CN107583698B

CN107583698B - Microfluidic chip and microfluidic device

Info

Publication number: CN107583698B
Application number: CN201711058624.9A
Authority: CN
Inventors: 徐友春
Original assignee: Tsinghua University
Current assignee: Tsinghua University
Priority date: 2017-11-01
Filing date: 2017-11-01
Publication date: 2023-04-14
Anticipated expiration: 2037-11-01
Also published as: CN107583698A

Abstract

The invention discloses a micro-fluidic chip and a micro-fluidic device, wherein the micro-fluidic chip comprises a base body, the base body is provided with an injection hole, a reaction unit and a flow path for communicating the injection hole with the reaction unit, the base body comprises a deformation part which can be deformed by hot pressing, the deformed deformation part is used for heat sealing the flow path, and any two reaction units are isolated by the deformed deformation part. The microfluidic chip disclosed by the invention effectively improves the isolation reliability and convenience. The microfluidic device disclosed by the invention comprises the microfluidic chip and the hot pressing piece for hot pressing the substrate to deform the deformation part.

Description

Microfluidic chip and microfluidic device

Technical Field

The invention relates to the technical field of microfluidics, in particular to a microfluidic chip and a microfluidic device.

Background

The microfluidic technology is a technology for processing or manipulating micro fluid by using a micro pipeline, and is widely applied to various test related fields such as cell culture, cell stimulation, cell analysis, nucleic acid extraction, nucleic acid amplification, biochemical detection, immunodetection, environmental monitoring and the like. The microfluidic technology is mainly realized through a microfluidic chip, a plurality of reaction units of the microfluidic chip are usually required to realize the reaction of a plurality of samples or the detection of a plurality of detection indexes, and specifically, when the parallel detection of a plurality of indexes is required, the distribution of liquid is required to be realized, namely, the same liquid is distributed to the reaction units for detecting different indexes. Centrifugal forces are typically used to dispense the liquid.

To ensure the accuracy of the test results, cross-contamination between individual reaction units should be avoided. Currently, air or mineral oil is used to isolate the individual reaction units.

Specifically, centrifugal force is generated by rotating the chip, liquid is distributed to each reaction unit under the driving of the centrifugal force, and the liquid between different reaction units is isolated by air in a pipeline or a cavity. However, the separation between the gas and liquid phases is not stable, and the liquids in different reaction units may contact each other along the wetting of the pipe wall to cause mutual diffusion, or the liquids in different reaction units contact each other due to volatilization and condensation of the liquids to cause cross contamination between different reaction units. In addition, because the compressibility of the air is relatively strong, if bubbles are generated in the reaction units due to heating or reaction, the expanded bubbles will extrude the liquid in the reaction units into the connecting pipeline or cavity occupied by the air originally, so that the liquids in different reaction units are contacted, and cross contamination is caused.

Mineral oil is used to isolate the different reaction units after the sample distribution is completed, but this method requires the use of aqueous and oil phases and requires stepwise addition to the apparatus, which is complicated to operate.

In summary, how to isolate each reaction unit to improve isolation reliability and convenience is an urgent problem to be solved by those skilled in the art.

Disclosure of Invention

The invention aims to provide a microfluidic chip which can be used for isolating each reaction unit so as to improve the isolation reliability and convenience. Another object of the present invention is to provide a microfluidic device having the above microfluidic chip.

In order to achieve the above purpose, the invention provides the following technical scheme:

a microfluidic chip comprises a base body, wherein the base body is provided with an injection hole, reaction units and a flow path for communicating the injection hole with the reaction units, the base body comprises a deformation portion capable of being deformed through hot pressing, the deformed deformation portion is used for heat sealing the flow path, and any two reaction units are isolated by the deformed deformation portion.

Preferably, the flow path includes: a distribution channel communicating with the injection hole, and an injection channel communicating with the distribution channel and the reaction unit; wherein the injection flow paths correspond to the reaction units one to one.

Preferably, when the substrate rotates, a direction of a centrifugal force at the injection flow path is parallel to an axial direction of the injection flow path, or an angle between the direction of the centrifugal force at the injection flow path and the axial direction of the injection flow path is not more than 80 degrees.

Preferably, the distribution flow path includes: a first distribution section communicating with the injection hole, a second distribution section communicating with the injection flow path, and a third distribution section communicating adjacent two of the second distribution sections; wherein the second distribution segment corresponds to the reaction units one by one.

Preferably, the second distribution segment projects towards the injection flow path, and the third distribution segment projects away from the injection flow path; the second distribution section is arc-shaped or V-shaped and the third distribution section is arc-shaped or V-shaped.

Preferably, the second distribution segment and the third distribution segment form a main distribution segment;

the main distribution sections are distributed along an arc line or a circle, the injection flow path extends along the radial direction of the main distribution section where the injection flow path is located, and the reaction units are located on the periphery of the main distribution section where the reaction units are located;

or the main distribution sections are distributed along a straight line, the straight line is perpendicular to the axial direction of the injection flow path, and the reaction unit is positioned on one side of the main distribution section where the reaction unit is positioned.

Preferably, the injection flow path passes through the deformation part, and the deformation part is deformed by hot pressing and then heat-sealed; alternatively, the distribution flow path includes: and a distribution flow path segment which communicates two adjacent injection flow paths, passes through the deforming part, and is heat-sealed after the deforming part is deformed by hot pressing.

