Micro-fluidic chip and immunoassay instrument

Abstract

The invention relates to a micro-fluidic chip and an immunoassay instrument. A micro-fluidic cavity is formed in a body; the microfluidic chamber comprises a first valve control structure, a second valve control structure, a third valve control structure, a fourth valve control structure, a first liquid cavity, a second liquid cavity, a first reaction cavity, a detection reaction cavity and a waste liquid cavity; the first liquid cavity, the first valve control structure, the first reaction cavity, the fourth valve control structure and the waste liquid cavity are communicated in sequence according to the distance from the rotating center from near to far, and the second liquid cavity, the second valve control structure, the detection reaction cavity, the third valve control structure and the waste liquid cavity are communicated in sequence. By designing a first liquid cavity, a second liquid cavity, a first reaction cavity and a detection reaction cavity which are matched with each other, the microfluidic chip is suitable for a delay one-step method and two-step method detection scheme of two-time reaction needing accurate quantification, so that the microfluidic chip can be matched with delay one-step method and two-step method immunoreactions; and the universality of the micro-fluidic chip, especially a disc-type micro-fluidic chip, is further expanded.

Description

Technical Field

[0001] The present application relates to the field of microfluidic chips, and in particular to microfluidic chips and immunoassay instruments. Background Art

[0002] Microfluidic chips are microanalysis systems that integrate sample pretreatment, mixing, reaction, separation, and detection into one or more chips. Analytical instruments using microfluidic chips can replace traditional, extensive laboratory work.

[0003] In addition, microfluidic chips require less sample, are easy to operate, and can accurately complete the entire process from sample preparation to result display in a relatively short period of time, effectively overcoming the experimental errors caused by manual operations in traditional laboratory work. Therefore, microfluidic chips have been increasingly used in chemical analysis, DNA sequencing, protein analysis, single cell analysis, single molecule analysis, food safety, environmental testing, and drug screening.

[0004] However, most traditional microfluidic disc chips are designed to realize biochemical reactions. The few microfluidic disc chips adapted for immune response are only suitable for one-step methods. There is a lack of microfluidic chips adapted for delayed one-step methods, especially disc chips. Summary of the invention

[0005] Based on this, it is necessary to provide a microfluidic chip and an immunoassay instrument.

[0006] In one embodiment, a microfluidic chip includes a body having a rotation center and a microfluidic chamber is opened in the body;

[0007] The microfluidic chamber comprises a first valve control structure, a second valve control structure, a third valve control structure, a fourth valve control structure, a first liquid chamber, a second liquid chamber, a first reaction chamber, a detection reaction chamber and a waste liquid chamber;

[0008] According to the distance from the rotation center from near to far, the first liquid chamber, the first valve control structure, the first reaction chamber, the fourth valve control structure and the detection reaction chamber are connected in sequence, and the second liquid chamber, the second valve control structure, the detection reaction chamber, the third valve control structure and the waste liquid chamber are connected in sequence.

[0009] The above-mentioned microfluidic chip, by designing a matching first liquid chamber, a second liquid chamber, a first reaction chamber and a detection reaction chamber, is suitable for delayed one-step and two-step detection schemes that require two reactions with precise quantification, thereby realizing delayed one-step or two-step microfluidic detection, so that the microfluidic chip can be matched with delayed one-step and two-step immune reactions, further broadening the versatility of microfluidic chips, especially disc-type microfluidic chips.

[0010] In one embodiment, the first liquid chamber and the first valve control structure are opened on one side of the body, and the second liquid chamber, the second valve control structure, the first reaction chamber, the fourth valve control structure, the detection reaction chamber, the third valve control structure and the waste liquid chamber are opened on the other side of the body; or

[0011] The first liquid chamber, the first valve control structure, the first reaction chamber and the fourth valve control structure are arranged on one side of the body, and the second liquid chamber, the second valve control structure, the detection reaction chamber, the third valve control structure and the waste liquid chamber are arranged on the other side of the body; or

[0012] The first liquid chamber, the first valve control structure, the first reaction chamber, the fourth valve control structure, the detection reaction chamber, the third valve control structure and the waste liquid chamber are provided on one side of the body, and the second liquid chamber and the second valve control structure are provided on the other side of the body; or

[0013] The first valve control structure, the second valve control structure, the third valve control structure, the fourth valve control structure, the first liquid chamber, the second liquid chamber, the first reaction chamber, the detection reaction chamber and the waste liquid chamber are opened on the same surface of the main body.

[0014] In one embodiment, the first valve control structure is configured to be closed at a speed lower than a preset first speed;

[0015] The second valve control structure is configured to be closed at a speed lower than a preset second speed;

[0016] The third valve control structure is configured to be closed at a speed lower than a preset third speed, so as to control the liquid in the first reaction chamber to flow to the waste liquid chamber;

[0017] The preset first speed is not higher than the preset second speed, and both the preset first speed and the preset second speed are lower than the preset third speed.

[0018] In one embodiment, according to the distance from the rotation center from near to far,

[0019] The inlet of the first valve control structure is connected to the bottom end of the first liquid chamber, and the inlet of the second valve control structure is connected to the bottom end of the second liquid chamber; or

[0020] The inlet of the third valve control structure is connected to the bottom end of the detection reaction chamber; or,

[0021] The inlet of the fourth valve control structure is connected to the bottom end of the first reaction chamber.

