CN108663531B - Sample quantitative unit and micro-fluidic chip with same - Google Patents
Sample quantitative unit and micro-fluidic chip with same Download PDFInfo
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- CN108663531B CN108663531B CN201810469303.6A CN201810469303A CN108663531B CN 108663531 B CN108663531 B CN 108663531B CN 201810469303 A CN201810469303 A CN 201810469303A CN 108663531 B CN108663531 B CN 108663531B
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1002—Reagent dispensers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00178—Special arrangements of analysers
- G01N2035/00237—Handling microquantities of analyte, e.g. microvalves, capillary networks
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
Abstract
The invention discloses a sample quantitative unit and a micro-fluidic chip with the same, wherein the sample quantitative unit comprises: the sample injection pool is communicated with a sample injection port of the microfluidic chip; the quantitative pool comprises a quantitative area and a waste liquid area which are communicated, wherein the quantitative area comprises a buffer area, a quantitative sub-area and a precipitation area which are sequentially communicated, the buffer area is communicated with the sample injection pool through a first capillary connecting pipe, the top of the quantitative sub-area is communicated with the waste liquid area, the bottom end of the waste liquid area is connected with the waste liquid pool, a sample enters the quantitative sub-area and the buffer area from the sample injection pool through the buffer area, and redundant samples enter the waste liquid area from the top of the quantitative sub-area; the sample treatment pool is connected with the quantitative subarea through a siphon pipe; wherein, the sample introduction pool, the quantitative pool and the sample processing pool are communicated with the atmosphere. The sample quantifying unit can realize accurate quantification of the sample, reduce errors and obviously improve the detection efficiency and the detection precision of the microfluidic chip.
Description
Technical Field
The invention relates to the field of analysis and detection, in particular to a sample quantitative unit and a microfluidic chip with the same.
Background
An important step essential for biochemical analysis is the collection and application of the sample. In quantitative analysis, the accuracy of the volume of the added sample directly affects the accuracy of the final detection result, so that the quantitative accuracy of the sample is very important for quantitative biochemical analysis. In conventional large-scale analytical instruments, such as fully automatic biochemical analyzers and immunoassays, the collection and quantification of the sample is achieved by pumping the sample through a sampling needle under the control of a plunger pump. The method has the defects of insufficient precision of processing trace samples and higher requirement on hardware, so the method is widely applied to large-scale automatic instruments and is not suitable for integrated and portable biochemical analysis devices. With the great rise of the health requirements of people, the central laboratory-like detection cannot fully meet the requirements of people, and people need to detect the disease at any time and any place, so that the construction of an integrated, automatic and miniaturized detection system becomes an important development direction for disease diagnosis and health monitoring. To achieve this goal, the development of sample quantification techniques suitable for portable analysis has become an important requirement. The micro-fluidic chip is a carrier for operating and analyzing trace liquid through a micron-sized pipeline and a cavity structure, is a key component of a portable analysis technology, and whether a quantitative unit in the micro-fluidic chip can achieve accurate quantification or not directly influences the accuracy of an analysis result.
Disclosure of Invention
The present invention is directed to solving, at least to some extent, one of the technical problems in the related art. Therefore, an object of the present invention is to provide a sample quantifying unit and a microfluidic chip having the same, wherein the sample quantifying unit can achieve accurate quantification of a sample, reduce errors, and significantly improve detection efficiency and detection accuracy of the microfluidic chip.
According to an aspect of the present invention, the present invention provides a sample quantifying unit of a microfluidic chip, according to an embodiment of the present invention, comprising:
the sample injection pool is communicated with a sample injection port of the microfluidic chip;
the quantitative cell comprises a quantitative region and a waste liquid region which are communicated, wherein the quantitative region comprises a buffer region, a quantitative subregion and a precipitation region which are communicated in sequence, the buffer region is communicated with the sample injection cell through a first capillary connecting pipe, the top of the quantitative subregion is communicated with the waste liquid region, the bottom end of the waste liquid region is connected with the waste liquid cell, a sample enters the quantitative subregion and the precipitation region from the sample injection cell through the buffer region, and redundant sample enters the waste liquid region from the top of the quantitative subregion;
the sample treatment pool is connected with the quantitative subarea through a siphon pipe;
wherein, the sample introduction pool, the quantitative pool and the sample processing pool are communicated with the atmosphere.
