Multi-volume droplet generation chip

Abstract

The present invention discloses a multi-volume micro-droplet generation chip. The multi-volume micro-droplet generation chip comprises an upper plate (1), a droplet generation disk (2) and a lower plate (3); the lower plate is arranged at the bottom of the droplet generation disk, the upper plate is arranged at the top of the droplet generation disk, and an operation port is arranged on the upper plate; an upper conductive layer (12) is arranged on the upper plate, a lower conductive layer (32) is arranged on the lower plate, and a plurality of droplet generation holes (21) are arranged at the inner bottom of the droplet generation disk; when a bias voltage is set between the upper conductive layer and the lower conductive layer, the hydrophobicity of the bottom of the droplet generation hole is less than the hydrophobicity of the top of the droplet generation hole; the apertures of the plurality of droplet generation holes are different. The multi-volume micro-droplet generation chip of the present invention is used to form a plurality of tiny droplets to meet the demand for a plurality of tiny droplets in research and development experiments in the fields of biology, chemistry and pharmaceuticals, without relying on external mechanical equipment, is compact and easy to carry, and has high-throughput generation capability.

Description

Technical Field

[0001] The present invention relates to a microfluidic technology, in particular to a multi-volume micro-droplet generation chip. Background Art

[0002] In some biological, chemical, and pharmaceutical fields, in some R&D experiments, it is often necessary to separate sample liquids into numerous tiny droplets to participate in some micro-reactions or serve as independent microreactors for high-throughput biological analysis, enzyme catalysis, and drug screening. For example, mixing microdroplets containing target DNA with reagents and performing PCR (polymerase chain reaction) amplification can achieve highly sensitive and accurate quantitative analysis, which is used in gene expression analysis, non-invasive prenatal genetic diagnosis, and embryonic genome editing. Multi-volume microdroplets can also be used for chemical synthesis and chemical reactions, providing efficient and rapid reaction space for fields such as chemical organic synthesis and nanomaterials. Microfluidic chips with multi-volume microdroplets can also be used in fields such as cell culture and liquid lenses. In other words, in many fields, there is a need to "separate sample liquids into numerous tiny droplets."

[0003] Currently, there are "digital microfluidic chips for generating multi-volume microdroplets" that can meet the above requirements. The current digital microfluidic chips for generating multi-volume microdroplets are mainly divided into two categories:

[0004] One type relies on external mechanical equipment to generate microdroplets. The equipment complexity of this method greatly limits the high integration and portability of microfluidic chips;

[0005] Another type generates microdroplets through methods such as electrowetting, thermocapillary force, and surface acoustic wave. Although these methods do not rely on external mechanical equipment, they generally suffer from insufficient throughput.

[0006] That is to say, existing technical equipment has various problems to a greater or lesser extent and is not very effective. Summary of the Invention

[0007] The purpose of the present invention is to provide a multi-volume micro-droplet generation chip, which is used to form a large number of micro-droplets to meet the needs of research and development experiments in the fields of biology, chemistry, and pharmaceuticals for a large number of micro-droplets.

[0008] In order to achieve the above technical objectives, the present invention adopts the following technical solutions:

[0009] A multi-volume micro-droplet generation chip comprises an upper plate, a droplet generation disk, and a lower plate; the lower plate is arranged at the bottom of the droplet generation disk, the upper plate is arranged at the top of the droplet generation disk, and the upper plate is provided with an operation port; the upper plate is provided with an upper conductive layer, the lower plate is provided with a lower conductive layer, and the inner bottom of the droplet generation disk is provided with a plurality of droplet generation holes; when a bias voltage is set between the upper conductive layer and the lower conductive layer, the hydrophobicity of the bottom of the droplet generation hole is less than the hydrophobicity of the top of the droplet generation hole.

[0010] Furthermore, the plurality of droplet generation holes have different pore sizes.

[0011] Furthermore, the operation ports provided on the upper plate include an inlet and an outlet.

[0012] Furthermore, a hydrophobic layer is provided on the surface of the upper electrode plate adjacent to the droplet generation disk.

[0013] Furthermore, the upper plate uses quartz glass as a substrate, and the lower plate uses quartz glass as a substrate.

