Airtightness monitoring system of thin film microfluidic chip

Abstract

This invention relates to the field of microfluidic chip airtightness monitoring technology, and more particularly to an airtightness monitoring system for a thin-film microfluidic chip, comprising: a thin-film microfluidic chip, including a first fluid channel for delivering reagents and a second fluid channel for delivering target blood; an airtightness monitoring component, including a pressurizing component for applying gas pressure and a gas leak sensor group for detecting gas pressure decay; a detection and analysis module for acquiring the capacitance values ​​of the inner walls of the first and second fluid channels respectively, and determining the area where water molecules are present based on the capacitance values; and a control module for determining the gas pressure compensation amount based on the horizontal displacement of the water molecule presence area, determining the pressurization rate of the pressurizing component based on the number of water molecule presence areas, and determining the airtightness monitoring duration based on the reduction in the area of ​​the water molecule presence area. This invention improves the accuracy of microfluidic chip airtightness monitoring.

Description

Technical Field

[0001] This invention relates to the field of microfluidic chip airtightness monitoring technology, and in particular to an airtightness monitoring system for thin-film microfluidic chips. Background Technology

[0002] Microfluidic chips, especially thin-film chips used to simulate vascular barrier functions such as the blood-brain barrier and intestinal barrier, have become a key platform for in vitro physiological and pathological research. The core of these chips lies in separating the upper and lower fluid channels through porous membranes, such as the cell culture chamber on the top side and the blood flow chamber on the bottom side, and culturing a monolayer of endothelial or epithelial cells on the membrane to simulate the selective permeability barrier in vivo. In such dynamic culture systems, the long-term and reliable airtightness of the chip interface, especially the membrane and cell layer, as well as the various sealed interfaces, is a fundamental prerequisite for experimental success. Loss of airtightness not only leads to culture medium leakage, contamination, and failure of pressure / flow rate control, but also directly damages the integrity of the cell layer and its barrier function. During long-term culture, biomolecules such as proteins in the culture medium will irreversibly adsorb onto the chip material interface, forming a monomolecular lubricating layer. This will significantly reduce the interfacial friction coefficient, making the interface more prone to slippage under the same mechanical stress, and accelerating the accumulation of residual strain. Therefore, there is an urgent need for an airtightness monitoring system for thin-film microfluidic chips.

[0003] Chinese Patent Publication No. CN112504564A discloses a device and method for detecting the airtightness of microfluidic chip film bonding. A feeding suction cup is located on the side of a feeding cylinder, which is movably connected to both the feeding cylinder and a rodless cylinder. A detection component is located on the front of the rodless cylinder, fixedly connected to both the cylinder and the feeding suction cup. A discharging component is located on the front of the detection component and movably connected to it. This application adds a driving device, a pressure head, and a detection platform to the device, eliminating the need for manual inspection and reducing labor costs. The error caused by the process was effectively reduced, and the detection yield was improved. By adding a feeding suction cup and a rodless cylinder to the device, the device can automatically load and unload materials. It can be seen that the airtightness detection device and method for microfluidic chip membrane bonding has the following problems: when the humidity of the laboratory environment increases, water molecules in the external environment tend to be adsorbed to the inner wall of the microchannel based on the capillary force of the microchannel to form a water molecule layer. During the pressure decay maintenance test, the migration of the water molecule layer will lead to insufficient actual gas pressure, and the periodic fluctuation of the detected pressure value due to the splitting of the water molecule layer will reduce the accuracy of airtightness monitoring of microfluidic chip. Summary of the Invention

[0004] To address these issues, the present invention provides an airtightness monitoring system for thin-film microfluidic chips, which overcomes the problems in the prior art where, when the humidity in the laboratory environment rises, water molecules in the external environment tend to adsorb onto the inner wall of the microchannel based on the capillary force of the microchannel, forming a water molecule layer. During pressure decay maintenance testing, the migration of the water molecule layer leads to insufficient actual applied gas pressure, and the periodic fluctuation of the detected pressure value due to the splitting of the water molecule layer causes a decrease in the accuracy of airtightness monitoring of the microfluidic chip.

