Microfluidic chip based on lyophilic and / or lyophobic microarrays to achieve flow control

Abstract

The present invention provides a microfluidic chip for realizing flow control based on a lyophilic and / or lyophobic microarray, and relates to the technical field of instant detection products. The microfluidic chip uses a flow controller to control the flow rate of liquid in a microchannel, and the flow controller includes a microarray formed by a plurality of array units; the array unit is a lyophobic layer or a lyophilic layer with a shape arranged on the surface of the microchannel; wherein, if the flow controller is a deceleration flow controller, it includes a microarray formed by a plurality of lyophobic array units, and the contact angle of the lyophobic array unit is greater than the microchannel; if the flow controller is an acceleration flow controller, it includes a microarray formed by a plurality of lyophilic array units, and the contact angle of the lyophilic array unit is less than the microchannel. The microfluidic chip uses a microarray formed by arranging array units to control the flow rate of liquid in a microchannel, and has the advantages of low cost, simple preparation, and no need for external drive.

Description

Technical Field

[0001] The present invention relates to the field of instant detection products, and in particular to a microfluidic chip for realizing flow control based on a lyophilic and / or lyophobic microarray. Background Art

[0002] Microfluidic chip, also known as chip laboratory, refers to a microfluidic device that integrates the basic operation units of biological and chemical sample preparation, reaction, separation, detection, cell culture, sorting, lysis, etc. involved in the chemical and biological fields on a chip of a few square centimeters. Microfluidic chip uses micro-electromechanical processing technology to construct a microfluidic system on the chip, and transfers the biochemical analysis process to a chip of a few square centimeters composed of interconnected paths and liquid phase chambers. After loading biological samples and reaction liquids, mechanical or non-mechanical driving methods are used to drive the liquid in the chip to flow into the chip, and one or more continuous reactions are carried out on the chip. With the continuous deepening of microfluidic chip research and commercialization requirements, the demand for small-batch, multi-variety, low-cost, disposable chips required in the research and development stage of new commercial microfluidic chip products is becoming increasingly urgent.

[0003] The characteristic scale of liquid flow in microfluidic chips is generally 0.1μm to 1mm. The liquid flowing in this micrometer-scale space is called microfluidic. Microfluidic chip is an integrated system composed of liquid driving, transmission, detection and other units, and the flow has a networked characteristic; secondly, the flow medium has various forms, including continuous flow, discrete droplets, ion flow, etc. Therefore, driving and controlling liquid samples at the microscale has become a key factor in the design process of microfluidic chips. Taking the POCT immunoassay chip as an example, it realizes a series of immunoassay processes through the construction of different functional areas. In this process, blood, as the object to be detected, undergoes antibody labeling, mixing, incubation and other steps in this microfluidic chip. Each step requires precise control of the flow rate of blood to ensure the accuracy of the final test results. For example: after passing through the coating area, the blood needs to be decelerated to ensure that the detected antigen in the blood is fully combined with the antibody in the coating area; when the blood flows to the waste liquid bin, the blood needs to be accelerated to ensure that the blood does not stay at the entrance of the waste liquid bin and affect the detection. Therefore, how to control the liquid flow rate in the microchannel to achieve microfluidic labeling and mixing has become the key in the design process of microfluidic chips.

[0004] There are many methods to drive and control microfluidics in microfluidic chips. The pressure flow drive method has the advantages of simple implementation, easy implementation, and low cost. However, the external drive pump makes it difficult to miniaturize, and there are problems with the interface between the pump and the chip, which limits its application in small batches, multiple varieties, and disposable chips. Although the use of electroosmotic flow to drive and control microfluidics can achieve quantitative control of flow rate, it has strict requirements on the physical and chemical properties of the chip substrate and the liquid. It requires that a double electric layer must be formed on the surface of the flow channel to achieve electroosmotic flow drive; in addition, the external current source required for electroosmotic flow drive will bring power consumption and Joule heat problems, affecting the activity of the reagent sample in the flow channel. Centrifugal force drive uses the centrifugal force generated by the chip when it moves in a circular motion driven by a micromotor as the driving force of the liquid flow. The flow rate of the liquid is adjusted and controlled by changing the rotation speed of the chip and designing different channel configurations. The flow limiting and switching control of the liquid on the chip requires the use of microvalves to complete. Centrifugal force-driven microfluidic chips have the advantages of low preparation cost, high throughput, and high integration, but they require the use of an external motor to achieve centrifugal force drive, have relatively high requirements for detection equipment, and require the introduction of capillary microvalves to limit and switch the inflow of liquids, which puts higher requirements on the preparation of the chip.

[0005] The method of using surface tension to drive and control the liquid in the microchannel does not need to integrate electrodes and external circuits in the chip, and has the advantage of low cost. The existing method of using surface tension to drive and control the liquid in the microchannel mainly uses a structural unit with projections of various shapes to constrain the flow path of the liquid in the microchannel, so as to increase the path of the liquid flow in the microchannel and slow down the flow rate of the liquid. For example, in the prior art, a comb-tooth type and a maze-type rectangular boss, or a raised rectangle or dot is used to form a delayed flow regulator in a microfluidic device, and the flow is constrained by a raised step-shaped flow channel, and the flow resistance is increased by increasing the length of the flow channel to achieve the purpose of slowing down the flow rate. However, due to the small size of the microfluidic chip, it is difficult to add a structural unit with a specific shape in the microchannel in the process, and the production cost will be increased. Therefore, an improved microfluidic chip for driving and controlling the flow rate of microfluids is necessary.