[0014] Compared with the prior art, the multi-volume micro-droplet generation chip of the present invention has the following advantages:

[0015] The multi-volume micro-droplet generation chip of the present invention is based on a droplet generation disk. Upper and lower conductive layers are disposed above and below the droplet generation disk, respectively. Numerous droplet generation holes are located on the inner bottom of the droplet generation disk. Applying a bias voltage between the upper and lower conductive layers allows sample liquid within the droplet generation disk to enter the droplet generation holes, forming numerous tiny droplets. This meets the demand for numerous tiny droplets in R&D experiments in the biological, chemical, and pharmaceutical fields. Compared to existing technologies and equipment for generating small droplets, the multi-volume micro-droplet generation chip of the present invention does not require external mechanical equipment. Furthermore, it is compact and portable, and has high-throughput generation capabilities. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a schematic structural diagram of the multi-volume micro-droplet generation chip of the present invention;

[0017] Figure 2 This is a cross-sectional view of the multi-volume microdroplet generation chip of the present invention. DETAILED DESCRIPTION

[0018] The present invention will be further described below with specific embodiments:

[0019] This embodiment provides a multi-volume micro-droplet generation chip for separating numerous tiny droplets of different sizes from a sample liquid to meet the needs of R&D experiments in the fields of biology, chemistry, and pharmaceuticals.

[0020] It should be noted that the sample liquid mentioned in this article refers to the aqueous solution containing DNA used in biological product research and development experiments.

[0021] See also Figure 1 The multi-volume micro-droplet generation chip of this embodiment is like a flat micro-container as a whole. The upper surface of the micro-container has two through holes, which are transparent to the interior of the micro-container.

[0022] Specifically,

[0023] The multi-volume micro-droplet generation chip is mainly composed of three parts: an upper electrode plate 1, a droplet generation disk 2 and a lower electrode plate 3.

[0024] The lower electrode plate 3 is located at the bottom of the entire multi-volume micro-droplet generation chip. On the one hand, the lower electrode plate 3 serves as the bottom foundation of the entire multi-volume micro-droplet generation chip. On the other hand, the lower electrode plate 3 is also used to set the lower conductive layer (described in detail later).

[0025] The upper electrode plate 1 is located at the top of the entire multi-volume micro-droplet generation chip. On the one hand, the upper electrode plate 1 is used to cover the droplet generation disk 2. On the other hand, the upper electrode plate 1 is also used to set the upper conductive layer (detailed introduction will be given later).

[0026] The droplet generation disk 2 is the main part of the entire multi-volume micro-droplet generation chip, and is located in the middle of the entire multi-volume micro-droplet generation chip, specifically, between the upper electrode plate 1 and the lower electrode plate 3.

[0027] In summary, the entire multi-volume micro-droplet generation chip is based on the droplet generation disk 2. Then, a lower electrode plate 3 is set at the bottom of the droplet generation disk 2, and an upper electrode plate 1 is set on the top of the droplet generation disk 2, thus forming the entire multi-volume micro-droplet generation chip.

[0028] See also Figure 2 The droplet generation tray 2 is the main component of the multi-volume micro-droplet generation chip. It is essentially a flat container with an open top. The inner bottom of the droplet generation tray 2 is provided with numerous small countersunk holes, which are referred to as "droplet generation holes" for ease of description. These droplet generation holes 21 have varying diameters to meet the varying droplet size requirements of various experiments, thereby achieving multi-volume droplets.

[0029] For the convenience of description, the internal space of the droplet generation plate 2 is divided into two parts. Specifically, the area occupied by all the droplet generation holes 21 inside the droplet generation plate 2 is called the liquid separation area, which is actually the inner bottom area of ​​the droplet generation plate 2; the area from top to bottom inside the droplet generation plate 2 is called the liquid storage area, which can also be understood as "all other upper area spaces inside the droplet generation plate 2 except the liquid separation area."

[0030] The upper electrode plate 1 covers the top of the droplet generation disk 2 to seal the droplet generation disk 2 (the upper electrode plate also has the function of "achieving electrowetting", which will be described in detail later).

[0031] Two through-holes are provided on the upper plate 1, which are referred to as the "two through-holes on the upper surface of the microcontainer" mentioned previously. For ease of description, these two through-holes are defined as a sample inlet 14 and a sample outlet 15, respectively. The function of the sample inlet 14 is to inject sample liquid into the droplet generation disk 2. The function of the sample outlet 15 is to remove excess sample liquid from the droplet generation disk 2 after droplet generation is completed.