[0005] To achieve the above objectives, the present invention provides a hermeticity monitoring system for a thin-film microfluidic chip, comprising: A thin-film microfluidic chip for obtaining target cells from blood includes a first fluid channel for delivering reagents and a second fluid channel disposed below the first fluid channel for delivering target blood. An airtightness monitoring component, which is connected to the thin-film microfluidic chip, is used to monitor the airtightness of the thin-film microfluidic chip. It includes a pressurization component for applying gas pressure to the first fluid channel and the second fluid channel, and a gas leakage sensor group respectively disposed at the outlet of the first fluid channel and the outlet of the second fluid channel for detecting the gas pressure decay. The detection and analysis module is connected to the thin-film microfluidic chip to obtain the capacitance values ​​of the inner walls of the first fluid channel and the second fluid channel, and to determine the area where water molecules exist based on the capacitance values. The control module, which is connected to the detection and analysis module, the airtightness monitoring component, and the thin-film microfluidic chip respectively, is used to determine the gas pressure compensation amount based on the horizontal displacement of the water molecule presence area, determine the pressurization rate of the pressurization component based on the number of water molecule presence areas within a unit number of monitoring cycles, and determine the airtightness monitoring duration based on the reduction in the area of ​​the water molecule presence area.

[0006] Furthermore, the detection and analysis module includes a dielectric sensor disposed on the outer wall of the first fluid channel to obtain the capacitance value of the inner wall of the first fluid channel and the capacitance value of the inner wall of the second fluid channel.

[0007] Furthermore, the detection and analysis module determines the largest region enclosed by the line connecting all capacitance value sampling points with capacitance values ​​greater than the preset capacitance value as the region where the water molecules exist.

[0008] Furthermore, the control module determines the compensation amount of the gas pressure by multiplying the horizontal displacement of the region where the water molecules exist with the displacement fitting conversion coefficient.

[0009] Furthermore, the control module is connected to the dielectric sensor and the pressurization component respectively, and is used to determine that the water molecule presence area has migrated to the area where the roughness of the channel inner wall has increased due to bio-adsorption and splits when the number of water molecule presence areas in the unit number monitoring period is greater than a preset number, and to reduce the pressurization rate of the pressurization component.

[0010] Furthermore, the pressurization rate is negatively correlated with the number of regions where water molecules are present.

[0011] Furthermore, the control module is connected to the dielectric sensor to determine that the water in the area where the water molecules exist is absorbed by the extracellular matrix remaining in the area where the roughness of the inner wall of the channel increases, based on the fact that the area reduction of the area where the water molecules exist is greater than a preset reduction, and to extend the airtightness monitoring time.

[0012] Furthermore, the duration of the airtightness monitoring is positively correlated with the amount of area reduction.

[0013] Furthermore, the area reduction is the difference between the area of ​​the water molecule presence region at the beginning of the unit area monitoring period and the area of ​​the water molecule presence region at the end of the monitoring period.

[0014] Furthermore, the start time of the unit area monitoring cycle corresponds to the end time of the unit quantity monitoring cycle.

[0015] Compared with the prior art, the beneficial effect of the present invention is that it determines the water molecule presence area based on the capacitance value. Under conditions of increased ambient humidity, the smaller the channel diameter, the greater the capillary force and the amplification effect of the microchannel size. Water molecules in the environment tend to adsorb onto the inner wall of the channel, forming a microscopic water molecule layer. The capacitance value of this water molecule layer is greater than that of the inner wall of the channel without water molecules. Therefore, the detection and analysis module determines the largest area enclosed by the line connecting all capacitance value sampling points with a capacitance value greater than a preset capacitance value as the water molecule presence area. By determining the water molecule presence area, the influencing factors on the airtightness monitoring of the microfluidic chip under high ambient humidity are characterized, thereby further realizing dynamic compensation of the airtightness monitoring parameters.

