CN110064453A - Spit liquid pipette tips, microlayer model generating means and generation method - Google Patents

Spit liquid pipette tips, microlayer model generating means and generation method Download PDF

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Publication number
CN110064453A
CN110064453A CN201810069887.8A CN201810069887A CN110064453A CN 110064453 A CN110064453 A CN 110064453A CN 201810069887 A CN201810069887 A CN 201810069887A CN 110064453 A CN110064453 A CN 110064453A
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China
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liquid
pipette tips
outlet end
liquid pipette
spitting
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CN201810069887.8A
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CN110064453B (en
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盛广济
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Sinaford (beijing) Medical Technology Co Ltd
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Sinaford (beijing) Medical Technology Co Ltd
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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
    • B01L3/02Burettes; Pipettes
    • B01L3/0241Drop counters; Drop formers

Abstract

Liquid pipette tips are spat for generate microlayer model the present invention relates to a kind of, including the needle stalk with hollow cavity and are set to the outlet end that the needle obstructs one end;Angle between the normal of the outlet end end face for spitting liquid pipette tips and the extending direction of needle stalk is less than or equal to 90 °.The invention further relates to include the above-mentioned microlayer model generating means and generation method for spitting liquid pipette tips.It is above-mentioned to spit liquid pipette tips, when spitting extending direction vibration of the liquid pipette tips along pipe main body, microlayer model from the outlet end for spitting liquid pipette tips fall to fall behind in second liquid viscous force and spit liquid pipette tips outlet end end face squeezing action under far from outlet end motion profile, microlayer model is avoided to be broken by outlet end, maintain the integrality for having generated microlayer model, at the same allow to spit liquid pipette tips along pipe main body extending direction fast vibration to quickly generate microlayer model.

Description

Spit liquid pipette tips, microlayer model generating means and generation method
Technical field
The present invention relates to the measurements of micro liquid, distribution technique field, and it is raw to spit liquid pipette tips, microlayer model more particularly to one kind At device and generation method.
Background technique
It examines at present in clinical medicine, nano material preparation, the application fields such as food and environment measuring, 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, a variety of microlayer model generation techniques are reported in the literature, such as membrane emulsification, spraying emulsion process, miniflow Control chip method, spit liquid pipette tips injection/gunite etc..Wherein, liquid pipette tips injection/gunite, which is spat, as newest microlayer model generates skill Art all has good application prospect in terms of the generation of microlayer model and in terms of consumables cost control.Traditional spits liquid pipette tips one As be in straight tube-like.When spitting liquid pipette tips and quickly being moved along the extending direction of itself close to one end of outlet end, it can break generated Microlayer model.In order to keep the integrality of the microlayer model generated, the vibration frequency for spitting liquid pipette tips must be reduced, the generation of microlayer model is caused Rate reduces.
Summary of the invention
Based on this, it is necessary to the integrality and microlayer model of generated microlayer model cannot be taken into account for traditional liquid pipette tips of spitting The problem of generating rate, provide the generating rate of a kind of integrality that can take into account generated microlayer model and microlayer model spits liquid rifle Head, microlayer model generating means and generation method.
One kind spitting liquid pipette tips, for generating microlayer model, including the needle stalk with hollow cavity and is set to the needle stalk one The outlet end at end;The normal of the outlet end end face for spitting liquid pipette tips and the needle stalk extending direction between angle be less than etc. In 90 °.
A kind of microlayer model generating means, including spitting liquid described in fluid driving mechanism, motion control mechanism and above scheme Pipette tips;The internal reservoir for spitting liquid pipette tips has the first liquid, and the liquid pipette tips of spitting are with outlet end and arrival end;The fluid Driving mechanism is connect with the arrival end for spitting liquid pipette tips, for that will be stored in first liquid spat inside liquid pipette tips from institute State the outlet end discharge for spitting liquid pipette tips;The motion control mechanism spits the outlet end of liquid pipette tips in second liquid described in being used to control Liquid level under generate setting track or setting speed or set the movement of acceleration, so as to spit the outlet ends of liquid pipette tips described in discharge The first liquid overcome surface tension and adhesive force to form microlayer model in second liquid.
A kind of microlayer model generation method, described in any item using the above scheme to spit liquid pipette tips, described spit in liquid pipette tips is stored up There is the first liquid, the microlayer model container for storing second liquid is provided;The first liquid is controlled from the outlet for spitting liquid pipette tips End is at the uniform velocity discharged;The extending direction that outlet end needle described in the liquid level lower edge of second liquid stalk of liquid pipette tips is spat described in control does speed Spend the periodic motion that size is in square-wave variations;The first half cycle of the outlet end periodic motion for spitting liquid pipette tips and later half period Interior, the velocity magnitude of the outlet end for spitting liquid pipette tips is identical, contrary;First liquid is any mutual not phase with second liquid Two kinds of molten liquid or two kinds of liquid with interfacial reaction.
A kind of microlayer model generation method, described in any item using the above scheme to spit liquid pipette tips, described spit in liquid pipette tips is stored up There is the first liquid, the microlayer model container for storing second liquid is provided;The first liquid is controlled from the outlet for spitting liquid pipette tips End is at the uniform velocity discharged;Extending direction of the outlet end of liquid pipette tips inside second liquid along needle stalk is spat described in control to be displaced In the periodic motion of sinusoidal variations;First liquid and second liquid are two kinds of arbitrarily immiscible liquid or have interfacial reaction Two kinds of liquid.
Above-mentioned to spit liquid pipette tips, when spitting extending direction vibration of the liquid pipette tips along pipe main body, microlayer model is from spitting liquid pipette tips Outlet end falls to fall behind in second liquid viscous force and spits the fortune under the squeezing action of the outlet end end face of liquid pipette tips far from outlet end Dynamic rail mark avoids microlayer model and is broken by outlet end, maintains the integrality for having generated microlayer model, while allowing to spit liquid pipette tips edge The extending direction fast vibration of pipe main body is to quickly generate microlayer model.
Detailed description of the invention
Fig. 1 is the overall structure diagram of digital pcr detector provided by the invention;
Fig. 2 is the microlayer model generating means of digital pcr detector provided by the invention;
Fig. 3 is the stress diagram of drop when exporting end motion for spitting liquid pipette tips that one embodiment of the invention provides;
Fig. 4 be the drop that provides of one embodiment of the invention with the outlet end motion for spitting liquid pipette tips when ideally viscous resistance Power changes schematic diagram;
Fig. 5 is to generate a microlayer model two periods of motion of the outlet end for spitting liquid pipette tips that one embodiment of the invention provides Process schematic;
Fig. 6 is to generate a microlayer model one period of motion of the outlet end for spitting liquid pipette tips that one embodiment of the invention provides Process schematic;
Fig. 7 is to generate two microlayer models one period of motion of the outlet end for spitting liquid pipette tips that one embodiment of the invention provides Process schematic;
Fig. 8 is the generating process schematic diagram for spitting microlayer model when liquid pipette tips are swung that one embodiment of the invention provides;
The generating process schematic diagram of microlayer model when Fig. 9 is the viscosity change for the second liquid that one embodiment of the invention provides;
Figure 10 is the generating process schematic diagram of microlayer model when liquid pipette tips are spat in the replacement that one embodiment of the invention provides;
Figure 11 is the outlet end for spitting liquid pipette tips that provides of one embodiment of the invention microlayer model under different motion profiles Generating process schematic diagram;
Figure 12 be another embodiment of the present invention provides the outlet end velocity variations schematic diagram for spitting liquid pipette tips;
Figure 13 is the outlet end structure schematic diagram for spitting liquid pipette tips that one embodiment of the invention provides;
Figure 14 be another embodiment of the present invention provides the outlet end structure schematic diagram for spitting liquid pipette tips;
Figure 15 spits liquid pipette tips structural schematic diagram for what one embodiment of the invention provided;
Figure 16 be another embodiment of the present invention provides spit liquid pipette tips structural schematic diagram;
Figure 17 is the process schematic that the chamfered structure that one embodiment of the invention provides spits that liquid pipette tips generate microlayer model;
Figure 18 be another embodiment of the present invention provides chamfered structure spit liquid pipette tips generate microlayer model process schematic;
Figure 19 is the process schematic that the bending structure that one embodiment of the invention provides spits that liquid pipette tips generate microlayer model;
Figure 20 be another embodiment of the present invention provides bending structure spit liquid pipette tips generate microlayer model process schematic.
Wherein:
1- digital pcr detector;10- microlayer model generating means;20- temperature control device;30- fluorescence signal detection device;40- Quantitative analysis device;50- controller;110- spits liquid pipette tips;111- arrival end;The outlet end 112-;113- needle stalk;114- pintle; 115- reservoir;116- card slot;195- drop;199- microlayer model;120- fluid driving mechanism 130- motion control mechanism;170- First controller;60- microlayer model container;699- second liquid;F1- buoyancy;F2- viscosity resistance;F3- maximum adhesion power;G- weight Power.
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.
It should be noted that it can directly on the other element when element is referred to as " being fixed on " another element Or there may also be elements placed in the middle.When an element is considered as " connection " another element, it, which can be, is directly connected to To another element or it may be simultaneously present centering elements.On the contrary, when element is referred to as " directly existing " another element "upper", There is no intermediary elements.Term as used herein "vertical", "horizontal", "left" and "right" and similar statement are For illustrative purposes.Various difference objects are in the ratio drafting convenient for enumerating explanation in embodiment attached drawing, rather than press practical group The ratio of part is drawn.
