A slit-type liquid sampling and detection chamber structure and sampling method
By designing the slit-type liquid sampling and detection chamber structure, using a semi-open cavity and multi-thickness detection zone, combined with exhaust holes and sampling notch, the problems of bubble interference and sample volume loss in the microfluidic sampling chip are solved, and the precise control of liquid samples and multi-parameter measurement are achieved.
Patent Information
- Application Number
- CN201910383419.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2019-05-09
- Publication Date
- 2025-07-18
- Estimated Expiration
- 2039-05-09
AI Technical Summary
The existing microfluidic sampling chips have problems such as bubble interference accuracy, sample volume loss, single injection method and limited application range in liquid sample analysis, and cannot take into account the needs of overall panoramic analysis and local precision analysis at the same time.
A slit type liquid sampling and detection chamber structure is designed, adopting a semi-open cavity design, multiple detection areas and diversion tank areas with different thicknesses are set up, and exhaust holes and sampling notches are equipped, which support two methods of active sample suction and passive sample injection. The inverted conical exhaust holes and transitional fillets are used to avoid bubble generation, and the precise control of liquid samples is achieved.
It realizes precise control of liquid samples, avoids bubble generation, takes into account the precision of overall panoramic analysis and local precision analysis, and provides a basis for multi-parameter measurement for biological analysis and chemical analysis.
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Figure CN111912669B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of biomedical detection, and particularly relates to a slit-type liquid sampling and detection chamber structure and a sampling method. Background Art
[0002] Whether it is biological analysis or chemical analysis, the analysis operation of liquid samples usually involves two steps, namely the sampling operation of liquid samples and the detection and analysis of liquid samples. How to quickly and accurately measure a trace amount of liquid samples and form a detection surface that meets the requirements is a key step in biological analysis or chemical analysis.
[0003] U.S. Patent Application US5,674,457 discloses a microfluidic sampling chip. The microfluidic sampling chip uses capillary force to drive the liquid sample to flow in the chip, including a substrate 01 and a detection chamber 02 with a measurement area 03 located in the substrate. The detection chamber 02 is a semi-open cavity formed by two parallel and spaced substrate surfaces. The open edge of the detection chamber 02 is provided with a sampling port 04, and the inner edge area of the detection chamber is provided with a diversion channel 05 for adjusting the liquid flow direction and speed. The diversion channel 05 communicates the sampling port 04 with the measurement area 03 and communicates with the outside atmosphere.
[0004] In the specific use process of the above chip, it is easy to form bubbles that are difficult to remove in the detection chamber, thereby affecting the accuracy of liquid measurement and seriously interfering with the results of optical analysis. The generation of bubbles stems from several links. During the sampling process, defects in the chip structure itself are likely to cause bubbles to form in the detection area; after sampling, it is necessary to wipe the residual sample at the injection port. During the wiping process, the liquid sample moves along the wiping direction and is drained out of the chip, resulting in a reduction in the sample volume in the detection area, and then bubbles are formed; when pre-packaging a drying reagent in the detection chamber of the chip, uneven distribution of the reagent will affect the shape of the front liquid surface of the liquid sample and is also likely to cause bubbles to form in the detection area; different angles of the chip for sucking the liquid sample result in changes in the shape of the front liquid surface of the liquid, thereby forming bubbles in the detection area; due to different physical and chemical properties of the liquid sample, the uncertainty of bubble formation in the detection area is more obvious. In addition, in some application scenarios, in order to prevent the liquid sample from being contaminated during the sampling process, it is necessary to first suck out the liquid sample with a pipette and then inject the liquid sample into the sampling chip through the pipette. However, the above chip is only suitable for directly sucking liquid samples and does not have a structural design that is compatible with injecting liquid samples with a pipette, thus limiting the application range.
[0005] The existing microfluidic sampling chips usually have the following defects in actual use:
[0006] A. Using a measurement area with a single thickness cannot meet the requirements of diversified parameter measurement: The sampling chip described above has a measurement area with a single thickness, making it impossible to simultaneously meet the requirements of the overall panoramic analysis of "large volume per unit area" liquid samples and the local precision analysis of "large area per unit volume" liquid samples during detection, which affects the precision and scope of application of the analysis.
[0007] B. Bubbles are easily generated during sample injection, affecting the subsequent measurement accuracy: The structure of the above sampling chip does not consider the relevant design to avoid the generation of bubbles, and the presence of bubbles will seriously interfere with subsequent precise analysis.
[0008] C. The sample after injection is prone to wiping loss and moving out loss, making it impossible to guarantee the accuracy of the sample volume.
