CN212632728U - Micro-fluidic chip and in-vitro detection device - Google Patents

Abstract

The utility model discloses a micro-fluidic chip and external detection device. The micro-fluidic chip is provided with a plurality of sample adding cavities, a separation cavity, a first waste liquid cavity, a first capillary flow channel, a buffer cavity and a quantitative cavity, wherein at least one sample adding cavity is connected with the buffer cavity sequentially through the separation cavity and the first capillary flow channel, so that different sample adding cavities can be selected according to the types of added sample solutions during sample adding. The micro-fluidic chip can distinguish different samples, is flexible and convenient to use, is favorable for reasonable use according to the properties of a sample solution, is favorable for reducing the waste of the sample solution, and saves the use amount of the samples.

Description

Micro-fluidic chip and in-vitro detection device

Technical Field

The utility model belongs to the technical field of external detection and specifically relates to a micro-fluidic chip and external detection device is related to.

Background

The In Vitro Diagnosis Industry (IVD) belongs to the pharmaceutical and biological industry, and refers to a process of taking samples such as blood, body fluid, and tissue from a human body, and detecting and verifying the samples by using In Vitro detection reagents, instruments, and the like so as to prevent, diagnose, treat and detect diseases, observe later stages, evaluate health, predict genetic diseases, and the like. In vitro diagnosis is divided into three major categories, biochemical diagnosis, immunological diagnosis and molecular diagnosis, and bedside rapid diagnosis POCT differentiated from biochemical, immunological and molecular diagnosis. The dry chemical reaction is one of biochemical diagnosis, and is to utilize biochemical reagent to react with specific substrate, and then to quantitatively detect the concentration of the target substance by an instrument, and to calculate some biochemical indexes of human body. The traditional biochemical diagnosis needs to be carried out on a large-scale biochemical analyzer, so that the problems of high reagent consumption, insufficient flexibility and the like are caused; the general dry biochemical POCT diagnosis mode is low in test throughput, and can test one or more samples and one or more items at a time. The microfluidic chip technology (Microfluidics) can integrate basic operation units such as sample preparation, reaction, separation, detection and the like in the processes of biological, chemical and medical analysis on a chip, automatically complete the whole analysis process, greatly improve the detection efficiency, and have the advantages of miniaturization, automation and the like, so the microfluidic chip technology is more and more widely applied to the field of POCT.

In the field of biochemical detection, represented by Abaxis company in the United states, a microfluidic chip for biochemical detection is developed first, and similar microfluidic chips such as Tianjin micro-nano cores, Chengdu Simat and the like are developed in China. The chip of the traditional product generally has only one test flow for processing samples, can not distinguish and process different types of samples, easily causes unnecessary sample waste, and has inflexible detection process.

SUMMERY OF THE UTILITY MODEL

In view of the above, it is desirable to provide a microfluidic chip capable of performing a differential process on different samples and an in vitro detection apparatus including the microfluidic chip.

A micro-fluidic chip is provided with a sample adding cavity, a separation cavity, a first waste liquid cavity, a first capillary flow channel, a buffer cavity and a quantitative cavity;

the sample adding cavity is provided with a plurality of sample adding holes, each sample adding cavity is connected with the buffer cavity, at least one sample adding cavity is connected with the buffer cavity through the separation cavity and the first capillary flow channel in sequence, the buffer cavity is connected with the quantitative cavity, and the separation cavity is also connected with the first waste liquid cavity;

the micro-fluidic chip is provided with a rotation center, the separation cavity is far away from the rotation center relative to the sample adding cavity connected with the separation cavity, the first waste liquid cavity is far away from the rotation center relative to the separation cavity, the buffer cavity is far away from the rotation center relative to the sample adding cavity connected with the buffer cavity, the first capillary flow channel gradually extends from one end connected with the separation cavity to the direction close to the rotation center, bends and then extends to the direction far away from the rotation center to be connected with the buffer cavity, the bending position is closer to the rotation center relative to the separation cavity and the buffer cavity, and the quantitative cavity is far away from the rotation center than the buffer cavity.

In one embodiment, the microfluidic chip further has a second capillary channel, and one end of the second capillary channel is connected to the quantitative cavity, and extends from the quantitative cavity to a direction close to the rotation center after being connected to the quantitative cavity, and extends from the second capillary channel to a direction away from the rotation center after being bent, so that the solution to be measured in the quantitative cavity is discharged from the other end.

In one embodiment, the microfluidic chip further has a liquid outlet permeation hole, one end of the liquid outlet permeation hole is connected to one end of the second capillary flow channel, which is used for discharging the solution to be tested, on the surface of the side where the second capillary flow channel is located, and the other end of the liquid outlet permeation hole is opened on the other side surface of the microfluidic chip.

In one embodiment, the microfluidic chip further comprises a second waste liquid chamber connected to the separation chamber via an overflow channel, wherein the overflow channel is closer to the rotation center than the second waste liquid chamber and the separation chamber.