[0022] Illustratively, in one embodiment, in order of distance from the rotation center from near to far, the bottom end of the first reaction chamber is higher than the top end of the detection reaction chamber.

[0023] In one embodiment, the first valve control structure, the second valve control structure and the third valve control structure are steam traps or capillary valves; or,

[0024] The fourth valve control structure is a siphon valve; or,

[0025] The first liquid chamber and the second liquid chamber are quantitative chambers for quantitatively containing liquid; or

[0026] The first reaction chamber and the detection reaction chamber are respectively pre-installed with reaction reagents; or,

[0027] The volume of the detection reaction chamber is greater than or equal to the sum of the volumes of the first liquid chamber and the second liquid chamber; or,

[0028] The volume of the waste liquid chamber is greater than or equal to the sum of the volumes of the first liquid chamber and the second liquid chamber.

[0029] In one embodiment, the fourth valve-controlled structure is a siphon valve, and the surface of the fourth valve-controlled structure is a hydrophilic layer;

[0030] In order of distance from the rotation center from near to far, the outlet of the fourth valve-controlled structure is connected to the uppermost end of the detection reaction chamber, and the uppermost end of the fourth valve-controlled structure is higher than the uppermost end of the first reaction chamber.

[0031] In one embodiment, the first liquid chamber and the second liquid chamber are quantitative chambers, and the volumes of the first liquid chamber and the second liquid chamber are the same or different.

[0032] In one embodiment, the shape of the first reaction chamber is selected from one of partial ellipse, partial circle, ellipse, circle, trapezoid, pear, rectangle and regular polygon; or,

[0033] The volume of the first reaction chamber is greater than or equal to the volume of the first liquid chamber; or,

[0034] The shape of the detection reaction chamber is selected from one of partial ellipse, partial circle, ellipse, circle, trapezoid, pear, rectangle and regular polygon; or,

[0035] The shape of the detection reaction chamber is set according to the light detection device; or,

[0036] The volume of the detection reaction chamber is larger than the volume of the first liquid chamber, the volume of the first reaction chamber, and the volume of the second liquid chamber; or,

[0037] The shape of the waste liquid chamber is selected from one of a partial ellipse, a partial circle, an ellipse, a circle, a trapezoid, a rectangle and a regular polygon; or,

[0038] The volume of the waste liquid chamber is greater than or equal to the sum of the volumes of the first liquid chamber, the second liquid chamber, the first reaction chamber, and the detection reaction chamber.

[0039] Illustratively, in one embodiment, the volume of the first reaction chamber is 1.5 to 2 times the volume of the first liquid chamber.

[0040] Exemplarily, in one embodiment, the volume of the detection reaction chamber is greater than or equal to 1.5 times the volume of the first liquid chamber, the volume of the detection reaction chamber is greater than or equal to 1.5 times the volume of the second liquid chamber, and the volume of the detection reaction chamber is greater than or equal to 1.5 times the volume of the first reaction chamber.

[0041] In one embodiment, the microfluidic chip is a disk-type microfluidic chip.

[0042] Illustratively, in one of the embodiments, the microfluidic chip is a single-disc microfluidic chip.

[0043] In one embodiment, in order of distance from the rotation center from near to far, the bottom end of the first reaction chamber is higher than the top end of the detection reaction chamber.

[0044] In one embodiment, an immunoassay instrument includes a centrifuge and the microfluidic chip described in any embodiment, wherein the microfluidic chip is disposed on a rotating shaft of the centrifuge. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the conventional technology, the drawings required for use in the embodiments or the conventional technology descriptions are briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0046] Figure 1 This is a schematic structural diagram of an embodiment of the microfluidic chip described in this application.

[0047] Figure 2 This is a schematic structural diagram of another embodiment of the microfluidic chip described in this application.

[0048] Figure 3 for Figure 2 A partial structural schematic diagram of the illustrated embodiment.

[0049] Figure 4 for Figure 3 Schematic diagram of the application of the illustrated embodiment.

[0050] Figure numerals: microfluidic chip 100, main body 110, rotation center 120, microfluidic chamber 130, first valve-controlled structure 131, second valve-controlled structure 132, third valve-controlled structure 133, fourth valve-controlled structure 134, first liquid chamber 135, second liquid chamber 136, first reaction chamber 137, detection reaction chamber 138, waste liquid chamber 139, centrifugal direction 140, liquid 200. DETAILED DESCRIPTION

[0051] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are described in detail below in conjunction with the accompanying drawings. In the following description, many specific details are set forth to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present application, so the present application is not limited by the specific embodiments disclosed below.

[0052] It should be noted that when a component is referred to as being "fixed to" or "disposed on" another component, it may be directly on the other component or there may also be a central component. When a component is considered to be "connected to" another component, it may be directly connected to the other component or there may be a central component at the same time. The terms "vertical", "horizontal", "upper", "lower", "left", "right" and similar expressions used in the specification of this application are for illustrative purposes only and do not represent the only implementation method.

[0053] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In the description of this application, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0054] In the present application, unless otherwise clearly specified and limited, a first feature being “above” or “below” a second feature may mean that the first feature is directly in contact with the second feature, or the first feature and the second feature are in contact indirectly through an intermediate medium. Moreover, a first feature being “above”, “above”, or “above” a second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. A first feature being “below”, “below”, or “below” a second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.

[0055] Unless otherwise defined, all technical and scientific terms used in the specification of this application have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application. The term "and / or" used in the specification of this application includes any and all combinations of one or more related listed items.

