WO2023019759A1 - Micro-droplet generation device - Google Patents

Micro-droplet generation device Download PDF

Info

Publication number
WO2023019759A1
WO2023019759A1 PCT/CN2021/129697 CN2021129697W WO2023019759A1 WO 2023019759 A1 WO2023019759 A1 WO 2023019759A1 CN 2021129697 W CN2021129697 W CN 2021129697W WO 2023019759 A1 WO2023019759 A1 WO 2023019759A1
Authority
WO
WIPO (PCT)
Prior art keywords
chip
sample
micro
flow channel
layer
Prior art date
Application number
PCT/CN2021/129697
Other languages
French (fr)
Chinese (zh)
Inventor
徐亚骏
郑文山
裴颢
徐云飞
Original Assignee
墨卓生物科技(浙江)有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 墨卓生物科技(浙江)有限公司 filed Critical 墨卓生物科技(浙江)有限公司
Publication of WO2023019759A1 publication Critical patent/WO2023019759A1/en

Links

Images

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip

Definitions

  • the invention relates to the field of biology, in particular to a micro droplet generating device.
  • Micro-droplet technology is a micro-nano technology that uses the interaction between flow shear force and surface tension to divide continuous fluid into discrete droplets of nanoliter and below volume in micro-scale channels.
  • liquid-liquid phase micro-droplets There are two main types of micro-droplets: gas-liquid phase droplets and liquid-liquid phase droplets.
  • the liquid-liquid phase micro-droplets have the advantages of small size, no diffusion between droplet samples, avoiding cross-contamination between samples, stable reaction conditions, and rapid mixing under proper control.
  • Liquid-liquid phase droplets are divided into “oil-in-water”, “water-in-oil”, “oil-in-water-in-oil” and “water-in-oil-in-water” according to the difference between the continuous phase and the dispersed phase.
  • the micro-droplet generation system can generate "water-in-oil” or “oil-in-water” micro-droplets with diameters on the order of microns (ie, 10-1000 ⁇ m), providing high-sensitivity, high-resolution micro-droplets for many application scenarios in the fields of biology, chemistry and materials. Efficient and high-throughput research site.
  • the 96-well plate is a commonly used experimental consumable in the biological field, but the micro-droplet generation device in the prior art is not compatible with the 96-well plate, and cannot directly generate the micro-droplet sample into the 96-well plate. After the micro-droplet generation device generates micro-droplets, it often needs to transfer the micro-droplets to the 96-well plate by other means and tools. The process is complicated and the contamination of the micro-droplet samples is easy to occur during the process. Therefore, it is difficult to use it as an experimental system with high universality in the fields of biology, chemistry and materials.
  • the technical problem to be solved by the present invention is to overcome the poor compatibility between the micro-droplet generating device and the 96-well plate in the prior art, and it is impossible to directly generate the micro-droplet sample into the 96-well plate. After the droplet generation device generates microdroplets, it often needs to transfer the microdroplets to the 96-well plate by other means and tools. .
  • a microdroplet generating device comprising:
  • the generating chip comprising a first compartment and a second compartment, the generating chip can generate liquid samples in the first compartment and the second compartment into micro-droplets;
  • a collection plate is a 96-well plate, and the collection plate includes collection holes;
  • connection base wraps the collection plate
  • connection base includes a chip support
  • the generated chip is placed and limited on the chip support
  • the collection plate is detachably mounted on the connection base seat.
  • the above structure is used to integrate the production chip and the 96-well plate as the collection plate through the connection base, so that the micro-droplets generated by the production chip can be directly collected by the 96-well plate as the collection plate.
  • the collection plate is detachably installed on the connection base, and it is also convenient to disassemble directly after collecting the micro-droplets for subsequent operations. There is no need to transfer the micro-droplets through other means and tools. The process is simple and the micro-droplet samples are not easily polluted during the process.
  • the generation chip includes a discharge tube through which the micro-droplets are discharged, and when the generation chip is placed and limited on the chip holder, the discharge tube extends into the collection hole.
  • the above-mentioned structural form is adopted, and through the limitation of the chip holder, when the generation chip is placed on it, the sample discharge tube can directly extend into the collection hole of the collection plate, so that the generation chip is aligned with the collection plate. At the same time, extending the sampling tube into the collection hole can also reduce the height of the droplet drop, reduce the kinetic energy of the droplet drop, and avoid the impact of the droplet from destroying the structure of the droplet.
  • the generating chip includes a plurality of chip modules
  • the chip module includes a plurality of chip units corresponding to the collection holes one by one, and the plurality of chip units are integrally formed to form a chip module.
  • the generated chip is composed of multiple identical chip modules, and each chip module contains multiple chip units, and each chip unit can generate micro-droplets independently.
  • the number of chip units and the collection corresponds one to one.
  • Each individual chip module is integrally formed, which facilitates the batch processing of the chip modules and reduces the production and maintenance costs of the generated chips.
  • the chip module is formed of thermoplastic or thermosetting material or glass.
  • thermoplastic materials such as thermoplastic materials, thermosetting materials, and glass are easy to process, and the cost is low, further reducing the cost of producing chips.
  • the generating chip includes:
  • sample application layer is arranged on the top of the generation chip, and the first compartment and the second compartment are provided on the sample application layer;
  • a sample layout layer the sample layout layer is arranged at the bottom of the generation chip, the sample layout tube is arranged on the sample layout layer, the top surface of the sample layout layer and the bottom surface of the sample application layer are attached to each other and merged seal;
  • the micro-channel layer, the top surface of the sampling layer and the bottom surface of the sample application layer are attached and sealed to form the micro-channel layer, and the micro-channel layer includes the first compartment and the row
  • the first flow channel communicated with the sample tube, the second flow channel communicated with the second compartment and the first flow channel, the second flow channel is along the vertical direction of the first flow channel and the first flow channel Generate area intersections.
  • the microchannel layer is formed by bonding or pasting the sample loading layer and the sample layout layer. the cost of microdroplet generation.
  • the top surface of the sampling layer and/or the bottom surface of the loading layer are recessed to form a first groove and a second groove, and the first groove and the second groove are connected with the The bottom surface of the sampling layer and/or the top surface of the sampling layer are attached and sealed to each other to form the first flow channel and the second flow channel.
  • the generation chip generates micro-droplets through the first flow channel and the second flow channel, and the first flow channel and the second flow channel are formed by the The grooves on the bottom surface are formed.
  • these grooves become flow channels for the flow and intersection of liquid samples, generating micro-droplets, making the chip highly integrated.
  • the first flow channel sequentially includes along the flow direction of the liquid sample: a first inlet connected to the first compartment, a buffer area, a generation area, and an outlet connected to the sample discharge pipe;
  • the buffer area includes a first extended flow channel and a second extended flow channel extending along the side of the first flow channel, and the first extended flow channel and the second extended flow channel communicate through a bent flow channel, so The first extended channel communicates with the first inlet, and the second extended channel communicates with the generating area.
  • the liquid sample enters the first flow channel from the first inlet through the first compartment, and meets the liquid sample in the second flow channel in the generation area to form micro-droplets, and then self-discharges from the outlet Tube out.
  • the buffer area is an extended section that is bent to one side and then returns to the direction of the original flow channel.
  • a buffer area that is extended to one side is set between the first inlet and the generation area, so that the liquid sample can pass through the flow channel after entering the flow channel. Stabilize in the extended buffer area to make the flow rate and uniformity relatively stable before entering the production area to produce micro-droplets, which can improve the generation effect of micro-droplets.
  • the first extended flow channel and the second extended flow channel are parallel to each other.
  • the above-mentioned structural form is adopted, the first extended flow channel and the second extended flow channel are parallel to each other, the distance between the two can be kept constant and the maximum distance can be maintained, and the sample layer and the sample layer can be bonded or arranged.
  • Packaging by means of adhesive stickers is easier and the packaging effect is better.
  • the sampling tube includes:
  • liquid discharge port is opened on one side of the bottom of the inner cavity
  • a diversion surface the diversion surface is arranged at the bottom of the inner cavity, one end of the diversion surface is against the wall of the cavity, and the other end of the diversion surface is inclined downward and extends to the liquid discharge port.
  • the above-mentioned structural form is adopted, and the sample discharge tube is connected to the outlet of the microchannel layer.
  • the bottom of the cavity flows to the diversion surface, and then slowly flows from the diversion surface to the discharge port to be discharged, which can avoid the direct drop of micro-droplets and excessive impact that may damage the structure of micro-droplets.
  • the sample discharge tube further includes a drainage part, the drainage part is arranged on the cavity wall on the side where the liquid discharge port is opened in the inner cavity, and the drainage part protrudes along the cavity wall. rises and extends toward the drain port, and the projection of the end of the drainage part in the vertical direction is located on the guide surface.
  • the above-mentioned structure is adopted, and a raised drainage part is provided above the cavity wall on the side where the discharge port is opened in the sample discharge tube, and the micro-droplets on the side cavity wall can be guided to the On the diversion surface, the micro-droplets are prevented from flowing directly from the side cavity wall from the liquid discharge port, and the diversion effect of the sample discharge tube is improved.
  • the positive progress effect of the present invention is: through the micro-droplet generation device disclosed in the present invention, the generation chip and the 96-well plate as the collection plate are integrated through the connection base, so that the micro-droplets generated by the production chip can be directly used as Collection plate for 96-well plate collection.
  • the collection plate is detachably installed on the connection base, and it is also convenient to disassemble directly after collecting the micro-droplets for subsequent operations. There is no need to transfer the micro-droplets through other means and tools. The process is simple and the micro-droplet samples are not easily polluted during the process.
  • FIG. 1 is a schematic structural diagram of a micro droplet generating device according to Embodiment 1 of the present invention.
  • FIG. 2 is a schematic diagram of the exploded structure of the micro-droplet generating device according to Embodiment 1 of the present invention.
  • FIG. 3 is a schematic diagram of a partial structure of a connecting base according to Embodiment 1 of the present invention.
  • FIG. 4 is a schematic structural diagram of a chip module according to Embodiment 1 of the present invention.
  • FIG. 5 is a schematic top view of the chip module according to Embodiment 1 of the present invention.
  • FIG. 6 is a schematic diagram of the connection structure between the chip module and the connection base according to Embodiment 1 of the present invention.
  • FIG. 7 is a schematic structural view of the microchannel layer in Example 1 of the present invention.
  • FIG. 8 is a schematic structural view of the microchannel layer in Example 1 of the present invention.
  • FIG. 9 is a schematic structural view of the microchannel layer in Example 1 of the present invention.
  • Fig. 10 is a schematic structural view of the sample-arranging tube according to Embodiment 2 of the present invention.
  • Fig. 11 is a schematic diagram of the internal structure of the sample-discharging tube according to Embodiment 2 of the present invention.
  • Second compartment 142 Second compartment 142
  • the droplet generating device of this embodiment includes a generating chip 1 , a collecting plate 3 and a connection base 2 .
  • the generation chip 1 includes a first compartment 141 and a second compartment 142 , and the generation chip 1 can generate liquid samples in the first compartment 141 and the second compartment 142 into micro-droplets.
  • the collection plate 3 is a 96-well plate, and the collection plate 3 includes collection holes 31 .
  • the connection base 2 wraps the collection plate 3 , the connection base 2 includes a chip holder 21 , the generated chip 1 is placed and limited on the chip holder 21 , and the collection plate 3 is detachably mounted on the connection base 2 .
  • the first compartment 141 and the second compartment 142 of the generation chip 1 are used to inject the water phase liquid and the oil phase liquid respectively.
  • the two compartments are respectively pressurized by a precision air control device, so that the liquid passes through the generation chip 1 to generate "water-in-oil” or “oil-in-water” micro-droplets, which are discharged into the collection hole 31 of the collection plate 3 .
  • the collection plate 3 of this embodiment is a 96-well plate, which is a commonly used experimental consumable in the field of biology.
  • the plate has 8*12 collection holes 31 .
  • the collecting plate 3 can also be composed of several 8-connected tubes.
  • the connecting base 2 of this embodiment is a square frame, and the connecting base 2 can be sleeved on the collecting plate 3 and wrapped around the collecting plate 3.
  • the buckle 22 is detachably fixed to the slot 32 on the collecting plate 3 . Make its connection with the collecting plate 3 more stable.
  • the slots 32 are arranged on both sides of the collecting plate 3
  • the buckles 22 are arranged at corresponding positions on both sides of the connecting base 2 .
  • the buckle 22 is arranged on one end of a connecting plate that can be bent to a certain extent, the other end of the connecting plate is fixed on the side of the connecting base 2, and the back side of the end of the connecting plate provided with the buckle 22 is also provided with a handle portion. Extend to the other end of the connecting plate. By squeezing the handle part, the connecting plate can be bent outwards, so that the buckle 22 is lifted so as to be inserted into or disengaged from the slot 32 of the collecting plate 3 .
