CN113441194A

CN113441194A - Micro-fluidic detection chip

Info

Publication number: CN113441194A
Application number: CN202010223588.2A
Authority: CN
Inventors: 盛况; 关一民
Original assignee: Shanghai Industrial Utechnology Research Institute
Current assignee: Shanghai Industrial Utechnology Research Institute
Priority date: 2020-03-26
Filing date: 2020-03-26
Publication date: 2021-09-28

Abstract

The invention provides a micro-fluidic detection chip, which comprises a flow channel plate, a micro pump, a front cover layer, a back cover layer and a plurality of micro valves, wherein the front of the flow channel plate is provided with a detection cavity, a waste liquid cavity and a plurality of sample adding cavities, the back of the flow channel plate is provided with the micro pump cavities, the bottom of each sample adding cavity is provided with a liquid inlet hole which vertically penetrates through the flow channel plate, the micro pump is placed in the micro pump cavity, at least one section of the micro valve and the liquid inlet hole are complementary in shape, and when the micro valve is inserted into the liquid inlet hole, liquid in the sample adding cavity cannot flow to a flow channel on the back of the flow channel plate through the liquid inlet hole. The micro-fluidic detection chip provided by the invention has a stable and reliable micro-fluidic flow channel, is provided with the micro pump and the simple and easy operable micro valve, can conveniently realize the switching of a multi-channel liquid path, can conveniently control the volume of reagents such as a sample and the like flowing through a detection concave cavity through the coordination work of the micro valve and the micro pump, and can measure the concentration of a substance to be detected in the sample in a short time.

Description

Micro-fluidic detection chip

Technical Field

The invention belongs to the field of biochemical detection and microfluidic control, and relates to a microfluidic detection chip.

Background

Biochemical detection refers to the detection of a target solution by biological or chemical means. Microfluidic chip technology (also known as lab-on-a-chip) integrates basic operation units related to biological, chemical and medical fields, such as sample preparation, reaction, separation, detection, etc., into a chip having a micro-channel with micrometer dimensions, and automatically completes the whole process of reaction and analysis.

How to provide a micro valve structure capable of being simply operated to realize convenient switching among a plurality of liquid paths of a microfluidic detection chip becomes an important technical problem to be solved urgently by technical personnel in the field.

Disclosure of Invention

The invention aims to provide a microfluidic detection chip, which is used for solving the problem that the switching of multiple liquid paths of the microfluidic detection chip is inconvenient in the prior art.

To achieve the above and other related objects, the present invention provides a microfluidic detection chip, including:

the flow channel plate is provided with a detection cavity, a waste liquid cavity and a plurality of sample adding cavities on the front side, and the back side of the flow channel plate is provided with a micropump cavity, wherein the bottom of the sample adding cavity is provided with a liquid inlet hole which vertically penetrates through the flow channel plate, a flow channel connecting hole which vertically penetrates through the flow channel plate is arranged between the detection cavity and the sample adding cavity, the detection cavity is communicated with the flow channel connecting hole through a flow channel arranged on the front side of the flow channel plate, the flow channel connecting hole is communicated with the liquid inlet hole through a flow channel arranged on the back side of the flow channel plate, a waste liquid output hole and a waste liquid input hole which vertically penetrates through the flow channel plate are arranged on the bottom surface of the micropump cavity, the waste liquid output hole is communicated with the detection cavity, and the waste liquid input hole is communicated with the waste liquid cavity;

the micropump is placed in the micropump concave cavity, a fluid inlet and a fluid outlet are formed in the front face of the micropump, the fluid inlet is communicated with the waste liquid output hole, and the fluid outlet is communicated with the waste liquid input hole;

the front cover layer is positioned on the front surface of the runner plate and covers the detection concave cavity, the runner connecting hole, the waste liquid output hole, the waste liquid input hole and the runner on the front surface of the runner plate;

the back cover layer is positioned on the back of the runner plate and covers the liquid inlet hole, the runner connecting hole and the runner on the back of the runner plate;

and the micro valves and the liquid inlet holes have at least one section of complementary shape, and when the micro valves are inserted into the liquid inlet holes, liquid in the sample adding concave cavity cannot flow to the flow channel on the back of the flow channel plate through the liquid inlet holes.

