Micro-fluidic chip

Abstract

The utility model provides a micro-fluidic chip which comprises a plate-shaped chip substrate (7) which is divided into an input layer, a reaction layer and a driving layer from top to bottom; a main flow channel (8), a plurality of first micro-fluidic pipelines (9), a plurality of second micro-fluidic pipelines (11), a plurality of fusion liquid channels (13) and a plurality of discharge liquid channels (16) are formed in the reaction layer; elastic films (17) are arranged at the bottoms of the plurality of reaction chambers (14); the driving layer is provided with an air chamber (5) and an air inlet (6); two first microfluidic pipelines (9) and two second microfluidic pipelines (11) on a main flow channel (8) form a group, are accurately controlled and fused through a microfluidic electronic micro-valve (10), are divided into multiple groups and are communicated with a plurality of reaction chambers (14), and the influence of multiple drugs or concentrations on cells is allowed to be tested at the same time; under the vibration action of the elastic film (17), the solution in the reaction chamber (14) is fully fused; and observation and comparative analysis are carried out through the transparent part of the input layer above each reaction chamber (14).

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of microfluidics, and particularly relates to a microfluidic chip. BACKGROUND

[0002] In the research of traditional biomedical engineering and cell biology, traditional cell experiment methods face many challenges and limitations. First, these experiments usually require a large number of cell samples, complex experimental procedures and tedious operation steps, resulting in low experimental efficiency. When multiple operations are involved, the complexity of the operation will further increase, making experimental design and implementation more difficult. In addition, traditional experimental methods cannot realize real-time comparison and synchronous monitoring between different operations, and cannot accurately control experimental parameters, affecting the accuracy and consistency of experimental results.

[0003] With the rapid development of modern science and technology, microfluidic technology plays an increasingly important role in medical diagnosis and health monitoring, biomedical research, environmental monitoring and protection, food safety and detection, etc.

[0004] Compared with traditional technology, microfluidic technology significantly improves the reaction efficiency and uniformity in the interaction of cells and drugs, making the experimental results more sensitive and accurate.

[0005] How to make the microfluidic chip have the functions of high-throughput, multi-channel parallel processing, comparability, reducing pollution and cross contamination risk has become a problem for technical personnel. CONTENT OF THE INVENTION

[0006] The application provides a microfluidic chip, which comprises:

[0007] a plate-shaped chip base, which is divided into an input layer, a reaction layer and a driving layer from top to bottom;

[0008] a first liquid inlet hole, a first liquid outlet hole, a plurality of second liquid inlet holes and a plurality of second liquid outlet holes are formed in the input layer;

[0009] a plurality of first microfluidic channels, a plurality of second microfluidic channels, a plurality of fusion liquid channels, a plurality of discharge liquid channels and a plurality of reaction chambers are formed in the reaction layer;

[0010] the driving layer is provided with an air chamber and an air inlet of the air chamber;

[0011] one end of the main flow channel is communicated with the first liquid inlet hole, and the other end is communicated with the first liquid outlet hole;

[0012] the inlet end of each of the plurality of first microfluidic channels is communicated with the main flow channel, and the inlet end of each of the second microfluidic channels is communicated with one of the second liquid inlet holes;

[0013] The outlet of each first micro-fluid channel and the outlet of one second micro-fluid channel are connected to the inlet end of one fusion liquid channel, and the outlet end of the fusion liquid channel is connected to a reaction chamber; a micro-fluid channel electric micro valve is arranged on the first micro-fluid channel and the second micro-fluid channel, and the micro-fluid channel electric micro valve can form micro droplets from solution;

[0014] The outlet end of the reaction chamber is connected to the inlet end of the discharge liquid channel, and the outlet end of the discharge liquid channel is connected to the second liquid outlet hole;

[0015] The bottom of the reaction chamber is composed of an elastic film, and the air chamber is located below the elastic film;

[0016] At least the part above the reaction chamber in the input layer is transparent.

[0017] Further, the air inlet is connected to a micro air pump, and the micro air pump is used to vibrate the elastic film.

[0018] Further, the micro-fluid chip further comprises an external circulation pipeline;

[0019] The two ends of the external circulation pipeline are connected to the inlet of the first liquid inlet hole and the outlet of the first liquid outlet hole, respectively;

[0020] The external circulation pipeline is provided with a liquid inlet and a circulation pump.

