Integrated meniscus tracking liquid micro-flow calibration device and use method thereof

Abstract

The invention relates to the technical field of micro-flow calibration, in particular to an integrated meniscus tracking liquid micro-flow calibration device and a using method thereof.The integrated meniscus tracking liquid micro-flow calibration device comprises a meniscus tracking flow calibration chip, a thermostat and a meniscus tracking device, the meniscus tracking flow calibration chip comprises a glass substrate and a PDMS channel bonded to the surface of the glass substrate, and the glass substrate is connected with the thermostat; the glass substrate is attached to a thermostat, the thermostat is used for ensuring that the temperature of the meniscus chip is constant, the meniscus tracking device comprises a linear motion unit and an image acquisition module, the linear motion unit is located below the meniscus chip and is used for tracking the meniscus in the meniscus tracking flow calibration chip, and the image acquisition module is used for acquiring the image of the meniscus in the meniscus tracking flow calibration chip. The image acquisition module is installed on the linear motion unit and used for monitoring the meniscus, the problem of verification and calibration of a liquid micro-flow sensor and a micro-injection pump is solved, and the value traceability of the liquid micro-flow is achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of micro-flow calibration, and particularly relates to an integrated meniscus-tracking liquid micro-flow calibration device and a using method thereof. Background Art

[0002] In terms of liquid flow rate verification and calibration, existing technical solutions are divided into two categories: mass method and volume method. Among them, the mass method is particularly widely used. Its basic principle is to measure the increment of liquid mass per unit time. During the calibration process, the instrument under test is connected in series in a pipeline with a flow generating device and a mass measuring device (such as an electronic scale, a balance, etc.). By comparing the indication change of the mass measuring device per unit time and the measured value of the instrument under test, the measurement accuracy is evaluated. In addition, there is also a liquid flow calibration device based on the volume method. Its principle is to calculate the flow rate according to the volume change of the fluid per unit time. Its typical representative is the volume tube. The volume tube is divided into an active volume tube and a passive volume tube according to different power sources. The former integrates a power source and can itself be used as a flow generating device; the latter is pushed by the fluid to drive a piston, thereby calculating the flow rate. The tube body (cylinder body) of the existing volume tube is generally made of carbon steel or stainless steel, and integrates optoelectronic / mechanical sensing elements to detect the piston displacement.

[0003] However, when the mass method is used for large-flow calibration, the influences of evaporation and slight vibration can be ignored. But when it is used for liquid micro-flow calibration, weak evaporation and slight vibration become non-negligible and become the main factors limiting the device accuracy. The existing volume method liquid flow calibration devices (such as volume tubes) have complex mechanical structures, usually integrating a large number of valves, transmission structures and detection elements. Therefore, the device volume is large, and it is difficult to be further miniaturized to meet the requirements of liquid micro-flow calibration. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide an integrated meniscus-tracking liquid micro-flow calibration device and a using method thereof to solve the current problems in liquid micro-flow verification and calibration.

[0005] Based on the above purpose, the present invention provides an integrated meniscus-tracking liquid micro-flow calibration device, including a meniscus-tracking flow calibration chip, a thermostat and a meniscus-tracking device:

[0006] The meniscus-tracking flow calibration chip includes a glass substrate and a PDMS channel bonded to its surface. The glass substrate is attached to the thermostat, and the thermostat is used to ensure the constant temperature of the meniscus chip.

[0007] The meniscus tracking device includes a linear motion unit and an image acquisition module. The linear motion unit is located below the meniscus chip and is used to track the meniscus in the meniscus tracking flow calibration chip. The image acquisition module is installed on the linear motion unit and is used to monitor the meniscus.

[0008] Preferably, the PDMS channel is a serpentine channel structure, including a micro liquid injection channel, a meniscus measurement channel, and a micro liquid discharge channel. The micro liquid injection channel and the micro liquid discharge channel are respectively connected to both ends of the meniscus measurement channel and are both straight channels. The meniscus measurement channel is composed of a combination of a straight channel and an arc channel.

