CN117537875A - Micro-flow measurement system and method based on micro-flow control chip - Google Patents
Micro-flow measurement system and method based on micro-flow control chip Download PDFInfo
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
- G01F1/00—Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
- G01F25/00—Testing or calibration of apparatus for measuring volume, volume flow or liquid level or for metering by volume
- G01F25/10—Testing or calibration of apparatus for measuring volume, volume flow or liquid level or for metering by volume of flowmeters
Abstract
The invention discloses a micro-flow measuring system and a method based on a micro-flow control chip, wherein the measuring system comprises the micro-flow control chip, a power mechanism, an object image acquisition mechanism and an analysis mechanism, and the micro-flow control chip is provided with a first flow channel, a second flow channel and a third flow channel; the measurement method is performed using a measurement system. The flow of the disperse phase fluid is calculated by the analysis mechanism according to the motion parameters of the microfluidic monomers, the analysis mechanism can be suitable for detecting different types of microfluidics, and the analysis mechanism can accurately reflect the actual flow of the solution according to the flow value obtained by the microfluidic monomer form and the motion parameters, so that the measurement accuracy of the microfluidic flow is improved.
Description
Technical Field
The invention relates to the technical field of micro-flow detection, in particular to a micro-flow measurement system and method based on a micro-flow control chip.
Background
The flow detection can perform quantitative analysis and study the fluid flow property in a microfluidic system, is important in microfluidic experiments, and because the microfluid flows at a scale similar to a micron, in the related art, the precision of a micro flowmeter adopted in a microfluidic laboratory is not high, the detection of the flow of the microfluid is inaccurate, the measurement principles of different flowmeters are different, the detection requirements of different types of microfluidic flows cannot be met, and the measurement of the microfluidic flow in the laboratory is limited.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems existing in the prior art. Therefore, the invention provides a micro-flow measurement system based on a micro-fluidic chip, which can improve the measurement accuracy of micro-fluid flow and is applicable to detection of different types of micro-fluid.
The invention also provides a measuring method of the micro-flow measuring system based on the micro-flow control chip.
According to an embodiment of the first aspect of the present invention, a microfluidic chip-based micro-flow measurement system includes:
the microfluidic chip is provided with a first flow channel, a second flow channel and a third flow channel, wherein the first flow channel is used for introducing disperse phase fluid, the second flow channel is used for introducing continuous phase fluid, and the third flow channel is provided with an intersection for allowing the disperse phase fluid and the continuous phase fluid to enter;
the power mechanism is used for providing power for the flow of the disperse phase fluid and the continuous phase fluid, so that the disperse phase fluid and the continuous phase fluid enter the third flow channel from the intersection through the flow, and the disperse phase fluid forms a plurality of micro-flow monomers and is dispersed in the continuous phase fluid;
the object image acquisition mechanism is used for acquiring the instantaneous form and motion information of the microfluidic monomer and forming object image information;
and the analysis mechanism is in communication connection with the object image acquisition mechanism, receives the object image information, recognizes the motion parameters of the microfluidic monomers according to the object image information, and calculates the flow of the disperse phase fluid.
The micro-flow measuring system based on the micro-fluidic chip provided by the embodiment of the invention has at least the following beneficial effects:
according to the invention, the immiscible two-phase fluid is introduced into the microfluidic chip, the disperse phase fluid and the continuous phase fluid are converged at the intersection and enter the third flow channel through the intersection under the power provided by the power mechanism, the disperse phase fluid forms a micro-flow monomer in the third flow channel, the object image acquisition mechanism acquires the instantaneous form and the motion information of the micro-flow monomer and transmits the instantaneous form and the motion information to the analysis mechanism, the analysis mechanism calculates the flow of the disperse phase fluid according to the motion parameters of the micro-flow monomer, so that the measurement system can be suitable for detecting micro-fluids of different types, and the analysis mechanism can accurately reflect the actual flow of the solution according to the flow value obtained according to the form and the motion parameters of the micro-flow monomer, thereby improving the measurement accuracy of the measurement system on the micro-flow of the micro-fluid.
According to some embodiments of the invention, a flow direction of the dispersed phase fluid and the continuous phase fluid within the third flow channel is defined as a first direction;
the projected area of the intersection formed on a plane perpendicular to the first direction is smaller than the projected area of the third flow passage formed on a plane perpendicular to the first direction;
and/or a projection of the intersection on a plane perpendicular to the first direction is located at a center of a projection of the third flow passage on a plane perpendicular to the first direction.
According to some embodiments of the invention, the second flow channel comprises a first branch and a second branch, the first branch and the second branch are respectively arranged at two sides of the first flow channel, continuous phase fluid in the first branch and the second branch both flow towards an outlet of the first flow channel, and the outlet of the first flow channel faces the intersection.
According to some embodiments of the invention, the power mechanism includes a first pressure pump and a second pressure pump, the first pressure pump being configured to pump a disperse phase fluid into a first flow channel and cause the disperse phase fluid to flow within the first flow channel; the second pressure pump is used for pumping continuous phase fluid into a second flow channel and enabling the continuous phase fluid to flow in the second flow channel.
According to some embodiments of the invention, the system further comprises a flow meter in communication with the analysis mechanism, the analysis mechanism being capable of calibrating the flow meter based on the calculated flow information.
