CN108816301A - Micro-fluidic chip and its packaging method, micro-fluidic chip encapsulation encapsulation accessory - Google Patents

Abstract

The invention discloses a microfluidic chip, a packaging method thereof, and packaging accessories for microfluidic chip packaging. The microfluidic chip is used for high-throughput analysis. The microfluidic chip includes: a chip body, and a chip body Rib on the back of the body. The ribs include edge ribs and/or inner ribs, wherein the edge ribs are annular and arranged along the edge of the chip body, and the edge of the chip body surrounds the inner ribs. The above-mentioned microfluidic chip strengthens the strength of the entire microfluidic chip by providing reinforcing ribs on the back of the chip body. When the chip body is packaged, there is stress to bend toward the front, and the ribs can resist the force of the chip body bending deformation, reducing The bending deformation of the chip body during packaging is reduced, and the flatness of the chip body after packaging is improved, that is, the flatness of the entire microfluidic chip is improved, especially for a microfluidic chip with a larger area, it is a microfluidic The chip can be adapted to the supporting instrument of the multi-well plate to provide the premise.

Description

Microfluidic chip and its packaging method, packaging accessories for microfluidic chip packaging

technical field

The invention relates to the field of microfluidic technology, and more specifically, to a microfluidic chip, a packaging method thereof, and a packaging accessory for microfluidic chip packaging.

Background technique

At present, in the field of high-throughput analysis, such as cell culture, immune ELISA reaction, nucleic acid amplification, etc., widely used reaction carriers or consumables are multi-well plates, such as 96-well plates and 384-well plates. There are a series of supporting instruments around the multi-well plate, such as a well-plate centrifuge, a row gun pipette, a PCR instrument, a microplate reader, etc. The cooperation of these instruments and multi-well plates has played an important role in the field of high-throughput analysis. However, the current automatic liquid operation of multi-well plates still requires large-scale instruments such as liquid transfer workstations to operate. convenient.

Microfluidic technology is a technology that controls fluids to complete various biological and chemical reactions through micropipes and microstructures with the assistance of external hardware. It has advantages in high-throughput and low reagent consumption analysis. In addition, microfluidic technology has advantages in fluid manipulation, so it is expected to solve the shortcomings of existing high-throughput analysis based on multi-well plates. However, while using the microfluidic chip to solve the shortcomings of the existing multi-well plate, it also encounters some difficulties. For example, how microfluidic chips are compatible with existing multi-well plate-based high-throughput analytical instruments. Users are accustomed to adding samples with a gun pipette, and using PCR instruments, microplate readers, etc. for biological reactions and detection. If the microfluidic chip cannot be adapted to these devices, it may be necessary to purchase special equipment for the microfluidic chip and be familiar with the relevant usage skills, which will increase the cost and inconvenience the use.

Therefore, how to design and process a microfluidic chip that is compatible with existing multi-well plate supporting instruments and used for high-throughput analysis has become an important requirement. However, microfluidic chips generally need to be thinner in order to conduct heat and optical detection well and consume less reagents. Since the area of the porous plate is larger, the microfluidic chip must have a larger area to fit it.

During packaging, the front of the microfluidic chip will be heated. Since the microfluidic chip is usually a polymer, the polymer will shrink after being heated and then cooled, causing the microfluidic chip to bend towards the front. As a result, the flatness of the microfluidic chip after packaging is poor, which affects the packaging quality. The larger the area of the microfluidic chip, the greater the impact of packaging on the flatness of the microfluidic chip. Therefore, how to improve the flatness of a large-area microfluidic chip to provide a prerequisite for the microfluidic chip to be compatible with the supporting instruments of the multi-well plate is an important problem that needs to be solved.

Contents of the invention

The purpose of the present invention is to provide a microfluidic chip for high-throughput analysis to improve the flatness of the microfluidic chip, thereby providing a premise for the microfluidic chip to be adapted to the supporting equipment of the porous plate. Another object of the present invention is to provide a packaging accessory for packaging a microfluidic chip and a packaging method for a microfluidic chip.

In order to achieve the above object, the present invention provides the following technical solutions:

A microfluidic chip for high-throughput analysis, comprising: a chip body, and ribs arranged on the back of the chip body.

Preferably, the ribs include edge ribs and/or inner ribs, wherein the edge ribs are ring-shaped and arranged along the edge of the chip body, and the edge of the chip body surrounds the inner ribs.

Preferably, when the ribs include internal ribs, there is no overlap between the reaction wells of the microfluidic chip and the projection of the internal ribs on the front surface of the chip body.

Preferably, when the ribs include edge ribs and inner ribs, the height of the edge ribs is higher than that of the inner ribs.

Preferably, the height of the internal reinforcing rib is 1mm-3mm, and the width of the internal reinforcing rib is 0.5mm-2mm.

Preferably, the reinforcing ribs include internal reinforcing ribs, and the internal reinforcing ribs include first internal reinforcing ribs and second internal reinforcing ribs arranged crosswise.

Preferably, the reinforcing ribs include internal reinforcing ribs, and the internal reinforcing ribs are strip-shaped and arranged along the length direction or width direction of the chip body.

Preferably, the ribs include edge ribs, the back of the chip body is provided with a protrusion, and the protrusions are flush with the edge ribs, the front of the chip body is provided with a sample hole, and the The sample injection holes are distributed on the protrusions.

