chambers is a common chamber having a plurality of inlet flow paths into which two or more different fluid substances flow respectively, and at least two outlet flow paths, and when one fluid substance flows into and from the common chamber, an inlet flow path for another fluid substance and the outlet flow paths are blocked by the external force.

Description

Cartridge for chemical reaction and manufacture method thereof and the mechanism that drives cartridge for chemical reaction
The application is that the application number of submitting on April 27th, 2005 is dividing an application of 200510068131.4 cartridge for chemical reaction and manufacture method thereof and the mechanism that drives cartridge for chemical reaction.
Technical field
The present invention relates to the method for a kind of cartridge for chemical reaction, manufacturing chemistry reaction box and the mechanism that drives cartridge for chemical reaction.Particularly relate to the improvement of synthesizing, dissolve, detect, separate etc. relevant liquid Supply Structure with solution.
Background technology
At present, test tube, beaker, transfer pipet etc. be used for generally that solution is synthetic, dissolving, detection, separation etc.For example, in advance substance A and substance B are packed in test tube, beaker or the similar device.Again substance A and B are injected other container (for example test tube or beaker), and mix and stir with the preparation substance C.For example, utilize optical radiation, temperature rise, dyeing, colorimetric or the like means to observe synthetic thus substance C.
Perhaps compounding substances is filtered or centrifuging, be used to extract target substance.
Such as the glassware of test tube or beaker, also be used for dissolving, for example dissolving in organic solvent.Under situation about detecting, substances A and reagent are put into container and observing response result equally.
On the other hand, in biological analyser or similar device, use a bag that is called " biochip ", it be make by flexible material and shape as a flat bag (for example, referring to a JP-A-2002-365299).
JP-A-2002-365299 is cited as correlation technique.
Figure 27 A and 27B are the structural drawing of the biochip described among the JP-A-2002-365299.Figure 27 A is the cut-open view of biochip, and Figure 27 B is the planimetric map of biochip.The center section shape of the flat blood taking bag 41 of edge sealing is as the bag of fish shape.The opening portion of this fish shape bag stops up with rubber plug 42.
In blood taking bag 41,, form collecting part 43, preprocessing part 44, coupling part 45 and waste liquid storage part 47 successively when from filling in 42 when inwardly seeing.In order to gather blood, will fill in 42 and insert in the syringe (not shown).In syringe inside, syringe needle stretches out so that penetrate plug 42.
In order to gather blood, the needle point of stretching at the syringe needle of syringe exterior thrusts in examined people's the health.The hook 431 of blood taking bag 41 is pulled outwardly to be stretched, and makes the collected collecting part 43 of blood.Behind the blood collection, take off syringe from blood taking bag 41.Then, as shown in figure 28, blood taking bag 41 is clipped between the rotation roller 61 and 62, and moves to preprocessing part 44 from collecting part 43, so that be crushed in extruding.The blood of gathering is delivered to preprocessing part 44.
Along with advancing of roller 61 and 62 positions, bag part 48 begins to be crushed, and the solution in the bag part 48 is washed valve 49 open, and flows into preprocessing part 44.Then, the solution in the bag part 50 flows into preprocessing part 44 by mode same as described above.When finishing pre-service in preprocessing part 44, roller is rotated further, so that the blood transport that will handle is to the coupling part 45.
DNA chip 46 is arranged in the coupling part 45, is used to hybridize (hybridization).The unnecessary blood or the solution that flow out from preprocessing part 44 are stored in the waste liquid storage part 47.By being arranged in the DNA chip status after outside reader is observed hybridization.
But, in the background technology method of using beaker, transfer pipet or the like, complicated operation, and have the problem that personal error is big and workload is big.
In addition, the problem of blood taking bag is, because blood taking bag does not have elasticity, so moving liquid easily.
In order to address these problems, attempt providing the container as box.As biochip, solution be transported to be arranged in the box and chamber connected to one another in (below be called " pond "), be used to carry out such as mixing and the processing of chemical reaction.But when the container as box was provided, also there are the following problems:
(1) when solution is transported to next pond, because contain air in the next pond in advance, so solution and air mixed.And solution back moves owing to the opposite pressure of air.
(2) when delivered solution, solution not only flows into next pond, and flows in the pond or flow channel of back, next pond.
(3) when heating or vibration solution, solution flows in other ponds.
(4) when beginning to inject sample, air is sneaked in the sample.And, because sample is manual injection the, quantitatively property poor (that is, the scheduled volume of sample can not reach the original bulk of reaction).
(5) though be easy to obtain simply for example potpourri (A+B) of solution A and B, can not obtain a kind of like this structure (decussate texture): from sample, extract and purification DNA by using silicon dioxide, magnetic or similar substance.
Summary of the invention
The purpose of this invention is to provide a kind of the have cartridge for chemical reaction of pin-point accuracy and high duplication, the method for making described cartridge for chemical reaction and the mechanism that drives described cartridge for chemical reaction.
(1) the invention provides a kind of cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, at least one chamber that flowing material flows into has the exhaust passage, and described exhaust passage is used for the chamber discharged air from self.
(2) the invention provides a kind of cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, flow channel and chamber in the two at least one volume before fluid stream passes goes into to flow passage or chamber be zero.
(3) the invention provides a kind of method of making as the described cartridge for chemical reaction of paragraph (2), comprise the steps: when rigid body and elastic body are engaged with each other the non-stick portion that formation and flow channel or chamber are not bonding.
(4) in the method as the described manufacturing chemistry reaction box of paragraph (3), the mode that non-stick portion forms is to apply non-adhesion substance before engaging.
(5) in the method as the described manufacturing chemistry reaction box of paragraph (3), the mode that non-stick portion forms is to cover corresponding zone when the plasma adhesion process, perhaps applies not by the material of plasma-activated at respective regions.
(6) in the method as the described manufacturing chemistry reaction box of paragraph (3), the mode that non-stick portion forms is an application of adhesive around respective regions, and at non-stick portion application of adhesive not.
(7) in the method as the described manufacturing chemistry reaction box of paragraph (3), non-stick portion forms non-adhesive surface, and its generation type is to embed the material imbedded with at least one non-adhesive surface in matrix.
(8) in method as the described manufacturing chemistry reaction box of paragraph (3), the mode that non-stick portion forms is that the material imbedded that will have at least one non-adhesive surface is arranged in the matrix that hardens in advance or in the elastic body, then comes the appropriate section of shaped resilient body or matrix by cast.
(9) the invention provides a kind of mechanism that drives cartridge for chemical reaction, it is the container of being made by elastic body that described cartridge for chemical reaction has at least a portion, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, described mechanism comprises pressures partially, and all input and output flow channels that described pressures partially will be connected to the chamber that flowing material is housed stop up simultaneously.
(10) the invention provides a kind of mechanism that drives as paragraph (1) or (2) described cartridge for chemical reaction, comprise pressures partially, all flow channels that described pressures partially will be connected to the chamber that flowing material is housed stop up simultaneously.
(11) in the mechanism as the described driving cartridge for chemical reaction of paragraph (9), pressures partially is to be used to roller that flowing material is moved.
(12) in the mechanism as the described driving cartridge for chemical reaction of paragraph (10), pressures partially is to be used to roller that flowing material is moved.
(13) in the mechanism as the described driving cartridge for chemical reaction of paragraph (9), at least one pressures partially is a flashboard.
(14) in the mechanism as the described driving cartridge for chemical reaction of paragraph (10), at least one pressures partially is a flashboard.
(15) in the mechanism as the described driving cartridge for chemical reaction of paragraph (9), a plurality of positions in a box are stopped up flowing material simultaneously.
(16) in the mechanism as the described driving cartridge for chemical reaction of paragraph (10), a plurality of positions in a box are stopped up flowing material simultaneously.
(17), stop up flowing material according to each step of chemical reaction in mechanism as the described driving cartridge for chemical reaction of paragraph (9).
(18), stop up flowing material according to each step of chemical reaction in mechanism as the described driving cartridge for chemical reaction of paragraph (10).
(19) in the mechanism as the described driving cartridge for chemical reaction of paragraph (9), at least one pressures partially moves after stopping up flowing material, in order to change the interior pressure of chamber.
(20) in the mechanism as the described driving cartridge for chemical reaction of paragraph (10), at least one pressures partially moves after stopping up flowing material, in order to change the interior pressure of chamber.
(21) the invention provides a kind of cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, a plurality of chambers are equidistantly to arrange, at least one chamber is the common chamber with a plurality of inlet flow channels and at least one outlet flow channel, described inlet flow channel flows into the different fluid material, and at least one chamber is vacant chamber, is used to regulate with the timing of predetermined fluid mass transport to common chamber.
(22) in as paragraph (1) or (2) described cartridge for chemical reaction, a plurality of chambers are with equidistant arrangement, at least one chamber is the common chamber with a plurality of inlet flow channels and at least one outlet flow channel, described inlet flow channel flows into the different fluid material, and at least one chamber is vacant chamber, is used to regulate with the timing of predetermined fluid mass transport to common chamber.
(23) in the mechanism that drives as the described cartridge for chemical reaction of paragraph (21), have a plurality of pressures partiallies, described pressures partially is arranged on the position of the flow channel that is used to stop up the chamber, wherein, a plurality of pressures partiallies move simultaneously along a direction, thus spacing ground delivered solution one by one.
(24) in the mechanism that drives as the described cartridge for chemical reaction of paragraph (22), have a plurality of pressures partiallies, described pressures partially is arranged on the position of the flow channel that is used to stop up the chamber, wherein, a plurality of pressures partiallies move simultaneously along a direction, thus spacing ground delivered solution one by one.
(25) the invention provides in a kind of cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, the inlet of flowing material is to be made of a plurality of injection parts that portion within it connects, and flowing material injects part from one and inject, so that air is injected the part discharge from other.
(26) as paragraph (1) or (2) described cartridge for chemical reaction, the inlet of flowing material is to be made of a plurality of injection parts that portion within it connects, and flowing material injects part from one and inject, so that air is injected the part discharge from other.
(27) the invention provides a kind of cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, described cartridge for chemical reaction also comprises: the inlet that is used to store the predetermined quantity of fluid material; And pumping unit, the flowing material that is used for being stored in the scheduled volume in the described inlet is drawn into inside.
(28) in as paragraph (1) or (2) described cartridge for chemical reaction, also have: the inlet that is used to store the predetermined quantity of fluid material; And pumping unit, the flowing material that is used for being stored in the scheduled volume in the described inlet is drawn into inside.
(29) the invention provides a kind of cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, at least one chamber is the common chamber with a plurality of inlet flow channels and at least two outlet flow channels, two or more different flowing materials flow into the inlet flow channel respectively, and flow into common chamber and when common chamber flows out when a kind of flowing material, stop up by external force common chamber other flowing materials the inlet flow channel and export flow channel.
(30) in as paragraph (1) or (2) described cartridge for chemical reaction, at least one chamber is the common chamber with a plurality of inlet flow channels and at least two outlet flow channels, two or more different flowing materials flow into the inlet flow channel respectively, and flow into common chamber and when common chamber flows out, stop up the inlet flow channel of other flowing materials and export flow channel when a kind of flowing material by external force.