According to a second aspect of the present invention, a microfluidic chip-based micro-flow measurement method is performed by using the microfluidic chip-based micro-flow measurement system of the first aspect, and includes:
feeding liquid: introducing a disperse phase fluid into the first flow channel and a continuous phase fluid into the second flow channel, driving the disperse phase fluid and the continuous phase fluid to enter the third flow channel through the intersection by a power mechanism, wherein the disperse phase fluid forms a plurality of micro-flow monomers and is dispersed in the continuous phase fluid;
object image acquisition: in the process of forming and flowing the micro-flow monomer, the object image acquisition mechanism acquires instantaneous form and motion information of the micro-flow monomer and forms object image information;
flow calculation: the analysis mechanism identifies the motion parameters of the microfluidic monomers according to the object image information and calculates the flow rate of the disperse phase fluid.
According to some embodiments of the invention, the step of feeding the liquid comprises:
the power mechanism comprises a pressure pump, the pressure pump pumps disperse phase fluid and continuous phase fluid into the microfluidic chip, and the required flow rate of the disperse phase fluid is set;
the flow calculation step further includes: and when the flow rate of the disperse phase fluid calculated by the analysis mechanism reaches a set value, the pressure pump stops working.
According to some embodiments of the invention, the object image acquisition step comprises: the object image acquisition mechanism shoots the generation process of the micro-flow monomer in time t; the flow calculation step includes: the analysis mechanism performs image processing on the object image information, and the motion parameters at least comprise the shape and the generation time of the microfluidic monomers.
According to some embodiments of the invention, the flow calculating step comprises:
Q 1 =n×v×t, where Q 1 And n is the number of the microfluidic monomers formed in the time t, and V is the volume of the microfluidic monomers.
According to some embodiments of the invention, further comprising:
calibrating: the flowmeter is arranged to be in communication connection with the analysis mechanism, and the analysis mechanism calibrates the flowmeter according to the calculated flow information.
Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.
Drawings
The invention is further described with reference to the accompanying drawings and examples, in which:
FIG. 1 is a schematic diagram of an embodiment of a microfluidic chip-based microfluidic measurement system according to the present invention;
FIG. 2 is a cross-sectional view of one embodiment of the microfluidic chip of FIG. 1;
FIG. 3 is a schematic representation of the formation of microfluidic monomers;
FIG. 4 is a flow meter calibration simulation of a dispersed phase fluid;
FIG. 5 is a flow meter calibration simulation of a continuous phase fluid.
Reference numerals:
the microfluidic chip 100, the first flow channel 110, the second flow channel 120, the first branch 121, the second branch 122, the third flow channel 130, the intersection 140, the first sample inlet 150, the second sample inlet 160 and the sample outlet 170; a power mechanism 200, a first pressure pump 210, a second pressure pump 220; an object image acquisition mechanism 300, a microscope 310, a high speed camera 320, a stage 330; an analysis mechanism 400; a collection container 500; a delivery line 600; a storage container 700; a flow meter 800.
Detailed Description
Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to like or similar elements or elements having like or similar functions throughout. The embodiments described below by referring to the drawings are illustrative only and are not to be construed as limiting the invention.
In the description of the present invention, it should be understood that references to orientation descriptions such as upper, lower, front, rear, left, right, etc. are based on the orientation or positional relationship shown in the drawings, are merely for convenience of description of the present invention and to simplify the description, and do not indicate or imply that the apparatus or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus should not be construed as limiting the present invention.
In the description of the present invention, the meaning of a number is one or more, the meaning of a number is two or more, and greater than, less than, exceeding, etc. are understood to exclude the present number, and the meaning of a number is understood to include the present number. The description of the first and second is for the purpose of distinguishing between technical features only and should not be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.
In the description of the present invention, unless explicitly defined otherwise, terms such as arrangement, installation, connection, etc. should be construed broadly and the specific meaning of the terms in the present invention can be reasonably determined by a person skilled in the art in combination with the specific contents of the technical scheme.
In the description of the present invention, the descriptions of the terms "one embodiment," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
In an embodiment of the present invention, a micro-flow measurement system (hereinafter referred to as a measurement system) based on a micro-fluidic chip 100 is provided, and referring to fig. 1 and 2, the measurement system includes a micro-fluidic chip 100, a power mechanism 200, a physical image acquisition mechanism 300, and an analysis mechanism 400, the micro-fluidic chip 100 has a first flow channel 110, a second flow channel 120, and a third flow channel 130, the first flow channel 110 is used for introducing a dispersed phase fluid, and the dispersed phase fluid can flow in the first flow channel 110, the second flow channel 120 is used for introducing a continuous phase fluid, and the continuous phase fluid can flow in the second flow channel 120, and the third flow channel 130 has an intersection 140 for the dispersed phase fluid and the continuous phase fluid to enter. The power mechanism 200 is configured to provide power for the flow of the dispersed phase fluid and the continuous phase fluid, so that the dispersed phase fluid and the continuous phase fluid are driven to flow to the intersection 140 and enter the third flow channel 130 through the intersection 140; referring to fig. 3, when the dispersed phase fluid and the continuous phase fluid enter the third flow channel 130 through the intersection 140, the dispersed phase fluid and the continuous phase fluid are converged at the intersection 140, the continuous phase fluid intercepts the dispersed phase fluid, and the dispersed phase fluid forms a plurality of microfluidic monomers 10 in the third flow channel 130 and is dispersed in the continuous phase fluid.
