Assembled micro-droplet generating device

Abstract

The invention relates to an assembled micro-droplet generation device which comprises a sample injection tube, a plain-end syringe needle, a silicone tube, a Luer tee joint, a capillary tube and a syringe which are connected in sequence, the silicone tube is used for fixing the capillary tube and sealing the plain-end syringe needle; interfaces at two ends of the Luer tee joint are respectively connected with the plain end syringe needle and the syringe, and the interface in the vertical direction is used for adding a continuous phase and balancing air pressure. The device can adjust the size of the liquid drop by adjusting the distance between the end face of the capillary tube and the push rod face of the injector, and is convenient to operate, high in compatibility, detachable and low in cost.

Description

Technical Field

[0001] The present invention belongs to the technical field of microfluidics, and particularly relates to an assembled micro-droplet generating device. Background Art

[0002] Microfluidics is a technology for manipulating tiny volumes of liquid in micro-scale chip channels. Using this technology, micro-droplets with high monodispersity, highly controllable size and structure can be produced. These micro-droplets have been widely used in fields such as drug delivery, biological templates, cell culture, and microreactors.

[0003] Common microfluidic chips for droplet preparation are divided into flat plate type and capillary type. Flat plate chips can achieve various complex-structured microfluidic channels and various droplet generation methods such as T-type and cross-focusing type with the help of advanced micro-nano processing and soft lithography techniques. Among them, the paper at https: / / doi.org / 10.1073 / pnas.1209186110 proposed a droplet microfluidic chip that uses surface tension rather than shear force, and the injection flow rate has a low impact on droplet size. However, the flat plate type is mostly made of polymers (the batch injection molding tooling cost is high, and the production efficiency of PDMS is relatively low), is not resistant to high temperature and organic solution corrosion, and it is difficult to disassemble and assemble the chip, which is not conducive to cleaning and reuse. Glass capillary microfluidic chips use capillaries as functional units for droplet generation and collection. Due to the excellent light transmittance, good high-pressure resistance, biocompatibility, stable surface properties, and resistance to organic solvent corrosion of glass, such chips have gradually become widely used micro-droplet preparation devices.

[0004] Glass capillary microfluidic chip devices (CN106622407A, CN102580799A, CN112517096A, CN113797986A, CN113058669A) usually co-axially nest hollow capillaries of different thicknesses. This co-axial nested microchannel structure can achieve the preparation of single emulsion micro-droplets or multiple emulsion micro-droplets with a core-shell structure. The co-axial nested device relies on the continuous phase liquid in the thick tube to cut the dispersed phase liquid in the thin tube to form droplets, and has high requirements for the stability of the liquid flow velocity; when preparing micro-droplets with a smaller size (diameter < 100 μm), the central thin tube needs to be sharpened, and there are deviations in the consistency of the sharpening; in addition, assembling the capillaries also has high requirements for concentricity and sealing, which all increase the preparation cost and usage threshold of the device. Therefore, there is a need to provide an assembled micro-droplet generating device with low preparation cost and convenient use. Summary of the Invention

[0005] To solve the problems in the above-mentioned existing technologies, such as the high threshold for the preparation of droplet microfluidic chips and the inconvenience in use, the present invention combines the mechanism of generating droplets by surface tension and capillaries to provide a micro-droplet generating device that is convenient to operate, highly compatible, has adjustable droplet sizes, is detachable (can be reused after cleaning), and has a low cost.

[0006] The present invention provides an assembled micro-droplet generating device, which includes a sampling tube, a flat-tip syringe needle, a silica gel tube, a Luer three-way fitting, a capillary tube, and a syringe connected in sequence; the silica gel tube is used to fix the capillary tube and seal the flat-tip syringe needle, allowing the dispersed-phase sample in the sampling tube to flow only through the capillary tube; the interfaces at both ends of the Luer three-way fitting are respectively connected to the flat-tip syringe needle and the syringe, and the interface in the vertical direction is used to add the continuous phase and balance the air pressure.

[0007] More preferably, the inner diameter of the silica gel tube is 0.1 - 0.5 mm smaller than the outer diameter of the capillary tube, and the outer diameter of the silica gel tube is 0.1 - 0.5 mm larger than the inner diameter of the interface of the Luer three-way fitting, so as to achieve the functions of sealing and fixing.

[0008] Preferably, the size of the micro-droplets is adjusted by controlling the distance between the end face of the capillary tube and the face of the syringe plunger.

[0009] Preferably, the capillary tube includes any one of a glass capillary tube or a stainless-steel capillary tube.

[0010] Preferably, the syringe includes any one of a glass syringe, a plastic syringe, or a metal syringe.

[0011] The present invention also provides an application of the above-mentioned assembled micro-droplet generating device in the preparation of micro-droplets.

[0012] Beneficial effects

[0013] (1) The device components of the present invention are all mature industrial products, which are convenient to obtain and have a low cost;

[0014] (2) In the present invention, the size of the droplets can be adjusted by adjusting the distance between the end face of the capillary tube and the face of the syringe plunger;

[0015] (3) The device of the present invention is detachable, can be reassembled and reused after cleaning, and is convenient to assemble with a low usage threshold;

[0016] (4) The device of the present invention is reliable and stable, and has a wide compatibility with reagents. Description of the Drawings

[0017] Figure 1 It is the (A) schematic diagram of the component parts, (B) schematic diagram of the device assembly, and (C) schematic diagram of the device use of the present invention.

