Disclosure of Invention
In order to solve the above problems, the present invention provides an improved slit type liquid sampling detection chamber structure.
The technical scheme adopted by the invention is as follows:
The utility model provides a slit type liquid sample detects cavity structure, includes sample detection chamber (2), sample detection chamber (2) is the semi-open cavity that two parallel cavity lateral walls (4) that have certain clearance formed, has detection zone (5), sampling port (7) and intercommunication sampling port (7) and guiding gutter district (6) of detection zone (5), and thickness H Inspection and detection of detection zone (5) is less than thickness H Guide rail of guiding gutter district (6), be provided with at least one exhaust hole (8) on sample detection chamber (2), exhaust hole (8) are inside and external atmospheric through-hole of intercommunication sample detection chamber (2), and it runs through one side wall or the symmetry of detection zone (5) or guiding gutter district (6).
In the slit type liquid sampling detection cavity structure, the exhaust hole (8) is an inverted cone-shaped through hole, the cone-shaped small end opening faces the detection area (5) or the inside of the diversion trench area (6), and the cone-shaped large end opening faces the outside atmosphere.
In the above slit type liquid sampling detection chamber structure, a detection area (5) is disposed in the sampling detection chamber (2), and the detection area (5) has a single thickness H Inspection and detection .
In the slit type liquid sampling detection cavity structure, the sampling detection cavity (2) is provided with a plurality of detection areas (5), the detection areas (5) are mutually independent and communicated, the thickness is the same or different, and the thickness of any detection area (5) is smaller than the thickness H Guide rail of the diversion trench area (6).
In the slit type liquid sampling detection cavity structure, the sampling detection cavity (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 through a diversion trench area (6).
In the slit type liquid sampling detection cavity structure, the sampling port (7) is positioned at the opening of the upper end edges of the two chip side walls (4) of the sampling detection cavity (2), wherein a sampling notch (9) is arranged at the upper end edge of one of the two cavity side walls (4) positioned at the sampling port (7) so as to inject a liquid sample through the sampling notch (9).
In the slit type liquid sampling detection cavity structure, the sampling port (7) is in a concave arc shape, and the value range of an included angle alpha between the tangent line of the downward sliding arc line of the sampling port and the horizontal reference surface of the sampling port (7) is 15-45 degrees.
In the slit type liquid sampling detection cavity structure, each detection area is provided with a corresponding sampling port.
In the slit type liquid sampling detection cavity structure, a sampling notch is arranged in each sampling port.
In the slit type liquid sampling detection cavity structure, the inner edge of the side wall (4) of the cavity is provided with a transition fillet (10), and the range of the transition fillet R is 0.2mm-1.5mm.
In the above-mentioned slit type liquid sampling detection chamber structure, the detection area (5) may be rectangular, square, trapezoid, circular or arc-shaped and other combinations of shapes, and each shape may be provided with a round angle, a right angle or a combination of round angles and right angles.
In the slit type liquid sampling detection cavity structure, the sampling detection cavity also comprises a pre-packaged liquid reagent, and the pre-packaging mode is that the liquid reagent is added into the sampling detection cavity through a sampling port or a sampling notch, and is dried or freeze-dried, and the reagent is pre-packaged in the sampling detection cavity.
The invention also provides a micro liquid sampling method, which adopts any slit type liquid sampling detection cavity structure to operate, and comprises the following steps:
Immersing a sampling port (7) of the slit type liquid sampling detection chamber structure into the pretreated liquid sample, actively sucking the liquid sample until the detection area (5) is full, or
The liquid sample after pretreatment is sucked by a liquid suction pipe, the liquid suction pipe is placed at a sampling notch (9) of a sampling port (7), and the liquid sample is injected into the cavity structure until the detection area (5) is filled.
