CN212284074U - Microfluid chip - Google Patents

Microfluid chip Download PDF

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Publication number
CN212284074U
CN212284074U CN202021209370.3U CN202021209370U CN212284074U CN 212284074 U CN212284074 U CN 212284074U CN 202021209370 U CN202021209370 U CN 202021209370U CN 212284074 U CN212284074 U CN 212284074U
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Prior art keywords
substrate
heat insulation
pcr reaction
microfluidic chip
liquid
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CN202021209370.3U
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Chinese (zh)
Inventor
刘琦
豆传国
胡立磊
胡春瑞
刘博�
陈昌
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Shanghai Sige Biotechnology Co ltd
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Shanghai Industrial Utechnology Research Institute
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Abstract

The utility model provides a microfluid chip, this microfluid chip include substrate, at least a set of microfluid structure and at least a set of heat-insulating groove structure, wherein, microfluid structure is arranged in the substrate to including liquid inlet, liquid input runner, PCR reaction chamber, liquid output runner and the liquid outlet that communicates in proper order, the substrate is run through from top to bottom to the heat-insulating groove structure, and wherein, a set of heat-insulating groove structure encloses into at least one accommodating area in the substrate, is equipped with at least a set of microfluid structure in an accommodating area. The utility model discloses a microfluid chip is equipped with the heat-proof tank structure, can realize rising fast and falling the temperature to shorten PCR reaction time greatly. The microfluid chip can realize high-precision integration, especially chip integration, through a silicon-based microfluid chip technology, thereby realizing portability and miniaturization of equipment, realizing large-scale mass production and being beneficial to reducing equipment cost. The microfluid chip of the utility model can be applied to the detection of nucleic acid substances in viruses, bacteria, cells and body fluid.

Description

Microfluid chip
Technical Field
The utility model belongs to the technical field of gene detection, a microfluid chip is related to.
Background
The new coronavirus COVID-19 outbreak at the end of 2019 has been diagnosed in more than 400 million infected people globally by 5 months in 2020, and more seriously, the number of infections is still rising and no obvious sign is yet reached in peak period, particularly in the United states. The reason for this serious consequence is that besides the susceptibility of new coronavirus, suspected infected person can not be detected and diagnosed in time, which results in the loss of optimal treatment opportunity and cross infection. If a rapid, convenient and low-cost detection method is implemented, new coronavirus screening is carried out on a human population, and particularly for asymptomatic infectors, centralized treatment and cold chain transportation and waiting during isolation are not needed during epidemic situation detection, so that the method is a means for effectively inhibiting virus infection diffusion. When the epidemic situation endangers the life and health of people, due to the reason of the epidemic situation, various countries implement measures for closing cities and even closing countries, and the economic development is seriously influenced, so that the detection method/equipment which is rapid, convenient and fast, has low cost and is easy to screen the crowd for virus infection is urgent.
There are three general approaches to virus detection: whole gene sequencing, nucleic acid detection and immune protein detection. For the epidemic situation, the CT technology also becomes a very important detection technology, but is expensive, inconvenient and not suitable for outdoor detection, such as customs and general clinics. In comparison, nucleic acid detection has significant advantages, including automated detection procedures, high-throughput, large platform-based detection of sample in and out, and real-time in-situ detection. However, most of the existing PCR (polymerase chain reaction) instruments for detecting nucleic acids on the market are not portable, have a slow speed (30 minutes or more for PCR amplification), and are expensive.
Therefore, how to provide a nucleic acid PCR ultrafast fluorescence detection technology and a portable device based on the miniaturization, chipization and high integration of detection process of silicon-based microfluidic chips becomes an important technical problem to be solved urgently by those skilled in the art.
SUMMERY OF THE UTILITY MODEL
In view of the above-mentioned shortcomings of the prior art, the present invention provides a microfluidic chip for solving the problems of the prior art, such as the lack of portability, the slow speed and the high price of the PCR instrument for detecting nucleic acid.
