Micro-fluidic chip and micro-fluidic system

Abstract

The invention discloses a micro-fluidic chip and a micro-fluidic system, and the micro-fluidic chip comprises a substrate which rotates around a centrifugal center; the liquid temporary storage pool is positioned on the proximal side of the substrate; the multiple reaction holes are located in the telecentric side of the liquid temporary storage pool, the distances from the reaction holes to the centrifugal center are the same, and the volume of the reaction holes is smaller than that of the liquid temporary storage pool; the distribution pipe is positioned on the telecentric side of the reaction hole, a liquid inlet is communicated with the liquid temporary storage pool, and a liquid outlet is communicated with the waste liquid pool; and the proximal end of the reaction hole is communicated with the position between the liquid inlet and the liquid outlet of the distribution pipe through a hole filling pipe. After a liquid sample enters the distribution pipe, the reaction holes are also filled in the process of gradually filling the distribution pipe. The distribution pipe is connected with the proximal end of the reaction hole through the hole filling pipe, so that the backflow problem of a liquid sample in the reaction hole can be relieved, the fluid crosstalk phenomenon of the reaction hole is relieved, and the detection accuracy is further improved.

Description

Technical Field

[0001] The present invention relates to the technical field of microfluidics, and particularly to a microfluidic chip and a microfluidic system. Background Art

[0002] With the rise and development of the in vitro diagnostic industry, the centrifugal force-driven microfluidic technology has attracted more and more attention due to its small size, easy control, low cost, and simple operation, and has been widely used in various biochemical, immunological, and molecular diagnostic products.

[0003] On a centrifugal force-driven microfluidic chip, the main flow direction of the liquid sample is the centrifugal force direction, from the centrifugal center to the outside. Therefore, in fluid design, the fluid steps are also arranged from the inside to the outside. A large amount of liquid sample near the inner side (centripetal side) will be transferred to the reaction wells near the outer side (centrifugal side) under the action of centrifugal force.

[0004] In the process of distributing and filling a large volume of liquid sample into multiple small-volume chambers, the commonly used method is to utilize the height difference of the centrifugal potential energy of different chambers. Under the action of centrifugal force, the liquid sample flows from the inner chamber to the outer chamber, and fills the small-volume chambers one by one according to the order of fluid passage.

[0005] However, in the process of filling the liquid sample by the above distribution method, there must be a period of liquid contact between different small-volume chambers, resulting in fluid crosstalk between the inlet and outlet of the small-volume chambers. If there are reaction reagents in the small-volume chambers and different reaction reagents may interfere with each other, the chip using the above liquid distribution method cannot avoid the error caused by fluid crosstalk.

[0006] Therefore, how to provide a microfluidic chip to avoid crosstalk during the liquid sample distribution process, thereby improving the detection accuracy, is a technical problem that needs to be solved urgently by those skilled in the art. Summary of the Invention

[0007] In view of this, the present invention provides a microfluidic chip to avoid crosstalk during the liquid sample distribution process, thereby improving the detection accuracy. In addition, the present invention also provides a microfluidic system having the above microfluidic chip.

[0008] To achieve the above object, the present invention provides the following technical solutions:

[0009] A microfluidic chip, which comprises:

[0010] A substrate that rotates around the centrifugal center;

[0011] A liquid storage pool located on the centripetal side of the substrate;

[0012] Reaction holes, the number of the reaction holes being multiple, the reaction holes being located on the centrifugal side of the liquid storage pool, and the distances from the reaction holes to the centrifugal center being the same, the volume of the reaction holes being smaller than the volume of the liquid storage pool;

[0013] A distribution pipe, the distribution pipe being located on the centrifugal side of the reaction holes, and the liquid inlet of the distribution pipe being communicated with the liquid storage pool, the liquid outlet of the distribution pipe being communicated with the waste liquid pool, and the centripetal end of the reaction hole being communicated with a position between the liquid inlet and the liquid outlet of the distribution pipe through a hole filling pipe.

[0014] Preferably, in the above-mentioned microfluidic chip, it further includes:

[0015] Liquid separation holes, the liquid separation holes being located on the centripetal side of the reaction holes, and the hole filling pipe being connected to the reaction holes through the liquid separation holes.

[0016] Preferably, in the above-mentioned microfluidic chip, the area and volume of the liquid separation holes are respectively smaller than the area and volume of the reaction holes;

[0017] The cross-sectional area of the hole filling pipe is smaller than the cross-sectional area of the centripetal end of the liquid separation hole.

[0018] Preferably, in the above-mentioned microfluidic chip, the hole filling pipe includes:

[0019] A first section, the first section connecting the centripetal end of the liquid separation hole and the distribution pipe;

[0020] A second section, the second section connecting the centrifugal end of the liquid separation hole and the centripetal end of the reaction hole.

