WO2023155142A1 - 微流控流道结构及微流控芯片 - Google Patents

微流控流道结构及微流控芯片 Download PDF

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Publication number
WO2023155142A1
WO2023155142A1 PCT/CN2022/076863 CN2022076863W WO2023155142A1 WO 2023155142 A1 WO2023155142 A1 WO 2023155142A1 CN 2022076863 W CN2022076863 W CN 2022076863W WO 2023155142 A1 WO2023155142 A1 WO 2023155142A1
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Prior art keywords
wall
diversion
area
flow
reaction
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PCT/CN2022/076863
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English (en)
French (fr)
Inventor
牟芸青
陈丹丹
丁丁
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京东方科技集团股份有限公司
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Priority to CN202280000215.6A priority Critical patent/CN117222895A/zh
Priority to PCT/CN2022/076863 priority patent/WO2023155142A1/zh
Publication of WO2023155142A1 publication Critical patent/WO2023155142A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices

Definitions

  • Embodiments of the present disclosure relate to but are not limited to the field of microfluidic technology, and specifically relate to a microfluidic channel structure and a microfluidic chip.
  • Microfluidic Chip is an important science and technology in this century.
  • microfluidic chip Due to the microstructure characteristics of the microfluidic chip, it is prone to problems such as uneven sample distribution and sample retention during the liquid feeding process, which will affect the sample utilization rate and detection accuracy and precision.
  • An embodiment of the present disclosure provides a microfluidic flow channel structure, including a main chamber, the main chamber includes at least two flow distribution areas and a reaction area, and the at least two flow distribution areas are respectively connected to the reaction area, wherein :
  • Each splitting area includes a first splitting wall, and an opening for liquid inlet is opened on the first splitting wall;
  • the opening of at least one diversion area is provided with a diversion structure, the diversion structure at least includes a first diversion wall, the first diversion wall is opposite to the first diversion wall, and the first diversion wall
  • a first distribution channel is formed between the flow wall and the first distribution wall, the opening serves as a liquid inlet of the first distribution channel, and the first distribution channel includes at least two liquid outlets.
  • An embodiment of the present disclosure provides a microfluidic chip including the above channel structure.
  • FIG. 1 is a schematic diagram of a structure of a microfluidic flow channel provided by an embodiment of the present disclosure
  • FIG. 2 is a schematic diagram of a microfluidic channel structure according to an embodiment of the present disclosure
  • Fig. 3a is a schematic diagram of a split flow area in the microfluidic channel structure shown in Fig. 2;
  • Figure 3b is a schematic diagram of the main chamber in the microfluidic channel structure shown in Figure 2;
  • Fig. 4a is the flow velocity distribution simulation result of the main chamber of the channel structure shown in Fig. 2;
  • Fig. 4b is the flow velocity distribution simulation result of related technical structure
  • Fig. 5a is the simulation result of the shear force distribution in the main chamber reaction zone of the flow channel structure shown in Fig. 2;
  • Fig. 5b is the simulation result of the shear force distribution in the reaction zone of the related technical structure
  • FIG. 6 is a schematic diagram of another microfluidic channel structure according to an embodiment of the present disclosure.
  • FIG. 7 is a schematic diagram of another microfluidic channel structure according to an embodiment of the present disclosure.
  • Fig. 8 is the flow velocity distribution simulation result of the flow channel structure main chamber shown in Fig. 7;
  • FIG. 9 is a schematic diagram of another microfluidic channel structure according to an embodiment of the present disclosure.
  • FIG. 10 is a schematic diagram of another microfluidic channel structure according to an embodiment of the present disclosure.
  • FIG. 11 is a schematic diagram of another microfluidic channel structure according to an embodiment of the present disclosure.
  • FIG. 12 is a schematic diagram of another microfluidic channel structure according to an embodiment of the present disclosure.
  • the 'thickness' involved refers to the dimension along the direction perpendicular to the upper and lower substrate planes (or the upper and lower surfaces of the flat chip).
  • the "length direction" of a part of the structure refers to the direction in which the liquid body moves
  • the "length” of a certain part of the structure refers to the dimension of the part of the structure along the direction of the liquid body.
  • the "width direction” refers to the direction perpendicular to the direction of the main body of the liquid
  • the "width” of a certain part of the structure refers to the dimension of the part of the structure along the direction perpendicular to the direction of the main body of the liquid.
  • Chip immunoassay technology is a new concept of biological detection technology that combines the specificity of antigen-antibody binding reaction with the principle of high-density integration of electronic chips.
  • a large number of antigens (or antibodies) are arranged together in high density to make a chip, which reacts with the patient's sample and biological specimen at the same time, and can obtain high-throughput detection results of all known antigens (or antibodies) in the chip at one time
  • the advanced detection method of biological information has the advantages of high throughput, rapidity, easy operation and high degree of automation.
  • the double-antibody sandwich immunochip method is a commonly used immunoassay method.
  • the fluorescent immunoassay chip developed for this purpose is a protein chip constructed using the specificity of antibody-antigen binding, that is, the immune response.
  • the capture protein and detection protein are pre-embedded on the chip respectively to form a protein microarray to realize multiple detection of markers. With the help of the fluorescence detection system to detect the markers, only one imaging is needed, and the results are automatically analyzed and printed by the software.
  • the small and portable design makes it have a very wide range of application scenarios.
  • the basic reaction process of the double-antibody sandwich immunochip method is as follows: firstly, the sample to be tested enters from the injection port, and then enters the first reaction area after passing through the first mixing area, which will correspond to the first reaction area.
  • the freeze-dried fluorescent antibody pre-embedded on the glass module reacts to redissolve the antibody, and the antigen specifically binds to the antibody.
  • the antigen in the sample After passing through the second mixing zone, the antigen in the sample fully reacts with the fluorescent antibody.
  • the capture antibody grafted on the glass module corresponding to the second reaction area reacts to form a double antibody sandwich.
  • the buffer is pumped from the injection port of the chip, and the reaction area Washing is performed to wash away uncaptured fluorescent antibodies, and the waste liquid flows into the waste liquid pool.
  • the chip is placed under a fluorescence microscope for optical signal detection, in order to determine the content of antigen in the sample.
  • the main problem encountered in the implementation process is that the freeze-dried antibodies embedded in the first reaction area cannot be effectively reconstituted, and most of the freeze-dried antibodies still remain on the chip substrate and do not react with the antigen in time.
  • the detection efficiency and accuracy of the chip cannot meet the expected requirements, and the samples and antibodies are not fully utilized, resulting in waste.
  • an embodiment of the present disclosure provides a microfluidic flow channel structure, as shown in FIG. Zones are respectively connected to the reaction zone, where:
  • Each splitting area includes a first splitting wall, and an opening for liquid inlet is opened on the first splitting wall;
  • the opening of at least one diversion area is provided with a diversion structure, the diversion structure at least includes a first diversion wall, the first diversion wall is opposite to the first diversion wall, and the first diversion wall
  • a first distribution channel is formed between the flow wall and the first distribution wall, the opening serves as a liquid inlet of the first distribution channel, and the first distribution channel includes at least two liquid outlets.
  • the liquid inlet can be located at any position of the first diversion channel, and the position of the liquid inlet of the first diversion channel can be changed by setting the position of the first diversion channel, for example, about the middle part of the first diversion wall can be set The position corresponds to the opening of the first distribution wall.
  • the liquid inlet of the first distribution channel is located in the middle of the first distribution channel, and the openings at both ends of the first distribution channel can be used as liquid outlets of the first distribution channel.
  • the first flow guide wall may also have openings, and the openings on the first flow guide wall may serve as liquid outlets of the first distribution channel, so that the first distribution channel has more liquid outlets. More liquid outlets can create more velocity components.
  • the first flow distribution channel can divide one flow of liquid entering the flow separation area into at least two flow paths, forming at least two flow paths of velocity components.
  • the first diversion wall can be arranged in parallel with the first diversion wall, that is, the widths of different positions of the first diversion channel are basically the same; or the first diversion wall and the first diversion wall can be arranged not in parallel.
  • the distance between one side of the first flow guide wall and the first flow divider wall is smaller than the distance between the other side of the first flow guide wall and the first flow divider wall (the distance perpendicular to the direction of liquid flow), that is Along the direction of liquid flow, the width of the first distribution channel becomes smaller or larger gradually.
  • the shape of the main control chamber can be a circle or a polygon.
  • the at least one flow diversion area may further include a second flow divider wall, one end of the first flow divider wall is connected to the second flow divider wall, and the flow guide structure may further include a second flow guide wall.
  • a flow wall one end of the first flow guide wall is connected to the second flow guide wall, the second flow guide wall is arranged opposite to the second flow guide wall, and the second flow guide wall is connected to the second flow guide wall
  • a second distributing channel is formed between the second distributing walls, and the second distributing channel communicates with the first distributing channel, for example, the second distributing channel communicates with the first liquid outlet of the first distributing channel.
  • the second distribution channel can play the role of extending the first distribution channel, can continuously guide the incoming liquid, and guide the incoming liquid to a desired position.
  • the flow diversion area may further include a third flow divider wall, an end of the first flow divider wall away from the second flow divider wall is connected to the third flow divider wall, and the flow guide structure It also includes a third flow guide wall, one end of the first flow guide wall away from the second flow guide wall is connected to the third flow guide wall, and the third flow guide wall is connected to the third flow guide wall
  • the walls are arranged opposite to each other, and a third flow channel is formed between the third flow guide wall and the third flow divider wall, and the third flow flow channel communicates with the first flow flow channel, for example, the third flow flow channel communicates with the first flow flow channel.
  • the second liquid outlet of the channel is connected.
  • the third distributing channel can also function to extend the first distributing channel, and can guide the liquid in the third distributing channel to a desired position.
  • the first flow-dividing wall is arc-shaped, straight-line, or broken-line; the first flow-guiding wall is arc-shaped Either straight or broken.
  • the shapes of the first flow dividing wall and the first flow guiding wall may be the same or different.
  • both the first diversion wall and the first diversion wall are arc-shaped, or the first diversion wall and the first diversion wall are both linear, or the first diversion wall is arc-shaped, and the first diversion wall is straight shape, or the first diversion wall is linear, the first diversion wall is arc-shaped, and so on.
  • both the first diversion wall and the first flow guide wall are arc-shaped, the resistance of liquid inlet can be reduced and the flow rate can be increased.
  • the second flow dividing wall is arc-shaped or straight; the second flow-guiding wall is arc-shaped or straight .
  • the shapes of the second flow-dividing wall and the second flow-guiding wall may be the same or different.
  • both the second diversion wall and the second diversion wall are arc-shaped, or both the second diversion wall and the second diversion wall are linear, or the second diversion wall is arc-shaped, and the second diversion wall is straight shape, or the second diversion wall is linear, and the second diversion wall is arc-shaped.
  • the width of the second distribution channel may be constant, or gradually decrease, or gradually increase.
  • the second flow dividing wall may be in a zigzag shape, and the second flow guiding wall may be in a zigzag shape.
  • the third flow dividing wall is arc-shaped or straight; the third flow-guiding wall is arc-shaped or straight .
  • the shapes of the third flow dividing wall and the third flow guiding wall may be the same or different.
  • both the third diversion wall and the third diversion wall are arc-shaped, or both the third diversion wall and the third diversion wall are linear, or the third diversion wall is arc-shaped, and the third diversion wall is straight shape, or the third diversion wall is linear, and the third diversion wall is arc-shaped.
  • the width of the third distribution channel may be constant, or gradually decrease, or gradually increase.
  • the third flow dividing wall may be in a zigzag shape, and the third flow guide wall may be in a zigzag shape.
  • the cross-section of the second dividing wall is U-shaped (as shown in the embodiment shown in FIG. 2 ), in other embodiments, the The cross-sectional shape of the second flow divider wall can also be other shapes, such as linear.
  • the second dividing wall can be connected to the side wall of the reaction zone, one end of the U-shaped second dividing wall can be connected to the first dividing wall, and the other end can be connected to the side wall of the reaction zone (hereinafter referred to as the reaction wall).
  • one end of the second splitter wall in the first splitter region is connected to the first splitter wall in the same splitter region, and the other end is connected to the reaction wall in the reaction region.
  • One end of the second dividing wall in the second dividing area is connected to the first dividing wall in the same dividing area, and the other end is connected to another reaction wall in the reaction area.
  • the third splitter wall of the first splitter area and the third splitter wall of the second splitter area may share the same splitter wall structure, and the splitter wall structure
  • the side facing the first distributing area serves as the third distributing wall of the first distributing area
  • the side of the distributing wall structure away from the first distributing area, that is, the side facing the second distributing area serves as the The third flow dividing wall of the second flow dividing area.