Referring to Figure 1, the present invention provides a kind of digital pcr detector 1, and the digital pcr detector 1 includes: microlayer model Generating means 10, temperature control device 20, fluorescence signal detection device 30, quantitative analysis device 40 and controller 50.Micro- liquid Generating means 10 are dripped to form multiple microlayer models for nucleic acid amplification reaction liquid droplet.The temperature control device 20 with it is described micro- Drop formation device 10 is connected by track, the multiple microlayer model is transferred to the temperature control device 20, carries out temperature Circulation realizes nucleic acid amplification.The fluorescence signal detection device 30 is oppositely arranged with the temperature control device 20, to expand nucleic acid The multiple microlayer model after increasing carries out detection of taking pictures.The quantitative analysis device 40 and the fluorescence signal detection device 30 are logical Data line connection is crossed, to realize the transmission of the multiple microlayer model fluorescence information, carries out quantitative analysis.The controller 50 divides Not with the microlayer model generating means 10, the temperature control device 20, fluorescence signal detection device 30 and quantitative analysis device 40 Connection, to control the microlayer model generating means 10, the temperature control device 20, fluorescence signal detection device 30 and quantitative point Analysis apparatus 40.
The digital pcr detector 1 can be by the microlayer model generating means 10, the temperature control device 20, the fluorescence Signal supervisory instrument 30 and the quantitative analysis device 40 are integrated, so that automation behaviour may be implemented in operator Make.The digital pcr detector 1 working efficiency with higher.
At work, the microlayer model generating means 10 can expand the determined nucleic acid digital pcr detector 1 Reaction solution carries out droplet, to form multiple microlayer models.The temperature control device 20 can carry out core to the multiple microlayer model Acid amplification.The fluorescence signal detection device 30 claps the change in fluorescence picture for surveying the multiple microlayer model in real time.By described more The change in fluorescence picture of a microlayer model, the change in fluorescence curve of available the multiple microlayer model.According to the change in fluorescence Curve, the Ct value of available the multiple microlayer model, and by the relationship of Ct value and starting copy number to the concentration of initial DNA Carry out quantitative analysis.Wherein, Ct value refers to recurring number experienced when the fluorescence signal of each microlayer model reaches the threshold value of setting.
The temperature control device 20 carries out nucleic acid amplification reaction to the multiple microlayer model, and is detected by the fluorescence signal Device 30 acquires the product signal of the multiple microlayer model after nucleic acid amplification reaction, such as fluorescence, UV absorption, turbidity letter Number.Difference using the multiple amplification with non-amplification microlayer model in composition, to the amount of droplets for obtaining target sequence amplification It is analyzed, the final quantitative analysis realized to nucleic acid molecules.Pass through the change in fluorescence figure of the multiple microlayer model of real-time monitoring The problem of piece, testing result has substantivity, can solve the false positive and false negative in the multiple microlayer model.
The digital pcr detector 1 is by the microlayer model generating means 10, the temperature control device 20, the fluorescence signal Detection device 30 and the quantitative analysis device 40 are integrated, so that automatic operation may be implemented in the operator, no Into improving work efficiency, also have the advantages that rapid reaction, reproducible, high sensitivity, high specificity and result are clear.
Clinical medicine is examined at present, nano material preparation, the application fields such as food and environment measuring, biochemical analysis are all to micro- Quantity of fluid precise manipulation has widespread demand.The core technology of submicroliter fluid handling first is that the liquid microlitre magnitude is further It is divided into nanoliter the drop of even picoliters volume, as micro- reaction system.The major technique branch that micro- reaction system generates It is that emulsification microlayer model generates.
Fig. 2 is referred to, in one embodiment, the microlayer model generating means 10 include spitting liquid pipette tips 110, fluid driving Mechanism 120, motion control mechanism 130 and the first controller 170.The liquid pipette tips 110 of spitting have outlet end and arrival end, and For storing the first liquid.Microlayer model generating means 10 can be used cooperatively with microlayer model container.It is stored up in the microlayer model container There is second liquid, the outlet end for spitting liquid pipette tips 110 is inserted under the liquid level of the second liquid.
Between first liquid and the second liquid it is immiscible or have interfacial reaction.First liquid and the second liquid Body can be any immiscible two kinds of liquid, and in one embodiment of the invention, first liquid is aqueous solution, described Second liquid be and the immiscible oil-based liquid of water, such as mineral oil (including n-tetradecane), vegetable oil, silicone oil and perfluoro alkane Oil etc., the drop of generation are aqueous solution droplets.Alternatively, first liquid be mineral oil, such as the tetradecane and n-hexane it is organic Phase, the second liquid are and the immiscible perfluorine oil of mineral oil.First liquid and second liquid can be not mutual Molten aqueous two-phase, in another embodiment of the present invention, first liquid be aqueous solution, the second liquid be with water not The waterborne liquid to dissolve each other, such as the first liquid are dextran solution, and second liquid is polyethylene glycol (PEG) aqueous solution, generation Drop is dextran solution drop.
First liquid and second liquid may be two kinds of liquid with interfacial reaction, in a reality of the invention It applies in example, first liquid is Na-alginate aqueous solution, and the second liquid is calcium oxide aqueous solution, as mass concentration is 1% calcium oxide aqueous solution, the two are calcium alginate gel bead there are interfacial reaction, the drop of generation.The application can be with Liquid pipette tips are spat by replacement or spit the component for flowing out the first liquid in liquid pipette tips, and multiple and different groups are sequentially formed in open containers Divide the drop with volume, both can be used to implement large batch of micro-volume high flux screening, the ultra micro of multi-step also may be implemented Biochemical reaction and detection are measured, is had broad application prospects.
The fluid driving mechanism 120 is connect with the arrival end for spitting liquid pipette tips 110, described spits liquid for that will be stored in First liquid inside pipette tips 110 is discharged from the outlet end for spitting liquid pipette tips 110.The motion control mechanism 130 is used Spit described in the control generated between the outlet end of liquid pipette tips 110 and the second liquid setting track or setting speed or setting plus The relative motion of speed, so that the first liquid of the outlet end for spitting liquid pipette tips 110 described in discharge overcomes surface tension and described spits Liquid pipette tips 110 form microlayer model to its adhesive force.First controller 170 respectively with the fluid driving mechanism 120 with And the motion control mechanism 130 connects, to control the fluid driving mechanism 120 and the motion control mechanism 130 Co-ordination.
In an embodiment of the present invention, under the drive of motion control mechanism 130, the outlet end 112 for spitting liquid pipette tips 110 exists The movement that velocity magnitude is in mechanical periodicity is done under second liquid liquid level, first half cycle and later half period in velocity magnitude variation Interior, the velocity magnitude for spitting the outlet end 112 of liquid pipette tips 110 is monotonically changed.Monotone variation refers to, in the first half of velocity magnitude variation In period or later half period, the velocity amplitude at the rear moment of the outlet end 112 of liquid pipette tips 110 is spat always greater than being equal to or less than Equal to the velocity amplitude at the preceding moment.For example, spitting the outlet end 112 of liquid pipette tips 110 in the first half cycle of velocity magnitude variation Velocity magnitude continues to increase or segment section continues to increase and segment section is constant.Correspondingly, in the later half period of velocity magnitude variation Interior, the velocity magnitude for spitting the outlet end 112 of liquid pipette tips 110 persistently reduces or segment section persistently reduces and segment section is constant.First Liquid forms the drop 195 for being attached to the outlet end 112 for spitting liquid pipette tips 110 after being discharged from the outlet end 112 for spitting liquid pipette tips 110. Drop 195 is detached from the outlet end for spitting liquid pipette tips 110 when 112 movement velocity of outlet end for spitting liquid pipette tips 110 reaches a certain size 112 form microlayer model 199.As shown in figure 3, microlayer model 199 before being detached from the outlet end 112 for spitting liquid pipette tips 110 suffered by Active force be respectively gravity G, second liquid 699 buoyancy f1, second liquid 699 viscosity resistance f2And spit liquid pipette tips 110 Outlet end 112 and drop 195 between maximum adhesion power f3.Microlayer model 199 spits the outlet end 112 of liquid pipette tips 110 being detached from Quality before is m, speed v, acceleration a2.Drop 195 is in the motion process of second liquid 699 by viscous force f2, again Power G, buoyancy f1And adhesive force f3Collective effect, i.e.,Liquid pipette tips are spat in the disengaging of drop 195 The condition of 110 outlet end 112 (generate a microlayer model 199) is
Spit the maximum value f of adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 1953With the table for spitting liquid pipette tips 110 Face free energy, drop 195 surface tension and spit liquid pipette tips 110 geometric dimension it is related.Liquid pipette tips 110 are spat by being attached to The drop 195 of outlet end 112 is reduced to spherical.By Stokes (Stokes) formula it is found that drop 195 is in second liquid 699 Suffered viscosity resistance f when middle movement2=6 π η rv, wherein η is the coefficient of viscosity of second liquid 699, and r is the half of drop 195 Diameter, v are the movement velocity of drop 195.During microlayer model 199 generates, the diameter range of general drop 195 picoliters extremely Microlitre the order of magnitude, and the coefficient of viscosity of second liquid 699 is generally bigger.Therefore generally haveAndTherefore, during spitting the outlet ends 112 of liquid pipette tips 110 and do speed change periodic motion under 699 liquid level of second liquid, Drop 195, which is detached from, to be spat the condition of the outlet end 112 (generate a microlayer model 199) of liquid pipette tips 110 and is approximately
Based on this, the present invention provides a kind of microlayer model generation method, comprising the following steps:
S211 is provided and is spat liquid pipette tips 110 with outlet end 112, spits and store the first liquid in liquid pipette tips 110;It provides The microlayer model container 60 of second liquid 699 is stored, microlayer model container 60 has opening;First liquid is with second liquid 699 Any two kinds of immiscible liquid or two kinds of liquid with interfacial reaction;
S212, the outlet end 112 for spitting liquid pipette tips 110 are inserted into the liquid level of second liquid 699 by the opening of microlayer model container 60 Under;
Velocity magnitude is done in mechanical periodicity in S213, the outlet end 112 for spitting liquid pipette tips 110 under 699 liquid level of second liquid Movement, in the first half cycle and later half period of velocity magnitude variation, the velocity magnitude for spitting the outlet end 112 of liquid pipette tips 110 is equal It is monotonically changed, while the first liquid is at the uniform velocity discharged by the outlet end 112 for spitting liquid pipette tips 110, the outlet end of liquid pipette tips 110 is spat in discharge 112 the first liquid forms the drop 195 for being attached to the outlet end 112 for spitting liquid pipette tips 110, and drop 195 is spitting liquid pipette tips 110 The outlet end 112 that liquid pipette tips 110 are spat in disengaging in the motion process of outlet end 112 forms microlayer model under 699 liquid level of second liquid 199。
Above-mentioned microlayer model generation method, spitting the outlet ends 112 of liquid pipette tips 110, to do speed under 699 liquid level of second liquid big The small movement in mechanical periodicity spits the outlet end of liquid pipette tips 110 in the first half cycle and later half period of velocity magnitude variation 112 velocity magnitude is monotonically changed.In motion process, viscous force f of the second liquid 699 to drop 1952With spitting liquid pipette tips The mechanical periodicity of 110 112 velocity magnitude of outlet end also shows mechanical periodicity.When the outlet end 112 and liquid for spitting liquid pipette tips 110 Maximum adhesion power f between drop 1953Less than second liquid 699 to the viscous force f of drop 1952When, drop 195 cannot with spit liquid The outlet end 112 of pipette tips 110 moves synchronously, and then the drop 195 for being attached to the outlet end 112 for spitting liquid pipette tips 110 is detached from The outlet end 112 for spitting liquid pipette tips 110 forms microlayer model 199 under 699 liquid level of second liquid.Micro- liquid provided by the present invention Generation method is dripped, speed change periodic motion is done under the liquid level of second liquid 699 to produce in the outlet end 112 for spitting liquid pipette tips 110 Raw microlayer model 199 is reduced when the outlet end 112 for spitting liquid pipette tips 110 moves to disturbance caused by second liquid 699, is protected The stability of 199 generating process of microlayer model is demonstrate,proved.