(31) in as the described cartridge for chemical reaction of paragraph (29), described other flowing materials flow into and the flow channel that flows out is formed on the position that the external force that is used to carry described a kind of flowing material stops up.
(32) in as the described cartridge for chemical reaction of paragraph (30), described other flowing materials flow into and the flow channel that flows out is formed on the position that the external force that is used to carry described a kind of flowing material stops up.
(33) in as the described cartridge for chemical reaction of paragraph (29), a plurality of chambers have projection, described projection is positioned at described external container, and is depressed when applying external force, and carries the flow channel of described a kind of flowing material to be formed in the recessed part between the projection.
(34) in as the described cartridge for chemical reaction of paragraph (30), a plurality of chambers have projection, described projection is positioned at described external container, and is depressed when applying external force, and carries the flow channel of described a kind of flowing material to be formed in the recessed part between the projection.
(35) in the mechanism that drives as the described cartridge for chemical reaction of paragraph (29), described other flowing material flows into and the flow channel of outflow is stopped up simultaneously by the pressures partially of the type of taking turns.
(36) in the mechanism that drives as the described cartridge for chemical reaction of paragraph (30), described other flowing material flows into and the flow channel of outflow is stopped up simultaneously by the pressures partially of the type of taking turns.
(37) in mechanism as paragraph (35) or (36) described driving cartridge for chemical reaction, described take turns the type pressures partially along the axis direction identical with the axis of the pressures partially of delivered solution move or rotate mobile, in order to stop up the flow channel that described other flowing material flows into and flows out.
(38) want in the mechanism of (29) described cartridge for chemical reaction as right in driving, the inlet flow channel of common chamber and outlet flow channel are to form radially from common chamber, and the pressures partially by the flow channel delivered solution, with the corresponding different axis directions of each flow channel of vessel surface on move.
(39) drive the mechanism that wants (30) described cartridge for chemical reaction as right, the inlet flow channel of common chamber and outlet flow channel are to form radially from common chamber, and the pressures partially by the flow channel delivered solution, with the corresponding different axis directions of each flow channel of vessel surface on move.
(40) the invention provides a kind of cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, at least one chamber is the common chamber with a plurality of inlet flow channels and at least two outlet flow channels, two or more different flowing materials flow into the inlet flow channel respectively, and a plurality of flow channels that pass common chamber are arranged on each back side and the front of described box.
(41) in as paragraph (1) or (2) described cartridge for chemical reaction, at least one chamber is the common chamber with a plurality of inlet flow channels and at least two outlet flow channels, two or more different flowing materials flow into the inlet flow channel respectively, and a plurality of flow channels that pass common chamber are arranged on each back side and the front of described box.
(42) the invention provides a kind of cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, at least one chamber is the common chamber with a plurality of flow channels, flow into and flow out described common chamber by two or more different flowing materials of described flow channel, the flow channel of common chamber is contiguous ground, center with the common chamber and arranges as the crow flies, and when a kind of flowing material flows into and flow out common chamber, stops up the flow channel that other flowing material flows into common chamber by external force.
(43) in as paragraph (1) or (2) described cartridge for chemical reaction, at least one chamber is the common chamber with a plurality of flow channels, by described flow channel, two or more different flowing materials flow into and flow out described common chamber, the flow channel of common chamber is contiguous ground, center with the common chamber and arranges as the crow flies, and when a kind of flowing material flows into and flow out common chamber, stop up the flow channel that other flowing material flows into common chamber by external force.
(44) in the mechanism that drives as the described cartridge for chemical reaction of paragraph (42), be used for the pressures partially that flowing material is transported to common chamber is arranged to clamp being equipped with and being transferred the chamber of flowing material, and described pressures partially moves in vessel surface upper edge rectilinear direction.
(45) in the mechanism that drives as the described cartridge for chemical reaction of paragraph (43), be used for the pressures partially that flowing material is transported to common chamber is arranged to clamp being equipped with and being transferred the chamber of flowing material, and described pressures partially moves in vessel surface upper edge rectilinear direction.
(46) the invention provides a kind of cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, a plurality of chambers are with equidistant arrangement, at least one chamber is the common chamber with a plurality of inlet flow channels and at least two outlet flow channels, described inlet flow channel flows into the different fluid material of two or more respectively, and when a kind of flowing material flows into and flow out common chamber, stops up the inlet flow channel that other flowing materials flow into by external force.
(47) as paragraph (1) or (2) described cartridge for chemical reaction, a plurality of chambers are with equidistant arrangement, at least one chamber is the common chamber with a plurality of inlet flow channels and at least two outlet flow channels, described inlet flow channel flows into the different fluid material of two or more respectively, and when a kind of flowing material flows into and flow out common chamber, stop up the inlet flow channel that other flowing materials flow into by external force.
(48) in the mechanism that drives as the described cartridge for chemical reaction of paragraph (46), the pressures partially of carrying the different fluid material is the independent one group of pressures partially that moves.
(49) in the mechanism that drives as the described cartridge for chemical reaction of paragraph (47), the pressures partially of carrying the different fluid material is the independent one group of pressures partially that moves.
(50) in the mechanism as paragraph (48) or (49) described driving cartridge for chemical reaction, described one group of pressures partially moves along at least two different directions at vessel surface.
(51) in the mechanism as the described driving cartridge for chemical reaction of paragraph (50), described both direction is perpendicular to one another.
(52) in as the described cartridge for chemical reaction of paragraph (46), the direction that is applied in the moving direction of pressures partially of external force and flow channel is different at vessel surface.
(53) in as the described cartridge for chemical reaction of paragraph (47), the direction that is applied in the moving direction of pressures partially of external force and flow channel is different at vessel surface.
(54) in as paragraph (52) or (53) described cartridge for chemical reaction, the direction of described flow channel is 90 ° or less than 90 ° angle with respect to the moving direction of pressures partially.
(55) in as the described cartridge for chemical reaction of paragraph (46), form rigid body at the vessel side of flow channel, and a part of flow channel is applied external force, so that forming part, rigid body stops up flow channel fully.
(56) in as the described cartridge for chemical reaction of paragraph (47), form rigid body at the vessel side of flow channel, and a part of flow channel is applied external force, so that forming part, rigid body stops up flow channel fully.
(57) in as the described cartridge for chemical reaction of paragraph (52), form rigid body at the vessel side of flow channel, and a part of flow channel is applied external force, so that forming part, rigid body stops up flow channel fully.
(58) in as the described cartridge for chemical reaction of paragraph (53), form rigid body at the vessel side of flow channel, and a part of flow channel is applied external force, so that forming part, rigid body stops up flow channel fully.
(59) in as the described cartridge for chemical reaction of paragraph (21), the capture material that is used for catching predetermined substance for good and all or provisionally is fixed on common chamber.
(60) in as the described cartridge for chemical reaction of paragraph (59), predetermined substance is an XC polymer.
(61) in as the described cartridge for chemical reaction of paragraph (60), XC polymer is DNA, RNA, protein, metabolin or sugar chain.
(62) in as the described cartridge for chemical reaction of paragraph (59), the capture material that provides is pearl, filtrator, fiber or the post of the surface modification that is used to catch.
(63) in as the described cartridge for chemical reaction of paragraph (62), described pearl is silicon dioxide, magnetic beads, bead or resin bead.
(64) the invention provides a kind of mechanism that drives cartridge for chemical reaction, it is the container of being made by elastic body that described cartridge for chemical reaction has at least a portion, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, external force is to produce by a direction extruding two dimensional panel from the elasticity side.
(65) driving in the mechanism as paragraph (1) or (2) described cartridge for chemical reaction, external force is to produce by a direction extruding two dimensional panel from the elasticity side.
(66) in the mechanism as the described driving cartridge for chemical reaction of paragraph (64), two dimensional panel has curvature it applies the surface of external force to flow channel or chamber on.
(67) in the mechanism as the described driving cartridge for chemical reaction of paragraph (65), two dimensional panel has curvature it applies the surface of external force to flow channel or chamber on.
(68) the invention provides a kind of mechanism that drives cartridge for chemical reaction, it is the container of being made by elastic body that described cartridge for chemical reaction has at least a portion, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction, wherein, described mechanism comprises: a plurality of pressures partiallies of extruding cartridge for chemical reaction; And the base part that is provided with pressures partially.
(69) in the mechanism as the described driving cartridge for chemical reaction of paragraph (68), a plurality of chambers are with equidistant arrangement, and pressures partially is with equidistantly arranging of equating with the chamber spacing.
(70) in the mechanism as paragraph (68) or (69) described driving cartridge for chemical reaction, described base part has opening, and actuator is inserted in the described opening.
(71) in the mechanism as paragraph (68) or (69) described driving cartridge for chemical reaction, also comprise: flashboard, it stops up the flowing material that flows along the direction perpendicular to the pressures partially moving direction.
(72) in the mechanism as paragraph (68) or (69) described driving cartridge for chemical reaction, pressures partially comprises: a plurality of rollers of extruding cartridge for chemical reaction; And a plurality of roller support sections that support described roller respectively.
(73) in the mechanism as the described driving cartridge for chemical reaction of paragraph (72), each roller support section has the groove that one of described roller inserts, and described groove niproll, to wrap up roller in greater than 180 ° of angular ranges.
(74) in the mechanism as the described driving cartridge for chemical reaction of paragraph (72), each roller support section has the roller retainer in its side.
(75) in the mechanism as paragraph (68) or (69) described driving cartridge for chemical reaction, each pressures partially has end portion, and described end portion has the curved surface of extruding cartridge for chemical reaction.
(76) in the mechanism as the described driving cartridge for chemical reaction of paragraph (75), curved surface is circular bend surface or non-circular curved surface.
(77) in mechanism, also comprise: be arranged between cartridge for chemical reaction and the pressures partially and be used to the member that reduces to rub as the described driving cartridge for chemical reaction of paragraph (75).
According to arriving the cartridge for chemical reaction described in (8) and the method for manufacturing chemistry reaction box at paragraph (1), because the exhaust passage of discharged air is arranged in the chamber of flowing material inflow from the chamber, therefore can prevent that flowing material from returning under the air back-pressure that is extruded, and prevent that air from entering.And, because any in flow channel and the chamber has the zero volume structure, therefore can reach effect same as described above.
According to the mechanism that arrives the cartridge for chemical reaction described in (24) and drive cartridge for chemical reaction at paragraph (9), owing to whole input and output flow channels that pressures partially is used for stopping up simultaneously the chamber that flowing material is housed are set, can prevent that therefore flowing material flows into next chamber and chamber afterwards, next chamber when the conveyance fluid material.And, can prevent that flowing material flows in other chamber when heating or vibration flowing material.
According at the cartridge for chemical reaction of paragraph (25) described in (28),, can prevent that therefore flowing material is when injecting sample and air mixed because the air in the flowing material can discharge from the porch.And, can be in box with the sample delivery of scheduled volume.
According to the mechanism that arrives cartridge for chemical reaction described in (63) and driving cartridge for chemical reaction at paragraph (29), because at least one chamber is a common chamber, this common chamber has two or more different fluid materials and flows into the inlet flow channel of common chamber by it, and have at least two outlet flow channels, when a kind of flowing material flows into or flow out common chamber, other flowing material flows into or the flow channel of outflow is stopped up by external force, so different fluid can be intersected with each other in common chamber.Therefore, can realize from sample extracting or the step of purification predetermined substance.
