CN114950580A - Micro-droplet generating device - Google Patents

Micro-droplet generating device Download PDF

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Publication number
CN114950580A
CN114950580A CN202110961284.0A CN202110961284A CN114950580A CN 114950580 A CN114950580 A CN 114950580A CN 202110961284 A CN202110961284 A CN 202110961284A CN 114950580 A CN114950580 A CN 114950580A
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China
Prior art keywords
chip
micro
flow channel
sample
layer
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CN202110961284.0A
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Chinese (zh)
Inventor
徐亚骏
郑文山
裴颢
徐云飞
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Mezhuo Biotechnology Zhejiang Co ltd
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Mezhuo Biotechnology Zhejiang Co ltd
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Priority to CN202110961284.0A priority Critical patent/CN114950580A/en
Priority to PCT/CN2021/129697 priority patent/WO2023019759A1/en
Publication of CN114950580A publication Critical patent/CN114950580A/en
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    • 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

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

The invention discloses a micro-droplet generating device, which comprises a generating chip, a first liquid sample collecting device and a second liquid sample collecting device, wherein the generating chip comprises a first compartment and a second compartment, and can generate liquid samples of the first compartment and the second compartment into micro-droplets; a collection plate comprising collection holes; connection base, connection base parcel collecting plate, connection base include the chip support, and it places and is spacing in the chip support to generate the chip, and collecting plate detachably installs on connection base. According to the micro-droplet generation device disclosed by the invention, the generation chip and the 96-well plate serving as the collection plate are integrated together through the connecting base, so that micro-droplets generated by the production chip can be directly collected by the 96-well plate serving as the collection plate. The collecting plate is detachably installed on the connecting base, and is convenient to directly disassemble after collecting the micro-droplets for subsequent operation without transferring the micro-droplets through other means and tools, so that the flow is simple and convenient, and the micro-droplet sample is not easily polluted in the process.

Description

Micro-droplet generating device
Technical Field
The invention relates to the field of biology, in particular to a micro-droplet generating device.
Background
The micro-droplet technology is a micro-nano technology for dividing and separating continuous fluid into droplets with discrete nano-scale volume and the volume below the discrete nano-scale volume by utilizing the interaction between flow shearing force and surface tension in a micro-scale channel.
The micro-droplet type is mainly two types, gas-liquid phase droplet and liquid-liquid phase droplet. The liquid-liquid phase micro-droplet has the advantages of small volume, no diffusion among droplet samples, capability of avoiding cross contamination among samples, stable reaction conditions, capability of realizing rapid mixing under proper control and the like.
The liquid-liquid phase droplets are classified into "oil-in-water", "water-in-oil", "oil-in-water-in-oil", and "water-in-oil-in-water", etc., 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 the diameter of micron order (namely 10-1000 mu m), and provides a research site with high sensitivity, high efficiency and high flux for a plurality of application scenes in the fields of biology, chemistry, materials and the like.
96 orifice plate is the experiment consumptive material that the biological field is commonly used, but the micro-droplet generating device of prior art is compatible relatively poor with 96 orifice plate, can't directly generate the micro-droplet sample to 96 orifice plate in, when in actual use, often need transfer the micro-droplet to 96 orifice plate through other means and instrument after the micro-droplet generating device produces the micro-droplet, the flow is complicated and the in-process produces the pollution of micro-droplet sample easily. Therefore, it is difficult to use the system as an experimental system with high universality in the fields of biology, chemistry, materials and the like.
Disclosure of Invention
The invention aims to overcome the defects that in the prior art, a micro-droplet generating device is poor in compatibility with a 96-well plate, a micro-droplet sample cannot be directly generated in the 96-well plate, and when the micro-droplet generating device is actually used, after micro-droplets are generated by the micro-droplet generating device, the micro-droplets are often transferred to the 96-well plate through other means and tools, the process is complicated, and pollution of the micro-droplet sample is easily generated in the process, and the micro-droplet generating device is provided.
