CN110045102A - Reagent sequence loading device, centrifugal microfluidic control device and analysis system - Google Patents

Reagent sequence loading device, centrifugal microfluidic control device and analysis system Download PDF

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CN110045102A
CN110045102A CN201910275523.XA CN201910275523A CN110045102A CN 110045102 A CN110045102 A CN 110045102A CN 201910275523 A CN201910275523 A CN 201910275523A CN 110045102 A CN110045102 A CN 110045102A
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chamber
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hydraulic control
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reagent
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CN110045102B (en
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汤明辉
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Shenzhen Chenghui Medical Technology Co ltd
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Shenzhen City Of Gang Zhu Medical Science And Technology Co Ltd
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    • 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
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing

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Abstract

This application involves reagent sequence loading device, centrifugal microfluidic control device and analysis system, reagent sequence loading device includes liquid outlet pipe, hydraulic control chamber, collection chamber and at least two load chambers;Liquid outlet pipe is connected to hydraulic control chamber and collection chamber, and liquid outlet pipe has the block structure;It loads chamber and is equipped with hydraulic control pipeline and load pipeline;Collection chamber, which is equipped with, collects lumen pore, and hydraulic control chamber is equipped with liquid injection hole, each to be connected to end different setting at a distance from liquid injection hole;With arranged from small to large ord at a distance from rotation center are as follows: position that LOADED CAVITY room is connected with its hydraulic control pipeline, load chamber, load chamber load the position that pipeline is connected with it.It realizes simply, reduces design difficulty and saved processing cost;, to control the time interval of different reagents loadeds, the time can have been reserved to reagent reaction or reagent processing by controlling centrifugal rotational speed;The sequence load of any number of reagent can be realized in different load chambers by adjusting different reagents.

Description

Reagent sequence loading device, centrifugal microfluidic control device and analysis system
Technical field
This application involves centrifugal microfluidic control field, more particularly to reagent sequence loading device, centrifugal microfluidic control device and Analysis system.
Background technique
Micro-fluidic (Microfluidics) refers to the handling liquids on submillimeter scale, wherein submillimeter scale is general Several hundred microns are arrived for several microns.Microflow control technique is by basic operation unit involved in biological and chemical field, even whole The function in a laboratory, including sampling, dilution, reaction, separation, detection etc. are integrated on a small chip, therefore also known as chip Laboratory (Lab-on-a-Chip).This chip is usually to be made of various liquid storage tanks and microchannel network interconnected, The sample process time can largely be shortened, and control liquid flowing by accurate, realize that the maximum of reagent consumptive material utilizes effect Rate.It is micro-fluidic to be tried for biomedical research, pharmaceutical synthesis screening, environmental monitoring and protection, health quarantine, judicial expertise, biology The application of the various fields such as the detection of agent provides extremely wide prospect.Microfluidic system refers to be grasped on submillimeter scale The device of draining body.It is micro-fluidic to be generally divided into following several big types: pressure (air pressure or hydraulic) drive-type in industrialization Micro-fluidic, centrifugal microfluidic control, drop is micro-fluidic, and digitlization is micro-fluidic, and papery is micro-fluidic etc..Centrifugal microfluidic control is under the jurisdiction of miniflow One branch of control is refered in particular to the flowing for driving liquid by rotation centrifugal microfluidic control chip, is existed to realize using centrifugal force Handling liquids on submillimeter scale.Basic operation unit involved in biological and chemical field is integrated in one by centrifugal microfluidic control On (disc-shaped) chip of a small-sized dish-style.Other than micro-fluidic specific advantage, since centrifugal microfluidic control only needs A motor is wanted to provide power required for liquid manipulation, so whole equipment more concision and compact.And on disc-type chip Ubiquitous centrifugal field can make liquid driven more effective, it is ensured that without residual liquid in pipeline, and can be effectively real The now sample separation based on density variation, also can allow parallel processing more simple.It is micro-fluidic to meet care diagnostic well (Point-of-care testing, POCT) minimizes the demand of instrument, and therefore, centrifugal microfluidic control is also more and more answered In care diagnostic (POCT).
Microfluidic applications in vitro diagnostic field when, extremely important and crucial operation is exactly to allow reagent according to certain Sequence react, finally obtain diagnostic result.And to realize that plurality of reagents reacts according to certain sequence, premise Condition seeks to realize that plurality of reagents is loaded into specified reaction chamber according to certain sequence.In centrifugal microfluidic control, reagent Sequence load relies primarily on valve to realize, the valve includes capillary valves, siphon valve, paraffin valve etc..Micro-fluidic chip is according to setting Revolving speed timing rotation when, different reagents can successively break through different valves, thus realize reagent sequence load.But valve Use often will increase the processing cost of entire micro-fluidic chip, and the sequence load realized with valve is often repeated It is difficult to be guaranteed with reliability.Also, in centrifugal microfluidic control, the realization of these valves is all less susceptible to.Capillary valves are to pipeline Requirement on machining accuracy it is very high, and capillary valves itself can be related with the contact angle of liquid reagent on the surface of the material, often not Same reagent needs different line sizes to realize the effect of capillary valves;Siphon valve needs to do at hydrophily siphon piping The technique requirement of reason, this processing is very high, often substantially increases the processing cost of chip;The thawing of paraffin is past in paraffin valve Toward needing instrument to carry out corresponding temperature control, the design difficulty of instrument is increased.
Summary of the invention
Based on this, it is necessary to provide a kind of reagent sequence loading device, centrifugal microfluidic control device and analysis system.
A kind of reagent sequence loading device, the reagent sequence loading device have rotation center and reagent sequence Loading device includes liquid outlet pipe, hydraulic control chamber, collection chamber and at least two load chambers;The liquid feeding end of the liquid outlet pipe It is connected to the hydraulic control chamber, the outlet end of the liquid outlet pipe is connected to the collection chamber, and the liquid outlet pipe, which has, increases resistance knot Structure;The reagent sequence loading device is respectively corresponded in each load chamber equipped with hydraulic control pipeline and load pipeline;It is described Collection chamber, which is equipped with, collects lumen pore, and the hydraulic control chamber is equipped with liquid injection hole, the liquid feeding end of the liquid injection hole and the liquid outlet pipe The both ends of the hydraulic control chamber are located at, and are arranged from small to large ord at a distance from the rotation center are as follows: the note Fluid apertures, the liquid feeding end of the liquid outlet pipe, the liquid outlet pipe outlet end;Each load chamber passes through its correspondence respectively The hydraulic control pipeline be connected to the hydraulic control chamber, and each hydraulic control pipeline have be connected with the hydraulic control chamber, And it is located at the connection end between the liquid feeding end and the liquid injection hole of the liquid outlet pipe, each connection end and the liquid injection hole The different setting of distance;Each load chamber is also connected to the collection chamber by its corresponding described load pipeline respectively, And arranged from small to large ord at a distance from the rotation center are as follows: the load chamber is connected with hydraulic control pipeline described in its Logical position, the load chamber, the load chamber and the position for loading pipeline described in its and being connected.