Preferably, the flow path section of the flow path heat-sealed by the deformation portion has an arc-shaped inner wall, and the protruding direction of the arc-shaped inner wall is opposite to the hot pressing direction of the substrate.

Preferably, the base body comprises at least two layers of substrates which are connected in a sealing mode, at least one layer of the substrates is an elastic substrate, and/or at least one layer of the substrates is a light-transmitting substrate.

Preferably, the base body comprises a first substrate and a second substrate which are hermetically connected; the injection hole is arranged on the first substrate or the second substrate, the reaction unit is arranged on the first substrate or the second substrate, and the thickness of the first substrate is larger than that of the second substrate; the flow path is arranged on the first substrate, or the flow path is arranged on the first substrate and the second substrate; the first substrate is provided with a concave structure at the deformation part.

Based on the microfluidic chip provided by the invention, the invention also provides a microfluidic device which comprises the microfluidic chip, wherein the microfluidic chip is any one of the microfluidic chips; the microfluidic device further includes a thermal compression member for thermally compressing the base body to deform the deformation portion.

Preferably, the hot press member has a hot press projection for hot pressing the base body.

Preferably, the heat pressing protrusion is annular; or the hot pressing bulges are blocky, and at least two hot pressing bulges are provided.

Preferably, the hot-pressing end face of the hot-pressing bulge is a curved surface and protrudes in the direction away from the connecting end of the hot-pressing bulge; or the hot-pressing end face of the hot-pressing bulge is a plane.

According to the micro-fluidic chip provided by the invention, the deformation part is arranged on the substrate, the deformation part can be deformed through hot pressing, and the deformed deformation part thermally seals the flow path, so that any two reaction units are isolated by the deformed deformation part, and each reaction unit is physically isolated by using the own deformation part of the substrate, and compared with the prior art adopting air isolation, the isolation reliability is effectively improved; simultaneously, deformation portion realizes warping through the hot pressing, and compared with the prior art that mineral oil is adopted to keep apart, only hot pressing one step can accomplish the isolation, has simplified the operation, has effectively improved the convenience.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

Fig. 1 is an exploded schematic view of a microfluidic chip according to a first embodiment of the present invention;

FIG. 2 is a schematic structural diagram of the first substrate shown in FIG. 1;

FIG. 3 is a schematic diagram of a schematic structure of a hot press in a microfluidic device according to an embodiment of the present invention;

FIG. 4 is a schematic view of another structure of a hot pressing member in a microfluidic device according to an embodiment of the present invention;

fig. 5 is a diagram illustrating a positional relationship between a hot pressing member and an injection flow path in a microfluidic device according to an embodiment of the present invention;

fig. 6 is a schematic structural diagram of a microfluidic device according to a first embodiment of the present invention after a second substrate is hot-pressed;

fig. 7 is a schematic diagram of a hot-pressing microfluidic chip of a hot-pressing member in a microfluidic device according to an embodiment of the present invention;

fig. 8 is a schematic structural view of a hot press in a microfluidic device according to a second embodiment of the present invention;

fig. 9 is a diagram illustrating a positional relationship between a thermal compression element and a distribution flow path in a microfluidic device according to a second embodiment of the present invention;

fig. 10 is a schematic structural diagram of a first substrate of a microfluidic chip according to a third embodiment of the present invention;

fig. 11 is another schematic structural diagram of the first substrate of the microfluidic chip according to the third embodiment of the present invention;

fig. 12 is a schematic structural diagram of a first substrate of a microfluidic chip according to a fourth embodiment of the present invention;

fig. 13 is another schematic structural diagram of the first substrate of the microfluidic chip according to the fourth embodiment of the present disclosure;

fig. 14 is a schematic structural diagram of a first substrate of a microfluidic chip according to a fifth embodiment of the present invention;

fig. 15 is another schematic structural diagram of the first substrate of the microfluidic chip according to the fifth embodiment of the present invention;

fig. 16 is a schematic structural diagram of a first substrate of a microfluidic chip according to a sixth embodiment of the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

As shown in fig. 1 to 2, 5 to 7, and 9 to 16, the microfluidic chip according to the embodiment of the present invention includes a substrate having an injection hole 14, a reaction unit 11, and a flow path communicating the injection hole 14 and the reaction unit 11. The substrate includes a deformable portion that can be deformed by hot pressing, the deformed deformable portion heat-seals the flow path, and any two reaction units 11 are isolated by the deformed deformable portion. It is understood that the number of reaction units 11 is at least two; the flow path is heat-sealed by the deformed portion, so that any two reaction units 11 are isolated by the deformed portion.

According to the microfluidic chip provided by the embodiment of the invention, the deformation part is arranged on the substrate, the deformation part can be deformed through hot pressing, and the deformed deformation part thermally seals the flow path, so that any two reaction units 11 are isolated by the deformed deformation part, and each reaction unit 11 is physically isolated by using the own deformation part of the substrate, and compared with the prior art adopting air isolation, the isolation reliability is effectively improved; simultaneously, deformation portion realizes warping through the hot pressing, and compared with the prior art that mineral oil is adopted to keep apart, only hot pressing one step can accomplish the isolation, has simplified the operation, has effectively improved the convenience.

