CN110075933A - Micro-droplet generation device, system and generation method - Google Patents

Micro-droplet generation device, system and generation method Download PDF

Info

Publication number
CN110075933A
CN110075933A CN201810073981.0A CN201810073981A CN110075933A CN 110075933 A CN110075933 A CN 110075933A CN 201810073981 A CN201810073981 A CN 201810073981A CN 110075933 A CN110075933 A CN 110075933A
Authority
CN
China
Prior art keywords
liquid
microchannel
microlayer model
opening
generating means
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CN201810073981.0A
Other languages
Chinese (zh)
Other versions
CN110075933B (en
Inventor
李昂
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beijing Zhiyu Biotechnology Ltd
Original Assignee
Beijing Zhiyu Biotechnology Ltd
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 Beijing Zhiyu Biotechnology Ltd filed Critical Beijing Zhiyu Biotechnology Ltd
Priority to CN201810073981.0A priority Critical patent/CN110075933B/en
Publication of CN110075933A publication Critical patent/CN110075933A/en
Application granted granted Critical
Publication of CN110075933B publication Critical patent/CN110075933B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502707—Containers 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 characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/50273—Containers 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 characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure

Abstract

The invention provides a micro-droplet generation device, a system and a method, and relates to the technical field of measuring and distributing of micro-liquid. The micro-droplet generating device comprises a micro-pipeline and a rotary vibration mechanism, wherein the micro-pipeline is provided with a first opening for outputting first liquid, and the rotary vibration mechanism is used for driving the micro-pipeline to rotate and vibrate. The micro-droplet generating device adopts the rotary vibration to drive the micro-pipeline, and under the action of high-frequency periodic inertia force and centrifugal force generated by the rotary vibration, the size of emulsified micro-droplets generated when liquid in the micro-pipeline is injected into another immiscible liquid is precisely controllable, so that the volume error generated by a large amount of droplets is controllable.