[0016] Furthermore, this invention uses a control module to determine the product of the horizontal displacement of the water molecule presence area and the displacement fitting conversion coefficient as the gas pressure compensation amount. Since water molecule migration requires overcoming the surface energy gradient of the channel inner wall during pressure holding tests to detect the airtightness of the first and second fluid channels of the thin-film microfluidic chip, a portion of the applied gas pressure acts on the water molecule presence area. Due to the physical obstruction of the water molecule presence area, the actual applied gas pressure is insufficient. During the gas pressure attenuation detection process by the gas leak sensor group, the gas pressure at the channel outlet decreases, leading to an underestimated pressure attenuation rate and a false pass rate in airtightness monitoring. The displacement fitting conversion coefficient represents the gas pressure corresponding to the displacement of the geometric center point of a unit water molecule presence area. By compensating the gas pressure applied by the pressurizing component using the calculated gas pressure compensation amount, a constant effective gas pressure is output by the pressurizing component, thereby further improving the accuracy of airtightness detection of the first and second fluid channels of the thin-film microfluidic chip.

[0017] Furthermore, this invention obtains the number of areas where water molecules exist within a unit number of monitoring cycles. If the number of areas where water molecules exist within a unit number of monitoring cycles is greater than a preset number, it indicates that during the pressure holding test, the roughness of the channel inner wall increases due to bioadsorption caused by cell culture. This bioadsorption occurs because, during cell culture on the microfluidic chip, small molecular weight proteins with high diffusion coefficients adsorb onto the channel inner wall when the cell culture medium contacts the microfluidic chip surface. These proteins are subsequently replaced by high-affinity large protein molecules, forming a non-uniform island structure on the channel inner wall surface. Simultaneously, the proteins undergo a change from a spherical structure to a fibrous structure on the surface. These adsorbed protein layers provide a basis for cell attachment. Cells recognize specific protein sequences through integrin receptors. When cells contact the channel inner wall surface, pseudopodia form initial attachment points, and subsequently, the cells apply... The traction force spreads along the inner wall of the channel, creating nanoscale gaps beneath the cell bodies. Stress concentration occurs around the attachment points, causing localized material deformation on the inner wall. This further increases the roughness of the inner wall, causing water molecules to tend to move closer to this roughened area, increasing its thickness. Since this roughened area is below the water molecule region, the influx of gas pressure forces the water molecules downwards, causing them to split. As the water molecules split, the total pressure applied by the pressurizing components is distributed between the effective pressure for detecting actual leaks and the energy consumed for the splitting. This further reduces the gas pressure at the channel outlet during the gas leak sensor group's detection of gas pressure attenuation, ultimately resulting in a decrease in the effective test pressure during the pressure attenuation test.

[0018] Furthermore, by reducing the pressurization rate of the pressurization component based on the fact that the number of water molecules in the monitoring period is greater than a preset number, the present invention reduces the energy consumed by the splitting of the water-containing area, thereby reducing the pressure change caused by the redistribution of the water phase. This reduces the contamination of the pressure decay slope by transient hydraulic interference, further reducing the probability of judging false leakage signals as real leaks, and thus improving the accuracy of airtightness monitoring.