[0009] Preferably, the thermostat includes a constant temperature water tank, a micro pump, a cooling fan, a return pipe, and an outlet pipe. The constant temperature water tank includes an upper layer and a lower layer, which are separated by a partition and connected at the edge. The micro pump includes two interfaces, which are respectively connected to the return pipe and the outlet pipe. The outlet pipe is connected to the upper layer of the constant temperature water tank in a parallel connection manner at both ends, and the return pipe is connected in parallel to the lower layer of the constant temperature water tank.

[0010] Preferably, the thermostat further includes a cooling fan, and the cooling fan is fixed to the outer wall of the upper layer of the constant temperature water tank through a heat-conducting copper sheet.

[0011] Preferably, the linear motion unit includes a stepper motor and a ball screw. The stepper motor is connected to the image acquisition module through the ball screw, and the ball screw drives the image acquisition module to achieve linear motion.

[0012] Preferably, the PDMS channel is made of a glass capillary, and the preparation method includes:

[0013] Heat-treat the glass capillary in air at 500 °C for 1 hour to remove the residues on the inner wall;

[0014] Hydrophobically treat the glass capillary with an octadecyltrichlorosilane solution. In this process, use a syringe with a hose to slowly inject the OTS solution into the capillary for 90 s to fully wet the inner wall, and blow out the remaining solution in the tube with nitrogen;

[0015] Place the glass capillary on a drying table for drying.

[0016] The present invention also provides a usage method of the above integrated meniscus tracking micro liquid flow calibration device, including:

[0017] Inject the flow rate to be measured into the PDMS channel, locate the initial position of the image acquisition module so that it captures the meniscus;

[0018] Taking the outer diameter of the meniscus measurement channel in the PDMS channel as a reference, establish the relationship between the image pixels and the real dimensions in the physical world. Use the functions of the OpenCV library to select the outer diameter, and then call the function to make the program return the coordinates of the region of interest selected by the user in pixels. Calibrate the scale through the actual size and the corresponding pixel size of the outer diameter;

[0019] Divide the image into different regions to simplify image analysis;

[0020] Use the gradient algorithm to determine the contour of the meniscus and return the coordinates of the pixel at the center point of the meniscus. The horizontal coordinate of this point is determined in pixels. Calculate the real displacement through the obtained scale, and obtain the volume flow rate of the liquid through the inner diameter of the channel.

[0021] Preferably, when injecting the flow rate to be measured into the PDMS channel, attach a heat-insulating film around the syringe, and connect the syringe to the meniscus tracking flow calibration chip through a constant-temperature pipeline.

[0022] Advantages of the present invention:

[0023] 1. Ultra-small flow measurement ability: By using surface modification technology to lower the meniscus and combining with the meniscus recognition algorithm based on the gradient operator (positioning accuracy <5μm), the lower limit of flow measurement of 10 nL / min is achieved.

[0024] 2. Significantly improved environmental robustness: The integrated constant-temperature system reduces the temperature sensitivity and can still maintain a measurement accuracy of less than 5% in an unshielded environment.

[0025] 3. High-efficiency automated operation: The closed-loop control system based on machine vision can achieve unattended measurement for 7×24 hours, and the sampling period can be flexibly adjusted between 1 s and 1 h.

[0026] 4. Miniaturization and integration: The core detection unit is integrated into a 20 mm×100 mm chip through microelectromechanical system technology (soft lithography). And the detection device is integrated, and the volume of the device is less than 400×400×200 mm. Description of the drawings

[0027] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following will briefly introduce the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings in the following description are only those of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0028] Figure 1 Schematic diagram of the meniscus tracking technology principle for the embodiment of the present invention;

[0029] Figure 2 This is a comparison diagram of the meniscus before and after adding a hydrophobic layer in the embodiment of the present invention, where Figure 2 (a) is before adding the hydrophobic layer, Figure 2 (b) is after adding the hydrophobic layer;

[0030] Figure 3 This is a tracking diagram of the meniscus position in the embodiment of the present invention, where Figure 3 (a) is the original diagram, Figure 3 (b) is the enhanced diagram, Figure 3 (c) is the diagram processed by the algorithm, Figure 3 (d) is the coordinate tracking diagram;

