Microfluidic Chip Facilitating Bubble Elimination

Abstract

The present invention discloses a microfluidic chip conducive to eliminating bubbles, which comprises a microfluidic chip body. The microfluidic chip body is composed of an upper substrate and a lower substrate which are arranged at intervals up and down. A microchannel for droplet movement is formed between the upper and lower substrates. An exhaust hole for discharging bubbles in the microchannel is opened on the upper substrate. The present invention adopts the method of opening exhaust holes at one side or / and both sides of the upper substrate of the microfluidic chip corresponding to the microchannel. Therefore, when bubbles are generated or encountered during the process of manipulating droplets to move along the microchannel by electro-wetting, with the movement of the droplets, the bubbles will be pushed to the side of the microchannel and come into contact with the exhaust holes in time, and then be discharged into the atmosphere. At the same time, the exhaust holes also have the function of pressure balance, which is beneficial to the injection of filling medium or droplets. The structure of this microfluidic chip is simple, without the need for additional installation of a bubble elimination device, nor the addition of chemical reagents, with low cost and good bubble elimination effect.

Description

Technical Field

[0001] The invention relates to a microfluidic chip, in particular to a microfluidic chip which is beneficial to eliminating bubbles. Background Art

[0002] Digital microfluidics is a technology that uses electrical signals on a chip to precisely control the movement of micro-amounts of liquid through an electrode array. Droplets are distributed, moved, stored, mixed, reacted or analyzed on a platform with a set of insulating electrodes. In digital microfluidics systems, electrowetting is a phenomenon in which the wettability of droplets on the substrate is changed by changing the voltage between the droplet and the insulating substrate, that is, changing the contact angle, causing the droplet to deform and displace. Compared with traditional microfluidics, digital microfluidics has the characteristics of low sample consumption, simple operation, strong parallel capability and high degree of automation. At the same time, it does not rely on components such as micropumps, microvalves or micromixers. Therefore, it is particularly suitable for highly integrated, high-performance and complex micro-analysis systems such as biology, chemistry and detection. However, in the process of electrowetting manipulation, the problem of bubbles has become a major obstacle to the movement of droplets. The sources of bubbles in the electrowetting system are mainly the following: (1) Bubbles dissolved in the filling medium or droplets, that is, some gases such as oxygen and carbon dioxide are often dissolved in the filling medium and droplets used for experiments or manipulation. (2) Bubbles introduced when adding medium or droplets to the microfluidic device, that is, when starting the microfluidic operation, the filling medium or droplets need to be injected into the microfluidic device. During this process, air will be injected into the microfluidic device along with the fluid due to manual operation; in addition, even if the filling medium completely fills the microfluidic device, air will remain in the corners of the device. (3) Bubbles generated by electrolysis during droplet driving, that is, during the electrowetting driving process of the droplets, some electrode blocks will leak electricity, resulting in bubbles generated by droplet electrolysis. (4) Bubbles generated by heating during high-temperature experiments and the expansion of bubbles, that is, when conducting high-temperature experiments or operations, bubbles or extremely small bubbles dissolved in the filling medium or droplets will expand due to heat and then escape to generate bubbles.

[0003] On digital microfluidic chips, droplets move in a directional manner along a predetermined channel path. If bubbles move or expand / contract on the microfluidic chip, or get stuck at a certain position in the driving path, it will hinder the manipulation of the droplets and destroy the stability of the drive. In severe cases, it may also damage the modified properties or coating structure of the upper and lower plate surfaces of the microfluidic chip. In addition, when performing photochemical detection on droplets, the presence of bubbles will also cause great interference to the detection results.

[0004] At present, there are mainly the following methods to eliminate bubbles:

[0005] 1. Physical defoaming method: Bubbles are broken by changing the viscosity or physical properties of the bubbles. Common methods include thermal method, ultrasonic method, electric method, vacuum method, etc. Although these methods do not change the chemical composition or properties of the filling medium or the droplets themselves, they require special equipment, with high usage and maintenance costs, and cannot handle a large number of bubbles. They are only applicable to certain emergency measures.

[0006] 2. Mechanical defoaming method: Compress or apply impact force to the bubbles, and use the sudden change of pressure such as shear force, compression force and impact force to break the bubbles to achieve the purpose of defoaming. According to its characteristics of acting on the bubbles, it is further divided into centrifugal method, compression method and impact method, etc. This type of method requires additional defoaming devices, with complex processes and high costs.

