CN102458630B - Microfluidic apparatus and method for generating a dispersion - Google Patents
Microfluidic apparatus and method for generating a dispersion Download PDFInfo
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- CN102458630B CN102458630B CN201080030504.8A CN201080030504A CN102458630B CN 102458630 B CN102458630 B CN 102458630B CN 201080030504 A CN201080030504 A CN 201080030504A CN 102458630 B CN102458630 B CN 102458630B
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/40—Mixing liquids with liquids; Emulsifying
- B01F23/41—Emulsifying
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/30—Injector mixers
- B01F25/31—Injector mixers in conduits or tubes through which the main component flows
- B01F25/314—Injector mixers in conduits or tubes through which the main component flows wherein additional components are introduced at the circumference of the conduit
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/30—Injector mixers
- B01F25/31—Injector mixers in conduits or tubes through which the main component flows
- B01F25/314—Injector mixers in conduits or tubes through which the main component flows wherein additional components are introduced at the circumference of the conduit
- B01F25/3142—Injector mixers in conduits or tubes through which the main component flows wherein additional components are introduced at the circumference of the conduit the conduit having a plurality of openings in the axial direction or in the circumferential direction
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00783—Laminate assemblies, i.e. the reactor comprising a stack of plates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00851—Additional features
- B01J2219/00858—Aspects relating to the size of the reactor
- B01J2219/0086—Dimensions of the flow channels
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00889—Mixing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00993—Design aspects
- B01J2219/00995—Mathematical modeling
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
- B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
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- Physical Or Chemical Processes And Apparatus (AREA)
- Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
Abstract
Microcfluidic apparatus (1) and method for generating a dispersion. The apparatus comprises a droplet formation unit (3) comprising a feed opening (2) for supplying a to-be-dispersed phase first substance to the droplet formation unit, and an oblong droplet formation opening (14) for forming droplets of the to-be- dispersed phase first substance in a continuous phase second substance, the droplet formation opening having a first, smallest dimension W and a second, largest dimension L, wherein the second dimension L of the droplet formation opening is more than fifty times the first dimension W of the droplet formation opening. The droplet formation unit has a third dimension D in a direction from the feed opening to the droplet formation opening, wherein the third dimension D is more than two and a half times the first dimension W. The microfluidic apparatus further comprises a feed structure, in fluid communication with the feed opening for feeding the to-be-dispersed phase first substance to the droplet formation unit, wherein a flow resistance of the droplet formation unit is larger than a flow resistance of the feed structure.
Description
Technical field
The present invention relates to for generation of the system of disperseing.The invention still further relates to for generation of the micro-channel device disperseing, comprise charging aperture that decentralized photo the first material is provided for providing, have and the guiding channel of second degree of depth that continuous phase material product is provided and provides is provided and forms the interface channel that fluid is connected between charging aperture and guiding channel, wherein interface channel opening is in guiding channel.
Background technology
In scientific research and industry, the monodisperse emulsion with 0.1-100 μ m drop size is very important.But traditional emulsifying technology produces the wide droplets size distribution of the coefficient of variation (CV) with typical approximately 40%.And, when heating, consume and enter the most of energy in product.
Recently, developed several new energy-conservation drop formation system that produces more monodisperse emulsions.
The known system for generation of disperseing that can produce highly single dispersant liquid drop is used so-called list to drip a technology, flow focusing apparatus for example, and same streaming system, T-shaped, Y type or intersect links, and microchannel.In these single system, feeding-passage will be treated the material dispersed guiding channel that offers guiding continuous phase material.At feeding-passage opening to the position in guiding channel, one next form drop (continuously).
Some of these single system produce the drop in expected range.But, think that volume productive rate is too low, does not have true correlation for fairly large application.
In order to realize higher volumetric productivity, it is useful expanding these systems.At aforementioned list, drip in system, form continuously drop, need the quality of drop forming unit (DFU) parallel.In the scissors system such as flow focusing, cocurrent flow device and different type of bond, treat that decentralized photo stream and continuous phase stream need to be accurately controlled in each DFU, because flow velocity has great impact to drop size.Therefore, the scissors system expanding for generation of drop is complicated, because it not only relates in conjunction with more drop forming unit, also comprises current control in drop forming unit, and this is minor matter absolutely not.
The another kind of known system for generation of disperseing is called so-called microchannel (MC) system.In micro channel systems, rectangular shaped feed passage will treat that decentralized photo product offers the guiding channel of guiding continuous phase (product matrix (product matrix)).Drop in microchannel forms and is often called spontaneous drop formation.In this micro channel systems, only need control to treat flowing of decentralized photo.Flow velocity is not the parameter that is applicable to regulate drop generation continuously, because drop forms, is not caused by shearing force, but the capillary instable nozzle geometry on the drop just forming causes by initiation.Low flow velocity is still for carry drop from DFU because otherwise it will be blocked by drop.
It seems that micro channel systems be more suitable for expanding; Especially people such as (M.Microfluid Nanofluid 2008,4,167) I.Kobayashi be it seems and got a good chance of to Kobayashi and its colleague's straight-through micro-channel device.By Kobayashi, use the straight-through MC plate with different channel sizes, successfully produce the monodisperse emulsion with 4.4-9.8 μ m liquid-drop diameter, 5.5-2.7%CV.Unfortunately, for the plate with minimum microchannel, the channel efficiency that produces the percentage of passage as drop is less than 1%, and for the plate with larger microchannel, channel efficiency can only arrive 12.3%.This may be due to the barometric gradient in system, if Abrahamse people AICHEJ.2004 such as (, 50,1364) A.J.Gijsbertsen-Abrahamse is for utilizing the micro-mesh similar to the system of Kobayashi to carry out emulsification institute extensive discussions.In addition, foozle also may cause the low channel efficiency of mentioning as Kobayashi and its colleague.
Kobayashi has also introduced sub-micron channel array people Colloids & surfaces A 296 (2007), 285 such as () I.Kobayashi, produces the drop with 1.5 μ m with high channel efficiency.This system has baroque shortcoming, because need very little boss, it has the height of the width of 7.4-8.8 μ m, the length of 3.2-5.5 μ m and 0.32-1.4 μ m.These structures are difficult to make relatively, when especially the size of all boss in system needs basic identical (for narrow droplets size distribution).
Target of the present invention is to provide a kind of system and/or device for generation of dispersion that is more suitable for expanding (scale-up).
Summary of the invention
The inventor recognizes, can wherein exist many drops to form mechanism by providing firm system and/or device for generation of disperseing to realize above-mentioned target, spontaneously produces the drop of a plurality of narrow dispersions from same drop forming unit simultaneously.
In order to realize above-mentioned target, according to the invention provides for generation of the micro fluidic device disperseing, comprise drop forming unit (DFU), drop forming unit comprises that charging aperture and rectangle drop form mouth, charging aperture will be for treating that decentralized photo the first material offers drop forming unit, rectangle drop forms a mouthful drop that is used for treating in continuous phase the second material formation decentralized photo the first material, drop forms mouth and has for example the first minimum dimension of width W and the second full-size of for example length L, wherein drop forms the more than 50 times of first size W that the second size L of mouth is drop formation mouth, drop forming unit has for example the 3rd size of depth D the direction that forms mouth from charging aperture to drop, wherein the 3rd dimension D is the more than 2.5 times of first size W, wherein micro fluidic device also comprise with for treating that decentralized photo the first material sends into the feeding structure that the charging aperture fluid of drop forming unit is communicated with, wherein the flow resistance of drop forming unit is greater than the flow resistance of feeding structure.During use, treat that decentralized photo the first material offers the charging aperture of drop forming unit by feeding structure, while continuous phase the second material appears at or the drop of flowing through forms mouth.Drop forms the position for the treatment of the interface existence between decentralized photo and continuous phase when mouthful restriction is used.Drop forming unit forms mouth at drop and is in the drop that continuous phase the second material forms the first material.