[0009] D. The sample injection method and application scenarios are limited: The structure of the above sampling chip cannot be compatible with two sample addition methods, namely active suction sampling and passive injection sampling. The sample and reagent can only be mixed in the detection cavity, which limits the scope of application. Summary of the Invention
[0010] To solve the above problems, the present invention provides an improved slit-type liquid sampling and detection chamber structure.
[0011] The technical solution adopted by the present invention is as follows:
[0012] A slit-type liquid sampling and detection chamber structure includes a sampling and detection chamber (2). The sampling and detection chamber (2) is a semi-open cavity formed by two parallel chamber side walls (4) with a certain gap, and has a detection area (5), a sampling port (7), and a diversion groove area (6) connecting the sampling port (7) and the detection area (5). The thickness H of the detection area (5) 检 is less than the thickness H of the diversion groove area (6) 导 , and at least one exhaust hole (8) is provided on the sampling and detection chamber (2). The exhaust hole (8) is a through hole connecting the inside of the sampling and detection chamber (2) with the outside atmosphere, and it penetrates one side wall of the detection area (5) or the diversion groove area (6) or symmetrically penetrates both side walls of the detection area (5) or the diversion groove area (6).
[0013] In the above slit-type liquid sampling and detection chamber structure, the exhaust hole (8) is an inverted conical through hole, with the small end of the cone opening towards the inside of the detection area (5) or the diversion groove area (6), and the large end of the cone opening towards the outside atmosphere.
[0014] In the above slit-type liquid sampling and detection chamber structure, there is one detection area (5) in the sampling and detection chamber (2), and the detection area (5) has a single thickness H 检 .
[0015] In the above slit-type liquid sampling and detection chamber structure, the sampling and detection chamber (2) is provided with a plurality of detection areas (5). The plurality of detection areas (5) are independent of each other and communicate with each other, and their thicknesses are the same or different. The thickness of any detection area (5) is less than the thickness H of the diversion groove area (6). 导 .
[0016] In the above slit-type liquid sampling and detection chamber structure, the sampling and detection chamber (2) is provided with two detection areas (5) with different thicknesses, namely a first detection area (51) and a second detection area (52). The first detection area (51) and the second detection area (52) are communicated by the diversion groove area (6).
[0017] In the above slit-type liquid sampling and detection chamber structure, the sampling port (7) is located at the upper edge openings of the two chip side walls (4) of the sampling and detection chamber (2). One of the two chamber side walls (4) is provided with a sampling notch (9) at the upper edge at the sampling port (7) to inject a liquid sample through the sampling notch (9).
[0018] In the above slit-type liquid sampling and detection chamber structure, the sampling port (7) is in a concave arc shape, and the value range of the angle α between the tangent of its downward sliding arc and the horizontal reference plane of the sampling port (7) is 15° to 45°.
[0019] In the above slit-type liquid sampling and detection chamber structure, each detection area is provided with a corresponding sampling port.
[0020] In the above slit-type liquid sampling and detection chamber structure, each sampling port is provided with a sampling notch.
[0021] In the above slit-type liquid sampling and detection chamber structure, the inner edge of the end of the chamber side wall (4) is provided with a transition fillet (10), and the range of the transition fillet R is 0.2 mm - 1.5 mm.
[0022] In the above slit-type liquid sampling and detection chamber structure, the detection area (5) can be a rectangle, a square, a trapezoid, a circle or a combination of an arc and other shapes, and each shape can be provided with a fillet, a right angle or a combination of a fillet and a right angle.
[0023] In the above slit-type liquid sampling and detection chamber structure, the sampling and detection chamber further includes a pre-packaged liquid reagent. The pre-packaging method is: adding the liquid reagent into the sampling and detection chamber through the sampling port or the sampling notch, drying or freeze-drying, and the reagent is pre-packaged in the sampling and detection chamber.
[0024] The present invention also provides a micro liquid sampling method, which is operated by using any of the above slit-type liquid sampling and detection chamber structures, and includes the following steps:
[0025] Dip the sampling port (7) of the slit-type liquid sampling and detection chamber structure into the pre-treated liquid sample, and actively suck the liquid sample until the detection area (5) is filled; or
[0026] Use a pipette to suck the pre-treated liquid sample, then place the pipette at the sampling notch (9) of the sampling port (7), and inject the liquid sample into the chamber structure until the detection area (5) is filled.