To achieve the above and other related objects, the present invention provides a microfluidic chip, including:
a substrate;
the microfluidic structure comprises a liquid inlet, a liquid input runner, a PCR reaction cavity, a liquid output runner and a liquid outlet which are sequentially communicated;
the substrate is provided with at least one group of heat insulation groove structures, the substrate penetrates through the at least one group of heat insulation groove structures from top to bottom, the group of heat insulation groove structures surround at least one containing area in the substrate, and at least one group of micro-fluid structures are arranged in one containing area.
Optionally, the PCR reaction chamber, the liquid input channel, and the liquid output channel are all opened from the upper surface of the substrate, and extend toward the lower surface of the substrate, but do not penetrate through the lower surface of the substrate.
Optionally, the microfluidic chip further comprises a cover plate, wherein the cover plate is located on the upper surface of the substrate and covers the PCR reaction chamber, the liquid input channel, and the liquid output channel.
Optionally, the openings of the liquid inlet and the liquid outlet are located on a lower surface or a side surface of the substrate.
Optionally, the liquid inlet and the liquid outlet are located at the periphery of the heat insulation groove structure, the heat insulation groove structure includes at least two separately disposed heat insulation grooves, wherein at least two heat insulation grooves are partially overlapped in the horizontal direction, and the liquid input flow channel and the liquid output flow channel both pass through an area between the two heat insulation grooves to enter the accommodating area to be connected with the PCR reaction chamber.
Optionally, the microfluidic chip comprises at least two sets of the microfluidic structures, wherein the PCR reaction chambers of different microfluidic structures are the same size.
Optionally, the microfluidic chip comprises at least two sets of the microfluidic structures, wherein the PCR reaction chambers of different microfluidic structures differ in size.
Optionally, the PCR reaction chamber has a width in the range of 0.1mm to 2mm and a length in the range of 1mm to 10 mm.
Optionally, the insulation groove structure comprises at least one insulation groove, and the insulation groove comprises at least one bending angle, and the bending angle is arc-shaped.
Optionally, the PCR reaction chamber has a serpentine shape that meanders back and forth.
As described above, the utility model discloses a microfluid chip is equipped with the heat-proof tank structure, can realize rising fast and falling the temperature to shorten PCR reaction time greatly, can shorten the PCR amplification process that generally needs more than 30 minutes within 5 minutes. And simultaneously, the utility model discloses an integration, especially the chipization of high accuracy are realized to silicon-based microfluid chip technology of microfluid chip accessible to realized portability, the miniaturization of equipment, and can extensive volume production, help reducing equipment cost. The utility model discloses a microfluid chip can be applied to the detection of the nucleic acid material in virus, bacterium, cell, the body fluid, can realize the short-term test, helps carrying out the quick examination to the crowd under the epidemic situation state.
Drawings
Fig. 1 a-1 b are schematic top views of a microfluidic chip according to an embodiment.
FIGS. 2 a-2 b are plan views of the structure of the thermal isolation channel and the liquid input and output channels of the microfluidic chip shown in FIGS. 1 a-1 b.
Fig. 3 is a plan view showing the structure of the heat insulation groove, the liquid inlet channel, and the liquid outlet channel according to the second embodiment.
FIG. 4 is a schematic top view of a microfluidic chip according to a second embodiment.
Fig. 5 is a plan view showing the structure of the heat insulating groove, the liquid inlet channel, and the liquid outlet channel in the third embodiment.
FIG. 6 is a schematic top view of a microfluidic chip according to a fourth embodiment.
Description of the element reference numerals
1 microfluidic chip
101 substrate
102 microfluidic structure
1021 liquid inlet
1022 liquid input flow passage
1023 PCR reaction chamber
1024 liquid output flow channel
1025 liquid outlet
103 heat insulation groove structure
1031 accommodating area
1032 Heat insulation groove
Detailed Description
The following description of the embodiments of the present invention is provided for illustrative purposes, and other advantages and effects of the present invention will be readily apparent to those skilled in the art from the disclosure herein. The present invention can also be implemented or applied through other different specific embodiments, and various details in the present specification can be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.