In addition, the sample quantifying unit of the microfluidic chip according to the above embodiment of the present invention may further have the following additional technical features:
in some embodiments of the present invention, the quantitative sub-zone is connected to the settling zone through a first constricted passage, and the first constricted passage is formed with a first quantitative outlet which is communicated with the siphon tube.
In some embodiments of the invention, the buffer region and the dosing sub-region are connected by a second constriction channel.
In some embodiments of the present invention, a junction of the first constriction channel and the quantitative sub-zone and the precipitation zone is formed with a chamfer, and a junction of the second constriction channel and the quantitative sub-zone and the buffer zone is formed with a chamfer.
In some embodiments of the invention, the maximum depth of both the buffer zone and the sedimentation zone is greater than the maximum depth of the quantification sub-zone.
In some embodiments of the invention, a sample application prevention pit is disposed on the first capillary connection tube, and the cross-sectional area of the sample application prevention pit is larger than that of the first capillary connection tube.
In some embodiments of the present invention, a sample buffer pool is formed at the bottom end of the sample inlet pool, the upper part of the buffer pool is communicated with the atmosphere, and the cross-sectional area of the sample buffer pool is larger than that of the sample inlet pool.
In some embodiments of the invention, the waste reservoir is connected to the waste zone by a third constricted channel.
In some embodiments of the present invention, the top of the settling zone is communicated with the waste liquid zone through a second capillary connecting pipe, so that the redundant sample enters the waste liquid zone from the settling zone, and the joint of the second capillary connecting pipe and the waste liquid zone is not higher than the highest point of the second contraction channel and not lower than the lowest point of the second contraction channel.
According to a second aspect of the present invention, the present invention provides a microfluidic chip having the sample quantification unit according to the previous embodiment.
Drawings
Fig. 1 is a schematic structural view of a sample quantifying unit according to an embodiment of the present invention.
Fig. 2 is a partial structural view of a sample quantifying unit according to an embodiment of the present invention.
FIG. 3 is a schematic view showing a quantifying process of the sample quantifying unit according to the embodiment of the present invention.
Fig. 4 shows a schematic view of a quantifying process of the sample quantifying unit according to one embodiment of the present invention.
Fig. 5 shows a schematic view of a quantifying process of the sample quantifying unit according to one embodiment of the present invention.
Fig. 6 is a schematic structural view of a sample quantifying unit according to another embodiment of the present invention.
Fig. 7 is a partial structural view of a sample-quantifying unit according to another embodiment of the present invention.
FIG. 8 is a schematic view showing a quantifying process of a sample quantifying unit according to another embodiment of the present invention.
FIG. 9 is a schematic view showing a quantifying process of a sample quantifying unit according to another embodiment of the present invention.
FIG. 10 is a schematic view showing a quantifying process of a sample quantifying unit according to another embodiment of the present invention.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are illustrative and intended to be illustrative of the invention and are not to be construed as limiting the invention.
A sample quantifying unit of a microfluidic chip according to an embodiment of the present invention is described below with reference to fig. 1 to 5.
As shown in fig. 1-2, the sample quantifying unit according to an embodiment of the present invention includes: the device comprises a sample injection pool 10, a quantification pool 20 and a sample processing pool 30, wherein the sample injection pool 10 is communicated with a sample injection port of the microfluidic chip; the quantitative pool 20 comprises a quantitative area 21 and a waste liquid area 22 which are communicated, wherein the quantitative area 21 comprises a buffer area 23, a quantitative sub-area 24 and a precipitation area 25 which are communicated in sequence, the buffer area 23 is communicated with the sample injection pool 10 through a first capillary connecting pipe 26, the top of the quantitative sub-area 24 is communicated with the waste liquid area 22, the bottom end of the waste liquid area 22 is connected with a waste liquid pool 27, and a sample enters the quantitative sub-area 24 and the precipitation area 25 from the sample injection pool 10 through the buffer area 23; the sample processing cell 30 is connected to the quantification sub-zone 24 by a siphon 40; wherein the sample introduction cell 10, the quantification cell 20 and the sample processing cell 30 are in communication with the atmosphere.