[0019] Furthermore, this invention characterizes the degree to which water in the region where water molecules are present is absorbed by the extracellular matrix remaining in the area with increased roughness of the channel wall, based on the reduction in the area of ​​the region where water molecules are present—that is, the difference between the area of ​​the region where water molecules are present at the beginning and the end of a unit area monitoring period. The beginning of the unit area monitoring period corresponds to the end of a unit number of monitoring periods. Specifically, after the area of ​​the water molecule-present region is detected to have split due to pressure being squeezed into the rough area, the area of ​​the split sub-region is measured. Extracellular matrix absorption generates a viscous anchoring effect, turning free water plugs into blockage points. This viscous anchoring effect introduces additional flow resistance in the initial stage of pressure decay testing, consuming the effective test pressure and affecting the accuracy of the gas leak sensor group in detecting gas pressure decay. This leads to the initial pressure fluctuations being misjudged as leaks. Therefore, by extending the airtightness monitoring time and increasing the acquisition of pressure decay data under stable conditions, the error in airtightness monitoring of the first and second fluid channels of the thin-film microfluidic chip caused by the initial flow resistance interference can be compensated, thereby improving the accuracy of airtightness monitoring. Attached Figure Description

[0020] Figure 1 This is an overall structural block diagram of the airtightness monitoring system for a thin-film microfluidic chip according to an embodiment of the present invention; Figure 2 This is a schematic diagram of the airtightness monitoring system for a thin-film microfluidic chip according to an embodiment of the present invention; Figure 3 This is a logic block diagram of the airtightness monitoring system for a thin-film microfluidic chip according to an embodiment of the present invention for determining the region where water molecules are present; Figure 4 This is a logic block diagram showing the determination of the airtightness monitoring duration for the airtightness monitoring system of the thin-film microfluidic chip according to an embodiment of the present invention.

[0021] Explanation of reference numerals in the attached drawings: 1-First fluid channel, 2-Second fluid channel, 3-Gas leak sensor group, 4-Dielectric sensor. Detailed Implementation

[0022] To make the objectives and advantages of the present invention clearer, the present invention will be further described below with reference to embodiments; it should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention.

[0023] Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention.

[0024] It should be noted that in the description of this invention, the terms "upper", "lower", "left", "right", "inner", "outer", etc., which indicate directions or positional relationships, are based on the directions or positional relationships shown in the accompanying drawings. This is only for the convenience of description and is not intended to indicate or imply that the device or element must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation of this invention.

[0025] Furthermore, it should be noted that, in the description of this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0026] Please see Figure 1 and Figure 2 The figures shown are a block diagram and a schematic diagram of the overall structure of the airtightness monitoring system for the thin-film microfluidic chip according to an embodiment of the present invention. The airtightness monitoring system for the thin-film microfluidic chip according to an embodiment of the present invention includes: A thin-film microfluidic chip for obtaining target cells from blood includes a first fluid channel 1 for delivering reagents and a second fluid channel 2 disposed below the first fluid channel for delivering target blood. An airtightness monitoring component, which is connected to the thin-film microfluidic chip, is used to monitor the airtightness of the thin-film microfluidic chip. It includes a pressurization component for applying gas pressure to the first fluid channel and the second fluid channel, and a gas leakage sensor group 3 respectively disposed at the outlet of the first fluid channel and the outlet of the second fluid channel for detecting the gas pressure decay. The detection and analysis module is connected to the thin-film microfluidic chip to obtain the capacitance values ​​of the inner walls of the first fluid channel and the second fluid channel, and to determine the area where water molecules exist based on the capacitance values. The control module, which is connected to the detection and analysis module, the airtightness monitoring component, and the thin-film microfluidic chip respectively, is used to determine the gas pressure compensation amount based on the horizontal displacement of the water molecule presence area, determine the pressurization rate of the pressurization component based on the number of water molecule presence areas within a unit number of monitoring cycles, and determine the airtightness monitoring duration based on the reduction in the area of ​​the water molecule presence area.

[0027] Specifically, the gas leak sensor group includes two gas leak meters.

[0028] Specifically, the reagents include ammonium chloride at concentrations of 0.15 mol / L to 0.17 mol / L, potassium bicarbonate at concentrations of 10 mmol / L to 15 mmol / L, and a mixed solution at concentrations of 0.1 mmol / L to 1.0 mmol / L.

[0029] Specifically, blood is peripheral venous blood.