Please refer to fig. 1a to fig. 6. It should be noted that the drawings provided in the present embodiment are only for illustrating the basic idea of the invention in a schematic manner, and only the components related to the invention are shown in the drawings rather than being drawn according to the number, shape and size of the components in actual implementation, and the form, quantity and proportion of the components in actual implementation may be changed at will, and the layout of the components may be more complicated.
Example one
In this embodiment, a microfluidic chip 1 is provided, please refer to fig. 1a or fig. 1b, which is a schematic top view of the microfluidic chip, and includes a substrate 101, at least one set of microfluidic structures 102 and at least one set of heat insulation groove structures 103, wherein the microfluidic structures 102 are located in the substrate 101 and include a liquid inlet 1021, a liquid input flow channel 1022, a PCR reaction chamber 1023, a liquid output flow channel 1024 and a liquid outlet 1025, which are sequentially connected, the heat insulation groove structures 103 vertically penetrate through the substrate 101, wherein one set of heat insulation groove structures 103 encloses at least one housing area 1031 in the substrate 101, and at least one set of microfluidic structures 102 is disposed in one housing area 1031. Fig. 1a shows a set of the heat shield structure 103 enclosing a receiving area 1031 in the substrate 101, and two sets of the microfluidic structure 102 are arranged in one receiving area 1031. Fig. 1b shows a set of said heat sink structures 103 enclosing a receiving area 1031 in said substrate 101, wherein four sets of said microfluidic structures 102 are arranged in one receiving area 1031.
For example, the PCR reaction chamber 1023, the liquid input flow channel 1022, and the liquid output flow channel 1024 are all open from the upper surface of the substrate 101, extend toward the lower surface of the substrate 101, and do not penetrate through the lower surface of the substrate 101.
Illustratively, the microfluidic chip further comprises a cover plate (not shown) disposed on the upper surface of the substrate 101 and covering the PCR reaction chamber 1023, the liquid input flow channel 1022, and the liquid output flow channel 1024. The cover plate is made of transparent material such as glass.
As an example, the openings of the liquid inlet 1021 and the liquid outlet 1025 are located on the lower surface of the substrate 101. Of course, in other embodiments, the openings of the liquid inlet 1021 and the liquid outlet 1025 may be located at the side of the substrate 101, and the protection scope of the present invention should not be limited too much.
Referring to fig. 2 a-2 b, there are shown plan layout views of the thermal isolation groove structure 103, the liquid input channel 1022 and the liquid output channel 1024 of the microfluidic chip shown in fig. 1 a-1 b, wherein the microfluidic chip of the present embodiment adopts an independent thermal isolation groove structure, that is, one microfluidic chip only includes one thermal isolation groove structure 103.
Illustratively, the heat shield slot structure 103 defines a receiving area 1031 in the substrate 101
As an example, the insulation slot structure 103 comprises at least two separately arranged insulation slots 1032, wherein at least two of the insulation slots partially overlap in the horizontal direction. In this embodiment, the heat insulation groove structure 103 includes four heat insulation grooves 1032, two of which are located in the inner ring, and the other two of which are located in the outer ring, two of which are not connected to allow the flow passage to pass through, and two of which are also not connected to allow the flow passage to pass through, wherein the passage of the inner ring is blocked by the heat insulation groove of the outer ring at the outer side, and the passage of the outer ring is blocked by the heat insulation groove of the inner ring at the inner side, so that the heat insulation groove structure 103 can enclose a substantially closed accommodating area 1031, thereby enhancing the heat insulation effect.
It should be noted that the heat insulation groove structure 103 may also include only one heat insulation groove, but the heat insulation effect is slightly inferior to that of the multi-layer heat insulation groove.
As an example, the thermal insulation groove includes at least one bending corner, and the bending corner is arc-shaped, for example, the bending corner adopts a round design scheme, which is beneficial to reducing chip stress, increasing pressure resistance of the chip in use, and preventing the chip from cracking.