  • the chip holder 21 is composed of a plurality of groups of corresponding bumps 211 arranged at intervals on the top of the two opposite sides of the connection base 2.
  • the edge of the chip is clamped in the notch 212 between the two protrusions 211 , and aligned with the collecting plate 3 clamped on the connection base 2 .
  • the connecting base 2 can also be connected with the collecting plate 3 in other ways without sheathing the collecting plate 3, such as making an upper frame structure and installing it on the top surface of the collecting plate 3, or making it into a base structure Put the collecting plate 3 directly into the connection base 2.
  • the chip holder 21 is not limited to the bump 211 and the notch 212 that are arranged on the edge, but also adopts a top surface that is provided with a mounting groove on the top of the connection base 2, or inside the connection base 2, the top of the collecting plate 3 It can be realized by adding a support structure on the surface, as long as the detachable installation of the collecting plate 3 and the fixing and limiting of the generation chip 1 can be realized.
  • the generation chip 1 is integrated with the 96-well plate as the collection plate 3 through the connection base 2, so that the micro-droplets generated by the production chip can be directly collected by the 96-well plate as the collection plate 3.
  • the collection plate 3 is detachably installed on the connection base 2, and it is also convenient to disassemble directly after collecting the micro-droplets for subsequent operations, without using other means and tools to transfer the micro-droplets, the process is simple and the micro-droplet samples are not easily polluted during the process .
  • the generation chip 1 includes a discharge tube 121 through which micro-droplets are discharged.
  • the discharge tube 121 extends into the collection hole 31 .
  • the sampling tube 121 is arranged on the bottom surface of the generation chip 1 and extends downward.
  • the sampling tube 121 of the generation chip 1 faces the collection port and extends into the into the collection hole 31.
  • the chip holder 21 when the generation chip 1 is placed on it, its sample tube 121 can directly extend into the collection hole 31 of the collection plate 3 , so that the generation chip 1 is aligned with the collection plate 3 . Simultaneously, extending the sampling tube 121 into the collecting hole 31 can also reduce the height of the droplet, reduce the kinetic energy of the droplet, and avoid the impact of the droplet from destroying the structure of the droplet.
  • the sample discharge port can only be aligned with the collection hole 31 without extending into the collection hole 31, but this structure can only ensure that the micro-droplets drip into the collection hole 31 but cannot reduce the dripping of the micro-droplets. kinetic energy.
  • the generation chip 1 includes several chip modules.
  • the chip module includes several chip units 14 corresponding to the collection holes 31 one by one.
  • the chip units 14 are integrally formed to form a chip module.
  • each chip unit 14 can independently generate micro-droplets, including a set of first compartments 141, second compartments 142 and sample tubes 121, and a single chip module has 8 chips arranged horizontally Unit 14.
  • the generation chip 1 of this embodiment is composed of 12 chip modules, and has 8*12 chip units 14 in total, corresponding to the 96-well plate as the collection plate 3 .
  • the arrangement direction and quantity of the chip units 14 of the chip module 13 are not limited thereto, and can be adjusted according to different usage scenarios and different requirements, as long as it can correspond to the collection hole 31 of the collection plate 3. Can.
  • the generation chip 1 is composed of a plurality of identical chip modules, and each chip module includes a plurality of chip units 14, each chip unit 14 can generate micro-droplets independently, and the number of chip units 14 is the same as that of the collection hole 31 of the collection plate 3. corresponding to each other.
  • Each individual chip module is integrally formed, which facilitates the batch processing of the chip modules and reduces the production and maintenance costs of generating the chip 1 .
  • the chip module is formed of thermoplastic material, thermosetting material, or glass. Such materials are easy to process and low in cost, further reducing the cost of producing the chip 1 .
  • thermoforming materials can also be used to make the product.
  • the generation chip 1 includes a sample application layer 11 , a sample discharge layer 12 and a microchannel layer 15 .
  • the sample application layer 11 is arranged on the top of the generation chip 1, and the first compartment 141 and the second compartment 142 are arranged on the sample application layer 11;
  • the layer 15 includes a first flow channel 16 communicating with the first compartment 141 and the sample discharge pipe 121, a second flow channel 17 communicating with the second compartment 142 and the first flow channel 16, and the second flow channel 17 is along the first flow channel 16.
  • the vertical direction of and the first channel 16 intersect in the generation area 18 .
  • the first compartment 141 communicates with the first flow channel 16 through the first inlet 143
  • the second compartment 142 communicates with the second flow channel 17 through the second inlet 144
  • the second flow channel 17 is in the generation area 18 communicates with the first flow channel 16 from both sides.
  • the liquid in the two compartments enters the two flow channels and flows toward the outlet 122 under the action of air pressure.
  • the liquid in the first compartment 141 flows through the generating region 18 in the first flow channel 16 , corresponding micro-droplets are generated under the flow shear force of the liquid in the second flow channel 17 .
  • top surface of the sample layout layer 12 and the bottom surface of the sample application layer 11 are attached to each other and packaged by bonding or other methods.
  • other common packaging methods such as adhesive stickers can also be used.
  • oil-in-water micro-droplets When the oil phase liquid is in the first compartment 141 and the water phase liquid is in the second compartment 142, "oil-in-water" micro-droplets can be generated;
  • the microchannel layer 15 in this embodiment is formed by bonding or pasting the sample application layer 11 and the sample discharge layer 12 .
  • an independent microchannel layer 15 may also be provided and communicated with the first inlet 143 , the second inlet 144 and the outlet 122 of the sampling layer 11 and the sampling layer 12 .
  • the microchannel layer 15 is formed by bonding or gluing the sample loading layer 11 and the sample layout layer 12.
  • the three-layer structure of the chip is tightly stacked and fitted, highly integrated, small in area and volume, and significantly reduces the cost of microdroplet generation .
  • the bottom surface of the top surface of the sampling layer 12 and/or the sample application layer 11 is depressed to form the first groove and the second groove, and the first groove and the second groove pass through the contact with the sample application layer 11.
  • the bottom surface and/or the top surface of the layout layer 12 form the first flow channel 16 and the second flow channel 17 by bonding or pasting.
  • both the first groove and the second groove are formed on the bottom surface of the sample application layer 11 .
  • the nesting layer 12 seals the grooves to form a flow channel by means of bonding or pasting.
  • the groove can also be formed on the top surface of the layout layer 12 , or be formed on both surfaces respectively.
  • the generation chip 1 generates micro-droplets through the first flow channel 16 and the second flow channel 17, and the first flow channel 16 and the second flow channel 17 are formed by the concave holes on the top surface of the layout layer 12 and/or the bottom surface of the sample application layer 11. Grooves are formed, and after the sampling layer 12 and the sample loading layer 11 are packaged by bonding or adhesive bonding, these grooves become flow channels for liquid samples to flow and meet, and micro-droplets are generated to make the chip highly integrated.
  • the first flow channel 16 sequentially includes along the flow direction of the liquid sample: a first inlet 143 connected to the first compartment 141 , a buffer area, a generation area 18 and an outlet 122 connected to the sample discharge pipe 121 .
  • the buffer area includes a first extended flow channel 161 and a second extended flow channel 162 extending along the side direction of the first flow channel 16, the first extended flow channel 161 and the second extended flow channel 162 communicate through a bent flow channel 163, the first extended flow channel
  • the flow channel 161 communicates with the first inlet 143
  • the second extended flow channel 162 communicates with the generating area 18 .
  • the second flow channel 17 extends from the position of the second outlet 122 from both sides respectively, and meets the first flow channel 16 from both sides of the vertical direction of the first flow channel 16 at the position of the generation area 18, and then Then lead to outlet 122 .
  • the first channel 16 first passes through a buffer zone extended by bending from the position of the first inlet 143 , and then extends to the generating area 18 where it meets the second channel 17 , and then leads to the position of the outlet 122 .
  • the buffer area of this embodiment is composed of a first extended flow channel 161 , a curved flow channel 163 and a second extended flow channel 162 .
  • the first extended flow channel 161 communicates with the first inlet 143 and extends laterally toward the first direction;
  • the bent flow channel 163 communicates with the tail end of the first extended flow channel 161 and bends upwards in the longitudinal direction;
  • the second extended flow channel 162 communicates with the bend
  • the end of the flow channel 163 extends laterally toward a second direction, wherein the first direction is opposite to the second direction. Therefore, the first extended flow channel 161 , the curved flow channel 163 and the second extended flow channel 162 are connected in a U-shaped structure, and the entire buffer area is in a spiral structure.
  • the buffer area can also be provided with more extended flow channels and curved flow channels 163 to form a multi-layer spiral structure to further extend the overall length of the buffer area and increase its flow stabilization effect.
  • using only one buffer zone with a bent structure can make the distance between the two extended flow channels the longest, and can reduce the gap between the sample loading layer 11 and the layout layer 12 by bonding or pasting, etc. The difficulty of encapsulation.
  • the liquid sample enters the first flow channel 16 from the first inlet 143 from the first compartment 141 , and meets the liquid sample in the second flow channel 17 in the generation area 18 to form micro-droplets, and then flows out from the sample discharge pipe 121 through the outlet 122 .
  • the buffer area is an extended section that is bent to one side and then returns to the direction of the original flow channel.
  • a buffer area extended to one side is set between the first inlet 143 and the generation area 18, so that the liquid sample can It can be stabilized in the extended buffer area to make the flow rate and uniformity relatively stable before entering the production area to produce micro-droplets, which can improve the generation effect of micro-droplets.
  • first extension channel 161 and the second extension channel 162 are parallel to each other.
  • the first extended flow channel 161 and the second extended flow channel 162 are parallel to each other, so that the distance between the two can be kept constant and the maximum distance can be maintained, so that the sample loading layer 11 and the sample layout layer 12 can be packaged by bonding or adhesive bonding. Easier and better encapsulation.
  • the sampling tube 121 of this embodiment includes an inner cavity 123 and a liquid outlet 124 , and the wall of the inner cavity 123 gradually converges from the top of the inner cavity 123 to the bottom of the inner cavity 123 .
  • the drain port 124 is opened at the bottom of the inner cavity 123 .
  • the inner cavity 123 is formed in the hollow of the sampling tube 121, and the top of the inner cavity 123 communicates with the outlet 122 of the microchannel layer 15, and the microdroplets formed by the microchannel layer 15 flow down from the outlet 122 along the wall of the inner cavity 123 . And drip from the drain port 124 at the bottom of the inner chamber 123 to the collecting hole 31 of the collecting plate 3 .
  • the structure of the micro-droplet generation device in this embodiment is roughly the same as that in Embodiment 1, and the same parts thereof will not be described again. The difference lies in the sample-discharging tube 121 in this embodiment.
  • the sample discharge tube 121 includes an inner cavity 123 , a liquid discharge port 124 and a flow guide surface 125 .
  • the cavity wall of the inner cavity 123 gradually converges from the top of the inner cavity 123 to the bottom of the inner cavity 123 .
  • the drain port 124 is opened on one side of the bottom of the inner cavity 123 .
  • the flow guide surface 125 is disposed at the bottom of the inner cavity 123 , one end of the flow guide surface 125 is against the wall of the cavity, and the other end of the flow guide surface 125 is inclined downward and extends to the liquid outlet 124 .
  • the interior of the sample discharge tube 121 is hollow to form an inner cavity 123, and the top of the inner cavity 123 communicates with the outlet 122 of the micro-channel layer 15, and the micro-droplets formed by the micro-channel layer 15 flow from the outlet 122 along the direction of the inner cavity 123.
  • the cavity wall flows downward.
  • the liquid discharge port 124 is opened at the bottom of the side of the sample discharge pipe 121 , and the flow guide surface 125 is provided at the bottom of the inner cavity 123 and slopes downward toward the liquid discharge port 124 along the wall of the inner cavity 123 .
  • micro-droplets can flow along the cavity wall of the inner cavity 123 to the bottom of the cavity to the guide surface 125, and then slowly flow from the guide surface 125 to the discharge port 124 to be discharged, which can avoid the possible damage to the micro-droplets due to excessive impact.
  • Micro-droplet structure
  • the sample discharge tube 121 also includes a drainage part 126.
  • the drainage part 126 is arranged on the cavity wall on the side where the liquid discharge port 124 is opened in the inner cavity 123.
  • the drainage part 126 protrudes along the cavity wall and drains toward The liquid port 124 extends, and the projection of the end of the drainage part 126 in the vertical direction is located on the flow guiding surface 125 .
  • the inclination angle of the drainage part 126 is slightly larger than the inclination angle of the cavity wall, and its end is located on the flow guide surface 125 in the vertical direction, so as to ensure that the micro-droplets dripping from the drainage part 126 can fall on the flow guide surface 125, to prevent micro-droplets from flowing out of the side chamber wall directly from the discharge port 124, and improve the diversion effect of the sample discharge tube 121.

