CN211099108U

CN211099108U - Sample introduction cavity of micro-fluidic chip and single-index micro-fluidic chip

Info

Publication number: CN211099108U
Application number: CN201920669941.2U
Authority: CN
Inventors: 许行尚; 杰弗瑞·陈; 于沛; 孙威严
Original assignee: Nanjing Lanyu Biological Technology Co Ltd
Current assignee: Nanjing Lanyu Biological Technology Co Ltd
Priority date: 2019-05-12
Filing date: 2019-05-12
Publication date: 2020-07-28
Anticipated expiration: 2029-05-12

Abstract

The utility model discloses a micro-fluidic chip advance kind chamber and single index micro-fluidic chip. The sample injection cavity of the microfluidic chip comprises a sample filtering pool and a sample injection part arranged at the mouth of the sample filtering pool; the sample filtering pool is arranged in a fan shape of the banana, a liquid outlet of the sample filtering pool is arranged on the side wall of the narrow side, and a flow guide area is arranged at the bottom of the sample filtering pool; the sample introduction part is provided with air holes, the bottom of the sample filtering pool is close to the side wall of the wide edge, a gas guide groove is arranged corresponding to each air hole, and a gas gathering area is arranged between each gas guide groove and the flow guide area; each air guide groove can be communicated with a corresponding air hole, and is communicated with the flow guide area through the air gathering area. Therefore, the utility model discloses increase the air guide groove at the bottom of the pool of filter blood pool to set up gaseous gathering area between air guide groove and water conservancy diversion district, thereby gaseous discharge when being convenient for advance kind reduces the bubble and produces.

Description

Sample introduction cavity of micro-fluidic chip and single-index micro-fluidic chip

Technical Field

The utility model relates to a micro-fluidic chip advances kind chamber.

The utility model discloses still relate to a single index micro-fluidic chip including above-mentioned appearance chamber of advancing.

Background

The immunochromatography diagnostic technique is a stable and practical technique, and is suitable for use in various point-of-care tests (POCTs) or in the field. In the immunochromatography reaction system, the CV is large due to systematic reasons, and accurate quantification cannot be achieved. The immunodiagnosis method based on the microfluidic technology can effectively avoid the problems.

Microfluidics is divided into passive and active. Wherein: passive microfluidic requires capillary forces to achieve lateral flow of liquid forward. However, the liquid flow rate cannot be uniform due to the different viscosities of different samples, especially whole blood samples. Active micro-fluidic can effectively avoid the above-mentioned problem, can give forward thrust, makes liquid even forward flow, avoids because the test value difference that different velocity of flow lead to. The active micro-fluidic power comprises centrifugal force driving, electrowetting driving and pressure driving (electrolytic pump, compressed gas pump, chemical decomposition pump and direct air pressure difference driving), but if the purpose of randomly controlling liquid flow is to be achieved, the driving force is required, valve control is required, and backflow prevention is required to prevent liquid from flowing back due to pressure removal.

Through years of research, the applicant provides an active microfluidic chip, such as chinese patent 201721237825.0, chinese patent 201710878470.1, and the like, and provides specific structures, such as chinese patent 201710377142.3, 201910018240.7, for a sample injection cavity therein.

Through practical application, the applicant finds that although the diversion strips are arranged in the sample filter pool mentioned in the Chinese patent 201910018240.7, the number, the shape and the size of the diversion strips at the wide end and the narrow end of the sample filter pool are the same, so that a sample is easy to stay at the wide front end of the diversion strips and the sample pool, and the sample is wasted. In addition, the arrangement mode of the diversion strips causes high filtering pressure of serum, and the serum is easily absorbed into the blood filtering paper.

In addition, in the past studies of the applicant, including the above-mentioned published chinese patent, since the micro flow channels for entering and exiting the reaction chamber are all provided on the front surface of the lower chip, gas tends to occupy the upper portion of the reaction chamber during actual use, and the serum flows out without filling the reaction chamber, that is, the quantitative determination of the reaction chamber cannot be achieved well.

SUMMERY OF THE UTILITY MODEL

The utility model provides a single index micro-fluidic chip, which changes the existing micro-fluidic chip, arranges a gas guide groove at the bottom of the hemofilter, and arranges a gas gathering area between the gas guide groove and the flow guide area, thereby facilitating the gas discharge; in addition, the utility model further changes the arrangement of the diversion strips at the bottom of the blood filter to effectively promote the concentrated filtration of the sample to enter the reaction chamber forwards, which is beneficial to the concentration of the air inlet direction, reduces the dead volume during the filtration and avoids the sample from being retained at the wider front end of the diversion strips and the sample pool to waste the sample; meanwhile, the cutoff caused by large air bubbles generated during air intake is reduced, the flow rate of filtered serum is accelerated, and the filtering efficiency is improved.

In order to achieve the technical purpose, the utility model adopts the following technical proposal:

a sample injection cavity for a microfluidic chip comprises a sample filtering pool and a sample injection part arranged at the mouth of the sample filtering pool; the sample filtering pool is arranged in a fan shape of the banana, a liquid outlet of the sample filtering pool is arranged on the side wall of the narrow side, and a flow guide area is arranged at the bottom of the sample filtering pool; the sample introduction part is provided with air holes, the bottom of the sample filtering pool is close to the side wall of the wide edge, a gas guide groove is arranged corresponding to each air hole, and a gas gathering area is arranged between each gas guide groove and the flow guide area;

each air guide groove can be communicated with a corresponding air hole, and is communicated with the flow guide area through the air gathering area.

