Liquid micro-flow control system and method and microfluidic detection device

Abstract

The present invention relates to the field of biological fluid detection and analysis technology, and discloses a liquid microflow control system and method, as well as a microfluidic detection device. The system includes: an air compressor, an air pressure controller, and a gas flow controller; the air compressor is connected to a liquid storage device for storing liquid to be processed via a first gas delivery pipeline, and the air compressor is connected in series with the air pressure controller, the gas flow controller, and the liquid storage device in sequence via a second gas delivery pipeline; the air pressure controller is connected to the liquid storage device via a third gas delivery pipeline; control valves are provided on the first gas delivery pipeline, the third gas delivery pipeline, and the second gas delivery pipeline section located between the air pressure controller and the gas flow controller; the air compressor, the air pressure controller, the gas flow controller, and the control valve are respectively connected to the control device signal. The present invention achieves precise control of liquid microflow in a non-contact manner.

Description

Technical Field

[0001] The present invention relates to the technical field of biological fluid detection and analysis, and in particular to a trace liquid flow rate control system and method and a microfluidic detection device. Background Art

[0002] Microfluidics refers to the science and technology involved in systems that use microchannels (with dimensions ranging from tens to hundreds of micrometers) to process or manipulate tiny fluids (with a volume of microliters). It is an emerging interdisciplinary subject involving chemistry, fluid physics, microelectronics, new materials, biology, and biomedical engineering.

[0003] Microfluidics has garnered significant attention in the field of biological fluid biopsy in recent years, with high-precision microfluidic flow rate control being one of the key challenges. Furthermore, the unique nature of fluid biopsy requires rapid, accurate, and non-contact testing. Furthermore, the components of the testing system that come into contact with the fluid are typically consumables, and disposable components often impose higher costs.

[0004] Currently, industry laboratories use semi-automatic syringe pumps that achieve micro-flow rate control through manual settings, which cannot avoid the reuse of syringe pumps. Furthermore, relying on a stepper motor to control the syringe's speed is not only inaccurate but also results in unstable flow rate control during the process, affecting experimental detection results. Furthermore, the motor-propelled syringe method is unable to sense changes in rear-end resistance, making partial blockages impossible to monitor. Therefore, this method is generally used primarily within laboratories, requiring extensive manual labor during the detection process, and is not ideal for large-scale commercialization. Summary of the Invention

[0005] (1) Technical issues to be solved

[0006] The purpose of the present invention is to address the deficiencies of the above-mentioned prior art and to provide a system and method for precisely controlling liquid microflow in a non-contact manner through constant flow air pressure control, as well as a microfluidic detection device.

[0007] (2) Technical solution

[0008] In order to solve the above problems, the present invention provides a liquid micro-flow control system, including: an air compressor, an air pressure controller and a gas flow controller; the air compressor is connected to a liquid storage device for storing liquid to be treated through a first gas delivery pipeline, and the air compressor is connected in series with the air pressure controller, the gas flow controller and the liquid storage device in sequence through a second gas delivery pipeline; the air pressure controller is connected to the liquid storage device through a third gas delivery pipeline; control valves are provided on the first gas delivery pipeline, the third gas delivery pipeline and the second gas delivery pipeline section located between the air pressure controller and the gas flow controller; the air compressor, the air pressure controller, the gas flow controller and the control valve are respectively connected to the control device signal.

[0009] Optionally, it further includes a pressure stabilizing container arranged on the second gas delivery pipeline and connected to the air compressor and the air pressure controller respectively.

[0010] Optionally, it further includes an air pressure sensor connected to the liquid storage device, for detecting the air pressure in the liquid storage device, and the air pressure sensor is connected to the control device signal.

[0011] Optionally, an alarm device is further included, and the alarm device is signal-connected to the control device.

