阅读说明：本技术 一种全血过滤和血浆定量微流控芯片 (Whole blood filtration and plasma quantitative micro-fluidic chip ) 是由 陈锦河 龙晓君 何丽珍 于 2020-12-04 设计创作，主要内容包括：本发明涉及一种微流控芯片,具体涉及一种全血过滤和血浆定量微流控芯片。包括芯片基板、硅胶盖、下压柱a、下压柱b；其中芯片基板由全血过滤区、血浆定量区、储气区、反应区、多余血浆聚集槽组成,其中各个区域通过气孔互连接通；全血过滤区内有全血滤膜,血浆定量区包括S型定量通道,储气区包括储气仓a、储气仓b,为半封闭圆柱结构；反应区包括磁微粒抗体储存池、碱性磷酸酶储存池、清洗液储存池a、清洗液储存池b、化学发光底物储存池。本发明兼具全血过滤和血浆定量功能,解决临床定量提取血浆的通病,满足临床快速诊断需求,与现有技术相比,具有操作简便、快速、成本低、用量少、污染少等特点。(The invention relates to a microfluidic chip, in particular to a whole blood filtration and plasma quantification microfluidic chip. The chip comprises a chip substrate, a silica gel cover, a lower pressing column a and a lower pressing column b; the chip substrate consists of a whole blood filtering area, a plasma quantifying area, a gas storage area, a reaction area and an excess plasma gathering groove, wherein all the areas are communicated with each other through air holes; the whole blood filtering area is internally provided with a whole blood filtering membrane, the plasma quantifying area comprises an S-shaped quantifying channel, and the gas storage area comprises a gas storage bin a and a gas storage bin b and is of a semi-closed cylindrical structure; the reaction area comprises a magnetic particle antibody storage pool, an alkaline phosphatase storage pool, a cleaning solution storage pool a, a cleaning solution storage pool b and a chemiluminescent substrate storage pool. The invention has the functions of whole blood filtration and plasma quantification, solves common problems of clinical quantitative plasma extraction, meets the clinical rapid diagnosis requirement, and has the characteristics of simple and convenient operation, rapidness, low cost, small dosage, less pollution and the like compared with the prior art.)

1. A whole blood filtration and plasma quantification microfluidic chip comprises a chip substrate, a silica gel cover, a lower pressure column a and a lower pressure column b;

the chip substrate consists of a whole blood filtering area, a plasma quantifying area, a gas storage area, a reaction area and an excess plasma gathering groove, wherein all the areas are communicated with each other through air holes; the whole blood filtering area is internally provided with a whole blood filtering membrane, the plasma quantifying area comprises an S-shaped quantifying channel, and the gas storage area comprises a gas storage bin a and a gas storage bin b and is of a semi-closed cylindrical structure; the reaction area comprises a magnetic particle antibody storage pool, an alkaline phosphatase storage pool, a cleaning solution storage pool a, a cleaning solution storage pool b and a chemiluminescent substrate storage pool; the gas storage bin a, the gas storage bin b, the lower pressing column a, the lower pressing column b, the whole blood filtering area, the reaction area and the redundant plasma gathering groove are located on the upper layer, the S-shaped quantitative channel is located on the lower layer, and the upper layer and the lower layer of the microfluidic chip are communicated through the air hole a, the air hole b, the air hole c, the plasma sample inlet, the plasma gathering notch and the plasma sample outlet respectively.

2. The whole blood filtration and plasma quantification microfluidic chip according to claim 1, wherein the chip substrate is provided with a silica gel cap positioning hole and a silica gel groove, and the silica gel cap positioning hole and the silica gel groove are embedded with the silica gel cap structure and used for fixing the silica gel cap.

3. The whole blood filtration and plasma quantification microfluidic chip according to claim 1, wherein the whole blood filtration section has a recess with a hollowed-out structure.

4. The whole blood filtering and plasma quantifying microfluidic chip according to claim 1, wherein the gas storage bin a is provided with a gas hole b connected with a gas hole c, and is communicated with the whole blood filtering area through a groove; the air hole a is formed in the air storage area b and is connected with the S-shaped quantitative channel; the plasma sample outlet is arranged on the S-shaped quantitative channel and communicated with the reaction area.

5. The whole blood filtration and plasma quantification microfluidic chip according to claim 1, wherein the whole blood filtration membrane adopts a double-layer membrane filtration mode.

6. The whole blood filtration and plasma quantification microfluidic chip according to claim 1, wherein the bottom of the whole blood filtration zone is concave relative to the upper filter membrane.