According to the mechanism that arrives the driving cartridge for chemical reaction described in (67) at paragraph (64), use has the two dimensional panel of curvature on the surface of contacting container, thereby moves described plate in squeeze receptacle.Therefore, because flow channel and chamber are pushed by the surface, therefore can prevent that solution and air from refluxing under the back-pressure effect.
According to mechanism at the driving cartridge for chemical reaction described in paragraph (68) and (69), stopped up by the pressures partially of box driving mechanism simultaneously because all input and output flow channels of the chamber of flowing material are housed, therefore can prevent that flowing material flows into the later chamber in next chamber and next chamber when the conveyance fluid material.And, can prevent that flowing material flows in other chamber when heating or vibration flowing material.And, can solution not squeezed back owing to the back-pressure of air.In addition, can realize by use silicon dioxide, magnetic or similar substance extracts and the structure (decussate texture) of purification DNA from sample.
Mechanism according at the driving cartridge for chemical reaction described in the paragraph (70) can insert actuator, and can apply vibration and heating or the like effect.
According to the mechanism at the driving cartridge for chemical reaction described in the paragraph (71), the flowing material that moves along the direction perpendicular to the pressures partially moving direction can be stopped up by flashboard.
According in the mechanism of paragraph (72) to the driving cartridge for chemical reaction described in (77), be set to curved surface owing in pressures partially, be provided with the end of roller or pressures partially, can reduce the friction between box and the pressures partially.When the end of pressures partially was set to curved surface, curved surface can be set to be suitable for the circular or non-circular curved surface of box material.Between box and curved surface the plate of being made by the antifriction part can be set, perhaps the surface of box can apply identical part, is used to make the gliding smoothing of pressures partially.
Description of drawings
Figure 1A and 1B are the external view of an embodiment of expression cartridge for chemical reaction of the present invention;
Fig. 2 explains that solution of the present invention is carried and the key diagram of air discharging;
Fig. 3 A is the key diagram of expression another embodiment of cartridge for chemical reaction of the present invention (zero volume structure) to 3D;
Fig. 4 A is the key diagram of first embodiment of explaining the method for manufacturing chemistry reaction box to 4C;
Fig. 5 A and 5B are the key diagrams of second embodiment of explaining the method for manufacturing chemistry reaction box;
Fig. 6 is the key diagram of the 3rd embodiment of explaining the method for manufacturing chemistry reaction box;
Fig. 7 A is the key diagram of expression first embodiment relevant with driving mechanism with chemical box to 7C;
Fig. 8 A is the key diagram of expression second embodiment relevant with driving mechanism with chemical box to 8D;
Fig. 9 A is the key diagram of expression three embodiment relevant with driving mechanism with chemical box to 9E;
Figure 10 A is the key diagram of expression four embodiment relevant with driving mechanism with chemical box to 10C;
Figure 11 A is the key diagram of expression five embodiment relevant with driving mechanism with chemical box with 11B;
Figure 12 A is the key diagram of expression six embodiment relevant with driving mechanism with chemical box with 12B;
Figure 13 A is the key diagram of expression seven embodiment relevant with driving mechanism with chemical box with 13B;
Figure 14 A is the key diagram of expression eight embodiment relevant with driving mechanism with chemical box to 14C;
Figure 15 A is the key diagram of expression nine embodiment relevant with driving mechanism with chemical box to 15C;
Figure 16 A is the key diagram of expression ten embodiment relevant with driving mechanism with chemical box to 16E;
Figure 17 A is the key diagram of expression ten one embodiment relevant with driving mechanism with chemical box to 17G;
Figure 18 A is the key diagram of expression ten two embodiment relevant with driving mechanism with chemical box to 18F;
Figure 19 A is the key diagram of expression ten three embodiment relevant with driving mechanism with chemical box to 19C;
Figure 20 is the key diagram of expression ten four embodiment relevant with driving mechanism with chemical box;
Figure 21 A is the key diagram of expression ten five embodiment relevant with driving mechanism with chemical box to 21C;
Figure 22 is the key diagram of expression ten six embodiment relevant with driving mechanism with chemical box;
Figure 23 A is the key diagram of expression ten seven embodiment relevant with driving mechanism with chemical box to 23C;
Figure 24 A is the key diagram of expression ten eight embodiment relevant with driving mechanism with chemical box with 24B;
Figure 25 is the key diagram of expression ten nine embodiment relevant with driving mechanism with chemical box;
Figure 26 is the key diagram of expression two ten embodiment relevant with driving mechanism with chemical box;
Figure 27 A and 27B are the structural drawing according to the biochip of background technology; And
Figure 28 is the key diagram of explanation according to the method for operating of the biochip of background technology.
Embodiment
Describe the present invention in detail below with reference to accompanying drawing.Figure 1A and 1B represent the external view of an embodiment of cartridge for chemical reaction of the present invention.
Figure 1A is the skeleton view of box, and Figure 1B is the planimetric map of box.Box 101 has elastic body 102, as the impermeability elastic caoutchouc, and the flat matrix of making by rigid material 103.In addition, can use viscoelastic body or plastomer elastic body 102 as box.This embodiment will describe under use elastic body situation as an example.
The example of material of matrix 103 can comprise glass, metal, rigid resin and elastic body.Elastic body 102 and matrix 103 can be by bonding or be bonded to each other by other means, other means for example be sorption (as, between PDMS (dimethyl silicone polymer) and the glass), ultrasonic Treatment, heating, plasma adhesion process or Vibration Welding.
Pond A1 to A7, flow channel 105a to 105f, inlet channel 104a is formed on the back side of elastic body 102, thereby forms depression towards elastic body 102 upper surfaces to 104c, public inlet channel 104, exhaust passage 106a to 106c and common exhaust passage 106.Swell projectedly towards the upper surface of elastic body 102 in the zone corresponding with pond and passage.Pond A1 is the cave of stock solution therein to A7.Flow channel 105a is connected to each other the pond to 105f.Air flows into to 104c by inlet channel 104a and is fed to pond A1, A2 and A4.Inlet channel 104a is connected to public inlet channel 104 to 104c.Air through exhaust passage 106a to 106c from pond A3, A5 with A7 discharging.Exhaust passage 106a is connected to common exhaust passage 106 to 106c.The flat of the back side of elastic body 102 except pond, flow channel, inlet channel and exhaust passage is attached to the front of matrix 103.As a result, pond, flow channel, inlet channel and exhaust passage and elastic body 102 and matrix 103 sealings, thus form a kind of like this structure that can prevent that solution from revealing.
The following describes the solution conveying operations of the box of such formation.
Fig. 2 is a key diagram of explaining that solution is carried and air discharges among the present invention.In Fig. 2, pond B1 and B2 are connected to each other by flow channel 107a.Near flow channel 107a and 107b open area ratio exhaust passage 108a and 108b narrow pond B1 and B2 outlet, thereby (for example form limiter, the aperture area of flow channel 107a and 107b equals the numerical value in 1/3 to 1/5 scope of exhaust passage 108a and 108b aperture area).As a result, the resistance that stops air to be discharged into flow channel 107a and 107b increases, thereby air flows into exhaust passage 108a and 108b.Specifically, the box operation is as follows:
Roller 109 is from the top extrusion box, thereby the recessed part in box front is crushed.When in this state, roller 109 rotates and moves right along the solid arrow direction, and the solution among the B1 of pond is discharged to the right side.As a result, solution flows into pond B2 by flow channel 107a.During this time, the air 110 among the B2 of pond is flowed into the solution extruding among the B2 of pond, thereby air 110 emits from the B2 of pond by exhaust passage 108b, shown in dotted arrow.
Because the exhaust passage 108a of solution supply side is stopped up by roller 109, so solution can not be leaked to exhaust passage one side, but remaining solution will be transported to pond B2 along with moving of roller 109 among the 108a of exhaust passage.As a result, can provide such box, return under the effect of air back-pressure so that can prevent the solution that is discharged from, and can prevent that air from mixing with solution.
Fig. 3 A is the key diagram of another embodiment of expression cartridge for chemical reaction of the present invention (zero volume structure) to 3D.
Fig. 3 A is the planimetric map of box.Shown in Fig. 3 B, box 111 comprises in the mode identical with top embodiment: have impermeability and flexible elastic body 117, and flat matrix 118.For example, elastic body 117 and matrix 118 can be made by PDMS (dimethyl silicone polymer).Pond C1 and flow channel 112 and 113 are arranged at the back side of elastic body 117.Pond C1 is the cave of stock solution.Solution flows into pond C1 by flow channel 112 and 113.
Except pond C1, also be provided with pond C2 and C3.Pond C2 is connected to pond C1 by flow channel 114.Pond C3 is connected to pond C2 by flow channel 115.In flow channel 114 and 115 and each zone of pond C2 and C3, elastic body 117 and matrix 118 are not bonded together, but are contacting with each other, thereby before solution flows into this zone or after flow of solution crosses this zone, the volume vanishing that this is regional.As a result, owing in each flow channel and pond, do not have air, therefore do not need deaeration.
Pond C1 and the flow channel 112 and 113 represented with solid line in Fig. 3 A are visible, because they swell projectedly on the surface of box 111.On the contrary, the flow channel 114 that dots among Fig. 3 A and 115 and pond C2 and C3 be invisible.
For delivered solution, the operation of box is as follows:
As shown in Figure 3A, roller 116 is from top extrusion box 111, so that the front of box 111 (flow channel 112 and 113 and pond C1) flattened.When roller 116 rotation and when the direction of arrow moves right, be stored in the flow of solution among the C1 of pond, so that flow into pond C2 through flow channel 114.Shown in Fig. 3 C, the flow channel 114 and the pond C2 that show zero volume become solution channel (flow channel 114) and liquid reservoir (pond C2) at this moment, because on the part of matrix 118, the solution that elastic body 117 is flowed into boosts at each flow channel 114 and pond C2.After flow of solution is crossed each flow channel 114 and pond C2, make the volume vanishing of each flow channel 114 and pond C2 owing to the restoring force of elastic body 117.
Shown in Fig. 3 D, flow channel 115 and pond C3 work in the same manner as described above, thereby along with the moving of roller 116, solution flows to pond C3 from pond C2 through flow channel 115.Before solution flowed into, the volume of each flow channel 115 and pond C3 was zero.Form solution channel (flow channel 115) and liquid reservoir (pond C3) along with the inflow of solution.Can form this structure is to be made by elastic body 117 because of this container.
An embodiment of the method for making the box with this zero volume structure will be described below.
Fig. 4 A is the key diagram of explaining first embodiment of cartridge manufacturing method to 4C.Below with reference to the step of Fig. 4 A to 4C explanation cartridge manufacturing method.
(1) preparation mask 119 and matrix 120 (Fig. 4 A);
(2) place mask 119 on the matrix 120 and carry out plasma adhesion process (Fig. 4 B).As a result, the part (dashed area) except that mask 119 is subjected to the plasma adhesion process so that by bonding (Fig. 4 C) on the matrix 120;
(3) mask 119 is taken off, matrix 120 is attached on the elastic body (not shown).Additional disclosure can be used not by the material alternative mask 119 of plasma-activated, this material is being coated on the non-stick portion 121 of matrix 120 before the plasma adhesion process.