[0006] In view of this, the present invention is proposed. Summary of the invention

[0007] The first purpose of the present invention is to provide a microfluidic chip for realizing flow control based on a lyophilic and / or lyophobic microarray, thereby alleviating the problem in the prior art of lacking a microfluidic chip that does not require an external drive and can effectively control the flow rate of liquid in the chip.

[0008] In order to solve the above technical problems, the present invention particularly adopts the following technical solutions:

[0009] A microfluidic chip for realizing flow control based on a lyophilic and / or lyophobic microarray, wherein the contact angle between a microchannel of the microfluidic chip and a liquid in a sample to be tested is θ0, and θ0<90°; and at least one flow controller is arranged on the microchannel;

[0010] The flow controller comprises a microarray formed by arranging a plurality of array units; the array unit is a liquid-repellent layer or a liquid-philic layer with a shape arranged on the surface of the microchannel;

[0011] Wherein, if the flow controller is a deceleration flow controller, the deceleration flow controller comprises a microarray composed of a plurality of lyophobic array units arranged, and the lyophobic array units are lyophobic array units with a contact angle θ relative to the liquid in the sample to be tested. s >θ0 array element;

[0012] If the flow controller is an accelerating flow controller, the accelerating flow controller comprises a microarray composed of a plurality of lyophilic array units arranged in a pattern, wherein the lyophilic array units have a contact angle θ relative to the liquid in the sample to be tested. q <θ0 array unit.

[0013] Preferably, the microarray is arranged in the following manner: the array elements form a plurality of mutually parallel rows;

[0014] Preferably, the rows of array units parallel to the liquid flow direction are also parallel to each other;

[0015] Preferably, the rows in the microarray are arranged in a staggered manner.

[0016] Preferably, the microarray is arranged in the following manner: the array units are arranged in an S-shape to form an S-shaped subarray spanning the cross section of the microfluidic channel; a plurality of the S-shaped subarrays are arranged in parallel perpendicular to the liquid flow direction to form a microarray;

[0017] Preferably, the rows of array units parallel to the liquid flow direction are also parallel to each other;

[0018] Preferably, a plurality of the S-shaped sub-arrays are arranged in a staggered manner.

[0019] Preferably, the microarray is arranged in the following manner: a number of the array units are arranged into subarrays, and the subarrays are arranged in a determinant manner; the subarrays preferably include U-shaped subarrays.

[0020] Preferably, the microarray is arranged in the following manner: the connecting lines of array units in adjacent rows are not parallel to the liquid flow direction.

[0021] Preferably, the shapes of the lyophobic layer and the lyophilic layer are independently rectangular, circular, diamond or triangular;

[0022] Preferably, the shape and area of ​​each array unit in the microarray are the same;

[0023] Preferably, the size of the array unit is 50-500 μm.

[0024] Preferably, the microfluidic chip further comprises a reaction module, and the sample to be detected first flows through at least one deceleration flow controller, then flows through the reaction module, and then flows through at least one acceleration flow controller.

[0025] Preferably, the microfluidic chip is used for POCT immunoassay; the microfluidic chip is provided with a sample injection port, a microchannel and a waste liquid bin in sequence from the liquid flow direction;

[0026] The sample to be tested flows from the microfluidic channel sequentially through the fluorescence module, the deceleration flow controller, the reaction module, the quality control module and the acceleration flow controller.

[0027] Preferably, the microchannel is treated with lyophilicity to make the contact angle θ0 of the microchannel less than 90°; the microchannel is mainly made of the following materials: styrene, polyethylene, polypropylene, polycarbonate, acrylonitrile-butadiene-styrene copolymer, polymethacrylate, polydimethylsiloxane, silicon, quartz or glass.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The microfluidic chip for realizing flow control based on a lyophilic and / or lyophobic microarray provided by the present invention drives the liquid in the microchannel to flow in through surface tension, and a microarray formed by array units is arranged in the microchannel, so that the liquid in the substance to be tested produces a deceleration or acceleration effect due to the change in the contact angle between the liquid and the array units when flowing through the microarray. The present invention adopts a surface tension (capillary force) driven method, and uses a microarray formed by array units to control the flow rate of the liquid in the microchannel. It has the advantages of low cost, simple preparation, and no need for external drive, and is a good choice for low-cost, disposable chip flow control solutions. Compared with other methods, the surface tension driven and controlled flow method of microfluids in microchannels has the advantages of easy automatic control and no need for external force, and is a good solution for rapid prototyping of small batches, multiple varieties, low cost, and disposable chips required for low cost in the research and development stage. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0031] Figure 1 Schematic diagram of capillary action;

[0032] Figure 2 The microfluidic chip provided in Example 1 of the present invention;

[0033] Figure 3 The arrangement of the microarray in the deceleration flow controller in the microfluidic chip provided in Example 1 of the present invention;

[0034] Figure 4 The arrangement of the microarray in the accelerating flow controller in the microfluidic chip provided in Example 1 of the present invention;

[0035] Figure 5 The arrangement of the microarray in the flow controller in the microfluidic chip provided in Example 2 of the present invention;

[0036] Figure 6 The arrangement of the microarray in the flow controller in the microfluidic chip provided in Example 3 of the present invention;

[0037] Figure 7 The arrangement of the microarray in the flow controller in the microfluidic chip provided in Example 4 of the present invention;

[0038] Figure 8 This is the arrangement of the microarray in the flow controller in the microfluidic chip provided in Example 5 of the present invention. DETAILED DESCRIPTION

[0039] The technical scheme of the present invention will be clearly and completely described below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work are within the scope of protection of the present invention. If the specific conditions are not specified in the embodiments, they are carried out according to the normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified in the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0040] In the description of the present invention, it should be noted that, if the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. appear, the orientation or position relationship indicated is based on the orientation or position relationship shown in the drawings, which is only for the convenience of describing the present invention and simplifying the description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, if the terms "first", "second", "third" appear, they are only used for descriptive purposes and cannot be understood as indicating or implying relative importance.

