CN216024956U - Micro-fluidic distribution chip - Google Patents

Abstract

The utility model relates to a micro-fluidic distribution chip, which comprises a sample adding hole, a sample adding pipeline, a distribution cavity, an exhaust pipeline, a sample outlet pipeline, an exhaust hole and a bypass pipeline which are sequentially communicated, wherein the bypass pipeline is communicated with the sample adding pipeline and the sample outlet pipeline and is used for enabling a fluid sample added through the sample adding hole to flow to the sample outlet pipeline through the bypass pipeline after the distribution cavity is filled with the fluid sample, and the trend of the fluid can be controlled by limiting the cross section area or the depth of each pipeline and cavity.

Description

Micro-fluidic distribution chip

Technical Field

The utility model relates to a micro-fluidic distribution chip, belonging to the technical field of micro-fluidic.

Background

In the fields of medicine, biology, chemistry, etc., it is often necessary to perform a variety of tests and procedures with a single sample, and it is necessary to utilize sample dispensing techniques. The existing sample distribution technology generally needs to use a liquid transfer device to suck samples for multiple times, and then the samples are respectively pumped into different reaction tanks or reaction tubes, so that impurities are easily introduced in the distribution process, and pollution is caused; meanwhile, in order to reduce the influence caused by sample volatilization, the volume of a single system to be distributed cannot be too small. The micro-fluidic technology is a technology which takes a micro-fluidic chip as a carrier, is mutually combined with chemical, biological and other subjects, and realizes the analysis and detection process on a platform in a miniaturization, integration and automation way. The microfluidic technology provides the possibility for the automatic transportation and distribution of the fluid. The utility model with the granted publication number of CN102671729B discloses a micro-fluidic chip for biochemical detection of many indexes, its reaction tank is walked or is connected in parallel, utilizes pneumatic little valve to realize the isolation between the reaction chamber, but the sample probably causes the cross contamination between the different position reaction tanks at the in-process that continuously flows, is unfavorable for the accurate analysis of reaction result. The utility model discloses a grant utility model patent with publication number CN110075935B discloses many indexes detect micro-fluidic card box and application method, and this method carries out sample distribution based on the rotary valve, when the rotary valve rotated to different gears, uses the syringe pump drive sample, can make the sample get into different reaction chambers, but this method structure is complicated, and is with high costs, and receives space limitation, and achievable distribution quantity is limited.

SUMMERY OF THE UTILITY MODEL

The utility model provides a microfluidic distribution chip which is simple in structure, convenient to manufacture and use, can ensure the purity of a sample while realizing automatic distribution of the sample, and further can complete multi-index parallel detection of the sample.

The technical scheme for solving the technical problems is as follows:

a micro-fluidic distribution chip comprises a sample adding hole, a sample feeding pipeline, a distribution cavity, an exhaust pipeline, a sample outlet pipeline, an exhaust hole, a bypass pipeline and a filtering unit which are sequentially communicated, wherein the bypass pipeline is communicated with the sample feeding pipeline and the sample outlet pipeline and is used for enabling fluid added through the sample adding hole to flow to the sample outlet pipeline through the bypass pipeline after the distribution cavity is filled with the fluid, the filtering unit comprises a filtering membrane arranged below the sample adding hole and a filtering cavity arranged below the filtering membrane, the filtering membrane is at least one layer, and the filtering cavity is communicated with the sample feeding pipeline; the micro-fluidic distribution chip further comprises interface valves arranged between the exhaust pipeline and the sample outlet pipeline, wherein the number of the interface valves is at least 1, and the interface valves are used for assisting in blocking fluid passing through the exhaust pipeline.

As a preferred scheme, the cross-sectional areas of the distribution cavity, the sample introduction pipeline, the bypass pipeline and the exhaust pipeline are sequentially decreased progressively.

As the preferred scheme, the depths of the sample introduction pipeline, the distribution cavity and the exhaust pipeline are the same, and the depths of the interface valve, the bypass pipeline and the sample introduction pipeline are sequentially decreased progressively.

As the preferred scheme, the micro-fluidic distribution chip comprises a chip body and a cover plate connected above the chip body, wherein the distribution cavity and the filter cavity are arranged on the chip body, and the sample adding hole, the sample introduction pipeline, the exhaust pipeline, the sample outlet pipeline, the exhaust hole and the bypass pipeline are arranged on the cover plate.