Abstract

A micro-droplet generation device, comprising: a generation chip (1), wherein the generation chip (1) comprises first compartments (141) and second compartments (142), and the generation chip (1) can generate micro-droplets by using liquid samples from the first compartments (141) and the second compartments (142); a collection plate (3), wherein the collection plate (3) comprises collection holes (31); and a connection base (2), wherein the connection base (2) wraps the collection plate (3), the connection base (2) comprises a chip support (21), the generation chip (1) is placed on and limited by the chip support (21), and the collection plate (3) is detachably mounted onto the connection base (2).

Description

微液滴生成装置micro droplet generation device
本申请要求申请日为2021年8月20日的中国专利申请CN202110961284.0的优先权。本申请引用上述中国专利申请的全文。This application claims the priority of the Chinese patent application CN202110961284.0 with the filing date of August 20, 2021. This application cites the full text of the above-mentioned Chinese patent application.
技术领域technical field
本发明涉及生物领域,特别涉及一种微液滴生成装置。The invention relates to the field of biology, in particular to a micro droplet generating device.
背景技术Background technique
微液滴技术是在微尺度通道内,利用流动剪切力与表面张力之间的相互作用将连续流体分割分离成离散的纳升级及以下体积的液滴的一种微纳技术。Micro-droplet technology is a micro-nano technology that uses the interaction between flow shear force and surface tension to divide continuous fluid into discrete droplets of nanoliter and below volume in micro-scale channels.
微液滴类型主要有气-液相液滴和液-液相液滴两种。液-液相微液滴由于体积小、液滴样品间无扩散、可避免样品间的交叉污染、反应条件稳定、适当操控下可实现迅速混合等优点。There are two main types of micro-droplets: gas-liquid phase droplets and liquid-liquid phase droplets. The liquid-liquid phase micro-droplets have the advantages of small size, no diffusion between droplet samples, avoiding cross-contamination between samples, stable reaction conditions, and rapid mixing under proper control.
液-液相液滴根据连续相和分散相的不同又分为“水包油”,“油包水”,“油包水包油”以及“水包油包水”等。Liquid-liquid phase droplets are divided into "oil-in-water", "water-in-oil", "oil-in-water-in-oil" and "water-in-oil-in-water" according to the difference between the continuous phase and the dispersed phase.
微液滴生成系统能生成直径在微米量级(即10-1000μm)“油包水”或“水包油”微液滴,为生物、化学和材料等领域的众多应用场景提供高灵敏、高效率和高通量的研究场所。The micro-droplet generation system can generate "water-in-oil" or "oil-in-water" micro-droplets with diameters on the order of microns (ie, 10-1000 μm), providing high-sensitivity, high-resolution micro-droplets for many application scenarios in the fields of biology, chemistry and materials. Efficient and high-throughput research site.
96孔板为生物领域常用的实验耗材,但现有技术的微液滴生成装置与96孔板兼容性较差,无法直接将微液滴样本生成到96孔板中,在实际使用时,在微液滴生成装置产生微液滴后往往需要通过其他手段和工具将微液滴转移至96孔板中,流程繁杂且过程中容易产生微液滴样本的污染。因此难以作为生物、化学和材料等领域普适性高的实验系统。The 96-well plate is a commonly used experimental consumable in the biological field, but the micro-droplet generation device in the prior art is not compatible with the 96-well plate, and cannot directly generate the micro-droplet sample into the 96-well plate. After the micro-droplet generation device generates micro-droplets, it often needs to transfer the micro-droplets to the 96-well plate by other means and tools. The process is complicated and the contamination of the micro-droplet samples is easy to occur during the process. Therefore, it is difficult to use it as an experimental system with high universality in the fields of biology, chemistry and materials.
发明内容Contents of the invention
本发明要解决的技术问题是为了克服现有技术中微液滴生成装置与96孔板兼容性较差,无法直接将微液滴样本生成到96孔板中,在实际使用时,在微液滴生成装置产生微液滴后往往需要通过其他手段和工具将微液滴转移至96孔板中,流程繁杂且过程中容易产生微液滴样本的污染的缺陷,提供一种微液滴生成装置。The technical problem to be solved by the present invention is to overcome the poor compatibility between the micro-droplet generating device and the 96-well plate in the prior art, and it is impossible to directly generate the micro-droplet sample into the 96-well plate. After the droplet generation device generates microdroplets, it often needs to transfer the microdroplets to the 96-well plate by other means and tools. .
本发明是通过下述技术方案来解决上述技术问题:The present invention solves the above technical problems through the following technical solutions:
一种微液滴生成装置,其包括:A microdroplet generating device comprising:
生成芯片,所述生成芯片包含第一隔室和第二隔室,所述生成芯片可将所述第一隔室和所述第二隔室的液体样本生成为微液滴;generating a chip, the generating chip comprising a first compartment and a second compartment, the generating chip can generate liquid samples in the first compartment and the second compartment into micro-droplets;
收集板,所述收集板为96孔板,所述收集板包括收集孔;A collection plate, the collection plate is a 96-well plate, and the collection plate includes collection holes;
连接基座,所述连接基座包裹所述收集板,所述连接基座包括芯片支架,所述生成芯片放置并限位于所述芯片支架,所述收集板可拆卸地安装在所述连接基座上。A connection base, the connection base wraps the collection plate, the connection base includes a chip support, the generated chip is placed and limited on the chip support, the collection plate is detachably mounted on the connection base seat.
在本方案中,采用上述结构形式,生成芯片与作为收集板的96孔板通过连接基座集成在一起,使得生产芯片生成的微液滴可以直接被作为收集板的96孔板收集。收集板可拆卸地安装于连接基座,也方便在收集微液滴后直接拆卸下来进行后续操作,无需通过其他手段和工具转移微液滴,流程简便且过程中不易污染微液滴样本。In this solution, the above structure is used to integrate the production chip and the 96-well plate as the collection plate through the connection base, so that the micro-droplets generated by the production chip can be directly collected by the 96-well plate as the collection plate. The collection plate is detachably installed on the connection base, and it is also convenient to disassemble directly after collecting the micro-droplets for subsequent operations. There is no need to transfer the micro-droplets through other means and tools. The process is simple and the micro-droplet samples are not easily polluted during the process.
较佳地,所述生成芯片包括排样管,所述微液滴通过所述排样管排出,当所述生成芯片放置并限位于所述芯片支架时,所述排样管伸入所述收集孔中。Preferably, the generation chip includes a discharge tube through which the micro-droplets are discharged, and when the generation chip is placed and limited on the chip holder, the discharge tube extends into the collection hole.
在本方案中,采用上述结构形式,通过芯片支架的限位,可以使得生成芯片放置在其上时其排样管直接伸入到收集板的收集孔中,使得生成芯片与收集板对位。同时,排样管伸入收集孔也可以减少微液滴滴落的高度,降低微液滴滴落的动能,避免滴落的冲击破坏微液滴结构。In this solution, the above-mentioned structural form is adopted, and through the limitation of the chip holder, when the generation chip is placed on it, the sample discharge tube can directly extend into the collection hole of the collection plate, so that the generation chip is aligned with the collection plate. At the same time, extending the sampling tube into the collection hole can also reduce the height of the droplet drop, reduce the kinetic energy of the droplet drop, and avoid the impact of the droplet from destroying the structure of the droplet.
较佳地,所述生成芯片包含若干芯片模块,所述芯片模块包括若干与所述收集孔一一对应的芯片单元,若干芯片单元一体成型形成芯片模块。Preferably, the generating chip includes a plurality of chip modules, the chip module includes a plurality of chip units corresponding to the collection holes one by one, and the plurality of chip units are integrally formed to form a chip module.
在本方案中,采用上述结构形式,生成芯片有多个相同的芯片模块组成,每个芯片模块上又包含多个芯片单元,每个芯片单元可单独生成微液滴,芯片单元的数量与收集板的收集孔的数量一一对应。每个单独的芯片模块一体成型,方便芯片模块的批量加工,可降低生成芯片的生产和维护成本。In this solution, the above-mentioned structure is adopted, and the generated chip is composed of multiple identical chip modules, and each chip module contains multiple chip units, and each chip unit can generate micro-droplets independently. The number of chip units and the collection The number of collection holes of the plate corresponds one to one. Each individual chip module is integrally formed, which facilitates the batch processing of the chip modules and reduces the production and maintenance costs of the generated chips.
较佳地,所述芯片模块由热塑材料或热固材料或玻璃形成。Preferably, the chip module is formed of thermoplastic or thermosetting material or glass.
在本方案中,采用上述结构形式,热塑材料、热固材料、玻璃等材料加工容易,成本低廉,进一步降低生成芯片的成本。In this solution, by adopting the above-mentioned structural form, materials such as thermoplastic materials, thermosetting materials, and glass are easy to process, and the cost is low, further reducing the cost of producing chips.
较佳地,所述生成芯片包括:Preferably, the generating chip includes:
加样层,所述加样层设于所述生成芯片的顶部,所述第一隔室和第二隔室设于所述加样层上;A sample application layer, the sample application layer is arranged on the top of the generation chip, and the first compartment and the second compartment are provided on the sample application layer;
排样层,所述排样层设于所述生成芯片的底部,所述排样管设于所述排样层上,所述排样层顶面与所述加样层的底面相互贴合并密封;A sample layout layer, the sample layout layer is arranged at the bottom of the generation chip, the sample layout tube is arranged on the sample layout layer, the top surface of the sample layout layer and the bottom surface of the sample application layer are attached to each other and merged seal;
微流道层,所述排样层顶面与所述加样层的底面相互贴合并密封形成所述微流道层, 所述微流道层包括与所述第一隔室和所述排样管联通的第一流道,与所述第二隔室以及所述第一流道连通的第二流道,所述第二流道沿所述第一流道的垂直方向和所述第一流道在生成区域交汇。The micro-channel layer, the top surface of the sampling layer and the bottom surface of the sample application layer are attached and sealed to form the micro-channel layer, and the micro-channel layer includes the first compartment and the row The first flow channel communicated with the sample tube, the second flow channel communicated with the second compartment and the first flow channel, the second flow channel is along the vertical direction of the first flow channel and the first flow channel Generate area intersections.
在本方案中,采用上述结构形式,微流道层由加样层和排样层以键合或胶贴等方式形成,芯片三层结构紧密层叠契合,高度集成,面积和体积小,显著降低了微液滴生成的成本。In this scheme, the above-mentioned structural form is adopted. The microchannel layer is formed by bonding or pasting the sample loading layer and the sample layout layer. the cost of microdroplet generation.
较佳地,所述排样层的顶面和/或所述加样层的底面凹陷形成第一凹槽和第二凹槽,所述第一凹槽和所述第二凹槽通过与所述加样层的底面和/或所述排样层的顶面相互贴合并密封形成所述第一流道和所述第二流道。Preferably, the top surface of the sampling layer and/or the bottom surface of the loading layer are recessed to form a first groove and a second groove, and the first groove and the second groove are connected with the The bottom surface of the sampling layer and/or the top surface of the sampling layer are attached and sealed to each other to form the first flow channel and the second flow channel.
在本方案中,采用上述结构形式,生成芯片通过第一流道和第二流道生成微液滴,第一流道和第二流道由设在排样层的顶面和/或加样层的底面的凹槽形成,在排样层和加样层以键合或胶贴等方式封装后,这些凹槽成为供液体样本流通交汇的流道,产生微液滴,使得芯片高度集成。In this solution, the above-mentioned structural form is adopted, and the generation chip generates micro-droplets through the first flow channel and the second flow channel, and the first flow channel and the second flow channel are formed by the The grooves on the bottom surface are formed. After the layout layer and the sample loading layer are packaged by bonding or adhesive bonding, these grooves become flow channels for the flow and intersection of liquid samples, generating micro-droplets, making the chip highly integrated.