Meanwhile, in the micro-fluidic chip provided by the embodiment of the invention, the deformation part is deformed by hot pressing, so that the deformation of the deformation part is simplified under the condition of ensuring the normal use of the matrix, the micro-fluidic chip is convenient to use, and the universality of the micro-fluidic chip is improved.

In the microfluidic chip provided in the above embodiment, the entire substrate may be deformed by hot pressing, or alternatively, only the deformed portion of the substrate may be deformed by hot pressing. For the convenience of production and manufacture, the whole base body is preferably deformed by hot pressing, and the deformed part and the base body are of an integrated structure.

In the microfluidic chip provided in the above embodiment, the flow path includes: a distribution channel 13 communicating with the injection hole 14, and an injection channel 12 communicating with the distribution channel 13; the injection flow paths 12 correspond to the reaction units 11 one to one. Of course, the structure of the flow path may be selected to be other, and is not limited to the above structure.

In order to ensure that no liquid to be detected or a small amount of liquid to be detected remains in the distribution flow path 13 after centrifugal distribution, it is preferable that the centrifugal force direction at the injection flow path 12 be parallel to the axial direction of the injection flow path 12 or the angle between the centrifugal force direction at the injection flow path 12 and the axial direction of the injection flow path 12 be not more than 80 degrees when the substrate is rotated.

It is understood that the injection flow path 12 is a straight flow path, i.e., the axial direction of the injection flow path 12 is a straight line; the direction of the centrifugal force at the injection flow path 12 has an angle with the axial direction of the injection flow path 12, which indicates that the direction of the centrifugal force at the injection flow path 12 is not parallel to the axial direction of the injection flow path 12.

In the above microfluidic chip, in order to avoid diffusion contamination between different reaction cells due to contact of liquids before heat sealing, it is preferable that the direction of the centrifugal force at the injection flow path 12 is parallel to the axial direction of the injection flow path 12 when the substrate is rotated.

Of course, the microfluidic chip may also be used in other centrifugal distribution manners, and is not limited to the above-mentioned manner.

In order to realize heat sealing through hot pressing, the flow path section which is heat sealed by the deformation part in the flow path is provided with an arc-shaped inner wall, and the protruding direction of the arc-shaped inner wall is opposite to the hot pressing direction of the base body. Of course, other shapes of the inner wall may be selected, such as, but not limited to, a U-shape.

In the micro-fluidic chip, one or two flow paths can be provided; when there are at least two flow paths, the injection holes 14 correspond to the flow paths one by one, or the injection holes 14 are one and the flow paths are connected in series.

In order to facilitate the injection of the liquid to be tested, the substrate also has vent holes 15 to vent the air inside the microfluidic chip. It is understood that the exhaust holes 15 and the injection holes 14 are respectively located at both ends of the flow path. The exhaust hole 15 and the injection hole 14 can be sealed by heat sealing or by gluing in the manner described in the present invention.

The specific structure of the flow path, the specific structure of the base, and the isolation method of the deformation portion may be specifically designed according to actual circumstances.

The micro-fluidic chip provided by the embodiment adopts a heat sealing mode, so that cross contamination among different reaction units 11 and potential pollution to the environment can be thoroughly avoided; the heat-sealing material used in the heat-sealing mode has various selection types, has the characteristics of transparency, lightness and thinness, and is easy for heat conduction and optical detection; different reaction substrates such as enzyme and substrate, antibody, primer, nucleic acid probe and the like can be put in each reaction unit 11 in advance, and the liquid to be detected enters the different reaction units 11 respectively to react with the reaction substrates, so that the purpose of multi-index analysis is achieved. The microfluidic chip can be widely applied to the fields of biological detection or medical inspection, such as biochemical analysis, immunoassay, nucleic acid amplification reaction or protein-receptor binding reaction.

Based on the microfluidic chip provided in the above embodiment, an embodiment of the present invention further provides a microfluidic device, which includes the microfluidic chip described in the above embodiment. In order to facilitate the hot-pressing deformation of the deformation portion, the microfluidic device further comprises a hot-pressing member 3 for hot-pressing the base body to deform the deformation portion.

Since the microfluidic chip has the technical effects and the microfluidic device has the microfluidic chip, the microfluidic device also has the corresponding technical effects, which is not described herein again; meanwhile, the micro-fluidic device realizes the hot-pressing deformation of the deformation part of the matrix by using the hot pressing piece 3, thereby being convenient for operation and simplifying the use.

The thermal pressing part 3 can be separated from the microfluidic chip, and after the two parts are separated, the deformation part is restored to the original state because the deformation part is made of the elastic material, and the thermally sealed flow path can be restored to the conduction state, so that the recovery of a product after reaction is facilitated. Of course, the deformed portion may not be restored to its original shape after the separation of the two, and the heat-sealed flow path may not be restored to the conduction state, which is not limited to the above case.

Based on the microfluidic device provided by the above embodiment, the embodiment of the present invention further provides a method for using the microfluidic device, and specifically, the method for using the microfluidic device includes the steps of:

s01) injecting liquid to be detected into the microfluidic chip:

specifically, the liquid to be detected is injected into the microfluidic chip from the injection hole 14.