  • the cross-sectional shape of the dividing wall structure is U-shaped, and one side of the U-shaped structure serves as the third dividing wall of the first dividing area, and the side end It is connected to the first diversion wall of the first diversion area, and the other side of the U-shaped structure is used as the third diversion wall of the second diversion area, and the end of this side is connected to the first diversion wall of the second diversion area, as shown in Figure 2 below , Fig. 6, Fig. 7, Fig. 9, the embodiment shown in Fig. 12.
  • two adjacent splitter regions may share a splitter channel, for example, for any two adjacent splitter regions: one end of the first splitter wall of the first splitter region and one end of the second splitter region One end of the first dividing wall is connected, the other end of the first dividing wall of the first dividing area is connected with the second dividing wall of the first dividing area, and the other end of the first dividing wall of the second dividing area is connected with the second dividing wall.
  • the second diversion wall of the diversion area is connected to the first diversion wall of the first diversion area and the first diversion wall of the second diversion area;
  • the diversion structure of the at least two diversion regions also includes a third diversion wall, the One end of the first flow guide wall away from the second flow guide wall is connected to the third flow guide wall;
  • the third flow guide wall of the first flow diversion area is connected to the third flow guide wall of the second flow diversion area
  • a third flow distribution channel is formed between the walls, and the third flow distribution channel communicates with the first flow distribution channel of the first flow distribution area and communicates with the first flow distribution channel of the second flow distribution area. At this time, the first flow distribution area and the second flow distribution area share the third flow distribution channel. Examples are shown in Figure 10 and Figure 11 below.
  • openings may be formed on the second flow divider wall. This opening can be used to increase the velocity component.
  • the reaction zone includes a first reaction wall and a second reaction wall, and the first reaction wall and the second reaction wall are arranged opposite to form a reaction zone inlet, a reaction channel and a reaction zone outlet, from From the inlet of the reaction zone to the outlet of the reaction zone, the width of the channel in the reaction zone decreases gradually.
  • the first reaction wall, the second reaction wall and the first flow divider walls of different flow divider regions can jointly form the outer contour of the main chamber.
  • the first reaction wall and the second reaction wall are arc-shaped, as shown in Fig. 2 , Fig. 7 , Fig. 10 , and Fig. 11.
  • first reaction wall and the second reaction wall are linear, as shown in the embodiment shown in Figure 6 below.
  • first reaction wall The wall and the second reaction wall may be in the shape of a zigzag; or,
  • the first reaction wall includes at least two reaction wall subsections connected in sequence, wherein at least one reaction wall subsection is arc-shaped, and at least one reaction wall subsection The section is linear;
  • the second reaction wall includes at least two reaction wall subsections connected in sequence, wherein at least one reaction wall subsection is arc-shaped, and at least one reaction wall subsection is linear, such as Fig. 9 below Example shown.
  • the microfluidic flow channel structure further includes at least two mixing areas, each of which is connected to at least one splitting area; each of the mixing areas includes a liquid inlet, a mixing The flow channel and the liquid outlet; the liquid inlets of the at least two mixing zones are connected, and the liquid outlet of each mixing zone is connected with the opening on the first dividing wall of a dividing zone.
  • the mixing channel is a serpentine channel, or may be in other channel shapes that facilitate mixing.
  • the microfluidic channel structure further includes a liquid outlet area, and the liquid outlet area includes one or more liquid outlet channels, each of which is connected to the reaction area.
  • the liquid outlet area includes multiple liquid outlet channels, the effect of increasing velocity gradient change, direction change and enhanced flow shear can be achieved by increasing the liquid outlet channels of the liquid outlet area, as shown in the embodiment shown in FIG. 7 below.
  • the embodiment of the present disclosure designs a microfluidic flow channel structure, which can better help antibody redissolution by increasing the velocity component of the incoming flow in the reaction area, increasing flow disturbance and local shearing of the antibody pre-embedded area.
  • it improves the reconstitution speed of the freeze-dried antibody in the reaction area, shortens the reaction time, and makes the chip more immediacy; and increases the reconstitution amount of the freeze-dried antibody sample, improves the accuracy and precision of the detection, and improves the immunity. Detection flux.
  • the amount of retained samples in the reaction zone can be reduced, and the utilization rate of samples can be improved.
  • the microfluidic flow channel structure may be a cavity formed by a first substrate and a second substrate pair box.
  • the microfluidic flow channel structure is formed by Divided into multiple functional areas, as shown in Figure 2, the microfluidic channel structure includes a liquid inlet area 100, at least two mixing areas 200, a main chamber 300 and a liquid outlet area 400, wherein the main chamber includes At least two split zones (310 and 330 as shown in FIG. 2 ) and one reaction zone 320 .
  • the liquid inlet area 100, the mixing area 200, the diversion area 310, the reaction area 320 and the liquid outlet area 400 are connected in sequence, so that the sample liquid enters from the liquid inlet area 100, mixes in the mixing area 200, passes through the diversion area 310, and After the reaction in the reaction zone 320 , it flows out from the liquid outlet zone 400 .
  • both the liquid inlet region 100 and the liquid outlet region 400 are linear channels, and the width of the channel ranges from 0.6mm to 1.0mm, such as 0.8mm, and the length of the channel can be set as required.
  • the liquid inlet area 100 is connected to the inlet of the mixing area 200, and the liquid inlet area 100 may have a first liquid inlet port 101 and a first liquid outlet port 102;
  • Each mixing zone 200 includes a second liquid inlet 201, a second liquid outlet 202 and a mixing channel, and each second liquid inlet 202 is connected to the first liquid outlet 102.
  • the mixing The uniform flow channel adopts a multiple bend design or a serpentine flow channel design, which is conducive to effective mixing.
  • other flow channel structures that are conducive to mixing can be used, and this article does not limit this; in order to simplify the structure , the channel width of the liquid inlet area can not be changed, and a plurality of second liquid inlet ports 201 can be connected to each other.
  • the liquid ports 201 are connected, the two second liquid inlet ports 201 are arranged opposite to each other, the first liquid outlet port is arranged vertically, and the three ports are arranged in a T-like shape.
  • the first splitting of the sample liquid can be realized.
  • the arrangement of the three ports can adopt other shapes, which is not limited in this paper, as long as the flow can be realized.
  • the main chamber 300 includes at least two splitter areas 310 and a reaction area 320 connected to the splitter areas 310, and the splitter areas 310 are connected to the mixing area 200 in one-to-one correspondence;
  • the main chamber 300 includes at least two third liquid inlet ports 301 and The third liquid outlet 302, the third liquid inlet 301 is located in the split area 310, each third liquid inlet 301 is connected to a second liquid outlet 202, the third liquid outlet 302 is located in the reaction zone 320, the third outlet
  • the liquid end 302 is connected to the liquid outlet area 400; in this example, the third liquid inlet port 301 corresponds to the second liquid outlet port 202 one-to-one, and the splitter area 310 corresponds to the mixing area 200 (the same number).
  • the sample liquid enters the diversion area 310 through the third liquid inlet port 301 , and enters the reaction area 320 after diversion.
  • each third liquid inlet 301 includes a connected first branch 3011 and a second branch.
  • the branch 3012, the first branch 3011 and the second branch 3012 are bent and connected, that is to say, the angle between the first branch and the second branch is greater than 0 degrees and less than 180 degrees ( ⁇ in FIG. 2 ).
  • One end of the first branch 3011 is connected to a second liquid outlet 202 of a mixing zone 200, the other end is connected to the second branch 3012, and one end of the second branch 3012 is connected to the first branch 3011 , and the other end is connected to the diversion area 310 .
  • the extension direction of the second branch can be set to be 90° ⁇ 5° (see ⁇ in FIG. 3 a ) to the direction of the side wall of the diversion area connected to the second branch or the direction of the tangential plane of the side wall of the diversion area.
  • a diversion structure 311 is provided at the port of the third liquid inlet 301, which diverts one path of sample liquid entering from the third liquid inlet 301 into two paths, that is, through the diversion structure, the The second split of the sample liquid, after the two splits, the sample liquid changes from one velocity component to four velocity components, which can enhance the flow shear and velocity disturbance, so that the freeze-dried antibody can be better reconstituted.
  • the main chamber has two third liquid inlet ports 301, and a diversion structure 311 is provided at the port of each third liquid inlet port, so that the two channels of sample liquid entering the main chamber can be guided as Four paths (shown by the black arrows in the diverging area in the figure), four flow velocity components can be formed.
  • the velocity of each flow velocity component may be the same.
  • Fig. 3 a illustrates the structure in the diversion region by taking a diversion region 310 as an example.
  • the structure of the diversion region 330 is the same as that of the diversion region 310.
  • the second divider wall 3102 connected to one end, and the third divider wall 3103 connected to the other end of the first divider wall 3101, wherein the first divider wall 3101 is arc-shaped, in this embodiment, as shown in Figure 3a Shown, the second divider wall 3102 and the third divider wall 3103 are designed as a U-shaped structure, one end of the U-shaped structure is connected to the first divider wall 3101, and the other end is used to connect with the reaction wall (321 or 322) of the reaction zone An opening for liquid inlet (the opening is connected to the third liquid inlet port 301 ) is opened on the first dividing wall 3101 , and optionally, the opening can be set at a middle position with the first dividing wall 3101 .
  • the two diversion areas are arranged adjacent to each other, and can share a U-shaped structure diversion wall.
  • the third flow divider wall 3103 of the first flow divider area 310 the side of the U-shaped structure flow divider wall 3103 close to the second flow divider area 330 serves as the third flow divider wall 3303 of the second flow divider area 330 .
  • the flow guide structure 311 includes a first flow guide wall 3111 , a second flow guide wall 3112 connected to one end of the first flow guide wall 3111 , and a third flow guide wall 3112 connected to the other end of the first flow guide wall 3111 .
  • the flow guide wall 3113 wherein the first flow guide wall 3111 can be similar to the first flow guide wall 3101, is arc-shaped, for example, the radius range of the first flow guide wall 3111 can be 2mm-6mm, for example, 4mm.
  • the first flow guide wall may be straight or broken line, and the second flow guide wall 3112 and the third flow guide wall 3113 are both straight.
  • a first diversion channel (arc channel) is formed between the first diversion wall 3111 and the first diversion wall 3101, and the distance D1 between the first diversion wall 3111 and the first diversion wall 3101 is the width of the first diversion channel
  • the width of the channel at other positions may be similar, and the average value range may be 0.6mm-1.0mm, for example, it may be 0.8mm.
  • the second flow guide wall 3112 and the side of the second flow guide wall 3102 close to the second flow guide wall 3112 form a second flow channel, and the third flow guide wall 3113 and the third flow guide wall 3103 are close to the side of the third flow guide wall 3113
  • a third distributing channel is formed, and the first distributing channel is respectively connected with the second distributing channel and the third distributing channel.
  • the distance D2 between the second flow guide wall 3112 and the second flow guide wall 3102 near the second flow guide wall 3112 can be compared with the third flow guide wall 3113 and the third flow guide wall 3103
  • the distance D3 between the sides close to the third guide wall 3113 is the same, and the value range of D2 and D3 is 0.6mm-1.0mm, for example, 0.8mm.
  • the second divider wall 3102 and the third divider wall 3103 can be sidewalls that reuse the entire main chamber, that is, as shown in Figure 2 and Figure 3a, the U-shaped second divider wall 3102 and the third divider wall
  • the dividing wall 3103 is also a part of the side wall of the main chamber 300 .
  • the extension direction of the U-shaped second diversion wall 3102 is the same as the extension direction of the second diversion wall 3112, and the depth L1 of the U-shaped second diversion wall 3102 extending to the interior of the main chamber can be in the range of 2.0mm-2.8mm, for example, 2.4 mm, the opening distance L2 of the U-shaped structure may range from 0.2 mm to 0.6 mm, for example, 0.4 mm.
  • the edge of the U-shaped second diverter wall 3102 extending to the interior of the main chamber is on the same plane (M in the figure) as the edge of the second flow guide wall 3112 extending to the interior of the main chamber.
  • the extension direction of the U-shaped third diversion wall 3103 is the same as the extension direction of the third diversion wall 3113, and the depth range of the U-shaped third diversion wall 3103 extending to the interior of the main chamber can be 2.0mm-2.8mm, for example is 2.4mm, and the opening distance of the U-shaped structure may range from 0.2mm to 0.6mm, for example, 0.4mm.