Inventor recognizes, by providing, there is the drop forming unit that rectangle drop forms mouth, can make many drops form mechanism occurs simultaneously, from same drop forming unit, spontaneously produce the drop of a plurality of narrow dispersions simultaneously, wherein rectangle drop form mouth have be the first size that forms mouthful of this drop 50 times of second above full-sizes, have and be 2.5 times of the 3rd above sizes of first size and there is the flow resistance larger than the flow resistance of feeding structure.Herein, drop forming unit can have very simple geometry.This should be appreciated that to produce a plurality of drops be also feasible simultaneously by the drop forming unit of a plurality of for example microchannels is for example set abreast on single substrate, although will produce beguine according to the more complicated geometry of micro fluidic device of the present invention.
Also possibly the second size L that, drop forms mouthful be 80 times of the first size W that forms mouthful of drop above, preferably 100 times above, be more preferably 150 times above, be most preferably 200-500 doubly more than.Make so more drop form from same feeding-passage simultaneously.Should be appreciated that hypothesis drop forming unit keeps geometry stable, the second size L that drop forms mouth can be even the more than 10.000 times of first size W.
Preferably, drop forming unit has cross section, this cross section is transverse to being preferably perpendicular to flow directional detection that charging aperture from drop forming unit forms mouthful to drop, cross section has the parallel first size of the first size W that forms mouthful with drop second size parallel with the second size L forming mouthful with drop, cross section is met the following conditions: the 3rd size of drop forming unit here for the scope of the degree of depth in the second size of drop forming unit be at least 50 times of first size of drop forming unit, the 3rd size of drop forming unit forms mouth from drop and measures to charging aperture, be equal to or greater than 2.5 times of first size of drop forming unit.
Preferably, drop forming unit has cross section, this cross section is transverse to being preferably perpendicular to flow directional detection that charging aperture from drop forming unit forms mouthful to drop, make the first size of drop forming unit be equal to or greater than the first size that liquid forms mouth, and cross section meets the following conditions: the 3rd size of drop forming unit here for the scope of the degree of depth in the second size of drop forming unit be at least 50 times of first size of drop forming unit, the 3rd size of drop forming unit forms mouth from drop and measures to charging aperture, be equal to or greater than 2.5 times of first size of drop forming unit.The 3rd size that has been found that this minimum helps drop forming unit so that many drops form mechanism generation simultaneously, spontaneously produces the drop of a plurality of narrow dispersions simultaneously from same drop forming unit.Also have been found that if the 3rd size is too little, for example, approximate the first size that drop forms mouth, will stop many drops to form simultaneously.The 3rd size that has been found that this minimum helps drop forming unit so that many drops form mechanism generation simultaneously, spontaneously produces the drop of a plurality of narrow dispersions simultaneously from same drop forming unit.Also have been found that if the 3rd size is too little, for example, approximate the first size that drop forms mouth, will stop many drops to form simultaneously.
Drop forming unit can form chamber, and chamber has between charging aperture and drop form mouthful and forms the hollow inside that fluid is communicated with.Then chamber can have cross section and the degree of depth as described in last paragraph.
Drop forming unit can have substantially invariable cross section.Substantially invariable cross section can form corresponding to drop the size of mouth.Substantially invariable cross section can be general rectangular.
In specific implementations, drop forming unit has (substantially) constant rectangular cross section, and rectangular cross section has the first size W corresponding with the first size W of drop formation mouth and the second size L corresponding with the second size L of drop formation mouth.In this case, drop forming unit has the 3rd dimension D, and wherein cross section is that (substantially) is constant in whole the 3rd dimension D.For this drop forming unit, think that the second size of drop forming unit is the more than 50 times of first size W of drop forming unit, the 3rd dimension D of drop forming unit is the more than 2.5 times of first size W of drop forming unit.
In the situation that not wishing by any theoretical restriction, the inventor finds: when inventor finds to use, in micro fluidic device according to the present invention, the minimum phase mutual edge distance that drop forms is liquid-drop diameter 2-7 times.When inventor finds to use in addition in micro fluidic device according to the present invention, the diameter D of formed drop
dropbe approximately the 5-8 of first size doubly.(D
drop=5W to 8W).
In the situation that not wishing by any theoretical restriction, the second size forming mouthful when drop is approximately that the first size that forms mouthful of drop is when more than 50 times, while being L/W > 50, micro fluidic device can form a plurality of drops from same drop forming unit simultaneously.
Be to be understood that, if drop forming unit has the substantially invariable rectangular cross section corresponding with the size (L * W) of drop formation mouth, wherein drop forming unit has depth D in the flow direction that forms mouth from charging aperture to drop, and the volume of interface channel is L * W * D.The flow resistance R of drop forming unit
dFUcan be by RDFU=KD/ (W
3l) estimate, wherein K is the constant of geometric correlation, and K equals 12 (referring to Perry ' s 7 in this case
thedition, formula 6-36 and 6-51).Should be appreciated that and can manufacture relatively easily the drop forming unit with substantially invariable rectangular cross section.
If feeding structure is chosen as to the passage with substantially constant rectangular cross section, feeding structure can be restricted to have and form the width W in the parallel direction of mouthful width W with drop
fs, the length L in the parallel direction of the length L forming mouthful with drop
fs, and the depth D in the parallel direction of the depth D with drop forming unit
fs.The flow resistance R of feeding structure
fsby R
fs=KD
fs/ (W
fs 3l
fs) estimate.In a preferred embodiment, the width W of feeding structure
fssubstantially equal the width W that drop forms mouth 14.Should be appreciated that in these embodiments, if D
fs/ L
fs< D/L, the flow resistance R of drop forming unit
dFUbe greater than the flow resistance R of feeding structure
fs.This provides simple design guideline for the possible geometry for according to micro fluidic device of the present invention.
The flow resistance that should be appreciated that drop forming unit can also be made for the flow resistance that is greater than feeding structure simply, and the cross section of feeding structure (far) is greater than the cross section of drop forming unit.
Preferably, treat that the material dispersed feed rate of sending into interface channel by charging aperture forms the material dispersed minimizing for the treatment of that can not make interface channel when being selected as making a plurality of drop.Inventor has been found that according to the length of drop forming unit, can be formed several so that hundreds of drops by single each microsecond of drop forming unit according to the present invention.Preferably, treat that material dispersed feed rate is at least that each microsecond is by 100 times of the volume of the drop being formed.For example, for the drop with the first size W of 1.2 μ m, form mouth, feed rate is at least preferably 11 microliters per second, preferably at least 30 μ l/s.Should be appreciated that feed rate may be subject to treating the impact of flow resistance of feeding-passage of the charging aperture of the material dispersed DFU of delivering to.
Should be appreciated that and from same feeding-passage, form the drop productive rate that a plurality of drops increase each DFU significantly, therefore make to be applicable to expanding well the output of drop according to device of the present invention simultaneously.The latter is useful to for example producing a large amount of dispersions, as detailed below.In addition for device according to the present invention, the flow velocity of continuous phase product is not the regulation parameter producing for drop, because shearing force is inoperative and drop is unstability generation in the surface tension on the drop forming by being caused by the geometry forming by drop mouthful.
In embodiment, micro fluidic device also comprises that wherein drop forms mouthful opening in guide structure for the second material of continuous phase and the collection structure of the drop that collection forms are provided.
In embodiment, by thering is the boss formation droplet-shaped of the width corresponding with the first size of drop formation mouth, become unit.Therefore, the micro fluidic device with simple geometry structure be can form, wherein can feeding structure and collection structure be connected by boss.