Preferably, the front surface of the chip body is provided with a groove and a main channel, the groove is sunk in the protrusion, and the end of the main channel communicating with the sample injection hole is located in the groove.

Preferably, the main flow path includes: a first distribution section communicated with the sample injection hole, a second distribution section communicated with the reaction well through a connecting flow path, and communicated with the first distribution section and the second A third distribution section of the distribution sections; wherein the cross-sectional area of the first distribution section is greater than the cross-sectional area of the third distribution section.

Preferably, the microfluidic chip is provided with a positioning structure for the positioning of an instrument matched with the porous plate.

Preferably, the spacing between the sample loading holes of the microfluidic chip is 4.5±0.2mm, or the spacing between the sample loading holes is 9±0.2mm;

The microfluidic chip is rectangular, and the reaction holes of the microfluidic chip are distributed in the form of a matrix;

The reaction wells are equally spaced in the form of 16×24, the row spacing of the reaction wells is 4.3mm-4.7mm, and the column spacing of the reaction wells is 4.3mm-4.7mm;

Or, the reaction wells are equally spaced in the form of 8×12, the row spacing of the reaction wells is 8.8mm-9.2mm, and the column spacing of the reaction wells is 8.8mm-9.2mm;

Or, the reaction wells are equally spaced in the form of 8×24, the row spacing of the reaction wells is 8.8mm-9.2mm, and the column spacing of the reaction wells is 4.3mm-4.7mm;

Or, the reaction wells are equally spaced in the form of 16×12, the row spacing of the reaction wells is 4.3mm-4.7mm, and the column spacing of the reaction wells is 8.8mm-9.2mm.

Preferably, the microfluidic chip further includes an exhaust structure disposed on the chip body, and the exhaust structure includes: an exhaust channel, and an exhaust hole communicating with the exhaust channel.

Preferably, the inlet section of the sample injection hole of the microfluidic chip is a gradually expanding section, and the inlet section gradually expands from the bottom end of the sample injection hole to the inlet end of the sample injection hole.

The microfluidic chip provided by the present invention strengthens the structural strength of the entire microfluidic chip by arranging reinforcing ribs on the back of the chip body. When the microfluidic chip is packaged, the chip body has the stress of bending toward the front, and the ribs can Resist the force of the bending deformation of the chip body, reduce the bending deformation of the chip body during packaging, and effectively improve the flatness of the chip body after packaging, that is, improve the flatness of the entire microfluidic chip, especially if the area is large The microfluidic chip provides a prerequisite for the microfluidic chip to be adapted to the multi-well plate supporting equipment.

Based on the microfluidic chip provided above, an embodiment of the present invention also provides a packaging accessory for microfluidic chip packaging, the packaging accessory for microfluidic chip packaging includes a support body that is an elastic member, and the support body is provided with A supporting structure capable of being fully attached to the back of the chip body, the supporting structure comprising: a matching structure capable of matching with the reinforcing rib.

Preferably, the ribs include edge ribs, the edge ribs are ring-shaped and arranged along the edge of the chip body; the back of the chip body is provided with a protrusion, and the protrusions and the edge ribs flush, the front of the chip body is provided with sample holes, and the sample holes are distributed on the protrusions;

The matching structure includes: a relief groove cooperating with the internal reinforcing rib, a first step structure cooperating with the edge reinforcing rib, and a second step structure cooperating with the protrusion.

Preferably, the support body includes a connected first support split body and a second support split body, and the relief groove and the first step structure are arranged on the first support split body;

The top surface of the second support split body is lower than the top surface of the first support split body, and the second support split body and the first support split body cooperate to form the second stepped structure;

Wherein, there is a gap between the first supporting body and the second supporting body.

Based on the microfluidic chip and the packaging accessories for microfluidic chip packaging provided above, the present invention also provides a packaging method for the microfluidic chip. The packaging method for the microfluidic chip includes the steps of:

Processing the first substrate and the second substrate, the front of the first substrate is provided with reaction holes, and the back of the first substrate is provided with reinforcing ribs;

Adding materials required for the reaction into the reaction well;

placing the first substrate on the packaging component, and bonding the back of the first substrate to the packaging component;

placing a second substrate on the front side of the first substrate, encapsulating the first substrate and the second substrate;

Wherein, the packaging accessory is the packaging accessory for microfluidic chip packaging described in any one of the above, and both the first base and the second base are elastic members.

Description of drawings

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 that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only It is an embodiment of the present invention, and those skilled in the art can also obtain other drawings according to the provided drawings without creative work.

Figure 1 is a schematic diagram of the back of the microfluidic chip provided by the embodiment of the present invention;

FIG. 2 is a schematic front view of the microfluidic chip in FIG. 1;

Figure 3 is a partially enlarged view of Figure 2;

Fig. 4 is a partial enlarged view of the flow path in the microfluidic chip provided by the embodiment of the present invention;

5 is a partial view of a perspective view of a microfluidic chip provided by an embodiment of the present invention;

Fig. 6 is a schematic diagram of sample loading in the microfluidic chip provided by the embodiment of the present invention;

Fig. 7 is a schematic structural diagram of a packaging accessory for microfluidic chip packaging provided by an embodiment of the present invention.