In the present embodiment, in step S213, the first liquid is continuously discharged by the outlet end 112 for spitting liquid pipette tips 110.Into One step, in step S213, the first liquid is discharged by spitting the outlet end 112 of liquid pipette tips 110 with constant flow velocity, is implied that equal Time interval in, be discharged spit liquid pipette tips 110 outlet end 112 the first liquid volume it is always equal.First liquid is by spitting The outlet end 112 of liquid pipette tips 110 is discharged with constant flow velocity, is conducive to the week by controlling the outlet end 112 for spitting liquid pipette tips 110 The movement of phase property, which is realized, generates volume microlayer model 199 of the same size.
Influence viscosity resistance f suffered when drop 195 moves in second liquid 6992Factor in, drop 195 Movement velocity v is easier to control.Before disengaging spits the outlet end 112 of liquid pipette tips 110 and forms microlayer model 199, drop 195 It keeps moving synchronously with the outlet end 112 for spitting liquid pipette tips 110.Therefore, the movement velocity v of drop 195 can spit liquid by control The movement velocity of the outlet end 112 of pipette tips 110 realizes accurate control.It controls the first liquid and liquid pipette tips is spat with the discharge of uniform flow velocity 110 outlet end 112, the size r of 195 radius of drop be spaced at a fixed time in also show periodic variation.It influences The viscosity resistance f suffered when being moved in second liquid 699 of drop 1952Factor in, the coefficient of viscosity η of second liquid 699 It can change in a certain range in use, but the variation range very little of the coefficient of viscosity η of second liquid 699.
Be changed without spit liquid pipette tips 110 and the first liquid in the case where, spit the surface free energy of liquid pipette tips 110, spit liquid rifle First 110 geometric dimension and the surface tension of drop 195 are spat between the outlet end 112 of liquid pipette tips 110 and drop 195 as influence Maximum adhesion power f3Two factors be determining.Therefore, be changed without spit liquid pipette tips 110 and the first liquid in the case where, spit The maximum value f of adhesive force between the outlet end 112 and drop 195 of liquid pipette tips 1103It is fixed.When spitting liquid pipette tips using multiple 110 simultaneously or sequentially generate microlayer model 199 when, spit the surface free energy of liquid pipette tips 110 and spit the geometric dimension of liquid pipette tips 110 Maximum adhesion power f between the outlet end 112 of liquid pipette tips 110 and drop 195 is spat as influence3Two factors be variation.But Batch machining can control the surface free energy for spitting liquid pipette tips 110 and spit the geometric dimension of liquid pipette tips 110 in certain section Variation.The surface tension of drop 195 spits maximum adhesion power f between the outlet end 112 of liquid pipette tips 110 and drop 195 as influence3 Another factor also only change to a very small extent.It spits and adheres between the outlet end 112 of liquid pipette tips 110 and drop 195 The maximum value f of power3Only fluctuated in the section of very little.
Therefore, viscosity resistance f suffered when drop 195 moves in second liquid 699 need to only be controlled2Greater than spitting liquid rifle The maximum value f of adhesive force between first 110 outlet end 112 and drop 1953Interval value.Due to being generated in same batch During microlayer model 199, the size r of 195 radius of drop should be fixed.Once experiment parameter determines, 195 radius of drop Size r is also just determined therewith.It is variation that the outlet ends 112 of liquid pipette tips 110, which is spat, in the subsurface movement velocity of second liquid 699 's.When the outlet end 112 for spitting liquid pipette tips 110 meets v > f in the subsurface movement velocity of second liquid 6993When/6 π η r, drop 195 form microlayer model 199 from the disengaging of outlet end 112 for spitting liquid pipette tips 110.
The movement of velocity magnitude mechanical periodicity is done under 699 liquid level of second liquid in the outlet end 112 for spitting liquid pipette tips 110.Control It makes the first liquid to be discharged with uniform flow velocity from the outlet end 112 for spitting liquid pipette tips 110, is attached to the outlet end for spitting liquid pipette tips 110 112 195 volume of drop is also uniformly to increase.First microlayer model 199 is fallen from the outlet end 112 for spitting liquid pipette tips 110 When, the radius of microlayer model 199 is known as critical radius, and the speed of microlayer model 199 becomes critical speed.Liquid pipette tips 110 are spat in adjustment The flow velocity of the outlet end 112 of liquid pipette tips 110 is spat in the period of motion of outlet end 112 and the discharge of the first liquid, so that by identical After time interval (multiple for spitting 112 period of motion of outlet end of liquid pipette tips 110), it is attached to the outlet end 112 for spitting liquid pipette tips 110 Drop 195 reach critical radius and critical speed simultaneously, the new formation of microlayer model 199.Since the first liquid is with uniform The outlet end 112 for spitting liquid pipette tips 110 is discharged in flow velocity, and the volume size of microlayer model 199 generated is identical.
As a kind of achievable form, in step S213, in a velocity magnitude period of change, liquid pipette tips are spat The velocity magnitude of 110 outlet end 112 is centrosymmetric using intermediate time point as midpoint.Further, in step S213, liquid is spat The outlet end 112 of pipette tips 110 is in cyclically-varying in the subsurface acceleration of second liquid 699, speed and motion profile.More Further, in step S213, the outlet ends 112 of liquid pipette tips 110 is spat in the subsurface velocity magnitude of second liquid 699 in cosine Curvilinear motion.
Optionally, in step S213, the outlet end 112 of liquid pipette tips 110 is spat in the subsurface movement rail of second liquid 699 Mark includes one of a variety of tracks such as straightway, arc section, polygon or a variety of combinations.In step S213, liquid rifle is spat The frequency of first 110 outlet end 112 periodic motion under 699 liquid level of second liquid between 0.1 hertz and 200 hertz, It is easy to accomplish in engineering.
Track is done under 699 liquid level of second liquid and is become as circular arc, speed in cosine in outlet end 112 to spit liquid pipette tips 110 For the periodic motion of change, pendulum motion is actually done in the outlet end 112 for spitting liquid pipette tips 110 at this time, and moving displacement can be with just Chord curve indicates, as shown in curve a in Fig. 4.Under the driving of flow control mechanism, the first liquid is with uniform flow velocity from spitting liquid The outlet end 112 of pipette tips 110 is discharged.Assuming that drop 195 does not depart from the outlet end 112 for spitting liquid pipette tips 110.By calculating, drop 195 viscosity resistance f suffered when being moved in second liquid 699It is viscousIt changes over time as shown in curve b in Fig. 4.First liquid With the initial stage that uniform flow velocity is discharged from the outlet end 112 for spitting liquid pipette tips 110, with the increase of 195 volume of drop, drop 195 radius r is also significantly increased.With the continuous increase of 195 radius r of drop, the at the uniform velocity increase of 195 volume of drop can only cause The slow increase of 195 radius r of drop.Therefore, it spits in preceding several swing periods of the outlet end 112 of liquid pipette tips 110, drop 195 Suffered viscosity resistance f when being moved in second liquid 6992Maximum value increase sharply, then gradually tend to be slowly increased. As shown in figure 4, the viscosity resistance f that drop 195 is suffered when moving in second liquid 6992Also show and spit liquid pipette tips 110 Outlet end 112 the similar periodicity of periodic motion, i.e., it is suffered viscous when drop 195 moves in second liquid 699 Resistance f2Change with the velocity variations for the outlet end 112 for spitting liquid pipette tips 110.In actual condition, when drop 195 is in the second liquid Suffered viscosity resistance f when being moved in body 6992Increase and be greater than and spits between the outlet end 112 of liquid pipette tips 110 and drop 195 The maximum value f of adhesive force3When, drop 195 falls off to form microlayer model 199 from the outlet end 112 for spitting liquid pipette tips 110.