Preferably, the first size that drop the forms mouthful for example width of boss is less more than 10 times than the degree of depth of the collection structure in the first size direction forming along drop mouthful, more preferably more than 50 times.Therefore the existence that, forms at drop the physical boundary that process that mouthful place forms droplet or bubble can directed passage is disturbed.
Preferably, the minimum first size that drop forms mouth is 0.05-25um, more preferably 0.1-2um.Inventor's discovery, device according to the present invention provides the drop of the diameter of 5-8 times with the first size that is about drop formation mouth.Therefore, the preferred size range that forms mouthful first size for drop provides the drop at expected range, and this expected range is for example 0.1-200 micron.
In one embodiment, preferably, feeding structure, collection structure and boss are coated with top (ceiling).
Can in substrate, process or use on for example substantially flat substrate interval to build micro fluidic device, this micro fluidic device is for example feeding structure, DFU (for example boss) and collection structure, and this processing is for example milling (milled), etching, formation route (routed), sandblast and/or injection molding.Preferably, etching in the semiconductor substrate of for example silicon substrate (for example, with essence photoetching process) feeding structure, DFU and collection structure, but other baseplate material is also possible, for example glass, metal (for example stainless steel) or condensate.Substrate can be coated with the top such as glass plate, for example, be bonded to substrate to seal each structure.Can also use first substrate as the top of second substrate.
Preferably, drop forming unit (for example boss) is forming in mouthful vertical direction and have depth D with drop, so that in use, treats material dispersedly substantially in whole the second size, to fill drop forming unit.The suitable degree of depth that should be appreciated that drop forming unit can depend on the surface tension for the treatment of between material dispersed and continuous phase material, and continuous phase material optionally comprises suitable emulsifying agent or stabilizing agent.It should also be understood that, the appropriate depth D of drop forming unit may depend on that drop forms the second size of mouth, for example, corresponding to the width W of drop forming unit or boss, and/or corresponding to the width W of the charging aperture in the parallel direction of the second size W forming mouthful with drop
f.
Should be appreciated that if the length L of charging aperture
fsubstantially be equal to or greater than the second size L that drop forms mouthful (length L of boss 8 for example
p), for example the depth D of the drop forming unit corresponding with the degree of depth of boss can be very short, for example the order of magnitude of several microns.On the other hand, if the length L of charging aperture
fmuch smaller than the second size L, the depth D of drop forming unit may need longlyer so, for example, substantially equal the second size L.
The invention still further relates to for generation of the system of disperseing, comprise a plurality of according to micro fluidic device of the present invention.
In embodiment, system comprises substrate, has a plurality of according to micro fluidic device of the present invention on substrate.Preferably, the feeding structure fluid of each device is communicated with.Preferably, the collection structure fluid of each device is communicated with.Preferably the drop forming unit of each device is arranged such that to treat material dispersed each drop forming unit flowing through side by side.Therefore, can obtain the system of the productive rate with increase.Should be appreciated that a plurality of these substrates can be connected and/or connect abreast.
Accompanying drawing explanation
By unrestriced embodiment, come with reference to the accompanying drawings that further the present invention will be described, wherein:
Fig. 1 illustrates the schematic diagram according to micro fluidic device of the present invention;
Fig. 2 illustrates the schematic diagram according to alternative micro fluidic device of the present invention;
Fig. 3 a-3e be illustrated in operating period in each stage according to the top view of micro fluidic device of the present invention;
Fig. 4 a and 4b illustrate according to the schematic diagram of the embodiment of system of the present invention;
Fig. 5 a illustrates the schematic diagram according to alternative micro fluidic device of the present invention;
Fig. 5 b illustrates the schematic diagram according to alternative micro fluidic device of the present invention;
Fig. 6 illustrates the distribution of sizes of the emulsion of utilizing exemplary microfluidic system generation, and the little picture of corner is the generation emulsion manifesting by microscope;
The typical shape at the interface during Fig. 7 a-7h is illustrated in drop and forms between oil phase and water; And
Fig. 8 illustrates the diagram that liquid-drop diameter changes with the variation that is applied to the pressure of feeding structure.
The specific embodiment
Fig. 1 illustrates according to the schematic diagram of micro fluidic device 1 of the present invention.In Fig. 1, device 1 comprises drop forming unit (DFU) 3.Drop forming unit 3 comprises charging aperture 2.Drop forming unit 3 also comprises that drop forms mouth 14.In Fig. 1, it is rectangular that drop forms mouthfuls 14, especially rectangle.Drop forms mouth 14 and has the first minimum dimension or width W.Drop forms mouth 14 and has the second full-size or length L.
In Fig. 1, drop forming unit 3 is designed to form the interface channel 6 that fluid is connected between charging aperture 2 and drop formation mouth 14.In this embodiment, interface channel 6 be designed to have the groove (slot) 8 of substantially constant cross section '.In this embodiment, the cross section of interface channel 6 is corresponding with size L and W that drop forms mouth 14.Therefore, in this embodiment, the width of drop forming unit 3 equals the width W that drop forms mouth 14.And in this embodiment, the length of drop forming unit 3 equals the length L that drop forms mouth 14.Interface channel 6 has depth D, is defined as the length on the direction that forms mouth 14 from charging aperture 2 to drop.In this embodiment, the degree of depth of drop forming unit 3 equals the depth D of interface channel 6.Although in Fig. 1, charging aperture 2 is less than drop and forms mouth 14, be to be understood that charging aperture 2 can also be equal to or greater than drop and form mouth 14.
It is noted that Fig. 1 is schematically, is not to draw in proportion.In this embodiment, the length L that drop forms mouth 14 can be for example 5500 μ m, and the width W that drop forms mouth 14 can be 2.6 μ m, and the depth D of interface channel 6 can be 25 μ m.Therefore, the second full-size L that drop forms mouth 14 forms the first size W of mouth 14 much larger than drop, large more than 4500 times here.Therefore the 3rd dimension D of drop forming unit 3 is greater than the first size W that drop forms mouth 14, is greater than here more than 9 times.
In the embodiment in figure 1, feeding structure 2 ' length L
fscan be for example 5500 μ m, feeding structure 2 ' width W
fscan be for example 2.6 μ m, feeding structure 2 ' depth D
fscan be 5 μ m.
In the embodiment in figure 1, the flow resistance R of drop forming unit 3
dFUcan pass through R
dFU=KD/ (W
3l) estimate, wherein, K is geometric correlation constant, and K equals 12 (referring to Perry ' s 7 in this case
thedition (Perry the 7th edition), formula 6-36 and 6-51).Therefore, the flow resistance of the drop forming unit 3 of Fig. 1 is about 3.1m
-3.The flow resistance R of feeding structure
fscan be by R
fs=KD
fs/ (W
fs 3l
fs) estimate.Therefore, the feeding structure 2 of Fig. 1 ' flow resistance be about 0.62m
-3.Therefore, in this embodiment, the flow resistance of drop forming unit 3 be greater than feeding structure 2 ' flow resistance.
Drop forming unit 3, charging aperture 2, drop form mouth 14 and interface channel 6, are arranged in this embodiment in substrate (substrate) 10.In this embodiment, charging aperture 2 is connected to treat that decentralized photo the first material offers drop forming unit 3 with feeding structure 2 ' fluid.In addition, during use, the device 1 of Fig. 1 can be set up so that droplet-shaped becomes mouth 14 to be communicated with the collection structure fluid at continuous phase the second material place, continuous phase the second material is appeared at or flow through drop formation mouth 14.
Can proceed as follows the micro fluidic device 1 of so far describing with respect to Fig. 1.