As a further improvement of the sample introduction cavity, the flow guide area is arranged at the bottom of the sample filtering pool and is divided into at least two areas in which fluids can be mutually communicated according to the flow direction of the fluids; each flow guide area is provided with a plurality of flow guide strips which are distributed in a gathering shape, and the distribution density of the flow guide strips in the flow guide area at the front end of the fluid flow is less than that of the flow guide strips in the flow guide area at the rear end of the fluid flow.

As a further improvement of the sample introduction cavity, the bottom of the sample filtering pool is sequentially provided with a first flow guide area and a second flow guide area according to the flow direction of fluid;

the flow guide strips of the first flow guide area comprise two types, namely a first flow guide body and a second flow guide body; the primary flow guide body and the secondary flow guide body are both raised in ribs, the size of the cross section of the primary flow guide body is larger than that of the cross section of the secondary flow guide body, and the length of the primary flow guide body is consistent with that of the secondary flow guide body; a plurality of secondary flow deflectors are uniformly distributed between two adjacent primary flow deflectors;

the second diversion area is provided with a diversion strip along the length extension direction of the first-stage diversion body at the position corresponding to the first-stage diversion body; the guide strips of the second guide area are raised ribs, and the size of the cross section of the raised ribs of the second guide area is not larger than that of the cross section of the first-stage guide body.

As a further improvement of the sample injection cavity, the number of the gas guide grooves is three;

one end of each air guide groove, which is close to the side wall of the wide edge of the sample filtering pool, is communicated with the three air holes arranged on the sample injection part in a one-to-one correspondence manner, and a gap at the other end of the air guide groove is arranged and communicated with the gas gathering area;

the first diversion area is provided with 3 first-stage diversion bodies, and the second diversion area is provided with three diversion bodies; and the size of the cross section of the ridge of the second diversion area is consistent with that of the cross section of the first diversion body.

Another technical object of the utility model is to provide a single index microfluidic chip, which comprises a chip body, wherein the chip body is provided with a sample introduction cavity, a quantitative reaction cavity, a mixing cavity and a waste liquid cavity; the sample introduction cavity comprises a sample filtering pool and a sample introduction part arranged at the inlet of the sample filtering pool; the sample filtering pool is arranged in a fan shape of the banana, a liquid outlet of the sample filtering pool is arranged on the side wall of the narrow side, and a flow guide area is arranged at the bottom of the sample filtering pool; the sample introduction part is provided with air holes, the bottom of the sample filtering pool is close to the side wall of the wide edge, a gas guide groove is arranged corresponding to each air hole, and a gas gathering area is arranged between each gas guide groove and the flow guide area;

As a further improvement of the single-index microfluidic chip, the chip body is of a three-piece structure and comprises an upper chip, a middle chip and a lower chip which are sequentially stacked from top to bottom;

one end of the quantitative reaction cavity is provided with a reaction reagent input micro-channel in a penetrating way, and the other end of the quantitative reaction cavity is provided with a reaction reagent output micro-channel in a penetrating way; the quantitative reaction cavity is divided into an upper part and a lower part which are an upper reaction cavity and a lower reaction cavity correspondingly; wherein:

the upper reaction cavity, the reaction reagent input micro-channel and the reaction reagent output micro-channel are all arranged on the back surface of the middle chip, and the lower reaction cavity is arranged on the front surface of the lower chip; the reaction reagent input micro-channel and the reaction reagent output micro-channel are respectively communicated with the upper reaction cavity.

As a further improvement of the single-index microfluidic chip, a coating antibody is arranged in the upper reaction cavity; the lower reaction cavity is provided with a fluorescence labeling antibody.

As a further improvement of the single-index microfluidic chip, the reaction cavity is olive-shaped and is formed by enclosing two arc-shaped wall surfaces arranged along the flow direction of the fluid, and the arc-shaped wall surfaces approach to a semicircular body.

As a further improvement of the single-index microfluidic chip, the chip body is provided with two external liquid path interfaces, namely a first external liquid path interface and a second external liquid path interface; wherein:

the second external liquid path interface is communicated with the reaction reagent input micro-channel of the reaction cavity through a second reagent conveying micro-channel a and a second reagent conveying micro-channel b in sequence;

the first external liquid path interface is communicated with the reagent input micro-channel of the mixing cavity after sequentially passing through the first reagent delivery micro-channel a and the first reagent delivery micro-channel b; the reagent output micro-channel of the mixing cavity is communicated with the second reagent delivery micro-channel through the first reagent delivery micro-channel c;

and anti-backflow structures are respectively arranged between the reagent input micro-channel of the mixing cavity and the first reagent conveying micro-channel a, between the reagent output micro-channel of the mixing cavity and the first reagent conveying micro-channel c, and between the second reagent conveying micro-channel a and the second reagent conveying micro-channel b.