[0030] Specifically, both the first fluid channel and the second fluid channel are made of cyclic olefin copolymers.

[0031] Specifically, the pressurization components include a pneumatic pump, a pressure controller, and a digital switching valve.

[0032] As will be understood by those skilled in the art, the operating principle and process of the pressurization component are conventional technical means well known to them, and therefore the operating principle and process of the pressurization component will not be described in detail here.

[0033] Specifically, the detection and analysis module includes a dielectric sensor 4 disposed on the outer wall of the first fluid channel to obtain the capacitance value of the inner wall of the first fluid channel and the capacitance value of the inner wall of the second fluid channel.

[0034] Please see Figure 3 As shown, it is a logic block diagram of the airtightness monitoring system of the thin film microfluidic chip in an embodiment of the present invention for determining the region where water molecules exist. The detection and analysis module determines the largest region enclosed by the line connecting all capacitance value sampling points with capacitance values ​​greater than the preset capacitance value as the region where water molecules exist.

[0035] Optionally, the preset capacitance value can be selected in the range of [15pF, 40pF].

[0036] Preferably, the preset capacitance value is 25pF.

[0037] In practice, this invention determines the water molecule presence area based on capacitance values. Under conditions of increased ambient humidity, the smaller the channel diameter, the greater the capillary force and the amplification effect of the microchannel size. Water molecules in the environment tend to adsorb onto the inner wall of the channel, forming a microscopic water molecule layer. The capacitance value of this water molecule layer is greater than that of the inner wall of the channel without water molecules. Therefore, the detection and analysis module determines the largest area enclosed by the line connecting all capacitance value sampling points with capacitance values ​​greater than a preset value as the water molecule presence area. By determining the water molecule presence area, the influencing factors on the airtightness monitoring of the microfluidic chip under high ambient humidity are characterized, thereby further realizing dynamic compensation of the airtightness monitoring parameters.

[0038] Specifically, the control module determines the compensation amount for the gas pressure by multiplying the horizontal displacement of the region where the water molecules exist and the displacement fitting conversion coefficient.

[0039] Specifically, the displacement fitting conversion coefficient is the gas pressure corresponding to the displacement of the geometric center point of the region where a unit water molecule exists, and the unit of the displacement fitting conversion coefficient is Pa / μm.

[0040] Those skilled in the art will understand that the displacement fitting conversion coefficient is an empirical parameter determined in the laboratory. Therefore, there is no limitation on the selectable range and preferred embodiment of the displacement fitting conversion coefficient. It is only necessary to satisfy the physical relationship between the horizontal displacement of the water molecule presence region and the gas pressure. Those skilled in the art can make adaptive adjustments to the specific value of the displacement fitting conversion coefficient according to actual application or production needs.

[0041] Optionally, the displacement fitting conversion coefficient can be selected in the range of [0.01 Pa / μm, 0.10 Pa / μm].

[0042] Preferably, the preferred embodiment of the displacement fitting conversion coefficient is 0.05 Pa / μm.

[0043] Specifically, the water molecule presence region is a two-dimensional planar region on the inner wall of the first fluid channel and the inner wall of the second fluid channel. The horizontal displacement of the water molecule presence region is obtained based on the position of the horizontal center of the water molecule presence region at a single time point.

[0044] In a specific embodiment, the horizontal displacement of the current water molecule region is 50 μm, the displacement fitting conversion coefficient is 0.05 Pa / μm, and the calculated gas pressure compensation is 50 μm × 0.05 Pa / μm = 2.5 Pa.

[0045] Specifically, the gas pressure actually applied to the first fluid channel and the second fluid channel is determined by the sum of the gas pressure compensation amount and the gas pressure of the pressurizing component.