[0041] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "connected" and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0042] The present invention provides a microfluidic chip for realizing flow control based on a lyophilic and / or lyophobic microarray, wherein the contact angle between a microchannel of the microfluidic chip and a liquid in a sample to be tested is θ0, and θ0<90°; at least one flow controller is arranged on the microchannel; the flow controller comprises a microarray formed by arranging a plurality of array units; the array unit is a lyophobic layer or a lyophilic layer having a shape and arranged on the surface of the microchannel;

[0043] Wherein, if the flow controller is a deceleration flow controller, the deceleration flow controller comprises a microarray composed of a plurality of lyophobic array units arranged, and the lyophobic array units are lyophobic array units with a contact angle θ relative to the liquid in the sample to be tested. s >θ0 array element;

[0044] If the flow controller is an accelerating flow controller, the accelerating flow controller comprises a microarray composed of a plurality of lyophilic array units arranged in a pattern, wherein the lyophilic array units have a contact angle θ relative to the liquid in the sample to be tested. q <θ0 array unit.

[0045] Capillary phenomenon refers to the phenomenon that the wetting liquid rises in the capillary (capillary lyophilicity) and the non-wetting liquid falls in the capillary (capillary lyophobicity). The tube that can produce obvious capillary phenomenon is called a capillary. The surface tension in the capillary conforms to Young's equation: Schematic diagram of liquid flowing into a capillary driven by surface tension Figure 1 As shown, where θ YThe contact angle is the angle between the tangent line of the gas-liquid interface at the intersection of the gas, liquid and solid phases and the solid-liquid boundary line on the liquid side. Y , is a measure of the degree of wetting; the contact angle θ Y Less than 90°, the capillary surface is wetted by the liquid in the capillary, and the contact angle θ Y When the angle is greater than 90°, the capillary surface is non-wetting relative to the liquid in the capillary. When the liquid contacts the wetting surface, the contact liquid surface presents a concave liquid surface under the action of the liquid surface tension; when the liquid contacts the non-wetting surface, the contact liquid surface presents a convex liquid surface under the action of the liquid surface tension; the liquid surface bends at the contact point between the liquid and the solid, and the curved part is called a meniscus. The capillary force is generated in the direction of the capillary force caused by the curvature of the liquid surface caused by the inner bay liquid surface on the three-phase interface. The direction of action always points to the concave surface of the meniscus, and the magnitude of the capillary force is proportional to the curvature of the meniscus. The microchannel in the microfluidic chip provided by the present invention acts as a capillary, and the contact angle between the microchannel of the microfluidic chip and the liquid phase in the sample to be tested is θ0, and θ0 is less than 90°. In the microchannel, the liquid presents a concave liquid surface due to the lyophilic effect of the meniscus, and the liquid flows under the drive of the surface tension.

[0046] The microfluidic chip provided by the present invention is further provided with at least one flow controller in the microchannel, and the flow controller includes a microarray formed by a plurality of array units, wherein the array unit is a liquid-repellent layer or a liquid-philic layer with a preset shape arranged on the surface of the microchannel, wherein liquid-repellent or liquid-philic refers to the wettability of the array unit to the liquid phase substance in the sample to be tested compared to the microchannel, and the specifics are as follows:

[0047] If the flow controller is used for deceleration, the array unit is a liquid-repellent array unit, and the liquid-repellent array unit has a contact angle θ s >θ0, a plurality of liquid-repellent array units are arranged into a micro-array for deceleration, so as to slow down the flow rate of the liquid in the micro-channel.

[0048] The contact angle of the liquid-repellent array unit satisfies θ s >θ0, the surface wettability of the liquid sample to the lyophobic array unit is worse than its surface wettability to the wall of the microfluidic matrix. According to Young's equation: It can be seen that after the liquid flows into the decelerated microarray, the surface tension decreases due to the increase in the contact angle, so that the driving effect of the surface tension on the liquid is weakened, which reduces the liquid flow rate.

[0049] At the same time, when the liquid flows through the decelerating microarray, it will preferentially flow along the path with a smaller contact angle. Therefore, when the decelerating microarray is distributed with lyophobic array units, the liquid always tends to avoid the lyophobic array units in the microarray, thereby increasing the total length of the path along which the liquid flows in the decelerating microarray, and further increasing the flow time. Therefore, a microarray for decelerating composed of a plurality of lyophobic array units can slow down the flow rate of the liquid in this area and increase the flow time of the liquid in this area. The flow rate slowing effect is relative to the base of the microfluidic channel.

[0050] If the flow controller is used for acceleration, the array unit is a lyophilic array unit, and the lyophilic array unit has a contact angle θ q <θ0, a plurality of lyophilic array units are arranged into a microarray for acceleration to increase the flow rate of the liquid in the microchannel.

[0051] The contact angle of the lyophilic array unit satisfies θ q <θ0, the surface wettability of the liquid sample to the lyophilic array unit is better than its surface wettability to the wall of the microfluidic matrix. According to Young's equation: It can be seen that after the liquid flows into the accelerated microarray, the surface tension increases due to the decrease in the contact angle, thereby enhancing the driving effect of the surface tension on the liquid and increasing the liquid flow rate.