As a further improvement of the single-index microfluidic chip, the second reagent conveying microchannel a is arranged on the front surface of the lower chip, and the second reagent conveying microchannel b is arranged on the back surface of the middle chip; the anti-backflow structure between the second reagent conveying micro-channel a and the second reagent conveying micro-channel b is a second anti-backflow structure and comprises a vertical channel a of the second anti-backflow structure, a vertical channel b of the second anti-backflow structure and an anti-backflow connecting channel of the second anti-backflow structure; the anti-backflow connecting flow channel of the second anti-backflow structure is arranged on the back surface of the upper chip, and two ends of the vertical flow channel of the second anti-backflow structure penetrate through the middle chip;

the second reagent conveying micro-channel a sequentially passes through the vertical channel b of the second anti-backflow structure, the anti-backflow connecting channel of the second anti-backflow structure and the vertical channel a of the second anti-backflow structure and then is connected with the second reagent conveying micro-channel b.

As a further improvement of the single-index microfluidic chip, the sample injection part of the sample injection cavity is arranged on the upper chip, the upper part and the lower part of the sample injection part are respectively the upper part and the lower part of the sample injection part, and the upper part of the sample injection part comprises two parts which are respectively a flow guide surface and a breathable boss; the flow guide surface is an arc flow guide surface which is arranged in a gradually reducing manner from outside to inside and is arranged close to the side wall of the narrow edge of the sample filtering pool; the air-permeable boss is arranged close to the side wall of the wide edge of the sample filtering pool, and the air holes are formed in the air-permeable boss;

the lower part of the sample injection part is provided with a sample injection hole, and the edge of the upper end of the sample injection hole is connected with the flow guide surface; the lower end of the sample inlet hole is communicated with the sample filtering pool through a middle layer through hole correspondingly arranged on the middle layer chip; the middle chip is provided with an arc-shaped paper pressing strip on the end face of the outer side of the middle through hole; the sample filtering pool is arranged on the front surface of the lower chip.

As a further improvement of the single-index microfluidic chip, the outlet of the sample filtering pool is communicated with a reaction reagent input microchannel of the reaction cavity through a first anti-backflow structure;

the first backflow prevention structure comprises a vertical flow channel a of the first backflow prevention structure, a vertical flow channel b of the first backflow prevention structure and a backflow prevention connecting flow channel of the first backflow prevention structure;

the anti-backflow connecting flow channel of the first anti-backflow structure is arranged on the back surface of the upper chip, and two ends of the vertical flow channel of the first anti-backflow structure penetrate through the middle chip;

the outlet of the sample filtering pool is communicated with the reaction reagent input micro-channel of the reaction cavity sequentially through the vertical channel a of the first anti-backflow structure, the anti-backflow connecting channel of the first anti-backflow structure and the vertical channel b of the first anti-backflow structure.

As a further improvement of the single-index microfluidic chip, the mixing cavity comprises a lower part of the mixing cavity arranged on the lower chip and an upper part of the mixing cavity arranged on the middle chip; the upper part of the mixing cavity can be enclosed with the lower part of the mixing cavity to form the mixing cavity.

According to foretell technical scheme, for prior art, the utility model has the advantages of as follows:

1. the utility model adds the air guide groove at the bottom of the filter, and arranges the gas gathering area between the air guide groove and the flow guide area, thereby facilitating the discharge of gas during sample introduction;

2. for being gas tank + intensive water conservancy diversion strip + sparse water conservancy diversion strip according to whole blood flow direction in proper order, the benefit that sets up like this is, whole blood sample gets into in the sample cell can concentrate in the cell body, there are 3 water conservancy diversion strips in whole advance advancing the appearance pond, more be favorable to the sample to concentrate to filter and get into the reaction chamber forward, be favorable to the direction of admitting air to concentrate, dead volume when reducing the filtration, the design has the sample to be detained at the front end of water conservancy diversion strip and sample cell broad before, extravagant sample.

3. The diversion strips are changed from dense to sparse, and the dense diversion strips are covered with the blood filtering paper, so that on one hand, the cutoff caused by large bubbles generated during air intake can be reduced to the maximum degree, on the other hand, the dense diversion strips can accelerate the flow rate of filtered serum, and the filtering efficiency is improved. The previously designed blood filter paper contacts the bottom surface between the 3 strips, the serum filtering pressure is high, and the serum can be absorbed into the blood filter paper. From the dense diversion strips to the evacuation diversion strips, the serum can be collected and continuously advance to enter the reaction cavity, if the serum is dense, the speed is reduced, and the front-end dense evacuation is comprehensively considered.

4. The micro-flow channel entering and exiting the reaction cavity is changed into the bottom surface of the middle-layer chip, so that gas can be discharged, the reaction cavity is guaranteed to be filled with sample serum, and if the micro-flow channel is arranged on the front surface of the lower layer, the gas can occupy the upper part of the reaction cavity, so that the serum flows out when the reaction cavity is not filled with the serum.

5. The reaction cavity is changed into a nearly circular shape with larger width and larger depth, and the two ends are designed in an arc shape, so that the reaction amount is increased, the reaction is concentrated, and then, the fluorescent signal is concentrated, and the detection is convenient. The design is also beneficial to uniformly mixing the reaction liquid in the reaction cavity, and the dead volume at two ends of the originally designed reaction cavity is reduced.

6. The reaction chamber antibody is set as follows: the coating antibody is arranged on the bottom surface of the middle chip, and the fluorescence labeling antibody is arranged on the front surface of the lower chip.

