CN109929749A - Micro-fluid self-driven micro-fluidic chip and its application method - Google Patents
Micro-fluid self-driven micro-fluidic chip and its application method Download PDFInfo
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Abstract
The present invention provides a kind of micro-fluid self-driven micro-fluidic chip and its application method, micro-fluid self-driven micro-fluidic chip of the invention includes substrate and case chip, and injection port, outlet, multiple reaction chambers and one or more main channel are formed between substrate and case chip；Injection port and outlet can be in communication with the outside, and main channel is connected to injection port and outlet, be provided with feed pathway and liquid outlet channel between each reaction chamber and a main channel；Main channel, reaction chamber, feed pathway and liquid outlet channel be located at substrate and/or the inner surface of case chip be water-wetted surface, and the cross-sectional area of feed pathway is less than the cross-sectional area of liquid outlet channel, in liquid flow path direction in main channel, feed pathway is located at the front side of liquid outlet channel；Oily phase reagent can be passed through after sample to be tested solution enters reaction chamber, in main channel to close feed pathway and liquid outlet channel.Micro-fluid self-driven micro-fluidic chip of the invention can realize sample to be tested solution from driving flowing loading, and no setting is required external drive equipment.
Description
Technical field
The present invention relates to micro-fluidic chip field, in particular to a kind of micro-fluid self-driven micro-fluidic chip and its application method.
Background technique
In the past 20 years, the annual new cancer cases in China are more than 2,200,000, meanwhile, new cases are still with annual 3%-5%
Speed increasing, cancer have become influence our people's life and health first cause of the death.The generation of cancer successively needs to undergo
Gene mutation, cancer cell generate, form the several steps of transfer diffusion of tumour to the end.Current Method for cancer diagnostics mainly has
Pathologic finding, imageological examination etc. will arrive a certain size until tumour growth, and cancer development to middle and later periods can just access more
Accurate detection is as a result, often miss the golden hour of patient.If can be during cancer cell division be value-added
The detection to mutated gene can be realized, Diagnostic Time is shifted to an earlier date, then the survival rate of many patients can be improved.It is a kind of highly sensitive
The nucleic acid detection method urgent need of degree high accuracy is suggested.
Currently, conventional nucleic acid detection method is to expand target nucleic acid molecules, signal amplification is realized.Mainly there is polymerase
Chain reaction (polymerase chain reaction, PCR), ring mediated isothermal amplification (loop-mediated
Isothermal amplification, LAMP) and recombinase polymeric enzymatic amplification (recombinase polymerase
Amplification, RPA) etc., wherein what is be most widely used is Real-Time Fluorescent Quantitative PCR Technique.And in PCR method, the
Then detection sensitivity is higher for three generations's digital pcr method, and it is single that DNA molecular to be measured is dispersed to thousands of reactions in advance by this method
In member, by counting the fluorescence intensity change before and after each reaction member PCR amplification, the DNA that initial sample can be obtained is dense
Degree, can be realized the quantitative detection of super low concentration sample of nucleic acid.It compares for traditional nucleic acid detection technique, digital pcr is examined
It is higher to survey sensitivity, detectable dynamic range is also wider, in cancer markers analysis, antenatal Non-invasive detection, environmental monitoring, food
The multiple fields such as product safety monitoring can access more accurate detection result.
Microfluidic chip technology is integrated into traditional biochemical analysis on one piece several square centimeters or even smaller chip,
It completes to test and analyze in micro/nano-scale channel in the chip and micro chamber.It is more suitable for combining with mononucleotide molecular detecting method
It uses, realizes highly sensitive, the detection of low amount of reagent.In the related manipulation of micro-fluidic chip, it will usually use syringe or
The device drives reagent such as air pump electric pump flows in the chips, this allows for chip operation complexity, and needs to be equipped with corresponding instrument
It can realize function.
Summary of the invention
In view of this, the present invention is directed to propose one kind without external drive equipment, can be realized from the self-powered for driving loading
Dynamic micro-fluidic chip.