The plasma adhesion process relevant with PDMS is a technique known (for example, referring to Plasma Materials Science Handbook, Ohmsha, Ltd., 1992), therefore omits its explanation.
Fig. 5 A and 5B are the key diagrams of second embodiment of explanation chemical reaction cartridge manufacturing method.Step below with reference to Fig. 5 A and 5B explanation cartridge manufacturing method.
(1) around the non-stick portion 125 of matrix 122, forms breach and add bonding agent 124, thereby breach is full of bonding agent 124.Breach can form by this way,, shown in Fig. 5 A, excises non-stick portion part in addition that is; Perhaps form by this way, that is, shown in Fig. 5 B, around non-stick portion, form groove.
(2) matrix 122 is attached on the elastic body 123.
Additional disclosure, the breach that is provided with in the matrix 122 is used to prevent that bonding agent 124 from flowing into non-stick portion.If, in matrix 122, breach is set with regard to unnecessary on non-stick portion 125, applying non-adhesion substance before the combination.
Fig. 6 is the key diagram of the 3rd embodiment of explanation chemical reaction cartridge manufacturing method.The step of cartridge manufacturing method is described below with reference to Fig. 6.
(1) material imbedded 128 that will have a non-adhesive surface places on the non-stick portion 129 of elastic body 127.
(2) raw material with matrix 126 waters on the elastic body 127 and curing (for example, casting forming) from the top.
As a result, except can imbedding material 128, elastic body 127 and matrix 126 are bonded to each other.Additional disclosure for example, can be imbedded material 128 and can be made by PDMS.
The structure of cartridge for chemical reaction will be described below and the driving mechanism of delivered solution in box.
Fig. 7 A is the key diagram of expression first embodiment relevant with cartridge for chemical reaction and driving mechanism to 7C.
In Fig. 7 A, roller 130a extrusion box will enter the flow channel 131a obstruction of the inlet of pond D1 as solution.Roller 130b stops up the flow channel 131b as outlet.When all entrance and exits in pond were stopped up in this way simultaneously by a plurality of rollers, solution flowed into next pond and flow channel and pond in addition, next pond in the time of can preventing delivered solution.
Shown in Fig. 7 B, stopped up by roller 130b near the taphole of pond D1, and make roller 130b not move roller 130b locking.When moving in this state lower roll 130a rotation and along the direction of arrow when being clipped between roller 130a and the 130b with urinal D1, the solution in the D1 of pond can be pressurized.
Shown in Fig. 7 C, stopped up by roller 130a near the solution of the pond D1 inlet, and the roller 130a that roller 130a locking is made can not move.Move so that when leaving pond D1 when roller 130b rotation and along the direction of arrow, the solution pressure in the D1 of pond can reduce.
Fig. 8 A is the key diagram of expression second embodiment relevant with cartridge for chemical reaction and driving mechanism to 8D.
Fig. 8 A, 8B and 8C represent the state variation when the direction of arrow moves along with roller 132a, 132b and 132c.Dash area represents to exist solution.Though this embodiment represents the zero volume structure and is used as the situation of pool structure, also can use the structure that is provided with the exhaust passage.
In Fig. 8 A, be respectively arranged with flow channel 133a and 133b among pond E1 and the E2 as the solution inlet.Pond E1 is connected to pond E3 by flow channel 133c.Pond E2 is connected to pond E3 by flow channel 133d.Pond E3 is provided with the flow channel 133e as taphole.Pond E1 and E2 are in alignment with each other, thereby can be by a roller while delivered solution.
Roller 132a stops up flow channel 133a and 133b.Roller 132b stops up flow channel 133c and 133d.As a result, can prevent that the solution in pond E1 and the E2 from flowing among the E3 of pond.
Fig. 8 B represents that roller 132a, 132b and 132c move, and make roller 132a be positioned on pond E1 and the E2, and roller 132b is positioned at the state on the E3 of pond.Solution in pond E1 and the E2 is extruded by roller 132a, thereby is in the pond and flow channel between roller 132a and the 132b, shown in dash area among the figure.
Fig. 8 C represents that roller 132a, 132b and 132c (132c is not shown) are moved further, and make roller 132a be positioned on flow channel 133c and the 133d, and roller 132b are positioned at the state on the flow channel 133e.All solution among pond E1 and the E2 are extruded by roller 132a, so that flow among the E3 of pond, shown in dash area among the figure.
Because roller 132a stops up flow channel 133c and 133d, can prevent that therefore the solution among the E3 of pond from refluxing.Simultaneously, because roller 132b stops up flow channel 133e, therefore can prevent that the solution among the E3 of pond from flowing in the next pond (not shown).
Owing to used the such structure of solution entrance and exit of stopping up each pond, therefore,, can prevent that also solution from flowing out from the pond even the solution that is stored in the pond is applied under the situation of effect from the heat or the vibration of box outside.
Though this embodiment represents the situation that two solution in the pond move in the pond and mix mutually in this pond, but, certainly the present invention also can be applied to solution is transported to the situation in another pond from a pond, thereby perhaps is applied to be provided with the situation that two or more ponds of containing solution to be mixed can make two or more solution mix.
Shown in Fig. 8 D, the present invention can be applied to the solution in the pond is assigned to two situations in the pond.In Fig. 8 D, the operation of each roller is identical to the operation of the roller shown in the 8C with Fig. 8 A.
In Fig. 8 D, the solution among the E4 of pond is extruded by the mobile of roller 132e, and is assigned to pond E5 and E6 through flow channel 133f and 133g.Because flow channel 133f and 133g are stopped up by roller 132e, flow channel 133h and 133i are stopped up by roller 132f simultaneously, can prevent that therefore solution from flowing out pond E5 and E6.
Though this embodiment represents that the outflow of solution is parallel to the positive roller that moves of box and stops up, and also can use such as at the blocking device that moves perpendicular to the box frontal, as flashboard, is used to stop up flow channel.
Fig. 9 A is the key diagram of expression three embodiment relevant with cartridge for chemical reaction and driving mechanism to 9E.To extract this embodiment of explanation under the XC polymer situation as an example, described XC polymer for example is DNA (DNA (deoxyribonucleic acid)), RNA (RNA (ribonucleic acid)), protein or sugar chain.
In 9E, be provided with pond F1 in the box at Fig. 9 A to F13.Pond F6 is connected to pond F9 as common pool to F8.Pond F6 forms a line in the left side of pond F9 to F8.Pond F1 and F2 are connected to the pond F6 as common pool.Pond F1 and F2 form a line in the left side of pond F6.Pond F3 and F5 are arranged in the same column that pond F1 and F2 lined up.Pond F3 connection pool F7, pond F5 connection pool F8.Pond F4 connection pool F5 is positioned at the left side of pond F5.
Pond F10 connection pool F9 is positioned at the right side of pond F9.Pond F11 is in line to F13, forms cascade with pond F10.
Go up equidistantly to arrange at horizontal direction (roller moving direction) in these ponds.Roller (representing with 134c for convenience) with reference number 134a, 134b with identical equidistantly the arranging of horizontal spacing in pond.
Additional disclosure, similar pond pattern is represented similar content.Though this embodiment represents to use the zero volume structure as pool structure, also can use the structure that is provided with the exhaust passage.Though this embodiment represents to use roller as pressures partially, also can use the piston-type actuator.
Fig. 9 A represents roller is set at the state that aligns with the entrance and exit in pond.Sample solution is pre-installed among the F1 of pond, and solvent soln is pre-installed among the F2 of pond, and DNA capture material (magnetic of surface modification) is pre-installed among the F3 of pond, and cleaning solution is pre-installed among the F4 of pond.Other pond is in the zero volume state.
Each roller rotates and moves along the solid arrow direction.Roller 134a, 134b and 134c push down the entrance and exit of pond F1 to F5, thereby prevent to flow out such as the fluid of sample solution.
Fig. 9 B represents each roller rotation and moves the state of the distance in a pond along the direction of arrow.Therefore, along with moving of roller 134b, the solvent soln among sample solution among the F1 of pond and the pond F2 mixes in the F6 of pond mutually, and the capture material among the F3 of pond flows into pond F7 simultaneously.
Along with moving of roller 134a, the cleaning solution among the F4 of pond flows into pond F5.Pond F7, F5 and F8 the time are the sky ponds in beginning, and regulate the timing that capture material and cleaning solution is transported to pond F9 as vacant pond.The existence of pond F7, F5 and F8 makes along with roller only moves on an axis and target solution is transported to arbitrary timing becomes possibility in the object pool.
In the F6 of pond, carry out the step of heating mixed solution to react.For example, use peltier-element (Peltier element) heating mixed solution.
Additional disclosure, the volume settings in each vacant pond are the volume that equals initially to be equipped with the pond of solution.
Each roller of state shown in Fig. 9 C presentation graphs 9B moves the state of the distance in a pond along direction of arrow rotation.Therefore, along with moving of roller 134b, the mixed solution among the F6 of pond mixes mutually in the F9 of pond with DNA capture material among the F7 of pond.Along with moving of roller 134a, the cleaning solution among the F5 of pond enters pond F8.
In the F9 of pond, DNA is trapped in the DNA capture material, and simultaneously the effect owing to magnetic field rests among the F9 of pond as the magnetic of capture material itself.
Each roller of state shown in Fig. 9 D presentation graphs 9C moves the state of the distance in a pond along direction of arrow rotation.Therefore, along with moving of roller 134b, the waste liquid in the F9 of pond after the capture dna enters pond F10.Along with moving of roller 134a, the cleaning solution among the F8 of pond enters pond F9.In the F9 of pond, cleaning solution cleans magnetic.
Each roller of state shown in Fig. 9 E presentation graphs 9D moves the state of the distance in a pond along direction of arrow rotation.Therefore, along with moving of roller 134b, the waste liquid among the F10 of pond enters pond F11.Along with moving of roller 134a, the cleaning solution after the service sink F9 enters pond F10.
As mentioned above, the DNA that is trapped in the magnetic is accumulated among the F9 of pond, thereby can extract DNA.
In addition, pearl, filtrator, post or the like can be used for capture dna.The example of pearl comprises silicon dioxide, magnetic beads, bead and resin bead.
Above-mentioned solution conveying mechanism is similar to the action of the shift register of digital circuit.This solution structure for conveying can be called " clock-type solution structure for conveying ".Be with the difference of electronic system: flow channel is to be provided with separately, is cleaned contaminated aqueous solution (mixing) because must prevent solvent soln.
Figure 10 A is the key diagram of expression four embodiment relevant with cartridge for chemical reaction and driving mechanism to 10C.
Figure 10 A imports solution to the inlet that 10C represents box 135 by this inlet.In Figure 10 A, inlet 137 is provided with the U-shaped passage, be used for direct solution flows to box from the outside of box 135 inside, and direct solution flows to the outside of container from the inside of box.U-shaped inlet 137 is connected to flow channel 138, is used for the processing of box 135 inside.No matter whether have solution, inlet 137 all has predetermined volume.Flow channel 138 has aforesaid zero volume structure.
Solution is injected into by syringe 136 and injects part 140a.Inject the side of part 140a at inlet 137.Come into existence and extruded by solution, discharge thereby make air inject part 140b, shown in the solid line arrow from another in the air of inlet 137.
