CN110058007A - Single channel micro-fluidic chip - Google Patents
Single channel micro-fluidic chip Download PDFInfo
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- CN110058007A CN110058007A CN201910391255.8A CN201910391255A CN110058007A CN 110058007 A CN110058007 A CN 110058007A CN 201910391255 A CN201910391255 A CN 201910391255A CN 110058007 A CN110058007 A CN 110058007A
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- backflow structure
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- 238000006243 chemical reaction Methods 0.000 claims abstract description 121
- 239000012530 fluid Substances 0.000 claims abstract description 104
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 36
- 239000007788 liquid Substances 0.000 claims abstract description 34
- 239000002699 waste material Substances 0.000 claims abstract description 24
- 238000003475 lamination Methods 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims description 11
- 238000009825 accumulation Methods 0.000 claims description 8
- 240000008790 Musa x paradisiaca Species 0.000 claims description 3
- 235000018290 Musa x paradisiaca Nutrition 0.000 claims description 3
- 240000007817 Olea europaea Species 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims 1
- 238000000576 coating method Methods 0.000 claims 1
- 210000002966 serum Anatomy 0.000 abstract description 12
- 238000013461 design Methods 0.000 description 6
- 238000002615 hemofiltration Methods 0.000 description 5
- 238000010276 construction Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 241001085205 Prenanthella exigua Species 0.000 description 1
- 244000010375 Talinum crassifolium Species 0.000 description 1
- 235000015055 Talinum crassifolium Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005868 electrolysis reaction Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000003317 immunochromatography Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000012123 point-of-care testing Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502723—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
- G01N33/525—Multi-layer analytical elements
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5302—Apparatus specially adapted for immunological test procedures
- G01N33/5304—Reaction vessels, e.g. agglutination plates
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/533—Production of labelled immunochemicals with fluorescent label
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00178—Special arrangements of analysers
- G01N2035/00237—Handling microquantities of analyte, e.g. microvalves, capillary networks
- G01N2035/00247—Microvalves
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
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- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
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- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Pathology (AREA)
- Urology & Nephrology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Clinical Laboratory Science (AREA)
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- Automatic Analysis And Handling Materials Therefor (AREA)
Abstract
The invention discloses a kind of single channel micro-fluidic chip, including chip body, the chip body is three-chip type structure, including successively the upper layer chip of lamination, middle layer chip and lower layer chip from top to bottom；Sample cavity, quantitative reaction chamber and waste liquid chamber are provided on the chip body；The quantitative reaction chamber, one end perforation are provided with reaction reagent input fluidic channels, and the other end, which then penetrates through, is provided with reaction reagent output fluid channel；And quantitative reaction chamber split settings are upper and lower two parts, correspond to top reaction chamber, lower part reaction chamber；Top reaction chamber, reaction reagent input fluidic channels, reaction reagent output fluid channel are all set in the back side of middle layer chip, and lower part reaction chamber is then set to the front of lower layer chip；Reaction reagent input fluidic channels, reaction reagent output fluid channel are connected to top reaction chamber respectively.It follows that gas can be discharged during sample introduction of the present invention, guarantees that quantitative reaction is intracavitary and be full of sample serum.
Description
Technical field
The present invention relates to a kind of single channel micro-fluidic chips.
Background technique
Lateral chromatography diagnostic techniques is immunized as a kind of stabilization and practical technology, is suitble to the real-time test in multiplicity
(POCT) or scene uses.In immunochromatography reaction system, cause CV big due to system, it is accurate fixed to be unable to reach
Amount.And the immune diagnostic method based on microflow control technique, the above problem can be effectively avoided.
It is micro-fluidic and be divided to passive type and two kinds active.Wherein: passive type is micro-fluidic to need capillary power to reach liquid
The forward lateral chromatography of body.But due to the viscosity of different samples especially whole blood sample difference, cause flow rate of liquid can not
It is unified.It is active micro-fluidic to give forward thrust, make the uniform flow forward of liquid it is possible to prevente effectively from the above problem,
It avoids because of test value difference caused by different in flow rate.Active micro-fluidic power has centrifugation power drive, electrowetting driving, pressure
Power drive (electrolysis pump, compressed gas pump, chemical breakdown pump, the driving of direct draught head), but if to reach arbitrarily control liquid
Body flowing purpose, not only to have motive force, also to there is valve control, also to have anti-return so as not to liquid because pressure removal and
Reflux.