[0021] Further, the outlet end of the reaction chamber is provided with a discharge micro electric valve.

[0022] Further, the inlet of the reaction chamber is located at the upper part, and the outlet is located at the lower part.

[0023] Further, the first micro-fluid channel, the second micro-fluid channel, the fusion liquid channel, the discharge liquid channel and the reaction chamber are all even numbers, and are symmetrically arranged on both sides of the main flow channel.

[0024] Further, the chip substrate is transparent.

[0025] Further, the elastic film is made of polydimethylsiloxane.

[0026] Further, the outlet of each first micro-fluid channel and the outlet of a plurality of second micro-fluid channels are connected to the inlet end of one fusion liquid channel, and the outlet end of the fusion liquid channel is connected to one reaction chamber.

[0027] Further, the air chamber and the air inlet are both provided with a plurality of air chambers; one air chamber is arranged below each reaction chamber.

[0028] The above technical scheme of the utility model has at least the following beneficial technical effects:

[0029] In the application, a plurality of branches of first micro-fluidic channels are arranged on the main flow channel, and the first micro-fluidic channels and the second micro-fluidic channels are two groups, the solution fusion is accurately controlled through the micro-fluidic channel electric micro valve, and is divided into multiple groups to communicate multiple reaction chambers, allowing multiple drugs or different drug concentrations to be tested simultaneously on cells. It is particularly useful in drug screening and high-throughput research, and can quickly screen out effective drug combinations; under the vibration action of the elastic diaphragm, the sample solution in the reaction chamber is fully fused and reacted; the transparent part of the input layer above each reaction chamber is beneficial to observation and comparative analysis, which helps to study the mechanism of the drug on the cells and obtain consistent and repeatable experimental results. BRIEF DESCRIPTION OF DRAWINGS

[0030] In order to more clearly illustrate the technical solutions in the embodiments of the present application or in the prior art, the drawings needed to be used in the embodiments will be briefly introduced as follows. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor on the basis of these drawings.

[0031] Fig. 1 is a top view of a micro-fluidic chip in an embodiment of the present application.

[0032] Fig. 2 is a top view of a micro-fluidic chip in an embodiment of the present application.

[0033] Fig. 3 is a partial front view of a micro-fluidic chip in an embodiment of the present application.

[0034] In the drawings, Figs. 1-3 The correspondence between the reference signs in the drawings and the component names is as follows:

[0035] 1, first liquid inlet hole; 2, first liquid outlet hole; 3, second liquid inlet hole; 4, second liquid outlet hole; 5, gas chamber; 6, gas inlet; 7, chip base; 8, main flow channel; 9, first micro-fluidic channel; 10, micro-fluidic channel electric micro valve; 11, second micro-fluidic channel; 13, fusion liquid channel; 14, reaction chamber; 15, reaction chamber liquid outlet pipe; 16, discharge liquid channel; 17, elastic diaphragm; 18, discharge micro-electric valve. DETAILED DESCRIPTION

[0036] For the purposes of making the objectives, technical solutions and advantages of the embodiments of the present application clearer, the embodiments of the present application will be described in detail below with reference to the drawings. However, those skilled in the art can understand that, in the embodiments of the present application, many technical details are presented in order to make the readers better understand the present application. However, the technical solutions claimed by the present application can be implemented even without these technical details and based on various changes and modifications of the following embodiments. The division of the following embodiments is for the convenience of description, and should not constitute any limitation on the specific implementation modes of the present application, and the embodiments can be combined with each other and mutually referenced without contradiction.

[0037] At present, there is a problem in the prior art of how to make the microfluidic chip have the functions of high-throughput, multi-channel parallel processing, comparability, reduction of pollution and cross-pollution risk and the like.

[0038] To solve the above problems, the present application provides a microfluidic chip, as shown in Fig. 1 、 2 and 3, comprising:

[0039] a plate-shaped chip base 7, which is divided into an input layer, a reaction layer and a driving layer from top to bottom; it should be noted that the above three layers are divided from the functional point of view in combination with the relative position relationship, and it does not mean that the entity of the chip base 7 must have a clear interlayer connecting surface, which can be integrally formed.