[0056] The present application discloses a microfluidic chip and an immunoassay instrument, which include some or all of the technical features of the following embodiments; that is, the microfluidic chip and the immunoassay instrument include some or all of the following structures. In one embodiment of the present application, a microfluidic chip includes a body having a rotation center and a microfluidic chamber is opened in the body; the microfluidic chamber includes a first valve control structure, a second valve control structure, a third valve control structure, a fourth valve control structure, a first liquid chamber, a second liquid chamber, a first reaction chamber, a detection reaction chamber and a waste liquid chamber; from near to far from the rotation center, the first liquid chamber, the first valve control structure, the first reaction chamber, the fourth valve control structure and the waste liquid chamber are sequentially connected, and the second liquid chamber, the second valve control structure, the detection reaction chamber, the third valve control structure and the waste liquid chamber are sequentially connected. The above-mentioned microfluidic chip, by designing the first liquid chamber, the second liquid chamber, the first reaction chamber and the detection reaction chamber to match each other, is suitable for the delayed one-step method and the two-step method detection schemes that require two reactions with precise quantification, thereby realizing the delayed one-step method or the two-step method microfluidic detection, so that the microfluidic chip can match the delayed one-step method and the two-step method immune reaction, further broadening the versatility of microfluidic chips, especially disc-type microfluidic chips. Figures 1 to 4 , the microfluidic chip is described in detail.

[0057] In one embodiment, a microfluidic chip 100 is Figure 1 As shown, it includes a main body 110 having a rotation center 120 and a microfluidic chamber 130 is opened in the main body 110; in the illustrated embodiment, the rotation center 120 of the microfluidic chip 100 is located outside the main body 110, and the microfluidic chip 100 is a disc-type microfluidic chip, and multiple microfluidic chips 100 can be placed in a rotating system.

[0058] For example, in one embodiment, a microfluidic chip 100 is Figure 2As shown, the microfluidic chip 100 is a single-disc microfluidic chip, the body 110 is circular, and the rotation center 120 is located in the body 110 and is the center of the circle of the body 110. In this embodiment, the microfluidic chip 100 is provided with only one microfluidic chamber 130 in its body 110; in other embodiments, the microfluidic chip 100 may also be provided with two or more microfluidic chambers 130 in its body 110, and the embodiments of the present application do not impose additional restrictions on this.

[0059] Combination Figure 2 and Figure 3 In each embodiment, the microfluidic chamber 130 includes a first valve control structure 131, a second valve control structure 132, a third valve control structure 133, a fourth valve control structure 134, a first liquid chamber 135, a second liquid chamber 136, a first reaction chamber 137, a detection reaction chamber 138 and a waste liquid chamber 139; Figure 4 In this embodiment, the first liquid chamber 135 and the second liquid chamber 136 are used to quantify the liquid 200; the valve control structure, including the first valve control structure 131, the second valve control structure 132, the third valve control structure 133 and the fourth valve control structure 134, is used to transfer the liquid 200; taking the fourth valve control structure 134 as an example, the fourth valve control structure 134 is used to transfer the liquid 200 in the first reaction chamber 137 to the detection reaction chamber 138 under specific conditions. The first reaction chamber 137 and the detection reaction chamber 138 are used to perform reactions such as immune reactions, and reaction reagents for reactions can be pre-set in the first reaction chamber 137 and the detection reaction chamber 138, and the waste liquid chamber 139 is used to receive waste liquid.

[0060] Furthermore, in the microfluidic chamber 130 , the first liquid chamber 135 and the second liquid chamber 136 are closest to the rotation center 120 relative to other structures, while the waste liquid chamber 139 is farthest from the rotation center 120 relative to other structures.

[0061] Specifically, in order of distance from the rotation center 120 from near to far, the first liquid chamber 135, the first valve-controlled structure 131, the first reaction chamber 137, the fourth valve-controlled structure 134 and the detection reaction chamber 138 are connected in sequence, and the second liquid chamber 136, the second valve-controlled structure 132, the detection reaction chamber 138, the third valve-controlled structure 133 and the waste liquid chamber 139 are connected in sequence; that is, in the centrifugal direction 140, in order of distance from the rotation center 120 from near to far, the first liquid chamber 135, the first valve-controlled structure 131, the first reaction chamber 137, the fourth valve-controlled structure 134 and the detection reaction chamber 138 are connected in sequence, and the second liquid chamber 136, the second valve-controlled structure 132, the detection reaction chamber 138, the third valve-controlled structure 133 and the waste liquid chamber 139 are connected in sequence.

[0062] With such a structural design, in a rotating environment, the first liquid chamber 135, the first valve-controlled structure 131 and the first reaction chamber 137 form a pre-reaction system, and the obtained preliminary reactant enters the detection reaction chamber 138 through the fourth valve-controlled structure 134; at this time, the second valve-controlled structure 132 can be opened in coordination, or the second valve-controlled structure 132 can be opened in advance, and the substance in the second liquid chamber 136 enters the detection reaction chamber 138 through the second valve-controlled structure 132, reacts with the preliminary reactant, and obtains the final reactant. After the detection in the detection reaction chamber 138 is completed, the final reactant enters the waste liquid chamber 139 through the third valve-controlled structure 133.