S02) carrying out centrifugal distribution:

specifically, the liquid in the microfluidic chip is centrifugally distributed, and the liquid enters the reaction unit 11. The microfluidic chip is typically mounted on a centrifuge device for centrifugal distribution. Preferably, during the centrifugal distribution, the centrifugal force direction at the injection flow path 12 is parallel to the axial direction of the injection flow path 12, or the included angle between the centrifugal force direction at the injection flow path 12 and the axial direction of the injection flow path 12 is not more than 80 degrees.

S03) hot pressing:

the substrate is hot-pressed by the heated hot-press member 3 to deform the deformed portion and isolate each reaction cell 11.

The sequence of steps S02 and S03 can be changed, and is not limited.

Because the microfluidic device has the technical effects, the use method of the microfluidic device also has corresponding technical effects, and the details are not repeated herein.

In order to better understand the technical solution provided by the present invention, the following five embodiments are adopted to specifically describe the microfluidic chip, the microfluidic device, and the method for using the microfluidic device provided by the present invention.

Example one

As shown in fig. 1 and fig. 2, in the microfluidic chip provided in this embodiment, on the basis of the microfluidic chip described above, the base includes a first substrate 1 and a second substrate 2 that are hermetically connected, where both the first substrate 1 and the second substrate 2 are circular. The centrifugal center of the microfluidic chip is the center of the first substrate 1. Of course, the substrate may be selected to include three or more layers of substrates, and is not limited to the above structure.

The reaction cell 11 has a cavity to receive a liquid to be detected. Specifically, the reaction unit 11 is provided on one side surface of the first substrate 1, and the reaction unit 11 is a blind hole. The reaction units 11 are plural and arranged at equal intervals in the circumferential direction of the first substrate 1.

The base body further has a discharge hole 15 communicating with the flow path, and the discharge hole 15 and the injection hole 14 are located at both ends of the flow path. The injection channel 12, the distribution channel 13, the injection hole 14, and the exhaust hole 15 are provided on the first substrate 1, and the injection channel 12 and the reaction unit 11 are located on the same side of the first substrate 1. The injection flow path 12 is located on the side of the reaction unit 11 closer to the axis of the first substrate 1, and the distribution flow path 13 is located on the side of the injection flow path 12 closer to the axis of the first substrate 1, that is, the reaction unit 11 and the injection flow path 12 are radially distributed.

In the first embodiment, the second substrate 2 is a flat plate. In practical applications, a portion of the structure on the first substrate 1 may be disposed on the second substrate 2, and for example, the distribution flow path 13 and the injection flow path 12 may be disposed on the second substrate 2. In addition, in order to facilitate the alignment and sealing of the first substrate 1 and the second substrate 2 and the assembly of the microfluidic chip and the centrifugal device, other structures may be further disposed on the microfluidic chip according to actual needs, and are not described herein again.

The distribution flow path 13 includes: a first distribution section 131 communicating with the injection holes 14, a second distribution section 132 communicating with the injection flow path 12, and a third distribution section 133 communicating with two adjacent second distribution sections 132; the second distribution segments 132 correspond to the reaction units 11 one to one.

In order to facilitate the centrifugal distribution and improve the distribution uniformity, the second distribution section 132 protrudes toward the injection flow path 12. Preferably, the second distribution segment 132 is arcuate or V-shaped. Further, the second distribution segment 132 is semicircular.

To facilitate the centrifugal distribution, the third distribution section 133 projects away from the injection flow path 12. Preferably, the third distribution section 133 is arcuate or V-shaped.

It will be appreciated that the V-shape may be rounded at the corners to facilitate centrifugal dispensing. Of course, the second distribution segment 132 and the third distribution segment 133 may be selected to have other shapes, and are not limited to the above structure.

When the substrate has the discharge holes 15, the distribution flow path 13 further includes a fourth distribution section 134, and the discharge holes 15 are communicated with the second distribution section 132 at the end through the fourth distribution section 134.

It should be noted that the second distribution segment 132 at the end refers to the second distribution segment 132 located furthest downstream in the flow direction of the liquid.

In the flow path, the second distribution section 132 and the third distribution section 133 form a main distribution section; in the first embodiment, the main distribution segments are distributed along a circle, the injection flow path 12 extends along the radial direction of the main distribution segment where the reaction unit 11 is located, and the reaction unit is located at the periphery of the main distribution segment where the reaction unit is located.

In the first embodiment, the injection flow path 12 passes through the deformation portion, and the deformation portion is deformed by hot pressing and then the injection flow path 12 is heat-sealed.

In the first embodiment, the method for using the microfluidic device with the microfluidic chip is as follows:

adding the liquid to be detected into a distribution flow path 13 of the microfluidic chip through an injection hole 14;

placing the microfluidic chip on a centrifugal device, centrifuging by taking the circle center of the microfluidic chip as the center, and centrifuging the liquid into a reaction unit 11 through a distribution flow path 13 and an injection flow path 12;

the base body is pressed from one side of the second substrate 2 by the hot pressing part 3, the base body is subjected to hot pressing deformation, the deformation part is subjected to hot pressing deformation, hot pressing sealing is realized on the injection flow path 12, the injection flow path 12 is subjected to hot sealing, thorough physical isolation is realized, any two reaction units 11 are isolated, and cross contamination among different reaction units 11 is avoided. Thereafter, the microfluidic chip may be subjected to subsequent reactions and detection.

