Rapid programmable generation device and method for cascade droplet array

Abstract

The invention discloses a rapid programmable generation device and method for a cascade droplet array. The device comprises a hydrophobic fan-shaped substrate, a scraper blade, a radially arranged hydrophilic stack point array and a driving device. Driving the mother liquid drops to move along the surface of the hydrophobic substrate through the rotation of the scraper, and dividing the mother liquid drops into micro-droplets residing in a hydrophilic area by utilizing the surface tension difference between the hydrophilic stack point and the hydrophobic substrate; the liquid drop volume is dynamically controlled by adjusting the rotating speed of the scraper blade or the diameter gradient distribution of the stack points, and the gradient liquid drop array is generated through single operation. The device does not need an external pump valve or a precise sealing device, has the advantages of open type passive operation, low cost, high flux, high stability and the like, is suitable for scenes of drug screening, single cell analysis, instant detection and the like, and remarkably improves the flexibility of micro-droplet generation and the experiment efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of microfluidic chips, and in particular to a device and method for quickly programmably generating a stepped droplet array. Background Art

[0002] As an important breakthrough in modern analytical science, microfluidic chip technology achieves high-throughput processing and reaction of biological samples through precise manipulation of microscale droplets, showing significant advantages in drug screening, single-cell analysis and point-of-care testing (POCT). Its miniaturized structure can significantly reduce reagent consumption, closed operation reduces cross-contamination, and it is easy to integrate with other detection modules, providing important technical support for precision medicine. However, traditional microfluidic chip systems have inherent limitations: the droplet size and spatial distribution are fixed at the chip design stage and lack dynamic adjustment capabilities. This rigid design requires the redevelopment of dedicated chips when experimental conditions change, significantly increasing R&D costs and time investment, and seriously restricting the flexibility and application scope of the technology.

[0003] Existing improvement schemes attempt to enhance droplet control capabilities through two approaches:

[0004] 1. Continuous flow droplet preparation: This relies on external pressure-controlled equipment to drive the fluid. Although it can achieve dynamic droplet adjustment, it places strict requirements on the sealing of the flow channel, and the equipment is complex and costly, making it difficult to meet the demand for portability.

[0005] 2. Discrete digital droplet generation: Discretely controlling droplets through electrodes or thermodynamic effects improves operational flexibility, but is limited by the physical mechanism and cannot simultaneously achieve high throughput, low consumption, and stable generation. Moreover, the throughput is limited by the device structure.

[0006] The above solutions have irreconcilable contradictions between key performance factors such as dynamic regulation, throughput, and equipment complexity. For example, the continuous flow method relies on a precise pump and valve system and is difficult to adapt to open scenarios; the discrete method is limited by low throughput and high energy consumption and cannot meet the needs of large-scale screening. In addition, existing technologies generally lack the ability to actively control the droplet volume gradient, and gradient droplet arrays are of great value in scenarios such as drug dose response testing and cell heterogeneity research. Therefore, there is an urgent need for a new microfluidic solution with a simple structure, no need for complex peripherals, and the ability to dynamically generate gradient droplet arrays, in order to break through the bottleneck of existing technologies and promote the wider application of this technology in precision medicine and high-throughput analysis. Summary of the Invention

[0007] In view of the defects of the prior art, the present invention provides a device and method for quickly and programmably generating a stepped droplet array.

[0008] In order to achieve the above object of the invention, the technical solution adopted by the present invention is as follows:

[0009] A rapid programmable generation device for a stepped droplet array, characterized by comprising: a hydrophobic fan-shaped substrate (1) for carrying mother droplets and guiding the flow of droplets;

[0010] A scraper (2) is provided above the hydrophobic sector-shaped base (1) and is not in direct contact with the surface of the water-transporting sector-shaped base, and is used to drive the mother liquid droplets to move;

[0011] A radially arranged hydrophilic stacking point array (3) is distributed on the surface of the hydrophobic sector-shaped substrate (1), and has a diameter and / or spacing gradient along the radial direction;

[0012] a driving device (4), connected to the scraper (2), for controlling the scraper to rotate at a preset angular velocity;

[0013] When the mother liquid droplets flow through the hydrophilic stack array (3) driven by the scraper (2), they are divided into micro-droplet arrays with a volume gradient due to the difference in hydrophilic and hydrophobic interfacial tension.