Description

Microlayer model generating means, system and generation method
Technical field
The present invention relates to the measurements of micro liquid, distribution technique field, more particularly to a kind of micro- liquid based on microchannel Drip generating means, system and generation method.
Background technique
It examines at present in clinical medicine, nano material preparation, the application fields such as food and environmental monitoring, biochemical analysis have To the widespread demand of micro liquid precise manipulation.The core technology of submicroliter fluid handling first is that the liquid of microlitre magnitude into One step is divided into nanoliter micro- reaction system of even picoliters volume.The major technique branch that micro- reaction system generates is emulsification Microlayer model generates.
In recent years, reporting a variety of microlayer model generation technique such as membrane emulsifications in the literature, being sprayed emulsion process, is micro-fluidic Chip method, microchannel injection/gunite etc..Recent patent number is the Chinese invention patent and publication number of ZL201410655191.5 The method that emulsification microlayer model is generated by microchannel has been advanced optimized for the Chinese patent application of CN104815709A.It emulsifies micro- These methods of drop all respectively have some disadvantages in practical applications.The Chinese invention of Patent No. ZL201410655191.5 Interface energy and hydrodynamic shear of the method for patent using micro liquid when gas liquid film converts, overcome liquid in microchannel The surface tension and adhesive force of outlet enable the drop for flowing out microchannel nozzle to be successfully detached from microchannel, and in immiscible liquid The controllable drop of size is formed in body.But this method needs microchannel cutting movement above and below liquid level, needs to microchannel Starting and final position relative to liquid level carry out high-precision positioning, difficult in Project Realization.Publication No. The method of the Chinese patent application of CN104815709A passes through circumference or spiral uniform motion of the microchannel in liquid and generates Shearing force cutting injection immiscible liquid and form drop, but this method due to microchannel generate drop size by (such as viscosity, the temperature of environment, the movement velocity, motion profile of liquid that be affected changed to various system factors Deng), and this error can increase with the quantity for generating drop and be accumulated, thus the volume size of high-volume drop formation is equal The control of one property is difficult.
Summary of the invention
Based on this, it is necessary to for current problem, provide a kind of microlayer model generating means that volumetric errors are small, simultaneously also Provide a kind of generation system and generation method using above-mentioned microlayer model generating means.
Above-mentioned purpose is achieved through the following technical solutions:
A kind of microlayer model generating means, including microchannel, the microchannel have the first opening of the first liquid of output, also Including whirling vibration mechanism, the whirling vibration mechanism is for driving the microchannel whirling vibration.
The microlayer model generating means further include fluid driving mechanism in one of the embodiments, the fluid driving Mechanism passes through the second opening in communication of tubule and the microchannel.
The whirling vibration mechanism includes rotating electric machine, rotary shaft and connector, the rotation in one of the embodiments, The output end of motor is connected with the rotary shaft, and the connector fixes company along with the perpendicular direction of the rotating shaft axis It connects in the rotary shaft, the microchannel is mounted on the connector.
The connector is tubulose in one of the embodiments, has the internal third opening and the 4th opening being connected, The tubule is connected in the third opening, and the second opening of the microchannel is connected in the 4th opening.
The microlayer model generating means further include withdraw of the needle mechanism in one of the embodiments, and the withdraw of the needle mechanism includes Withdraw of the needle plate and withdraw of the needle plate driving assembly, withdraw of the needle hole is offered on the withdraw of the needle plate, and the withdraw of the needle hole is set in the outer of the connector Portion, the second opening of the microchannel are set in the outside of the 4th opening, and, the withdraw of the needle plate opposite with the withdraw of the needle plate Driving assembly is for driving the withdraw of the needle plate to move to the direction of the microchannel.
The outside of the 4th opening of the connector is in up big and down small round table-like in one of the embodiments,.
The withdraw of the needle plate driving assembly includes withdraw of the needle plate driving motor, the first lead screw and in one of the embodiments, One feed screw nut, the output end of the withdraw of the needle plate driving motor are connected with first lead screw, first feed screw nut with First lead screw is coupled, and the withdraw of the needle plate is connected with first feed screw nut.The withdraw of the needle under another structure Plate driving assembly includes: the first cylinder and the first fixture nut, and the first cylinder is fixedly mounted in mounting bracket, the first fixed spiral shell Mother is coupled with the first cylinder piston rod front end, and withdraw of the needle plate is connected with the first fixture nut.
The whirling vibration mechanism further includes mounting bracket in one of the embodiments, the rotating electric machine and described Withdraw of the needle plate driving motor is respectively and fixedly installed in the mounting bracket.
The microlayer model generating means further include longitudinal moving mechanism in one of the embodiments, the longitudinal movement Mechanism includes the first mounting plate, longitudinal movement driving assembly and longitudinal sliding motion component, and the mounting bracket passes through described longitudinal sliding Dynamic component is mounted on first mounting plate, and the longitudinal movement driving assembly is for driving the mounting bracket along described Longitudinal sliding motion component slippage.
The longitudinal movement driving assembly includes longitudinal movement driving motor, the second lead screw in one of the embodiments, With the second feed screw nut, the longitudinal movement driving motor is fixedly mounted on first mounting plate, and the longitudinal movement is driven The output end of dynamic motor is connected with second lead screw, and second feed screw nut is coupled with second lead screw, institute Mounting bracket is stated to be connected with second feed screw nut.The longitudinal movement driving assembly includes: longitudinal direction under another structure Carrier wheel driving motor, first gear and the first rack gear, longitudinal movement gear drive motor are fixedly mounted in mounting bracket, The output end of longitudinal movement driving motor is connected with first gear, and the first rack gear is fixed on the first mounting plate, the first rack gear It is coupled with first gear.
The fluid driving mechanism includes syringe and injector drive component, the note in one of the embodiments, The liquid in-out mouth of emitter passes through the second opening in communication of the tubule and the microchannel.
The fluid driving mechanism further includes three-way diverter valve and fluid reservoir, the micro-pipe in one of the embodiments, Second opening in road, the liquid outlet of the liquid in-out mouth of the syringe and the fluid reservoir connect with three of the three-way diverter valve Mouth is connected.
The microchannel, connector, tubule, syringe and three-way diverter valve are respectively multiple in one of the embodiments, Multiple connectors are alternatively arranged in the rotary shaft, and multiple microchannels are separately mounted on the connector, often The both ends of tubule described in root are open respectively with the second of a microchannel and the first interface of a three-way diverter valve It is connected, the liquid in-out mouth of each syringe is connected with the second interface of a three-way diverter valve, the liquid storage The liquid outlet of tank is connected with the third interface of multiple three-way diverter valves.
The fluid driving mechanism further includes mounting blocks in one of the embodiments, multiple three-way diverter valves and The syringe is fixedly mounted on the mounting blocks, offered in the mounting blocks multiple first runners, multiple second flow channels, One third flow channel and multiple liquid separation runners, the both ends of each first runner respectively with a tubule and a threeway The first interface of reversal valve is connected, the both ends of each second flow channel respectively with the liquid in-out mouth of syringe and The second interface of one three-way diverter valve is connected, the third flow channel and the fluid reservoir and multiple liquid separation runners It is connected, each liquid separation runner is connected with the third interface of a three-way diverter valve.
The injector drive component includes injector drive motor, third lead screw and in one of the embodiments, Three feed screw nuts, the output end of the injector drive motor are connected with the third lead screw, the third feed screw nut with The third lead screw is coupled, and the push rod of multiple syringes is connected with the third feed screw nut.Another structure Lower syringe driving assembly includes: syringe gear drive motor, second gear and the second rack gear, injector drive motor it is defeated Outlet is connected with second gear, and the second rack gear is connected with the second mounting plate, and the second rack gear is coupled with second gear, more The push rod of a syringe is connected by connector with syringe gear drive motor.
The fluid driving mechanism further includes the second mounting plate in one of the embodiments, mounting blocks and described Injector drive motor is fixedly mounted on second mounting plate.
The fluid driving mechanism further includes integrating mounting plate in one of the embodiments, the mounting blocks, the note Emitter driving motor, the longitudinal movement driving motor, the longitudinal sliding motion component are fixedly mounted on described integrate on mounting plate.
The rotating electric machine is galvanometer motor in one of the embodiments,.
In one of the embodiments, between the first opening and the second opening of the microchannel have volume be 10 μ L~ The liquid storage chamber of 100 μ L.
The present invention also provides a kind of microlayer models to generate system, including microlayer model generating means and life described in any of the above item At container, the second liquid immiscible with first liquid is contained in the generation container, the whirling vibration mechanism uses In driving the whirling vibration under the second liquid liquid level in the generation container of the first opening of the microchannel, make the first liquid Microlayer model is generated under second liquid liquid level.
In one of the embodiments, further include sample container, first liquid is contained in the sample container.