As shown in fig. 3, the hot-pressing member 3 of the first embodiment has a hot-pressing protrusion 31 for hot-pressing a substrate, and the hot-pressing protrusion 31 is ring-shaped. It can be understood that the hot-pressing protrusions 31 are aligned with the distribution direction of the reaction units 11. After the thermal pressing member 3 is aligned with the microfluidic chip, the thermal pressing protrusion 31 is opposite to the position of the deformation portion in the microfluidic chip, i.e. the position of the injection flow path 12 in the microfluidic chip, as shown in fig. 4.

The thermal pressing member 3 is heated to a predetermined temperature, and presses a deformation portion of the microfluidic chip, i.e., a position where the injection flow path 12 is located, at a predetermined pressure. Under the combined action of heat and pressure, the deformed portion is deformed, that is, the second substrate 2 is deformed and fused with the first substrate 1 thereunder, and the injection flow path 12 is heat-sealed, as shown in fig. 6.

The specific values of the preset temperature and the preset pressure are designed according to actual needs, and the specific values are not limited herein.

The above-mentioned thermal pressing member 3 is a rigid structure having a strong mechanical strength, for example, the thermal pressing member 3 is a metal material, or the thermal pressing member 3 is composed of a metal and a high-temperature resistant polymer, and all regions of the second substrate 2 pressed by the thermal pressing member 3 are dented during the heat-sealing process, as shown in fig. 5. After the heat press 3 is removed, the second substrate 2 finally maintains the structure shown in fig. 5. In this embodiment the thermal compression element 3 and the microfluidic chip do not need to be precisely aligned to ensure that all injection flow paths 12 are heat sealed.

In the first embodiment, in order to facilitate the hot pressing deformation, the hot pressing protrusion 31 is tapered from the connecting end to the hot pressing end. Specifically, the end of the hot-pressing protrusion 31 connected to the hot-pressing member 3 is a connection end of the hot-pressing protrusion 31, and the end of the hot-pressing protrusion 31 for contacting the deformation portion is a hot-pressing end of the hot-pressing protrusion 31, as shown in fig. 3 and 6.

Further, the cross section of the heat pressing protrusion 31 is trapezoidal, as shown in fig. 6, the cross section of the heat pressing protrusion 31 isbase:Sub>A section obtained by cutting alongbase:Sub>A-base:Sub>A in fig. 3. This design is advantageous in maintaining the mechanical strength of the heat pressing projection 31. Of course, the cross section of the heat pressing protrusion 31 may be triangular, but is not limited thereto.

In addition, the hot-pressing end face of the hot-pressing protrusion 31 is a curved surface and protrudes in a direction away from the connecting end of the hot-pressing protrusion 31; alternatively, the hot-pressing end face of the hot-pressing projection 31 is a flat face. Therefore, the hot-pressing bulge 31 is prevented from piercing the second substrate 2 in the hot-pressing process due to sharp corners, and the probability that the hot-pressing bulge 31 is damaged is reduced. Further, the top surface of the heat pressing protrusion 31 is a circular arc surface.

In the first embodiment, the heat pressing protrusion 31 may be annular, as shown in fig. 3. Of course, it is also possible to select the hot pressing protrusions 31 as a segmented structure, specifically, the hot pressing protrusions 31 are block-shaped, there are at least two hot pressing protrusions 31, and the distribution directions of the hot pressing protrusions 31 along the reaction unit 11 are the same, specifically, the hot pressing protrusions 31 correspond to the injection flow paths 12 one by one, as shown in fig. 7. Further, the top end of the heat pressing protrusion 31 can be completely matched with the structure of the injection flow path 12, and by selecting a proper material and heat sealing temperature, pressure and time, the deformation of the position corresponding to the second substrate 2 and the heat melting of the injection flow path 12 can be realized without substantially changing the structure of the first substrate 1. Of course, it is also possible to select that both the second substrate 2 and the first substrate 1 are deformed, and ensure that the deformed portion of the first substrate 1 and the deformed portion of the second substrate 2 are in abutting sealing, so as to achieve thorough physical isolation of the reaction unit 11.

The top of the heat pressing protrusion 31 of the heat pressing member 3 may be an elastic structure, which will deform adaptively when pressed to contact the substrate, so as to match and heat seal the second substrate 2 with the injection channel 12 on the first substrate 1. Further, with this embodiment, the inner wall of the injection flow path 12 on the first substrate 1 is an arc-shaped inner wall, and the protruding direction of the arc-shaped inner wall is opposite to the hot pressing direction of the substrates, i.e., the arc-shaped inner wall protrudes away from the second substrate 2, so that there is no dead angle in the heat sealing.

The material of the first substrate 1 is a high molecular polymer and/or a metal material. The high molecular polymer is polymethyl methacrylate, polycarbonate, polypropylene or the like. The first substrate 1 is formed by injection molding, laser engraving, or machining. The second substrate 2 is the same base material as the first substrate 1 or a heat-seal film matching the first substrate 1.

