CN109569755B - Liquid drop mass production device - Google Patents

Liquid drop mass production device Download PDF

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Publication number
CN109569755B
CN109569755B CN201910036027.9A CN201910036027A CN109569755B CN 109569755 B CN109569755 B CN 109569755B CN 201910036027 A CN201910036027 A CN 201910036027A CN 109569755 B CN109569755 B CN 109569755B
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China
Prior art keywords
chip
oil phase
valve
phase branch
valve body
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CN201910036027.9A
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Chinese (zh)
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CN109569755A (en
Inventor
谢孝民
孙玉平
聂富强
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Suzhou Wenhao Microfluidic Technology Co ltd
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Suzhou Wenhao Microfluidic Technology Co ltd
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Priority to CN201910036027.9A priority Critical patent/CN109569755B/en
Publication of CN109569755A publication Critical patent/CN109569755A/en
Priority to PCT/CN2019/116222 priority patent/WO2020147381A1/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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0633Valves, specific forms thereof with moving parts
    • B01L2400/0644Valves, specific forms thereof with moving parts rotary valves

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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)
  • Lift Valve (AREA)
  • Check Valves (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

The invention discloses a droplet mass production device, which comprises at least one droplet generation group, wherein the droplet generation group comprises a valve body, a plug valve block is fixedly arranged on the valve body, a through water phase main runner and an oil phase main runner are arranged on the side surface of the plug valve block, and are respectively connected with a vertical water phase branch runner and an oil phase branch runner and are communicated with the plug valve block; the plug valve block is provided with a chip position for placing the microfluidic chip, and the valve body is provided with a chip frame for fixing the microfluidic chip and a pressing mechanism for pressing the chip frame; the side surface of the valve body is provided with a pair of valve holes which are respectively horizontally communicated with the water phase branch flow passage and the oil phase branch flow passage, a pair of cock valve rods are inserted into the valve holes, and through holes are formed in the cock valve rods; when the cock valve rod is rotated, the water phase branch flow passage and the oil phase branch flow passage can be switched on and off. The liquid drop mass production device can realize the on-off of the flow channel by only rotating the valve rod of the cock, and is convenient to use.