In order to achieve the above objectives, the technical scheme of the present invention is realized as follows:
A kind of micro-fluid self-driven micro-fluidic chip, for accommodating sample to be tested solution, the micro-fluid self-driven micro-fluidic chip includes base
Bottom and case chip, at least one the substrate and case chip are colourless transparent material；The case chip, which posts and fixes, to be connected to
On one surface of the substrate, be formed between the substrate and case chip injection port, outlet, multiple reaction chambers and one or
A plurality of main channel；The injection port and outlet can be in communication with the outside, and the main channel is connected to the injection port and outlet,
Feed pathway and liquid outlet channel are provided between each reaction chamber and a main channel；
The main channel, reaction chamber, feed pathway and liquid outlet channel the inner surface for being located at the substrate and/or case chip
For water-wetted surface, and the cross-sectional area of the feed pathway is less than the cross-sectional area of the liquid outlet channel, in the main channel
Liquid flow path direction on, the feed pathway is located at the front side of liquid outlet channel so that by injection port enter the sample to be tested it is molten
Liquid can enter in the reaction chamber under capillary power drive；
Also, the sample to be tested solution enter the reaction chamber after, can be passed through in the main channel oily phase reagent with
Close the feed pathway and liquid outlet channel.
Further, the substrate is made of substrate or the substrate by substrate and fits in anti-on the substrate
Layer is answered to constitute.
Further, the substrate and the conversion zone are silicon wafer, and the case chip is sheet glass.
Further, the injection port, outlet, main channel, reaction chamber, feed pathway and liquid outlet channel pass through etching side
Method is formed in the substrate.
Further, the width of the main channel is 5 μm~5mm, is highly 5 μm~3mm.
Further, the width of the feed pathway is 5 μm~3mm, is highly 5 μm~3mm；The width of the liquid outlet channel
Degree is 5 μm~3mm, is highly 5 μm~3mm.
Further, the feed pathway, the liquid outlet channel, the main channel cross-sectional area be sequentially increased.
Further, the oily phase reagent is one of mineral oil, silicone oil, fluorocarbon oil or paraffin oil or a variety of mixing
Object.
Further, the main channel is set as a plurality of, and is provided between a plurality of main channel and the outlet
Waste liquid pool.
Compared with the existing technology, present invention has the advantage that
Micro-fluid self-driven micro-fluidic chip of the present invention, capillary masterpiece of the sample to be tested solution that injection port enters in channel
Under, from injection port flow forward, when reaching feed pathway, reaction chamber can be entered under the capillary force effect of the feed pathway
It is interior, because the relationship that feed pathway is different with the front and back position relationship and cross-sectional area of liquid outlet channel, sample to be tested are molten
The capillary force that liquid is subject in feed pathway is bigger, it is thus possible to enter in corresponding reaction chamber from feed pathway, and driving a reaction
Intracavitary air flows in main channel from liquid outlet channel.After being continuously added into sample to be tested solution, all reaction chambers can be by
It fills up.Thus can realize sample to be tested solution flows loading from driving, and it is not necessary that external drive equipment is arranged on outer boundary, simultaneously
It can also further prevent the impurity pollution detection sample in environment, and then the sample after amplification can also be avoided to produce environment
Raw pollution.
Present invention also proposes the application methods of micro-fluid self-driven micro-fluidic chip as above comprising following steps:
A, the DNA of sample to be tested or RNA is mixed with the nucleic acid amplification reaction reagent with fluorescence probe or fluorescent dye,
Obtain sample to be tested solution；
B, sample to be tested solution is added at the injection port of micro-fluid self-driven micro-fluidic chip, so that driving of the solution in capillary force
Under flow into main channel first, finally successively flow into feed pathway, reaction chamber, liquid outlet channel, until be full of all channels and reaction
Chamber；
C, oily phase reagent incompatible with water is added in injection port, by pressure-driven make oily phase reagent along primary passageway stream to
Waste liquid pool, and the sample to be tested solution in main channel is made to be driven by oily phase reagent and flow to waste liquid pool, until being full of in main channel
Oily phase reagent, reaction chamber are chambers are individually isolated；
D, injection port and outlet are closed；
E, chip is placed in real-time fluorescence quantitative PCR system, carries out real-time fluorescence acquisition testing, and obtain fluorescence signal
Change curve；Alternatively, chip is placed in In situPCR system, carries out digital pcr amplified reaction and use fluorescence after reaction
Acquisition system carries out fluorescence imaging to reaction cavity region, acquires the fluorescence intensity signals of each reaction chamber, and setting one is glimmering
Intensity threshold, and be more than the reaction chamber of the threshold value for the positive, the number of statistics positive reaction chamber is pushed away using Poisson distribution
Calculating is led, the original copy number of detection sample is obtained, and realizes absolute quantitation.