[0027] The beneficial effects of the present invention are as follows: The slit-type liquid sampling and detection chamber structure of the present invention is provided with a semi-open sampling and detection chamber. The sampling and detection chamber has a sampling port, a detection area, and a diversion groove area connecting the sampling port and the detection area. The thickness of the detection area is less than that of the diversion groove area, and a plurality of exhaust holes are provided on the diversion groove area and / or the detection area. This chamber structure can achieve two sample addition methods, namely active sampling and passive injection, by setting sampling notches, exhaust holes, and one or multiple detection areas with different thicknesses, avoiding the generation of bubbles, achieving precise control of the liquid sample volume, and simultaneously taking into account the precision of overall panoramic analysis and local precision analysis, laying a foundation for multi-parameter measurement of liquid samples in biological analysis and chemical analysis. Brief Description of the Drawings
[0028] Figure 1 is a schematic structural diagram of an existing sampling chip;
[0029] Figure 2A is a schematic plan view of Embodiment 1 of the chamber structure of the present invention;
[0030] Figure 2B is a schematic three-dimensional view of Embodiment 1 of the chamber structure of the present invention
[0031] Figure 2C is Figure 2A a cross-sectional view taken along line A-A in
[0032] Figure 3A is a schematic plan view of Embodiment 2 of the chamber structure of the present invention;
[0033] Figure 3B is a schematic three-dimensional view of Embodiment 2 of the chamber structure of the present invention;
[0034] Figure 3C is Figure 3A a cross-sectional view taken along line B-B in
[0035] Figure 4A is a schematic plan view of Embodiment 3 of the chamber structure of the present invention;
[0036] Figure 4B is a schematic three-dimensional view of Embodiment 3 of the chamber structure of the present invention;
[0037] Figure 4CYes Figure 4A is a sectional view taken along line C1-C1 in
[0038] Figure 4D Yes Figure 4A is a sectional view taken along line C2-C2 in
[0039] Figure 5A is a schematic plan view of the fourth embodiment of the chamber structure of the present invention;
[0040] Figure 5B is a schematic three-dimensional view of the fourth embodiment of the chamber structure of the present invention.
[0041] In the figure, the reference numerals are represented as:
[0042] 01 - Substrate, 02 - Detection chamber, 03 - Measurement area, 04 - Sampling port, 05 - Diversion channel;
[0043] 1 - Slit-type liquid sampling detection chamber structure; 2 - Sampling detection chamber;
[0044] 5 - Detection area, 51 - First detection area, 52 - Second detection area; 6 - Diversion groove area;
[0045] 7 - Sampling port, 71 - First sampling port, 72 - Second sampling port; 9 - Sampling notch, 91 - First sampling notch, 92 - Second notch; 8 - Exhaust hole, 81 - First exhaust hole, 82 - Second exhaust hole;
[0046] 4 - Chamber side wall, 10 - Transition fillet, 11 - Liquid bridge surface. Detailed implementation manners
[0047] In order to solve the problems existing in the detection chamber structure in the existing microfluidic sampling chip, such as the inability to simultaneously take into account the precision of overall panoramic analysis and local precision analysis, the existence of bubble interference, low sampling accuracy, single sample injection method, and limited application range, the present invention provides a slit-type liquid sampling detection chamber structure and a sampling method. The chamber structure includes a sampling detection chamber, and the sampling detection chamber is a semi-open cavity formed by two parallel chamber side walls with a certain gap, having multiple sampling methods, a design of one or multiple detection areas with different thicknesses, and a design of a diversion groove area and an exhaust hole for connecting the sampling port and the detection area; by setting a sampling notch, an exhaust hole, and one or multiple detection areas with different thicknesses, the chamber structure can achieve two sample injection methods, namely active sampling and passive injection, avoid the generation of bubbles, achieve precise control of the liquid sample volume, contribute to achieving the precision of simultaneously taking into account overall panoramic analysis and local precision analysis, and lay a foundation for multi-parameter measurement of liquid samples in biological analysis and chemical analysis..
[0048] The following will describe in detail the slit-type liquid sampling and detection chamber structure and sampling method of the present invention in combination with Embodiments 1 to 4 and the accompanying drawings.
[0049] Example 1
[0050] Figure 2A - Figure 2C This is an example of the slit-type liquid sampling and detection chamber structure of the present invention. Figure 2A - Figure 2C In the shown Embodiment 1, the chamber structure includes a sampling and detection chamber 2, and the sampling and detection chamber 2 is a semi-open cavity formed by two parallel chamber side walls 4 with a certain gap, including a sampling port 7, a sampling notch 9, a detection area 5, and a diversion groove area 6 that connects the sampling port 7 and the detection area 5. Among them:
[0051] The sampling port 7 is located at the upper edge opening of the two chip side walls 4 of the sampling and detection chamber 2, and is similar to Figure 1 the existing detection chamber shown. Through the sampling port 7, sampling can be carried out by the active suction method under the action of capillary force.