In one embodiment, the microfluidic chip further comprises a liquid separation channel, wherein the liquid separation channel is connected with the buffer cavity and extends from the connecting end to the other end of the buffer cavity around the rotation center;

the quantitative cavity is provided with a plurality of cavities, the plurality of cavities are distributed around the rotating center outside the liquid separation flow channel, and each cavity is connected with the liquid separation flow channel.

In one embodiment, the microfluidic chip further has a first permeation hole and a second permeation hole penetrating through the microfluidic chip;

the micro-fluidic chip is provided with two opposite side surfaces which are respectively a first surface and a second surface, the buffer cavity and the liquid separation flow channel are respectively positioned on the first surface and the second surface, one end of the first permeation hole is connected with the buffer cavity on the first surface, and the other end of the first permeation hole is connected with the liquid separation flow channel on the second surface;

the quantitative cavity is positioned on the first surface, one end of the second permeation hole is connected with the liquid separation flow channel on the second surface, and the other end of the second permeation hole is connected with the corresponding quantitative cavity on the first surface.

In one embodiment, the microfluidic chip further has a third permeation hole and a quality control cavity, the quality control cavity is located on the first surface, the third permeation hole penetrates through the microfluidic chip, one end of the third permeation hole is connected to the position, close to the tail end, of the liquid separation flow channel on the second surface, and the other end of the third permeation hole is connected to the quality control cavity on the first surface.

In one embodiment, the microfluidic chip further has a fourth permeation hole and a third waste liquid cavity, the third waste liquid cavity is located on the first surface, the fourth permeation hole penetrates through the microfluidic chip, one end of the fourth permeation hole is connected with the tail end of the liquid separation flow channel on the second surface, and the other end of the fourth permeation hole is connected with the third waste liquid cavity on the first surface.

In one embodiment, the partial cavities are directly provided with air holes for exhausting air, and the partial cavities are exhausted through the air holes arranged on other cavities connected with the partial cavities, and the air holes are closer to the rotation center relative to the cavities directly connected with the partial cavities.

In one embodiment, the two interconnected chambers or the interconnected chambers and the orifice are connected by a microchannel.

In one embodiment, the sample application chamber is disposed about the center of rotation; and/or

The size of the sample adding cavity is gradually increased from one end of the sample adding to the other end of the sample adding cavity.

In one embodiment, the microfluidic chip is further provided with a positioning hole.

An in vitro detection device is characterized by comprising the microfluidic chip and a detection mechanism of any one of the embodiments, wherein the detection mechanism is communicated with the quantitative cavity and is used for detecting a sample in the quantitative cavity.

In one embodiment, the detection mechanism is a dry chemical strip.

In one embodiment, the dry chemical test paper comprises a support layer, and a reaction indicating layer and a diffusion layer which are sequentially stacked on the support layer, wherein the reaction indicating layer contains a reaction reagent and an indicating reagent which can react with a target substance in a sample to be detected, and the diffusion layer faces to a quantitative cavity through a sample inlet of the diffusion layer.

In one embodiment, the microfluidic chip is provided with mounting grooves around each quantitative cavity, and the detection mechanism is embedded in each mounting groove and communicated with the quantitative cavity.

The microfluidic chip is provided with a plurality of sample adding cavities, a separation cavity, a first waste liquid cavity, a first capillary flow channel, a buffer cavity and a quantitative cavity, wherein at least one sample adding cavity is connected with the buffer cavity through the separation cavity and the first capillary flow channel in sequence, so that different sample adding cavities can be selected according to the type of a sample solution added during sample adding, for example, when a whole blood sample needs to be detected, the whole blood sample can be added into the sample adding cavity connected with the separation cavity, then, under the centrifugal action, the separation of blood cells and serum (or plasma) in the whole blood sample solution can be realized, impurities such as the blood cells and the like can be centrifugally deposited in the first waste liquid cavity, and the serum is left in the separation cavity; and if a serum sample needs to be detected, the serum sample can be directly added into the sample adding cavity connected with the buffer cavity, and subsequent quantification and detection processes can be directly carried out without carrying out centrifugal separation on the serum sample. The micro-fluidic chip can distinguish different samples, is flexible and convenient to use, is favorable for reasonable use according to the properties of a sample solution, is favorable for reducing the waste of the sample solution, and saves the use amount of the samples.

Drawings

Fig. 1, fig. 2 and fig. 3 are schematic diagrams of front, back and side structures of a microfluidic chip according to an embodiment of the present invention.

FIG. 4 is a schematic diagram of a dry chemical strip.

Fig. 5-1 to 5-14 are schematic diagrams of the processes of separating, quantifying and detecting the whole blood sample solution by the microfluidic chip.

Fig. 6 is a schematic diagram of the microfluidic chip for implementing sample addition of a serum sample.