The slit type liquid sampling detection cavity structure has the beneficial effects that the slit type liquid sampling detection cavity structure is provided with the semi-open type sampling detection cavity, the sampling detection cavity is provided with the sampling port, the detection area and the diversion trench area communicated with the sampling port and the detection area, the thickness of the detection area is smaller than that of the diversion trench area, and the diversion trench area and/or the detection area are provided with the plurality of vent holes.
Detailed Description
In order to solve the problems that the precision of the whole panoramic analysis and the local precise analysis cannot be simultaneously considered, the bubble interference exists, the sampling precision is low, the sampling mode is single, the application range is limited and the like in the detection cavity structure in the traditional microfluidic sampling chip, the invention provides a slit type liquid sampling detection cavity structure and a sampling method, the cavity structure comprises a sampling detection cavity, the sampling detection cavity is a semi-open cavity formed by two parallel cavity side walls with a certain gap, and the semi-open cavity is provided with a plurality of detection areas with multi-mode sampling and one or different thickness, and a diversion trench area design and an exhaust hole design for communicating a sampling port and the detection areas; the cavity structure can realize two sample adding modes of active sample suction and passive sample injection by arranging the sampling notch, the exhaust hole and one or a plurality of detection areas with different thicknesses, so that the generation of bubbles is avoided, the accurate control of the liquid sample quantity is realized, the precision of overall panoramic analysis and local precise analysis is facilitated, and a foundation is laid for the multi-parameter measurement of the liquid sample for biological analysis and chemical analysis. .
The slit type liquid sampling detection chamber structure and the sampling method according to the present invention will be described in detail with reference to the first to fourth embodiments and the accompanying drawings.
Example 1
Fig. 2A-2C illustrate an exemplary slit-type liquid sampling detection chamber structure according to the present invention. In the first embodiment shown in fig. 2A-2C, the chamber structure includes a sampling detection chamber 2, the sampling detection chamber 2 is a semi-open cavity formed by two parallel chamber sidewalls 4 with a certain gap, and includes a sampling port 7, a sampling notch 9, a detection area 5, and a flow guiding groove area 6 communicating the sampling port 7 and the detection area 5, wherein:
The sampling port 7 is located at the opening of the upper end edges of the two chip side walls 4 of the sampling detection cavity 2, and similar to the existing detection cavity shown in fig. 1, the sampling port 7 can be used for sampling under the action of capillary force in an active sucking mode.
The detection area 5 is positioned in the sampling detection cavity 2, the detection area 5 can be rectangular, square, trapezoid, round or arc-shaped or combined with other shapes, each shape can be provided with a round angle, a right angle or a combination of round angles and right angles, the specific shape of the detection area 5 is not limited, the detection area 5 has single thickness H Inspection and detection , the thickness range of the detection area 5 is generally 60-120 mu m, a detection surface is formed by a sample entering the detection area 5, the detection area 5 with large thickness is formed, the sample carrying capacity per unit area of the detection surface is large, the depth of field is large, the method is suitable for overall panoramic analysis of liquid samples, the spreading area of the liquid samples with small thickness and the same volume on the detection surface is large, and the method is suitable for local precise analysis of the liquid samples.
The diversion trench area 6 is positioned in the sampling detection cavity 2 and communicated with the sampling port 7 and the detection area 5, and the thickness range of the diversion trench area 6 is generally 120-500 μm. As shown in fig. 2C, the thickness of the detection area 5 is smaller than that of the diversion trench area 6, and the liquid sample enters the flow path formed by the diversion trench area 6 through the sampling port 7 to be uniformly and rapidly introduced and fill the whole sampling detection cavity 2.