[0052] At the same time, when the liquid flows through the accelerated microarray, it will preferentially choose a path with a smaller contact angle to flow. Therefore, when the accelerated microarray is distributed with lyophilic array units, the liquid always tends to approach the lyophilic array units and directly pass through the microarray. The lyophilic microarray hardly increases the length of the path through which the liquid flows. Therefore, a microarray composed of several lyophilic units arranged for acceleration can increase the flow rate of the liquid in this area and reduce the flow time of the liquid in this area. The effect of accelerating the flow rate is relative to the substrate of the microchannel.

[0053] The speed-changing effect of the microarray formed by the arrangement of array units on the liquid flow rate is only effective when the meniscus of the capillary flow passes through this area. After the meniscus of the capillary flow flows through the microarray, its speed-changing effect disappears and has no effect on the speed of the capillary flow in the subsequent flow channel. In addition, the flow controller not only has the function of regulating the flow rate, but also can achieve the mixing of the liquid and solid phase medium in the microchannel, and the various media will not form deposition and retention in the microarray during the mixing process.

[0054] In summary, the microfluidic chip for realizing flow control based on lyophilic and / or lyophobic microarray provided by the present invention drives the liquid in the microchannel to flow in through surface tension, and a microarray formed by array units is arranged in the microchannel, so that the liquid in the substance to be tested produces a deceleration or acceleration effect due to the change in the contact angle between the liquid and the array units when flowing through the microarray. The present invention adopts a surface tension (capillary force) driven method, and uses a microarray formed by array units to control the flow rate of the liquid in the microchannel. It has the advantages of low cost, simple preparation, and no need for external drive. It is a good choice for low-cost, disposable chip flow control solutions. Compared with other methods, the surface tension drive and control method of the flow of microfluids in the microchannel has the advantages of easy automatic control and no external force. It is a good solution for rapid prototyping of small batches, multiple varieties, low cost, and disposable chips required for low cost in the research and development stage.

[0055] It should be noted that the contact angle θ0 between the microchannel of the present invention and the liquid in the sample to be tested is less than 90°. The microchannel can be prepared by directly using a lyophilic material to make it wettable to the sample to be tested; or it can be made wettable by performing a lyophilic treatment on the material used to prepare the microchannel. The present invention does not limit the method of lyophilic treatment. Any material surface modification method acceptable in the art can be used for lyophilic treatment of the microchannel surface, such as but not limited to plasma treatment, ultraviolet irradiation, chemical vapor deposition, lyophilic material coating or surface functionalization grafting. In some optional embodiments, the microchannel can be made of the following materials: styrene, polyethylene, polypropylene, polycarbonate, acrylonitrile-butadiene-styrene copolymer, polymethacrylate, polydimethylsiloxane, silicon, quartz or glass.

[0056] The array unit described in the present invention is a lyophobic layer or a lyophilic layer distributed on the surface of the microfluidic channel, and the lyophobic layer or the lyophilic layer has a certain shape independently on the surface of the microfluidic channel. It should be noted that the present invention does not limit the preparation method of the lyophobic layer or the lyophilic layer, for example, it can be but not limited to etching method, deposition method, template method, phase separation method, jet printing method or nanoparticle method, etc. It can be understood that as long as a lyophobic layer or a lyophilic layer with a preset shape can be prepared on the surface of the microfluidic channel as an array unit. It is preferred to spray the lyophobic substance or the lyophilic substance on the surface of the microfluidic channel by an extremely small amount of jet spotting machine, and form an array unit after solidification; wherein the lyophobic substance can be, for example, but not limited to, lyophobic substances such as fatty acids, sodium fatty acids, gelatin, casein or ink; the lyophilic substance can be, for example, but not limited to, proteins or hydrogels, etc.; it should be noted that the present invention does not limit the materials constituting the array unit, as long as it meets the contact angle θ of the lyophobic array unit relative to the liquid in the sample to be tested. s >θ0, the contact angle θ of the lyophilic array unit relative to the liquid in the sample to be tested q<θ0. The present invention controls the flow rate by preparing a liquid-repelling or liquid-philic liquid-repelling layer or a liquid-philic layer with a certain shape on the microchannel as an array unit. Compared with the microfluidic chip preparation method of constructing a structural unit with protrusions of various shapes in the microchannel to constrain the flow path of the liquid in the microchannel, it is simpler. It is only necessary to construct a liquid-repelling array unit or a liquid-philic array unit distributed according to a microarray on the microchannel according to a general solid-phase modification method.

[0057] The microfluidic chip for realizing flow control based on lyophilic and / or lyophobic microarrays provided by the present invention can also constrain the flow path of the fluid in the microchannel by changing the arrangement of the array units in the microarray, the shape of the array units, and the distribution density of the array units in the microarray, thereby realizing flow control of the liquid sample to control the time for the liquid sample to pass through the channel; different arrangements of the array units have different changes in the flow rate of the liquid in the microchannel. By slowing down the flow rate of the liquid sample and increasing the flow time, the detected substance in the liquid sample can be promoted to fully complete the biochemical reaction; increasing the flow rate of the liquid can prevent the liquid sample from being retained in the detection area, thereby improving the sensitivity and accuracy of the microfluidic chip. In some optional embodiments, a number of array units can be arranged in a microarray according to, for example, but not limited to, a determinant arrangement, a circumferential arrangement, or a discrete arrangement.

[0058] In some optional embodiments, the microarray is arranged in the following manner: the array units form a plurality of mutually parallel rows, and the rows are perpendicular to the liquid flow direction. In some preferred embodiments, the array units in this arrangement also form a plurality of mutually parallel columns, that is, arranged in a determinant-column manner; in other preferred embodiments, the rows in the microarray are arranged in a staggered manner, wherein the staggered arrangement means that the center lines of the array units at the end of the adjacent rows on the same side cannot form a straight line perpendicular to the row; the center lines of the array units at the end of the alternate rows on the same side form a straight line perpendicular to the row.