[0031] Figure 4 This is a block diagram of the PID position closed-loop control of the meniscus tracking device in the embodiment of the present invention;

[0032] Figure 5 This is a schematic structural diagram of the integrated meniscus tracking liquid micro-flow calibration device in the embodiment of the present invention;

[0033] Figure 6 This is a top-view structural diagram of the integrated meniscus tracking liquid micro-flow calibration device in the embodiment of the present invention;

[0034] Figure 7 This is a front-view structural diagram of the integrated meniscus tracking liquid micro-flow calibration device in the embodiment of the present invention;

[0035] Figure 8 This is a schematic structural diagram of the meniscus tracking flow calibration chip in the embodiment of the present invention.

[0036] The marks in the figure are: 1, 2, 3, cooling fans; 4, constant temperature water bath; 5, meniscus tracking flow calibration chip; 5-1, glass substrate; 5-2, micro-liquid injection channel; 5-3, meniscus measurement channel; 5-4, micro-liquid discharge channel; 6, fill light; 7, industrial camera; 8, 10, guide rods; 9, ball screw; 11, water outlet pipe; 12, water return pipe; 13, micro pump; 14, stepper motor. Detailed implementation manners

[0037] To make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below in conjunction with specific embodiments.

[0038] It should be noted that, unless otherwise defined, the technical terms or scientific terms used in the present invention shall have the ordinary meanings understood by those with ordinary skills in the field to which the present invention pertains. The "first", "second" and similar terms used in the present invention do not denote any order, quantity or importance, but are only used to distinguish different components. Words such as "including" or "comprising" mean that the elements or objects appearing before this word cover the elements or objects listed after this word and their equivalents, without excluding other elements or objects. Words such as "connected" or "coupled" are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "Upper", "lower", "left", "right", etc. are only used to represent relative position relationships. When the absolute position of the object being described changes, the relative position relationship may also change accordingly.

[0039] The present invention provides an integrated meniscus tracking micro liquid flow calibration device, which can realize the digital verification and calibration of micro liquid flow. The device consists of a meniscus tracking flow calibration chip, a temperature control device, a linear motion unit, a camera, etc. The working principle is as Figure 1 shown. During the working process, the liquid is injected into the meniscus tracking flow calibration chip by a micro syringe pump. A meniscus is formed at the front end of the liquid during the flow process in the chip. By detecting the displacement of the meniscus, flow rate data can be obtained. Structurally, the device consists of a meniscus tracking flow calibration chip 5, a thermostat, a linear motion unit, an industrial camera 7, etc.:

[0040] Among them, the meniscus tracking flow calibration chip 5: is the place where the liquid meniscus is generated and detected. The chip is prepared by soft lithography technology and includes a glass substrate 5-1 and a PDMS channel bonded to its surface. As Figure 8 shown, the PDMS channel is a serpentine channel structure, including a micro liquid injection channel 5-2, a meniscus measurement channel 5-3, and a micro liquid discharge channel 5-4. The glass substrate 5-1 is attached to the surface of the constant temperature water tank 4 in the constant temperature heat exchange device. Among them, both the micro liquid injection channel 5-2 and the micro liquid discharge channel 5-4 are straight channels, and the meniscus measurement channel 5-3 is composed of a combination of a straight channel and an arc channel. The channel width is 0.1 - 5 mm, and the height is 0.01 - 0.2 mm.

[0041] Thermostat: Changes in temperature will have a certain impact on the flow state of the tiny liquid in the meniscus chip, thus affecting the quantity transfer. The purpose of this device is to maintain a constant temperature state when the tiny liquid circulates. This part consists of a constant temperature water bath 4, a micro pump 13, three cooling fans 1, 2, 3, a return pipe 12 and a water outlet pipe 11. The micro pump 13 has two interfaces. The front is connected to the return pipe 12, and the upper part is connected to the water outlet pipe 11. The water outlet pipe 11 is connected to the upper layer of the constant temperature water bath 4 in a parallel connection at both ends; The constant temperature water bath 4 is divided into upper and lower layers, and the upper and lower layers are separated by a middle partition. Three cooling fans 1, 2, 3 are fixed on the outer wall of the upper layer through heat-conducting copper sheets. The upper and lower layers are connected at the inner edge of the constant temperature water bath 4, and the outer wall of the lower layer is connected in parallel to the water outlet pipe 11. The constant temperature heat exchange device ensures the constancy of the meniscus tracking flow calibration chip 5 through the flow of the internal coolant and the operation of the cooling fans 1, 2, 3.

