阅读说明：本技术 基于微流控技术的免疫磁珠化学发光分析系统及工作方法 (Immune magnetic bead chemiluminescence analysis system based on microfluidic technology and working method ) 是由 程林 金烨琦 赵逸祥 章诗校 余波 于 2019-10-21 设计创作，主要内容包括：本发明提供了基于微流控技术的免疫磁珠化学发光分析系统及工作方法,所述分析系统包括具有多个检测腔的微流控盘片,第一控制装置包括第一承载件和多个第一磁力件；第二控制装置包括第二承载件、沿着所述第二承载件的旋转中心呈周向分布的多个相对旋转中心倾斜设置的槽、第三磁力件和设置在槽内的第二磁力件,所述第三磁力件设置在相邻的槽之间；所述第一控制装置固定设置,所述第二控制装置和微流控盘片相对静止；在竖直方向上,所述第一控制装置、微流控盘片和第二控制装置自上而下或自下而上地依次设置。本发明具有结构简单、操作方便、分析效率高等优点。(The invention provides an immunomagnetic bead chemiluminescence analysis system based on a microfluidic technology and a working method thereof, wherein the analysis system comprises a microfluidic disc with a plurality of detection cavities, and a first control device comprises a first bearing part and a plurality of first magnetic parts; the second control device comprises a second bearing piece, a plurality of grooves which are distributed along the rotation center of the second bearing piece in a circumferential direction and are obliquely arranged relative to the rotation center, a third magnetic piece and a second magnetic piece arranged in the grooves, wherein the third magnetic piece is arranged between the adjacent grooves; the first control device is fixedly arranged, and the second control device and the microfluidic disc are relatively static; in the vertical direction, the first control device, the microfluidic disc and the second control device are sequentially arranged from top to bottom or from bottom to top. The invention has the advantages of simple structure, convenient operation, high analysis efficiency and the like.)

1. An immunomagnetic bead chemiluminescence analysis system based on microfluidic technology comprises a microfluidic disc, wherein the microfluidic disc is provided with a plurality of detection cavities; the method is characterized in that: the analysis system further comprises:

the first control device comprises a first bearing piece and a plurality of first magnetic pieces circumferentially distributed along the center of the first bearing piece;

the second control device comprises a second bearing piece, a plurality of grooves which are distributed along the rotation center of the second bearing piece in a circumferential direction and are obliquely arranged relative to the rotation center, a third magnetic piece and a second magnetic piece arranged in the grooves, wherein the third magnetic piece is arranged between the adjacent grooves; in a free state, under the action of the third magnetic member, the second magnetic member is positioned at the end part with the minimum rotation radius of the groove; in the rotating state, the second magnetic piece is thrown to the end part with the largest rotating radius of the groove;

the first control device is fixedly arranged, and the second control device and the microfluidic disc are relatively static; in the vertical direction, the first control device, the microfluidic disc and the second control device are sequentially arranged from top to bottom or from bottom to top.

2. The microfluidic technology-based immunomagnetic bead chemiluminescence analysis system of claim 1, wherein: the projection of the detection chamber on the horizontal plane and the projection of the end of the groove with the largest radius of rotation on the horizontal plane have an overlap.

3. The microfluidic technology-based immunomagnetic bead chemiluminescence analysis system of claim 2, wherein: and the connecting line of the center of the first bearing piece and the rotation center of the second bearing piece is vertical to the rotation surface of the microfluidic disc.

4. The microfluidic technology-based immunomagnetic bead chemiluminescence analysis system of claim 1, wherein: the distance from the center of the first magnetic piece to the center of the first bearing piece is equal to the rotation radius of the center of the detection cavity.

5. The microfluidic technology-based immunomagnetic bead chemiluminescence analysis system of claim 1, wherein: the third magnetic force piece comprises two magnetic force pieces, and a connecting line between the two magnetic force pieces and the rotating center forms a non-isosceles triangle.

6. The microfluidic technology-based immunomagnetic bead chemiluminescence analysis system of claim 1, wherein: the outer edge of the second bearing part is provided with at least two extending parts extending along the direction parallel to the central axis of the second bearing part, and the microfluidic disc is clamped in the area enclosed by the extending parts.

7. The microfluidic technology-based immunomagnetic bead chemiluminescence analysis system of claim 6, wherein: the edge of the microfluidic disc is provided with a notch, and the side wall of the extension part opposite to the microfluidic disc is provided with a protrusion suitable for being clamped into the notch.

8. The microfluidic technology-based immunomagnetic bead chemiluminescence analysis system of claim 7, wherein: the notch and the bulge are columnar.