Then, shown in Figure 10 B, roller 139a and 139b make injection part 140a and 140b be stopped up by roller 139a simultaneously, and flow channel 138 are stopped up from top extrusion box 135 by roller 139b.The rotation of two rollers is also moved along the dotted arrow direction, enters into flow channel 138 so that the 137 interior solution that will enter the mouths are extruded, shown in the solid line arrow.
Can prevent solution and air mixed by this way.And, the solution of scheduled volume in the U-shaped part can be transported in the box.
In addition, shown in Figure 10 C, part attenuation gradually can be injected towards each in the box surface of inlet 137.In this case, inlet 137 can easily be stopped up by roller 139a, thereby can prevent solution and air mixed.
Figure 11 A is the key diagram of expression five embodiment relevant with cartridge for chemical reaction and driving mechanism with 11B.
Figure 11 A and 11B represent the inlet of box.In Figure 11 A, inlet 141 connects dome type pond G1 by flow channel 144a.Pond G1 is also connected to and is used for solution is transported to flow channel 144b in the box.
Though this embodiment represents to use the situation of zero volume structure as flow channel structure, also can use the structure that is provided with the exhaust passage to substitute.Though use roller as pressures partially, also can use the piston-type actuator to substitute.
Roller 143a moves to the left side from the right side of pond G1 earlier, so that the air in the dome is emitted from 141 1 sides that enter the mouth.Roller 143a extruding is also stopped up flow channel 144a.Under this state, a large amount of sample solutions 142 inject inlet 141.Then, roller 143a moves along the direction of arrow, thus extruding pond G1.Because along with the effort through pond G1 of roller 143a recovers its virgin state, so solution 142 is inhaled among the G1 of pond.As a result, in can solution suction pit G1 with scheduled volume.When roller 143a also pushed through pond G1 and stops up flow channel 144b, flow channel 144a was also stopped up in roller 143b extruding.
As mentioned above, a part remains in inlet 141 with the solution of air mixed, thereby can prevent that air from entering in the solution.And, the initial amount of the solution of scheduled volume as reaction can be provided.
Additional disclosure, this inlet can with above-mentioned U-shaped inlet associating use.The box surface structure of inlet can be by the mode gradually attenuation identical with U-shaped inlet.
Figure 12 A is the key diagram of expression six embodiment relevant with cartridge for chemical reaction and driving mechanism with 12B.
This embodiment will describe under extraction XC polymer situation as an example, and described XC polymer for example can be DNA, RNA, protein, metabolin or sugar chain.
In Figure 12 A and 12B, sample mix solution such as blood and solvent soln is contained among the H1 of pond, DNA capture material such as silicon dioxide and amino magnetic (magnetic of surface modification) is contained among the H2 of pond, waste liquid is contained among the H3 of pond, extract solvent and be contained among the H4 of pond, the solution that extracted DNA is contained among the H5 of pond.
Arrange in the mode of right-angled intersection in these ponds, makes at least two kinds of different solution to flow into the common pool with at least two outlet flow channels from the moving passage of various flows.This box has such decussate texture: wherein common pool is positioned at central authorities, and other pond arranges radially and be connected with common pool by flow channel that from common pool this box drives as follows:
(1) catches step
The DNA that is contained among the H1 of pond has negative electricity, and the silicon dioxide and the amino magnetic that are among the H2 of pond have positive electricity.Based on this reason, when solution when pond H1 is transported to pond H3, DNA is hunted down (seizure) in the H2 of pond.Residual solution is transported among the H3 of pond as waste liquid.
(2) drain steps
After catching step with the extraction solvent delivery among the H4 of pond in the H2 of pond when regulating pH value and temperature, DNA breaks away from from capture material.DNA is transported to pond H5, thereby obtains extracting the solution of DNA.
In this step, from the situation that pond H1 is transported to pond H3, must prevent that solution is transported among pond H4 and the H5 for solution.From the situation that pond H4 is transported to pond H5, must prevent that solution is transported to pond H1 and H3 for solution equally.
Based on this reason, when the solution among the H1 of pond was transported to pond H3, the flow channel that leads to pond H4 and H5 was stopped up by flashboard 145a and 145b, shown in Figure 12 A.And when the solution among the H4 of pond was transported to pond H5, the flow channel of pond H1 and H3 was by the obstruction of flashboard 145c and 145d, shown in Figure 12 B.Additional disclosure, each flashboard can be the rollers of delivered solution.
Though this embodiment represents to use the situation of zero volume structure as the structure of each pond and flow channel, also can use the structure that is provided with the exhaust passage to substitute.Though not shown roller in order to delivered solution, also can use the piston-type actuator to substitute as pressures partially.
Pearl, filtrator, post, fiber or the like can be used as magnetic.The example of pearl comprises silicon dioxide, magnetic beads, bead and resin bead.
As mentioned above, for example, can be implemented in PCR (polymer chain reaction) amplify after by using silicon dioxide, magnetic or similar substance extracts nucleic acid from sample and the structure (decussate texture) of purify (for example, products of separated from unreacting substance).
Figure 13 A is the key diagram of expression seven embodiment relevant with cartridge for chemical reaction and driving mechanism with 3B.
This embodiment also can realize catching step and drain steps.
In Figure 13 A and 13B, be contained among the I1 of pond such as the sample mix solution of blood and solvent soln.DNA capture material such as silicon dioxide, amino magnetic (magnetic of surface modification) etc. is contained among the I2 of pond.Waste liquid is stored among the I3 of pond, extracts solvent and is contained among the I4 of pond, and the solution that extracted DNA is contained among the I5 of pond.Pond I1, I3, I4 and I5 are connected to pond I2 by flow channel.Be provided for applying the roller of external force,, and stop up the flow channel that is not used in delivered solution so that solution passes through particular pool or flow channel is carried.The arrangement in this pond is right-angled intersection, so that at least two kinds of different solutions flow into the common pool with at least two outlet flow channels from the moving passage of various flows.
Specifically, as shown in FIG. 13A, roller 146a and 146b rotate and move along the direction of arrow, thereby the solution among the I1 of pond is extruded solution is transported to pond I2.Dash area represents to come by it passage of delivered solution.At this moment, roller 146b stops up and makes pond I2 and I4 interconnect and make pond I2 and the interconnective flow channel of I5.Therefore, after the XC polymer in the sample was trapped in pond I2, the solution that is transported to pond I2 was transported to pond I3 as waste liquid.
When roller 146a and 146b further moved to position shown in Figure 13 B, roller 146a extruded the extraction solvent among the I3 of pond and stop up and makes pond I2 and I1 interconnect and make pond I2 and the interconnective flow channel of I3.Based on this reason, the extraction solvent among the I4 of pond is transported to pond I2.In the I2 of pond, DNA breaks away from from capture material.The extraction that obtains thus the solution of DNA be transported to pond I5.Though this embodiment represents to use the situation of zero volume structure as pool structure, also can use the structure that is provided with the exhaust passage to substitute.Though use roller as pressures partially, also can use the piston-type actuator to substitute.
As mentioned above, for example, although this is a kind of simple structure, also can be implemented in PCR amplify after by using silicon dioxide, magnetic or similar substance extracts nucleic acid from sample and the structure (decussate texture) of purify (for example, products of separated from unreacting substance).
Figure 14 A is the key diagram of expression eight embodiment relevant with cartridge for chemical reaction and driving mechanism to 14C.
This embodiment can realize that also XC polymer catches step and drain steps.
, in 14C, be contained among the J1 of pond at Figure 14 A such as the sample mix solution of blood and solvent soln.DNA capture material such as silicon dioxide, amino magnetic (magnetic of surface modification) etc. is contained among the J2 of pond.Waste liquid is stored among the J3 of pond, extracts solvent and is contained among the J4 of pond.The solution that extracted DNA is contained among the J5 of pond.Pond J1, J3, J4 and J5 are connected to pond J2 by flow channel.Layout is used to apply the roller of external force, so that one of these rollers are transported to solution in particular pool or the flow channel, and other roller stops up the flow channel that is not used for delivered solution.The layout in these ponds is right-angled intersections, thereby at least two kinds of different solutions flow into the common pool with at least two outlet flow channels from the moving passage of various flows.
These ponds have projection 176a to 176h in the part of touch roll, and described roller applies external force from the box container outside.Two interconnected each flow channels in pond are formed on recess between the projection in two ponds.
Additional disclosure, projection can be formed on the box or on the roller.When two ponds were pushed by a roller, projection can have such structure, and promptly projection does not extend to flow channel, thereby does not stop up flow channel.
Though this embodiment represents to use the situation of zero volume structure as pool structure, also can use the structure that is provided with the exhaust passage to substitute.Though use roller as pressures partially, also can use the piston-type actuator to substitute.
Specifically, shown in Figure 14 A, roller 147a rotates and moves along the direction of arrow, pushes projection 176a and 176b simultaneously.As a result, the solution among the J1 of pond is extruded, so that be transported to pond J2.Dash area is represented S shape flow channel, by this flow channel delivered solution.At this moment, roller 147b stops up and is positioned at projection 176d below and makes pond J2 and J4 be connected to each other and make pond J2 and the interconnected flow channel of J5.Therefore, after the XC polymer of sample solution in sample that is transported to pond J2 is trapped in pond J2, be transported among the J3 of pond as waste liquid.
When roller 147a and 147b further moved to position shown in Figure 14 B, roller 147b extruded the extraction solvent among the J4 of pond.At this moment, roller 147a stops up and is positioned at projection 176a below and makes pond J2 and J1 be connected to each other and make pond J2 and the interconnected flow channel of J3.Based on this reason, the extraction solvent among the J4 of pond is transported among the J2 of pond.In the J2 of pond, DNA breaks away from from capture material.With the extraction that so obtains the solution of DNA be transported to pond J5.
Though Figure 14 A and 14B are illustrated in the situation that S shape flow channel is set between the pond, also can use the flow channel in the outside, pond shown in Figure 14 C to substitute.
As mentioned above, for example, can be implemented in PCR amplify after by using silicon dioxide, magnetic or similar substance extracts nucleic acid from sample and the structure (decussate texture) of purify (for example, products of separated from unreacting substance).
Figure 15 A is the key diagram of expression nine embodiment relevant with cartridge for chemical reaction and driving mechanism to 15C.
This embodiment can realize that also XC polymer catches step and drain steps.
, in 15C, be contained among the K1 of pond at Figure 15 A such as the sample mix solution of blood and solvent soln.DNA capture material such as silicon dioxide, amino magnetic (magnetic of surface modification) etc. is contained among the K2 of pond.Waste liquid is stored among the K3 of pond, extracts solvent and is contained among the K4 of pond, and the solution that extracted DNA is contained among the K5 of pond.
Though this embodiment represents to use the situation of zero volume structure as pool structure, also can use the structure that is provided with the exhaust passage to substitute.Though use roller as pressures partially, also can use the piston-type actuator to substitute.Pond K1, K3, K4 and K5 are connected to pond K2 by flow channel.The layout in these ponds is intersected, thereby at least two kinds of different solutions flow into the common pool with at least two outlet flow channels from the moving passage of various flows.Except through (leading to common pool) the input and output side of any other flow channel the flow channel of common pool simultaneously by a roller obstruction.