The reference numerals are explained below:

10: microfluidic chip, 101: rotation center, 102: first surface, 103: second surface, 104: chip body, 105: covering a film;

11: sample application chamber, 110: well, 111: first sample application chamber, 112: a second sample application cavity; 12: a separation chamber; 13: a first waste liquid chamber; 14: the first capillary flow channel 14a, 14b and 14c are respectively the front section, the bending vertex and the rear section of the first capillary flow channel; 15: a buffer cavity; 16: a quantitative cavity; 17: a second capillary flow passage, 17a, 17b and 17c are respectively the front section, the bending vertex and the rear section of the second capillary flow passage; 18: liquid outlet permeation holes; 19: second waste liquid cavity, 191: an overflow channel; 20: a flow dividing channel; 21: a first penetration hole; 22: a second penetration hole; 23: a third penetration hole; 24: a quality control cavity; 25: a fourth penetration hole; 26: a third waste liquid chamber; 27: air holes are formed; 28: a micro flow channel; 29: positioning holes; 30: mounting grooves;

40: dry chemical test paper, 41: support layer, 42: reaction indicating layer, 43: a diffusion layer.

Detailed Description

In order to facilitate understanding of the present invention, the present invention will be described more fully hereinafter with reference to the accompanying drawings. The preferred embodiments of the present invention are shown in the drawings. The invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

It should be noted that when an element is referred to as being "connected" to another element, it may be directly connected to the other element or intervening elements may be present, such as through a microchannel connection.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

Referring to fig. 1 and 2, an embodiment of the present invention provides a microfluidic chip 10, which includes a sample-adding cavity 11, a separation cavity 12, a first waste liquid cavity 13, a first capillary channel 14, a buffer cavity 15, and a quantitative cavity 16. The sample addition chamber 11 has a sample addition hole 110. In this embodiment, there are a plurality of sample-adding cavities 11, each sample-adding cavity 11 is connected to the buffer cavity 15, and at least one sample-adding cavity 11 is connected to the buffer cavity 15 through the separation cavity 12 and the first capillary channel 14 in sequence. The buffer chamber 15 is connected to the quantitative chamber 16. The separation chamber 12 is also connected to a first waste chamber 13.

The center of the microfluidic chip 10 is a rotation mounting part having a rotation center 101, which is the rotation center of the microfluidic chip during centrifugal operation 101. The separation chamber 12 is further from the rotation center 101 than the sample application chamber 11 connected thereto, the first waste liquid chamber 13 is further from the rotation center 101 than the separation chamber 12, the buffer chamber 15 is further from the rotation center 101 than the sample application chamber 11 connected thereto, the first capillary channel 14 extends from the end connected to the separation chamber 12 in a direction gradually approaching the rotation center 101 (may be a direction gradually approaching the rotation center 101, for example, but not limited to, a radial direction toward the rotation center 101) and is bent to extend in a direction away from the rotation center 101 (may be a direction gradually departing the rotation center 101, for example, but not limited to, a radial direction away from the rotation center 101) to connect to the buffer chamber 15, and the bent position is closer to the rotation center 101 than the separation chamber 12 and the buffer chamber 15, and the quantitative chamber 16 is further from the rotation center 101 than the buffer chamber 15.

For example, in the illustrated embodiment, there are two sample application cavities 11, namely a first sample application cavity 111 and a second sample application cavity 112. Wherein, the first sample adding cavity 111 is connected with the buffer cavity 15 through the separation cavity 12 and the first capillary flow channel 14, and the second sample adding cavity 112 is directly connected with the buffer cavity 15. The direct connection described herein refers to that two connected objects are not connected via other cavities, but is not limited to a structure in which a micro flow channel, a capillary flow channel, or the like is provided for communication between the two objects.

Further, in the illustrated specific example, the first sample application chamber 111 and the second sample application chamber 112 are both disposed around the rotation center 101. The first sample adding cavity 111 is used for adding sample solutions such as whole blood and the like, has a large volume, is close to the rotating center 101 from head to tail, and needs to perform centrifugal separation on the added sample solutions; the second sample application chamber 112 is used for adding sample solution such as serum or plasma, and has a relatively small volume, so that the added sample solution does not need to be centrifuged. Preferably, the sample application chamber 11 has a size gradually increasing from one end of the sample application to the other end thereof, so that the sample solution flows in the chamber and smoothly flows from one end to the other end to facilitate the sample application. The term "surround" as used herein may or may not be a closed loop, and may for example encompass a sector having an angle greater than 180 ° or a sector having an angle around 90 °, etc., it being understood that the angle of the central angle of the sector is not limited, depending on the amount of sample to be added.

In the particular example shown, the microfluidic chip 10 also has a second capillary flow channel 17. One end of the second capillary channel 17 is connected to the quantitative cavity 16, and extends from the direction close to the rotation center 101 after being connected to the quantitative cavity 16, and extends from the direction far away from the rotation center 101 after being bent, so as to discharge the solution to be measured in the quantitative cavity 16 from the other end.