7. The whole blood filtration and plasma quantification microfluidic chip according to claim 1, wherein the S-shaped quantification channel has a channel width of preferably 0.1-2mm and a channel depth of preferably 0.1-1 mm; the plasma quantitative area adopts a capillary automatic quantitative mode, and the plasma sample outlet and the pore diameter of the air hole a have certain heights.

8. The whole blood filtration and plasma quantification microfluidic chip according to claim 1, wherein the S-shaped quantification channel has an opening as a plasma collection notch.

9. The whole blood filtration and plasma quantification microfluidic chip according to claim 1, wherein the lower pressure column a is capable of effectively compressing a volume of air to make the whole blood pass through the filter membrane and become plasma.

10. The whole blood filtration and plasma quantification microfluidic chip according to claim 1, wherein the lower pressure column a and the lower pressure column b are both provided with a silica gel ring positioning groove to ensure air tightness of the channel.

Technical Field

The invention relates to a microfluidic chip, in particular to a whole blood filtration and plasma quantification microfluidic chip.

Background

The biochemical medical detection of human blood can provide important information reflecting the health condition of human body. At present, most of samples for clinical human blood detection are plasma, and most of plasma extraction needs to rely on additional equipment, such as a centrifuge and the like. Most of centrifuge equipment is large in volume and inconvenient to carry, so that the detection place is limited, time is consumed, and rapid detection of diseases is not facilitated; mature filter membrane products are available on the market, but suitable filter devices for separating whole blood with a filter membrane are lacking.

The current quantitative sampling mode in clinic mainly comprises two modes, wherein one mode is that clinical personnel use a pipette to manually sample, and the other mode is that an automatic instrument adopts a mechanical sampling needle to sample. Both methods have certain defects, manual sampling has the defect of inaccurate sampling, and mechanical sampling has high requirements on instruments, complex operation and high cost.

The micro-fluidic chip technology integrates basic operation units such as sample preparation, reaction, separation, detection and the like in the biological, chemical and medical analysis processes into a micron-scale chip, and automatically completes the whole analysis process. The device has the advantages of miniaturization and automation, high flux, less consumption of detection reagents, less sample consumption, less pollution and the like, and is very suitable for the field of medical instruments.

Disclosure of Invention

The invention aims to overcome the defects of the prior art, provides the whole blood filtration and plasma quantification microfluidic chip, has the functions of whole blood filtration and plasma quantification, solves the common problems of clinical quantitative plasma extraction, and meets the clinical rapid diagnosis requirement.

In order to solve the technical problems, the invention adopts the technical scheme that:

a whole blood filtration and plasma quantification microfluidic chip comprises a chip substrate, a silica gel cover, a lower pressure column a and a lower pressure column b.

The chip substrate consists of a whole blood filtering area, a plasma quantifying area, a gas storage area, a reaction area and an excess plasma gathering groove, wherein all the areas are communicated with each other through air holes; the whole blood filtering area is internally provided with a whole blood filtering membrane, the plasma quantifying area comprises an S-shaped quantifying channel, and the gas storage area comprises a gas storage bin a and a gas storage bin b and is of a semi-closed cylindrical structure; the reaction area comprises a magnetic particle antibody storage pool, an alkaline phosphatase storage pool, a cleaning solution storage pool a, a cleaning solution storage pool b and a chemiluminescent substrate storage pool; the gas storage bin a, the gas storage bin b, the whole blood filtering area, the reaction area and the redundant plasma gathering tank are located on the upper layer, the S-shaped quantitative channel is located on the lower layer, and the upper layer and the lower layer of the microfluidic chip are communicated through the air hole a, the air hole b, the air hole c, the plasma sample inlet, the plasma gathering notch and the plasma sample outlet respectively.

In the scheme, the gas storage bin a and the gas storage bin b respectively collect gas with certain volume, the compression column a is pressed to generate certain pressure, the certain pressure is transmitted to the filtering area through the air hole to push the whole blood sample in the whole blood filtering area to be filtered, the filtered plasma automatically fills the S-shaped quantitative channel under the capillary action principle, the redundant plasma enters the redundant plasma collection tank to be stored, and the redundant gas is discharged through the exhaust hole; pressing the pressing column b to generate certain pressure to push the plasma in the S-shaped quantitative channel to be pumped into the reaction area; at the moment, the plasma pumped into the reaction area from the S-shaped quantitative channel is the quantitative plasma of the microfluidic chip, and the whole blood filtration and the plasma quantification can be rapidly realized in the process.