[0032] The sample inlet 14 and the sample outlet 15 are collectively referred to as an operation port. In other embodiments, one operation port may be used to simultaneously realize the functions of the sample inlet 14 and the sample outlet 15 .

[0033] The lower electrode plate 3 is provided at the bottom of the droplet generation disk 2 as a bottom foundation, thereby being able to support the overall structure of the multi-volume micro-droplet generation chip.

[0034] The upper electrode plate 1 is provided with an upper conductive layer 12, and the lower electrode plate 3 is provided with a lower conductive layer 32. Specifically, the upper conductive layer 12 is provided on the side of the upper electrode plate 1 adjacent to the droplet generation disk 2, that is, on the lower side of the upper electrode plate 1; the lower conductive layer 32 is provided on the side of the lower electrode plate 3 adjacent to the droplet generation disk 2, that is, on the upper side of the lower electrode plate 3.

[0035] Taking the droplet generation tray 2 as a reference, the upper conductive layer 12 is disposed on the top of the droplet generation tray 2, and the lower conductive layer 32 is disposed on the bottom of the droplet generation tray 2. In this way, when a bias voltage is applied between the upper conductive layer 12 and the lower conductive layer 32, the effect of "transitioning the bottom of the droplet generation hole from hydrophobic to hydrophilic" can be achieved.

[0036] In addition, a hydrophobic layer 13 is provided on the side of the upper electrode plate 1 adjacent to the droplet generation disk 2. The hydrophobic layer 13 is provided on the side of the upper conductive layer 12 adjacent to the droplet generation disk 2. In other words, the hydrophobic layer 13 is actually located on the bottom surface of the entire upper electrode plate 1. The purpose of providing the hydrophobic layer 13 is to ensure that the sample liquid in the droplet generation disk 2 does not adhere to the upper electrode plate 1.

[0037] It should be noted that, in this embodiment, the upper electrode plate 1 uses quartz glass 11 as a substrate, and then an upper conductive layer 12 and a hydrophobic layer 13 are provided on the quartz glass 11 to form a complete upper electrode plate 1; the lower electrode plate 3 uses quartz glass 31 as a substrate, and then a lower conductive layer 32 is provided on the quartz glass 31 to form a complete lower electrode plate 3.

[0038] The multi-volume micro-droplet generation chip of this embodiment is specifically used as follows:

[0039] The sample liquid is injected into the droplet generation plate 2 from the injection port 14 on the upper electrode plate 1. Under the action of surface tension, the sample liquid in the droplet generation plate 2 does not enter the droplet generation hole 21, but is suspended above the droplet generation hole 21;

[0040] A bias voltage is connected between the upper conductive layer 12 of the upper electrode 1 and the lower conductive layer 32 of the lower electrode 3. The upper conductive layer 12 is grounded, and the lower conductive layer 32 is connected to a power source. Under the action of the bias voltage, according to the Lippman-Young equation, the inner bottom surface of the droplet generation hole 21 changes from hydrophobic to hydrophilic. For each droplet generation hole 21, the hydrophobicity of its bottom is much smaller than that of its top. As a result, the sample liquid originally suspended above the droplet generation hole 21 will enter the droplet generation hole 21, thereby forming tiny droplets in the droplet generation hole 21.

[0041] Then, at the sample outlet 15, use an existing pipette to suck out all the excess sample liquid in the droplet generation plate 2 that is not in the droplet generation hole 21;

[0042] Finally, the bias voltage between the upper conductive layer 12 and the lower conductive layer 32 is disconnected.

[0043] At this time, each droplet generation hole 21 in the droplet generation plate 2 contains a tiny droplet, and these tiny droplets can be used in research and development experiments in the fields of biology, chemistry, and pharmaceuticals.

[0044] It should be noted that there are certain requirements for the distance between the upper conductive layer 12 and the lower conductive layer 32 and the droplet generation hole 21 in the droplet generation disk 2. The purpose is to ensure that there is a place to store the droplets when they first enter, and the solution is required to be able to contact the upper electrode 1 after entering (before power is turned on). To this end, the configuration size of the upper electrode 1, the droplet generation disk 2 and the lower electrode 3 combined together should ensure that the distance between the upper conductive layer 12 and the lower conductive layer 32 and the droplet generation hole 21 in the droplet generation disk 2 meets the requirements.