[0021] Preferably, in the above-mentioned microfluidic chip, for the distribution pipe, the centrifugal potential energy of the liquid inlet end is higher than the centrifugal potential energy of the liquid outlet end;

[0022] Or,

[0023] For the distribution pipe, the centrifugal potential energy of the liquid inlet end is equal to the centrifugal potential energy of the liquid outlet end.

[0024] Preferably, in the above-mentioned microfluidic chip, it further includes a ventilation channel, and the ventilation channel is used for exhausting air from the reaction holes, the liquid storage pool and the waste liquid pool.

[0025] Preferably, in the above-mentioned microfluidic chip, the ventilation channel includes:

[0026] A first pipeline, the first pipeline communicating the liquid storage pool with the atmosphere;

[0027] A second pipe, the first end of the second pipe is communicated with the proximal end of the reaction hole, the second end is communicated with the atmosphere, the second pipes are connected to the reaction holes in a one-to-one correspondence, and the second ends of all the second pipes are communicated;

[0028] A third pipe, the third pipe communicates the waste liquid pool with the atmosphere.

[0029] Preferably, in the above microfluidic chip, the waste liquid pool is communicated with the liquid outlet through a siphon tube, and the centrifugal potential energy of the proximal end of the siphon tube is higher than that of the proximal end of the hole filling tube.

[0030] Preferably, in the above microfluidic chip, the siphon tube includes:

[0031] An inclined section, the first end of the inclined section is communicated with the liquid outlet of the distribution pipe, and the inclined section is a pipe extending obliquely away from the center of centrifugation;

[0032] A bent section, the second end of the inclined section is communicated with one end of the bent section, the other end of the bent section is communicated with the waste liquid pool, and the bent section is a U-shaped pipe protruding towards the center of centrifugation.

[0033] A microfluidic system includes a microfluidic chip, wherein the microfluidic chip is the microfluidic chip described in any one of the above.

[0034] The present invention discloses a microfluidic chip, which arranges a distribution pipe at the distal end of a reaction hole and connects the distribution pipe and the reaction hole through a hole filling pipe. After a liquid sample enters the distribution pipe, during the process of gradually filling the distribution pipe, the reaction hole will also be filled. Since the distribution pipe is connected to the proximal end of the reaction hole through the hole filling pipe, the problem of backflow of the liquid sample in the reaction hole can be alleviated, thereby alleviating the fluid crosstalk phenomenon in the reaction hole, and further improving the detection accuracy. Description of the Drawings

[0035] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0036] Figure 1 It is the front view of the microfluidic chip disclosed in the embodiment of the present invention;

[0037] Figure 2 It is the structural schematic diagram of the microfluidic chip disclosed in the embodiment of the present invention;

[0038] Figure 3Schematic diagram of the liquid distribution process of the microfluidic chip disclosed in the embodiments of the present invention;

[0039] Figure 4 is Figure 3 Partial enlarged view of A in;

[0040] Figure 5 is Figure 3 Partial enlarged view of B in. Specific embodiments

[0041] The present invention discloses a microfluidic chip, which avoids crosstalk during the liquid sample distribution process, thereby improving the detection accuracy. In addition, the present invention also discloses a microfluidic system having the above microfluidic chip.

[0042] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0043] Hereinafter, the terms "first" and "second" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features.

[0044] As Figure 1 and Figure 2 shown, the embodiments of the present invention include a microfluidic chip, which includes a core body, a liquid storage pool 2, a connecting pipe 3, a distribution pipe 4, a hole filling pipe 5, a reaction hole 7 and a waste liquid pool 10.

[0045] Among them, the core body is rotatably connected around the centrifugal center 1, and the shape and size of the core body can be set according to different needs, and all are within the protection scope.

[0046] The above-mentioned liquid storage pool 2 and reaction hole 7 are arranged on the core body. It can be understood that the liquid storage pool 2 is a space for containing liquid, and the reaction hole 7 is a through hole or blind hole opened on the core body. The waste liquid pool 10 is located on the far side of the distribution pipe 4 (the side away from the centrifugal center 1), and the waste liquid pool 10 is communicated with the distribution pipe 4 to accommodate excess liquid.

[0047] It should be noted that the microfluidic chip can form a liquid storage pool 2 and a waste liquid pool 10 between the core body and the cover plate by buckling.

[0048] The liquid storage pool 2 and the reaction holes 7 are both on the chip body. The liquid storage pool 2 is located on the centripetal side of the reaction holes 7, that is, compared with the reaction holes 7, the liquid storage pool 2 is closer to the centrifugal center 1. Therefore, the centrifugal potential energy of the liquid storage pool 2 is higher than that of the reaction holes 7.,

[0049] It should be noted that the closer to the centrifugal center 1, the higher the centrifugal potential energy. The following text refers to this explanation.,

[0050] In some embodiments, there are multiple reaction holes 7, and the distances from the reaction holes 7 to the centrifugal center 1 are the same to ensure that all the reaction holes 7 have the same centrifugal potential energy. For Figure 1 example, the chip body is a fan-shaped structure, and the centers of all the reaction holes 7 are located on a circle with the centrifugal center 1 as the center. In some embodiments, the reaction holes 7 are evenly arranged at equal angles on this circle.,