Mentioned reagent sequence loading device, suitable for centrifugal microfluidic control device, design is very ingenious, without using each Kind valve, it is only necessary to be under centrifugation rotation environment and can be realized as plurality of reagents sequence load, realization is simple, reduces design Difficulty and processing cost is saved;It especially can be by controlling centrifugal rotational speed, thus between the time for controlling different reagents loadeds Every, to reagent reaction or reagent processing reserved the time;Further, by adjusting different reagents in different load chambers It can realize the sequence load of any number of reagent.
The liquid outlet pipe has the block structure in one of the embodiments, and the block structure is used for matching rotation Speed setting, the through-rate of liquid outlet pipe when controlling rotation.
The block structure includes bending section at least two to be connected in one of the embodiments,.
In one of the embodiments, the block structure include reduce setting pass through area.
The reagent sequence loading device has hydrophobic material ontology, the outlet tube in one of the embodiments, Road, the hydraulic control chamber, the collection chamber and each load chamber are opened in the hydrophobic material ontology.
The reagent sequence loading device includes three load chambers in one of the embodiments, described in three Load chamber is respectively the first reagents loaded chamber, the second reagents loaded chamber and third reagents loaded chamber, and with the note The distance of fluid apertures arranges from small to large ord are as follows: the connection end of the first reagents loaded chamber, second reagents loaded The connection end for being connected to end, the third reagents loaded chamber of chamber.
The collection chamber includes collecting chamber, obtains chamber and waste liquid chamber in one of the embodiments, with the collection The line of the center of chamber and the rotation center is line of reference, and the acquisition chamber and the waste liquid chamber are located at the reference The two sides of line;Each load chamber passes through its corresponding described load pipeline respectively and is connected to the collecting chamber, the outlet tube The outlet end in road is connected to the waste liquid chamber;The collecting chamber is connected to the acquisition chamber by obtaining pipeline, and the collecting chamber is also logical It crosses waste solution channel and is connected to the waste liquid chamber;The acquisition chamber, which is equipped with, obtains lumen pore, and the acquisition lumen pore is located at the acquisition chamber and leans on The position of the nearly rotation center and with the acquisition pipeline enclosure every setting;The waste liquid chamber is equipped with waste liquid lumen pore, the waste liquid Lumen pore is located at the waste liquid chamber closest to the position of the hydraulic control chamber and is arranged with the outlet end interval of the liquid outlet pipe.
The collecting chamber is equipped with outlet in one of the embodiments, and the collecting chamber is respectively communicated with by the outlet The acquisition chamber and the waste liquid chamber;The outlet is equipped with filter membrane.
A kind of centrifugal microfluidic control device comprising any one reagent sequence loading device.
Above-mentioned centrifugal microfluidic control device, design is very ingenious, without using various valves, it is only necessary to be in centrifugation swivel becket It can be realized as plurality of reagents sequence under border to load, realize the design difficulty for simply reducing reagent sequence load and save Processing cost;Especially, to control the time interval of different reagents loadeds, reagent can be given anti-by controlling centrifugal rotational speed It answers and has reserved the time;Further, any number of examination can be realized in different load chambers by adjusting different reagents The sequence of agent loads.
A kind of analysis system comprising the centrifugal microfluidic control device.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of one embodiment of the application;Fig. 2 is enlarged diagram at the A of embodiment illustrated in fig. 1;Figure 3 be the schematic diagram of another direction of embodiment illustrated in fig. 1;Fig. 4 is the diminution schematic diagram of the other direction of embodiment illustrated in fig. 1;Figure 5 be the schematic diagram of another direction of embodiment illustrated in fig. 1;Fig. 6 is enlarged diagram at the B of Fig. 5 illustrated embodiment;Fig. 7 is Fig. 1 The schematic diagram of another direction of illustrated embodiment;Fig. 8 is enlarged diagram at the C of embodiment illustrated in fig. 7;Fig. 9 is that the application is another The structural schematic diagram of embodiment;Figure 10 is the diminution schematic diagram of the other direction of embodiment illustrated in fig. 9;Figure 11 is real shown in Fig. 9 Apply the schematic diagram of another direction of example;Figure 12 is the schematic diagram of another direction of embodiment illustrated in fig. 9;Figure 13 is to implement shown in Figure 12 Enlarged diagram at the D of example;Figure 14 is enlarged diagram at the F of embodiment illustrated in fig. 13;Figure 15 is embodiment illustrated in fig. 12 Enlarged diagram at E;Figure 16 is the schematic diagram of another direction of embodiment illustrated in fig. 9;Figure 17 is at the G of embodiment illustrated in fig. 16 Enlarged diagram;Figure 18 is enlarged diagram at the H of embodiment illustrated in fig. 16.
Specific embodiment
In order to make the above objects, features, and advantages of the present application more apparent, with reference to the accompanying drawing to the application Specific embodiment be described in detail.Many details are explained in the following description in order to fully understand this Application.But the application can be implemented with being much different from other way described herein, those skilled in the art can be Without prejudice to doing similar improvement in the case where the application intension, therefore the application is not limited by the specific embodiments disclosed below. In the application one embodiment, a kind of reagent sequence loading device, with rotation center and reagent sequence loading device packet Include liquid outlet pipe, hydraulic control chamber, collection chamber and at least two load chambers;The liquid feeding end of liquid outlet pipe is connected to hydraulic control chamber, out The outlet end in liquid pipe road is connected to collection chamber;Reagent sequence loading device is respectively corresponded in each load chamber equipped with hydraulic control pipe Road and load pipeline;Collection chamber, which is equipped with, collects lumen pore, and hydraulic control chamber is equipped with liquid injection hole, the feed liquor of liquid injection hole and liquid outlet pipe End is located at the both ends of hydraulic control chamber, and arranges from small to large ord at a distance from rotation center are as follows: liquid injection hole goes out liquid The outlet end of the liquid feeding end of pipeline, liquid outlet pipe;Each load chamber passes through its corresponding hydraulic control pipeline connection liquid controling cavity respectively Room, and each hydraulic control pipeline has the company between the liquid feeding end and liquid injection hole for being connected with hydraulic control chamber and being located at liquid outlet pipe Go side, it is each to be connected to end different setting at a distance from liquid injection hole;Each load chamber also passes through its corresponding load pipeline connection respectively Collection chamber, and arranged from small to large ord at a distance from rotation center are as follows: LOADED CAVITY room is connected with its hydraulic control pipeline Position, load chamber, load chamber load the position that pipeline is connected with it.Mentioned reagent sequence loading device, be suitable for from In heart micro fluidic device, design is very ingenious, without using various valves, it is only necessary to which being in can be real under centrifugation rotation environment Existing plurality of reagents sequence loads, and realizes simply, reduces design difficulty and saved processing cost;Control can especially be passed through Centrifugal rotational speed processed has reserved the time to reagent reaction or reagent processing to control the time interval of different reagents loadeds; Further, the sequence load of any number of reagent can be realized in different load chambers by adjusting different reagents.Wherein In one embodiment, reagent sequence loading device includes the part-structure or entire infrastructure of following embodiment;That is reagent sequence adds It carries and