[0045] The multi-volume micro-droplet generation chip of this embodiment has the following advantages:

[0046] The multi-volume micro-droplet generation chip of this embodiment is based on a droplet generation disk 2. An upper conductive layer 12 and a lower conductive layer 32 are respectively provided above and below the droplet generation disk 2. Numerous droplet generation holes 21 are provided at the inner bottom of the droplet generation disk 2. As long as a bias voltage is applied between the upper conductive layer 12 and the lower conductive layer 32, the sample liquid in the droplet generation disk 2 can enter the droplet generation holes 21, thereby forming numerous tiny droplets, thereby meeting the demand for numerous tiny droplets in R&D experiments in the biological, chemical, and pharmaceutical fields.

[0047] Compared with existing technical equipment for generating small droplets, the multi-volume micro-droplet generation chip of this embodiment does not need to rely on external mechanical equipment. Moreover, it is small in size, easy to carry, and has high-throughput generation capabilities.

[0048] In addition, the multi-volume micro-droplet generation chip of this embodiment has the following advantages:

[0049] 1. High-throughput generation of large-volume droplets on the same multi-volume micro-droplet generation chip: By controlling the size and number of the liquid separation zones, high-throughput generation of multi-volume droplets is possible;

[0050] 2. High-throughput droplet generation without auxiliary equipment: Droplet generation relies on the electrowetting effect and does not require other equipment, greatly improving the portability and integration of the device.

[0051] Next, the specific method for manufacturing the multi-volume micro-droplet generation chip of this embodiment is introduced:

[0052] 1. Ultrasonic clean the purchased ITO glass substrate in acetone for 3 minutes, then in isopropyl alcohol for 5 minutes, and finally in deionized water for 5 minutes. Then, blow dry the substrate surface with a nitrogen gun and dry it on a hot plate at 100°C for 5 minutes.

[0053] 2. Spin-coat the cleaned ITO with the PDMS solution at 3000 rpm for 1 minute. Then, use soft lithography to create the separation area. Place the glass mold on the PDMS surface, using a 2μm gauge to control the spacing. Place the mold on a hot plate to cure for 2 hours at 65°C.

[0054] 3. Prepare the top plate 1 by spin-coating the Teflon solution onto the cleaned ITO using a spin coater at 3000 rpm for 1 minute. Then, dry the top plate on a hot plate at 100°C for 30 minutes. Next, use a laser cutter to cut the sample inlet 14 and sample outlet 15 into the top plate 1.

[0055] 4. Assembly: Place the upper plate 1 on the droplet generation tray 2, using the sidewalls of the tray to control the spacing. The multi-volume micro-droplet generation chip is then placed in a vacuum chamber for bonding at a vacuum level of -0.06 MPa for 30 minutes.

[0056] The above are only preferred embodiments of the present invention and are not intended to limit the scope of protection of the present invention. Therefore, any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A multi-volume micro-droplet generation chip, characterized by: The multi-volume micro-droplet generation chip comprises an upper plate (1), a droplet generation disk (2), and a lower plate (3); the lower plate (3) is arranged at the bottom of the droplet generation disk (2), the upper plate (1) is arranged at the top of the droplet generation disk (2), and an operation port is provided on the upper plate (1); An upper conductive layer (12) is provided on the upper electrode plate (1), a lower conductive layer (32) is provided on the lower electrode plate (3), and a plurality of droplet generation holes (21) are provided on the inner bottom of the droplet generation disk (2); When a bias voltage is set between the upper conductive layer (12) and the lower conductive layer (32), the hydrophobicity of the bottom of the droplet generation hole (21) is smaller than the hydrophobicity of the top of the droplet generation hole (21).

2. The multi-volume micro-droplet generation chip according to claim 1, characterized in that: The plurality of droplet generation holes (21) have different pore sizes.

3. The multi-volume micro-droplet generation chip according to claim 1, characterized in that: The operating ports provided on the upper electrode plate (1) include a sample inlet (14) and a sample outlet (15).

4. The multi-volume micro-droplet generation chip according to claim 1, characterized in that: A hydrophobic layer (13) is provided on the surface of the upper electrode plate (1) that is adjacent to the droplet generation disk (2).

5. The multi-volume micro-droplet generation chip according to claim 1, characterized in that: The upper electrode plate (1) uses quartz glass (11) as a substrate, and the lower electrode plate (3) uses quartz glass (31) as a substrate.

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