[0012] The present invention also provides a liquid micro-flow control method, using the above-mentioned liquid micro-flow rate control system, comprising the following steps:

[0013] S1. Closing the control valves provided on the second gas delivery pipeline and the third gas delivery pipeline through the control device;

[0014] S2. The container containing the liquid to be tested is sealedly connected to the liquid reservoir via the liquid delivery pipe via the input end of the liquid reservoir; the air compressor is activated by the control device to provide negative pressure to the liquid reservoir via the first gas delivery pipe to pump the liquid to be tested into the liquid reservoir; and then the air compressor is stopped;

[0015] S3, closing the control valve provided on the first gas delivery pipeline by the control device, opening the control valve provided on the third gas delivery pipeline, and starting the air compressor; adjusting the air pressure controller to deliver gas to the liquid storage device so that the air pressure in the liquid storage device reaches a set value;

[0016] S4. Close the control valve provided on the third gas delivery pipeline through the control device, open the control valve provided on the second gas delivery pipeline, deliver gas into the liquid storage at a set flow rate through the gas flow controller, and discharge the liquid to be tested in the liquid storage at a set flow rate.

[0017] Optionally, in step S3, the air compressor is started to deliver gas to the pressure stabilizing container, and then the gas is delivered to the air pressure controller through the pressure stabilizing container.

[0018] Optionally, in step S4, when the air pressure sensor detects that the gas pressure in the liquid storage exceeds a set threshold, the alarm device sounds an alarm through sound and light signals.

[0019] The present invention further provides a microfluidic detection device, comprising the above-mentioned liquid microflow control system and a microfluidic detection package, wherein the microfluidic detection package comprises: a liquid storage device and a microfluidic chip connected to the outlet end of the liquid storage device.

[0020] (3) Beneficial effects

[0021] The liquid microflow control system and method, as well as the microfluidic detection device, provided by the present invention, utilize an air pressure controller and a gas flow controller to achieve precise control of liquid microflow in a non-contact manner. The air pressure controller can rapidly increase the liquid surface pressure of the liquid to be tested in the liquid reservoir, while the gas flow controller can fine-tune the liquid surface pressure of the liquid to be tested in the liquid reservoir. Furthermore, the flow rate of the gas input to the liquid reservoir can be precisely set as needed, thereby precisely controlling the microflow rate of the liquid to be tested in the microfluidic chip. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort.

[0023] Figure 1 Schematic diagram of a liquid micro-flow control system in an embodiment of the present invention;

[0024] Figure 2 4 is a process flow chart of the liquid micro-flow control method in an embodiment of the present invention.

[0025] The reference numerals in the accompanying drawings are:

[0026] 1. Air compressor, 2. Air pressure controller, 3. Gas flow controller, 4. Liquid storage, 5. Pressure-stabilizing container, 6. Air pressure sensor, 7. Microfluidic chip, 10. First gas delivery pipeline, 20. Second gas delivery pipeline, 30. Third gas delivery pipeline, 40. Control valve. DETAILED DESCRIPTION

[0027] The following embodiments of the present invention are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

[0028] like Figure 1 As shown, an embodiment of the present invention provides a liquid micro-flow control system, including: an air compressor 1, an air pressure controller 2 and a gas flow controller 3.

[0029] The air compressor 1 is connected to a liquid storage device 4 for storing liquid to be treated via a first gas delivery pipeline 10. A control valve 40 is provided on the first gas delivery pipeline 10 for controlling the gas transmission in the first gas delivery pipeline 10. The air compressor 1 is connected in series with an air pressure controller 2, a gas flow controller 3, and a liquid storage device 4 via a second gas delivery pipeline 20. A control valve 40 is provided on the section of the second gas delivery pipeline 20 located between the air pressure controller 2 and the gas flow controller 3 for controlling the gas transmission between the air pressure controller 2 and the gas flow controller 3 in the second gas delivery pipeline 20. The air pressure controller 2 is also connected to the liquid storage device 4 via a third gas delivery pipeline 30, thereby providing two parallel gas delivery channels between the air pressure controller 2 and the liquid storage device 4. A control valve 40 is also provided on the third gas delivery pipeline 30 for controlling the gas transmission in the third gas delivery pipeline 30.