The object image obtaining mechanism 300 is used for obtaining instantaneous form and motion information of the microfluidic cell 10, and forming object image information, and transmitting the object image information to the analyzing mechanism 400, wherein the analyzing mechanism 400 is in communication connection with the object image obtaining mechanism 300, and receives the object image information, the communication connection is not limited to wire connection, bluetooth, wiFi, infrared docking and the like, and the analyzing mechanism 400 recognizes motion parameters of the microfluidic cell 10 according to the object image information, and calculates flow rates of the dispersed phase fluid and the continuous phase fluid. The analysis mechanism 400 obtains the shape of the microfluidic cell 10 according to the shape of the microfluidic cell 10 in the object image information, and obtains the number of the microfluidic cell 10 formed in a certain period according to the motion information of the microfluidic cell 10 in the object image information, and the analysis mechanism 400 obtains the volumes of the microfluidic cell 10 according to the shape of the microfluidic cell 10, wherein the sum of the volumes of all the microfluidic cell 10 formed in the period is the flow rate of the disperse phase fluid in the period.
It will be appreciated that the flow rate of the dispersed phase fluid is not limited to the above manner, for example, the dispersed phase fluid may be further obtained by providing a collection container 500 at the outlet of the third flow channel 130, where the collection container 500 is used for collecting the microfluidic monomer 10 and the continuous phase fluid entering the third flow channel 130 in a certain period of time, obtaining the form and the number of the microfluidic monomer 10 in the collection container 500, and calculating the sum of the volumes of the microfluidic monomer 10 in the collection container 500 to obtain the flow rate of the dispersed phase fluid in the time.
Therefore, the invention utilizes the two-phase fluid which are not mutually dissolved to be introduced into the microfluidic chip 100, the disperse phase fluid and the continuous phase fluid are converged at the intersection 140 and enter the third flow channel 130 through the intersection 140 under the power provided by the power mechanism 200, the disperse phase fluid forms the microfluidic monomer 10 in the third flow channel 130, the object image acquisition mechanism 300 acquires the instantaneous form and the motion information of the microfluidic monomer 10 and transmits the instantaneous form and the motion information to the analysis mechanism 400, the analysis mechanism 400 calculates the flow of the disperse phase fluid according to the motion parameters of the microfluidic monomer 10, so that the measurement system can be suitable for detecting different types of microfluid, and the analysis mechanism 400 calculates the actual flow of the reaction solution according to the form of the microfluidic monomer 10 and the flow value obtained by the motion parameters, thereby improving the measurement accuracy of the measurement system on the microfluidic flow.
It should be noted that the fluid to which the measurement system of the present invention is directed may be a gas or a liquid, and the dispersed phase fluid is not limited to a single-component liquid, a multi-component liquid, air, a single-component gas, a mixed gas, and the like, and the continuous phase fluid is not limited to a single-component liquid, a multi-component liquid, and the like. When the dispersed phase fluid is a gas, the dispersed phase fluid is subjected to the interfacial tension with the continuous phase fluid to generate micro-bubbles when entering the third flow channel 130 through the intersection 140, and when the dispersed phase fluid is a liquid, the dispersed phase fluid is subjected to the interfacial tension with the continuous phase fluid to generate micro-droplets when entering the third flow channel through the intersection 140. That is, the microfluidic cell 10 may be a microbubble or a microdroplet, and since the two-phase fluid is not miscible, there is a clear boundary between the microfluidic cell 10 and the continuous phase fluid, so that the object image acquisition mechanism 300 can acquire clear and precise object image information.
In addition, the analysis mechanism 400 of the present invention is also capable of calculating the flow rate of the continuous phase fluid. Illustratively, the continuous phase fluid is contained within a reservoir and is input from the reservoir into the microfluidic chip 100, and the analysis mechanism 400 obtains the flow rate of the continuous phase fluid over a period of time by taking the difference in volume of the liquid within the reservoir before and after that period of time. Alternatively, the analysis means 400 obtains the difference in weight of the continuous phase fluid before and after a certain period of time, and obtains the flow rate of the continuous phase fluid before and after the certain period of time by combining the density of the continuous phase fluid. It can be appreciated that the acquisition of the continuous phase fluid gravimetric check can be achieved by placing the reservoir on a balance or the like having a weighing function; the continuous phase volume change can be obtained by pre-obtaining the sectional area of the inner cavity of the liquid storage tank, detecting the liquid level of the continuous phase fluid in the liquid storage tank through a liquid level meter, and obtaining the liquid level difference before and after a certain period of time, thereby obtaining the volume difference of the continuous phase fluid before and after the certain period of time.
It should be noted that, compared with the flow rate of the dispersed phase fluid, the flow rate of the continuous phase fluid is larger, and for the dispersed phase fluid with smaller flow rate and less obvious weight change before and after the measurement period, the simple comparison of the weight and the volume before and after a certain period is not applicable, and the shorter the measurement period is, the smaller the flow rate of the dispersed phase fluid is, and the larger the error is generated; conventional flowmeters can only detect common fluids, such as water, ethanol, and the like, and for fluids with complex components, the fluid flow characteristics are affected by viscosity, temperature, and other factors, and conventional flowmeters cannot realize accurate detection. The mode of acquiring the form and motion information of the microfluidic monomer 10 to calculate the microfluidic flow is not limited by the microfluidic flow, the microfluidic flow characteristics and the microfluidic type, and can meet the measurement requirement of the microfluidic flow under a small scale (such as tens to hundreds of micrometers).