In one of the embodiments, further include supplies racks, is placed in the supplies racks described for microchannel.
It in one of the embodiments, further include translating device, the translating device is able to drive the microlayer model and generates Device moves above the generation container, the sample container or the supplies racks.
The present invention also provides a kind of microlayer model generation methods, generate system, packet using microlayer model described in any of the above item Include following steps:
S100, below the first opening insertion second liquid liquid level generated in container of the microchannel；
S200 starts whirling vibration mechanism, drives the first of the microchannel to be open and rotates below second liquid liquid level Vibration, while the first liquid in the microchannel is pushed, so that the first liquid enters in second liquid from first opening, Microlayer model is formed under the whirling vibration of first opening.
In one of the embodiments, in the step S100, the first opening of the microchannel is inserted into the generation Below second liquid liquid level in container and second liquid liquid level is in 30 °~90 ° of angle.
In one of the embodiments, in the step S200, the first opening of the microchannel is relative to the second liquid The distance in body fluid face is between 0.05mm~10mm.
It is described in whirling vibration mechanism vibration processes in one of the embodiments, in the step S200 The swing angle of the whirling vibration of microchannel is 0.1 °~10 °.
The vibration frequency of the whirling vibration mechanism is 1Hz~1000Hz in one of the embodiments,.
The volume of the microlayer model is 1pL~100nL in one of the embodiments,.
In one of the embodiments, in the step S200, the first liquid in the microchannel is at the uniform velocity pushed, is made Obtain the microlayer model that first liquid generates fixed number within each whirling vibration period of first opening.
Further include step S110 in one of the embodiments, before the step S100, microchannel is mounted on institute It states in whirling vibration mechanism.
Further include step S210 in one of the embodiments, after the step S200, microchannel is held from generation After being removed in device, microchannel is disassembled from the whirling vibration mechanism.
Further include step S120 in one of the embodiments, after the step S110, infuses first liquid Enter in the microchannel.
In one of the embodiments, in the step S120, first liquid passes through the first of the microchannel Opening sucks in the microchannel.
In one of the embodiments, in the step S200, by pushing driving liquid into the microchannel, make institute The first liquid stated in microchannel enters in second liquid from first opening.
The beneficial effects of the present invention are:
Microlayer model generating means of the invention use whirling vibration and drive microchannel, what is generated by whirling vibration Under the action of high frequency periodic inertia force and centrifugal force, liquid is generated when being injected into another immiscible liquid in microchannel It is accurate controllable to emulsify microlayer model size, so that the volumetric errors of high-volume drop formation are controllable.
The present invention filters out various preferred parameters by many experiments, so that perturbed problem, life to liquid level generation It is more easier to be able to good solution with uniformity problem and liquid crushing problem generated at drop.
Detailed description of the invention
Fig. 1 is the structural schematic diagram of microlayer model generating means of the present invention；
Fig. 2 is the whirling vibration schematic diagram of microlayer model generating means of the present invention；
Fig. 3 is that the microlayer model of microlayer model generating means of the present invention generates schematic diagram；
Fig. 4 is situation schematic diagram microchannel and any vibrating motor not being connected in the prior art；
Fig. 5 is feelings microchannel being fixed in the prior art on the vibrating motor that one can produce linear uniform motion Shape schematic diagram；
Fig. 6 can be with the situation in whirling vibration mechanism for microchannel is fixed on one in microlayer model generating means of the present invention Schematic diagram；
Fig. 7 is the Study on Relative Factors schematic diagram for influencing microlayer model and generating；
Fig. 8 is the main view of microlayer model generating means embodiment of the present invention；
Fig. 9 is the front sectional view of microlayer model generating means embodiment of the present invention；
Figure 10 is the left view of microlayer model generating means embodiment of the present invention；
Figure 11 is the rearview of microlayer model generating means embodiment of the present invention；
Figure 12 is the cross-sectional view at the A-A in Figure 11；
Figure 13 is the partial enlarged view in Figure 12 at C；
Figure 14 is the partial enlarged view in Figure 12 at D；
Figure 15 is the cross-sectional view at the B-B in Figure 12；
Figure 16 is the rearview of microlayer model generating means another kind embodiment of the present invention；
Figure 17 is the front sectional view of microlayer model generating means another kind embodiment of the present invention；
Figure 18 is the main view of microlayer model generating means another kind embodiment of the present invention；
Figure 19 is the left view of microlayer model generating means another kind embodiment of the present invention；
Figure 20 is closed-loop control vibration angle or the Principle of Electric Engine figure of position involved in microlayer model generating means of the present invention；
Figure 21 is a kind of flow chart of embodiment of microlayer model generation method of the present invention；
Figure 22 is the flow chart of the another embodiment of microlayer model generation method of the present invention；
Figure 23 is the effect picture that the embodiment of the present invention 1 generates microlayer model；
Figure 24 is the effect picture that the embodiment of the present invention 2 generates microlayer model.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, by the following examples, it and combines attached Figure, the present invention will be described in further detail.It should be appreciated that specific embodiment described herein is only to explain this hair It is bright, it is not intended to limit the present invention.
As shown in Figure 1, the present invention provides a kind of microlayer model generating means, including microchannel 100, microchannel 100 have The first opening 110 for exporting the first liquid 130, further includes whirling vibration mechanism 200, and whirling vibration mechanism 200 is micro- for driving 100 whirling vibration of pipeline.As shown in Fig. 2, whirling vibration mechanism 200 drives microchannel 100 around 221 whirling vibration of the centre of oscillation (i.e. reciprocally swinging), so that the first opening 110 of microchannel 100 also generates whirling vibration, thus in the liquid level of second liquid 610 Lower generation microlayer model 131.
As shown in Figure 1, for the generation microlayer models 131 for enabling the first opening 110 of microchannel 100 to continue, microlayer model Generating means further include fluid driving mechanism 300, the second opening that fluid driving mechanism 300 passes through tubule 310 and microchannel 100 120 are connected.Second opening 120 of microchannel 100 is communicated with the first opening 110, and fluid driving mechanism 300 can pass through tubule 310 apply stable driving force into microchannel 100, enable 130 steady and continuous of the first liquid in microchannel 100 from Outflow generates microlayer model 131 in one opening 110.
Drop formation method provided by the present invention is an extremely complex dynamic process, has several factors to influence drop The volume of generation.Principal element has: the surface tension of drop (between microchannel opening area, the first and second liquid surface Can gap it is related), the adhesive force (being influenced by pipeline openings of sizes and surface properties) between microchannel opening and drop；Shearing Power (speed and droplet surface area moved by second liquid viscosity, microchannel determines), centrifugal force (quality, micro-pipe with drop The swing radial acceleration in road is related) and tangential inertial force (the swing tangential acceleration and drop mass with microchannel are at just Than).Centrifugal force is substantially exactly radial inertial force in fact.
As shown in figure 3, the first opening 110 due to microchannel 100 generates rotation under the driving of whirling vibration mechanism 200 Movement, so that the microlayer model that the first liquid 130 in microchannel 100 is formed in the nozzle of the first opening 110 of microchannel 100 131 131 tables of speed and microlayer model moved in the nozzle of the first opening 110 of viscosity, microchannel 100 by second liquid 610 The swing of the nozzle of first opening 110 of the quality and microchannel 100 of shearing force and microlayer model 131 that area determines radially adds The relevant centrifugal force of speed and swing tangential acceleration and microlayer model with the nozzle of the first of microchannel 100 the opening 110 Under the collective effect of the directly proportional tangential inertial force of 131 mass so that microlayer model 131 under the liquid level of second liquid 610 take off The nozzle of the first opening 110 from microchannel 100.
By the whirling vibration mode of microlayer model generating means of the present invention (referring to Fig. 6-7), (reference is schemed with other modes below It is compared analysis, 4-5) to illustrate the present invention peculiar technical effect obtained.It is important to note that all below Analysis is all to carry out force analysis using 130 drop of the first liquid of outflow microchannel as independent object, in figures 4-7 with void 130 drop of the first liquid of wire frame representation is independent system.
Fig. 4 is situation schematic diagram microchannel and any vibrating motor not being connected in the prior art.In the prior art, when Fluid drive apparatus constantly pass through microchannel 100 at the uniform velocity by the first liquid 130 inject second liquid 610 when, drop can slowly not It is disconnected to increase.Because liquid volume is incompressible, then droplet size is also at the uniform velocity to become larger under conditions of at the uniform velocity injecting.Effect There are the surface tension for keeping drop not depart from and adhesive force on drop, in addition there are also downward gravity.When drop rises to When critical size (volume shown in cut-off rule in referring to fig. 4), suffered gravity overcomes surface tension and adhesive force to fall off.Because of drop Microlitre magnitude gravity must be grown to be possible to overcome tension and adhesive force, this method cannot generate by nanoliter characterized by Microlayer model.