As preferred scheme, the micro-fluidic distribution chip includes the chip body and connects in the apron of chip body top, distribution chamber, filter chamber, application of sample hole, introduction pipeline, exhaust duct, play appearance pipeline, exhaust hole and bypass pipeline all set up in on the chip body, the micro-fluidic distribution chip still including set up in transition pipeline between introduction pipeline and the distribution chamber.

Preferably, the microfluidic distribution chip further comprises a flash chamber disposed between the sample outlet pipe and the vent hole, and the flash chamber is used for storing redundant fluid samples.

Preferably, an optical detection sensor is arranged at the overflow cavity and used for detecting the filling amount of the fluid.

Preferably, the dispensing chamber has a pre-stored reagent for reaction with the sample to complete the detection.

As the preferred scheme, a set of distribution unit is formed by the sample introduction pipeline, the distribution cavity, the exhaust pipeline, the interface valve, the sample outlet pipeline and the bypass pipeline, a plurality of sets of distribution units can be arranged on each distribution unit, and the adjacent distribution units are communicated with the sample introduction pipeline of the next unit through the sample outlet pipeline of the previous unit.

The microfluidic distribution chip provided by the utility model has the following beneficial effects:

(1) the sample distribution device has the advantages of simple structure, convenience in manufacture and use, automatic distribution of samples is realized, the purity of the samples can be ensured, and cross contamination of fluids among different cavities can be avoided;

(2) through structural optimization and introduction of an interface valve, the microfluidic distribution chip provided by the utility model can be compatible with fluids with different properties, and particularly can effectively improve the compatibility with a low-surface-energy sample;

(3) the introduction of the filtering unit can realize the serum separation of the whole blood sample, thereby realizing the detection of indexes such as biochemistry or immunity by taking the serum as the sample;

(4) the device has a large compatible range for the pressure or flow rate of the driving liquid, thereby completing the multi-index parallel detection of the sample.

Drawings

Fig. 1 is a schematic overall structure diagram of a microfluidic distribution chip according to embodiment 1 of the present invention;

FIG. 2 is a top view of a chip body in example 1 of a microfluidic distribution chip according to the present invention;

fig. 3 is a bottom view of a cover plate in an embodiment 1 of a microfluidic distribution chip according to the present invention;

FIG. 4 is an exploded view of a microfluidic distribution chip according to example 1 of the present invention;

FIG. 5 is a top view of a chip body in example 2 of a microfluidic distribution chip according to the present invention;

FIG. 6 is a schematic diagram of the overall structure of a microfluidic distribution chip according to example 2 of the present invention;

FIG. 7 is a top view of the chip body in example 3 of the microfluidic distribution chip of the present invention;

FIG. 8 is a graph of driving pressure versus fill time for a sample of water in accordance with the present invention;

FIG. 9 is a driving pressure versus fill time for a sample of the present invention in 50% aqueous ethanol;

FIG. 10 is a graph of the relationship of driving pressure and fill time for filling the dispensing chamber after a whole blood sample has passed through the filter unit in accordance with the present invention.

In the figure, 1, a chip body, 2, a cover plate, 11.21.31, a distribution cavity, 12.22.32, a sample adding hole, 13.23.33, a sample feeding pipeline, 14.24.34, a bypass pipeline, 15.25.35, an exhaust pipeline, 16.26.36, an interface valve, 17.27.37, a sample outlet pipeline, 18, an overflow cavity, 19.29.39, an exhaust hole, 20, a transition pipeline, 41, a filter cavity and 42 are filter membranes.

Detailed Description

The principles and features of this invention are described below in conjunction with the following drawings, which are set forth to illustrate, but are not to be construed to limit the scope of the utility model.

Example 1

Referring to fig. 1 to 4, the microfluidic distribution chip provided in this embodiment includes a chip body 1 and a cover plate 2, and the chip body 1 and the cover plate 2 may be hermetically engaged by double-sided adhesive, thermocompression bonding, ultrasonic welding, laser welding, and the like. The chip body 1 is provided with a distribution cavity 11, the cover plate 2 is provided with a sample adding hole 12, a sample feeding pipeline 13, a bypass pipeline 14, an exhaust pipeline 15, a sample outlet pipeline 17 and an exhaust hole 19. The sample adding hole 12, the sample feeding pipeline 13, the distribution cavity 11, the exhaust pipeline 15, the sample outlet pipeline 17 and the exhaust hole 19 are communicated in sequence, and the bypass pipeline 14 is communicated with the sample feeding pipeline 13 and the sample outlet pipeline 17.