[0052] The detection area 5 is located inside the sampling and detection chamber 2. The shape of the detection area 5 can be rectangular, square, trapezoidal, circular, or a combination of an arc and other shapes, and each shape can be provided with rounded corners, right angles, or a combination of rounded corners and right angles. The present invention does not limit the specific shape of the detection area 5; the detection area 5 has a single thickness H 检 , and the thickness range of the detection area 5 is generally 60μm - 120μm. When the sample enters the detection area 5, a detection surface is formed. For a detection area 5 with a large thickness, the sample carrying capacity per unit area of the detection surface is large and the depth of field is large, which is suitable for the overall panoramic analysis of liquid samples; for a small thickness, the spreading area of the same volume of liquid sample on the detection surface is large, which is suitable for the local precision analysis of liquid samples.
[0053] The diversion groove area 6 is located inside the sampling and detection chamber 2 and is connected to the sampling port 7 and the detection area 5. The thickness range of the diversion groove area 6 is generally 120μm - 500μm. As Figure 2C shown, the thickness of the detection area 5 is less than the thickness of the diversion groove area 6, and the liquid sample enters from the sampling port 7 and is uniformly and quickly introduced and filled into the entire sampling and detection chamber 2 through the flow path formed by the diversion groove area 6.
[0054] The thickness of the detection area 5 and the thickness of the diversion groove area 6 determine the flow state of the liquid sample to be measured in the diversion groove area 6 and the spreading state in the detection area 5. The liquid sample to be measured enters the diversion groove area 6 through the sampling port 7. The sample inhalation stage belongs to the pure inertial rising stage under the action of capillary force. According to the formula 1) of the pure inertial rising stage of capillary flow, the relationship between the volume of the liquid sample to be measured inhaled and the thickness of the detection area 5 can be obtained:
[0055]
[0056] In order to ensure that the liquid sample continuously flows from the flow channel area 6 into the detection area 5 under the action of capillary force and fills the sampling detection cavity 2, the capillary force is required to be greater than zero. 检 , the thickness of the guide groove area H 导 The following relationship exists:
[0057]
[0058] Specifically, in this embodiment, the detection area 5 is provided with one, which is located in the sampling detection cavity 2 and has a single thickness H 检 , its shape is a rounded rectangle. When the thickness H of the detection area 5 检 When the thickness is large, the detection surface formed on the chamber side wall 4 has a large depth of field and a large sample carrying capacity per unit area, which is suitable for the overall panoramic analysis of the liquid sample. The thickness of the detection area 5 is preferably 90 μm-120 μm; when the thickness H of the detection area 5 is 检 When the thickness is small, the depth of field of the detection surface formed on the chamber side wall 4 is small and the sample spreading area per unit volume is large, which is suitable for local precision analysis of liquid samples. The thickness of the detection area 5 is preferably 60μm-90μm.
[0059] Furthermore, a sampling notch 9 is provided at the upper edge of one of the two chip side walls 4 at the sampling port 7, so that the sample can be added through the sampling notch 9 by injection. The sampling port 7 and the sampling notch 9 are compatible with both active injection and passive suction liquid sampling modes. In this embodiment, the sampling port 7 is concavely arc-shaped, and the angle α between the tangent of its downward arc (the arc on the left side is shown in the figure) and the horizontal reference plane of the sampling port 7 is (see Figure 2A ), can determine the direction of the liquid sample to be tested entering the flow channel area 6, so as to ensure that the liquid sample to be tested spontaneously flows into the detection area 5 in a predetermined manner and fills the detection area 5. The preferred range of the angle α is 15° to 45°.
[0060] Specifically, the guide groove area 6 is located in the sampling and detection cavity 2, connecting the sampling port 7 and the detection area 5, and the thickness H of the guide groove area 6 is 导 Greater than the thickness H of the detection area 5 检 , try to avoid bubbles during the injection process; to ensure that the liquid sample to be tested can flow continuously from the guide groove area 6 into the detection area 5 and fill it under the action of capillary force, the capillary pressure is required to be greater than zero. The calculation of the capillary force refers to formula 2).