The deformable portion of the first substrate 1 and/or the second substrate 2 is an elastic material at normal temperature, and is deformable and elastic after being heated to a certain temperature, which is a characteristic of many high molecular polymers.

The first substrate 1 and the second substrate 2 can be sealed and attached through hot-press sealing, hot-press welding, laser welding, ultrasonic welding, glue sealing or other prior art packaging, and sealing connection is achieved. For example, one of the first substrate 1 and the second substrate 2 is a substrate having a single-sided adhesive.

For the convenience of detection, the second substrate 2 and/or the first substrate 1 are transparent substrates.

Example two

In the microfluidic chip provided in the second embodiment, the position of the deformation portion is changed based on the first embodiment. Specifically, after the sample is directly injected into the distribution flow path 13 through the injection hole 14 or enters the distribution flow path 13 through other operations or via other cavities or pipes, the distribution flow path 13 may be directly heat-sealed. Specifically, the distribution flow path 13 includes: and a distribution flow path section which communicates two adjacent injection flow paths 12, passes through the deforming portion, and is heat-sealed after the deforming portion is deformed by heat pressing, that is, the deforming portion heat-seals the distribution flow path section.

Since the reaction units 11 are distributed along the circumference of the first substrate 1, the hot pressing protrusions 31 of the hot pressing member 3 are plural and distributed along the circumference, so that the hot pressing protrusions 31 are in the same direction as the distribution direction of the reaction units 11, as shown in fig. 8.

As shown in fig. 9, after the hot pressing member 3 is fitted to the microfluidic chip, the hot pressing protrusion 31 will correspond to the distribution flow path segment.

In the second embodiment, the microfluidic device is used as follows:

firstly, adding liquid to be detected into a distribution flow path 13 of the microfluidic chip from an injection hole 14;

the hot pressing part 3 presses the substrate from one side of the second substrate 2 to perform hot pressing sealing on the distribution flow path section of the distribution flow path 13, so that the distribution flow path section is blocked, the liquid in the distribution flow path 13 is physically separated into a section of structure, and each section of structure corresponds to one reaction unit 11;

the microfluidic chip after hot pressing is placed on a centrifugal device, centrifugation is performed by taking the center of the circle of the first substrate 1 as the center, namely, the centrifugation is performed by taking the center of the circle of the microfluidic chip as the center, and liquid is centrifuged by the distribution flow path 13 subjected to heat sealing through the injection flow path 12 and enters the reaction unit 11. Thereafter, the microfluidic chip may be subjected to subsequent reactions and detection.

In this operation, the distribution flow path 13 is uniformly blocked, and the volume of the liquid held by heat sealing in the distribution flow path 13 is uniformly controlled, which is advantageous for achieving the uniformity of the liquid volume of each reaction unit 11. After the distribution flow path 13 is heat-sealed by the heat press 3, each heat-sealed portion is integrated with the injection flow path 12 and the reaction unit 11 connected thereto and physically isolated from each other, thereby fundamentally preventing cross-contamination.

In the second embodiment, the following may also be added on the basis of the first embodiment: the distribution flow path segment passes through the deformation portion, and the deformation portion heat-seals the distribution flow path segment after being deformed by heat pressing.

The second distribution segment 132 of the distribution flow path segments may pass through the deformation portion, and alternatively, the third distribution segment 133 of the divided flow path segments may pass through the deformation portion. The latter is preferably selected in order to simplify the structure.

Please refer to embodiment one, which is not mentioned in the second embodiment, and will not be described herein again.

EXAMPLE III

As shown in fig. 10 and fig. 11, the microfluidic chip structure provided in the third embodiment changes the distribution of the distribution flow path 13 and the communication relationship between the injection hole 14 and the distribution flow path 13 on the basis of the first embodiment. Specifically, the flow path further includes a reservoir 16 provided on the first substrate 1, wherein the injection hole 14 communicates with the reservoir 16, and the reservoir 16 communicates with the distribution flow path 13, so that the injection hole 14 communicates with the distribution flow path 13 through the reservoir 16. The shape and size of the reservoir 16 are designed according to actual needs, and are not limited in the embodiment of the present invention.

In the third embodiment, the liquid to be detected is not directly fed into the distribution channel 13, but is fed into the liquid reservoir 16, and finally enters the reaction unit 11 through the distribution channel 13 and the injection channel 12 by centrifugation or the like.

In the third embodiment, the main distribution section is distributed along an arc, the injection flow path 12 extends along the radial direction of the main distribution section, and the reaction unit 11 is located at the periphery of the main distribution section. The main distribution sections are distributed along an arc line, and the arc line can be formed by combining a plurality of sections of arc lines with different radiuses and also can be an arc line with the same radius.

As shown in fig. 10, the main distribution section is the portion of the distribution flow path 13 between the first distribution section 131 and the fourth distribution section 134. The second distribution segment 132 and the third distribution segment 133 are not labeled in fig. 10.

As shown in fig. 10, the first distribution section 131 may be a siphon tube having lyophilic properties; alternatively, the first distribution segment 131 may be a thin conduit, as shown in FIG. 11. The embodiment of the present invention does not limit the specific structure of the first distributing section 131.

Please refer to the first embodiment and/or the second embodiment for technical solutions not mentioned in the third embodiment, which are not described herein again.