The distribution cavity 11 on the chip body 1, the sample injection pipeline 13 on the cover plate 2, the bypass pipeline 14, the exhaust pipeline 15 and the sample outlet pipeline 17 form a set of distribution units, the number of the distribution units can be set randomly according to the test requirement during actual use, and the sample outlet pipeline 17 of the previous unit and the sample injection pipeline 13 of the next unit are communicated between the adjacent distribution units.

In this embodiment, the cross-sectional area of the bypass duct 14 is smaller than that of the sample introduction duct 13, and the cross-sectional area of the exhaust duct 15 is smaller than that of the bypass duct 14, specifically, the ratio of the cross-sectional areas of the sample introduction duct 13, the bypass duct 14, and the exhaust duct 15 may be 10-30: 3-7: 1, and more specifically, the ratio of the cross-sectional areas of the three is 18:6: 1. In use, a fluid sample is introduced through the loading port 12 and a positive pressure is applied to the loading port 12 or a negative pressure is applied to the vent port 19, thereby continuously driving the sample. After passing through the sample introduction pipe 13, the fluid sample can enter two flow paths, namely a bypass pipe 14 and a distribution cavity 11, the cross-sectional area of the bypass pipe 14 is smaller, and the flow resistance is larger, so that the fluid sample in the sample introduction pipe 13 can preferentially enter the distribution cavity 11, and when the distribution cavity 11 is filled with liquid, the fluid sample can enter an exhaust pipe 15, and because the cross-sectional area of the exhaust pipe 15 is smaller than that of the bypass pipe 14, the fluid sample can preferentially pass through the bypass pipe 14, and then flows into a sample outlet pipe 17 through the bypass pipe 14 to be merged into the next distribution unit.

When a surfactant component or an organic solvent is contained in the fluid sample, the liquid may fill the air vent duct 15 by capillary force, despite the small cross-sectional area and the large flow resistance of the air vent duct 15. In order to improve the reliability of the structure and avoid cross contamination between the distribution chambers 11, an interface valve 16 is added at the exhaust pipe 15, specifically, the interface valve 16 is arranged between the exhaust pipe 15 and the sample outlet pipe 17, the structure is arranged such that the pipe width is suddenly enlarged, the pipe depth is suddenly enlarged or both are suddenly enlarged, when the fluid sample fills the front section of the exhaust pipe 15 and reaches the interface valve 16, the fluid sample is blocked in the pipe due to the action of surface tension and cannot enter the interface valve 16, the structure can further block the fluid sample from passing through the exhaust pipe 15, the reliability of the structure is improved, and the allowable fluid driving pressure range of the structure is wider. If the fluid sample still has a relatively fast flow rate through the vent line 15 to the interface valve 16, the interface valve 16 may not be able to adequately block the fluid sample, which may increase the number of interface valves 16 and further improve the reliability of the structure. When the liquid enters the next parallel distribution unit through the bypass duct 14 and the sample outlet duct 17, a section of air remains in the exhaust duct 15, so that it is ensured that the liquid in the distribution chamber 11 cannot flow out of the chamber during the continuous driving of the sample, and cross contamination is avoided. By repeating the above dispensing process, the fluid sample can enter each dispensing chamber 11 of the chip body 1 in turn.

According to the microfluidic distribution chip provided by the utility model, when the fluid sample is water or an aqueous solution, the sample is driven at a constant pressure, as shown in fig. 8, the driving pressure is within a range of 50-3000 Pa, stable sample distribution can be realized by the structure, and the time for completing filling is shorter when the pressure is higher. When the driving pressure is lower than 50Pa, the fluid is not driven enough, and when the driving pressure is higher than 3000Pa, the flow speed of the sample is too high, and when the distribution cavity is not full, the sample has a probability of passing through the bypass pipeline, so that the distribution structure fails. When the fluid sample contains low-surface-energy components such as surfactant or organic solvent, the sample is subjected to larger capillary force in the pipeline, so that the sample is easier to pass through a fine structure, and the compatibility of the structure to the low-surface-energy sample can be effectively improved through the optimization of the structure and the introduction of the interface valve, for example, when the sample is 50% ethanol aqueous solution, as shown in fig. 9, the structure can realize stable sample distribution under the driving pressure of 20-800 Pa.