Applicant passes through years of researches, proposes a kind of active micro-fluidic chip, such as Chinese patent
201721237825.0, Chinese patent 201710878470.1 etc., and it is directed to sample cavity therein, specific structure is provided,
Such as Chinese patent 201710377142.3,201910018240.7.
In previous research, the chip structure (referring to above-mentioned each patent) that applicant proposes, the disengaging runner of reaction chamber,
It should be other than the runner with anti-return effect, other micro-fluidic runners are substantially arranged in lower layer chip.This
The arrangement of sample has the disadvantage that the gas in reaction chamber can occupy the top of reaction chamber, and serum underfill is caused to be reacted
Chamber flows out, i.e., the quantitative of reaction chamber may be not accurate enough, to influence experimental precision.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of single channel micro-fluidic chips, by changing existing miniflow
Chip is controlled, by the back side for being arranged at middle layer chip into and out of runner of quantitative reaction chamber.Then during sample introduction, gas can be arranged
Out, guarantee quantitative reaction it is intracavitary be full of sample serum, prevent quantitative reaction chamber into and out of runner at lower layer chip front, gas
Body may occupy the top of quantitative reaction chamber, and serum underfill reaction chamber is caused to flow out.In addition, such arrangement,
The depth of quantitative reaction chamber can be increased.
To realize that above-mentioned technical purpose, the present invention will take the following technical solution:
A kind of single channel micro-fluidic chip, including chip body, the chip body be three-chip type structure, including from top to bottom according to
Upper layer chip, middle layer chip and the lower layer chip of secondary lamination；Be provided on the chip body sample cavity, quantitative reaction chamber with
And waste liquid chamber；The quantitative reaction chamber, one end perforation are provided with reaction reagent input fluidic channels, and the other end is then penetrated through and is provided with
Reaction reagent exports fluid channel；And quantitative reaction chamber split settings are upper and lower two parts, correspond to top reaction chamber, lower part
Reaction chamber；Wherein:
Top reaction chamber, reaction reagent input fluidic channels, reaction reagent output fluid channel are all set in the back side of middle layer chip, and
Lower part reaction chamber is then set to the front of lower layer chip；Reaction reagent input fluidic channels, reaction reagent output fluid channel respectively with
The connection of top reaction chamber.
Further, the reaction reagent input fluidic channels include two branches, respectively fluid channel a, fluid channel b；
An external fluid path interface is provided on the chip body；
External fluid path interface is connect by external fluid path input fluidic channels with fluid channel b；
The outlet of sample cavity is connect with fluid channel a；
And anti-return is provided between external fluid path input fluidic channels and fluid channel b, between the outlet of sample cavity and fluid channel a
Structure.
Further, the Anti-backflow structure between external fluid path input fluidic channels and fluid channel b is the second Anti-backflow structure,
The vertical runner a of vertical runner b, the second Anti-backflow structure including the second Anti-backflow structure, the second Anti-backflow structure are prevented back
Flow connecting passage；
The front of external fluid path input fluidic channels setting lower layer chip, the anti-return connecting passage of the second Anti-backflow structure are set to
The vertical runner b at the back side of upper layer chip, the second Anti-backflow structure is arranged through middle layer chip；
External fluid path input fluidic channels successively pass through the vertical runner b of the second Anti-backflow structure, the second Anti-backflow structure is prevented back
After the vertical runner a for flowing connecting passage, the second Anti-backflow structure, it is connected to fluid channel b.
Further, the outlet of sample cavity is connected to by the first Anti-backflow structure with fluid channel a；
First Anti-backflow structure includes the vertical runner a of the first Anti-backflow structure, the vertical runner b of the first Anti-backflow structure,
The anti-return connecting passage of one Anti-backflow structure；
The front of lower layer chip is arranged in the outlet of sample cavity, and the vertical runner a of the first Anti-backflow structure is set through middle layer chip
It sets, the back side of upper layer chip is arranged in the anti-return connecting passage of the first Anti-backflow structure；
The outlet of sample cavity passes sequentially through the anti-return connection of the vertical runner a of the first Anti-backflow structure, the first Anti-backflow structure
Runner, the first Anti-backflow structure vertical runner b after, be connected to fluid channel a.