The application method of micro-fluid self-driven micro-fluidic chip of the invention can be realized real-time fluorescence quantitative PCR detection or number
Formula PCR detection, and its no setting is required structure such as micro-valve Micropump, experimental cost is lower, while its reaction chamber surrounding is sealing state,
Also have many advantages, such as that vaporization prevention, anti-syncretizing effect are good.
Detailed description of the invention
The attached drawing for constituting a part of the invention is used to provide further understanding of the present invention, schematic reality of the invention
It applies example and its explanation is used to explain the present invention, do not constitute improper limitations of the present invention.In the accompanying drawings:
Fig. 1 is the schematic diagram of micro-fluid self-driven micro-fluidic chip described in the embodiment of the present invention one；
Fig. 2 is the schematic diagram of micro-fluid self-driven micro-fluidic chip described in the embodiment of the present invention two；
Fig. 3 is the partial enlarged view in Fig. 2 at I.
Description of symbols:
1- substrate, 11- injection port, 12- outlet, the main channel 13-, 14- reaction chamber, 15- feed pathway, it is logical that 16- goes out liquid
Road, 17- waste liquid pool, 2- case chip, 21- sample introduction through-hole, 22- go out sample through-hole.
Specific embodiment
It should be noted that in the absence of conflict, the feature in embodiment and embodiment in the present invention can phase
Mutually combination.
The present invention will be described in detail below with reference to the accompanying drawings and embodiments.
Embodiment one
This implementation is related to a kind of micro-fluid self-driven micro-fluidic chip, is used to accommodate sample to be tested solution, so as to sample to be tested
Solution carries out the various detection operations such as real-time fluorescence quantitative PCR detection or digital P CR detection.It as shown in Figure 1, should be certainly
Driving micro-fluidic chip includes substrate 1 and case chip 2, at least one in substrate 1 and case chip 2 is colourless transparent material,
The colourless transparent material also should be itself low Poison simultaneously, and the present embodiment low Poison characteristic is generally in PCR reagent institute
With under the excitation wavelength irradiation of fluorescence probe such as FAM, HEX, VIC, CY3, TAMRA, ROX, CY5, material is excited glimmering
Luminous intensity is less than the fluorescence intensity for the fluorescein that concentration is 10e-8mol/L.Sample to be tested can be made molten by the low Poison characteristic
The fluorescence of liquid can be detected instrument reception.
The material of substrate 1, which preferably uses, to be had good biocompatibility, is not easy to adsorb the material of the substances such as nucleic acid, and
It is also preferred that using the material of good heat conduction effect.Specifically in the present embodiment, the case chip 2 is using can be with the glass of light transmission
Piece, and what substrate 1 was then selected is silicon wafer.Certainly, in other embodiments of the present invention, the substrate 1 and case chip 2 can select simultaneously
It can also be its for meeting the present embodiment micro-fluidic chip setting requirements with the transparent materials such as sheet glass or substrate 1 and case chip 2
Its material.
In Fig. 1, in order to clearly show that the structure of case chip 2 Yu substrate 1, the case chip 2 and substrate 1 have been separated centainly
Distance.And in practical applications, which, which posts and fixes, is connected on a surface of substrate 1, and in connection case chip
2 with substrate 1 when, according to the difference of the selection of material, pressure sintering, laser welding, ultrasonic welding, low-temperature bonding, electrostatic can be used
The modes such as bonding, adhesive bonding.
It is still shown by fig. 1, injection port 11, outlet 12, multiple reaction chambers is formed between substrate 1 and case chip 2
14 and a main channel 13.Specifically, the injection port 11, outlet 12, multiple reaction chambers 14 and a main channel 13 are
It is formed in by the method for etching on the surface of substrate 1.Be provided on case chip 2 respectively with injection port 11 and outlet 12
The sample introduction through-hole 21 of consistency from top to bottom and out sample through-hole 22 enable injection port 11 and outlet 12 to be in communication with the outside.Main channel
13 both ends are connected to the injection port 11 and outlet 12 respectively, and sample solution to be detected instills the injection port from sample introduction through-hole 21
After 11, outlet 12 can be flowed to by main channel 13, and flow out from outlet 12.In each reaction chamber 14 and main channel 13
Between be provided with feed pathway 15 and liquid outlet channel 16.