Optionally, the liquid inlet hole and the micro valve are both provided with a section of inclined side wall which is inclined inwards from top to bottom, and when the micro valve is inserted into the liquid inlet hole, the inclined side wall of the liquid inlet hole is tightly attached to the inclined side wall of the micro valve.

Optionally, the cross sections of the liquid inlet hole and a section of the micro valve with the inclined side wall are both circular or both polygonal.

Optionally, the side wall of the liquid inlet hole is vertical, and the side wall of the part of the micro valve inserted into the liquid inlet hole is vertical.

Optionally, the cross section of the liquid inlet hole and the cross section of the part of the micro valve inserted into the liquid inlet hole are both circular or both polygonal.

Optionally, when the micro valve is inserted into the liquid inlet hole and the axes coincide, the distance between the outer wall of the micro valve and the inner wall of the liquid inlet hole is less than 0.02 mm.

Optionally, the material of the flow channel plate includes acrylic, and the material of the micro valve includes any one of acrylic and polydimethylsiloxane.

Optionally, the micropump comprises any one of a thermal bubble micropump, a syringe pump, a peristaltic pump, and a piezoelectric pump.

Optionally, the front cover layer comprises a pressure membrane and the back cover layer comprises a pressure membrane.

As described above, the microfluidic detection chip of the invention has a stable and reliable microfluidic flow channel, is provided with the micropump and the simple and operable micro valve, can conveniently realize the switching of a multi-channel liquid path, can conveniently control the volume of reagents such as a sample and the like flowing through the detection cavity through the coordination work of the micro valve and the micropump, and can quantitatively measure the concentration of a substance to be detected in the sample in a short time.

Drawings

Fig. 1 shows a top view of the flow field plate.

Fig. 2 is a bottom view of the runner plate.

Fig. 3 shows a schematic diagram of a silicon wafer for detecting signals.

Fig. 4 is a perspective view showing the construction of the micro pump.

Fig. 5 is a schematic structural diagram of the front cover layer.

Fig. 6 is a schematic structural view of the back cover layer.

Fig. 7 is a perspective view of the microvalve.

Fig. 8 shows the assembling and aligning manner of the microfluidic detection chip.

Fig. 9 is a schematic structural diagram of the microfluidic detection chip after being assembled.

Fig. 10 and 11 are two sectional views of the assembled microfluidic detection chip.

FIG. 12 is a sectional view of the flow field plate having the sample addition cavity and the liquid inlet hole.

FIG. 13 is a cross-sectional view of the microvalve positioned over but not inserted into the fluid inlet hole.

FIG. 14 is a cross-sectional view of the microvalve inserted in the fluid inlet hole.

Fig. 15 and 16 are schematic views showing that the side wall of the liquid inlet hole is vertical, and the side wall of the portion of the micro valve inserted into the liquid inlet hole is also vertical.

Description of the element reference numerals

1 flow passage plate

101 detecting a cavity

102 waste liquid cavity

103 sample loading cavity

104 micropump concave cavity

105 liquid inlet hole

106 flow passage connecting hole

107 flow passage

108 flow passage

109 waste liquid outlet

110 waste liquid input hole

111 flow passage

2 micropump

201 fluid inlet

202 fluid outlet

3 front face covering layer

301 opening

4 back side cover layer

5 micro valve

6 silicon wafer

Detailed Description

The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.

Please refer to fig. 1 to 16. It should be noted that the drawings provided in the present embodiment are only for illustrating the basic idea of the present invention, and the components related to the present invention are only shown in the drawings rather than drawn according to the number, shape and size of the components in actual implementation, and the type, quantity and proportion of the components in actual implementation may be changed freely, and the layout of the components may be more complicated.

Example one

The embodiment provides a microfluidic detection chip, which comprises a flow channel plate 1, a micro pump 2, a front cover layer 3, a back cover layer 4 and a plurality of micro valves 5.