The sample quantitative unit realizes the driving and the volume quantification of the fluid in the sample by using a centrifugal force, and relative to a centrifugal center, the position relation of the sample quantitative unit is as follows: the sample feeding pool 10 is closest to the centrifugal center, the first capillary connecting pipe 26 is located at one side of the sample feeding pool 10 away from the centrifugal center and connected with the same, the quantitative pool 20 is compared with the first capillary connecting pipe 26 and is away from the centrifugal center and connected with the same, the sample processing pool 30 is compared with the quantitative pool 20 and is away from the centrifugal center, the quantitative sub-area 24 of the quantitative pool 30 is connected to one end of the siphon tube 40, and the other end is connected with one side of the sample processing pool 30 close to the centrifugal center. For the quantification chamber 20, the buffer area 23 is close to the centrifugal center, the quantification sub-area 24 is directly connected with the part of the buffer area 23 far from the centrifugal center, the sedimentation area 25 is directly connected with the side of the quantification sub-area 24 far from the centrifugal center, and the waste liquid area 22 is connected with the side of the quantification sub-area 24 and arranged in parallel.
Referring to fig. 2, the sub-metering area 24 is connected to the settling area 25 via a first converging passage 28, and a first metering outlet is formed in the first converging passage 28 and is in communication with the siphon tube 40.
Thus, the volume difference between the level position 1 and the level position 2 at the second quantification outlet is the quantification volume of the sample (see FIGS. 4-5). Therefore, the inventor connects the quantitative sub-region 24 and the sedimentation region 25 through the first contraction channel 28, thereby significantly reducing the liquid surface area at the first quantitative outlet, thereby effectively reducing the volume change between the two liquid surfaces, improving the quantitative accuracy of the sample, reducing the deviation among multiple batches of samples, and in addition, reducing the liquid surface area at the first quantitative outlet, and effectively avoiding sucking out too large sample due to inertia after siphon of the siphon 40, so as to further improve the quantitative accuracy of the sample.
Specifically, the shapes of the buffer zone 23, the quantitative sub-zone 24 and the precipitation zone 25 are not particularly limited. As shown in fig. 2, the quantitative section 21 has an overall rectangular shape in which the volume sizes of the buffer zone 23, the quantitative sub-zone 24 and the sedimentation zone 25 are adjusted to a desired volume amount by adjusting the depth, and specifically, the depth of the buffer zone 23 and the sedimentation zone 25 is greater than the depth of the quantitative sub-zone 24. The first constricting channel 28 also forms a narrow channel of constant width and smaller depth by reducing its depth. Therefore, for multiple quantification, even if a narrow channel has a certain liquid level error, the influence of the narrow channel on the volume of the whole sample is very small, so that the quantification error can be effectively reduced, and the quantification accuracy is improved.
Further, the junction of the first constriction channel 28 with the dosing and settling zone 24, 25 is chamfered. Therefore, air blockage or residue of centrifugal sediment in the area of the connection part when the chip is centrifuged can be avoided.
Further, the maximum depth of both the buffer zone 23 and the settling zone 25 is greater than the maximum depth of the quantification sub-zone 24. Since the liquid sample at the quantitative sub-area 24 needs to be transferred into the sample processing pool 30 by centrifugation, designing the quantitative sub-area 24 to a shallower depth facilitates formation of a longer height difference in the direction of centrifugal force, thereby facilitating transfer of the sample in the quantitative sub-area 24 during centrifugation, while the buffer area 23 and the sedimentation area 25 are used for temporarily containing the liquid sample and containing possible sediments in the sample, respectively, and therefore, designing the depth to be slightly larger than the quantitative sub-area 24 can save the area of the chip.
Further, as shown in fig. 2, a sample addition preventing pit 11 is provided on the first capillary connecting tube 26, and a cross-sectional area of the sample addition preventing pit 11 is larger than a cross-sectional area of the first capillary connecting tube 26. Thus, the sample addition preventing well 11 has a deeper and larger volume than the first capillary connecting tube 26, so that the interface valve can be formed to reduce the probability that the sample is excessively added to the quantitative cell 20 in advance.