[0042] Linear motion unit: This part realizes the real-time tracking of the meniscus in the meniscus tracking flow calibration chip 5. The meniscus tracking device is located below the meniscus tracking flow calibration chip 5. The stepping motor 14 fixed on one side is connected to the industrial camera 7 through the ball screw 9. The ball screw 9, the guide rod 8 and the guide rod 10 drive the industrial camera 7 to achieve linear motion. The industrial camera 7 is fixed on the moving platform of the ball screw 9, and the lens of the industrial camera 7 is directly facing the meniscus measurement channel 5-3 to ensure that the meniscus can be monitored by the camera in real time. In order to monitor better, a supplementary light 6 can also be set.

[0043] During the measurement process, the shape of the meniscus is crucial for the measurement accuracy of its displacement, and the capillary force in the channel will cause significant changes in the meniscus. During the invention process, the influence of the hydrophilic and hydrophobic properties of the inner surface of the channel was studied. In addition, experimental studies such as the design of the hardware platform, image recognition and motion control algorithms were also involved. The research contents involved in the invention process are as follows:

[0044] 1. Based on numerical simulation and experimental exploration of the relationship between the meniscus shape, liquid properties and wall properties, determine the channel material parameters of the meniscus tracking system, and establish the physical / chemical modification method of the wall surface.

[0045] 2. Build a hardware platform for the meniscus tracking liquid micro flow calibration device, mainly including the meniscus tracking flow calibration chip 5, thermostat, linear motion unit, industrial camera 7, etc.

[0046] 3. Based on digital image processing technology, construct a meniscus tracking algorithm, and establish a meniscus tracking system in combination with motion control technology.

[0047] The core detection unit of the present invention can be integrated into a 20mm×100mm chip through microelectromechanical system technology (soft lithography). And the detection device has been integrated, and the volume of the device is less than 400×400×200mm.

[0048] This specification also provides the following specific embodiments:

[0049] Embodiment 1:

[0050] 1. Heat the glass capillary in air at 500 °C for 1 hour to remove the residues on the inner wall; treat the capillary hydrophobically with octadecyltrichlorosilane (OTS) solution. In this process, use a syringe with a hose to slowly inject the OTS solution into the capillary for 90 s to fully wet the inner wall. To prevent blockage, blow out the remaining solution in the tube with nitrogen. Then place the capillary on a drying table for drying. Thus, a PDMS channel is obtained. The comparison diagrams of the meniscus before and after adding the hydrophobic layer are as Figure 2 shown.

[0051] 2. After the flow rate is generated by a Harvard microsyringe pump, it is connected to the PDMS channel through a constant-temperature pipeline. Install the industrial camera 7 on the ball screw 9 driven by the stepper motor 14 so that it can continuously capture the displacement of the meniscus in the capillary.

[0052] 3. Scale calibration: With the outer diameter of the capillary as a reference, establish the relationship between the image pixels and the real dimensions in the physical world. Use the function of the OpenCV library to select the outer diameter, and then call the function to make the program return the coordinates of the region of interest (ROI) selected by the user in pixels. The scale can be calibrated through the actual size and the corresponding pixel size of the outer diameter.

[0053] 4. Image segmentation: Select a suitable method to subdivide the image into different regions to simplify image analysis.

[0054] 5. Determination of the meniscus position: Use the gradient algorithm to determine the contour of the meniscus and return the coordinates of the pixel at the center point of the meniscus. The horizontal coordinate of this point is determined in pixels. Calculate the real displacement through the scale obtained in 3, and obtain the volumetric flow rate of the liquid through the inner diameter of the channel. During the processing, the original image (a) forms image (b) through image enhancement, and the result obtained by processing with the gradient algorithm is shown in figure (c). Determine the meniscus coordinates through edge recognition and generate a coordinate tracking diagram (d) as Figure 3 shown;

[0055] The gradient algorithm uses the Sobel operator, which is a classic image processing tool for edge detection. Its core idea is to calculate the brightness gradient (i.e., the rate of change of brightness) of each pixel point in the image to locate the edges (regions with drastic changes in brightness).