In an embodiment of the present invention, as shown in figure 5, control spit liquid pipette tips 110 outlet end 112 do track be circular arc, Displacement is in the swing of sinusoidal variations.Be changed without spit liquid pipette tips 110 and the first liquid in the case where, spit the outlet of liquid pipette tips 110 The maximum value f of adhesive force between end 112 and drop 1953It is fixed.With being attached to the outlet end for spitting liquid pipette tips 110 112 195 radius r of drop constantly increases, the viscosity resistance f suffered when moving in second liquid 699 of drop 1952Also constantly increase Greatly.The viscosity resistance f suffered when being moved in second liquid 699 of drop 1952Greater than spit the outlet ends 112 of liquid pipette tips 110 with The maximum value f of adhesive force between drop 1953Moment, drop 195 falls off to form micro- liquid from the outlet end 112 for spitting liquid pipette tips 110 Dripping is drop I in 199, Fig. 5.Into in the generation circulation of next round microlayer model 199.
In the present embodiment, the maximum value f of adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 195 is spat3=1.8 ×10-4N, the hunting frequency for spitting the outlet end 112 of liquid pipette tips 110 is 50 hertz.Position is done in the outlet end 112 for spitting liquid pipette tips 110 It moves and generates first microlayer model 199 in the second period end of the pendulum motion of sinusoidal variations, be drop I in Fig. 5.It is generating The initial stage of second microlayer model 199, although the movement velocity for spitting the outlet end 112 of liquid pipette tips 110 is reduced, due to It is attached to and spits the 195 radius r of drop of the outlet end 112 of liquid pipette tips 110 and increase very fast, drop 195 moves in second liquid 699 When suffered viscosity resistance f2There is no decline to show small-scale increase instead at once.Hereafter, 195 radius r of drop is slow It is slow to increase, the viscosity resistance f suffered when being moved in second liquid 699 of drop 1952Depending mainly on the outlet for spitting liquid pipette tips 110 The movement velocity at end 112 changes and changes.
When the first liquid of control spits the outlet end 112 of liquid pipette tips 110 with even velocity of flow discharge, going out for liquid pipette tips 110 is spat Mouth end 112 generates and the equal bodies of a upper microlayer model 199 again at the time of generating two periods of motion after a upper microlayer model 199 Long-pending new drop 195 is drop II in Fig. 5.And spit at this time liquid pipette tips 110 outlet end 112 movement velocity also with two It is identical before the period of motion.Isometric new drop 195 is from the outlet end 112 for spitting liquid pipette tips 110 with a upper microlayer model 199 It falls off.It is common in the pendulum motion of sinusoidal variations that displacement is done in the outlet end 112 for being at the uniform velocity discharged and spitting liquid pipette tips 110 of first liquid It ensure that the volume size homogeneity for generating microlayer model 199.
In an embodiment of the present invention, as shown in fig. 6, control spit liquid pipette tips 110 outlet end 112 do track be circular arc, Displacement is in the swing of sinusoidal variations.Be changed without spit liquid pipette tips 110 and the first liquid in the case where, spit the outlet of liquid pipette tips 110 The maximum value f of adhesive force between end 112 and drop 1953It is fixed.With being attached to the outlet end for spitting liquid pipette tips 110 112 195 radius r of drop constantly increases, the viscosity resistance f suffered when moving in second liquid 699 of drop 1952Also constantly increase Greatly.The viscosity resistance f suffered when being moved in second liquid 699 of drop 1952Greater than spit the outlet ends 112 of liquid pipette tips 110 with The maximum value f of adhesive force between drop 1953Moment, drop 195 falls off to form micro- liquid from the outlet end 112 for spitting liquid pipette tips 110 Drop 199.Into in the generation circulation of next round microlayer model 199.
In the present embodiment, the maximum value f of adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 195 is spat3=1.5 ×10-4N, the hunting frequency for spitting the outlet end 112 of liquid pipette tips 110 is 50 hertz.Position is done in the outlet end 112 for spitting liquid pipette tips 110 It moves and generates first microlayer model 199 in a cycle end of the pendulum motion of sinusoidal variations, be drop I in Fig. 6.It is generating The initial stage of second microlayer model 199, although the movement velocity for spitting the outlet end 112 of liquid pipette tips 110 is reduced, due to It is attached to and spits the 195 radius r of drop of the outlet end 112 of liquid pipette tips 110 and increase very fast, drop 195 moves in second liquid 699 When suffered viscosity resistance f2There is no decline to show small-scale increase instead at once.Hereafter, 195 radius r of drop is slow It is slow to increase, the viscosity resistance f suffered when being moved in second liquid 699 of drop 1952Depending mainly on the outlet for spitting liquid pipette tips 110 The movement velocity at end 112 changes and changes.
When the first liquid of control spits the outlet end 112 of liquid pipette tips 110 with even velocity of flow discharge, going out for liquid pipette tips 110 is spat Mouth end 112 generates and the equal bodies of a upper microlayer model 199 again at the time of generating a period of motion after a upper microlayer model 199 Long-pending new drop 195, and spit at this time liquid pipette tips 110 outlet end 112 movement velocity also with phase before a period of motion Together.Isometric new drop 195 falls off from the outlet end 112 for spitting liquid pipette tips 110 with a upper microlayer model 199, is liquid in Fig. 6 Drip II.So circulation generates drop III, drop IV etc..The outlet end 112 for being at the uniform velocity discharged and spitting liquid pipette tips 110 of first liquid Do the volume size homogeneity that the pendulum motion common guarantee that displacement is in sinusoidal variations generates microlayer model 199.
In an embodiment of the present invention, as shown in Figures 7 and 8, it does track and is in the outlet end 112 that liquid pipette tips 110 are spat in control Circular arc, displacement are in the swing of sinusoidal variations.Be changed without spit liquid pipette tips 110 and the first liquid in the case where, spit liquid pipette tips 110 The maximum value f of adhesive force between outlet end 112 and drop 1953It is fixed.With being attached to the outlet end for spitting liquid pipette tips 110 112 195 radius r of drop constantly increases, the viscosity resistance f suffered when moving in second liquid 699 of drop 1952Also not It is disconnected to increase.The viscosity resistance f suffered when being moved in second liquid 699 of drop 1952Greater than the outlet end for spitting liquid pipette tips 110 The maximum value f of adhesive force between 112 and drop 1953Moment, drop 195 falls off shape from the outlet end 112 for spitting liquid pipette tips 110 It is drop I in Fig. 7 at microlayer model 199.Into in the generation circulation of next round microlayer model 199.
In the present embodiment, the maximum value f of adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 195 is spat3=1.0 ×10-4N, the hunting frequency for spitting the outlet end 112 of liquid pipette tips 110 is 50 hertz.Position is done in the outlet end 112 for spitting liquid pipette tips 110 The boost phase for moving the first half cycle of the pendulum motion in sinusoidal variations generates first microlayer model 199, is drop I in Fig. 7.? The initial stage for generating second microlayer model 199, when the movement velocity for the outlet end 112 for spitting liquid pipette tips 110 is reduced, but by Increase comparatively fast in the 195 radius r of drop for being attached to the outlet end 112 for spitting liquid pipette tips 110, drop 195 is transported in second liquid 699 Suffered viscosity resistance f when dynamic2There is no decline to show small-scale increase instead at once.Hereafter, 195 radius r of drop It is slowly increased, the viscosity resistance f suffered when being moved in second liquid 699 of drop 1952Depending mainly on spit liquid pipette tips 110 go out The movement velocity at mouth end 112 changes and changes.
Control the outlet end 112 that the first liquid spits liquid pipette tips 110 with even velocity of flow discharge.Spit the outlet end of liquid pipette tips 110 112 generate second microlayer model 199 in the later half period boost phase for doing pendulum motion of the displacement in sinusoidal variations, are in Fig. 7 Drop II.Then into the stage for stably generating microlayer model 199.The outlet end 112 for spitting liquid pipette tips 110 generates second microlayer model The new drop 195 isometric with second microlayer model 199 is generated at the time of half of period of motion after 199 again, and is spat at this time The movement velocity of the outlet end 112 of liquid pipette tips 110 is also identical as before half of period of motion.With the equal bodies of second microlayer model 199 Long-pending new drop 195 falls off from the outlet end 112 for spitting liquid pipette tips 110, so recycles, generate drop III shown in fig. 7, Drop IV, drop V etc..Do the pendulum that displacement is in sinusoidal variations in the outlet end 112 for being at the uniform velocity discharged and spitting liquid pipette tips 110 of first liquid The dynamic volume size homogeneity for moving common guarantee and generating microlayer model 199.
It is detached from it can be seen from the above, being attached to and spitting the drop 195 of the outlet end 112 of liquid pipette tips 110 and spits the outlets of liquid pipette tips 110 The condition at end 112 (generating a microlayer model 199) is approximately:It is spat controlling the first liquid with even velocity of flow discharge In the case where the outlet end 112 of liquid pipette tips 110, the uniform condition of volume of microlayer model 199 generated is: microlayer model 199 constant durations fall off from the outlet end 112 for spitting liquid pipette tips 110.