[0063] Exemplarily, it can be seen from the above description that although the above embodiment is essentially a two-step method, only one microfluidic chip is needed. In a system, two reactions that require precise quantification can be achieved through one centrifugation operation, thereby improving the detection efficiency. It is compatible with three immunological methodologies, namely, the one-step method, the delayed one-step method, and the two-step method, and can adapt to more projects. Some embodiments may also be referred to as delayed one-step detection or two-step detection, that is, a delayed one-step detection scheme and a two-step detection scheme are provided, thereby realizing microfluidic detection of delayed one-step immunological method and microfluidic detection of two-step immunological method, so that the microfluidic chip 100 can be matched with the delayed one-step immunological reaction and the two-step immunological reaction, further broadening the versatility of the microfluidic chip 100, especially the disc-type microfluidic chip.

[0064] For example, in one embodiment, Figure 4As shown, the second liquid chamber 136 contains liquid 200, and the liquid 200 can be divided into reaction liquid, diluent and cleaning liquid according to the functional design; in other embodiments, the first liquid chamber 135 can also contain liquid 200. For strict reaction conditions, the liquid 200 contained in the first liquid chamber 135 and the second liquid chamber 136 is precisely quantitative. In one embodiment, the first reaction chamber 137 and / or the detection reaction chamber 138 can also contain liquid 200 to achieve functions such as participating in the reaction, diluting the solute or cleaning. Such a structural design is conducive to coordinating two controlled reactions in the same centrifugal operation without replacing the microfluidic chip 100, thereby providing a microfluidic detection scheme that is compatible with the two-step method and the delayed one-step method, which not only improves the efficiency of immune response detection, but also improves the precision of the detection results, and is also conducive to reducing the amount of microfluidic chip 100.

[0065] In one embodiment, the first valve control structure 131 is set to be closed at a speed lower than the preset first speed; the second valve control structure 132 is set to be closed at a speed lower than the preset second speed; the third valve control structure 133 is set to be closed at a speed lower than the preset third speed, so as to control the liquid 200 in the first reaction chamber 137 to flow to the waste liquid chamber 139; wherein the preset first speed is not higher than the preset second speed, and the preset first speed and the preset second speed are both lower than the preset third speed. As an example, the preset first speed is the same as the preset second speed, and the preset first speed and the preset second speed are both lower than the preset third speed. Exemplarily, in one embodiment, the preset first speed is 500rpm, that is, 500 rpm, the preset second speed is 800rpm, and the preset third speed is 1000rpm; that is, the preset first speed is lower than the preset second speed, and the preset second speed is lower than the preset third speed. Alternatively, the preset first speed is 800rpm, the preset second speed is 800rpm, and the preset third speed is 1000rpm; that is, the preset first speed is the same as the preset second speed, and the preset first speed and the preset second speed are both lower than the preset third speed. Alternatively, the preset first speed is 1000rpm, the preset second speed is 2000rpm, and the preset third speed is 3000rpm. The rest of the embodiments are analogous and will not be described in detail. Specifically, the preset first speed, the preset second speed and the preset third speed can be set or adjusted according to actual conditions, and the embodiments of the present application do not impose additional restrictions on this. Such a design can realize the switch control of the first valve control structure 131, the second valve control structure 132 and the third valve control structure 133 through simple centrifugal speed control, thereby completing the detection scheme of the delayed one-step method and the two-step method for two reactions that require precise quantification, which has the advantages of convenience, practicality and speed.

[0066] Exemplarily, the liquid transfer process of the microfluidic chip 100 through speed control is described as follows: the second liquid enters the second liquid chamber 136 from the back flow channel, and enters the first reaction chamber 137 under the action of the second speed; and, under the action of the second speed, the second liquid will not pass through the fourth valve control structure 134, and the fourth valve control structure 134 is in a closed state. When the microfluidic chip 100 stops rotating, the second liquid passes through the fourth valve control structure 134 under the capillary action, and the fourth valve control structure 134 is in an open state, and the second liquid enters the detection reaction chamber 138 from the first reaction chamber 137 under the action of the second speed; after the second liquid is incubated in the detection reaction chamber 138, it enters the waste liquid chamber 139 under the action of the third speed; similarly, the first liquid enters the first liquid chamber 135 from the front flow channel, enters the detection reaction chamber 138 under the action of the first speed, and after the first liquid is incubated in the detection reaction chamber 138, it enters the waste liquid chamber 139 under the action of the third speed.