The invention solves the technical problems through the following technical scheme:
a micro-droplet generation apparatus, comprising:
a generation chip comprising a first compartment and a second compartment, the generation chip being capable of generating liquid samples of the first compartment and the second compartment as microdroplets;
a collection plate that is a 96-well plate comprising collection wells;
the connection base wraps the collecting plate, the connection base comprises a chip support, the generated chips are placed and limited on the chip support, and the collecting plate is detachably mounted on the connection base.
In the scheme, the structure is adopted, the generation chip and the 96-well plate as the collection plate are integrated together through the connecting base, so that micro-droplets generated by the production chip can be directly collected by the 96-well plate as the collection plate. The collecting plate is detachably mounted on the connecting base, and can be conveniently directly detached to perform subsequent operation after collecting micro liquid drops without transferring the micro liquid drops through other means and tools, so that the flow is simple and convenient, and the micro liquid drop sample is not easily polluted in the process.
Preferably, the generating chip comprises a sampling pipe, the micro liquid drops are discharged through the sampling pipe, and when the generating chip is placed and limited on the chip support, the sampling pipe extends into the collecting hole.
In this scheme, adopt above-mentioned structural style, spacing through chip support can so that generate in its arranging the pipe directly stretches into the collecting hole of collecting plate when the chip is placed above that for generate the chip and counterpoint with the collecting plate. Meanwhile, the height of the micro liquid drops can be reduced by extending the sampling pipe into the collecting hole, the kinetic energy of the micro liquid drops is reduced, and the micro liquid drop structure is prevented from being damaged by the impact of the micro liquid drops.
Preferably, the generated chip comprises a plurality of chip modules, each chip module comprises a plurality of chip units corresponding to the collecting holes one by one, and the plurality of chip units are integrally formed to form the chip module.
In this scheme, adopt above-mentioned structural style, it has a plurality of the same chip module to constitute to generate the chip, contains a plurality of chip units again on every chip module, and every chip unit can generate little liquid drop alone, and the quantity of chip unit and the quantity one-to-one of the collection hole of collection board. Each single chip module is integrally formed, so that the chip modules can be conveniently processed in batches, and the production and maintenance cost of the generated chips can be reduced.
Preferably, the chip module is formed of a thermoplastic material or a thermosetting material or glass.
In the scheme, the structural form is adopted, so that materials such as thermoplastic materials, thermosetting materials, glass and the like are easy to process, the cost is low, and the cost for generating the chip is further reduced.
Preferably, the generating chip includes:
the sample adding layer is arranged on the top of the generated chip, and the first compartment and the second compartment are arranged on the sample adding layer;
the sample arrangement layer is arranged at the bottom of the generated chip, the sample arrangement pipe is arranged on the sample arrangement layer, and the top surface of the sample arrangement layer and the bottom surface of the sample adding layer are mutually attached and sealed;
the micro-fluidic layer, the lofting layer top surface with the bottom surface on application of sample layer pastes each other and sealed formation the micro-fluidic layer, the micro-fluidic layer include with first compartment with the first runner of pilot tube UNICOM, with the second compartment with the second runner of first runner intercommunication, the second runner is followed the vertical direction of first runner with first runner crosses in the generation region.
In this scheme, adopt above-mentioned structural style, the micro flow channel layer is formed with modes such as bonding or glue subsides by application of sample layer and stock layout layer, and the close range upon range of fit of chip three layer construction, high integration, area and small, are showing the cost that has reduced little liquid drop and generate.
Preferably, the top surface of the sample discharge layer and/or the bottom surface of the sample addition layer are recessed to form a first groove and a second groove, and the first groove and the second groove are mutually attached and sealed with the bottom surface of the sample addition layer and/or the top surface of the sample discharge layer to form the first flow channel and the second flow channel.
In the scheme, the generation chip generates micro liquid drops through the first flow channel and the second flow channel by adopting the structural form, the first flow channel and the second flow channel are formed by grooves arranged on the top surface of the sample discharging layer and/or the bottom surface of the sample adding layer, and after the sample discharging layer and the sample adding layer are packaged in a bonding or adhesive tape mode and the like, the grooves become flow channels for liquid samples to flow and intersect, so that the micro liquid drops are generated, and the chip is highly integrated.