[0056] The present invention uses a horizontal direction gradient convolution kernel to perform a convolution operation on the original image, obtain the horizontal gradient of each pixel region, and determine the position of the meniscus from the gradient value.

[0057] 6. Motion control: Within one measurement cycle, the linear motion platform remains stationary. After the measurement cycle ends and the system calculates the flow measurement value, the linear motion platform moves directionally within a short period of time to restore the liquid level to the initial position of the previous cycle. The motion control algorithm is implemented by a PID closed-loop algorithm, and the structural block diagram is as Figure 4 shown. Specifically, after one measurement cycle, the position of the meniscus shifts in the field of view. It is necessary to use a closed-loop algorithm to drive the linear platform carrying the camera to make the camera move relative to the capillary and move the meniscus to the initial position. Among them, the pixel offset is used as the deviation amount in the PID algorithm. The P parameter determines the step size driven by the stepper motor according to the magnitude of the deviation. The I parameter eliminates the steady-state error in the case of small deviations. The D parameter improves the dynamic process to make it reach the predetermined position more stably and quickly.

[0058] Example 2:

[0059] 1. Components required for building the experimental device: syringe pump (flow generator), meniscus tracking flow calibration chip 5, syringe, hose connection line, LED lamp, computer, and USB camera.

[0060] 2. Set the syringe pump to 10 μL / min and set the inner diameter of the channel of the meniscus tracking flow calibration chip 5 to 300 μm.

[0061] 3. First, set the constant temperature water tank, connect it to the syringe through a catheter to provide a constant temperature environment of 4°C, and attach a layer of heat insulation film around the syringe. Connect the syringe to the meniscus tracking flow calibration chip through a hose connection line. Manually position the initial position of the camera and capture the meniscus part in the field of view. By knowing the distance that the meniscus moves over time and the inner diameter of the chip channel, the flow rate of the fluid and its related uncertainties can be calculated.

[0062] 4. Use the OpenCV and Pyside libraries to build a user observation interface, and this page also includes: start, end, Canney operator debugging, and scale calibration. Through scale calibration, set the relationship between pixel points and the actual distance.

[0063] 5. The distance corresponding to each pixel point in the image is 5 μm, and this value is denoted as M. Suppose the change in the x value within a certain period of time is Δx, then the moving distance L of the meniscus in the capillary can be expressed as:

[0064] L = Δx · M

[0065] 6. Let the time for the meniscus to move during continuous pumping be ΔT. Given that the inner radius of the capillary r = 150 μm, the volumetric flow rate Qv of the pump can be expressed as

[0066]

[0067] The key points of the present invention include:

[0068] 1. The present invention performs surface treatment on the inner surface of the channel. By changing the hydrophilicity and hydrophobicity of the inner wall of the channel, the constancy of the geometric shape of the meniscus is maintained, and a stable and recognizable meniscus is generated.

[0069] 2. Temperature changes will have a greater impact on the micro-flow measurement technology of volumetric method. It is mainly manifested that the liquid volume will expand and contract with temperature, thus affecting the liquid level position and resulting in deviation of the measurement result. The present invention sets a thermostat to control the temperature of the liquid to be measured, greatly reducing the adverse effects brought by temperature fluctuations.

[0070] 3. The present invention conducts an integrated and automated design for the device, which can perform long-term continuous measurement in a state without supervision, meets the actual needs of micro-flow calibration and verification of liquids, and does not require long-term on-site attendance by staff.

[0071] 4. The present invention uses soft lithography technology to process the flow detection chip and prepares a micro-scale liquid channel. The high processing accuracy can ensure the measurement accuracy.