Referring to fig. 1 and 2, fig. 1 is a top view of the flow channel plate 1, and fig. 2 is a bottom view of the flow channel plate 1. The front surface of the flow channel plate 1 is provided with a detection cavity 101, a waste liquid cavity 102 and a plurality of sample adding cavities 103, the back surface of the flow channel plate 1 is provided with a micro-pump cavity 104, wherein, the bottom of the sample adding cavity 103 is provided with a liquid inlet hole 105 which vertically penetrates through the runner plate 1, a flow channel connecting hole 106 which vertically penetrates through the flow channel plate 1 is arranged between the detection cavity 101 and the sample adding cavity 103, the detection cavity 101 is communicated with the flow channel connecting hole 106 through a flow channel 107 arranged on the front surface of the flow channel plate 1, the flow channel connecting hole 106 is communicated with the liquid inlet hole 105 through a flow channel 108 arranged on the back surface of the flow channel plate 1, the bottom surface of the micro-pump concave cavity 104 is provided with a waste liquid output hole 109 and a waste liquid input hole 110 which vertically penetrate through the runner plate 1, the waste output aperture 109 communicates with the detection cavity 101 and the waste input aperture 110 communicates with the waste cavity 102.

Specifically, the detection cavity 101 of the flow channel plate 1 can be used for detecting the concentration of the detected substance in the unknown solution, and for example, a silicon wafer 6 (shown in fig. 3) for detecting signals can be placed in the detection cavity 101 of the flow channel plate 1 to complete the required detection.

Illustratively, the waste liquid outlet 109 communicates with the detection cavity 101 through a flow channel 111 provided on the front surface of the flow channel plate 1. Each of the flow path connection holes 106 may be connected to the detection cavity 101 through an independent flow path, or may be connected to the detection cavity 101 through a flow path that is finally merged. FIG. 1 shows the case where each of the flow path connecting holes 106 is connected to the detection cavity 101 through the finally merged flow path 107

As an example, the material of the flow channel plate 1 includes, but is not limited to, acrylic.

By way of example, the flow field plates 1 have dimensions of 80mm by 60mm by 10mm, the sample application wells 103 have dimensions of 10mm by 3mm, the flow fields have a width of 1mm by 0.2mm, the waste wells 102 have dimensions of 15mm by 3mm, and the wafers 6 placed in the detection wells 101 have a size of 5.2mm by 0.5 mm.

It should be noted that, for different reaction systems, the number of the sample-adding cavities is not limited to 3, and the specific size of the flow channel plate, each cavity therein, and the flow channel can be adjusted according to the number of the sample-adding cavities and the volume of the solution to be detected, and the protection scope of the present invention should not be limited excessively herein.

Please refer to fig. 4, which is a perspective view of the micro pump 2. The micro pump 2 is disposed in the micro pump cavity 104 on the back of the flow channel plate 1 to drive fluid, the micro pump 2 is provided with a fluid inlet 201 and a fluid outlet 202 on the front, the fluid inlet 201 is communicated with the waste fluid output hole 109 of the flow channel plate 1 to receive waste fluid flowing out from the detection cavity 101, and the fluid outlet 202 is communicated with the waste fluid input hole 110 of the flow channel plate 1 to pump the waste fluid into the waste fluid cavity 102.

By way of example, the micro-pump 2 includes, but is not limited to, any one of a thermal bubble micro-pump, a syringe pump, a peristaltic pump, and a piezoelectric pump. In this embodiment, the micro pump 2 is exemplified by a thermal bubble micro pump, the fluid inlet and the fluid outlet of the thermal bubble micro pump have a size radius of 0.5mm, and the center distance between the two ports is 4.58 mm. In other embodiments, the size and distance of the fluid inlet and outlet can be adjusted according to the requirement, and the protection scope of the present invention should not be limited too much.

Referring to fig. 5, a schematic structural diagram of the front surface covering layer 3 is shown, where the front surface covering layer 3 is located on the front surface of the flow channel plate 1 and covers the detection cavity 101, the flow channel connection hole 106, the waste liquid output hole 109, the waste liquid input hole 110, and the flow channel on the front surface of the flow channel plate 1.