[0061] The structural design of the first embodiment is suitable for applications where the characteristic signal related to the parameter to be measured of the liquid sample is weak, or where only an overall panoramic analysis or a local precise analysis is required. According to the application, a detection area 5 with a single thickness is selected, and a suitable thickness H is set. 检 , in order to perform high-precision measurement of the overall panorama of liquid samples or high-precision analysis of local details.
[0062] Of course, in this embodiment, a detection area 5 may also have multiple thicknesses H 检1 , H 检2 etc., and each thickness value of the detection area 5 is less than the thickness of the diversion groove area 6. The capillary force that drives the liquid sample to be measured into the sampling and detection cavity 2 and the thicknesses of each part of the detection area 5 and the thickness H of the diversion groove area 导 still satisfy Equation (2). When the sample enters the detection area 5 with variable thickness, detection surfaces with different depths of field and different spreading states can be formed. Data processing of the liquid samples in the detection areas with different thicknesses can simultaneously take into account the precision measurement of the overall panorama and local details.
[0063] Example 2
[0064] Figure 3A - Figure 3C FIG. shows the structure of the second embodiment of the microfluidic chip of the present invention. The structure of the second embodiment is a further improvement on the basis of the structure of the first embodiment. The difference between its structure and that of the first embodiment lies in that:
[0065] In order to further avoid the generation of bubbles, at least one exhaust hole 8 is provided on the sampling and detection cavity 2. The exhaust hole 8 is a through hole that connects the inside of the sampling and detection cavity 2 to the outside atmosphere, and can be located on one side or both sides of the detection area 5 or the diversion groove area 6, and can be a symmetric or asymmetric through hole, that is, the exhaust hole 8 penetrates one side wall of the detection area 5 or the diversion groove area 6 or symmetrically penetrates both side walls of the detection area 5 or the diversion groove area 6. Preferably, the exhaust hole 8 is an inverted conical through hole, that is, the small end of the cone opens towards the inside of the diversion groove area 6, and the large end of the cone opens towards the outside atmosphere (see Figure 2C ).
[0066] The advantages of the inverted conical exhaust hole are as follows: First, using the surface tension between the liquid sample to be measured and the gas, the bubbles can be more easily discharged. The exhaust method based on the inverted cone hole proposed by the present invention is not affected by the sampling angle and distance, and can effectively discharge bubbles under different sampling methods; in the case where reagents need to be pre-encapsulated in the sampling and detection cavity 2, since the contact surface between the reagent and the outside environment is very small, when the reagent is added to the sampling and detection cavity 2, its drying process is long. Using the design of the exhaust hole 8 can increase the contact surface between the reagent and the outside environment, accelerate the drying and uniform distribution of the reagent, thereby avoiding the generation of bubbles in various situations; for the function of accurately controlling the sample volume, when the liquid sample to be measured enters the exhaust hole, it is not easy to overflow due to the action of surface tension; the exhaust hole 8 is provided on one side or both sides of the sampling and detection cavity 2. After sampling, only the side of the chip needs to be wiped, avoiding the loss of the liquid sample due to wiping the sampling port; at the same time, the inverted cone hole structure further reduces the possibility of liquid wiping loss.
[0067] The side walls 4 of the chip can all be used for the measurement and analysis of subsequent liquid samples. To prevent the liquid sample to be measured from flowing out under the action of gravity when the microfluidic chip is moved, a transition fillet 10 is provided at the inner edge of the end of the side wall 4 of the chip, and the range of the transition fillet R is 0.2 mm - 1.5 mm. When the microfluidic chip is loaded with samples, a stable liquid bridge surface 11 is formed at the transition fillets 10 at the ends of the two side walls 4 of the chip, which can effectively balance the gravity of the liquid sample to be measured and prevent it from flowing out.
[0068] Specifically, as Figure 3C shown, there are two exhaust holes 8, namely the first exhaust hole 81 and the second exhaust hole 82, which are respectively located at the front end (the position before the liquid sample to be measured enters the detection area 5) and the rear end (the position after the liquid sample to be measured flows out of the detection area 5) of the diversion groove area 6, and are symmetric inverted conical through holes penetrating the diversion groove area 6, which can further avoid the generation of bubbles.
[0069] The other structures of the second embodiment are the same as those of the first embodiment. For the technical solutions not mentioned in the second embodiment, please refer to the first embodiment and will not be elaborated here.