[0067] In one embodiment, according to the distance from the rotation center 120 from near to far, the inlet of the first valve control structure 131 is connected to the bottom end of the first liquid chamber 135, and the inlet of the second valve control structure 132 is connected to the bottom end of the second liquid chamber 136, that is, the inlet of the first valve control structure 131 is connected to the bottom end of the first liquid chamber 135, that is, the inlet of the first valve control structure 131 is connected to the position of the first liquid chamber 135 farthest from the rotation center 120, and the rest of the embodiments are similar and will not be described in detail. In one embodiment, according to the distance from the rotation center 120 from near to far, the inlet of the third valve control structure 133 is connected to the bottom end of the detection reaction chamber 138. In one embodiment, according to the distance from the rotation center 120 from near to far, the inlet of the fourth valve control structure 134 is connected to the bottom end of the first reaction chamber 137. In one embodiment, according to the distance from the rotation center 120 from near to far, the bottom end of the first reaction chamber 137 is higher than the top end of the detection reaction chamber 138. For example, in one embodiment, the bottom of the first reaction chamber 137 is higher than the top of the detection reaction chamber 138 in terms of the distance from the rotation center 120. The methodology of traditional disc-type microfluidic chips is mostly biochemical reactions, which are difficult to adapt to delayed one-step or two-step immune reactions. The main limitations are: the immune reaction requires precise quantification, the immune reaction requires multiple rounds of cleaning, the valve control structure needs to be reused multiple times, and the delayed one-step or two-step method requires two incubations. Therefore, it is necessary to design two reaction chambers for incubation, and the reaction is carried out in a certain order. The process of dispensing liquid from the disc-type microfluidic chip to the reaction chamber is usually controlled by a hydrophobic valve or a capillary valve, but both the hydrophobic valve and the capillary valve are difficult to achieve liquid control in two reaction chambers. The present application provides a microfluidic chamber design that can achieve quantification, mixing, and reaction by designing a first liquid chamber 135, a second liquid chamber 136, a first reaction chamber 137, and a detection reaction chamber 138 that are matched with each other, and realizes the application of a disc-type microfluidic chip adapted to a delayed one-step immune reaction or a two-step immune reaction, so that the microfluidic chip 100 can match more methodologies, and the microfluidic chip 100 can match the delayed one-step and two-step immune reactions, thereby solving the problem that traditional disc-type microfluidic chips are difficult to adapt to delayed one-step and two-step immune reactions, and further broadens the versatility of the microfluidic chip 100, especially the disc-type microfluidic chip.

[0068] In one embodiment, the first valve control structure 131, the second valve control structure 132 and the third valve control structure 133 are hydrophobic valves or capillary valves. In one embodiment, the valve opening speed of the first valve control structure 131 and the second valve control structure 132 is less than the valve opening speed of the third valve control structure 133. The first valve control structure 131 and the second valve control structure 132 block the first liquid chamber 135 and the second liquid chamber 136, such as the liquid 200 in the quantitative chamber, from flowing to the reaction chamber at a low speed, thereby realizing the quantitative function of the quantitative chamber. The valve opening speed of the third valve control structure 133 is higher than that of the first valve control structure 131 and the second valve control structure 132, and can block the liquid 200 in the reaction chamber from flowing to the waste liquid chamber 139 when the first valve control structure 131 is opened. The inlet of the first valve control structure 131 should be located at the bottom of the first liquid chamber 135, and the inlet of the second valve control structure 132 should be located at the bottom of the second liquid chamber 136. Such a design is conducive to accurately controlling the flow direction of the liquid 200 in the microfluidic chamber 130, ensuring that the reactions in the first reaction chamber 137 and the detection reaction chamber 138 can be completed accurately and quantitatively according to the design objectives.

[0069] In one embodiment, the fourth valve-controlled structure 134 is a siphon valve. In one embodiment, the fourth valve-controlled structure 134 is a siphon valve, and the surface of the fourth valve-controlled structure 134 is a hydrophilic layer; from near to far from the rotation center 120, the outlet of the fourth valve-controlled structure 134 is connected to the uppermost end of the detection reaction chamber 138, and the uppermost end of the fourth valve-controlled structure 134 is higher than the uppermost end of the first reaction chamber 137, that is, the minimum distance between the fourth valve-controlled structure 134 and the rotation center 120 is less than the minimum distance between the first reaction chamber 137 and the rotation center 120. Exemplarily, the uppermost end of the fourth valve-controlled structure 134 is higher than the uppermost end of the detection reaction chamber 138, that is, the minimum distance between the fourth valve-controlled structure 134 and the rotation center 120 is less than the minimum distance between the detection reaction chamber 138 and the rotation center 120. Among them, the uppermost end is the position closest to the rotation center 120, that is, the position with the smallest distance from the rotation center 120. In one embodiment, the surface of the fourth valve-controlled structure 134 is a hydrophilic material, and the liquid 200 can fill the fourth valve-controlled structure 134 under capillary action. The inlet of the fourth valve-controlled structure 134 is located at the bottom of the first reaction chamber 137, and the outlet of the fourth valve-controlled structure 134 is located at the upper end of the detection reaction chamber 138. The high point of the fourth valve-controlled structure 134 should be higher than the high point of the first reaction chamber 137. Compared with the traditional hydrophobic valve and capillary valve scheme, such a design can accurately control the switch of the fourth valve-controlled structure 134 by controlling the centrifugal speed, effectively meeting the technical requirements of the delayed one-step method and the two-step method requiring two incubations, so that the microfluidic chip 100 can match both the delayed one-step method and the two-step method immunoreaction.

[0070] In one embodiment, the first liquid chamber 135 and the second liquid chamber 136 are quantitative chambers for quantitatively accommodating the liquid 200; in one embodiment, the first liquid chamber 135 and the second liquid chamber 136 are quantitative chambers, and the volumes of the first liquid chamber 135 and the second liquid chamber 136 are the same or different. Such a structural design is conducive to accurately adding the liquid 200 to the first liquid chamber 135 and / or the second liquid chamber 136, and controlling the two reactions that require precise quantification from the source, thereby helping to improve the test precision of the microfluidic chip 100.

[0071] In one embodiment, the first reaction chamber 137 and the detection reaction chamber 138 are respectively pre-set with reaction reagents; the reaction chamber, including the first reaction chamber 137 and the detection reaction chamber 138, contains the reagent to be reacted, namely the reaction reagent, which can be liquid, solid, or a solid-liquid mixture. Exemplarily, in one embodiment, the reaction reagent is one or more of a solid reagent, a freeze-dried reagent, a liquid reagent, a solid-phase reagent adsorbed on the chamber, etc. Exemplarily, in one embodiment, the reaction reagent is encapsulated in the first reaction chamber 137 and / or the detection reaction chamber 138 for release under preset conditions, and the preset conditions include at least one of the centrifugal speed and the ambient temperature. With such a structural design, the reaction reagent has a relatively long shelf life and is not easy to be transferred to other locations before the valve control structure is opened, so as not to affect the accuracy of the two reactions.