sets including some technical characteristics below or all technical features.It is in one of the embodiments, as shown in Figure 1, a kind of Reagent sequence loading device is used to be arranged in the centrifugal microfluidic control device with rotation center, that is, reagent sequence loads Device has rotation center 999 or can rotate along rotation center 999.Reagent sequence load dress in one of the embodiments, It sets with cylindrical body 100, reagent sequence loading device has the cylinder of flat pattern in one of the embodiments, Ontology.Reagent sequence loading device has rectangular body or centrosymmetric structure ontology for example just in one of the embodiments, Polygonal bodies.Reagent sequence loading device includes liquid outlet pipe, hydraulic control chamber, collection chamber in one of the embodiments, And at least two load chambers, wherein hydraulic control chamber is realized for liquid level position by filling liquid and its when rotated Reagent sequence load control, collection chamber are used to collect the liquid in hydraulic control chamber by liquid outlet pipe, and load chamber is for holding Setting needs reagent to be loaded, and different load chamber is used to accommodate different reagent, and in each embodiment, reagent is liquid; In one of the embodiments, as shown in Fig. 1, Fig. 3 and Fig. 5, reagent sequence loading device includes liquid outlet pipe 220, liquid controling cavity Room 200, collection chamber 600 and three load chambers press reagents loaded sequence, three LOADED CAVITYs in one of the embodiments, Room is respectively the first reagents loaded chamber 300, the second reagents loaded chamber 400 and third reagents loaded chamber 500;And with note The distance of fluid apertures 210 arranges from small to large ord are as follows: the connection end of the first reagents loaded chamber, the second reagents loaded chamber Connection end, third reagents loaded chamber connection end;As shown in Fig. 1 to Fig. 3 and Fig. 5 to Fig. 8, i.e. the first reagents loaded chamber Connection end 415 and liquid injection hole of the connection end 315 of room 300 at a distance from liquid injection hole 210 less than the second reagents loaded chamber 400 210 distance, the connection end 415 of the second reagents loaded chamber 400 are less than third reagents loaded chamber at a distance from liquid injection hole 210 At a distance from liquid injection hole 210, this is in order to ensure reagents loaded sequence, first plus the first reagents loaded at the connection end 515 of room 500 The first reagent such as sample in chamber, then plus the second reagents loaded chamber in the second reagent such as cleaning solution, finally plus Third reagent such as eluent in three reagents loaded chambers.It is understood that when needing to adjust reagents loaded sequence, Only the indoor reagent sites of LOADED CAVITY need to be adjusted, or adjustment load chamber, using simple, conveniently.
Reagent sequence loading device has hydrophobic material ontology, liquid outlet pipe 220, hydraulic control in one of the embodiments, Chamber 200, collection chamber 600 and each load chamber are opened in hydrophobic material ontology.In the embodiment, i.e., cylindrical sheet Body 100 is hydrophobic material ontology.Reagent sequence loading device has hydrophobic plastic ontology in one of the embodiments, i.e., Cylindrical body 100 is hydrophobic plastic ontology, liquid outlet pipe 220, hydraulic control chamber 200, collection chamber 600 and each LOADED CAVITY Room is opened in hydrophobic plastic ontology;Hydrophobic plastic ontology includes the body construction of hydrophobic plastic, or is carried out The body construction of the plastics of surface-hydrophobicized processing.Further, in one of the embodiments, hydrophobic material ontology or dredge Water-based plastic ontology is PMMA (polymethyl methacrylate, polymethyl methacrylate), PDMS (polydimethylsiloxane, dimethyl silicone polymer), PC (Polycarbonate, polycarbonate), ABS (Acrylonitrile-Butadiene-Styrene, acrylonitrile-butadiene-styrene copolymer), COC (copolymers Of cycloolefin, cyclic olefine copolymer) or COP (Cyclo Olefin Polymer, cyclic olefin polymer) product.It adopts With the design of hydrophobic material ontology such as hydrophobic plastic ontology, be conducive to the hydrophobicity for enhancing liquid outlet pipe and hydraulic control pipeline, To avoid the liquid especially water of hydraulic control chamber from entering or swimmingly enter liquid outlet pipe and/or hydraulic control pipeline, Jin Eryi The liquid of aspect control hydraulic control chamber enters the rate of collection chamber or waste liquid chamber, with the reaction of control sample-adding or sample-adding processing Time, on the other hand avoid the liquid of hydraulic control chamber from entering load chamber by hydraulic control pipeline.Hydrophobic plastic ontology is A kind of the block structure.
In one of the embodiments, please also refer to Fig. 6, the liquid feeding end 221 of liquid outlet pipe 220 is connected to hydraulic control chamber 200, the outlet end 222 of liquid outlet pipe is connected to collection chamber 600;Please also refer to Fig. 9, the liquid feeding end 221 of liquid outlet pipe 220 Pass through area by what area was greater than that the first connection end 315, second is connected to any one of end 415 and third connecting end 515. Such design, the liquid advantageously allowed in hydraulic control chamber 200 are flowed out from the liquid feeding end 221 of liquid outlet pipe 220.
Reagent sequence loading device is respectively corresponded in each load chamber equipped with hydraulic control pipe in one of the embodiments, Road and load pipeline;As shown in Figure 1, reagent sequence loading device is equipped with the first reagent of connection in the first reagents loaded chamber 300 The the first hydraulic control pipeline 310 and the first load pipeline 320 of chamber 300 are loaded, reagent sequence loading device is in the second reagents loaded Chamber 400 is equipped with the second hydraulic control pipeline 410 and the second load pipeline 420 of the second reagents loaded chamber 400 of connection, and reagent is suitable Sequence loading device is equipped with the third hydraulic control pipeline 510 of connection third reagents loaded chamber 500 in third reagents loaded chamber 500 And third loads pipeline 520.Respectively load chamber passes through its corresponding hydraulic control pipeline connection respectively in one of the embodiments, Hydraulic control chamber, and each hydraulic control pipeline have the liquid feeding end 221 that is connected with hydraulic control chamber 200 and is located at liquid outlet pipe 220 with Connection end between liquid injection hole 210, it is each to be connected to end different setting at a distance from liquid injection hole 210;Extremely such as Fig. 1 to Fig. 3 and Fig. 5 Shown in Fig. 8, the first reagents loaded chamber 300 is connected to hydraulic control chamber 200 by the first hydraulic control pipeline 310, is managed by the first load Road 320 is connected to collection chamber 600;There is first hydraulic control pipeline 310 the one one connecting tube the 311, the 1st of sequential communication to connect Pipe 312, the one or three connecting tube 313 and the one or four connecting tube 314, and have first to connect in the end of the one one connecting tube 311 Go side 315, the first connection end 315 are connected to the 200, the 1st connecting tube 314 of hydraulic control chamber and are connected to the first reagents loaded chamber 300; Second reagents loaded chamber 400 is connected to hydraulic control chamber 200 by the second hydraulic control pipeline 410, is connected by the second load pipeline 420 Logical collection chamber 600;Second hydraulic control pipeline 410 have the 2nd 1 connecting tube 411 of sequential communication, the two or two connecting tube 412, Two or three connecting tube 414 and the two or four connecting tube 414, and there is the second connection end in the end of the 2nd 1 connecting tube 411 415, the second connection end 415 is connected to the 200, the 2nd 4 connecting tube 414 of hydraulic control chamber and is connected to the second reagents loaded chamber 400;Third Reagents loaded chamber 500 is connected to hydraulic control chamber 200 by third hydraulic control pipeline 510, loads the connection of pipeline 520 by third and receives Collect chamber 600;Third hydraulic control pipeline 510 has the 3rd 1 connecting tube 511, the three or two connecting tube 512, third of sequential communication Three connecting tubes 513 and the three or four connecting tube 514, and there is third connecting end 515 in the end of the 3rd 1 connecting tube 511, the Tee joint end 515 is connected to the 200, the 3rd 4 connecting tube 514 of hydraulic control chamber and is connected to third reagents loaded chamber 500.