Detailed ways

The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some, not all, embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

The microfluidic chip provided by the embodiment of the present invention is used for high-throughput analysis, and the microfluidic chip includes a chip body.

In order to maintain good thermal conductivity and good optical transparency of the microfluidic chip, the thickness of the chip body is set to be thin, and the thickness of the chip body is preferably selected to be 0.5mm-3mm. In order to improve the flatness of a large-area microfluidic chip after packaging, in the microfluidic chip provided by the present invention, a reinforcing rib is provided on the back of the chip body, as shown in FIG. 1 .

It should be noted that the back of the chip body refers to the part of the chip body on the same side as the sample injection end of the sample injection hole 7 . The back of the chip body refers to the surface of the chip body on the same side as the sample loading end of the sample injection hole 7; the front of the chip body is opposite to the back of the chip body.

For the above microfluidic chip, the structural strength of the entire microfluidic chip is enhanced by providing reinforcing ribs on the back of the chip body. When packaged by thermocompression sealing, laser welding, ultrasonic welding and other packaging methods, the chip body made of high molecular polymer will shrink after being heated and then cooled, causing the chip body to have the stress of bending toward the front, and the ribs can resist the chip. The bending deformation of the main body reduces the bending deformation of the chip body during packaging, effectively improves the flatness of the chip body after packaging, that is, improves the flatness of the entire microfluidic chip, especially the microfluidic chip with a large area. The fluidic chip provides the premise for the microfluidic chip to be adapted to the multi-well plate supporting instrument.

It can be understood that the supporting equipment for the multi-well plate includes sample loading equipment such as a row gun, and reaction detection equipment such as a PCR instrument and a microplate reader. The specific type of the supporting instrument for the porous plate is selected according to actual needs, which is not limited in the embodiment of the present invention.

For the location, shape and number of ribs, design according to actual needs. Preferably, the above-mentioned reinforcing ribs include edge reinforcing ribs 4 , which are ring-shaped and arranged along the edge of the chip body.

In a practical application process, the above-mentioned reinforcing ribs can also be selected to include internal reinforcing ribs, and the edge of the above-mentioned chip body surrounds the internal reinforcing ribs. When the ribs include edge ribs 4 , the edge ribs 4 are located on the periphery of the inner ribs, that is, the inner ribs are located inside the edge ribs 4 .

When the above-mentioned reinforcing ribs include internal reinforcing ribs, the projection of the reaction well 11 of the above-mentioned microfluidic chip and the projection of the internal reinforcing ribs on the front of the chip body has no overlap, effectively avoiding the impact of the presence of internal reinforcing ribs on the reaction well 11. Heat transfer and optical detection are adversely affected.

Of course, on the premise of ensuring the heat transfer of the reaction well 11 and normal optical detection, the projection of the reaction well 11 and the internal rib on the front surface of the chip body may also choose to have an overlapping portion, and the overlapping portion should be as small as possible.

When the above-mentioned internal ribs ensure the flatness of the plane of the microfluidic chip, the shrinkage of the microfluidic chip at the internal ribs during injection molding should be avoided as much as possible. In order to achieve the above purpose, the inner reinforcement is chosen as a narrower and taller structure. Preferably, the height of the internal reinforcing rib is 1mm-3mm, and the width of the internal reinforcing rib is 0.5mm-2mm.

The specific structure of the internal reinforcing ribs is also designed according to actual needs. For example, in order to effectively improve the strength, the internal reinforcing ribs include first internal reinforcing ribs 5 and second internal reinforcing ribs 6 arranged crosswise. The first internal reinforcing rib 5 may be one, or more than two; the second internal reinforcing rib 6 may be one, or more than two.

The above-mentioned internal reinforcing ribs are strip-shaped. Further, the above-mentioned internal reinforcing ribs are arranged along the length direction or the width direction of the chip body. At this time, if the internal reinforcing ribs include the first internal reinforcing ribs 5 and the second internal reinforcing ribs 6 arranged crosswise, the first internal reinforcing ribs 5 are preferably arranged along the length direction of the chip body, and the second internal reinforcing ribs 6 are arranged along the length direction of the chip body. The width direction setting of the main body. It can be understood that, at this time, the chip body is rectangular.

Certainly, the above-mentioned internal reinforcing ribs may also be selected to be in other shapes and arranged along other directions, and are not limited to the above-mentioned embodiments.

When the above-mentioned ribs include edge ribs 4, the edge ribs 4 can be directly used for the clamping of the microfluidic chip, so the height of the edge ribs 4 is selected to be higher, preferably the height of the edge ribs 4 is 4mm-8mm . Further, when the above-mentioned reinforcing ribs include edge reinforcing ribs 4 and internal reinforcing ribs, the height of the edge reinforcing ribs 4 is higher than that of the internal reinforcing ribs.

When the above-mentioned reinforcing ribs include edge reinforcing ribs 4, the back of the above-mentioned chip body is provided with a protrusion 8, and the protrusion 8 is flush with the edge reinforcing ribs 4, and the chip body is provided with a sampling hole 7, and the sampling holes 7 are distributed on the protrusion. 8, as shown in Figure 1. In this way, the supporting surface on the back of the chip body is enlarged, which is convenient for placing the microfluidic chip.