Preferably, the first flow channel sequentially comprises, in the flow direction of the liquid sample: a first inlet communicated with the first compartment, the buffer area, the generation area and an outlet communicated with the sampling pipe;
the buffer area comprises a first extension flow channel and a second extension flow channel which extend along the side face direction of the first flow channel, the first extension flow channel is communicated with the second extension flow channel through a bent flow channel, the first extension flow channel is communicated with the first inlet, and the second extension flow channel is communicated with the generation area.
In the scheme, the structure is adopted, the liquid sample enters the first flow channel from the first compartment through the first inlet, and is intersected with the liquid sample in the second flow channel in the generation area to form micro liquid drops, and then the micro liquid drops flow out from the sample discharge pipe through the outlet. The buffer area is an extension section which returns to the direction of the original flow channel after being bent to one side, the buffer area which is extended to one side is arranged between the first inlet and the generation area, so that a liquid sample can be stabilized in the extended buffer area after entering the flow channel, the flow speed of the liquid sample is relatively stable with the uniform degree, and then the liquid sample enters the production area to produce micro-droplets, and the generation effect of the micro-droplets can be improved.
Preferably, the first extension flow channel and the second extension flow channel are parallel to each other.
In this scheme, adopt above-mentioned structural style, first extension runner is parallel to each other with second extension runner, can make distance between the two invariable and keep the maximum distance, can make application of sample layer and stock layout layer with the encapsulation of modes such as bonding or glue paste easier, the encapsulation effect is better.
Preferably, the sampling pipe comprises:
the cavity wall of the inner cavity gradually converges from the top of the inner cavity to the bottom of the inner cavity;
the liquid outlet is formed in one side of the bottom of the inner cavity;
the flow guide surface is arranged at the bottom of the inner cavity, one end of the flow guide surface props against the cavity wall, and the other end of the flow guide surface inclines downwards and extends to the liquid outlet.
In this scheme, adopt above-mentioned structural style, the export on drainage tube intercommunication micro flow path layer, the micro-droplet on micro flow path layer flows into the inner chamber on drainage layer after the export flows to can follow the chamber wall of inner chamber and flow to the chamber bottom on the water conservancy diversion face, slowly flow to the leakage fluid dram by the water conservancy diversion face again and discharge, can avoid the direct drippage of micro-droplet to drop and strike too big probably harm micro-droplet structure.
Preferably, the drainage tube further comprises a drainage portion, the drainage portion is arranged on the cavity wall on one side, provided with the liquid discharge port, of the inner cavity, the drainage portion extends towards the liquid discharge port along the protrusion of the cavity wall, and the projection of the tail end of the drainage portion in the vertical direction is located on the flow guide surface.
In this scheme, adopt above-mentioned structural style, the chamber wall top that the leakage fluid dram one side was seted up to the array tube still is equipped with bellied drainage portion, and the micro-droplet on this side cavity wall is guided to the water conservancy diversion face on to accessible protrusion structure, avoids the micro-droplet to flow out from this side cavity wall is direct from the leakage fluid dram, promotes the water conservancy diversion effect of array tube.
The positive progress effects of the invention are as follows: according to the micro-droplet generation device disclosed by the invention, the generation chip and the 96-well plate serving as the collection plate are integrated together through the connecting base, so that micro-droplets generated by the production chip can be directly collected by the 96-well plate serving as the collection plate. The collecting plate is detachably mounted on the connecting base, and can be conveniently directly detached to perform subsequent operation after collecting micro liquid drops without transferring the micro liquid drops through other means and tools, so that the flow is simple and convenient, and the micro liquid drop sample is not easily polluted in the process.
Drawings
Fig. 1 is a schematic structural view of a droplet generating apparatus according to embodiment 1 of the present invention.
Fig. 2 is an exploded view of a droplet generator according to embodiment 1 of the present invention.
Fig. 3 is a partial structural schematic view of the connection 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 a chip module according to embodiment 1 of the present invention.
Fig. 6 is a schematic view of a connection structure between a chip module and a connection base according to embodiment 1 of the present invention.
Fig. 7 is a schematic structural view of a micro channel layer in embodiment 1 of the present invention.
Fig. 8 is a schematic structural view of a micro channel layer in embodiment 1 of the present invention.