[0030] The air compressor 1, the air pressure controller 2, the gas flow controller 3 and the control valve 40 provided on the first, second and third gas delivery pipelines are respectively connected to the control device (not shown in the figure) by signal, so that the control device can control the start, operation and stop of the air compressor 1, the air pressure controller 2 and the gas flow controller 3 and the opening and closing of the control valve 40. In this embodiment, the air compressor 1 can not only provide positive pressure gas to the system, but also form negative pressure in the pipeline in the system; the air pressure controller 2 can be a precision air pressure regulating valve, which obtains a certain air pressure by adjusting the air volume. The gas flow controller 3 can be a constant flow gas flow controller, which can achieve continuous, high-precision, trace gas flow control, for example, 10±0.01 ml / min. The control valve 40 can be a solenoid valve. The control device can be implemented by a single-chip microcomputer, which can achieve a control speed of milliseconds.

[0031] In one embodiment, a pressure stabilizing container 5 is provided between the air compressor 1 and the air pressure controller 2. The pressure stabilizing container 5 is connected to the air compressor 1 and the air pressure controller 2 respectively through a second gas delivery pipeline 20. The pressure stabilizing container 5 can be used to store the gas delivered from the air compressor 1.

[0032] In one embodiment, a pressure sensor 6 is provided in communication with the liquid reservoir 4 for detecting the pressure in the liquid reservoir 4. The pressure sensor 6 is signal-connected to the control device so that the control device can read the pressure data in the liquid reservoir 4 detected by the pressure sensor 6.

[0033] In one embodiment, an alarm device is provided which is connected to the control device signal. When the air pressure value in the liquid storage 4 read by the control device exceeds a set threshold, the control device causes the alarm device to alarm through sound and light signals.

[0034] like Figure 2 As shown, an embodiment of the present invention further provides a liquid micro-flow control method, which uses the above-mentioned liquid micro-flow rate control system and includes the following steps:

[0035] S1. Close the control valves 40 provided on the second gas delivery pipeline 20 and the third gas delivery pipeline 30 through the control device.

[0036] Before step S1, the ends of the first gas delivery pipeline 10, the second gas delivery pipeline 20, and the third gas delivery pipeline 30 are respectively sealed and connected to the liquid reservoir 4 through the input end of the liquid reservoir 4. A predetermined device, such as a quick gas pipe joint, can be used to enable the ends of the first gas delivery pipeline 10, the second gas delivery pipeline 20, and the third gas delivery pipeline 30 to be conveniently and quickly sealed and connected to the input end of the liquid reservoir 4.

[0037] S2. The container containing the liquid to be tested is sealedly connected to the liquid reservoir 4 via the liquid delivery pipe and the input end of the liquid reservoir 4; the air compressor 1 is started by the control device to provide negative pressure to the liquid reservoir 4 via the first gas delivery pipe 10 to pump the liquid to be tested into the liquid reservoir 4; then the air compressor 1 is stopped.

[0038] The container holding the test liquid can be a test tube containing a blood sample. The liquid delivery tube can also be sealed to the input section of the liquid reservoir 4 via a quick-release air pipe connector. The air compressor 1 is activated to expel the gas from the liquid reservoir 4 through the first gas delivery pipe 10, creating a negative pressure within the liquid reservoir 4. The pressure differential then pumps the test liquid from the test tube into the liquid reservoir 4. The control device then stops the air compressor 1.

[0039] S3. Close the control valve 40 provided on the first gas delivery pipeline 10 through the control device, and open the control valve 40 provided on the third gas delivery pipeline 30; start the air compressor 1; adjust the air pressure controller 2 to deliver gas to the liquid storage 4 so that the air pressure in the liquid storage 4 reaches the set value.

[0040] In step S3, the air compressor (1) is started to deliver gas to the pressure-stabilizing container (5), and then the gas is delivered to the air pressure controller (2) through the pressure-stabilizing container (5).