In order to further optimize the above technical solution, as shown in Figure 2 and Figure 3, the front of the above-mentioned chip body is provided with a groove 14 and a main channel 13, the groove 14 is sunk in the protrusion 8, and the main channel 13 communicates with the sample injection hole 7 One end is located in the groove 14; the positive end surface of the sample injection hole 7 is flush with the front surface of the chip body.

It can be understood that the positive end surface of the sample loading hole 7 refers to the end surface of the sample loading hole 7 on the same side as the front surface of the chip body. The positive end surface of the main channel 13 is also flush with the front surface of the chip body. The positive end surface of the main channel 13 refers to the end surface of the main channel 13 on the same side as the front surface of the chip body.

The above structure is beneficial to the flatness and packaging of the microfluidic chip from three aspects:

1) Avoid the unevenness of the surface of the chip body during injection molding due to the solid structure of the protrusion 8, which is not conducive to the packaging of the microfluidic chip;

2) The front area of the chip body at the groove is reduced, because the larger the plane, the more difficult it is to realize the sealing without trapping air bubbles, so that it is easy to seal and thus easy to package;

3) The groove 14 makes only the area close to the sample injection hole 7 and the area where the main flow channel 13 communicates with the sample injection hole 7 in the plane of the front of the chip body, and the chip body is only close to the main flow channel during heat sealing or welding. 13 and the area near the sample injection hole 7 are in contact with the heat source, which is conducive to more reliable heat sealing or welding of these areas. Especially this place is located on the edge of the chip body. Compared with the central area of the chip, the heat dissipation is faster. The existence of the groove 14 will make the sample hole 7, the area of the part where the main channel 13 communicates with the sample hole 7 and the periphery of the chip body Isolation by air can effectively reduce the difference in package effects of different chip bodies caused by surrounding heat dissipation.

The above-mentioned groove 14 may be one, or more than two. In order to simplify the production, the above-mentioned groove 14 is one and is in the shape of a strip.

As shown in FIG. 3 and FIG. 4 , in the above-mentioned microfluidic chip, the main channel 13 communicates with the sample injection hole 7 and the reaction hole 11 . The above-mentioned main channel 13 includes: a first distribution section 131 communicated with the sample injection hole 7, a second distribution section 132 communicated with the reaction hole 11 through the connecting flow channel 12, and a second distribution section 132 communicated with the first distribution section 131 and the second distribution section 132. Three allocation segments 133 . It should be noted that, the second distribution section 132 corresponds to the reaction holes 11 one by one.

Preferably, the cross-sectional area of the first distribution section 131 is larger than the cross-sectional area of the third distribution section 133 . This structure brings two advantages:

1) The first distribution section 131 is directly connected to the sample injection hole 7, and the sample injection hole 7 is located inside the protrusion 8, then the first distribution section 131 will cross the edge of the protrusion 8, as shown in Figure 3, after heat sealing Or during ultrasonic welding, the edge portion of the protrusion 8 is under a greater force due to the direct support of the thicker edge of the protrusion 8, resulting in a larger deformation of the chip body when it is heated and deformed. If the first distribution section 131 is relatively large The rules may be directly deformed and blocked. Therefore, the thicker first distribution section 131 can avoid this problem;

2) The first distribution section 131 is directly connected to the sample injection port 7, and its larger cross-section brings a larger storage volume, and the liquid or air contained there does not participate in the subsequent distribution to the reaction well 11, so the The liquid or air contained in it can act as a buffer, which can reduce the requirements on the accuracy of the sample volume and the method of sample addition.

The above-mentioned connecting flow path 12 will partially or completely block the connecting flow path 12 after being heat-sealed and deformed. In order to facilitate its blockage, the above-mentioned connecting flow path 12 has a smaller aspect ratio. The ratio is 0.01-0.50.

In order to facilitate the matching of the microfluidic chip with the supporting instruments of the porous plate, the microfluidic chip is provided with a positioning structure 3 for positioning with the supporting instruments of the porous plate. It can be understood that the above-mentioned perforated plate matching instrument or accessories adapted to the perforated plate supporting instrument also have a structure for positioning and cooperating with the positioning structure 3 to ensure positioning.

It should be noted that the above positioning structure 3 can also be used to correct the deformation of the microfluidic chip.

The above-mentioned positioning structure 3 may be a positioning hole, a positioning column, a positioning groove, and the like. If the positioning structure 3 is a positioning column, then when the chip body is heat-sealed with a film, the film used for heat sealing needs to get out of the positioning column, which requires the structure and positioning of the film. In order to facilitate the packaging of the chip body, the above-mentioned positioning structure 3 is preferably selected as the positioning hole. At this time, the chip body has no protrusions, that is, no protrusions block the film, and the film can be directly pasted and heat-sealed.

The number of positioning structures 3 is selected according to actual needs. In order to improve the positioning effect, it is preferable to select at least two positioning structures 3 above. Further, there are four positioning structures 3, two positioning structures 3 are located at one end of the microfluidic chip, and the other two positioning structures 3 are located at the other end of the microfluidic chip.

Preferably, the distance between the sample injection holes 7 is 4.5±0.2mm or 9±0.2mm. In this way, it is convenient for the microfluidic chip to be matched with the commonly used row gun and pipette for the porous plate, thereby facilitating the operation of the microfluidic chip.