9. The method for operating an immunomagnetic bead chemiluminescence analysis system based on microfluidic technology according to any of claims 1-8, wherein the method comprises:

an incubation stage: under the action of the third magnetic member, the second magnetic member is positioned at the end part with the minimum rotating radius of the groove and is far away from the detection cavity; at the same time, the user can select the desired position,

the intersection point of a vertical line passing through the center of the detection cavity and the first bearing piece is positioned between two adjacent first magnetic force pieces;

a cleaning stage: under the action of the third magnetic member, the second magnetic member is positioned at the end part with the minimum rotating radius of the groove and is far away from the detection cavity; at the same time, the user can select the desired position,

rotating the microfluidic disc and the second control device so that a vertical line passing through the center of the detection chamber passes through the first magnetic member, and the magnetic beads in the detection chamber are attracted to the upper wall of the detection chamber by the first magnetic member; after that time, the user can use the device,

the microfluidic disc rotates forwards and backwards, the magnetic beads move back and forth clockwise and anticlockwise in the detection cavity and move between the upper wall and the lower wall of the detection cavity, and the moving magnetic beads are cleaned by the cleaning solution;

a waste discharge stage: and rotating the microfluidic disc and the second control device, throwing the second magnetic part to the end part with the largest rotating radius of the groove, and attracting the magnetic beads in the detection cavity by the second magnetic part.

10. The method of operation of claim 9, wherein: the working method further comprises the following steps:

a reaction stage: under the action of the third magnetic member, the second magnetic member is positioned at the end part with the minimum rotating radius of the groove and is far away from the detection cavity; at the same time, the user can select the desired position,

rotating the microfluidic disc and the second control device so that a vertical line passing through the center of the detection chamber passes through the first magnetic member, and the magnetic beads in the detection chamber are attracted to the upper wall of the detection chamber by the first magnetic member; after that time, the user can use the device,

the microfluidic disc rotates forwards and backwards, the magnetic beads move back and forth clockwise and anticlockwise in the detection cavity and move between the upper wall and the lower wall of the detection cavity, and the moving magnetic beads react with the substrate.

Technical Field

The invention relates to microfluidics, in particular to an immunomagnetic bead chemiluminescence analysis system based on a microfluidics technology and a working method thereof.

Background

Microfluidic technology refers to the science and technology involved in systems that process or manipulate microfluidics using tens to hundreds of microns of tubing, and is an emerging interdiscipline that involves chemical, fluid physical, microelectronic, new materials, biological, and biomedical engineering.

The centrifugal micro-fluidic system is a micro-fluidic system which is based on micro-electro-mechanical technology, integrates valves, flow pipelines, mixing reactors, sample adding, separating, detecting and other parts involved in the processes of sampling, preprocessing, derivation, mixing, detecting and the like of chemical analysis on a CD-shaped disc, and realizes the detection and analysis of liquid flow by taking centrifugal force as the driving force of the liquid flow. By utilizing the principle of centrifugal speed control, the operation process of the experiment can be easily controlled by a program, and the whole experiment process can be completed by adding a reagent and running the program for detection personnel to obtain an experiment result.

Chemiluminescence immunoassay (CLIA) is a detection and analysis technique for various antigens, haptens, antibodies, hormones, enzymes, drugs and the like by combining a chemiluminescence assay technique with high sensitivity and a high specificity immunoreaction. In order to improve the loss of the antigen-antibody coating, magnetic beads are generally used as carriers, the magnetic beads are injected into a reaction tank for reaction and coating, and the release of the magnetic beads is controlled by a magnet to realize the separation.

Chemiluminescent immunoassays comprise two components, an immunoreaction system and a chemiluminescent assay system. The chemiluminescence system is characterized in that chemiluminescence substances are catalyzed by a catalyst and oxidized by an oxidant to form an excited intermediate, the excited intermediate emits photons when returning to a stable ground state, and the yield of light quanta is measured by a luminescence signal determinator. The immune reaction system is to label the luminous substance directly on the antigen or antibody. The enzyme is used on a luminescent substrate.

The manipulation of the microfluidic centrifugal magnetic particles can solve the manipulation problem of magnetic beads in the items such as chemiluminescence and the like, and the cleaning link is well cleaned in a mixed oscillation mode, so that the cleaning is more thorough.