Further, the sample cavity includes the sample introduction part filtered sample pond and filter sample Chi Chikou is arranged in；Filter sample pond is set
It sets in the front of lower layer chip, is arranged in bajiao banana sector, and the liquid outlet for filtering sample pond is arranged in narrow side side wall, and filter the pond in sample pond
Bottom is provided with guiding region；Sample introduction part is provided with air hole, the bottom of pond in the filter sample pond at the position of broadside side wall,
Corresponding to each air hole, it is provided with an air slot, air accumulation area is provided between each air slot and guiding region；
Further, guiding region flows to, being at least separated into two fluids can be interconnected in the bottom of pond in filter sample pond according to fluid
Region；In each guiding region, several flow guide bars being distributed in shape is gathered are all had, and flow to the water conservancy diversion of front end in fluid
The distribution density of flow guide bar is less than the distribution density that flow guide bar in the guiding region of rear end is flowed in fluid in area.
Further, the bottom of pond in the filter sample pond is disposed with the first guiding region, the second water conservancy diversion according to fluid flow direction
Area；
Flow guide bar possessed by first guiding region includes two classes, respectively level-one baffle, secondary baffle；Level-one is led
Fluid, secondary baffle are cord protrusion, and the cross sectional dimensions of level-one baffle is greater than the cross section ruler of secondary baffle
It is very little, and the length of level-one baffle is consistent with the secondary length of baffle；Between two adjacent level-one baffles, it is uniformly distributed
There are several secondary baffles；
Second guiding region, at position corresponding with level-one baffle, each along the length extension side of level-one baffle
To being disposed with a flow guide bar；The flow guide bar of second guiding region is raised for cord, and the cross section of the second guiding region cord protrusion
Size is not more than the cross sectional dimensions of level-one baffle.
Further, there are three air slot tools；
Each air slot nestles up three air holes one-to-one correspondence set by the one end for filtering sample pond broadside side wall and sample introduction part and passes through
It is logical, and the other end notch of air slot is arranged, and penetrates through with air accumulation area；
First guiding region has 3 level-one baffles, and the second guiding region has three baffles；And second guiding region cord it is convex
The cross sectional dimensions risen is consistent with the cross sectional dimensions of level-one baffle.
Further, the sample introduction part of the sample cavity is set to upper layer chip, including upper and lower two parts, respectively into
Sample part top, sample introduction part lower part, in which:
Sample introduction part top includes two parts, respectively guide face and ventilative boss；Guide face is tapered from outside to inside sets
The arcwall face set, and close to filter sample pond narrow side side wall setting；Ventilative boss is close to filter sample pond broadside side wall setting, air hole setting
On ventilative boss；
Sample introduction part lower part has sample holes, and the upper end-face edge of sample holes is connect with guide face；And the lower end of sample holes then passes through
The middle layer through-hole being correspondingly arranged on the chip of middle layer and the perforation of filter sample pond；Arc is arranged in the end face outside of through-hole in middle level in middle layer chip
Shape platen item；The front of lower layer chip is arranged in filter sample pond.
Further, coated antibody is provided in the reaction chamber of top；Fluorescent labeled antibody is provided in the reaction chamber of lower part.
Further, the sample cavity is in olive shape, and enclosing along two curved walls of fluid flow direction arrangement
At, and curved wall levels off to semicircular body.
Further, reaction chamber successively passes through reaction reagent output fluid channel, waste liquid output fluid channel is connect with waste liquid chamber；
Waste liquid output fluid channel is set to the front of lower layer chip, and waste liquid output fluid channel and reaction reagent output fluid channel it
Between be provided with conductive rubber micro-valve.
According to above-mentioned technical solution, compared with the existing technology, the present invention has the advantage that
1. the fluid channel of present invention disengaging quantitative reaction chamber is changed to the back side of chip in middle level, so that gas is discharged, guarantee quantitative
Sample serum is full of in reaction chamber, prevent quantitative reaction chamber into and out of runner at lower layer chip front, gas may occupy
The top of quantitative reaction chamber causes serum underfill reaction chamber to flow out.In addition, such arrangement, can increase quantitative
The depth of reaction chamber.
2. bottom of pond of the present invention in hemofiltration pond increases air slot, and air accumulation is arranged between air slot and guiding region
Area, consequently facilitating when sample introduction gas discharge；
3. being successively gas grooves+intensive flow guide bar+evacuation flow guide bar by whole blood flow direction, the benefit being arranged in this way is whole blood
Sample, which enters in sample cell, to be concentrated in groove body, is relatively previously had 3 flow guide bars in entire sample inlet pool, is more advantageous in sample set
Filtering moves forward into reaction chamber, is conducive to airintake direction concentration, reduces dead volume when filtering, it is stagnant that Previous designs have sample
Flow guide bar and the wider front end of sample cell are stayed in, sample is wasted.