The injection port 11 of the present embodiment preferably can for circle, and its diameter preferably can for 0.5mm, 1mm, 1.2mm,
1.5mm or 2mm highly can be 0.1mm, 0.2mm or 0.3mm.Outlet 12 also, it is preferred that be it is round, and diameter compared with
Good can be 0.5mm, 1mm, 2mm, 3mm, 4mm or 5mm, and height then can be 0.1mm, 0.2mm or 0.3mm.
It should be noted that the injection port 11, outlet 12, multiple reaction chambers 14, main channel 13, feed pathway 15 and go out
Liquid channel 16 also can be set on case chip 2 other than it can be set on the base 1 or simultaneous processing be in 1 He of substrate
On case chip 2.After case chip 2 is posted and fixed on the surface of substrate 1, injection port 11, outlet 12, multiple reaction chambers
14, main channel 13, feed pathway 15 and these structures of liquid outlet channel 16 have been located between substrate 1 and case chip 2, react at this time
Chamber 14, main channel 13, feed pathway 15 and liquid outlet channel 16 are closed between substrate 1 and case chip 2, and can only pass through injection port
11 and outlet 12 be connected to ambient atmosphere.
In addition, also should be noted that for substrate 1 in the present embodiment, which can be only to be made of a substrate,
And the structure for the micro-fluidic chip being made of at this time the substrate and case chip 2 can be found in it is described above.Alternatively, this implementation
The substrate of example can also be made of a substrate and the conversion zone fitted on the substrate, and can etch engrave in conversion zone at this time
The structures such as empty channel and reaction chamber correspond to conversion zone substrate just as bottom, and case chip then as upper layer, is made with this
It obtains micro-fluidic chip and forms three-decker, this is two-layer structure when being only made of substrate different from substrate 1.Substrate and reaction
Layer is preferred still can be for using silicon wafer.
The present embodiment is located at substrate 1 and/or envelope main channel 13, reaction chamber 14, feed pathway 15 and liquid outlet channel 16
The inner surface of load 2 is water-wetted surface, and the cross-sectional area of feed pathway 15 is less than the cross-sectional area of liquid outlet channel 16, main logical
In liquid flow path direction in road 13, feed pathway 15 is located at the front side of liquid outlet channel 16, that is to say, that the liquid in main channel 13
When flowing, feed pathway 15 can be touched first, then just contact liquid outlet channel 16.Water-wetted surface above-mentioned can be by silica
Layer composition.
By above-mentioned setting, the sample to be tested solution that injection port 11 enters under the capillary force effect of main channel 13, from
11 flow forward of injection port can enter reaction chamber under the capillary force effect of the feed pathway 15 when reaching feed pathway 15
In 14, because the relationship that feed pathway 15 is different with the front and back position relationship and cross-sectional area of liquid outlet channel 16, to be measured
The capillary force that sample solution is subject in feed pathway 15 is bigger, it is thus possible to enter corresponding reaction chamber 14 from feed pathway 15
It is interior, and the air in driving a reaction chamber 14 flows in main channel 13 from liquid outlet channel 16.After being continuously added into sample to be tested solution, institute
Some reaction chambers 14 can be filled.In this way, which the micro-fluid self-driven micro-fluidic chip of the present embodiment just realizes sample to be tested
Solution flows loading from driving, it is not necessary that external drive equipment is arranged in the external world.
In the present embodiment, along the liquid flow path direction in main channel 13, the feed pathway 15 and the angle of main channel 13 are less than
90 °, liquid outlet channel 16 and the angle of main channel 13 are then greater than or equal to 90 °, in this way, which sample to be tested solution can be more suitable
It is freely low to enter in feed pathway 15.In addition, feed pathway 15 in the present embodiment, liquid outlet channel 16 and main channel 13 it is transversal
Area is also sequentially increased setting, and since under equal conditions, the cross-sectional area in channel is smaller, internal capillary power is bigger, therefore
15 cross-sectional area of feed pathway is less than liquid outlet channel 16, it is ensured that the capillary force in feed pathway 15 is than the hair in liquid outlet channel 16
Thin power is high, and sample to be tested solution can be entered continuously in reaction chamber 14 from feed pathway 15, and will be in reaction chamber 14
Air be discharged from liquid outlet channel 16, and flow quantity is not less than liquid outlet channel 16 in the unit time in feed pathway 15.