The current conventional way is: the magnetic beads are only controlled to be cleaned by a magnet below the microfluidic disc, and the scheme has the main defects that:

magnet can only adsorb the below lower surface of detecting the groove with the magnetic bead, when just reversing to vibrate the mixing magnetic bead, the magnetic bead of group is difficult to be shaken by the bottom, leads to wasing not thoroughly, can cause abluent effect deviation to have remaining reactant not wash, causes the result distortion, simultaneously also not thoroughly when reacting with the substrate.

Disclosure of Invention

In order to overcome the defects in the prior art, the invention provides an immunomagnetic bead chemiluminescence analysis system which is accurate in analysis and based on a microfluidic technology.

The purpose of the invention is realized by the following technical scheme:

an immunomagnetic bead chemiluminescence analysis system based on microfluidic technology comprises a microfluidic disc, wherein the microfluidic disc is provided with a plurality of detection cavities; the analysis system further comprises:

the first control device comprises a first bearing piece and a plurality of first magnetic pieces circumferentially distributed along the center of the first bearing piece;

the second control device comprises a second bearing piece, a plurality of grooves which are distributed along the rotation center of the second bearing piece in a circumferential direction and are obliquely arranged relative to the rotation center, a third magnetic piece and a second magnetic piece arranged in the grooves, wherein the third magnetic piece is arranged between the adjacent grooves; in a free state, under the action of the third magnetic member, the second magnetic member is positioned at the end part with the minimum rotation radius of the groove; in the rotating state, the second magnetic piece is thrown to the end part with the largest rotating radius of the groove;

the first control device is fixedly arranged, and the second control device and the microfluidic disc are relatively static; in the vertical direction, the first control device, the microfluidic disc and the second control device are sequentially arranged from top to bottom or from bottom to top.

The invention also aims to provide a working method of the immunomagnetic bead chemiluminescence analysis system based on the microfluidic technology, and the aim of the invention is realized by the following technical scheme:

according to the working method of the immunomagnetic bead chemiluminescence analysis system based on the microfluidic technology, the working method comprises the following steps:

an incubation stage: under the action of the third magnetic member, the second magnetic member is positioned at the end part with the minimum rotating radius of the groove and is far away from the detection cavity; at the same time, the user can select the desired position,

the intersection point of a vertical line passing through the center of the detection cavity and the first bearing piece is positioned between two adjacent first magnetic force pieces;

a cleaning stage: under the action of the third magnetic member, the second magnetic member is positioned at the end part with the minimum rotating radius of the groove and is far away from the detection cavity; at the same time, the user can select the desired position,

rotating the microfluidic disc and the second control device so that a vertical line passing through the center of the detection chamber passes through the first magnetic member, and the magnetic beads in the detection chamber are attracted to the upper wall of the detection chamber by the first magnetic member; after that time, the user can use the device,

the microfluidic disc rotates forwards and backwards, the magnetic beads move back and forth clockwise and anticlockwise in the detection cavity and move between the upper wall and the lower wall of the detection cavity, and the moving magnetic beads are cleaned by the cleaning solution;

a waste discharge stage: and rotating the microfluidic disc and the second control device, throwing the second magnetic part to the end part with the largest rotating radius of the groove, and attracting the magnetic beads in the detection cavity by the second magnetic part.

Compared with the prior art, the invention has the beneficial effects that:

1. the analysis is accurate;

through the first control device and the second control device, the magnetic beads are more sufficiently and thoroughly cleaned in the cleaning stage, and the magnetic beads and the substrate fully react in the reaction stage, so that the accuracy of subsequent analysis is improved;

2. the static first magnetic force piece, the second magnetic force piece and the third magnetic force piece of motion are independently controlled respectively, and it is easier to realize in the magnetic bead control, has avoided the phenomenon of losing of magnetic bead.

Drawings

The disclosure of the present invention will become more readily understood with reference to the accompanying drawings. As is readily understood by those skilled in the art: these drawings are only for illustrating the technical solutions of the present invention and are not intended to limit the scope of the present invention. In the figure:

FIG. 1 is a schematic diagram of an immunomagnetic bead chemiluminescence analysis system based on microfluidic technology according to an embodiment of the invention;

fig. 2 is a schematic configuration diagram of a second control device according to an embodiment of the present invention.

Detailed Description

Fig. 1-2 and the following description depict alternative embodiments of the invention to teach those skilled in the art how to make and reproduce the invention. Some conventional aspects have been simplified or omitted for the purpose of teaching the present invention. Those skilled in the art will appreciate that variations or substitutions from these embodiments will be within the scope of the invention. Those skilled in the art will appreciate that the features described below can be combined in various ways to form multiple variations of the invention. Thus, the present invention is not limited to the following alternative embodiments, but is only limited by the claims and their equivalents.