Fig. 5 is feelings microchannel being fixed in the prior art on the vibrating motor that one can produce linear uniform motion Shape schematic diagram.As shown in figure 5, in the prior art, when fluid drive apparatus constantly passes through microchannel 100 at the uniform velocity for the first liquid When 130 injection second liquid 610, drop slowly can constantly increase.Because liquid volume is incompressible, then at the uniform velocity injecting Under the conditions of, droplet size is also at the uniform velocity to become larger.The places different from situation shown in Fig. 4 are, while starting linear motor driving Microchannel 100 is at the uniform velocity moved along a straight line to the left.So, the stress condition of drop is as shown in figure 5, because drop and second liquid There is relative motion between 610 by shearing force to the right, the speed and surface area of shearing force and drop are positively correlated.Thus even In fast situation, this power increases as droplet size increases.Gravity is far smaller than shearing force and is ignored.In a certain critical body Product (referring to shown in Fig. 5 cut-off rule), is exactly drop separation micro-pipe road junction when shearing force overcomes surface tension and adhesive force At the time of.Because of the fluctuation of environment and system, this critical size has disturbance up and down, this is to cause droplet size non-uniform Principal element (referring to shown in dotted line a in Fig. 7).Under this uniform motion, error brought by this disturbance is very big (preceding The prior arts such as first patent mentioned by microchannel drop formation technology and background technology part in Fig. 4-5 are stated all to exist This problem).
Fig. 6 can be with the situation in whirling vibration mechanism for microchannel is fixed on one in microlayer model generating means of the present invention Schematic diagram.As shown in fig. 6, the first liquid 130 is at the uniform velocity injected the second liquid when fluid drive apparatus constantly passes through microchannel 100 When body 610, by high-frequency swing so that the velocity variations of microchannel 100 have a high frequency modulated, so that drop institute The resultant force that gets rid of being subject to also has a high frequency modulated.This, which gets rid of resultant force, is merged by shearing force, centrifugal force and tangential inertial force Made of.When critical point has disturbance, the power that gets rid of of this high frequency variation is enough to break through disturbing for critical point in a very short period of time It is dynamic, so that disturbance bring volumetric errors minimum (because drop at the uniform velocity increases in fluid drive apparatus driving lower volume, So meaning that volumetric errors are small less the time required to breaking through critical disturbance).As shown in Figure 7, here it is apparent that same critical Under disturbance, microchannel, which is fixed on one, to be far smaller than situation with the volumetric errors 1 that the swing on rotary vibrating motor generates The volumetric errors 2 at the uniform velocity generated in two.
As shown in Fig. 8, Fig. 9 and Figure 10, as a preferred embodiment, the rotation in drop formation device of the present invention Vibrating mechanism 200 includes rotating electric machine 210, rotary shaft 220 and connector 230, the output end and rotary shaft 220 of rotating electric machine 210 It is connected, connector 230 is fixedly connected in rotary shaft 220 along the direction with 220 axis perpendicular of rotary shaft, microchannel 100 It is mounted on connector 230.Rotating electric machine 210 can drive rotary shaft 220 and connector 230 centered on the axis of rotary shaft 220 Rotary oscillation, so as to drive 100 whirling vibration of microchannel.Whirling vibration mechanism 200 in drop formation device of the present invention It can also be using other rotation drive devices, such as oscillating cylinder, rotating electromagnet etc..
In the present embodiment, microchannel 100 is the tubular structure that both ends all have opening, for the ease of installing microchannel 100, connector 230 is also tubulose, and in conjunction with shown in Figure 13, tubular configured joint 230 has the internal third opening 231 and the 4th being connected Opening 232, tubule 310 are connected in third opening 231, and the second opening 120 of microchannel 100 is connected in the 4th opening 232. The fluid driving forces that fluid driving mechanism 300 exports can steadily act on microchannel 100 by tubule 310 and connector 230 It is interior, so that the outflow from the first opening 110 of 130 steady and continuous of the first liquid in microchannel 100 is generated microlayer model 131.
Since microlayer model generating means of the present invention can be used in field of biological detection, in order to avoid the intersection of biomaterial Pollution, microchannel 100 are usually disposable, to need each used microchannel 100 from connector 230 It disassembles, in order to improve removal efficiency, microlayer model generating means of the present invention further include withdraw of the needle mechanism 400, in conjunction with Figure 12 and figure Shown in 13, withdraw of the needle mechanism 400 includes withdraw of the needle plate 410 and withdraw of the needle plate driving assembly 420, offers withdraw of the needle hole on withdraw of the needle plate 410 411, withdraw of the needle hole 411 is set in the outside of connector 230, and the second opening 120 of microchannel 100 is set in the outer of the 4th opening 232 Portion, and it is opposite with withdraw of the needle plate 410, withdraw of the needle plate driving assembly 420 is used to that withdraw of the needle plate 410 to be driven to move to the direction of microchannel 100, When withdraw of the needle plate 410 is resisted against the second opening 120 of microchannel 100, it is applied with to microchannel 100 and disengages it from connector 230 Squeezing action power, withdraw of the needle plate 410, which continues movement, to release microchannel 100 from connector 230, later, withdraw of the needle plate driving group Part 420 drives withdraw of the needle plate 410 to move to the direction close to tubule 310, can be sleeved on connector convenient for next microchannel 100 On 230.In addition to withdraw of the needle mechanism provided by the present embodiment, point of microchannel and connector can also be realized using other structures From for example, by using claw clamping microchannel, being pulled microchannel from connector pull-up by the movement of driving claw makes the two separation.
As a preferred embodiment, for the ease of mounting and dismounting microchannel 100, the 4th opening of connector 230 232 outside is in up big and down small round table-like, the resistance that reduction microchannel 100 mounts and dismounts.
Specifically, withdraw of the needle plate driving assembly 420 includes withdraw of the needle plate driving motor 421, the first lead screw 422 and the first lead screw spiral shell Mother 423, withdraw of the needle plate driving motor 421 is fixedly mounted in mounting bracket 240, the output end of withdraw of the needle plate driving motor 421 and the One lead screw 422 is connected, and the first feed screw nut 423 is coupled with the first lead screw 422, withdraw of the needle plate 410 and the first feed screw nut 423 are connected.The rotary motion that first feed screw nut 423 and the cooperation of the first lead screw 422 export withdraw of the needle plate driving motor 421 turns Become the first feed screw nut 423 along the linear motion in 422 axial direction of the first lead screw, so as to drive withdraw of the needle plate 410 to carry out Linear motion, it is of course also possible to use the linear drives component of other forms is to drive withdraw of the needle plate 410.Such as cylinder driving.
Such as Figure 18, the withdraw of the needle plate driving assembly 420 of another scheme includes the first cylinder 1421 and the first fixture nut 1422, the first cylinder 1421 is fixedly mounted in mounting bracket 240,1421 piston rod of the first fixture nut 1422 and the first cylinder Front end is coupled, and withdraw of the needle plate 410 is connected with the first fixture nut 1422.When gas injects the first cylinder 1421, the first gas 1421 front end of cylinder piston rod is protruding, is axially moved along piston rod.1421 piston of first fixture nut 1422 and the first cylinder The axial movement that first cylinder 1421 exports is transferred to withdraw of the needle plate 410 by the cooperation of bar front end, so as to drive withdraw of the needle plate 410 into Row linear motion, carries out the withdraw of the needle.
Further, whirling vibration mechanism 200 further includes mounting bracket 240, rotating electric machine 210 and withdraw of the needle plate driving motor 421 are respectively and fixedly installed in mounting bracket 240, and the both ends of rotary shaft 220 are spindle rotationally arranged in mounting bracket by bearing In 240, the structure of whirling vibration mechanism 200 is enable to step up to gather, stablize.
Further, as shown in connection with fig. 9, microlayer model generating means further include longitudinal moving mechanism 500, vertically move machine Structure 500 includes the first mounting plate 510, longitudinal movement driving assembly 520 and longitudinal sliding motion component 530, and mounting bracket 240 passes through vertical Be mounted on the first mounting plate 510 to slide assemblies 530, longitudinal movement driving assembly 520 for drive mounting bracket 240 along Longitudinal sliding motion component 530 slides.Under the action of vertically moving driving assembly 520, mounting bracket 240 can drive whirling vibration Mechanism 200 moves in the longitudinal direction, i.e., the connector 230 in rotary shaft 220 can move in the longitudinal direction.Existed by control joint 230 It is vertical to move up, microchannel 100 on connector 230 synchronizing moving in the longitudinal direction can be driven, when needing the of microchannel 100 When below one opening insertion second liquid liquid level, microchannel 100 can be driven to move downward by control longitudinal moving mechanism 500 To predetermined altitude；When need by microchannel 100 remove when, can by control longitudinal moving mechanism 500 drive microchannel 100 to Upper movement.Longitudinal moving mechanism 500 also loads microchannel 100 for connector 230 automatically and provides condition, when needing microchannel 100 when being mounted on connector 230, and microchannel 100 can be placed on to 230 lower section of connector, the second of microchannel 100 is made to be open 120 alignment connectors 230, starting longitudinal movement driving assembly 520, drive connector 230 to move down, open the 4th of connector 230 Mouth 232 is inserted into the second opening 120 of microchannel 100, then connector 230 is driven to move up reset again.Also, in connector After loading microchannel 100 on 230, longitudinal movement driving assembly 520, which can also drive microchannel 100 to move down, makes first to open Mouth 110 is inserted under the liquid level of second liquids 610, carries out whirling vibration to manufacture microlayer model.
Specifically, in conjunction with shown in Fig. 8 and Fig. 9, longitudinal movement driving assembly 520 includes longitudinal movement driving motor 521, the Two lead screws 522 and the second feed screw nut 523, longitudinal movement driving motor 521 is fixedly mounted on the first mounting plate 510, longitudinal The output end of mobile driving motor is connected with the second lead screw 522, and the second feed screw nut 523 is coupled with the second lead screw 522, Mounting bracket 240 is connected with the second feed screw nut 523.Second feed screw nut 523 and the cooperation of the second lead screw 522 will longitudinal movements The rotary motion that driving motor 521 exports is changed into the second feed screw nut 523 and transports along the straight line in 522 axial direction of the second lead screw It is dynamic, so as to drive mounting bracket 240 to move along a straight line, it is of course also possible to use the linear drives component of other forms To drive mounting bracket 240.Such as rack drives.