[0040] The input layer is provided with a first liquid inlet hole 1, a first liquid outlet hole 2, a plurality of second liquid inlet holes 3 and a plurality of second liquid outlet holes 4; each hole is usually vertically upward. The reaction layer is provided with a main flow channel 8, a plurality of first microfluidic channels 9, a plurality of second microfluidic channels 11, a plurality of fusion liquid channels 13, a plurality of discharge liquid channels 16 and a plurality of reaction chambers 14; the driving layer is provided with an air chamber 5 and an air inlet 6 of the air chamber 5;

[0041] Specifically, the first liquid inlet hole 1 and the first liquid outlet hole 2 are connected at both ends of the main flow channel 8 respectively; the first microfluidic channel 9 is a branch on the main flow channel 8; one first microfluidic channel 9 and one second microfluidic channel 11 form a group, and the downstream of the two is connected to one fusion liquid channel 13.

[0042] In the experiment, the cell solution enters the main flow channel 8 from the first inlet hole 1 and is dispersed into a plurality of first micro-fluidic channels 9, and the first micro-fluidic channels 9 are provided with micro-fluidic channel electric micro valves 10, which can control the flow or stagnation of the cell solution, the amount and flow rate of the solution flowing through, and can form small droplets one by one. The drug solution enters a second micro-fluidic channel 11 connected with the second inlet hole 3 from the second inlet hole 3, and the second micro-fluidic channel 11 is also provided with micro-fluidic channel electric micro valves 10, which can form small droplets of the drug solution one by one; by controlling the flow rate, the small droplets of the cell solution in the first micro-fluidic channel 9 and the small droplets of the drug solution in the second micro-fluidic channel 11 are accurately fused one by one in the fusion liquid channel 13, the error is reduced, and the sample solution is formed; the fused sample solution enters the reaction chamber 14 for further reaction. The sample solution in the reaction chamber 14 can be discharged through the discharge liquid channel 16 downstream of the reaction chamber 14 and the second outlet hole 4. The first micro-fluidic channel 9 and the second micro-fluidic channel 11 are in the micron scale, the Reynolds number of the fluid is small (usually less than 1), the flow is laminar flow rather than turbulent flow, which ensures that the liquid molecules flow along parallel paths and are not easy to mix, so that the small droplets in the respective micro-fluidic channels are separated one by one, and then the small droplets of the cell solution and the small droplets of the drug are accurately contacted one by one in the fusion liquid channel 13 to form an integral whole. In the laminar flow state, liquid mixing mainly relies on molecular diffusion, and the smaller the flow channel size, the faster the diffusion speed. The droplets in the micro-fluidic channel are extremely small in size, and the solute diffusion path is short, which promotes rapid mixing of the solution.

[0043] The bottom of the reaction chamber 14 is composed of an elastic film 17, and the air chamber 5 is located below the elastic film 17; the elastic film 17 can be deformed and vibrated by blowing or sucking air into the air chamber 5 from the outside of the chip through the air inlet 6, and the sample solution in the reaction chamber 14 is moved and fully mixed and reacted by the vibration of the elastic film 17. The high surface-to-volume ratio of the first micro-fluidic channel 9 and the second micro-fluidic channel 11 and the elastic film 17 device can reduce the reaction time, make the contact between the drug and the cell more sufficient, and the reaction speed faster, so that the user can obtain the reaction result of the cell to the drug faster, and improve the experimental efficiency.

[0044] In the input layer, at least part of the reaction chamber 14 is transparent, so that the reaction of the cells, chromosomes, etc. in the reaction chamber 14 with the drug can be directly observed or observed under a microscope.

[0045] In the present application, a plurality of first micro-fluidic channels 9 are arranged on the main flow channel 8, and the first micro-fluidic channels 9 and the second micro-fluidic channels 11 are two groups, which are precisely controlled by the micro-fluidic valve 10 to fuse the solutions, and are divided into multiple groups in multiple reaction chambers 14, allowing multiple drugs or different drug concentrations to be tested simultaneously on cells. It is particularly useful in drug screening and high-throughput research, which can quickly screen out effective drug combinations; under the vibration of the elastic membrane 17, the sample solution in the reaction chamber 14 is fully fused and reacted; the transparent part of the input layer above each reaction chamber 14 is beneficial to observation and comparative analysis, which helps to study the mechanism of the drug on the cells and obtain more consistent and repeatable experimental results.