[0072] Those of ordinary skill in the art should understand that: The discussion of any embodiment above is only exemplary and is not intended to imply that the scope of the present invention is limited to these examples; under the concept of the present invention, the technical features in the above embodiments or different embodiments can also be combined, and the steps can be implemented in any order, and there are many other variations in different aspects of the present invention as described above, which are not provided in detail for the sake of brevity. Any omission, modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. An integrated meniscus tracking liquid micro flow calibration device, characterized in that: Includes meniscus tracking flow calibration chip, thermostat and meniscus tracking device: The meniscus tracking flow calibration chip comprises a glass substrate and a PDMS channel bonded to the surface thereof, wherein the glass substrate is attached to a thermostat, and the thermostat is used to ensure the constant temperature of the meniscus chip; The meniscus tracking device includes a linear motion unit and an image acquisition module. The linear motion unit is located below the meniscus chip and is used to track the meniscus in the meniscus tracking flow calibration chip. The image acquisition module is installed on the linear motion unit and is used to monitor the meniscus.

2. The integrated meniscus tracking liquid micro flow calibration device according to claim 1 is characterized in that: The PDMS channel is a serpentine channel structure, including a tiny liquid injection channel, a meniscus measurement channel and a tiny liquid discharge channel. The tiny liquid injection channel and the tiny liquid discharge channel are respectively connected to the two ends of the meniscus measurement channel, and both are straight channels. The meniscus measurement channel is composed of a straight channel and a circular arc channel.

3. The integrated meniscus tracking liquid micro flow calibration device according to claim 1 is characterized in that: The thermostat includes a constant temperature water tank, a micro pump, a cooling fan, a return pipe and an outlet pipe. The constant temperature water tank includes an upper layer and a lower layer, which are separated by a partition and connected at the edge. The micro pump includes two interfaces, which are respectively connected to the return pipe and the outlet pipe. The outlet pipe is connected to the upper layer of the constant temperature water tank in parallel at both ends, and the return pipe is connected in parallel to the lower layer of the constant temperature water tank.

4. The integrated meniscus tracking liquid micro flow calibration device according to claim 3 is characterized in that: The thermostat also includes a heat dissipation fan, which is fixed to the upper outer wall of the thermostatic water tank through a heat-conducting copper sheet.

5. The integrated meniscus tracking liquid micro flow calibration device according to claim 1 is characterized in that: The linear motion unit includes a stepper motor and a ball screw. The stepper motor is connected to the image acquisition module via the ball screw, and the ball screw drives the image acquisition module to achieve linear motion.

6. The integrated meniscus tracking liquid micro flow calibration device according to claim 1, characterized in that: The PDMS channel is made of a glass capillary, and the preparation method includes: Heat treat the glass capillary at 500℃ in air for 1 hour to eliminate the residue on the inner wall; The glass capillary was treated with octadecyltrichlorosilane solution for hydrophobicity. In this process, the OTS solution was slowly injected into the capillary for 90 seconds using a syringe and a hose to fully wet the inner wall, and the remaining solution in the tube was blown out with nitrogen. Place the glass capillary on a drying table to dry.

7. A method for using the integrated meniscus tracking liquid micro-flow calibration device as claimed in any one of claims 1 to 6, characterized in that: The method comprises: The flow to be measured is injected into the PDMS channel, and the initial position of the image acquisition module is positioned so that it captures the meniscus; Taking the outer diameter of the meniscus measurement channel in the PDMS channel as a reference, the relationship between the image pixels and the real dimensions of the physical world is established. The outer diameter is selected using the function of the OpenCV library. The function is then called to allow the program to return the coordinates of the user-selected region of interest in pixels. The scale is calibrated by the actual size of the outer diameter and the corresponding pixel size. Subdivide the image into different regions to simplify image analysis; The gradient algorithm is used to determine the contour of the meniscus and return the coordinates of the pixel at the center of the meniscus. The horizontal coordinate of this point is determined in pixels. The true displacement is calculated using the obtained scale, and the volume flow rate of the liquid is obtained using the inner diameter of the channel.

8. The method for using the integrated meniscus tracking liquid micro-flow calibration device according to claim 7, characterized in that: When the flow to be measured is injected into the PDMS channel, a layer of insulation film is attached to the periphery of the syringe, and the syringe is connected to the meniscus tracking flow calibration chip through a constant temperature pipe.

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