WO2002041996A1 - Inlet for microfluidic devices - Google Patents

Inlet for microfluidic devices Download PDF

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Publication number
WO2002041996A1
WO2002041996A1 PCT/GB2001/005222 GB0105222W WO0241996A1 WO 2002041996 A1 WO2002041996 A1 WO 2002041996A1 GB 0105222 W GB0105222 W GB 0105222W WO 0241996 A1 WO0241996 A1 WO 0241996A1
Authority
WO
WIPO (PCT)
Prior art keywords
liquid
array
inlet
microfluidic device
around
Prior art date
Application number
PCT/GB2001/005222
Other languages
English (en)
French (fr)
Inventor
Helen Andersson
Göran Stemme
Wouter Van Der Wijngaart
Original Assignee
Pyrosequencing Ab
Samuels, Adrian, James
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 Pyrosequencing Ab, Samuels, Adrian, James filed Critical Pyrosequencing Ab
Priority to AU2002223903A priority Critical patent/AU2002223903A1/en
Publication of WO2002041996A1 publication Critical patent/WO2002041996A1/en

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5088Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above confining liquids at a location by surface tension, e.g. virtual wells on plates, wires

Definitions

  • This invention relates to microfluidic devices, and methods of facilitating transfer of liquids onto and the storage of liquids on such devices.
  • microtiter plates are plastics plate with a number of wells, closed at the bottom and capable of holding a certain volume of liquid. Liquid reagents are added to the wells manually with pipettes, or by a robot.
  • Microtiter plates are inexpensive and generally convenient, although do suffer from some drawbacks. For example, since the wells are each essentially a closed system, the by-products of any reactions which take place will accumulate in the wells. Another drawback is that the wells of a microtiter plate are relatively large in volume and thus may not be very suitable for reactions which utilise small volumes of liquid.
  • micro-machined silicon chips for chemical analysis . These are normally planar with inlet and outlet holes formed to provide access to the interior of the chip.
  • glue interconnecting tubes onto the inlets and outlets.
  • this itself causes several problems . Firstly, it is difficult to align the interconnecting tubes to the inlet/outlet holes . Secondly, there is the danger that the inlet or outlet hole could accidentally be filled with glue.
  • interconnecting tubes usually introduce relatively large dead volumes into the system which is undesirable in the context of low volume assays . Finally, the glueing process must be carried out manually and is therefore relatively labour intensive.
  • micro-machined systems are essentially two dimensional which means that only very small volumes of liquid may be stored on the chips without taking up a large surface area. It has also been appreciated that there exists a considerable risk of overflow and therefore cross- contamination in micro-array chip systems.
  • the present invention aims to provide an improved arrangement and when viewed from a first aspect provides a icrofluidic device comprising a liquid inlet having an inlet mouth and liquid confinement means provided around said inlet mouth to confine liquid placed at said mouth to a predetermined area around the mouth.
  • a icrofluidic device comprising a liquid inlet having an inlet mouth and liquid confinement means provided around said inlet mouth to confine liquid placed at said mouth to a predetermined area around the mouth.
  • each inlet may be provided with its own reservoir.
  • the liquid confinement means may comprise a region of hydrophobic material .
  • hydrophobic material is intended to denote a material with greater hydrophobicity than the surrounding surface of the device and does not connote any particular absolute level of hydrophobicity.
  • the hydrophobic material comprises lithographically defined hydrophobic patches on the substrate of the device.
  • the device may be of silicon with channels to receive the hydrophobic patches being formed by Deep Reactive Ion Etching (DRIE) .
  • the hydrophobic material comprises silicone or octafluorocyclobutane (C 4 F 8 ) .
  • the liquid confinement means may comprise a suitable geometric structure, preferably defined by the substrate of the microfluidic device.
  • the liquid confinement means comprises a change in surface height of the device.
  • the inlet mouth and the area around it to which the liquid is to be confined may be located in a recess on the device with the liquid confinement means being defined by the side walls of the recess.
  • the edge of the confinement area may be defined by a channel around the inlet mouth.
  • the liquid confinement means may comprise any combination of the above.
  • the principles of the present invention may also bring benefit if they are applied to more than one inlet. For example, it may be desirable in some circumstances always to apply liquid simultaneously to two or more liquid inlets. In this case, it need be necessary only to confine the liquid to within an area surrounding two or more inlet mouths since cross- contamination between these fluid inlets is not an issue .
  • the invention provides a microfluidic device comprising an array of liquid inlets and liquid confinement means provided around said array of inlets to confine liquid placed on said array to a predetermined area around the array.
  • the individual liquid inlets within the array may simply be formed as in known arrangements.
  • at least one or more and preferably all of the liquid inlets further comprise liquid confinement means around them.
  • the fluids confinement means surrounding the individual fluid inlet mouths may be of the same form as that around the array, of a different form but the same as one another or may, as convenient, be of separate forms .