[0059] In some optional embodiments, the microarray is arranged in the following manner: the array units are arranged in an S-shape to form an S-shaped subarray across the cross section of the microfluidic channel, and a plurality of the S-shaped subarrays are arranged in parallel to form a microarray perpendicular to the liquid flow direction. In some preferred embodiments, the rows of array units parallel to the liquid flow direction are also parallel to each other; in other preferred embodiments, a plurality of the S-shaped subarrays are arranged in a staggered manner, wherein the staggered arrangement means that the center line of the array units at the end of the adjacent S-shaped subarrays on the same side is not parallel to the liquid flow direction; the center line of the array units at the end of the adjacent S-shaped subarrays on the same side is parallel to the liquid flow direction.

[0060] In some optional embodiments, the microarray is arranged as follows: a number of the array units are arranged into subarrays, and the subarrays are arranged in columns; the subarray is preferably composed of a number of the array units arranged into a U-shaped subarray, and the U-shaped subarray is arranged in columns to form a microarray. Optionally, the bottom of the U-shaped subarray is set at a position away from the microfluidic inlet, or at a position away from the microfluidic outlet, or can be randomly distributed.

[0061] In some optional embodiments, the microarray is arranged in the following manner: the array units are discretely distributed on the microchannel surface, and the discrete distribution means that the connecting lines of the array units in adjacent rows are not parallel to the liquid flow direction. Preferably, the array is discretely arranged in the following manner: the array units form a plurality of mutually parallel rows, and the connecting line of the center lines of any two array units in two adjacent rows is not parallel to the liquid flow direction.

[0062] It should be noted that the “direction of liquid flow” mentioned above refers to the direction of liquid flow when the liquid does not flow through the flow controller in the microchannel.

[0063] In some optional embodiments, the shapes of the liquid-repellent layer or the liquid-philic layer serving as the array unit are independent of each other, for example, may be but not limited to at least one of a circle, a regular polygon and an irregular polygon; in some preferred embodiments, the shapes include rectangles, circles, diamonds or triangles, wherein the array units constituting the microarray are preferably composed of array units of the same shape and area, and further preferably, the scale of each array unit is 50 to 500 μm, for example, may be but not limited to 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm or 500 μm.

[0064] It should be noted that the microfluidic chip provided by the present invention is provided with at least one flow controller, and the flow controller can be a deceleration flow controller or an acceleration flow controller. Optionally, one or more deceleration flow controllers can be provided in the microchannel of the microfluidic chip to slow down the flow of the liquid in the sample to be tested, for example, it can be used to make the sample to be tested react more fully in the reaction area of ​​the microchannel; Optionally, one or more acceleration flow controllers can be provided in the microchannel of the microfluidic chip to increase the flow of the liquid in the sample to be tested, for example, to make the sample to be tested quickly discharged from the microchannel or a functional area. Optionally, an acceleration flow controller or a deceleration flow controller can also be provided at intervals in the microchannel to meet the needs of a specific reaction environment.

[0065] In some preferred embodiments, the microfluidic chip further comprises a reaction module, and the sample to be tested first flows through at least one deceleration flow controller, then flows through the reaction module, and then flows through at least one acceleration flow controller. When the sample to be tested enters the microchannel, the flow rate is first slowed down by at least one deceleration flow controller to increase the retention time of the sample in the reaction module, thereby making the reaction more complete; after the reaction is completed, the sample to be tested flows through at least one acceleration flow controller to avoid the sample to be tested from being retained in the microchannel.

[0066] The beneficial effects of the present invention are further described below in conjunction with the preferred embodiments:

[0067] Example 1

[0068] The microfluidic chip provided in this embodiment is a POCT immunoassay chip. POCT (Point-of-care testing) is also known as on-site testing or immediate testing. POCT is defined as a clinical test performed by clinical personnel who have not received clinical laboratory science training or by the patient themselves (self-testing) close to the patient's treatment site. POCT is based on traditional laboratory medicine and is all rapid tests and clinical applications performed outside traditional, core or central laboratories.

[0069] The POCT immunoassay chip is provided with a sample loading port 3, a microfluidic channel 6 and a waste liquid bin 10 in sequence; a fluorescence module 4, a deceleration flow controller 5, a reaction module 7, a quality control module 8 and an acceleration flow controller 9 are arranged in sequence on the microfluidic channel 6 from the position close to the sample loading module; the deceleration flow controller 5 is arranged into a microarray by a liquid-repelling array unit 501; the acceleration flow controller 9 is arranged into a microarray by a liquid-loving array unit 901. The POCT immunoassay chip is formed by bonding a chip upper plate 1 and a chip lower plate 2. The material of the chip upper plate 1 and the chip lower plate 2 is polystyrene (PS), which is made by an injection molding process. The upper wall surface of the microfluidic channel 6 is formed by the chip upper plate 1, and the side wall surface and the lower wall surface of the microfluidic channel 6 are both formed by the chip lower plate 2. The formed microfluidic channel 6 has a height of 100 μm, a width of 4 mm, and a length of 80 mm.

[0070] After the chip upper plate 1 and the chip lower plate 2 were ultrasonically cleaned with ethanol and deionized water respectively, the surface was activated by plasma, and oxygen plasma was treated (process parameters were 150w, 100pa, 100s), and then the amino groups were grafted by soaking in APTES solution for 30min, APTES: ethanol = 1:40 (volume ratio), washed, and dried at 80 degrees for 30min, and a lyophilic microfluidic channel 6 with a surface contact angle of 75° was obtained. The contact angle of the blood sample on the surface of the chip upper plate 1 and the chip lower plate 2 was 75°.