In one embodiment, the chip substrate is provided with a silica gel cover positioning hole and a silica gel groove which are embedded with the silica gel cover structure and used for fixing the silica gel cover.

In one embodiment, the whole blood filtration zone has a recess in the form of a hollowed-out structure that allows gas to pass through.

In one embodiment, the air storage bin a is internally provided with an air hole b which is connected with an air hole c and then communicated with the whole blood filtering area through a groove; the air hole a is arranged in the air storage bin b and is connected with the S-shaped quantitative channel; the plasma outlet is arranged on the S-shaped quantitative channel and communicated with the reaction area.

In one embodiment, the whole blood filter membrane adopts a double-layer membrane filtration mode, the upper layer filter membrane is a filter membrane with a large pore size, the pore size is preferably 1-10 μm, and the filter membrane type is a glass cellulose membrane or a polytetrafluoroethylene filter membrane; the lower filter membrane is a filter membrane with small pore size, and the pore size is preferably 0.1-3 μm of polytetrafluoroethylene filter membrane or polyether sulfone filter membrane.

In one embodiment, the bottom of the whole blood filtration zone is concave relative to the filter membrane above; when impurities such as red blood cells pass through the filter membrane, the design can effectively buffer pressure and effectively prevent hemolysis.

In one embodiment, the S-shaped quantitative channel in the plasma quantitative region has a channel width of preferably 0.1-2mm and a channel depth of preferably 0.1-1 mm; the plasma quantitative region mainly adopts a capillary automatic quantitative mode, the plasma outlet and the pore diameter of the air hole a have certain height, preferably 2mm-20mm, and the continuous flow of quantitative plasma is prevented under the action of gravity, so that accurate quantification is realized.

In one embodiment, the S-shaped quantitative passage has an opening as a plasma gathering notch, and the function of the S-shaped quantitative passage is to discharge the excess air and the excess plasma to the excess plasma gathering groove, so that the air is prevented from entering the quantitative area, the generation of air bubbles is reduced, and the plasma quantification is facilitated.

In one embodiment, the lower pressure column a can effectively compress a certain volume of air, so that the whole blood passes through the filter membrane and becomes plasma, auxiliary devices such as a peristaltic pump and the like are not needed, and the cost is low.

In one embodiment, silica gel ring positioning grooves are arranged on the lower pressing column a and the lower pressing column b to ensure the air tightness of the channel.

The invention provides a whole blood filtration and plasma quantification microfluidic chip, which can realize the functions of whole blood filtration and plasma quantification on the same chip, solve the common problems of clinical quantitative plasma extraction and meet the clinical rapid diagnosis requirements.

Drawings

Fig. 1 is a schematic diagram of the whole structure of a whole blood filtration and plasma quantification microfluidic chip provided in the embodiment of the present invention.

Fig. 2 is a schematic diagram of the upper layer structure of the whole blood filtration and plasma quantification microfluidic chip provided in the embodiment of the invention.

Fig. 3 is a schematic diagram of the lower layer structure of the whole blood filtration and plasma quantification microfluidic chip provided in the embodiment of the invention.

Fig. 4 is a schematic view of a structure of a push-down column according to an embodiment of the present invention.

Fig. 5 is a schematic structural diagram of a silicone cap according to an embodiment of the present invention.

Detailed Description

The drawings are for illustration purposes only and are not to be construed as limiting the invention; for the purpose of better illustrating the embodiments, certain features of the drawings may be omitted, enlarged or reduced, and do not represent the size of an actual product; it will be understood by those skilled in the art that certain well-known structures in the drawings and descriptions thereof may be omitted. The positional relationships depicted in the drawings are for illustrative purposes only and are not to be construed as limiting the invention.

The same or similar reference numerals in the drawings of the embodiments of the present invention correspond to the same or similar components; in the description of the present invention, it should be understood that if there is an orientation or positional relationship indicated by the terms "upper", "lower", "left", "right", etc. based on the orientation or positional relationship shown in the drawings, it is only for convenience of describing the present invention and simplifying the description, but it is not intended to indicate or imply that the referred device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and therefore, the terms describing the positional relationship in the drawings are only used for illustrative purposes and are not to be construed as limiting the present patent, and the specific meaning of the terms may be understood by those skilled in the art according to specific circumstances.