  • the edge of the third flow dividing wall 3103 extending to the interior of the main chamber is on the same plane (N in the figure) as the edge of the third flow guiding wall 3113 extending to the interior of the main chamber.
  • a protruding structure 312 can be provided inside the main chamber, which can be used as a side wall of the diverging area to provide a channel for the sample liquid.
  • the freeze-dried antibodies are pre-embedded in the reaction zone 320.
  • the antibody can be freeze-dried on the target carrier, placed in the reaction area 320 of the first substrate, and then the second substrate and the first substrate are packaged to realize the pre-embedding of the antibody.
  • the size of the target carrier can be but not limited to a rectangle, and the size is slightly smaller than the size of the reaction zone 320. In this way, the target carrier can be directly put into the interlayer between the first substrate and the second substrate during packaging, and the freeze-dried first antibody It will not be damaged, and when reconstituted, the primary antibody will not remain on the detection chip.
  • the reaction zone 320 is designed as a semicircular structure, and the distance between the first reaction wall and the second reaction wall, that is, the width of the reaction channel, gradually decreases from the entrance of the reaction zone to the exit of the reaction zone. Small, to allow room and time for an adequate response.
  • the reaction zone 320 includes a first reaction wall 321 and a second reaction wall 322, and the first reaction wall 321 and the second reaction wall 322 are arranged opposite to each other to form a reaction zone inlet, a reaction channel and a reaction zone outlet.
  • both the first reaction wall 321 and the second reaction wall 322 are arc-shaped, and one end of the first reaction wall 321 is connected with one end of the second flow distribution wall 3102 of a flow separation area 310, and the other end is connected with The first liquid outlet wall 401 of the liquid outlet area is connected, and one end of the second reaction wall 322 is connected with an end of the second flow divider wall 3302 of another split flow area (330 among the figures), and the other end is connected with the second liquid outlet wall of the liquid outlet area.
  • the two outlet walls 402 are connected.
  • the first diversion walls 3101 of the two diversion areas are arc-shaped
  • the first reaction wall 321 and the second reaction wall 322 of the reaction area are also arc-shaped
  • the main chamber composed of several arcs is Quasi-circular
  • the outer diameter range of such a circular shape may be 7.8mm-11.6mm, for example, 9.6mm.
  • the front end of the main chamber 300 has a double liquid inlet structure, and the rear end has an arc-shaped single liquid outlet structure.
  • the sample liquid passes through the liquid inlet area, after passing through the two symmetrical multiple curved flow channel structure mixing areas, it enters the two split flow areas from the two inlets with curved structures, and each sample liquid is divided into two again, and finally Four velocity components are formed and enter the reaction zone.
  • the reaction area four channels of sample liquid react with the pre-embedded freeze-dried antibody, and finally the reacted liquid flows out from the liquid outlet area. Therefore, the structure of the microfluidic channel in this embodiment is a structure of four velocity components.
  • the entire chip thickness range can be 1.0mm-1.4mm, for example, 1.2mm.
  • Figure 2 shows the channel structure etched on the first substrate, and the entire channel height range can be 0.2mm-0.4mm.
  • mm such as 0.3mm
  • the flow channel width range can be 0.6mm-1.0mm, such as 0.8mm, such as the flow channel in the liquid inlet area, the flow channel in the mixing area, the flow channel in the split area and the liquid outlet area the runner.
  • FIG. 4a shows the flow velocity distribution of the main chamber structure of this embodiment
  • Fig. 4b shows the flow velocity distribution of the related technology structure
  • Fig. 5a shows the distribution of shear force in the reaction zone structure of the main chamber of this embodiment
  • Fig. 5b shows the distribution of shear force in the reaction zone of the structure of the related technology.
  • the rectangular box in Figure 5 is the pre-embedded area of the freeze-dried antibody, that is, the area containing the aforementioned target carrier.
  • Fig. 6 is a schematic diagram of another microfluidic channel structure according to an embodiment of the present disclosure. Similar to the embodiment in Fig. The chamber 300 and the liquid outlet area 400 , wherein the main chamber includes at least two flow distribution areas 310 and one reaction area 320 .
  • the liquid inlet area 100, the mixing area 200, the diversion area 310, the reaction area 320 and the liquid outlet area 400 are connected in sequence, so that the sample liquid enters from the liquid inlet area 100, mixes in the mixing area 200, passes through the diversion area 310, and After the reaction in the reaction zone 320 , it flows out from the liquid outlet zone 400 .
  • the microfluidic channel structure is still a four-velocity component structure.
  • reaction zone 320 is designed as a conical structure, and the width of the reaction channel gradually decreases from the entrance of the reaction zone to the exit of the reaction zone.
  • the reaction zone 320 includes a first reaction wall 321 and a second reaction wall 322.
  • the first reaction wall 321 and the second reaction wall 322 are linear, and one end of the first reaction wall 321 is connected to a split flow area 310 One end of the second dividing wall 3102 away from the first dividing wall 3101 is connected, the other end is connected with the first liquid outlet wall 401 of the liquid outlet area, and one end of the second reaction wall 322 is connected with the second side of the other dividing area 330 One end of the dividing wall (3302 in the figure) away from the first dividing wall (3301 in the figure) is connected, and the other end is connected with the second liquid outlet wall 402 in the liquid outlet area.
  • the structure of the reaction zone which is wide at the front and narrow at the back, enables the pre-embedded freeze-dried antibody to be subjected to greater impact and shear, which helps to achieve antibody reconstitution, improves the efficiency of the reaction, and then improves the accuracy and precision of detection.
  • the front end of the main chamber 300 has a double liquid inlet structure, and the rear end has a tapered single liquid outlet structure.
  • the sample liquid passes through the liquid inlet area, after passing through the mixing area with two symmetrical multiple curved channel structures, it flows from The two inlets with bent structures enter into two split flow areas respectively, and each sample liquid is divided into two, finally forming four velocity components, which enter the conical reaction area.
  • the single-input and double-output structure of each split area forms an inverted bifurcated structure as a whole, and the reaction zone of the conical structure just exists in the outlet area of the inverted bifurcated structure. This area is based on the principles of structure and fluid mechanics. Stronger eddy currents will be formed than ordinary planar areas, which can increase local fluid disturbances, thereby helping to improve reaction efficiency at the structural level, thereby improving the accuracy and precision of detection.
  • Fig. 7 is a schematic diagram of another microfluidic flow channel structure in the embodiment of the present disclosure, similar to the embodiment in Fig.
  • the chamber 300 and the liquid outlet area 400 wherein the main chamber includes at least two flow distribution areas 310 and one reaction area 320 .
  • the liquid inlet area 100, the mixing area 200, the diversion area 310, the reaction area 320 and the liquid outlet area 400 are connected in sequence, so that the sample liquid enters from the liquid inlet area 100, mixes in the mixing area 200, passes through the diversion area 310, and After the reaction in the reaction zone 320 , it flows out from the liquid outlet zone 400 .
  • the microfluidic channel structure is still a four-velocity component structure.
  • the main chamber 300 includes at least two third liquid outlets 302 , and FIG. 7 shows three third liquid outlets 302 as an example.
  • the liquid outlet area 400 includes at least two liquid outlet channels 401 , and FIG. 7 shows three liquid outlet channels 401 as an example. Two symmetrical liquid outlet channels are newly added, and the liquid in the three liquid outlet channels finally flows to the next reaction area together.
  • the purpose of increasing the liquid outlet and the corresponding liquid outlet channel is to further change the flow field in the reaction zone.
  • Fig. 9 is a schematic diagram of another microfluidic flow channel structure according to an embodiment of the present disclosure. Similar to the embodiment in Fig. The chamber 300 and the liquid outlet area 400 , wherein the main chamber includes at least two flow distribution areas 310 and one reaction area 320 .
  • the liquid inlet area 100, the mixing area 200, the diversion area 310, the reaction area 320 and the liquid outlet area 400 are connected in sequence, so that the sample liquid enters from the liquid inlet area 100, mixes in the mixing area 200, passes through the diversion area 310, and After the reaction in the reaction zone 320 , it flows out from the liquid outlet zone 400 .
  • the microfluidic channel structure is still a four-velocity component structure.
  • the first diversion wall 3101 in the diversion area 310 is not an arc-shaped structure, but a broken-line structure, including three broken-line segments connected end to end: the first split-line segment 3101a, the second broken-line segment
  • the two split line segments 3101b and the third split line segment 3101c have an opening for liquid inlet on the fold line segment located in the middle (for example, the second fold line segment 3101b in the figure).
  • the opening can be set on the The middle position of the polyline segment.
  • the adjacent positions of the two distributing areas share a U-shaped structure dividing wall. 3102 is linear, and the length of the second diversion wall 3102 is less than the length of the second diversion wall 3112 in the same diversion area.
  • the second diversion wall far away from the first diversion area 310 in the second diversion area 330 ( Figure middle 3302) is also linear, and the length of the second diversion wall (3302 in the figure) is shorter than the length of the second diversion wall (3312 in the figure) in the same diversion area.
  • the first flow guide wall 3111 in the flow guide structure 311 is not arc-shaped, but a broken line structure, including three broken line segments connected end to end: the first flow guide broken line segment 3111a, the second flow guide broken line segment 3111b and the third guide fold line segment 3111c.
  • the fourth diversion channel is formed between the second diversion folded line segment 3101b and the second diversion fold line segment 3111b
  • the fifth diversion channel is formed between the first diversion fold line segment 3101a and the first diversion fold line segment 3111a
  • the A sixth flow channel is formed between the second flow guide wall 3102 and the second flow guide wall 3112, and the fourth flow channel, the fifth flow channel and the sixth flow channel are connected.
  • the seventh diversion channel is formed between the third diversion fold line segment 3101c and the third diversion fold line segment 3111c
  • the sixth diversion channel is formed between the second diversion wall 3102 and the second diversion wall 3112
  • An eighth distribution channel is formed between 3113 and the third distribution wall 3103, and the fourth distribution channel, the seventh distribution channel and the eighth distribution channel are connected.
  • one path of sample liquid enters the split area from the third liquid inlet port 301, and then passes through the fourth split channel to form two paths.
  • One path of sample liquid enters the reaction area through the fifth split channel and the sixth split channel.
  • Another channel of sample liquid enters the reaction area through the seventh and eighth distribution channels.
  • the first diversion wall and the first flow guide wall are both broken-line structures, and in other embodiments, the first diversion wall and the first guide wall in the same diversion area can be Different shapes are used, for example, in a diversion area, the first diversion wall is arc-shaped, and the first diversion wall is a broken line, or in a diversion area, the first diversion wall is a fold line, and the first diversion wall is an arc shape.
  • the designs of the two flow distribution areas located in the same main chamber can be different, for example, the first flow distribution wall and the first flow guide wall of the first flow distribution area adopt a zigzag structure, and the second flow distribution area in the second flow distribution area adopts a zigzag structure.
  • Both the first diversion wall and the first diversion wall adopt arc-shaped structures; or the first diversion wall and the first diversion wall in the first diversion area adopt different shapes, and the first diversion wall and the first diversion wall in the second diversion area The same shape is adopted; or the first diversion wall and the first diversion wall in the first diversion area adopt the same shape, and the first diversion wall and the first diversion wall in the second diversion area adopt different shapes.
  • a flow guide structure is set in the first flow diversion area, and no flow guide structure is set in the second flow diversion area, or no flow guide structure is set in the first flow diversion area, and a flow guide structure is set in the second flow diversion area .
  • Not all examples are given for other permutations and combinations of the design of the contour structure of the diversion wall and the shape and structure of the diversion structure in the above diversion area.
  • the reaction zone 320 is designed as a conical structure.
  • the reaction zone includes a first reaction wall 321 and a second reaction wall 322 opposite to each other.
  • the first reaction wall 321 includes a first reaction wall subsection 3211 and a second reaction wall subsection 3212 connected in sequence, wherein the first reaction wall subsection 3211 is an arc, the second reaction wall subsection 3212 is a straight line, and the second reaction wall subsection 3212 is a straight line.
  • Wall 322 includes the third reaction wall subsection 3221 and the fourth reaction wall subsection 3222 connected in sequence, wherein the third reaction wall subsection 3221 is an arc, the second reaction wall subsection 3222 is a straight line, and the first reaction wall subsection 3211 is opposite to the third reaction wall subsection 3221, and the second reaction wall subsection 3212 is opposite to the fourth reaction wall subsection 3222.
  • the reaction zone formed by the first reaction wall 321 and the second reaction wall 322 is in the shape of a truncated cone.