[0046] In a specific embodiment, the chip substrate 7 serves as a basic structure to provide a stable platform for the remaining components, and its material can be polydimethylsiloxane (PDMS). PDMS has excellent transparency, low autofluorescence, good biocompatibility, stable chemical properties, is suitable for making micron-level structures, is simple to mold, has relatively low cost, and is suitable for biological and medical experiments.

[0047] Preferably, the gas inlet 6 and the gas chamber 5 are connected through a gas channel, and the gas inlet 6 is used to connect a micro air pump for vibrating the elastic membrane 17. The micro air pump adjusts the frequency of gas in and out to adjust the frequency and amplitude of the deformation of the elastic membrane 17, which drives the solution in the reaction chamber 14 to mix fully, and is particularly suitable for experiments with long reaction time or dyeing. After the experiment is completed, the adjustable deformation of the elastic membrane 17 realizes the thorough cleaning of the reaction chamber 14, ensuring that the chip can be reused. Alternatively, the rate of vibration of the elastic membrane 17 is 50-100 times per minute, preferably 60 times per minute, which simulates the state of blood flow in the reaction chamber 14, and the cell solution in the experiment can better reflect its behavior in the living body, making the experimental results more physiologically relevant.

[0048] In an embodiment, the micro-fluidic chip further comprises an external circulation channel; the two ends of the external circulation channel are respectively connected to the inlet of the first liquid inlet hole 1 and the outlet of the first liquid outlet hole 2; the external circulation channel is provided with a liquid inlet and a circulation pump, so that the solution in the main flow channel 8 flows and the experiment can continue. In addition, the external circulation channel and the main flow channel 8, the first micro-fluidic channel 9, the second micro-fluidic channel 11, the fusion liquid channel 13, the reaction chamber 14, the discharge liquid channel 16, etc. form a closed system, reducing the risk of external pollution; different pipeline systems also reduce the cross contamination between samples, thereby improving the reliability of the experiment.

[0049] In an embodiment, the outlet end of the reaction chamber 14 is provided with a discharge micro-electric valve 18 to control the discharge of the reacted sample solution, avoiding backflow or stagnation. Optionally, the discharge micro-electric valve 18 is downstream of a reaction chamber outlet pipe 15, and a plurality of reaction chamber outlet pipes 15 converge into a discharge liquid channel 16, and then the reacted solution is discharged through the second outlet hole 4.

[0050] In an embodiment, the inlet of the reaction chamber 14 is located at the upper part, and the outlet is located at the lower part, so that the inlet and outlet of the solution are smooth, and the sample solution does not affect the timing and proportion of the fusion of the cell solution droplets and the drug solution droplets due to backflow.

[0051] Optionally, the first micro-fluidic channel 9, the second micro-fluidic channel 11, the fusion liquid channel 13, the discharge liquid channel 16, and the reaction chamber 14 are all even numbers, and are symmetrically arranged on both sides of the main flow channel 8. The symmetric arrangement balances the initial flow, pressure, etc. in different first micro-fluidic channels 9, making it easy to control the same and stable reaction conditions.

[0052] In an embodiment, the chip substrate 7 is made of transparent material, which can be observed under an oil immersion microscope for real-time monitoring of the conditions of each channel and the reaction chamber 14. The chip is provided with a plurality of reaction chambers 14 to support simultaneous performance of multiple experiments, and can perform experiment comparison between the plurality of reaction chambers 14.

[0053] Preferably, the elastic film 17 is made of polydimethylsiloxane (PDMS). PDMS also has excellent elasticity and adjustable deformation ability, which can be deformed under the pressure adjustment of the air chamber 5 to promote the full mixing of the solution in the reaction chamber 14. In addition, the chip substrate 7 and the elastic film 17 can be made of PDMS, and the transparency of PDMS also helps the microscopic observation.

[0054] In an optional embodiment, two or more drugs are needed to be sequentially fused with the same cell solution during the experiment, so in this optional embodiment, the outlet of each first micro-fluidic channel 9 and the outlet of a plurality of second micro-fluidic channels 11 converge into the inlet end of a fusion liquid channel 13, and the outlet end of the fusion liquid channel 13 is connected to a reaction chamber 14.

[0055] Optionally, the air chamber 5 and the air inlet 6 are both provided with a plurality of air chambers 5 and air inlets 6. Each reaction chamber 14 is provided with an air chamber 5 below to individually control the vibration frequency of the elastic film 17 of each reaction chamber 14.

