EP2321538A1 - Dispositif microfluidique - Google Patents

Dispositif microfluidique

Info

Publication number
EP2321538A1
EP2321538A1 EP09775618A EP09775618A EP2321538A1 EP 2321538 A1 EP2321538 A1 EP 2321538A1 EP 09775618 A EP09775618 A EP 09775618A EP 09775618 A EP09775618 A EP 09775618A EP 2321538 A1 EP2321538 A1 EP 2321538A1
Authority
EP
European Patent Office
Prior art keywords
channel
inlet
channels
fluid
dispensing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP09775618A
Other languages
German (de)
English (en)
Other versions
EP2321538B1 (fr
Inventor
Andreas Rigler
Michael Vellekoop
Bernhard Lendl
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Technische Universitaet Wien
Original Assignee
Technische Universitaet Wien
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Technische Universitaet Wien filed Critical Technische Universitaet Wien
Publication of EP2321538A1 publication Critical patent/EP2321538A1/fr
Application granted granted Critical
Publication of EP2321538B1 publication Critical patent/EP2321538B1/fr
Not-in-force legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • 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
    • B01F25/31422—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 with a plurality of perforations in the axial direction only
    • 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

Definitions

  • the present invention relates to microfluidic devices for dispensing fluids or fluid mixtures.
  • Well-mixed fluid mixtures are useful in laminar flow systems, e.g. In microfluidic systems, it is difficult to produce since, especially due to lack of turbulence, but also due to short path lengths, no adequate mixing of the supplied fluids, in particular in the case of liquids, can occur.
  • the mixing between different fluid streams flowing in a channel is thus almost exclusively limited to diffusion processes.
  • cable routing is problematic because of the difficult-to-use third dimension.
  • EP 1 187 671 B1 discloses the introduction of several fluids via inlet channels with correspondingly different tapering cross sections into a mixing chamber of a "micromixer".
  • the taper of the channels extends longitudinally, ie towards the mixing chamber, and the surface of the inlet openings is normal to the longitudinal axis thereof.
  • the channels cross each other without contact and form a common outlet cross section at the mixing chamber. This pressure losses are compensated in the supply lines.
  • the problem that with lateral supply of fluids due to pressure losses in the transverse direction of a mixing channel different amounts of fluid in these are introduced does not occur in this embodiment of a microfluidic device and therefore remains unmentioned.
  • Fig. 1 An example of E. Kauffmann, N.C. Damton, R.H. Austin, C. Blatt and K. Gerwert in "Lifetimes of intermediates in the /? -Heet to ⁇ -helical transition of / Mactoglobulin by using a diffusional IR mixer", PNAS 98, 6646-6649 (2001), is presented in Fig. 1 shown schematically.
  • Several fluid streams are introduced via supply channels in a (horizontal in the figure) mixing channel.
  • the feed channels lead from one side of the mixing channel to this and open at the bottom in a row in this one, wherein the cross section of the inlets at the mouth points rectangular, i. is slit-shaped.
  • the object of the present invention was to provide a microfluidic device, with the above problems in terms of pressure loss and supply line can be solved.
  • a microfluidic device for dispensing a fluid or fluid mixture comprising: an output channel, at least one main fluid supply channel, each into at least one secondary supply channel substantially in the plane of the dispensing channel and laterally thereof which in turn merges into an inlet channel located above or below the discharge channel, which opens into the discharge channel from at least one inlet opening from above or below, with the characteristic that the at least one inlet channel has a cross-sectional shape which changes in its longitudinal direction and / or the at least one inlet opening tion has a changing in the transverse direction of the output channel opening width.
  • the inlet channel Due to this cross-sectional shape of the inlet channel, which changes in its longitudinal direction, and / or the width of the inlet opening (s) in the transverse direction of the outlet channel, varying amounts of fluid can be introduced from it into the outlet channel at different points in the inlet channel. Depending on the shape, locally variable pressure conditions are created, and thus the flow rate and consequently the amount of fluid over the width of the discharge channel are established. For example, the unequal amount of fluid delivered into the dispensing channel due to the pressure difference between the two ends of the inlet channel (s) may be compensated for by widening the inlet channel to the farther end so that there is a larger interface between Inlet and outlet channel for fluid transfer is available.
  • a uniformly thick fluid layer over the width of the discharge channel can be introduced into the latter.
  • smaller or larger amounts of fluid e.g. a fluid gradient can be introduced into it, which can be useful not only for mixing purposes, but also, for example, for chemical reactions in this channel.
  • the fluid (s) is / are not specifically limited. These may be any flowable materials or mixtures thereof.
  • the invention is used in connection with liquids or liquid / gas mixtures, since the advantages of the invention are particularly effective here.
  • one or more inlet openings may be provided in the discharge channel for each inlet channel.