Referring back to FIG. 1a or FIG. 1b, the liquid inlet 1021 and the liquid outlet 1025 are located at the periphery of the heat insulation groove structure 103, and the liquid inlet channel 1022 and the liquid outlet channel 1024 pass through the area between the two heat insulation grooves to enter the housing area 1031 and connect with the PCR reaction chamber 1023.
As an example, the liquid inlet 1021 and the liquid outlet 1025 can be configured in different shapes for easy differentiation, for example, the liquid inlet 1021 is configured in a circle, and the liquid outlet 1025 is configured in a square, and the diameter of the circle or the side length of the square is between 0.5mm and 2 mm. Of course, in other embodiments, the liquid inlet 1021 and the liquid outlet 1025 may take other shapes, and the protection scope of the present invention should not be limited too much.
As an example, the PCR reaction chamber 1023 has a serpentine shape meandering back and forth, and the serpentine PCR reaction chamber 1023 is designed to effectively prevent the generation of air bubbles and improve the space utilization. In this embodiment, the width of the PCR reaction chamber 1023 is in the range of 0.1mm to 2mm, the length is in the range of 1mm to 10mm, and the area of the entire microfluidic chip is in the range of 10mm × 10mm to 50mm × 50 mm.
It should be noted that, in this embodiment, one housing area 1031 enclosed by the heat insulation slot structure 103 includes two sets of the microfluidic structures 102, and the lengths of the PCR reaction chambers 1023 of the two sets of the microfluidic structures 102 are the same. However, in other embodiments, the heat insulation slot structure 103 may also include other numbers of the microfluidic structures, such as 1-10 sets, in a housing area 1031 enclosed by the heat insulation slot structure, and when at least two sets of the microfluidic structures are included, the lengths of the PCR reaction chambers 1023 of different microfluidic structures may also be different. In addition, in other embodiments, the shape and size of the PCR reaction chamber 1023 and the area of the microfluidic chip can be adjusted according to needs, for example, the PCR reaction chamber 1023 is a square with a side length of 2mm-20mm, which should not unduly limit the scope of the present invention.
By way of example, the substrate 101 includes, but is not limited to, any one of a silicon substrate, an aluminum nitride substrate, a ceramic substrate, a metal substrate, or a plastic substrate, in this embodiment, a silicon substrate is preferably used, wherein the cover plate can be coupled to the silicon substrate through a direct bonding method, the microfluidic structure 102 can be processed through an etching method, and the heat insulation groove structure 103 can be etched through the silicon substrate, so that the PCR reaction chamber 1023 and most of the flow channels are thermally insulated from the peripheral silicon substrate.
The microfluid chip of this embodiment is equipped with the heat-insulating tank structure, can realize fast rising and falling the temperature to shorten PCR reaction time greatly, can shorten the PCR amplification process that usually needs more than 30 minutes to within 5 minutes. And simultaneously, the utility model discloses an integration, especially the chipization of high accuracy are realized to silicon-based microfluid chip technology of microfluid chip accessible to realized portability, the miniaturization of equipment, and can extensive volume production, help reducing equipment cost. Utilize the utility model discloses a quick detection can be realized to the microfluid chip, helps carrying out quick examination to the crowd under the epidemic situation state. Overcomes the defects of the traditional virus detection technology and equipment, and realizes a portable, miniaturized and highly integrated chip PCR ultrafast fluorescence detection technology.
Example two
The present embodiment adopts substantially the same technical solution as the first embodiment, except that in the first embodiment, the heat insulation groove structure 103 of the microfluidic chip adopts an independent heat insulation groove structure, and the heat insulation groove structure 103 encloses only one receiving area 1031 in the substrate 101, whereas in the first embodiment, the heat insulation groove structure 103 of the microfluidic chip adopts a shared heat insulation groove, that is, one heat insulation groove structure 103 encloses a plurality of receiving areas 1031.
Referring to fig. 3, a plan layout view of the heat insulation slot structure 103, the liquid inlet channel 1022 and the liquid outlet channel 1024 in the present embodiment is shown, wherein one heat insulation slot structure 103 encloses four receiving areas 1031 in the substrate 101.