To treat decentralized photo the first Substance P
doffer charging aperture 2.In this embodiment, will treat material dispersed P
dthe feed rate that offers charging aperture 2 can be about 340 μ l/s.By continuous phase the second Substance P
coffer collection structure and form mouth 14 to appear at drop.In this embodiment, continuous phase can be water.In this embodiment, treat that decentralized photo can be oil phase or gas phase.Applying pressure is poor so that treat material dispersed P
dwith respect to continuous phase Substance P
cin superpressure.Superpressure can be about 0.01-10bar.
Treat material dispersed P
dvia charging aperture 2, flow into drop forming unit 3.Treat material dispersed P
dreplacement is present in to the continuous phase Substance P in drop forming unit 3
c, here in interface channel 6, until drop forming unit 3 is treated material dispersed filling substantially completely.
When continuing to treat material dispersed P
dwhile sending in charging aperture 2, at drop, form mouthful 14 places drop formation will occur.Can in a plurality of positions that form the length L of mouth 14 along drop, drops occur forms simultaneously.It will be very uniform at drop, forming mouthful drop size that 14 places form.When forming, drop will be forced to leave drop forming unit 3 and enter continuous phase Substance P
c(stream) in.
Fig. 2 illustrates according to the schematic diagram of alternative micro fluidic device 1 of the present invention.In Fig. 2, device 1 comprise feeding structure 2 '.Feeding structure 2 ' have depth D
fswith the first width W
fs.In Fig. 2, device 1 also comprises collection structure 4.Collection structure has depth D
cswith the second width W
cs.In Fig. 2, device 1 also comprises drop forming unit 3, drop forming unit 3 be designed to feeding structure 2 ' with collection structure 4 between form the interface channel 6 that fluid is connected.In this embodiment, drop forming unit 3 is designed to boss (plateau) 8.Drop forming unit 3 and feeding structure 2 ' at charging aperture 2 place's fluids, be communicated with.
In this embodiment, feeding structure 2 ', collection structure 4 and drop forming unit 3 be arranged on substrate 10.Towards top side, structure 2,4,6 tegmentum 12 sealings, shown in broken lines in Fig. 2.Should be appreciated that and replace independent lid 12, other substrate can also be placed in to the top of substrate 10, with the top side of enclosed construction 2,4,6.
In Fig. 2, interface channel 6 forms mouthful 14 place's openings in collection structure 4 at rectangular drop.
Should be appreciated that in this embodiment, drop forms the first minimum dimension of mouth 14 or the width W of width W and boss 8
pcorresponding.Should be appreciated that in this embodiment, drop forms the second full-size of mouth 14 or the length L of length L and boss 8
pcorresponding.
It is noted that Fig. 2 is schematically, does not draw in proportion.In this embodiment, the length L that drop forms mouth 14 can be for example 500 μ m, and the width W that drop forms mouth 14 can be 1.2 μ m, and the depth D of interface channel 6 can be 200 μ m.Therefore, the second full-size L that drop forms mouth 14 forms the first size W of mouth 14 much larger than drop, large more than 190 times here.More common, the second full-size L that drop forms mouth 14 forms the first size W of mouth 14 much larger than drop, large more than 50 times.Have been found that if the second size L be 80 times of first size W above, preferably more than 100 times, can obtain better result.Should be appreciated that in Fig. 2, drop forming unit has constant cross section, and this cross section is perpendicular to flow directional detection that charging aperture from drop forming unit forms mouthful to drop.In this embodiment, the first size W of drop forming unit
pequal the first size W that drop forms mouth.In addition, cross section meets the following conditions: the second size L of drop forming unit
pat least the first size W of drop forming unit
p50 times.
The 3rd dimension D of drop forming unit 3 is greater than the first size W that drop forms mouth 14, large more than 166 times here.More common, the 3rd dimension D of drop forming unit is greater than the first size W that drop forms mouth 14, large more than 2.5 times.Have been found that if the 3rd dimension D be 5 times of first size W above, preferably more than 10 times, can obtain better result.Should be appreciated that in the embodiment of Fig. 2 the cross section (W of drop forming unit
p, L
p) meet the following conditions: form mouthful scope of the 3rd dimension D of the 14 drop forming units of measuring to charging aperture 2 from drop in, the second size L of drop forming unit
pat least the first size W of drop forming unit
p50 times, the first size W that wherein this 3rd dimension D is drop forming unit
pmore than 2.5 times.
In the embodiment of Fig. 2, feeding structure 2 ' width W
fssubstantially equal the width W of drop forming unit 3.In this embodiment, feeding structure 2 ' length L
fs300 μ m.In this embodiment, feeding structure 2 ' depth D
fs40 μ m.
In the embodiment of Fig. 2, the flow resistance R of drop forming unit 3
dFUcan be by R
dFU=KD/ (W
3l) estimate, wherein K is geometric correlation constant, and K equals 12 (referring to Perry ' s 7 in this case
thedition (Perry the 7th edition), formula 6-36 and 6-51).Therefore, the flow resistance of the drop forming unit 3 of Fig. 2 is about 2.78m
-3.The flow resistance R of feeding structure
fscan be by R
fs=KD
fs/ (W
fs 3l
fs) estimate.Therefore, the feeding structure 2 of Fig. 2 ' flow resistance be about 0.93m
-3.Therefore, in this embodiment, the flow resistance of drop forming unit 3 be greater than feeding structure 2 ' flow resistance.
In Fig. 2, drop forms the width W that mouthful 14 first minimum dimension W are less than collection structure 4
cs.Preferably, first size W is than the width W of collection structure 4
csgmore than little 10 times, preferably more than 50 times.
Can proceed as follows the micro fluidic device 2 of so far describing with respect to Fig. 2.
Direction at arrow F (referring to Fig. 3 a), will be treated decentralized photo the first Substance P
dvia feeding structure 2 ' offer drop forming unit 3.In this embodiment, will treat material dispersed P
dthe feed rate that offers charging aperture 2 can be about 11 μ l/s.In the direction of arrow G (referring to Fig. 3 a), by continuous phase the second Substance P
coffer collection structure 4.In this embodiment, continuous phase can be water.In this embodiment, treat that decentralized photo can be oil phase or gas phase.Applying pressure is poor so that treat material dispersed P
dwith respect to continuous phase material in superpressure.Superpressure can be approximately 0.01-10bar.
Treat material dispersed P
dflow through charging aperture 2 and enter boss 8 (referring to Fig. 3 b).Treat material dispersed P
dthe continuous phase P existing on boss 8 will be replaced
cproduct, until boss is treated material dispersed covering (referring to Fig. 3 c) substantially completely.It should be noted that the turning of boss 8 may not treated material dispersed because laplace pressure is poor.Then drop forming unit 3 will be treated that dispersed substance fills substantially completely.
When continuing to treat material dispersed P
dwhile sending into charging aperture 2, be there is to drop in 16 places, the edge at boss 8 and form (referring to Fig. 3 d).Can in a plurality of positions at 16 places, edge at boss 8, drop occur forms simultaneously.The size of the drop forming at 16 places, edge of boss 8 will be very uniform.Moreover, because laplace pressure is poor, can not use the turning of boss 8.
When forming, drop will enter in collection structure 4, and will be by continuous phase Substance P
cthe mobile separating device 1 (referring to Fig. 3 e) that is forced to.
Boss 8 width (W
p) and collection structure 4 width (W
cs) between difference be considered to play a role in spontaneous drop produces.Preferably, the width W of collection structure 4
csat least than the width W of boss 8
plarge 10 times, more preferably at least large 50 times, most preferably at least large 80 times.