Such as Figure 17, the longitudinal movement driving assembly 520 of another scheme includes that the longitudinal movement gear with power interruption braking drives Dynamic motor 1521, first gear 1522 and the first rack gear 1523, longitudinal movement gear drive motor 1521 are fixedly mounted on installation On bracket 240, the output end for vertically moving driving motor is connected with first gear 1522, and the first rack gear 1523 is fixed on first On mounting plate 510, the first rack gear 1523 is coupled with first gear 1522.First gear 1522 and the cooperation of the first rack gear 1523 The rotary motion that gear drive motor 1521 exports will be vertically moved and be changed into longitudinal movement gear drive motor 1521 and first Gear 1522 is along the linear motion in 1523 axial direction of the first rack gear, so as to drive mounting bracket 240 to move along a straight line, It is of course also possible to use the linear drives component of other forms is to drive mounting bracket 240.
As shown in Figure 10, Figure 11 and Figure 12, the fluid driving mechanism 300 in present embodiment includes syringe 350 and note The liquid in-out mouth of emitter driving assembly 320, syringe 350 is connected by tubule 310 with the second opening 120 of microchannel 100. The push rod 351 of syringe 350 slides in the cylinder of syringe 350 under the drive of injector drive component 320, pushes wherein Driving liquid entered in microchannel 100 by tubule 310 and connector 230, the first liquid 130 into microchannel 100 provides stream Body driving force.Fluid driving mechanism provided by the present invention is not limited to the above embodiment, for example, can also be using wriggling Pump, pressure-driven pump, pneumatic-driven pump or driven by electroosmosis pump etc..
Further, as shown in figure 12, fluid driving mechanism 300 further includes three-way diverter valve 330 and fluid reservoir, microchannel 100 the second opening 120, the liquid outlet of the liquid in-out mouth of syringe 350 and fluid reservoir and three interfaces of three-way diverter valve 330 It is connected.Three-way diverter valve 330 at least can control fluid driving mechanism 300 and realize following two mode: one, making syringe 350 liquid in-out mouth is connected with the second opening 120 of microchannel 100, under the drive of injector drive component 320, injection Device 350 provides liquid driven power to microchannel 100, for the first liquid in microchannel 100 to be released from the first opening 110, Or the first liquid is drawn into microchannel 100 from the first opening 110；Two, make the liquid in-out mouth and liquid storage of syringe 350 Tank is connected, and under the drive of injector drive component 320, the driving liquid in fluid reservoir is drawn into injection by syringe 350 In the tube body of device 350, or will be in the driving liquid push-in fluid reservoir in syringe 350.
In conjunction with shown in Fig. 8, Fig. 9 and Figure 11, in order to improve the formation efficiency of microlayer model, implementation as one preferred Mode, microchannel 100, connector 230, tubule 310 and syringe 350 are respectively multiple, and multiple connectors 230 are in rotary shaft 220 Be alternatively arranged, multiple microchannels 100 are separately mounted on a connector 230, the both ends of every tubule 310 respectively with a micro-pipe Second opening in road 100 is connected with the first interface of three-way diverter valve 330, the liquid in-out mouth of each syringe 350 and threeway The second interface of reversal valve 330 is connected, and the liquid outlet of fluid reservoir is connected with the third interface of three-way diverter valve 330.It is multiple Microchannel 100 can carry out the work of microlayer model generation simultaneously under the driving of syringe 350 and rotating electric machine 210, and one three The microlayer model that logical reversal valve 330 may be implemented to control multiple microchannels 100 simultaneously generates state.
As a preferred embodiment, multiple microchannels 100, connector 230, tubule 310 and injection can also be corresponded to Multiple three-way diverter valves 330 are arranged in device 350, by multiple three-way diverter valves 330 respectively with multiple tubules 310 and multiple syringes 350 are connected, in this way can be raw to the microlayer model of multiple microchannels 100 by realizing to multiple three-way diverter valve independent controls It is independently controlled at state.
Further, in conjunction with shown in Figure 12, Figure 14 and 15, fluid driving mechanism 300 further includes mounting blocks 340, Duo Gesan Logical reversal valve 330 and syringe 350 are fixedly mounted on mounting blocks 340, offered in mounting blocks 340 multiple first runners 341, 342, third flow channels 343 of multiple second flow channels and multiple liquid separation runners 344, the both ends of each first runner 341 respectively with A piece tubule 310 is connected with the first interface of a three-way diverter valve 330, and the both ends of each second flow channel 342 are respectively with one The liquid in-out mouth of a syringe 350 and the second interface of a three-way diverter valve 330 are connected, third flow channel 343 and fluid reservoir It is connected with multiple liquid separation runners 344, each liquid separation runner 344 is connected with the third interface of a three-way diverter valve 330.
Specifically, as shown in connection with fig. 10, injector drive component 320 includes injector drive motor 321, third lead screw 322 and third feed screw nut 323, the output end of injector drive motor 321 be connected with third lead screw 322, third lead screw spiral shell Mother 323 is coupled with third lead screw 322, and the push rod 351 of multiple syringes 350 passes through connector (not shown) and third Feed screw nut 323 is connected.Third feed screw nut 323 and third lead screw 322 cooperate the rotation for exporting injector drive motor 321 Transhipment turn becomes third feed screw nut 323 along the linear motion in 322 axial direction of third lead screw, so as to drive syringe 350 push rod 351 moves along a straight line, it is of course also possible to use the linear drives component of other forms is with driving push rod 351. Such as rack drives.
Such as Figure 16, the injector drive component 320 of another scheme includes the syringe gear driving electricity with power interruption braking Machine 1321, second gear 1322 and the second rack gear 1323, output end and 1322 phase of second gear of injector drive motor 1321 Connection, the second rack gear 1323 are connected with the second mounting plate 360, and the second rack gear 1323 is coupled with second gear 1322, more The push rod 351 of a syringe 350 is connected by connector (not shown) with syringe gear drive motor 1321.Second Gear 1322 and the second rack gear 1323, which cooperate, is changed into syringe gear for the rotary motion that injector drive motor 1321 exports Driving motor 1321 and second gear 1322 are along the linear motion in 1323 axial direction of the second rack gear, so as to drive syringe The 351 of 350 move along a straight line, it is of course also possible to use the linear drives component of other forms is with driving push rod 351.
Further, fluid driving mechanism 300 further includes the second mounting plate 360, mounting blocks 340 and injector drive electricity Machine 321 is fixedly mounted on the second mounting plate 360, and the second mounting plate 360 keeps 300 structure of fluid driving mechanism more compact and steady It is fixed.The first mounting plate can also be merged setting with the second mounting plate simultaneously, to save space, such as shown in Figure 19, can will infused Emitter driving assembly 320, which is mounted on, to be integrated on mounting plate 1360, remaining installation goes driving method not change.
As a preferred embodiment, rotating electric machine 210 can use galvanometer motor, galvanometer motor can be provided surely Fixed and high speed reciprocating rotary wobbling action, and the amplitude of oscillation and frequency can be set as desired, greatly improve the micro- liquid of the present invention Drip the scope of application of generating means.Meanwhile withdraw of the needle plate driving motor 421, longitudinal movement driving motor 521, injector drive electricity Machine 321 can use stepper motor, and stepper motor and the cooperation of screw-nut structure can accurately control the stroke of linear motion, Improve the degree of automation.
Preferably, rotating electric machine 210 is vibrated using the motor with closed-loop control vibration angle or position by closed-loop control Angle or the motor driven whirling vibration mechanism 200 of position carry out whirling vibration, thus the swing of accurate control microchannel 100 Track, to be further reduced environment and the disturbance of system bring.This method another advantage is that adjustable system Parameter makes critical size that can reach (arrow is signified in such as Fig. 7) in a swing period.This means that each is revolved Transhipment only generates a drop in the dynamic period.Make the change of the droplet size brought by various environmental factors fluctuate in this way Change will not accumulate next cycle.Thus large batch of it can generate drop of uniform size.This point be also other Announcement passes through advantage not available for mechanical movement generation nanoliter/picoliters magnitude emulsion droplet scheme.
Below in conjunction with the application of Figure 16 elaboration closed-loop control vibration angle or the motor of position in the present invention.Closed-loop control Vibration angle or the motor of position include the components such as infrared position sensor, control circuit and signal processing circuit.In the present invention In, infrared position sensor is installed in the rotary shaft 220 of whirling vibration mechanism 200, by infrared position sensor its institute The position signal of acquisition is fed back into control circuit, and control circuit is according to PID automation control principle respectively to the position of feedback Signal has done ratio, has integrated, processing of differentiating, and the signal processing electricity of binding site feedforward and speed ring, electric current loop etc. Road, absolute position when realizing motor movement accurately control.It can be kept away using closed-loop control vibration angle or the motor of position Exempt from other vibrating motors to be loaded environmental change by complexity and cause the change of vibration position, is conducive to accurately control in engineering Droplet size and formation speed processed.
In the present embodiment, having volume between the first opening 110 and the second opening 120 of microchannel 100 is 10 μ L The liquid storage chamber of~100 μ L, the liquid storage chamber can store a certain amount of first liquid, guarantee that the first liquid generates requirement enough Microlayer model, meanwhile, liquid storage chamber can also prevent the first liquid to be inhaled into connector 230 by microchannel 100, in tubule 310, Safeguards system will not be contaminated by the sample.