The maximum value f of adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 195 is spat in influence3Factor include: to spit The surface tension of the surface free energies of liquid pipette tips 110, geometric dimension and the first liquid.Liquid pipette tips 110 and first are spat being changed without In the case where liquid, the maximum value f of adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 195 is spat3It is fixed.It influences The viscosity resistance f suffered when being moved in second liquid 699 of drop 1952Factor include: second liquid 699 viscous system Number η, the radius r of drop 195 and the movement velocity v of drop 195.The outlet end 112 for spitting liquid pipette tips 110 is at the uniform velocity discharged in first liquid When, the radius r of drop 195 is determined by the interval time that microlayer model 199 generates.Drop 195 spits the outlet of liquid pipette tips 110 being detached from It is moved synchronously before end 112 with the outlet end 112 for spitting liquid pipette tips 110, can realize that accurate control is spat by motion control mechanism 130 The movement velocity of the outlet end 112 of liquid pipette tips 110.Coefficient of viscosity η meeting in the generating process of drop 195 of second liquid 699 Change in a certain range, but the variation range very little of the coefficient of viscosity η of second liquid 699.As shown in figure 9, curve a expression is spat The change in displacement of the outlet end 112 of liquid pipette tips 110, curve b and curve c are when the coefficient of viscosity η of second liquid 699 is in very little The generating process curve of microlayer model 199 when changing in range.When the coefficient of viscosity η of second liquid 699 becomes to a very small extent It, only can be at the generation moment of very a small range change microlayer model 199 when change.Between the generation time without changing microlayer model 199 Every.As shown in figure 9, the generation time interval of microlayer model 199 represented by curve b and curve c is half period t/2, guarantee The volume size homogeneity of generated microlayer model 199.
As shown in Figure 10, when liquid pipette tips 110 are spat in replacement or temperature change etc. causes the surface tension of the first liquid to occur When variation, the maximum value f of adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 195 is spat3It is difficult to control accurately, therefore such as 199 volume of microlayer model that fruit generates is to f3Change in a certain range it is insensitive, then to generate single-size microlayer model 199 It is of great significance.In Figure 10, curve a indicates to spit the change in displacement of the outlet end 112 of liquid pipette tips 110, and curve b and curve c are The generating process curve of microlayer model 199 in the case that liquid pipette tips 110 are spat in replacement.After liquid pipette tips 110 are spat in replacement, liquid pipette tips are spat The maximum value f of adhesive force between 110 outlet end 112 and drop 1953Fluctuation will lead to drop 195 and fall off in a certain range When spit the corresponding different speed in outlet end 112 of liquid pipette tips 110.But after the generation of microlayer model 199 reaches stable state, liquid The speed for the outlet end 112 that drop 195 spits liquid pipette tips 110 when falling off is fixed in each swing period, as shown in Figure 10, The generation time interval of microlayer model 199 represented by curve b and curve c is half period t/2.Therefore it can guarantee microlayer model 199 interval times generated were fixed.It is raw when the flow velocity that the outlet end 112 of liquid pipette tips 110 is spat in the discharge of the first liquid is fixed At the volume of microlayer model 199 be uniform.The flow velocity that the outlet end 112 of liquid pipette tips 110 is spat in the discharge of the first liquid is adjusted simultaneously And hunting frequency of the outlet end 112 of liquid pipette tips 110 in second liquid 699 is spat, uniform volume microlayer model can be controlled simultaneously 199 volume size and generating rate.
Spat in above-described embodiment liquid pipette tips 110 outlet end 112 do displacement be in sinusoidal variations periodic motion when, to attachment The maximum value f of power3And viscosity resistance f2Variation have certain tolerance, i.e. the maximum value f of adhesive force3Or viscosity resistance f2 When changing in a certain range, it still is able to generate the uniform microlayer model 199 of volume.When the outlet end for spitting liquid pipette tips 110 112 do displacement be in sinusoidal variations periodic motion when, guarantee generate the uniform microlayer model 199 of volume under the premise of, can The maximum value f of the adhesive force of tolerance3Variation range be known as plateau.The presence of plateau is for spitting the processing of liquid pipette tips 110 And the control that microlayer model 199 generates temperature has great importance.The presence of plateau, which allows to reduce to a certain extent, spits liquid The requirement on machining accuracy of pipette tips 110, even if being had differences between batch surface free energy of processing spat between liquid pipette tips 110, Also the uniform microlayer model 199 of volume can be generated.Similarly, the presence of plateau also allows to reduce micro- liquid to a certain extent Drip the temperature control requirement of 199 generating process.
The presence of plateau allows to reduce the requirement on machining accuracy for spitting liquid pipette tips 110 or microlayer model 199 to a certain extent The temperature control requirement of generating process further reduced consumables cost and control cost in 199 generating process of microlayer model.On It states and generates two microlayer models 199 in each period of motion for spitting the outlet end 112 of liquid pipette tips 110 in embodiment, it is readily appreciated that It is that only the periodic motion that displacement is in sinusoidal variations is done in the outlet end 112 of disgusting liquid pipette tips 110, when the outlet end for spitting liquid pipette tips 110 It is generated in 112 each period of motion and generates a microlayer model 199 in a microlayer model 199 or the every two period of motion When, still to the maximum value f of adhesive force3And viscosity resistance f2Variation have certain tolerance, also all there is plateau.
Since the generation of microlayer model 199 is hardly influenced by the gravity and inertia force of microlayer model 199.Therefore micro- liquid is generated When dripping 199, the outlet end 112 for spitting liquid pipette tips 110 can do the week that displacement is in sinusoidal variations in second liquid 699 along any direction Phase movement.The motion profile for spitting the outlet end 112 of liquid pipette tips 110 is the track of camber line, straight line or other shapes.
As shown in (1) in Figure 11, in an embodiment of the present invention, the inclination insertion second liquid 699 of liquid pipette tips 110 is spat Interior, the outlet end 112 for spitting liquid pipette tips 110 generates microlayer model 199 in 699 liquid level lower swing of second liquid.It can be achieved as one kind Mode, as shown in (2) in Figure 11, it is horizontal straight that track is done in the outlet end 112 for spitting liquid pipette tips 110 in second liquid 699 Line, displacement are in the periodic motion of sinusoidal variations to generate microlayer model 199.As another achievable mode, in Figure 11 (3) shown in, it is vertical straight line, displacement in sinusoidal variations that track is done in second liquid 699 in the outlet end 112 for spitting liquid pipette tips 110 Periodic motion is to generate microlayer model 199.
As shown in figure 12, in an alternative embodiment of the invention, in step S213, a cycle of velocity magnitude variation Interior, spitting the outlet ends 112 of liquid pipette tips 110 in first half cycle and later half period is uniform variable motion.Further, in step S213 In, the outlet end 112 for spitting liquid pipette tips 110 is equal with the acceleration magnitude in later half period in first half cycle.Control the first liquid with The outlet end 112 for spitting liquid pipette tips 110 is discharged in even velocity of flow.With the continuous discharge of the first liquid, it is attached to and spits liquid pipette tips 110 The viscosity resistance f that the drop 195 of outlet end 112 is subject to during the motion2Also constantly increase.As viscosity resistance f2Greater than drop 195 and spit the maximum value f of adhesive force between liquid pipette tips 1103When, drop 195 forms microlayer model 199 from the disengaging of liquid pipette tips 110 is spat. In the generating process for subsequently entering next microlayer model 199.The motion frequency and fortune of the outlet end 112 of liquid pipette tips 110 are spat in control Dynamic speed is adapted with the flow velocity of the first liquid, to guarantee to generate the volume homogeneity of microlayer model 199.
One embodiment of the invention provides and a kind of spits liquid pipette tips 110 for generate microlayer model 199 comprising has hollow The needle stalk 113 of cavity and the outlet end 112 for being set to 113 one end of needle stalk.Spit the normal of 112 end face of outlet end of liquid pipette tips 110 Angle between the extending direction of needle stalk 113 is less than or equal to 90 °.It shakes spitting extending direction of the liquid pipette tips 110 along pipe main body When dynamic, microlayer model 199 falls to fall behind in 699 viscous force of second liquid from the outlet end 112 for spitting liquid pipette tips 110 and spits liquid pipette tips 110 112 end face of outlet end squeezing action under far from outlet end 112 motion profile, avoid microlayer model 199 by outlet end 112 Break, maintain the integrality for having generated microlayer model 199, while it is fast along the extending direction of pipe main body to allow to spit liquid pipette tips 110 Speed vibration is to quickly generate microlayer model 199.
As shown in figure 13, as a kind of achievable mode, liquid pipette tips 110 is spat in straight tube-like, spit the outlet of liquid pipette tips 110 End 112 is chamfered structure.The outlet end 112 for spitting liquid pipette tips 110 is chamfer, the integrality of generated microlayer model 199 is taken into account And microlayer model 199 formation efficiency while, have that structure is simple, be easily achieved, manufacturing cost is low, batch machining is with high accuracy Feature.Further, spit 112 end face of outlet end of liquid pipette tips 110 normal and needle stalk 113 extending direction between angle between Between 15 ° -75 °, the extension for spitting the normal and needle stalk 113 of 112 end face of outlet end of liquid pipette tips 110 can be designed according to actual condition Angle between direction.Spit the angle between the normal of 112 end face of outlet end of liquid pipette tips 110 and the extending direction of needle stalk 113 It should not be too large or too small, in order to avoid influence the generation of microlayer model 199 or break microlayer model 199.Further, liquid pipette tips 110 are spat 112 end face of outlet end normal and needle stalk 113 extending direction between angle between 30 ° -60 °.Specifically, spitting liquid Angle between the extending direction of normal and the needle stalk 113 of 112 end face of outlet end of pipette tips 110 is 45 °.45° angle can not only Guarantee being successfully generated for microlayer model 199, additionally it is possible to which generated 199 detachment of microlayer model is effectively opened to the movement of outlet end 112 Track avoids the outlet end for spitting liquid pipette tips 110 112 from breaking generated microlayer model 199.