The thickness of the detection area 5 and the thickness of the flow guiding groove area 6 determine the flowing state of the liquid sample to be detected in the flow guiding groove area 6 and the spreading state in the detection area 5. The liquid sample to be tested enters the diversion trench area 6 through the sampling port 7, the sample suction stage belongs to the pure inertia rising stage under the action of capillary force, and the relationship between the sucked liquid sample to be tested and the thickness of the detection area 5 can be obtained according to the formula 1) of the pure inertia rising stage of capillary flow:
In order to ensure that the liquid sample continuously flows from the channel region 6 into the detection region 5 under capillary force and fills the sampling detection chamber 2, it is required that the capillary force is greater than zero. The capillary force has the following relation with the thickness H Inspection and detection of the detection zone 5 and the thickness H Guide rail of the diversion trench zone:
Specifically, in this embodiment, one detection area 5 is disposed in the sampling detection chamber 2, and has a single thickness H Inspection and detection , which is a rounded rectangle. When the thickness H Inspection and detection of the detection area 5 is larger, the depth of field of the detection surface formed on the side wall 4 of the cavity is large, the carrying capacity of the sample in unit area is large, the method is suitable for overall panoramic analysis of liquid samples, the thickness of the detection area 5 is preferably 90-120 mu m, when the thickness H Inspection and detection of the detection area 5 is smaller, the depth of field of the detection surface formed on the side wall 4 of the cavity is small, the spreading area of the sample in unit volume is large, the method is suitable for local precise analysis of the liquid samples, and the thickness of the detection area 5 is preferably 60-90 mu m.
Furthermore, a sampling notch 9 is provided at the upper end edge of one of the two chip side walls 4 at the sampling port 7, so that the sample can be conveniently added from the sampling notch 9 by injection. The sampling port 7 and the sampling notch 9 are compatible with the liquid sampling modes of active sample injection and passive sample suction. In this embodiment, the sampling port 7 is in a concave arc shape, and the angle α (see fig. 2A) between the tangent line of the downward sliding arc (the left arc is shown in the figure) and the horizontal reference plane of the sampling port 7 can determine the flow direction of the liquid sample to be measured entering the flow guiding slot area 6, so as to ensure that the liquid sample to be measured spontaneously flows into the detection area 5 and fills up in a predetermined manner. The preferable range of the angle alpha is 15-45 degrees.
Specifically, the flow guiding groove region 6 is positioned in the sampling detection cavity 2 and is communicated with the sampling port 7 and the detection region 5, the thickness H Guide rail of the flow guiding groove region 6 is larger than the thickness H Inspection and detection of the detection region 5, bubbles are avoided as much as possible in the sample injection process, and in order to ensure that a liquid sample to be detected can continuously flow from the flow guiding groove region 6 into the detection region 5 and is filled under the action of capillary force, the capillary pressure is required to be larger than zero, and the calculation of the capillary force is referred to as reference type 2).
The structural design of the first embodiment is suitable for application occasions where the marking signals related to the parameters to be measured of the liquid sample are weak, or only the whole panoramic analysis or only the local precise analysis is needed, and according to the application occasions, the detection area 5 with single thickness is selected, and the proper thickness H Inspection and detection is set so as to perform the whole panoramic high-precision measurement or the local detail high-precision analysis of the liquid sample.
Of course, in this embodiment, one detection area 5 may also have a plurality of thicknesses H Inspection and detection 1,H Inspection and detection 2, and the thickness values of the detection areas 5 are smaller than the thickness of the flow guiding groove area 6, so that the relationship between the capillary force driving the liquid sample to be detected into the sampling detection cavity 2 and the thickness of the detection area 5 and the thickness H Guide rail of the flow guiding groove area still satisfies the formula 2). The sample enters the detection area 5 with thickness variation, detection surfaces with different depth of field and different spreading states can be formed, and the precision measurement of the whole panorama and the local detail can be simultaneously considered by carrying out data processing on the liquid sample in the detection areas with different thicknesses.