[0051] The number of the reaction holes 7 can be set according to different needs, and the distance between adjacent reaction holes 7 is not specifically limited, and any number of reaction holes 7 and any distance size are within the protection scope.,

[0052] In some embodiments, the volume of the reaction holes 7 is smaller than the volume of the liquid storage pool 2. Specifically, the volume of the liquid storage pool 2 is greater than the sum of the volumes of all the reaction holes 7 to ensure that all the reaction holes 7 can be filled with liquid samples.,

[0053] The distribution pipe 4 is located on the centrifugal side of the reaction holes 7, that is, along the direction of the centrifugal force, the liquid storage pool 2, the reaction holes 7, the distribution pipe 4, and the waste liquid pool 10 are arranged in sequence.,

[0054] The liquid inlet end of the distribution pipe 4 is communicated with the liquid storage pool 2. Specifically, it is connected through the connecting pipe 3. One end of the connecting pipe 3 is connected to the centrifugal end of the liquid storage pool 2, and the other end is connected to the liquid inlet of the distribution pipe 4, while the liquid outlet of the distribution pipe 4 is connected to the waste liquid pool 10. In some embodiments, the liquid inlet of the distribution pipe 4 is located at one end in the length direction of the distribution pipe 4, and the liquid outlet of the distribution pipe 4 is located at the other end in the length direction of the distribution pipe 4.,

[0055] In some embodiments, the liquid outlet of the distribution pipe 4 and the waste liquid pool 10 are communicated through, including but not limited to, the siphon tube 9. Optionally, the waste liquid pool 10 is the outermost long liquid tank.,

[0056] In some embodiments, the above-mentioned liquid inlet can be located at the centripetal end of the distribution pipe 4, and the liquid outlet can be located at the centrifugal end of the distribution pipe 4.,

[0057] It should be noted that one end of the same component close to the centrifugal center 1 is the centripetal end, and the end far from the centrifugal center 1 is the centrifugal end, and the centrifugal potential energy of the centripetal end of the same component is higher than that of the centrifugal end. The following text refers to this explanation.,

[0058] In some embodiments, the proximal end of the reaction well 7 is communicated with a position between the liquid inlet and the liquid outlet of the distribution pipe 4 through a hole filling pipe 5, so that the liquid sample can flow into the reaction well 7 through the hole filling pipe 5 while gradually filling the distribution pipe 4.

[0059] It should be noted that the flow resistance is controlled by the pipe thickness (the thinner the pipe, the greater the flow resistance) and the pipe length (the longer the pipe, the greater the flow resistance). Therefore, the thickness and length of the hole filling pipe 5 can be adjusted to enable the liquid sample to enter the reaction well 7 simultaneously or sequentially.

[0060] In the embodiments of the present invention, the distribution pipe 4 is arranged on the distal side of the reaction well 7, and the distribution pipe 4 is connected to the reaction well 7 through the hole filling pipe 5. During the process of gradually filling the distribution pipe 4 with the liquid sample, the reaction well 7 will also be filled (including filling the reaction wells 7 sequentially or simultaneously). Since the distribution pipe 4 is connected to the proximal end of the reaction well 7 through the hole filling pipe 5, the problem of liquid sample backflow in the reaction well 7 can be alleviated, thereby alleviating the fluid crosstalk phenomenon in the reaction well 7 and improving the detection accuracy.

[0061] It should be noted that in some embodiments, the connecting pipe 3 and the distribution pipe 4 can be an integral pipe fitting with the same diameter; of course, the connecting pipe 3 and the distribution pipe 4 can also be pipe fittings with different diameters. For example, the end of the connecting pipe 3 connected to the liquid storage tank 2 is closer to the centrifugal center 1 than the end connected to the distribution pipe 4, and the average cross-sectional area of the connecting pipe 3 is not greater than that of the distribution pipe. The cross-sectional shape of the connecting pipe 3 includes, but is not limited to, a rectangle, a rounded rectangle, a semicircle, a semi-ellipse, a polygon, a rounded polygon, or a combination of the foregoing shapes.

[0062] A siphon structure, an interface valve, an air embolism or other structures can be arranged on the connecting pipe 3. In some embodiments, the width range of the connecting pipe 3 includes, but is not limited to, 0.1 mm - 1 mm, and more preferably 0.2 mm - 0.5 mm; the depth of the connecting pipe 3 is in the same range as the width of the connecting pipe 3, and there is no mutual limitation between the two; in the whole pipeline, the width and depth of the connecting pipe 3 may vary.