Preferably, microchannel 100 can be made of nonrigid material, have certain flexibility.Certain flexibility refers to micro-pipe It is certain that under the driving of whirling vibration mechanism 200 the motion path of first opening 110 of microchannel 100 can have in road 100 Standing wave phenomena.Using the microchannel made of the material with certain flexibility, liquid level is generated to further reduce Disturbance be more easier, uniformly so that generating drop, while also further reducing liquid crushing phenomenon generated.
In the present embodiment, microchannel 100 is made of the polypropylene material of low-surface-energy；Tubule 310 is by Teflon (Teflon) material is made.
In embodiments, the spout diameter of the first opening 110 of microchannel 100 is 1 μm -250 μm, it is highly preferred that micro- The spout diameter of first opening 110 of pipeline 100 is 10 μm -100 μm.
The present invention also provides a kind of microlayer models to generate system, and the microlayer model including any of the above-described embodiment generates dress Container 600 is set and generated, generates in container 600 and is contained with the second liquid 610 immiscible with the first liquid 130, whirling vibration Mechanism 200 is used to drive the first opening 110 of microchannel 100 generating the 610 liquid level backspin rotational oscillation of second liquid in container 600 It is dynamic, so that the first liquid 130 is generated microlayer model under second liquid liquid level.Container 600 is wherein generated for holding second liquid 610, stable environmental condition is provided for microlayer model generation, while the microlayer model generated can also be stored in second liquid 610, Convenient for subsequent processing.
Preferably, for the density of second liquid 610 less than the density of the first liquid 130, the microlayer model generated in this way is gradually The bottom for generating container 600 is sunk to, and container bottom can be laid in, is more advantageous to subsequent processing.
Further include sample container in the generation system of present embodiment, the first liquid 130 be contained in sample container, into Before row microlayer model generates, it can control microchannel 100 and aspirate the first liquid 130 in sample container, be allowed to be stored in micro-pipe In liquid storage chamber in road 100, convenient for the required amount of microlayer model of generation of steady and continuous later.
Further, the generation system of present embodiment further includes supplies racks, and promising microchannel is placed in supplies racks 100, supplies racks can store original microchannel 100, and the state for making microchannel 100 keep placing vertically is convenient for connector 230 load microchannel 100 automatically under the driving of longitudinal moving mechanism 500.
As a preferred embodiment, it further includes translating device, translating device energy that microlayer model of the present invention, which generates system, It enough drives microlayer model generating means to move above generation container 600, sample container or supplies racks, container 600, sample will be generated Container and supplies racks are mounted on the same platform, may be implemented to load microchannel 100, the first liquid 130 of suction and microlayer model Generation step is worked continuously.Translating device can take various forms, such as synchronous belt traction, rack-and-pinion, feed screw nut Or the prior arts such as linear motor, then this does not repeat them here.
System is generated based on the microlayer model in any of the above-described embodiment as shown in figure 17, the present invention also provides a kind of micro- Drop formation method, comprising the following steps:
S100 generates 110 insertion of the first opening of microchannel 100 below the second liquid liquid level in container 600；
S200 starts whirling vibration mechanism 200, and the first opening 110 of driving microchannel 100 is below second liquid liquid level Whirling vibration, while pushing the first liquid 130 in microchannel 100, so that the first liquid 130 enters the from the first opening 110 In two liquid, microlayer model is formed under the whirling vibration of the first opening 110.
Specifically, in step s 200, by pushing driving liquid into microchannel 100, making the first liquid in microchannel 100 Body 130 enters in second liquid from the first opening 110, using driving liquid as the medium of transmitting driving force, can make driving force Transmitting it is more stable.
As an alternative embodiment, in the step s 100,110 insertion of the first opening of microchannel 100, which generates, to be held Below second liquid liquid level in device 600 and second liquid liquid level is in 30 °~90 ° of angle.
As an alternative embodiment, in step s 200, the first opening of microchannel 100 is relative to second liquid The distance of liquid level is between 0.05mm~10mm.
As an alternative embodiment, in step s 200, in whirling vibration mechanism vibration processes, microchannel The swing angle of 100 whirling vibration is 0.1 °~10 °.
As an alternative embodiment, the vibration frequency of whirling vibration mechanism is 1Hz~1000Hz.
As an alternative embodiment, the volume of microlayer model is 1pL~100nL.It can be by changing injection speed To change the generation size of microlayer model, technical staff can adjust injection speed according to the requirement of the size to microlayer model.It is excellent Selection of land, fluid driving mechanism 300 at the uniform velocity push the first liquid 130 in microchannel 100 with the speed of 50nL/s~1000nL/s.
As an alternative embodiment, in step s 200, the first liquid 130 at the uniform velocity in push microchannel 100, So that the first liquid 130 generates the microlayer model of fixed number within each whirling vibration period of the first opening 110.By adjusting The amplitude and/or frequency of whirling vibration mechanism 200, so that rotation of first liquid 130 in the first opening 110 of microchannel 100 A microlayer model is only generated under effect of vibration in each period.User is according to the work of microlayer model generating means whirling vibration Time and frequency, it is estimated that the generation sum of microlayer model.
As shown in figure 18, it in the another embodiment of microlayer model generation method of the present invention, before step S100, also wraps Step S110 is included, microchannel 100 is mounted in whirling vibration mechanism 200, which can be by controlling longitudinal moving mechanism Connector 230 in 500 drive whirling vibration mechanisms 200 is moved to microchannel 100 to realize automatic loading.
It further include step S210 after step S200, by microchannel 100 after being removed in generation container 600, by micro-pipe Road 100 is disassembled from whirling vibration mechanism 200, which can be realized by control withdraw of the needle mechanism 400.
After step silo, further include step S120, make in the first liquid 130 injection microchannel 100.The step can be with It is realized by control fluid driving mechanism 300.
Specifically, in the step s 120, the 110 sucking microchannel of the first opening that the first liquid 130 passes through microchannel 100 In 100.
Embodiment 1
Microchannel 100, which is used, is made microchannel by hardness for the non-rigid polypropylene material of shore D42.Microchannel 100 The spout diameter of first opening 110 is 150 microns, outer diameter is 300 microns, vibration radius length is 6 centimetres.Whirling vibration mechanism 200 vibration frequency is 100Hz, Oscillation Amplitude voltage is 700mVpp.The amplitude of first opening 110 of microchannel 100 is 0.1 Millimeter.
First opening 110 of microchannel 100 is connect by connector 230 and tubule 310 with fluid driving mechanism 300；It will be micro- First opening 110 of pipeline 100 is inserted with the liquid level with second liquid 610 (in the present embodiment for mineral oil) at 30 degree of angle Enter below the liquid level of second liquid 610, so that the nozzle center of the first opening 110 of microchannel 100 is to second liquid 610 The vertical range of liquid level be 1.5mm, push the syringe 350 in fluid driving mechanism 300 by its first intracavitary liquid 130 Shift onto microchannel 100 first opening 110 nozzle at；Start whirling vibration mechanism 200, drives the first of microchannel 100 Be open 110 whirling vibrations；Starting fluid driving mechanism 300 at the uniform velocity pushes the first liquid in microchannel 100 with the speed of 100nL/s Body 130, so that the first liquid 130 is when the continuous rotation of the first opening 110 is vibrated 3 minutes under the liquid level of second liquid 610 It is continuously generated microlayer model.Drop (the droplet radius of a 1nL can be stably generated within each vibration period of microchannel 100 For 0.13mm).If 610 density of second liquid selected is less than the first liquid 130, the microlayer model generated can be in gravity Under overcome buoyancy in second liquid 610 and the bottom of the container of automatic sedimentation.Figure 19 is generated the effect of microlayer model by embodiment 1 Fruit figure.
Embodiment 2
Microchannel is made using stainless steel in microchannel 100, and the spout diameter of the first opening 110 is 60 microns, outer diameter is 200 microns, vibration radius length be 5 centimetres.The vibration frequency of whirling vibration mechanism 200 is 100Hz, Oscillation Amplitude voltage is 400mVpp.The amplitude of first opening 110 of microchannel 100 is 1 millimeter.
Second opening 120 of microchannel 100 is connect by connector 230 and tubule 310 with fluid driving mechanism 300；It will be micro- First opening 110 of pipeline 100 is inserted under the liquid level of second liquid 610 with the liquid level with second liquid 610 at 90 degree of angle Side, so that the vertical range of liquid level of nozzle center to the second liquid 610 of the first opening 110 of microchannel 100 is 1.5mm pushes the syringe 350 in fluid driving mechanism 300 to shift its first intracavitary liquid 130 the of microchannel 100 onto At the nozzle of one opening 110；Start whirling vibration mechanism 200, the first 110 whirling vibrations of opening of driving microchannel 100；Starting Fluid driving mechanism 300 at the uniform velocity pushes the first liquid 130 in microchannel 100 with the speed of 100nL/s, so that the first liquid 130 are continuously generated microlayer model under the liquid level of second liquid 610 when the continuous rotation of the first opening 110 is vibrated 3 minutes.? The drop (droplet radius 0.125mm) of a 1nL can be stably generated in each vibration period of capillary.If select the Less than the first liquid 130, then the microlayer model generated can overcome under the effect of gravity in second liquid 610 two liquid, 610 density The bottom of buoyancy and the oil vessel of automatic sedimentation.Figure 20 is generated the effect picture of microlayer model by embodiment 2.
Only several embodiments of the present invention are expressed for above embodiments, and the description thereof is more specific and detailed, but can not Therefore limitations on the scope of the patent of the present invention are interpreted as.It should be pointed out that for those of ordinary skill in the art, Without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection model of the invention It encloses.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.