[0007] 3. Chemical defoaming method: The chemical defoaming method is to add chemical agents such as defoamers to the medium or reagent to change some properties of the medium or reagent to achieve the purpose of defoaming. The chemical defoaming method is convenient to use, has a high defoaming rate, and does not require special equipment. However, the defoamer may change the performance of the filling medium or the droplets themselves, damage the system composition and even cause secondary pollution.

[0008] 4. Natural defoaming method: The natural defoaming method is caused by the liquid film between the bubbles seeping along the oil-water interface, the gas diffusion between the bubbles and the rupture of some single bubble films. Dehydration shrinkage is the basic process of bubble rupture, which occurs under the action of gravity. The result of this action process is to gradually thin the liquid film of the bubbles, thereby causing the bubbles to rupture and achieve defoaming; this method takes a long time and has low efficiency for defoaming.

[0009] Chinese Patent No. CN102373153B discloses a bubble removal device for a microfluidic channel. In this device, a cavity is provided at the liquid inlet of the microfluidic channel for buffering the liquid and capturing bubbles; an air bubble drainage bypass is connected to the upper opening of the cavity for discharging the bubbles captured by the cavity. The device has a simple structure, is easy to manufacture, has no influence on the normal liquid flow in the microfluidic channel, and has a high bubble removal efficiency. However, the use conditions of this device are limited, and it can only remove the bubbles introduced during the input of the reagent. It is still not easy to remove the bubbles in a complex system or in the microfluidic channel. Chinese Patent No. CN205761221U discloses a disc-shaped microfluidic chip with a bubble removal function. The chip includes a card slot and a detection unit. The detection unit includes a sample inlet, a sample pool, a vent, a reaction pool and a detection pool. The reaction pool is connected to the vent. The reagent is pre-fixed at a specific position in the chip, and then the liquid to be detected is added into the chip through the sample inlet for reaction. The bubbles generated during the reaction enter the detection pool through centrifugation and are all discharged through the vent. This method does not interfere with the photometric detection. However, this method is complex in design and processing and is only applicable to reactions with bubble generation. Summary of the Invention

[0010] The object of the present invention is to provide a microfluidic chip that is conducive to eliminating bubbles and ensure the stable movement of droplets on the microfluidic chip.

[0011] To achieve the above object, the present invention can adopt the following technical solutions:

[0012] The microfluidic chip that is conducive to eliminating bubbles according to the present invention includes a microfluidic chip body, which is composed of an upper substrate and a lower substrate arranged at intervals up and down. A microchannel for droplet movement is formed between the upper and lower substrates; an exhaust hole for discharging bubbles in the microchannel is opened on the upper substrate.

[0013] Optionally, there are multiple exhaust holes, which are respectively opened at one side or / and both sides of the upper substrate corresponding to the microchannel.

[0014] Optionally, the horizontal distance from the exhaust hole to the electrode on the side close to the electrode is 0.1 - 2 mm.

[0015] Optionally, the cross-section of the exhaust hole is circular, oval, rectangular, polygonal or strip-shaped.

[0016] Optionally, the longitudinal section of the exhaust hole is rectangular, regular frustum-shaped, inverted frustum-shaped, or a combined shape of frustum-shaped and rectangular.

[0017] Optionally, a layer of breathable filter membrane is attached to the upper orifice of the exhaust hole for free gas exchange and to avoid external contamination.

[0018] Optionally, the diameter of the exhaust hole ≥ 1 / 3 of the height of the fluid channel, which is more conducive to the discharge of bubbles.

[0019] Optionally, the upper substrate is composed of an upper insulating substrate, a common electrode, and an upper hydrophobic layer stacked in sequence from top to bottom; the lower substrate is composed of a lower insulating substrate, a driving electrode array, a dielectric layer, and a lower hydrophobic layer stacked in sequence from bottom to top; the driving electrode array is composed of multiple electrodes arranged along the set microchannel for driving the droplet to move along the microchannel under electro-wetting operation.

[0020] The present invention adopts the method of opening exhaust holes at one side or / and both sides of the upper substrate of the microfluidic chip corresponding to the microchannel. Therefore, during the process of electro-wetting to drive the droplet to move along the microchannel, if bubbles are generated or encountered, as the droplet moves, the bubbles will be pushed to the side of the microchannel and come into contact with the exhaust holes in time, and then be discharged into the atmosphere. At the same time, the exhaust holes also have the function of pressure balance, which is conducive to the injection of filling medium or droplets. The structure of this microfluidic chip is simple, does not require additional installation of a bubble elimination device, nor the addition of chemical reagents, has low cost, and good bubble elimination effect. Description of the Drawings

[0021] Figure 1 It is a schematic structural diagram of the microfluidic chip body described in Embodiment 1 of the present invention.