Example four

As shown in fig. 12 and 13, in the microfluidic chip provided in the fourth embodiment, the reaction units 11 are distributed along the circumferential direction of the first substrate 1, and the reaction units 11 are distributed in a plurality of circles. In particular, the reaction units 11 are realized in a multi-turn distribution, there being at least two ways.

As shown in fig. 12, the number of flow paths, injection holes 14, and exhaust holes 15 was changed on the basis of the first embodiment. Specifically, the flow paths are distributed along a circle, the number of the flow paths is two, the flow paths are sequentially distributed along the radial direction, the injection holes 14 and the exhaust holes 15 correspond to the flow paths one by one, and each flow path is provided with the reaction unit 11 communicated with the flow path. Accordingly, the number of deformed portions and the number of the heat-pressing projections 31 also need to be increased to ensure isolation of each reaction unit 11.

The structure of each circle is the same as that described in the first embodiment. Of course, the number of the flow paths can be more than three, and the number of other structures can be adjusted correspondingly.

The microfluidic chip provided in the fourth embodiment may also have a structure as shown in fig. 13, and the number of flow paths is changed based on the third embodiment. Specifically, the flow paths are distributed along an arc, two flow paths are distributed sequentially along the radial direction, two adjacent flow paths are communicated, and any two flow paths are connected in series, that is, the flow paths are connected sequentially in series, and at this time, the injection hole 14 and the exhaust hole 15 are both one. The structure can effectively utilize the internal space of the microfluidic chip to realize multi-index synchronous detection; meanwhile, on the premise of arranging the reaction units 11 with the same number, the volume of the microfluidic chip can be effectively reduced.

Of course, it is also possible to vary the distribution of the distribution flow paths 13 on the basis of the third embodiment, in particular, the main distribution section is distributed along a spiral line, the injection flow path 12 extends along the radial direction of the arc in which it lies, and the reaction unit 11 is located at the periphery of the main distribution section in which it lies.

Please refer to at least one of the first embodiment, the second embodiment, and the third embodiment for technical solutions not mentioned in the fourth embodiment, which will not be described herein again.

EXAMPLE five

As shown in fig. 14 and 15, in the microfluidic chip provided in this fifth embodiment, on the basis of the above embodiments, the shape of the substrate is changed, and the substrate has a fan shape, a diamond shape, a rectangular shape, and the like.

As shown in fig. 14, the base body is designed to be fan-shaped on the basis of the third embodiment. Of course, on the basis of the first and fourth embodiments, the base body is designed to be fan-shaped. The base body is designed into a fan shape, so that the operation of a plurality of micro-fluidic chips under the same centrifugal device is facilitated, and the combination of multiple indexes and the synchronous reaction and detection of a plurality of liquids to be detected are facilitated. In this case, the main distribution segment is preferably selected to have an arc shape. In the fourth embodiment, the main distribution section is a portion of the distribution flow path 13 between the first distribution section 131 and the fourth distribution section 134, as shown in fig. 14. The second distribution segment 132 and the third distribution segment 133 are not labeled in fig. 14.

As shown in FIG. 15, the matrix may be rectangular, and in this case, the reaction units 11 are distributed more regularly, which is advantageous for detecting the substrate and the reaction result. When the substrate is rectangular, the main distribution section is preferably selected to be arranged along a line perpendicular to the axial direction of the injection flow path 12, and the reaction unit 11 is located at one side of the main distribution section where it is located. It is understood that the axial direction of the injection flow path 12 is the extending direction of the injection flow path.

When the number of the flow paths is at least two, it is preferable that the distribution directions of the main distribution segments are parallel. At this time, it is preferable that any two flow paths do not communicate, that is, the injection holes 14 and the exhaust holes 15 each correspond to a flow path one to one.

EXAMPLE six

In the microfluidic chip provided by the sixth embodiment, on the basis of the above embodiments, the first substrate 1 and the second substrate 2 are both made of thin film materials, that is, the first substrate 1 and the second substrate 2 are both made of thin films, and the processing method thereof may be injection molding, plastic sucking, blow molding or stamping.

Preferably, the film material used for the first substrate 1 and/or the second substrate 2 is an elastic material, so that the first substrate 1 and/or the second substrate 2 is an elastic substrate, i.e. an elastic film. Specifically, the material of the first substrate 1 and/or the second substrate 2 is a material having a certain elasticity, such as COP (cyclic Olefin Polymer), COC (cyclic Olefin Polymer), PP (Polypropylene), PET (polyethylene terephthalate), and PC (Polycarbonate) aluminum foil.

Further, the film materials used for the first substrate 1 and the second substrate 2 are both elastic materials. Since the first substrate 1 is made of a thin and elastic material, the substrate can be hot-pressed from the side of the second substrate 2 by the hot-pressing member 3, and the first substrate 1 can also be hot-pressed from the side of the first substrate 1, so that the film is deformed and heat-sealed, and different reaction units 11 are physically isolated.