[0063] It should be noted that the diameters of the connecting pipe 3, the distribution pipe 4 and the hole filling pipe 5 meet the following requirements:

[0064] During the sequential filling process of each reaction well 7, it is required that the dispensing pipe 4 is relatively thin (with a small diameter) to ensure a relatively high flow resistance in the dispensing pipe 4, so that the liquid can start to enter the filling pipe 5 against the centrifugal force when it encounters the filling pipe 5. That is, to meet the above requirements, the filling pipe 5 cannot be much thinner than the dispensing pipe 4. Therefore, the cross-sectional areas of the connecting pipe 3, the dispensing pipe 4, and the filling pipe 5 satisfy: the ratio range of the connecting pipe 3 to the dispensing pipe 4 is: 3:1 to 1:3, preferably 3:2 to 2:3. The ratio range of the dispensing pipe 4 to the filling pipe 5 is: 3:1 - 1:1, that is, the diameter of the dispensing pipe 4 ≥ the diameter of the filling pipe 5. If the filling pipe 5 is too thick, it will cause the liquid level in the liquid surface of the ventilation channel at the proximal end of the reaction well 7 with a higher ranking to rise too high before the dispensing pipe 4 is filled, and even enter the upper horizontal ventilation channel.

[0065] During the synchronous filling process of all reaction wells 7, it is required that the dispensing pipe 4 is the thickest and has the lowest flow resistance inside. When filling the liquid, it tends to be filled from the distal end to the proximal end gradually. Therefore, the ratio relationship range between the cross-sectional area of the connecting pipe 3 and the cross-sectional area of the dispensing pipe 4 includes but is not limited to 1:2 - 1:10, and more preferably 1:4 - 1:7; if the area difference is too small, the tendency of the liquid to flow from the connecting pipe 3 to the end of the dispensing pipe 4 is relatively strong. At this time, the liquid tends to flow from the liquid inlet of the dispensing pipe 4 to the liquid outlet, rather than being filled from the distal end to the proximal end of the dispensing pipe 4 gradually. The filling pipes 5 are not evenly stressed, and the liquid will enter the filling pipe 5 with a higher ranking against the centrifugal force, and it is impossible to ensure that all reaction wells 7 are filled simultaneously; if the area difference is too large, since the liquid in the dispensing pipe 4 will eventually be discharged after the filling is completed, the too large volume of the dispensing pipe 4 will cause a large amount of liquid waste.

[0066] In the way that there is no requirement for the filling order of the reaction wells 7, only requiring that all reaction wells 7 are filled and the first sections 51 of the connecting pipe 3, the dispensing pipe 4, and the filling pipe 5 are emptied, the requirement for the thickness relationship between the connecting pipe 3, the dispensing pipe 4, and the filling pipe 5 is the lowest, only requiring that the filling pipe 5 cannot be thicker than the dispensing pipe 4.

[0067] The included angle range formed by the filling pipe 5 and the dispensing pipe 4 includes but is not limited to 60° - 120°; more preferably 80° - 100°.

[0068] The microfluidic chip in some embodiments further includes a liquid separation hole 6. Specifically, the liquid separation hole 6 is located on the proximal side of the reaction well 7, so that the centrifugal potential energy of the liquid separation hole 6 is higher than that of the reaction well 7, and the filling pipe 5 is connected to the reaction well 7 through the liquid separation hole 6.

[0069] By setting the liquid separation holes 6, after the liquid sample enters the reaction holes 7 through the filling hole tube 5 and the liquid separation holes 6, the gas in the liquid separation holes 6 will gather at the proximal end of the liquid separation holes 6 under the extrusion of the liquid sample. Under the action of the gas at the proximal end of the liquid separation holes 6, a gas embolism, that is, a gas seal, can be formed to further prevent fluid crosstalk between the reaction holes 7.

[0070] Specifically, the specific method for avoiding crosstalk adopted in this application is as follows: during the filling process of the small-volume chamber, the liquid that has come into contact with the reagent in the small-volume chamber is always separated from and does not come into contact with the liquid continuously entering the small-volume chamber; after all the small-volume chambers are filled, all the liquid in the pipeline used to fill the small-volume chambers will be discharged; at this time, the liquids in each small-volume chamber are independent, and no matter whether the liquid is subjected to centrifugal force (outward) or Euler force (clockwise / counterclockwise acceleration, that is, force to the left / right) at this time, the liquids in each small-volume chamber will not come into contact with each other.

[0071] Figure 1 and Figure 2 In [specific reference], the distribution pipe 4 can be an arc-shaped pipe concentric with or close to the centrifugal center 1. In some embodiments, the two are concentric, and the centrifugal potential energy at each part of the arc-shaped pipe is the same. At this time, the upward forces of the liquid sample received by all the filling hole tubes 5 are equal, and the filling progress of all the reaction holes 7 is the same. In some embodiments, the distribution pipe 4 can also be an arc-shaped pipe, and there is a centrifugal potential energy difference at both circumferential ends of the distribution pipe 4. The side close to the centrifugal center 1 is the proximal end, and the side far from the centrifugal center 1 is the distal end. The liquid inlet is located on the proximal side, and the liquid outlet is located on the distal side. According to the order in which the liquid in the distribution pipe 4 passes through each filling hole tube 5, sequential filling of the reaction holes 7 can be achieved.