Further, as shown in fig. 2, the waste liquid pool 27 is connected to the waste liquid region 22 through a third constriction passage 271. The third contraction channel 271 has a thin and shallow structure, and forms an interface valve effect with the waste liquid region 22 and the waste liquid pool 27 of the deep quantification pool 20 with a large area, so that a sample with high wettability can be prevented from entering the quantification region 21 of the quantification pool 20 from the waste liquid pool 27, and the influence of the sample on quantification is avoided.
Referring to fig. 3 to 5, the working principle and the working process of the sample quantifying unit are as follows: the sample is added into the sample inlet cell 10 through the sample inlet of the microfluidic chip by capillary action or an external liquid-transferring device, and the entered sample stays at the sample-adding stopping pit 11 under the action of the interface valve (fig. 3). By centrifuging the microfluidic chip, the sample in the sample inlet cell 10 enters the quantification cell 20 through the first capillary connection tube 26, the sample which is added to the sum of the volumes of the precipitation zone 25 and the quantification sub-zone 24 in the quantification cell 20 enters the waste liquid zone 22, and the waste liquid enters the waste liquid cell 27 through the third contraction channel (fig. 4). After a suitable centrifugation speed and centrifugation time, if solid particles in the sample, such as blood cells in whole blood, etc., will enter the sedimentation zone 25 under the centrifugal force, and the supernatant, such as serum, will remain in the quantification zone 24. By slowing the centrifugation speed of the chip or stopping the centrifugation of the chip for a while, the supernatant portion of the quantitative sub-region 24 will fill the siphon tube 40 by capillary action. When the microfluidic chip is centrifuged again, a part of the supernatant in the quantitative sub-region 24 will be siphoned under the centrifugal force, and a fixed volume of the sample will enter the sample processing cell 30 (fig. 5) for subsequent analysis.
In the above operation, as shown in fig. 4-5, the sample volume entering the sample processing cell 30 is determined by the volume difference between the position 1 and the position 2 of the quantification pool 20, the interface of the liquid is compressed to a circle along the centrifugal center by the centrifugal force, the two positions are determined by the structure of the chip and the related force during centrifugation, and the sample volume deviation of different quantification is mainly derived from the deviation of the two positions before and after the centrifugation quantification of the chip under the condition of the determined chip structure and the consistent structure between different chips. According to the basic principle of centrifugal microfluidics, position 1 is mainly determined by the position of the connection of the dosing sub-zone 24 and the waste zone 22 of the dosing cell 20, while position 2 is mainly determined by the position of the connection of the siphon 40 with the dosing sub-zone 24. In the above embodiment of the present invention, the inventor connects the quantitative sub-region 24 and the sedimentation region 25 through the first contraction channel 28, so as to significantly reduce the liquid surface area at the first quantitative outlet, thereby effectively reducing the volume change between the two liquid surfaces, and improving the accurate quantitative determination of the sample.
Therefore, the sample quantifying unit provided by the embodiment of the invention has a simple structure, is easy to operate, can be operated by non-professionals, does not need to use devices with higher cost, such as a plunger pump and the like, reduces the cost, and can be combined with other structures on a chip to perform subsequent analysis to form a complete sample processing and analyzing system, thereby facilitating integrated and portable operation. The sample quantifying unit provided by the embodiment of the invention can be used in the fields of biological detection, water pollutant detection, pesticide residue detection and the like, such as the sampling detection of body fluid or water sample, milk, fruit juice, pollutant containing heavy metal ions, organic pollutant, inorganic pollutant, pesticide residue and the like, of whole blood, serum, plasma, urine, sweat, saliva, semen, amniotic fluid and the like.
A sample quantifying unit of a microfluidic chip according to another embodiment of the present invention is described below with reference to fig. 6 to 10.
Referring to fig. 6 to 7, the sample quantifying unit according to an embodiment of the present invention includes: the device comprises a sample injection pool 10, a quantification pool 20 and a sample processing pool 30, wherein the sample injection pool 10 is communicated with a sample injection port of the microfluidic chip; the quantitative pool 20 comprises a quantitative area 21 and a waste liquid area 22 which are communicated, wherein the quantitative area 21 comprises a buffer area 23, a quantitative sub-area 24 and a precipitation area 25 which are communicated in sequence, the buffer area 23 is communicated with the sample injection pool 10 through a first capillary connecting pipe 26, the top of the quantitative sub-area 24 is communicated with the waste liquid area 22, the bottom end of the waste liquid area 22 is connected with a waste liquid pool 27, and a sample enters the quantitative sub-area 24 and the precipitation area 25 from the sample injection pool 10 through the buffer area 23; the sample processing cell 30 is connected to the quantification sub-zone 24 by a siphon 40; wherein the sample introduction cell 10, the quantification cell 20 and the sample processing cell 30 are in communication with the atmosphere.