Drawings

Fig. 1 is a schematic structural diagram of a sample introduction cavity of a microfluidic chip according to the present invention;

FIG. 2 is a top view of FIG. 1;

FIG. 3 is a schematic perspective view of the sample cell of FIG. 1;

in fig. 3: 31-1, air guide grooves; 31-2, a first diversion body of the first diversion area; 31-3, a secondary flow conductor of the first flow guiding zone; 31-4, a second flow guide zone; 31-5, the wide side wall of the sample filtering pool; 31-6, a liquid outlet of the sample filtering pool; 31-7 and a gas gathering area.

Fig. 4 is a schematic perspective view of a single-index microfluidic chip according to the present invention;

fig. 5 is an exploded view of the single index microfluidic chip of the present invention;

in fig. 5: 1-upper chip; 2-middle layer chip; 3-lower chip;

FIG. 6 is a front view of the upper chip of FIG. 4;

FIG. 7 is a rear view of the upper chip of FIG. 4;

in fig. 6 and 7: 1-1, a sample injection part of a sample injection cavity; 1-2, air holes; 1-3, an external gas circuit interface of the sample injection part; 1-4, sample inlet holes of the sample inlet part; 1-5, a flow guide surface of the sample injection part; 1-6, a first external liquid circuit interface; 1-7, a second external liquid path interface; 1-8, conductive rubber micro-valve; 1-9, an exhaust hole of the waste liquid cavity; 1-10, an anti-backflow connecting flow channel of a second anti-backflow structure; 1-11, an anti-backflow connecting flow channel of the first anti-backflow structure; 1-12, a waste liquid chamber cover plate; 1-13, and a third backflow prevention structure connected with a micro-channel; 1-14, and an anti-backflow connecting micro-channel of a fourth anti-backflow structure;

FIG. 8 is a front view of the middle layer chip of FIG. 4;

FIG. 9 is a rear view of the middle layer chip of FIG. 4;

in fig. 8 and 9: 2-1, injecting sample part middle layer air holes; 2-2, a middle layer through hole of the sample inlet hole; 2-3, arc-shaped paper pressing strips; 2-4, a vertical flow channel a of the first backflow prevention structure; 2-5, a vertical flow passage b of the first backflow prevention structure; 2-6, a vertical runner a of a second backflow prevention structure; 2-7, a vertical flow passage b of a second backflow prevention structure; 2-8, a first reagent delivery micro-channel a; 2-9, a mark setting area; 2-10, a middle layer structure of the conductive rubber micro valve; 2-11, a middle layer rectangular through hole of the waste liquid cavity; 2-12, a second reagent delivery micro-channel b; 2-13, the lower part of the uniform mixing cavity; 2-14, a vertical flow passage a of a fourth backflow prevention structure; 2-15, an upper reaction chamber; 2-16, outputting a reaction reagent micro-channel; 2-17, a middle layer exhaust hole of the waste liquid cavity; 2-18, a second liquid path through hole; 2-19, a vertical flow passage a of a third backflow prevention structure; 2-20, the upper part of the uniform mixing cavity; 2-21, a middle layer caulking groove of the waste liquid cavity; 2-22, inputting a reaction reagent into the micro-channel; 2-23, a first reagent delivery micro-channel c;

FIG. 10 is a front view of the lower chip of FIG. 4;

FIG. 11 is a rear view of the lower chip of FIG. 4;

in fig. 10 and 11: 31-a sample filtering pool; 32-a lower reaction chamber; 33-second reagent delivery micro flow channel a; 34-the lower part of the mixing cavity; 35-first reagent delivery micro flow channel b; 36-microfluidic flow channel c; 37-waste liquid pool end ear; 38-rectangular waste liquid pool; 39-limiting strip of absorbent paper.

Detailed Description

The technical solutions in the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, not all embodiments. The following description of at least one exemplary embodiment is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. Based on the embodiments in the present invention, all other embodiments obtained by a person skilled in the art without creative efforts belong to the protection scope of the present invention. Unless specifically stated otherwise, the relative arrangement of the components and steps, expressions, and numerical values set forth in these embodiments do not limit the scope of the present invention. Meanwhile, it should be understood that the sizes of the respective portions shown in the drawings are not drawn in an actual proportional relationship for the convenience of description. Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate. In all examples shown and discussed herein, any particular value should be construed as merely illustrative, and not limiting. Thus, other examples of the exemplary embodiments may have different values.

Spatially relative terms, such as "above … …," "above … …," "above … …," "above," and the like, may be used herein for ease of description to describe one device or feature's spatial relationship to another device or feature as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is turned over, devices described as "above" or "on" other devices or configurations would then be oriented "below" or "under" the other devices or configurations. Thus, the exemplary term "above … …" can include both an orientation of "above … …" and "below … …". The device may also be oriented in other different ways (rotated 90 degrees or at other orientations).