[0072] In some embodiments, the height difference range between the proximal end and the distal end of the distribution pipe 4 includes but is not limited to 1 mm - 20 mm, and more preferably 3 mm - 15 mm; if the height difference is too small, it may cause the final emptying failure of the distribution pipe 4 or fail to ensure the sequential filling of the reaction holes 7; if the height difference is too large, it will occupy too much core area and also fail to ensure the sequential filling of the reaction holes 7.

[0073] It should be noted that when sequential hole filling is required, there are height difference requirements at both ends of the distribution pipe 4 in terms of length; when synchronous hole filling is required or there is no requirement for the hole filling order, there is no height difference requirement for the distribution pipe 4. The height difference in this article is the distance difference between two different positions to the centrifugal center.

[0074] To prevent the liquid level in the second pipe 82 at the proximal end of the reaction hole 7 from being too high, the following must be ensured: the second pipe 82 at the proximal end of the reaction hole 7 is thin enough to provide flow resistance to prevent the liquid from surging upward against the centrifugal force, and the cross-sectional area ratio of the second pipe 82 to the hole-filling pipe 5 is ≤ 1:3; due to the addition of the liquid separation hole 6, when both the reaction hole 7 and the second section 52 of the hole-filling pipe are filled with liquid, the air in the liquid separation hole 6 will form a significant embolism effect on the entry of the liquid in the first section 51 of the hole-filling pipe 5, thereby preventing the continuous inflow of the liquid and preventing the liquid level in the second pipe 82 at the proximal end of the reaction hole 7 from surging too high.

[0075] In the following, the sequential filling of the reaction holes 7 is taken as an example for illustration. For the simultaneous filling of the reaction holes 7, the description below can be referred to. The difference is that during the flow of the liquid sample along the distribution pipe 4, the liquid sample flows forward and upward simultaneously to achieve the sequential filling of the reaction holes 7. After the liquid sample fills the distribution pipe 4 forward, it then flows upward to achieve the synchronous filling of the reaction holes 7.

[0076] Combined with Figure 1 and Figure 2 As shown, the hole-filling pipe 5 in the embodiment of the present invention includes: a first section 51 and a second section 52.

[0077] Among them, the first section 51 is connected to the proximal end of the distribution pipe 4 and the liquid separation hole 6; the second section 52 is connected to the distal end of the liquid separation hole 6 and the proximal end of the reaction hole 7. Optionally, the distance range from the connection of the second section 52 to the reaction hole 7 to the proximal end of the reaction hole 7 can be 0 mm - 1.5 mm; more preferably 0 mm - 0.5 mm, so as to facilitate the connection of the reaction hole 7 to the ventilation channel.

[0078] Combined with Figure 3 in (b) and Figure 4 As shown, during the diffusion of the liquid sample from the liquid inlet to the liquid outlet direction, the liquid sample enters the liquid separation hole 6 through the first section 51, and under the action of the centrifugal force, the liquid sample in the liquid separation hole 6 flows into the reaction hole 7 through the second section 52. During the flow of the liquid sample, the air in the liquid separation hole 6 will be pushed and pulled by the liquid at its proximal end and distal end respectively. However, since the air density is lower than that of the liquid sample, under the action of the centrifugal force, the air sandwiched by the liquid in the liquid separation hole 6 will tend to float rather than sink. At the same time, the cross-sectional area of the hole-filling pipe 5 is smaller than the cross-sectional area of the proximal end of the liquid separation hole 6. Therefore, there is a sudden change in area at the connection between the hole-filling pipe 5 and the liquid separation hole 6, and the liquid cannot completely push out the gas in the liquid separation hole 6. Thus, the air will form an air embolism that slightly blocks the liquid at the proximal end inside the liquid separation hole 6, that is, an air embolism is formed between the first section 51 and the liquid separation hole 6.

[0079] In some embodiments, the liquid separation hole 6 includes, but is not limited to, a spherical space. The diameter of the hole filling tube 5 is smaller than the diameter of the liquid separation hole 6. Therefore, when the liquid sample in the hole filling tube 5 enters the liquid separation hole 6, a situation of sudden area change will occur.

[0080] It should be noted that when the reaction hole 7 is not filled, under the action of centrifugal force, the liquid at the proximal end and the distal end of the liquid separation hole 6 is pushed up and pulled down respectively. A slight air embolism cannot prevent the inflow of liquid. However, after the reaction hole 7 is filled, there is only the upward thrust at the proximal end of the liquid separation hole 6, and no longer the downward pull at the distal end of the liquid separation hole 6. At this time, the significantly enhanced air embolism can ensure that no more liquid enters. See Figure 4 In [the figure], the liquid level height of the second pipeline 82 at the proximal end of the filled reaction hole 7 is limited by the gas embolism in the liquid separation hole 6 and the flow resistance of the second pipeline 82, and this liquid level height will not continue to rise.