4. flow guide bar is changed to by intensively to evacuating, hemofiltration paper being covered on intensive flow guide bar, on the one hand can utmostly be subtracted
Cutout caused by the air pocket generated when few air inlet, on the other hand intensive flow guide bar can accelerate the flow velocity of post-filtered sera, mention
Filtration efficiency.Previously designed hemofiltration paper contacts the bottom surface between 3 flow guide bars, and it is big that serum filters out pressure, thereby increases and it is possible to cause
Serum is absorbed into hemofiltration paper.By intensive flow guide bar to evacuation flow guide bar, serum can be made to collect and moved on into reaction
Chamber can reduce speed if all intensities, comprehensively consider and be set as the intensive rear end evacuation in front end.
5. reaction chamber is changed to, width is bigger, the bigger subcircular of depth, and both ends are cambered design, increase reacting dose, make
Reaction is concentrated, and then fluorescence signal is concentrated, convenient for detection.This designs the mixing for being also beneficial to reaction solution in reaction chamber, reduces former
Design the dead volume at reaction chamber both ends.
6. the setting of reaction chamber antibody are as follows: coated antibody die bottom surface in middle level, fluorescent labeled antibody lower layer chip just
Face.
Detailed description of the invention
Fig. 1 is the schematic perspective view of single channel micro-fluidic chip of the present invention；
Fig. 2 is the explosive view of single channel micro-fluidic chip of the present invention；
In Fig. 2: the chip of the upper layer 1-；The middle layer 2- chip；3- lower layer chip；
Fig. 3 is the front view of Fig. 2 chip at the middle and upper levels；
Fig. 4 is the rearview of Fig. 2 chip at the middle and upper levels；
In Fig. 3, Fig. 4: the sample introduction part of 10- sample cavity；11- air hole；The guide face of 12- sample introduction part；13- sample introduction part
Sample holes；The external fluid path interface of 14-；15- conductive rubber micro-valve；16- waste liquid chamber gas vent；17- waste liquid chamber lid plate；18- first
The anti-return connecting passage of Anti-backflow structure；The anti-return connecting passage of the second Anti-backflow structure of 19-；
Fig. 5 is the front view of middle layer chip in Fig. 2；
Fig. 6 is the rearview of middle layer chip in Fig. 2；
In Fig. 5, Fig. 6: 2-1, sample introduction part middle layer air hole；2-2, middle layer through-hole；2-3, sample introduction part arc platen item；2-4,
The vertical runner a of first Anti-backflow structure；The vertical runner b of 2-5, the first Anti-backflow structure；2-6, second Anti-backflow structure
Vertical runner a；The vertical runner b of 2-7, the second Anti-backflow structure；The middle layer through-hole of 2-8, external fluid path interface；2-9, waste liquid chamber
Bar shaped cover board；The media layer damage of 2-10, conductive rubber micro-valve；The middle layer square through hole of 2-11, waste liquid chamber；2-12, waste liquid chamber
The middle layer through-hole of gas vent；2-13, top reaction chamber；2-14, fluid channel a；2-15, fluid channel b；2-16, reaction reagent output
Fluid channel；
Fig. 7 is the front view of lower layer chip in Fig. 2；
Fig. 8 is the rearview of lower layer chip in Fig. 2；
In Fig. 7, Fig. 8: 31- filters sample pond；The external fluid path input fluidic channels of 32-；The lower part 33- reaction chamber；34- waste liquid exports miniflow
Road；35- strip waste liquid pool；36- rectangle waste liquid pool；37- waterleaf paper positive stop strip；
Fig. 9 is the amplification schematic perspective view in filter sample pond of the present invention；
In Fig. 9: 31-1, air slot；31-2, the first guiding region level-one baffle；31-3, the first guiding region secondary water conservancy diversion
Body；31-4, the second guiding region；31-5, the broadside side wall for filtering sample pond；31-6, the liquid outlet for filtering sample pond；31-7, air accumulation area.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Below
Description only actually at least one exemplary embodiment be it is illustrative, never as to the present invention and its application or make
Any restrictions.Based on the embodiments of the present invention, those of ordinary skill in the art are not making creative work premise
Under every other embodiment obtained, shall fall within the protection scope of the present invention.Unless specifically stated otherwise, otherwise in these realities
The positioned opposite of component and step described in example, expression formula and numerical value is applied not limit the scope of the invention.Meanwhile it should be bright
White, for ease of description, the size of various pieces shown in attached drawing is not to draw according to actual proportionate relationship.It is right
The technology known to person of ordinary skill in the relevant, method and apparatus may be not discussed in detail, but in the appropriate case, institute
Stating technology, method and apparatus should be considered as authorizing part of specification.In shown here and discussion all examples, appoint
What occurrence should be construed as merely illustratively, not as limitation.Therefore, the other examples of exemplary embodiment can
With different values.