Further, the microfluidic distribution chip provided by this embodiment further includes a filtering unit, the filtering unit includes a filtering membrane 42 disposed below the sample adding hole 12 and a filtering cavity 41 disposed below the filtering membrane 42, and the filtering cavity 41 is communicated with the sample injection pipeline 13. The filtering membrane 42 is preferably a substance having a porous structure, such as Polysulfone (PS), Polyarylsulfone (PASF), Polyethersulfone (PES), Polyethylene (PE), Polycarbonate (PC), etc., and may include only one layer of filtering membrane, or may be a combination of two or three or more layers of filtering membranes, depending on the substance to be filtered in the sample, and the filtering unit may be used directly or after treatment, such as coating with an antibody against a specific substance. In the field of in vitro diagnosis, the serum is often required to be used as a sample for detecting indexes such as biochemistry or immunity, in the traditional method, large-scale equipment such as a centrifuge is usually required for separating the serum from the whole blood, the operation is complicated, the requirement on experimental conditions is higher, in the embodiment, a filtering unit is integrated at a sample introduction end, so that the serum separation of the whole blood sample is realized, because parameters such as blood viscosity, hematocrit and the like of different people have obvious differences, the driving pressure required in the blood filtration process also has larger differences, and meanwhile, serum sample components passing through a filtering membrane 42 also have certain differences. When the sample is blood, blood cells are filtered from the blood sample passing through the sample application hole 12 by the filter unit, and the obtained plasma or serum flows into the sample application channel. Because the viscosity and hematocrit of different blood samples have obvious difference, the driving pressure drop generated after the sample passes through the filtering membrane fluctuates in a wider range, as shown in fig. 10, the distribution structure of the embodiment can realize stable sample distribution under the driving pressure of 2000Pa-4000Pa, and therefore, the distribution structure can be well matched with various filtering and pretreatment modules for use.

Preferably, the microfluidic distribution chip provided in this embodiment further includes an overflow cavity 18 disposed between the sample outlet 17 and the air vent 19, and when the sample distribution is completed and the fluid sample continues to be driven, the excess fluid sample and the samples in the sample inlet 13 and the bypass 14 will flow into the overflow cavity 18. Due to the large flow resistance of the vent line 15, the liquid in the dispensing chamber 11 will remain in place, providing isolation of the dispensed sample. When the sample is less, the samples in the sample introduction pipe 13 and the bypass pipe 14 can be used for filling the subsequent distribution cavity 11, so that high sample utilization rate is realized. Still further, an optical detection sensor may be provided at the overflow chamber 18 to determine from the transmitted signal that no fluid sample has entered the overflow chamber 18 for determining whether the filling process is complete and whether the sample volume is sufficient.

Preferably, the dispensing chamber 11 may have a pre-stored lyophilized or air-dried reagent, which reacts with the sample to perform the corresponding testing function.

Example 2

Fig. 5 and 6 schematically show a second embodiment of the microfluidic chip provided by the present invention, which has substantially the same configuration as the microfluidic chip provided by the first embodiment, wherein structures having similar functions are given similar reference numerals, and for the sake of brevity, only the differences will be described in detail herein.

Different from the first embodiment, in the second embodiment, all the channels and cavities are disposed on the chip body 1, that is, the distribution cavity 21, the filter cavity 41, the sample adding hole 22, the sample introduction channel 23, the exhaust channel 25, the sample outlet channel 27, the exhaust hole 29, the bypass channel 24 and the interface valve 26 are disposed on the chip body 1, and when the depths of the sample introduction channel 23 and the distribution cavity 21 are different, in order to avoid the abrupt change of the channel depths from affecting the distribution of the fluid, the transition channel 20 is introduced between the sample introduction channel 23 and the distribution cavity 21, so that the cross-sectional area of the fluid channel is smoothly transited, and the reliability of the structure is improved.

Example 3

Fig. 7 schematically shows a third embodiment of the microfluidic chip provided by the present invention, which has substantially the same components and connection relationships as the microfluidic chip provided by the first embodiment, wherein structures having similar functions are assigned with similar reference numerals, and for the sake of brevity, only the differences will be described in detail herein.

Different from the first embodiment, in the third embodiment, all the channels and cavities are disposed on the chip body 1, that is, the distribution cavity 31, the filter cavity 41, the sample adding hole 32, the sample feeding channel 33, the gas discharging channel 35, the sample discharging channel 37, the gas discharging hole 39, the bypass channel 34 and the interface valve 36 are disposed on the chip body 1, which is different from the first embodiment and the second embodiment that the flow resistance is controlled by the change of the channel cross-sectional area, and this embodiment realizes the ordered filling of the distribution cavity 31 by using the change of the channel depth, and this embodiment is often suitable for the case that when the required amount of the distributed sample is small, the cross-sectional area of the distribution cavity 31 is smaller than the cross-sectional area of the bypass channel 34, and the distribution of the fluid sample cannot be realized by the difference of the flow resistance.