Description

Liquid drop mass production device
Technical Field
The invention relates to the technical field of microfluid control, in particular to a liquid drop mass production device.
Background
With the development and maturation of droplet control technology, microfluidic droplet systems have become an important platform for chemical and biological research on microscopic dimensions, and are successfully applied to the fields of molecular and cell biology and analytical chemistry research such as protein crystallization, enzyme analysis, chemical synthesis, single-molecule/single-cell research, and the like, and droplet diameters in many cases in the fields have a critical influence on experimental effects.
Microfluidic-based chips have been widely used to generate micro-droplets. Researchers use soft lithography to process micro-droplet chips with micron scale. First, researchers use thick photoresists (e.g., SU-8 thick photoresists) and conventional photolithographic techniques to machine molds with micron precision and high aspect ratios on the surface of silicon-based substrates. Then, the PDMS precursor and its cross-linking agent mixed solution are cast on the surface of the mould. And (3) carrying out temperature rise curing treatment and die separation to prepare the elastic PDMS micro-fluidic structure chip with complementary structure. The PDMS microfluidic structure chip and the glass substrate are subjected to a reversible bonding step to finally form a packaged microfluidic chip for droplet generation.
And after the micro-droplet chip is successfully prepared, punching holes are formed in a sample inlet and a micro-droplet generation outlet of the micro-droplet chip by using a machining process, and assembling a sample inlet pipe and a sample outlet pipe. The "oil phase" sample, the "water phase" sample was manually aspirated into the syringe. Then, the "oil phase" sample, the "water phase" sample is injected into the micro-droplet chip through the sample injection tube by an external syringe pump. Finally, the resulting microdroplets are collected via a sample tube into a conventional assay consumable, such as an EP tube.
The current droplet mass production device has the advantages that the on-off of the water phase flow channel and the oil phase flow channel is realized by adopting a rotary drawing structure or a needle valve structure, but the drawing structure has low efficiency and large force, and the scheme is feasible but the actual use effect is not ideal.
Disclosure of Invention
The invention aims to solve the technical problem of providing a liquid drop mass production device, which adopts a cock mechanism to control the on-off of a flow channel, and can realize the on-off of the flow channel by only rotating a cock valve rod, thereby being convenient to use.
In order to solve the technical problems, the invention provides a droplet mass production device, which comprises at least one droplet generation group;
the liquid drop generating set comprises a valve body, a plug valve block is fixedly arranged on the valve body, a through water phase main runner and an oil phase main runner are arranged on the side face of the plug valve block, a vertical water phase branch runner and an oil phase branch runner are respectively connected to the water phase main runner and the oil phase main runner, and the water phase branch runner and the oil phase branch runner are communicated with the plug valve block; the plug valve block is provided with a chip position for placing the microfluidic chip, and the valve body is provided with a chip frame for fixing the microfluidic chip and a pressing mechanism for pressing the chip frame;
the side surface of the valve body is provided with a pair of valve holes which are respectively horizontally communicated with the water phase branch flow passage and the oil phase branch flow passage, a pair of cock valve rods are inserted into the valve holes, and the cock valve rods are provided with through holes; when the cock valve rod is rotated, the water phase branch flow passage and the oil phase branch flow passage can be switched on and off.
Preferably, sealing rings are sleeved on the positions, located on two sides of the water phase branch flow passage and the oil phase branch flow passage, of the cock valve rod.
Preferably, the plug valve block is provided with filters at the outlets of the water phase branch flow passage and the oil phase branch flow passage.
Preferably, grooves are formed in the plug valve block at the outlets of the water phase branch flow channel and the oil phase branch flow channel, and chip sealing gaskets are arranged in the grooves.
Preferably, the chip rack comprises a first chip rack and a second chip rack, wherein the first chip rack is L-shaped, one end of the first chip rack is inserted into a slot on the valve body, and the other end of the first chip rack is attached to the valve body; the second chip frame is horizontally and fixedly connected to the first chip frame and is pressed by the pressing mechanism.
Preferably, a rubber pad positioning strip is arranged at the front end of the second chip frame.
Preferably, the compressing mechanism comprises a compressing block, a connecting block, a compression bar and a pair of connecting rods, wherein the compressing block is used for compressing the chip rack, and the top of the compressing block is rotationally connected to the connecting block; the two sides of the valve body are fixedly provided with valve body clamping plates, the connecting block and the pressure rod are hinged to the valve body clamping plates, and the connecting block and the pressure rod are movably connected through a pair of connecting rods.
Preferably, the droplet mass production device comprises at least two groups of droplet generation groups which are connected in parallel, the water phase main flow channel and the oil phase main flow channel on the two adjacent droplet generation groups are correspondingly communicated, and the communicating part is provided with a sealing ring.
Preferably, the droplet mass production device further comprises a valve body support, and the plurality of parallel droplet generation groups are locked on the valve body support through fixing pieces.
Preferably, the valve body support is formed with an aqueous phase joint and an oil phase joint which are respectively communicated with the aqueous phase main runner and the oil phase main runner.