In the embodiment in figure 1, the volume V of the interface channel 6 of DFU 3 is about 3.57510
5μ m
3.In addition the volume V of drop to be formed,
dropbe at least about 1150 μ m
3(65W
3).Therefore, the volume of interface channel 1 is approximately 310 times of volume of drop to be formed.
In the embodiment of Fig. 2, the volume V of the interface channel 6 of DFU is about 1.210
5μ m
3.In addition the volume V of drop to be formed,
dropbe at least about 112 μ m
3(65W
3).Therefore, the volume of interface channel is approximately 1070 times of volume of drop to be formed.
More generally, to be preferably selected as making it be at least the volume V of drop to be formed to the volume V of interface channel 6
drop100 times.Therefore, interface channel can comprise q.s treat material dispersed, with will the treat material dispersed drops that form to a plurality of that provide simultaneously.
Should be appreciated that in the embodiment of Fig. 1 and Fig. 2, will treat material dispersed P
dthe feed rate of delivering to interface channel 6 by charging aperture 2 is at least every microsecond droplet size V to be formed
drop100 times.Should be appreciated that therefore, when feed rate is selected as making a plurality of drop, forms and can not make the material dispersed minimizing for the treatment of in interface channel.
Micro fluidic device according to the present invention is very suitable for expanding and processing with effective means.For modern lithographic technique, manufacturing groove or boss is not large challenge.In addition, can consider that micro fluidic device 1 is automatically to regulate; The drop formation position that forms mouth 14 along drop can be simultaneously in a plurality of positions.In addition, the operation of micro fluidic device is simple.After supercharging, interface channel 6 fillings need material dispersed, and for example, even if there is certain disturbing factor (stain of dust) that affects flow pattern, the length L relatively large with respect to its width W that drop forms mouth 14 filled interface channel 6 regularly.
Should be appreciated that by placing in mode side by side a plurality ofly according to micro fluidic device of the present invention, can suitably expand.Additionally or alternately, can increase drop and form mouthfuls 14 length-width ratio, to increase, can be used for the region that drop forms.For example possibly, the length L that drop forms mouth is the more than 150 times of width W, or even more than 250 times or 500 times.Preferably, for thering is the feeding structure of the drop forming unit of this aspect ratio, be designed so that the flow resistance of feeding structure is less than the flow resistance of drop forming unit.
Fig. 4 a illustrate comprise a plurality of according to micro fluidic device of the present invention and for generation of the embodiment of the system of disperseing.In the embodiment of Fig. 4 a, single substrate 10 comprise a plurality of drop forming unit 3.i (i=1,2,3 ...), drop forming unit 3.i is designed to connect the interface channel 6.i of public feeding structure 2 and public collection structure 4.In this embodiment, each interface channel 6.i of a plurality of interface channel 6.i forms boss 8.i.In this embodiment, feeding structure 2 ' width W
fsbe selected as being greater than the width W of boss 8.i
p, and the length L of the feeding-passage of each device
fsequal the length L of the boss of each device
p.Therefore, the flow resistance for the feeding structure of each device can easily be chosen as the charging resistance that is less than each drop forming unit.
System shown in Fig. 4 a can comprise lid 12 as shown in Figure 2.Also possibly, stack a plurality of according to the substrate of Fig. 4 a, each substrate be subsequently formed for next under the lid of substrate.If the substrate stacking is removably connected, for example to clip together, substrate can relative to each other be removed, with cleaning base plate easily.
Fig. 4 b illustrate comprise a plurality of according to micro fluidic device of the present invention and for generation of another embodiment of the system of disperseing.In the embodiment of Fig. 4 b, single substrate 10 comprise a plurality of drop forming unit 3.i that are designed to interface channel 6.i (i=1,2,3 ...), each interface channel 6.i ends at drop and forms a mouthful 14.i place.In the embodiment of Fig. 4 b, interface channel 6.i is designed to groove as shown in Figure 1.And in this embodiment, all interface channel 6.i can be communicated with public feeding structure 2 ' fluid, and/or opening is in public collection structure 4.
It should be noted that in Fig. 4 a feeding structure 2 ' the lead to length L at interface channel 6.i place
fssubstantially equal the length L that interface channel 6 leads to collection structure 4 places
p.The whole width that therefore it should be understood that boss 8.i can easily fill need material dispersed.Here with reference to also Fig. 2 and 3c in that case, feeding structure 2 ' in the length L at interface channel 6 places wherein
fsbe less than drop and form mouthful 14.i in the length L at collection structure 4 places, the whole width of boss is filled and is needed to be disperseed product.
Should be appreciated that if charging aperture in the length L at interface channel 6 places
fssubstantially be equal to or greater than the second size L that drop forms mouthful (length L of boss 8 for example
p), for example with the depth D of boss 8
pthe depth D of corresponding interface channel can be very short, for example the order of magnitude of several microns.
On the other hand, if charging aperture in the length L at interface channel 6 places
fsfar be narrower than the second size L, interface channel 6 depth D may need longlyer so, for example, substantially equal the second size L, so that treat material dispersed P
dfill the whole length L of interface channel 6.
Should be appreciated that if feeding structure 2 ' in the length L at drop forming unit 3 places
fssubstantially be equal to or greater than the second size L that drop forms mouthful (length L of boss 8 for example
p), can easily make the flow resistance of drop forming unit 3 be greater than the flow resistance of feeding structure.
The system shown in Fig. 4 b that should be appreciated that can be called the platy structure 10 with a plurality of grooves.It is the more than 50 times of width that the length L of these grooves and width W are selected as making length.Groove can be designed to have essentially identical size so that the charging aperture of each groove and drop form a mouthful 14.i.In the case, the depth D of each drop forming unit equals the thickness of platy structure 10.It is at least 2.5 times of width W of groove that the depth D of each drop forming unit is selected as making depth D.Should be appreciated that feeding structure can be formed by hollow space, this hollow space is arranged near the bottom side place, charging aperture 2 of platy structure and is communicated with described charging aperture fluid.The size of this feeding structure can be easily designed to make the flow resistance of feeding structure to be less than the flow resistance of the drop forming unit of combination.Therefore, can guarantee for drop forming unit suitably fill treat material dispersed.
Fig. 5 a illustrates another embodiment for generation of the micro fluidic device 1 disperseing.In Fig. 5 a, device 1 comprises drop forming unit (DFU) 3.Drop forming unit 3 comprises charging aperture 2.Drop forming unit 3 also comprises that drop forms mouth 14.In Fig. 5 a, drop form mouthfuls 14 comprise a plurality of sections of 15.j (j=1,2,3 ...), a plurality of sections of 15.j are joined together to form drop and form mouthfuls 14, it is the more than 50 times of width that drop forms mouth that drop forms total (expansion) length of mouthfuls 14.The turning that should be appreciated that each section of joint in drop formation mouth 14 can be used as droplet nucleation structure, to help forming a plurality of drops simultaneously.More normally, this one-tenth nuclear structure can form by the variation of the direction of drop formation mouth in the plane at drop formation mouth.
Fig. 5 b illustrates the another embodiment for generation of the micro fluidic device 1 disperseing.In Fig. 5 b, device 1 comprises drop forming unit (DFU) 3.Drop forming unit 3 comprises charging aperture 2.Drop forming unit 3 also comprises that drop forms mouth 14.In Fig. 5 b, drop forming unit 3 comprise a plurality of one-tenth nuclear structure 17.k (k=1,2,3 ...).In this embodiment, this one-tenth nuclear structure 17.k is designed to the width W of local widening drop forming unit 3.Become nuclear structure as the optimum position producing for drop.Preferably, the distance between two adjacent one-tenth nuclear structures is selected as being less than the distance at " automatically " generation drop place in the situation that not becoming nuclear structure.As already described, the diameter D of the drop of formation
drop5 to 8 times of (D that are about first size
drop=5W to 8W).Therefore, the distance between two adjacent one-tenth nuclear structures is preferably selected as 8W or less, more preferably 5W or less.Preferably, the distance between two adjacent one-tenth nuclear structures is not less than D
drop.