  • the microfluidic device preferably comprises a micro-machined substrate, preferably of or comprising silicon.
  • the substrate is formed using Deep Reactive Ion Etching (DRIE) .
  • DRIE Deep Reactive Ion Etching
  • Figure 1 shows schematically a fluid inlet of a microfluidic device embodying the present invention
  • Figure 2 shows the fluid inlet of Figure 1 after the application of a drop of liquid
  • Figure 3 shows schematically a fluid inlet of a second embodiment of the invention
  • Figure 4 shows the fluid inlet of Figure 3 after the application of a draft liquid
  • Figure 5 shows schematically two fluid inlets of a third embodiment of the invention
  • Figure 6 shows a fourth embodiment of the invention
  • FIG. 7 shows a further embodiment employing two types of liquid confinement means
  • Figure 8 shows the embodiment of Figure -7 after the application of a small drop of liquid
  • Figure 9 shows the embodiment of Figure 7 after the application of a large drop of liquid
  • FIGS 10 to 12 show further possible embodiment of the invention.
  • Figure 1 there may be seen a close- up, cross-sectional view of a microfluidic device in accordance with a first embodiment of the invention.
  • the device comprises a substrate 10 in which a fluid inlet duct 25 is formed. by.
  • the fluid duct 25 conveys liquid to a reaction chamber in the device (not shown) .
  • the hydrophobic material 40 has a greater hydrophobicity than the surface 15 of the device which surrounds it .
  • the hydrophobic material 40 defines a confinement area 55 within it.
  • the device shown in Fig 1 is fabricated using Deep Reactive Ion Etching (DRIE) of 525 micrometre thick p- doped silicon wafers in a standard ion-coupled plasma etcher (Surface Technology Systems, UK) using 1.5 micrometre thick photoresist as the etch mask.
  • DRIE Deep Reactive Ion Etching
  • FIG. 2 shows the fluid inlet after a drop of liquid 60 has been applied to it.
  • the hydrophobic patch 40 confines the area of contact between the liquid 60 and the surface 15 of the substrate to within the confinement area 55. This allows some liquid 60a to enter the inlet duct 25 whilst surface tension retains the remainder of the liquid 60 in a bulb 60b outside the inlet duct 25.
  • the bulb 60b will supply further liquid. It will therefore be seen that a significantly increased volume of liquid may be stored on the device but taking up relatively little surface area. In a particular example it was found that
  • FIG. 3 A second embodiment of the invention is shown in Figures 3 and 4.
  • the confinement area 55 is defined by an annular channel 50 around the mouth 12 of the inlet duct.
  • the channel 50 has precisely the same effect as the hydrophobic patch of the previously described embodiment in that it prevents the liquid 60 from spreading outside the confinement area 55 thereby preventing cross-contamination and facilitating storage of liquid in a bulb 60b above the inlet mouth 12 as is clear from Figure .
  • Figure 5 shows a further embodiment which is similar to that shown in Figures 1 and 2 except that, in this embodiment, the confinement area 30 includes an array of fluid inlet mouths 12, two of which may be seen in Figure 5.
  • a larger volume of liquid is placed onto the confinement area 30 and may thus enter all of the fluid inlet mouths 12 within the confinement area simultaneously. It will also be appreciated that an even larger volume of liquid may be stored above the upper surface 15 of the device before it is drawn in to the fluid inlet ducts 25 to be used.
  • the embodiment in Figure 6 depicts a further possible arrangement for a confinement area 30 which includes an array of fluid inlets 25.
  • the mouths 12 of the fluid inlets are located within a recess in the substrate 10 of the device, the walls 50 of which define the edges of the confinement area 30.
  • liquid placed in the confinement area may be stored before it is required and drawn in to the individual fluid inlets 25 simultaneously through capillary action or, alternatively, could be drawn selectively only into some of the fluid inlets 25 by applying a suction force on those particular inlets.
  • FIG 7 shows a further embodiment of the invention which combines the features of the embodiment of Figure 1 with those of the embodiment of Figures 3 and 4.
  • two fluid inlet mouths 12 are individually surrounded by channels 50 defining confinement areas 55.
  • a region of hydrophobic material in the form of silicone tape 42 is provided around the array of fluid inlets 25. This defines a larger confinement area which encompasses the array of fluid inlet mouths 12.
  • a relatively small volume of liquid may be applied to the individual fluid inlet mouths 12 as shown by the dashed outlines 62.
  • different liquids may be applied to each of the fluid inlet mouths 12 with a very low risk of cross-contamination.
  • the same liquid may be allowed to enter all of the fluid inlets 25 in the array simultaneously .
  • Figures 10, 11 and 12 show various combinations of confinement means for individual fluid inlets and arrays of inlets respectively.
  • the embodiment of Figure 10 shows rings of hydrophobic material 40 defining confinement areas around the individual fluid inlets 12 whilst a channel 50 delimits a confinement area which contains the array of fluid inlets 12.
  • a further channel 54 may be seen inwardly of the channel 50 defining the confinement area for the array of inlets. This additional channel 54 provides a marginal increase in the fluid storage capacity above the chip .
  • both the array confinement area 30 and the individual confinement areas 55 are defined by respective areas of hydrophobic material 42, 40.
  • Figure 12 has the overall and individual confinement areas 30, 55 defined by respective channels 56, 50 around the array and individual inlets.