较佳地,所述第一流道沿液体样本的流动方向依次包括:连通第一隔室的第一入口、缓冲区域、生成区域和连通排样管的出口;Preferably, the first flow channel sequentially includes along the flow direction of the liquid sample: a first inlet connected to the first compartment, a buffer area, a generation area, and an outlet connected to the sample discharge pipe;
所述缓冲区域包括沿所述第一流道侧面方向延伸的第一延长流道和第二延长流道,所述第一延长流道和所述第二延长流道通过弯折流道连通,所述第一延长流道连通所述第一入口,所述第二延长流道连通所述生成区域。The buffer area includes a first extended flow channel and a second extended flow channel extending along the side of the first flow channel, and the first extended flow channel and the second extended flow channel communicate through a bent flow channel, so The first extended channel communicates with the first inlet, and the second extended channel communicates with the generating area.
在本方案中,采用上述结构形式,液体样本从第一隔室由第一入口进入第一流道,并与第二流道的液体样本在生成区域交汇形成微液滴,再由出口自排样管流出。缓冲区域为一段通过向一侧弯折后再返回原流道方向的延长段,在第一入口和生成区域之间设置向一侧延长的缓冲区域,可使得液体样本在进入流道后可以在延长的缓冲区域内进行稳定,使其流速与均匀程度相对稳定后再进入生产区域生产微液滴,可提升微液滴的生成效果。In this scheme, the above structure is adopted, the liquid sample enters the first flow channel from the first inlet through the first compartment, and meets the liquid sample in the second flow channel in the generation area to form micro-droplets, and then self-discharges from the outlet Tube out. The buffer area is an extended section that is bent to one side and then returns to the direction of the original flow channel. A buffer area that is extended to one side is set between the first inlet and the generation area, so that the liquid sample can pass through the flow channel after entering the flow channel. Stabilize in the extended buffer area to make the flow rate and uniformity relatively stable before entering the production area to produce micro-droplets, which can improve the generation effect of micro-droplets.
较佳地,所述第一延长流道与所述第二延长流道相互平行。Preferably, the first extended flow channel and the second extended flow channel are parallel to each other.
在本方案中,采用上述结构形式,第一延长流道与第二延长流道相互平行,可使两者间的距离恒定并保持最大距离,可使得加样层和排样层以键合或胶贴等方式的封装更容易,封装效果更好。In this solution, the above-mentioned structural form is adopted, the first extended flow channel and the second extended flow channel are parallel to each other, the distance between the two can be kept constant and the maximum distance can be maintained, and the sample layer and the sample layer can be bonded or arranged. Packaging by means of adhesive stickers is easier and the packaging effect is better.
较佳地,所述排样管包括:Preferably, the sampling tube includes:
内腔,所述内腔的腔壁自内腔顶部向内腔底部逐渐收敛;an inner cavity, the cavity wall of which gradually converges from the top of the cavity to the bottom of the cavity;
排液口,所述排液口开设于所述内腔的底部的一侧;a liquid discharge port, the liquid discharge port is opened on one side of the bottom of the inner cavity;
导流面,所述导流面设于所述内腔的底部,所述导流面一端抵住所述腔壁,所述导流面的另一端向下倾斜并延伸至所述排液口。A diversion surface, the diversion surface is arranged at the bottom of the inner cavity, one end of the diversion surface is against the wall of the cavity, and the other end of the diversion surface is inclined downward and extends to the liquid discharge port.
在本方案中,采用上述结构形式,排样管连通微流道层的出口,微流道层的微液滴从出口流出后流入排样层的内腔,并可沿内腔的腔壁向腔底流动至导流面上,再由导流面缓慢流至排液口排出,可以避免微液滴直接滴落冲击过大可能损害微液滴结构。In this scheme, the above-mentioned structural form is adopted, and the sample discharge tube is connected to the outlet of the microchannel layer. The bottom of the cavity flows to the diversion surface, and then slowly flows from the diversion surface to the discharge port to be discharged, which can avoid the direct drop of micro-droplets and excessive impact that may damage the structure of micro-droplets.
较佳地,所述排样管还包括引流部,所述引流部设于所述内腔开设所述排液口的一侧的所述腔壁上,所述引流部沿所述腔壁凸起并向所述排液口延伸,所述引流部的末端在垂直方向上的投影位于所述导流面上。Preferably, the sample discharge tube further includes a drainage part, the drainage part is arranged on the cavity wall on the side where the liquid discharge port is opened in the inner cavity, and the drainage part protrudes along the cavity wall. rises and extends toward the drain port, and the projection of the end of the drainage part in the vertical direction is located on the guide surface.
在本方案中,采用上述结构形式,排样管开设排液口一侧的腔壁上方还设有凸起的引流部,可通过凸出结构将该侧腔壁上的微液滴导引至导流面上,避免微液滴从该侧腔壁直接从排液口流出,提升排样管的导流效果。In this solution, the above-mentioned structure is adopted, and a raised drainage part is provided above the cavity wall on the side where the discharge port is opened in the sample discharge tube, and the micro-droplets on the side cavity wall can be guided to the On the diversion surface, the micro-droplets are prevented from flowing directly from the side cavity wall from the liquid discharge port, and the diversion effect of the sample discharge tube is improved.
本发明的积极进步效果在于:通过本发明所公开的微液滴生成装置,生成芯片与作为收集板的96孔板通过连接基座集成在一起,使得生产芯片生成的微液滴可以直接被作为收集板的96孔板收集。收集板可拆卸地安装于连接基座,也方便在收集微液滴后直接拆卸下来进行后续操作,无需通过其他手段和工具转移微液滴,流程简便且过程中不易污染微液滴样本。The positive progress effect of the present invention is: through the micro-droplet generation device disclosed in the present invention, the generation chip and the 96-well plate as the collection plate are integrated through the connection base, so that the micro-droplets generated by the production chip can be directly used as Collection plate for 96-well plate collection. The collection plate is detachably installed on the connection base, and it is also convenient to disassemble directly after collecting the micro-droplets for subsequent operations. There is no need to transfer the micro-droplets through other means and tools. The process is simple and the micro-droplet samples are not easily polluted during the process.
附图说明Description of drawings
图1为本发明实施例1的微液滴生成装置结构示意图。FIG. 1 is a schematic structural diagram of a micro droplet generating device according to Embodiment 1 of the present invention.
图2为本发明实施例1的微液滴生成装置的爆炸结构示意图。FIG. 2 is a schematic diagram of the exploded structure of the micro-droplet generating device according to Embodiment 1 of the present invention.
图3为本发明实施例1的连接基座的局部结构示意图。FIG. 3 is a schematic diagram of a partial structure of a connecting base according to Embodiment 1 of the present invention.
图4为本发明实施例1的芯片模块的结构示意图。FIG. 4 is a schematic structural diagram of a chip module according to Embodiment 1 of the present invention.
图5为本发明实施例1的芯片模块的俯视结构示意图。FIG. 5 is a schematic top view of the chip module according to Embodiment 1 of the present invention.
图6为本发明实施例1的芯片模块与连接基座的连接结构示意图。FIG. 6 is a schematic diagram of the connection structure between the chip module and the connection base according to Embodiment 1 of the present invention.
图7为本发明实施例1的微流道层的结构示意图。FIG. 7 is a schematic structural view of the microchannel layer in Example 1 of the present invention.
图8为本发明实施例1的微流道层的结构示意图。FIG. 8 is a schematic structural view of the microchannel layer in Example 1 of the present invention.
图9为本发明实施例1的微流道层的结构示意图。FIG. 9 is a schematic structural view of the microchannel layer in Example 1 of the present invention.
图10为本发明实施例2的排样管的结构示意图。Fig. 10 is a schematic structural view of the sample-arranging tube according to Embodiment 2 of the present invention.
图11为本发明实施例2的排样管的内部结构示意图。Fig. 11 is a schematic diagram of the internal structure of the sample-discharging tube according to Embodiment 2 of the present invention.
附图标记说明:Explanation of reference signs:
生成芯片1generate chip 1
加样层11 Loading layer 11
排样层12 layout layer 12
排样管121 Sample tube 121
出口122 Exit 122
内腔123 Lumen 123
排液口124 Drain 124
导流面125 diversion surface 125
引流部126 Drain 126
芯片模组13 Chip Module 13
芯片单元14 chip unit 14
第一隔室141 first compartment 141
第一入口143 First entrance 143
第二入口144 Second entrance 144
第二隔室142 Second compartment 142
微流道层15 Microfluidic layer 15
第一流道16 First runner 16
第一延长流道161First extended runner 161
第二延长流道162Second extended runner 162
弯折流道163 Bend runner 163
第二流道17 Second runner 17
生成区域18spawn area 18
连接基座2 Connect base 2
芯片支架21 Chip Holder 21
凸块211 Bump 211
槽口212 Notch 212
卡扣22 Buckle 22
收集板3 collection plate 3
收集孔31 Collection hole 31
卡槽32 Card slot 32
具体实施方式Detailed ways
下面通过实施例的方式进一步说明本发明,但并不因此将本发明限制在所述的实施例范围之中。The present invention is further illustrated below by means of examples, but the present invention is not limited to the scope of the examples.
实施例一Embodiment one
如图1-3所示,本实施例的微液滴生成装置包括生成芯片1、收集板3和连接基座2组成。生成芯片1包含第一隔室141和第二隔室142,生成芯片1可将第一隔室141和第二隔室142的液体样本生成为微液滴。收集板3为96孔板,收集板3包括收集孔31。连接基座2包裹收集板3,连接基座2包括芯片支架21,生成芯片1放置并限位于芯片支架21,收集板3可拆卸地安装在连接基座2上。As shown in FIGS. 1-3 , the droplet generating device of this embodiment includes a generating chip 1 , a collecting plate 3 and a connection base 2 . The generation chip 1 includes a first compartment 141 and a second compartment 142 , and the generation chip 1 can generate liquid samples in the first compartment 141 and the second compartment 142 into micro-droplets. The collection plate 3 is a 96-well plate, and the collection plate 3 includes collection holes 31 . The connection base 2 wraps the collection plate 3 , the connection base 2 includes a chip holder 21 , the generated chip 1 is placed and limited on the chip holder 21 , and the collection plate 3 is detachably mounted on the connection base 2 .
本实施例中,生成芯片1的第一隔室141和第二隔室142用于分别注入水相液体和油相液体。通过精密气控装置分别对两个隔室进行加压,使得液体通过生成芯片1生成“油包水”或者“水包油”的微液滴,在排出至收集板3的收集孔31中。In this embodiment, the first compartment 141 and the second compartment 142 of the generation chip 1 are used to inject the water phase liquid and the oil phase liquid respectively. The two compartments are respectively pressurized by a precision air control device, so that the liquid passes through the generation chip 1 to generate "water-in-oil" or "oil-in-water" micro-droplets, which are discharged into the collection hole 31 of the collection plate 3 .
本实施例的收集板3为96孔板,是生物领域常用的实验耗材,该板上具有8*12个收集孔31。在其他实施例中,收集板3也可由若干个8连排管组成。The collection plate 3 of this embodiment is a 96-well plate, which is a commonly used experimental consumable in the field of biology. The plate has 8*12 collection holes 31 . In other embodiments, the collecting plate 3 can also be composed of several 8-connected tubes.
如图2、3所示,本实施例的连接基座2为方框型,连接基座2可以套设在收集板3上并包裹在收集板3的四周,通过连接基座2上的卡扣22与收集板3上的卡槽32实现可拆卸地固定。使其与收集板3的连接更为稳固。卡槽32设置在收集板3的两侧,卡扣22则设于连接基座2两侧的对应位置。卡扣22设在一个可进行一定程度弯折的连接板的一端上,连接板的另一端固定于连接基座2侧面,连接板设置卡扣22一端的背面还设有一手柄部,该手柄部向连接板的另一端延伸。通过挤压该手柄部可使连接板向外弯折,使得卡扣22抬起以便嵌入或者脱出收集板3的卡槽32。As shown in Figures 2 and 3, the connecting base 2 of this embodiment is a square frame, and the connecting base 2 can be sleeved on the collecting plate 3 and wrapped around the collecting plate 3. The buckle 22 is detachably fixed to the slot 32 on the collecting plate 3 . Make its connection with the collecting plate 3 more stable. The slots 32 are arranged on both sides of the collecting plate 3 , and the buckles 22 are arranged at corresponding positions on both sides of the connecting base 2 . The buckle 22 is arranged on one end of a connecting plate that can be bent to a certain extent, the other end of the connecting plate is fixed on the side of the connecting base 2, and the back side of the end of the connecting plate provided with the buckle 22 is also provided with a handle portion. Extend to the other end of the connecting plate. By squeezing the handle part, the connecting plate can be bent outwards, so that the buckle 22 is lifted so as to be inserted into or disengaged from the slot 32 of the collecting plate 3 .