Please also refer to Fig. 6, the first hydraulic control pipeline 310 is connected with hydraulic control chamber 200 and has first to be connected to end 315, Second hydraulic control pipeline 410 is connected with hydraulic control chamber 200 and has the second connection end 415, third hydraulic control pipeline 510 and hydraulic control Chamber 200 is connected and has third connecting end 515, and the first connection end 315, second is connected to end 415 and third connecting end 515 With setting different at a distance from liquid injection hole 210, such design, reagent sequence loading device rotation when, 200 liquid of hydraulic control chamber Liquid feeding end 221 of the face from liquid injection hole 210 to liquid outlet pipe 220 slowly declines, and sequentially drops to the connection of the first connection end 315, second Hold 415, third connecting end 515;When the liquid level in hydraulic control chamber 200 drops to the first 315 or less connection end, the first hydraulic control pipe Road 310 is connected to external environment by the first connection end 315, hydraulic control chamber 200 and liquid injection hole 210, in atmospheric pressure and centrifugation Under the collective effect of power, the first reagent in the first reagents loaded chamber 300 enters collection chamber from the first load pipeline 320 600;When the liquid level in hydraulic control chamber 200 drops to the second 415 or less connection end, the second hydraulic control pipeline 410 passes through the second connection End 415, hydraulic control chamber 200 and liquid injection hole 210 are connected to external environment, under the collective effect of atmospheric pressure and centrifugal force, second The second reagent in reagents loaded chamber 400 enters collection chamber 600 from the second load pipeline 420;When in hydraulic control chamber 200 Liquid level when dropping to 515 or less third connecting end, third hydraulic control pipeline 510 by third connecting end 515, hydraulic control chamber 200 and Liquid injection hole 210 is connected to external environment, under the collective effect of atmospheric pressure and centrifugal force, in third reagents loaded chamber 500 Third reagent from third load pipeline 520 enter collection chamber 600;It thereby realizes and controls or be known as without valve The reagent sequence load effect of water seal enclosed control, it is to be understood that the present embodiment is by taking three load chambers as an example, in fact In the application of border, the quantity for loading chamber can be 2,4,5,6 or more, and the quantity of the load chamber of the present embodiment should not be managed Solution is the limitation for the protection scope of the application.
In one of the embodiments, referring to Figure 4 together, collection chamber 600, which is equipped with, collects lumen pore 610, hydraulic control chamber 200 are equipped with liquid injection hole 210, collect the relative position of lumen pore 610 and liquid injection hole 210 in one of the embodiments, according to reagent The rotation direction of sequence loading device is arranged or the rotation direction of reagent sequence loading device determine collect lumen pore 610 with The relative position of liquid injection hole 210, as shown in Figure 1, reagent sequence loading device or cylindrical body 100 rotate clockwise, hydraulic control Liquid in chamber 200 slowly flows into collection chamber 600 along liquid outlet pipe 220.In one of the embodiments, such as Fig. 1, Fig. 3 And shown in Fig. 7, collect lumen pore 610 be located at collection chamber 600 closest to the position of hydraulic control chamber 200 and collect lumen pore 610 and The outlet end 222 of liquid outlet pipe 220 is spaced setting.
Liquid injection hole 210 and the liquid feeding end 221 of liquid outlet pipe 220 are located at hydraulic control chamber in one of the embodiments, 200 both ends, and arranged from small to large ord at a distance from rotation center are as follows: the liquid feeding end of liquid injection hole 210, liquid outlet pipe 221, the outlet end 222 of liquid outlet pipe;That is, liquid injection hole 210 is less than the liquid feeding end 221 of liquid outlet pipe at a distance from rotation center At a distance from rotation center, the liquid feeding end 221 of liquid outlet pipe is less than the outlet end 222 of liquid outlet pipe at a distance from rotation center At a distance from rotation center;Also that is, the torque of liquid injection hole 210 is less than the torque of the liquid feeding end 221 of liquid outlet pipe, liquid outlet pipe Liquid feeding end 221 torque be less than liquid outlet pipe outlet end 222 torque, remaining embodiment and so on.In this way, can be with Ensure under normal apocarpy, for embodiment illustrated in fig. 1, normal apocarpy is to rotate clockwise;Hydraulic control chamber at this time Liquid in 200 can flow to outlet end 222 from the liquid feeding end 221 of liquid outlet pipe 220, rather than overflow from liquid injection hole 210.Such as Shown in Fig. 1 to Fig. 8, the shape of liquid outlet pipe 220 is a kind of the block structure.
Respectively load chamber is also connected to collection chamber by its corresponding load pipeline respectively in one of the embodiments, And arranged from small to large ord at a distance from rotation center are as follows: position that LOADED CAVITY room is connected with its hydraulic control pipeline, load Chamber, load chamber load the position that pipeline is connected with it.As shown in Figure 1, the first reagents loaded chamber 300 passes through first It loads pipeline 320 and is connected to collection chamber 600, the second reagents loaded chamber 400 is connected to collecting chamber by the second load pipeline 420 Room 600, third reagents loaded chamber 500 load pipeline 520 by third and are connected to collection chamber 600, the first hydraulic control pipeline 310 The positional distance rotation center being connected with the first reagents loaded chamber 300 is nearest, the first load pipeline 320 and the first reagent The positional distance rotation center that load chamber 300 is connected is farthest, and the first reagents loaded chamber 300 is placed in the middle apart from rotation center, Remaining embodiment and so on.Such reagent sequence loading device, suitable for centrifugal microfluidic control device, without using each Kind valve, it is only necessary to be under centrifugation rotation environment and can be realized as plurality of reagents sequence load, by adjusting different reagents not The sequence load that any number of reagent can be realized with load chamber, realizes simply, reduces design difficulty and saved processing Cost;Especially can by controlling centrifugal rotational speed, to control the time interval of different reagents loadeds, to reagent reaction or The time has been reserved in the processing of person's reagent.