Example two
Fig. 3A to 3C show the structure of a second embodiment of the microfluidic chip of the present invention. The structure of the second embodiment is a further improvement on the structure of the first embodiment, and is different from the structure of the first embodiment in that:
In order to further avoid the generation of bubbles, the sampling detection cavity 2 is provided with at least one air vent 8, the air vent 8 is a through hole for communicating the inside of the sampling detection cavity 2 with the outside atmosphere, and may be located at one side or two sides of the detection area 5 or the diversion trench area 6, and may be a symmetrical or asymmetrical through hole, that is, the air vent 8 penetrates through a side wall of the detection area 5 or the diversion trench area 6 or penetrates through two side walls of the detection area 5 or the diversion trench area 6 symmetrically. Preferably, the vent hole 8 is an inverted cone-shaped through hole, i.e. the small end of the cone-shaped opening faces the inside of the diversion trench area 6, and the large end of the cone-shaped opening faces the outside atmosphere (see fig. 2C).
The inverted cone-shaped vent hole has the advantages that firstly, the surface tension of a liquid sample to be tested and gas is utilized to enable bubbles to be discharged more easily, the inverted cone-hole-based vent mode provided by the invention is not influenced by sampling angles and distances, bubbles can be discharged effectively in different sampling modes, under the condition that reagents are required to be packaged in the sampling detection cavity 2 in advance, the contact surface between the reagents and the external environment is very small, the drying process is long after the reagents are added into the sampling detection cavity 2, the contact surface between the reagents and the external environment can be increased by utilizing the design of the vent hole 8, the drying and uniform distribution of the reagents are accelerated, so that bubbles in various conditions are avoided, the effect of accurately controlling the sample quantity is achieved, the vent hole 8 is arranged on one side or two sides of the sampling detection cavity 2 and is only required to wipe the side surface of a chip after sampling is finished, the loss of the liquid sample due to the sampling port is avoided, and meanwhile, the inverted cone hole structure further reduces the possibility of liquid wiping loss.
The chip side wall 4 can be used for measuring and analyzing subsequent liquid samples, in order to prevent the liquid sample to be measured from flowing out under the action of gravity when the microfluidic chip is moved, the inner edge of the end edge of the chip side wall 4 is provided with a transition fillet 10, and the range of the transition fillet R is 0.2mm-1.5mm. After the microfluidic chip is injected, a stable liquid bridge surface 11 is formed at the transition rounded corners 10 of the end edges of the two chip side walls 4 of the liquid sample, so that the gravity of the liquid to be measured can be effectively balanced and the liquid can not flow out.
Specifically, as shown in fig. 3C, two exhaust holes 8, i.e., a first exhaust hole 81 and a second exhaust hole 82, 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 trench area 6, and are symmetrical inverted cone-shaped through holes penetrating through the diversion trench area 6, so that bubbles can be further avoided.
Other structures of the second embodiment are the same as those of the first embodiment, and the technical solution not mentioned in the second embodiment is referred to the first embodiment, and will not be described herein.
Example III
Fig. 4A to 4D show the structure of a third embodiment of the microfluidic chip of the present invention. The structure of the third embodiment is a further improvement on the structure of the second and/or first embodiment, and is different from the structure of the second and/or first embodiment in that:
In this embodiment, two detection areas 5 are provided, namely a first detection area 51 and a second detection area 52, and the two detection areas are mutually independent (arranged at intervals) and are communicated, and the two detection areas are communicated by a diversion trench area 6. In this embodiment, the two detection areas are rectangular with rounded corners and right angles, and the thickness is H Inspection and detection 1、H Inspection and detection 2, where the thickness H Inspection and detection 1 of the first detection area 51 is large, the depth of field of the detection surface formed by the liquid sample to be detected in the first detection area 51 is large, the carrying capacity of the sample in unit area is large, and the liquid sample to be detected is suitable for accurately measuring liquid in the whole panorama of the sample, the thickness H Inspection and detection 1 of the second detection area 52 is small, the depth of field of the detection surface formed by the liquid sample to be detected in the second detection area 52 is small, and the spreading area of the sample in unit volume is large, and the liquid sample can be used for accurately analyzing the local details of the liquid sample. The embodiment is provided with two detection areas 51 and 52 with different thicknesses, and the overall panorama and the local fine precision measurement can be simultaneously considered. The two detection areas 51 and 52 are connected by the diversion trench area 6 having a uniform thickness, and of course, the thickness of the two detection areas is smaller than that of the diversion trench area.