[0071] The deceleration flow controller 5 is located behind the fluorescent module 4 and is used for deceleration and mixing control of the blood sample. A mixed solution of 0.5% sodium fatty acid and 70% ethanol is sprayed onto the surface of the microchannel 6 by an ultra-micro jet spotter, and a lyophobic array unit 501 is formed after solidification. The contact angle between the lyophobic array unit 501 and the blood sample is 120° to 150°. Each lyophobic array unit 501 is a circular lyophobic layer with a diameter of 200 μm, and the thickness is negligible relative to the height of the microchannel 6.

[0072] The microarray of the deceleration flow controller 5 is composed of a liquid-repellent array unit 501 as follows: Figure 2 The arrangement method shown in the figure is that the microarray is composed of 7 parallel rows composed of 77 lyophobic array units 501, and the rows are arranged alternately. Each row is distributed with 11 lyophobic array units 501, and the distance between the centers of two adjacent lyophobic array units 501 in the same row is 350μm; the distance between the centers of two adjacent lyophobic array units 501 in two adjacent rows is 700μm. An S-shaped flow space is constructed by the lyophobic array units 501, such as Figure 3 As shown, the flow path of the liquid is constrained, and the flow resistance of the meniscus of capillary flow is increased.

[0073] When the blood sample flows through the deceleration flow controller 5, the contact angle of the microarray suddenly increases, forming a flow resistance, thereby hindering the flow. After the sample flows through the deceleration flow controller 5, since the flow channel is filled with the sample, it will not continue to hinder the flow and will not affect the flow rate in the subsequent flow channel. The deceleration flow controller 5 will also mix the antigens and antibodies in the blood sample flowing through here. And the detected substance will not be retained or deposited when passing through this area. The deceleration flow controller 5 can slow down the flow rate of the sample by 80% (7.83mm / s→1.56mm / s).

[0074] The accelerating flow controller 9 for increasing speed is located before the waste liquid bin 10 and is used for accelerating control of the blood sample to ensure that the sample does not accumulate and stop before the waste liquid bin 10. A 1% glycoprotein solution is sprayed onto the surface of the microchannel 6 by an ultra-micro jet spotter, and after solidification, a lyophilic array unit 901 is formed. The contact angle between the lyophilic array unit 901 and the blood sample is 15° to 60°. Each lyophilic array unit 901 is a circular lyophilic layer with a diameter of 200 μm, and the thickness is negligible relative to the height of the microchannel 6.

[0075] The microarray of the accelerating flow controller 9 is arranged by the lyophilic array unit 901 in the following manner: Figure 4As shown. The lyophilic array units 901 are arranged in an S-shape to form an S-shaped subarray 910 that spans the cross section of the microfluidic channel 6. Each S-shaped subarray 910 is composed of 11 lyophilic array units 901, and the microarray contains a total of 8 S-shaped subarrays 910. In the same S-shaped subarray 910, the distance between the centers of two adjacent lyophilic array units 901 is 300 μm. The distance between the centers of the two lyophilic array units 901 with the closest center distance in adjacent S-shaped subarrays 910 is 500 μm. Several of the S-shaped subarrays 910 are arranged in parallel perpendicular to the liquid flow direction to form a microarray, and the columns of the lyophilic array units 901 parallel to the liquid flow direction are also parallel to each other.

[0076] When the blood sample flows through the accelerating flow controller 9, due to the presence of the evenly arranged lyophilic array units 901, the sample will preferentially enter the microarray for flow, and because the contact angle at this location is reduced, the driving force (surface tension, capillary force) during the blood sample flow at the microarray increases, thereby increasing the flow rate of the blood sample in the microchannel 6. The S-shaped arrangement of the lyophilic array units 901 here avoids the blood sample from staying and aggregating in the channel, ensuring the flow rate of the subsequent liquid, and the accelerating flow controller 9 can increase the flow rate of the sample by 217% (2.43 mm / s→7.70 mm / s).

[0077] Among them, the fluorescent module 4 is coated with antibodies coated with markers, and the quality control module 8 is coated with antibodies against the antibodies coated with the fluorescent module 4; the collected blood sample flows through the fluorescent module 4 from the injection port 3, and the antigens carried by the blood sample are labeled with antibodies with markers, and flow into the deceleration flow controller 5 after reaction and mixing. When the blood sample flows through the deceleration flow controller 5, the flow resistance will be formed due to the sudden increase in the contact angle of the microarray, thereby hindering the flow; at the same time, the mixing of antigens and antibodies in the blood sample flowing through here is promoted, and the deceleration flow controller 5 can slow down the flow rate of the sample by 80%. The decelerated blood sample can be fully mixed in the reaction module 7, and then flow through the quality control module 8 to detect whether the test is effective. Before the blood sample flows to the waste liquid bin 10, the blood sample first flows through the acceleration flow controller 9 to accelerate the blood sample to ensure that the blood will not stay at the entrance of the waste liquid bin and affect the detection.

[0078] The microfluidic chip provided in this embodiment drives the surface tension of the liquid to be tested in the microchannel 6, and changes the speed of the sample to be tested in the microchannel 6 by the liquid-repelling and liquid-philic microarrays set in the microchannel 6. By slowing down the flow speed of the liquid or increasing the flow time, it can be ensured that the sample can be fully mixed, incubated and reacted with the reaction reagent in the microfluidic chip. By increasing the flow speed of the liquid, the sample can be prevented from being retained in the reaction module 7, thereby improving the sensitivity and accuracy of POCT detection. In addition, the above-mentioned microfluidic chip does not need to provide an external driving device, is small in size, low in cost, and can meet the needs of POCT.