[0014] Preferably, the surface of the hydrophobic sector-shaped substrate (1) is modified with fluorosilane, and the liquid-solid contact angle is greater than 150° and the sliding angle is less than 5°.

[0015] Preferably, the edge of the working surface of the scraper (2) is a cutting edge structure with a thickness of 0.1-1 mm, and its material is selected from one of stainless steel, aluminum oxide, PDMS or fluorinated ethylene propylene copolymer, and the working surface is coated with a carbon fluoride coating.

[0016] Preferably, the hydrophilic stacking point array (3) is formed by selectively removing the substrate surface modification layer by femtosecond laser, the liquid-solid contact angle of each stacking point is 30° to 80°, and the diameters along the radial direction are distributed in an arithmetic progression or a geometric progression.

[0017] Preferably, the driving device (4) is a motor or a spring, which controls the rotation speed of the scraper (2) to be 2-30 revolutions per minute.

[0018] The present invention also discloses a method for generating a micro-droplet array based on the above device, comprising the following steps:

[0019] Step S1: adding the mother solution dropwise to the surface of the hydrophobic sector-shaped substrate (1), ensuring that the droplet volume covers at least one hydrophilic stack point;

[0020] Step S2: starting the driving device (4) to rotate the scraper (2) at a set angular velocity, driving the mother liquid droplets to move radially;

[0021] Step S3: When the mother liquid droplets flow through the hydrophilic stacking point array (3), micro droplets are separated due to the interfacial tension difference between the hydrophilic stacking points and the hydrophobic substrate (1), and remain on the surface of each hydrophilic stacking point;

[0022] Step S4: By adjusting the angular velocity of the scraper (2) or the diameter distribution parameters of the hydrophilic stack points, micro-droplet arrays with different volume gradients are generated.

[0023] Furthermore, in step S4, the linear speed of the scraper is changed by adjusting the rotation speed of the driving device (4) in real time, thereby achieving dynamic control of the droplet volume.

[0024] Compared with the prior art, the advantages of the present invention are:

[0025] 1. Efficient generation of gradient droplet arrays: Through the synergistic effect of radially arranged hydrophilic stacks and hydrophobic fan-shaped substrates (1), combined with the directional drive of the scraper, a microdroplet array with a volume gradient can be generated at one time in a single operation, meeting the diverse needs of scenarios such as drug dose response testing and multi-concentration biochemical reactions.

[0026] 2. Dynamically controllable droplet volume adjustment: By adjusting the speed of the drive device to change the linear speed of the scraper or designing a diameter gradient distribution of hydrophilic stack points, the droplet volume can be precisely controlled in real time without redesigning or replacing the chip, significantly improving experimental flexibility and efficiency.

[0027] 3. Open passive operation: The droplet generation process does not rely on external pumps, valves, electric fields or thermodynamic control equipment. The droplets are spontaneously divided only by the difference in hydrophilic and hydrophobic interfacial tension, which greatly reduces the complexity and energy consumption of the equipment. It is suitable for open environments and scenarios with strict requirements on device portability (such as POCT testing).

[0028] 4. Low cost and high compatibility: The technology for hydrophilic and hydrophobic modification of solid surfaces is mature and can be prepared in batches; the material selection of hydrophobic substrates and scrapers is wide (glass, PDMS, etc.), which is compatible with conventional microfluidic chip processing technology, significantly reducing production costs.

[0029] 5. High throughput and high stability: Radially distributed hydrophilic stacking points allow a mother droplet to continuously generate multiple droplets in a single sweep, increasing the throughput several times compared to traditional discrete droplet generation technology. At the same time, droplet retention relies on the stable hydrophilic and hydrophobic properties of the substrate surface, preventing droplet fusion or displacement and ensuring experimental repeatability.