The sample quantitative unit realizes the driving and the volume quantification of the fluid in the sample by using a centrifugal force, and relative to a centrifugal center, the position relation of the sample quantitative unit is as follows: the sample feeding pool 10 is closest to the centrifugal center, the first capillary connecting pipe 26 is located at one side of the sample feeding pool 10 away from the centrifugal center and connected with the same, the quantitative pool 20 is compared with the first capillary connecting pipe 26 and is away from the centrifugal center and connected with the same, the sample processing pool 30 is compared with the quantitative pool 20 and is away from the centrifugal center, the quantitative sub-area 24 of the quantitative pool 30 is connected to one end of the siphon tube 40, and the other end is connected with one side of the sample processing pool 30 close to the centrifugal center. For the quantification chamber 20, the buffer area 23 is close to the centrifugal center, the quantification sub-area 24 is directly connected with the part of the buffer area 23 far from the centrifugal center, the sedimentation area 25 is directly connected with the side of the quantification sub-area 24 far from the centrifugal center, and the waste liquid area 22 is connected with the side of the quantification sub-area 24 and arranged in parallel.
Further, referring to fig. 7, the buffer region 23 and the quantitative sub-region 24 are connected by a second constriction channel 29; the quantitative sub-zone 24 is connected with the settling zone 25 through a first contraction passage 28, and a first quantitative outlet is formed on the first contraction passage 28 and communicated with the siphon 40.
Further, as shown in fig. 7, the top of the settling zone 25 is communicated with the waste liquid zone 22 through a second capillary connection tube 50, so that the excessive sample enters the waste liquid zone 22 through the second capillary connection tube 50, and the connection position of the second capillary connection tube 50 and the waste liquid zone 22 is not higher than the highest point of the second contracted passage 29 and not lower than the lowest point of the second contracted passage 29. A second capillary connection 50 forms a second metering outlet where it joins the waste zone 22.
Therefore, the second capillary connecting pipe 50 is arranged to communicate the top of the settling zone 25 with the waste liquid zone 22, so that the redundant sample can enter the waste liquid zone 22 from the settling zone 25, and the problem that the cross section of the second contraction passage 29 cannot be too small due to air blockage at the upper end when the sample centrifugally enters the quantitative sub-zone 24 can be avoided. Since the second capillary connection tube 50 is provided so as to be able to communicate with the atmosphere, the cross-sectional area of the second constricted passage 29 at the upper end of the quantitative section 21 can be reduced appropriately, and the smaller cross-sectional area causes the slight change in height at the position 1 on the second constricted passage 29 to have less influence on the error in the quantitative volume, whereby the quantitative accuracy can be further improved.
In addition, the volume difference between the liquid level position 1 at the second quantitative outlet and the liquid level position 2 at the first quantitative outlet is the quantitative volume of the sample (see fig. 9-10). Therefore, the inventors connected the buffer zone 23 and the quantitative sub-zone 24 through the second constriction channel 29, and connected the quantitative sub-zone 24 and the precipitation zone 25 through the first constriction channel 28. And are arranged on the first and second constricted passages 28, 29 at the first and second metering outlets, respectively, thereby significantly reducing the liquid surface area at the first metering outlet and the liquid surface area at the second constricted passage 29. Therefore, the volume change between the two liquid surfaces can be effectively reduced, the quantitative accuracy of the samples is improved, and the deviation among multiple batches of samples is reduced; in addition, the liquid level area at the first quantitative outlet is reduced, and the phenomenon that excessive large samples are sucked out due to inertia after siphoning of the siphon 40 can be effectively avoided, so that the quantitative accuracy of the samples is further improved.