Load chamber is also equipped with liquid injection hole in one of the embodiments, in this way, can be directly by liquid injection hole to adding Carry chamber injection liquid, such as sample liquid, cleaning solution or eluent etc..It loads and is equipped in chamber in one of the embodiments, Liquid storage container and liquid storage container, which have, releases liquid structure.Liquid structure is released in one of the embodiments, releases liquid structure or heat for rotation It is molten to release liquid structure.Rotation releases liquid structure for releasing the liquid in liquid storage container under rotation status.Hot melt is released liquid structure and is used for The liquid in liquid storage container is released at a certain temperature.Further, in one of the embodiments, liquid storage container have open Mouth and the paraffin coating portion for being covered on opening, paraffin coating portion is for melting at a certain temperature and releasing in liquid storage container Liquid.Such design releases the liquid in liquid storage container in which can be convenient by heating method or rotation mode.At it In middle one embodiment, it includes film layer and its rotational burst part that liquid structure is released in rotation.Rotational burst part is used to turn in rotation When having moved given pace, rupture film layer to release the liquid in liquid storage container.Liquid storage holds in one of the embodiments, Device is equipped with open region, punctures part, elastic component and film layer, and film layer punctures part for closing open region, the connection of elastic component one end, separately One end is fixed in load chamber, punctures part for cooperating elastic component to generate displacement to puncture film layer in centrifugation.Further Ground loads be equipped with liquid reagent in chamber in one of the embodiments,.Liquid reagent is arranged in one of the embodiments, In hot melt wrapping layer, hot melt wrapping layer is set in load chamber.Liquid reagent is set in one of the embodiments, In wrapping layer, wrapping layer is set in load chamber and wrapping layer is equipped with using the closed open region of hot melt layer.
Load chamber is equipped with opening and is covered on the closure portion of opening in one of the embodiments,.Such design, Closure portion can directly be opened, sample or other need reagent to be loaded by opening merging load chamber, then again It is closed by closure portion.Such design is realized in reagent merging load chamber in which can be convenient.
Hydraulic control pipeline is 0.001 to 0.03 square millimeter by area in one of the embodiments,;Further, Hydraulic control pipeline has circular by section in one of the embodiments, is also referred to as cross section, radius by section It is 0.01784 millimeter to 0.09772 millimeter;Alternatively, hydraulic control pipeline have rectangle by section, the length is 0.05mm extremely 0.3mm, width are 0.02mm to 0.1mm;Further, hydraulic control pipeline has passing through for rectangle in one of the embodiments, Section, the length is 0.2mm, width 0.1mm.For the restriction by area, be conducive to avoid the liquid in hydraulic control chamber Along hydraulic control pipeline flow into load chamber along, also that is, when hydraulic control pipeline it is smaller by area when, in hydraulic control chamber Liquid inflow has certain drag effect;Especially cooperation uses hydrophobic material ontology such as hydrophobic plastic ontology, energy Enough in the state of hydraulic control chamber hydraulically full such as water, remains to prevent the liquid in hydraulic control chamber to flow into along hydraulic control pipeline and add It carries in chamber, to realize the technical effect that but there is valve action without valve.In one of the embodiments, such as Fig. 1 and Fig. 6 Shown, the first connection end 315, second is connected to end 415 and third connecting end 515 and arrives the distance of rotation center 999, respectively less than goes out The liquid feeding end 221 in liquid pipe road 220 arrives the distance of rotation center 999, and also the respectively less than outlet end 222 of liquid outlet pipe is into rotation The distance of the heart 999, such design, also for ensuring that the liquid in rotation, in hydraulic control chamber 200 passes through liquid outlet pipe 220 outflows, without flowing into the first hydraulic control pipeline 310, the second hydraulic control pipeline 410 and third hydraulic control pipeline 510.
Further, liquid outlet pipe is greater than each hydraulic control pipeline by area and passes through face in one of the embodiments, Product, such design, it is advantageously ensured that the liquid in hydraulic control chamber is flowed out by liquid outlet pipe, without flowing into rotation In each hydraulic control pipeline.Liquid outlet pipe has the block structure in one of the embodiments,;The block structure is for increasing outlet tube Liquid flowing resistance inside road so that the liquid of hydraulic control chamber will not too quickly from liquid outlet pipe flow out to collection chamber or In its waste liquid chamber.The block structure is arranged for matching rotation speed in one of the embodiments, with liquid out when control rotation The through-rate of pipeline;Further, the block structure extends setting in one of the embodiments,.One embodiment wherein In, the block structure include at least two to be connected bending section or reduce setting pass through area;One embodiment wherein In, the block structure include at least two to be connected bending section and reduce setting pass through area;Further, wherein one In a embodiment, as shown in Figures 1 to 8, the block structure has single Z-shaped or S-shaped structure;Or the block structure has head and the tail Connected multiple Z-shaped or S-shaped structure, i.e. the block structure include many places bending section being connected.In one of the embodiments, The block structure is 0.01 to 0.1 square millimeter, such as 0.0625 square millimeter etc. by area.
In one of the embodiments, as shown in FIG. 9 and 10, collection chamber include collecting chamber 700, obtain chamber 800 with Waste liquid chamber 900 obtains chamber 800 and waste liquid chamber 900 is distinguished using the line of the center of collecting chamber 700 and rotation center as line of reference Positioned at the two sides of line of reference;Each load chamber passes through its corresponding load pipeline connection collecting chamber 700 respectively, also referring to The outlet end 222 of Figure 11 and Figure 12, liquid outlet pipe are connected to waste liquid chamber 900;Collecting chamber 700 is obtained by obtaining the connection of pipeline 720 Chamber 800, collecting chamber 700 are also connected to waste liquid chamber 900 by waste solution channel 730;It obtains chamber 800 and is equipped with acquisition lumen pore 810, obtain Lumen pore 810, which is located at, to be obtained chamber 800 close to the position of rotation center and is arranged with the interval of pipeline 720 is obtained;Waste liquid chamber 900 is equipped with Waste liquid lumen pore 910, waste liquid lumen pore 910 be located at waste liquid chamber 900 closest to the position of hydraulic control chamber 200 and with liquid outlet pipe go out The setting of the interval of liquid end 222;Such design, when rotating clockwise, the liquid in hydraulic control chamber 200 is flowed from liquid outlet pipe 220 Entering in waste liquid chamber 900, the liquid in collecting chamber 700 flows into waste liquid chamber 900 from waste solution channel 730, when rotating counterclockwise, Liquid in collecting chamber 700 flows into acquisition chamber 800 from pipeline 720 is obtained.In one of the embodiments, also referring to Figure 15 and Figure 16, collecting chamber 700 are equipped with outlet 710, and collecting chamber 700 is respectively communicated with by outlet 710 and obtains chamber 800 and waste liquid Chamber 900;In one of the embodiments, also referring to Figure 15 and Figure 17, outlet 710 is equipped with filter membrane 740;Further, Outlet 710 is equipped with a pair of of mounting hole, and the structure of mounting hole and its closing are similar to liquid injection hole, match the shape of filter membrane and be arranged, Outlet is packed into filter membrane, then closes a pair of of mounting hole for when installing filter membrane, opening a pair of of mounting hole;In replacement filter membrane When, a pair of of mounting hole is opened, used filter membrane is disclosed, then new filter membrane is installed, closes a pair of of mounting hole.In each embodiment, tool The filter membrane type and model of body with no restriction, are adapted to the target object of centrifugal microfluidic control.In one of the embodiments, Also referring to Fig. 9 and Figure 18, the first connection end 315 is at a distance from liquid injection hole 210 less than the second connection end 415 and liquid injection hole 210 distance, the second connection end 415 are less than third connecting end 515 at a distance from liquid injection hole 210 at a distance from liquid injection hole 210, And first is connected to the distance that end 315, second is connected to end 415 and rotation center 999 is arrived at third connecting end 515, respectively less than outlet tube The liquid feeding end 221 in road 220 arrives the distance of rotation center 999, and also respectively less than the outlet end 222 of liquid outlet pipe arrives rotation center 999 Distance.