Fig. 9 is a schematic structural view of a micro channel layer in embodiment 1 of the present invention.
Fig. 10 is a schematic structural view of a sampling pipe according to embodiment 2 of the present invention.
Fig. 11 is a schematic view of the internal structure of a sampling pipe according to embodiment 2 of the present invention.
Description of reference numerals:
generating chip 1
Sample addition layer 11
Stock layout layer 12
Sampling pipe 121
An outlet 122
Inner cavity 123
Liquid discharge port 124
Flow guide surface 125
Drainage portion 126
Chip module 13
Chip unit 14
First compartment 141
First inlet 143
Second inlet 144
Second compartment 142
The micro flow channel layer 15
First flow passage 16
First extension flow path 161
Second extension flow passage 162
Bent flow passage 163
Second flow path 17
Generating the region 18
Connection base 2
Chip holder 21
Bump 211
Notch 212
Buckle 22
Collecting plate 3
Collecting hole 31
Card slot 32
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.
Example one
As shown in fig. 1 to 3, the micro-droplet generating device of the present embodiment includes a generating chip 1, a collecting plate 3, and a connection base 2. The generation chip 1 comprises a first compartment 141 and a second compartment 142, and the generation chip 1 can generate the liquid sample of 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 comprises collection wells 31. Connecting base 2 parcel collecting plate 3, connecting base 2 includes chip support 21, generates that chip 1 places and spacing in chip support 21, and collecting plate 3 detachable installs on connecting base 2.
In this embodiment, the first and second compartments 141 and 142 of the production chip 1 are used to inject the aqueous phase liquid and the oil phase liquid, respectively. The two compartments are pressurized by precise pneumatic control means, so that the liquid is discharged into the collection wells 31 of the collection plate 3 by generating micro-droplets of "water in oil" or "oil in water" by the generating chip 1.
The collection plate 3 of this embodiment is a 96-well plate, which is a consumable material for experiments commonly used in the field of biology, and has 8 × 12 collection wells 31. In other embodiments, the collecting plate 3 may also consist of several 8 rows of tubes.
As shown in fig. 2 and 3, the connection base 2 of the present embodiment is a square frame, and the connection base 2 can be sleeved on the collecting plate 3 and wrapped around the collecting plate 3, and is detachably fixed to the clamping groove 32 of the collecting plate 3 through the buckle 22 of the connection base 2. Making its connection to the collecting plate 3 more stable. The locking slots 32 are disposed on both sides of the collecting plate 3, and the locking hooks 22 are disposed on corresponding positions on both sides of the connecting base 2. The buckle 22 is arranged at one end of a connecting plate which can be bent to a certain degree, the other end of the connecting plate is fixed on the side surface of the connecting base 2, and the back surface of one end of the connecting plate, which is provided with the buckle 22, is also provided with a handle part which extends to the other end of the connecting plate. The handle portion is squeezed to bend the web outwardly so that the catch 22 is lifted to engage or disengage the catch 32 of the collector plate 3.
As shown in fig. 2 and 3, the chip holder 21 is composed of two opposite side tops of the connection base 2 and a plurality of sets of corresponding bumps 211 arranged at intervals, when the chip is placed on the connection base 2, the edge of the chip is clamped in the notch 212 between the two bumps 211 and aligned with the collection plate 3 clamped on the connection base 2.
In other embodiments, the connection base 2 may also be connected to the collecting plate 3 in other ways without sleeving the collecting plate 3, such as making an upper frame structure installed on the top surface of the collecting plate 3, or making a base structure to directly place the collecting plate 3 into the connection base 2. The chip holder 21 is not limited to the protrusion 211 and the notch 212 disposed at the edge, and is realized by adding a top surface with a mounting groove on the top of the connection base 2, or by adding a support structure on the top surface of the collection plate 3 inside the connection base 2, as long as the detachable mounting of the collection plate 3 and the fixing and limiting of the generated chip 1 can be realized.