[0022] Figure 2 It is a schematic layout diagram of the relative positional relationship between the driving electrode array and the exhaust hole described in Embodiment 1.

[0023] Figure 3 It is a schematic structural diagram of the upper substrate described in Embodiment 1.

[0024] Figure 4 It is a schematic layout diagram of the relative positional relationship between the driving electrode array, the heating area and the exhaust hole described in Embodiment 2.

[0025] Figure 5 It is a schematic structural diagram of the upper substrate described in Embodiment 2.

[0026] Figure 6 It is a schematic structural diagram of the exhaust hole with a rectangular longitudinal section according to the present invention.

[0027] Figure 7 It is a schematic structural diagram of the exhaust hole with a waterproof and breathable filter membrane attached to the upper orifice according to the present invention.

[0028] Figure 8 It is a schematic structural diagram of the exhaust hole with a frustum of a right circular cone longitudinal section according to the present invention.

[0029] Figure 9 It is a schematic structural diagram of the exhaust hole with a rectangular upper part and a frustum of a right circular cone lower part in the longitudinal section according to the present invention.

[0030] Figure 10 It is a schematic structural diagram of the exhaust hole with an inverted frustum of a right circular cone longitudinal section according to the present invention.

[0031] Figure 11 It is a schematic structural diagram of the exhaust hole with an inverted frustum of a right circular cone upper part and a rectangular lower part in the longitudinal section according to the present invention.

[0032] Figure 12 It is a schematic structural diagram of the exhaust hole with an inverted frustum of a right circular cone upper part, a frustum of a right circular cone lower part and a rectangular middle part in the longitudinal section according to the present invention. Detailed implementation manners

[0033] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0034] It should be noted that all the directional indications (such as up, down, left, right, front, back...) in the embodiments of the present invention are only used to explain the relative positional relationship, movement conditions, etc. between components in a specific posture (as shown in the attached drawings). If the specific posture changes, the directional indications will also change accordingly.

[0035] In the present invention, unless otherwise clearly defined and limited, the terms "connection", "fixation", etc. should be understood in a broad sense. For example, "fixation" can be a fixed connection, a detachable connection, or integrated; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two components or the interaction relationship between two components, unless otherwise clearly limited. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific situations.

[0036] In addition, in the present invention, descriptions such as "first", "second", etc. are only for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the quantity of the indicated technical features. Thus, the features defined with "first" and "second" can explicitly or implicitly include at least one of such features.

[0037] In addition, the meaning of "and / or" appearing throughout the text is to include three parallel solutions. Taking "A and / or B" as an example, it includes solution A, or solution B, or a solution that satisfies both A and B simultaneously. In addition, the technical solutions between various embodiments can be combined with each other, but it must be based on the ability of those of ordinary skill in the art to implement. When the combination of technical solutions results in contradictions or cannot be implemented, it should be considered that such a combination of technical solutions does not exist and is not within the protection scope required by the present invention.

[0038] Embodiment 1:

[0039] As Figure 1 shown, the microfluidic chip beneficial to eliminating bubbles according to the present invention includes a microfluidic chip body, which is composed of an upper substrate and a lower substrate arranged at intervals up and down. The opposite surfaces of the upper and lower substrates are both hydrophobic coatings. After the upper and lower substrates are sealed to form a cartridge, a gap is formed between the upper and lower substrates for filling a fluid to form a microchannel 2 for the movement of droplet 1.

[0040] The upper substrate is composed of an upper insulating substrate 3, a common electrode 4, and an upper hydrophobic layer 5 stacked in sequence from top to bottom; among them, the upper insulating substrate 3 and the upper hydrophobic layer 5 are made of transparent materials to facilitate observing the movement state of droplet 1 along the microchannel 2.

[0041] The lower substrate is composed of a lower insulating substrate 6, a driving electrode array 7, a dielectric layer 8, and a lower hydrophobic layer 9 stacked in sequence from bottom to top; the driving electrode array 7 is composed of a plurality of electrodes arranged along the set microchannel 2, and the driving electrode array 7 is used to drive the droplet 1 to move along the microchannel 2 under the electro-wetting operation.

[0042] Advantageously or exemplarily, as Figure 2 , 3 shown, an exhaust hole 10 for exhausting the bubbles in the microchannel 2 is provided on the upper substrate, and the diameter of the exhaust hole 10 ≥ 1 / 3 of the height of the fluid channel, and it is opened at a position with a relatively large gap height of the microchannel 2, which is more conducive to the discharge of bubbles.