In the microfluidic chip provided by the sixth embodiment, for a thicker substrate, the concave structure 17 may be disposed at the deformation portion of the substrate, and the thickness of the deformation portion is smaller than that of the first base 1, so that the deformation portion becomes thinner, which is beneficial to hot-pressing the deformation portion, and hot-pressing deformation of the deformation portion is achieved. Specifically, when the first substrate 1 is thick, in order to facilitate hot pressing from the side where the first base 1 is located, the concave structure 17 is provided at the deformed portion of the first base 1 to thin the deformed portion so that the thickness of the deformed portion is smaller than that of the first base 1, as shown in fig. 16, so that the deformed portion is easily deformed by hot pressing to achieve heat sealing with the second substrate 2.

As shown in fig. 16, in addition to the fifth embodiment, a concave structure 17 is provided at the deformed portion of the first substrate 1. Of course, the above modifications can be made on the basis of other embodiments, and are not described herein again.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A microfluidic chip is characterized by comprising a base body, wherein the base body is provided with an injection hole (14), reaction units (11) and a flow path for communicating the injection hole (14) with the reaction units (11), the base body comprises a deformation part which can be deformed through hot pressing, the deformed deformation part heat-seals the flow path, and any two reaction units (11) are isolated by the deformed deformation part;

the base body is hot-pressed by a hot pressing member (3) to deform the deformation portion, and the hot pressing member (3) can be separated from the microfluidic chip; after the thermal pressing piece (3) is separated from the microfluidic chip, the deformation part is restored to the original state, and the flow path subjected to heat sealing can be restored to a conduction state.

2. The microfluidic chip according to claim 1, wherein the flow path comprises: a distribution channel (13) communicating with the injection hole (14), and an injection channel (12) communicating the distribution channel (13) with the reaction unit (11); wherein the injection flow paths (12) correspond to the reaction units (11) one to one.

3. The microfluidic chip according to claim 2, wherein when the substrate rotates, the direction of the centrifugal force at the injection flow path (12) is parallel to the axial direction of the injection flow path (12), or the angle between the direction of the centrifugal force at the injection flow path (12) and the axial direction of the injection flow path (12) is not more than 80 degrees.

4. The microfluidic chip according to claim 2, wherein the distribution flow path (13) comprises: a first distribution section (131) communicating with the injection hole (14), a second distribution section (132) communicating with the injection flow path (12), and a third distribution section (133) communicating two adjacent second distribution sections (132); wherein the second distribution segments (132) correspond one-to-one to the reaction units (11).

5. Microfluidic chip according to claim 4, wherein the second distribution segment (132) projects towards the injection flow path (12) and the third distribution segment (133) projects away from the injection flow path (12); the second distribution section (132) is arc-shaped or V-shaped, and the third distribution section (133) is arc-shaped or V-shaped.

6. Microfluidic chip according to claim 4, wherein the second distribution segment (132) and the third distribution segment (133) form a main distribution segment;

the main distribution sections are distributed along an arc line or a circle, the injection flow path (12) extends along the radial direction of the main distribution section where the injection flow path is located, and the reaction unit (11) is located on the periphery of the main distribution section where the reaction unit is located;

or the main distribution sections are distributed along a straight line, the straight line is perpendicular to the axial direction of the injection flow path (12), and the reaction unit (11) is positioned on one side of the main distribution section where the reaction unit is positioned.

7. The microfluidic chip according to claim 2, wherein the injection flow path (12) passes through the deformation portion, and the deformation portion is deformed by heat pressing and then heat-seals the injection flow path (12);

alternatively, the distribution channel (13) includes: a distribution flow path segment which communicates with two adjacent injection flow paths (12), passes through the deformation portion, and is heat-sealed after the deformation portion is heat-press deformed.

8. The microfluidic chip according to claim 1, wherein the flow path segment of the flow path heat-sealed by the deformation portion has an arc-shaped inner wall, and the protruding direction of the arc-shaped inner wall is opposite to the hot pressing direction of the substrate.

9. The microfluidic chip according to claim 1, wherein the substrate comprises at least two layers of substrates hermetically connected, at least one layer of the substrates is an elastic substrate, and/or at least one layer of the substrates is a light-transmissive substrate.

10. Microfluidic chip according to any of claims 1 to 9, wherein the matrix comprises a first substrate (1) and a second substrate (2) hermetically connected; the injection hole (14) is arranged on the first substrate (1) or the second substrate (2), the reaction unit (11) is arranged on the first substrate (1) or the second substrate (2), and the thickness of the first substrate (1) is larger than that of the second substrate (2); the flow path is provided on the first substrate (1), or the flow path is provided on the first substrate (1) and the second substrate (2); the first substrate (1) is provided with a concave structure (17) at the deformation part.

11. A microfluidic device comprising a microfluidic chip, wherein the microfluidic chip is as claimed in any one of claims 1-10; the microfluidic device further includes a heat pressing member (3) for heat pressing the base body to deform the deformation portion.

12. The microfluidic device according to claim 11, wherein the hot press (3) has hot press protrusions (31) for hot pressing the substrate.

13. The microfluidic device according to claim 12, wherein the thermocompression bump (31) is annular; or the hot-pressing bulges (31) are blocky, and at least two hot-pressing bulges (31) are provided.

14. The microfluidic device according to claim 12, wherein the hot-pressing end surface of the hot-pressing protrusion (31) is curved and protrudes away from the connecting end of the hot-pressing protrusion (31); or the hot-pressing end surface of the hot-pressing bulge (31) is a plane.