[0046] In implementation, this invention uses a control module to determine the product of the horizontal displacement of the water molecule presence area and the displacement fitting conversion coefficient as the gas pressure compensation amount. When performing a pressure holding test to detect the airtightness of the first and second fluid channels of the thin-film microfluidic chip, water molecule migration requires overcoming the surface energy gradient of the channel's inner wall. Therefore, a portion of the applied gas pressure acts on the water molecule presence area. Due to the physical obstruction of the water molecule presence area, the actual applied gas pressure is insufficient. During the gas leak sensor group's detection of gas pressure attenuation, the gas pressure at the channel outlet decreases, leading to an underestimated pressure attenuation rate and a false pass rate in airtightness monitoring. The displacement fitting conversion coefficient represents the gas pressure corresponding to the displacement of the geometric center point of a unit water molecule presence area. By calculating the gas pressure compensation amount, the gas pressure applied by the pressurizing component is compensated, further ensuring a constant effective gas pressure output by the pressurizing component, thereby further improving the accuracy of airtightness detection of the first and second fluid channels of the thin-film microfluidic chip.

[0047] Specifically, the control module is connected to the dielectric sensor and the pressurization component respectively, and is used to determine that the water molecules in the monitoring period are greater than a preset number, and that the water molecules migrate to the region where the roughness of the channel wall increases due to biosorption and splits, and reduce the pressurization rate of the pressurization component.

[0048] Optional, the preset quantity can be selected from [4, 6].

[0049] Preferably, the preset number of preferred embodiments is 5.

[0050] Specifically, the monitoring cycle for each unit quantity is 2 seconds.

[0051] In practice, this invention obtains the number of areas where water molecules exist within a unit number of monitoring cycles. If the number of areas where water molecules exist within a unit number of monitoring cycles is greater than a preset number, it indicates that during pressure maintenance testing, the roughness of the channel inner wall is increased due to bioadsorption caused by cell culture. This bioadsorption occurs because, during cell culture on the microfluidic chip, small molecular weight, high diffusion coefficient proteins adsorb onto the channel inner wall when the cell culture medium contacts the microfluidic chip surface. These proteins are subsequently replaced by high-affinity large protein molecules, forming a non-uniform island structure on the channel inner wall surface. Simultaneously, the proteins undergo a change from a spherical structure to a fibrous structure on the surface. These adsorbed protein layers provide a basis for cell attachment. Cells recognize specific protein sequences through integrin receptors. When cells contact the channel inner wall surface, pseudopodia form initial attachment points, and subsequently, the cells apply... The traction force spreads along the inner wall of the channel, creating nanoscale gaps beneath the cell bodies. Stress concentration occurs around the attachment points, causing localized material deformation on the inner wall. This further increases the roughness of the inner wall, causing water molecules to tend to move closer to this roughened area, increasing its thickness. Since this roughened area is below the water molecule region, the influx of gas pressure forces the water molecules downwards, causing them to split. As the water molecules split, the total pressure applied by the pressurizing components is distributed between the effective pressure for detecting actual leaks and the energy consumed for the splitting. This further reduces the gas pressure at the channel outlet during the gas leak sensor group's detection of gas pressure attenuation, ultimately resulting in a decrease in the effective test pressure during the pressure attenuation test.

[0052] Specifically, the pressurization rate is negatively correlated with the number of regions where water molecules are present.

[0053] In practice, when the number exceeds the preset number by no more than 2, the pressurization rate is adjusted to 95% of the current pressurization rate. When the number exceeds the preset number by more than 2, the pressurization rate is reduced by 1 Pa / s for each additional 1. In a specific embodiment, the current number is 8, the current pressurization rate is 3000 Pa / s, and the reduced pressurization rate is 3000 Pa / s × 95% - (1 / 1) × 1 Pa / s = 2849 Pa / s.

[0054] Specifically, the pressurization rate is adjusted by adjusting the air pump of the pressurization component.