[0070] Example 3
[0071] Figure 4A - Figure 4D The structure of the third embodiment of the microfluidic chip of the present invention is shown. The structure of the third embodiment is a further improvement based on the structure of the second embodiment and / or the first embodiment. The differences between its structure and the structure of the second embodiment and / or the first embodiment are as follows:
[0072] In this embodiment, there are two detection areas 5, namely the first detection area 51 and the second detection area 52, and the two detection areas are independent of each other (set at intervals) and connected, and the two detection areas are connected by the diversion groove area 6. In this embodiment, both detection areas are rectangles combined with rounded corners and right angles, and the thicknesses are H 检1 , H 检2 , respectively. Among them, the thickness H 检1 of the first detection area 51 is larger. The depth of field of the detection surface formed by the liquid sample to be measured in the first detection area 51 is large, and the sample carrying capacity per unit area is large, which is suitable for the precise measurement of the overall panorama of the sample; the thickness H 检1 of the second detection area 52 is small. The depth of field of the detection surface formed by the liquid sample to be measured in the second detection area 52 is small, and the spreading area of the sample per unit volume is large, which can be used for the precise analysis of local details of the liquid sample. This embodiment sets two detection areas 51 and 52 with different thicknesses to simultaneously take into account the precision measurement of the overall panorama and local fineness. The two detection areas 51 and 52 are connected by the diversion groove area 6 with a uniform thickness. Of course, the thicknesses of the two detection areas are both smaller than the thickness of the diversion groove area.
[0073] Specifically, in this embodiment, there are four exhaust holes 8, namely a first exhaust hole 81, a second exhaust hole 82, a third exhaust hole 83, and a fourth exhaust hole 84. Among them, the first exhaust hole 81 and the second exhaust hole 82 are respectively located at the front end (the position before the liquid sample to be tested enters the detection area 51) and the rear end (the position after the liquid sample to be tested flows out of the detection area 52) of the diversion groove area 6. The third exhaust hole 83 is arranged on the first detection area 51, and the fourth exhaust hole 84 is arranged on the second detection area 52. The exhaust holes 8 are all symmetric inverted conical through holes penetrating the diversion groove area 6 or the detection area 5, which can further avoid the generation of bubbles.
[0074] Obviously, multiple detection areas 5 can also have the same thickness, and this thickness value is less than the thickness value of the diversion groove area 6. By setting different detection areas 5, it is helpful to analyze the accuracy and consistency of the detection results of each detection area 5.
[0075] The other structures of the third embodiment are the same as those of the second embodiment and / or the first embodiment, and will not be elaborated here.
[0076] Example 4
[0077] Figure 5A and Figure 5B FIG. shows the structure of the fourth embodiment of the microfluidic chip of the present invention. The structure of the fourth embodiment is a further improvement based on the structure of the third embodiment. The difference between its structure and that of the third embodiment lies in:
[0078] In this embodiment, there are two sampling ports 7, namely a first sampling port 71 and a second sampling port 72. The corresponding first sampling port 71 is provided with a first sampling notch 91, and the second sampling port 72 is provided with a second sampling notch 92. Sampling ports (the first sampling port 71 and the second sampling port 72) are correspondingly set for each detection area (the first detection area 51 and the second detection area 52). For a detection area with a larger thickness, a larger liquid sample carrying capacity per unit area is required. By adding corresponding sampling ports, it is possible to avoid the shortage of the liquid sample amount caused by a single sampling port.
[0079] Specifically, multiple diversion groove areas 6 can be set (it means that different diversion groove areas with different thicknesses and being interconnected are called different diversion groove areas). Each diversion groove area 6 corresponds to a corresponding detection area 5, which is convenient for the liquid sample to flow into the corresponding detection area 5 controllably and quickly. By setting diversion groove areas 6 and detection areas 5 with different thicknesses, the adjustment of different liquid flow rates and liquid laminar flow characteristics can be achieved. The thickness of the detection area 5 is less than the thickness of all diversion groove areas 6; similarly, the diversion groove area 6 can be set as one (the diversion groove area 6 with the same thickness and being interconnected is called the same diversion groove area), and multiple detection areas 5 correspond to the same diversion groove area 6.
[0080] Specifically, by adjusting the angle α between the tangent of the downward arc of the sampling port 7 and the horizontal reference plane of the sampling port 7, the specific orientation of the liquid sample to be measured entering the diversion trough area 6 can be specified, so as to ensure that the liquid sample to be measured spontaneously flows into the detection area 5 in a specific manner until it is full. The preferred range of the angle α is 15° to 45°.
[0081] The material of the chamber structure of the present invention can be selected from any one or a combination of optical-grade transparent polymers, glass, and quartz, ensuring high light transmittance and low fluorescence spontaneous performance.