[0043] According to the design requirements, a plurality of exhaust holes 10 can be provided, which are respectively arranged on one side or / and both sides of the driving electrode array 7 corresponding to the microchannel 2. The cross-section of each exhaust hole 10 is set to be strip-shaped and arranged along the direction of the microchannel 2, so that during the movement of the droplet 1, the bubbles displaced by the droplet 1 can just contact the exhaust hole 10 and the bubbles can be smoothly exhausted; the horizontal distance between the exhaust hole 10 and the driving electrode array 7 on the side close to the electrode is selected between 0.1 - 2 mm. If the distance is too close, the droplet 1 is likely to get stuck on the edge of the exhaust hole 10, and if it is too far, the effect of timely and effectively exhausting the bubbles cannot be achieved.

[0044] Advantageously or exemplarily, as an embodiment, as Figure 6 , 7 shown, the longitudinal section of the exhaust hole 10 is set to be a rectangular structure, and a breathable filter membrane 11 is attached to the upper orifice of the exhaust hole 10, which is used for both freely exchanging gases and avoiding external pollution.

[0045] Of course, according to the needs, the longitudinal section of the exhaust hole 10 can also be set to be a frustum of a right circular cone structure as shown in Figure 8 , or a structure with a rectangular upper part and a frustum of a right circular cone lower part as shown in Figure 9 .

[0046] According to the needs, the longitudinal section of the exhaust hole 10 can also be set to be an inverted frustum of a right circular cone structure as shown in Figure 10 , or a structure with an inverted frustum of a right circular cone upper part and a rectangular lower part as shown in Figure 11 , or a schematic structural diagram with an inverted frustum of a right circular cone upper part, a frustum of a right circular cone lower part, and a rectangular middle part as shown in Figure 12 .

[0047] Embodiment 2:

[0048] As Figure 4 , 5 shown, the difference between this embodiment and Embodiment 1 is that a heating area 12 is further provided on the microfluidic chip body, and the air hole row 10 is arranged around the heating area 12.

[0049] When the present invention works, the filling medium phase and the droplet 1 are injected into the microfluidic chip body from the sample injection hole. Electrowetting is used to control the droplet 1 to move, separate, merge, mix and other actions on a predetermined path. During the movement of the droplet 1, the bubbles generated or encountered on the moving path will be displaced to the side of the path along with the movement of the droplet 1. There is just a corresponding exhaust hole 10 designed at this position, and the bubbles are directly discharged out of the microfluidic system through the exhaust hole 10.

[0050] The setting of the exhaust hole 10 is more conducive to use in a complex system. For example, in the heating state, the higher the temperature, the faster the generation speed and the larger the number of bubbles. This structure can discharge the bubbles in time when the droplet 1 performs any action.

Claims

1. A microfluidic chip conducive to bubble elimination, comprising a microfluidic chip body, characterized in that: The microfluidic chip body is composed of an upper substrate and a lower substrate which are arranged at intervals up and down. A microchannel for droplet movement is formed between the upper and lower substrates. An exhaust hole for discharging air bubbles in the microchannel is opened on the upper substrate. The upper substrate is composed of an upper insulating substrate, a common electrode, and an upper hydrophobic layer which are stacked in sequence from top to bottom. The lower substrate is composed of a lower insulating substrate, a driving electrode array, a dielectric layer, and a lower hydrophobic layer which are stacked in sequence from bottom to top. The driving electrode array is composed of a plurality of driving electrodes arranged along the set microchannel. There are a plurality of the exhaust holes, which are respectively opened at positions on one side or / and both sides of the upper substrate corresponding to the microchannel. The horizontal distance from the side of the exhaust hole close to the driving electrode to the driving electrode is 0.1-2 mm. The diameter of the exhaust hole is ≥ 1 / 3 of the height of the fluid channel.

2. The microfluidic chip according to claim 1, which is conducive to eliminating bubbles, wherein: The cross-section of the exhaust hole is circular, elliptical, rectangular, polygonal or strip-shaped.

3. The microfluidic chip according to claim 1, which is conducive to eliminating air bubbles, wherein: The longitudinal section of the exhaust hole is rectangular, frustum-shaped, inverted frustum-shaped, or a combined shape of frustum-shaped and rectangular.

4. The microfluidic chip according to claim 1, which is conducive to eliminating bubbles, wherein: A layer of breathable filter membrane is attached to the upper orifice of the exhaust hole.

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