如图2、3所示,芯片支架21由连接基座2相对的两个侧边顶部有间隔设有多组对应的凸块211组成,当芯片放置于连接基座2上时,芯片的边缘则卡设于两凸块211之间的槽口212内,并与卡设在连接基座2上的收集板3对位。As shown in Figures 2 and 3, the chip holder 21 is composed of a plurality of groups of corresponding bumps 211 arranged at intervals on the top of the two opposite sides of the connection base 2. When the chip is placed on the connection base 2, the edge of the chip Then it is clamped in the notch 212 between the two protrusions 211 , and aligned with the collecting plate 3 clamped on the connection base 2 .
在其他实施例中,连接基座2也可不套设包裹收集板3而采用其他方式与收集板3连接,如制作成上框结构安设在收集板3的顶面上,或制作成底座结构将收集板3直接放入连接基座2内。而芯片支架21也不局限于设置于边缘的凸块211和槽口212,也采用在连接基座2顶部增加一个设有安装槽的顶面,或者在连接基座2内部,收集板3顶面上增加支撑结构等方式实现,只要能实现收集板3的可拆卸安装以及生成芯片1的固定与限位即可。In other embodiments, the connecting base 2 can also be connected with the collecting plate 3 in other ways without sheathing the collecting plate 3, such as making an upper frame structure and installing it on the top surface of the collecting plate 3, or making it into a base structure Put the collecting plate 3 directly into the connection base 2. And the chip holder 21 is not limited to the bump 211 and the notch 212 that are arranged on the edge, but also adopts a top surface that is provided with a mounting groove on the top of the connection base 2, or inside the connection base 2, the top of the collecting plate 3 It can be realized by adding a support structure on the surface, as long as the detachable installation of the collecting plate 3 and the fixing and limiting of the generation chip 1 can be realized.
生成芯片1与作为收集板3的96孔板通过连接基座2集成在一起,使得生产芯片生 成的微液滴可以直接被作为收集板3的96孔板收集。收集板3可拆卸地安装于连接基座2,也方便在收集微液滴后直接拆卸下来进行后续操作,无需通过其他手段和工具转移微液滴,流程简便且过程中不易污染微液滴样本。The generation chip 1 is integrated with the 96-well plate as the collection plate 3 through the connection base 2, so that the micro-droplets generated by the production chip can be directly collected by the 96-well plate as the collection plate 3. The collection plate 3 is detachably installed on the connection base 2, and it is also convenient to disassemble directly after collecting the micro-droplets for subsequent operations, without using other means and tools to transfer the micro-droplets, the process is simple and the micro-droplet samples are not easily polluted during the process .
如图2所示,生成芯片1包括排样管121,微液滴通过排样管121排出,当生成芯片1放置并限位于芯片支架21时,排样管121伸入收集孔31中。As shown in FIG. 2 , the generation chip 1 includes a discharge tube 121 through which micro-droplets are discharged. When the generation chip 1 is placed and limited to the chip holder 21 , the discharge tube 121 extends into the collection hole 31 .
本实施例中,排样管121设于生成芯片1的底面上并向下延伸,当生成芯片1卡设在槽口212时,生成芯片1的排样管121正对收集口并伸入至收集孔31中。In this embodiment, the sampling tube 121 is arranged on the bottom surface of the generation chip 1 and extends downward. When the generation chip 1 is stuck in the notch 212, the sampling tube 121 of the generation chip 1 faces the collection port and extends into the into the collection hole 31.
通过芯片支架21的限位,可以使得生成芯片1放置在其上时其排样管121直接伸入到收集板3的收集孔31中,使得生成芯片1与收集板3对位。同时,排样管121伸入收集孔31也可以减少微液滴滴落的高度,降低微液滴滴落的动能,避免滴落的冲击破坏微液滴结构。Through the limitation of the chip holder 21 , when the generation chip 1 is placed on it, its sample tube 121 can directly extend into the collection hole 31 of the collection plate 3 , so that the generation chip 1 is aligned with the collection plate 3 . Simultaneously, extending the sampling tube 121 into the collecting hole 31 can also reduce the height of the droplet, reduce the kinetic energy of the droplet, and avoid the impact of the droplet from destroying the structure of the droplet.
在其他实施例中,排样口也可仅对准收集孔31而不伸入收集孔31中,只是这种结构仅能保证微液滴滴入收集孔31中但无法降低微液滴滴落的动能。In other embodiments, the sample discharge port can only be aligned with the collection hole 31 without extending into the collection hole 31, but this structure can only ensure that the micro-droplets drip into the collection hole 31 but cannot reduce the dripping of the micro-droplets. kinetic energy.
如图1-5所示,生成芯片1包含若干芯片模块,芯片模块包括若干与收集孔31一一对应的芯片单元14,若干芯片单元14一体成型形成芯片模块。As shown in FIGS. 1-5 , the generation chip 1 includes several chip modules. The chip module includes several chip units 14 corresponding to the collection holes 31 one by one. The chip units 14 are integrally formed to form a chip module.
本实施例中,每个芯片单元14都可以单独生成微液滴,包括一组第一隔室141、第二隔室142和排样管121,一个单独的芯片模块具有8个横向排列的芯片单元14。本实施例的生成芯片1由12个芯片模块组成,共具有8*12个芯片单元14,与作为收集板3的96孔板相对应。In this embodiment, each chip unit 14 can independently generate micro-droplets, including a set of first compartments 141, second compartments 142 and sample tubes 121, and a single chip module has 8 chips arranged horizontally Unit 14. The generation chip 1 of this embodiment is composed of 12 chip modules, and has 8*12 chip units 14 in total, corresponding to the 96-well plate as the collection plate 3 .
在其他实施例中,芯片模组13的芯片单元14排列方向和数量也不局限于此,可以根据使用场景的不同和需求的不同进行调整,只要保证能够与收集板3的收集孔31对应即可。In other embodiments, the arrangement direction and quantity of the chip units 14 of the chip module 13 are not limited thereto, and can be adjusted according to different usage scenarios and different requirements, as long as it can correspond to the collection hole 31 of the collection plate 3. Can.
生成芯片1有多个相同的芯片模块组成,每个芯片模块上又包含多个芯片单元14,每个芯片单元14可单独生成微液滴,芯片单元14的数量与收集板3的收集孔31的数量一一对应。每个单独的芯片模块一体成型,方便芯片模块的批量加工,可降低生成芯片1的生产和维护成本。The generation chip 1 is composed of a plurality of identical chip modules, and each chip module includes a plurality of chip units 14, each chip unit 14 can generate micro-droplets independently, and the number of chip units 14 is the same as that of the collection hole 31 of the collection plate 3. corresponding to each other. Each individual chip module is integrally formed, which facilitates the batch processing of the chip modules and reduces the production and maintenance costs of generating the chip 1 .
本实施例中,芯片模块由热塑材料、热固材料、玻璃形成。该类材料加工容易,成本低廉,进一步降低生成芯片1的成本。In this embodiment, the chip module is formed of thermoplastic material, thermosetting material, or glass. Such materials are easy to process and low in cost, further reducing the cost of producing the chip 1 .
在其他实施例中,也可使用其他常见的热成型材料制成本产品。In other embodiments, other common thermoforming materials can also be used to make the product.
如图2-8所示,生成芯片1包括加样层11,排样层12和微流道层15。加样层11设于生成芯片1的顶部,第一隔室141和第二隔室142设于加样层11上;排样层12设于 生成芯片1的底部,排样管121设于排样层12上,排样层12顶面与加样层11的底面相互贴合并密封;排样层12顶面与加样层11的底面相互贴合并密封形成微流道层15,微流道层15包括与第一隔室141和排样管121联通的第一流道16,与第二隔室142以及第一流道16连通的第二流道17,第二流道17沿第一流道16的垂直方向和第一流道16在生成区域18交汇。As shown in FIGS. 2-8 , the generation chip 1 includes a sample application layer 11 , a sample discharge layer 12 and a microchannel layer 15 . The sample application layer 11 is arranged on the top of the generation chip 1, and the first compartment 141 and the second compartment 142 are arranged on the sample application layer 11; On the sample layer 12, the top surface of the sample layout layer 12 and the bottom surface of the sample application layer 11 are mutually bonded and sealed; The layer 15 includes a first flow channel 16 communicating with the first compartment 141 and the sample discharge pipe 121, a second flow channel 17 communicating with the second compartment 142 and the first flow channel 16, and the second flow channel 17 is along the first flow channel 16. The vertical direction of and the first channel 16 intersect in the generation area 18 .
本实施例中,第一隔室141通过第一入口143与第一流道16相连通,第二隔室142通过第二入口144与第二流道17相连通,第二流道17在生成区域18从两侧与第一流道16连通。两隔室的液体通过气压作用下进入两流道中向出口122方向流动。第一隔室141中的液体在第一流道16内流经生成区域18时,在第二流道17的液体的流动剪切力作用下生成相应微液滴。In this embodiment, the first compartment 141 communicates with the first flow channel 16 through the first inlet 143, the second compartment 142 communicates with the second flow channel 17 through the second inlet 144, and the second flow channel 17 is in the generation area 18 communicates with the first flow channel 16 from both sides. The liquid in the two compartments enters the two flow channels and flows toward the outlet 122 under the action of air pressure. When the liquid in the first compartment 141 flows through the generating region 18 in the first flow channel 16 , corresponding micro-droplets are generated under the flow shear force of the liquid in the second flow channel 17 .
本实施例中,排样层12顶面与加样层11的底面相互贴合并以键合等方式封装,在其他实施例中,也可选用胶贴等其他常见的封装方式。In this embodiment, the top surface of the sample layout layer 12 and the bottom surface of the sample application layer 11 are attached to each other and packaged by bonding or other methods. In other embodiments, other common packaging methods such as adhesive stickers can also be used.
当第一隔室141内为油相液体,第二隔室142内为水相液体时,可以生成“水包油”微液滴;When the oil phase liquid is in the first compartment 141 and the water phase liquid is in the second compartment 142, "oil-in-water" micro-droplets can be generated;
当第一隔室141内为水相液体,第二隔室142内为油相液体时,可以生成“油包水”微液滴。When the liquid in the first compartment 141 is in the water phase and the liquid in the second compartment 142 is in the oil phase, "water-in-oil" micro-droplets can be generated.
本实施例的微流道层15由加样层11和排样层12以键合或胶贴等方式形成。在其他实施例中,也可以另设一层独立的微流道层15并与加样层11和排样层12的第一入口143,第二入口144以及出口122连通。The microchannel layer 15 in this embodiment is formed by bonding or pasting the sample application layer 11 and the sample discharge layer 12 . In other embodiments, an independent microchannel layer 15 may also be provided and communicated with the first inlet 143 , the second inlet 144 and the outlet 122 of the sampling layer 11 and the sampling layer 12 .
微流道层15由加样层11和排样层12以键合或胶贴等方式形成,芯片三层结构紧密层叠契合,高度集成,面积和体积小,显著降低了微液滴生成的成本。The microchannel layer 15 is formed by bonding or gluing the sample loading layer 11 and the sample layout layer 12. The three-layer structure of the chip is tightly stacked and fitted, highly integrated, small in area and volume, and significantly reduces the cost of microdroplet generation .
如图7所示,排样层12的顶面和/或加样层11的底面凹陷形成第一凹槽和第二凹槽,第一凹槽和第二凹槽通过与加样层11的底面和/或排样层12的顶面以键合或胶贴等方式形成第一流道16和第二流道17。As shown in Figure 7, the bottom surface of the top surface of the sampling layer 12 and/or the sample application layer 11 is depressed to form the first groove and the second groove, and the first groove and the second groove pass through the contact with the sample application layer 11. The bottom surface and/or the top surface of the layout layer 12 form the first flow channel 16 and the second flow channel 17 by bonding or pasting.
本实施例中,第一凹槽和第二凹槽都形成在加样层11的底面。排样层12通过键合或胶贴等方式将凹槽封闭形成流道。In this embodiment, both the first groove and the second groove are formed on the bottom surface of the sample application layer 11 . The nesting layer 12 seals the grooves to form a flow channel by means of bonding or pasting.