As shown in figure 14, as another achievable mode, needle stalk 113 is close to the outlet end 112 for spitting liquid pipette tips 110 Part includes bending structure.The outlet end 112 for spitting liquid pipette tips 110 is bent, the integrality of generated microlayer model 199 is taken into account And microlayer model 199 formation efficiency while, have that structure is simple, be easily achieved, manufacturing cost is low, batch machining is with high accuracy Feature.Further, spit 112 end face of outlet end of liquid pipette tips 110 normal and needle stalk 113 extending direction between angle between Between 15 ° -75 °, the extension for spitting the normal and needle stalk 113 of 112 end face of outlet end of liquid pipette tips 110 can be designed according to actual condition Angle between direction.Spit the angle between the normal of 112 end face of outlet end of liquid pipette tips 110 and the extending direction of needle stalk 113 It should not be too large or too small, in order to avoid influence the generation of microlayer model 199 or break microlayer model 199.Further, liquid pipette tips 110 are spat 112 end face of outlet end normal and needle stalk 113 extending direction between angle between 30 ° -60 °.Specifically, spitting liquid Angle between the extending direction of normal and the needle stalk 113 of 112 end face of outlet end of pipette tips 110 is 45 °.45° angle can not only Guarantee being successfully generated for microlayer model 199, additionally it is possible to which generated 199 detachment of microlayer model is effectively opened to the movement of outlet end 112 Track avoids the outlet end for spitting liquid pipette tips 110 112 from breaking generated microlayer model 199.
Optionally, needle stalk 113 close to spit liquid pipette tips 110 outlet ends 112 bending structure have broken line, arc section, One of smooth curve section, straightway etc. or combination.As shown in figure 14, in the present embodiment.Needle stalk 113 is close to spit liquid rifle The part of first 110 outlet end 112 has transition circle segmental arc, the specifically combination of arc section and straightway.In process It is easy to process by the circular arc bending of straight tube-like spat liquid pipette tips 110 and carry out set angle.
As shown in Figure 15 and Figure 16, the liquid pipette tips 110 of spitting that one embodiment of the invention provides further include pintle 114, pintle 114 Reservoir 115 with the extending direction perforation pintle 114 along pintle 114.One end of reservoir 115 and needle stalk 113 is far from spitting One end of the outlet end 112 of liquid pipette tips 110 is connected to, and the one end of pintle 114 far from needle stalk 113 is the arrival end for spitting liquid pipette tips 110 111.It is fixedly connected between pintle 114 and needle stalk 113.The first liquid for generating microlayer model 199 can be stored in needle in advance In bolt 114, continuous, batch generation microlayer model 199 can be realized.Further, table in the one end of pintle 114 far from needle stalk 113 Face offers card slot 116.Card slot 116 can be realized to be detachably connected with fluid driving mechanism 120.Convenient for spitting liquid pipette tips 110 Replacement.
Also a kind of 199 generating means of microlayer model of the present invention, for generating microlayer model 199 under 699 liquid level of second liquid.It is micro- 199 generating means of drop include fluid driving mechanism 120, motion control mechanism 130 and above scheme is described in any item spits liquid Pipette tips 110.The internal reservoir for spitting liquid pipette tips 110 has the first liquid, spits liquid pipette tips 110 with outlet end 112 and arrival end 111. Fluid driving mechanism 120 is connect with the arrival end 111 for spitting liquid pipette tips 110, for that will be stored in spit inside liquid pipette tips 110 first Liquid is discharged from the outlet end 112 for spitting liquid pipette tips 110.Motion control mechanism 130 is for controlling the outlet end for spitting liquid pipette tips 110 112 generate setting track or setting speed under the liquid level of second liquid 699 or set the movement of acceleration, so that liquid is spat in discharge First liquid of the outlet end 112 of pipette tips 110 overcomes surface tension and adhesive force to form microlayer model 199 in second liquid 699.
It is provided by the invention to spit generation microlayer model 199 during liquid pipette tips 110 move under 699 liquid level of second liquid. As a kind of achievable mode, velocity magnitude is done in side in the outlet end 112 for spitting liquid pipette tips 110 under 699 liquid level of second liquid The movement of wave variation, acceleration magnitude a1.First liquid is formed after being discharged from the outlet end 112 for spitting liquid pipette tips 110 and is attached to Spit the drop 195 of the outlet end 112 of liquid pipette tips 110.The moment that drop 195 instantaneously accelerates in the outlet end 112 for spitting liquid pipette tips 110 It is detached from the formation of outlet end 112 microlayer model 199 for spitting liquid pipette tips 110.As shown in figure 3, microlayer model 199 spits liquid pipette tips 110 in disengaging Outlet end 112 before suffered active force be respectively gravity G, second liquid 699 buoyancy f1, second liquid 699 Viscosity resistance f2And spit maximum adhesion power f between the outlet end 112 of liquid pipette tips 110 and drop 1953.Microlayer model 199 is de- It is m from the quality before the outlet end 112 for spitting liquid pipette tips 110, acceleration magnitude a2.According to Newton interpolation algorithm, easily It obtains
Spit the maximum value f of adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 1953With the table for spitting liquid pipette tips 110 Face free energy, drop 195 surface tension and spit liquid pipette tips 110 geometric dimension it is related.Spit the outlet end of liquid pipette tips 110 112 when doing instantaneous accelerated motion, spits the outlet end 112 of liquid pipette tips 110 to the direction of 195 adhesive force of drop and the direction of acceleration It is identical.The drop 195 for being attached to the outlet end 112 for spitting liquid pipette tips 110 is reduced to spherical.By Stokes (Stokes) formula It is found that the viscosity resistance f that drop 195 is suffered when moving in second liquid 6992=6 π η rv, wherein η is second liquid 699 The coefficient of viscosity, r be drop 195 radius, v be drop 195 movement velocity.Wink is done in the outlet end 112 for spitting liquid pipette tips 110 When accelerate before the speed of drop 195 be zero, therefore moment that drop 195 instantaneously accelerates in the outlet end 112 for spitting liquid pipette tips 110 The viscosity resistance f being subject in second liquid 6992It is zero or minimum.During microlayer model 199 generates, general drop 195 Diameter range picoliters to microlitre the order of magnitude, and the buoyancy f of the gravity G of drop 195 and second liquid 6991It is contrary, Therefore the buoyancy f of the gravity G of drop 195 and second liquid 6991Vector sum be about zero.ExistBy Newton interpolation algorithm it is found that instantaneous acceleration is done in the outlet end 112 for spitting liquid pipette tips 110 When movement, the attainable peak acceleration in second liquid 699 of drop 195 is a2≈f3/ m, wherein m is the matter of drop 195 Amount.The condition that the outlet end 112 (generating a microlayer model 199) of liquid pipette tips 110 is spat in the disengaging of drop 195 is approximately: a2≈(f3/ M) < a1
Spit the maximum value f of adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 1953With the table for spitting liquid pipette tips 110 Face free energy, drop 195 surface tension and spit liquid pipette tips 110 geometric dimension it is related.Spit the outlet end of liquid pipette tips 110 112 when doing instantaneous accelerated motion, spits the outlet end 112 of liquid pipette tips 110 to the direction of 195 adhesive force of drop and the direction of acceleration It is identical.The drop 195 for being attached to the outlet end 112 for spitting liquid pipette tips 110 is reduced to spherical.By Stokes (Stokes) formula It is found that the viscosity resistance f that drop 195 is suffered when moving in second liquid 6992=6 π η rv, wherein η is second liquid 699 The coefficient of viscosity, r be drop 195 radius, v be drop 195 movement velocity.Wink is done in the outlet end 112 for spitting liquid pipette tips 110 When accelerate before the speed of drop 195 be zero, therefore moment that drop 195 instantaneously accelerates in the outlet end 112 for spitting liquid pipette tips 110 The viscosity resistance f being subject in second liquid 6992It is zero or minimum.During microlayer model 199 generates, general drop 195 Diameter range picoliters to microlitre the order of magnitude, and the buoyancy f of the gravity G of drop 195 and second liquid 6991It is contrary, Therefore the buoyancy f of the gravity G of drop 195 and second liquid 6991Vector sum be about zero.ExistBy Newton interpolation algorithm it is found that instantaneous acceleration is done in the outlet end 112 for spitting liquid pipette tips 110 When movement, the attainable peak acceleration in second liquid 699 of drop 195 is a2≈f3/ m, wherein m is the matter of drop 195 Amount.The condition that the outlet end 112 (generating a microlayer model 199) of liquid pipette tips 110 is spat in the disengaging of drop 195 is approximately: a2≈(f3/ M) < a1
Under the drive of motion control mechanism 130, the instantaneously acceleration of outlet end 112 for spitting liquid pipette tips 110 can be accurately controlled The size of degree.As long as the value for controlling each instantaneous acceleration in outlet end 112 for spitting liquid pipette tips 110 is larger, liquid pipette tips 110 are spat Instantaneous accelerate is done in outlet end 112 can effectively generate drop 195.Optionally, in the outlet end 112 for spitting liquid pipette tips 110 A period of motion in, form one or two or multiple microlayer models 199.