Specifically, shown in Figure 15 A, roller 148a rotates and moves along the direction of arrow, the solution among the K1 of pond is extruded and this solution is transported to pond K2.Dash area represents to come by it passage of delivered solution.At this moment, roller 148c stops up and makes pond K4 and the interconnective flow channel of K5 by pond K2, and described roller 148c shape is as wheel and have the structure of pressurizeing in the opposite end.Therefore, after the XC polymer of sample solution in sample that is transported to pond K2 is trapped in pond K2, be transported among the K3 of pond as waste liquid.
Then, roller 148c moves after on the axis identical with 148b with roller 148a, and obstruction makes pond K2 and K1 interconnect and make pond K2 and the interconnective flow channel of K3.When roller 148a and 148b further moved to position shown in Figure 15 B, roller 148a extruded the extraction solvent among the K4 of pond.Therefore, with the extraction solvent delivery among the K4 of pond in the K2 of pond.In the K2 of pond, DNA breaks away from from capture material.The extraction that obtains thus the solution of DNA be transported among the K5 of pond.
If the flow channel that is used for delivered solution unlike Figure 15 A be parallel shown in the 15B, but intersect, then roller 148c can not parallelly move, but rotates shown in Figure 15 C, to change blocked flow channel.
As mentioned above, for example, can be implemented in PCR and use silicon dioxide, magnetic or similar substance from sample, to extract nucleic acid after amplifying and the structure (decussate texture) of purify (for example, products of separated from unreacting substance).
Figure 16 A is the key diagram of expression ten embodiment relevant with cartridge for chemical reaction and driving mechanism to 16E.
This embodiment can realize that also XC polymer catches step and drain steps.
, in 16E, be contained among the L1 of pond at Figure 16 A such as the sample mix solution of blood and solvent soln.DNA capture material such as silicon dioxide, amino magnetic (magnetic of surface modification) etc. is contained among the L2 of pond.Waste liquid is stored among the L3 of pond, extracts solvent and is contained among the L4 of pond, and the solution that extracted DNA is contained among the L5 of pond.
Though this embodiment represents to use the situation of zero volume structure as pool structure, also can use the structure that is provided with the exhaust passage to substitute.Though use roller as pressures partially, also can use the piston-type actuator to substitute.
Pond L1, L3, L4 and L5 are connected to pond L2 by flow channel.The layout in these ponds is intersected, thereby at least two kinds of different solutions flow into the common pool with at least two outlet flow channels from the moving passage of various flows.(leading to common pool) input and output side of any other flow channel except the flow channel that passes common pool is stopped up by a roller simultaneously.A kind of decussate texture is provided, and wherein common pool is arranged in central authorities, and other pond is arranged radially and is connected with common pool by flow channel from common pool.
Be used on the different axis directions on box surface, moving respectively, as vertical direction (Y) and horizontal direction (X) by the roller of flow channel delivered solution.
Specifically, shown in Figure 16 A, roller 149a and 149b rotation is also moved along the direction of arrow, so that the solution among the L1 of pond is extruded, and this solution is transported to pond L2.Dash area represents to come by it passage of delivered solution.At this moment, roller 149c stops up and makes pond L2 and the interconnective flow channel of L4, and roller 149d obstruction makes pond L2 and the interconnective flow channel of L5.Therefore, after the XC polymer of sample solution in sample that is transported to pond L2 is trapped in pond L2, be transported among the L3 of pond as waste liquid.
Then, roller 149c moves near pond L4 inlet (not shown), so that the extraction solvent among the L4 of pond is extruded.To make pond L1 and the interconnective flow channel of L2 and make pond L3 and the interconnective flow channel of L2 in order to stop up, roller 149a and 149b move to flow channel.
When roller 149c and 149d when the direction of arrow shown in Figure 16 B moves, the extraction solvent among the L4 of pond is transported among the L2 of pond.In the L2 of pond, DNA breaks away from from capture material.The extraction that obtains like this solution of DNA be transported among the L5 of pond.At this moment, if desired, roller 149c can move with the surface from box and leave once.
On the other hand, roller can be designed to the structure shown in Figure 16 C,, further is transported to the L2 of pond from pond L4 by roller 149c and 149d from the solution that pond L6 is transported to pond L4 and L7 by roller 149e and 149f.
Shown in Figure 16 D, the quantity of flow channel intersected with each other can be three or more.Angle between the adjacent flow channels needs not to be 90 °.In addition, in this embodiment,, then can provide a kind of structure that makes one of described roller place opposite side (the box back side), shown in Figure 16 E if roller collides each other.In Figure 16 E, box 150 has elastic body 151a and the 151b that is made by airtight elastic caoutchouc or similar substance, and the flat matrix of being made by rigid material 152.Matrix 152 is clipped between elastic body 151a and the 151b and combination with it.Between elastic body 151a and the matrix 152 and between elastic body 151b and matrix 152 flow channel 156a and 156b are being set respectively.These flow channels are the flow channels that pass common pool.
Matrix 152 is provided with through hole 153, makes flow channel 156a and 156b be connected to each other by through hole 153.154 1 sides have roller 149m in the front of box 150, so that by flow channel 156a delivered solution.155 1 sides are provided with roller 149n at the back side of box 150, so that by flow channel 156b delivered solution.Therefore, never collision mutually of roller 149m and 149n.
Additional disclosure can be used viscoelastic body or plastomer elastic body 151a and the 151b as box.
Glass, metal, rigid resin or elastic body can be used as the material of matrix 152.By bonding or by other means (for example attract (as, between PDMS and the glass), ultrasonic Treatment, heating, plasma adhesion process or Vibration Welding), elastic body 151a and 151b and matrix 152 can be bonded to each other.
As mentioned above, for example, can be implemented in PCR amplify after by using silicon dioxide, magnetic or similar substance extracts nucleic acid from sample and the structure (decussate texture) of purify (for example, products of separated from unreacting substance).
Figure 17 A is the key diagram of expression ten one embodiment relevant with cartridge for chemical reaction and driving mechanism to 17G.
This embodiment can realize that also XC polymer catches step and drain steps.Additional disclosure, this embodiment also can describe to extract under the DNA situation as an example.
In 17G, sample 158 is the sample mix solution such as blood and solvent soln at Figure 17 A, and it is contained among the M1 of pond.DNA capture material 159 such as silicon dioxide, amino magnetic (magnetic of surface modification) etc. is contained among the M2 of pond.Capture material is fixed among the M2 of pond by the magnetic force that is arranged at outside magnet.Extracting buffer solution 160 is contained among the M3 of pond.Pond M1 and M3 are connected to pond M2 by flow channel, and are arranged so that one of described roller applies the solution that external force is carried particular pool or flow channel, and other roller stops up the flow channel that is not used for delivered solution simultaneously.These pond cross arrangements are passed common pool for use in the flow channel of delivered solution with blocked flow channel.Pass the flow channel line spread of common pool, so that with the common pool be center and close to each other.The a plurality of pressures partiallies that solution are transported to flow channel respectively move on the arranging line of the flow channel on box surface.
Though not shown, be used to inject the flow channel of sample and be separately positioned on pond M1 and M3 as the flow channel that extracts products export.Specifically, the state variation shown in Figure 17 A is to state shown in Figure 17 G.Shown in Figure 17 A, roller 157a stops up the inlet of pond M1, and roller 157b stops up and makes pond M1 and the interconnective flow channel of M2, and roller 157c stops up the outlet of pond M3.
Roller 157a and 157b rotate and move along the direction of arrow.Roller 157a extrudes the sample among the M1 of pond 158, then stops up the flow channel of connection pool M1 and M2.Roller 157b begins to move to stop up the passage of connection pool M2 and M3 from making the interconnective flow channel of pond M1 and M2.As a result, the sample delivery among the M1 of pond is arrived pond M2.
Then, shown in Figure 17 B, roller 157a moves back to (along the direction of arrow) its original position.When this moved back and forth when repetition, sample 158 and capture material were mixed with each other in the M2 of pond effectively.Like this, finished DNA has been captured step in the magnetic.When catching step when finishing, roller 157a returns initial position, and roller 157b stops up the flow channel (Figure 17 C) of connection pool M2 and M3.
Then, shown in Figure 17 D, roller 157b and 157c move along the direction of arrow.Roller 157b returns its original position (shown in Figure 17 A), pushes pond M2 simultaneously, thereby removes a part of sample 158 remaining among the M2 of pond.Roller 157c extrudes the extraction buffer solution 160 among the M3 of pond, will extract buffer solution 160 and be transported among the M2 of pond, and obstruction makes pond M2 and the interconnective flow channel of M3 (Figure 17 E).In this state, when keeping M2, carry out DNA and break away from processing.
When finishing DNA disengaging processing, roller 157b and 157c move (opposite with direction shown in Figure 17 D) along the direction of arrow shown in Figure 17 F.Roller 157b extrudes the extraction product among the M2 of pond and then stops up and makes pond M2 and the interconnective flow channel of M3.Roller 157c begins to move from making the interconnective flow channel of pond M2 and M3, and returns initial position (Figure 17 G).As a result, extract product and be transported to pond M3.Like this, finish the DNA extraction step.
Figure 18 A is the key diagram of expression ten two embodiment relevant with cartridge for chemical reaction and driving mechanism to 18F.
This embodiment can realize that also XC polymer catches step and drain steps.Additional disclosure, this embodiment also can describe under with extraction DNA situation as an example, and is similar with the 11 embodiment.
In 18F, sample 162 is the sample mix solution such as blood and solvent soln at Figure 18 A, and sample 162 is contained among the N1 of pond.DNA capture material 163 such as silicon dioxide, amino magnetic (magnetic of surface modification) etc. is contained among the N2 of pond.Capture material is fixed among the N2 of pond by the magnetic force that is arranged at outside magnet.Extracting buffer solution 164 is contained among the N3 of pond.Pond N1 and N3 are connected to pond N2 by flow channel, and are disposed such the solution that one of feasible roller that applies external force is carried particular pool or flow channel, and other roller stops up the flow channel that is not used for delivered solution.These pond cross arrangements are passed common pool for use in the flow channel of delivered solution with blocked flow channel.Pass the flow channel line spread of common pool, so that with the common pool be center and close to each other.The a plurality of pressures partiallies that solution are transported to flow channel respectively move on the arranging line of box surface flow passage.Though not shown, be used to inject the flow channel of sample and be separately positioned on pond N1 and N3 as the flow channel that extracts products export.
Concretely, the state variation shown in Figure 18 A is to state shown in Figure 18 F.Shown in Figure 18 A, roller 161a stops up the inlet of pond N1, and roller 161b stops up and makes pond N1 and the interconnective flow channel of N2, and roller 161c stops up the outlet of pond N3.
Roller 161a and 161b rotate and move along the direction of arrow.Roller 161a extrudes the sample among the N1 of pond 162, then stops up the flow channel of connection pool N1 and N2.Roller 161b begins to move to stop up the flow channel of connection pool N2 and N3 from making the interconnective flow channel of pond N1 and N2.As a result, the sample among the N1 of pond 162 is transported to pond N2.