The object image obtaining mechanism 300 may include a microscope 310, and the form and flow of the microfluidic monomer may be observed by the microscope 310, and the object image obtaining mechanism 300 may also select a high-speed camera 320, where the high-speed camera 320 has the characteristics of high frame rate, short exposure time and high resolution, and may capture the instantaneous form and movement information of the microfluidic monomer 10; for example, before the object image information is acquired, the coarse focusing spiral and the fine focusing spiral of the high-speed camera 320 are adjusted, and the proper light source intensity and the shooting frame rate are adjusted, so that the shooting area of the high-speed camera is provided with a two-phase fluid interface with clear outline, the micro-fluid monomer 10 and the continuous phase fluid in the image shot by the high-speed camera 320 are ensured to have higher contrast, and the acquisition precision of the object image information is improved. After the two-phase fluid starts flowing, the generation state of the micro-fluid monomer 10 is observed in real time through the high-speed camera 320, after the generation state of the micro-fluid monomer 10 is stable, the high-speed camera 320 acquires object image information, and the high-speed camera 320 shoots and records the generation process of the micro-fluid monomer 10 in a certain time period to form the object image information. The object image obtaining mechanism 300 is further provided with a platform 330 for placing the microfluidic chip 100, so that the microfluidic chip 100 keeps stable in position in the measuring process, and a height camera shoots towards the microfluidic chip 100; the stage 330 may move along at least one direction to ensure that the photographing region of the high-speed camera 320 can cover the microfluidic chip 100 and can acquire the form and motion information of the microfluidic cell 10.
The analysis means 400 is not limited to an industrial personal computer, a PLC analysis module, or the like provided with data analysis and signal transmission functions, and the analysis means 400 receives and analyzes the object image information after the object image acquisition means 300 has completed the object image acquisition. Illustratively, an image processing module is preset in the analysis mechanism 400, and performs image analysis and processing on object image information, and extracts parameters such as the shape (including, but not limited to, diameter, height, width, etc.) of the microfluidic cell 10 and the time interval at which the microfluidic cell 10 is formed; a preset calculation module in the analysis mechanism 400 calculates the volume of a single microfluidic monomer 10 according to the shape parameters of the microfluidic monomer 10, and obtains 10 numbers of the microfluidic monomer 10 formed in a certain time through the formation time interval of the microfluidic monomer 10, wherein the volume of the microfluidic monomer 10 in the time period is the flow rate of the disperse phase fluid in the time period; the analysis mechanism 400 obtains the flow rate of the continuous phase fluid over a period of time by taking the volume difference of the continuous phase fluid before and after the period of time.
It can be appreciated that, in order to facilitate the object image obtaining mechanism 300 to observe the formation state of the microfluidic cell 10, the microfluidic chip 100 is made of transparent or semitransparent material, so that the object image obtaining mechanism 300 can obtain object image information of a relatively clear two-phase solution through shooting, which is beneficial to improving the recognition precision of the motion parameters of the microfluidic cell 10 and the calculation precision of the flow of the dispersed phase fluid by the analysis mechanism 400.
In the conventional microfluidic chip 100, due to the structural limitation inside the chip, the formed micro droplets can only be in a thin pancake shape, which results in inconsistent diameter and height of the micro droplets after entering the third flow channel 130, large error in shape and volume measurement of the micro droplets, and relatively complex and expensive chip fabrication. The microfluidic chip 100 is formed in a 3D printing mode, is simple and convenient to manufacture, can form a complex microfluidic channel inside the chip, can flexibly adjust the size and shape of the channel, and is convenient to control the channel precision. The microfluidic chip 100 may be made of a translucent resin material; after the chip is prepared, post-treatment, such as washing uncured resin material in a micro flow channel in the chip with absolute ethyl alcohol, can be performed to make the chip transparent so as to observe the generation and flow process of the micro flow monomer 10 and identify the outline of the micro flow monomer 10.
Defining the flow direction of the dispersed phase fluid and the continuous phase fluid in the third flow channel 130 as a first direction, in one embodiment of the present invention, a projected area of the intersection 140 formed on a plane perpendicular to the first direction is smaller than a projected area of the third flow channel 130 formed on a plane perpendicular to the first direction; in this way, when the disperse phase fluid and the continuous phase fluid pass through the intersection 140, the disperse phase fluid is intercepted by the continuous phase fluid, the fluid is greatly influenced by the surface tension in the microfluidic chip 100 and is far greater than the gravity of the fluid, after the disperse phase fluid enters the third flow channel 130, the disperse phase fluid is freely diffused under the action of the tension on the interface between the disperse phase fluid and the continuous phase fluid due to the expansion of the channel section, and the approximately spherical microfluidic monomer 10 is formed, so that the actual fluid drop or bubble form can be simulated, the volume calculation error of the microfluidic monomer 10 is reduced, and the micro-flow measurement accuracy is improved.