For ease of description, spatially relative term can be used herein, as " ... on ", " ... top ",
" ... upper surface ", " above " etc., for describing such as a device shown in the figure or feature and other devices or spy
The spatial relation of sign.It should be understood that spatially relative term is intended to comprising the orientation in addition to device described in figure
Except different direction in use or operation.For example, being described as if the device in attached drawing is squeezed " in other devices
It will be positioned as " under other devices or construction after part or construction top " or the device of " on other devices or construction "
Side " or " under other devices or construction ".Thus, exemplary term " ... top " may include " ... top " and
" in ... lower section " two kinds of orientation.The device can also be positioned with other different modes and (is rotated by 90 ° or in other orientation).
As shown in Figure 1 to 9, single channel micro-fluidic chip of the present invention, including chip body, the chip body are
Three-chip type structure, including successively the upper layer chip 1 of lamination, middle layer chip 2 and lower layer chip 3 from top to bottom；The chip sheet
Sample cavity, quantitative reaction chamber and waste liquid chamber are provided on body；The quantitative reaction chamber, one end perforation are provided with reaction reagent
Input fluidic channels, the other end, which then penetrates through, is provided with reaction reagent output fluid channel 2-16；And quantitative reaction chamber split settings be it is upper,
Lower two parts, correspond to top reaction chamber 2-13, lower part reaction chamber 33；Wherein:
Coated antibody is provided in the reaction chamber 2-13 of top；Fluorescent labeled antibody is provided in lower part reaction chamber 33.
Top reaction chamber 2-13, reaction reagent input fluidic channels, reaction reagent output fluid channel 2-16 are all set in middle layer
The back side of chip 2, and lower part reaction chamber 33 is then set to the front of lower layer chip 3；Reaction reagent input fluidic channels, reaction reagent
Output fluid channel 2-16 is connected to top reaction chamber 2-13 respectively.Reaction chamber in this way, can drain in reaction chamber as much as possible
Gas guarantees to be full of sample serum in reaction chamber, if reaction reagent input fluidic channels, reaction reagent output fluid channel 2-16 exist
3 front of lower layer chip, gas may occupy reaction chamber top, serum underfill quantitative reaction chamber caused to flow out.Meanwhile also
Reaction chamber size can be increased, so that reaction chamber depth is bigger.
The reaction reagent input fluidic channels include two branches, respectively fluid channel a2-14, fluid channel b2-15；It is described
An external fluid path interface 14 is provided on chip body；External fluid path interface 14 by external fluid path input fluidic channels 32 with it is micro-
Runner b2-15 connection；The outlet of sample cavity is connect with fluid channel a2-14；And external fluid path input fluidic channels 32 and fluid channel b2-
Anti-backflow structure is provided between 15, between the outlet of sample cavity and fluid channel a2-14.
Anti-backflow structure between external fluid path input fluidic channels 32 and fluid channel b2-15 is the second Anti-backflow structure, packet
Include the vertical runner b2-7 of the second Anti-backflow structure, the vertical runner a2-6 of the second Anti-backflow structure, the second Anti-backflow structure
Anti-return connecting passage 19；The front of lower layer chip 3 is arranged in external fluid path input fluidic channels 32, and the second Anti-backflow structure is prevented back
Stream connecting passage 19 is set to the back side of upper layer chip 1, and the vertical runner b2-7 of the second Anti-backflow structure is set through middle layer chip 2
It sets；External fluid path input fluidic channels 32 are successively by the vertical runner b2-7 of the second Anti-backflow structure, the second Anti-backflow structure
Anti-return connecting passage 19, the second Anti-backflow structure vertical runner a2-6 after, be connected to fluid channel b2-15.