[0041] The control device can be used to close the control valve 40 provided on the first gas delivery pipeline 10, thereby stopping the gas communication between the air compressor 1 and the liquid reservoir 4. The control device starts the air compressor 1 to deliver gas to the pressure-stabilizing container 5. When the gas pressure stored in the pressure-stabilizing container 5 reaches the desired value, the control device can be used to shut down the air compressor 1. Subsequently, only the gas in the pressure-stabilizing container 5 is used to control the flow rate of the liquid to be measured in the liquid reservoir 4. This can reduce the operating time of the air compressor 1.

[0042] The control device opens the control valve 40 on the third gas delivery pipeline 30 and adjusts the air pressure controller 2, allowing the gas in the pressure-stabilizing container 5 to enter the liquid reservoir 4 through the air pressure controller 2 and the third gas delivery pipeline 30. The air pressure controller 2 can adjust the air supply to the liquid reservoir 4 based on the air pressure value fed back from the liquid reservoir 4, thereby adjusting the air pressure in the liquid reservoir 4 until it reaches the set value.

[0043] S4. Close the control valve 40 provided on the third gas delivery pipeline 30 through the control device, open the control valve 40 provided on the second gas delivery pipeline 20, deliver gas to the liquid storage 4 at a set flow rate through the gas flow controller 3, and discharge the liquid to be tested in the liquid storage 4 at a set flow rate.

[0044] The control valve 40 provided on the third gas delivery pipeline 30 is closed to stop the gas supply from the gas pressure controller 2 directly to the liquid reservoir 4. The control valve 40 provided on the second gas delivery pipeline 20 is opened to allow the gas output from the pressure stabilizing container 5 to be input into the liquid reservoir 4 through the gas pressure controller 2 and the gas flow controller 3.

[0045] When the outlet of the liquid storage device 4 is connected to a detection device for performing relevant detection, for example, connected to a microfluidic chip, the liquid to be tested in the liquid storage device 4 flows into the microfluidic chip under the action of pressure. Since the resistance inside the microfluidic chip is constant, controlling the liquid surface pressure of the liquid to be tested in the liquid storage device 4 can control the flow rate of the liquid to be tested in the microfluidic chip. In the enclosed space formed between the liquid surface of the liquid to be tested and the output port of the gas flow controller 3, the liquid surface pressure of the liquid to be tested in the liquid storage device 4 can be fine-tuned by the gas flow controller 3, and the liquid surface pressure can reach a state of equilibrium, that is, the liquid surface pressure remains unchanged. In this state, the volume of gas entering the liquid storage device 4 is equal to the volume of liquid flowing out of the liquid storage device 4. The gas is transported into the liquid storage device 4 at a set flow rate through the gas flow controller 3, so that the liquid to be tested in the liquid storage device 4 flows into the microfluidic chip at a set flow rate.

[0046] The control device can calculate the flow rate of the liquid to be tested based on the liquid surface pressure in the liquid storage 4 detected by the air pressure sensor 6 and the flow rate of the gas output by the gas flow controller 3, or it can control the liquid surface pressure of the liquid to be tested in equilibrium by controlling the flow rate of the gas output by the gas flow controller 3 to control the flow rate of the liquid to be tested.

[0047] The control device sets the gas flow rate input into the liquid reservoir 4 by setting the gas flow controller 3 and measuring the change in the liquid surface pressure per unit time in the liquid reservoir 4. According to the ideal gas state equation, PV = nRT, where P is the liquid surface pressure of the liquid to be tested in the liquid reservoir 4; V is the volume of gas flowing into the liquid reservoir 4 per unit time; n is the number of moles of gas, R is the molar gas constant, and T is the thermodynamic temperature. The actual air gas state equation has a compressibility coefficient Z at room temperature and high pressure, such that PV / nRT = Z. Given a constant compressibility coefficient Z, this formula can be used to calculate the required liquid surface pressure of the liquid to be tested in the liquid reservoir 4 and the flow rate of the gas input to the gas flow controller 3 in order to achieve the set flow rate for the liquid to be tested entering the microfluidic chip. The control device can also rapidly adjust the liquid surface pressure of the liquid to be tested in the liquid reservoir 4 based on the detected flow rate to achieve the set flow rate.