In addition, the projection of the intersection 140 formed on the plane perpendicular to the first direction is disposed at the center of the projection of the third flow passage 130 formed on the plane perpendicular to the first direction in the present invention; in this way, after the dispersed phase fluid is intercepted by the continuous phase fluid and enters the third flow channel 130, the dispersed phase fluid can be uniformly dispersed to the periphery, so that the microfluidic cell 10 is maximally approximately spherical, and the volume and flow calculation errors are further reduced.
In one embodiment, the intersection 140 and the third flow channel 130 are formed with a circular or regular polygon in projection on a plane perpendicular to the first direction; the initial form of the microfluidic monomer 10 formed after the dispersed phase fluid is cut off when entering the third fluid channel through the intersection 140 is a more regular form, and as the microfluidic monomer 10 continuously flows and diffuses in the third fluid channel, the microfluidic monomer 10 can maximally approach to a sphere under the action of interfacial tension, so that the volume of the microfluidic monomer 10 and the flow calculation error of the microfluidic can be further reduced.
In the present invention, the second flow channel 120 includes a first branch 121 and a second branch 122, the first branch 121 and the second branch 122 are disposed on two sides of the first flow channel 110, the continuous phase fluid in the first branch 121 and the second branch 122 both flow towards the outlet of the first flow channel 110, and the outlet of the first flow channel 110 faces the intersection 140. The continuous phase fluid in the first branch 121 and the continuous phase fluid in the second branch 122 are oppositely extruded to separate the continuous phase fluid and form the microfluidic cell 10, so that the microfluidic cell 10 is formed more efficiently, and the formed microfluidic cell 10 is more regular in shape due to the opposite separation of the continuous phase fluid, which is beneficial to the later diffusion into a sphere.
The size and shape of the microfluidic cell 10 are related to the shape and size of the first flow channel 110, the second flow channel 120, the third flow channel 130, and the intersection 140, and the size and shape of the microfluidic cell 10 can be adjusted by changing parameters such as the cross-sectional shapes and sizes of the first flow channel 110, the second flow channel 120, the third flow channel 130, and the intersection 140. The second flow channel 120 is configured to include two branches, so that the size and shape of the microfluidic cell 10 are more controllable by amplifying the relevant factors of the size and shape adjustment of the microfluidic cell 10, and the formation of the spherical microfluidic cell 10 is facilitated.
Further, by changing the parameters such as the cross-sectional shapes and the sizes of the first flow channel 110, the second flow channel 120, the third flow channel 130 and the intersection 140, the micro-flow monomers 10 can flow in parallel in the third flow channel 130, and the micro-flow monomers 10 formed in sequence enter the third flow channel 130 one by one and are arranged at intervals along the first direction, so that the micro-flow monomers 10 are prevented from blocking each other, and the object image obtaining mechanism 300 can obtain a relatively clear profile of the micro-flow monomers 10.
The microfluidic chip 100 further comprises a first sample inlet 150 and a second sample inlet 160, wherein the first sample inlet 150 is communicated with the first flow channel 110, the second sample inlet 160 is communicated with the second flow channel 120, the disperse phase fluid enters the first flow channel 110 through the first sample inlet 150, and the continuous phase fluid enters the second flow channel 120 through the second sample inlet 160; the microfluidic chip 100 may further include a sample outlet 170, where the sample outlet 170 is connected to an outlet of the third flow channel 130, so that the continuous phase fluid entering the third flow channel 130 flows out with the microfluidic cell 10. The measurement system further comprises a conveying pipeline 600 and a storage container 700, wherein a plurality of storage containers 700 can be arranged, and the storage container 700 is used for containing dispersed phase fluid, continuous phase fluid and mixed fluid of micro-fluid monomers 10 and continuous phase fluid discharged through the third flow channel 130; taking the dispersed phase fluid as an example, the dispersed phase fluid is stored in the storage container 700, one end of the conveying pipeline 600 is connected with the storage container 700, the other end of the conveying pipeline 600 is communicated with the first sample inlet 150, and the dispersed phase fluid is conveyed to the first flow channel 110 through the conveying pipeline 600 and the first sample inlet 150.
The power mechanism 200 of the present invention includes a first pressure pump 210 and a second pressure pump 220, wherein the first pressure pump 210 is used for pumping the disperse phase fluid into the first flow channel 110 and making the disperse phase fluid flow in the first flow channel 110, and the second pressure pump 220 is used for pumping the continuous phase fluid into the second flow channel 120 and making the continuous phase fluid flow in the second flow channel 120. Compared with the traditional injection pump, peristaltic pump, centrifugal drive and other modes, the pressure pump can provide stable and adjustable pressure, can accurately control the fluid flow rate, provides flow power for fluid through the pressure pump, ensures that the flow control of the whole system is more stable, and can ensure the reliability of fluid calculation results.
Specifically, taking the dispersed phase fluid as an example, the first pressure pump 210 is connected to the conveying pipeline 600, and under the power provided by the first pressure pump 210, the dispersed phase fluid in the storage container 700 enters the conveying pipeline 600 and enters the first flow channel 110 through the first sample inlet 150.
It will be appreciated that the first pressure pump 210 may be communicatively connected to the analysis mechanism 400, and the required flow rate of the dispersed phase fluid may be input to the analysis mechanism 400 in advance before the measurement is performed, and when the flow rate calculated by the analysis mechanism 400 reaches the set value, the analysis mechanism 400 sends an instruction to the first pressure pump 210 to stop the operation of the first pressure pump 210, and the dispersed phase fluid and the continuous phase fluid stop flowing into the third flow channel 130, so that the dispersed phase fluid with the required flow rate is obtained through the third flow channel 130.