The outlet of sample cavity is connected to by the first Anti-backflow structure with fluid channel a2-14；First Anti-backflow structure includes the
The vertical runner a2-4 of one Anti-backflow structure, the vertical runner b2-5 of the first Anti-backflow structure, the first Anti-backflow structure are prevented back
Flow connecting passage 18；The front of lower layer chip 3 is arranged in the outlet of sample cavity, and the vertical runner a2-4 of the first Anti-backflow structure is passed through
The setting of middle layer chip 2 is worn, the back side of upper layer chip 1 is arranged in the anti-return connecting passage 18 of the first Anti-backflow structure；Sample cavity
Outlet pass sequentially through the vertical runner a2-4 of the first Anti-backflow structure, the first Anti-backflow structure anti-return connecting passage 18,
After the vertical runner b2-5 of first Anti-backflow structure, it is connected to fluid channel a2-14.
The sample cavity, as shown in figure 9, including filter sample pond 31 and the sample introduction part 10 that filter sample Chi Chikou is arranged in；Filter
The front of lower layer chip 3 is arranged in sample pond, is arranged in bajiao banana sector, and the liquid outlet 31-6 for filtering sample pond is arranged in narrow side side wall,
And the bottom of pond for filtering sample pond is provided with guiding region；Sample introduction part 10 is provided with air hole 11, the bottom of pond in the filter sample pond in close proximity to
At the position of broadside side wall 31-5, corresponds to each air hole 11, be provided with air slot a 31-1, each air slot 31-1
Air accumulation area 31-7 is provided between guiding region；
Guiding region flows to according to fluid in the bottom of pond in filter sample pond, is at least separated into the region that two fluids can be interconnected；?
Each guiding region all has several flow guide bars being distributed in shape is gathered, and flows to water conservancy diversion in the guiding region of front end in fluid
The distribution density of item is less than the distribution density that flow guide bar in the guiding region of rear end is flowed in fluid.Flow guide bar is by intensively to thin
It dissipates, covering hemofiltration paper on intensive flow guide bar, cutout caused by the air pocket generated when on the one hand can utmostly reduce air inlet,
On the other hand intensive flow guide bar can accelerate the flow velocity of post-filtered sera, improve filter efficiency.In addition, by intensive flow guide bar to dredge
Flow guide bar is dissipated, serum can be made to collect and moved on into reaction chamber, speed can be reduced if all intensities, synthesis is examined
Worry is set as the intensive rear end evacuation in front end.
In attached drawing: the bottom of pond in filter sample pond is disposed with the first guiding region, the second guiding region 31-4 according to fluid flow direction；
Flow guide bar possessed by first guiding region includes two classes, respectively level-one baffle 31-2, secondary baffle 31-
3；Level-one baffle 31-2, secondary baffle 31-3 are cord protrusion, and the cross sectional dimensions of level-one baffle 31-2 is greater than
The cross sectional dimensions of secondary baffle 31-3, and the length of level-one baffle 31-2 is consistent with the length of secondary baffle 31-3；
Between two adjacent level-one baffle 31-2, it is evenly distributed with several secondary baffle 31-3；The second guiding region 31-
4, at position corresponding with level-one baffle 31-2, each along the length extending direction of level-one baffle 31-2, it is disposed with one
Root flow guide bar；The flow guide bar of second guiding region 31-4 is raised for cord, and the cross section ruler of the second guiding region 31-4 cord protrusion
The very little cross sectional dimensions no more than level-one baffle 31-2.
Volume based on sample cavity itself, in the present invention, there are three the described air slot 31-1 tools；Each air slot 31-1 is tight
It corresponds and penetrates through against three air holes 11 set by one end of filter sample pond broadside side wall 31-5 and sample introduction part 10, and lead
The other end notch of air drain 31-1 is arranged, and penetrates through with air accumulation area 31-7；First guiding region has 3 level-one baffle 31-
2, and the second guiding region 31-4 has three baffles；And second the cross sectional dimensions of guiding region 31-4 cord protrusion led with level-one
The cross sectional dimensions of fluid 31-2 is consistent.
The sample introduction part 10 of the sample cavity is set to upper layer chip 1, including upper and lower two parts, respectively sample introduction part
10 tops, 10 lower part of sample introduction part, in which:
10 top of sample introduction part includes two parts, respectively guide face 12 and ventilative boss；Guide face 12 is from outside to inside
The arcwall face of tapered setting, and close to filter sample pond narrow side side wall setting；Ventilative boss is arranged close to filter sample pond broadside side wall 31-5,
The setting of air hole 11 is on ventilative boss；
10 lower part of sample introduction part has sample holes 13, and the upper end-face edge of sample holes 13 is connect with guide face 12；And sample holes 13
Lower end then passes through the middle layer through-hole being correspondingly arranged on middle layer chip 2 and the perforation of filter sample pond；The outside of the through-hole in middle level of middle layer chip 2
Arc platen 2-3 is set on end face；The front of lower layer chip 3 is arranged in filter sample pond.