[0055] In practice, this invention reduces the pressurization rate of the pressurizing component by monitoring the number of water molecules in the area within a unit quantity monitoring period as greater than a preset number. This reduces the energy consumed by the splitting of the water-containing area, thereby reducing the pressure change caused by the redistribution of the water phase. This also reduces the contamination of the pressure decay slope by transient hydraulic interference, further reducing the probability of mistaking a false leak signal for a real leak, thus improving the accuracy of airtightness monitoring.

[0056] Please see Figure 4 As shown, it is a logic block diagram of the airtightness monitoring system of the thin-film microfluidic chip in an embodiment of the present invention for determining the airtightness monitoring duration. The control module is connected to the dielectric sensor and is used to determine that the water in the area where the water molecules exist is absorbed by the extracellular matrix remaining in the area where the roughness of the inner wall of the channel increases, based on the fact that the area reduction of the water molecule presence area is greater than a preset reduction amount, and to extend the airtightness monitoring duration.

[0057] Optionally, the preset range for the reduction amount is [4]. 10 ].

[0058] Preferably, the preset reduction amount is 5 in the preferred embodiment. .

[0059] Specifically, the duration of airtightness monitoring is adjusted by changing the length of the stabilization period in the airtightness monitoring.

[0060] Specifically, the stabilization period in airtightness monitoring is the time period following the closing moment of the digital switching valve of the pressurization component after the target pressure is reached.

[0061] Optionally, the target pressure can be selected within a range of [2 kPa, 4 kPa].

[0062] Preferably, the target pressure in the preferred embodiment is 3 kPa.

[0063] As will be understood by those skilled in the art, adjusting the stabilization period in airtightness monitoring is a conventional technique well-known to them, and therefore the adjustment of the stabilization period in airtightness monitoring will not be elaborated here.

[0064] Specifically, the duration of the airtightness monitoring is positively correlated with the amount of area reduction.

[0065] In implementation, when the reduction in the area where water molecules exist is greater than the preset reduction value, the value is within 2. If the airtightness monitoring duration is within a certain range, the monitoring duration will be adjusted to 1.1 times the current monitoring duration. If the decrease in the area where water molecules exist exceeds the preset decrease value by more than 2... At that time, more than 2 Each time exceeding 1 By extending the airtightness monitoring time by 1 second, in one specific embodiment, the current area reduction is 9. The current airtightness monitoring time is 15 seconds, and the extended airtightness monitoring time is 15 seconds × 1.1 + (2 / 1 ) × 1s = 18.5s.

[0066] Specifically, the reduction in area is the difference between the area of ​​the region where water molecules exist at the beginning of the unit area monitoring period and the area of ​​the region where water molecules exist at the end of the monitoring period.

[0067] Specifically, the monitoring cycle per unit area is 5 seconds.

[0068] Specifically, the start time of the unit area monitoring cycle corresponds to the end time of the unit quantity monitoring cycle.

[0069] In practice, this invention characterizes the degree to which water in the region where water molecules are present is absorbed by the extracellular matrix remaining in the area with increased roughness of the channel wall, based on the reduction in the area of ​​the region where water molecules are present—that is, the difference between the area of ​​the region where water molecules are present at the beginning and the end of a unit area monitoring period. The beginning of the unit area monitoring period corresponds to the end of a unit number of monitoring periods. Specifically, after the area of ​​the water molecule-present region is detected to have split due to pressure and being squeezed into a rough area, the area of ​​the split sub-region is measured. Extracellular matrix absorption generates a viscous anchoring effect, turning free water plugs into blockage points. This viscous anchoring effect introduces additional flow resistance in the initial stage of pressure decay testing, consuming the effective test pressure and affecting the accuracy of the gas leak sensor group in detecting gas pressure decay. This leads to the initial pressure fluctuations being misjudged as leaks. Therefore, by extending the airtightness monitoring time and increasing the acquisition of pressure decay data under stable conditions, the error in airtightness monitoring of the first and second fluid channels of the thin-film microfluidic chip caused by the initial flow resistance interference can be compensated, thereby improving the accuracy of airtightness monitoring.