Preferably, the liquid drop mass production device further comprises two groups of constant pressure pumps and raw material storage sealing bottles which are communicated with each other, and the raw material storage sealing bottles are respectively connected to the water phase connector and the oil phase connector through rubber hoses.
The invention has the beneficial effects that:
according to the liquid drop mass production device, the side face of the valve body is provided with the valve hole penetrating through the water phase branch flow passage and the oil phase branch flow passage, the valve hole is inserted with the cock valve rod, and the cock valve rod is provided with the through hole; the water phase branch flow channel and the oil phase branch flow channel can be switched on and off by rotating the cock valve rod, so that a complicated operation flow after a chip is blocked is avoided, and the yield is ensured;
the liquid drop mass production device consists of a variable number of liquid drop generating groups which are arranged in parallel, and can produce liquid drops in batches; according to the requirement of the productivity, the productivity can be adjusted by adding and subtracting drop generating groups; the quality of liquid drop production can be monitored in a single group, when a liquid drop problem occurs in one group, the operation can be stopped for the group, and the production of other groups is not influenced, so that the quantity and efficiency bottlenecks of conventional single-group liquid drop production are overcome.
Drawings
FIG. 1 is a schematic view of a droplet mass production apparatus according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of the configuration of a single drop generating set of FIG. 1;
FIG. 3 is a side view of the single drop generating set of FIG. 1;
FIG. 4 is a cross-sectional view taken along section A-A of FIG. 3;
FIG. 5 is a cross-sectional view taken along section B-B of FIG. 3;
FIG. 6 is a cross-sectional view taken along section C-C of FIG. 3;
the reference numerals in the figures illustrate:
100. a valve body bracket; 110. a water phase joint; 120. an oil phase joint; 130. a fixing member;
200. a droplet generation group; 210. a valve body; 211. a valve body clamping plate; 220. a plug valve block; 221. a water phase main flow passage; 222. an oil phase main flow passage; 223. a water phase branch flow passage; 224. an oil phase branch flow channel; 230. a tap stem; 231. a torsion bar; 232. a through hole; 241. a first chip carrier; 242. a second chip rack; 243. a rubber cushion positioning strip; 251. a compaction block; 252. a connecting block; 253. a connecting rod; 254. a compression bar; 260. and (3) sealing rings.
Detailed Description
The present invention will be further described with reference to the accompanying drawings and specific examples, which are not intended to be limiting, so that those skilled in the art will better understand the invention and practice it.
Referring to fig. 1, an embodiment of a droplet mass production apparatus of the present invention is used to generate micro droplets in cooperation with a microfluidic chip. The valve comprises six groups of parallel droplet generation groups 200 and a pair of valve body brackets 100, wherein the valve body brackets 100 are positioned at two sides of the droplet generation groups 200, and the six groups of droplet generation groups 200 are locked and fixed together through fixing pieces 130. An aqueous phase connector 110 and an oil phase connector 120 are screwed to a valve body holder 100 for communicating the external aqueous phase and the oil phase.
Specifically, referring to fig. 2 to 3, each droplet generation unit 200 includes a valve body 210, a plug valve block 220 is fixedly disposed on the valve body 210, and valve body clamping plates 211 are fixedly disposed on both sides of the valve body 210.
The side of the plug valve block 220 is provided with a water phase main runner 221 and an oil phase main runner 222 which are communicated, the water phase main runner 221 and the oil phase main runner 222 are respectively connected with a vertical water phase branch runner 223 and an oil phase branch runner, and the water phase branch runner 223 and the oil phase branch runner are communicated with the plug valve block 220. Among them, the aqueous phase main flow channel 221 and the oil phase main flow channel 222 serve to transport aqueous phase and oil phase between the respective valves, and the aqueous phase sub flow channel 223 and the oil phase sub flow channel serve to guide the aqueous phase and the oil phase into the microfluidic chip to generate micro droplets. When the multiple sets of droplet generation sets 200 are connected in parallel, the water phase main flow channel 221 and the oil phase main flow channel 222 on two adjacent droplet generation sets 200 are correspondingly communicated, and a sealing ring 260 is arranged at the communicating position to prevent leakage.
In order to realize the on-off of the water phase branch flow channel 223 and the oil phase branch flow channel so as to control the generation of micro liquid drops, in the invention, a pair of valve holes which horizontally penetrate through the water phase branch flow channel 223 and the oil phase branch flow channel are respectively arranged on the side surface of the valve body 210, a plug valve rod 230 is inserted into each valve hole, and a part of the plug valve rod 230 positioned in the water phase branch flow channel 223 or the oil phase branch flow channel is provided with a through hole 232. Therefore, when the cock stem 230 is rotated so that the direction of the through hole 232 coincides with the water phase branch flow passage 223 or the oil phase branch flow passage, the water phase branch flow passage 223 or the oil phase branch flow passage is conducted at this time; when the cock stem 230 is rotated such that the through hole 232 faces the inner wall of the water phase branch flow passage 223 or the oil phase branch flow passage, the water phase branch flow passage 223 or the oil phase branch flow passage is interrupted. In order to facilitate rotation of the tap stem 230, in this embodiment, a torsion bar 231 is provided on a portion of the tap stem 230 protruding from the valve hole. In addition, in order to prevent leakage, sealing rings 260 are respectively sleeved on the cock stem 230 at positions on both sides of the water phase branch flow passage 223 and the oil phase branch flow passage 224.