Specifically, the depths of the sample introduction pipeline 33, the distribution cavity 31 and the exhaust pipeline 35 are the same, the depth of the bypass pipeline 34 is greater than that of the sample introduction pipeline 33, the depth of the interface valve 36 is greater than that of the bypass pipeline 34, the depth ratio of the interface valve 36, the bypass pipeline 34 and the sample introduction pipeline 33 is 4-10:1.5-2.5:1, and more specifically, the depth ratio of the three is 5:2: 1. Because there is a depth jump between the bypass channel 34 and the sample inlet channel 33, an interface valve effect is generated at the junction of the two to block the passage of the fluid, and there is no depth jump at the interface between the sample inlet channel 33 and the distribution chamber 31, the fluid sample will preferentially fill the distribution chamber 31, after the distribution chamber 31 is filled, the fluid sample will enter the exhaust channel 35 and contact the interface valve 36, because the depth of the interface valve 36 is greater than that of the bypass channel 34, the effect of blocking the passage of the fluid is stronger, and therefore the fluid sample will stop at the interface valve 36, enter the sample outlet channel 37 through the bypass channel 34, and flow into the next distribution unit, and then the process is repeated to realize the distribution of the sample.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the utility model, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims (10)

1. The utility model provides a micro-fluidic distribution chip, includes the sample adding hole, advance kind pipeline, distribution chamber, exhaust duct, play appearance pipeline and the exhaust hole that communicate in proper order, its characterized in that still includes:

the bypass pipeline is communicated with the sample inlet pipeline and the sample outlet pipeline and is used for enabling the fluid added through the sample adding hole to flow to the sample outlet pipeline through the bypass pipeline after the distribution cavity is filled with the fluid;

the filtering unit comprises a filtering membrane arranged below the sample adding hole and a filtering cavity arranged below the filtering membrane, the filtering membrane is at least one layer, and the filtering cavity is communicated with the sample feeding pipeline;

and the interface valve is arranged between the exhaust pipeline and the sample outlet pipeline and is used for assisting in blocking fluid passing through the exhaust pipeline.

2. The microfluidic distribution chip of claim 1, wherein the cross-sectional areas of the distribution chamber, the sample inlet channel, the bypass channel, and the exhaust channel decrease in sequence.

3. The microfluidic distribution chip of claim 1, wherein the interface valve number is at least 1.

4. The microfluidic distribution chip of claim 3, wherein the sample inlet channel, the distribution cavity, and the exhaust channel have the same depth, and the interface valve, the bypass channel, and the sample inlet channel have successively decreasing depths.

5. The microfluidic distribution chip according to claim 1, wherein the microfluidic distribution chip comprises a chip body and a cover plate connected to the chip body, the distribution chamber and the filter chamber are disposed on the chip body, and the sample adding hole, the sample feeding pipeline, the exhaust pipeline, the sample outlet pipeline, the exhaust hole and the bypass pipeline are disposed on the cover plate.

6. The microfluidic distribution chip according to claim 1, wherein the microfluidic distribution chip comprises a chip body and a cover plate connected above the chip body, the distribution cavity, the filter cavity, the sample adding hole, the sample feeding pipeline, the exhaust pipeline, the sample discharging pipeline, the exhaust hole and the bypass pipeline are all disposed on the chip body, and a transition pipeline is connected between the sample feeding pipeline and the distribution cavity.

7. The microfluidic distribution chip according to any one of claims 1 to 6, further comprising an overflow chamber disposed between the sample outlet channel and the gas vent, wherein the overflow chamber is used for storing an excess fluid sample.

8. The microfluidic distribution chip of claim 7, wherein the overflow chamber is provided with an optical detection sensor for detecting a filling amount of the fluid.

9. The microfluidic distribution chip according to any of claims 1 to 6, wherein a reaction reagent is pre-stored in the distribution chamber for reaction with the sample to complete the detection.

10. The microfluidic distribution chip according to claim 1, wherein the sample inlet channel, the distribution cavity, the exhaust channel, the interface valve, the sample outlet channel, and the bypass channel form a set of distribution units, wherein several sets of distribution units are disposed, and adjacent distribution units are connected to each other through the sample outlet channel of the previous unit and the sample inlet channel of the next unit.

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