As shown in fig. 1 to 3, the sample injection cavity for a microfluidic chip of the present invention includes a sample filtering tank 31 and a sample injection part 1-1 disposed at a tank port of the sample filtering tank 31; as shown in fig. 3, the sample filtering pool 31 is arranged in a fan shape of banana, the liquid outlet 31-6 of the sample filtering pool 31 is arranged on the side wall of the narrow side, and the bottom of the sample filtering pool 31 is provided with a flow guiding area; the sample injection part 1-1 is provided with air holes 1-2, the bottom of the sample filtering pool 31 is provided with an air guide groove 31-1 corresponding to each air hole 1-2 at the position close to the wide side wall 31-5, and an air gathering area 31-7 is arranged between each air guide groove 31-1 and the flow guide area; each air guide groove 31-1 can be communicated with a corresponding air hole 1-2, and simultaneously, each air guide groove 31-1 is communicated with the flow guide area through the air gathering area 31-7.

The diversion area is arranged at the bottom of the sample filtering pool 31 and is divided into at least two areas which can be mutually communicated according to the flow direction of the fluid; each flow guide area is provided with a plurality of flow guide strips which are distributed in a gathering shape, and the distribution density of the flow guide strips in the flow guide area at the front end of the fluid flow is less than that of the flow guide strips in the flow guide area at the rear end of the fluid flow. The guide strips are from dense to sparse, and the dense guide strips are covered with the blood filtering paper, so that on one hand, the flow breaking caused by large bubbles generated during air intake can be reduced to the maximum degree, on the other hand, the dense guide strips can accelerate the flow rate of filtered serum, and the filtering efficiency is improved. In addition, from the dense diversion strips to the evacuation diversion strips, the serum can be collected to continuously advance into the reaction cavity, if the serum is dense, the speed is reduced, and the front dense end and the rear dense end are comprehensively considered to be evacuated.

In the drawings: the bottom of the sample filtering pool 31 is provided with a first flow guide area and a second flow guide area 31-4 in sequence according to the flow direction of the fluid;

the first diversion area is provided with diversion strips which comprise two types, namely a first diversion body 31-2 and a second diversion body 31-3; the first-stage flow guide body 31-2 and the second-stage flow guide body 31-3 are both provided with ridge protrusions, the cross section size of the first-stage flow guide body 31-2 is larger than that of the second-stage flow guide body 31-3, and the length of the first-stage flow guide body 31-2 is consistent with that of the second-stage flow guide body 31-3; a plurality of secondary flow deflectors 31-3 are uniformly distributed between two adjacent primary flow deflectors 31-2; the second diversion area 31-4 is provided with a diversion strip along the length extension direction of the first-stage diversion body 31-2 at the position corresponding to the first-stage diversion body 31-2; the flow guide strips of the second flow guide area 31-4 are rib protrusions, and the cross section size of the rib protrusions of the second flow guide area 31-4 is not larger than the cross section size of the first-stage flow guide body 31-2.

Based on the volume of the sample introduction cavity, three gas guide grooves 31-1 are arranged in the utility model; one end of each air guide groove 31-1, which is close to the wide side wall 31-5 of the sample filtering pool 31, is communicated with three air holes 1-2 arranged on the sample injection part 1-1 in a one-to-one correspondence way, and the other end of the air guide groove 31-1 is arranged with a gap and is communicated with a gas gathering area 31-7; the first flow guiding zone has 3 first flow guiding bodies 31-2, and the second flow guiding zone 31-4 has three flow guiding bodies; and the cross-sectional dimension of the ridge protrusion of the second flow guide zone 31-4 is consistent with the cross-sectional dimension of the first-stage flow guide body 31-2.

As shown in fig. 4 to 11, the utility model discloses a single-index microfluidic chip, which comprises a chip body, wherein a sample introduction cavity, a quantitative reaction cavity, a mixing cavity and a waste liquid cavity are arranged on the chip body; the sample introduction cavity comprises a sample filtering pool 31 and a sample introduction part 1-1 arranged at the pool port of the sample filtering pool 31; the sample filtering pool 31 shown in fig. 3 is adopted, and specifically: the sample filtering pool 31 is arranged in a fan shape of a banana, a liquid outlet 31-6 of the sample filtering pool 31 is arranged on the side wall of the narrow side, and a flow guide area is arranged at the bottom of the sample filtering pool 31; the sample injection part 1-1 is provided with air holes 1-2, the bottom of the sample filtering pool 31 is provided with an air guide groove 31-1 corresponding to each air hole 1-2 at the position close to the wide side wall 31-5, and an air gathering area 31-7 is arranged between each air guide groove 31-1 and the flow guide area; each air guide groove 31-1 can be communicated with a corresponding air hole 1-2, and simultaneously, each air guide groove 31-1 is communicated with the flow guide area through the air gathering area 31-7.

As shown in fig. 5 to 11, the chip body has a three-piece structure, and includes an upper chip, a middle chip, and a lower chip stacked in sequence from top to bottom; one end of the quantitative reaction cavity is provided with a reaction reagent input micro-channel 2-22 in a run-through way, and the other end of the quantitative reaction cavity is provided with a reaction reagent output micro-channel 2-16 in a run-through way; the quantitative reaction cavity is divided into an upper part and a lower part which are correspondingly an upper reaction cavity 2-15 and a lower reaction cavity 32; wherein: the upper reaction chamber 2-15, the reaction reagent input micro flow channel 2-22 and the reaction reagent output micro flow channel 2-16 are all arranged on the back of the middle chip, and the lower reaction chamber 32 is arranged on the front of the lower chip; the reaction reagent input micro-channels 2-22 and the reaction reagent output micro-channels 2-16 are respectively communicated with the upper reaction cavity 2-15. A coating antibody is arranged in the upper reaction cavity 2-15; the lower reaction chamber 32 is provided with a fluorescent-labeled antibody. The reaction chamber is arranged in such a way, so that gas in the reaction chamber can be discharged as far as possible, the reaction chamber is full of sample serum, and if the micro-channel is arranged on the front surface of the lower layer, the gas can occupy the upper part of the reaction chamber, so that the serum flows out when the reaction chamber is not full of the serum. Meanwhile, the size of the reaction cavity can be increased, so that the depth of the reaction cavity is larger.