In one embodiment of the present invention, the measurement system further includes a flowmeter 800, where the flowmeter 800 is communicatively connected to the analysis mechanism 400, and the analysis mechanism 400 can calibrate the flowmeter 800 according to the calculated flow information, so that the flowmeter 800 can be suitable for micro-flow detection of different types of fluids, and the detection accuracy of the flowmeter 800 is improved. It can be appreciated that the conventional flowmeter can only detect conventional fluids (such as water, ethanol, etc.), and the accuracy of detecting the fluid of complex components is not high, in this embodiment, the measurement system can not only accurately detect the micro-fluid, but also calibrate the flowmeter with the detected flow value, so that the flowmeter can be applied to the corresponding type of fluid detection later. The flow meter marked in the embodiment is used for detecting the fluid flow, so that the detection cost can be reduced, and the detection precision requirement of micro-flow can be met.
The calibration curve of the flowmeter 800 is simulated using the continuous phase fluid as an ethanol solution and the disperse phase fluid as silicone oil as examples. FIG. 4 shows a flow meter calibration simulation curve for a dispersed phase fluid, with the origin of the coordinate system being the initial point for acquiring experimental data, the horizontal axis Q in Vertical axis Q for a predetermined input flow rate out To measure the actual output flow of the system, the different curves represent different types of flow meters 800, respectively, such as curve S for a small flow meter and curve M for a medium flow meter. It will be appreciated that the analysis mechanism 400 can be based on different Q' s in Corresponding Q out Automatically forming a simulated curve of the dispersed phase fluid and attaching to an internal program of the flowmeter 800; q can be enhanced by curve modeling of flowmeter 800 in And Q is equal to out When a certain Q is required out At the time, the corresponding Q is obtained through the simulation curve of the disperse phase fluid in Further, the Q is set in the measurement system in The required Q can be obtained out The operation convenience is high.
Similarly, FIG. 5 is a flow meter calibration simulation curve for a continuous phase fluid, with the origin of the coordinate system being the initial point of the experimental data, the horizontal axis Q in Vertical axis Q for a predetermined input flow rate out To measure the actual output flow of the system, different curves represent different concentrations of ethanol solution, e.g., curve f20 represents 20% ethanol solution and curve f50 represents 50% ethanol solution. It will be appreciated that the analysis mechanism 400 can be based on different Q' s in Corresponding Q out Automatically forming a simulated curve for the continuous phase fluid and attaching to the internal programming of the flowmeter 800; q can be enhanced by curve modeling of flowmeter 800 in And Q is equal to out When a certain Q is required out When the corresponding Q is obtained through the simulation curve of the continuous phase fluid in Further, the Q is set in the measurement system in The required Q can be obtained out Convenient operationThe degree is high.
In some embodiments, the power mechanism 200 and the flowmeter 800 are both in communication connection with the analysis mechanism 400, the flowmeter 800 feeds detected flow data back to the analysis mechanism 400 in real time, the analysis mechanism 400 compares the set flow of the measurement system with the detected data of the flowmeter 800, and adjusts the power mechanism 200; taking the power mechanism 200 as an example, power is provided by the pressure pump, if the detected flow rate of the flowmeter 800 is smaller than the set flow rate, a command is sent to the pressure pump to reduce the pressure of the pressure pump; if the detected flow rate of the flow meter 800 is greater than the set flow rate, a command is sent to the pressure pump to increase the pressure of the pressure pump.
In other embodiments, the power unit 200 is directly connected to the flow meter 800 in a communication manner, and the power unit 200 is powered by a pressure pump, for example, the flow meter 800 feeds the detected flow data back to the pressure pump in real time, if the detected flow is smaller than the set flow, the pressure pump reduces the pressure, and if the detected flow is larger than the set flow, the pressure pump increases the pressure. It will be appreciated that the pressure pump in the power unit 200 is directly connected to the flow meter 800 in a communication manner, the pressure pump can quickly feed back and adjust the system pressure, and the pressure pump and the flow meter can be selected from the group of products to form a measurement system.
The measuring process of the measuring system in the invention is as follows: adjusting the position of the platform 330 to enable the microfluidic chip 100 to be located in a shooting range required by the object image acquisition mechanism 300; adjusting the focal length, light source intensity, etc. of the object image acquisition mechanism 300 to acquire a clear-contoured two-phase fluid interface; the power mechanism 200 provides power for the dispersed phase fluid and the continuous phase fluid, which enter the microfluidic chip 100 and form the microfluidic cell 10 in the third flow channel 130; the object image acquisition mechanism 300 acquires instantaneous form and motion information of the microfluidic cell 10 in a certain period of time and transmits the instantaneous form and motion information to the analysis mechanism 400; the analysis mechanism 400 analyzes the motion parameters of the microfluidic cell 10 and calculates the flow rate of the dispersed phase fluid over the period of time.