[0048] Assume that the equivalent volume of gas per second flowing into the closed area of ​​the liquid storage 4 through the gas flow controller 3 is V 气 , which can be set by the control device; the current gas volume in the liquid storage 4 is V, and the gas pressure is P. When the pressure difference is very small, assuming that the compression coefficient Z is equal, then

[0049] PV 气 =ΔnRTZ

[0050] Where Δn is the number of moles of gas added;

[0051] P(V+V 气 )=(n+Δn)RTZ

[0052] Where n is the number of moles of gas in the enclosed area of ​​the liquid reservoir 4 before the addition of gas;

[0053] The volume of liquid discharged from the closed area in the liquid reservoir 4 is V 液 After this second, the air pressure in the closed area of ​​the liquid storage 4 becomes P2.

[0054] P2(V+V 液 )=(n+Δn)RTZ

[0055] P2(V+V 液 )=P(V+V 气 )

[0056] V 液 =P(V+V 气 ) / P2-V

[0057] When the closed area in the liquid reservoir 4 is in equilibrium, P2=P, from which it can be concluded that

[0058] V 液 =V 气

[0059] In summary, by controlling the surface pressure of the liquid to be tested in the liquid reservoir 4, the flow rate of the liquid to be tested in the microfluidic chip can be controlled. The surface pressure and liquid flow rate are positively correlated. The ideal gas equation allows for real-time observation of the flow rate, and the speed of the flow rate control response depends on the speed of adjusting the surface pressure. Maintaining constant pressure after reaching the final velocity achieves the desired controlled flow rate. When bubbles, dust, or other particles clog the microfluidic chip, increasing resistance and causing the flow rate of the liquid to be tested to decrease, the surface pressure of the liquid to be tested in the liquid reservoir 4 increases. The air pressure sensor 6 transmits the detected pressure value to the control device. The control device increases the flow rate of the delivered gas through the gas flow controller 3, thereby increasing the pressure and restoring the flow rate of the liquid to be tested to the set flow rate. If the surface pressure of the liquid to be tested in the liquid reservoir 4 continues to increase and exceeds a set threshold, the control device controls the alarm device (not shown) to sound an alarm through an audible and visual signal. Simultaneously, the gas flow controller 3 is controlled to stop delivering gas to the liquid reservoir 4.

[0060] like Figure 1As shown, an embodiment of the present invention further provides a microfluidic detection device, comprising the aforementioned liquid microflow control system and a microfluidic detection package. The microfluidic detection package comprises a liquid reservoir 4 and a microfluidic chip 7 connected to the outlet of the liquid reservoir 4. During the detection process, the microfluidic detection package can be an independent consumable package. By quickly connecting and disconnecting from the liquid microflow control system, it can achieve non-contact and precise control of the liquid microflow during the detection process. Moreover, since the independent consumable package can be produced in large quantities, the cost of the detection is reduced.

[0061] The liquid microflow control system and method and the microfluidic detection device provided by the present invention can achieve precise control of the liquid microflow in a non-contact manner through an air pressure controller and a gas flow controller. The air pressure controller can quickly increase the liquid surface pressure of the liquid to be tested in the liquid storage device, and the gas flow controller can fine-tune the liquid surface pressure of the liquid to be tested in the liquid storage device, and can accurately set the flow rate of the gas input to the liquid storage device as needed, thereby accurately controlling the microflow rate of the liquid to be tested in the microfluidic chip. In addition, the system is small in size and low in power consumption. The microfluidic detection package can be produced in large quantities as an independent consumable package, reducing the cost of detection.

[0062] In the present invention, terms such as "upper", "lower", "left", "right", "front", "back", "vertical", "horizontal", "side", "bottom", etc. indicating directions or positional relationships are based on the directions or positional relationships shown in the accompanying drawings. They are relational words determined only for the convenience of describing the structural relationships of the various parts or elements of the present invention, and do not specifically refer to any part or element in the present invention, and should not be understood as limiting the present invention.