[0072] In one embodiment, the shape of the first reaction chamber 137 is selected from one of partial ellipse, partial circle, ellipse, circle, trapezoid, pear, rectangle and regular polygon; or, in one embodiment, the volume of the first reaction chamber 137 is greater than or equal to the volume of the first liquid chamber 135. Exemplarily, in one embodiment, the volume of the first reaction chamber 137 is 1.5 to 2 times the volume of the first liquid chamber 135. In one embodiment, the shape of the first reaction chamber 137 can be various shapes such as circle, square, pear, rectangle, etc., and its volume should be greater than the volume of the first liquid chamber 135, and preferably, its volume is 1.5 to 2 times the volume of the first liquid chamber 135. The first reaction chamber 137 is closer to the center of the microfluidic disc chip than the detection reaction chamber 138, and preferably, the bottom end of the first reaction chamber 137 is higher than the top end of the detection reaction chamber 138. Such a structural design can ensure that the reaction in the first reaction chamber 137 is started first, completed first and the preliminary reactants are obtained, and then the fourth valve-controlled structure 134 is opened after adjusting the centrifugal speed, and the preliminary reactants enter the detection reaction chamber 138; at this time, the substance in the second liquid chamber 136 can be synchronously passed through the second valve-controlled structure 132 to enter the detection reaction chamber 138, or the substance in the second liquid chamber 136 can be pre-passed into the detection reaction chamber 138 through the second valve-controlled structure 132, and then the reaction and detection are completed in the detection reaction chamber 138.

[0073] In one embodiment, the shape of the detection reaction chamber 138 is selected from one of partial ellipse, partial circle, ellipse, circle, trapezoid, pear, rectangle and regular polygon; or, in one embodiment, the shape of the detection reaction chamber 138 is set according to the light detection device. In one embodiment, the shape of the detection reaction chamber 138 can be various shapes such as circle, square, pear, rectangle, etc., and its shape matches the light detection device. In one embodiment, the volume of the detection reaction chamber 138 is greater than the volume of the first liquid chamber 135, the volume of the first reaction chamber 137 and the volume of the second liquid chamber 136, that is, the volume of the detection reaction chamber 138 is greater than the volume of the second liquid chamber 136, the volume of the detection reaction chamber 138 is greater than the volume of the first liquid chamber 135, and the volume of the detection reaction chamber 138 is greater than the volume of the first reaction chamber 137. More preferably, the volume of the detection reaction chamber 138 is 1.5 to 2 times the larger volume of the second liquid chamber 136 and the first liquid chamber 135. In one embodiment, the volume of the detection reaction chamber 138 is greater than or equal to the sum of the volumes of the first liquid chamber 135 and the second liquid chamber 136; in one embodiment, the volume of the detection reaction chamber 138 is greater than or equal to the sum of the volumes of the first liquid chamber 135, the first reaction chamber 137, and the second liquid chamber 136. In one embodiment, the volume of the detection reaction chamber 138 is greater than or equal to 1.5 times the volume of the first liquid chamber 135, the volume of the detection reaction chamber 138 is greater than or equal to 1.5 times the volume of the second liquid chamber 136, and the volume of the detection reaction chamber 138 is greater than or equal to 1.5 times the volume of the first reaction chamber 137. For example, in one embodiment, the volume of the detection reaction chamber 138 is greater than or equal to 1.5 to 2 times the sum of the volumes of the first liquid chamber 135 and the second liquid chamber 136; or, the volume of the detection reaction chamber 138 is greater than or equal to 1.5 to 2 times the volume of the larger of the first liquid chamber 135 and the second liquid chamber 136. Such a structural design is suitable for two reactions that require precise quantification, so that the second step reaction can be accurately controlled in the detection reaction chamber 138, and all the liquid will not overflow, and finally enter the waste liquid chamber 139 in a controlled manner.

[0074] In one embodiment, the waste liquid chamber 139 is used to receive the liquid 200 discharged from the detection reaction chamber 138, and its shape can be circular, elliptical, square, rectangular or other shapes. In one embodiment, the shape of the waste liquid chamber 139 is selected from one of a partial ellipse, a partial circle, an ellipse, a circle, a trapezoid, a rectangle and a regular polygon. In one embodiment, the volume of the waste liquid chamber 139 is greater than or equal to the sum of the volumes of the first liquid chamber 135 and the second liquid chamber 136. In one embodiment, the volume of the waste liquid chamber 139 is greater than or equal to the sum of the volumes of the first liquid chamber 135, the second liquid chamber 136, the first reaction chamber 137 and the detection reaction chamber 138. Such a structural design is conducive to concentrating all the liquids of the reaction in the waste liquid chamber 139, so as to facilitate the cleaning work after the detection is completed.