In the embodiment of Fig. 5 b, drop forming unit 3 be designed grooving 8 '.Should be appreciated that and can also in being designed to the drop forming unit of boss 8, be provided as nuclear structure.
So far the embodiment illustrating can be by by interface channel 6 and optionally by feeding structure 2 ' etch into substrate 10 and produce from top side with collection structure 4.Therefore in the embodiment of Fig. 2, all structures 2 ', 4,6 top side can extend (for example covering 12 bottom surface) in a plane, and due to the stand out of each structure, the bottom side of structure can be extended in different planes.In the embodiment in figure 1, feeding structure 2 ' be processed into the thickness that runs through substrate 10 with interface channel 6.Interface channel 6 forms mouthful 14 place's openings in collection structure 4 at rectangular drop.It should be noted that in Fig. 1, collection structure 4 is partly limited by the end face 22 of substrate.But different geometries is also feasible.
In the embodiment of Fig. 2-4a, continuous phase product is along flowing through collection structure 4 with the substantially parallel direction of full-size L of drop formation mouth 14.But in the embodiment of Fig. 1 and 4b, the direction that continuous phase product can be parallel along the minimum dimension W with drop formation mouth 14 flows through collection structure 4.
embodiment
The silicon microchip substrate 10 of 1.5x1.5cm is provided.With deep reaction ion etching (DRIE) technology (Micronit Microfluidics, Holland) etching on silicon microchip be also referred to as passage (aschannel) 2 ', 4,6 structure.Glass plate 12 is bonded on the top of microchip with closed channel.By this way by silicon and glass passage 2 ', be formed for producing the required water-wetted surface of emulsion oil-in-water product in 4,6.Micro fluidic device comprises the wide (W of 200 μ m
fs) and the dark (D of 100 μ m
fs) oil inlet passage 2 '.Continuous phase collection channel 4 is also the wide (W of 200 μ m
cs) and the dark (D of 100 μ m
cs).Feeding-passage 2 ' and collection channel 4 between, exist and to there is regular length (L
p=500 μ m) and the degree of depth (D
p=200 μ m) boss 8.Use has one of two kinds of width (W
p=2.6 μ m or 1.2 μ m) boss 8.Therefore, drop formation mouth has respectively the length L of 500 μ m and the width W of 2.6 μ m or 1.2 μ m.Boss 8 is used as drop forming unit in this system.Tested respectively and there are 1.2 μ m boss width W
p(dotted line) and 2.6 μ m boss width W
ptwo systems of (solid line).Fig. 2 has provided the sound impression of micro fluidic device, but whether completely proportionally draw.
Treat decentralized photo product P
dbeing for example oil, is hexadecane (viscosity η=3.34mPas, as the Merck KGaA of Darmstadt, Germany is provided) in this embodiment, and this is treated to decentralized photo product is directed to boss 8 via oil inlet passage 2.In this embodiment, use digital pressure controller (Bronkhorst, Holland) to arrange and control institute's applied pressure.By Lapalce's law, determine that hexadecane flows to pressure required on boss 8.If pressure surpasses this value, oil flows on boss 8, and will form mouthful 14 places at drop and form drops, and wherein drop forms mouthful 14 places at drop and 16 falls into collection channel 4 from edge, and collection channel 4 guides in this embodiment as continuous phase product P
cmilliQ ultra-pure water, MilliQ ultra-pure water has the 1%SDS as surfactant.
At the drop at 16 places, edge of boss 8, form a plurality of positions of the edge that simultaneously occurs in boss, although the turning of boss 8 is because laplace pressure is poor and do not use.By the constant pressure applying on oil, can be greater than 300Hz frequency with each drop forming unit and form single hexadecane drop that disperses.By graphical analysis with utilize Mastersizer 2000 (Malvern Instrument Ltd., Britain) to analyze the drop size of the emulsion producing by two kinds of pilot systems.In Fig. 6, described the droplets size distribution producing.For the system of the 2.6 μ m boss degree of depth, the average drop size of volume weighting is that 15.55 μ m, span (Span) are 0.346 (CV=16%).For the system of 1.2 μ m boss width, these values are respectively 7.20 μ m and 0.236 (CV～10%).To sum up, the emulsion of generation has narrow distribution, especially when the emulsion forming with homogenizing is compared.
In order to study in further detail drop forming process, make the continuous close-up image of single drop.The typical shape at the interface during Fig. 7 a-7h is illustrated in drop and forms between oil phase and water.During use, the interface between oil phase and water is present in drop and forms a mouthful place.Each of Fig. 7 a-7h has the expression of time, and image is in this time place's acquisition.
Drop becomes along with the time greatly, has caused the reduction of laplace pressure in drop.Drop in Fig. 7 a-7h is still connected to boss by neck N.Very, near 16 places, edge of boss 8, the local pressure in neck N is by the laplace pressure approximating in drop.Pressure on boss 8 and neck N is determined by two curvature; In this case, in them (x-z plane) is fixed as the numerical value (R of a half width of boss
p1=W
p/ 2).Curvature (R in x-y plane
p2) can there is different values, and if because become the reduction of pressure in large drop, droplet radius (R
d) become the fixedly curvature (R on boss 8
p1) twice large, the curvature (R in x-y plane
p2) must become negative.We are described as 2 σ/R by this
d(t)=σ/R
p1-σ/R
p2(t).Although R before drop forms
p2very large, once but there is drop, R
p2just adopt much smaller value.Back-pressure σ/R
p2(t) make neck N stable, so neck N can stablize a period of time.
It should be noted that being conventionally applicable to form mouthful power (dynamics) for the treatment of the interface between decentralized photo product and continuous phase product at place at drop causes constriction (necking), and the power in the micro channel systems of this power and prior art is different.Conventionally, treat that the interface between decentralized photo and continuous phase is present in drop formation mouthful place.Obviously, protrude to the outside of drop forming unit at interface, forms position enter in continuous phase product at drop, and drop can retreat near these drops formation positions.Yet, on average, treat that the interface between decentralized photo and continuous phase is present in drop formation mouthful place.In addition,, in micro fluidic device according to the present invention, drop forms a plurality of positions in the length that simultaneously occurs in drop formation mouth 14; Therefore, whole drop forms mouth and has promoted productive rate.
In the feature film of making, the curvature of having observed in x-y plane becomes more and more negative really in time.Curvature R in each of Fig. 7 a-7h
p2corresponding with these values, it supports the explanation of observed interface behavior.In addition, away from drop, form position, local pressure is by the local pressure higher than neck, and this is the R by the interface along away from neck
p1increase causes.Along with R
p2be forced to reduce, near edge, produce quasistatic neck.This may be that laplace pressure in drop causes, so neck no longer changes greatly and fast with the change of drop.In this case, as long as the oil mass in inflow drop is no more than the oil mass of the peripheral region inflow neck from boss, drop adheres to maintenance.Obviously, once flow out to surpass, supply with, drop just will separate.Although see that interface can retreat a little near drop forms position, obviously during drop forms, the oil on boss can not reduce.In addition oil-feed speed, is selected as being enough to supplement the oil existing on boss.