By way of example, the front cover layer 3 includes, but is not limited to, a pressure membrane.

As an example, the front cover layer 3 is a whole piece, and an opening 301 is provided at a position of the front cover layer 3 opposite to the waste liquid cavity 102 and the sample adding cavity 103.

In other embodiments, the front cover layer 3 may also be a plurality of pieces, for example, the portion covering the detection cavity 101 may be a single piece, so as to pre-assemble other portions of the microfluidic detection chip, and then place a silicon chip or other carrier for detecting signals into the detection cavity 101 at a specific time, which should not unduly limit the scope of the present invention.

Referring to fig. 6, a schematic structural diagram of the back cover layer 4 is shown, where the back cover layer 4 is located on the back of the channel plate 1 and covers the liquid inlet hole 105, the channel connecting hole 106 and the channel on the back of the channel plate 1.

By way of example, the backside cover layer 4 includes, but is not limited to, a pressure membrane.

As an example, the back cover layer 4 is a single piece.

Fig. 7 is a schematic perspective view of the micro valve 5. At least one section of the micro valve 5 and the liquid inlet hole 105 have complementary shapes, when the micro valve 5 is inserted into the liquid inlet hole 105, the liquid in the sample adding cavity 103 cannot flow to the flow channel on the back of the flow channel plate 1 through the liquid inlet hole 105, so that multi-channel liquid path switching can be realized. The operation of the microvalve 5 may be performed manually, or by a robotic arm, etc., and should not unduly limit the scope of the present invention.

As an example, the material of the micro valve 5 includes, but is not limited to, any one of acryl and Polydimethylsiloxane (PDMS).

Please refer to fig. 8, which shows the assembling and aligning manner of the microfluidic chip.

As an example, during the assembly of the microfluidic detection chip, the micro pump 2 may be first bonded into the micro pump cavity 104 by an AB adhesive or other adhesives (e.g., double-sided adhesive, thermal curing adhesive, UV adhesive, etc.) (where the fluid inlet 201 of the micro pump 2 is communicated with the waste fluid outlet 109 at the bottom of the micro pump cavity 104, and the fluid outlet 202 of the micro pump 2 is communicated with the waste fluid inlet 110 at the bottom of the micro pump cavity 104), and the antibody-modified silicon wafer 6 is placed into the detection cavity 101 (the silicon wafer may also be bonded to the bottom of the detection cavity by an adhesive), and then the pressure membranes (the front surface cover layer 3 and the back surface cover layer 4) are connected to the front surface and the back surface of the flow channel plate 1 by pressure extrusion.

Please refer to fig. 9, which is a schematic structural diagram of the assembled microfluidic detection chip, wherein one of the microvalves 5 is in a release state to open the corresponding liquid path, and the other microvalves are disposed in the corresponding liquid inlet holes to cut off the corresponding liquid path.

Referring to fig. 10 and 11, two cross-sectional views of the assembled microfluidic chip are shown.

Referring to fig. 12 to 14, fig. 12 is a cross-sectional view of a portion of the flow field plate 1 having the sample application cavity 103 and the liquid inlet hole 105, fig. 13 is a cross-sectional view of the micro valve 5 positioned above the liquid inlet hole 105 but not inserted into the liquid inlet hole 105, and fig. 14 is a cross-sectional view of the micro valve 5 inserted into the liquid inlet hole 105.

For example, the liquid inlet 105 and the micro valve 5 each have a section of inclined side wall that is inclined inward from top to bottom, that is, the contact portion between the liquid inlet 105 and the micro valve 5 is tapered, and when the micro valve 5 is inserted into the liquid inlet 105, the inclined side wall of the liquid inlet 105 is tightly attached to the inclined side wall of the micro valve 5.