In order to facilitate the matching of the microfluidic chip with the supporting instruments of the porous plate, the above-mentioned microfluidic chip is rectangular, and the reaction wells 11 of the microfluidic chip are distributed in the form of a matrix. It can be understood that the reaction wells 11 are distributed on the chip body. The above-mentioned microfluidic chip is in the shape of a rectangle, and rounded or chamfered structures can be arranged at the top corners of the microfluidic chip.

The length and width of the aforementioned microfluidic chip are selected according to the size of the actual porous plate. For example, the microfluidic chip is about 127.76mm long and 85.48mm wide, which is the same as a standard 96 or 384-well plate. This embodiment of the present invention makes no additional limitation.

The reaction wells 11 of the above-mentioned microfluidic chip are distributed in the same way as the reaction wells on the porous plate, so as to ensure matching with the supporting instruments of the porous plate.

For example, the distribution of the reaction wells 11 of the above-mentioned microfluidic chip is consistent with that of the 96-well plate, or the distribution of the reaction wells 11 of the above-mentioned microfluidic chip is consistent with that of the 384-well plate. Specifically, the reaction wells 11 are equally spaced in the form of 16×24, the row spacing of the reaction wells 11 is 4.3mm-4.7mm, and the column spacing of the reaction wells 11 is 4.3mm-4.7mm; or, the reaction wells 11 are arranged at 8×24 12 are equally spaced, the row spacing of the reaction wells 11 is 8.8mm-9.2mm, and the column spacing of the reaction wells 11 is 8.8mm-9.2mm; or, the reaction wells 11 are equally spaced in the form of 8×24, and the reaction wells The row spacing of 11 is 8.8mm-9.2mm, and the column spacing of reaction wells 11 is 4.3mm-4.7mm; or, the reaction wells 11 are equally spaced in the form of 16×12, and the row spacing of reaction wells 11 is 4.3mm-4.7mm mm, the column spacing of the reaction wells 11 is 8.8mm-9.2mm.

The size of the above reaction wells 11 is adapted to the supporting instruments of standard 96-well plate or 384-well plate, such as real-time fluorescent PCR instrument or microplate reader.

Of course, the distribution of the reaction wells 11 at other distances can also be selected, as long as the distribution of the reaction wells 11 of the microfluidic chip is consistent with the distribution of the reaction wells on the porous plate.

When the chip body is in the packaging process, due to the larger area of the chip body, air bubbles are more likely to be generated. In order to discharge air bubbles or avoid generation of air bubbles, the above-mentioned microfluidic chip further includes an exhaust structure 2, as shown in FIG. 2 , the exhaust structure 2 includes: an exhaust channel, and an exhaust hole communicating with the exhaust channel. It can be understood that the exhaust hole runs through the chip body to ensure exhaust.

Preferably, the above-mentioned exhaust channel is arranged on the edge of the chip body; there are multiple exhaust holes, which are evenly distributed in the exhaust channel.

Further, the above-mentioned chip body has a rectangular shape, and there are two exhaust channels, one exhaust channel is arranged along the width direction of the chip body, and the other exhaust channel is arranged along the length direction of the chip body.

Certainly, the exhaust structure 2 may also be designed in other shapes and structures, and is not limited thereto.

As shown in FIG. 5 and FIG. 6 , the inlet section of the sampling hole 7 of the above-mentioned microfluidic chip is a gradually expanding section, and the inlet section gradually expands from the bottom end of the sampling hole 7 to the sampling end of the sampling hole 7 .

With the structure of the above-mentioned sample hole 7, when the pipette tip is inserted into the sample hole 7, the bottom of the inlet section of the sample hole 7 can block the pipette tip, and can ensure that the end of the pipette tip does not touch the first The two bases realize the close contact between the pipette tip and the sample hole 7, ensuring that the liquid will not leak during the sample addition; at the same time, the inlet section of the sample hole 7 is convenient for the insertion and positioning of the pipette tip, and can also accommodate A small amount of liquid spilled when the pipette tip is pulled out after the injection is completed, thereby avoiding contamination of the sample.

The above-mentioned chip main body includes: a first substrate 1 and a second substrate that are packaged and connected. Specifically, the second base body is covered on the first base body 1 and sealed with the first base body 1 . It should be noted that the second substrate is not shown in the figure. Of course, the above-mentioned chip body can also be selected to be composed of at least three layers of substrates, and is not limited to two layers of substrates, ie, the first substrate 1 and the second substrate. The reaction holes 11 and the flow paths connected to the reaction holes 11 are all set on the first base body 1 . The strength of the first base body 1 is relatively low, and it is preferable to choose reinforcing ribs to be set on the first base body 1 . For the specific position of the rib, choose according to actual needs. In order to prevent the ribs from affecting the reaction holes 11 and flow paths of the microfluidic chip, the ribs are preferably arranged on the back of the first base 1 , that is, the side of the first base 1 away from the second base.

Due to thermal compression sealing, laser welding, ultrasonic welding and other packaging methods, the front side of the first base 1 will be heated, and the high molecular polymer will shrink after being heated, which will cause the first base 1 to bend toward the front side. At the same time, the ribs on the back of the first base body 1 can just resist the bending and deformation of the first base body 1, thereby improving the flatness of the first base body 1 after packaging, and further improving the stability of the entire chip body after packaging. Flatness, that is, the flatness of the microfluidic chip is improved.