The present embodiment feed pathway 15 and liquid outlet channel 16 intersect the arranged for interval of place with main channel 13, in this way when to be measured
When sample solution is flowed along main channel 13, enough solution can be made to be first into feed pathway 15, and by reaction chamber
Air in 14 is pressed into liquid outlet channel 16, these air can prevent sample to be tested solution from entering liquid outlet channel 16, thus more
It is easy for reaction chamber 14 to be full of.
In the present embodiment, it is highly 5 μm of -3mm that the width of main channel 13, which is 5 μm of -5mm, and preferred, main channel 13
Width can be 10 μm -500 μm, such as 20 μm, 50 μm, 100 μm, 200 μm, 250 μm, 300 μm, 400 μm, the height of main channel 13
It can be 10 μm -500 μm, such as 20 μm, 50 μm, 100 μm, 200 μm, 250 μm, 300 μm, 400 μm.
The width of feed pathway 15 is 5 μm of -3mm, is highly 5 μm of -3mm, and preferred, and the width of feed pathway 15 can be
5 μm -500 μm, such as 10 μm, 20 μm, 50 μm, 100 μm, 200 μm, 250 μm, 300 μm, 400 μm, the height of feed pathway 15 can
It is 5 μm -500 μm, such as 10 μm, 20 μm, 50 μm, 100 μm, 200 μm, 250 μm, 300 μm, 400 μm.
The width of liquid outlet channel 16 is 5 μm of -3mm, is highly 5 μm of -3mm, and preferred, and the width of liquid outlet channel 16 can be
5 μm -500 μm, such as 10 μm, 20 μm, 50 μm, 100 μm, 200 μm, 250 μm, 300 μm, 400 μm, the height of liquid outlet channel 16 can
It is 5 μm -500 μm, such as 10 μm, 20 μm, 50 μm, 100 μm, 200 μm, 250 μm, 300 μm, 400 μm.
In the present embodiment, after sample to be tested solution enters reaction chamber 14, oily mutually examination can be passed through into main channel 13
Agent, the oil phase reagent type is unlimited, may be, for example, one of mineral oil, silicone oil, fluorocarbon oil or paraffin oil, or can also be several
Mixture.Due to having had been filled with sample to be tested solution in reaction chamber 14, feed pathway 15 and liquid outlet channel 16, and it is to be measured
Sample solution be it is aqueous, it is incompatible with oil, therefore oily phase reagent will not enter feed pathway 15 and liquid outlet channel 16, thus may be used
With the state for making sample to be tested solution remain dispersed in each reaction chamber by oily phase reagent and being sealed.Sample-adding terminates
Afterwards, using transparency, high, adhesive tape resistant to high temperature is attached to chip surface, closes injection port 11 and outlet 12.
No drive can be realized by the design and material surface tension of structure in the micro-fluid self-driven micro-fluidic chip of the present embodiment
Dynamic sample introduction is not necessarily to external transfer tube and other driving equipments, and sample-adding process is simple and convenient, in routine experiment environment and various
Special complex experimental enviroment kind detection nucleic acid provides more convenient mode of operation, can also greatly reduce testing cost.Together
When, the chip sample introduction made of this method is quick, can be improved detection speed, greatly shortens the waiting time.
In addition, the applied sample amount of sample to be tested solution needed for the micro-fluid self-driven micro-fluidic chip of the present embodiment is micro updating, for
The demand of sample and reagent is small, it is possible to reduce the difficulty of measured's sample collection, while amount of reagent can also be reduced,
Reduce cost.And the sample introduction of sample to be tested solution and dispersion in closed chip, then amplification with result detection without
Sample is taken out again, all processes do not contact with external environment, the impurity pollution detection sample that can be effectively prevent in environment
This, while the pollution that can also be generated to avoid the sample after amplification for environment.
And compared with the nucleic acid detection chips such as traditional real-time fluorescence quantitative PCR, the micro-fluid self-driven micro-fluidic chip of the present embodiment
Have the function of dispensing reagents, can not only realize traditional detection of nucleic acids, additionally it is possible to realize that digital nucleic acid detects.Digital nucleic acid inspection
Survey method can be realized more highly sensitive and more high accuracy nucleic acid absolute quantitation detection, can theoretically realize unimolecule core
Acid detection.In cancer early screening, cancer with diagnosis, noninvasive Prenatal Screening, organ transplant distribution type etc. for detection sensitivity
And can there be wide application space in the higher field of accuracy requirement.