[0082] Obviously, the slit-type liquid sampling and detection chamber structure of the present invention is not limited to the structure described in the above embodiments. Based on the concept of the present invention, simple addition or subtraction of the number of detection areas, diversion trough areas, sampling ports (with sampling notches), and exhaust holes, transformation of shapes, positions, or combination forms all belong to the disclosure content of the present invention.
[0083] In the above slit-type liquid sampling and detection chamber structure, detection reagents can also be pre-encapsulated. The encapsulation method is as follows: The liquid reagent to be pre-encapsulated is added into the sampling and detection chamber 2 of the microfluidic chip through the sampling port 7 or the sampling notch 9 of the microfluidic chip, and then dried or freeze-dried. The reagent is pre-encapsulated in the detection chamber. In this way, when detecting, the liquid sample is inhaled or injected into the sampling and detection chamber 2 through the sampling port 7 or the sampling notch 9, and thus the liquid sample addition and the reaction between the sample and the reagent are completed simultaneously in the detection chamber.
[0084] The slit-type liquid sampling and detection chamber structure of the above embodiments has the following outstanding features and technical effects:
[0085] 1) The sampling and detection chamber 2 of the present invention adopts a semi-open cavity structure. In the case of reagent pre-encapsulation, a smooth gas path accelerates the speed and uniformity of reagent encapsulation, and prevents bubbles from forming due to disordered liquid flow during subsequent sampling.
[0086] 2) By setting multiple detection areas 5 with different thicknesses, the detection surface formed by the detection area 5 with a large thickness has a large sample load per unit area, which is suitable for the overall panoramic and accurate measurement of liquid samples. The detection surface formed by the detection area 5 with a small thickness has a large spreading area per unit volume of the liquid sample, which is suitable for the local detailed precision analysis of liquid samples, so as to achieve multi-parameter accurate measurement of the same liquid sample in one time.
[0087] 3) Through the connection and thickness design of the diversion trough area 6 and the detection area 5, the controllable and smooth flow of the liquid sample from the diversion trough area 6 to the detection area 5 is realized, and the formation of bubbles due to the disorder of the liquid front is prevented.
[0088] 4) By adjusting the angle α between the tangent of the downward arc of the sampling port 7 and the horizontal reference plane of the sampling port 7, the liquid sample can enter and fill the sampling and detection chamber 2 in a way of being actively sucked by capillary force; through the design of the sampling notch 9 of the sampling port 7, the liquid sample can enter the detection area 5 and fill it in a way of passive capillary injection, so as to achieve the compatibility of two modes of active sampling and passive injection;
[0089] 5) Through the design of the shape, position (flow guide groove area 6 and / or detection area 5), and quantity of the exhaust hole 8, while the gas path can smoothly and effectively discharge gas to prevent bubbles, the liquid sample can be prevented from overflowing due to the capillary flow inertia force; through the design of the distribution of the exhaust hole 8, the exhaust hole 8 is distributed on one side of the sampling and detection chamber 2 or symmetrically arranged on both sides. After sampling, only the side of the sampling and detection chamber 2 needs to be wiped, avoiding the loss of the liquid sample due to wiping the sampling port;
[0090] 6) By setting a transition fillet 10 on the inner rib of the upper edge of the side wall 4 of the chip, a stable liquid bridge surface 11 can be formed for the liquid at the edge of the sampling and detection chamber 2, avoiding the liquid sample from flowing out due to the action of gravity during the movement of the microfluidic chip.
[0091] Sampling method
[0092] The chamber structure of the present invention is usually integrally formed with the support substrate or fixed to the front end of the support substrate. After sampling the liquid sample, it is placed in a corresponding detection and analysis instrument for detection. There are two sampling methods. One is active sampling based on capillary force, that is, the sampling port 7 of the chamber structure is immersed in the liquid sample or reagent, and the liquid is actively sucked by capillary force to the detection area 5 and filled; the other is passive injection based on a pipette, that is, a pipette is used to suck the liquid sample or reagent, the pipette is placed at the sampling notch 9 of the sampling port 7, and the liquid is added to the detection area 5 in the chamber structure and filled, thus completing the sampling operation.
[0093] The above slit-type liquid sampling and detection chamber structure is applicable to the sampling operation of trace liquid samples, such as the analysis of the composition and content of liquid samples. The slit-type liquid sampling and detection chamber structure of the present invention has two sample addition methods: passive sampling and active injection. The liquid reagent can be mixed with the liquid sample outside the chamber structure, or the liquid reagent can be pre-packaged in the chamber structure. According to the different sample addition methods and whether reagent pre-packaging is required, the sampling operation of the liquid sample to be tested is also different.