[0079] Example 2

[0080] The microfluidic chip provided in this embodiment is a POCT immune detection chip. The difference from Embodiment 1 is that the arrangement of the microarrays in the deceleration flow controller 5 and the acceleration flow controller 9 is different. In this embodiment, the arrangement of the microarrays in the deceleration flow controller 5 and the acceleration flow controller 9 is the same. The arrangement of the microarrays in the deceleration flow controller 5 is taken as an example below:

[0081] The microarray of the deceleration flow controller 5 is composed of a liquid-repellent array unit 501 as follows: Figure 5 The arrangement method shown in the figure has a total of 84 lyophobic array units 501. The lyophobic array units 501 are arranged into a U-shaped sub-array 520, and each U-shaped sub-array 520 is composed of 7 lyophobic array units 501, wherein three lyophobic array units 501 are arranged at the bottom of the U-shaped sub-array 520 and perpendicular to the liquid flow direction, and the distance between the centers of two adjacent lyophobic array units 501 is 300μm; two lyophobic array units 501 are arranged at the two side walls of the U-shaped sub-array 520 and parallel to the liquid flow direction, and the distance between the centers of two adjacent lyophobic array units 501 is 300μm. The bottom of the U-shaped sub-array 520 is farther away from the sample injection port 3 than the top of the U-shaped sub-array 520.

[0082] The microarray of the deceleration flow controller 5 has 12 U-shaped sub-arrays 520 distributed in columns and rows. In the flow direction perpendicular to the sample, each row is provided with 3 rows of evenly distributed U-shaped sub-arrays 520, and the distance between each adjacent U-shaped sub-array 520 is 500 μm; in the direction parallel to the sample flow, 4 columns of U-shaped sub-arrays 520 are provided, and the center distance between adjacent U-shaped sub-arrays 520 in each column is 800 μm.

[0083] When the liquid sample flows through the deceleration flow controller 5, due to the presence of the microarray formed by the lyophobic array units, the liquid sample will preferentially seek a path with a smaller contact angle to flow through here, thereby increasing the flow path of the capillary flow and reducing the flow speed of the liquid in the microchannel when it flows through this area. The deceleration flow controller 5 of this embodiment slows down the flow speed of the sample by 52% (7.83mm / s→3.75mm / s).

[0084] When the liquid sample flows through the accelerating flow controller 9, due to the presence of the evenly arranged lyophilic array units 901, the sample will preferentially enter the microarray for flow, and the contact angle at this location is reduced, resulting in an increase in the driving force (surface tension, capillary force) during the flow of the liquid sample at the microarray, thereby increasing the flow rate of the liquid sample in the microchannel 6. The S-shaped arrangement of the lyophilic array units 901 here avoids the liquid sample from staying and aggregating in the channel, ensuring the subsequent flow rate of the liquid, and the accelerating flow controller 9 can increase the flow rate of the sample by 68% (2.43 mm / s→4.08 mm / s).

[0085] Example 3

[0086] The microfluidic chip provided in this embodiment is a POCT immune detection chip. The difference from Example 2 is that the arrangement of the microarrays in the deceleration flow controller 5 and the acceleration flow controller 9 is different. In this embodiment, the arrangement of the microarrays in the deceleration flow controller 5 and the acceleration flow controller 9 is the same. The arrangement of the microarray in the deceleration flow controller 5 is taken as an example below: the bottom of the U-shaped subarray 520 in the deceleration flow controller 5 is farther away from the waste liquid bin 10 than the top of the U-shaped subarray 520, such as Figure 6 As shown, the deceleration flow controller 5 can reduce the flow velocity of the sample by 36% (7.83 mm / s→5.01 mm / s). The acceleration flow controller 9 can increase the flow velocity of the sample by 83% (2.43 mm / s→4.45 mm / s).

[0087] Example 4

[0088] The microfluidic chip provided in this embodiment is a POCT immune detection chip. The difference from Embodiment 1 is that the arrangement of the microarrays in the deceleration flow controller 5 and the acceleration flow controller 9 is different. In this embodiment, the arrangement of the microarrays in the deceleration flow controller 5 and the acceleration flow controller 9 is the same. The arrangement of the microarrays in the deceleration flow controller 5 is taken as an example below:

[0089] The microarray of the deceleration flow controller 5 is composed of a liquid-repellent array unit 501 as follows: Figure 7The arrangement method shown is a discrete arrangement. The microarray in the deceleration flow controller 5 is composed of 11 parallel rows consisting of 82 lyophobic array units 501, the rows are perpendicular to the liquid flow direction, the row spacing is 500μm, and the distance between the centers of adjacent lyophobic array units 501 in the same row is 450μm; the odd rows are composed of 7 lyophobic array units 501, and the even rows are composed of 8 lyophobic array units 501; the lyophobic array units 501 in two adjacent rows are evenly staggered, that is, the center line of any two lyophobic array units 501 closest to each other in adjacent rows is not parallel to the liquid flow direction, and the center line of any two lyophobic array units 501 closest to each other in the alternate rows is parallel to the liquid flow direction.

[0090] When the liquid sample flows through the discretely arranged microarray, it will preferentially seek a path with a smaller contact angle to flow, thereby increasing the flow path of the capillary flow, thereby reducing the flow speed of the liquid in the microchannel 6 when it flows through this area. The deceleration flow controller 5 can reduce the flow speed of the sample by 68% (7.83 mm / s→2.46 mm / s).