Further, in the illustrated specific example, the microfluidic chip 10 also has a liquid outlet permeation hole 18. One end of the liquid outlet permeation hole 18 is connected to one end of the second capillary flow channel 17, which is used for discharging the solution to be detected, on the surface of the side where the second capillary flow channel 17 is located, and the other end is opened on the surface of the other side of the microfluidic chip 10, so as to lead out the sample solution to be detected, for example, to a test strip or other detection mechanism.

In the particular example shown, the microfluidic chip 10 also has a second waste chamber 19. The second waste liquid chamber 19 is connected to the separation chamber 12 via an overflow channel 191. The overflow channel 191 is closer to the rotation center 101 with respect to the second waste liquid chamber 19 and the separation chamber 12. When the separation chamber 12 and the first waste chamber 13 are filled with liquid, the excess liquid enters the second waste chamber 19 through the liquid flow channel 191. In the illustrated example, the second waste liquid chamber 19 is elongated as a whole, and has one end close to the rotation center 101 and the other end away from the rotation center 101.

In the particular example shown, the microfluidic chip 10 also has a liquid separation channel 20. The liquid separation flow path 20 is connected to the buffer chamber 15 and extends from the connection end to the other end thereof around the rotation center 101. Further, there are a plurality of quantitative cavities 16, and the plurality of quantitative cavities 16 are distributed around the rotation center 101 outside the liquid separation flow channel 20, and each quantitative cavity 16 is connected to the liquid separation flow channel 20.

In the illustrated embodiment, each of the quantitative cavity 16, the second capillary flow passage 17 and the outlet liquid-penetrating hole 18 constitutes a quantitative detection unit, and thus the microfluidic chip 10 has a plurality of quantitative detection units around the rotation center 101 thereof. Through setting up a plurality of quantitative determination units, can realize the ration many times to sample solution, can be used for carrying out repeated detection many times to the same index of same sample to guarantee the accuracy of testing result, perhaps detect a plurality of different indexes of same sample, with each item index of comprehensive reflection sample solution. The microfluidic chip 10 with a plurality of quantitative detection units has high integration level, and can significantly improve single detection flux.

As shown in fig. 1 and 2, the illustrated microfluidic chip 10 further has a first penetration hole 21 and a second penetration hole 22 penetrating the microfluidic chip 10. The microfluidic chip 10 has two opposite side surfaces, a first surface 102 and a second surface 103. Buffer cavity 15 and liquid separation flow channel 20 are located on first surface 102 and second surface 103, respectively. One end of the first penetration hole 21 is connected to the buffer chamber 15 at the first surface 102, and the other end is connected to the liquid separation flow channel 20 at the second surface 103. The quantitative cavity 16 is located on the first surface 102, the second penetration holes 22 are multiple, one end of each second penetration hole 22 is connected with the liquid separation flow channel 20 on the second surface 103, and the other end is connected with the corresponding quantitative cavity 16 on the first surface 102.

By arranging the liquid separation channel 20 on the other surface of the microfluidic chip 10, the integration level of the microfluidic chip 10 can be improved within a certain size range, which is beneficial to reducing the size of the microfluidic chip 10 and the miniaturization and portability design of products.

In the specific example shown in the figure, the microfluidic chip 10 further has a third penetration hole 23 and a quality control cavity 24. The quality control cavity 24 is located on the first surface 102, the third penetration hole 23 penetrates through the microfluidic chip 10, one end of the third penetration hole 23 is connected with the position, close to the tail end, of the liquid separation flow channel 20 on the second surface 103, and the other end of the third penetration hole is connected with the quality control cavity 24 on the first surface 102. Through setting up matter accuse cavity 24, can judge whether to fill with liquid in each ration cavity 16 through observing whether the liquid in the matter accuse cavity 24 exists to can be accurate carry out the ration to sample solution, avoid appearing not filling with sample solution in some ration cavities 16 and appearing the problem that the detection volume of each quantitative determination unit is inconsistent and influence the testing result accuracy and reliability and take place.

In the illustrated specific example, the microfluidic chip 10 further has a fourth permeation hole 25 and a third waste chamber 26. The third waste liquid cavity 26 is located on the first surface 102, the fourth penetration hole 25 penetrates through the microfluidic chip 10, one end of the fourth penetration hole 25 is connected with the tail end of the liquid separation flow channel 20 at the second surface 103, and the other end is connected with the third waste liquid cavity 26 at the first surface 102. Further, in the illustrated example, the third waste liquid chamber 26 is disposed around the rotation center 101 at the outer side of each quantitative determination unit, and the size of the third waste liquid chamber 26 is large, so that a sufficient volume can be reserved to contain the excess sample solution to be determined, and thus some sample solution can be added slightly during sample addition, thereby preventing the sample solution to be determined from being not filled in part of the quantitative chamber 16 due to insufficient sample solution.