[0081] During the process of filling the reaction hole 7, the flow directions of the liquid in the first section 51 and the second section 52 on both sides of the liquid separation hole 6 are the same. Therefore, the effect of the air embolism in the liquid separation hole 6 is very slight, and the hole filling process of the liquid sample will not be blocked. However, under the action of this slight air embolism, the liquid in the first section 51 and the second section 52 will not come into direct contact, thus further avoiding fluid crosstalk and improving the detection accuracy.

[0082] In some embodiments, the second section 52 is a bent pipeline. By bending the second section 52 and ensuring that the highest point at the proximal end of the second section 52 remains unchanged, it does not affect the entry of the liquid sample into the reaction hole 7. After the second section 52 is bent, the distance between the reaction hole 7 and the second section 52 can be extended, which is beneficial to avoiding fluid crosstalk between the second section 52 and the first section 51. The first section 51 includes a straight pipe section connected to the distribution pipe 4 and an arc pipe section connected to the straight pipe section, and this arc pipe section extends towards the centrifugal center 1 to the highest point and then bends reversely and extends to the reaction hole 7 to bypass the position of the liquid separation hole 6. Due to the positional relationship between the liquid separation hole 6 and the reaction hole 7, the whole hole filling tube 5 extends towards the centrifugal center 1 and then bends and extends in a direction away from the centrifugal center 1. In some embodiments, the height difference range between the proximal end of the hole filling tube 5 and the proximal end of the reaction hole 7 includes, but is not limited to, 1 mm - 10 mm, and more preferably 2 mm - 5 mm.

[0083] The ratio range of the width of the hole filling tube 5 to the width of the liquid separation hole 6 includes, but is not limited to, 1 / 3 - 1 / 10; more preferably 1 / 5 - 1 / 8; the ratio range of the depth of the hole filling tube 5 to the liquid separation hole 6 is 1 / 4 - 1 / 30; more preferably 1 / 5 - 1 / 15.

[0084] It should be noted that the shapes and sizes of the first section 51 and the second section 52 in the embodiments of the present application can be set according to different needs, and any pipeline that can satisfy the above connection relationship is within the protection scope.

[0085] Combined Figure 1 and Figure 2 As shown, in the embodiment of the present invention, the area of the liquid separation hole 6 is smaller than that of the reaction hole 7, and the volume of the liquid separation hole 6 is smaller than that of the reaction hole 7. By the above settings, the waste of liquid samples can be reduced.

[0086] The microfluidic chip in a further embodiment further includes a ventilation channel 8, and the ventilation channel 8 is used for exhausting air from the reaction hole 7, the liquid storage pool 2, and the waste liquid pool 10. By exhausting air from the reaction hole 7, the liquid storage pool 2, and the waste liquid pool 10 through the ventilation channel 8, it can ensure that the liquid sample smoothly enters the reaction hole 7 and the liquid storage pool 2, and finally drains to the waste liquid pool 10.

[0087] In some embodiments, the ventilation channel 8 includes: a first pipe 81, a second pipe 82, and a third pipe 83.

[0088] Among them, the first pipe 81 communicates the liquid storage pool 2 with the atmosphere. During the process of the liquid sample entering the liquid storage pool 2, the air in the liquid storage pool 2 is discharged from the liquid storage pool 2 through the first pipe 81 to ensure that the liquid sample can smoothly fill the liquid storage pool 2, so as to ensure that when a sufficient amount of liquid enters the liquid storage pool 2, the liquid will not be squeezed out of the liquid storage pool 2.

[0089] The first end of the second pipe 82 is connected to the proximal end of the reaction hole 7, the second end is connected to the atmosphere, the second pipe 82 is connected to the reaction hole 7 in a one-to-one correspondence, and the second ends of all the second pipes 82 are connected. During the process of the liquid sample entering the reaction hole 7, the air in the reaction hole 7 can be discharged through the second pipe 82 to ensure that the liquid sample can smoothly fill the reaction hole 7.

[0090] The third pipe 83 communicates the waste liquid pool 10 with the atmosphere. During the process of the liquid sample entering the waste liquid pool 10, the air in the waste liquid pool 10 is discharged from the waste liquid pool 10 through the third pipe 83.

[0091] Combined Figure 1 and Figure 2 As shown, in the present application, the waste liquid pool 10 is located on the distal side of the distribution pipe 4, and the liquid outlet of the distribution pipe 4 is connected to the waste liquid pool 10 through a siphon pipe 9, and the centrifugal potential energy of the proximal end of the siphon pipe 9 is higher than that of the proximal end of the hole filling pipe 5, that is, the proximal end of the siphon pipe 9 is higher than the proximal end of the hole filling pipe 5. Therefore, during the continuous downward hole filling process of the liquid sample in the hole filling pipe 5, the liquid will not cross the proximal end of the siphon pipe 9 in advance before filling all the reaction holes 7, thereby ensuring that each reaction hole 7 is filled with the liquid sample.