The production chip 1 is integrated with a 96-well plate as a collection plate 3 by a connection base 2 so that micro-droplets produced by the production chip can be directly collected by the 96-well plate as the collection plate 3. Collecting plate 3 detachably installs in connection base 2, also conveniently collects the little liquid drop after direct dismantlement get off carry out subsequent operation, need not to shift the little liquid drop through other means and instrument, the flow is simple and convenient and the difficult little liquid drop sample of polluting of in-process.
As shown in fig. 2, the production chip 1 includes a sample discharge tube 121, the micro-droplets are discharged through the sample discharge tube 121, and when the production chip 1 is placed and retained on the chip holder 21, the sample discharge tube 121 extends into the collection hole 31.
In this embodiment, the sampling tube 121 is disposed on the bottom surface of the production chip 1 and extends downward, and when the production chip 1 is mounted on the notch 212, the sampling tube 121 of the production chip 1 faces the collection port and extends into the collection hole 31.
By the limit of the chip support 21, the sampling tube 121 of the generated chip 1 can directly extend into the collecting hole 31 of the collecting plate 3 when the generated chip is placed on the chip support, so that the generated chip 1 and the collecting plate 3 are aligned. Meanwhile, the height of the micro-droplet dropping can be reduced by extending the sampling pipe 121 into the collecting hole 31, the kinetic energy of the micro-droplet dropping is reduced, and the micro-droplet structure is prevented from being damaged by the dropping impact.
In other embodiments, the discharge port may be only aligned with the collection well 31 and not extend into the collection well 31, but this structure only ensures the micro-droplets to drop into the collection well 31 but does not reduce the kinetic energy of the micro-droplets.
As shown in fig. 1 to 5, the generated chip 1 includes a plurality of chip modules, each chip module includes a plurality of chip units 14 corresponding to the collecting holes 31, and the plurality of chip units 14 are integrally formed to form the chip module.
In this embodiment, each chip unit 14 can individually generate micro droplets, and includes a set of first compartments 141, second compartments 142, and a plurality of sample tubes 121, and a single chip module has 8 chip units 14 arranged laterally. The generated chip 1 of the present embodiment is composed of 12 chip modules, has 8 × 12 chip units 14 in total, and corresponds to a 96-well plate as the collection plate 3.
In other embodiments, the arrangement direction and the number of the chip units 14 of the chip module 13 are not limited thereto, and may be adjusted according to different use scenes and different requirements, as long as the chip units can be ensured to correspond to the collecting holes 31 of the collecting plate 3.
The generation chip 1 is composed of a plurality of identical chip modules, each chip module comprises a plurality of chip units 14, each chip unit 14 can independently generate micro droplets, and the number of the chip units 14 corresponds to the number of the collection holes 31 of the collection plate 3 one by one. Each individual chip module is integrally formed, so that the chip modules can be conveniently processed in batch, and the production and maintenance cost of the generated chip 1 can be reduced.
In this embodiment, the chip module is formed of a thermoplastic material, a thermosetting material, and glass. The material is easy to process and low in cost, and the cost for generating the chip 1 is further reduced.
In other embodiments, other common thermoforming materials may be used to make the product.
As shown in FIGS. 2 to 8, the production chip 1 includes a sample addition layer 11, a sample discharge layer 12, and a micro flow channel layer 15. The sample adding layer 11 is arranged on the top of the generated chip 1, and the first compartment 141 and the second compartment 142 are arranged on the sample adding layer 11; the sample discharging layer 12 is arranged at the bottom of the generating chip 1, the sample discharging pipe 121 is arranged on the sample discharging layer 12, and the top surface of the sample discharging layer 12 and the bottom surface of the sample adding layer 11 are mutually attached and sealed; the top surface of the sample discharging layer 12 and the bottom surface of the sample adding layer 11 are attached to each other and sealed to form a micro flow channel layer 15, the micro flow channel layer 15 includes a first flow channel 16 communicating with the first compartment 141 and the sample discharging tube 121, and a second flow channel 17 communicating with the second compartment 142 and the first flow channel 16, and the second flow channel 17 intersects with the first flow channel 16 in the generation region 18 along the vertical direction of the first flow channel 16.