In addition, compared with current existing digital pcr platform, the micro-fluid self-driven micro-fluidic chip of the present embodiment without be equipped with into
Sampling instrument can substantially reduce the cost of manufacture of chip without the structures such as micro-valve Micropump are made on chip.Simultaneously as
Reaction chamber surrounding is sealing state, is only connected with main channel section, compared to the digital pcr chip of drop and microflute type
Speech, vaporization prevention, anti-syncretizing effect are more preferable.Meanwhile the volume of reaction chamber is fixed, homogeneity is also higher, the sensitivity of detection with
Accuracy is also more preferable.
Embodiment two
This implementation is related to a kind of micro-fluid self-driven micro-fluidic chip, has substantially with the micro-fluid self-driven micro-fluidic chip in embodiment one
Identical structure, the difference is that in the present embodiment, main channel 13 is set as a plurality of in conjunction with shown in Fig. 2 and Fig. 3,
And waste liquid pool 17 is provided between these main channels 13 and outlet 12, the structure of reaction chamber 14 is rectangular.Each main channel 13
In solution to be detected or oily phase reagent be able to enter in waste liquid pool 17, then flow to outlet 12.
In addition, the micro-fluid self-driven micro-fluidic chip of the present embodiment is using, to carry out real-time fluorescence quantitative PCR detection or number
When word PCR detection of nucleic acids, specific application method includes the following steps, and sample to be tested solution hereinafter can be commercialization
HBV DNA fragmentation.And the micro-fluid self-driven micro-fluidic chip of embodiment one also can refer to step as described below when in use.
Specifically, the application method of the micro-fluid self-driven micro-fluidic chip of the present embodiment includes:
Step a, by the DNA of sample to be tested or RNA and the nucleic acid amplification reaction reagent with fluorescence probe or fluorescent dye
Mixing, obtains sample to be tested solution；
Step b, sample to be tested solution is added at the injection port of micro-fluid self-driven micro-fluidic chip, so that solution is in capillary force
Main channel is flowed under driving first, finally successively flows into feed pathway, reaction chamber, liquid outlet channel, until full of all channels and
Reaction chamber；
Step c, oily phase reagent incompatible with water is added in injection port, makes oily phase reagent along main channel by pressure-driven
Waste liquid pool is flowed to, and the sample to be tested solution in main channel is made to be driven by oily phase reagent and flow to waste liquid pool, until in main channel
Full of oily phase reagent, reaction chamber is chambers are individually isolated；
Step d, injection port and outlet are closed；
Step e, chip is placed in real-time fluorescence quantitative PCR system, carries out real-time fluorescence acquisition testing, and obtain fluorescence
Signal intensity curve.Alternatively, chip is placed in In situPCR system, digital pcr amplified reaction is carried out, after reaction, is used
Fluorescent collecting system carries out fluorescence imaging to reaction cavity region, acquires the fluorescence intensity signals of each reaction chamber, and be arranged one
A fluorescence intensity threshold value, and be more than the reaction chamber of the threshold value for the positive, the number of statistics positive reaction chamber utilizes Poisson point
Cloth, which derives, to be calculated, and the original copy number of detection sample is obtained, and realizes absolute quantitation.
The micro-fluid self-driven micro-fluidic chip of the present embodiment can be realized real-time fluorescence quantitative PCR detection or digital P CR inspection
It surveys, the structures such as micro-valve Micropump that no setting is required, experimental cost is low, and reaction chamber surrounding is sealing state, vaporization prevention, anti-syncretizing effect
It is good.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Within mind and principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (10)
1. a kind of micro-fluid self-driven micro-fluidic chip, for accommodating sample to be tested solution, it is characterised in that: described from the micro-fluidic core of driving
Piece includes substrate and case chip, and at least one the substrate and case chip are colourless transparent material；The case chip is bonded and consolidates
Surely it is connected on a surface of the substrate, injection port, outlet, multiple reaction chambers is formed between the substrate and case chip
And one or more main channel；The injection port and outlet can be in communication with the outside, and the main channel is with the injection port and out
The connection of sample mouth, is provided with feed pathway and liquid outlet channel between each reaction chamber and a main channel；
The main channel, reaction chamber, feed pathway and liquid outlet channel the be located at substrate and/or the inner surface of case chip be parent
Water surface, and the cross-sectional area of the feed pathway is less than the cross-sectional area of the liquid outlet channel, the liquid in the main channel
It flows on direction, the feed pathway is located at the front side of liquid outlet channel, so that the sample to be tested solution energy entered by injection port
It is enough to enter in the reaction chamber under capillary power drive；
Also, after the sample to be tested solution enters the reaction chamber, oily phase reagent can be passed through in the main channel to close
The feed pathway and liquid outlet channel.