Landscapes

  • 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)
  • Optical Measuring Cells (AREA)
PCT/GB2001/005222 2000-11-27 2001-11-27 Inlet for microfluidic devices WO2002041996A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002223903A AU2002223903A1 (en) 2000-11-27 2001-11-27 Inlet for microfluidic devices

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0004352-1 2000-11-27
SE0004352A SE0004352D0 (sv) 2000-11-27 2000-11-27 System och metod för anslutning av vätskor i ett mikrofluidiskt flödescellsystem

Publications (1)

Publication Number Publication Date
WO2002041996A1 true WO2002041996A1 (en) 2002-05-30

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2001/005222 WO2002041996A1 (en) 2000-11-27 2001-11-27 Inlet for microfluidic devices

Country Status (3)

Country Link
AU (1) AU2002223903A1 (sv)
SE (1) SE0004352D0 (sv)
WO (1) WO2002041996A1 (sv)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002058846A3 (en) * 2001-01-24 2003-04-24 Univ Michigan Micromachined device for receiving and retaining at least one liquid droplet, method of making the device and method of using the device
FR2848477A1 (fr) * 2002-12-17 2004-06-18 Commissariat Energie Atomique Procede et dispositif de confinement d'un liquide
WO2004103891A1 (en) * 2003-05-23 2004-12-02 Gyros Patent Ab Fluidic functions based on non-wettable surfaces
WO2006088162A1 (ja) * 2005-02-18 2006-08-24 National University Corporation Saitama University 多種微量試料の注入、移行方法
GB2544152A (en) * 2015-08-26 2017-05-10 Emulate Inc Perfusion manifold assembly
WO2018002596A1 (en) * 2016-06-27 2018-01-04 Fluidic Analytics Limited Improvements in or relating to sample loading into a microfluidic device

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999010735A1 (en) * 1997-08-28 1999-03-04 Caliper Technologies Corporation Improved controller/detector interfaces for microfluidic systems
EP0905515A2 (de) * 1997-09-25 1999-03-31 Basf Aktiengesellschaft Analytisches Messverfahren und seine Verwendung
WO1999043432A1 (en) * 1998-02-24 1999-09-02 Caliper Technologies Corporation Microfluidic devices and systems incorporating cover layers
EP0969083A1 (en) * 1997-08-29 2000-01-05 Olympus Optical Co., Ltd. Dna capillary
US6090251A (en) * 1997-06-06 2000-07-18 Caliper Technologies, Inc. Microfabricated structures for facilitating fluid introduction into microfluidic devices
WO2000067907A2 (en) * 1999-05-11 2000-11-16 Aclara Biosciences, Inc. Sample evaporative control
WO2001007161A1 (en) * 1999-07-23 2001-02-01 Merck & Co., Inc. Method and apparatus for transferring small volume liquid samples