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 communicates with the first flow channel 16 from both sides in the generation region 18. The liquid in the two compartments enters the two channels by the air pressure and flows towards the outlet 122. When the liquid in the first compartment 141 flows through the generation region 18 within the first flow channel 16, the respective micro-droplets are generated under the action of the flow shear force of the liquid in the second flow channel 17.
In this embodiment, the top surface of the sample discharging layer 12 and the bottom surface of the sample adding layer 11 are bonded and packaged, and in other embodiments, other common packaging methods such as adhesive tape may be used.
When the first compartment 141 is filled with an oil phase liquid and the second compartment 142 is filled with an aqueous phase liquid, oil-in-water microdroplets can be generated;
when the first compartment 141 is filled with an aqueous liquid and the second compartment 142 is filled with an oil liquid, water-in-oil microdroplets may be generated.
The micro flow channel layer 15 of this embodiment is formed by bonding or pasting the sample addition layer 11 and the sample discharge layer 12. In other embodiments, a separate microfluidic layer 15 may be further provided and is in communication with the sample application layer 11 and the first inlet 143, the second inlet 144, and the outlet 122 of the sample discharge layer 12.
The micro-channel layer 15 is formed by the sample adding layer 11 and the sample discharging layer 12 in a bonding or adhesive bonding mode, the three-layer structure of the chip is tightly laminated and matched, the integration is high, the area and the volume are small, and the generation cost of micro-droplets is obviously reduced.
As shown in fig. 7, the top surface of the sample application layer 12 and/or the bottom surface of the sample application layer 11 are recessed to form a first groove and a second groove, and the first groove and the second groove are bonded or bonded to the bottom surface of the sample application layer 11 and/or the top surface of the sample application layer 12 to form a first flow channel 16 and a second flow channel 17.
In this embodiment, the first groove and the second groove are both formed on the bottom surface of the sample addition layer 11. The stock-form layer 12 seals the groove by bonding or gluing to form a flow channel.
In other embodiments, the grooves may be formed on the top surface of the loft layer 12, or on both surfaces, respectively.
The generating chip 1 generates micro-droplets through the first flow channel 16 and the second flow channel 17, the first flow channel 16 and the second flow channel 17 are formed by grooves arranged on the top surface of the sample discharging layer 12 and/or the bottom surface of the sample adding layer 11, after the sample discharging layer 12 and the sample adding layer 11 are packaged in a bonding or adhesive bonding mode, the grooves become flow channels for liquid samples to flow and intersect, micro-droplets are generated, and the chip is highly integrated.
As shown in fig. 8, the first flow channel 16 includes, in order in the flow direction of the liquid sample: a first inlet 143 communicating with the first compartment 141, the buffer zone, the generation zone 18 and an outlet 122 communicating with the drainage tube 121. The buffer area includes a first extension flow path 161 and a second extension flow path 162 extending in a side direction of the first flow path 16, the first extension flow path 161 and the second extension flow path 162 are communicated by a bent flow path 163, the first extension flow path 161 is communicated with the first inlet 143, and the second extension flow path 162 is communicated with the generation area 18.
In this embodiment, the second flow path 17 extends from the second outlet 122 from both sides, and meets the first flow path 16 from both sides of the first flow path 16 in the vertical direction at the position of the generation region 18, and then is conducted to the outlet 122. The first flow channel 16 passes through a buffer region extended by bending from the first inlet 143, then extends to the generation region 18 to meet the second flow channel 17, and then is conducted to the outlet 122.
As shown in fig. 8, the buffering area of the present embodiment is composed of a first extending channel 161 which is communicated with the first inlet 143 and extends in a transverse direction, a bent channel 163 which is communicated with the tail end of the first extending channel 161 and is bent in a longitudinal direction, and a second extending channel 162 which is communicated with the tail end of the bent channel 163 and extends in a direction opposite to the direction in which the first extending channel 161 extends in the transverse direction. The whole buffer area is of a spiral structure.
In other embodiments, the buffer region may also be provided with more extended flow channels and bent flow channels 163, so that the buffer region is in a multi-layer spiral structure to further extend the overall length of the buffer region and increase the flow stabilizing effect. However, under the condition that the total length is not changed, the distance between the two extended flow channels can be longest by using only one buffer region with a bending structure, and the difficulty of packaging between the sample adding layer 11 and the sample discharging layer 12 in a bonding or adhesive manner can be reduced.