Referring to fig. 4-6, grooves are formed on the plug valve block 220 at positions of the water phase branch flow passage 223 and the oil phase branch flow passage outlets, and a chip sealing pad 212212 is disposed in the grooves. When the microfluidic chip is placed on the chip position, the water phase inlet and the oil phase inlet on the chip are respectively communicated with the corresponding grooves, so that the water phase and the oil phase can enter the corresponding micro-channels of the chip. In this embodiment, filters are further disposed at the outlets of the water phase branch flow passage 223 and the oil phase branch flow passage.
The valve body clamping plate 211 is further provided with a chip frame for fixing the microfluidic chip, in this embodiment, the chip frame specifically includes a first chip frame 241 and a second chip frame 242, where the first chip frame 241 is L-shaped, one end of the first chip frame is inserted into a slot on the valve body 210, and the other end is attached to the top of the valve body clamping plate 211; the second chip frame 242 is horizontally and fixedly connected to the first chip frame 241 by screws.
The valve body 210 is further fixedly provided with a pressing mechanism for pressing the chip rack, in this embodiment, the pressing mechanism includes a pressing block 251, a connecting block 252, a pressing rod 254 and a pair of connecting rods 253, a cylindrical rotating rod 255 is formed at the top of the pressing block 251, the connecting block 252 is wholly triangular, a groove matched with the rotating rod 255 is formed at the front end of the bottom of the connecting block 252, and the rotating rod 255 is embedded in the groove, so that the pressing block 251 can rotate along the connecting block 252. The lower part of the rear end of the connecting block 252 and the middle part of the pressing rod 254 are both hinged on the valve body clamping plate 211, and the upper part of the rear end of the connecting block 252 and the front end of the pressing rod 254 are movably connected through a pair of connecting rods 253. The working flow of the pressing mechanism of the embodiment is as follows: when the pressing rod 254 is pulled upwards, the front end of the pressing rod 254 moves downwards to drive the connecting rod 253, so that the connecting block 252 rotates clockwise along the hinge joint of the lower part of the connecting block 252, the front end of the connecting block 252 tilts upwards to drive the pressing block 251 to lift, and accordingly loosening is achieved. When the pressing rod 254 is pulled downwards, the front end part of the pressing rod 254 moves upwards to drive the connecting rod 253, so that the connecting block 252 rotates anticlockwise along the hinge joint at the lower part of the connecting block 252, and the front end of the connecting block 252 moves downwards to drive the compressing block 251 to descend; when the compression bar 254 is in the horizontal state, the compression mechanism is in the critical state, at this time, the compression force of the compression block 251 on the chip rack is suddenly increased, and the compression bar 254 is in the self-locking state.
Since the chip is provided with a plurality of micro-droplet outlets, a plurality of external pipelines are required to be connected to lead out micro-droplets. In this embodiment, a plurality of pipeline positioning rubber pads, preferably fluorine rubber pads, are arranged at the connection position of the external pipeline and the micro-droplet outlet, and play roles in positioning the pipeline and sealing. In addition, a rubber pad positioning strip 243 for fixing the pipe positioning rubber pad is provided at the front end of the second chip frame 242.
In one embodiment, the droplet mass production apparatus further comprises two groups of constant pressure pumps and raw material storage sealing bottles which are mutually communicated, and the raw material storage sealing bottles are respectively connected to the water phase joint 110 and the oil phase joint 120 through rubber hoses. Wherein the raw material storage seal bottle is used for storing the water phase and the oil phase, and the water phase or the oil phase is pressed onto the water phase joint 110 and the oil phase joint 120 by generating pressure by the constant pressure pump. In other embodiments, a filter and/or flow meter is also provided between the feedstock storage containment vial and the water phase connection 110 and oil phase connection 120.
In the droplet mass production device of the embodiment, a valve hole penetrating through the water phase branch flow passage and the oil phase branch flow passage is formed in the side face of the valve body, a cock valve rod is inserted into the valve hole, and a through hole is formed in the cock valve rod; the water phase branch flow channel and the oil phase branch flow channel can be switched on and off by rotating the cock valve rod, so that a complicated operation flow after a chip is blocked is avoided, and the yield is ensured;
secondly, the droplet mass production device of the embodiment consists of a variable number of droplet generation groups which are arranged in parallel, so that droplets can be produced in batches; according to the requirement of the productivity, the productivity can be adjusted by adding and subtracting drop generating groups; in addition, each droplet generation group can independently generate droplets without mutual influence, so that the quality of droplet production can be monitored in a single group, when a droplet problem occurs in one group, the operation can be stopped in the group, the production of other groups is not influenced, and the bottleneck of the quantity and efficiency of conventional single-group droplet production is overcome;
and when the pressing rod is in a horizontal state, the pressing mechanism is in a critical state, and the pressing force of the pressing block on the chip rack is suddenly increased, so that the chip rack is firmly pressed, and the pressing rod is in a self-locking state, so that the pressing mechanism can be effectively prevented from being loosened in the working process.
The above-described embodiments are merely preferred embodiments for fully explaining the present invention, and the scope of the present invention is not limited thereto. Equivalent substitutions and modifications will occur to those skilled in the art based on the present invention, and are intended to be within the scope of the present invention. The protection scope of the invention is subject to the claims.