在其他实施例中,该凹槽也可形成于排样层12的顶面,或者分别形成在两面上。In other embodiments, the groove can also be formed on the top surface of the layout layer 12 , or be formed on both surfaces respectively.
生成芯片1通过第一流道16和第二流道17生成微液滴,第一流道16和第二流道17由设在排样层12的顶面和/或加样层11的底面的凹槽形成,在排样层12和加样层11以键合或胶贴等方式封装后,这些凹槽成为供液体样本流通交汇的流道,产生微液滴,使得芯片高度集成。The generation chip 1 generates micro-droplets through the first flow channel 16 and the second flow channel 17, and the first flow channel 16 and the second flow channel 17 are formed by the concave holes on the top surface of the layout layer 12 and/or the bottom surface of the sample application layer 11. Grooves are formed, and after the sampling layer 12 and the sample loading layer 11 are packaged by bonding or adhesive bonding, these grooves become flow channels for liquid samples to flow and meet, and micro-droplets are generated to make the chip highly integrated.
如图8所示,第一流道16沿液体样本的流动方向依次包括:连通第一隔室141的第一入口143、缓冲区域、生成区域18和连通排样管121的出口122。缓冲区域包括沿第一流道16侧面方向延伸的第一延长流道161和第二延长流道162,第一延长流道161和第二延长流道162通过弯折流道163连通,第一延长流道161连通第一入口143,第二延长流道162连通生成区域18。As shown in FIG. 8 , the first flow channel 16 sequentially includes along the flow direction of the liquid sample: a first inlet 143 connected to the first compartment 141 , a buffer area, a generation area 18 and an outlet 122 connected to the sample discharge pipe 121 . The buffer area includes a first extended flow channel 161 and a second extended flow channel 162 extending along the side direction of the first flow channel 16, the first extended flow channel 161 and the second extended flow channel 162 communicate through a bent flow channel 163, the first extended flow channel The flow channel 161 communicates with the first inlet 143 , and the second extended flow channel 162 communicates with the generating area 18 .
本实施例中,第二流道17自第二出口122位置,从两侧以分别延伸出去,并在生成区域18位置从第一流道16的垂直方向的两侧与第一流道16交汇,然后再导通至出口122。而第一流道16则从第一入口143位置先经过一个通过弯折方式延长的缓冲区域后,再延伸到生成区域18与第二流道17交汇,再导通至出口122位置。In this embodiment, the second flow channel 17 extends from the position of the second outlet 122 from both sides respectively, and meets the first flow channel 16 from both sides of the vertical direction of the first flow channel 16 at the position of the generation area 18, and then Then lead to outlet 122 . The first channel 16 first passes through a buffer zone extended by bending from the position of the first inlet 143 , and then extends to the generating area 18 where it meets the second channel 17 , and then leads to the position of the outlet 122 .
如图8所示,本实施例的缓冲区域由第一延长流道161、弯折流道163以及第二延长流道162组成。第一延长流道161连通第一入口143并沿横向朝第一方向延伸,弯折流道163连通第一延长流道161尾端并沿纵向向上弯折,第二延长流道162连通弯折流道163尾端并沿横向朝第二方向延伸,其中,第一方向和第二方向相反。从而第一延长流道161、弯折流道163以及第二延长流道162连接为U型结构,缓冲区域整个呈一个螺旋式结构。As shown in FIG. 8 , the buffer area of this embodiment is composed of a first extended flow channel 161 , a curved flow channel 163 and a second extended flow channel 162 . The first extended flow channel 161 communicates with the first inlet 143 and extends laterally toward the first direction; the bent flow channel 163 communicates with the tail end of the first extended flow channel 161 and bends upwards in the longitudinal direction; the second extended flow channel 162 communicates with the bend The end of the flow channel 163 extends laterally toward a second direction, wherein the first direction is opposite to the second direction. Therefore, the first extended flow channel 161 , the curved flow channel 163 and the second extended flow channel 162 are connected in a U-shaped structure, and the entire buffer area is in a spiral structure.
在其他实施例中,缓冲区域也可设置更多延长流道和弯折流道163,使其呈多层螺旋结构以进一步延长缓冲区域的整体长度,增加其稳流效果。但在总长度不变的情况下,只使用一个弯折结构的缓冲区域可使得两延长流道的距离最长,可以降低加样层11和排样层12之间以键合或胶贴等方式封装的难度。In other embodiments, the buffer area can also be provided with more extended flow channels and curved flow channels 163 to form a multi-layer spiral structure to further extend the overall length of the buffer area and increase its flow stabilization effect. However, under the condition that the total length remains constant, using only one buffer zone with a bent structure can make the distance between the two extended flow channels the longest, and can reduce the gap between the sample loading layer 11 and the layout layer 12 by bonding or pasting, etc. The difficulty of encapsulation.
液体样本从第一隔室141由第一入口143进入第一流道16,并与第二流道17的液体样本在生成区域18交汇形成微液滴,再由出口122自排样管121流出。缓冲区域为一段通过向一侧弯折后再返回原流道方向的延长段,在第一入口143和生成区域18之间设置向一侧延长的缓冲区域,可使得液体样本在进入流道后可以在延长的缓冲区域内进行稳定,使其流速与均匀程度相对稳定后再进入生产区域生产微液滴,可提升微液滴的生成效果。The liquid sample enters the first flow channel 16 from the first inlet 143 from the first compartment 141 , and meets the liquid sample in the second flow channel 17 in the generation area 18 to form micro-droplets, and then flows out from the sample discharge pipe 121 through the outlet 122 . The buffer area is an extended section that is bent to one side and then returns to the direction of the original flow channel. A buffer area extended to one side is set between the first inlet 143 and the generation area 18, so that the liquid sample can It can be stabilized in the extended buffer area to make the flow rate and uniformity relatively stable before entering the production area to produce micro-droplets, which can improve the generation effect of micro-droplets.
如图8所示,第一延长流道161与第二延长流道162相互平行。As shown in FIG. 8 , the first extension channel 161 and the second extension channel 162 are parallel to each other.
第一延长流道161与第二延长流道162相互平行,可使两者间的距离恒定并保持最大距离,可使得加样层11和排样层12的以键合或胶贴等方式封装更容易,封装效果更好。The first extended flow channel 161 and the second extended flow channel 162 are parallel to each other, so that the distance between the two can be kept constant and the maximum distance can be maintained, so that the sample loading layer 11 and the sample layout layer 12 can be packaged by bonding or adhesive bonding. Easier and better encapsulation.
如图9所示,本实施例的排样管121包括内腔123和排液口124,内腔123的腔壁自内腔123顶部向内腔123底部逐渐收敛。排液口124开设于内腔123的底部。As shown in FIG. 9 , the sampling tube 121 of this embodiment includes an inner cavity 123 and a liquid outlet 124 , and the wall of the inner cavity 123 gradually converges from the top of the inner cavity 123 to the bottom of the inner cavity 123 . The drain port 124 is opened at the bottom of the inner cavity 123 .
排样管121内部中空形成内腔123,内腔123的顶部连通微流道层15的出口122,微流道层15形成的微液滴自该出口122沿内腔123的腔壁向下流动。并从内腔123底部的排液口124滴落至收集板3的收集孔31中。The inner cavity 123 is formed in the hollow of the sampling tube 121, and the top of the inner cavity 123 communicates with the outlet 122 of the microchannel layer 15, and the microdroplets formed by the microchannel layer 15 flow down from the outlet 122 along the wall of the inner cavity 123 . And drip from the drain port 124 at the bottom of the inner chamber 123 to the collecting hole 31 of the collecting plate 3 .
实施例二Embodiment two
本实施的微液滴生成装置其结构与实施例一大致相同,对其相同部分不再赘述,不同之处在于本实施例的排样管121。The structure of the micro-droplet generation device in this embodiment is roughly the same as that in Embodiment 1, and the same parts thereof will not be described again. The difference lies in the sample-discharging tube 121 in this embodiment.
如图10、11所示,排样管121包括内腔123,排液口124和导流面125。内腔123的腔壁自内腔123顶部向内腔123底部逐渐收敛。排液口124开设于内腔123的底部的一侧。导流面125设于内腔123的底部,导流面125一端抵住腔壁,导流面125的另一端向下倾斜并延伸至排液口124。As shown in FIGS. 10 and 11 , the sample discharge tube 121 includes an inner cavity 123 , a liquid discharge port 124 and a flow guide surface 125 . The cavity wall of the inner cavity 123 gradually converges from the top of the inner cavity 123 to the bottom of the inner cavity 123 . The drain port 124 is opened on one side of the bottom of the inner cavity 123 . The flow guide surface 125 is disposed at the bottom of the inner cavity 123 , one end of the flow guide surface 125 is against the wall of the cavity, and the other end of the flow guide surface 125 is inclined downward and extends to the liquid outlet 124 .
本实施例中,排样管121内部中空形成内腔123,内腔123的顶部连通微流道层15的出口122,微流道层15形成的微液滴自该出口122沿内腔123的腔壁向下流动。排液口124开设于排样管121的侧面底部,导流面125则是设于内腔123底部沿着内腔123腔壁向排液口124向下倾斜的斜面。In this embodiment, the interior of the sample discharge tube 121 is hollow to form an inner cavity 123, and the top of the inner cavity 123 communicates with the outlet 122 of the micro-channel layer 15, and the micro-droplets formed by the micro-channel layer 15 flow from the outlet 122 along the direction of the inner cavity 123. The cavity wall flows downward. The liquid discharge port 124 is opened at the bottom of the side of the sample discharge pipe 121 , and the flow guide surface 125 is provided at the bottom of the inner cavity 123 and slopes downward toward the liquid discharge port 124 along the wall of the inner cavity 123 .
微液滴可沿内腔123的腔壁向腔底流动至导流面125上,再由导流面125缓慢流至排液口124排出,可以避免微液滴直接滴落冲击过大可能损害微液滴结构。The micro-droplets can flow along the cavity wall of the inner cavity 123 to the bottom of the cavity to the guide surface 125, and then slowly flow from the guide surface 125 to the discharge port 124 to be discharged, which can avoid the possible damage to the micro-droplets due to excessive impact. Micro-droplet structure.
如图10,11所示,排样管121还包括引流部126,引流部126设于内腔123开设排液口124的一侧的腔壁上,引流部126沿腔壁凸起并向排液口124延伸,引流部126的末端在垂直方向上的投影位于导流面125上。As shown in Figures 10 and 11, the sample discharge tube 121 also includes a drainage part 126. The drainage part 126 is arranged on the cavity wall on the side where the liquid discharge port 124 is opened in the inner cavity 123. The drainage part 126 protrudes along the cavity wall and drains toward The liquid port 124 extends, and the projection of the end of the drainage part 126 in the vertical direction is located on the flow guiding surface 125 .
本实施例中,引流部126的倾斜角度略大于腔壁的倾斜角度,并且其末端在垂直方向上位于导流面125上,保证从引流部126滴落的微液滴可落在导流面125上,避免微液滴从该侧腔壁直接从排液口124流出,提升排样管121的导流效果。In this embodiment, the inclination angle of the drainage part 126 is slightly larger than the inclination angle of the cavity wall, and its end is located on the flow guide surface 125 in the vertical direction, so as to ensure that the micro-droplets dripping from the drainage part 126 can fall on the flow guide surface 125, to prevent micro-droplets from flowing out of the side chamber wall directly from the discharge port 124, and improve the diversion effect of the sample discharge tube 121.
虽然以上描述了本发明的具体实施方式,但是本领域的技术人员应当理解,这仅是举例说明,本发明的保护范围是由所附权利要求书限定的。本领域的技术人员在不背离本发明的原理和实质的前提下,可以对这些实施方式做出多种变更或修改,但这些变更和修改均落入本发明的保护范围。Although the specific implementation of the present invention has been described above, those skilled in the art should understand that this is only an example, and the protection scope of the present invention is defined by the appended claims. Those skilled in the art can make various changes or modifications to these embodiments without departing from the principle and essence of the present invention, but these changes and modifications all fall within the protection scope of the present invention.