[0075] In one embodiment, the first liquid chamber 135 and the first valve control structure 131 are opened on one side of the body 110, and the second liquid chamber 136, the second valve control structure 132, the first reaction chamber 137, the fourth valve control structure 134, the detection reaction chamber 138, the third valve control structure 133 and the waste liquid chamber 139 are opened on the other side of the body 110; as an example, the first liquid chamber 135 and the first valve control structure 131 are both located on the back side of the chip, and the second liquid chamber 136, the second valve control structure 132, the third valve control structure 133, the first reaction chamber 137, the fourth valve control structure 134, the detection reaction chamber 138, and the waste liquid chamber 139 are all located on the front side of the chip. It can be understood that the front side of the chip is opposite to the back side of the chip, and either side can be used as the front side. Since the first liquid chamber 135 and the second liquid chamber 136 need to accommodate the liquid 200, after the first liquid chamber 135 and / or the second liquid chamber 136 accommodate the liquid 200, a film or a thin sheet is used to seal them to prevent the liquid 200 from splashing out after flipping or during high-speed centrifugation. Such a design makes full use of the thickness of the main body 110 and is particularly suitable for detection applications with a small amount of reaction liquid. The reasonable position distribution of the first liquid chamber 135, the second liquid chamber 136, the first reaction chamber 137 and the detection reaction chamber 138 greatly reduces the occupied area of ​​the microfluidic chamber 130 on the main body 110. When applied to a single-disc microfluidic chip, a larger number of microfluidic chambers 130 can be arranged on a microfluidic chip 100. Compared with the traditional single-sided distribution design, this embodiment adopts a double-sided distribution design. If the number of microfluidic chambers 130 is not increased and the original detection flux is maintained, the volume of the microfluidic chip 100 is relatively smaller, and the weight of the main body 110 can be reduced by about 13% to 19%, which is not only conducive to reducing the product appearance and reducing the production cost, but also conducive to reducing the motor load.

[0076] In one embodiment, the first liquid chamber 135, the first valve control structure 131, the first reaction chamber 137 and the fourth valve control structure 134 are opened on one side of the body 110, and the second liquid chamber 136, the second valve control structure 132, the detection reaction chamber 138, the third valve control structure 133 and the waste liquid chamber 139 are opened on the other side of the body 110; or, in one embodiment, the first liquid chamber 135, the first valve control structure 131, the first reaction chamber 137, the fourth valve control structure 134, the detection reaction chamber 138, the third valve control structure 133 and the waste liquid chamber 139 are opened on the other side of the body 110. The cavity 138, the third valve control structure 133 and the waste liquid cavity 139 are opened on one side of the body 110, and the second liquid cavity 136 and the second valve control structure 132 are opened on the other side of the body 110; or, in one embodiment, the first valve control structure 131, the second valve control structure 132, the third valve control structure 133, the fourth valve control structure 134, the first liquid cavity 135, the second liquid cavity 136, the first reaction cavity 137, the detection reaction cavity 138 and the waste liquid cavity 139 are opened on the same side of the body 110. The rest of the embodiments are similar and will not be described in detail.

[0077] In one embodiment, an immunoassay instrument includes a centrifuge and the microfluidic chip 100 of any embodiment, wherein the microfluidic chip 100 is disposed on the rotating shaft of the centrifuge. It is understandable that since the immunoassay instrument adopts the microfluidic chip 100 of any embodiment, it has the beneficial technical effects brought by the microfluidic chip 100, which will not be described in detail here.

[0078] As an example, an immunoassay instrument includes a centrifuge and a microfluidic chip 100, wherein the microfluidic chip 100 includes a main body 110 having a rotation center 120 and a microfluidic chamber 130 is opened in the main body 110; the microfluidic chamber 130 includes a first valve control structure 131, a second valve control structure 132, a third valve control structure 133, a fourth valve control structure 134, a first liquid chamber 135, a second liquid chamber 136, a first reaction chamber 137, a detection reaction chamber 138 and a waste liquid chamber 139; from near to far from the rotation center 120, the first liquid chamber 135, the first valve control structure 131, the first reaction chamber 137, the fourth valve control structure 134 and the detection reaction chamber 138 are sequentially connected, and the second liquid chamber 136, the second valve control structure 132, the detection reaction chamber 138, the third valve control structure 133 and the waste liquid chamber 139 are sequentially connected. In this embodiment, the body 110 is disposed on the rotating shaft of the centrifuge, and the rotating center 120 is disposed corresponding to the rotating shaft. For example, the body 110 can be directly disposed on the rotating shaft, or indirectly disposed on the rotating shaft through an intermediate piece. The embodiments of the present application do not impose additional restrictions on this. It is only necessary for the centrifuge to drive the body 110 to rotate through the rotating shaft, so that each valve control structure of the microfluidic chamber 130 can be controlled by rotation.

[0079] It should be noted that other embodiments of the present application also include microfluidic chips and immunoassay instruments that can be implemented by combining the technical features in the above embodiments.

[0080] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0081] The above-described embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the scope of patent protection of the present application shall be subject to the attached claims.

Claims

1. A microfluidic chip (100), characterized in that: It comprises a body (110) having a rotation center (120) and a microfluidic chamber (130) is provided in the body (110); The microfluidic chamber (130) comprises a first valve control structure (131), a second valve control structure (132), a third valve control structure (133), a fourth valve control structure (134), a first liquid chamber (135), a second liquid chamber (136), a first reaction chamber (137), a detection reaction chamber (138), and a waste liquid chamber (139); In order of distance from the rotation center (120) from near to far, the first liquid chamber (135), the first valve control structure (131), the first reaction chamber (137), the fourth valve control structure (134) and the detection reaction chamber (138) are sequentially connected and arranged, and the second liquid chamber (136), the second valve control structure (132), the detection reaction chamber (138), the third valve control structure (133) and the waste liquid chamber (139) are sequentially connected and arranged.