The aspect of being concerned about is liquid-drop diameter D
dropdependence to institute's applied pressure in system, as shown in Figure 8.In this embodiment, utilize image analysis software (ImagePro Plus) to determine D
drop, and measured 100 drops.The increase of institute's applied pressure causes the substantially invariable D at lower pressure place
drop(approximately 7 μ m).Therefore, wide actual pressure scope can be used, at this wide actual pressure scope place, monodisperse emulsion can be formed.In this pressure limit, be 250-350mbar (millibar) in this embodiment, with comparing in inflow drop, the oily supply on boss is seldom.At higher institute applied pressure place, liquid-drop diameter increases with the increase of institute's applied pressure.Have been found that if difference is larger between the flow resistance of feeding structure and the flow resistance of drop forming unit, make so the substantially invariable pressure limit of liquid-drop diameter larger.Can also compare the drop forming unit that its larger drop forms the flow resistance at mouth place with the flow resistance at charging aperture place by providing to have, for example, from charging aperture to drop, form the drop forming unit that mouthful length L reduces, expand pressure limit.
Have been found that and determine that the key factor of the liquid-drop diameter (referring to Fig. 8) in pressure independent scope is boss width W
p.Liquid-drop diameter can be weighed with boss width, is approximately 5-8 times of boss width, for example, be approximately 6 times of boss width.
In the above description, with reference to the specific embodiment of embodiment of the present invention, the present invention has been described.But, significantly in the situation that do not depart from the of the present invention wider spirit and scope of setting forth as claim, can carry out various modifications and variations.
In Fig. 4 a and 4b, feeding structure 2 ' and collection structure 4 be substantially parallel.For example, also possibly, feeding structure formation branch and collection structure are around branch.In this embodiment, interface channel can be directed or otherwise directed substantially radially.
In the embodiment of Fig. 2, the width of feeding structure equals the width of interface channel substantially.In the embodiment of Fig. 4 a, the width of feeding structure equals the width of collection structure substantially.The width that should be appreciated that feeding structure can be selected to adapt to application.Preferably, the width of feeding structure is selected as making feeding structure can not form flow restriction so that produce excessive pressure drops in treating decentralized photo product.
In these embodiments, treat that decentralized photo product is liquid fat or oil-phase product (or gas), continuous phase product is liquid water-phase product.Should be appreciated that the product that can also use other.
For example likely, to be allocated is water substance mutually, and continuous phase is oil, to form for example water in oil dispersion.Also may form following dispersion, comprise: the solid matter in the oil of water bag (nanosuspension), enter (biodegradable) Polymer Solution in water, enter (biodegradable) macromolecule in water and medicine solution, enter lipid (by dissolving) in water and medicine mixture, enter monomer (solution) in water, enter oligomer (solution) in water, enter oil/solvent in water, the mixture of cosolvent, macromolecule, oil, lipid, active matter.All these can also have extra composition, for example pharmaceutic adjuvant, surfactant, stabilizing agent, thickener with (suitable) magnetic, radioactive, can be radiolabeled, fluorescence or phosphorescence become to grade.Conventionally, dispersion to be formed can be for example any lipophilic fluid mixture and/or solution and/or the suspension entering in any hydrophilic fluid mixture and/or solution and/or suspension, and vice versa.
Also possibly, will utilize the drop forming according to micro fluidic device of the present invention to be transformed into microparticle, nano particle or capsule (capsule).In addition, can use various technology, for example cooling, solvent extraction, solvent evaporate, are separated, (suspension) polymerization or other chemical reaction.
Drop can be as the seed as a seed swelling technology part, for generation of particle.
Especially, by utilizing the particle forming according to the drop of micro fluidic device generation of the present invention, can be for controlled release drug administration and/or for the application in the separation process of life sciences industry.Embodiment is PLGA microballoon, magnetic high-molecular or the bead based on delivery system.Particle is based on contrast preparation.
The all right conduct of drop is at the reative cell such as in emulsion-based PCR.
For example also possibly, treat that decentralized photo product is gas (mixture) or steam, with the dispersion of manufacturing bubble in (liquid state) continuous phase product.
Alternately, likely, continuous phase product is gas (mixture) or steam, to for example manufacture drop mist in air.This drop for example can be dried to produce product spray-dired to be disperseed.
Also possibly, treat that decentralized photo product has been to disperse.For example likely, treat that decentralized photo product is the dispersion of the water-phase product such as water in the oil-phase product such as oily.Therefore, micro fluidic device can be created in the fine dispersion of the water-filled oil droplet in water continuous phase product for example, for example, for so-called " light " food.Herein, the water in oil droplet can comprise additive, for example spices, colouring agent and/or medicine.
Also possibly, product to be disperseed is premix, for example, comprise that the rough segmentation of large drop is loose.By forming mouth according to the drop of micro fluidic device of the present invention, provide premix, make the large drop in premix be decomposed into the droplet being distributed in continuous phase product.At this, consider that the drop size that reduces by this way premix forms the generation disperseing, and has compared with droplet and/or narrower droplets size distribution.
But other modification, modification and replacement are also possible.Therefore, this description, drawings and Examples are only considered as illustrative rather than restrictive.
In claims, any reference marker of placing in bracket is not interpreted as limiting claim.Word " comprises " does not get rid of further feature or the step of not listing in the claims.In addition, word " (a and an) " should not be interpreted as " only one " and refer to " at least one ", and does not get rid of a plurality of.Some means of recording in mutually different claim do not represent that the combination of these means can not be for useful situation.
Claims (24)
1. for produce the micro fluidic device (1) of the dispersion of the first material at the second material, comprising:
Drop forming unit (3), comprises interface channel (6),
Described interface channel (6) at one end has: single charging aperture (2), and for treating the first material (P of decentralized photo
d) offer described drop forming unit;
Described interface channel (6) has at the other end: single rectangle drop forms mouthful (14), for the second material (P in continuous phase
c) in treat the first material (P of decentralized photo described in forming
d) drop,
Described drop forms mouthful (14) and has width (W) and length (L),
(2') wherein said micro fluidic device also comprises feeding structure and collection structure (4), and (2') described feeding structure is communicated with described single charging aperture (2) fluid, for by described the first material (P that treats decentralized photo
d) offering described drop forming unit (3), described collection structure (4) is for providing the second material (P of described continuous phase
c), wherein said drop forms mouthful (14) opening in described collection structure (4),
The length (L) that wherein said drop forms mouthful (14) is that described drop forms the more than 80 times of width (W) of mouthful (14),
Described interface channel (6) has the first size parallel with the width (W) of described drop formation mouthful (14), second size and the degree of depth (D) from described drop formation mouth (14) to described charging aperture (2) direction parallel with the length (L) of described drop formation mouth (14), the first size of described interface channel (6) is equal to or greater than the width (W) that described drop forms mouthful (14)
Described interface channel (6) has cross section, described cross section forms the direction of mouthful (14) to described drop transverse to the described charging aperture (2) from described interface channel (6), described cross section meets following condition: at described charging aperture (2) and described drop, form within the scope of the entire depth between mouthful (14), the second size of described interface channel (6) is at least 50 times of first size of described interface channel (6), the described degree of depth (D) is that described drop forms the more than 2.5 times of width (W) of mouthful (14)
Flow resistance (the R of described drop forming unit (3)
dFU) be set to larger than described feeding structure flow resistance (R (2')
fs), to be formed mouthful (14) by described single rectangle drop, produce a plurality of drops simultaneously.
2. micro fluidic device according to claim 1, wherein, the length (L) that described drop forms mouthful (14) is that described drop forms the more than 100 times of width (W) of mouthful (14).
3. micro fluidic device according to claim 1, wherein, described interface channel (6) has width (W) and cross section corresponding to length (L) that substantially invariable and described drop forms mouthful (14).
4. micro fluidic device according to claim 1, wherein, described interface channel (6) has the cross section that forms the width (W) of mouthful (14) and general rectangular corresponding to length (L) with described drop.