  • the second reaction wall subsection 3212 and the fourth reaction wall subsection 3222 extend in the same direction, the second reaction wall subsection 3212 is vertically connected to the first liquid outlet wall 401, and the fourth reaction wall subsection 3222 is connected to the second reaction wall subsection 3222.
  • the outlet walls 402 are connected vertically.
  • the value range of the angle ⁇ between the second reaction wall subsection 3212 and the first liquid outlet wall 401 may be greater than 90 degrees and less than 180 degrees. From the entrance of the reaction zone to the exit of the reaction zone, the width of the reaction channel gradually decreases.
  • the reaction zone 320 includes a first reaction wall 321 and a second reaction wall 322.
  • the first reaction wall 321 and the second reaction wall 322 are arc-shaped, and one end of the first reaction wall 321 is connected to a split flow area.
  • the second diversion wall 3102 of 310 is connected to one end away from the first diversion wall 3101 (in the figure, the end of the first diversion broken line segment 3101a away from the second diversion broken line segment 3101b) is connected, and the other end is connected to the first outlet of the liquid outlet area.
  • the liquid wall 401 is connected, and one end of the second reaction wall 322 is connected with an end of the second split wall 3102 of the other split area 330 away from the first split wall 3101, and the other end is connected with the second liquid outlet wall 402 of the liquid outlet area. connect.
  • the front end of the main chamber 300 has a double liquid inlet structure, and the rear end has an arc-shaped single liquid outlet structure.
  • the sample liquid passes through the liquid inlet area, after passing through the two symmetrical multiple curved flow channel structure mixing areas, it enters the two split flow areas from the two inlets with curved structures, and each sample liquid is divided into two again, and finally Forming four velocity components, it can be seen that the structure of the microfluidic channel in this embodiment is still a structure of four velocity components.
  • the diversion area adopts a linear diversion structure
  • the reaction area adopts a frustum-shaped structure and an arc shape as the area outline, which can reduce the flow stagnation area and low flow caused by the inwardly extending channel structure of the arc profile.
  • the area of the "dead volume" area of the flow rate improves the sample utilization rate.
  • Fig. 10 is a schematic diagram of another microfluidic channel structure according to an embodiment of the present disclosure. Similar to the embodiment in Fig. The chamber 300 and the liquid outlet area 400 , wherein the main chamber includes at least two flow distribution areas 310 and one reaction area 320 .
  • the liquid inlet area 100, the mixing area 200, the diversion area 310, the reaction area 320 and the liquid outlet area 400 are connected in sequence, so that the sample liquid enters from the liquid inlet area 100, mixes in the mixing area 200, passes through the diversion area 310, and After the reaction in the reaction zone 320 , it flows out from the liquid outlet zone 400 .
  • the difference from the embodiment in FIG. 2 is that in this embodiment, two adjacent flow distribution areas share one flow distribution channel, that is, the structure of the microfluidic channel in this embodiment is a three-velocity component structure.
  • the first flow divider area 310 includes a first flow divider wall 3101 and a second flow divider wall 3102 connected to one end of the first flow divider wall 3101, wherein,
  • the first dividing wall 3101 is arc-shaped.
  • the second dividing wall 3102 is designed as a U-shaped structure. One end of the U-shaped structure is connected to the first dividing wall 3101, and the other end is used to connect with the reaction zone. Reaction wall connection.
  • the first flow guide structure 311 in the first flow diversion area 310 includes a first flow guide wall 3111, a second flow guide wall 3112 and a third flow guide wall 3113, wherein the first flow guide wall 3111 is opposite to the first flow guide wall 3101 and It is provided that the first flow distribution channel is formed, and the second flow guide wall 3112 is arranged opposite to the second flow distribution wall 3102 to form the second flow distribution channel.
  • the second splitter area 330 includes a first splitter wall (3301 in the figure), a second splitter wall (3302 in the figure) connected to one end of the first splitter wall (3301 in the figure), wherein the first splitter wall (3301 in the figure) ) is arc-shaped, in this embodiment, the second splitter wall (3302 in the figure) is designed as a U-shaped structure, one end of the U-shaped structure is connected with the first splitter wall (3301 in the figure), and the other end is used for Connected to the reaction wall of the reaction zone.
  • the first diversion structure (331 in the figure) in the second diversion area 330 includes a first diversion wall (3311 in the figure), a second diversion wall (3312 in the figure) and a third diversion wall (3313 in the figure) , wherein the first diversion wall (3311 in the figure) is opposite to the first diversion wall (3301 in the figure), forming the first diversion channel, the second diversion wall (3312 in the figure) and the second diversion wall (3301 in the figure) 3302) opposite each other to form a second shunt channel.
  • the first diversion wall 3101 of the first diversion area is connected to the first diversion wall (3301 among the figures) of the second diversion area, and the third diversion wall 3113 of the first diversion area is connected to the third diversion wall (3301) of the second diversion area. 3313) in the figure form a third shunt channel, which is connected with the first shunt channel of the first shunt area and the second shunt channel of the second shunt area respectively, so that two adjacent shunt areas share one Shunt channel.
  • the first divider wall 3101 of the first divider region 310 is connected to the first divider wall 3301 of the second divider region 330 , and the divider walls 3101 and 3301 form an integral structure, for example, the first divider region 310
  • One end of the first dividing wall 3101 away from the second dividing wall 3102 in the first dividing area is connected to an end of the first dividing wall 3301 in the second dividing area 330 away from the second dividing wall 3302 in the second dividing area.
  • the first dividing wall (3101 and 3301) in each dividing area is provided with an opening for liquid inlet.
  • the opening can be arranged in the middle of the first dividing wall.
  • Fig. 11 is a schematic diagram of another microfluidic flow channel structure according to an embodiment of the present disclosure. Similar to the embodiment in Fig. 10, the microfluidic flow channel structure in this embodiment includes a liquid inlet area 100 and at least two mixing areas 200. The chamber 300 and the liquid outlet area 400 , wherein the main chamber includes at least two flow distribution areas 310 and one reaction area 320 . The liquid inlet area 100, the mixing area 200, the diversion area 310, the reaction area 320 and the liquid outlet area 400 are connected in sequence, so that the sample liquid enters from the liquid inlet area 100, mixes in the mixing area 200, passes through the diversion area 310, and After the reaction in the reaction zone 320 , it flows out from the liquid outlet zone 400 .
  • openings are opened on the second diversion wall 3102 of the U-shaped structure in the diversion area, which can increase the velocity component of one path.
  • opening an opening on the second flow wall of the U-shaped structure in the second flow area can increase one speed component, so the structure of the microfluidic flow channel in this embodiment is a five-velocity component structure.
  • both the first flow distribution area and the second flow distribution area are provided with openings, and in other embodiments, openings may be provided only on the second flow distribution wall of one flow distribution area.
  • openings on the second dividing wall the possibility of setting openings on other dividing walls is not excluded.
  • Fig. 12 is a schematic diagram of another microfluidic channel structure according to an embodiment of the present disclosure. Similar to the embodiment in Fig. 11, the microfluidic channel structure in this embodiment includes a liquid inlet area 100 and at least two mixing areas 200. The chamber 300 and the liquid outlet area 400 , wherein the main chamber includes at least two flow distribution areas 310 and one reaction area 320 . The liquid inlet area 100, the mixing area 200, the diversion area 310, the reaction area 320 and the liquid outlet area 400 are connected in sequence, so that the sample liquid enters from the liquid inlet area 100, mixes in the mixing area 200, passes through the diversion area 310, and After the reaction in the reaction zone 320 , it flows out from the liquid outlet zone 400 .
  • the two diversion areas do not have a common diversion channel, That is, the scheme in which the two flow distribution areas share the U-shaped structure flow distribution wall in the embodiment shown in FIG. 2 is adopted.
  • the structure of the microfluidic flow channel is a six-velocity component structure, that is, the sample liquid has six velocity components in the split area.
  • the design of the flow channel structure in the microfluidic chip can enhance the reconstitution effect of the freeze-dried antibody, which is beneficial to the reaction and detection of the double-antibody sandwich immune chip, reduces the reaction time, and improves the detection accuracy.
  • the embodiments herein can be combined with each other without conflict.
  • the structure of the split area shown in Figure 2 can be combined with the structure of the reaction area shown in the embodiment of Figure 9 to form a main chamber; or the structure of the split area shown in Figure 9 can be combined with the structure of the reaction area shown in Figure 2 structure or combined with the reaction zone structure shown in Figure 6 as the main chamber; or the shunt zone structure shown in Figure 10 can be combined with the reaction zone structure shown in Figure 6 or with the reaction zone structure shown in Figure 9 as the main chamber; or,
  • the diversion zone structure shown in Figure 11 can be combined with the reaction zone structure shown in Figure 6 or with the reaction zone structure shown in Figure 9 as the main chamber; or the diversion zone structure shown in Figure 12 can be combined with the reaction zone structure shown in Figure 6 or with the reaction zone structure shown in Figure 6
  • the structure of the reaction zone shown in Figure 9 is combined with the main chamber.
  • the aforementioned various main chamber structures can be combined with the liquid outlet area structure shown in FIG. 7 .
  • Other permutations and combinations of the internal design and outer contour structure design of the diversion area, the reaction area, and the liquid outlet area in the above-mentioned flow channel design are not fully listed.
  • An embodiment of the present disclosure also provides a microfluidic chip comprising the microfluidic channel structure described in any one of the above embodiments. There may also be other channel structures in the microfluidic chip, which is not limited herein.
  • the antigen P to be tested has two epitopes A and B, and there are two corresponding antibodies a and b that can be Specifically combined with it, arbitrarily or through selection, a can be chemically or physically fixed on the surface of the chip detection area (the inner surface of the main chamber reaction area of the microfluidic channel structure), and then will contain the antigen P to be tested.
  • the sample liquid in the main chamber has a greater velocity gradient change, direction change and greater flow shear, so that the freeze-dried antibody can be better reconstituted , improve the reconstitution speed of freeze-dried antibodies in the reaction area, improve the immediacy of microfluidic chips, increase the reconstitution amount of freeze-dried antibody samples, improve the accuracy and precision of test results, and improve the throughput of immunoassays , and reduce the amount of retained samples in the reaction area to improve the antigen-antibody reaction efficiency in the fluorescent immune chip, improve the utilization rate of samples, and improve the accuracy and effectiveness of detection.
  • connection should be understood in a broad sense, for example, it can be a fixed connection or a A detachable connection, or an integral connection; it may be a mechanical connection or an electrical connection; it may be a direct connection or an indirect connection through an intermediary, and it may be an internal communication between two components.
  • installation can be a fixed connection or a A detachable connection, or an integral connection; it may be a mechanical connection or an electrical connection; it may be a direct connection or an indirect connection through an intermediary, and it may be an internal communication between two components.