Claims (10)

1. The liquid drop mass production device comprises at least one group of liquid drop generation groups, and is characterized in that the liquid drop generation groups comprise a valve body, a plug valve block is fixedly arranged on the valve body, a through water phase main runner and an oil phase main runner are arranged on the side face of the plug valve block, vertical water phase branch runners and oil phase branch runners are respectively connected to the water phase main runner and the oil phase main runner, and the water phase branch runners and the oil phase branch runners are communicated with the plug valve block; the plug valve block is provided with a chip position for placing the microfluidic chip, and the valve body is provided with a chip frame for fixing the microfluidic chip and a pressing mechanism for pressing the chip frame;
the side surface of the valve body is provided with a pair of valve holes which are respectively horizontally communicated with the water phase branch flow passage and the oil phase branch flow passage, a pair of cock valve rods are inserted into the valve holes, and the cock valve rods are provided with through holes; when the cock valve rod is rotated, the water phase branch flow passage and the oil phase branch flow passage can be switched on and off.
2. The drop mass production device of claim 1, wherein sealing rings are sleeved on the cock valve rod at positions on both sides of the water phase branch flow channel and the oil phase branch flow channel.
3. The drop mass production device of claim 1, wherein filters are disposed on the plug valve block at the outlets of the water phase branch flow channel and the oil phase branch flow channel.
4. The drop mass production device of claim 1, wherein grooves are formed in the plug valve block at the outlets of the water phase branch flow channel and the oil phase branch flow channel, and chip sealing gaskets are arranged in the grooves.
5. The drop mass production device of claim 1, wherein the chip rack comprises a first chip rack and a second chip rack, the first chip rack is L-shaped, one end of the first chip rack is inserted into a slot on the valve body, and the other end of the first chip rack is attached to the valve body; the second chip frame is horizontally and fixedly connected to the first chip frame and is pressed by the pressing mechanism.
6. The drop mass production device of claim 5, wherein a front end of the second chip frame is provided with a rubber pad locating bar.
7. The drop mass production device of claim 5, wherein the hold-down mechanism comprises a hold-down block, a connecting block, a compression bar, and a pair of links, the hold-down block being configured to hold down the chip carrier, the top of the hold-down block being rotatably connected to the connecting block; the two sides of the valve body are fixedly provided with valve body clamping plates, the connecting block and the pressure rod are hinged to the valve body clamping plates, and the connecting block and the pressure rod are movably connected through a pair of connecting rods.
8. The droplet production apparatus according to claim 1, comprising at least two droplet generation groups connected in parallel, wherein the water phase main flow channel and the oil phase main flow channel on two adjacent droplet generation groups are correspondingly communicated, and a sealing ring is arranged at the communicating position.
9. The drop mass production device of claim 8, further comprising a valve body bracket to which a plurality of parallel drop generating sets are secured by a fastener lock.
10. The drop mass production device of claim 9, wherein the valve body holder is formed with an aqueous phase joint and an oil phase joint which are respectively communicated with the aqueous phase main flow passage and the oil phase main flow passage.
CN201910036027.9A 2019-01-15 2019-01-15 Liquid drop mass production device Active CN109569755B (en)

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CN201910036027.9A CN109569755B (en) 2019-01-15 2019-01-15 Liquid drop mass production device
PCT/CN2019/116222 WO2020147381A1 (en) 2019-01-15 2019-11-07 Droplet mass production device

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CN109569755B (en) * 2019-01-15 2024-03-12 苏州汶颢微流控技术股份有限公司 Liquid drop mass production device
CN110479393B (en) * 2019-08-24 2021-11-12 苏州德运康瑞生物科技有限公司 Programmable micro-fluidic chip surface modification dyeing instrument
CN110747105A (en) * 2019-11-28 2020-02-04 北京擎科生物科技有限公司 Common-channel liquid pumping device

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