The invention also provides a micro-flow measurement method (hereinafter referred to as measurement method) based on the micro-fluidic chip 100, wherein the measurement method is executed by the measurement system and comprises the following steps:
feeding liquid: introducing a disperse phase fluid into the first flow channel 110 and introducing a continuous phase fluid into the second flow channel 120, driving the disperse phase fluid and the continuous phase fluid to flow through the power mechanism 200, and entering the third flow channel 130 through the intersection 140, so that the disperse phase fluid forms a plurality of micro-fluid monomers 10 and is dispersed in the continuous phase fluid;
object image acquisition: in the process of forming and flowing the micro-fluid monomer 10, the object image acquisition mechanism 300 acquires instantaneous form and motion information of the micro-fluid monomer 10 and forms object image information;
flow calculation: analysis mechanism 400 identifies the motion parameters of microfluidic cell 10 based on the object image information and calculates the flow rate of the dispersed phase fluid.
The invention utilizes the two-phase fluid which is not mutually dissolved to be led into the micro-fluidic chip 100, the object image acquisition mechanism 300 acquires the instantaneous form and the motion information of the micro-fluidic monomer 10 and transmits the instantaneous form and the motion information to the analysis mechanism 400, and the analysis mechanism 400 calculates the flow of the disperse phase fluid according to the motion parameters of the micro-fluidic monomer 10, so that the measurement system can be suitable for detecting different types of micro-fluids, and the measurement precision of the flow of the micro-fluid is improved.
Specifically, the microfluidic chip 100 is made of a transparent or semitransparent material by 3D printing, and is cleaned after the preparation is completed. The measuring system is provided with a storage container 700 for storing the disperse phase fluid and the continuous phase fluid respectively, and the power mechanism 200 comprises a pressure pump which provides flowing power for the disperse phase fluid and the continuous phase fluid; before liquid feeding, the prepared disperse phase fluid and continuous phase fluid are respectively added into different storage containers 700, the pressure value of a pressure pump is set, and the set value of the required flow is input into an analysis mechanism 400; adjusting shooting parameters of the object image acquisition mechanism 300, such as focal length, brightness, shooting range and the like, so that a part to be shot of the microfluidic chip 100 is arranged in a shooting area of the object image acquisition mechanism 300; after starting liquid feeding, the generation state of the micro-fluid monomer 10 is observed in real time through the object image acquisition mechanism 300, but after the generation state of the micro-fluid monomer 10 is stable, the object image acquisition mechanism 300 shoots the instantaneous form and the generation process of the micro-fluid monomer 10 in a certain time period to form object image information, and the object image information is transmitted to the analysis mechanism 400; the analysis means 400 performs image analysis and processing on the object image information, and obtains motion parameters such as the shape of the microfluidic element 10, the generation time interval, and the like, and obtains the flow rate of the dispersed phase fluid in the time period from the motion parameters.
In one embodiment, the object image acquisition step includes: the object image acquisition mechanism 300 photographs the generation process of the microfluidic cell 10 within time t; the flow calculation step specifically comprises the following steps: the analysis means 400 performs image processing on the object image information and obtains motion parameters including at least the shape and the generation time of the microfluidic cell 10. The analysis means 400 calculates the volume of the microfluidic cell 10 and the flow rate of the dispersed phase fluid at time t from the shape and the generation time of the microfluidic cell 10.
Specifically, Q 1 =n×v×t, where Q 1 For the flow rate of the dispersed phase fluid over time t, n is the number of microfluidic elements 10 formed over time t and V is the volume of microfluidic elements 10. It can be understood that in the present invention, the microfluidic chip is prepared by a 3D printing method, and is configured by a channel inside the chip, so that the microfluidic chip 10 can be freely diffused and shaped as a sphere after entering the third flow channel 130, in which case, the analysis mechanism 400 can calculate the volume V of the microfluidic chip 10 by processing the image to obtain the diameter of the microfluidic chip 10. When the microfluidic cell 10 is of another shape, such as a cylindrical shape, the analysis mechanism 400 obtains the diameter and the height of the microfluidic cell 10 by a process diagram, so as to calculate the volume V of the microfluidic cell 10.
For continuous phase fluid, analysis mechanism 400 obtains the volume difference DeltaV, then Q for the continuous phase fluid before and after time t 2 =Δv, where Q 2 Is the flow rate of the continuous phase fluid over time t. The Δv may be obtained by weighing a difference in weight of the storage container 700 for storing the continuous phase fluid before and after time t, and obtaining a difference in volume of the continuous phase fluid before and after time t by combining the density of the continuous phase fluid; alternatively, the volume difference of the continuous phase fluid before and after time t is obtained by detecting the liquid level difference of the continuous phase fluid before and after time t in the storage container 700 and combining the sectional area of the inner cavity of the storage container 700.
In the invention, before the object image acquisition mechanism 300 acquires object image information, an object image scale built in the object image acquisition mechanism 300 is calibrated to obtain the proportional relation between the scale and the actual size length, and the relation between the object image size and the actual size is established, so that the actual volume of the microfluidic monomer 10 can be obtained at a later stage.
In the present invention, the power mechanism 200 pumps the disperse phase fluid and the continuous phase fluid into the microfluidic chip 100 in a pressure pump manner, and sets a required flow rate of the disperse phase fluid, and the flow rate calculating step further includes: when the flow rate of the dispersed phase fluid calculated by the analysis means 400 reaches a set value, the analysis means 400 sends a command to the pressure pump to stop the pressure pump, thereby obtaining the dispersed phase fluid at a desired flow rate.