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Abstract

一种微流控流道结构及微流控芯片。微流控流道结构包括主腔室(300)，主腔室(300)包括至少两个分流区(310,330)和一个反应区(320)，至少两个分流区(310,330)分别与反应区(320)连接，其中：每个分流区(310,330)包括第一分流壁(3101,3301)，第一分流壁(3101,3301)上开设有用于进液的开口；至少一个分流区(310,330)的开口处设置有导流结构(311,331)，导流结构(311,331)至少包括第一导流壁(3111,3311)，第一导流壁(3111,3311)与第一分流壁(3101,3301)相对设置，第一导流壁(3111,3311)与第一分流壁(3101,3301)之间形成第一分流通道，开口作为第一分流通道的进液口，第一分流通道包括至少两个出液口。

Description

微流控流道结构及微流控芯片 技术领域
本公开实施例涉及但不限于微流控技术领域，具体涉及一种微流控流道结构及微流控芯片。
背景技术
微流控芯片(Microfluidic Chip)是本世纪一项重要的科学技术。美国《Business 2.0》杂志封面文章曾将微流控芯片列为改变世界的七种技术之一。它能够在一块几平方厘米的芯片上构建化学或生物实验室。它把生物和化学领域中涉及的多种反应和流程集成到一起，通过芯片上的微通道网络，以可控流体来实现各种想要的功能。
由于微流控芯片具有微结构特征，其在进液过程中容易出现样本分布不均，出现样本滞留等问题，从而影响样本利用率和检测准确性和精度。
发明内容
以下是对本文详细描述的主题的概述。本概述并非是为了限制权利要求的保护范围。
本公开实施例提供了一种微流控流道结构，包括主腔室，所述主腔室包括至少两个分流区和一个反应区，所述至少两个分流区分别与反应区连接，其中：
每个分流区包括第一分流壁，所述第一分流壁上开设有用于进液的开口；
至少一个分流区的所述开口处设置有导流结构，所述导流结构至少包括第一导流壁，所述第一导流壁与所述第一分流壁相对设置，所述第一导流壁与所述第一分流壁之间形成第一分流通道，所述开口作为所述第一分流通道的进液口，所述第一分流通道包括至少两个出液口。
本公开实施例提供了一种包括上述流道结构的微流控芯片。
当然，实施本公开的任一产品或方法并不一定需要同时达到以上所述的所有优点。本公开的其它特征和优点将在随后的说明书实施例中阐述，并且，部分地从说明书实施例中变得显而易见，或者通过实施本公开实施例而了解。本公开实施例的目的和其他优点可通过在说明书、权利要求书以及附图中所特别指出的结构来实现和获得。
在阅读并理解了附图和详细描述后，可以明白其他方面。
附图说明
附图用来提供对本公开技术方案的进一步理解，并且构成说明书的一部分，与本公开的实施例一起用于解释本公开的技术方案，并不构成对本公开技术方案的限制。附图中部件的形状和大小不反映真实比例，目的只是示意说明本公开内容。
图1为本公开实施例提供一种微流控流道结构示意图；
图2为本公开实施例一种微流控流道结构的示意图；
图3a为图2所示微流控流道结构中一个分流区示意图；
图3b为图2所示微流控流道结构中主腔室示意图；
图4a为图2所示流道结构主腔室的流速分布仿真结果；
图4b为相关技术结构的流速分布仿真结果；
图5a为图2所示流道结构主腔室反应区的剪切力分布仿真结果；
图5b为相关技术结构的反应区剪切力分布仿真结果；
图6为本公开实施例另一种微流控流道结构的示意图；
图7为本公开实施例另一种微流控流道结构的示意图；
图8为图7所示流道结构主腔室的流速分布仿真结果；
图9为本公开实施例另一种微流控流道结构的示意图；
图10为本公开实施例另一种微流控流道结构的示意图；
图11为本公开实施例另一种微流控流道结构的示意图；
图12为本公开实施例另一种微流控流道结构的示意图。
具体实施方式
以下实施例用于说明本公开，但不用来限制本公开的范围。需要说明的是，在不冲突的情况下，本公开中的实施例及实施例中的特征可以相互任意组合。
本公开实施例提供的微流控流道结构中，涉及的‘厚度’，即是指沿垂直于上下基板平面(或平板芯片的上下两侧表面)方向的尺寸。本公开实施例中，涉及的部分结构的‘长度方向’，是指液体主体走向的方向，某部分结构的‘长度’，是指该部分结构沿液体主体走向方向上的尺寸。相应地，‘宽度方向’，是指垂直于液体主体走向的方向，某部分结构的‘宽度’，即是指该部分结构沿垂直于液体主体走向的方向上的尺寸。
芯片免疫分析技术是一种将抗原抗体结合反应的特异性与电子芯片高密度集成原理相结合产生的一种全新概念的生物检测技术，是将几个、几十个，甚至几万个或更高数量的抗原(或抗体)高密度排列在一起制成芯片，与患者待检样品与生物标本同时进行反应，可一次获得芯片中所有已知抗原(或抗体)的检测结果的高通量取得生物信息的先进检测方法，具有通量高、快速、操作简便、自动化程度高等优点。根据载体不同，可分为：平板芯片、微球芯片、液体芯片；根据实验原理不同，可分为：双抗体夹心法免疫芯片、间接法免疫芯片、竞争法免疫芯片、免疫-PCR芯片；根据检测方法不同，可分为：酶标免疫芯片、放射性同位素免疫芯片、荧光免疫芯片、金标免疫芯片。
其中，双抗体夹心免疫芯片法是一种常用的免疫检测方法。为此开发的荧光免疫分析芯片是利用抗体与抗原结合的特异性即免疫反应来构建的蛋白芯片。将捕获蛋白和检测蛋白分别预埋在芯片上，形成蛋白质的微阵列，实现标志物的多联检。借助荧光检测系统对标记物进行检测，只需一次成像，由软件自动分析、打印结果。小型便携化的设计，使其具有非常广泛的应用场景。
相关技术中，双抗体夹心免疫芯片法的基本反应流程为，首先将待检测 样本从进样口进入，经过第一个混匀区后进入第一个反应区，会与第一个反应区对应的玻璃模块上预埋的冻干荧光抗体反应，使抗体复溶，抗原与抗体特异性结合，之后经过第二个混匀区后，样本中的抗原与荧光抗体充分反应，当此抗原抗体对到达第二个反应区时，与第二个反应区对应的玻璃模块上接枝的捕获抗体反应，形成双抗夹心，反应完成后从芯片的进样口泵入缓冲液，对反应后的区域进行冲洗，清洗掉没有被捕获的荧光抗体，废液流入废液池。将芯片放置于荧光显微镜下进行光学信号检测，以此来判断样本中抗原的含量。
然而，实施过程中遇到的主要问题是第一个反应区中预埋的冻干抗体不能够有效地复溶，大部分冻干抗体还残留在芯片基板上，没有及时与抗原进行反应，这使得芯片的检出效率和准确度达不到预期的要求，另外样本和抗体都没有得到充分利用，形成浪费。
为此，本公开实施例提供一种微流控流道结构，如图1所示，包括主腔室，所述主腔室包括至少两个分流区和一个反应区，所述至少两个分流区分别与反应区连接，其中：
每个分流区包括第一分流壁，所述第一分流壁上开设有用于进液的开口；
至少一个分流区的所述开口处设置有导流结构，所述导流结构至少包括第一导流壁，所述第一导流壁与所述第一分流壁相对设置，所述第一导流壁与所述第一分流壁之间形成第一分流通道，所述开口作为所述第一分流通道的进液口，所述第一分流通道包括至少两个出液口。
例如，进液口可以位于第一分流通道的任意位置，通过第一导流壁的位置的设定可以改变第一分流通道进液口的位置，例如，可以设置第一导流壁的约中部位置对应第一分流壁的开口，此时第一分流通道的进液口位于第一分流通道的中部，第一分流通道两端的开口可以作为第一分流通道的出液口。
可选地，第一导流壁还可以开设开口，该第一导流壁上的开口可以作为第一分流通道的出液口，使得第一分流通道具有更多的出液口。更多的出液口可以形成更多的速度分量。
该第一分流通道可以实现将进入分流区的一路液体分流为至少两路，形 成至少两路速度分量。通过在主腔室设置分流区，并在至少一个分流区内设置导流结构，可以增加进入反应区的样本液体的速度分量，增加反应区的流动扰动和局部剪切，可以更好的帮助抗体复溶，提高复溶量，提高检测的准确性和精度。
可选地，第一分流壁可以与第一导流壁平行设置，即第一分流通道不同位置的宽度基本相同；或者第一分流壁可以与第一导流壁可不平行设置，当不平行设置时，第一导流壁的一侧与第一分流壁之间的距离小于第一导流壁的另一侧与第一分流壁之间的距离(垂直于液体流动方向上的距离)，即沿液体流动方向，第一分流通道的宽度逐渐变小，或者逐渐变大。
在平行于微流控流道结构的平面上，所述主控室的形状可以是类圆形，或是多边形。
在示例性实施例中，所述至少一个分流区还可包括第二分流壁，所述第一分流壁的一端部与所述第二分流壁连接，所述导流结构还可包括第二导流壁，所述第一导流壁的一端部与所述第二导流壁连接，所述第二导流壁与所述第二分流壁相对设置，所述第二导流壁与所述第二分流壁之间形成第二分流通道，所述第二分流通道与所述第一分流通道连通，例如第二分流通道与第一分流通道的第一出液口连通。该第二分流通道可以起到延长第一分流通道的作用，可以对进液进行持续导向，将进液引导至需要的位置。
在示例性实施例中，所述分流区还可包括第三分流壁，所述第一分流壁的远离所述第二分流壁的一端部与所述第三分流壁连接，所述导流结构还包括第三导流壁，所述第一导流壁的远离所述第二导流壁的一端部与所述第三导流壁连接，所述第三导流壁与所述第三分流壁相对设置，所述第三导流壁与所述第三分流壁之间形成第三分流通道，所述第三分流通道与所述第一分流通道连通，例如第三分流通道与第一分流通道的第二出液口连通。该第三分流通道同样可以起到延长第一分流通道的作用，可以对第三分流通道中的液体进行导向，将其引导至需要的位置。
在示例性实施例中，在平行于所述微流控流道结构的平面上，所述第一分流壁呈弧线形或直线形或折线形；所述第一导流壁呈弧线形或直线形或折线形。第一分流壁与第一导流壁的形状可以相同或者可以不同。例如第一分 流壁和第一导流壁均呈弧线形，或者第一分流壁和第一导流壁均呈直线形，或者第一分流壁呈弧线形，第一导流壁呈直线形，或者第一分流壁呈直线形，第一导流壁成弧线形等等。当第一分流壁与第一导流壁均为弧线形时，可以减少进液的阻力，增加流速。
在示例性实施例中，在平行于所述微流控流道结构的平面上，所述第二分流壁呈弧线形或直线形；所述第二导流壁呈弧线形或直线形。第二分流壁与第二导流壁的形状可以相同或者可以不同。例如第二分流壁和第二导流壁均呈弧线形，或者第二分流壁和第二导流壁均呈直线形，或者第二分流壁呈弧线形，第二导流壁呈直线形，或者第二分流壁呈直线形，第二导流壁成弧线形。沿液体流动方向，第二分流通道的宽度可以不变，或者逐渐变小，或者逐渐变大。在其他示例性实施例中，所述第二分流壁可为折线形，所述第二导流壁可为折线形。
在示例性实施例中，在平行于所述微流控流道结构的平面上，所述第三分流壁呈弧线形或直线形；所述第三导流壁呈弧线形或直线形。第三分流壁与第三导流壁的形状可以相同或者可以不同。例如第三分流壁和第三导流壁均呈弧线形，或者第三分流壁和第三导流壁均呈直线形，或者第三分流壁呈弧线形，第三导流壁呈直线形，或者第三分流壁呈直线形，第三导流壁成弧线形。沿液体流动方向，第三分流通道的宽度可以不变，或者逐渐变小，或者逐渐变大。在其他示例性实施例中，所述第三分流壁可为折线形，所述第三导流壁可为折线形。
在示例性实施例中，在平行于所述微流控流道结构的平面上，所述第二分流壁的截面为U字形(如图2所示实施例)，在其他实施例中，该第二分流壁的截面形状还可以为其他形状，例如直线形。该第二分流壁可以与反应区侧壁连接，U字形第二分流壁的一端部可以与第一分流壁连接，另一端部可以与反应区侧壁(以下称为反应壁)连接。
以主腔室包含两个分流区为例，第一分流区的第二分流壁的一端部与同一分流区的第一分流壁连接，另一端部与反应区的反应壁连接。第二分流区的第二分流壁的一端部与同一分流区的第一分流壁连接，另一端部与反应区的另一反应壁连接。当主腔室包括三个或三个以上分流区时，多个分流区可 以相邻设置，相邻设置的多个分流区中最靠外侧的两个分流区与反应区的连接同上述第一分流区和第二分流区。
在示例性实施例中，对于相邻的任意两个分流区，其中：第一分流区的第三分流壁与第二分流区的第三分流壁可以共用同一分流壁结构，所述分流壁结构朝向所述第一分流区的一侧作为所述第一分流区的第三分流壁，所述分流壁结构远离第一分流区的一侧即朝向所述第二分流区的一侧作为所述第二分流区的第三分流壁。
例如，在平行于所述微流控流道结构的平面上，所述分流壁结构的截面形状为U形，U形结构的一侧作为第一分流区的第三分流壁，该侧端部与第一分流区的第一分流壁连接，U形结构的另一侧作为第二分流区的第三分流壁，该侧端部与第二分流区的第一分流壁连接，如下文中图2、图6、图7、图9、图12所示实施例。