Claims (11)

  1. 一种微液滴生成装置,其特征在于,其包括:A micro droplet generating device is characterized in that it comprises:
    生成芯片,所述生成芯片包含第一隔室和第二隔室,所述生成芯片可将所述第一隔室和所述第二隔室的液体样本生成为微液滴;generating a chip, the generating chip comprising a first compartment and a second compartment, the generating chip can generate liquid samples in the first compartment and the second compartment into micro-droplets;
    收集板,所述收集板包括收集孔;a collection plate comprising collection holes;
    连接基座,所述连接基座包裹所述收集板,所述连接基座包括芯片支架,所述生成芯片放置并限位于所述芯片支架,所述收集板可拆卸地安装在所述连接基座上。A connection base, the connection base wraps the collection plate, the connection base includes a chip support, the generated chip is placed and limited on the chip support, the collection plate is detachably mounted on the connection base seat.
  2. 如权利要求1所述的微液滴生成装置,其特征在于,所述收集板为96孔板。The micro droplet generating device according to claim 1, wherein the collecting plate is a 96-well plate.
  3. 如权利要求1或2所述的微液滴生成装置,其特征在于,所述生成芯片包括排样管,所述微液滴通过所述排样管排出,当所述生成芯片放置并限位于所述芯片支架时,所述排样管伸入所述收集孔中。The micro-droplet generation device according to claim 1 or 2, wherein the generation chip comprises a sample discharge tube, and the micro-droplets are discharged through the sample discharge tube, when the generation chip is placed and limited to When the chip is supported, the sample discharge tube extends into the collection hole.
  4. 如权利要求1-3中至少一项所述的微液滴生成装置,其特征在于,所述生成芯片包含若干芯片模块,所述芯片模块包括若干与所述收集孔一一对应的芯片单元,若干芯片单元一体成型形成芯片模块。The device for generating microdroplets according to at least one of claims 1-3, wherein the generating chip comprises a plurality of chip modules, and the chip module includes a plurality of chip units one-to-one corresponding to the collection holes, Several chip units are integrally molded to form a chip module.
  5. 如权利要求4所述的微液滴生成装置,其特征在于,所述芯片模块由热塑材料或热固材料或玻璃材料形成。The micro droplet generating device according to claim 4, wherein the chip module is formed of thermoplastic material or thermosetting material or glass material.
  6. 如权利要求3-5中至少一项所述的微液滴生成装置,其特征在于,所述生成芯片包括:The microdroplet generating device according to at least one of claims 3-5, wherein the generating chip comprises:
    加样层,所述加样层设于所述生成芯片的顶部,所述第一隔室和第二隔室设于所述加样层上;A sample application layer, the sample application layer is arranged on the top of the generation chip, and the first compartment and the second compartment are provided on the sample application layer;
    排样层,所述排样层设于所述生成芯片的底部,所述排样管设于所述排样层上,所述排样层顶面与所述加样层的底面相互贴合并密封;A sample layout layer, the sample layout layer is arranged at the bottom of the generation chip, the sample layout tube is arranged on the sample layout layer, the top surface of the sample layout layer and the bottom surface of the sample application layer are attached to each other and merged seal;
    微流道层,所述排样层顶面与所述加样层的底面相互贴合并密封形成所述微流道层,所述微流道层包括与所述第一隔室和所述排样管联通的第一流道,与所述第二隔室以及所述第一流道连通的第二流道,所述第二流道沿所述第一流道的垂直方向和所述第一流道在生成区域交汇。The micro-channel layer, the top surface of the sampling layer and the bottom surface of the sample-loading layer are attached and sealed to form the micro-channel layer, and the micro-channel layer includes the first compartment and the row The first flow channel communicated with the sample tube, the second flow channel communicated with the second compartment and the first flow channel, the second flow channel is along the vertical direction of the first flow channel and the first flow channel Generate area intersections.
  7. 如权利要求6所述的微液滴生成装置,其特征在于,所述排样层的顶面和/或所述加样层的底面凹陷形成第一凹槽和第二凹槽,所述第一凹槽和所述第二凹槽通过与所述加样层的底面和/或所述排样层的顶面相互贴合并密封形成所述第一流道和所述第二流道。The micro-droplet generating device according to claim 6, wherein the top surface of the sample discharge layer and/or the bottom surface of the sample application layer are depressed to form a first groove and a second groove, and the first groove The first flow path and the second flow path are formed by a groove and the second groove being attached to and sealed with the bottom surface of the sample application layer and/or the top surface of the sample discharge layer.
  8. 如权利要求6或7所述的微液滴生成装置,其特征在于,所述第一流道沿液体样本的流动方向依次包括:连通第一隔室的第一入口、缓冲区域、生成区域和连通排样管的出口;The micro-droplet generating device according to claim 6 or 7, wherein the first flow channel sequentially comprises along the flow direction of the liquid sample: a first inlet communicating with the first compartment, a buffer area, a generating area, and a communication area. The outlet of the sample tube;
    所述缓冲区域包括沿所述第一流道侧面方向延伸的第一延长流道和第二延长流道,所述第一延长流道和所述第二延长流道通过弯折流道连通,所述第一延长流道连通所述第一入口,所述第二延长流道连通所述生成区域。The buffer area includes a first extended flow channel and a second extended flow channel extending along the side of the first flow channel, and the first extended flow channel and the second extended flow channel communicate through a bent flow channel, so The first extended channel communicates with the first inlet, and the second extended channel communicates with the generating area.
  9. 如权利要求8所述的微液滴生成装置,其特征在于,所述第一延长流道与所述第二延长流道相互平行。The micro droplet generating device according to claim 8, wherein the first extended channel and the second extended channel are parallel to each other.
  10. 如权利要求3-9中至少一项所述的微液滴生成装置,其特征在于,所述排样管包括:The microdroplet generating device according to at least one of claims 3-9, wherein the sample discharge tube comprises:
    内腔,所述内腔的腔壁自内腔顶部向内腔底部逐渐收敛;an inner cavity, the cavity wall of which gradually converges from the top of the cavity to the bottom of the cavity;
    排液口,所述排液口开设于所述内腔的底部的一侧;a liquid discharge port, the liquid discharge port is opened on one side of the bottom of the inner cavity;
    导流面,所述导流面设于所述内腔的底部,所述导流面自所述腔壁位置向下倾斜并延伸至所述排液口。A diversion surface, the diversion surface is arranged at the bottom of the inner cavity, the diversion surface is inclined downward from the position of the cavity wall and extends to the liquid discharge port.
  11. 如权利要求10所述的微液滴生成装置,其特征在于,所述排样管还包括引流部,所述引流部设于所述内腔开设所述排液口的一侧的所述腔壁上,所述引流部沿所述腔壁凸起并向所述排液口延伸,所述引流部的末端在垂直方向上的投影位于所述导流面上。The micro-droplet generating device according to claim 10, wherein the sample discharge tube further comprises a drainage part, and the drainage part is arranged in the cavity on the side where the liquid discharge port is opened in the inner cavity. On the wall, the drainage part protrudes along the chamber wall and extends toward the liquid discharge port, and the projection of the end of the drainage part in the vertical direction is located on the flow guide surface.
PCT/CN2021/129697 2021-08-20 2021-11-10 Micro-droplet generation device WO2023019759A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202110961284.0 2021-08-20
CN202110961284.0A CN114950580A (en) 2021-08-20 2021-08-20 Micro-droplet generating device