Specifically, in this embodiment, four exhaust holes 8 are provided, which are a first exhaust hole 81, a second exhaust hole 82, a third exhaust hole 83, and a fourth exhaust hole 84, where the first exhaust hole 81 and the second exhaust hole 82 are located at the front end (the position before the liquid sample to be measured enters the detection area 51) and the rear end (the position after the liquid sample to be measured flows out of the detection area 52) of the diversion trench area 6, respectively, the third exhaust hole 83 is disposed on the first detection area 51, the fourth exhaust hole 84 is disposed on the second detection area 52, and the exhaust holes 8 are symmetrical inverted cone-shaped through holes penetrating through the diversion trench area 6 or the detection area 5, so that bubbles can be further avoided.
Obviously, the plurality of detection areas 5 can also have the same thickness, and the thickness value is smaller than that of the diversion trench area 6, so that the accuracy and consistency of the detection results of the detection areas 5 can be analyzed by arranging different detection areas 5.
Other structures of the third embodiment are the same as those of the second and/or first embodiments, and will not be described here again.
Example IV
Fig. 5A and 5B show the structure of a fourth embodiment of the microfluidic chip of the present invention. The structure of the fourth embodiment is a further improvement on the structure of the third embodiment, and is different from the structure of the third embodiment in that:
In this embodiment, two sampling ports 7 are provided, 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, the corresponding 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 provided for each detection area (the first detection area 51 and the second detection area 52), and for the detection area with larger thickness, a larger liquid sample carrying capacity per unit area is required, and the corresponding sampling ports are additionally provided to avoid the shortage of the liquid sample amount caused by the single sampling port.
Specifically, the flow guiding groove areas 6 can be provided with a plurality of flow guiding groove areas (the flow guiding groove areas with different thicknesses which are mutually communicated are called different flow guiding groove areas), each flow guiding groove area 6 corresponds to a corresponding detection area 5, so that a liquid sample can flow into the corresponding detection area 5 controllably and quickly, different liquid flow rates and adjustment of laminar flow characteristics of the liquid can be realized by arranging the flow guiding groove areas 6 with different thicknesses and the detection areas 5, the thickness of the detection areas 5 is smaller than that of all the flow guiding groove areas 6, and similarly, the flow guiding groove areas 6 can be provided as one flow guiding groove area (the flow guiding groove areas 6 with the same thickness and which are mutually communicated are called the same flow guiding groove area), and the plurality of detection areas 5 correspond to the same flow guiding groove area 6.
Specifically, by adjusting the included angle α between the tangent line of the downward sliding 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 trench area 6 can be specified, so that the liquid sample to be measured can be ensured to spontaneously flow into the detection area 5 until the liquid sample is full in a specific manner. The preferable range of the angle alpha is 15-45 degrees.
The material of the chamber structure of the invention can be any one or a combination of a plurality of optical grade transparent polymers, glass and quartz, so as to ensure high light transmittance and low fluorescence autonomy.
Obviously, the slit type liquid sampling detection chamber structure of the present invention is not limited to the structure described in the above embodiments, and the number, the changing shape, the position or the combination form of the detection area, the diversion trench area, the sampling port (with the sampling notch), the exhaust hole are simply increased or decreased based on the concept of the present invention.
The slit type liquid sampling detection chamber structure can also be used for pre-packaging detection reagents. The packaging mode is that liquid reagent to be pre-packaged is added into a sampling detection cavity 2 of the microfluidic chip through a sampling port 7 or a sampling notch 9 of the microfluidic chip, and is dried or freeze-dried, and the reagent is pre-packaged in the detection cavity. In this way, when the liquid sample is to be detected, the liquid sample is sucked or injected into the sampling detection cavity 2 through the sampling port 7 or the sampling notch 9, namely, the sample adding of the liquid sample and the reaction of the sample and the reagent are simultaneously completed in the detection cavity.