Referring to fig. 4, a schematic top view of the microfluidic chip of this embodiment is shown, wherein four receiving areas 1031 surrounded by the heat insulation groove structure 103 are respectively provided with a PCR reaction chamber 1023, and each PCR reaction chamber 1023 is respectively provided with an independent liquid inlet 1021, a liquid input channel 1022, a liquid output channel 1024, and a liquid outlet 1025. That is, the microfluidic chip in this embodiment has 4 channels of reaction chambers, which can be used to test a positive sample, a negative sample as a control group, and two samples to be tested, respectively.
For example, the four housing regions 1031 have the same area, and the four PCR reaction chambers 1023 have the same size and are symmetrically disposed.
It should be noted that, in other embodiments, one of the heat insulation slot structures 103 may also enclose other numbers of receiving areas 1031 in the substrate 101, for example, 2 to 10, the size of each receiving area 1031 may be the same or different, the number of the PCR reaction chambers 1023 in each receiving area 1031 is also not limited to 1, for example, 1 to 10, and the size and shape of each PCR reaction chamber 1023 may also be adjusted as required, which should not unduly limit the protection scope of the present invention.
EXAMPLE III
The present embodiment adopts substantially the same technical solution as the second embodiment, except that in the second embodiment, the heat insulation groove structure of the microfluidic chip adopts a shared heat insulation groove structure, while the microfluidic chip in the present embodiment adopts a discrete heat insulation groove structure, that is, the microfluidic chip includes a plurality of separately arranged heat insulation groove structures.
Referring to fig. 5, a plan layout view of the thermal insulation slot structure 103, the liquid input channel 1022 and the liquid output channel 1024 in the present embodiment is shown, wherein the microfluidic chip includes four independent thermal insulation slot structures 103, and each thermal insulation slot structure 103 encloses a receiving area 1031 in the substrate 101.
It should be noted that, in other embodiments, the microfluidic chip may also include other numbers of independent thermal insulation groove structures 103, for example, 2 to 10, each independent thermal insulation groove structure 103 may not only enclose one housing area 1031, for example, 2 to 10, the size of each housing area 1031 may be the same or different, the number of PCR reaction chambers 1023 in each housing area 1031 is also not limited to 1, for example, 1 to 10, and the size and shape of each PCR reaction chamber 1023 may also be adjusted as required, which should not unduly limit the protection scope of the present invention.
Example four
This embodiment uses substantially the same technical solution as the first embodiment, except that in the first embodiment, when the microfluidic chip includes two or four PCR reaction chambers 1023, the multiple PCR reaction chambers 1023 are symmetrically arranged, while in this embodiment, the microfluidic chip includes four PCR reaction chambers 1023, and the four PCR reaction chambers 1023 are asymmetrically arranged.
Referring to fig. 6, a schematic top view of the microfluidic chip of this embodiment is shown, wherein four PCR reaction chambers 1023 are respectively disposed in the accommodation region 1031 surrounded by the heat insulation groove structure 103, two of the PCR reaction chambers 1023 have longer length (about 2/3 of the whole reaction region area), and the other two of the PCR reaction chambers 1023 have shorter length (about 1/3 of the whole reaction region area). In practical applications, the two PCR reaction chambers 1023 with shorter length can be used as a control test for the negative sample and the positive sample, respectively, and the two PCR reaction chambers 1023 with longer length can be used as a measured sample channel.
It should be noted that, in this embodiment, the channels of the inner ring are not completely blocked by the heat insulation grooves of the outer ring on the outer side, while a part of the channels of the outer ring are completely blocked by the heat insulation grooves of the inner ring on the inner side, and another part of the channels are not blocked by the heat insulation grooves of the inner ring on the inner side, but because the width of the unblocked channels is very small, a strong heat insulation effect can still be achieved. Of course, in other embodiments, the design of the heat insulation slot may be more complicated, so that there is no unblocked passage to obtain better heat insulation effect, and the protection scope of the present invention should not be limited too much here.