  • the single inlet opening can be formed from the upper edges of the inlet channel, which is completely open towards the outlet channel, and thus occupies the entire interface between the inlet channel and the outlet channel. This simplifies the manufacture of such microfluidic devices, as will be described later.
  • the shapes of the inlet channels and the respective inlet openings may be the same or different from each other in all embodiments of the invention, which enables a targeted adjustment of the amount of fluid entering the zone across the width of the outlet channel.
  • the inlet channel in the region of the junction for example, wedge-shaped, taper or widen
  • the inlet opening for example, has a regular rectangular shape.
  • a plurality of openings for example slot-shaped or circular or even oval, can be provided per single-channel (which sometimes has a changing cross-section), etc.
  • the cross-sectional shape of the at least one inlet channel or the shape of the at least one inlet opening changes is not particularly limited and can be adapted to the respective applications of the device.
  • the cross-sectional shape changes linearly, so that the pressure loss over the length of the channel can be well balanced and a uniform distribution of the fluids or fluid mixtures in the transverse direction of the discharge channel is ensured.
  • the resulting fluid flow behavior can be well simulated and optimized by means of computer programs. Because the pressure drop in the channels is exponential, for purely physical considerations, a corresponding exponential change in cross-section would be a potentially even better solution to this problem.
  • Such courses are in practice - at least in the current production techniques - but only at significantly higher cost feasible and therefore currently not preferred.
  • the width of the at least one inlet channel increases in the transverse direction of the dispensing channel, ie at the end there is a larger area available for the fluid transition from the respective inlet channel to the dispensing channel so as to compensate for the pressure drop.
  • the width of the inlet channel can increase both at its upper and lower edges and at only one of them. That is, the inlet duct does not necessarily have to have side walls normal to the plane of the discharge duct, as will be explained later.
  • a variable depth of the channels affects the feed into the dispensing channel, however, a depression of the inlet channels towards the end thereof tends to be an enhancement of the latter due to the larger cross-sectional area
  • Pressure drop causes, while by decreasing depth (and thus associated smaller cross-sectional area) again the pressure drop can be compensated.
  • Channels as well as the shape of the channels - e.g. forming round or square branches - the flow rate of the fluid to the inlet ports can be determined.
  • these agents can be used both instead of and in combination with other, for example, mechanical control agents, e.g. Micropumps, valves, etc. are used.
  • all inlet ports are on the same side of the dispensing channel, i. above or below the same, arranged, as shown schematically in the later discussed in more detail Fig. 3 and 5, where all inlet channels are shown from below the discharge channel in this merging. This arrangement is easier to produce in the manufacture of microfluidic devices.
  • the main supply channels merge into a plurality of sub-supply and associated intake ports, and also preferably, a plurality of main supply ports are provided.
  • These preferably comprise one or more first main feed channels for introducing a first fluid and one or more a plurality of second main supply channels for introducing a second fluid. This makes it possible to introduce several layers of fluids, also in each case several layers of several fluids, one above the other into the output channel, which improves and accelerates the mixing of two or more fluids, since more than one interface between the fluids for diffusion is available.
  • the sub-feed and associated multi-fluid inlet channels preferably lead from opposite sides to the dispensing channel because, due to the difficult-to-use third dimension, superposition of the channels in microfluidic devices is hardly possible.
  • a plurality of first secondary supply and inlet channels and a plurality of second secondary supply and inlet channels "comb-shaped" from opposite sides (as will be explained in more detail below) interlock with the dispensing channel or open into it.
  • the device according to the invention also makes it possible to combine immiscible liquids, so that a solute can diffuse from one phase into the immiscible other phase.
  • the device does not serve as a mixer but as a micro-extractor.
  • the device according to the invention a well controllable mixing by diffusion of two or more layers of miscible fluids is possible. This achieves a reproducible diffusion mixing time behavior whose behavior depends on the properties of the fluids used (inter alia the diffusion coefficient), the flow rate and the layer thicknesses. In this way, a higher mixing quality is achieved compared to the prior art.
  • the invention relates to the use of a just described device for dispensing a plurality of fluids, which are preferably dispensed in the form of layers.
  • the layers can be the same or have different layer thicknesses, since this can be determined over the cross section of the inlet channels and / or the inlet openings.
  • the fluids are at least partially mixed during delivery due to diffusion at the interfaces between the layers.
  • FIG. 1 is a schematic representation of a micromixer according to the prior art described above.
  • FIG. 2 is a schematic representation of an embodiment of the device according to the invention for introducing a fluid into a dispensing channel via a main feed channel branching into two secondary feed and inlet channels.
  • Fig. 3 is a longitudinal sectional view of the embodiment of Fig. 2 along the line A-A.
  • FIG. 4 is a cross-sectional view of three possible embodiments of the apparatus of FIG. 2 taken along line B-B.
  • FIG. 4 is a cross-sectional view of three possible embodiments of the apparatus of FIG. 2 taken along line B-B.
  • Fig. 5 is a schematic representation of an embodiment of the device according to the invention for introducing two fluids via "comb-shaped" intermeshing inlet channels in an output channel.
  • FIG. 6 is a cross-sectional view of the embodiment of FIG. 5.
  • FIG. 7 is a schematic detail view of various embodiments of an intake passage having a varying cross section.
  • FIG. 8 is a schematic detail view of various embodiments of intake ports in the intake ports.
  • Fig. 9 is a longitudinal sectional view of alternative embodiments of the apparatus of Fig. 2 taken along line A-A.
  • Fig. 1 shows, as mentioned, a known embodiment of a microfluidic device according to the prior art.
  • this apparatus three separate feed channels 2, 2 ', 2 "for liquids in a row in a, here horizontally extending mixing channel 5.
  • a stream of a liquid sample is passed between each buffer stream in the channel, In order to mix these in.
  • the feeding of the three streams takes place from the same side of the mixing channel 5 - in Fig. 1, in
  • microfluidics are defined differently in the literature, for the purposes of the present invention, devices are to be understood as having dimensions such that the cross-sectional area of the channels is on the order of a square millimeter or less.
  • One of the problems of such and similar devices solved by the invention is that the amount of fluid entering the mixing channel at both ends of the respective inlet channel is different due to the pressure drop from one end to the other.
  • FIG. 2 shows a simple embodiment of a microfluidic device according to the invention, which serves mainly to illustrate the principle of the invention.
  • a microfluidic device could not be used as a micromixer but, for example, as a connector between two (micro) lines extending in different spatial directions or as a single channel for fluid (especially liquid) delivery, e.g. in inkjet printers, serve.
  • a fluid in the device shown in Fig. 2, a fluid can be passed into an output channel 5, as indicated by the arrows.
  • the fluid is via a main supply channel 1, which branches into two secondary supply channels 2, 2 ', which in turn pass into two inlet channels 3, 3' to the output channel 5 and through - in the figures consistently dotted - inlet openings 4, 4 'introduced into this ,
  • the present invention makes it possible to compensate for the pressure losses occurring in the case of elongated line junctions and the different quantities of fluid delivered in connection therewith, wherein the cross-sectional shapes of the inlet channels or inlet openings can be adapted precisely to the respective conditions.
  • those in the transverse direction where, for example, round, oval or polygonal cross-sections can be used, are essential, so that not necessarily parallel vertical side walls of the channels must be present. This also affects the pressure ratios in the respective sections of the channels.
  • Two exemplary embodiments of inlet channels with non-parallel sidewalls are shown in FIG. 9 and will be described in more detail later. However, the main and secondary supply channels can also have such non-parallel walls.
  • the cross-section of the respective inlet channel that of the associated inlet opening (s) or even both may change.
  • a "wedge-shaped" i. linear variation of the cross sections are shown, whose course is also the same at the inlet channel and opening, as indicated by the parallelism of the lines.
  • arbitrary combinations of different cross-sectional shapes can be used as long as the flow behavior of the fluid or fluids in the device according to the invention is thereby advantageously influenced.
  • any other shapes, with curves, waves, corners, edges, teeth and the like, are possible, all of which are intended to be within the scope of the present invention.
  • inlet openings can also be provided per inlet channel, which in turn can have any desired shapes.
  • a sequence of slit or circular openings-in the longitudinal and / or transverse direction- is thinkable and feasible, through which the openings in the inlet channel are admitted. led fluid enters the dispense channel at multiple, discrete locations.
  • an inlet channel with linear, e.g. wedge-shaped or conical, or curved tapered cross-section and extending in the longitudinal direction of the inlet channel, slot-shaped inlet opening with a regular rectangular cross-section.
  • the tapering cross-section of the channel then equalizes the pressure drop toward the farther end of the opening so that in turn equal amounts of fluid can enter the discharge channel at both ends of the opening.
  • the cross-section of the inlet or inlet channel upstream of the junction can also change in order to influence pressure differences in the supply lines. This can be done in known manner, i. As in the above-mentioned EP 118.767 B1, by tapering design of the channels 1 and / or 2 or 2 'to the output channel 5 through out. In this way, it can be ensured that the same amount of fluid is delivered to all inlet channels in the case of a main feed channel branching into a plurality of secondary feed and corresponding inlet channels, which results in equal layer thicknesses of the fluid in the output channel.
  • FIG. 3 shows a schematic longitudinal sectional view of the embodiment of Fig. 2 along the line AA, from which it appears that both inlet channels 3 and 3 'from the same side, namely from below, open into the outlet channel 5. This is contrary to the manufacturing technology of microfluidic devices. In addition, the side walls of the inlet channels 3 and 3 'are formed in parallel. Alternatives will be described later in connection with FIG. Fig. 4 shows schematically three possible cross-sectional views of the embodiment of Fig. 2 along the line BB. It can be seen that the cross-section of the inlet channel 3 1 can not only - as shown in FIG.
  • Fig. 4c shows an embodiment with a constant depth of the inlet channel 3 ', which represents a presently preferred embodiment due to the ease of manufacture.
  • Fig. 5 shows an embodiment of the device according to the invention, in which two fluids are supplied from opposite sides of the discharge channel 5 to this.
  • a first fluid is analogous to the embodiment of Figure 2 via a main supply channel 1, which branches into two secondary supply channels 2 and 2 1 and in the sequence in two inlet channels 3 and 3 1 , introduced.
  • a second fluid via the analog components 10, 20/20 'and 30/30'.
  • the cross-sectional shapes that change in the mouth region can be combined again as desired. For clarity, wedge-shaped cross sections are again shown.
  • two layers of the two fluids are alternately introduced into the output channel, whereby a total of three interfaces for the diffusion between the two fluids are available.
  • this effect can be further enhanced. This significantly speeds up mass transfer between the fluids, such that such devices are excellent micromixers or, in the case of immiscible liquids, micro-extractors.
  • a profile of the device according to the invention with an aspect ratio of 1:10 for the inlet channels and / or the inlet opening is used for many-in particular aqueous-fluids.
  • an aspect ratio (width difference: length) of 1:10 an expansion of the (eg wedge-shaped) Channel of, for example, 10.0 microns at the beginning of the inlet channel to 20.0 microns at its end over a length of the inlet channel of 100.0 microns understood.
  • a readily reproducible time behavior of the mixing is achieved by diffusion of two or more fluids, the quality of the mixing also being decisively influenced by the mixing behavior (diffusion coefficients) of the fluids and the flow velocities.
  • FIG. 5 like the previously discussed embodiment of FIGS. 2 to 4, eliminates the problem of pressure differences in the inlet region into the outlet channel.
  • the supply of two different fluids from opposite sides is a new and advantageous solution to the problem of routing in microfluidic devices. Because of the difficult-to-use third dimension, intersecting lines are virtually impossible to manufacture, so that several supply channels - and not merely inlet channels - were required for alternately supplying a plurality of streams of the same fluid, as explained in connection with FIG.
  • FIG. 6 shows a longitudinal sectional view of the embodiment from FIG. 5 along the line AA from FIG. 5. From this it can be seen that all the inlet channels 3, 3 ", 30 and 30 'enter the outlet channel 5 from the same side, again from below This again counteracts the fabrication technique of microfluidic devices where the channels are etched into an existing substrate, cut, etc. Since the line AA in Fig.
  • the thickness of the inlet channel pairs is 3
  • the walls of the inlet ducts need not necessarily be perpendicular, ie normal to the plane of the discharge duct, as shown in FIG
  • the quantity of fluid passing from the respective inlet channel into the outlet channel and thus the layer thickness can likewise be increased the fluid can be controlled at this point of the output channel.
  • Such a change in cross section of the inlet channels is also within the scope of the present invention. 7 shows by way of example schematically different embodiments of the cross-sectional changes of the inlet channels in the plane of the discharge channel.
  • FIG. 8 shows various embodiments of the shapes of the inlet openings, wherein the sake of clarity, the inlet channels are plotted without changing cross-section. In fact, however, any combination of the embodiments shown in FIGS. 7 and 8 and any other embodiments are possible since the invention is by no means limited to the embodiments shown or discussed herein.
  • FIG. 9 shows alternative embodiments of the inlet channels 3 and 3 'from FIG. 3 with non-parallel side walls, which can also be combined with any of the previously described channel cross-section changes and aperture shapes.
  • Channel 3 is here exemplarily with oval cross-section, i. with bulged side walls, represented;
  • Channel 3 ' however, with a downwardly tapered cross-section.
  • additional measures may also be taken on the channel sidewalls, such as e.g. Grooves, grooves, grooves, corrugations and the like in order to influence and optimize the flow behavior of the fluids in the channels.
  • the present invention is a valuable resource. Advances in the state of the art in the field of microfluidics, since it solves existing problems in a relatively simple manner by providing devices that are inexpensive and can be produced by known methods. Accordingly, there is no doubt about the industrial applicability of the invention.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Micromachines (AREA)

Abstract

L'invention concerne un dispositif microfluidique destiné à délivrer un fluide ou un mélange de fluides, comprenant un canal d'évacuation (5), au moins un canal principal d'alimentation en fluide (1, 10) placé sensiblement dans le plan du canal d'évacuation (5) et aboutissant à côté de celui-ci, qui débouche dans au moins un canal annexe d'alimentation (2, 2', 20, 20'), lequel de son côté débouche dans un canal d'amenée (3, 3, 30, 30') se trouvant au-dessus ou en dessous du canal d'évacuation (5), qui est caractérisé en ce qu'au moins un canal d'amenée (3, 3, 30, 30') présente une coupe transversale qui se modifie dans la longueur et/ou qu'au moins un orifice d'amenée (4, 4, 40, 40') présente une largeur d'ouverture variable dans le sens transversal du canal d'évcuation (5).
EP09775618A 2008-08-28 2009-08-27 Dispositif microfluidique Not-in-force EP2321538B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT0133508A AT507226B1 (de) 2008-08-28 2008-08-28 Mikrofluidvorrichtung
PCT/AT2009/000336 WO2010022428A1 (fr) 2008-08-28 2009-08-27 Dispositif microfluidique

Publications (2)

Publication Number Publication Date
EP2321538A1 true EP2321538A1 (fr) 2011-05-18
EP2321538B1 EP2321538B1 (fr) 2012-12-19

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP09775618A Not-in-force EP2321538B1 (fr) 2008-08-28 2009-08-27 Dispositif microfluidique

Country Status (4)

Country Link
US (1) US20110194995A1 (fr)
EP (1) EP2321538B1 (fr)
AT (1) AT507226B1 (fr)
WO (1) WO2010022428A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6395539B2 (ja) * 2014-09-24 2018-09-26 キヤノン株式会社 液体吐出ヘッド用基板の製造方法、及びシリコン基板の加工方法
CN106076135B (zh) 2016-08-01 2019-04-16 江苏揽山环境科技股份有限公司 微气泡发生装置
US11185830B2 (en) 2017-09-06 2021-11-30 Waters Technologies Corporation Fluid mixer
WO2021030245A1 (fr) * 2019-08-12 2021-02-18 Waters Technologies Corporation Mélangeur pour système de chromatographie

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Publication number Priority date Publication date Assignee Title
US6890093B2 (en) * 2000-08-07 2005-05-10 Nanostream, Inc. Multi-stream microfludic mixers
US7470408B2 (en) * 2003-12-18 2008-12-30 Velocys In situ mixing in microchannels
CN101224402B (zh) * 2006-09-01 2012-06-27 东曹株式会社 微小流路结构及采用它的微小颗粒制造方法

Non-Patent Citations (1)

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Title
See references of WO2010022428A1 *

Also Published As

Publication number Publication date
EP2321538B1 (fr) 2012-12-19
WO2010022428A1 (fr) 2010-03-04
AT507226A1 (de) 2010-03-15
US20110194995A1 (en) 2011-08-11
AT507226B1 (de) 2010-09-15

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