[0063] In the description of the present invention, it should be noted that, unless otherwise expressly specified or limited, the terms "mounted," "connected," and "connected" should be understood in a broad sense. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to mechanical connections or signal connections; they can refer to direct connections or indirect connections through an intermediate medium; and they can refer to internal communication between two components. Those skilled in the art will understand the specific meanings of the above terms in the present invention based on the specific circumstances, and they should not be construed as limitations on the present invention.

[0064] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components and / or combinations thereof.

[0065] The above embodiments are intended to illustrate the present invention only and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the embodiments, it should be understood by those skilled in the art that various combinations, modifications, or equivalent substitutions of the technical solutions of the present invention do not depart from the spirit and scope of the technical solutions of the present invention and should be encompassed by the scope of the claims of the present invention.

Claims

1. A liquid micro-flow control system, characterized in that: include: An air compressor (1), an air pressure controller (2), and a gas flow controller (3); The air compressor (1) is connected to a liquid storage (4) for storing liquid to be treated via a first gas delivery pipeline (10); The air compressor (1) is connected in series with the air pressure controller (2), the gas flow controller (3) and the liquid storage (4) in sequence through a second gas delivery pipeline (20); The air pressure controller (2) is connected to the liquid storage (4) via a third gas delivery pipeline (30); The first gas delivery pipeline (10), the third gas delivery pipeline (30), and the section of the second gas delivery pipeline (20) located between the gas pressure controller (2) and the gas flow controller (3) are provided with a control valve (40); The air compressor (1), the air pressure controller (2), the gas flow controller (3) and the control valve (40) are respectively connected to the control device by signal; The liquid micro-flow control system further comprises an air pressure sensor (6) connected to the liquid storage (4) for detecting the air pressure in the liquid storage (4); the air pressure sensor (6) is signal-connected to the control device.

2. The liquid micro-flow control system according to claim 1, characterized in that: It also includes a pressure stabilizing container (5) arranged on the second gas delivery pipeline (20) and connected to the air compressor (1) and the air pressure controller (2) respectively.

3. The liquid micro-flow control system according to claim 2, characterized in that: It also includes an alarm device, which is connected to the control device by signal.

4. A liquid micro-flow control method, characterized in that: The liquid micro-flow control system according to any one of claims 1 to 3 comprises the following steps: S1. Closing the control valves (40) provided on the second gas delivery pipeline (20) and the third gas delivery pipeline (30) through the control device; S2, the container containing the liquid to be tested is sealedly connected to the liquid storage (4) via the liquid delivery pipe and the input end of the liquid storage (4); the air compressor (1) is started by the control device, and negative pressure is provided to the liquid storage (4) via the first gas delivery pipe (10), so as to pump the liquid to be tested into the liquid storage (4); and then the air compressor (1) is stopped; S3, closing the control valve (40) provided on the first gas delivery pipeline (10) through the control device, opening the control valve (40) provided on the third gas delivery pipeline (30), and starting the air compressor (1); adjusting the air pressure controller (2) to deliver gas into the liquid storage (4) so ​​that the air pressure in the liquid storage (4) reaches a set value; S4. The control valve (40) provided on the third gas delivery pipeline (30) is closed by the control device, the control valve (40) provided on the second gas delivery pipeline (20) is opened, and gas is delivered to the liquid storage (4) at a set flow rate through the gas flow controller (3), and the liquid to be tested in the liquid storage (4) is discharged at a set flow rate.

5. The liquid micro-flow control method according to claim 4, characterized in that: In step S3, the air compressor (1) is started to deliver gas to the pressure-stabilizing container (5), and then the gas is delivered to the air pressure controller (2) through the pressure-stabilizing container (5).

6. The liquid micro-flow control method according to claim 4, characterized in that: In step S4, when the air pressure sensor (6) detects that the gas pressure in the liquid storage (4) exceeds a set threshold, the alarm device sounds an alarm through sound and light signals.

7. A microfluidic detection device, characterized in that: comprising a liquid micro-flow control system and a microfluidic detection package according to any one of claims 1 to 3, The microfluidic detection comprises: a liquid storage (4) and a microfluidic chip (7) connected to the outlet end of the liquid storage (4).

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