Claims (36)

1. a kind of microlayer model generating means, including microchannel (100), the microchannel (100) has output the first liquid (130) First opening (110), which is characterized in that further include whirling vibration mechanism (200), the whirling vibration mechanism (200) is used for Drive the microchannel (100) whirling vibration.
2. microlayer model generating means according to claim 1, which is characterized in that the microlayer model generating means further include stream Body driving mechanism (300), the second opening that the fluid driving mechanism (300) passes through tubule (310) and the microchannel (100) (120) it is connected.
3. microlayer model generating means according to claim 2, which is characterized in that the whirling vibration mechanism (200) includes Rotating electric machine (210), rotary shaft (220) and connector (230), the output end of the rotating electric machine (210) and the rotary shaft (220) it is connected, the connector (230) is fixedly connected on described along the direction with the rotary shaft (220) axis perpendicular In rotary shaft (220), the microchannel (100) is mounted on the connector (230).
4. microlayer model generating means according to claim 3, which is characterized in that the connector (230) is tubulose, is had interior The third opening (231) and the 4th opening (232) that portion is connected, the tubule (310) are connected to the third opening (231) On, the second opening (120) of the microchannel (100) is connected in the 4th opening (232).
5. microlayer model generating means according to claim 4, which is characterized in that the microlayer model generating means further include moving back Needle mechanism (400), the withdraw of the needle structure (400) is for separating the microchannel (100) with the connector (230).
6. microlayer model generating means according to claim 5, which is characterized in that the withdraw of the needle mechanism (400) includes the withdraw of the needle Plate (410) and withdraw of the needle plate driving assembly (420) offer withdraw of the needle hole (411) on the withdraw of the needle plate (410), the withdraw of the needle hole (411) it is set in the outside of the connector (230), the second opening (120) of the microchannel (100) is set in the described 4th and opens The outside of mouth (232), and relatively with the withdraw of the needle plate (410), the withdraw of the needle plate driving assembly (420) is for driving the withdraw of the needle The direction of plate (410) Xiang Suoshu microchannel (100) moves.
7. microlayer model generating means according to claim 6, which is characterized in that the 4th opening of the connector (230) (232) outside is in up big and down small round table-like.
8. microlayer model generating means according to claim 6, which is characterized in that the withdraw of the needle plate driving assembly (420) can Realized by screw structure or air cylinder structure: screw structure includes withdraw of the needle plate driving motor (421), the first lead screw (422) and first Feed screw nut (423), the output end of the withdraw of the needle plate driving motor (421) are connected with first lead screw (422), and described One feed screw nut (423) is coupled with first lead screw (422), the withdraw of the needle plate (410) and first feed screw nut (423) it is connected；It include the first cylinder (1421), the first fixture nut (1422) under air cylinder structure.First cylinder (1421) piston rod front end is coupled with first fixture nut (1423), and the withdraw of the needle plate (410) is solid with described first Determine nut (1423) to be connected.
9. microlayer model generating means according to claim 8, which is characterized in that the whirling vibration mechanism (200) is also wrapped It includes mounting bracket (240), the rotating electric machine (210) and the withdraw of the needle plate driving motor (421), the first cylinder (1421) are respectively It is fixedly mounted on the mounting bracket (240).
10. microlayer model generating means according to claim 9, which is characterized in that the microlayer model generating means further include Longitudinal moving mechanism (500), the longitudinal moving mechanism (500) include the first mounting plate (510), longitudinal movement driving assembly (520) and longitudinal sliding motion component (530), the mounting bracket (240) are mounted on described by the longitudinal sliding motion component (530) On first mounting plate (510), the longitudinal movement driving assembly (520) is for driving the mounting bracket (240) along described Longitudinal sliding motion component (530) sliding.
11. microlayer model generating means according to claim 10, which is characterized in that the longitudinal movement driving assembly can be by Screw structure or rack structure are realized: screw structure includes longitudinal movement driving motor (521), the second lead screw (522) and second Feed screw nut (523), the longitudinal movement driving motor (521) are fixedly mounted on first mounting plate (510), described vertical It is connected to the output end of mobile driving motor with second lead screw (522), second feed screw nut (523) and described the Two lead screws (522) are coupled, and the mounting bracket (240) is connected with second feed screw nut (523)；Rack structure packet Include longitudinal movement gear drive motor (1521), first gear (1522) and the first rack gear (1523), the longitudinal movement gear Driving motor (1521) is fixedly mounted on the bracket (240), the output of longitudinal movement gear drive motor (1521) End is connected with the first gear (1522), and first rack gear (1523) is coupled with the first gear (1522), First rack gear (1523) is fixedly mounted on first mounting plate (510).
12. microlayer model generating means according to claim 3, which is characterized in that the fluid driving mechanism (300) includes Syringe (350) and injector drive component (320), the liquid in-out mouth of the syringe (350) by the tubule (310) with Second opening (120) of the microchannel (100) is connected.
13. microlayer model generating means according to claim 12, which is characterized in that the fluid driving mechanism (300) is also Including three-way diverter valve (330) and fluid reservoir, the second opening (120) of the microchannel (100), the syringe (350) The liquid outlet of liquid in-out mouth and the fluid reservoir is connected with three interfaces of the three-way diverter valve (330).
14. microlayer model generating means according to claim 13, which is characterized in that the microchannel (100), connector (230), tubule (310) and syringe (350) are respectively multiple, between multiple connectors (230) are on the rotary shaft (220) Every arrangement, multiple microchannels (100) are separately mounted on the connector (230), and the two of the every tubule (310) End is connected with the first interface of the second opening of a microchannel (100) and the three-way diverter valve (330) respectively, often The liquid in-out mouth of a syringe (350) is connected with the second interface of the three-way diverter valve (330), the fluid reservoir Liquid outlet is connected with the third interface of the three-way diverter valve (330).
15. microlayer model generating means according to claim 14, which is characterized in that the three-way diverter valve (330) is more A, the first interface of each three-way diverter valve (330) is connected with a tubule (310), each triple valve (330) second interface is connected with the liquid in-out mouth of a syringe (350), multiple three-way diverter valves (330) Third interface be connected simultaneously with the liquid outlet of the fluid reservoir.
16. microlayer model generating means according to claim 15, which is characterized in that the fluid driving mechanism (300) is also Including mounting blocks (340), multiple three-way diverter valves (330) and the syringe (350) are fixedly mounted on the mounting blocks (340) on, multiple first runners (341), multiple second flow channels (342), a third stream are offered in the mounting blocks (340) Road (343) and multiple liquid separation runners (344), the both ends of each first runner (341) respectively with a tubule (310) and one The first interface of a three-way diverter valve (330) is connected, the both ends of each second flow channel (342) respectively with an institute The second interface of the liquid in-out mouth and a three-way diverter valve (330) of stating syringe (350) is connected, the third flow channel (343) it is connected with the fluid reservoir and multiple liquid separation runners (344), each liquid separation runner (344) and an institute The third interface for stating three-way diverter valve (330) is connected.When being driven using rack structure, the syringe gear driving electricity Machine (1321) is fixedly mounted on the mounting blocks (340).
17. microlayer model generating means according to claim 14, which is characterized in that the injector drive component (320) Can be realized by screw structure or rack structure: screw structure includes injector drive motor (321), third lead screw (322) and the Three feed screw nuts (323), the output end of the injector drive motor (321) is connected with the third lead screw (322), described Third feed screw nut (323) is coupled with the third lead screw (322), the push rod (351) of multiple syringes (350) with The third feed screw nut (323) is connected；Rack structure includes syringe gear drive motor (1321), second gear (1322) and the second rack gear (1323), output end and the second gear (1322) phase of the injector drive motor (1321) Connection, second rack gear (1323) are coupled with the second gear (1322), the fixed peace of second rack gear (1323) On second mounting plate (360), the push rod (351) and the syringe gear of multiple syringes (350) are driven Motor (1321) is connected.
18. microlayer model generating means according to claim 17, which is characterized in that the fluid driving mechanism (300) is also Including the second mounting plate (360), the mounting blocks (340) and the injector drive motor (321) are fixedly mounted on described On two mounting plates (360), or it is fixedly mounted on first mounting plate (510).
19. microlayer model generating means according to claim 18, which is characterized in that the fluid driving mechanism (300) is another A kind of structure further includes integrating mounting plate (1360), the mounting blocks (340), the injector drive motor (321), described vertical Described integrate on mounting plate (1360) is fixedly mounted on to mobile driving motor (521), the longitudinal sliding motion component (530).
20. microlayer model generating means according to claim 2, which is characterized in that the first opening of the microchannel (100) (110) liquid storage chamber for being 10 μ of μ L~100 L with volume between the second opening (120).
21. a kind of microlayer model generates system, which is characterized in that raw including the described in any item microlayer models of such as claim 1 to 20 At device and container (600) are generated, described generate is contained with the immiscible with first liquid (130) in container (600) Two liquid, the whirling vibration mechanism (200) are used to drive the first of the microchannel (100) to be open (110) in the generation Whirling vibration under second liquid liquid level in container (600) makes the first liquid (130) generate micro- liquid under second liquid liquid level Drop.
22. microlayer model according to claim 21 generates system, which is characterized in that it further include sample container, the sample First liquid (130) is contained in container.
23. microlayer model according to claim 22 generates system, which is characterized in that it further include supplies racks, the supplies racks On be placed with it is described for microchannel (100).
24. the microlayer model according to claim 22 or 23 generates system, which is characterized in that it further include translating device, it is described Translating device is able to drive the microlayer model generating means in the generation container (600), the sample container or the consumptive material It is mobile above frame.
25. a kind of microlayer model generation method, which is characterized in that using such as the described in any item microlayer models lifes of claim 19 to 22 At system, comprising the following steps:
S100, by the first opening (110) insertion second liquid liquid generated in container (600) of the microchannel (100) Below face；
S200 starts whirling vibration mechanism (200), drives the first of the microchannel (100) to be open (110) in second liquid liquid Whirling vibration below face, while pushing the first liquid (130) in the microchannel (100), so that the first liquid (130) is from institute It states the first opening (110) to enter in second liquid, forms microlayer model under the whirling vibration of first opening (110).
26. microlayer model generation method according to claim 25, which is characterized in that described micro- in the step S100 First opening (110) insertion of pipeline (100) the second liquid liquid level lower section generated in container (600) and second liquid liquid Face is in 30 °~90 ° of angle.
27. microlayer model generation method according to claim 25, which is characterized in that described micro- in the step S200 Pipeline (100) first opening relative to second liquid liquid level distance between 0.05mm~10mm.
28. microlayer model generation method according to claim 25, which is characterized in that in the step S200, described In whirling vibration mechanism vibration processes, the swing angle of the whirling vibration of the microchannel (100) is 0.1 °~10 °.
29. microlayer model generation method according to claim 25, which is characterized in that the vibration frequency of the whirling vibration mechanism Rate is 1Hz~1000Hz.
30. microlayer model generation method according to claim 25, which is characterized in that the volume of the microlayer model be 1pL~ 100nL。
31. microlayer model generation method according to claim 25, which is characterized in that in the step S200, at the uniform velocity push away The first liquid (130) in the microchannel (100) is sent, so that first liquid (130) is in first opening (110) The microlayer model of fixed number is generated in each whirling vibration period.
32. microlayer model generation method according to claim 25, which is characterized in that before the step S100, also wrap Step S110 is included, microchannel (100) is mounted on the whirling vibration mechanism (200).
33. microlayer model generation method according to claim 32, which is characterized in that after the step S200, also wrap Step S210 is included, by microchannel (100) after generating and removing in container (600), by microchannel (100) from the rotational vibrator Structure disassembles on (200).
34. microlayer model generation method according to claim 32, which is characterized in that after the step S110, also wrap Step S120 is included, injects first liquid (130) in the microchannel (100).
35. microlayer model generation method according to claim 34, which is characterized in that in the step S120, described One liquid (130) is sucked in the microchannel (100) by first opening (110) of the microchannel (100).
36. microlayer model generation method according to claim 25, which is characterized in that in the step S200, pass through to Push driving liquid in the microchannel (100), makes the first liquid (130) in the microchannel (100) be open from described first (110) enter in second liquid.
CN201810073981.0A 2018-01-25 2018-01-25 Micro-droplet generation device, system and generation method Active CN110075933B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810073981.0A CN110075933B (en) 2018-01-25 2018-01-25 Micro-droplet generation device, system and generation method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810073981.0A CN110075933B (en) 2018-01-25 2018-01-25 Micro-droplet generation device, system and generation method