[0070] The technical solution of the present invention has been described above with reference to the preferred embodiments shown in the accompanying drawings. However, it will be readily understood by those skilled in the art that the scope of protection of the present invention is obviously not limited to these specific embodiments. Without departing from the principles of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will all fall within the scope of protection of the present invention.

Claims

1. A hermeticity monitoring system for a thin-film microfluidic chip, characterized in that, include: A thin-film microfluidic chip for obtaining target cells from blood includes a first fluid channel for delivering reagents and a second fluid channel disposed below the first fluid channel for delivering target blood. An airtightness monitoring component, which is connected to the thin-film microfluidic chip, is used to monitor the airtightness of the thin-film microfluidic chip. It includes a pressurization component for applying gas pressure to the first fluid channel and the second fluid channel, and a gas leakage sensor group respectively disposed at the outlet of the first fluid channel and the outlet of the second fluid channel for detecting the gas pressure decay. The detection and analysis module is connected to the thin-film microfluidic chip to obtain the capacitance values ​​of the inner walls of the first fluid channel and the second fluid channel, and to determine the area where water molecules exist based on the capacitance values. The control module, which is connected to the detection and analysis module, the airtightness monitoring component, and the thin-film microfluidic chip respectively, is used to determine the gas pressure compensation amount based on the horizontal displacement of the water molecule presence area, determine the pressurization rate of the pressurization component based on the number of water molecule presence areas within a unit number of monitoring cycles, and determine the airtightness monitoring duration based on the reduction in the area of ​​the water molecule presence area.

2. The system for monitoring the air tightness of a thin-film microfluidic chip according to claim 1, wherein, The detection and analysis module includes a dielectric sensor disposed on the outer wall of the first fluid channel to obtain the capacitance value of the inner wall of the first fluid channel and the capacitance value of the inner wall of the second fluid channel.

3. The airtightness monitoring system for thin-film microfluidic chips according to claim 2, characterized in that, The detection and analysis module determines the largest region enclosed by the line connecting all capacitance value sampling points with capacitance values ​​greater than the preset capacitance value as the region where water molecules exist.

4. The system for monitoring the air tightness of a thin-film microfluidic chip according to claim 3, wherein, The control module determines the compensation amount for the gas pressure as the product of the horizontal displacement of the region where the water molecules exist and the displacement fitting conversion coefficient.

5. The system for monitoring the air-tightness of a thin-film microfluidic chip according to claim 4, wherein, The control module is connected to the dielectric sensor and the pressurization component respectively. It is used to determine that the water molecules in the monitoring period are greater than a preset number, and that the water molecules migrate to the region where the roughness of the channel wall increases due to biosorption and splits, and then reduce the pressurization rate of the pressurization component.

6. The system for monitoring the air-tightness of a thin-film microfluidic chip according to claim 5, wherein, The pressurization rate is negatively correlated with the number of regions where water molecules are present.

7. The airtightness monitoring system for a thin-film microfluidic chip according to claim 6, characterized in that, The control module is connected to the dielectric sensor and is used to determine that the water in the area where the water molecules exist is absorbed by the extracellular matrix remaining in the area where the roughness of the inner wall of the channel increases, based on the fact that the area reduction of the area where the water molecules exist is greater than a preset reduction amount, and to extend the airtightness monitoring time.

8. The airtightness monitoring system for a thin-film microfluidic chip according to claim 7, characterized in that, The duration of the airtightness monitoring is positively correlated with the amount of area reduction.

9. The system for monitoring the air-tightness of a thin-film microfluidic chip according to claim 8, wherein, The area reduction is the difference between the area of ​​the region where water molecules exist at the beginning and the area of ​​the region where water molecules exist at the end of the monitoring period per unit area.

10. The system for monitoring the air-tightness of a thin-film microfluidic chip according to claim 9, wherein, The start time of the unit area monitoring cycle corresponds to the end time of the unit quantity monitoring cycle.

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