[0091] The arrangement of the microarray in the accelerating flow controller 9 in the microfluidic channel 6 of this embodiment is the same as the arrangement of the microarray in the decelerating flow controller 5. When the liquid sample flows through this discretely arranged microarray, the liquid sample will preferentially seek a path with a smaller contact angle to flow when flowing through here, thereby reducing the flow path of the capillary flow, thereby reducing the flow speed of the liquid in the microfluidic channel 6 when flowing through this area. The accelerating flow controller 9 can increase the flow speed of the sample by 158% (2.43mm / s→6.27mm / s).

[0092] Example 5

[0093] The microfluidic chip provided in this embodiment is a POCT immune detection chip. The difference from Embodiment 1 is that the arrangement of the microarrays in the deceleration flow controller 5 and the acceleration flow controller 9 is different. In this embodiment, the arrangement of the microarrays in the deceleration flow controller 5 and the acceleration flow controller 9 is the same. The arrangement of the microarrays in the deceleration flow controller 5 is taken as an example below:

[0094] The microarray of the deceleration flow controller 5 is arranged by the lyophobic array unit 501 in the following manner: Figure 8As shown. The lyophobic array units 501 are arranged in an S-shape to form an S-shaped subarray 910 that spans the cross section of the microfluidic channel 6. Each S-shaped subarray 910 is composed of 12 lyophilic array units 901, and the microarray contains a total of 6 S-shaped subarrays 910. The center distance between two adjacent lyophobic array units 501 in the same S-shaped subarray is 300 μm. Adjacent S-shaped subarrays 910 are arranged in a staggered manner. The staggered arrangement means that the center line connection of the array units at the end of the adjacent S-shaped subarrays 910 on the same side is not parallel to the liquid flow direction; the center line connection of the array units at the end of the spaced S-shaped subarrays 910 on the same side is parallel to the liquid flow direction.

[0095] An S-shaped flow space is constructed by the spaced S-shaped sub-arrays 910. When the liquid sample flows through the microarray formed by the S-shaped staggered arrangement of the lyophobic array units 501, it will preferentially flow through the area with a smaller contact angle, thereby flowing in the S-shaped flow space formed by the S-shaped sub-arrays 910, increasing the flow length of the liquid sample, thereby reducing the flow speed of the liquid in the microchannel when it flows through this area. The deceleration flow controller 5 can slow down the flow speed of the sample by 70% (7.83mm / s→2.31mm / s). The acceleration flow controller 9 can increase the flow speed of the sample by 57% (2.43mm / s→3.82mm / s).

[0096] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A microfluidic chip for realizing flow control based on a lyophilic and / or lyophobic microarray, wherein the contact angle between the microchannel of the microfluidic chip and the liquid in the sample to be tested is θ0, and θ0 < 90°; a deceleration flow controller and an acceleration flow controller are arranged on the microchannel; The flow controller comprises a microarray formed by arranging a plurality of array units; the array unit is a liquid-repellent layer or a liquid-philic layer with a shape arranged on the surface of the microchannel; The deceleration flow controller comprises a microarray formed by arranging a plurality of lyophobic array units, wherein the lyophobic array unit is a lyophobic layer with a shape arranged on the surface of the microchannel, and the contact angle θ of the lyophobic array unit relative to the liquid in the sample to be tested is s >θ0; The microarray of the deceleration flow controller is arranged as follows: The array units are arranged in an S-shape to form an S-shaped subarray across the cross section of the microfluidic channel, and a plurality of the S-shaped subarrays are arranged in parallel perpendicular to the liquid flow direction to form a microarray, and a plurality of the S-shaped subarrays are arranged in a staggered manner; Or, the connecting lines of the array units in adjacent rows are not parallel to the liquid flow direction, and the connecting line between the centers of any two closest array units in the alternate row is parallel to the liquid flow direction; The accelerating flow controller comprises a microarray composed of a plurality of lyophilic array units, wherein the lyophilic array unit is a lyophilic layer with a shape arranged on the surface of the microchannel, and the contact angle θ of the lyophilic array unit relative to the liquid in the sample to be tested is q <θ0; The microarray of the accelerating flow controller is arranged in the following manner: the array units are arranged in an S-shape to form an S-shaped subarray spanning the cross section of the microchannel; a plurality of the S-shaped subarrays are arranged in parallel perpendicular to the liquid flow direction to form a microarray, and the rows of the array units parallel to the liquid flow direction are also parallel to each other; The shape and area of ​​each array unit in the microarray are the same, and the scale of the array unit is 50-500 μm.

2. The microfluidic chip according to claim 1, characterized in that: The shapes of the liquid-repellent layer and the liquid-philic layer are independently rectangular, circular, diamond or triangular.

3. The microfluidic chip according to claim 1 or 2, characterized in that: The microfluidic chip also includes a reaction module. The sample to be detected first flows through at least one deceleration flow controller, then flows through the reaction module, and then flows through at least one acceleration flow controller.

4. The microfluidic chip according to claim 1 or 2, characterized in that: The microfluidic chip is used for POCT immunoassay; the microfluidic chip is provided with a sample addition port, a microchannel and a waste liquid bin in sequence from the liquid flow direction; The sample to be tested flows from the microfluidic channel sequentially through the fluorescence module, the deceleration flow controller, the reaction module, the quality control module and the acceleration flow controller.

5. The microfluidic chip according to claim 1 or 2, characterized in that: The microchannel is treated with lyophilicity to make the contact angle θ0 of the microchannel less than 90°; the microchannel is mainly made of the following materials: styrene, polyethylene, polypropylene, polycarbonate, acrylonitrile-butadiene-styrene copolymer, polymethacrylate, polydimethylsiloxane, silicon, quartz or glass.

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