在示例性实施例中，相邻的两个分流区可以共用一分流通道，例如，对于相邻的任意两个分流区：第一分流区的第一分流壁的一端部与第二分流区的第一分流壁的一端部连接，第一分流区的第一分流壁的另一端部与第一分流区的第二分流壁连接，第二分流区的第一分流壁的另一端部与第二分流区的第二分流壁连接第一分流区的第一分流壁与第二分流区的第一分流壁连接；所述至少两个分流区的导流结构还包括第三导流壁，所述第一导流壁远离所述第二导流壁的一端部与所述第三导流壁连接；所述第一分流区的第三导流壁与所述第二分流区的第三导流壁之间形成第三分流通道，所述第三分流通道与所述第一分流区的第一分流通道连通，以及与所述第二分流区的第一分流通道连通。此时，第一分流区与第二分流区共用第三分流通道。如下文中图10、图11所示实施例。
在示例性实施例中，所述第二分流壁上可以开设有开口。该开口可用于增加速度分量。如下文中图11、图12所示实施例。
在示例性实施例中，所述反应区包括第一反应壁和第二反应壁，所述第一反应壁和第二反应壁相对而设，形成反应区入口、反应通道和反应区出口，从所述反应区入口到所述反应区出口方向，所述反应区通道的宽度逐渐减小。第一反应壁、第二反应壁与不同分流区的第一分流壁可以共同组成主腔室的 外轮廓。
在示例性实施例中，在平行于所述微流控流道结构的平面上，所述第一反应壁和第二反应壁呈弧线形，如下文中图2、图7、图10、图11、图12所示实施例；或者，
在平行于所述微流控流道结构的平面上，所述第一反应壁和第二反应壁呈直线形，如下文中图6所示实施例，在其他实施例中，所述第一反应壁和第二反应壁可以呈折线形；或者，
在平行于所述微流控流道结构的平面上，所述第一反应壁包括依次连接的至少两个反应壁子段，其中至少一个反应壁子段呈弧线形，至少一个反应壁子段呈直线形；所述第二反应壁包括依次连接的至少两个反应壁子段，其中至少一个反应壁子段呈弧线形，至少一个反应壁子段呈直线形，例如下文中图9所示实施例。
在示例性实施例中，所述微流控流道结构还包括至少两个混匀区，每个混匀区与至少一个分流区连接；每个所述混匀区包括进液端、混匀流道和出液端；所述至少两个混匀区的进液端连通，每个混匀区的出液端与一个分流区的第一分流壁上的所述开口连通。
在示例性实施例中，所述混匀通道为蛇形通道，或者可以是其他有利于混匀的通道形状。
在示例性实施例中，所述微流控流道结构还包括出液区，所述出液区包括一个或多个出液通道，每个出液通道与所述反应区连接。当出液区包括多个出液通道时，通过增加出液区的出液通道可以达到增加速度梯度变化、方向变化和增强流动剪切的作用，如下文中图7所示实施例。
本公开实施例设计了一种微流控流道结构，该结构通过增加反应区来流速度分量，增加流动扰动和抗体预埋区的局部剪切来更好帮助抗体复溶。一方面提高了反应区冻干抗体的复溶速度，缩短反应时间，使芯片的即时性更高；并且增加了冻干抗体样品的复溶量，提高了检测的准确性和精度，提高了免疫检测通量。另一方面，减少反应区滞留样本量，提高样本利用率。
图2为本公开实施例一种微流控流道结构的示意图，该微流控流道结构可以是由第一基板和第二基板对盒形成的腔体，该微流控流道结构被划分成多个功能区，如图2所示，该微流控流道结构包括进液区100，至少两个混匀区200、主腔室300和出液区400，其中，主腔室包括至少两个分流区(如图2所示310和330)以及一个反应区320。进液区100、混匀区200、分流区310、反应区320和出液区400依次相连，使得样本液体从进液区100进入，在混匀区200混匀、通过分流区310分流、在反应区320发生反应后，从出液区400流出。
在本示例中进液区100和出液区400均为直线型通道，通道的宽度范围为0.6mm至1.0mm，例如为0.8mm，通道的长度可根据需要设定。进液区100与混匀区200的入口连接，进液区100可以具有第一进液端101和第一出液端102；
每个混匀区200包括一个第二进液端201，一个第二出液端202和混匀流道，每个第二进液端202与第一出液端102连接，本示例中，混匀流道采用多重弯道设计或称为蛇形流道设计，有利于有效混匀，在其他实施例中可以采用其他有利于混匀的流道结构，本文对此不做限制；为了简化结构，可以不改变进液区通道宽度，并且可以将多个第二进液端201进行连通设计，如图2所示，第一出液端202分别与两个混匀区的两个第二进液端201连接，两个第二进液端201相对设置，第一出液端沿垂直方向设置，三个端口呈类T字形排列。在本示例中，通过设置两个混匀区200将流入的样品液体分为两路(见图中第二进液端口处黑色箭头所示)，可实现对样本液体的第一次分流。三个端口的排列方式可以采用其他形状，本文对此不做限制，只要能实现分流即可。虽然本实施例以两个混匀区为例进行说明，但本领域技术人员可知，在其他实施例中，混匀区可以设置为多个。
主腔室300包括至少两个分流区310以及与分流区310连接的反应区320，分流区310与混匀区200一一对应连接；主腔室300包括至少两个第三进液端301和第三出液端302，第三进液端301位于分流区310，每个第三进液端301与一个第二出液端202连接，第三出液端302位于反应区320，第三出液端302与出液区400连接；在本示例中，第三进液端301与第二出液端202 的一一对应，分流区310与混匀区200的一一对应(数量相同)。样本液体经第三进液端301进入分流区310，经导流后进入反应区320。
在本示例中，为保证样本液体进入分流区的方向和位置，第三进液端301处通道为弯折结构设计，每个第三进液端301包括相连的第一支路3011和第二支路3012，第一支路3011与第二支路3012弯折连接，也就是说第一支路与第二支路之间具有大于0度小于180度的夹角(图2中α)。第一支路3011的一端部与一个混匀区200的一个第二出液端202相连，另一端部与第二支路3012连接，第二支路3012的一端部与第一支路3011相连，另一端部与分流区310连接。可选地，可以设置第二支路的延伸方向和与该第二支路连接的分流区侧壁方向或分流区侧壁的切面方向呈90度±5度(见图3a中β)。
在每个分流区中，第三进液端301的端口处设置有导流结构311，将从第三进液端301的进入的一路样本液体导流为两路，即通过导流结构实现对样本液体的第二次分流，经过两次分流后的样本液体从一个速度分量变为4个速度分量，可以增强流动剪切和速度扰动，从而使冻干抗体能够更好的复溶。在本示例中，主腔室具有两个第三进液端301，在每个第三进液端的端口处均设置导流结构311，则可将进入主腔室的两路样本液体导流为四路(见图中分流区中黑色箭头所示)，即可形成四个流速度分量。当微流控流道结构对称时，每路流速度分量的速度可能相同。
图3a以一个分流区310为例说明分流区内的结构，分流区330的结构与分流区310的结构相同，在本示例中，分流区310包括第一分流壁3101，与第一分流壁3101一端部连接的第二分流壁3102，以及与第一分流壁3101另一端部连接的第三分流壁3103，其中，第一分流壁3101为弧线形，在本实施例中，如图3a所示，第二分流壁3102和第三分流壁3103设计为U形结构，U形结构的一端部与第一分流壁3101连接，另一端部用于与反应区的反应壁(321或322)连接，第一分流壁3101上开设有用于进液的开口(该开口与第三进液端301连接)，可选地，该开口可以设置与第一分流壁3101的中间位置。在其他实施例中，第二分流壁3102和第三分流壁3103可以为其他形状，例如可以为直线形。
在图2所示示例中，两个分流区相邻设置，可以共用一U形结构分流壁， 如图2所示，图中U形结构分流壁3103的靠近第一分流区310的一侧作为第一分流区310的第三分流壁3103，U形结构分流壁3103的靠近第二分流区330的一侧作为第二分流区330的第三分流壁3303。
在本示例中，导流结构311包括第一导流壁3111，与第一导流壁3111一端部连接的第二导流壁3112，以及与第一导流壁3111另一端部连接的第三导流壁3113，其中第一导流壁3111可以与第一分流壁3101类似，为弧线形，例如，第一导流壁3111的半径范围可以为2mm-6mm，例如为4mm。在其他实施例中，第一导流壁可以为直线形或折线形，第二导流壁3112和第三导流壁3113均为直线形。第一导流壁3111与第一分流壁3101之间形成一第一分流通道(弧形通道)，第一导流壁3111与第一分流壁3101之间的距离D1即第一分流通道的宽度可以与其他位置通道宽度类似，均值范围可以为0.6mm-1.0mm，例如可以是0.8mm。第二导流壁3112与第二分流壁3102靠近第二导流壁3112的一侧形成第二分流通道，第三导流壁3113与第三分流壁3103靠近第三导流壁3113的一侧形成第三分流通道，第一分流通道分别与第二分流通道和第三分流通道连接。第二导流壁3112与第二分流壁3102靠近第二导流壁3112一侧之间的距离D2(即第二分流通道的宽度)，可以与第三导流壁3113与第三分流壁3103靠近第三导流壁3113一侧之间的距离D3(即第三分流通道的宽度)相同，D2和D3的取值范围为0.6mm-1.0mm，例如0.8mm。
以图3a所示一个分流区为例，一路样本液体从第三进液端301进入分流区后，经过第一分流通道形成两路，一路样本液体通过第二分流通道进入反应区，另一路样本液体通过第三分流通道进入反应区。
在示例性实施例中，第二分流壁3102和第三分流壁3103可以是复用整个主腔室的侧壁，即如图2和图3a所示，U形第二分流壁3102和第三分流壁3103同时也是主腔室300侧壁的一部分。U形第二分流壁3102的延伸方向与第二导流壁3112的延伸方向相同，U形第二分流壁3102向主腔室内部延伸的深度L1的范围可以为2.0mm-2.8mm，例如为2.4mm，U形结构的开口距离L2的范围可以为0.2mm-0.6mm，例如为0.4mm。可选地，U形第二分流壁3102向主腔室内部延伸的边缘与第二导流壁3112向主腔室内部延伸 的边缘在同一平面(图中M)上。同样地，U形第三分流壁3103的延伸方向与第三导流壁3113的延伸方向相同，U形第三分流壁3103向主腔室内部延伸的深度范围可以为2.0mm-2.8mm，例如为2.4mm，U形结构的开口距离的范围可以为0.2mm-0.6mm，例如为0.4mm。可选地，第三分流壁3103向主腔室内部延伸的边缘与第三导流壁3113向主腔室内部延伸的边缘在同一平面(图中N)上。
在其他实施例中，如图3b所示，可以在主腔室内部设置凸起结构312，可作为分流区的侧壁，用于为样本液体提供通道。
在本实施例中，四路液体样本进入反应区320，反应区320中预埋有冻干抗体。在示例性实施例中，可将抗体冻干于目标载体上，放置于第一基板的反应区320，再将第二基板与第一基板封装，实现抗体的预埋。通过将预埋的抗体提前冻干到目标载体并封装于反应区，相比直接冻干到检测芯片上的方式，可以有效减少抗体试剂在检测芯片上的残留，并且防止了冻干后的抗体试剂被破坏。目标载体的大小可以为但不限于矩形，且尺寸略小于反应区320的尺寸，这样，在封装时可以直接将目标载体放进第一基板与第二基板的夹层中，冻干的第一抗体不会受到破坏，且在复溶的时候，第一抗体不会残留在检测芯片上。
在本示例中，反应区320设计为类半圆形结构，从反应区入口到反应区出口方向，所述第一反应壁与所述第二反应壁之间的距离即反应通道的宽度逐渐减小，可以为充分反应提供了预留的空间和时间。反应区320包括第一反应壁321和第二反应壁322，第一反应壁321和第二反应壁322相对而设，形成反应区入口、反应通道和反应区出口。在本示例中，第一反应壁321和第二反应壁322均为圆弧形，第一反应壁321的一端部与一个分流区310的第二分流壁3102的一端部连接，另一端部与出液区的第一出液壁401连接，第二反应壁322的一端部与另一个分流区(图中330)的第二分流壁3302的一端部连接，另一端部与出液区的第二出液壁402连接。
在本示例中，两个分流区的第一分流壁3101均为圆弧形，反应区的第一反应壁321和第二反应壁322也为圆弧形，若干圆弧组成的主腔室为类圆形，该类圆形的外径范围可以为7.8mm-11.6mm，例如为9.6mm。
本实施例主腔室300前端为双进液口结构，后端为圆弧形单出液口结构。样品液体经过进液区后，通过两个对称的多重弯曲流道结构混匀区后，从两个具有弯折结构的入口分别进入两个分流区，每路样本液体再一分为二，最终形成四个速度分量，进入反应区。在反应区，四路样本液体与预埋的冻干抗体反应，最终反应过后的液体从出液区流出。故本实施例微流控流道结构为四速度分量结构。
在本示例中，整个芯片厚度范围可以为1.0mm-1.4mm，例如为1.2mm，图2中显示的是第一基板上刻蚀的流道结构，整个流道高度范围可以为0.2mm-0.4mm，例如为0.3mm，流道宽度范围可以为0.6mm-1.0mm，例如为0.8mm，例如进液区的流道、混匀区中的流道、分流区中的流道和出液区的流道。