The above-mentioned chip body may be the above-mentioned first base body 1 , or the above-mentioned chip body may optionally include a connected first base body 1 and a second base body.

In the above-mentioned microfluidic chip, there are multiple reaction holes 11 and sample injection holes 7, the sample injection holes 7 are located at both ends of the main channel 13, and the connecting channel 12 and the reaction well 11 are located on the same surface of the first substrate 1, The sample injection hole 7 runs through the first base body 1 . The overall distribution of the main channels 13 is parallel to the distribution of the reaction holes 11 , and the connecting flow channels 12 correspond to the reaction holes 11 one by one. The main flow path 13 may be one, or two or more. The above-mentioned reaction hole 11 has a cavity to accommodate the liquid to be detected. The reaction hole 11 is opened on one side of the first substrate 1, and the reaction hole 11 is a blind hole.

In order to facilitate centrifugal distribution and improve distribution uniformity, the above-mentioned second distribution section 132 protrudes toward the connecting flow path 12 . Preferably, the second distribution section 132 is arc-shaped or V-shaped. Further, the second distributing section 132 is semicircular. It can be understood that rounded corners can be provided at the above-mentioned V-shaped sharp corners to facilitate centrifugal distribution. Of course, the second distribution section 132 can also be selected to have other shapes, and is not limited to the above-mentioned structure.

Further, in order to facilitate more uniform centrifugal distribution of samples, the cross-sectional area of the second distribution section 132 is larger than the cross-sectional area of the third distribution section 133 .

Based on the microfluidic chip provided in the above embodiments, the embodiment of the present invention also provides a packaging accessory for microfluidic chip packaging. As shown in Figure 7, the packaging accessory for microfluidic chip packaging includes a support for elastic parts body, the support body is provided with a support structure that can be fully attached to the back of the first base body 1 , and the support structure includes: a matching structure that can cooperate with the ribs on the back of the first base body 1 .

The support structure of the above-mentioned support body can be completely attached to the back of the first base body 1, thus realizing the support for the first base body 1; since the support body is an elastic member, the packaging accessories will be deformed after being combined with the first base body 1 under pressure. Being able to adapt to the structure and shape of the first base body 1 enables the first base body 1 to be better packaged even when there is a certain curvature and local unevenness.

If the above-mentioned ribs include edge ribs 4, the edge ribs 4 are annular and arranged along the edge of the chip body, the back of the chip body is provided with a protrusion 8, the protrusion 8 is flush with the edge rib 4, and the front of the chip body is provided with There are sample injection holes 7, and the sample injection holes 7 are distributed on the protrusion 8, then the above-mentioned matching structure includes: a relief groove 01 that cooperates with the internal reinforcement rib, a first step structure 02 that cooperates with the edge reinforcement rib 4, and The second stepped structure 03 that the protrusion 8 cooperates with.

In order to improve the elasticity of the support body, so as to ensure that the first base body 1 can be better packaged in the case of certain curvature and local unevenness, the above support body includes a first support split body 05 connected to a second support split body 06, The relief groove 01 and the first step structure 02 are arranged on the first support split body 05; the top surface of the second support split body 06 is lower than the top surface of the first support split body 05, and the second support split body 06 and the second support split body 06 A supporting split body 05 cooperates to form a second stepped structure 03 ; wherein, there is a gap 04 between the first supporting split body 05 and the second supporting split body 06 . The gap 04 is narrow and deep.

By setting the above-mentioned gap 04, the freedom of movement of the second stepped structure is increased, and the elasticity of the whole structure is improved, so that the whole structure can be better adapted to the first base body 1 .

The above-mentioned packaging accessories are preferably elastic plastic parts such as silicone parts and rubber parts, and the above-mentioned packaging accessories are made by machining or injection molding.

Because the packaging accessories are elastic plastic parts, and the thermal conductivity of elastic plastic parts is poor, in the packaging methods that will heat the microfluidic chip, such as thermocompression sealing, laser welding, and ultrasonic welding, the packaging accessories reduce the number of microfluidic chips. The amount of heat dissipation, thereby reducing the energy consumption during packaging, that is, reducing the degree of heating on the front of the microfluidic chip, thereby reducing the deformation of the front of the microfluidic chip caused by the above heating, which is conducive to ensuring that the microfluidic chip Flatness after encapsulation.

Based on the packaging accessories for microfluidic chip packaging provided in the above embodiments, the embodiment of the present invention also provides a packaging method for a microfluidic chip. The packaging method for a microfluidic chip includes the steps of:

1) Processing substrate:

Specifically, the first substrate 1 and the second substrate are processed, the first substrate 1 is provided with reaction holes 11 on the front, and the back of the first substrate 1 is provided with reinforcing ribs. Both the first base body 1 and the second base body are elastic parts. The material of the first base 1 is high molecular polymer. The high molecular polymer mentioned above is polymethyl methacrylate, polycarbonate, or polypropylene. The above-mentioned first base body 1 is formed by injection molding, laser engraving or mechanical processing. The second base is the same substrate as the first base 1 , or the second base is a heat-sealing film matching the first base 1 . For the convenience of detection, the above-mentioned first base body 1 and/or the second base body is a light-transmitting base body.