[0018] Figure 2It is a diagram showing the relationship between the flow rate and the generated droplet size of different capillary inner diameters under the condition that the distance between the capillary end face and the syringe push rod face in the device of the present invention is 25 μm.

[0019] Figure 3 It is a diagram showing the relationship between the flow rate and the generated droplet size of different capillary inner diameters under different conditions of the distance between the capillary end face and the syringe push rod face in the device of the present invention.

[0020] Figure 4 It is a micrograph of droplets generated with the change of flow rate at a constant gap distance of 25 μm for the droplet diameter in the present invention: (a) 0.3 μL / min, (b) 0.5 μL / min, (c) 0.7 μL / min, and (d) 1.2 μL / min; (e) the relationship between the size of the generated droplets and the flow rate of the dispersed phase.

[0021] Figure 5 It is the droplets generated by the device of the present invention under the conditions of a capillary inner diameter of 70 μm, a distance of 25 μm between the capillary end face and the syringe push rod face, and a dispersed phase injection flow rate of 1 μL / min: (a) after 0 h, (b) after 24 h.

[0022] Reference numerals: 1 - sampling tube, 2 - flat - mouth injection needle, 3 - silica gel tube, 4 - Luer three - way fitting, 5 - capillary, 6 - syringe. Detailed implementation manners

[0023] The following further elaborates the present invention in combination with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0024] Embodiment

[0025] This embodiment provides an assembled micro - droplet generation device, as Figure 1 shown, which includes a sampling tube 1, a flat - mouth syringe needle 2, a silica gel tube 3, a Luer three - way fitting 4, a glass capillary 5, and a glass syringe 6 connected in sequence; the silica gel tube 3 is used to fix the glass capillary 5 and seal the flat - mouth syringe needle 2; the interfaces at both ends of the Luer three - way fitting 4 are respectively connected to the flat - mouth syringe needle 2 and the glass syringe 6, and the interface in the vertical direction is used to add the continuous phase and balance the air pressure.

[0026] Hydrophobize the glass capillary and glass syringe with Sigmacote reagent. Connect each component in sequence to complete the assembly. Set the distance between the capillary end face and the syringe plunger face to 25 μm. Select mineral oil containing 3% EM90 as the continuous phase and pure water as the dispersed phase. The outer diameter of the capillary is 150 μm. Investigate the relationship between the flow rate and the generated droplet size for different capillary inner diameters. The results are as Figure 2 shown. These results indicate that a device capable of generating droplets with different size ranges can be obtained by adjusting the inner diameter size of the capillary, and the device has high flexibility.

[0027] Set the injection flow rate of the dispersed phase to 0.3 μL / min. Use an optical microscope to control the distance between the capillary end face and the syringe plunger face. Investigate the relationship between different face distances and droplet sizes. The results are as Figure 3 shown. These results indicate that when small-sized droplets need to be prepared, it can be achieved by precisely controlling the distance between the capillary end face and the syringe plunger face. When preparing large droplets, the face distance can be increased, and at this time, the droplet size is not sensitive to the distance.

[0028] Set the distance between the capillary end face and the syringe plunger face to 25 μm. Investigate the influence of different injection flow rates of the dispersed phase on the droplet size. The results are as Figure 4 shown. These results indicate that at low flow rates, the droplet size is not sensitive to changes in the flow rate, and the requirement for the stability of the flow velocity is low.

[0029] According to the above comparative test results, set the preferred parameters (capillary inner diameter 70 μm, distance between the capillary end face and the syringe plunger face 25 μm, injection flow rate of the dispersed phase 1 uL / min) to generate droplets, and characterize the generated droplets. The results are shown in Figure 5 , showing the stability and consistency of the device.

Claims

1. An assembled micro-droplet generating device, characterized in that: The assembled micro-droplet generating device comprises an injection tube, a flat syringe needle, a silicone tube, a Luer tee, a capillary and a syringe which are connected in sequence; the silicone tube is used to fix the capillary and seal the flat syringe needle; the interfaces at both ends of the Luer tee are respectively connected to the flat syringe needle and the syringe, and the vertical interface is used to add a continuous phase and balance the gas pressure.

2. The assembled micro-droplet generating device according to claim 1, characterized in that: The inner diameter of the silicone tube is 0.1-0.5 mm smaller than the outer diameter of the capillary tube, and the outer diameter of the silicone tube is 0.1-0.5 mm larger than the inner diameter of the Luer tee joint.

3. The assembled micro-droplet generating device according to claim 1, characterized in that: The size of the micro droplet is adjusted by controlling the distance between the capillary end surface and the syringe plunger surface.

4. The assembled micro-droplet generating device according to claim 1, characterized in that: The capillary tube includes any one of a glass capillary tube and a stainless steel capillary tube.

5. The assembled micro-droplet generating device according to claim 1, characterized in that: The syringe includes any one of a glass syringe, a plastic syringe or a metal syringe.

6. Use of the assembled micro-droplet generating device according to any one of claims 1 to 5 in preparing micro-droplets.

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