For example, when the micro valve 5 is inserted into the liquid inlet hole 105, the bottom surface of the micro valve 5 may reach the plane of the bottom surface of the flow channel plate 1, or may not reach the plane of the bottom surface of the flow channel plate 1. As shown in fig. 14, it is more advantageous to press downward so that the micro valve 5 is in close contact with the side wall of the liquid inlet hole in the case where the bottom surface of the micro valve 5 does not reach the plane of the bottom surface of the flow channel plate 1 when the micro valve 5 is inserted into the liquid inlet hole 105.

As an example, the cross sections of the liquid inlet hole 105 and a section of the microvalve 5 having an inclined sidewall are both circular or polygonal, and correspondingly, the corresponding portion of the microvalve 5 is truncated cone-shaped or truncated pyramid-shaped.

Referring to fig. 15 and 16, in another embodiment, the sidewall of the liquid inlet 105 may be vertical, and the sidewall of the portion of the micro valve 5 inserted into the liquid inlet 105 is also vertical.

As an example, as shown in fig. 16, in the case that the side wall of the liquid inlet 105 is vertical, when the micro valve 5 is inserted into the liquid inlet 105 and the axes are coincident, the distance between the outer wall of the micro valve 5 and the inner wall of the liquid inlet 105 is less than 0.02mm, that is, the size of the micro valve 5 is slightly smaller than the size of the liquid inlet 105, so that the micro valve 5 can be placed into the liquid inlet 105, and at the same time, the effect of one micro valve can be achieved by means of the difference of the flow resistance at the liquid inlet 105.

It should be noted that fig. 16 shows a case where the bottom surface of the micro valve 5 is in contact with the back cover layer 4 when the micro valve 5 is inserted into the liquid inlet 105, and in other embodiments, the bottom surface of the micro valve 5 may not be in contact with the back cover layer 4 when the micro valve 5 is inserted into the liquid inlet 105.

As an example, the cross section of the liquid inlet hole 105 and the cross section of the portion of the micro valve 5 inserted into the liquid inlet hole 105 are both circular or polygonal, and correspondingly, the corresponding portion of the micro valve 5 is cylindrical or prismatic.

It should be noted that in other embodiments, the contour of the micro valve 5 and the liquid inlet 105 may have other shapes, and it is only necessary to satisfy the complementary shape so that the liquid path can be cut off when the micro valve 5 is inserted into the liquid inlet 105, and the protection scope of the present invention should not be limited too much here.

The microfluidic detection chip of the embodiment has a stable and reliable microfluidic flow channel, is provided with the micropump and the simple and operable micro valve, can conveniently realize the switching of a multi-channel liquid path, can conveniently control the volume of reagents such as a sample and the like flowing through the detection cavity through the coordination work of the micro valve and the micropump, and can measure the concentration of a substance to be detected in the sample in a short time.

Example two

In this embodiment, the microfluidic detection chip described in the first embodiment is used for detecting small molecule samples.

Referring to fig. 9 and 10, the microfluidic detection chip sequentially includes, from right to left, three liquid inlet cavities, three tapered microvalves for switching liquid paths, a flow channel, a reaction cavity in which a modified silicon-resistant wafer is placed, a heat bubble micropump, and a waste liquid cavity.

And respectively adding excessive tested samples, marked secondary antibodies and cleaning fluid into the three liquid inlet cavities. The first step is to plug the liquid inlet of the liquid inlet concave cavity containing the secondary antibody and the cleaning liquid by a conical acrylic micro valve, open the heat bubble micro pump until the calculated volume of the sample to be measured is passed, and close the heat bubble micro pump. And secondly, blocking a liquid inlet of a liquid inlet concave cavity containing the tested sample and the marked secondary antibody by using the same acrylic micro valve, opening the hot bubble micro pump, cleaning the redundant tested sample, and closing the hot bubble micro pump. And thirdly, continuously plugging a liquid inlet of a liquid inlet concave cavity containing the sample to be detected and the cleaning liquid by using an acrylic micro valve, opening the hot bubble micro pump until the calculated volume of the secondary antibody reagent is passed, and closing the hot bubble micro pump. The fourth step repeats the operation of the second step, the only difference being that this time the excess secondary antibody reagent is washed. And finally, in the fifth step, the reacted microfluidic detection chip is placed under an instrument special for reading fluorescence intensity to read fluorescence values, and each different fluorescence value corresponds to a corresponding sample concentration.