[0030] 6. Wide application adaptability: The generated gradient droplet array can be directly used in biological experiments such as cell culture and drug screening. It can also be seamlessly integrated with analytical equipment such as microscopes and spectrometers to provide standardized microreaction units for multi-dimensional biochemical analysis. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 Schematic diagram of the structure of a fan-shaped micro-droplet array generating device according to an embodiment of the present invention;

[0032] Figure 2This is a schematic diagram of the principle of droplet generation according to an embodiment of the present invention;

[0033] Figure 3 This is a flow chart of a method for generating a fan-shaped micro-droplet array according to an embodiment of the present invention. DETAILED DESCRIPTION

[0034] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to the accompanying drawings and examples.

[0035] like Figure 1 As shown, the present invention provides a rapid programmable generation device for a stepped droplet array, comprising a hydrophobic fan-shaped substrate 1, a scraper 2, a hydrophilic stack 3 and a motor drive device 4.

[0036] The hydrophobic sector-shaped substrate 1 has a solid-liquid contact angle with the sample liquid greater than 90°. A dropper is used to drop a sufficient volume of mother liquid droplets on the substrate to ensure that the droplet volume can completely cover the hydrophilic stack points 3 under external force.

[0037] The scraper 2 is fixed on the hydrophobic substrate by a bracket to ensure that there is a certain distance between the bottom of the working surface and the surface of the hydrophobic substrate.

[0038] The hydrophilic stack point 3: the solid-liquid contact angle with the sample liquid should be less than 60°.

[0039] The driving device is a spring, a motor or other device capable of regulating the speed of the scraper.

[0040] like Figure 2 As shown, hydrophilic regions are created on the surface of a hydrophobic substrate, thereby changing the contact characteristics of the liquid on the substrate. When the liquid flows over the substrate under the action of an external force, the three-phase line (water-liquid-gas) of the liquid at the hydrophilic / hydrophobic interface changes, and finally a droplet is formed in the hydrophilic region. At the same time, different driving speeds affect the effect of the surface tension difference, resulting in different droplet volumes.

[0041] The droplet generation workflow of the present invention is as follows ( Figure 3 ):

[0042] Step A: Use a pipette to drop a sufficient volume of mother solution onto the substrate, ensuring that the droplet volume can completely cover the hydrophilic stack point 3 under external force. Go to step B;

[0043] Step B: The motor drives the scraper to move the mother liquid droplets through the hydrophilic stack point 3. Go to step C;

[0044] Step C: The difference in hydrophobic properties between the hydrophobic surface and the hydrophilic stacking point 3 results in different surface tensions for the droplets. This surface tension difference causes the mother droplet to separate into microdroplets that remain on the hydrophilic stacking point 3. The process then proceeds to Step D.

[0045] Step D: Because the hydrophilic stacking points 3 are distributed radially, the parent droplet has different linear velocities when passing through hydrophilic stacking points 3 with different curvature radii. Different driving speeds affect the surface tension difference and capillary absorption time, resulting in different droplet volumes. Finally, a gradient droplet array with different volumes is generated in a single process. Proceed to Step E.

[0046] The volume of the microdroplet is determined by the following formula:

[0047] Where V is the droplet volume, σ is the liquid-gas surface tension, d is the hydrophilic stack point diameter, v is the scraper linear velocity, and k is a correction coefficient related to the solution properties.

[0048] Step E: By adjusting the angular velocity of the motor-driven scraper, the volume of the generated droplets can be easily and quickly controlled in real time.

[0049] The hydrophobic sector-shaped substrate 1 is entirely made of glass with a nano-silica coating and fluorosilane modification on the surface to ensure that the liquid-solid contact angle is greater than 150° and the rolling angle is less than 5°.

[0050] The shape of the scraper is characterized by a cutting edge structure with a thickness of 0.1-1 mm at the edge of the working surface, and ensuring that the length is greater than or equal to the curvature radius of the fan-shaped hydrophobic substrate. The rigid material is stainless steel or alumina, and the flexible material is PDMS or fluorinated ethylene propylene copolymer. At the same time, the working surface is coated with a fluorinated carbon coating to ensure that the liquid will not adhere to the scraper surface and affect the preparation process.