The liquid sample enters the first flow channel 16 from the first compartment 141 through the first inlet 143, and meets the liquid sample in the second flow channel 17 at the generation region 18 to form micro-droplets, and then flows out of the sample discharge tube 121 through the outlet 122. The buffer area is an extension section which is bent to one side and then returns to the original flow channel direction, the buffer area which is extended to one side is arranged between the first inlet 143 and the generation area 18, so that a liquid sample can be stabilized in the extended buffer area after entering the flow channel, the flow speed and the uniformity degree of the liquid sample are relatively stable, then the liquid sample enters the production area to produce micro-droplets, and the generation effect of the micro-droplets can be improved.
As shown in fig. 8, the first extension flow path 161 and the second extension flow path 162 are parallel to each other.
The first extension flow channel 161 and the second extension flow channel 162 are parallel to each other, so that the distance between the first extension flow channel and the second extension flow channel is constant and the maximum distance is kept, and the sample adding layer 11 and the sample discharging layer 12 can be packaged more easily in a bonding or adhesive manner, and the packaging effect is better.
As shown in fig. 9, the sampling pipe 121 of the present embodiment includes an inner cavity 123 and a liquid discharge port 124, and the wall of the inner cavity 123 gradually converges from the top of the inner cavity 123 toward the bottom of the inner cavity 123. The drain port 124 opens at the bottom of the internal cavity 123.
The interior of the sample discharge pipe 121 is hollow to form an inner cavity 123, the top of the inner cavity 123 is communicated with the outlet 122 of the micro-flow channel layer 15, and micro-droplets formed by the micro-flow channel layer 15 flow downwards from the outlet 122 along the wall of the inner cavity 123. And drops from the liquid discharge port 124 at the bottom of the inner cavity 123 into the collecting hole 31 of the collecting plate 3.
Example two
The structure of the droplet generating apparatus of this embodiment is substantially the same as that of the first embodiment, and the same parts are not described again, but the difference is the sample discharge tube 121 of this embodiment.
As shown in fig. 10 and 11, the drainage tube 121 includes an inner cavity 123, a drainage port 124 and a diversion surface 125. The walls of the lumen 123 converge from the top of the lumen 123 to the bottom of the lumen 123. The drain port 124 opens on one side of the bottom of the internal 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 abuts against the cavity wall, and the other end of the flow guide surface 125 inclines downward and extends to the liquid outlet 124.
In this embodiment, the inside of the sample discharge tube 121 is hollow to form an inner cavity 123, the top of the inner cavity 123 is communicated with the outlet 122 of the micro flow channel layer 15, and micro droplets formed by the micro flow channel layer 15 flow downwards from the outlet 122 along the wall of the inner cavity 123. The liquid outlet 124 is arranged at the bottom of the side surface of the sampling pipe 121, and the flow guide surface 125 is an inclined surface which is arranged at the bottom of the inner cavity 123 and inclines downwards towards the liquid outlet 124 along the cavity wall of the inner cavity 123.
The micro-droplets can flow to the bottom of the cavity along the cavity wall of the inner cavity 123 to the flow guide surface 125, and then slowly flow to the liquid discharge port 124 from the flow guide surface 125 to be discharged, so that the micro-droplet structure can be prevented from being damaged due to overlarge direct dropping impact of the micro-droplets.
As shown in fig. 10 and 11, the sampling tube 121 further includes a drainage portion 126, the drainage portion 126 is disposed on a cavity wall of the inner cavity 123 on a side where the liquid discharge port 124 is opened, the drainage portion 126 protrudes along the cavity wall and extends toward the liquid discharge port 124, and a projection of a distal end of the drainage portion 126 in a vertical direction is located on the flow guide surface 125.
In this embodiment, the inclination angle of the drainage portion 126 is slightly larger than the inclination angle of the cavity wall, and the end of the drainage portion is located on the flow guide surface 125 in the vertical direction, so that the micro-droplets dropped from the drainage portion 126 can be ensured to fall on the flow guide surface 125, the micro-droplets are prevented from directly flowing out from the liquid discharge port 124 from the cavity wall on the side, and the flow guide effect of the sampling tube 121 is improved.