[0056] Optionally, the size of the chip is 3cm x 5cm, and the size of the main flow channel 8 is 0.5cm 2×4cm, the width of the microfluidic channel is between 10 microns and 100 microns. The reaction chamber 14 can be circular, with a diameter of 4-6 mm and a depth of 1-2 mm; the diameter of the cell droplet and the drug droplet is between 10 μm and 500 μm. In the microfluidic chip, the size of the droplet is micron level, so its surface area is very large relative to the volume, so the enhanced reaction rate of more surface area can improve the contact area with the reactants, thereby accelerating the rate of chemical reaction or biological reaction. Better dispersion and mixing, small droplets can be quickly dispersed in the chip, enhancing the mixing efficiency.

[0057] It should be noted that the chip base 7 of the present application also has some necessary lines and pipelines, such as the control circuit of the microfluidic channel microvalve 10 and the discharge microvalve 18, and the external liquid outlet pipeline communicated with the second liquid outlet hole. By controlling the flow rate, fluid channel structure and droplet generation conditions of the solution in the first microfluidic channel 9 and the second microfluidic channel 11 from the external control circuit, the accurate contact and fusion of the droplets in the reaction chamber 14 are ensured, and the full reaction is promoted. The droplets have high stability and can be individually manipulated in a multi-channel system, reducing the risk of rupture or loss of control.

[0058] The chip of the present application can also be integrated with sensors, such as sensors for detecting changes in cell metabolism, sensors for monitoring the pH value of the solution, and sensors for monitoring the oxygen concentration. A variety of sensors track the response of cells to drugs in real time, improving the speed and quality of data acquisition.

[0059] In order to intuitively show the application and effect of the microfluidic chip in the present application, the following two groups of experiments are carried out:

[0060] Experiment 1: Multi-channel drug effect on cells

[0061] Experimental materials and equipment:

[0062] Microfluidic chip, containing four reaction chambers 14.

[0063] Experimental sample:

[0064] Cell suspension: human cervical cancer cells HeLa, concentration 1×10 6 cells / mL.

[0065] Drug solution: anticancer drug doxorubicin, concentration 0.1 μM, 1 μM and 10 μM (divided into three groups).

[0066] Culture medium: cell culture medium containing fetal bovine serum and basic nutrients.

[0067] Equipment: microscope, sensor (for detecting cell metabolites).

[0068] Experimental steps

[0069] (1) Cell solution loading

[0070] HeLa cell suspension was filled into the 4 first microfluidic channels 9 through the first inlet hole 1 (or inlet port).

[0071] (2) Drug solution loading

[0072] The drug channels of the 4 channels were filled with 0.1 μM, 1 μM and 10 μM doxorubicin drug and control solution at the same time.

[0073] (3) Reaction stage

[0074] The microfluidic channel microvalves 10 were opened at the same time, so that the cell suspension and the drug solution generated droplets in the respective microfluidic channels, and the bacterial suspension droplets and the drug solution droplets were fully mixed one by one in the fusion channel 13; then they entered the reaction chamber 14, and the deformation of the elastic membrane 17 realized the full mixing reaction, maintained the fluid stability in the reaction chamber 14, and the reaction time was set to 4 hours.

[0075] (4) Monitoring

[0076] The cell morphology changes were observed in real time under a microscope, and the metabolic data (such as glucose consumption and lactic acid production) were recorded using a sensor.

[0077] (5) Experiment end and cleaning

[0078] The residual cells and reaction products were completely discharged through the deformation of the elastic membrane 17, and the reaction chamber 14 was cleaned for repeated use.

[0079] Experimental data and results analysis as shown in Table 1 and Table 2

[0080] Table 1 Microscopic imaging quantitative analysis

[0081]

[0082] Table 2 Metabolic data statistical analysis

[0083]

[0084] Cell survival and apoptosis analysis

[0085] The increase of drug concentration significantly reduced the cell survival rate and increased the cell apoptosis rate. Especially at the concentration of 10 μM, the cell survival rate was only 9.8%, and the apoptosis rate was as high as 90.2%, indicating that doxorubicin had strong cytotoxic effect at high concentration.