Then, shown in Figure 18 B, roller 161a and 161b move back to (along the direction of arrow) its original position.When this moved back and forth when repetition, sample 162 and capture material 163 were mixed with each other in the M2 of pond effectively.Like this, finish DNA is captured operation in the magnetic.When finishing when catching step, roller 161a and 161b return initial position (Figure 18 C).As a result, remove the also dry sample that remains among the N2 of pond.
Then, shown in Figure 18 C, roller 161c moves along the direction of arrow.Roller 161c extrudes the DNA buffer solution 164 among the N3 of pond, DNA buffer solution 164 is transported among the N2 of pond, and obstruction makes pond N2 and the interconnective flow channel of N3 (Figure 18 D).In this state, when keeping N2, carry out DNA and magnetic disengaging processing.
When the DNA disengaging was finished dealing with, roller 161b and 161c moved (opposite with direction shown in Figure 18 C) along the direction of arrow shown in Figure 18 E.Roller 161b extrudes the extraction product among the N2 of pond and then stops up and makes pond N2 and the interconnective flow channel of N3.Roller 161c begins to move from making the interconnective flow channel of pond N2 and N3, and returns initial position (Figure 18 F).As a result, extract product and be transported to pond N3.Like this, the DNA extraction step is finished.
Figure 19 A is the key diagram of expression ten three embodiment relevant with cartridge for chemical reaction and driving mechanism to 19C.This embodiment describes under extraction XC polymer situation as an example, and XC polymer wherein for example is DNA, RNA, protein or sugar chain.
In 19C, be provided with pond 01 to 023 at Figure 19 A in the box.Pond 01 to 014 is arranged on epimere P1, and pond 07 to 09 is connected to that 010 left side forms a line as the pond 010 of common pool and in the pond.Pond 01 and 02 is connected to that 07 left side forms a line as the pond 07 of common pool and in the pond.Pond 03 comes in the identical row with pond 01 and 02 with 06.Pond 03 is connected to pond 08, and pond 06 is connected to pond 09.Pond 05 and 04 is connected to pond 06 step by step, thereby 06 left side is arranged in delegation in the pond.
Pond 011 is connected to pond 010, so that come the right side in pond 010.Pond 012 to 014 is connected to pond 011 step by step, thereby is in line.These ponds in a lateral direction (roller moving direction) equidistantly to arrange.Arrange with the intervals identical with the roller that dash area is represented with the horizontal spacing in pond.Pond 015 to 023 is arranged at hypomere P2, and is so that equidistantly to be in line, consistent with the upright position in epimere pond.Pond 019 and 020 is connected to pond 010.The arrangement position in pond 019 is corresponding to the row in pond 07 to 09.The arrangement position in pond 020 is corresponding to the row in pond 011.010 below, pond is provided with a space.Arrange step by step in this left side, space in pond 019 to 015, and arrange step by step on this right side, space in pond 020 to 023.
The roller of epimere P1 and hypomere P2 is arranged with the intervals identical with the horizontal spacing in pond, and stops up the flow channel of connection pool respectively.Though this embodiment represents to use the situation of zero volume structure as the structure in pond, also can use the structure that is provided with the exhaust passage to substitute.Though use roller as pressures partially, also can use the piston-type actuator to substitute.
In Figure 19 A, sample solution is contained in the pond 01, and solvent soln is contained in the pond 02, and DNA capture material (magnetic of surface modification) is contained in the pond 03, and cleaning solution is contained in pond 04 and 05, extracts buffer solution and is contained in the pond 015.The volume in any other pond is zero.
In Figure 19 A, each roller among the epimere P1 rotates and moves along the solid arrow direction.Along with moving of roller, what mobile and Fig. 9 A of the material of adorning described in the 9E in the pond in is identical, and the general is brief description below.But, because cleaning solution is contained in pond 04 and 05, so pond 010 is cleaned twice.
When the roller among epimere P1 rotation and along the direction of arrow move a pond apart from the time, the solvent soln in sample solution in the pond 01 and the pond 02 mixes in pond 07 mutually.Capture material in the pond 03 moves to pond 08.Cleaning solution in the pond 04 and 05 moves in pond 05 and 06.
In pond 07, mixed solution is heated and carries out course of reaction.For example, use peltier-element heating mixed solution.
When roller be further rotated and along the direction of arrow move a pond apart from the time, the DNA capture material in mixed solution in the pond 07 and the pond 08 is mixed with each other in pond 010.Cleaning solution in the pond 05 and 06 moves to pond 06 and 09.
In pond 010, DNA is captured in the DNA capture material.The magnetic field that is applied in as the magnetic of capture material itself is captured in the pond 010.
When roller be further rotated and along the solid arrow direction move a pond apart from the time, the waste liquid after the DNA that has been hunted down in pond 010 moves in the pond 011, the cleaning solution in the pond 09 moves in the pond 010, the cleaning solution in the pond 06 moves to pond 09.In pond 010, utilize the magnetic cleaning solution to carry out and clean, this is as first clean cycle.
When roller be further rotated and along the direction of arrow move a pond apart from the time, the waste liquid in the pond 011 moves to pond 012.Cleaning solution after cleaning in the pond 010 moves to pond 011.The cleaning solution of second clean cycle is transported in the pond 010.Along with moving of roller next time, from pond 010, shift out cleaning solution.The cleaning solution 167a of first clean cycle is transported in the pond 012, and the cleaning solution 167b of second clean cycle is transported in the pond 011.
As a result, the magnetic 166 that wherein contains captive DNA is retained in the pond 010, thereby can extract DNA.With aforesaid operations side by side, the roller of hypomere P2 is along the same moved further of roller of solid arrow direction and epimere P1.Extracting buffer solution 165 moves in the pond 019, shown in dotted arrow.
It is the sky pond that additional disclosure, pond 016 to 018 begin, and it extracts the vacant pond that buffer solution 165 is transported to the timing in pond 010 as regulating.The existence in vacant pond makes regularly becomes possibility according to the single shaft of roller to moving at random regulator solution to carry.
On the point, two clean cycle in the pond 010 are finished at this moment.Cleaning solution shifts out from pond 010.Then, the locking of the roller group of epimere P1 only has the roller group of hypomere P2 to move.As a result, the extraction buffer solution in the pond 019 of hypomere P2 is transported to pond 010, shown in dotted arrow.In pond 010, DNA spin off (Figure 19 B).
At this, the roller group of epimere P1 and hypomere P2 moves simultaneously.As a result, the extraction in the pond 010 the solution 168 (product) of DNA be transported in the pond 020.Like this, the DNA extraction step is finished (Figure 19 C).The shift register of above-mentioned solution conveying mechanism and digital circuit or the action of similar device are similar.Therefore, can think that generally the mobile of roller group is clock-type.
Figure 20 is the key diagram of expression ten four embodiment relevant with cartridge for chemical reaction and driving mechanism.This embodiment disposes by this way: the arrangement of the roller that dash area among the 13 embodiment (Figure 19 A is to 19C) is represented changes tertiary structure into by two-layer configuration, add stage casing P3 to equally spaced roller group, the column position in pond 010 is in stage casing P3, and the horizontal level relation does not become.Arrange with the intervals identical with the roller among the hypomere P2 at epimere P1, and stop up the flow channel of connection pool respectively with the horizontal spacing in pond.
In Figure 20, sample solution is contained in the pond 01, and solvent soln is contained in the pond 02, and DNA capture material (magnetic of surface modification) is contained in the pond 03, and cleaning solution is contained in pond 04 and 05, extracts buffer solution and is contained in the pond 015, and the volume in any other pond is zero.
Though this embodiment represents to use the situation of zero volume structure as the structure in pond, also can use the structure that is provided with the exhaust passage to substitute.Though use roller as pressures partially, also can use the piston-type actuator to substitute.Every grade roller moves the distance in 5 ponds along the solid arrow direction.As a result, the mixed solution of sample solution and solvent soln and DNA capture material are transported in the pond 010.DNA is trapped in the magnetic.Cleaning solution 167a and 167b are transported in the pond 010.After the cleaning, cleaning solution 167a and 167b are transported in pond 011 and 012.As a result, there is the magnetic 166 that contains captive DNA in the pond 010.
At this moment, because the roller of hypomere P2 moves by mode same as described above, shown in dotted arrow, the extraction buffer solution 165 in the pond 015 moves to pond 019.Then, when the roller group of epimere P1 stopped, the roller group of stage casing P3 and hypomere P2 moved the distance in a pond along the solid arrow direction.Extraction buffer solution 165 in the pond 019 is transported to pond 010, thereby DNA is spun off from capture material.Then, the roller group of stage casing P3 and hypomere P2 moves the distance in a pond again.The extraction that obtains thus the solution of DNA 010 be transported to pond 020 from the pond.
As mentioned above, because the flow channel that pond 010 and pond 07,08,09 are connected with 011 is stopped up by the roller of epimere P1 in the DNA extraction step, can prevent that therefore DNA from being polluted (mixing) by the residual solution of DNA capture material and cleaning solution.
Figure 21 A is the key diagram of expression ten five embodiment relevant with cartridge for chemical reaction and driving mechanism to 21C.
In Figure 21 A, arrange with Width along its length in the pond that vertical line is represented, makes to interconnect by flow channel at length direction and Width pond adjacent one another are.In this arrangement architecture, independently arrange with the roller that dash area is represented, all be clipped between the adjacent roller in every row or every row with urinal.The roller group of Z-axis (X-axis) and transverse axis (Y-axis) moves in turn, so that every kind of solution can move into place in the pond of optional position.
In order to prevent the interference between X and the Y roller, when relying on pressurization to carry out solution when carrying by X and Y roller group from similar face, Y leaves from box when X moves.X and Y can preferably be arranged in the back side and front respectively.In this case, used box is the box with following structure: the matrix shown in Figure 16 E is clipped between the elastic body, and flow channel is arranged at that the matrix apparent surface goes up and interconnects by through hole.The roller group designs like this, makes a delegation or a row roller wholely to move, and perhaps the several rollers in delegation or the row can wholely move.Additional disclosure, the structure of flow channel is not limited to the reticulate texture of length direction shown in Figure 21 A and Width.The zone that can have no flow channel between the adjacent pool.Shown in Figure 21 B, flow channel can be provided with obliquely.Pond size to each other can be different with the degree of depth.
In Figure 21 B, when flow channel is provided with being tilted, even be that every kind of solution also can move on any direction of XY under the situation of unidirectional mobile roller at roller.
For example, when three roller groups that shown in Figure 21 B, are provided with move and the roller group of the roller group of the roller group of epimere R1, stage casing R2 and hypomere R3 synchronized with each other when mobile, the solution among the Q1 of pond moves to pond Q2 and Q3.When the roller group of the roller group of epimere R1 and stage casing R2 moves and synchronized with each other when mobile, the solution among the Q3 of pond moves to pond Q4, Q5 and Q6.When the roller group of the roller group of stage casing R2 and hypomere R3 was moved further, solution moved among the Q7 of pond.
Additional disclosure in roller is arranged on structure on X and the Y-axis like this, exists solution to remain in the trend of the flow channel between the roller.In this case, shown in Figure 21 C, rigid body 170 can be arranged in a part of flow channel between elastic body 171 and the matrix 172, thereby can stop up flow channel fully when roller 169 extruding rigid bodies 170.For example, rigid body 170 can form in such a way: rigid body 170 is embedded in the elastic body 171; Perhaps form by this way: with a part of elastic body 171 sclerosis.