2) Spotting:

Add the materials required for the reaction into the reaction well 11. Add biological materials required for the reaction, such as primers, probes, enzymes, etc. The liquid volatilizes or lyophilizes and solidifies into the reaction well 11 to complete sample application. In addition, solidified biological materials, such as freeze-dried balls of biological reagents, can also be added to the reaction well 11 .

3) Package:

The first substrate 1 is placed on the packaging accessory, and the back of the first substrate 1 is bonded to the packaging accessory; the second substrate is placed on the front of the first substrate 1, and the first substrate 1 and the second substrate are packaged. The above-mentioned packaging accessories are the packaging accessories for microfluidic chip packaging described in the above-mentioned embodiments.

The above-mentioned first matrix 1 and the second matrix are elastic materials at room temperature, and can be deformed and elastic after being heated to a certain temperature, which is a characteristic of many polymers. The above-mentioned first base 1 and the second base can be packaged and bonded by existing technologies such as thermocompression sealing, laser welding, ultrasonic welding, or glue sealing, so as to realize hermetically sealed connection. For example, one of the above-mentioned first base 1 and the second base is a base with single-sided adhesive.

Since the first substrate 1 has a complex uneven structure, packaging accessories are used to assist packaging. The back side of the first substrate 1 faces the packaging component and is combined therewith. The above-mentioned packaging components enable the first substrate 1 to be better packaged even when there is a certain curvature and local unevenness.

The microfluidic chip packaging method provided by the embodiment of the present invention uses packaging accessories to package the first substrate 1 and the second substrate, so that the first substrate 1 can be better packaged even when there is a certain curvature and local unevenness. Encapsulation, it is convenient to realize high-efficiency non-leakage encapsulation, and improves the encapsulation effect.

In addition, because the packaging accessories are elastic plastic parts, and the thermal conductivity of elastic plastic parts is poor, in the packaging methods that will heat the microfluidic chip, such as thermocompression sealing, laser welding, and ultrasonic welding, the packaging accessories reduce the microfluidic flow rate. Control the heat dissipation of the chip, thereby reducing the energy consumption during packaging, that is, reducing the heating degree of the front of the microfluidic chip, thereby reducing the deformation of the front of the microfluidic chip caused by the above heating, which is conducive to ensuring the microfluidic Control the flatness of the chip after packaging.

The method for using the above-mentioned microfluidic chip includes steps:

1) Sample injection:

The sample to be detected is injected into the main channel 13 of the microfluidic chip through the sample injection hole 7 .

2) Seal the sample port:

After the sample injection is completed, the above-mentioned sample injection hole 7 can be sealed by means of heat sealing or glue.

3) Centrifuge to distribute the sample:

Place the microfluidic chip on the centrifuge device, centrifuge the main channel of the microfluidic chip toward the centrifugal center and the reaction well 11 is away from the centrifugal center, and the sample enters the reaction well 11 from the main channel 13 through the connecting channel 12 . During the above centrifugal distribution process, the direction of the centrifugal force at the connecting flow path 12 is parallel to the axial direction of the connecting flow path 12, or the angle between the direction of the centrifugal force at the connecting flow path 12 and the axial direction of the connecting flow path 12 is not greater than 80° Spend.

4) Isolate the reaction well:

For the microfluidic chip that has been distributed by centrifugation, it is placed on the supporting device of the microfluidic chip, and part or all of the flow path 12 is connected by heat and pressure, so that the chip is partially deformed and isolated, thereby achieving physical isolation of each reaction well 11 , effectively improving the isolation reliability, avoiding cross-contamination and environmental pollution by reaction products.

5) Reaction and detection:

After isolation, the chip is reacted and detected by an instrument matched with a conventional multi-well plate, such as a real-time fluorescent PCR instrument, a microplate reader, and the like.

The specific type of the instrument matched with the above-mentioned porous plate can be selected according to the actual needs, and the embodiment of the present invention does not limit the type of the matched instrument.

The above description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention will not 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 (19)