In the illustrated embodiment, the air holes 27 are directly formed in some of the cavities to exhaust air, and the air holes 27 are formed in other cavities connected to some of the cavities to exhaust air, and each air hole 27 is closer to the rotation center 101 than the cavity directly connected to the air hole. For example, the first sample-adding cavity 111 and the second sample-adding cavity 112 are both provided with air vents 27, and preferably, both share one air vent 27; for another example, each of the quantitative cavity 16, the second waste liquid cavity 19, the quality control cavity 24 and the third waste liquid cavity 26 is independently provided with an air vent 27.

In the particular example shown, two interconnected chambers or chambers and wells are connected by microchannels 28. For example, the first sample adding cavity 111 and the separation cavity 12, the separation cavity 12 and the first waste liquid cavity 13, and the respective cavities and the corresponding air vents 27 are connected by micro channels 28.

The capillary flow channels described herein (e.g., the first capillary flow channel 14 and the second capillary flow channel 17) are flow channel structures that are smaller in size (e.g., width and/or depth) than the fluidic channel 28. In one specific example, each capillary flow passage main body portion has a V-shape with a bent portion near the rotation center 101. Preferably, the width of each capillary flow channel is 0.1 mm-0.2 mm, and the depth is 0.1 mm-0.2 mm; or the width of each capillary flow passage is 0.2 mm-0.5 mm, and the depth is 0.2 mm-0.5 mm. When the width of each capillary flow passage is 0.1 mm-0.2 mm and the depth is 0.1 mm-0.2 mm, surface treatment is not needed, and when the width of each capillary flow passage is 0.2 mm-0.5 mm and the depth is 0.2 mm-0.5 mm, the flow passage wall of each capillary flow passage is preferably subjected to surface treatment by inert substances such as PEG4000 and the like. Further preferably, each capillary flow passage has a width of 0.2mm and a depth of 0.2 mm. Each capillary channel allows the sample solution to flow to the other end thereof by capillary action after the sample solution enters. It is further preferred that each capillary flow passage has different dimensions in different sections, for example 0.2mm wide and 0.2mm deep at the bend and 0.5mm wide and 0.2mm deep at other locations to facilitate liquid flow and local wicking and capillarity.

The PEG4000 surface treatment can be, but is not limited to, adding 1 wt% PEG4000 solution into a capillary flow channel, and naturally drying to form the PEG4000 surface treatment. The PEG4000 surface treatment is beneficial to increasing the capillary force of the capillary flow channel, and the PEG4000 belongs to an inert substance in a reaction system and generally does not react with a sample, a detection reagent and the like, so that the detection result is not influenced.

The distance from the bent vertex position of each capillary channel to the rotation center 101 is smaller than the distance from the whole cavity directly connected with the capillary channel to the rotation center 101, so that a sample solution flows along with the capillary channel during centrifugation, but the sample solution cannot flow to the bent vertex position of the capillary channel due to the fact that the centrifugal force is larger than the capillary force, and therefore the capillary channel can play a role of a valve during centrifugal separation of the sample solution, and the closing effect is achieved during quantification and detection of the sample solution.

By designing the micro-fluidic chip 10 with the structure, the sample solution can be separated and quantified by one-time centrifugation, the operation is simple, and the efficiency of separating and quantifying the sample solution is improved.

Further, the microfluidic chip 10 has a positioning hole 29. By designing the positioning holes 29, it is convenient for the matched detection equipment to identify the position of the microfluidic chip 10, so as to determine the relative position of the detection mechanism, such as dry chemical test paper, mounted on the microfluidic chip 10 on the chip 10, and thus determine the detection item corresponding to each detection mechanism, so as to complete the detection and obtain the corresponding result.

In one specific example, as shown in fig. 3, the microfluidic chip 10 includes a chip body 104 and cover films 105 covering both side surfaces of the chip body 104.

The sample adding cavity 11, the separation cavity 12, the first waste liquid cavity 13, the first capillary flow channel 14, the buffer cavity 15, the quantitative cavity 16, the second capillary flow channel 17, the second waste liquid cavity 19, the liquid flow channel 191, the liquid separating flow channel 20, the quality control cavity 24, the third waste liquid cavity 26 and the micro flow channel 28 for connecting the cavities are all located on the same side surface of the chip body 104, such as the first surface 102, the air vent 27 is arranged on the cover film 105 on the side, and the liquid separating flow channel 20 is located on the surface of the other side of the chip body 104, such as the second surface 103.

The chip body 104 and the cover films 105 on the two sides cooperate to form various cavity and flow channel (micro-flow channel, capillary flow channel, etc.) structures of the microfluidic chip 10. Specifically, the grooves of the cavities and the flow channel structures are pre-formed on the chip body 104, and then the grooves are covered and sealed on the front surface of the chip body 104 through the cover film 12, so that the cavities and the flow channel structures can be packaged to form a complete cavity and flow channel structure.