[0092] In some embodiments, the siphon pipe 9 includes: an inclined section 91 and a bent section 92.

[0093] Among them, the first end of the inclined section 91 is communicated with the liquid outlet of the distribution pipe 4, the second end of the inclined section 91 is communicated with one end of the bent section 92, and the other end of the bent section 92 is communicated with the waste liquid pool 10.

[0094] The inclined section 91 is a pipe extending obliquely towards the direction close to the far center side; the bent section 92 is a U-shaped pipe protruding towards the centrifugal center 1.

[0095] It should be noted that the inclined section 91 is arranged obliquely, so that there is a section of the siphon pipe 9 where the centrifugal potential energy is lower than the far center end of the distribution pipe 4, so as to ensure that the liquid sample in the distribution pipe 4 can be discharged with the highest efficiency, so as to ensure that all the liquid in the distribution pipe 4 enters the siphon pipe 9 during the siphon process. In some embodiments, the range of the descending amplitude of the inclined section 91 descending towards the far center end includes but is not limited to 0.2 mm - 2 mm, and further preferably 0.3 mm - 1 mm.

[0096] The above content describes the specific structure of the microfluidic chip. The following will describe Figures 3 to 5 the liquid filling process of the microfluidic chip in combination with

[0097] Among them, Figure 3 In (a) of, when the microfluidic chip is in a static state, the liquid storage pool 2 contains a liquid sample to be sub-packaged. Among them, the shaded part in (a) indicates the liquid sample.

[0098] Figure 3 In (b) of and Figure 4 it shows that during the first centrifugation, when the microfluidic chip rotates around the centrifugal center 1, under the drive of centrifugal force, the liquid sample in the liquid storage pool 2 enters the distribution pipe 4 through the connecting pipe 3 and starts to fill the reaction holes 7 in sequence through the filling hole pipe 5.

[0099] When the liquid sample flows to the connection part of the distribution pipe 4 and the filling hole pipe 5, a part of the liquid sample flows along the distribution pipe 4 towards the direction of the siphon pipe 9 under the action of centrifugal force; a part of the liquid sample flows along the direction of the filling hole pipe 5.

[0100] After the first reaction well 7 is filled, since the liquid sample cannot continue to enter the reaction well 7, under the action of centrifugal force, a small amount of the liquid sample will enter the second pipe 82 above the reaction well 7, and the liquid level will slightly exceed the distal end of the liquid separation hole 6. During this process, although the liquid sample in the filling pipe 5 still tends to flow into the liquid separation hole 6 under the action of centrifugal force, the structure connected to the distal end of the liquid separation hole 6 is already filled with the liquid sample. The newly entered liquid sample can only squeeze the volume of the air in the liquid separation hole 6 to further compress the gas, or enter the second pipe 82 above the reaction well 7 through the connected pipe. When the liquid level in the second pipe 82 rises to near the proximal end of the filling pipe 5, the liquid level in the second pipe 82 and the compressed air in the liquid separation hole 6 form a sufficient counteraction to the inflow of the liquid sample in the filling pipe 5 (it can be understood that the air embolism effect is strong enough and the liquid level height in the second pipe 82 together prevent the continuous inflow of the liquid), so that the liquid sample cannot continue to enter the liquid separation hole 6. At the same time, the liquid in the distribution pipe 4 still flows towards the siphon 9 and fills each reaction well 7 in turn.

[0101] Figure 3 of (c) and Figure 5 In, after all the reaction wells 7 are filled, the liquid sample will continue to fill the siphon 9 forward. Since the distal end of the liquid storage tank 2 is higher than the proximal end of the siphon 9, a sufficient amount of the liquid sample will cross the proximal end of the siphon 9 and fill it.

[0102] During the process of filling the liquid sample in the siphon 9, according to the principle of communicating vessels, the liquid in each filling pipe 5 also tends to enter the reaction well 7 through the liquid separation hole 6, and finally the liquid level in the second pipe 82 of the reaction well 7 is the same as the height of the proximal end of the siphon 9; in this state, since the first section 51 and the second section 52 are both filled with the liquid sample, the gas in the liquid separation hole 6 cannot be discharged and is only under the pressure of the liquid at the proximal end of the liquid separation hole 6, so the gas is compressed by the force, which plays a certain role in preventing the liquid from entering the liquid separation hole 6, making the liquid level in the second pipe 82 not rise to the same height as the proximal end of the siphon 9.

[0103] Figure 3 As shown in (d) of, after the siphon 9 is filled, according to the siphon effect, the residual liquid in the liquid storage tank 2, the connecting pipe 3, the distribution pipe 4 and the liquid sample in the first section 51 will all flow into the waste liquid tank 10 through the siphon 9; while the liquid in the second section 52 and the reaction well 7 will stay in place because they are separated by the liquid separation hole 6, thus completing the distribution of the liquid sample and ensuring the independence of each reaction well 7.