1. A microfluidic chip for high-throughput analysis, characterized in that it comprises: a chip body, and ribs arranged on the back of the chip body. 2. The microfluidic chip according to claim 1, characterized in that, the ribs include edge ribs (4) and/or internal ribs, wherein the edge ribs (4) are annular and extend along the The edge of the chip body is arranged, and the edge of the chip body surrounds the internal reinforcing rib. 3. The microfluidic chip according to claim 2, characterized in that, when the reinforcing ribs include internal reinforcing ribs, the reaction hole (11) of the microfluidic chip and the internal reinforcing ribs are in the The projection on the front side of the chip body has no overlap. 4. The microfluidic chip according to claim 2, characterized in that, the height of the internal reinforcing rib is 1mm-3mm, and the width of the internal reinforcing rib is 0.5mm-2mm. 5. The microfluidic chip according to claim 2, characterized in that, the reinforcing ribs comprise internal reinforcing ribs, and the internal reinforcing ribs comprise first internal reinforcing ribs (5) and second internal reinforcing ribs arranged crosswise (6). 6 . The microfluidic chip according to claim 2 , wherein the reinforcing ribs include internal reinforcing ribs, and the internal reinforcing ribs are strip-shaped and arranged along the length direction or width direction of the chip body. 7 . 7. The microfluidic chip according to claim 2, characterized in that, when the ribs include edge ribs (4) and internal ribs, the height of the edge ribs (4) is higher than the The height of the inner rib. 8. microfluidic chip according to claim 2, is characterized in that, described reinforcing rib comprises edge reinforcing rib (4), and the back of described chip body is provided with protrusion (8), and described protrusion (8 ) is flush with the edge ribs (4), the chip body is provided with sample holes (7), and the sample holes (7) are distributed on the protrusions (8). 9. The microfluidic chip according to claim 8, characterized in that, the front of the chip body is provided with a groove (14) and a main channel (13), and the groove (14) is sunk in the protrusion (8), one end of the main channel (13) communicating with the sample injection hole (7) is located in the groove; the positive end surface of the sample injection hole (7) is flush with the front surface of the chip together. 10. The microfluidic chip according to claim 9, characterized in that, the main flow path (13) comprises: a first distribution section (131) communicated with the sample injection hole (7), through the connection flow path (12) a second distribution section (132) communicating with the reaction hole (11), a third distribution section (133) communicating with the first distribution section (131) and the second distribution section (132); Wherein, the cross-sectional area of the first distribution section (131) is larger than the cross-sectional area of the third distribution section (133). 11 . The microfluidic chip according to claim 1 , characterized in that, the microfluidic chip is provided with a positioning structure ( 3 ) for locating an instrument matched with a porous plate. 12 . 12. The microfluidic chip according to claim 1, characterized in that, The distance between the sample holes (7) of the microfluidic chip is 4.5±0.2mm, or the distance between the sample holes (7) is 9±0.2mm; The microfluidic chip is rectangular, and the reaction holes (11) of the microfluidic chip are distributed in the form of a matrix; The reaction wells (11) are equally spaced in the form of 16×24, the row spacing of the reaction wells (11) is 4.3mm-4.7mm, and the column spacing of the reaction wells (11) is 4.3mm-4.7mm ; Or, the reaction wells (11) are equally spaced in the form of 8×12, the row spacing of the reaction wells (11) is 8.8mm-9.2mm, and the column spacing of the reaction wells (11) is 8.8mm-9.2mm. 9.2mm; Or, the reaction wells (11) are equally spaced in the form of 8×24, the row spacing of the reaction wells (11) is 8.8mm-9.2mm, and the column spacing of the reaction wells (11) is 4.3mm-9.2mm. 4.7mm; Or, the reaction wells (11) are equally spaced in the form of 16×12, the row spacing of the reaction wells (11) is 4.3mm-4.7mm, and the column spacing of the reaction wells (11) is 8.8mm-4.7mm. 9.2mm. 13. The microfluidic chip according to claim 1, further comprising an exhaust structure (2) arranged on the chip body, the exhaust structure (2) comprising: an exhaust channel, and The exhaust hole connected with the exhaust channel. 14. The microfluidic chip according to claim 1, characterized in that, the inlet section of the sample injection hole (7) of the microfluidic chip is a gradually expanding section, and the inlet section starts from the sample injection hole The bottom end of (7) expands gradually to the sample injection end of the sample injection hole (7). 15. The microfluidic chip according to any one of claims 1-14, characterized in that, the chip body comprises a packaged first base (1) and a second base connected together, the microfluidic chip The reaction hole (11) is arranged on the first base (1); the reinforcing rib is arranged on the back of the first base (1). 16. A packaging accessory for microfluidic chip packaging according to claim 15, characterized in that it includes a support body that is an elastic member, and the support body is provided with a back surface capable of connecting with the first substrate (1). A fully fitted support structure, the support structure includes: a matching structure capable of cooperating with the reinforcing rib. 17. The packaging accessory for microfluidic chip packaging according to claim 16, characterized in that, The reinforcing ribs include edge reinforcing ribs (4), which are annular and arranged along the edge of the chip body; the back of the chip body is provided with a protrusion (8), and the protrusion (8) flush with the edge ribs (4), the front of the chip body is provided with sample holes (7), and the sample holes (7) are distributed on the protrusions (8); The matching structure includes: a relief groove (01) cooperating with the internal reinforcing rib, a first step structure (02) cooperating with the edge reinforcing rib (4), cooperating with the protrusion (8) The second step structure of (03). 18. The packaging accessory for microfluidic chip packaging according to claim 17, characterized in that, The support body includes a first support split body (05) and a second support split body (06), the relief groove (01) and the first step structure (02) are arranged on the first support body split(05); The top surface of the second support split body (06) is lower than the top surface of the first support split body (05), and the second support split body (06) and the first support split body (05) ) cooperate to form the second stepped structure (03); Wherein, there is a gap (04) between the first supporting body (05) and the second supporting body (06). 19. A packaging method for a microfluidic chip, comprising the steps of: Processing the first substrate (1) and the second substrate, the front of the first substrate (1) is provided with a reaction hole (11), and the back of the first substrate (1) is provided with reinforcing ribs; Add the materials required for the reaction into the reaction hole (11); placing the first substrate (1) on the packaging component, the back of the first substrate (1) is bonded to the packaging component, placing the second substrate on the front of the first substrate (1), and packaging said first substrate (1) and said second substrate; Wherein, the packaging accessory is the packaging accessory for microfluidic chip packaging according to any one of claims 16-18, and both the first base (1) and the second base are elastic members.