[0086] Metabolic activity changes

[0087] With the increase of drug concentration, glucose consumption and lactic acid production gradually decreased. At low concentration (0.1 μM), cell metabolic activity decreased slightly; at medium concentration (1 μM), metabolic activity decreased significantly; at high concentration (10 μM), metabolism almost stopped; this indicates that drug concentration and metabolic inhibition show a significant positive correlation.

[0088] Conclusion:

[0089] Doxorubicin showed obvious concentration-dependent inhibition on HeLa cells. The higher the concentration, the lower the cell survival rate, and the stronger the inhibition of metabolic activity.

[0090] The data showed that the IC50 was 1 μM, indicating that this concentration was the critical point for doxorubicin to effectively inhibit the growth of HeLa cells, providing a reference for subsequent dose optimization.

[0091] The experimental results verified the application potential of the microfluidic chip in high-efficiency screening of anticancer drugs, and provided reliable data support for the evaluation and mechanism research of anticancer drugs.

[0092] Experiment 2:

[0093] Multi-chip multi-channel antibacterial drug screening experiment

[0094] Chip: 3 microfluidic chips with 4 independent reaction chambers 14.

[0095] Experimental samples:

[0096] Bacterial suspension: Staphylococcus aureus, concentration 1 × 10 8 CFU / mL.

[0097] Drug solution: Drug A: ampicillin (1 μg / mL, 10 μg / mL, 100 μg / mL).

[0098] Drug B: Ceftriaxone (1 μg / mL, 10 μg / mL, 100 μg / mL).

[0099] Drug C: Vancomycin (1 μg / mL, 10 μg / mL, 100 μg / mL).

[0100] Control group: physiological saline without antibacterial drugs.

[0101] Experimental steps

[0102] (1) Load bacterial suspension

[0103] Through the first inlet hole 1, inject Staphylococcus aureus suspension into the main flow channel 8, and ensure that the bacterial solution is evenly distributed in each first microfluidic channel 9.

[0104] (2) Load drug solution

[0105] Chip 1: Inject 1 μg / mL, 10 μg / mL, 100 μg / mL concentration of drug A and control solution into the second microfluidic channel 11 of each of the four channels simultaneously, fill the channel.

[0106] The rest of the chips are injected with each drug at each concentration in this way.

[0107] (3) Reaction stage

[0108] Simultaneously open the microfluidic channel microvalve 10, so that the bacterial suspension and drug solution form droplets in the respective microfluidic channels, and the bacterial suspension droplets and drug solution droplets are fully mixed one by one in the fusion channel 13. Subsequently enter the reaction chamber 14, and the elastic membrane 17 in the reaction chamber 14 is deformed by adjusting the air chamber 5, to ensure that the drug and bacteria are in full contact and maintain a stable reaction environment. The reaction time is set to 6 hours.

[0109] (4) Real-time monitoring

[0110] The basic situation of the bacteria and metabolic parameters (such as pH change, oxygen consumption) are observed in real time through a microscope and a sensor.

[0111] (5) Experiment end and cleaning

[0112] The residual cells and reaction liquid are completely discharged by deforming the elastic membrane 17, and the reaction chamber 14 is cleaned for repeated use.

[0113] The experimental data and result analysis are shown in Tables 3 and 4:

[0114] Table 3 Bacterial growth inhibition rate

[0115]

[0116] Metabolic data statistics

[0117]

[0118] Bacterial growth inhibition effect: Vancomycin has the strongest bacteriostatic effect at a low concentration (10 μg / mL), with an inhibition rate close to 90%, and almost completely inhibits bacterial growth (99.1%) at 100 μg / mL. Ceftriaxone is second, and ampicillin achieves significant bacteriostatic effect (94.2%) only at a high concentration (100 μg / mL).

[0119] Metabolic activity analysis:

[0120] Increasing the concentration of the drug significantly reduces the metabolic activity of the bacteria. Vancomycin has already reduced the oxygen consumption rate by 73.9% at a concentration of 10 μg / mL, while ampicillin needs to reach 100 μg / mL to achieve a similar effect.

[0121] Drug efficacy comparison: Vancomycin showed the best antibacterial effect, and the metabolic inhibition was obvious, which was the most effective antibacterial drug among the three drugs; Ceftriaxone was the second, and Ampicillin had relatively weak effect.