2. micro-fluid self-driven micro-fluidic chip according to claim 1, it is characterised in that: the substrate is made of substrate, or
The substrate is made of substrate and the conversion zone fitted on the substrate.
3. micro-fluid self-driven micro-fluidic chip according to claim 2, it is characterised in that: the substrate and the conversion zone are silicon
Piece, the case chip are sheet glass.
4. micro-fluid self-driven micro-fluidic chip according to claim 1, it is characterised in that: the injection port, outlet, master are logical
Road, reaction chamber, feed pathway and liquid outlet channel are formed in the substrate by lithographic method.
5. micro-fluid self-driven micro-fluidic chip according to claim 1, it is characterised in that: the width of the main channel be 5 μm~
5mm is highly 5 μm~3mm.
6. micro-fluid self-driven micro-fluidic chip according to claim 1, it is characterised in that: the width of the feed pathway is 5 μm
~3mm is highly 5 μm~3mm；The width of the liquid outlet channel is 5 μm~3mm, is highly 5 μm~3mm.
7. micro-fluid self-driven micro-fluidic chip according to claim 1, it is characterised in that: the feed pathway, the liquid out are logical
Road, the main channel cross-sectional area be sequentially increased.
8. micro-fluid self-driven micro-fluidic chip according to claim 1, it is characterised in that: the oil phase reagent is mineral oil, silicon
One of oil, fluorocarbon oil or paraffin oil or a variety of mixtures.
9. micro-fluid self-driven micro-fluidic chip according to any one of claim 1 to 8, it is characterised in that: the main channel is set
It is set to a plurality of, and is provided with waste liquid pool between a plurality of main channel and the outlet.
10. a kind of application method of micro-fluid self-driven micro-fluidic chip as claimed in claim 9, it is characterised in that: this method includes
Following steps:
A, the DNA of sample to be tested or RNA is mixed with the nucleic acid amplification reaction reagent with fluorescence probe or fluorescent dye, is obtained
Sample to be tested solution；
B, sample to be tested solution is added at the injection port of micro-fluid self-driven micro-fluidic chip, so that solution is first under the driving of capillary force
Main channel is first flowed into, feed pathway, reaction chamber, liquid outlet channel are finally successively flowed into, until being full of all channels and reaction chamber；
C, oily phase reagent incompatible with water is added in injection port, makes oily phase reagent along primary passageway stream to waste liquid by pressure-driven
Pond, and the sample to be tested solution in main channel is made to be driven by oily phase reagent and flow to waste liquid pool, until full of oily phase in main channel
Reagent, reaction chamber are chambers are individually isolated；
D, injection port and outlet are closed；
E, micro-fluid self-driven micro-fluidic chip is placed in real-time fluorescence quantitative PCR system, carries out real-time fluorescence acquisition testing, and obtain
Fluorescence signal change curve；Alternatively, micro-fluid self-driven micro-fluidic chip is placed in In situPCR system, it is anti-to carry out digital pcr amplification
It answers, after reaction, using fluorescent collecting system, fluorescence imaging is carried out to reaction cavity region, acquires the glimmering of each reaction chamber
Light intensity signal, and a fluorescence intensity threshold value is set, and is more than the reaction chamber of the threshold value to be positive, statistics positive reaction chamber
The number of room is derived using Poisson distribution and is calculated, and the original copy number of detection sample is obtained, and realizes absolute quantitation.
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| PCT/CN2020/081497 WO2020192742A1 (en) | 2019-03-27 | 2020-03-26 | Self-driven microfluidic chip and method for using same |
| EP20779964.4A EP3933027A4 (en) | 2019-03-27 | 2020-03-26 | Self-driven microfluidic chip and method for using same |
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Also Published As
| Publication number | Publication date |
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| EP3933027A4 (en) | 2022-04-27 |
| EP3933027A1 (en) | 2022-01-05 |
| CN109929749B (en) | 2021-07-27 |
| WO2020192742A1 (en) | 2020-10-01 |
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