EXAMPLE III

In this embodiment, the microfluidic detection chip described in the first embodiment is used for sample detection by a sandwich enzyme-linked immunosorbent assay.

The required microfluidic detection chip in this embodiment is substantially the same as the microfluidic detection chip shown in fig. 9, except that the number of the required liquid inlet cavities is changed from three to four.

The specific detection process is as follows: and adding antigens, namely a sample reagent, an antibody B reagent matched with the primary antibody, a secondary antibody reagent and a cleaning solution into the four liquid inlet cavities respectively. According to the procedure of example two, the sample reagent, the wash solution, the antibody B reagent, the wash solution, the secondary antibody reagent, and the wash solution were sequentially added. And then placing the microfluidic detection chip under an instrument special for reading fluorescence intensity to read a fluorescence value, so as to obtain the corresponding sample concentration.

Example four

In this example, the microfluidic detection chip described in the first example was used to perform a chemiluminescent immunoassay sample detection.

The required microfluidic detection chip in this embodiment is substantially the same as the microfluidic detection chip shown in fig. 9, except that the number of the required liquid inlet cavities is changed from three to five.

The specific detection process is as follows: and adding antigens, namely a sample reagent, an antibody B reagent matched with the primary antibody, a secondary antibody reagent, a luminescent substrate reagent and a cleaning solution into the five liquid inlet cavities respectively. According to the operation of the second embodiment, the sample reagent, the cleaning solution, the antibody B reagent, the cleaning solution, the secondary antibody reagent, the cleaning solution, and the luminescent substrate reagent are sequentially subjected to standing reaction for a certain time. And then placing the microfluidic detection chip under an instrument special for reading fluorescence intensity to read a fluorescence value, so as to obtain the corresponding sample concentration.

In summary, the microfluidic detection chip of the present invention has a stable and reliable microfluidic channel, and is configured with a micro pump and a simple and easy operable micro valve, so as to conveniently realize switching of a multi-channel liquid path, conveniently control the volume of reagents such as a sample flowing through a detection cavity through the coordination operation of the micro valve and the micro pump, and quantitatively measure the concentration of a substance to be detected in the sample in a short time. Therefore, the invention effectively overcomes various defects in the prior art and has high industrial utilization value.

The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.

Claims

1. A microfluidic detection chip, comprising:

2. The microfluidic detection chip of claim 1, wherein: the liquid inlet hole and the micro valve are both provided with a section of inclined side wall which inclines inwards from top to bottom, and when the micro valve is inserted into the liquid inlet hole, the inclined side wall of the liquid inlet hole is clung to the inclined side wall of the micro valve.

3. The microfluidic detection chip of claim 2, wherein: the cross sections of the liquid inlet hole and the section of the micro valve with the inclined side wall are both circular or polygonal.

4. The microfluidic detection chip of claim 1, wherein: the side wall of the liquid inlet hole is vertical, and the side wall of the part of the micro valve inserted into the liquid inlet hole is vertical.

5. The microfluidic detection chip of claim 4, wherein: the cross section of the liquid inlet hole and the cross section of the part of the micro valve inserted into the liquid inlet hole are both circular or polygonal.

6. The microfluidic detection chip of claim 4, wherein: when the micro valve is inserted into the liquid inlet hole and the axes are coincident, the distance between the outer wall of the micro valve and the inner wall of the liquid inlet hole is less than 0.02 mm.

7. The microfluidic detection chip of claim 1, wherein: the material of flow field plate includes ya keli, the material of microvalve includes arbitrary one in ya keli and polydimethylsiloxane.

8. The microfluidic detection chip of claim 1, wherein: the micropump comprises any one of a thermal bubble micropump, a syringe pump, a peristaltic pump and a piezoelectric pump.

9. The microfluidic detection chip of claim 1, wherein: the front cover layer comprises a pressure film, and the back cover layer comprises a pressure film.