EXAMPLE five
In this embodiment, the microfluidic chip of any one of the first to fourth embodiments is applied to gene detection, such as detection of nucleic acids in viruses, bacteria, cells, and body fluids, wherein the detected viruses include, but are not limited to, the novel coronavirus COVID-19. Wherein, the PCR amplification process of the nucleic acid detection process is performed in the PCR reaction chamber 1023 of the microfluidic chip.
To sum up, the utility model discloses a microfluid chip is equipped with the heat-proof tank structure, can realize rising the temperature fast to shorten PCR reaction time greatly, can shorten the PCR amplification process that generally needs more than 30 minutes within 5 minutes. And simultaneously, the utility model discloses an integration, especially the chipization of high accuracy are realized to silicon-based microfluid chip technology of microfluid chip accessible to realized portability, the miniaturization of equipment, and can extensive volume production, help reducing equipment cost. The utility model discloses a microfluid chip can be applied to the detection of the nucleic acid material in virus, bacterium, cell, the body fluid to can realize short-term test, help carrying out quick examination to the crowd under the epidemic situation state. Therefore, the utility model effectively overcomes various defects in the prior art and has high industrial utilization value.
The above embodiments are merely illustrative of the principles and effects of the present invention, and are not to be construed as limiting the invention. Modifications and variations can be made to the above-described embodiments by those skilled in the art without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which may 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 (10)

1. A microfluidic chip, comprising:
a substrate;
the microfluidic structure comprises a liquid inlet, a liquid input runner, a PCR reaction cavity, a liquid output runner and a liquid outlet which are sequentially communicated;
the substrate is provided with at least one group of heat insulation groove structures, the substrate penetrates through the at least one group of heat insulation groove structures from top to bottom, the group of heat insulation groove structures surround at least one containing area in the substrate, and at least one group of micro-fluid structures are arranged in one containing area.
2. The microfluidic chip of claim 1, wherein: the PCR reaction cavity, the liquid input flow channel and the liquid output flow channel are all opened from the upper surface of the substrate, extend towards the direction of the lower surface of the substrate and do not penetrate through the lower surface of the substrate.
3. The microfluidic chip of claim 2, wherein: the microfluidic chip further comprises a cover plate, wherein the cover plate is positioned on the upper surface of the substrate and covers the PCR reaction cavity, the liquid input flow channel and the liquid output flow channel.
4. The microfluidic chip of claim 1, wherein: the openings of the liquid inlet and the liquid outlet are positioned on the lower surface or the side surface of the substrate.
5. The microfluidic chip of claim 1, wherein: the liquid inlet and the liquid outlet are located on the periphery of the heat insulation groove structure, the heat insulation groove structure comprises at least two separately arranged heat insulation grooves, at least two heat insulation grooves are partially overlapped in the horizontal direction, and the liquid input flow channel and the liquid output flow channel penetrate through an area between the two heat insulation grooves to enter the accommodating area to be connected with the PCR reaction cavity.
6. The microfluidic chip of claim 1, wherein: the microfluidic chip comprises at least two groups of the microfluidic structures, wherein the sizes of the PCR reaction cavities of different microfluidic structures are the same.
7. The microfluidic chip of claim 1, wherein: the microfluidic chip comprises at least two groups of the microfluidic structures, wherein the sizes of the PCR reaction chambers of different microfluidic structures are different.
8. The microfluidic chip of claim 1, wherein: the width range of the PCR reaction cavity is 0.1mm-2mm, and the length range is 1mm-10 mm.
9. The microfluidic chip of claim 1, wherein: the heat insulation groove structure comprises at least one heat insulation groove, the heat insulation groove comprises at least one bending angle, and the bending angle is arc-shaped.
10. The microfluidic chip of claim 1, wherein: the PCR reaction chamber has a serpentine shape that meanders back and forth.
CN202021209370.3U 2020-06-24 2020-06-24 Microfluid chip Active CN212284074U (en)

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Effective date of registration: 20211108

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