The reaction cavity is olive-shaped and is formed by enclosing two arc-shaped wall surfaces arranged along the flow direction of the fluid, and the arc-shaped wall surfaces approach to a semicircular body. The size of the reaction cavity can be further increased by the arrangement form, so that the width of the reaction cavity is larger, the reaction amount is increased, the reaction is concentrated, and then the fluorescent signal is concentrated, thereby facilitating the detection. The design is also beneficial to uniformly mixing the reaction liquid in the reaction cavity, and the dead volume at two ends of the originally designed reaction cavity is reduced.

The chip body is provided with two external liquid path interfaces, namely a first external liquid path interface 1-6 and a second external liquid path interface 1-7; wherein:

and the second external liquid path interface 1-7 is used for externally connecting the color developing agent/cleaning agent and is communicated with the reaction reagent input micro-channel 2-22 of the reaction cavity through a second reagent conveying micro-channel a33 and a second reagent conveying micro-channel b2-12 in sequence.

The first external liquid path interface 1-6 is used for externally connecting the blending buffer solution, sequentially passes through the first reagent conveying micro-channel a2-8 and the first reagent conveying micro-channel b35, and then is communicated with the reagent input micro-channel of the blending cavity; the reagent output micro-channel of the mixing cavity is communicated with the second reagent delivery micro-channel through the first reagent delivery micro-channel c 2-23; anti-backflow structures are arranged between the reagent input micro-channel of the mixing cavity and the first reagent conveying micro-channel a2-8, between the reagent output micro-channel of the mixing cavity and the first reagent conveying micro-channel c2-23, and between the second reagent conveying micro-channel a33 and the second reagent conveying micro-channel b 2-12.

The second reagent conveying micro-channel a33 is arranged on the front surface of the lower chip, the second external liquid path interface 1-7 can be communicated with the second reagent conveying micro-channel a33 only by passing through a second liquid path through hole 2-18 which is arranged on the middle chip in a penetrating way, and the second reagent conveying micro-channel b2-12 is arranged on the back surface of the middle chip; the anti-backflow structure between the second reagent conveying micro-channel a33 and the second reagent conveying micro-channel b2-12 is a second anti-backflow structure and comprises a vertical channel a2-6 of the second anti-backflow structure, a vertical channel b2-7 of the second anti-backflow structure and an anti-backflow connecting channel 1-10 of the second anti-backflow structure; the anti-backflow connecting flow channels 1-10 of the second anti-backflow structure are arranged on the back surface of the upper chip, and two ends of the vertical flow channel b2-7 of the second anti-backflow structure penetrate through the middle chip; the second reagent conveying micro-channel a33 passes through the vertical channel b2-7 of the second anti-backflow structure, the anti-backflow connecting channel 1-10 of the second anti-backflow structure and the vertical channel a2-6 of the second anti-backflow structure in sequence and then is connected with the second reagent conveying micro-channel b 2-12.

The sample introduction part 1-1 of the sample introduction cavity is arranged on the upper chip and comprises an upper part and a lower part which are respectively the upper part of the sample introduction part 1-1 and the lower part of the sample introduction part 1-1, and the upper part of the sample introduction part 1-1 comprises two parts which are respectively a flow guide surface 1-5 and a breathable boss; and the periphery of the sample injection part is provided with an external gas circuit interface on the front surface of the upper chip so as to be connected with an external gas source and push the sample to flow into the quantitative reaction cavity from the sample injection cavity. The flow guide surface is an arc flow guide surface 1-5 which is arranged from outside to inside in a gradually reducing way and is arranged close to the side wall of the narrow edge of the sample filtering pool 31; the air-permeable boss is arranged close to the wide side wall 31-5 of the sample filtering pool 31, and the air holes 1-2 are arranged on the air-permeable boss; the lower part of the sample introduction part 1-1 is provided with a sample introduction hole 1-4, and the edge of the upper end of the sample introduction hole 1-4 is connected with the flow guide surface; the lower ends of the sample inlet holes 1-4 are communicated with the sample filtering pool 31 through a middle layer through hole correspondingly arranged on the middle layer chip; the middle chip is provided with arc-shaped paper pressing strips 2-3 on the end face of the outer side of the middle through hole; the sample well 31 is provided on the front surface of the lower chip.

The reaction reagent output micro-channels 2-16 are connected with the waste liquid cavity through the micro-fluidic channel c 36. And conductive rubber micro valves 1-8 are arranged between the reaction reagent output micro channels 2-16 passing through the micro flow channel c 36.