While specific embodiments of the invention have been described above, it will be appreciated by those skilled in the art that this is by way of example only, and that the scope of the invention is defined by the appended claims. Various changes and modifications to these embodiments may be made by those skilled in the art without departing from the spirit and scope of the invention, and these changes and modifications are within the scope of the invention.

Claims (11)

1. A micro-droplet generator, comprising:
a generation chip comprising a first compartment and a second compartment, the generation chip being capable of generating liquid samples of the first compartment and the second compartment as microdroplets;
a collection plate comprising collection wells;
the connection base wraps the collecting plate, the connection base comprises a chip support, the generated chips are placed and limited on the chip support, and the collecting plate is detachably mounted on the connection base.
2. The micro-droplet generation apparatus of claim 1, wherein the collection plate is a 96-well plate.
3. The micro-droplet generating device of claim 1, wherein the generating chip comprises a sampling tube through which the micro-droplets are discharged, and wherein the sampling tube extends into the collecting hole when the generating chip is placed on and retained by the chip holder.
4. The micro-droplet generator of claim 1, wherein the generating chip comprises a plurality of chip modules, each chip module comprises a plurality of chip units corresponding to the collecting holes, and the plurality of chip units are integrally formed to form the chip module.
5. The microdroplet generating device of claim 4, wherein the chip module is formed from a thermoplastic material or a thermoset material or a glass material.
6. A microdroplet generating device as claimed in claim 3, wherein the generating chip comprises:
the sample adding layer is arranged on the top of the generated chip, and the first compartment and the second compartment are arranged on the sample adding layer;
the sample arrangement layer is arranged at the bottom of the generated chip, the sample arrangement pipe is arranged on the sample arrangement layer, and the top surface of the sample arrangement layer and the bottom surface of the sample adding layer are mutually attached and sealed;
the micro flow channel layer, the drainage layer top surface with the bottom surface on application of sample layer pastes each other and sealed formation the micro flow channel layer, the micro flow channel layer include with first compartment with the first runner of sample discharge pipe UNICOM, with the second compartment with the second runner of first runner intercommunication, the second runner is followed the vertical direction of first runner with first runner is at the regional intersection that generates.
7. The micro-droplet generating device according to claim 6, wherein the top surface of the sample application layer and/or the bottom surface of the sample application layer are recessed to form a first groove and a second groove, and the first groove and the second groove form the first flow channel and the second flow channel by being attached to and sealed with the bottom surface of the sample application layer and/or the top surface of the sample application layer.
8. The micro-droplet generating apparatus of claim 6, wherein the first flow channel comprises, in order along the flow direction of the liquid sample: a first inlet communicated with the first compartment, the buffer area, the generation area and an outlet communicated with the sampling pipe;
the buffer area comprises a first extension flow channel and a second extension flow channel which extend along the side face direction of the first flow channel, the first extension flow channel is communicated with the second extension flow channel through a bent flow channel, the first extension flow channel is communicated with the first inlet, and the second extension flow channel is communicated with the generation area.
9. The apparatus of claim 8, wherein the first elongated flow channel and the second elongated flow channel are parallel to each other.
10. A microdroplet generating device as claimed in claim 3, wherein the drainage tube comprises:
the cavity wall of the inner cavity gradually converges from the top of the inner cavity to the bottom of the inner cavity;
the liquid discharge port is formed in one side of the bottom of the inner cavity;
the flow guide surface is arranged at the bottom of the inner cavity, and the flow guide surface inclines downwards from the cavity wall position and extends to the liquid outlet.
11. The apparatus as claimed in claim 10, wherein the sampling tube further comprises a drainage portion, the drainage portion is disposed on the cavity wall at a side of the inner cavity where the liquid outlet is disposed, the drainage portion protrudes along the cavity wall and extends toward the liquid outlet, and a projection of a distal end of the drainage portion in a vertical direction is located on the flow guide surface.
CN202110961284.0A 2021-08-20 2021-08-20 Micro-droplet generating device Pending CN114950580A (en)

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