In addition, the quantitative reaction chamber is in olive shape in the present invention, pass through two arcwalls along fluid flow direction arrangement
Face encloses, and curved wall levels off to semicircular body, and quantitative reaction chamber is similar round structure at this time.Such arrangement form,
Reaction chamber size can be further increased, so that reaction chamber width is bigger, increases reacting dose, concentrates reaction, then fluorescence is believed
Number concentrate, convenient for detection.This designs the mixing for being also beneficial to reaction solution in reaction chamber, reduces the dead volume at former design reaction chamber both ends
Product.
Reaction chamber successively passes through reaction reagent output fluid channel 2-16, waste liquid output fluid channel 34 is connect with waste liquid chamber；It is useless
Liquid output fluid channel 34 is set to the front of lower layer chip 3, and waste liquid output fluid channel 34 and reaction reagent export fluid channel 2-
Conductive rubber micro-valve 15 is provided between 16.
About waste liquid chamber, the specific configuration of conductive rubber micro-valve 15, applicant has in the Chinese patent declared before
It more describes in detail, in the application, this two pieces of contents are without place is especially improved, and details are not described herein.
Claims (12)
1. a kind of single channel micro-fluidic chip, including chip body, the chip body is three-chip type structure, including from top to bottom
Successively the upper layer chip of lamination, middle layer chip and lower layer chip；Sample cavity, quantitative reaction chamber are provided on the chip body
And waste liquid chamber；It is characterized in that, the quantitative reaction chamber, one end perforation is provided with reaction reagent input fluidic channels, another
Then perforation is provided with reaction reagent output fluid channel at end；And quantitative reaction chamber split settings are upper and lower two parts, are corresponded to
Portion's reaction chamber, lower part reaction chamber；Wherein:
Top reaction chamber, reaction reagent input fluidic channels, reaction reagent output fluid channel are all set in the back side of middle layer chip, and
Lower part reaction chamber is then set to the front of lower layer chip；Reaction reagent input fluidic channels, reaction reagent output fluid channel respectively with
The connection of top reaction chamber.
2. single channel micro-fluidic chip according to claim 1, which is characterized in that the reaction reagent input fluidic channels packet
Include two branches, respectively fluid channel a, fluid channel b；
An external fluid path interface is provided on the chip body；
External fluid path interface is connect by external fluid path input fluidic channels with fluid channel b；
The outlet of sample cavity is connect with fluid channel a；
And anti-return is provided between external fluid path input fluidic channels and fluid channel b, between the outlet of sample cavity and fluid channel a
Structure.
3. single channel micro-fluidic chip according to claim 2, which is characterized in that external fluid path input fluidic channels and miniflow
Anti-backflow structure between road b is the second Anti-backflow structure, vertical runner b, the second anti-return including the second Anti-backflow structure
The anti-return connecting passage of the vertical runner a of structure, the second Anti-backflow structure；
The front of external fluid path input fluidic channels setting lower layer chip, the anti-return connecting passage of the second Anti-backflow structure are set to
The vertical runner b at the back side of upper layer chip, the second Anti-backflow structure is arranged through middle layer chip；
External fluid path input fluidic channels successively pass through the vertical runner b of the second Anti-backflow structure, the second Anti-backflow structure is prevented back
After the vertical runner a for flowing connecting passage, the second Anti-backflow structure, it is connected to fluid channel b.
4. single channel micro-fluidic chip according to claim 2 or 3, which is characterized in that the outlet of sample cavity passes through first
Anti-backflow structure is connected to fluid channel a；
First Anti-backflow structure includes the vertical runner a of the first Anti-backflow structure, the vertical runner b of the first Anti-backflow structure,
The anti-return connecting passage of one Anti-backflow structure；
The front of lower layer chip is arranged in the outlet of sample cavity, and the vertical runner a of the first Anti-backflow structure is set through middle layer chip
It sets, the back side of upper layer chip is arranged in the anti-return connecting passage of the first Anti-backflow structure；
The outlet of sample cavity passes sequentially through the anti-return connection of the vertical runner a of the first Anti-backflow structure, the first Anti-backflow structure
Runner, the first Anti-backflow structure vertical runner b after, be connected to fluid channel a.