The material of the chip body 104 may be, but not limited to, a single crystal silicon wafer, quartz, glass, or a polymer organic polymer material, such as polymethyl methacrylate (PMMA), Polydimethylsiloxane (PDMS), Polycarbonate (PC), or hydrogel. The entire chip body 104 is preferably disk-shaped to facilitate mounting and to ensure stability of the centrifugation process.

The cover film 105 may be made of the same material as the chip body 104, and may also be an adhesive tape with adhesiveness, such as a pressure sensitive adhesive tape, a double-sided adhesive tape, or a die-cut adhesive tape, which is matched with the chip body 104 to form the entire microfluidic chip 10. It is understood that in other specific examples, the microfluidic chip 10 may be formed by welding using a costly ultrasonic welding technique or integrally formed by using a 3D printing technique.

The utility model also provides an external detection device of an embodiment, it includes the micro-fluidic chip 10 and the detection mechanism in any above-mentioned specific example, and detection mechanism is used for detecting the sample in the ration cavity 16.

In one particular example, the detection mechanism is a dry chemical strip. The detection mechanism is communicated with the quantitative cavity 16.

More specifically, as shown in fig. 4, the dry chemical test paper 40 may include a support layer 41 and a reaction indicating layer 42 and a diffusion layer 43 sequentially stacked on the support layer 41. The reaction indication layer 42 contains a reaction reagent and an indication reagent capable of reacting with a target substance in a sample to be detected, and the diffusion layer 43 is communicated with the quantitative cavity 16 through a sample inlet, such as but not limited to being communicated with the liquid outlet permeation hole 18 through a sample inlet. The reactive agent and the indicator agent in the reaction indicating layer 42 may be in the same layer or may be separately provided in different sub-layers. It is understood that in other specific examples, the detection mechanism is not limited to dry chemical test strips, but may be various other test strips or reactors.

In a specific example, the microfluidic chip 10 is provided with mounting grooves 30 around each quantitative detection unit. A detection mechanism such as dry chemical paper 40 may be embedded in each mounting groove 30.

The microfluidic chip 10 has a plurality of sample-adding cavities 11, a separation cavity 12, a first waste liquid cavity 13, a first capillary channel 14, a buffer cavity 15 and a quantitative cavity 16, wherein at least one sample-adding cavity 11 is connected with the buffer cavity 15 through the separation cavity 12 and the first capillary channel 14 in sequence, so that different sample-adding cavities 11 can be selected according to the type of a sample solution added during sample addition, for example, when a whole blood sample needs to be detected, the whole blood sample can be added into the sample-adding cavity 11 connected with the separation cavity 12, and then blood cells and serum (or plasma) in the whole blood sample solution can be separated under the centrifugal action, impurities such as the blood cells can be centrifugally deposited in the first waste liquid cavity 13, and the serum remains in the separation cavity 12; in addition, when a serum sample needs to be detected, the serum sample can be directly added into the sample adding cavity 11 connected with the buffer cavity 15, and subsequent quantification and detection processes can be directly performed without performing centrifugal separation on the serum sample. The micro-fluidic chip 10 can distinguish different samples, is flexible and convenient to use, is favorable for reasonable use according to the properties of a sample solution, is favorable for reducing the waste of the sample solution, and saves the use amount of the samples.

Specifically, taking the microfluidic chip 10 shown in fig. 1 and 2 as an example, when detecting a whole blood sample and a pure serum (or plasma) sample, the following operations can be performed, but are not limited to.

For whole blood samples, the overall test procedure includes three phases: separating, quantifying and detecting. The separation is a process of separating serum and blood cells by high-speed centrifugation, the quantification is a quantification of the amount of serum required for the test in each quantification chamber 16, and the detection is a process of leading the serum obtained in the quantification process out to a detection mechanism for detection. The whole process can be referred to as follows:

as shown in fig. 5-1, the whole blood sample is first added into the first sample adding cavity 111, and the excess air in the first sample adding cavity 111 is discharged through the corresponding air vent 27;

after the whole blood sample is added, the microfluidic chip 10 is installed in equipment with a centrifugal function, high-speed centrifugation is started, the rotating speed is controlled to be 3000-6000 rpm, as shown in fig. 5-2, the whole blood sample flows into the separation cavity 12 and the first waste liquid cavity 13, redundant whole blood sample flows into the second waste liquid cavity 19 through the liquid flow channel 191, and redundant air in the cavity is discharged through the air holes 27 formed in the second waste liquid cavity 19;