Figure 22 is the key diagram of expression ten six embodiment relevant with cartridge for chemical reaction and driving mechanism.
Though the foregoing description represents to use roller or the piston-type actuator situation as pressures partially, but can use two dimensional panel or crawler belt (Caterpillar (registered trademark)) as pressures partially 173, this two dimensional panel or crawler belt its with surface that container such as pond 175 contacts on have curvature, thereby two dimensional panel or crawler belt can move along the direction of arrow, while extrusion box 174, as shown in figure 22.According to this measure,, therefore can prevent that solution or air from refluxing because of the back-pressure effect because flow channel or pond are subjected to a surface extruding.
Figure 23 A is the arrangement plan of the 17 embodiment of expression cartridge for chemical reaction of the present invention and driving mechanism to 23C.
Figure 23 A is the skeleton view of expression the 17 embodiment.In Figure 23 A, roller 201a, 201b and 201c are supported by arm 202a, 202b and 202c as the roller support section respectively.Arm 202a, 202b and 202c are fixed on the base part 203, and base part 203 shape pictures are dull and stereotyped and as the pedestal of keeping arm.Perhaps base part 203 can be cast in case with arm 202a, 202b and 202c monolithic molding.For example, the material of roller, arm and base part can be metal, fluororesin or the combination of the two.Every pair roller and arm form the pressures partially that box is exerted pressure.
Base part 203 is fixed on the mechanical stage (not shown) that can move along X, Y and Z-direction.When mechanical stage moved up and down, roller 201a exerted pressure to box 205.Box is fixed on the mechanical stage.When base part 203 when being subjected to mechanical stage control time move left and right, roller 201a, 201b and 201c rotation and extrusion box when moving, thus the solution level in the box 205 is moved.
Base part 203 has opening portion 204a and 204b.Actuator 206a inserts in each opening portion, shown in Figure 23 B.Figure 23 B is the side view of expression the 17 embodiment.For example, the shape of actuator 206a is as metal rod.Actuator 206a exerts pressure, vibrates, heats, cools off box 205 or similarly effect, is used for quickening the chemical reaction of box 205.For example, use piezoelectric element, use peltier-element heating and cooling box box pressurization and vibration.
Figure 23 C is that the expression roller is fixed to the structure on the arm.Roller 201a inserts and is arranged among the groove 207a of arm 202a end.The groove 207a backing roll 201a of arm 202a, the angle of wrapping up roller 201a simultaneously surpasses 180 °, shown in single-point line among the figure.That is, because the diameter of roller 201a is greater than the opening of groove 207a, so roller 201a is stuck among the groove 207a of arm 202a, and its principle is as the ball in the ball pen, thereby can prevent that roller 201a from coming off from groove 207a.
Retainer 208a shape for example, is made by fluororesin as film.Behind roller 201a insertion groove 207a, retainer 208a is attached to the surface of the opposite side of groove 207a, is used to prevent that roller 201a from coming off.Additional disclosure can magnetically be attracted to roller 201a on the arm 202a.
According to this structure, the roller group can be arranged on the box, so that be adjacent to be arranged in two row or the multirow, and need not come backing roll by any redundant space on the side.
Figure 24 A and 24B are the structural drawing of the 18 embodiment of expression cartridge for chemical reaction of the present invention and driving mechanism.Figure 24 A is a skeleton view, and the structure of expression is that flashboard 209a is arranged on the side between arm 202a and the 202b, and flashboard 209b is arranged on the side between arm 202b and the 202c.Flashboard 209a and 209b can extrusion box, stop up with the flow channel with box.Each flashboard can be driven by peltier-element.
Figure 24 B is a planimetric map, represents following a kind of state: roller group 201a is arranged in two row adjacent one another are to 201d and roller group 201e to 201h.The box driving mechanism is rendered as ladder-shaped, and dotted line is represented roller.Roller 201a is fixed on the base part 225 by arm to 201d.Roller 201e is fixed on the base part 226 by arm to 201h.Be provided with opening portion 204a in the base part 225 to 204c, be provided with opening portion 204d in the base part 226 to 204f.Actuator (not shown) inserts opening portion 204a in 204c, and inserts opening portion 204d in 204f.Flashboard 209a to 2091 is arranged on the side of base part 225 and 226.These flashboards stop up the solution that flows along the direction perpendicular to the roller moving direction.
Figure 25 is the structural drawing of the 19 embodiment of expression cartridge for chemical reaction of the present invention and driving mechanism.
Figure 25 represents the state of roller group from the above and below extrusion box.Roller 212a and 212b are supported by arm 213a and 213b respectively, and arm 213a and 213b are fixed on the flat base seat part 214.
Based on the vertical moving that is fixed on the base part 214 on the mechanical stage (not shown), roller 212a and 212b are from top extrusion box 210.When base part 214 is subjected to mechanical stage control time move left and right, roller rotation and extrusion box when moving.Like this, the solution level in the box 210 is moved.
Roller 216a and 216b are supported by arm 217a and 217b respectively, and arm 217a and 217b are fixed on the flat base seat part 218.Based on the vertical moving that is fixed on the base part 218 on the mechanical stage (not shown), roller 216a and 216b are from below extrusion box 210.When base part 218 is subjected to mechanical stage control time move left and right, roller rotation and extrusion box when moving.Like this, the solution level in the box 210 is moved.
Actuator 215 is exerted pressure, vibrates, heats, is cooled off or the like from the top to box 210 upper surfaces, thereby quickens the chemical reaction in the box 210.Actuator 219 is exerted pressure, vibrates, heats, is cooled off or the like from the below to box 210 lower surfaces, thereby quickens the chemical reaction in the box 210.
Box 210 portion within it has matrix 211.Matrix 211 is made by rigid material (for example, glass or resin).The box 210 of Xing Chenging can stand from the above and below applied pressure like this.According to this structure, the solution in flow channel or the pond can move separately, and matrix 211 is sandwiched in the box 210 between described flow channel or described pond.If in the residing a part of matrix in pond, form aperture, shown in Figure 16 E, can mobile top solution and bottom solution pass matrix 211.Additional disclosure, or this embodiment can be provided with flashboard in the side.
Figure 26 is the structural drawing of the 20 embodiment of expression cartridge for chemical reaction of the present invention and driving mechanism.Base part 220 has the opening portion 223a and the 223b of the actuator that forms by mode same as described above, and the arm 221a that does not have any roller is to 221c.This provides the pressures partially of another kind of form.Arm 221a forms curved surface 222a, 222b and 222c to the end of 221c.The effect of curved surface comes place of rollers, is used to reduce the friction between box 224 and each arm.Even under with the situation of arm to the box pressurization, box also can easily move horizontally.Therefore, need not any roller and just can be implemented in delivered solution in the box.
For example, each arm is made by fluororesin.If on the box surface, fluorocarbon resin sheet is set or box is fluororesin-coated, then can reduce friction more significantly.
In this case, each arm end portion can form roller the curved surface that can not form.Therefore, when each arm end portion formed non-circular curved surface (for example parabola, hyperboloid or sinusoidal curve), each arm end portion can be shaped according to the material of box, thereby can realize effective extruding.
The quantity of the quantity of arm, the quantity of roller, flashboard, quantity of actuator or the like are not limited to the quantity shown in the accompanying drawing.Can change these quantity if desired.
For example, above-mentioned box driving mechanism may be embodied as Fig. 9 A to 9E, Figure 19 A to 19C, Figure 20 or the box driving mechanism shown in Figure 21 B.In this case, roller is with equidistantly fixing of equating with the spacing in pond in the box.
For example, in the box shown in the 9E, roller is with equidistantly arranging of equating with the horizontal spacing in pond at Fig. 9 A.Though Fig. 9 A only expresses roller to 9E, Fig. 9 A to the part shown in the 9E be Figure 23 A to the driving mechanism shown in the 23C, and these rollers support by the arm that is fixed on base part, described base part is fixed on the mechanical stage.By this way, the box driving mechanism can drive about the box and move left and right.Base part is provided with opening, so that be in the position corresponding with the pond.Insert at actuator under the situation of opening, can apply vibration, heating or the like.
According to this structure, the input and output flow channel that the chamber of flowing material wherein is housed is all stopped up simultaneously by each pressures partially of box driving mechanism.Therefore, when the conveyance fluid material, can prevent that not only flowing material from flowing into next chamber, and prevent to flow in the later chamber, next pond.And, when solution is heated or vibrate, can prevent that solution from flowing in another chamber.And, can prevent that solution from being pushed back by the back-pressure of air.In addition, can realize by utilizing silicon dioxide, magnetic or similar substance from sample, to extract and the structure (decussate texture) of purification DNA.
The present invention is not limited to the above embodiments, under the situation that does not break away from spirit of the present invention, can comprise more changes and improvements.

Claims (3)

1. cartridge for chemical reaction, comprise that at least a portion is the container of being made by elastic body, wherein, form a plurality of chambers in the described container, so that a plurality of chambers connect by flow channel or arrange joinably, external force is applied on the elastic body from external container, so that flowing material in flow channel or the chamber or the flowing material that is present in simultaneously in flow channel and the chamber move, so that carry out chemical reaction
Wherein, at least one chamber is the common chamber with a plurality of inlet flow channels and at least two outlet flow channels, and two or more different flowing materials flow into the inlet flow channel respectively, and
When a kind of flowing material flows into common chamber and when common chamber flows out, stop up by external force common chamber other flowing materials the inlet flow channel and export flow channel.
2. cartridge for chemical reaction as claimed in claim 1,
Wherein, described other flowing materials flow into and the flow channel that flows out is formed on the position that the external force that is used to carry described a kind of flowing material stops up.
3. cartridge for chemical reaction as claimed in claim 1,
Wherein, a plurality of chambers have projection, and described projection is positioned at described external container, and are depressed when applying external force, and
Carry the flow channel of described a kind of flowing material to be formed in the recessed part between the projection.
CN200710148081XA 2004-04-28 2005-04-27 Chemical reaction cartridge, method of producing chemical reaction cartridge, and mechanism for driving chemical reaction cartridge Active CN101109760B (en)

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JP2004204085 2004-07-12
JP2004204085A JP4379716B2 (en) 2004-07-12 2004-07-12 Cartridge drive mechanism for chemical reaction
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GB2453310A (en) 2006-07-05 2009-04-08 Aida Eng Ltd Micro passage chip, and fluid transferring method
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JP2009210327A (en) * 2008-03-03 2009-09-17 Yokogawa Electric Corp Chemical reaction cartridge, mixture generating method, and control device of chemical reaction cartridge
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CN110732358B (en) * 2019-11-25 2022-04-01 北京世纪沃德生物科技有限公司 Liquid inlet method of reaction chamber of microfluidic chip
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CN101183111A (en) 2008-05-21
CN101183110A (en) 2008-05-21
CN101187668A (en) 2008-05-28
CN101118244A (en) 2008-02-06
JP2005313065A (en) 2005-11-10
CN1690705A (en) 2005-11-02
JP4375101B2 (en) 2009-12-02
CN101109760A (en) 2008-01-23
CN100476425C (en) 2009-04-08

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