5. micro fluidic device according to claim 1, wherein, the width (W of described charging aperture
fs) substantially equal the width (W) that described drop forms mouthful (14).
6. micro fluidic device according to claim 1, wherein, described feeding structure has the degree of depth (D
fs) and length (L
fs), the ratio (D of the degree of depth of described feeding structure and length
fs/ L
fs) be less than described drop and form mouthful degree of depth of (14) and the ratio (D/L) of length.
7. micro fluidic device according to claim 1, wherein, described drop forming unit (3) forms the corresponding width (W of the width (W) of mouthful (14) by having with described drop
p) boss (8) form.
8. micro fluidic device according to claim 1, wherein, described drop forms the width (W) of mouthful (14) than the width (W of described collection structure (4)
cs) little more than 10 times.
9. micro fluidic device according to claim 1, wherein, described drop forms the width (W) of mouthful (14) than the width (W of described collection structure (4)
cs) little more than 50 times.
10. micro fluidic device according to claim 1, wherein, the width (W) that described drop forms mouthful (14) is 0.05-25 μ m.
11. micro fluidic devices according to claim 1, wherein, the width (W) that described drop forms mouthful (14) is 0.1-5 μ m.
12. micro fluidic devices according to claim 1, wherein, described drop forms mouthful (14) and/or whole drop forming unit (3) is formed in substrate and/or use interval to be built on substrate.
13. micro fluidic devices according to claim 1, wherein, described drop form mouthful (14) and/or whole drop forming unit (3) by milling, etching, formation route, sandblast and/or injection molding in substrate.
14. micro fluidic devices according to claim 1, wherein, described drop forms mouthful (14) and/or whole drop forming unit (3) is used interval to be built on substantially flat substrate.
15. micro fluidic devices according to claim 1, wherein, described feeding structure (2') and/or described collection structure (4) is formed in substrate and/or use interval to be built on substrate.
16. micro fluidic devices according to claim 1, wherein, described feeding structure (2') and/or described collection structure (4) by milling, etching, formation route, sandblast and/or injection molding in substrate.
17. micro fluidic devices according to claim 1, wherein, described feeding structure (2') and/or described collection structure (4) use interval to be built on substantially flat substrate.
18. micro fluidic devices according to claim 1, wherein, the degree of depth (D) of described drop forming unit (3) makes in use, described in treat the first material (P of decentralized photo
d) substantially in the whole length (L) of described drop formation mouthful (14), above fill described drop forming unit (3).
19. micro fluidic devices according to claim 1, wherein, described drop forming unit (3) comprises that at least one becomes nuclear structure.
20. micro fluidic devices according to claim 19, wherein, described one-tenth nuclear structure comprises that described drop forms the part increase of width (W) of mouthful (14) and/or the variation of the direction of described drop formation mouthful (14).
21. for generation of the system of disperseing, and comprises a plurality of according to the micro fluidic device (1) described in any one in aforementioned claim 1-20.
22. systems according to claim 21, comprise substrate, have a plurality of according to the micro fluidic device (1) described in any one in aforementioned claim 1-20 in described substrate.
23. systems according to claim 21, wherein, described micro fluidic device (1) is micro fluidic device according to claim 3, wherein, the feeding structure of each device (1) (2') fluid is communicated with, collection structure (4) fluid of each device (1) is communicated with, and the drop forming unit (3) of each device (1) is arranged side by side.
24. for produce the method for the dispersion of the first material at the second material, and device or right to use in described method right to use requirement 1-20 described in any one require the system described in 21, and described method comprises:
The first material (P of decentralized photo will be treated
d) by the described single charging aperture (2) of at least one drop forming unit (3), offer described at least one drop forming unit (3);
Described single drop in described at least one drop forming unit (3) forms the second material (P that mouthful (14) locate to provide continuous phase
c); And
By described interface channel, make described the first material (P
d) and described the second material (P
c) engage, by described single rectangle drop, form mouthful (14) and produce a plurality of drops simultaneously.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL2002862A NL2002862C2 (en) | 2009-05-08 | 2009-05-08 | Microfluidic apparatus and method for generating a dispersion. |
| NL2002862 | 2009-05-08 | ||
| PCT/NL2010/050268 WO2010128858A1 (en) | 2009-05-08 | 2010-05-10 | Microfluidic apparatus and method for generating a dispersion |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102458630A CN102458630A (en) | 2012-05-16 |
| CN102458630B true CN102458630B (en) | 2014-08-13 |
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| CN201080030504.8A Expired - Fee Related CN102458630B (en) | 2009-05-08 | 2010-05-10 | Microfluidic apparatus and method for generating a dispersion |
Country Status (4)
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| EP (1) | EP2427266A1 (en) |
| CN (1) | CN102458630B (en) |
| NL (1) | NL2002862C2 (en) |
| WO (1) | WO2010128858A1 (en) |
Families Citing this family (16)
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| WO2014018562A1 (en) * | 2012-07-23 | 2014-01-30 | Bio-Rad Laboratories, Inc. | Droplet generation system with features for sample positioning |
| SG11201510439PA (en) * | 2013-06-21 | 2016-01-28 | Bio Rad Laboratories | Microfluidic system with fluid pickups |
| CN103343090B (en) * | 2013-07-12 | 2014-09-17 | 湖南工程学院 | Integrated multifunctional controllable cell control and analysis micro-fluidic chip and application thereof |
| EP2962751B1 (en) * | 2014-07-03 | 2017-04-05 | Helmholtz-Zentrum Geesthacht Zentrum für Material- und Küstenforschung GmbH | Method of forming droplets in a multiple-phase system |
| US10544413B2 (en) | 2017-05-18 | 2020-01-28 | 10X Genomics, Inc. | Methods and systems for sorting droplets and beads |
| CN110945139B (en) | 2017-05-18 | 2023-09-05 | 10X基因组学有限公司 | Method and system for sorting droplets and beads |
| US10610865B2 (en) | 2017-08-22 | 2020-04-07 | 10X Genomics, Inc. | Droplet forming devices and system with differential surface properties |
| WO2019083852A1 (en) | 2017-10-26 | 2019-05-02 | 10X Genomics, Inc. | Microfluidic channel networks for partitioning |
| US20190321791A1 (en) * | 2018-04-19 | 2019-10-24 | President And Fellows Of Harvard College | Apparatus and method for forming emulsions |
| US11130120B2 (en) * | 2018-10-01 | 2021-09-28 | Lifeng XIAO | Micro-pipette tip for forming micro-droplets |
| CN109351368B (en) * | 2018-10-23 | 2021-04-30 | 深圳市博瑞生物科技有限公司 | Micro-fluidic chip |
| CN113747974A (en) * | 2019-02-28 | 2021-12-03 | 10X基因组学有限公司 | Apparatus, system, and method for improving droplet formation efficiency |
| US11919002B2 (en) | 2019-08-20 | 2024-03-05 | 10X Genomics, Inc. | Devices and methods for generating and recovering droplets |
| EP4119221A4 (en) * | 2020-03-13 | 2024-04-17 | Japan Science and Technology Agency | Microdroplet/bubble generation device |
| CN115335141A (en) | 2020-04-01 | 2022-11-11 | 默克专利股份有限公司 | Emulsifying device |
| CN113278494A (en) * | 2021-05-07 | 2021-08-20 | 深圳市第二人民医院(深圳市转化医学研究院) | Digital PCR microdroplet generation chip |
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2427266A1 (en) | 2012-03-14 |
| WO2010128858A1 (en) | 2010-11-11 |
| CN102458630A (en) | 2012-05-16 |
| NL2002862C2 (en) | 2010-11-09 |
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