Example 1

As shown in fig. 1 to 5, the whole blood filtration and plasma quantification microfluidic chip includes a chip substrate 1, a silica gel cap 2, a lower pressure column a 3, and a lower pressure column b 4. The chip substrate consists of a whole blood filtering area 21, a plasma quantitative area, a gas storage area, a reaction area and an excess plasma gathering groove 23, wherein all the areas are communicated with each other through air holes; a whole blood filter membrane is arranged in the whole blood filtering area 21, the plasma quantifying area comprises an S-shaped quantifying channel 22, and the gas storage area comprises a gas storage bin a 16 and a gas storage bin b 18 and is of a semi-closed cylindrical structure; the reaction area comprises a magnetic particle antibody storage pool 5, an alkaline phosphatase storage pool 6, a cleaning solution storage pool a 7, a cleaning solution storage pool b 8 and a chemiluminescent substrate storage pool 9. The chip substrate 1 is provided with a silica gel cover positioning hole 12 and a silica gel groove 20 which are embedded with a silica gel cover structure, and 25 is a fixing column for fixing the silica gel cover. All set up silica gel circle constant head tank 24 on the lower compression leg, ensured the passageway gas tightness.

As shown in fig. 2, on the upper layer of the microfluidic chip, the air hole b 15 and the air hole c 14 in the air storage chamber a 16 are connected, wherein the groove 19 is an opening of the whole blood filtering area, and the air in the air storage chamber a 16 can enter the whole blood filtering area through the groove 19 and then is communicated with the S-shaped quantitative channel 22 through the plasma sample inlet 13.

A volume of whole blood is added to the whole blood filtration zone 21, which is covered with a silica gel cover 2. According to the air pump principle, the air with a certain volume in the air storage bin a 16 sequentially passes through the air hole b 15, the air hole c 14 and the groove 19 under the pressure of the compression column a 3 and finally enters the whole blood filtering area 21, so that the whole blood sequentially passes through the double-layer whole blood filtering membrane, the upper layer filtering membrane intercepts large particles such as red blood cells, the lower layer filtering membrane intercepts small particle impurities, the liquid passing through the filtering membrane is in a plasma state, and the whole blood filtering function is realized.

Example 2

The invention provides a micro-fluidic chip capable of realizing whole blood filtration and plasma quantification, which is the same as the micro-fluidic chip in the previous embodiment and comprises a chip substrate 1, a silica gel cover 2, a lower pressure column a 3 and a lower pressure column b 4. The chip substrate consists of a whole blood filtering area 21, a plasma quantitative area, a gas storage area, a reaction area and an excess plasma gathering groove, wherein all the areas are communicated with each other through air holes; a whole blood filter membrane is arranged in the whole blood filtering area 21, the plasma quantifying area comprises an S-shaped quantifying channel 22, and the gas storage area comprises a gas storage bin a 16 and a gas storage bin b 18 and is of a semi-closed cylindrical structure; the reaction area comprises a magnetic particle antibody storage pool 5, an alkaline phosphatase storage pool 6, a cleaning solution storage pool a 7, a cleaning solution storage pool b 8 and a chemiluminescent substrate storage pool 9. The chip substrate 1 is provided with a silica gel cover positioning hole 12 and a silica gel groove 20 which are embedded with a silica gel cover structure, and 25 is a fixing column for fixing the silica gel cover. All set up silica gel circle constant head tank 24 on the lower compression leg, ensured the passageway gas tightness.

On the upper layer of the microfluidic chip, an air hole b 15 and an air hole c 14 in an air storage bin a 16 are connected, wherein a groove 19 is an opening of the whole blood filtering area, air in the air storage bin a 16 can enter the whole blood filtering area through the groove 19, and then the air is communicated with an S-shaped quantitative channel 22 through a plasma sample inlet 13.

As shown in figures 2 to 3, the plasma obtained by filtering and separating the whole blood with the whole blood filter membrane flows out through the plasma sample inlet 13, and automatically fills the S-shaped quantitative channel 22 under the capillary action principle, the excess plasma enters the excess plasma collecting groove 23 through the plasma collecting notch 11 for storage, and the excess gas is discharged through the vent hole 25. The width of the S-shaped quantitative channel 22 of the microfluidic chip is preferably 0.1-2mm, and the depth of the channel is preferably 0.1-1 mm. The air with a certain volume in the air storage bin b 18 passes through the air hole a 17 by pressing the pressure column b 4, and the plasma in the S-shaped quantitative channel 22 is pushed to be pumped into the reaction area through the plasma outlet 10 to continue the subsequent chemiluminescence reaction. The plasma pumped into the reaction area from the S-shaped quantitative channel 22 is the quantitative plasma of the microfluidic chip, and the plasma quantitative function can be realized in the process.

It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.