Hydraulic control pipeline is 0.001 to 0.03 square millimeter by area in one of the embodiments,;Liquid outlet pipe With the block structure;The block structure include at least two to be connected bending section and/or reduce setting pass through area;Reagent Sequence loading device has hydrophobic plastic ontology, liquid outlet pipe 220, hydraulic control chamber 200, collection chamber 600 and each LOADED CAVITY Room is opened in hydrophobic plastic ontology;Collection chamber includes collecting chamber 700, obtains chamber 800 and waste liquid chamber 900, to collect The center of chamber 700 and the line of rotation center are line of reference, obtain chamber 800 and waste liquid chamber 900 is located at the two of line of reference Side;Each load chamber passes through its corresponding load pipeline connection collecting chamber 700 respectively, and the connection of outlet end 222 of liquid outlet pipe is useless Sap cavity 900;Collecting chamber 700 obtains chamber 800 by obtaining the connection of pipeline 720, and collecting chamber 700 is also connected by waste solution channel 730 Logical waste liquid chamber 900;It obtains chamber 800 and is equipped with acquisition lumen pore 810, acquisition lumen pore 810, which is located at, obtains chamber 800 close to rotation center Position and with obtain pipeline 720 interval be arranged;Waste liquid chamber 900 is equipped with waste liquid lumen pore 910, and waste liquid lumen pore 910 is located at waste liquid chamber 900 closest to hydraulic control chamber 200 position and with the outlet end of liquid outlet pipe 222 be spaced be arranged;Collecting chamber 700 is equipped with outlet 710, collecting chamber 700 is respectively communicated with by outlet 710 and obtains chamber 800 and waste liquid chamber 900;Outlet 710 is equipped with filter membrane 740;Reagent Sequence loading device includes three load chambers, and three load chambers are respectively the sample chamber for being used to accommodate sample liquid, are used for The cleaning solution chamber of cleaning solution and the eluent chamber for accommodating eluent are accommodated, and is pressed at a distance from liquid injection hole 210 from small It is arranged to big sequence are as follows: the connection end for being connected to end, eluent chamber for being connected to end, cleaning solution chamber of sample chamber;That is, examination Agent sequence loading device includes three load chambers, and three load chambers are respectively the examination of the first reagents loaded chamber 300, second Agent loads chamber 400 and third reagents loaded chamber 500, and the first reagents loaded chamber 300 is sample chamber, and the second reagent adds Load chamber 400 is cleaning solution chamber, and third reagents loaded chamber is eluent chamber, the connection end of the first reagents loaded chamber 315 be the connection end of sample chamber, and the connection end 415 of the second reagents loaded chamber is the connection end of cleaning solution chamber, third examination The connection end 515 that agent loads chamber is the connection end of eluent chamber.
Reagent sequence loading device and its concrete application are continued to explain below with reference to Fig. 1 to Fig. 8, it is past by liquid injection hole 210 Liquid, such as water are injected in hydraulic control chamber 200, the liquid level of the liquid of injection will exceed the first hydraulic control pipeline 310 and hydraulic control chamber 200 connector i.e. first is connected to end 315.First reagents loaded chamber 300, the second reagents loaded chamber 400 and third reagent Load chamber 500 in preset liquid reagent, or in other embodiments reagent sequence loading device in the first reagents loaded Chamber 300, the second reagents loaded chamber 400 and third reagents loaded chamber 500 are respectively equipped with liquid injection hole;It is sealed after the completion of fluid injection Good corresponding liquid injection hole, the mode of sealing of hole include but is not limited to paraffin envelope, mucilage sealing, adhesive tape envelope etc..In the present embodiment, first Liquid storage container is preset in reagents loaded chamber 300, the second reagents loaded chamber 400 and third reagents loaded chamber 500, Reagent is preset in liquid storage container.It is understood that 3 kinds of reagents may be implemented in the reagent sequence loading device of the present embodiment Sequence loads, and in other embodiments, the reagent sequence loading device of the application may be implemented plurality of reagents sequence and load, packet It includes but is not limited to 3 kinds.In one of the embodiments, by taking dilution step as an example, one of load chamber is dilution chamber, that is, dilute Reagents loaded chamber is released, dilution is set in hot melt wrapping layer, and hot melt wrapping layer is set in dilution chamber.One wherein In embodiment, dilution is set in wrapping layer, and wrapping layer is set in dilution chamber and wrapping layer is equipped with and is closed using hot melt layer Opening.Liquid storage container is viscous in one of the embodiments, is set in dilution chamber.Each LOADED CAVITY in one of the embodiments, It is equipped with liquid storage container and liquid storage container in room has and releases the liquid storage container of liquid structure/in one of the embodiments, with aluminium foil Layer.Liquid storage container is equipped with opening, thorn part, elastic component and sealer in one of the embodiments, and sealer is for closing opening, bullet Property part one end connection thorn part, the other end be fixed on load chamber such as dilution chamber in, thorn part be used for centrifugation when cooperate elastic component Displacement is generated to puncture sealer.
In use, firstly, for having hot melt to release the liquid storage container of liquid structure, using heating method by the first reagent Load the liquid release in the liquid storage container in chamber 300, the second reagents loaded chamber 400 and third reagents loaded chamber 500 Into corresponding cavity room.The liquid storage container for releasing liquid structure is rotated for having, is for example centrifuged at a relatively high speed using centrifugation, It will be in the liquid storage container in the first reagents loaded chamber 300, the second reagents loaded chamber 400 and third reagents loaded chamber 500 Liquid reagent be discharged into corresponding cavity room.
Secondly as the first hydraulic control pipeline 310, the second hydraulic control pipeline 410 and third hydraulic control pipeline 510 and hydraulic control chamber The first connection end 315, second between 200 is connected to end 415, third connecting end 515 respectively by the liquid in hydraulic control chamber 200 Sealing, therefore due to the effect of atmospheric pressure, especially cooperate the inhibition such as hydrophobic plastic ontology etc. of microtubule, Liquid reagent in first reagents loaded chamber 300, the second reagents loaded chamber 400 and third reagents loaded chamber 500 will not It is flowed into collection chamber 600.
Again, it is less than connection end and the rotation center of any load chamber at a distance from rotation center due to liquid injection hole 210 Distance, it is any load chamber connection end at a distance from rotation center less than liquid outlet pipe liquid feeding end 221 and rotation center Distance, the liquid feeding end 221 of liquid outlet pipe at a distance from rotation center be less than liquid outlet pipe outlet end 222 and rotation center Distance, under the effect of middle low-speed centrifugal, liquid in hydraulic control chamber 200 is flowed into collection chamber by liquid outlet pipe 220 In 600.Liquid outlet pipe 220 is designed as continuous curved snake pipe in one of the embodiments,.Further, wherein In one embodiment, the design of liquid outlet pipe 220 is required to increasing liquid flowing resistance, including but not limited to small size pipeline Or the design of snake pipe, to play the effect for increasing liquid flowing resistance.
