US20140227148A1 - Microfluidic Structure Having Recesses - Google Patents

Microfluidic Structure Having Recesses Download PDF

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Publication number
US20140227148A1
US20140227148A1 US14/127,341 US201214127341A US2014227148A1 US 20140227148 A1 US20140227148 A1 US 20140227148A1 US 201214127341 A US201214127341 A US 201214127341A US 2014227148 A1 US2014227148 A1 US 2014227148A1
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United States
Prior art keywords
cavity
recess
liquid
region
microfluidic structure
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Abandoned
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US14/127,341
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English (en)
Inventor
Dirk Kurowski
Oliver Paul
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Boehringer Ingelheim Microparts GmbH
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Boehringer Ingelheim Microparts GmbH
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Assigned to BOEHRINGER INGELHEIM MICROPARTS GMBH reassignment BOEHRINGER INGELHEIM MICROPARTS GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: PAUL, OLIVER, KUROWSKI, DIRK
Publication of US20140227148A1 publication Critical patent/US20140227148A1/en
Abandoned legal-status Critical Current

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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
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • 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
    • 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
    • B01L3/502738—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 integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0642—Filling fluids into wells by specific techniques
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0858—Side walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions
    • 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
    • B01L3/502723—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 venting arrangements
    • 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
    • B01L3/502753—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 bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation

Definitions

  • the invention relates to a microfluidic structure comprising at least one cavity with at least one inlet opening and at least one outlet opening, the cavity being adapted to be filled with a liquid or have a liquid flow through it, and at least one element being provided within the cavity which at least temporarily stops and/or at least partly diverts the liquid as it flows within the cavity.
  • Microfluidic structures are components of microfluidic platforms or microfluidic components and essentially comprise cavities and/or channels in which sample liquids that are to be investigated or manipulated can be held and transported by suitable means (e.g. by capillary forces, pressure differences created) to reaction sites provided accordingly.
  • the present invention encompasses microfluidic platforms such as for example sample carriers, test strips, biosensors or the like which may be used for carrying out individual tests or measurements.
  • microfluidic platforms such as for example sample carriers, test strips, biosensors or the like which may be used for carrying out individual tests or measurements.
  • biological liquids e.g. blood, urine or saliva
  • pathogens and incompatibilities e.g. glucose, blood sugar or cholesterol (blood fat).
  • corresponding detection reactions or entire reaction cascades take place on the microfluidic platforms.
  • the biological sample liquid may be transported by suitable means to the reaction site or sites provided for this purpose.
  • This transporting of the sample liquid may be carried out for example by passive capillary forces (using corresponding capillary systems or microchannels) or by means of active actuating elements.
  • Injection or membrane pumps for example, may be used as the active actuating elements and may be located outside the microfluidic platform or on the platform and produce a corresponding pressure within a microfluidic structure consisting in particular of microchannels and microcavities.
  • microfluidic platforms comprise a sample input region of the order of a few millimetres in size for introducing a quantity of sample liquid of the order of a few microlitres, while the sample liquid (such as blood) has to be transported through a microchannel or through a microchannel system to corresponding cavities containing for example chemical reagents in dried form.
  • microfluidic platform or microfluidic component Therefore, to compensate, more space has to be provided on the microfluidic platform or microfluidic component. This should be avoided in particular for microfluidic platforms, on account of the associated increase in manufacturing costs.
  • a microfluidic structure or a microfluidic platform for filling without any air bubbles is known from DE 103 60 220 A1.
  • a cavity is provided having an inlet opening and an outlet opening.
  • the cavity comprises microstructural elements in the form of pillars. This region forms an area of increased capillary force.
  • the increased capillary force initially causes total wetting, free from air bubbles, of the entry region of the cavity with the sample liquid.
  • the part of the cavity facing the outlet opening is only wetted subsequently.
  • a ramp is provided in the cavity which raises the level of the cavity base to the level of the outlet opening.
  • An arrangement of this kind is unsatisfactory for filling cavities that are large, particularly broad (at right angles to the direction of inflow or throughflow of the liquid) and irregularly shaped.
  • the invention is therefore based on the problem of improving a microfluidic structure according to the preamble of claim 1 so as to allow improved filling, particularly of large cavities, particularly substantially free from air bubbles.
  • the invention therefore starts from a microfluidic structure comprising at least one cavity having at least one inlet opening and at least one outlet opening, the cavity being adapted to be filled with a liquid or have such a liquid flow through it and within the cavity is provided at least one element which at least temporarily stops and/or at least partially deflects the liquid as it flows within the cavity.
  • the at least one element is formed by a recess provided in a wall of the cavity, which has at least one first region at which the liquid is at least temporarily stopped and/or at least partially deflected and at least one second region at which the liquid preferably flows into the recess.
  • the liquid flows immediately, i.e. without any appreciable stop, into the recess and, beyond a specified fill level of the recess, also draws the liquid that has initially stopped in the first region of the recess into the recess with it.
  • the liquid in the cavity can be controlled such that the cavity is filled uniformly and substantially free from air bubbles. This is possible even with cavities that are large, particularly wide and irregular in shape which have, for example, a fill volume of the order of about 10 ⁇ l to 10 ml.
  • the above-mentioned wall of the cavity may be, for example, a base of the cavity.
  • any other walls of the cavity are also conceivable.
  • the wall in a suitable configuration of a lid closing of the cavity, the wall may also be formed by the latter, for example. A combination of these two possibilities is also possible, for example.
  • the second region is formed by a ramp-like transition which starts from a base level of the cavity and extends to a base level of the recess.
  • This ramp-like transition ensures, in a simple manner, that the sample liquid flows into the recess at this point, without stopping, and fills the recess.
  • the ramp-like transition starting from a boundary edge of the recess, forms an angle of about 10° to 60°, most preferably about 45°, with a base plane of the cavity. Tests have shown that the desired flow characteristics of the liquid can best be achieved by such a choice of geometric parameters.
  • the second region could also be formed by a “soft” transition, for example by a convex or concave rounded portion.
  • a notch-like structure (looking at the recess in plan view) is also conceivable.
  • the first region is expediently formed by a boundary edge of the recess at which the convergent walls that form the boundary edge enclose an angle of less than 120°, preferably approximately between 95° and 70°, most preferably about 90°.
  • the first region reliably forms a capillary stop at which the inflowing liquid is initially stopped or deflected.
  • the at least one recess is of elongate configuration, the at least one first region facing an incoming liquid and the at least one second region being remote from an incoming liquid.
  • the incoming liquid can be controlled so that initially it reaches the first region, is stopped there, deflected and on reaching the second region preferably runs into the recess (without any appreciable stop) and fills it.
  • the desired control of the liquid can be adapted to the specific length of a cavity.
  • the recess may be approximately rectangular, for example, in plan view. However, it may also be of a different shape in plan view, for example arcuate. This may be expedient, for example, when the cavity that is to be filled is also of arcuate configuration in its longitudinal extent.
  • a plurality of recesses are provided which are arranged alternately, starting from the side walls of the cavity.
  • the at least one first region extends substantially over the entire length of a longitudinal side of the at least one recess and the at least one second region extends over only part of the length of another longitudinal side.
  • the invention also relates to a microfluidic platform having at least one microfluidic structure according to at least one of claims 1 to 7 .
  • a microfluidic platform thus configured can be manufactured cheaply and meets high demands for a reliable, particularly bubble-free filling of the cavities present.
  • FIG. 1 shows a microfluidic structure according to a first preferred embodiment in plan view, in schematic form
  • FIG. 2 is a sectional view of the microfluidic structure along section line II in FIG. 1 ,
  • FIG. 3 is a detailed view III from FIG. 2 .
  • FIGS. 4 a to 4 f show different stages of filling the microfluidic structure according to FIG. 1 with a liquid
  • FIG. 5 shows a microfluidic structure in plan view according to a second embodiment, in schematic form
  • FIG. 6 shows a microfluidic structure in plan view according to a third embodiment, in schematic form
  • FIG. 7 shows a microfluidic structure according to the prior art
  • FIG. 8 shows a sectional view along section line VIII in FIG. 7 .
  • FIGS. 1 to 3 First of all, reference will be made to FIGS. 1 to 3 .
  • the microfluidic structure 1 comprises a cavity 10 which has a fill volume of about 15 ⁇ l.
  • the cavity 10 is irregularly shaped and is provided with an inlet opening 11 which connects the cavity 10 to a fill channel 16 .
  • the fill channel 16 itself may be connected to a fill opening (for example a sample input region) which is not specifically designated.
  • the cavity 10 On the other side the cavity 10 is provided with an outlet opening 12 which for example opens up the fluidic connection to a venting channel 17 .
  • a capillary stop 24 In the region of the outlet opening 12 a capillary stop 24 is also provided in conventional manner.
  • the cavity 10 may be connected through an outlet opening with another microchannel 18 (shown by dashed lines) if a liquid is to be transported through the cavity 10 into another cavity, for example (not shown).
  • the cavity 10 is a comparatively large cavity measuring about 12 mm wide, 36 mm long and about 1.5 mm deep.
  • Each recess 13 is substantially rectangular in appearance, in plan view, with a length L and a width B.
  • the recesses 13 are arranged alternately, starting from longitudinal sides of the cavity 10 .
  • each recess 13 comprises a first region 14 which faces an incoming liquid F (see FIG. 4 ) and at which the incoming liquid F is at least temporarily stopped and/or at least partly deflected.
  • each recess 13 is provided with a second region 15 at which an incoming liquid F flows into the recess 13 without being stopped.
  • the cavity 10 is closed off by a cover 21 (for example a film attached by adhesion) and comprises a base 19 .
  • Each recess 13 comprises a base 20 .
  • FIG. 3 shows that the first region 14 (capillary) is formed by a boundary edge 22 of the recess 13 at which the convergent walls forming the boundary edge 22 make an angle ⁇ which is 90°.
  • ⁇ which is 90°.
  • other angles are naturally possible and may be greater than or less than 90°.
  • the second region 15 is formed by a ramp-like transition R which, starting from the base level 19 of the cavity 10 , extends to a base level 20 of the recess 13 .
  • the ramp-like transition R starting from a boundary edge 23 of the recess 13 , forms an ⁇ of about 45 degrees with the base plane 19 of the cavity 10 .
  • angles greater than or less than 45° are possible.
  • the second region 15 does not necessarily have to be formed by a ramp-like transition but that other embodiments are also possible.
  • FIG. 3 shows that the second region may for example also be formed by a “soft” transition, for example a concave 15 ′′ or convex 15 ′′′ rounded portion.
  • the inflowing liquid F first of all flows onto the first of the cavities 13 in a direction of flow S ( FIG. 4 a ).
  • the liquid F is initially stopped and deflected at the first region 14 or at the boundary edge 22 ( FIG. 4 b ).
  • the liquid F continues on to the first region 14 of the second recess 13 and again to the second region 15 of the first recess 13 , as a result of which the liquid F fills the first recess 13 through the second region 15 (cf. the dashed arrow in FIG. 4 c ).
  • the liquid F is then stopped and deflected again at the first region 14 of the second recess 13 and the cavity 10 is filled completely, initially leaving the second recess 13 free (cf. FIG. 4 d ).
  • the second recess 13 is also filled through the second region 15 (ramp-like transition (R)).
  • the liquid front of the liquid F then extends to the first region 14 of the last recess 13 ( FIG. 4 e ).
  • the liquid F is again initially stopped and deflected until it then reaches the second region 15 of the last recess 13 and, proceeding from that point, fills the latter.
  • the filling process extends as far as the capillary stop 24 in the region of the outlet opening 12 and proceeds with substantially no air inclusions (air bubbles) (cf. FIG. 4 f ).
  • the liquid F is directed in a substantially meandering configuration through the cavity 10 .
  • FIGS. 1 to 4 show that the second region 15 does not extend over the entire length L of a recess 13 but makes up only part of this length. Moreover, the region 15 also occupies a width which is significantly less than the width B of the recess 13 as a whole. In particular, the width of the region 15 is preferably less than half the width B of the recess 13 . As a result it is possible to make good use of the volume of the recess 13 with an adequate fill function of the region 15 .
  • the regions 15 are positioned on the longitudinal sides of the recesses 13 remote from the incoming liquid F, it is also possible, however, to provide such regions at least partly on the transverse sides of the recesses 13 (cf. the dashed lines 15 ′ in FIG. 1 ). It is also possible to provide a plurality of such regions on a recess (cf. also reference numerals 43 in FIG. 6 ).
  • FIG. 5 now shows a second embodiment 3 of a microfluidic structure of a microfluidic component 4 .
  • the microfluidic structure 3 comprises a cavity 30 with slightly differently configured recesses 31 .
  • Each recess 31 is in turn provided with a first region 32 in the form of a stop edge (capillary stop) which faces the direction of flow S of an incoming liquid.
  • a second region 33 in the form of a ramp, the region 33 extending over an entire length L of the recess 31 .
  • the width of the region 33 in turn amounts to at most only half a width B of the recess 31 .
  • a meandering flow is created for an incoming liquid by the alternating arrangement of the recesses 31 .
  • a microfluidic structure 5 on a microfluidic component 6 is shown which (in contrast to the preceding embodiments) has a cavity 40 which is curved, viewed in the direction of inflow S of a liquid.
  • each recess 41 having a longitudinal extent L and being of a curved configuration over this length L. Moreover it is apparent that each recess 41 is in turn provided with a first region 42 in the form of a stop edge (comparable with region 14 of the first embodiment) and, at the longitudinal side remote from the incoming liquid, comprises two regions 43 in the form of a ramp (comparable with the region 15 in the first embodiment).
  • a cavity 50 comprises not recesses but bars 51 .
  • the bars 51 are arranged alternately, starting from longitudinal sides of the cavity 50 , and are intended to allow a meandering flow of an incoming liquid (not shown) and hence filling of the cavity 50 substantially free from air bubbles.
  • the bars 51 start from a base 53 of the cavity 50 and extend to a cover 52 which closes off the cavity 50 at the top.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Micromachines (AREA)
US14/127,341 2011-07-05 2012-07-02 Microfluidic Structure Having Recesses Abandoned US20140227148A1 (en)

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JP6240785B2 (ja) * 2013-12-20 2017-11-29 スリーエム イノベイティブ プロパティズ カンパニー サンプルの濃縮及び検出のためのシステム及び方法
US10357909B2 (en) * 2014-05-30 2019-07-23 Absolute Exhibits, Inc. Thermoset in-mold finishing film
TWI499637B (zh) * 2014-06-20 2015-09-11 Ind Tech Res Inst 發泡體及包含其之發光裝置
GB201617869D0 (en) 2016-10-21 2016-12-07 Blacktrace Holdings Limited A microfluidic device

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US9409171B2 (en) 2016-08-09
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