As shown in figure 17, in an embodiment of the present invention, the normal and pipeline of 112 end face of outlet end of liquid pipette tips 110 are spat Angle between the extending direction of main body is 45 °, spits the outlet end 112 of liquid pipette tips 110 in chamfered structure.Second liquid 699 Liquid level upward, is spat liquid pipette tips 110 and is arranged vertically.Track is done under 699 liquid level of second liquid in the outlet end 112 for spitting liquid pipette tips 110 It is in the movement of square-wave variations for vertical line segment, velocity magnitude.Within a period of motion of the outlet end 112 for spitting liquid pipette tips 110 Generate a microlayer model 199.It spits and stores the first liquid in liquid pipette tips 110.Liquid pipette tips 110 are spat in the control of fluid driving mechanism 120 The first isometric liquid is discharged from outlet end 112 within each period of motion for spitting liquid pipette tips 110.Liquid pipette tips are spat when being attached to When the drop 195 of 110 outlet end 112 reaches setting volume size, the outlet end 112 of liquid pipette tips 110 is spat by upper limit position It is a with size1Acceleration instantaneously accelerate downwards, while be attached to spit the outlet end 112 of liquid pipette tips 110 drop 195 be detached from The outlet end 112 for spitting liquid pipette tips 110 forms microlayer model 199.In 699 viscous force of second liquid and spit the outlet ends of liquid pipette tips 110 Under the squeezing action of 112 end faces, motion profile of the microlayer model 199 far from outlet end 112 and close to spitting the side walls of liquid pipette tips 110. The outlet end 112 for spitting liquid pipette tips 110 continues to move downward, and the outlet for spitting liquid pipette tips 110 is still discharged in the first liquid at the same time End 112 forms the drop 195 for being attached to the outlet end 112 for spitting liquid pipette tips 110.When the outlet end 112 for spitting liquid pipette tips 110 moves to When lower limit position, the outlet end 112 for spitting liquid pipette tips 110 is moved upwards by lower limit position.In the outlet end for spitting liquid pipette tips 110 112 moved upwards by lower limit position during the first liquid the outlet end 112 for spitting liquid pipette tips 110 is still discharged, be attached to 195 volume of drop for spitting the outlet end 112 of liquid pipette tips 110 increases.When the outlet end 112 for spitting liquid pipette tips 110 moves to limes superiors When position, it is attached to the 195 volume size of drop for spitting the outlet end 112 of liquid pipette tips 110 and the last microlayer model 199 to fall off Volume is equal in magnitude.Spit the outlet ends 112 of liquid pipette tips 110 again by upper limit position with size for a1Acceleration it is instantaneous downwards Acceleration forms new microlayer model 199, so recycles.
As shown in figure 18, in an embodiment of the present invention, the normal and pipeline of 112 end face of outlet end of liquid pipette tips 110 are spat Angle between the extending direction of main body is 45 °, spits the outlet end 112 of liquid pipette tips 110 in chamfered structure.Second liquid 699 Liquid level upward, is spat liquid pipette tips 110 and is arranged vertically.Track is done under 699 liquid level of second liquid in the outlet end 112 for spitting liquid pipette tips 110 It is in the movement of square-wave variations for vertical line segment, velocity magnitude.Within a period of motion of the outlet end 112 for spitting liquid pipette tips 110 Generate two microlayer models 199.It spits and stores the first liquid in liquid pipette tips 110.Fluid driving mechanism 120 controls the first liquid with equal Uniform flow speed is discharged from outlet end 112.When the drop 195 for being attached to the outlet end 112 for spitting liquid pipette tips 110 reaches setting volume size When, spit the outlet ends 112 of liquid pipette tips 110 by upper limit position with size for a1Acceleration instantaneously accelerate downwards, adhere to simultaneously Drop 195 in the outlet end 112 for spitting liquid pipette tips 110 is detached from the formation of outlet end 112 microlayer model 199 for spitting liquid pipette tips 110.? It two liquid, 699 viscous force and spits under the squeezing action of 112 end face of outlet end of liquid pipette tips 110, microlayer model 199 is far from outlet end 112 motion profile and close to spitting the side walls of liquid pipette tips 110.Continue to move downward in the outlet end 112 for spitting liquid pipette tips 110.With this Simultaneously the first liquid still be discharged spit liquid pipette tips 110 outlet end 112 formation be attached to the outlet end 112 for spitting liquid pipette tips 110 Drop 195 is attached to 195 volume of the drop increase for spitting the outlet end 112 of liquid pipette tips 110.
When the outlet end 112 for spitting liquid pipette tips 110 moves to lower limit position, it is attached to the outlet end for spitting liquid pipette tips 110 112 195 volume size of drop and the volume for the microlayer model 199 that the last time falls off are equal in magnitude.Spit the outlet end of liquid pipette tips 110 112 by lower limit position be a with size1Acceleration instantaneously accelerate upwards, the drop 195 for being attached to outlet end 112 detaches Mouth end 112 forms new microlayer model 199.The outlet end 112 for spitting liquid pipette tips 110 is in the microlayer model generated when lower limit position 199 only move upwards a small distance under the action of the adhesive force of outlet end 112, just start in second liquid 699 gradually Landing.The first liquid, which is still discharged, during the outlet end 112 for spitting liquid pipette tips 110 is moved upwards by lower limit position spits liquid The outlet end 112 of pipette tips 110 is attached to 195 volume of the drop increase for spitting the outlet end 112 of liquid pipette tips 110.When spitting liquid pipette tips When 110 outlet end 112 moves to upper limit position, be attached to spit the outlet end 112 of liquid pipette tips 110 195 volume of drop it is big It is small equal in magnitude with the volume of the last microlayer model 199 to fall off.The outlet end 112 of liquid pipette tips 110 is spat again by limes superiors position It sets with size as a1Acceleration downwards instantaneously accelerate form new microlayer model 199, so recycle.When spit liquid pipette tips 110 go out When mouth end 112 is moved downward by upper limit position again, if still having micro- liquid in the footprint immediately below outlet end 112 Drop 199 then hits generated microlayer model 199 by the drop 195 for being attached to outlet end 112, and generated microlayer model 199 is along out The normal movement of mouth 112 end face of end is with the motion profile far from outlet end 112.
It is provided by the invention to spit generation microlayer model 199 during liquid pipette tips 110 move under 699 liquid level of second liquid. As another achievable mode, the outlet end 112 for spitting liquid pipette tips 110 does above-mentioned displacement under 699 liquid level of second liquid and is in The movement of sinusoidal variations.
As shown in figure 19, in an embodiment of the present invention, the normal and pipeline of 112 end face of outlet end of liquid pipette tips 110 are spat Angle between the extending direction of main body is 45 °, and needle stalk 113 is bending knot close to the part for the outlet end 112 for spitting liquid pipette tips 110 Structure.The liquid level of second liquid 699 upward, is spat liquid pipette tips 110 and is arranged vertically.The outlet end 112 of liquid pipette tips 110 is spat in second liquid Done under 699 liquid levels track be vertical line segment, displacement be in sinusoidal variations movement.At one of the outlet end 112 for spitting liquid pipette tips 110 A microlayer model 199 is generated in the period of motion.It spits and stores the first liquid in liquid pipette tips 110.The control of fluid driving mechanism 120 is spat The first isometric liquid is discharged in liquid pipette tips 110 within each period of motion for spitting liquid pipette tips 110 from outlet end 112.Spitting liquid It does displacement and generates first microlayer model in the acceleration decline stage of the linear motion of sinusoidal variations in the outlet end 112 of pipette tips 110 199.The initial stage of second microlayer model 199 is being generated, there are downward deceleration ranks although spitting the outlet ends 112 of liquid pipette tips 110 Section, but spit the 195 radius r of drop of the outlet end 112 of liquid pipette tips 110 due to being attached to and increase very fast, drop 195 is in second liquid Suffered viscosity resistance f when being moved in 6992There is no decline to show small-scale increase instead at once.Hereafter, drop 195 radius r are slowly increased, the viscosity resistance f suffered when moving in second liquid 699 of drop 1952Depending mainly on spitting liquid pipette tips The movement velocity of 110 outlet end 112 changes and changes.Spit liquid pipette tips 110 outlet end 112 drop to extreme position after start Rise, at the same time, is attached to and spits the volume of the drop 195 of outlet end 112 of liquid pipette tips 110 and constantly increase.
When the first liquid of control spits the outlet end 112 of liquid pipette tips 110 with even velocity of flow discharge, going out for liquid pipette tips 110 is spat Mouth end 112 generates and the equal bodies of a upper microlayer model 199 again at the time of generating a period of motion after a upper microlayer model 199 Long-pending new drop 195, and spit at this time liquid pipette tips 110 outlet end 112 movement velocity also with phase before a period of motion Together.Isometric new drop 195 falls off from the outlet end 112 for spitting liquid pipette tips 110 with a upper microlayer model 199, so recycles. Do the pendulum motion common guarantee that displacement is in sinusoidal variations in the outlet end 112 for being at the uniform velocity discharged and spitting liquid pipette tips 110 of first liquid Generate the volume size homogeneity of microlayer model 199.When the outlet end 112 for spitting liquid pipette tips 110 is downward by upper limit position again When movement, if microlayer model 199 is still had in the footprint immediately below outlet end 112, by being attached to outlet end 112 Drop 195 hits generated microlayer model 199, generated microlayer model 199 along 112 end face of outlet end normal movement with separate The motion profile of outlet end 112.