Publications (2)

Publication Number Publication Date
CN110075933A true CN110075933A (en) 2019-08-02
CN110075933B CN110075933B (en) 2022-05-13

Family

ID=67412009

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810073981.0A Active CN110075933B (en) 2018-01-25 2018-01-25 Micro-droplet generation device, system and generation method

Country Status (1)

Country Link
CN (1) CN110075933B (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110841734A (en) * 2019-12-06 2020-02-28 中国科学院长春光学精密机械与物理研究所 Digital PCR device and single-pump liquid drop generating system thereof
CN112452365A (en) * 2020-11-23 2021-03-09 无锡市夸克微智造科技有限责任公司 Micro-machining fluid device
CN113769808A (en) * 2021-09-21 2021-12-10 南京理工大学 Rotary liquid drop generator
CN114453041A (en) * 2022-03-08 2022-05-10 广州大学 Micro-droplet preparation device
CN115138407A (en) * 2022-06-17 2022-10-04 深圳大学 Double-aqueous-phase microcapsule generating device and generating method thereof
CN115228526A (en) * 2022-07-04 2022-10-25 福州安林生物科技有限公司 Micro-pipeline-based liquid drop generation method
WO2023025289A1 (en) * 2021-08-26 2023-03-02 北京达微生物科技有限公司 Control device for micro-droplet preparation and micro-droplet preparation method

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1542516A1 (en) * 2003-12-08 2005-06-15 Sentelic Corporation Heat dissipating microdevice and method of making the same
US20050232823A1 (en) * 2001-01-17 2005-10-20 Irm Llc Sample Deposition Method and System
CN203941178U (en) * 2011-05-20 2014-11-12 珀金埃尔默保健科学公司 Laboratory parts and liquid loading and unloading system and complementary flowable materials handling system
CN104450891A (en) * 2014-11-17 2015-03-25 中国科学院微生物研究所 Method and system for digital quantitative analysis of nucleic acid amplification based on micro-droplet
EP3023152A1 (en) * 2014-11-20 2016-05-25 Friedrich-Alexander-Universität Erlangen-Nürnberg Method for producing a liquid sample for analysis by use of radiation
CN106635777A (en) * 2016-11-15 2017-05-10 杭州凯基科技有限公司 Gene micro-drop granule chip making device and gene micro-drop granule chip making method
CN107321398A (en) * 2017-06-27 2017-11-07 中国科学院长春光学精密机械与物理研究所 A kind of drop spontaneously forms the system and method with control

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050232823A1 (en) * 2001-01-17 2005-10-20 Irm Llc Sample Deposition Method and System
EP1542516A1 (en) * 2003-12-08 2005-06-15 Sentelic Corporation Heat dissipating microdevice and method of making the same
CN203941178U (en) * 2011-05-20 2014-11-12 珀金埃尔默保健科学公司 Laboratory parts and liquid loading and unloading system and complementary flowable materials handling system
CN104450891A (en) * 2014-11-17 2015-03-25 中国科学院微生物研究所 Method and system for digital quantitative analysis of nucleic acid amplification based on micro-droplet
EP3023152A1 (en) * 2014-11-20 2016-05-25 Friedrich-Alexander-Universität Erlangen-Nürnberg Method for producing a liquid sample for analysis by use of radiation
CN106635777A (en) * 2016-11-15 2017-05-10 杭州凯基科技有限公司 Gene micro-drop granule chip making device and gene micro-drop granule chip making method
CN107321398A (en) * 2017-06-27 2017-11-07 中国科学院长春光学精密机械与物理研究所 A kind of drop spontaneously forms the system and method with control

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110841734A (en) * 2019-12-06 2020-02-28 中国科学院长春光学精密机械与物理研究所 Digital PCR device and single-pump liquid drop generating system thereof
CN112452365A (en) * 2020-11-23 2021-03-09 无锡市夸克微智造科技有限责任公司 Micro-machining fluid device
CN112452365B (en) * 2020-11-23 2021-12-07 无锡市夸克微智造科技有限责任公司 Micro-machining fluid device
WO2023025289A1 (en) * 2021-08-26 2023-03-02 北京达微生物科技有限公司 Control device for micro-droplet preparation and micro-droplet preparation method
CN113769808A (en) * 2021-09-21 2021-12-10 南京理工大学 Rotary liquid drop generator
CN114453041A (en) * 2022-03-08 2022-05-10 广州大学 Micro-droplet preparation device
CN115138407A (en) * 2022-06-17 2022-10-04 深圳大学 Double-aqueous-phase microcapsule generating device and generating method thereof
CN115228526A (en) * 2022-07-04 2022-10-25 福州安林生物科技有限公司 Micro-pipeline-based liquid drop generation method

Also Published As

Publication number Publication date
CN110075933B (en) 2022-05-13

Similar Documents

Publication Publication Date Title
CN110075933A (en) Micro-droplet generation device, system and generation method
EP3887049B1 (en) Spinning vessel systems and methods for mixing, suspending particulates, aliquoting, washing magnetic beads, and concentrating analytes
CN104324769B (en) Generation method based on the drop of microchannel
CN208711740U (en) A kind of suction head apparatus generated for microlayer model
CA2864138C (en) High-speed on demand droplet generation and single cell encapsulation driven by induced cavitation
WO2020007098A1 (en) Digital pcr chip, and droplet generation system and detection system containing same
CN210287370U (en) Biological ink box, biological ink box assembly, microsphere preparation equipment, shell layer assembly equipment, biological brick preparation instrument, biological ink preparation instrument and biological ink preparation system
CN109137096B (en) Microfluidic device for preparing microspheres and fibers
CN109908986B (en) Liquid drop generation system based on asymmetric outlet capillary and application method
CN110684650A (en) Liquid drop generation system for digital PCR detection and digital PCR detection method
JP7220366B2 (en) MOTION CONTROL MECHANISM, LIQUID EJECTING PIPETTIP, MICRO-DROPLET GENERATING DEVICE AND METHOD, FLUID DRIVING MECHANISM AND FLUID DRIVING METHOD, MICRO-DROPLET GENERATING METHOD, AND SURFACE-TREATING METHOD OF LIQUID-JETTING PIPETTIP
CN101110278A (en) Method for preparing fusion pallet based on micro-fluid
CN217910483U (en) Control device for preparing micro-droplets
CN208949317U (en) Digital pcr chip and digital pcr detection system
CN216224451U (en) Asymmetric vibration micro-droplet generation mechanism
US20230149918A1 (en) Droplet generation method, system and application
CN205760697U (en) A kind of membrane emulsifier
EP4023336A1 (en) Sample adding needle for preparing microdroplets and microdroplet preparation method
CN110508223B (en) Preparation method and preparation mechanism of embryo microsphere, and preparation method and preparation device of microsphere
CN110064452B (en) Method for producing micro-droplets
CN110684828A (en) Digital PCR chip, digital PCR detection system and detection method
CN212663478U (en) Device for preparing uniform single emulsion drops in high flux
CN114011481B (en) Piezoelectric capillary liquid drop preparation device and application method thereof
CN113769808A (en) Rotary liquid drop generator
CN115106140A (en) Asymmetric vibration micro-droplet generation mechanism

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
PE01 Entry into force of the registration of the contract for pledge of patent right
PE01 Entry into force of the registration of the contract for pledge of patent right

Denomination of invention: Micro droplet generation device, system, and generation method

Effective date of registration: 20230726

Granted publication date: 20220513

Pledgee: Fengxian Branch of Shanghai Rural Commercial Bank Co.,Ltd.

Pledgor: BEIJING ZHIYU BIOTECHNOLOGY Ltd.

Registration number: Y2023310000403