[0051] The hydrophilic stack point 3 uses a femtosecond laser to selectively remove the surface modification layer, and the controllable laser direct writing changes the micro-nano structure at the stack point to increase the hydrophilicity, ensuring that the liquid-solid contact angle can be controlled within the range of 30° to 80°.

[0052] The scraper 2 is fixed on the hydrophobic substrate by a bracket, ensuring that the distance between the bottom of the working surface and the hydrophobic substrate is less than or equal to 0.1 mm.

[0053] The rotation speed of the scraper 2 should be between 2 rpm and 30 rpm, which can adapt to the droplet generation requirements under different experimental conditions.

[0054] Those skilled in the art will appreciate that the embodiments described herein are intended to help readers understand the implementation methods of the present invention, and it should be understood that the scope of protection of the present invention is not limited to such specific descriptions and embodiments. Those skilled in the art can make various other specific variations and combinations based on the technical teachings disclosed in the present invention without departing from the essence of the present invention, and such variations and combinations are still within the scope of protection of the present invention.

Claims

1. A rapid programmable device for generating a stepped droplet array, characterized in that: include: A hydrophobic fan-shaped substrate (1) for carrying mother liquid droplets and guiding the flow of droplets; A scraper (2) is provided above the hydrophobic sector-shaped base (1) and is not in direct contact with the surface of the water-transporting sector-shaped base, and is used to drive the mother liquid droplets to move; A radially arranged hydrophilic stacking point array (3) is distributed on the surface of the hydrophobic sector-shaped substrate (1), and has a diameter and / or spacing gradient along the radial direction; a driving device (4), connected to the scraper (2), for controlling the scraper to rotate at a preset angular velocity; When the mother liquid droplets flow through the hydrophilic stack array (3) driven by the scraper (2), they are divided into micro-droplet arrays with a volume gradient due to the difference in hydrophilic and hydrophobic interfacial tension.

2. The fan-shaped micro-droplet array generating device according to claim 1, characterized in that: The surface of the hydrophobic sector-shaped substrate (1) is modified with fluorosilane, and the liquid-solid contact angle is greater than 150° and the rolling angle is less than 5°.

3. The fan-shaped micro-droplet array generating device according to claim 1, characterized in that: The edge of the working surface of the scraper (2) is a cutting edge structure with a thickness of 0.1-1 mm, and its material is selected from one of stainless steel, aluminum oxide, PDMS or fluorinated ethylene propylene copolymer, and the working surface is coated with a carbon fluoride coating.

4. The fan-shaped micro-droplet array generating device according to claim 1, characterized in that: The hydrophilic stacking point array (3) is formed by selectively removing the substrate surface modification layer by femtosecond laser, the liquid-solid contact angle of each stacking point is 30° to 80°, and the diameters along the radial direction are distributed in an arithmetic progression or a geometric progression.

5. The fan-shaped micro-droplet array generating device according to claim 1, characterized in that: The driving device (4) is a motor or a spring, which controls the rotation speed of the scraper (2) to be 2-30 revolutions per minute.

6. A method for generating a micro-droplet array based on the device according to any one of claims 1 to 5, characterized in that: The following steps are involved: Step S1: adding the mother solution dropwise to the surface of the hydrophobic sector-shaped substrate (1), ensuring that the droplet volume covers at least one hydrophilic stack point; Step S2: starting the driving device (4) to rotate the scraper (2) at a set angular velocity, driving the mother liquid droplets to move radially; Step S3: When the mother liquid droplets flow through the hydrophilic stacking point array (3), micro droplets are separated due to the interfacial tension difference between the hydrophilic stacking points and the hydrophobic substrate (1), and remain on the surface of each hydrophilic stacking point; Step S4: By adjusting the angular velocity of the scraper (2) or the diameter distribution parameters of the hydrophilic stack points, micro-droplet arrays with different volume gradients are generated.

7. The method for generating a micro-droplet array according to claim 6, wherein: In step S4, the linear speed of the scraper is changed by adjusting the rotation speed of the driving device (4) in real time, thereby achieving dynamic control of the droplet volume.

Images