continuing centrifugation, as shown in fig. 5-3, under the action of centrifugal force, the serum and blood cells in the whole blood sample are separated, the blood cells are totally gathered in the first waste liquid cavity 13 under the action of centrifugal force, and the serum is retained in the separation cavity 12; meanwhile, a part of the serum enters the first capillary flow channel 14 connected with the separation cavity 12, as shown in fig. 5-4, since the centrifugal force is greater than the capillary force in the first capillary flow channel 14, the serum entering the first capillary flow channel 14 does not flow when reaching the highest point of the separation cavity 12 and stays at the front section 14a, and the position of the first capillary flow channel 14 close to the bending vertex of the rotation center 101 is closer to the rotation center than the whole separation cavity 12, so the serum does not cross the bending vertex 14b and does not enter the rear section 14c, and the first capillary flow channel 14 plays a role of a valve when the whole blood sample is centrifugally separated;

as shown in fig. 5-5, 5-6 and 5-7, after the whole blood sample is centrifugally separated, centrifugation is stopped, at this time, the serum in the first capillary flow channel 14 flows along the inside of the first capillary flow channel 14 under the action of capillary force, and finally enters the buffer cavity 15 from the rear section 14c beyond the bending vertex 14b, then centrifugation is continuously started, the separated serum sample enters the first permeation hole 21 through the buffer cavity 15, enters the liquid separation flow channel 20, is subjected to liquid separation through the liquid separation flow channel 20, and is guided to each quantitative cavity 16 through the second permeation hole 22;

as shown in fig. 5-8 and 5-9, after each quantitative cavity 16 is filled with a serum sample, the redundant serum sample enters the quality control cavity 24 through the third penetration hole 23, the state of the quality control cavity 24 can be detected by the testing instrument, whether serum exists therein is detected, when serum exists in the quality control cavity 24, it is indicated that each quantitative cavity 16 is filled with serum, the subsequent detection can be normally performed, when no serum exists in the quality control cavity 24, it is indicated that a part of the quantitative cavity 16 is not filled, at this time, the testing instrument can give a prompt that quality inspection needs to be performed, a corresponding reagent can be set in the quality control cavity 24, and whether liquid enters the quality control cavity is prompted by observing the color change of the quality control cavity 24;

as shown in fig. 5-10, when the quality control cavity 24 is also filled with liquid, the excess liquid will enter the third waste liquid cavity 26 to be collected;

meanwhile, as shown in fig. 5 to 11, liquid also enters the second capillary flow channel 17 connected to each quantitative cavity 16, and since the centrifugal force is greater than the capillary force, the liquid entering the second capillary flow channel 17 also stops at a position flush with the quantitative cavity 16, that is, in the front section 17a, since the bent vertex 17b is closer to the rotation center than the whole quantitative cavity 16, the liquid does not cross the bent vertex 17b and further enters the rear section 17c, the second capillary flow channel 17 functions as a valve during centrifugation, and during high-speed centrifugation, the valve is closed, so that the liquid is effectively retained in each quantitative cavity 16, and the smooth progress of the whole quantitative process is controlled;

when the quantification process is finished, the centrifugation is stopped, as shown in fig. 5-12 and fig. 5-13, and the liquid in the second capillary flow channel 17 flows along the second capillary flow channel 17 under the action of the capillary force and finally goes over the bending peak 17b to enter the rear section 17c, at this time, as shown in fig. 5-14, the low-speed centrifugation can be started, for example, the liquid can be promoted to enter the detection mechanism such as the dry chemical test strip from the rear section 17c via the liquid outlet permeation hole 18 under the rotation speed of 1000-.

When the sample solution is serum, the whole process only needs to comprise quantification and detection. Correspondingly, as shown in fig. 6, the serum sample is added into the second sample adding cavity 112, and centrifugation is started, so that the serum sample enters the separating channel 20 via the buffer cavity 15, and finally enters each quantitative cavity 16. For the serum sample, the operation of separating whole blood is not required to be repeated, and the serum sample is directly added into the second sample adding cavity 112, so that the sample dosage can be reduced, the detection flow is shortened, and the detection efficiency can be effectively improved.

The microfluidic chip 10 can be used for multiple purposes, is used for detecting different types of sample solutions, and is simple and convenient to operate and high in flexibility. Particularly, the capillary flow channel is used as a valve, and compared with the traditional method of controlling sample detection by using a water-soluble film and the like, the method is more rapid and convenient.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only represent some embodiments of the present invention, and the description thereof is specific and detailed, but not to be construed as limiting the scope of the present invention. It should be noted that, for those skilled in the art, without departing from the spirit of the present invention, several variations and modifications can be made, which are within the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the appended claims.

Claims (16)

1. A micro-fluidic chip is characterized in that a sample adding cavity, a separation cavity, a first waste liquid cavity, a first capillary flow channel, a buffer cavity and a quantitative cavity are arranged on the micro-fluidic chip;

the sample adding cavity is provided with a plurality of sample adding holes, each sample adding cavity is connected with the buffer cavity, at least one sample adding cavity is connected with the buffer cavity through the separation cavity and the first capillary flow channel in sequence, the buffer cavity is connected with the quantitative cavity, and the separation cavity is also connected with the first waste liquid cavity;

the micro-fluidic chip is provided with a rotation center, the separation cavity is far away from the rotation center relative to the sample adding cavity connected with the separation cavity, the first waste liquid cavity is far away from the rotation center relative to the separation cavity, the buffer cavity is far away from the rotation center relative to the sample adding cavity connected with the buffer cavity, the first capillary flow channel gradually extends from one end connected with the separation cavity to the direction close to the rotation center, bends and then extends to the direction far away from the rotation center to be connected with the buffer cavity, the bending position is closer to the rotation center relative to the separation cavity and the buffer cavity, and the quantitative cavity is far away from the rotation center than the buffer cavity.