Publications (1)

Publication Number Publication Date
WO2023019759A1 true WO2023019759A1 (en) 2023-02-23

Family

ID=82972993

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/129697 WO2023019759A1 (en) 2021-08-20 2021-11-10 Micro-droplet generation device

Country Status (2)

Country Link
CN (1) CN114950580A (en)
WO (1) WO2023019759A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113512494B (en) * 2021-05-06 2024-03-22 中国科学院上海高等研究院 Cell micro-fluidic culture chip

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007210114A (en) * 2006-02-07 2007-08-23 Brother Ind Ltd Inkjet head
CN207981204U (en) * 2017-11-06 2018-10-19 北京天健惠康生物科技有限公司 Microlayer model generates system
CN109746059A (en) * 2017-11-06 2019-05-14 北京新羿生物科技有限公司 Microlayer model generates system
CN110787846A (en) * 2019-11-05 2020-02-14 华中科技大学 One-step double-layer micro-droplet generation device and method

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007210114A (en) * 2006-02-07 2007-08-23 Brother Ind Ltd Inkjet head
CN207981204U (en) * 2017-11-06 2018-10-19 北京天健惠康生物科技有限公司 Microlayer model generates system
CN109746059A (en) * 2017-11-06 2019-05-14 北京新羿生物科技有限公司 Microlayer model generates system
CN110787846A (en) * 2019-11-05 2020-02-14 华中科技大学 One-step double-layer micro-droplet generation device and method

Also Published As

Publication number Publication date
CN114950580A (en) 2022-08-30

Similar Documents

Publication Publication Date Title
US7686029B2 (en) Microfluidic device for trapping air bubbles
CN101868730B (en) Microfluidic chip for analysis of fluid sample
CN109738224B (en) Microfluidic system with fluid collection tubes
US20120051947A1 (en) Method Of Pumping Fluid Through A Microfluidic Device
JP2013527022A (en) System and method for automatic formation and manipulation of liquid mixtures.
EP1623760B1 (en) Micro fluid chip
US6905657B2 (en) Methods and devices for storing and dispensing liquids
WO2023019759A1 (en) Micro-droplet generation device
CN109395788A (en) A kind of intraluminal fluid dripping is for chip apparatus
US11130120B2 (en) Micro-pipette tip for forming micro-droplets
US20080112850A1 (en) Micro Total Analysis Chip and Micro Total Analysis System
CN107847929A (en) Micro fluidic plate
CN111957361A (en) Micro-droplet preparation system, micro-fluidic chip and design method thereof
CN101178398A (en) Micro total analysis chip and micro total analysis system
JP4381670B2 (en) Reactor
CN110804531B (en) Intestinal microorganism detection system based on micro-droplets
JP3782796B2 (en) Liquid injection structure
CN215823099U (en) Micro-droplet generating device
CN110756233A (en) Micro-droplet preparation system, micro-fluidic chip and micro-droplet preparation method
CN112795989B (en) Micro-drop type digital polymerase chain reaction chip
KR101934856B1 (en) Microfluidic Chip with an Ideal-mixing Micro-tank
CN105214746B (en) The movable micro-fluidic chip of channel side wall specified location
CN209362517U (en) A kind of intraluminal fluid dripping is for chip structure
JP2006055770A (en) Microchannel structure
CN212396772U (en) Micro-droplet preparation system and micro-fluidic chip

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21953994

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE