CN102458630A - Microfluidic apparatus and method for generating a dispersion - Google Patents
Microfluidic apparatus and method for generating a dispersion Download PDFInfo
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- CN102458630A CN102458630A CN2010800305048A CN201080030504A CN102458630A CN 102458630 A CN102458630 A CN 102458630A CN 2010800305048 A CN2010800305048 A CN 2010800305048A CN 201080030504 A CN201080030504 A CN 201080030504A CN 102458630 A CN102458630 A CN 102458630A
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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
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 be used to produce the system of dispersion.The invention still further relates to the micro-channel device that is used to produce dispersion; Comprise being used to provide the charging aperture of treating decentralized photo first material, having the guiding channel that can be second degree of depth that continuous phase material product is provided and provides and between charging aperture and guiding channel, forming the interface channel that fluid is connected that wherein the 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 with coefficient of variation (CV) of typical about 40%.And, when heating, consume the most of energy that gets in the product.
Recently, develop several kinds of new energy-conservation drops that produce more monodisperse emulsions and formed system.
A kind of known system that is used to produce dispersion that can produce highly single dispersant liquid drop uses so-called list to drip technology, flow focusing apparatus for example, and same streaming system, T type, Y type or intersect link, and the microchannel.In these single system, feeding-passage will be treated the material dispersed guiding channel that offers guiding continuous phase material.In the position of feeding-passage opening in the guiding channel, one next form drop (continuously).
Some of these single system produce the drop in the expected range.But, think that the 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 enlarging these systems.The list of mentioning in front drips in the system, forms drop continuously, needs the quality of drop formation unit (DFU) parallel.In scissors system, treat that decentralized photo stream and continuous phase stream need be accurately controlled in each DFU, because flow velocity has great influence to drop size such as flow focusing, cocurrent flow device and different type of bond.Therefore, it is complicated enlarging the scissors system be used to produce drop, combines more drop to form the unit because it not only relates to, and comprises that also drop forms current control in the unit, and this is minor matter absolutely not.
The system that another kind of known being used to produces dispersion is called so-called microchannel (MC) system.In micro channel systems, the rectangular shaped feed passage will treat that the decentralized photo product offers the guiding channel of guiding continuous phase (product matrix (product matrix)).Drop in the microchannel forms and often is called spontaneous drop formation.In this micro channel systems, only need control and treat flowing of decentralized photo.Continuously flow velocity is not to be applicable to regulate the parameter that drop produces, be not caused by shearing force because drop forms, but through cause on the drop that is just forming capillary instable nozzle geometry caused.Low flow velocity still is used for carrying drop from DFU because otherwise it will be blocked by drop.
It seems that micro channel systems be more suitable for enlarging; Especially people such as (M.Microfluid Nanofluid 2008,4,167) I.Kobayashi it seems and got a good chance of to Kobayashi and its colleague's straight-through micro-channel device.Through Kobayashi, use straight-through MC plate with different channel sizes, successfully produce 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 of percentage that produces passage as drop is less than 1%, and for the plate with big microchannel, channel efficiency can only arrive 12.3%.This possibly be because the barometric gradient in the system, like Abrahamse people AICHEJ.2004 such as (, 50,1364) A.J.Gijsbertsen-Abrahamse for utilizing the micro-mesh similar to carry out emulsification institute extensive discussions with the system of Kobayashi.In addition, foozle also possibly cause the low passage efficient of mentioning like 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 efficient.This system has baroque shortcoming, because need very little boss, it has the width of 7.4-8.8 μ m, the length of 3.2-5.5 μ m and the height of 0.32-1.4 μ m.These structures are difficult to make relatively, especially when the size of all boss in the system needs basic identical (being used for narrow droplets size distribution).
Target of the present invention provides a kind of system and/or device of being used to produce dispersion that is more suitable for enlarging (scale-up).
Summary of the invention
The inventor recognizes, can realize above-mentioned target through the system and/or the device that provide firm being used to produce dispersion, wherein exists many drops to form mechanism, forms the unit from same drop simultaneously and spontaneously produces the drop of a plurality of narrow dispersions.
In order to realize above-mentioned target; According to the invention provides the micro fluidic device that is used to produce dispersion; Comprise that drop forms unit (DFU); Drop forms the unit and comprises that charging aperture and rectangle drop form mouth, and charging aperture is used for treating that decentralized photo first material offers drop and forms the unit, and the rectangle drop forms mouth and is used for forming the drop of treating decentralized photo first material at continuous phase second material; Drop forms mouth and has for example first minimum dimension of width W and second full-size of for example length L; Wherein the second size L of drop formation mouth is more than 50 times of first size W that drop forms mouth, and drop forms the unit and to the direction of drop formation mouth, has for example the 3rd size of depth D from charging aperture, and wherein the 3rd dimension D is more than 2.5 times of first size W; Wherein micro fluidic device also comprises and is used for treating that decentralized photo first material sends into the feeding structure that charging aperture fluid that drop forms the unit is communicated with, and wherein the flow resistance of drop formation unit is greater than the flow resistance of feeding structure.During use, treat that decentralized photo first material offers the charging aperture that drop forms the unit through feeding structure, while continuous phase second material appears at or the drop of flowing through forms mouth.Drop forms a mouthful position that limits the interface existence of treating when using between decentralized photo and the continuous phase.Drop forms the unit and is in the drop that continuous phase second material forms first material at drop formation mouth.
The inventor recognizes; Has the drop formation unit that the rectangle drop forms mouth through providing; Can make many drops form mechanism simultaneously takes place; Form the drop that spontaneously produces a plurality of narrow dispersions the unit from same drop simultaneously, wherein the rectangle drop form mouth have be the first size that forms mouthful of this drop second full-size more than 50 times, have and be the 3rd size more than 2.5 times of first size and have the flow resistance bigger than the flow resistance of feeding structure.Among this paper, drop forms the unit can have very simple geometric structure.This should be appreciated that it also is feasible producing a plurality of drops simultaneously through the drop formation unit that a plurality of for example microchannels for example are set on single substrate abreast, although will produce beguine according to the more complicated geometry of micro fluidic device of the present invention.
Also possible is, the second size L that drop forms mouthful be more than 80 times of first size W that form mouthful of drop, preferably more than 100 times, be more preferably more than 150 times, most preferably be 200-500 doubly more than.More drop is formed from same feeding-passage simultaneously.Should be appreciated that and suppose that drop forms the unit and keeps geometry stable, drop forms the second size L of mouth even can be more than 10.000 times of first size W.
Preferably; Drop forms the unit and has cross section; This cross section forms flow directional detection that the charging aperture the unit forms mouthful to drop transverse to being preferably perpendicular to from drop; Cross section has parallel first size of the first size W that forms mouthful with drop and the second parallel size of the second size L that forms mouthful with drop; Make cross section meet the following conditions: second size that the 3rd size that forms the unit at drop forms the unit for drop in the scope of the degree of depth here is 50 times of the drop first size that forms the unit at least; The 3rd size that drop forms the unit forms from drop and mouthful measures to charging aperture, is equal to or greater than 2.5 times of first size that drop forms the unit.
Preferably; Drop forms the unit and has cross section; This cross section forms flow directional detection that the charging aperture the unit forms mouthful to drop transverse to being preferably perpendicular to from drop; The first size that makes drop form the unit is equal to or greater than the first size that liquid forms mouth; And cross section meets the following conditions: second size that the 3rd size that forms the unit at drop forms the unit for drop in the scope of the degree of depth here is 50 times of the drop first size that forms the unit at least, and the 3rd size that drop forms the unit forms from drop and mouthful measures to charging aperture, is equal to or greater than 2.5 times of first size that drop forms the unit.The 3rd size that has been found that this minimum helps drop to form the unit so that many drops form the mechanism generation simultaneously, forms the drop that spontaneously produces a plurality of narrow dispersions the unit from same drop simultaneously.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 to form the unit so that many drops form the mechanism generation simultaneously, forms the drop that spontaneously produces a plurality of narrow dispersions the unit from same drop simultaneously.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 forms the unit can form the chamber, and the chamber has the hollow that the formation fluid is communicated with between charging aperture and drop formation mouth.The chamber can have like the described cross section of last paragraph and the degree of depth then.
Drop forms the unit can have substantially invariable cross section.Substantially invariable cross section can form the size of mouth corresponding to drop.Substantially invariable cross section can be a general rectangular.
In specific implementations, drop forms the unit and has (basically) constant rectangular cross section, rectangular cross section have the corresponding first size W of the first size W that forms mouthful with drop and with the second corresponding size L of the second size L of drop formation mouth.In this case, drop forms the unit and has the 3rd dimension D, and wherein cross section is that (basically) is constant on whole the 3rd dimension D.Form the unit for this drop, think that second size of drop formation unit is more than 50 times of first size W that drop forms the unit, the 3rd dimension D that drop forms the unit is more than 2.5 times of first size W that drop forms the unit.
Under not hoping by the situation of any one theory, the inventor finds: in micro fluidic device according to the present invention, the minimum phase mutual edge distance that drop forms was liquid-drop diameter 2-7 times when the inventor found to use.When the inventor finds to use in addition in micro fluidic device according to the present invention, the diameter D of formed drop
DropApproximately be first size 5-8 doubly.(D
Drop=5W to 8W).
Under not hoping by the situation of any one theory, second size that forms mouthful when drop is the first size that forms mouthful of drop more than 50 times the time approximately, i.e. L/W＞50 o'clock, and micro fluidic device can form the unit from same drop simultaneously form a plurality of drops.
Be to be understood that; If forming the unit, drop has the size that forms mouthful with drop (the corresponding substantially invariable rectangular cross section of L * W); Wherein drop formation unit has depth D in the flow direction that from the charging aperture to the drop, forms mouth, and the volume of interface channel is L * W * D.Drop forms the flow resistance R of unit
DFUCan be by RDFU=KD/ (W
3L) estimate that wherein K is the constant of geometric correlation, K equals 12 (referring to Perry ' s 7 in this case
ThEdition, formula 6-36 and 6-51).Should be appreciated that can more easily make the drop with substantially invariable rectangular cross section forms the unit.
If feeding structure is chosen as 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 that forms mouthful with drop
Fs, and forming the depth D in the parallel direction of the depth D of unit with drop
FsThe 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
FsBasically equal the width W that drop forms mouth 14.Should be appreciated that in these embodiments, if D
Fs/ L
Fs＜D/L, drop forms the flow resistance R of unit
DFUFlow resistance R greater than feeding structure
FsThis is to be used for according to the possible geometry of micro fluidic device of the present invention simple design guideline being provided.
The flow resistance that should be appreciated that drop formation unit can also be made for the flow resistance greater than feeding structure simply, and promptly the cross section of feeding structure (far) forms the cross section of unit greater than drop.
Preferably, treating that the material dispersed feed rate of sending into interface channel through charging aperture is selected as forms the material dispersed minimizing of treating that can not make interface channel when making a plurality of drop.The inventor has been found that the length that forms the unit according to drop, forms each microsecond of unit by single drop according to the present invention and can form several so that hundreds of drops.Preferably, treat that material dispersed feed rate is each microsecond with 100 times of the volume of the drop that is formed at least.For example, for the drop formation mouth of the first size W with 1.2 μ m, feed rate preferably is 11 microliters per second at least, preferably at least 30 μ l/s.Should be appreciated that feed rate possibly receive the influence with the flow resistance of the feeding-passage of the charging aperture of treating the material dispersed DFU of delivering to.
Should be appreciated that simultaneously to form the drop productive rate that a plurality of drops increase each DFU significantly, therefore make according to the suitable well output that enlarges drop of device of the present invention from same feeding-passage.The latter is useful to for example producing a large amount of dispersions, the following detailed description.In addition for device according to the present invention; The flow velocity of continuous phase product is not to be used for the regulation parameter that drop produces, because shearing force is inoperative and drop is through being produced by the unstability in the surface tension on the drop that forms that geometry caused that forms mouth through drop.
In embodiment, micro fluidic device also comprises second material and the collection structure of collecting the drop that forms that is used to provide continuous phase, and wherein drop forms mouthful opening in guide structure.
In embodiment, form droplet-shaped through boss and become the unit with width corresponding with the first size of drop formation mouth.Therefore, micro fluidic device be can form, wherein can feeding structure and collection structure be connected through boss with simple geometry structure.
Preferably, the first size that drop the forms mouthful for example width of boss is littler more than 10 times than the degree of depth of the collection structure in the first size direction that forms along drop mouthful, more preferably more than 50 times.Therefore, forming the existence that process that mouthful place forms droplet or bubble can not be directed the physical boundary of passage at drop disturbs.
Preferably, the minimum first size that drop forms mouth is 0.05-25um, more preferably is 0.1-2um.The inventor finds that device according to the present invention provides the drop of the 5-8 diameter doubly with the first size that is about drop formation mouth.Therefore, the preferred size range that is used for drop formation mouthful first size is provided at the drop of expected range, and this expected range for example is the 0.1-200 micron.
In one embodiment, preferably, feeding structure, collection structure and boss are coated with top (ceiling).
Can in substrate, process is perhaps for example using the interval to build micro fluidic device on the basic flat substrate; This micro fluidic device for example is feeding structure, DFU (for example boss) and collection structure, and this processing for example is 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 the essence photoetching process) feeding structure, DFU and collection structure, but other baseplate material also is possible, for example glass, metal (for example stainless steel) or condensate.Substrate can be coated with the top such as glass plate, for example is bonded to substrate to seal each structure.Can also use the top of first substrate as second substrate.
Preferably, drop forms unit (for example boss) and in the direction vertical with drop formation mouth, has depth D, so that in use, treats that the material dispersed drop of on whole second size, filling basically forms the unit.The proper depth that should be appreciated that drop formation unit can depend on the surface tension of treating between material dispersed and the continuous phase material, and the continuous phase material randomly comprises suitable emulsifying agent or stabilizing agent.It should also be understood that; The appropriate depth D that drop forms the unit possibly depend on that drop forms second size of mouth; For example form the width W of unit or boss corresponding to drop, and/or corresponding to the width W of the charging aperture in the parallel direction of the second size W that forms mouthful with drop
f
Should be appreciated that if the length L of charging aperture
fBasically be equal to or greater than the second size L that drop the forms mouthful (length L of boss 8 for example
p), the depth D of then for example corresponding with the degree of depth of boss drop formation unit can be very short, for example several microns the order of magnitude.On the other hand, if the length L of charging aperture
fMuch smaller than the second size L, the depth D of drop formation unit maybe be longer so, for example equals the second size L basically.
The invention still further relates to the system that is used to produce dispersion, comprise a plurality of according to micro fluidic device of the present invention.
In embodiment, system comprises substrate, on substrate, has a plurality of according to micro fluidic device of the present invention.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 of each device formation unit is arranged such that and treats that material dispersed each drop that flows through side by side forms unit.Therefore, can obtain to have the system of the productive rate of increase.Should be appreciated that a plurality of these substrates can be connected and/or connection abreast.
Description of drawings
To come that further the present invention will be described with reference to accompanying drawing through unrestriced embodiment, wherein:
Fig. 1 illustrates the sketch map according to micro fluidic device of the present invention;
Fig. 2 illustrates the sketch map according to alternative micro fluidic device of the present invention;
Fig. 3 a-3e is illustrated in the vertical view according to micro fluidic device of the present invention in operating period in each stage;
Fig. 4 a and 4b illustrate the sketch map according to system implementation example of the present invention;
Fig. 5 a illustrates the sketch map according to alternative micro fluidic device of the present invention;
Fig. 5 b illustrates the sketch map according to alternative micro fluidic device of the present invention;
Fig. 6 illustrates the Size Distribution of the emulsion of utilizing exemplary microfluidic system generation, and the little picture of corner is the generation emulsion that manifests through microscope;
The typical shape at the interface during Fig. 7 a-7h is illustrated in drop and forms between oil phase and the water; And
Fig. 8 illustrates the diagram that liquid-drop diameter changes with the variation of the pressure that is applied to feeding structure.
The specific embodiment
Fig. 1 illustrates the sketch map according to micro fluidic device 1 of the present invention.In Fig. 1, device 1 comprises that drop forms unit (DFU) 3.Drop forms unit 3 and comprises charging aperture 2.Drop forms unit 3 and comprises that also drop forms mouth 14.In Fig. 1, it is rectangular that drop forms mouthfuls 14, especially rectangle.Drop forms mouth 14 and has first minimum dimension or width W.Drop forms mouth 14 and has second full-size or length L.
In Fig. 1, drop forms unit 3 and is designed to form the interface channel 6 that the formation fluid is connected between the mouth 14 at charging aperture 2 and drop.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 that drop forms unit 3 equals the width W that drop forms mouth 14.And in this embodiment, the length that drop forms 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 formation unit 3 equals the depth D of interface channel 6.Though in Fig. 1, charging aperture 2 forms mouth 14 less than drop, 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 for example can be 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, drop forms the first size W of the second full-size L of mouth 14 much larger than drop formation mouth 14, and is big here more than 4500 times.Therefore drop forms the first size W of the 3rd dimension D of unit 3 greater than drop formation mouth 14, here greater than more than 9 times.
In the embodiment in figure 1, feeding structure 2 ' length L
FsFor example can be 5500 μ m, feeding structure 2 ' width W
FsFor example can be 2.6 μ m, feeding structure 2 ' depth D
FsCan be 5 μ m.
In the embodiment in figure 1, drop forms the flow resistance R of unit 3
DFUCan pass through R
DFU=KD/ (W
3L) estimate that wherein, K is the geometric correlation constant, 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 of Fig. 1 formation unit 3 is about 3.1m
-3The 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
-3Therefore, in this embodiment, the flow resistance that drop forms unit 3 greater than feeding structure 2 ' flow resistance.
Can operate as follows the micro fluidic device of so far describing 1 with respect to Fig. 1.
To treat decentralized photo 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.With continuous phase 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.The applying pressure difference is so that treat material dispersed P
DWith respect to the continuous phase Substance P
CBe in superpressure.Superpressure can be about 0.01-10bar.
Treat material dispersed P
DFlow into drop via charging aperture 2 and form unit 3.Treat material dispersed P
DReplacement is present in drop forms the continuous phase Substance P in the unit 3
C, in interface channel 6, form unit 3 up to drop and treated material dispersed filling basically fully here.
When continuing to treat material dispersed P
DWhen sending in the charging aperture 2, form mouthful 14 places at drop drop formation will take place.Can in a plurality of positions of the length L that forms mouth 14 along drop drops take place simultaneously forms.It will be very uniform forming mouthful drop size of 14 places formation at drop.When forming, drop will be compelled to leave drop and form unit 3 and get into the continuous phase Substance P
C(stream) in.
Fig. 2 illustrates the sketch map according to alternative micro fluidic device 1 of the present invention.In Fig. 2, the device 1 comprise feeding structure 2 '.Feeding structure 2 ' have depth D
FsWith first width W
FsIn Fig. 2, device 1 also comprises collection structure 4.Collection structure has depth D
CsWith second width W
CsIn Fig. 2, device 1 comprises that also drop forms unit 3, drop form unit 3 be designed to feeding structure 2 ' with collection structure 4 between the interface channel 6 that is connected of formation fluid.In this embodiment, drop forms unit 3 and is designed to boss (plateau) 8.Drop formation unit 3 and feeding structure 2 ' be communicated with at charging aperture 2 places' fluids.
In this embodiment, feeding structure 2 ', collection structure 4 and drop form unit 3 and be arranged on the substrate 10.Towards the top side, 12 sealings of structure 2,4,6 tegmentums, shown in broken lines among Fig. 2.Should be appreciated that to replace independent lid 12, can also other substrate be placed 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 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 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 for example can be 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, drop forms the first size W of the second full-size L of mouth 14 much larger than drop formation mouth 14, and is big here more than 190 times.More common, drop forms the first size W of the second full-size L of mouth 14 much larger than drop formation mouth 14, and is promptly big more than 50 times.Have been found that if the second size L is more than 80 times of first size W, preferred more than 100 times, can obtain better result.Should be appreciated that in Fig. 2 drop forms the unit and has constant cross section, this cross section is perpendicular to from drop and forms flow directional detection that the charging aperture the unit forms mouthful to drop.In this embodiment, drop forms the first size W of unit
pEqual the first size W that drop forms mouth.In addition, cross section meets the following conditions: drop forms the second size L of unit
pAt least be the first size W that drop forms the unit
p50 times.
Drop forms the first size W of the 3rd dimension D of unit 3 greater than drop formation mouth 14, and is big here more than 166 times.More common, drop forms the first size W of the 3rd dimension D of unit greater than drop formation mouth 14, and is promptly big more than 2.5 times.Have been found that if the 3rd dimension D is more than 5 times of first size W, preferably more than 10 times, can obtains better result.Should be appreciated that in the embodiment of Fig. 2 drop forms the cross section (W of unit
p, L
p) meet the following conditions: forming mouth 14 from drop in the scope of the 3rd dimension D of the drops formation unit that charging aperture 2 is measured, drop forms the second size L of unit
pAt least be the first size W that drop forms the unit
p50 times, wherein this 3rd dimension D is the first size W that drop forms the unit
pMore than 2.5 times.
In the embodiment of Fig. 2, feeding structure 2 ' width W
FsBasically equal the width W that drop forms unit 3.In this embodiment, feeding structure 2 ' length L
FsBe 300 μ m.In this embodiment, feeding structure 2 ' depth D
FsBe 40 μ m.
In the embodiment of Fig. 2, drop forms the flow resistance R of unit 3
DFUCan be by R
DFU=KD/ (W
3L) estimate that wherein K is the geometric correlation constant, 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 of Fig. 2 formation unit 3 is about 2.78m
-3The 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
-3Therefore, in this embodiment, the flow resistance that drop forms unit 3 greater than feeding structure 2 ' flow resistance.
In Fig. 2, drop forms the width W of mouthful 14 first minimum dimension W less than collection structure 4
CsPreferably, first size W is than the width W of collection structure 4
CsgLittle more than 10 times, preferred more than 50 times.
Can operate as follows the micro fluidic device of so far describing 2 with respect to Fig. 2.
Direction at arrow F (referring to Fig. 3 a), will be treated decentralized photo first Substance P
DForm unit 3 via feeding structure 2 ' offer drop.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), with continuous phase 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.The applying pressure difference is so that treat material dispersed P
DBe in superpressure with respect to the continuous phase material.Superpressure can be 0.01-10bar approximately.
Treat material dispersed P
DFlow through charging aperture 2 and get into boss 8 (referring to Fig. 3 b).Treat material dispersed P
DWith replacing the continuous phase P that exists on the boss 8
CProduct is treated material dispersed covering (referring to Fig. 3 c) basically fully up to boss.Should be noted that the turning of boss 8 possibly not treated material dispersed because laplace pressure is poor.Drop forms unit 3 and will be treated the dispersed substance filling basically fully then.
When continuing to treat material dispersed P
DWhen sending into charging aperture 2, will drop take place at 16 places, edge of boss 8 and form (referring to Fig. 3 d).Can be simultaneously in a plurality of positions at 16 places, edge of boss 8 drops taking place forms.The size of the drop that forms at 16 places, edge of boss 8 will be very uniform.Moreover, because laplace pressure is poor, the turning that can not use boss 8.
When forming, drop will get in the collection structure 4, and will be through the continuous phase Substance P
CThe compelled separating device 1 (referring to Fig. 3 e) that flows.
In the embodiment in figure 1, the volume V of the interface channel 6 of DFU 3 is about 3.57510
5μ m
3In 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 310 times of volume of drop to be formed approximately.
In the embodiment of Fig. 2, the volume V of the interface channel 6 of DFU is about 1.210
5μ m
3In 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 1070 times of volume of drop to be formed approximately.
More generally, the volume V of interface channel 6 preferably is selected as and makes that it is the volume V of drop to be formed at least
Drop100 times.Therefore, interface channel can comprise q.s treat material dispersed, will treat the material dispersed drops that form simultaneously to a plurality of that provide.
Should be appreciated that and in the embodiment of Fig. 1 and Fig. 2, will treat material dispersed P
DThe feed rate of delivering to interface channel 6 through charging aperture 2 is every microsecond droplet size V to be formed at least
Drop100 times.Should be appreciated that therefore feed rate is selected as to form when making a plurality of drop and can make the material dispersed minimizing of treating in the interface channel.
Micro fluidic device according to the present invention is very suitable for enlarging processing with effective means.For the lithographic technique in modern times, making groove or boss is not big challenge.In addition, can consider that micro fluidic device 1 is self-regulating; 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 the supercharging, interface channel 6 fillings remain material dispersed, even there is certain disturbing factor (the for example stain of dust) that influences flow pattern, the length L big relatively with respect to its width W that drop forms mouth 14 makes interface channel 6 by filling regularly.
Should be appreciated that through placing a plurality ofly, can suitably enlarge according to micro fluidic device of the present invention with mode side by side.Additionally or alternately, can increase drop and form mouthfuls 14 length-width ratio, can be used for the zone that drop forms with increase.For example possibly, the length L that drop forms mouthful is more than 150 times of width W, perhaps even more than 250 times or 500 times.Preferably, the feeding structure that the drop that is used to have this aspect ratio forms the unit is designed so that the flow resistance of feeding structure forms the flow resistance of unit less than drop.
Fig. 4 a illustrate comprise a plurality of according to micro fluidic device of the present invention and be used to produce the system implementation example of dispersion.In the embodiment of Fig. 4 a, single substrate 10 comprise a plurality of drops form unit 3.i (i=1,2,3 ...), drop forms the interface channel 6.i that unit 3.i is designed to connect 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 width W greater than 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
pTherefore, the flow resistance that is used for the feeding structure of each device can easily be chosen as the charging resistance that forms the unit less than each drop.
System shown in Fig. 4 a can comprise lid as shown in Figure 2 12.Also possible is, stacks a plurality of substrates according to Fig. 4 a, each substrate subsequently be formed for next under the lid of substrate.If the substrate that stacks 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 be used to produce another embodiment of the system of dispersion.Among the embodiment of Fig. 4 b, single substrate 10 comprise a plurality of drops that are designed to interface channel 6.i form unit 3.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.
Should be noted that in Fig. 4 a feeding structure 2 ' the lead to length L at interface channel 6.i place
FsBasically equal the length L that interface channel 6 leads to collection structure 4 places
pThe whole width that therefore it should be understood that boss 8.i can easily fill remain material dispersed.Here with reference to also Fig. 2 under the sort of situation and 3c, feeding structure 2 ' wherein in the length L at interface channel 6 places
FsForm the length L of mouthful 14.i at collection structure 4 places less than drop, the whole width of boss is filled and is remained to be disperseed product.
Should be appreciated that if charging aperture in the length L at interface channel 6 places
FsBasically be equal to or greater than the second size L that drop the forms mouthful (length L of boss 8 for example
p), then for example with the depth D of boss 8
pThe depth D of corresponding interface channel can be very short, for example several microns the order of magnitude.
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 maybe be longer so, for example equals the second size L basically, so that treat material dispersed P
DFill the whole length L of interface channel 6.
Should be appreciated that if feeding structure 2 ' form the length L at 3 places, unit at drop
FsBasically be equal to or greater than the second size L that drop the forms mouthful (length L of boss 8 for example
p), then can easily make drop form the flow resistance of the flow resistance of unit 3 greater than 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.The length L of these grooves and width W are selected as and make that length is more than 50 times of width.Groove can be designed so that the charging aperture of each groove and drop form a mouthful 14.i has essentially identical size.In the case, the depth D of each drop formation unit equals the thickness of platy structure 10.The depth D that each drop forms the unit is selected as and makes depth D is 2.5 times of width W of groove at least.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 with said charging aperture fluid and is communicated with.The size of this feeding structure can easily be designed to make the flow resistance of feeding structure to form the flow resistance of unit less than the drop that combines.Therefore, can guarantee for drop form the unit suitably fill treat material dispersed.
Fig. 5 a illustrates another embodiment of the micro fluidic device 1 that is used to produce dispersion.In Fig. 5 a, device 1 comprises that drop forms unit (DFU) 3.Drop forms unit 3 and comprises charging aperture 2.Drop forms unit 3 and comprises that also drop forms mouth 14.In Fig. 5 a, drop form mouthfuls 14 comprise a plurality of sections 15.j (j=1,2,3 ...), a plurality of sections 15.j are joined together to form drop and form mouthfuls 14, it is 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 joint in drop formation mouth 14 can be used as the droplet nucleation structure, to help to form simultaneously a plurality of drops.More normally, this one-tenth nuclear structure can form through the variation of the direction of drop formation mouth in the plane that forms mouth at drop.
Fig. 5 b illustrates the another embodiment of the micro fluidic device 1 that is used to produce dispersion.In Fig. 5 b, device 1 comprises that drop forms unit (DFU) 3.Drop forms unit 3 and comprises charging aperture 2.Drop forms unit 3 and comprises that also drop forms mouth 14.In Fig. 5 b, drop form 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 that drop formation unit 3 is widened in the part.Become nuclear structure as being used for the optimum position that drop produces.Preferably, the distance between two adjacent one-tenth nuclear structures be selected as less than under the situation that does not become nuclear structure " automatically " produce the distance at drop place.As explained, 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 preferably is selected as 8W or littler, more preferably 5W or littler.Preferably, the distance between two adjacent one-tenth nuclear structures is not less than D
Drop
In the embodiment of Fig. 5 b, drop form unit 3 be designed grooving 8 '.Should be appreciated that to form in the unit at the drop that is designed to boss 8 and be provided as nuclear structure.
So far the embodiment that illustrates can be through with interface channel 6 and randomly feeding structure 2 ' with collection structure 4 is etched into the substrate 10 from the top side and produce.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 owing to the stand out of each structure, the bottom side of structure can be extended in different plane.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.Should be noted that in Fig. 1 collection structure 4 is partly limited the end face 22 of substrate.But the different geometric structure also is feasible.
In the embodiment of Fig. 2-4a, collection structure 4 is flow through with the substantially parallel direction of full-size L that drop forms mouth 14 in continuous phase product edge.But in the embodiment of Fig. 1 and 4b, the continuous phase product can flow through collection structure 4 with the parallel direction of minimum dimension W that drop forms mouth 14 in the edge.
Embodiment
The silicon microchip substrate 10 of 1.5x1.5cm is provided.With deep reaction ion etching (DRIE) technology (Micronit Microfluidics, Holland) etching on the silicon microchip also be called as passage (aschannel) 2 ', 4,6 structure.Glass plate 12 is bonded on the top of microchip with closed channel.By this way through 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 also is 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 to have 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 the length L of 500 μ m and the width W of 2.6 μ m or 1.2 μ m respectively.Boss 8 is used as drop and forms the unit in this system.Tested respectively and had 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 fully proportionally draw.
Treat the decentralized photo product P
DFor example being oil, is hexadecane (viscosity η=3.34mPas is provided like the Merck KGaA of Darmstadt, Germany) in this embodiment, and this is treated that the decentralized photo product is directed to boss 8 via oil inlet passage 2.In this embodiment, use digital pressure controller (Bronkhorst, Holland) to be provided with and to control institute's applied pressure.Confirm that through Lapalce's law hexadecane flows to pressure required on the boss 8.If pressure surpasses this value, oil flows on the boss 8, and will form mouthful 14 places at drop and form a drop, and wherein drop forms mouthful 14 places at drop and 16 falls into collection channel 4 from the edge, and collection channel 4 guides in this embodiment as the continuous phase product P
CThe MilliQ ultra-pure water, the MilliQ ultra-pure water has the 1%SDS as surfactant.
Form a plurality of positions of the edge that occurs in boss simultaneously at the drop at 16 places, edge of boss 8, though the turning of boss 8 is because laplace pressure difference and not using.Through the constant compression force that on oil, applies, can form the unit with each drop and form single hexadecane drop that disperses greater than the 300Hz frequency.Through graphical analysis with utilize Mastersizer 2000 (Malvern Instr Ltd., Britain) to analyze the drop size of the emulsion that produces through two kinds of pilot systems.In Fig. 6, described the droplets size distribution that produces.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 comparing with the emulsion that homogenizing forms.
In order to study the drop forming process in further detail, 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 the water.During use, the interface between oil phase and the water is present in drop and forms a mouthful place.Each of Fig. 7 a-7h all 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 the drop.Drop among Fig. 7 a-7h still is connected to boss through neck N.Near 16 places, edge of boss 8, the local pressure among the neck N will approximate the laplace pressure in the drop very.Pressure on boss 8 and the neck N is confirmed through 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 the x-y plane
P2) can have different values, and if because become the reduction of pressure in the big drop, droplet radius (R
d) become the fixedly curvature (R on the boss 8
P1) twice big, the curvature (R in the x-y plane
P2) must become negative.We are described as 2 σ/R with this
d(t)=σ/R
P1-σ/R
P2(t).Although R before drop forms
P2Very big, but in case drop, R appear
P2Just adopt much little value.Back-pressure σ/R
P2(t) make neck N stable, so neck N can stablize a period of time.
Should be noted that to be applicable to that usually forming mouthful power (dynamics) of treating the interface between decentralized photo product and the 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.Usually, treat that the interface between decentralized photo and the continuous phase is present in drop formation mouthful place.Obviously, protrude to the outside that drop forms the unit at the interface, forms the position at drop and get in the continuous phase product, and drop can be retreated near these drops formation positions.Yet, on average, treat that the interface between decentralized photo and the 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 on the length that occurs in drop formation mouth 14 simultaneously; Therefore, whole drop forms mouth and has promoted productive rate.
In the feature film of making, the curvature of having observed in the 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, form the position away from drop, local pressure will be higher than the local pressure of neck, and this is by the R of edge away from the interface of neck
P1Increase causes.Along with R
P2Compelled reducing, produce the quasistatic neck near on the edge of.This possibly be to be caused by the laplace pressure in the drop, so neck no longer changes with the change of drop greatly and fast.In this case, be no more than the oil mass that peripheral region from the boss flows into neck as long as flow into oil mass in the drop, drop adheres to maintenance.Obviously, supply with in case flow out to surpass, drop just will separate.Can near drop forms the position, retreat a little though see the interface, obviously the oil on the boss can not reduce during drop forms.In addition, oil-feed speed is selected as is enough to replenish the oil that exists on the boss.
The aspect of being concerned about is liquid-drop diameter D
DropTo the dependence of institute's applied pressure in the system, as shown in Figure 8.In this embodiment, utilize image analysis software (ImagePro Plus) to confirm D
Drop, and measured 100 drops.The increase of institute's applied pressure causes the substantially invariable D at the lower pressure place
Drop(about 7 μ m).Therefore, wide actual pressure scope can be used, monodisperse emulsion can be formed at this wide actual pressure scope place.In this pressure limit, be 250-350mbar (millibar) in this embodiment, with comparing in the inflow drop, the supply of the oil on the 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 form between the flow resistance of unit difference at the flow resistance of feeding structure and drop greatlyyer, make the substantially invariable pressure limit of liquid-drop diameter bigger so.Can also compare the drop formation unit that its bigger drop forms mouthful flow resistance at place through providing to have with the flow resistance at charging aperture place, the drop that for example formation mouthful length L reduces from the charging aperture to the drop forms the unit, enlarges pressure limit.
Have been found that the key factor of confirming the liquid-drop diameter (referring to Fig. 8) in the pressure independent scope is the boss width W
pLiquid-drop diameter can be weighed with the boss width, is 5-8 times of boss width approximately, for example is 6 times of boss width approximately.
In above-mentioned explanation, the present invention has been described with reference to the specific embodiment of embodiment of the present invention.But, under the situation that does not break away from the of the present invention wideer spirit set forth like claim and scope, can carry out various modifications and variation significantly.
In Fig. 4 a and 4b, feeding structure 2 ' with collection structure 4 be substantially parallel.For example, also possible is that feeding structure formation branch and collection structure are around branch.In this embodiment, interface channel can be directed basically radially or otherwise directed.
In the embodiment of Fig. 2, the width of feeding structure equals the width of interface channel basically.In the embodiment of Fig. 4 a, the width of feeding structure equals the width of collection structure basically.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 and makes feeding structure can not form flow restriction so that in treating the decentralized photo product, produce excessive pressure drops.
In these embodiment, treat that the decentralized photo product is liquid fat or oil-phase product (or gas), the continuous phase product is liquid water-phase product.Should be appreciated that the product that can also use other.
For example possible is, to be allocated is water substance mutually, and continuous phase is oil, to form for example water in oil dispersion.Also possibly form following dispersion, comprise: the mixture of the mixture of the solution of (biodegradable) Polymer Solution in the solid matter in the oil of water bag (nanometer suspension liquid), the entering water, (biodegradable) macromolecule in the entering water and medicine, the lipid (by dissolving) in the entering water and medicine, the monomer (solution) in the entering water, the oligomer (solution) in the entering water, the oil/solvent in the entering water, 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.Usually, dispersion to be formed for example can be any lipophilic fluid mixture and/or solution and/or the suspension that gets in any hydrophilic fluid mixture and/or solution and/or the suspension, and vice versa.
Also possible is that utilization is transformed into microparticle, nano particle or capsule (capsule) according to the drop that micro fluidic device of the present invention forms.In addition, can use various technology, for example cooling, solvent extraction, solvent evaporate, are separated, (suspension) polymerization or other chemical reaction.
Drop can be used to produce particle as the seed as a seed swelling technology part.
Especially, the particle that the drop that is produced according to micro fluidic device of the present invention by utilization forms can be used for controlled release drug administration and/or be used for the application in the separation process of life science industry.Embodiment is based on PLGA microballoon, magnetic high-molecular or the bead of delivery system.Particle is based on contrast preparation.
Drop can also be as such as the reative cell among the emulsion PCR.
For example also possible is to treat that the decentralized photo product is gas (mixture) or steam, in (liquid state) continuous phase product, to make bubbles dispersion.
Alternately, possible is that the continuous phase product is gas (mixture) or steam, so that for example in air, make the drop mist.This drop for example can be dried to produce product spray-dired to be disperseed.
Also possible is to treat that the decentralized photo product has been to disperse.For example possible is, treats that the decentralized photo product is such as the dispersion such as the water-phase product of water in the oil-phase product of oil.Therefore, micro fluidic device can be created in the fine dispersion of the water-filled oil droplet in the water continuous phase product for example, for example is used for so-called " light " food.Among this paper, the water in the oil droplet can comprise additive, for example spices, colouring agent and/or medicine.
Also possible is that product to be disperseed is a premix, for example comprises that the rough segmentation of big drop is loose.Form mouth through drop premix is provided, make the big drop in the premix be decomposed into the droplet that is distributed in the continuous phase product according to micro fluidic device of the present invention.Consider that at this drop size that reduces premix by this way forms the generation that disperses, and promptly has than droplet and/or narrower droplets size distribution.
But other modification, modification and replacement also are possible.Therefore, this specification, accompanying drawing and embodiment only are regarded as illustrative rather than restrictive.
In claims, any reference marker of placing in the bracket is not interpreted as the restriction claim.Speech " comprises " does not get rid of further feature or the step of in claim, not listing.In addition, speech " (a and an) " should not be interpreted as " only one " and be meant " at least one ", and does not get rid of a plurality of.Some means of in mutually different claim, putting down in writing do not represent that the combination of these means can not be used for useful situation.
Claims (18)
1. be used to produce the micro fluidic device of dispersion, comprise:
Drop forms the unit, comprising:
-charging aperture is used for treating that decentralized photo first material offers said drop and forms the unit; With
-rectangle drop forms mouth; Be used for forming the said drop of treating decentralized photo first material at continuous phase second material; Said drop formation mouth has the first minimum dimension W and the second full-size L, and the said second size L that wherein said drop forms mouth is more than 50 times of said first size W that said drop forms mouth;
Second size that the said second size L that said drop forms the unit and has the parallel first size of the said first size W that forms mouthful with said drop, forms mouthful with said drop is parallel and forming three dimension D of mouth to said charging aperture direction from said drop; The first size that said drop forms the unit is equal to or greater than the said first size W that said drop forms mouth
Said drop forms the unit and has cross section; Said cross section is the orientation measurement that forms mouthful to said drop transverse to the said charging aperture that forms from said drop the unit; Said cross section satisfies following condition: to form second size of unit be 50 times of the said drop first size that forms the unit at least for said drop in the scope of said the 3rd dimension D, and said the 3rd dimension D is more than 2.5 times of said first size W that said drop forms mouthful;
Said micro fluidic device comprises also and is used for that said decentralized photo first material of treating is sent into the feeding structure that the said charging aperture fluid of said drop formation unit is communicated with that said drop forms the flow resistance of the flow resistance of unit greater than said feeding structure.
2. micro fluidic device according to claim 1, wherein, the said second size L that said drop forms mouth is more than 80 times of first size that said drop forms mouth, preferably more than 100 times.
3. according to each the described micro fluidic device in the aforementioned claim, also comprise:
Collection structure is used to provide said continuous phase second material, and wherein said drop forms mouthful opening in collection structure.
4. according to each the described micro fluidic device in the aforementioned claim, wherein, said drop forms the unit and has the corresponding cross section of size that substantially invariable and said drop forms mouth, and this cross section for example is a general rectangular.
5. according to each the described micro fluidic device in the aforementioned claim, wherein, the width W of said charging aperture
FsBasically equal the said width W that said drop forms mouth.
6. according to each the described micro fluidic device in the aforementioned claim, wherein, the ratio (D of the degree of depth of said feeding structure and length
Fs/ L
Fs) form the degree of depth of mouth and the ratio (D/L) of length less than said drop.
7. according to each the described micro fluidic device in the aforementioned claim, wherein, said drop forms the unit and forms by having the boss that forms the corresponding width of first size of mouth with said drop.
8. micro fluidic device according to claim 3, wherein, said drop forms the width W of the first size of mouth than said collection structure
CsLittle more than 10 times, more preferably more than 50 times.
9. according to each the described micro fluidic device in the aforementioned claim, wherein, the first size that said drop forms mouth is 0.05-25 μ m, more preferably is 0.1-5 μ m.
10. according to each the described micro fluidic device in the aforementioned claim; Wherein, Said drop forms mouth and/or whole drop formation unit is formed in the substrate and/or use the interval to be built on the for example flat substantially substrate, and said processing for example is milling, etching, formation route, sandblast and/or injection molding.
11. according to each the described micro fluidic device in the aforementioned claim; Wherein, Said feeding structure and/or said collection structure are formed in the substrate and/or use and be built at interval on the for example basic flat substrate, and said processing for example is milling, etching, formation route, sandblast and/or injection molding.
12. according to each the described micro fluidic device in the aforementioned claim, wherein, the depth D that said drop forms the unit makes that in use the said decentralized photo product of treating is filled said drop basically and formed the unit on whole said second size.
13. according to each the described micro fluidic device in the aforementioned claim, wherein, said drop forms the unit and comprises that at least one becomes nuclear structure.
14. micro fluidic device according to claim 13, wherein, said one-tenth nuclear structure comprises that the part of the width of said drop formation mouth increases or the variation of the direction of said drop formation mouth.
15. be used to produce the system of dispersion, comprise a plurality of according to each the described micro fluidic device in the aforementioned claim.
16. system according to claim 15 comprises substrate, has a plurality of according to each the described micro fluidic device among the aforementioned claim 1-14 in the said substrate.
17. according to claim 15 or 16 described systems, wherein, said micro fluidic device is a micro fluidic device according to claim 3; Wherein, The feeding structure fluid of each device is communicated with, and the collection structure fluid of each device is communicated with, and the drop of each device forms the unit and is arranged side by side.
18. be used to produce the method for dispersion, comprise:
With treating that decentralized photo first product offers said drop formation unit through the charging aperture that drop forms the unit;
A drop formation mouthful place that forms the unit at said drop provides continuous phase second product; And
Through forming the interface channel that the formation fluid is connected between the mouth at said charging aperture and said drop, said first product and said second product are engaged,
Wherein, said drop formation mouth is rectangular, and the second full-size L that said drop forms mouth is more than 50 times of the first minimum dimension W that said drop forms mouth.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL2002862 | 2009-05-08 | ||
| NL2002862A NL2002862C2 (en) | 2009-05-08 | 2009-05-08 | Microfluidic apparatus and method for generating a dispersion. |
| 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 true CN102458630A (en) | 2012-05-16 |
| CN102458630B 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)
| Country | Link |
|---|---|
| EP (1) | EP2427266A1 (en) |
| CN (1) | CN102458630B (en) |
| NL (1) | NL2002862C2 (en) |
| WO (1) | WO2010128858A1 (en) |
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| CN103343090A (en) * | 2013-07-12 | 2013-10-09 | 湖南工程学院 | Integrated multifunctional controllable cell control and analysis micro-fluidic chip and application thereof |
| CN109738224A (en) * | 2013-06-21 | 2019-05-10 | 伯乐生命医学产品有限公司 | Microfluidic system with fluid collection pipe |
| 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 |
| CN115279482A (en) * | 2020-03-13 | 2022-11-01 | 国立研究开发法人科学技术振兴机构 | Micro-droplet and bubble generating device |
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| US20140024023A1 (en) * | 2012-07-23 | 2014-01-23 | Bio- Rad Laboratories, Inc | Droplet generation system with features for sample positioning |
| 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 |
| CN117143960A (en) | 2017-05-18 | 2023-12-01 | 10X基因组学有限公司 | Method and system for sorting droplets and beads |
| US10357771B2 (en) | 2017-08-22 | 2019-07-23 | 10X Genomics, Inc. | Method of producing emulsions |
| 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 |
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| WO2020176882A1 (en) * | 2019-02-28 | 2020-09-03 | 10X Genomics, Inc. | Devices, systems, and methods for increasing droplet formation efficiency |
| US11919002B2 (en) | 2019-08-20 | 2024-03-05 | 10X Genomics, Inc. | Devices and methods for generating and recovering droplets |
| JP2023520063A (en) | 2020-04-01 | 2023-05-15 | メルク パテント ゲーエムベーハー | Emulsifying equipment |
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2427266A1 (en) | 2012-03-14 |
| WO2010128858A1 (en) | 2010-11-11 |
| CN102458630B (en) | 2014-08-13 |
| NL2002862C2 (en) | 2010-11-09 |
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