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6090251A (en) * 1997-06-06 2000-07-18 Caliper Technologies, Inc. Microfabricated structures for facilitating fluid introduction into microfluidic devices
WO1999010735A1 (en) * 1997-08-28 1999-03-04 Caliper Technologies Corporation Improved controller/detector interfaces for microfluidic systems
EP0969083A1 (en) * 1997-08-29 2000-01-05 Olympus Optical Co., Ltd. Dna capillary
EP0905515A2 (de) * 1997-09-25 1999-03-31 Basf Aktiengesellschaft Analytisches Messverfahren und seine Verwendung
WO1999043432A1 (en) * 1998-02-24 1999-09-02 Caliper Technologies Corporation Microfluidic devices and systems incorporating cover layers
WO2000067907A2 (en) * 1999-05-11 2000-11-16 Aclara Biosciences, Inc. Sample evaporative control
WO2001007161A1 (en) * 1999-07-23 2001-02-01 Merck & Co., Inc. Method and apparatus for transferring small volume liquid samples

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002058846A3 (en) * 2001-01-24 2003-04-24 Univ Michigan Micromachined device for receiving and retaining at least one liquid droplet, method of making the device and method of using the device
US6764652B2 (en) 2001-01-24 2004-07-20 The Regents Of The University Of Michigan Micromachined device for receiving and retaining at least one liquid droplet, method of making the device and method of using the device
US7438851B2 (en) 2001-01-24 2008-10-21 The Regents Of The University Of Michigan Microsensor with a well having a membrane disposed therein
FR2848477A1 (fr) * 2002-12-17 2004-06-18 Commissariat Energie Atomique Procede et dispositif de confinement d'un liquide
WO2004057405A2 (fr) * 2002-12-17 2004-07-08 Commissariat A L'energie Atomique Procede et dispositif de confinement d'un liquide
WO2004057405A3 (fr) * 2002-12-17 2004-08-19 Commissariat Energie Atomique Procede et dispositif de confinement d'un liquide
WO2004103891A1 (en) * 2003-05-23 2004-12-02 Gyros Patent Ab Fluidic functions based on non-wettable surfaces
WO2004103890A1 (en) * 2003-05-23 2004-12-02 Gyros Patent Ab Hydrophilic/hydrophobic surfaces
US7833486B2 (en) 2003-05-23 2010-11-16 Gyros Patent Ab Hydrophilic/hydrophobic surfaces
WO2006088162A1 (ja) * 2005-02-18 2006-08-24 National University Corporation Saitama University 多種微量試料の注入、移行方法
US8664005B2 (en) 2005-02-18 2014-03-04 National University Corporation Saitama University Method for introducing and transferring multiple minute quantity samples
US10519410B2 (en) 2015-08-26 2019-12-31 Emulate, Inc Pressure manifold and culture module
GB2544152A (en) * 2015-08-26 2017-05-10 Emulate Inc Perfusion manifold assembly
EP3341465A4 (en) * 2015-08-26 2018-11-07 Emulate, Inc. Perfusion manifold assembly
US10125342B2 (en) 2015-08-26 2018-11-13 EMULATE, Inc. Droplet fluid connections
US10184102B2 (en) 2015-08-26 2019-01-22 EMULATE, Inc. Controlling pressure
US10233416B2 (en) 2015-08-26 2019-03-19 EMULATE, Inc. Pressure manifold and culture module
US10273441B2 (en) 2015-08-26 2019-04-30 EMULATE, Inc. Perfusion manifold assembly
US11920114B2 (en) 2015-08-26 2024-03-05 EMULATE, Inc. Controlling pressure
EP3656844A1 (en) * 2015-08-26 2020-05-27 Emulate, Inc. Perfusion manifold assembly
US10689608B2 (en) 2015-08-26 2020-06-23 EMULATE, Inc. Droplet fluid connections
US10913924B2 (en) 2015-08-26 2021-02-09 EMULATE, Inc. Controlling pressure
US10988722B2 (en) 2015-08-26 2021-04-27 EMULATE, Inc. Perfusion manifold assembly
US10988721B2 (en) 2015-08-26 2021-04-27 EMULATE, Inc. Controlling pressure
US11820966B2 (en) 2015-08-26 2023-11-21 EMULATE, Inc. Pressure manifold and culture module
US11834641B2 (en) 2015-08-26 2023-12-05 EMULATE, Inc. Controlling pressure
WO2018002596A1 (en) * 2016-06-27 2018-01-04 Fluidic Analytics Limited Improvements in or relating to sample loading into a microfluidic device

Also Published As

Publication number Publication date
AU2002223903A1 (en) 2002-06-03
SE0004352D0 (sv) 2000-11-27

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