[0104] Combining the above process, it can be seen that due to the liquid separation function of the liquid separation holes 6, the liquid in the reaction holes 7 that may contain reagents will not come into contact with the liquid at the proximal end of the liquid separation holes 6, so reagent interference between the reaction holes 7 will not occur. In addition, after the distribution is completed, since there is no liquid in the distribution pipe 4 and the first section 51, even if the centrifugal speed of the chip is changed to mix the reagents in the reaction holes 7 and the liquid sample shakes violently, the liquid in the reaction holes 7 and the adjacent pipes (the second section 52 and the second pipe 82) is restricted by the structural shape and will not come into contact with the liquid in the waste liquid pool 10 or other reaction holes 7, thus affecting the test results.

[0105] When the reagent reaction principle is related to nucleic acid amplification, to ensure that the amplification products will not cause pollution to the outside world, it is required that all liquids and gases in the microfluidic chip are completely isolated from the outside world. Therefore, the corresponding ventilation channels 8 need to achieve complete internal circulation ventilation, and each ventilation channel will be connected to other structures to ensure that when a structure has liquid entering, the gas therein will necessarily flow through the ventilation channel and finally flow to the structure where the liquid is discharged.

[0106] In addition, an embodiment of the present invention also discloses a microfluidic system, including a microfluidic chip, wherein the microfluidic chip is the microfluidic chip disclosed in the above embodiment. Therefore, the microfluidic system with this microfluidic chip also has all the above technical effects, which will not be elaborated one by one here.

[0107] The various embodiments in this specification are described in a progressive manner. Each embodiment focuses on the differences from other embodiments. The same or similar parts among the various embodiments can be referred to each other.

[0108] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but will be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A microfluidic chip, characterized in that, Comprising: A substrate that rotates around the centrifugal center; A liquid storage pool located on the centripetal side of the substrate; Reaction holes, the number of which is multiple, the reaction holes are located on the centrifugal side of the liquid storage pool, and the distances from the reaction holes to the centrifugal center are the same. The volume of the reaction holes is smaller than the volume of the liquid storage pool; A distribution pipe located on the centrifugal side of the reaction holes. The liquid inlet of the distribution pipe communicates with the liquid storage pool, the liquid outlet of the distribution pipe communicates with a waste liquid pool, and the centripetal end of the reaction hole communicates with a position between the liquid inlet and the liquid outlet of the distribution pipe through a hole filling pipe.

2. The microfluidic chip according to claim 1, wherein Further comprising: Liquid separation holes located on the centripetal side of the reaction holes, and the hole filling pipe is connected to the reaction holes through the liquid separation holes.

3. The microfluidic chip according to claim 2, characterized in that, The area and volume of the liquid separation holes are respectively smaller than the area and volume of the reaction holes; The cross-sectional area of the hole filling pipe is smaller than the cross-sectional area of the centripetal end of the liquid separation hole.

4. The microfluidic chip according to claim 2, characterized in that, The hole filling pipe comprises: A first section connecting the centripetal end of the liquid separation hole and the distribution pipe; A second section connecting the centrifugal end of the liquid separation hole and the centripetal end of the reaction hole.

5. The microfluidic chip according to claim 1, characterized in that, For the distribution pipe, the centrifugal potential energy of the liquid inlet end is higher than that of the liquid outlet end; Or, For the distribution pipe, the centrifugal potential energy of the liquid inlet end is equal to that of the liquid outlet end.

6. The microfluidic chip according to any one of claims 1 to 5, characterized in that, Further comprising a ventilation channel for exhausting air from the reaction holes, the liquid storage pool and the waste liquid pool.

7. The microfluidic chip according to claim 6, wherein, The ventilation channel comprises: A first pipe communicating the liquid storage pool with the atmosphere; A second pipe, the first end of which communicates with the centripetal end of the reaction hole, the second end of which communicates with the atmosphere, the second pipe is connected to the reaction holes one by one, and the second ends of all the second pipes communicate; A third pipe communicating the waste liquid pool with the atmosphere.

8. The microfluidic chip according to claim 6, wherein The waste liquid pool is communicated with the liquid outlet through a siphon, and the centrifugal potential energy of the centripetal end of the siphon is higher than that of the centripetal end of the hole filling pipe.

9. The microfluidic chip according to claim 8, characterized in that, The siphon comprises: An inclined section, the first end of which communicates with the liquid outlet of the distribution pipe, and the inclined section is a pipe extending obliquely away from the centrifugal center; A bent section, the second end of the inclined section communicates with one end of the bent section, and the other end of the bent section communicates with the waste liquid pool, and the bent section is a U-shaped pipe protruding towards the centrifugal center.

10. A microfluidic system, comprising a microfluidic chip, characterized in that, The microfluidic chip is the microfluidic chip according to any one of claims 1 to 9.

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