5. single channel micro-fluidic chip according to claim 4, which is characterized in that the sample cavity include filter sample pond and
The sample introduction part of filter sample Chi Chikou is set；The front of lower layer chip is arranged in filter sample pond, is arranged in bajiao banana sector, and filters sample pond
Liquid outlet be arranged in narrow side side wall, and the bottom of pond for filtering sample pond is provided with guiding region；Sample introduction part is provided with air hole, the filter
The bottom of pond in sample pond corresponds to each air hole, is provided with an air slot, respectively leads at the position of broadside side wall
Air accumulation area is provided between air drain and guiding region.
6. single channel micro-fluidic chip according to claim 5, which is characterized in that pressed in the bottom of pond in filter sample pond guiding region
It is flowed to according to fluid, is at least separated into the region that two fluids can be interconnected；In each guiding region, all have several in poly-
Hold together the flow guide bar of shape distribution, and is less than in the distribution density that fluid flows to flow guide bar in the guiding region of front end and is flowed in fluid
The distribution density of flow guide bar in the guiding region of rear end.
7. single channel micro-fluidic chip according to claim 6, which is characterized in that the bottom of pond in the filter sample pond is according to stream
Body flow direction is disposed with the first guiding region, the second guiding region；
Flow guide bar possessed by first guiding region includes two classes, respectively level-one baffle, secondary baffle；Level-one is led
Fluid, secondary baffle are cord protrusion, and the cross sectional dimensions of level-one baffle is greater than the cross section ruler of secondary baffle
It is very little, and the length of level-one baffle is consistent with the secondary length of baffle；Between two adjacent level-one baffles, it is uniformly distributed
There are several secondary baffles；
Second guiding region, at position corresponding with level-one baffle, each along the length extension side of level-one baffle
To being disposed with a flow guide bar；The flow guide bar of second guiding region is raised for cord, and the cross section of the second guiding region cord protrusion
Size is not more than the cross sectional dimensions of level-one baffle.
8. single channel micro-fluidic chip according to claim 7, which is characterized in that there are three the air slot tools；
Each air slot nestles up three air holes one-to-one correspondence set by the one end for filtering sample pond broadside side wall and sample introduction part and passes through
It is logical, and the other end notch of air slot is arranged, and penetrates through with air accumulation area；
First guiding region has 3 level-one baffles, and the second guiding region has three baffles；And second guiding region cord it is convex
The cross sectional dimensions risen is consistent with the cross sectional dimensions of level-one baffle.
9. single channel micro-fluidic chip according to claim 5, which is characterized in that the sample introduction part of the sample cavity is arranged
In upper layer chip, including upper and lower two parts, respectively sample introduction part top, sample introduction part lower part, in which:
Sample introduction part top includes two parts, respectively guide face and ventilative boss；Guide face is tapered from outside to inside sets
The arcwall face set, and close to filter sample pond narrow side side wall setting；Ventilative boss is close to filter sample pond broadside side wall setting, air hole setting
On ventilative boss；
Sample introduction part lower part has sample holes, and the upper end-face edge of sample holes is connect with guide face；And the lower end of sample holes then passes through
The middle layer through-hole being correspondingly arranged on the chip of middle layer and the perforation of filter sample pond；Arc is arranged in the end face outside of through-hole in middle level in middle layer chip
Shape platen item；The front of lower layer chip is arranged in filter sample pond.
10. single channel micro-fluidic chip according to claim 1, which is characterized in that be provided with coating in the reaction chamber of top
Antibody；Fluorescent labeled antibody is provided in the reaction chamber of lower part.
11. single channel micro-fluidic chip according to claim 1, which is characterized in that the sample cavity is in olive shape, is passed through
It is enclosed along two curved walls of fluid flow direction arrangement, and curved wall levels off to semicircular body.
12. single channel micro-fluidic chip according to claim 1, which is characterized in that reaction chamber successively passes through reaction reagent
Output fluid channel, waste liquid output fluid channel are connect with waste liquid chamber；
Waste liquid output fluid channel is set to the front of lower layer chip, and waste liquid output fluid channel and reaction reagent output fluid channel it
Between be provided with conductive rubber micro-valve.
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| TWI765205B (en) * | 2019-12-31 | 2022-05-21 | 台灣嘉碩科技股份有限公司 | Planar apparatus for volumetric body fluid collection and manufacturing method thereof |
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| CN110058007B (en) | 2024-10-18 |
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