Specifically, the shapes of the buffer zone 23, the quantitative sub-zone 24 and the precipitation zone 25 are not particularly limited. As shown in fig. 7, the buffer zone 23, the quantitative sub-zone 24 and the sedimentation zone 25 are formed in an irregular oval shape, and the first constriction passage 28 and the second constriction passage 29 are passages having a smaller diameter. Therefore, for multiple times of quantification, even if a thin contraction channel has a certain liquid level error, the influence of the thin contraction channel on the volume of the whole sample is very small, so that the quantification error can be effectively reduced, and the quantification accuracy is improved.
Further, as shown in fig. 6, a sample addition preventing pit 11 is provided in the first capillary connecting tube 26, and a cross-sectional area of the sample addition preventing pit 11 is larger than a cross-sectional area of the first capillary connecting tube 26. Thus, the sample addition preventing well 11 has a deeper and larger volume than the first capillary connecting tube 26, so that the interface valve can be formed to reduce the probability that the sample is excessively added to the quantitative cell 20 in advance.
Further, as shown in fig. 6, a sample injection buffer pool 12 is formed at the bottom end of the sample injection pool 10, the upper portion of the buffer pool 12 is communicated with the atmosphere, and the cross-sectional area of the sample injection buffer pool 12 is larger than that of the sample injection pool 10.
Referring to fig. 8 to 10, the working principle and working process of the sample quantifying structure are as follows: the sample is added into the sample injection pool 10 through the sample injection port by capillary action or an external liquid transfer device, the entered sample can stop at the sample injection buffer pool 12 under the action of the interface valve (figure 8), if the sample is injected in a proper amount, the sample can only fill part of the volume of the sample injection buffer pool 12, and does not enter the subsequent structure of the microfluidic chip. By centrifuging the microfluidic chip, the sample in the sample inlet cell 10 enters the quantification cell 20 through the first capillary connection tube 26, the sample with the sum of the volumes of the precipitation zone 25 and the quantification sub-zone 24 in the quantification cell 10 enters the waste liquid zone 22 through the second capillary connection tube 50, and the waste liquid enters the waste liquid cell 27 through the third contraction channel (fig. 9). After a suitable centrifugation speed and centrifugation time, if solid particles in the sample, such as blood cells in whole blood, etc., will enter the sedimentation zone 25 under the centrifugal force, and the supernatant, such as serum, will remain in the quantification zone 24. By slowing the centrifugation speed of the chip or stopping the centrifugation of the chip for a while, the supernatant portion of the quantitative sub-region 24 will fill the siphon tube 40 by capillary action. By re-centrifuging the chip, a portion of the supernatant in the quantification sub-zone 24 will be siphoned by centrifugal force and a fixed volume of sample will enter the sample processing cell 30 (FIG. 10) for subsequent analysis.
In the above operation, as shown in fig. 8 to 10, with respect to the sample quantifying unit of the above embodiment, since the second capillary connection tube 50 is provided to connect the quantifying section 21 to the atmosphere through the waste liquid section 22, it is possible to avoid the fear that the cross section of the second constricted passage 29 cannot be made too small due to air clogging when the sample is centrifuged into the upper end of the quantifying section 21. Since the second capillary connection tube 50 is provided so as to be able to communicate with the atmosphere, the cross-sectional area of the second constricted passage 29 at the upper end of the quantitative section 21 can be reduced appropriately, and the smaller cross-sectional area causes the slight change in height at the position 1 on the second constricted passage 29 to have less influence on the error in the quantitative volume, whereby the quantitative accuracy can be further improved.
According to a second aspect of the present invention, the present invention provides a microfluidic chip having the sample quantification unit according to the previous embodiment. The microfluidic chip having the sample quantifying unit of the above embodiment can thereby significantly improve the quantifying accuracy thereof.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.
Claims (7)
1. A sample quantifying unit of a microfluidic chip, comprising:
the sample injection pool is communicated with a sample injection port of the microfluidic chip;
the quantitative cell comprises a quantitative region and a waste liquid region which are communicated, wherein the quantitative region comprises a buffer region, a quantitative subregion and a precipitation region which are sequentially communicated, the buffer region is communicated with the sample injection cell through a first capillary connecting pipe, the top of the quantitative subregion is communicated with the waste liquid region, the bottom end of the waste liquid region is connected with the waste liquid cell, and a sample enters the quantitative subregion and the precipitation region from the sample injection cell through the buffer region;
the sample treatment pool is connected with the quantitative subarea through a siphon pipe;
wherein the sample introduction pool, the quantitative pool and the sample processing pool are communicated with the atmosphere,
the quantitative sub-area is connected with the precipitation area through a first contraction channel, a first quantitative outlet is formed in the first contraction channel and communicated with the siphon, the maximum depths of the buffer area and the precipitation area are both larger than the maximum depth of the quantitative sub-area, and the buffer area is connected with the quantitative sub-area through a second contraction channel.