Finally, liquid feeding end 221 of 200 liquid level of hydraulic control chamber from liquid injection hole 210 to liquid outlet pipe 220 slowly declines, sequence Drop to the first connection end 315, second connection end 415, third connecting end 515;When the liquid level in hydraulic control chamber 200 drops to first When being connected to 315 or less end, the first hydraulic control pipeline 310 is connected to by the first connection end 315, hydraulic control chamber 200 and liquid injection hole 210 External environment, under the collective effect of atmospheric pressure and centrifugal force, the first reagent in the first reagents loaded chamber 300 is from One load pipeline 320 enters collection chamber 600;When the liquid level in hydraulic control chamber 200 drops to the second 415 or less connection end, the Two hydraulic control pipelines 410 are connected to external environment by the second connection end 415, hydraulic control chamber 200 and liquid injection hole 210, in atmospheric pressure Under power and the collective effect of centrifugal force, the second reagent in the second reagents loaded chamber 400 enters from the second load pipeline 420 Collection chamber 600;When the liquid level in hydraulic control chamber 200 drops to 515 or less third connecting end, third hydraulic control pipeline 510 passes through Third connecting end 515, hydraulic control chamber 200 and liquid injection hole 210 are connected to external environment, in atmospheric pressure and the common work of centrifugal force Under, the third reagent in third reagents loaded chamber 500 enters collection chamber 600 from third load pipeline 520, thus real The sequence load of reagent is showed.Such design, it can be ensured that reagents loaded sequence, first plus the first reagent such as sample, then plus Second reagent such as cleaning solution, finally plus third reagent such as eluent.In centrifugal process, it can also be centrifuged by control Revolving speed, so that the speed of the liquid flowing in hydraulic control chamber 200 is controlled, thus the first reagents loaded chamber 300, second of control The time interval of the release of liquid reagent in reagents loaded chamber 400 and third reagents loaded chamber 500.
Below by taking nucleic acid purification as an example, reagent sequence loading device is continued to explain in conjunction with Fig. 9 to Figure 18 and its is specifically answered With in molecular diagnostic procedure, the nucleic acid purification in nucleic acid extraction step is very crucial, and since nucleic acid purification is related to The sequence of several liquid reagents loads, and is often difficult to be integrated into micro-fluidic chip or other centrifugal microfluidic control devices, and uses The application related embodiment is realized in which then can be convenient.
Sample after cracking, cleaning solution, eluent pass through liquid injection hole (not showing in fluid injection hole pattern) respectively and are added to first In reagents loaded chamber 300, the second reagents loaded chamber 400 and third reagents loaded chamber 500, liquid injection hole is then sealed.Or Person's method preset using reagent, by the sample after cracking, cleaning solution, eluent is preset in respectively in three liquid storage containers, and three A liquid storage container is preset at the first reagents loaded chamber 300, the second reagents loaded chamber 400 and third reagents loaded respectively again In chamber 500, the first reagents loaded chamber 300 is as the sample chamber for accommodating sample liquid, the second reagents loaded chamber 400 as the cleaning solution chamber for accommodating cleaning solution, and third reagents loaded chamber 500 is as accommodating washing for eluent De- sap cavity room, specific reagent is preset and method for releasing is as before, repeat no more.
Water is then injected into hydraulic control chamber 200 by liquid injection hole 210, until liquid level do not had the first hydraulic control pipeline 310 with The interface of hydraulic control chamber 200 i.e. first is connected at end 315.
Reagent sequence loading device or its rotation center are fixed in rotation system, such as by reagent sequence loading device The position of rotation center be fixed on motor rotation axis;Or the centrifugal microfluidic control where reagent sequence loading device is filled It sets and is fixed in rotation system, such as the position of the rotation center of centrifugal microfluidic control device is fixed on motor rotation axis;This step Suddenly sequence can be interchanged with previous step.
It rotates clockwise and reagent sequence loading device or centrifugal microfluidic control device, liquid is for example rotated clockwise with 1500rpm Liquid begins through snakelike liquid outlet pipe 220 and flows into waste liquid chamber 900 in control chamber 200.When liquid level in hydraulic control chamber 200 When being connected at end 315 lower than the first hydraulic control pipeline 310 with the interface of hydraulic control chamber 200 i.e. first, the first reagents loaded chamber 300 are communicated with the atmosphere by liquid injection hole 210, and the sample after cracking in the first reagents loaded chamber 300 is through the first load pipeline 320 flow out in collecting chamber 700, when filter membrane 740 by outlet 710, such as DNA of the nucleic acid in sample after cracking or RNA etc. has been retained on pellosil, and waste liquid is under the action of Coriolis force (Coriolis force) through waste solution channel 730 It fully enters in waste liquid chamber 900.In the present embodiment, filter membrane 740 is pellosil, and concrete model and specification are selected according to demand and be It can.Coriolis force is straight since inertia phase generates rotating system to the particle to move along a straight line in rotating system A kind of description of the offset of line movement.Coriolis force inertia possessed by the object of which movement.When a particle relative to When inertial system moves in a straight line, relative to rotating system, track is a curve, according to the theory of Newtonian mechanics, with rotation System is reference system, and the linear motion of this particle deviates the effect that former directive tendency is summed up as an applied force, i.e., For Coriolis force.
It continuing to rotate, liquid continues through snakelike liquid outlet pipe 220 and flows into waste liquid chamber 900 in hydraulic control chamber 200, When liquid level is connected at end 415 with the interface of hydraulic control chamber 200 i.e. second lower than the second hydraulic control pipeline 410 in hydraulic control chamber 200 When, the second reagents loaded chamber 400 is communicated with the atmosphere by liquid injection hole 210, the cleaning solution in the second reagents loaded chamber 400 It is flowed out in collecting chamber 700 through the second load pipeline 420, when by exporting 710 filter membrane 740, to the nucleic acid on filter membrane 740 (DNA or RNA) is cleaned, and waste liquid fully enters waste liquid chamber 900 through waste solution channel 730 under the action of Coriolis force In.
It rotates counterclockwise and reagent sequence loading device or centrifugal microfluidic control device, liquid is for example rotated counterclockwise with 1500rpm Liquid continues through snakelike liquid outlet pipe 220 and flows into waste liquid chamber 900 in control chamber 200, when liquid level in hydraulic control chamber 200 When lower than at interface, that is, third connecting end 515 of third hydraulic control pipeline 510 and hydraulic control chamber 200, third reagents loaded chamber 500 are communicated with the atmosphere by liquid injection hole 210, and the eluent in third reagents loaded chamber 500 is flowed through third load pipeline 520 Out, into collecting chamber 700, when by exporting 710 filter membrane 740, the nucleic acid (DNA or RNA) on filter membrane 740 is washed De-, the nucleic acid solution after elution is obtained pipeline 720 under the action of Coriolis force and is fully entered in acquisition chamber 800.