2. The microfluidic chip (100) according to claim 1, characterized in that: The first liquid chamber (135) and the first valve control structure (131) are opened on one side of the body (110), and the second liquid chamber (136), the second valve control structure (132), the first reaction chamber (137), the fourth valve control structure (134), the detection reaction chamber (138), the third valve control structure (133) and the waste liquid chamber (139) are opened on the other side of the body (110); or, The first liquid chamber (135), the first valve control structure (131), the first reaction chamber (137) and the fourth valve control structure (134) are opened on one side of the body (110), and the second liquid chamber (136), the second valve control structure (132), the detection reaction chamber (138), the third valve control structure (133) and the waste liquid chamber (139) are opened on the other side of the body (110); or, The first liquid chamber (135), the first valve control structure (131), the first reaction chamber (137), the fourth valve control structure (134), the detection reaction chamber (138), the third valve control structure (133) and the waste liquid chamber (139) are provided on one side of the body (110), and the second liquid chamber (136) and the second valve control structure (132) are provided on the other side of the body (110); or, The first valve control structure (131), the second valve control structure (132), the third valve control structure (133), the fourth valve control structure (134), the first liquid chamber (135), the second liquid chamber (136), the first reaction chamber (137), the detection reaction chamber (138) and the waste liquid chamber (139) are opened on the same surface of the main body (110).

3. The microfluidic chip (100) according to claim 1, characterized in that: The first valve control structure (131) is configured to be closed at a speed lower than a preset first speed; The second valve control structure (132) is configured to be closed at a speed lower than a preset second speed; The third valve control structure (133) is configured to be closed at a speed lower than a preset third rotation speed, so as to control the liquid (200) in the first reaction chamber (137) to flow toward the waste liquid chamber (139); The preset first speed is not higher than the preset second speed, and both the preset first speed and the preset second speed are lower than the preset third speed.

4. The microfluidic chip (100) according to claim 1, characterized in that: According to the distance from the rotation center (120) from near to far, The inlet of the first valve control structure (131) is connected to the bottom end of the first liquid chamber (135), and the inlet of the second valve control structure (132) is connected to the bottom end of the second liquid chamber (136); or, The inlet of the third valve control structure (133) is connected to the bottom end of the detection reaction chamber (138); or, The inlet of the fourth valve control structure (134) is connected to the bottom end of the first reaction chamber (137).

5. The microfluidic chip (100) according to claim 1, characterized in that: The first valve control structure (131), the second valve control structure (132), and the third valve control structure (133) are steam traps or capillary valves; or, The fourth valve control structure (134) is a siphon valve; or, The first liquid chamber (135) and the second liquid chamber (136) are quantitative chambers for quantitatively containing liquid (200); or, The first reaction chamber (137) and the detection reaction chamber (138) are respectively pre-installed with reaction reagents; or, The volume of the detection reaction chamber (138) is greater than or equal to the sum of the volumes of the first liquid chamber (135) and the second liquid chamber (136); or, The volume of the waste liquid chamber (139) is greater than or equal to the sum of the volumes of the first liquid chamber (135) and the second liquid chamber (136).

6. The microfluidic chip (100) according to claim 1, characterized in that: The fourth valve-controlled structure (134) is a siphon valve, and the surface of the fourth valve-controlled structure (134) is a hydrophilic layer; In order of distance from the rotation center (120) from near to far, the outlet of the fourth valve control structure (134) is connected to the uppermost end of the detection reaction chamber (138), and the uppermost end of the fourth valve control structure (134) is higher than the uppermost end of the first reaction chamber (137).

7. The microfluidic chip (100) according to claim 1, characterized in that: The first liquid chamber (135) and the second liquid chamber (136) are quantitative chambers, and the volumes of the first liquid chamber (135) and the second liquid chamber (136) are the same or different.

8. The microfluidic chip (100) according to claim 1, characterized in that: The shape of the first reaction chamber (137) is selected from one of a partial ellipse, a partial circle, an ellipse, a circle, a trapezoid, a pear, a rectangle and a regular polygon; or, The volume of the first reaction chamber (137) is greater than or equal to the volume of the first liquid chamber (135); or, The shape of the detection reaction chamber (138) is selected from one of a partial ellipse, a partial circle, an ellipse, a circle, a trapezoid, a pear, a rectangle and a regular polygon; or, The shape of the detection reaction chamber (138) is set according to the light detection device; or, The volume of the detection reaction chamber (138) is greater than the volume of the first liquid chamber (135), the volume of the first reaction chamber (137), and the volume of the second liquid chamber (136); or, The shape of the waste liquid chamber (139) is selected from a partial ellipse, a partial circle, an ellipse, a circle, a trapezoid, a rectangle and a regular polygon; or, The volume of the waste liquid chamber (139) is greater than or equal to the sum of the volumes of the first liquid chamber (135), the second liquid chamber (136), the first reaction chamber (137), and the detection reaction chamber (138).

9. The microfluidic chip (100) according to any one of claims 1 to 8, characterized in that: The microfluidic chip (100) is a disc-type microfluidic chip.

10. An immunoassay instrument, characterized in that: It comprises a centrifuge and the microfluidic chip (100) according to any one of claims 1 to 9, wherein the microfluidic chip (100) is arranged on a rotating shaft of the centrifuge.

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