2. The sample quantifying unit of the microfluidic chip according to claim 1, wherein a junction of the first constriction channel and the quantifying subregion and the precipitation region is formed with a chamfer, and a junction of the second constriction channel and the quantifying subregion and the buffer region is formed with a chamfer.
3. The sample quantifying unit of the microfluidic chip according to any one of claims 1 or 2, wherein the first capillary connecting tube is provided with a sample application prevention pit, and a cross-sectional area of the sample application prevention pit is larger than a cross-sectional area of the first capillary connecting tube.
4. The sample quantifying unit of the microfluidic chip according to claim 3, wherein a sample feeding buffer pool is formed at a bottom end of the sample feeding pool, an upper portion of the buffer pool is communicated with the atmosphere, and a cross-sectional area of the sample feeding buffer pool is larger than that of the sample feeding pool.
5. The sample quantifying unit of the microfluidic chip according to claim 4, wherein the waste liquid pool is connected to the waste liquid region through a third constriction channel.
6. The sample quantifying unit of the microfluidic chip according to claim 5, wherein the top of the sedimentation region is communicated with the waste liquid region through a second capillary connection tube, so that the excess sample enters the waste liquid region through the second capillary connection tube, and the connection position of the second capillary connection tube and the waste liquid region is not higher than the highest point of the second contraction channel and not lower than the lowest point of the second contraction channel.
7. A microfluidic chip characterized in that it has a sample quantifying unit according to any one of claims 1 to 6.
Priority Applications (1)
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| CN109939752A (en) * | 2018-12-11 | 2019-06-28 | 安博特纳米生物科技有限公司 | Micro-channel structure and biological detection platform |
| CN110508335A (en) * | 2019-03-27 | 2019-11-29 | 广州万孚生物技术股份有限公司 | Micro-fluidic chip and vitro detection device containing the micro-fluidic chip |
| CN110016435B (en) * | 2019-05-16 | 2020-11-03 | 西安交通大学 | Centrifugal micro-fluidic chip for extracting free nucleic acid and method for extracting free nucleic acid by using centrifugal micro-fluidic chip |
| CN110586209A (en) * | 2019-08-28 | 2019-12-20 | 广州万孚生物技术股份有限公司 | Micro-fluidic chip and in-vitro detection device comprising same |
| CN110568202B (en) * | 2019-09-12 | 2022-05-24 | 重庆科技学院 | Automatic sample separation constant volume immunofluorescence quantitative rapid detection micro-fluidic chip |
| CN110773246B (en) * | 2019-11-01 | 2021-12-14 | 上海速创诊断产品有限公司 | Micro-fluidic chip and kit for detecting hypersensitive troponin |
| CN110732357B (en) * | 2019-11-25 | 2021-11-19 | 北京世纪沃德生物科技有限公司 | Sample shunting pipeline of micro-fluidic chip |
| CN111495445B (en) * | 2020-02-28 | 2022-01-14 | 南北兄弟药业投资有限公司 | Test tray and test system |
| CN111426847A (en) * | 2020-04-10 | 2020-07-17 | 上海速创诊断产品有限公司 | Microfluidic chip, detection kit, microfluidic detection system and application thereof |
| CN113617401B (en) * | 2020-05-08 | 2023-06-06 | 浙江普施康生物科技有限公司 | Centrifugal detection flow channel, detection device and detection method |
| CN113237800A (en) * | 2021-06-03 | 2021-08-10 | 浙江盛域医疗技术有限公司 | Platelet detection micro-fluidic chip |
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| CN102253226B (en) * | 2011-04-07 | 2013-06-05 | 天津微纳芯科技有限公司 | Integrated chip for single-reagent and multi-reagent detection and detection method |
| TWI550274B (en) * | 2014-08-20 | 2016-09-21 | 紹興普施康生物科技有限公司 | Microfluidics based analyzer and method for operation thereof |
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