2. The microfluidic chip according to claim 1, further comprising a second capillary channel, wherein one end of the second capillary channel is connected to the quantitative cavity, and extends from the quantitative cavity to a direction close to the rotation center and bends to a direction away from the rotation center, so as to discharge the solution to be tested in the quantitative cavity from the other end.

3. The microfluidic chip according to claim 2, further comprising a liquid outlet penetration hole, wherein one end of the liquid outlet penetration hole is connected to one end of the second capillary flow channel for discharging the solution to be tested on the surface of the second capillary flow channel on one side, and the other end of the liquid outlet penetration hole is open on the surface of the microfluidic chip on the other side.

4. The microfluidic chip of claim 1, further comprising a second waste chamber connected to the separation chamber by an overflow channel, wherein the overflow channel is closer to the center of rotation than the second waste chamber and the separation chamber.

5. The microfluidic chip according to any one of claims 1 to 4, further comprising a liquid separation channel connected to the buffer cavity and extending from the connection end to the other end around the rotation center;

the quantitative cavity is provided with a plurality of cavities, the plurality of cavities are distributed around the rotating center outside the liquid separation flow channel, and each cavity is connected with the liquid separation flow channel.

6. The microfluidic chip according to claim 5, further comprising a first and a second permeation hole penetrating the microfluidic chip;

the micro-fluidic chip is provided with two opposite side surfaces which are respectively a first surface and a second surface, the buffer cavity and the liquid separation flow channel are respectively positioned on the first surface and the second surface, one end of the first permeation hole is connected with the buffer cavity on the first surface, and the other end of the first permeation hole is connected with the liquid separation flow channel on the second surface;

the quantitative cavity is positioned on the first surface, one end of the second permeation hole is connected with the liquid separation flow channel on the second surface, and the other end of the second permeation hole is connected with the corresponding quantitative cavity on the first surface.

7. The microfluidic chip according to claim 6, further comprising a third permeation hole and a quality control cavity, wherein the quality control cavity is located on the first surface, the third permeation hole penetrates through the microfluidic chip, one end of the third permeation hole is connected to the position, close to the tail end, of the liquid separation channel on the second surface, and the other end of the third permeation hole is connected to the quality control cavity on the first surface.

8. The microfluidic chip according to claim 6, further comprising a fourth permeation hole and a third waste liquid cavity, wherein the third waste liquid cavity is located on the first surface, the fourth permeation hole penetrates through the microfluidic chip, one end of the fourth permeation hole is connected to the tail end of the liquid separation channel on the second surface, and the other end of the fourth permeation hole is connected to the third waste liquid cavity on the first surface.

9. The microfluidic chip according to any of claims 1 to 4 and 6 to 8, wherein some of the cavities are directly provided with air holes for exhausting air, and some of the cavities are exhausted through air holes provided in other cavities connected thereto, and the air holes are closer to the rotation center than the cavities directly connected thereto.

10. The microfluidic chip according to any of claims 1 to 4 and 6 to 8, wherein the two interconnected cavities or the interconnected cavities and the wells are connected by a microchannel.

11. The microfluidic chip according to any of claims 1 to 4 and 6 to 8, wherein the sample application chamber is disposed around the rotation center; and/or

The size of the sample adding cavity is gradually increased from one end of the sample adding to the other end of the sample adding cavity.

12. The microfluidic chip according to any of claims 1 to 4 and 6 to 8, wherein the microfluidic chip further comprises a positioning hole.

13. An in vitro detection device, comprising the microfluidic chip according to any one of claims 1 to 12 and a detection mechanism, wherein the detection mechanism is communicated with the quantitative cavity, and the detection mechanism is used for detecting a sample in the quantitative cavity.

14. The in vitro test device of claim 13, wherein the test mechanism is a dry chemical strip.

15. The in-vitro detection device according to claim 14, wherein the dry chemical test paper comprises a support layer, and a reaction indication layer and a diffusion layer which are sequentially stacked on the support layer, the reaction indication layer contains a reaction reagent and an indication reagent which can react with a target substance in a sample to be detected, and the diffusion layer faces the quantitative cavity through a sample inlet of the diffusion layer.

16. The in vitro detection device according to any one of claims 13 to 15, wherein the microfluidic chip is provided with mounting grooves around each of the quantitative cavities, and the detection mechanism is embedded in each of the mounting grooves and communicated with the quantitative cavity.

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