用专业流体仿真软件Ansys Fluent对图2所示结构的实际效果进行模拟评估，并与当前项目中采用的结构进行对比，仿真结果如图4和图5所示。图4a中为本实施例主腔室结构的流速分布情况，图4b为相关技术结构的流速分布情况。图5a为本实施例主腔室反应区结构的剪切力分布情况，图5b为相关技术结构的反应区剪切力分布情况。根据仿真结果可以看到，用导流结构进行分流后，反应区具有更大的速度梯度变化、方向变化和强度更大的流动剪切，从而使得冻干抗体能够更好地复溶。图5中矩形框部分为冻干抗体预埋区，即包含前述目标载体的区域。
图6为本公开实施例另一种微流控流道结构的示意图，与图2实施例类似，本实施例微流控流道结构包括进液区100、至少两个混匀区200，主腔室300和出液区400，其中主腔室包括至少两个分流区310以及一个反应区320。进液区100、混匀区200、分流区310、反应区320和出液区400依次相连，使得样本液体从进液区100进入，在混匀区200混匀、通过分流区310分流、在反应区320发生反应后，从出液区400流出。本实施例微流控流道结构仍为四速度分量结构。
与图2实施例不同的是，本实施例中，反应区320设计为锥形结构，从反应区入口到反应区出口方向，反应通道的宽度逐渐减小。反应区320包括第一反应壁321和第二反应壁322，在本示例中，第一反应壁321和第二反 应壁322均为直线形，第一反应壁321的一端部与一个分流区310的第二分流壁3102远离第一分流壁3101的一端部连接，另一端部与出液区的第一出液壁401连接，第二反应壁322的一端部与另一个分流区330的第二分流壁(图中3302)远离第一分流壁(图中3301)的一端部连接，另一端部与出液区的第二出液壁402连接。
前宽后窄的反应区结构使得其上预埋的冻干抗体能够受到更大的冲击和剪切，帮助实现抗体复溶，提高反应的效率，进而提高检测的准确性和精度。
本实施例主腔室300前端为双进液口结构，后端为锥形单出液口结构，样品液体经过进液区后，通过两个对称的多重弯曲流道结构混匀区后，从两个具有弯折结构的入口分别进入两个分流区，每路样本液体再一分为二，最终形成四个速度分量，进入锥形反应区。每个分流区的单输入双输出结构，在整体上形成了一个倒分叉结构，而锥形结构的反应区恰好存在于倒分叉结构的出口区域，该区域从结构学和流体力学原理上会比普通的平面区域形成更强的涡流，可以增加局部的流体扰动，从而在结构学层面帮助提高反应效率，进而提高检测的准确度和精度。
图7为本公开实施例另一种微流控流道结构的示意图，与图2实施例类似，本实施例微流控流道结构包括进液区100、至少两个混匀区200，主腔室300和出液区400，其中主腔室包括至少两个分流区310以及一个反应区320。进液区100、混匀区200、分流区310、反应区320和出液区400依次相连，使得样本液体从进液区100进入，在混匀区200混匀、通过分流区310分流、在反应区320发生反应后，从出液区400流出。本实施例微流控流道结构仍为四速度分量结构。
与图2所述实施例不同的是，本实施例中，主腔室300包括至少两个第三出液端302，图7以包括三个第三出液端302为例示出。相应地，出液区400包括至少两个出液通道401，图7以包括三个出液通道401为例示出。新增两个对称的出液通道，三个出液通道中的液体最终共同流到下一个反应区。增加出液端和对应出液通道的目的是为了进一步改变反应区内的流场情况，利用增加分叉分流出口的数量来加强靠近出液区400的速度扰动和流场剪切，该结构产生效果已通过仿真进行验证，如图8所示。
图9为本公开实施例另一种微流控流道结构的示意图，与图2实施例类似，本实施例微流控流道结构包括进液区100、至少两个混匀区200，主腔室300和出液区400，其中主腔室包括至少两个分流区310以及一个反应区320。进液区100、混匀区200、分流区310、反应区320和出液区400依次相连，使得样本液体从进液区100进入，在混匀区200混匀、通过分流区310分流、在反应区320发生反应后，从出液区400流出。本实施例微流控流道结构仍为四速度分量结构。
与图2所述实施例不同的是，分流区310中的第一分流壁3101不是弧线形结构，而是折线形结构，包括三个首尾相连的折线段：第一分流折线段3101a、第二分流折线段3101b和第三分流折线段3101c，在其中位于中间位置的折线段(例如图中第二折线段3101b)上开设有用于进液的开口，可选地，该开口可以设置于该折线段的中间位置。
在本实施例中，与图2示例中相同的是两个分流区相邻位置共用一U形结构分流壁，不同的是，第一分流区310中远离第二分流区330的第二分流壁3102为直线形，且该第二分流壁3102的长度小于同一分流区内第二导流壁3112的长度，同样地，第二分流区330中远离第一分流区310的第二分流壁(图中3302)也为直线形，且该第二分流壁(图中3302)的长度小于同一分流区内第二导流壁(图中3312)的长度。
在本示例中，导流结构311中第一导流壁3111不是弧线形，而是折线形结构，包括三个首尾相连的折线段：第一导流折线段3111a、第二导流折线段3111b和第三导流折线段3111c。
在本示例中，第二分流折线段3101b与第二导流折线段3111b之间形成第四分流通道，第一分流折线段3101a与第一导流折线段3111a之间形成第五分流通道，第二分流壁3102与第二导流壁3112之间形成第六分流通道，第四分流通道、第五分流通道和第六分流通道相连接。对称地，第三分流折线段3101c与第三导流折线段3111c之间形成第七分流通道，第二分流壁3102与第二导流壁3112之间形成第六分流通道，第三导流壁3113与第三分流壁3103之间形成第八分流通道，第四分流通道、第七分流通道和第八分流通道相连接。以一个分流区为例进行说明，一路样本液体从第三进液端301 进入分流区后，经过第四分流通道形成两路，一路样本液体通过第五分流通道和第六分流通道进入反应区，另一路样本液体通过第七分流通道和第八分流通道进入反应区。
在本实施例中，在一个分流区中，第一分流壁和第一导流壁均为折线形结构，在其他实施例中，同一个分流区的第一分流壁和第一导流壁可以采用不同形状，例如在一个分流区中，第一分流壁为弧形，第一导流壁为折线形，或者在一个分流区中，第一分流壁为折线形，第一导流壁为弧形。在其他实施例中，位于同一主腔室内的两个分流区的设计可以不同，例如第一分流区的第一分流壁和第一导流壁均采用折线形结构，第二分流区中的第一分流壁和第一导流壁均采用弧形结构；或者第一分流区内第一分流壁和第一导流壁采用不同形状，第二分流区内第一分流壁和第一导流壁采用相同形状；或者第一分流区内第一分流壁和第一导流壁采用相同形状，第二分流区内第一分流壁和第一导流壁采用不同形状。或者在示例性实施例中，第一分流区内设置导流结构，第二分流区内不设置导流结构，或者第一分流区内不设置导流结构，第二分流区内设置导流结构。关于上述分流区中分流壁轮廓结构设计以及导流结构的形状结构设计的其他排列组合形式未进行全部举例。在示例性实施例中，不排除一个分流区中设置有导流结构，另一个分流区中不设置导流结构的情况。
在本实施例中，反应区320设计为圆台状结构。反应区包括相对而设的第一反应壁321和第二反应壁322。第一反应壁321包括依次连接的第一反应壁子段3211和第二反应壁子段3212，其中第一反应壁子段3211为弧线，第二反应壁子段3212为直线，第二反应壁322包括依次连接的第三反应壁子段3221和第四反应壁子段3222，其中第三反应壁子段3221为弧线，第二反应壁子段3222为直线，第一反应壁子段3211和第三反应壁子段3221相对而设，第二反应壁子段3212和第四反应壁子段3222相对而设。第一反应壁321和第二反应壁322形成的反应区为圆台状。在本示例中第二反应壁子段3212和第四反应壁子段3222延伸方向相同，第二反应壁子段3212与第一出液壁401垂直连接，第四反应壁子段3222与第二出液壁402垂直连接。在其他实施例中，第二反应壁子段3212和第一出液壁401之间的夹角γ的取值范围可 以是大于90度小于180度。从反应区入口到反应区出口方向，反应通道的宽度逐渐减小。反应区320包括第一反应壁321和第二反应壁322，在本示例中，第一反应壁321和第二反应壁322均为弧线形，第一反应壁321的一端部与一个分流区310的第二分流壁3102远离第一分流壁3101的一端部(图中为第一分流折线段3101a远离第二分流折线段3101b的一端部)连接，另一端部与出液区的第一出液壁401连接，第二反应壁322的一端部与另一个分流区330的第二分流壁3102远离第一分流壁3101的一端部连接，另一端部与出液区的第二出液壁402连接。
本实施例主腔室300前端为双进液口结构，后端为圆弧形单出液口结构。样品液体经过进液区后，通过两个对称的多重弯曲流道结构混匀区后，从两个具有弯折结构的入口分别进入两个分流区，每路样本液体再一分为二，最终形成四个速度分量，可见本实施例微流控流道结构仍为四速度分量结构。，本示例中分流区采用了直线型的分流结构，反应区采用了圆台状结构并用弧线形作为区域轮廓，可以减少圆弧形轮廓由于向内延伸的沟道结构造成的流动滞留区、低流速“死体积”区的面积(例如图4a中圆弧形反应区上部和下部的区域)，提高样本利用率。
图10为本公开实施例另一种微流控流道结构的示意图，与图2实施例类似，本实施例微流控流道结构包括进液区100、至少两个混匀区200，主腔室300和出液区400，其中主腔室包括至少两个分流区310以及一个反应区320。进液区100、混匀区200、分流区310、反应区320和出液区400依次相连，使得样本液体从进液区100进入，在混匀区200混匀、通过分流区310分流、在反应区320发生反应后，从出液区400流出。
与图2实施例不同的是，本实施例中，相邻两个分流区共用一个分流通道，即本实施例微流控流道结构为三速度分量结构。
与图2实施例不同的是，本实施例中没有第三分流壁3103，第一分流区310包括第一分流壁3101，与第一分流壁3101一端部连接的第二分流壁3102，其中，第一分流壁3101为弧线形，在本实施例中，第二分流壁3102设计为U形结构，U形结构的一端部与第一分流壁3101连接，另一端部用于与反应区的反应壁连接。第一分流区310中的第一导流结构311包括第一导流壁 3111，第二导流壁3112和第三导流壁3113，其中第一导流壁3111与第一分流壁3101相对而设，形成第一分流通道，第二导流壁3112与第二分流壁3102相对而设，形成第二分流通道。第二分流区330包括第一分流壁(图中3301)，与第一分流壁(图中3301)一端部连接的第二分流壁(图中3302)，其中，第一分流壁(图中3301)为弧线形，在本实施例中，第二分流壁(图中3302)设计为U形结构，U形结构的一端部与第一分流壁(图中3301)连接，另一端部用于与反应区的反应壁连接。第二分流区330中的第一导流结构(图中331)包括第一导流壁(图中3311)，第二导流壁(图中3312)和第三导流壁(图中3313)，其中第一导流壁(图中3311)与第一分流壁(图中3301)相对而设，形成第一分流通道，第二导流壁(图中3312)与第二分流壁(图中3302)相对而设，形成第二分流通道。第一分流区的第一分流壁3101和第二分流区的第一分流壁(图中3301)相连，第一分流区的第三导流壁3113与第二分流区的第三导流壁(图中3313)之间形成第三分流通道，该第三分流通道分别与第一分流区的第一分流通道和第二分流区的第二分流通道连接，以实现相邻两个分流区共用一个分流通道。在图10所述示例中，第一分流区310的第一分流壁3101与第二分流区330的第一分流壁3301连接，分流壁3101与3301形成一整体结构，例如，第一分流区310的第一分流壁3101远离所述第一分流区第二分流壁3102的一端部与第二分流区330的第一分流壁3301远离所述第二分流区第二分流壁3302的一端部连接。
每个分流区中的第一分流壁(3101和3301)上均开设有用于进液的开口，可选地，该开口可以设置与第一分流壁的中间位置。
图11为本公开实施例另一种微流控流道结构的示意图，与图10实施例类似，本实施例微流控流道结构包括进液区100、至少两个混匀区200，主腔室300和出液区400，其中主腔室包括至少两个分流区310以及一个反应区320。进液区100、混匀区200、分流区310、反应区320和出液区400依次相连，使得样本液体从进液区100进入，在混匀区200混匀、通过分流区310分流、在反应区320发生反应后，从出液区400流出。
与图10实施例不同的是，本实施例中，以第一分流区为例，分流区中U形结构的第二分流壁3102上开设开口，可以增加一路速度分量。同样地，在 第二分流区的U形结构的第二分流壁上开设开口，可以增加一路速度分量，则本实施例微流控流道结构为五速度分量结构。