In this way, it is achieved that the reagent sequence loading device for being simply to centrifugal microfluidic control plurality of reagents sequence load, So that the sequence loading method of plurality of reagents does not need additional valve gear, realizes simply, not will increase additional processing technology And cost, it is only necessary to which micro-fluidic chip, which is in constant centrifugal rotational speed, can realize the sequence load of reagent, and only need letter Single change reagent sites or LOADED CAVITY number of chambers amount can realize the sequence load of any kind reagent, can also pass through control Centrifugal rotational speed processed has reserved the time to reagent reaction or reagent processing to control the time interval of different reagents loadeds. In other embodiments, the purifying of nucleic acid needs cleaning process twice, and reagent sequence loading device designs four load chambers, Two of them are respectively as cleaning solution chamber, wherein accommodating cleaning solution;The sample after cracking, first may be implemented in this way The sequence of secondary cleaning solution, second of cleaning solution and eluent loads, remaining embodiment and so on.
A kind of centrifugal microfluidic control device in one of the embodiments, comprising the sequence of reagent described in any embodiment adds It carries and sets.Above-mentioned centrifugal microfluidic control device, design is very ingenious, without using various valves, it is only necessary to be in centrifugation rotation environment Under can be realized as plurality of reagents sequence and load, realize it is simple, reduce the design difficulty of reagent sequence load and saved plus Work cost;It, to control the time interval of different reagents loadeds, can especially be reacted to reagent by controlling centrifugal rotational speed Or the time has been reserved in reagent processing;Further, it can be realized arbitrarily by adjusting different reagents in different load chambers The sequence load of kind reagent.
A kind of analysis system in one of the embodiments, comprising centrifugal microfluidic control device described in any embodiment. Above-mentioned analysis system can be used in the analysis such as nucleic acid, albumen, cell, tissue, pathogen and virus, without using various valves, Only needing to be in can be realized as plurality of reagents sequence under centrifugation rotation environment and loads, realize it is simple, reduce reagent sequence plus The design difficulty of load and processing cost is saved.Analysis system is foranalysis of nucleic acids system, packet in one of the embodiments, Include any embodiment centrifugal microfluidic control device.
It should be noted that the other embodiments of the application further include, the mutually group of the technical characteristic in the various embodiments described above Close reagent sequence loading device, centrifugal microfluidic control device and the analysis system that is formed by, can implement.Above embodiments Each technical characteristic can be combined arbitrarily, for simplicity of description, not all to each technical characteristic in above-described embodiment Possible combination is all described, as long as being all considered to be this theory however, there is no contradiction in the combination of these technical features The range that bright secretary carries.Above embodiments only express the several embodiments of the application, and the description thereof is more specific and detailed, But it cannot be understood as the limitations to claim.It should be pointed out that for the ordinary skill people of this field For member, without departing from the concept of this application, various modifications and improvements can be made, these belong to the application Protection scope.Therefore, the scope of patent protection of the application should be determined by the appended claims.

Claims (10)

1. a kind of reagent sequence loading device, which is characterized in that the reagent sequence loading device has rotation center and described Reagent sequence loading device includes liquid outlet pipe, hydraulic control chamber, collection chamber and at least two load chambers;
The liquid feeding end of the liquid outlet pipe is connected to the hydraulic control chamber, and the outlet end of the liquid outlet pipe is connected to the collecting chamber Room,
The reagent sequence loading device is respectively corresponded in each load chamber equipped with hydraulic control pipeline and load pipeline;
The collection chamber, which is equipped with, collects lumen pore, and the hydraulic control chamber is equipped with liquid injection hole, the liquid injection hole and the liquid outlet pipe Liquid feeding end be located at the both ends of the hydraulic control chamber, and arranged from small to large ord at a distance from the rotation center Are as follows: the liquid injection hole, the liquid feeding end of the liquid outlet pipe, the liquid outlet pipe outlet end;
Each load chamber passes through its corresponding described hydraulic control pipeline respectively and is connected to the hydraulic control chamber, and each hydraulic control Pipeline has the connection between the liquid feeding end and the liquid injection hole for being connected with the hydraulic control chamber and being located at the liquid outlet pipe End, each connection end different setting at a distance from the liquid injection hole;
Each load chamber also respectively by its corresponding described load pipeline connection collection chamber, and with the rotation The distance at center arranges from small to large ord are as follows: the load chamber and hydraulic control pipeline is connected described in its position, described Load chamber, the load chamber and the position that is connected of pipeline is loaded described in its.
2. reagent sequence loading device according to claim 1, which is characterized in that the liquid outlet pipe has the block structure, The block structure is arranged for matching rotation speed, the through-rate of liquid outlet pipe when controlling rotation.
3. reagent sequence loading device according to claim 2, which is characterized in that the block structure include be connected to Bending section at few two.
4. reagent sequence loading device according to claim 2, which is characterized in that the block structure includes reducing setting Pass through area.
5. reagent sequence loading device according to claim 1, which is characterized in that the reagent sequence loading device, which has, to be dredged Water material body, the liquid outlet pipe, the hydraulic control chamber, the collection chamber and each load chamber are opened in described In hydrophobic material ontology.
6. reagent sequence loading device according to claim 1, which is characterized in that the reagent sequence loading device includes three A load chamber, three load chambers are respectively the first reagents loaded chamber, the second reagents loaded chamber and third Reagents loaded chamber, and arranged from small to large ord at a distance from the liquid injection hole are as follows: the first reagents loaded chamber It is connected to the connection end for being connected to end, the third reagents loaded chamber at end, the second reagents loaded chamber.
7. according to claim 1 to reagent sequence loading device described in any one of 6, which is characterized in that collection chamber's packet It includes collecting chamber, obtain chamber and waste liquid chamber, it is described to obtain using the line of the center of the collecting chamber and the rotation center as line of reference Chamber and the waste liquid chamber is taken to be located at the two sides of the line of reference;
Each load chamber passes through its corresponding described load pipeline respectively and is connected to the collecting chamber, and the liquid outlet pipe goes out Liquid end is connected to the waste liquid chamber;
The collecting chamber is connected to the acquisition chamber by obtaining pipeline, and the collecting chamber also passes through waste solution channel and is connected to the waste liquid Chamber;
The acquisition chamber be equipped with obtain lumen pore, it is described obtain lumen pore be located at it is described acquisition chamber close to the rotation center position and With the acquisition pipeline enclosure every setting;
The waste liquid chamber is equipped with waste liquid lumen pore, and the waste liquid lumen pore is located at the waste liquid chamber closest to the position of the hydraulic control chamber And it is arranged with the outlet end interval of the liquid outlet pipe.
8. reagent sequence loading device according to claim 7, which is characterized in that the collecting chamber is equipped with outlet, the receipts Collection chamber is respectively communicated with the acquisition chamber and the waste liquid chamber by the outlet;The outlet is equipped with filter membrane.
9. a kind of centrifugal microfluidic control device, which is characterized in that add including the reagent sequence as described in any one of claims 1 to 8 It carries and sets.
10. a kind of analysis system, which is characterized in that including centrifugal microfluidic control device as claimed in claim 9.
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