The outlet of the sample filtering pool 31 is communicated with the reaction reagent input micro-channel 2-22 of the reaction cavity through a first anti-backflow structure;

the first backflow prevention structure comprises a vertical flow channel a2-4 of the first backflow prevention structure, a vertical flow channel b2-5 of the first backflow prevention structure and backflow prevention connecting flow channels 1-11 of the first backflow prevention structure;

the anti-backflow connecting flow channel 1-11 of the first anti-backflow structure is arranged on the back surface of the upper chip, and two ends of the vertical flow channel a2-4 of the first anti-backflow structure penetrate through the middle chip;

the outlet of the sample filtering pool 31 is communicated with the reaction reagent input micro flow channel 2-22 of the reaction cavity sequentially through the vertical flow channel a2-4 of the first anti-backflow structure, the anti-backflow connecting flow channel 1-11 of the first anti-backflow structure and the vertical flow channel b2-5 of the first anti-backflow structure.

The mixing cavity comprises a mixing cavity lower part 34 arranged on the lower layer chip, and mixing cavity lower parts 2-13 and mixing cavity upper parts 2-20 arranged on the middle layer chip; the upper part of the mixing cavity can be enclosed with the lower part of the mixing cavity to form the mixing cavity, and the upper part of the mixing cavity is arranged in an outward convex shape.

Two ends of the mixing cavity are respectively and correspondingly provided with a reagent input micro-channel and a reagent output micro-channel according to the fluid conveying direction; and the reagent input micro-channel of the mixing cavity and the reagent output micro-channel of the mixing cavity are both arranged on the front surface of the middle-layer chip. A fourth backflow prevention structure is arranged between the reagent input micro-channel of the mixing cavity and the first reagent conveying micro-channel b35, and a third backflow prevention structure is arranged between the reagent output micro-channel of the mixing cavity and the first reagent conveying micro-channel c 2-23.

The third backflow prevention structure and the fourth backflow prevention structure are similar to the first backflow prevention structure and the second backflow prevention structure in specific structure. Wherein: the third backflow prevention structure comprises backflow prevention connecting micro channels 1-13 of the third backflow prevention structure and vertical channels a2-19 of the third backflow prevention structure; the fourth anti-backflow structure comprises anti-backflow connecting micro channels 1-14 of the fourth anti-backflow structure and vertical channels a2-14 of the fourth anti-backflow structure; the anti-backflow connecting micro-channels 1-13 of the third anti-backflow structure and the anti-backflow connecting micro-channels 1-14 of the fourth anti-backflow structure are arranged at corresponding positions on the back surface of the upper-layer chip. The vertical flow channels a2-19 of the third backflow prevention structure and the vertical flow channels a2-14 of the fourth backflow prevention structure are through holes at corresponding positions on the middle chip.

Mixing buffer flow path:

after flowing into the chip body through the first external liquid path interface, the blending buffer solution sequentially flows through the first reagent conveying micro-channel a2-8 and the first reagent conveying micro-channel b35, sequentially flows through the vertical channel a2-14 of the fourth anti-backflow structure, the anti-backflow connecting micro-channel 1-14 of the fourth anti-backflow structure and the reagent input micro-channel of the blending cavity, and then flows into the blending cavity. The mixed reagent mixed in the mixing cavity sequentially passes through a reagent output micro-channel of the mixing cavity, a backflow prevention connecting micro-channel 1-13 of a backflow prevention structure, a vertical channel a2-19 of the backflow prevention structure, a first reagent conveying micro-channel c2-23 and a second reagent conveying micro-channel b2-12, and then flows into the reaction cavity (an upper reaction cavity 2-15 and a lower reaction cavity 32) through a reaction reagent input micro-channel 2-22.

External connection of cleaning solution/developer flow path:

after the cleaning liquid/color developing agent flows into the chip body through the second external liquid path interface, the cleaning liquid/color developing agent flows into the second reagent conveying micro-channel a33 through the second liquid path through holes 2-18, then sequentially flows through the vertical channel b2-7 of the second anti-backflow structure, the anti-backflow connecting channel 1-10 of the second anti-backflow structure, the vertical channel a2-6 of the second anti-backflow structure and the second reagent conveying micro-channel b2-12, and then flows into the reaction cavities (the upper reaction cavity 2-15 and the lower reaction cavity 32) through the reaction reagent conveying micro-channels 2-22.

A sample injection flow path:

adding a sample into the sample injection cavity; then, an external gas path interface assembled by the sample injection part is communicated with an external gas source, and a sample passes through a liquid outlet of the sample filtering pool 31 under the pressure action of the external gas source, sequentially passes through a vertical flow channel a2-4 of the first anti-backflow structure, an anti-backflow connecting flow channel 1-11 of the first anti-backflow structure, a vertical flow channel b2-5 of the first anti-backflow structure and a reaction reagent input micro flow channel 2-22 of the reaction cavity, and then flows into the reaction cavity (an upper reaction cavity 2-15 and a lower reaction cavity 32) through the reaction reagent input micro flow channel 2-22.

Reaction chamber outlet flow path:

the cleaning waste liquid in the reaction cavity flows into the waste liquid cavity after sequentially passing through the reaction reagent output micro-flow channel 2-16, the conductive rubber micro-valve and the micro-flow channel c 36.

Regarding the specific structure of the waste liquid cavity and the conductive rubber micro valve, the applicant has detailed descriptions in the previously-filed chinese patents, and these two contents have no special improvement in the present application, and are not described herein again.