The measuring method further comprises a calibration step for calibrating the flowmeter 800, specifically, the flowmeter 800 is communicatively connected to the analysis mechanism 400, the analysis mechanism 400 can perform data interaction with the flowmeter 800, the analysis mechanism 400 calibrates the flowmeter 800 according to the calculated flow information, so that the flowmeter 800 can be suitable for micro-flow detection of different types of fluids, and the detection precision of the flowmeter 800 is improved. The measuring method not only can accurately detect the microfluid, but also can calibrate the flowmeter 800 by the detected flow value, is convenient for the flowmeter 800 to be applied to the corresponding type of fluid detection in the later period, can reduce the detection cost and meets the detection precision requirement of the microfluid.
The embodiments of the present invention have been described in detail with reference to the accompanying drawings, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge of one of ordinary skill in the art without departing from the spirit of the present invention. Furthermore, embodiments of the invention and features of the embodiments may be combined with each other without conflict.
Claims (10)
1. Micro-flow measurement system based on micro-fluidic chip, characterized by comprising:
the microfluidic chip is provided with a first flow channel, a second flow channel and a third flow channel, wherein the first flow channel is used for introducing disperse phase fluid, the second flow channel is used for introducing continuous phase fluid, and the third flow channel is provided with an intersection for allowing the disperse phase fluid and the continuous phase fluid to enter;
the power mechanism is used for providing power for the flow of the disperse phase fluid and the continuous phase fluid, so that the disperse phase fluid and the continuous phase fluid enter the third flow channel from the intersection through the flow, and the disperse phase fluid forms a plurality of micro-flow monomers and is dispersed in the continuous phase fluid;
the object image acquisition mechanism is used for acquiring the instantaneous form and motion information of the microfluidic monomer and forming object image information;
and the analysis mechanism is in communication connection with the object image acquisition mechanism, receives the object image information, recognizes the motion parameters of the microfluidic monomers according to the object image information, and calculates the flow of the disperse phase fluid.
2. The microfluidic chip-based micro flow measurement system according to claim 1, wherein a flow direction of the dispersed phase fluid and the continuous phase fluid in the third flow channel is defined as a first direction;
the projected area of the intersection formed on a plane perpendicular to the first direction is smaller than the projected area of the third flow passage formed on a plane perpendicular to the first direction;
and/or a projection of the intersection on a plane perpendicular to the first direction is located at a center of a projection of the third flow passage on a plane perpendicular to the first direction.
3. The microfluidic chip-based micro-flow measurement system according to claim 1, wherein the second flow channel comprises a first branch and a second branch, the first branch and the second branch are respectively arranged at two sides of the first flow channel, continuous phase fluids in the first branch and the second branch both flow towards an outlet of the first flow channel, and an outlet of the first flow channel faces the intersection.
4. The microfluidic chip-based micro flow measurement system according to claim 1, wherein the power mechanism comprises a first pressure pump and a second pressure pump, the first pressure pump being configured to pump a disperse phase fluid into a first flow channel and cause the disperse phase fluid to flow in the first flow channel; the second pressure pump is used for pumping continuous phase fluid into a second flow channel and enabling the continuous phase fluid to flow in the second flow channel.
5. The microfluidic chip-based micro-flow measurement system of claim 1, further comprising a flow meter communicatively coupled to the analysis mechanism, the analysis mechanism capable of calibrating the flow meter based on the calculated flow information.
6. A microfluidic chip-based micro flow measurement method, characterized in that it is performed using the microfluidic chip-based micro flow measurement system according to any one of claims 1 to 5, comprising:
feeding liquid: introducing a disperse phase fluid into the first flow channel and a continuous phase fluid into the second flow channel, driving the disperse phase fluid and the continuous phase fluid to enter the third flow channel through the intersection by a power mechanism, wherein the disperse phase fluid forms a plurality of micro-flow monomers and is dispersed in the continuous phase fluid;
object image acquisition: in the process of forming and flowing the micro-flow monomer, the object image acquisition mechanism acquires instantaneous form and motion information of the micro-flow monomer and forms object image information;
flow calculation: the analysis mechanism identifies the motion parameters of the microfluidic monomers according to the object image information and calculates the flow rate of the disperse phase fluid.
7. The microfluidic chip-based micro flow measurement method according to claim 6, wherein the liquid feeding step comprises:
the power mechanism comprises a pressure pump, the pressure pump pumps disperse phase fluid and continuous phase fluid into the microfluidic chip, and the required flow rate of the disperse phase fluid is set;
the flow calculation step further includes: and when the flow rate of the disperse phase fluid calculated by the analysis mechanism reaches a set value, the pressure pump stops working.
8. The microfluidic chip-based micro flow measurement method according to claim 6, wherein the object image acquisition step comprises: the object image acquisition mechanism shoots the generation process of the micro-flow monomer in time t; the flow calculation step includes: the analysis mechanism performs image processing on the object image information, and the motion parameters at least comprise the shape and the generation time of the microfluidic monomers.
9. The microfluidic chip-based micro flow measurement method according to claim 6, wherein the flow calculation step comprises:
Q 1 =n×v×t, where Q 1 And n is the number of the microfluidic monomers formed in the time t, and V is the volume of the microfluidic monomers.
10. The microfluidic chip-based micro flow measurement method according to claim 6, further comprising:
calibrating: the flowmeter is arranged to be in communication connection with the analysis mechanism, and the analysis mechanism calibrates the flowmeter according to the calculated flow information.
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