在本实施例中，第一分流区和第二分流区均设置有开口，在其他实施例中，可以只在一个分流区的第二分流壁上设置开口。另外，除了在第二分流壁上设置开口外，不排除在其他分流壁上设置开口的可能。
图12为本公开实施例另一种微流控流道结构的示意图，与图11实施例类似，本实施例微流控流道结构包括进液区100、至少两个混匀区200，主腔室300和出液区400，其中主腔室包括至少两个分流区310以及一个反应区320。进液区100、混匀区200、分流区310、反应区320和出液区400依次相连，使得样本液体从进液区100进入，在混匀区200混匀、通过分流区310分流、在反应区320发生反应后，从出液区400流出。
与图11实施例相同的是，分流区中的U形结构的第二分流壁上开设有开口，以增加一路速度分量，与图11实施例不同的是，两个分流区没有共用分流通道，即采用图2所示实施例中两分流区共用U形结构分流壁的方案。本实施例微流控流道结构为六速度分量结构，即样品液体在分流区有6个速度分量。
综上所述，上述对于微流控芯片中流道结构的设计可以达到增强冻干抗体复溶的效果，利于双抗夹心免疫芯片的反应和检测，降低了反应时间，提高了检测准确性。
本文中实施例在不冲突的情况下，可以相互组合。以分流区为例说明，例如图2中所示分流区结构可以与图9实施例所示反应区结构组合为一个主腔室；或者图9所示分流区结构可以与图2所示反应区结构或与图6所示反应区结构组合为主腔室；或者图10所示分流区结构可以与图6所示反应区结构或与图9所示反应区结构组合为主腔室；或者，图11所示分流区结构可以与图6所示反应区结构或与图9所示反应区结构组合为主腔室；或者图12所示分流区结构可以与图6所示反应区结构或与图9所示反应区结构组合为主腔室。在示例性实施例中，前述多种主腔室结构均可以分别与图7所示出液区结构组合。关于上述流道设计中分流区、反应区以及出液区的内部设计、外轮廓结构设计的其它排列组合形式未进行全部列举。
本公开实施例还提供一种包括上述任一实施例所述的微流控流道结构的微流控芯片。该微流控芯片中还可以有其他流道结构，本文对此不做限制。
以采用本公开实施例的微流道结构实现双抗体荧光免疫夹心法为例，简化地，假定待测抗原P存在两个抗原决定簇A与B，相对应的有两种抗体a与b可与之特异结合，随意的或者经过选择的，可以将a通过化学或者物理方法固定在芯片检测区表面(微流控流道结构的主腔室反应区内表面)，而后将含有待测抗原P的样本流过检测区，部分P将被a捕获而被固定下来，接下来向芯片内通入已被荧光标记的抗体b，抗体b同样可以与P结合，被固定下来的P可以继续捕获抗体b，最后进行清洗(已捕获的抗原、抗体不会被洗掉)，这样通过荧光检测，如果发现存在荧光，及说明样本中含有P。由于本公开实施例的微流控流道结构的设计使得主腔室的样本液体具有更大的速度梯度变化、方向变化和强度更大的流动剪切，使得冻干抗体能够更好地复溶，提高了反应区冻干抗体的复溶速度，提高了微流控芯片的即时性，增加了冻干抗体样品的复溶量，提高了检测结果的精准性和精度，提高了免疫检测通量，并且，减少反应区内滞留样本量来提高荧光免疫芯片中抗原抗体反应效率，提高了样本的利用率，提高检测的精度和有效性。
需要说明的是，本公开实施例所述的微流控流道结构的结构形状和尺寸比例等并不限于上述实施例中的记载，可以根据实际需求进行调整，本公开的实施例对此不作限制。另外，本公开的附图仅用于示意性的说明其结构形状和大概比例，并不对本公开实施例微流控流道结构的尺寸和比例进行限制。
在本公开实施例的描述中，需要理解的是，术语“中部”、“上”、“下”、“前”、“后”、“竖直”、“水平”、“顶”、“底”“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本公开和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本公开的限制。
在本公开实施例的描述中，需要说明的是，除非另有明确的规定和限定，术语“安装”、“相连”、“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接；可以是机械连接，也可以是电连接；可以 是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通。对于本领域的普通技术人员而言，可以根据情况理解上述术语在本公开中的含义。
本公开中的“约”，是指不严格限定界限，允许工艺和测量误差范围内的数值。
虽然本公开所揭露的实施方式如上，但所述的内容仅为便于理解本公开而采用的实施方式，并非用以限定本公开。任何本公开所属领域内的技术人员，在不脱离本公开所揭露的精神和范围的前提下，可以在实施的形式及细节上进行任何的修改与变化，但本公开的专利保护范围，仍须以所附的权利要求书所界定的范围为准。

Claims (17)

  1. 一种微流控流道结构，包括主腔室，所述主腔室包括至少两个分流区和一个反应区，所述至少两个分流区分别与反应区连接，其中：
    每个分流区包括第一分流壁，所述第一分流壁上开设有用于进液的开口；
    至少一个分流区的所述开口处设置有导流结构，所述导流结构至少包括第一导流壁，所述第一导流壁与所述第一分流壁相对设置，所述第一导流壁与所述第一分流壁之间形成第一分流通道，所述开口作为所述第一分流通道的进液口，所述第一分流通道包括至少两个出液口。
  2. 根据权利要求1所述的微流控流道结构，其中，
    所述至少一个分流区还包括第二分流壁，所述第一分流壁的一端部与所述第二分流壁连接，所述导流结构还包括第二导流壁，所述第一导流壁的一端部与所述第二导流壁连接，所述第二导流壁与所述第二分流壁相对设置，所述第二导流壁与所述第二分流壁之间形成第二分流通道，所述第二分流通道与所述第一分流通道连通。
  3. 根据权利要求2所述的微流控流道结构，其中，
    所述分流区还包括第三分流壁，所述第一分流壁的远离所述第二分流壁的一端部与所述第三分流壁连接，所述导流结构还包括第三导流壁，所述第一导流壁的远离所述第二导流壁的一端部与所述第三导流壁连接，所述第三导流壁与所述第三分流壁相对设置，所述第三导流壁与所述第三分流壁之间形成第三分流通道，所述第三分流通道与所述第一分流通道连通。
  4. 根据权利要求3所述的微流控流道结构，其中，
    所述至少两个分流区相邻，对于相邻的任意两个分流区，其中：第一分流区的第三分流壁与第二分流区的第三分流壁共用同一分流壁结构，所述分流壁结构朝向所述第一分流区的一侧作为所述第一分流区的第三分流壁，所述分流壁结构远离第一分流区的一侧作为所述第二分流区的第三分流壁。
  5. 根据权利要求4所述的微流控流道结构，其中，
    在平行于所述微流控流道结构的平面上，所述分流壁结构的截面为U字 形。
  6. 根据权利要求2所述的微流控流道结构，其中，
    所述至少两个分流区相邻，对于相邻的任意两个分流区，其中：第一分流区的第一分流壁的一端部与第二分流区的第一分流壁的一端部连接，第一分流区的第一分流壁的另一端部与第一分流区的第二分流壁连接，第二分流区的第一分流壁的另一端部与第二分流区的第二分流壁连接；
    所述至少两个分流区的导流结构还包括第三导流壁，所述第一导流壁远离所述第二导流壁的一端部与所述第三导流壁连接；
    所述第一分流区的第三导流壁与所述第二分流区的第三导流壁之间形成第三分流通道，所述第三分流通道与所述第一分流区的第一分流通道连通，以及与所述第二分流区的第一分流通道连通。
  7. 根据权利要求1-6中任一项所述的微流控流道结构，其中，
    在平行于所述微流控流道结构的平面上，所述第一分流壁呈弧线形或直线形或折线形；所述第一导流壁呈弧线形或直线形或折线形。
  8. 根据权利要求2-6中任一项所述的微流控流道结构，其中，
    在平行于所述微流控流道结构的平面上，所述第二分流壁呈弧线形或直线形；所述第二导流壁呈弧线形或直线形。
  9. 根据权利要求3-5中任一项所述的微流控流道结构，其中，
    在平行于所述微流控流道结构的平面上，所述第三分流壁呈弧线形或直线形；所述第三导流壁呈弧线形或直线形。
  10. 根据权利要求2-6中任一项所述的微流控流道结构，其中，
    在平行于所述微流控流道结构的平面上，所述第二分流壁的截面为U字形。
  11. 根据权利要求2-6、8-10中任一项所述的微流控流道结构，其中，
    所述第二分流壁上开设有开口。
  12. 根据权利要求1-11中任一项所述的微流控流道结构，其中，
    所述反应区包括第一反应壁和第二反应壁，所述第一反应壁和第二反应 壁相对而设，形成反应区入口、反应通道和反应区出口，从所述反应区入口到所述反应区出口方向，所述反应区通道的宽度逐渐减小。
  13. 根据权利要求12所述的微流控流道结构，其中，在平行于所述微流控流道结构的平面上，
    所述第一反应壁和第二反应壁呈弧线形；或者
    所述第一反应壁和第二反应壁呈直线形或折线形；或者
    所述第一反应壁包括依次连接的至少两个反应壁子段，其中至少一个反应壁子段呈弧线形，至少一个反应壁子段呈直线形；所述第二反应壁包括依次连接的至少两个反应壁子段，其中至少一个反应壁子段呈弧线形，至少一个反应壁子段呈直线形。
  14. 根据权利要求1-13中任一项所述的微流控流道结构，还包括，
    至少两个混匀区，每个混匀区与至少一个分流区连接；
    每个所述混匀区包括进液端、混匀流道和出液端；
    所述至少两个混匀区的进液端连通，每个混匀区的出液端与一个分流区的第一分流壁上的所述开口连通。
  15. 根据权利要求14所述的微流控流道结构，其中，
    所述混匀通道为蛇形通道。
  16. 根据权利要求1-15中任一项所述的微流控流道结构，还包括出液区，
    所述出液区包括一个或多个出液通道，每个出液通道与所述反应区连接。
  17. 一种微流控芯片，包括根据权利要求1至16任一项所述的微流控流道结构。
PCT/CN2022/076863 2022-02-18 2022-02-18 微流控流道结构及微流控芯片 WO2023155142A1 (zh)

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Publication number Priority date Publication date Assignee Title
US20040262223A1 (en) * 2001-07-27 2004-12-30 President And Fellows Of Harvard College Laminar mixing apparatus and methods
CN106492719A (zh) * 2016-10-31 2017-03-15 山东豪迈化工技术有限公司 一种微反应器
CN106492718A (zh) * 2016-10-31 2017-03-15 山东豪迈化工技术有限公司 一种芯片型微反应通道及微反应器
CN110813393A (zh) * 2018-08-08 2020-02-21 苏州含光微纳科技有限公司 改善低流速液体流动界面的结构及免疫微流控芯片
CN113198403A (zh) * 2021-05-10 2021-08-03 南京科技职业学院 一种微通道反应器
CN113786869A (zh) * 2021-09-10 2021-12-14 北京京东方技术开发有限公司 一种检测芯片、设备及方法

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040262223A1 (en) * 2001-07-27 2004-12-30 President And Fellows Of Harvard College Laminar mixing apparatus and methods
CN106492719A (zh) * 2016-10-31 2017-03-15 山东豪迈化工技术有限公司 一种微反应器
CN106492718A (zh) * 2016-10-31 2017-03-15 山东豪迈化工技术有限公司 一种芯片型微反应通道及微反应器
CN110813393A (zh) * 2018-08-08 2020-02-21 苏州含光微纳科技有限公司 改善低流速液体流动界面的结构及免疫微流控芯片
CN113198403A (zh) * 2021-05-10 2021-08-03 南京科技职业学院 一种微通道反应器
CN113786869A (zh) * 2021-09-10 2021-12-14 北京京东方技术开发有限公司 一种检测芯片、设备及方法

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