The slit type liquid sampling detection chamber structure of the above embodiment has the following outstanding characteristics and technical effects:
1) According to the invention, the sampling detection cavity 2 adopts a semi-open cavity structure, so that the speed and uniformity of reagent packaging are accelerated by a smooth gas path under the condition that reagent pre-packaging is required, and bubbles are prevented from being formed due to unsmooth liquid flow in the subsequent sampling process;
2) By arranging a plurality of detection areas 5 with different thicknesses, the carrying capacity of the sample in the unit area of the detection surface formed by the detection areas 5 with large thickness is large, so that the method is suitable for the overall panoramic accurate measurement of a liquid sample, and the spreading area of the liquid sample in the unit volume of the detection surface formed by the detection areas 5 with small thickness is large, and is suitable for the local detail accurate analysis of the liquid sample, thereby realizing the one-time completion of the multi-parameter accurate measurement of the same liquid sample;
3) Through the connection and thickness design of the diversion trench area 6 and the detection area 5, the controllable and smooth flow of the liquid sample from the diversion trench area 6 to the detection area 5 is realized, and the turbulence of the front surface of the liquid is prevented from forming bubbles;
4) Through the design of the sampling notch 9 of the sampling port 7, the liquid sample can enter the detection area 5 and be filled in a passive capillary sample injection mode, thereby realizing the compatibility of two modes of active sample suction and passive sample injection;
5) Through the design of the shape, the positions (the diversion trench areas 6 and/or the detection areas 5) and the number of the vent holes 8, the gas can be smoothly and effectively discharged from the gas path to prevent bubbles, and meanwhile, liquid samples are prevented from overflowing due to capillary flow inertia force;
6) The transition fillet 10 is arranged on the inner edge of the upper end edge of the chip side wall 4, so that the liquid at the edge of the sampling detection cavity 2 can form a stable liquid bridge surface 11, and the liquid sample is prevented from flowing out due to the action of gravity in the moving process of the microfluidic chip.
Sampling method
The cavity structure of the invention is generally integrally formed with the supporting substrate or fixed at the front end of the supporting substrate, and the liquid sample is sampled and then placed into a corresponding detection and analysis instrument for detection. The sampling mode includes two types, namely active sample suction based on capillary force, namely, a sampling port 7 of a chamber structure is immersed in liquid sample or reagent, liquid is actively sucked to a detection area 5 through the capillary force and is filled, and passive sample injection based on a liquid suction pipe, namely, the liquid sample or reagent is sucked by the liquid suction pipe, the liquid suction pipe is placed at a sampling notch 9 of the sampling port 7, and the liquid is added into the detection area 5 in the chamber structure and is filled, so that the sampling operation is completed.
The slit type liquid sampling detection chamber structure is suitable for sampling operation of micro liquid samples, such as liquid sample composition and content analysis. The slit type liquid sampling detection cavity structure has two sample adding modes of passive sample suction and active sample injection, liquid reagents can be mixed with liquid samples outside the cavity structure, the liquid reagents can be pre-packaged in the cavity structure, and sampling operations of liquid samples to be detected are different according to different sample adding modes and whether the pre-packaged reagents are needed or not.
The sampling method comprises immersing the sampling port 7 of the slit liquid sampling detection chamber structure into the pretreated liquid sample, actively sucking the liquid sample into the detection zone 5 and filling, or
The liquid sample after pretreatment is sucked by a liquid suction pipe, then the liquid suction pipe is arranged at a sampling notch 9 of a sampling port 7, and the liquid sample is injected into a detection area 5 in the cavity structure and is filled.
It will be appreciated by those skilled in the art that these examples are intended to illustrate the invention and not to limit the scope of the invention, and that various equivalent variations and modifications to the invention are within the scope of the present disclosure.