[0122] Conclusion: The microfluidic chip-based antibacterial drug screening experiment provides an efficient and accurate screening platform. Vancomycin shows excellent antibacterial effect at low concentration, and is suitable for clinical drug selection. The experimental results provide data support for subsequent drug research and optimization of treatment plan.

[0123] It should be understood that the above specific embodiments of the present application are only used for illustrative or explanatory purposes of the principles of the present application, and do not constitute a limitation of the present application. Therefore, any modification, equivalent replacement, improvement, etc. made without departing from the spirit and scope of the present application shall be included in the protection scope of the present application. In addition, the claims attached to the present application are intended to cover all variations and modifications falling within the scope and boundary of the appended claims, or the equivalent forms of such scope and boundary.

Claims

1. A microfluidic chip, characterized by, The chip base (7) is divided into an input layer, a reaction layer and a driving layer from top to bottom. The input layer is provided with a first liquid inlet hole (1), a first liquid outlet hole (2), a plurality of second liquid inlet holes (3) and a plurality of second liquid outlet holes (4); the reaction layer is provided with a main flow channel (8), a plurality of first micro-fluidic channels (9), a plurality of second micro-fluidic channels (11), a plurality of fusion liquid channels (13), a plurality of discharge liquid channels (16) and a plurality of reaction chambers (14); and the driving layer is provided with an air chamber (5) and an air inlet (6) of the air chamber (5). One end of the main flow channel (8) is communicated with the first liquid inlet hole (1), and the other end is communicated with the first liquid outlet hole (2). The inlet end of each of the plurality of first micro-fluidic channels (9) is communicated with the main flow channel (8); and the inlet end of each of the plurality of second micro-fluidic channels (11) is communicated with one of the second liquid inlet holes (3). The outlet of each of the first micro-fluidic channels (9) and the outlet of one of the second micro-fluidic channels (11) are communicated with the inlet end of one of the fusion liquid channels (13), and the outlet end of the fusion liquid channel (13) is communicated with one of the reaction chambers (14); and each of the first micro-fluidic channels (9) and the second micro-fluidic channels (11) is provided with a micro-fluidic channel electric micro valve (10), which can form a micro droplet of solution. The outlet end of the reaction chamber (14) is communicated with the inlet end of the discharge liquid channel (16), and the outlet end of the discharge liquid channel (16) is communicated with the second liquid outlet hole (4). The bottom of the reaction chamber (14) is composed of an elastic film (17), and the air chamber (5) is located below the elastic film (17). At least the portion above the reaction chamber (14) in the input layer is made of transparent material. The air inlet (6) is connected with a micro air pump, and the micro air pump is used to vibrate the elastic film (17).

2. The microfluidic chip of claim 1, wherein, Further comprising an external circulation pipeline.

3. The microfluidic chip of claim 1, wherein, The two ends of the external circulation pipeline are respectively communicated with the inlet of the first liquid inlet hole (1) and the outlet of the first liquid outlet hole (2). The external circulation pipeline is provided with a liquid inlet and a circulation pump. The outlet end of the reaction chamber (14) is provided with a discharge micro electric valve (18).

4. The microfluidic chip of claim 1, wherein, The inlet of the reaction chamber (14) is located at the upper portion, and the outlet is located at the lower portion.

5. The microfluidic chip of claim 1, wherein, The first micro-fluidic channels (9), the second micro-fluidic channels (11), the fusion liquid channels (13), the discharge liquid channels (16) and the reaction chambers (14) are all even in number and are symmetrically arranged on both sides of the main flow channel (8).

6. The microfluidic chip of claim 1, wherein, The chip base (7) is made of transparent material.

7. The microfluidic chip of claim 1, wherein, The elastic film (17) is made of polydimethylsiloxane.

8. The microfluidic chip of claim 1, wherein, The outlet of each of the first micro-fluidic channels (9) and the outlets of the plurality of second micro-fluidic channels (11) are communicated with the inlet end of one of the fusion liquid channels (13), and the outlet end of the fusion liquid channel (13) is communicated with one of the reaction chambers (14).

9. The microfluidic chip of claim 1, wherein, The air chamber (5) and the air inlet (6) are both provided with a plurality of air chambers (5); and one air chamber (5) is arranged below each of the reaction chambers (14).

10. The microfluidic chip of claim 1, wherein, ​

Images