As shown in figure 20, in an embodiment of the present invention, the normal and pipeline of 112 end face of outlet end of liquid pipette tips 110 are spat Angle between the extending direction of main body is 45 °, and needle stalk 113 is bending knot close to the part for the outlet end 112 for spitting liquid pipette tips 110 Structure.The liquid level of second liquid 699 upward, is spat liquid pipette tips 110 and is arranged vertically.The outlet end 112 of liquid pipette tips 110 is spat in second liquid Done under 699 liquid levels track be vertical line segment, displacement be in sinusoidal variations movement.At one of the outlet end 112 for spitting liquid pipette tips 110 Two microlayer models 199 are generated in the period of motion.It spits and stores the first liquid in liquid pipette tips 110.The control of fluid driving mechanism 120 the One liquid is discharged with even velocity of flow from outlet end 112.With 195 radius of drop for being attached to the outlet end for spitting liquid pipette tips 110 112 R constantly increases, the viscosity resistance f suffered when moving in second liquid 699 of drop 1952Also constantly increase.When spitting liquid pipette tips When 110 outlet end 112 is in downward boost phase, the viscosity resistance suffered when being moved in second liquid 699 of drop 195 f2Greater than the maximum value f for spitting adhesive force between the outlet end 112 of liquid pipette tips 110 and drop 1953, drop 195 is from spitting liquid pipette tips 110 Outlet end 112 fall off to form microlayer model 199.In 699 viscous force of second liquid and spit 112 end faces of outlet end of liquid pipette tips 110 Squeezing action under, motion profile of the microlayer model 199 far from outlet end 112 and close to spitting the side walls of liquid pipette tips 110.
The outlet end 112 for spitting liquid pipette tips 110 continues to move downward, and the outlet end 112 for spitting liquid pipette tips 110 drops to limit position It postpones and begins to ramp up.The first liquid, which is still discharged, at the same time spits the outlet ends 112 of liquid pipette tips 110 and is formed and be attached to and spit liquid pipette tips The drop 195 of 110 outlet end 112 is attached to 195 volume of the drop increase for spitting the outlet end 112 of liquid pipette tips 110.It is generating The initial stage of second microlayer model 199, when the movement velocity for the outlet end 112 for spitting liquid pipette tips 110 is reduced, but due to attached 195 radius r of drop in the outlet end 112 for spitting liquid pipette tips 110 increase it is very fast, when drop 195 moves in second liquid 699 Suffered viscosity resistance f2There is no decline to show small-scale increase instead at once.Hereafter, 195 radius r of drop is slow Increase, the viscosity resistance f suffered when being moved in second liquid 699 of drop 1952Depending mainly on the outlet end for spitting liquid pipette tips 110 112 movement velocity changes and changes.
After the time interval of half period, the outlet end 112 for spitting liquid pipette tips 110 is in upward boost phase.It is attached to and spits The 195 volume size of drop of the outlet end 112 of liquid pipette tips 110 and the volume for the microlayer model 199 that the last time falls off are equal in magnitude, together When spit liquid pipette tips 110 outlet end 112 velocity magnitude it is also identical as before half period, be attached to the drop 195 of outlet end 112 It is detached from outlet end 112 and forms new microlayer model 199.The outlet end 112 of spitting liquid pipette tips 110 is in be generated when upward boost phase Microlayer model 199 only moves upwards a small distance under the action of the adhesive force of outlet end 112, just starts in second liquid 699 In gradually land.The first liquid, which is still discharged, at the same time spits the outlet ends 112 of liquid pipette tips 110 and is formed and be attached to and spit liquid pipette tips The drop 195 of 110 outlet end 112 is attached to 195 volume of the drop increase for spitting the outlet end 112 of liquid pipette tips 110.Half week After the time interval of phase, the outlet end 112 for spitting liquid pipette tips 110 is in downward boost phase.It is attached to the outlet for spitting liquid pipette tips 110 The 195 volume size of drop at end 112 and the volume for the microlayer model 199 that the last time falls off are equal in magnitude, while spitting liquid pipette tips 110 The velocity magnitude of outlet end 112 is also identical as before half period, and the drop 195 for being attached to outlet end 112 is detached from 112 shape of outlet end The microlayer model 199 of Cheng Xin so recycles.Control the outlet end 112 that the first liquid spits liquid pipette tips 110 with even velocity of flow discharge.It spits The outlet end 112 of liquid pipette tips 110 do track be vertical line segment, displacement in sinusoidal variations movement later half period boost phase After generating second microlayer model 199, into the stage for stably generating microlayer model 199.The at the uniform velocity discharge of first liquid and spit liquid rifle The volume size that the pendulum motion common guarantee that displacement is in sinusoidal variations generation microlayer model 199 is done in first 110 outlet end 112 is equal One property.When the outlet end 112 for spitting liquid pipette tips 110 is moved downward by upper limit position again, if immediately below outlet end 112 Microlayer model 199 is still had in footprint, then generated microlayer model is hit by the drop 195 for being attached to outlet end 112 199, generated microlayer model 199 along 112 end face of outlet end normal movement with far from outlet end 112 motion profile.
Microlayer model generating means and generation method provided by the invention are in clinical medicine inspection, nano material preparation, food And the application fields such as environment measuring, biochemical analysis are all widely used.It is provided by the invention in a specific application environment The generating means and generation method of microlayer model 199 apply polymerase chain reaction (Polymerase Chain Reaction, PCR in).
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to above-mentioned reality It applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited In contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously Limitations on the scope of the patent of the present invention therefore cannot be interpreted as.It should be pointed out that for those of ordinary skill in the art For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to guarantor of the invention Protect range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.

Claims (12)

1. one kind spits liquid pipette tips, for generating microlayer model, which is characterized in that including the needle stalk with hollow cavity and be set to institute State the outlet end that needle obstructs one end;Folder between the normal of the outlet end end face for spitting liquid pipette tips and the extending direction of needle stalk Angle is less than or equal to 90 °.
2. according to claim 1 spit liquid pipette tips, which is characterized in that the liquid pipette tips of spitting are described to spit liquid rifle in straight tube-like The outlet end of head is chamfered structure.
3. according to claim 1 spit liquid pipette tips, which is characterized in that the needle stalk is close to the outlet end for spitting liquid pipette tips Part include bending structure.
4. according to claim 3 spit liquid pipette tips, which is characterized in that the needle stalk is close to the outlet end for spitting liquid pipette tips Bending structure have transition circle segmental arc.
5. according to claim 1-4 spit liquid pipette tips, which is characterized in that further include pintle, the pintle has The reservoir of the pintle is penetrated through along the extending direction of the pintle;It is spat with needle stalk far from described one end of the reservoir One end of the outlet end of liquid pipette tips is connected to, and the pintle is the arrival end for spitting liquid pipette tips far from one end that the needle obstructs.
6. according to claim 5 spit liquid pipette tips, which is characterized in that one end inner surface that the pintle obstructs far from the needle Offer card slot.
7. according to claim 1-4 spit liquid pipette tips, which is characterized in that the outlet end end face for spitting liquid pipette tips Normal and the needle stalk extending direction between angle between 15 ° -75 °.
8. according to claim 7 spit liquid pipette tips, which is characterized in that the normal of the outlet end end face for spitting liquid pipette tips with Angle between the extending direction of the needle stalk is between 30 ° -60 °.
9. according to claim 8 spit liquid pipette tips, which is characterized in that the normal of the outlet end end face for spitting liquid pipette tips with Angle between the extending direction of the needle stalk is 45 °.
10. a kind of microlayer model generating means, which is characterized in that including fluid driving mechanism, motion control mechanism and claim 1-9 is described in any item to spit liquid pipette tips;The internal reservoir for spitting liquid pipette tips has the first liquid, and the liquid pipette tips of spitting have outlet End and arrival end;The fluid driving mechanism is connect with the arrival end for spitting liquid pipette tips, described spits liquid rifle for that will be stored in The first liquid inside head is discharged from the outlet end for spitting liquid pipette tips;The motion control mechanism spits liquid rifle described in being used to control The outlet end of head generates setting track or setting speed under the liquid level of second liquid or sets the movement of acceleration, so that discharge First liquid of the outlet end for spitting liquid pipette tips overcomes surface tension and adhesive force to form microlayer model in second liquid.
11. a kind of microlayer model generation method, which is characterized in that liquid pipette tips are spat using claim 1-9 is described in any item, it is described It spits and stores the first liquid in liquid pipette tips, the microlayer model container for storing second liquid is provided;The first liquid is controlled to spit from described The outlet end of liquid pipette tips is at the uniform velocity discharged;Outlet end needle described in the liquid level lower edge of second liquid stalk of liquid pipette tips is spat described in control Extending direction does the periodic motion that velocity magnitude is in square-wave variations;The first half cycle of the outlet end periodic motion for spitting liquid pipette tips Within the later half period, the velocity magnitude of the outlet end for spitting liquid pipette tips is identical, contrary;First liquid is with second liquid Any two kinds of immiscible liquid or two kinds of liquid with interfacial reaction.
12. a kind of microlayer model generation method, which is characterized in that liquid pipette tips are spat using claim 1-9 is described in any item, it is described It spits and stores the first liquid in liquid pipette tips, the microlayer model container for storing second liquid is provided;The first liquid is controlled to spit from described The outlet end of liquid pipette tips is at the uniform velocity discharged;Prolonging inside second liquid along what the needle obstructed the outlet end that liquid pipette tips are spat described in control It stretches direction and does the periodic motion that displacement is in sinusoidal variations;First liquid and second liquid be any two kinds of immiscible liquid or Two kinds of liquid with interfacial reaction.
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