[0094] The sampling method includes the following steps: immersing the sampling port 7 of the slit-type liquid sampling and detection chamber structure in the pre-treated liquid sample, and actively sucking the liquid sample to the detection area 5 and filling it; or
[0095] Use a pipette to aspirate the pretreated liquid sample, then place the pipette at the sampling notch 9 of the sampling port 7, and inject the liquid sample into the detection area 5 in the chamber structure and fill it up.
[0096] Those skilled in the art should understand that these embodiments are only used to illustrate the present invention and do not limit the scope of the present invention. All equivalent variations and modifications made to the present invention belong to the disclosure content of the present invention.
Claims
1. A slit-type liquid sampling and detection chamber structure, comprising a sampling and detection chamber (2). The sampling and detection chamber (2) is a semi-open cavity formed by two parallel chamber side walls (4) with a certain gap, and has a detection area (5), a sampling port (7), and a diversion groove area (6) connecting the sampling port (7) and the detection area (5). The thickness of the detection area (5) is less than the thickness of the diversion groove area (6) , and at least one exhaust hole (8) is provided on the sampling and detection chamber (2). The exhaust hole (8) is a through hole connecting the inside of the sampling and detection chamber (2) and the outside atmosphere, and penetrates one side wall of the detection area (5) or the diversion groove area (6), or symmetrically penetrates both side walls of the detection area (5) or the diversion groove area (6); The sampling and detection chamber (2) is provided with a plurality of detection areas (5), the plurality of detection areas (5) are independent of each other and communicate with each other, and have different thicknesses; The exhaust hole (8) is an inverted conical through hole, the small end opening of the cone faces the inside of the detection area (5) or the diversion groove area (6), and the large end opening of the cone faces the outside atmosphere; The detection area (5) is in the shape of a rectangle, a square, a trapezoid, a circle or a combination of an arc and other shapes, and each shape is provided with rounded corners, right angles or a combination of rounded corners and right angles.
2. The slit-type liquid sampling and detection chamber structure according to claim 1, characterized in that, A detection area (5) is provided in the sampling detection cavity (2), and the detection area (5) has a single thickness .
3. The slit-type liquid sampling and detection chamber structure according to claim 1, wherein The sampling and detection chamber (2) is provided with two detection areas (5) with different thicknesses, namely a first detection area (51) and a second detection area (52), and the first detection area (51) and the second detection area (52) are communicated by a diversion groove area (6).
4. The slit-type liquid sampling and detection chamber structure according to any one of claims 1 to 3, characterized in that, The sampling port (7) is located at the upper edge opening of the two chip side walls (4) of the sampling and detection chamber (2), and one of the two chamber side walls (4) is provided with a sampling notch (9) at the upper edge at the sampling port (7) to inject a liquid sample through the sampling notch (9).
5. The slit-type liquid sampling and detection chamber structure according to any one of claims 1 to 3, characterized in that, The sampling port (7) is in a concave arc shape, and the included angle α between the tangent of the downward sliding arc and the horizontal reference plane of the sampling port (7) ranges from 15° to 45°.
6. The slit-type liquid sampling and detection chamber structure according to claim 1 or 3, characterized in that, Each detection area is provided with a corresponding sampling port.
7. The slit-type liquid sampling and detection chamber structure according to claim 6, characterized in that, Each sampling port is provided with a sampling notch.
8. The slit-type liquid sampling and detection chamber structure according to any one of claims 1 to 3, characterized in that, The inner edge of the end of the chamber side wall (4) is provided with a transition fillet (10), and the range of the transition fillet R is 0.2 mm - 1.5 mm.
9. The slit-type liquid sampling and detection chamber structure according to any one of claims 1 to 3, characterized in that, The sampling and detection chamber also includes a pre-packaged liquid reagent, and the pre-packaging method is: adding the liquid reagent into the sampling and detection chamber through the sampling port or the sampling notch, drying or freeze-drying, and the reagent is pre-packaged in the sampling and detection chamber.
10. A method for sampling trace liquid, which is operated by using the slit-type liquid sampling and detection chamber structure according to any one of claims 1 to 9, and includes the following steps: Immersing the sampling port (7) of the slit-type liquid sampling and detection chamber structure into the pre-treated liquid sample, and actively sucking the liquid sample until the detection area (5) is filled; or Sucking the pre-treated liquid sample with a pipette, and then placing the pipette at the sampling notch (9) of the sampling port (7) to inject the liquid sample into the chamber structure until the detection area (5) is filled.
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