Single index micro-fluidic chip, what adopt is that the two-step process carries out sample detection, specifically is:

the first step is that the coating antibody in the quantitative reaction cavity reacts with the sample, and then the sample is cleaned by cleaning solution; and the second step is to inject a blending buffer solution into a blending cavity, a fluorescence labeling antibody is embedded in the blending cavity, the blending buffer solution enters a quantitative reaction cavity after blending for reaction, and then the blending buffer solution is cleaned and placed into a detection instrument for detecting a fluorescence signal. Compared with a one-step method, the two-step method effectively avoids the combination of the coated antibody, the labeled antibody and other non-specificities, and improves the accuracy of the detection result.

Claims

1. A sample injection cavity of a microfluidic chip comprises a sample filtering pool and a sample injection part arranged at the mouth of the sample filtering pool; the sample filtering pool is arranged in a fan shape of the banana, a liquid outlet of the sample filtering pool is arranged on the side wall of the narrow side, and a flow guide area is arranged at the bottom of the sample filtering pool; the sample introduction part is provided with air holes, and the sample filtration part is characterized in that the bottom of the sample filtration pool is provided with an air guide groove corresponding to each air hole at a position close to the side wall of the wide edge, and a gas gathering area is arranged between each air guide groove and the flow guide area;

2. The sample introduction chamber of the microfluidic chip according to claim 1, wherein the flow guide region is at the bottom of the sample filtration cell and is divided into at least two regions where fluids can be communicated with each other according to the fluid flow direction; each flow guide area is provided with a plurality of flow guide strips which are distributed in a gathering shape, and the distribution density of the flow guide strips in the flow guide area at the front end of the fluid flow is less than that of the flow guide strips in the flow guide area at the rear end of the fluid flow.

3. The sample introduction chamber of the microfluidic chip according to claim 2, wherein the bottom of the sample filtration cell is sequentially provided with a first flow guide region and a second flow guide region according to a fluid flow direction;

4. The sample introduction chamber of the microfluidic chip according to claim 3, wherein the number of the gas guide grooves is three;

5. A single-index microfluidic chip comprises a chip body, wherein a sample injection cavity, a quantitative reaction cavity, a mixing cavity and a waste liquid cavity are arranged on the chip body; the sample introduction cavity comprises a sample filtering pool and a sample introduction part arranged at the inlet of the sample filtering pool; the sample filtering pool is arranged in a fan shape of the banana, a liquid outlet of the sample filtering pool is arranged on the side wall of the narrow side, and a flow guide area is arranged at the bottom of the sample filtering pool; the sample introduction part is provided with air holes, and the sample filtration part is characterized in that the bottom of the sample filtration pool is provided with an air guide groove corresponding to each air hole at a position close to the side wall of the wide edge, and a gas gathering area is arranged between each air guide groove and the flow guide area;

6. The single index microfluidic chip of claim 5, wherein the chip body is of a three-piece structure including an upper chip, a middle chip and a lower chip stacked in sequence from top to bottom;

7. The single index microfluidic chip of claim 6, wherein a coating antibody is disposed in the upper reaction chamber; the lower reaction cavity is provided with a fluorescence labeling antibody.

8. The single index microfluidic chip of claim 6, wherein the reaction chamber is olive-shaped and is enclosed by two arc-shaped walls arranged along the fluid flow direction, and the arc-shaped walls approach a semi-circle.

9. The single index microfluidic chip according to claim 6, wherein the chip body is provided with two external liquid path interfaces, namely a first external liquid path interface and a second external liquid path interface; wherein:

10. The single index microfluidic chip according to claim 8, wherein the second reagent delivery microchannel a is disposed on the front surface of the lower chip, and the second reagent delivery microchannel b is disposed on the back surface of the middle chip; the anti-backflow structure between the second reagent conveying micro-channel a and the second reagent conveying micro-channel b is a second anti-backflow structure and comprises a vertical channel a of the second anti-backflow structure, a vertical channel b of the second anti-backflow structure and an anti-backflow connecting channel of the second anti-backflow structure; the anti-backflow connecting flow channel of the second anti-backflow structure is arranged on the back surface of the upper chip, and two ends of the vertical flow channel of the second anti-backflow structure penetrate through the middle chip;

11. The single index microfluidic chip of claim 7, wherein the sample introduction part of the sample introduction cavity is disposed on the upper chip, and the upper and lower parts are respectively an upper part of the sample introduction part and a lower part of the sample introduction part, and the upper part of the sample introduction part comprises two parts, respectively a flow guide surface and a gas-permeable boss; the flow guide surface is an arc flow guide surface which is arranged in a gradually reducing manner from outside to inside and is arranged close to the side wall of the narrow edge of the sample filtering pool; the air-permeable boss is arranged close to the side wall of the wide edge of the sample filtering pool, and the air holes are formed in the air-permeable boss;

12. The single index microfluidic chip according to claim 11, wherein the outlet of the sample filtering cell is communicated with the reaction reagent input microchannel of the reaction chamber through a first anti-backflow structure;

13. The single index microfluidic chip of claim 7, wherein the mixing chamber comprises a lower mixing chamber portion disposed on the lower chip and an upper mixing chamber portion disposed on the middle chip; the upper part of the mixing cavity can be enclosed with the lower part of the mixing cavity to form the mixing cavity.